Cumulenes in Click Reactions

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Cumulenes in Click Reactions HENRI ULRICH

A John Wiley and Sons, Ltd., Publication

Cumulenes in Click Reactions

Cumulenes in Click Reactions HENRI ULRICH

A John Wiley and Sons, Ltd., Publication

This edition first published 2009 C 2009 John Wiley & Sons Ltd Registered office John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com. The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for every situation. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data Ulrich, Henri, 1925– Cumulenes in click reactions / Henri Ulrich. p. cm. Includes bibliographical references and index. ISBN 978-0-470-77932-3 (cloth) 1. Alkenes. 2. Chemical reactions. I. Title. QD305.H7U54 2009 547 .412–dc22 2009033775 A catalogue record for this book is available from the British Library. ISBN 978-0-470-77932-3 Set in 10/12pt Times by Aptara Inc., New Delhi, India Printed and bound in Great Britain by CPI Antony Rowe, Chippenham, Wiltshire

Contents Preface Acknowledgements

ix xi

1

General Introduction References

1 12

2

1-Carbon Cumulenes 2.1 Sulfines, R2 C S O 2.1.1 Introduction 2.1.2 Dimerization Reactions 2.1.3 Cycloaddition Reactions References 2.2 Sulfenes, R2 C S(O) O 2.2.1 Introduction 2.2.2 Dimerization Reactions 2.2.3 Cycloaddition Reactions References 2.3 Other 1-Carbon Cumulenes 2.3.1 Thiocarbonyl S-Imides 2.3.2 Thiocarbonyl S-Sulfides 2.3.3 1-Aza-2-azoniaallene Salts References

13 13 13 14 15 23 25 25 26 26 32 33 33 37 39 44

3

2-Carbon Cumulenes 3.1 Carbon Oxides, O C O, :C O 3.1.1 Introduction 3.1.2 Cycloaddition Reactions 3.1.3 Insertion Reactions References 3.2 Carbon Sulfides, S C S, S C O 3.2.1 Introduction 3.2.2 Cycloaddition Reactions 3.2.3 Insertion Reactions References 3.3 Carbon Nitrides 3.3.1 Isocyanates, RN C O References

45 45 45 47 60 61 64 64 65 75 77 79 79 156

vi

Contents

3.4

3.3.2 Isothiocyanates, RN C S References 3.3.3 Carbodiimides, RN C NR References Center Carbon Phosphorallenes, P C P 3.4.1 Introduction 3.4.2 Dimerization Reactions 3.4.3 Cycloaddition Reactions References

168 194 197 232 236 236 236 238 241

4 1,2-Dicarbon Cumulenes 4.1 Ketenes, R2 C C O 4.1.1 Introduction 4.1.2 Dimerization Reactions 4.1.3 Trimerization Reactions 4.1.4 Cycloaddition Reactions References 4.2 Thioketenes, R2 C C S 4.2.1 Introduction 4.2.2 Dimerization Reactions 4.2.3 Cycloaddition Reactions References 4.3 Ketenimines, R2 C C NR 4.3.1 Introduction 4.3.2 Dimerization Reactions 4.3.3 Cycloaddition Reactions References 4.4 1-Silaallenes, R2 C C Si 4.4.1 Introduction 4.4.2 Dimerization Reactions 4.4.3 Cycloaddition Reactions References 4.5 1-Phosphaallenes, R2 C C P 4.5.1 Introduction 4.5.2 Dimerization Reactions 4.5.3 Cycloaddition Reactions References 4.6 Other Metal Allenes 4.6.1 Introduction 4.6.2 Cycloaddition Reactions References

243 243 243 244 252 254 312 321 321 322 323 335 337 337 337 339 363 366 366 366 367 368 368 368 369 370 376 377 377 378 389

5 1,3-Dicarbon Cumulenes 5.1 Thiocarbonyl S-ylides, R2 C S CH2 5.2 2-Azaallenium Salts, R2 C N+ CR2 5.3 1-Oxa-3-azoniabutatriene Salts, R2 C N+ C O

391 391 394 395

Contents

vii

5.4 1-Thia-3-azabutatriene Salts, R2 C N+ C S 5.5 Phosphorus Ylides References

396 397 397

6

1,2,3-Tricarbon Cumulenes 6.1 Allenes, R2 C C CR2 6.1.1 Introduction 6.1.2 Dimerization Reactions 6.1.3 Oligomerization Reactions 6.1.4 Cycloaddition Reactions References 6.2 [3] Cumulenes, R2 C C C CR2 6.2.1 Introduction 6.2.2 Dimerization Reactions 6.2.3 Trimerization Reactions 6.2.4 Cycloaddition Reactions References 6.3 [4] Cumulenes, R2 C C C C CR2 6.3.1 Introduction 6.3.2 Dimerization Reactions 6.3.3 Cycloaddition Reactions References 6.4 [5] Cumulenes, R2 C C C C C CR2 6.4.1 Introduction 6.4.2 Dimerization Reactions 6.4.3 Cycloaddition Reactions References

399 399 399 402 410 412 456 462 462 462 464 465 468 469 469 469 470 470 470 470 471 472 473

7

Noncarbon Cumulenes 7.1 Azides, RN N N 7.1.1 Introduction 7.1.2 Oligomers 7.1.3 [3+2] Cycloaddition Reactions References 7.1.4 Some Applications in Modifications of Biopolymers Application References 7.2 Triazaallenium Salts, RN N+ NR 7.2.1 Introduction 7.2.2 Cycloaddition Reactions References 7.3 Sulfur Oxides 7.3.1 Introduction 7.3.2 Sulfur Dioxide, O S O 7.3.3 Sulfur Trioxide, O SO2 References

475 475 475 476 477 492 495 499 501 501 501 502 503 503 504 510 515

viii

Contents

7.4

Sulfur Nitrides 517 7.4.1 N -Sulfinylamines, RN S O and N -Thiosulfinylamines, RN S S 517 526 7.4.2 Sulfurdiimines, RN S NR 529 7.4.3 N -Sulfonylamines, RN SO2 and Hexavalent Sulfurdiimides 533 7.4.4 Dithionitronium Salts, S N+ N References 536 538 7.5 Cationic Boron Cumulenes, R2 N B NR 7.5.1 Introduction 538 7.5.2 Cycloadditions 539 References 540

Index

541

Preface The advent of azide/alkyne ‘click’ chemistry, reintroduced by Sharpless and Meldal earlier this century, has prompted an avalanche of publications in the fields of biochemistry, material science and biopolymers. As of 2008, more than 1000 publications on this subject are listed on the Sharpless website. I have noticed that gradually other [3+2] and [4+2] cycloaddition reactions are included, indicating that cycloaddition chemistry is useful for construction and modification of biopolymers. Especially, the [3+2] ‘Huisgen’ chemistry is useful because in addition to azides many other 1,3-dipolar species react with dipolarophiles at room temperature and the yields often approach quantitative. There is also renewed interest in [4+2] Diels–Alder chemistry. The Nobel Laureates involved in cycloaddition chemistry include Sharpless (2001), Staudinger (1953), Diels and Alder (1950) and Wittig (1979) and today’s emphasis on green chemistry has accelerated research in this field. For example, cycloaddition reactions of carbon dioxide could be of interest for sequestering of greenhouse gases. In addition, sulfur dioxide readily undergoes cycloaddition reactions with dienes. I was first introduced to more exotic azide chemistry during my research work at Ohio State University in the early 1950s where we synthesized highly explosive oligo azides. Soon afterwards, at the former Donald S Gilmore Research Laboratories of the Upjohn Company in North Haven, Connecticut, working on isocyanates and carbodiimides, I realized the enormous potential of these cumulenes for high-yielding addition reactions. In 1967, I published a book on Cycloaddition Reactions of Heterocumulenes and in the following forty years a wealth of new information has become available. Especially, highly reactive 1,3-dipolar compounds generated in situ, such as 1-aza-2-azoniaallene salts (Chapter 2, Section 2.3.3), triazaallenium salts (Chapter 7, Section 7.2) and dithionitronium salts (Chapter 7, Section 7.4.4), react readily with numerous dipolarophiles to form [3+2] cycloadducts in very high yield. In addition, ring-opening of three-remembered ring compounds generates 1,3-dipolar species, which readily react with suitable dipolarophiles. Some of these reactions can be conducted in the absence of solvents. Photochemical intramolecular cyclization reactions of allenes occur at room temperature in the solid state in quantitative yields, indicating their enormous potential for green chemistry. The cumulenes discussed in this book are subdivided into carbon- and noncarbon cumulenes, and the 1-carbon cumulenes (sulfines, sulfenes, thiocarbonyl S-imides and thiocarbonyl S-sulfides) are excellent dipolar species. The 2-carbon or the center-carbon cumulenes (carbon dioxide and carbon sulfides) are less reactive but their imides (isocyanates, isothiocyantes and carbodiimides) readily participate in many of the discussed reactions. The 1,2-dicarbon cumulenes (ketenes, thioketenes and ketenimenes) similarly participate in cycloaddition reactions, as well as the more exotic 1,2-dicarbon cumulenes (1-silaalene, 1-phosphaallene and other metal allenes). In contrast, 1,3-dicarbon cumulenes are only

x

Preface

minor participants but thiocarbonyl S-ylides (Chapter 5, Section 5.1) as well as 2azaallenium salts (Chapter 5, Section 5.2) are excellent 1,3-dipolar reagents. Tricarbon cumulenes, such as allenes (Chapter 6, Section 6.1) and the higher allenes (Chapter 6, Sections 6.2 to 6.4) also participate readily in inter- and intramolecular cycloaddition reactions. Last, but not least, non-carbon cumulenes (azides, sulfur oxides and sulfur nitrides) are highly reactive in cycloaddition reactions. This present text should prove valuable to researchers and technologists in organic, bioorganic and polymer chemistry, especially in the emerging fields of proteomics and nanotechnology. Henri Ulrich

Acknowledgements I would like to acknowledge the contributions of many of my friends and colleagues in the global chemistry community, especially Dr Frank Seela, formerly at the University of Osnabruck, Dr Gert Kolllenz, formerly at the Karl Franzen University of Graz and Dr Ernst Schaumann, the Technical University of Clausthal-Zellerfeld. In addition, Drs Mloston, Alvarez, Maslivets, Vogel and Jochims have provided numerous reprints of their work in cycloaddition reactions. Dr Huisgen, the pioneer of dipolar cycloaddition reactions, also provided valuable input. In my earlier work on isocyanates and carbodiimides the valuable contributions of Professor Dr W von Eggers-Doering, formerly at Harvard University, are gratefully acknowledged. Last but not least, I would like to thank my wife Franziska for her patience, constant encouragement and support of this undertaking.

1 General Introduction Click chemistry, as introduced by Kolb and Sharpless in 2001 1 , relates mainly to the Cu(i) catalyzed [3+2] cycloaddition reaction of azides with alkynes. This copper catalyzed cycloaddition reaction is highly useful for attaching fluorescent or other markers to a wide variety of biomolecules. Although azides are often unstable at elevated temperatures, they are stable at physiological conditions, have no intrinsic toxicity and have extraordinary chemical selectivity. Proteins and glycans have already been labeled with azides in laboratory mice using enzyme inhibitors and sugar azides. Azides have cumulative double bonds and they are only a small section of the cumulenes encountered in organic chemistry. Cumulenes are often not stable at room temperature and they are isolated as their cyclic dimers, formed in a click reaction. In this case a [2+2] cycloaddition reaction occurs, and often no catalyst is required. Some of the more exotic cumulenes are matrix isolated at low temperatures. For example, alkyliminopropadienones, RN C C C O, the mono imides of carbon suboxide, are unstable. However, the neopentyl-, mesityl- and o-t-butylphenyl derivatives can be isolated at room temperature and their nucleophilic reactions provide a wide variety of heterocyclic compounds 2 . Several of the early Nobel prize winners were involved in the click reactions of cumulenes. For example, the [2+2] cycloaddition reaction of ketenes and imines to give β-lactames is often referred too as the Staudinger reaction. Another Nobel Laureate, Sheehan, has used this reaction to synthesize penicillin antibiotics. The reaction of iminophosphoranes with other cumulenes is called the aza–Wittig reaction. Also, Wittig received the Nobel Prize for his pioneering work in phosphorous chemistry. The [3+2] cycloaddition reactions, which include the cycloaddition of azides to alkynes named by Sharpless, also a Nobel Laureate, as a click reaction, are sometimes referred to as Huisgen reactions. Rolf Huisgen has extensively investigated the [3+2] dipolar cycloaddition reactions 3 . The [4+2] cycloaddition reactions are called Diels–Alder reactions, again named after two early Nobel Laureates. The best example of a click polymerization reaction is the polyaddition reaction of diisocyanates with dioles or polyols to produce polyurethanes. This reaction was discovered Cumulenes in Click Reactions Henri Ulrich C 2009 John Wiley & Sons, Ltd

2


by Otto Bayer, at the IG Farben Laboratories (now Bayer AG) in 1937, and today the world wide consumption of polyurethanes exceeds 10 million tons per annum. In the formation of polyurethanes no solvents are required, the yields are quantitative and most reactions are conducted at room temperature. An exception is the RIM (reaction injection molding) of automotive bumpers which is conducted at elevated temperatures to increase the production rate. When this polymerization is conducted continously in an extruder, the finished polymers are extruded, chopped and collected in drums. An example is the production of thermoplastic segmented polyurethane elastomers, appropriately sold by Dow under the tradename ‘Pellethane’ 4 . In the reaction of thermoset reaction polymers spray technology is also applied. For example, flexible polyurethane foams are continuously produced in buns and semirigid and rigid insulation foams are directly sprayed onto the substrate. Dendritic polymers are also constructed by reacting 1,3,5-benzene triisocyanate with amines 5 . Copolymerization reactions of cumulenes are also of some significance. For example, copolymerization of carbon monoxide with alkenes affords polyketones, which are biodegradable and they also could undergo subsequent crosslinking reactions on the carbonyl group. When carbon dioxide is copolymerized with alkenes, polyesters are obtained. The polyaddition reactions of diketenes with diols to produce polyesters is not used, because of the tendency of ketenes to undergo dimerization reactions. Also, sulfur dioxide can be copolymerized with alkenes to produce polysulfones. Some of the cumulenes undergo homo-polymerization reactions. The homo-polymers derived from isocyanates and carbodiimides are of no commercial value because the homopolymers ‘unzip’ on heating. Intractable thermoset polymers are obtained from carbon suboxide or carbon disulfide. More often the click reaction is used in the modification of biopolymers. An example is sugar-derived imaging in live animals. Glycans in live zebrafish embryos light up when the embryos are fed azide-derived sugars and are subsequently treated with difluorinated cyclooctyne derived probes 6 . Elastin-like hybrid polymers, based on the reaction of azide-terminated poly (ethylene oxide) (PEO) and alkyne functionalized peptides, are also developed. These polymers are intended to grow new vocal cords 7 . The cyclodimerization reaction of cumulenes is their most common click reaction, especially when the monomers are not stable at room temperature. Some of the cyclodimers serve as a ready source of the monomers, which are generated in situ and are trapped with suitable reagents. Sometimes, the retro reactions provide new cumulenes. In this book the latter reactions are referred to as ‘exchange reactions’. Cyclodimerization reactions can occur across either one of the cumulative double bonds giving rise to the formation of head-to-head or head-to-tail cyclodimers. The stable headto-tail cyclodimers of ketenes and the head-to-head cyclodimers of isocyanates are good examples and only one type of cyclodimer is formed. In contrast, allenes often provide mixtures of cyclodimers. A ‘super-click reaction’ is observed in the cyclodimerization of bis-allenes, which occurs at room temperature in the solid state upon irradiation to give the cyclodimers in quantitative yields 8 . The first example of a cumulene click reaction, the cyclodimerization of phenyl isocyanate, was reported by Hofmann in 1860 9 . In later years numerous cycloaddition reactions of cumulenes with a wide variety of double or triple bonded substrates were observed 10 . In addition to the cycloaddition reactions of cumulenes their insertion reactions into numerous single bonds also often proceed at room temperature in high yields 10 . In fact,

General Introduction

3

even some nucleophilic reactions of cumulenes can be considered to involve click reactions, i.e. they occur at room temperature, sometimes without a solvent to produce linear reaction products in quantitative yields. Perhaps the most important click reaction in chemistry is the neutralization of an acid by a base which can be conducted at room temperature, often in water and the yields are always quantitative. The most general definition of click chemistry is a reaction which proceeds at room temperature, often without a solvent or catalyst, to give the reaction product in close to quantitative yields. The yields in the reactions in this book are by no means optimized, but they often approach quantitative. As an industrial chemist I am well aware that yields can be dramatically increased with modest process development efforts. Sometimes, a change of reaction temperature can have a dramatic effect, as demonstrated by Wilson and Fu who obtained a < 2 % yield of β-lactones in their [2+2] cycloaddition reaction of ketenes with aldehydes at room temperature, while at −78 ◦ C a 92 % yield of the cycloadduct is obtained 11 . The yields shown in the selected examples in this book are often the higher yields reported by the authors. More comprehensive lists can be found in my relatively recent books on isocyanates 12 and carbodiimides 13 . Of course, comprehensive lists of cycloadducts of heterocumulenes are also found in my 1967 book 10 . Huisgen’s introduction of the dipolar [3+2] cycloaddition reaction has provided an enormous variety of synthetically useful click reactions. The example quoted by Kolb and Sharpless 1 is ‘only the tip of the iceberg’. Over 1000 literature references on this reaction were reported in recent years. I had summarized the cycloaddition reactions of heterocumulenes in 1967 10 , but in the meantime many new cumulenes have emerged and the cycloaddition reactions of carbon cumulenes, such as allenes, butatrienes and higher cumulenes, are also well investigated. The cycloaddition reactions of cumulenes generally produce three- to six-membered ring compounds, which often cannot be obtained in a one-step reaction. When the cumulene or the substrate contain metal to carbon bonds, metallacycles are readily produced. Organometalic compounds are readily obtained in the insertion reactions of the cumulenes. In the latter reactions, linear compounds are obtained. Click chemistry therefore can provide not only a vast number of cyclic compounds but also numerous linear compounds and even linear and crosslinked polymers which have commercial significance. Often the initially formed bonds at low temperature are not the ones that are isolated at room temperature. Also the electronic configurations play a part in product formation. For example, in the [2+2] cycloaddition reaction involving two carbodiimides the more nucleophilic carbodiimide attacks the more electrophilic carbodiimide giving rise to the formation of only one reaction product. The latter reactions proceed stepwise, while sometimes concerted reactions are observed. Sterical hindrance also plays an important role in product formation. We have utilized N-methyl-N -t-butylcarbodiimide as a probe in determining the structure of the derived cycloadducts, because the reaction always proceeds via addition across the C N bond with the methyl substituent. For example, in the [2+2] cycloaddition reaction with benzoyl isocyanate the reaction proceeds across the C O bond of the isocyanate, because t-butyl isocyanate is the only product generated in the retro reaction 14 . By definition, cumulenes are compounds with double bonds adjacent to each other. The parent compound of carbon cumulenes is allene, CH2 C CH2 , in which the center as well

4


as the terminal atoms are carbon. Extension of the double bonded system produces the higher cumulenes and often the number of double bonds are used to identify the higher cumulenes. When one or more of the atoms in the cumulative system are hetero atoms, such as oxygen, nitrogen, sulfur or selenium, they are known as heterocumulenes. The carbon containing heterocumulenes are sometimes referred to as heteroallenes. I have organized the cumulenes according to the number of carbon atoms in the cumulative system. In Chapter 2 I have treated the cumulenes with one carbon atom in the beginning of the cumulative system. With the exception of the 1-aza-2-azoniaallene salts, the compounds are sulfur derivatives. The thiocarbonyl S-sulfides are excellent 1,3-dipoles, which participate in numerous [3+2] cycloaddition reactions. Huisgen has reviewed their chemistry in 1997 15 . In Chapter 3 the cumulenes with a center carbon atom are treated, which include the carbon oxides, carbon sulfides and carbon nitrides (isocyanates, isothiocyanates and carbodiimides). In this chapter the chemistry of carbon dioxide is of considerable interest, because the sequestering of carbon dioxide is a major problem in coping with global warming. The chemistry of isocyanates relates to polyurethanes, which are major industrial polymers, and carbodiimides play an important role in proteomics, the building blocks of life. Center carbon phosphaallenes and diarsaallenes are also treated in Chapter 3. The 1,2dicarbon cumulenes are described in Chapter 4, which encompass the ketenes, thioketenes, ketenimines, 1-silaallenes, 1-phosphaallenes, as well as some metal allenes. In Chapter 5 the 1,3-dicarbon cumulenes, which are not too well known, are treated, and in Chapter 6 the ‘all-carbon’ cumulenes are summarized. This chapter encompasses the allenes and the higher carbon cumulenes. Higher carbon cumulenes have been detected in interstellar space by microwave spectroscopy, and in recent years many of the higher carbon monoxides, C2 O to C6 O and carbon dioxides, carbon monosulfides and carbon disulfides, have been matrix isolated at low temperatures. The carbon monoxides and carbon monosulfides have a linear carbene like structure. Finally in Chapter 7 the non-carbon cumulenes are described. This latter chapter includes the azides. Cationic cumulenes are also known, and especially the azaallenium salts are known for their 1,3-dipolar character. These cationic cumulene salts undergo numerous [3+2] cycloaddition reactions with suitable dipolarophiles to give five-membered ring heterocycles, often in quantitative yields. The cycloaddition reactions of all of the cumulenes under discussion are of considerable importance because in almost all cases only one compound is isolated in high yield. This renders these reactions as the most useful method to synthesize cyclic or heterocyclic compounds, which are often otherwise difficult to synthesize. The first book on the reactions of carbon cumulenes, treating the cycloaddition reactions of ketenes in depth, was written by Staudinger in 1912 16 . Staudinger already realized that cycloaddition reactions of ketenes are common, and often ketenes were only isolated as cyclodimers. The cyclodimers of isocyanates became prominent in the development of polyurethanes in the IG Farben Laboratory in Leverkusen, Germany in the early 1930s 17 , and the cyclotrimerization of diisocyanates led to the development of polyisocyanurate foams, with thermal stability superior to rigid polyurethane foams in the 1960s. Today, polyisocyanurate foams are used in the insulation of the fuel tank of the space shuttle. Also, carbodiimide derived cellular plastics with improved thermal stability are of interest 18 . In recent years, cumulene derived polymers became of interest as one-dimensional molecular wires.


5

The chemical reactivity of the cumulenes under discussion ranges from highly reactive species to almost inert compounds. While some cumulenes can only be generated in a matrix at low temperatures, others are indefinitely stable at room temperature. For example, sulfines and sulfenes are only generated in situ, but some cumulenes with bulky substituents are sometimes isolated at room temperature: for example, :C C S was detected in interstellar space by microwave spectroscopy, and its spectrum was later verified by matrix isolation spectroscopy. In contrast, some cumulenes, such as carbon dioxide and carbon disulfide, are often used as solvents in organic reactions or in the extraction of natural products. The reactivity of some center carbon heterocumulenes in nucleophilic reactions is as follows: isocyanates > ketenes > carbodiimides > isothiocyanates. However these reactivities do not relate to the reactivities in cycloaddition reactions. Often reactive cumulenes are isolated as their cyclodimers. Aromatic diisocyanates are more reactive than aliphatic diisocyanates in nucleophilic as well as cycloaddition reactions. Substituents attached to the cumulative system can influence their reactivity. The effect of the substituents can be both steric or electronic. For example, steric hindrance is often applied to stabilize a cumulene system, which normally cannot be isolated. For example, 2,4,6-trimethyl-phenyl groups are used in phosphorus cumulenes for this purpose, and 2,4,6-trichlorophenyl groups are used to stabilize 1,3-diaza-2-azaallenium cations. Also, ortho methyl groups in phenyl substituents are often sufficient to prevent cycloaddition reactions. An example is the selective dimerization of 2,4-tolylene diisocyanate involving the isocyanate group para to the methyl group. In methyl-t-butylcarbodiimide the [2+2] cycloaddition reactions proceed across the less hindered C N bond. Also, substituents attached to phenyl groups in aromatic cumulenes influence their reactivity. For example in isocyanates electron withdrawing groups increase the electrophilicity of the center carbon atom, whereas electron donating groups reduce the electrophilicity. The reactivity of isocyanates in cycloaddition reactions is greatly enhanced in carbonyl-, thiocarbonyl-, imidoyl- and sulfonyl-isocyanates. While the sulfonyl isocyanates undergo [2+2] cycloaddition reactions readily, they do not undergo cyclodi- or trimerization reactions. The reactivity of ketenes in cycloaddition reactions is as follows: diphenylketene > dimethylketene > butylethylketene > ketene 19 . The mechanism of the cycloaddition reactions of cumulenes involve concerted one-step processes as well as two-step processes, and both types of mechanisms are encountered. It seems that concerted processes are more the exception, and ionic linear 1:1 intermediates are sometimes trapped in cycloaddition reactions. The sometimes encountered [2+2+2] six-membered ring cycloadducts exemplify the stepwise reactions. The cycloaddition reactions are subdivided into di-, tri- and oligomerization reactions, [2+1]-, [2+2]-, [3+2]- and [4+2] cycloaddition reactions and other cycloaddition reactions. The insertion reactions into single bonds are also discussed. The cyclodimerization or cyclotrimerization reactions are special examples of the [2+2] and the [2+2+2] cycloaddition reactions, respectively. The cumulenes vary in their tendency to undergo these reactions. The highly reactive species, such as sulfines, sulfenes, thioketenes, carbon suboxide and some ketenes, are not stable in their monomeric form. Other cumulenes have an intermediate reactivity, i.e. they can be obtained in the monomeric state at room temperature and only heat or added catalysts cause di- or trimerization reactions. In this group, with decreasing order of reactivity, are allenes, phosphorus cumulenes, isocyanates, carbodiimides and isothiocyanates.

6


In the cumulative systems, X C Y (X = CR2 , NR; Y = O, S, NR), in RP C X (X = O, S, NR) and in R3 P C C X (X = O, NR) three types of dimeric species are visualized. When the cycloaddition reaction proceeds across the C X double bond the cyclodimer 1 is formed. When the reaction proceeds across the C Y bonds the cyclodimer 2 is obtained and when the reaction proceeds across both bonds the asymmetric cyclodimer 3 is isolated. y

x

x

y

x

y

x

y

y

y x

x 1

3

2

The cyclodimers 1 and 2 have an axis of symmetry, because dissociation in both directions affords the same products. Cyclodimer 3 has no axis of symmetry and cleavage in both possible directions affords different products. All three types of cyclodimers are encountered in the cumulenes X C Y and the asymmetric dimers often undergo thermolysis contrary to their mode of formation. A typical example is cyclodimer 3 derived from dimethylketene, which affords tetramethylallene and carbon dioxide on thermolysis. In the cycloaddition reaction of higher cumulenes different types of cyclodimers are encountered. In [3] cumulenes the cycloaddition can occur across the center bonds to form [4] radialenes 4 or across their end groups to give cyclodimers 5 and 6. R

R •

R2

R

R

R2

R R

•

•

R2

R2

• R R 4

5

6

Radialenes are also obtained from [5] cumulenes. Pentatetraenes dimerize across their end double bonds to form 7 or one of the center double bonds to give 8. R •

• •

•

R2

R2

R

R

R R

R •

•

R R

R

R R

R 7

8

As a general rule ketenes undergo non-catalyzed [2+2] cycloaddition reactions across their C C bonds, with the exception of ketene itself. In contrast, disubstituted thioketenes undergo cyclodimerization across their C S bonds. Mono substituted thioketenes undergo dimerization via a [3+2] cycloaddition reaction, also involving the C S bonds.


7

N-Isothiocyanatodimethylamine 9 dimerizes at room temperature in less than one minute via a [3+2] cycloaddition to give 10, which rearranges in solution to form 11 20 .

Me2NN C

Me2N N S S N

S

MeN

SMe

N

NMe2 9

N

S

NMe2

10

11

Another type of dimerization is observed in heterocumulenes, having the cumulative system attached to a carbonyl-, thiocarbonyl- or an imidoyl-group. Although these heterocumulenes can dimerize via a [2+2] cycloaddition sequence, more often a Diels–Alder-like [4+2] cycloaddition reaction occurs giving rise to the formation of six-membered ring heterocyclic dimers. Often these heterocumulenes are only generated in situ because they undergo rapid dimerization at room temperature. An example is the dimerization of thioacyl isocyanates in which the heterocumulene reacts as diene and dienophile to give the cyclodimer 12 21 .

N R

•

N

S

O

S

O

N

R

N

R

+ S

R

S

O

O 12

Thermal dissociation of the cyclodimers often generates the reactive monomers. Dimeric intermediates are also postulated as intermediates in the exchange reaction of similar and different cumulenes. In these reactions thermal equilibria are established via [2+2] cycloaddition sequences. For example, in the heating of an isocyanate with a differently substituted carbodiimide a four-membered ring intermediate 13 is generated, which can either regenerate the starting materials or form a new set of heterocumulenes. When one of the new products is constantly removed from the reaction mixture (for example, the lowest boiling R1 N C O) the reaction produces the new set of heterocumulenes exclusively 22 . O RN C

O + R 1N

C NR1

RN NR1

R1N

C

O + RN C

NR1

R1N 13

Upon addition of a second equivalent of RN C O the sequence can be repeated, and the final product is RN C NR. The conversion of two equivalents of isocyanate into carbodiimide and carbon dioxide also involves an asymmetric isocyanate dimer as an intermediate. The cyclotrimerization of carbon cumulenes is usually initiated by heat or catalysis. Especially, the use of a catalyst assures that trimerization can be accomplished in quantitative yields. The base catalyzed cyclotrimerization reaction seems to be limited to ketenes, isocyanates, isothiocyanates and carbodiimides. In the trialkylphosphine catalyzed trimerization of methyl isocyanate an asymmetric trimer is obtained.

8


Interesting is the participation of sulfonyl isocyanates and sulfonyl carbodiimides in mixed trimerization reactions although these monomers do not undergo cyclotrimerization reactions themselves. For example, dicyclohexylcarbodiimide reacts with two equivalents of N-p-toluenesulfonyl-N -cyclohexylcarbodiimide to give the six membered ring [2+2+2] cycloadduct 14 in 93 % yield 23 . NR RN C

NR + 2 R1SO2N

C

NSO2 R1

RN

NR

RN

N

NR

SO2 R1 14

In cycloaddition reactions of carbon cumulenes with suitable substrates, [2+1], [2+2], [3+2] and [4+2] cycloaddition reactions giving rise to the formation of cyclic compounds are observed. In general, [2+1] cycloaddition reactions afford three-membered ring compounds with an attached double bond, and sometimes the initially formed cycloadducts rearrange to form an isomeric three-membered ring cycloadduct. An example is the addition of diphenylcarbene to dialkylthioketenes where the initially formed cycloadduct 15 on photolysis produces the isomer 16, with bulky substituents on the three-membered ring 24 . R2 R R 1R 2C

C S

1R2C

Ph

S

R1

S

+ :CPh2

Ph

Ph 15

Ph 16

The carbenes, incuding carbon monoxide and isocyanides, readily participate in these cycloaddition reactions and because of their lone pair of electrons they can be considered to be pseudocumulenes. Also, [4+1] cycloadditions of carbon monoxide or isocyanides to 1,3-dienes are observed to afford five-membered ring cycloadducts 17, often in high yields. + :C

X

X 17

A similar reaction, resulting in the formation of five-membered ring sulfur heterocycles 18, is the cheletropic addition of sulfur dioxide to 1,3-dienes. O + :SO2

S 18

O


9

The lone pair of electrons on sulfur dioxide can also participate in free radical annulation reactions with formation of sulfolanes 19.

()

n

+ SO2 •

()

n

• SO2

()

n

S

O O

19

Carbon cumulenes undergo [2+2] cycloaddition reaction with numerous double or triple bonded substrates to give four-membered ring cycloadducts. Examples of cycloaddition to C≡C, C C, C O, C N, C S, N O, N N. N S. S O, P C, P O, P N and P S bonds are known. When the two adjacent double bonds in the cumulenes are different, cycloaddition across either one of the double bonds occurs, and sometimes addition across both bonds is observed. However, more often the cycloaddition reactions follow only one pathway. As a general rule, in ketenes the non-catalyzed cycloaddition occurs preferentially across the C C bond, whereas catalyzed cycloaddition reactions proceed across the C O bond. In thioketenes, isothiocyanates and sulfenes addition mainly occurs across the C S bond. In isocyanates addition across the C N bond is preferred. The cycloaddition to isolated C C bonds is generally slow, and only highly reactive species, such as sulfonyl isocyanates, react well. The cycloaddition to activated olefins, such as allenes, cyclopentadiene, styrene etc., occurs more readily and many sulfonyl isocyanates and ketenes react at room temperature. The less reactive olefins, such as ethylene, react in the presence of nickel (0) compounds to give five-membered ring metallacycles. Substitution of the olefins by amino or alkoxy groups increases their reactivity in cycloaddition reactions. The approximate order of reactivity is: vinyl ethers < enamines < ketene O,O-acetals < ketene N,N-acetals < tetraalkoxyethylene or tetraaminoethylene. In [2+2] cycloaddition reactions of carbon cumulenes, often only one four-membered ring compound is obtained. This reaction is of considerable importance in the synthesis of βlactams from ketenes and C N double bond containing substrates. The β-lactam structure is present in a variety of antibiotics. Also, β-thiolactams are obtained from thioketenes and imines. The obtained four-membered ring cycloadducts sometimes rearrange to more stable linear products. When the substrate has β-hydrogen atoms attached to the cumulative system, rearrangement to the linear product is the preferred mode of reaction. Also, fragmentation of the initially formed cycloadduct is sometimes observed. Compounds containing phosphorous double bonds are special cases, because the reaction with heterocumulenes across C O or C S bonds affords phosphorous oxides or sulfides with generation of a new double bond. These reactions are generally referred to as Staudinger or Wittig reactions. A well known example is the aza–Wittig reaction involving iminophosphoranes and isocyanates. A concerted four-centered transition state is postulated in order to explain the retention of configuration observed in these reactions. The P N bonds in heterocyclic compounds often undergo [2+2] cycloaddition reactions with heterocumulenes. The cumulative double bonds in cumulenes can also participate in [2+2] cycloaddition reactions with the same or another cumulene to give rise to the formation of four-membered ring cycloadducts.

10


The general nature of these reactions was first recognized by Staudinger and his coworkers in the reaction of ketenes with olefins. Huisgen and his coworkers 25 demonstrated that the cycloaddition reaction of diphenylketene with vinyl ethers is stereospecific, indicating a concerted one-step mechanism. However, more often the [2+2] cycloaddition reactions proceed in a stepwise fashion. In recent examples it was demonstrated that the initial reaction of ketenes with several substrates produces adducts which are different from the isolated ones (see Chapter 4, Section 4.1.4.2) 26 . Also switter ionic intermediates are detected by low temperature spectroscopy. For example, Machiguchi and coworkers 27 have detected the formation of 1,4-switter ionic species as intermediates in the reaction of bis(trifluoromethyl)ketene with ethyl vinyl ether. Also in the reaction of a carbodiimide with diphenylketene in liquid sulfur dioxide the [2+2+1] cycloadduct 21 is obtained by trapping the linear adduct 20 28 . RN C NR + Ph2C

C

O

RN O

C

CPh2 20

NR

NR + SO2

RN O

O S

Ph Ph

O

21

The linear ionic intermediate can also be intercepted with either one of the reagents, for example, in the cycloaddition reaction of ketenes with aliphatic imines (Chapter 4, Section 4.1.4.2). Sometimes [2+2+2] cycloadducts resulting from the reaction of the initially formed linear adduct with either one of the reagents are observed. The basicity of the imine plays a role because aliphatic imines react in this manner, while aromatic imines produce the four-membered ring [2+2] cycloadducts 29 . Substituents attached to the cumulenes can influence the mechanism of the cycloaddition reactions by rendering one molecule more nucleophilic and thereby deciding the course of the addition, i.e. determine which molecule is the electron donor to attack the electrophilic center of the other molecule 30 . The [3+2] cycloaddition reactions of cumulenes as 1,3-dipolarophiles are also well known. Huisgen in 1963 3 demonstrated the wide scope of the dipolar [3+2] cycloaddition reactions, which often proceed in high yields, and consequently these reactions rival the Diels–Alder reactions as valuable synthetic tools. The oldest example of a [3+2] cycloaddition reaction is the reaction of isocyanates with nitrones, discovered by Beckmann in 1890 31 , but the general character of this reaction was discovered much later. Because of the dual character of heterocumulenes, such as isocyanates, the reaction can occur across either one of the double bonds and sometimes both reaction products are isolated. In general, the [3+2] cycloaddition reaction proceeds across the same double bonds, which also participate in the [2+2] cycloaddition reactions. Ketenes react predominantly across their C C bonds, isocyanates across their C N bonds and sulfenes across their C S bonds. The 1,3-dipolar systems involved in the cycloaddition reaction with cumulenes include azides, nitrile oxides, nitrile imines, nitrones, azomethine imines and diazo compounds. However, some 1,3-dipolar systems are also generated in the reaction of precursors with catalysts. Examples include the reaction of alkylene oxides, alkylene sulfides and alkylene carbonates with heterocumulenes. Carbon cumulenes also participate as 1,3-dipols in [3+2] cycloaddition reactions. Examples include thiocarbonyl sulfides, R2 C S S, and 1-aza-2azoniaallenes.


11

The [4+2] cycloaddition reaction of dienes with dienophiles, which is generally known as the Diels–Alder reaction, is one of the most useful reactions in synthetic organic chemistry. Many examples of carbon cumulenes participating as dienes, dienophiles, or both, are known. Even aryl substituted cumulenes sometimes react as dienes in [4+2] cycloaddition reactions. A 1,4-dipolar cycloaddition reaction also affords six-membered ring cycloadducts. For example, a 1,4-dipol can be generated in the reaction of ketenes with N-heterocycles, such as pyridine. The generated dipol 22 undergoes cycloaddition reaction with a second molecule of the ketene to give the cycloadduct 23. Staudinger had assigned structure 23 to the cycloadducts but later work demonstrated that part of the cycloadducts had the isomeric structure 24. R 2C

C O+

+ R2C

+

N

N CR2

O 22

C

N

O O

R R 23

R R O

or

N R

O

R R O

R 24

I have also included in this book the insertion reactions of carbon cumulenes into polarized metal single bonds, which can be perceived as an initial [2+2] cycloaddition, which subsequently rearranges to give a linear adduct. The reactivity of the metal substituent appears to be NR2 > OR > SR. When the metal compound contains several reactive groups, stepwise insertion occurs. For example, Sn(OR)4 reacts with phenyl isocyanate to give the tetracarbamate Sn[N(Ph)COOR]4 . Mixed insertion products are obtained using different isocyanates. In the insertion reactions of carbodiimides sometimes ionic cyclic amidinate complexes are formed. A variety of other cyclization reactions are also observed with many of the carbon cumulenes. Especially, allenes and ketenes undergo many of these reactions and gold catalysis has achieved a new dimension in selectivity. From bis-allenes, complex natural products, such as 18,19 norsteroids, are generated in one step. In order to monitor the cycloaddition reactions of carbon cumulenes infrared spectroscopy is most useful, because their asymmetric stretching absorption at approximately 2300–1900 cm−1 occurs in a region which is relatively undisturbed. Although fundamentally four vibrations can be visualized in the linear cumulene system (two stretching and two bending vibrations) only the stretching vibrations are of significance, and often the symmetric stretching absorptions of cumulenes at approximately 1400–1100 cm−1 are too weak to be recognized because of the proximity of methyl and methylene absorptions in this region. Proton magnetic resonance spectroscopy can also be used to identify carbon cumulenes. The protons attached to the same carbon atom to which the cumulene group is attached are deshielded by the cumulene group and the chemical shifts of these protons are sufficiently separated from that of ordinary alkyl protons to allow characterization and also quantitization. Of course, this method is only of value in the aliphatic series because in aryl substituted cumulenes only β protons are present and the deshielding effect is minimized. The reactions shown in this book, up to 2008, are only examples to demonstrate the general scope of cumulene click reactions. New reactions are being reported constantly and many new reactions are expected to be discovered at an ever increasing rate.

12


References 1. H.C. Kolb, M.G. Finn and K.B. Sharpless, Angew. Chem. Int. Ed. 40, 2004 (2001). 2. H. Bibas, D.W.J. Moloney, R. Neumann, M. Shtaiwi, P.V. Bernhardt and C. Wentrup, J. Org. Chem. 67, 2619 (2002). 3. R. Huisgen, Angew. Chem. Int. Ed. 2, 565 (1963). 4. H.W. Bonk, A.A. Sadarnopoli, H. Ulrich and A.A.R. Sayigh, J. Elastoplastics 3, 157 (1971). 5. S.J. Atkinson, V. Ellis, S.E. Boyd and C.L. Brown, New J. Chem. 31, 155 (2007). 6. C&EN, May 5, 2008, p. 8. 7. C&EN, September 22, 2008, p. 80. 8. F. Toda, Eur. J. Org. Chem. 1377 (2000). 9. A.W. Hofmann, Chem. Ber. 3, 761 (1860). 10. H. Ulrich, Cycloaddition Reactions of Heterocumulenes, Academic Press, New York, USA, 1967. 11. J.E. Wilson and G.C. Fu, Angew. Chem. Int. Ed. 43, 6358 (2004). 12. H. Ulrich, Chemistry and Technology of Isocyanates, John Wiley & Sons Ltd, Chichester, UK, 1996. 13. H. Ulrich, Chemistry and Technology of Carbodiimides, John Wiley & Sons Ltd, Chichester, UK, 2007. 14. H. Ulrich, B. Tucker and A.A.R. Sayigh, J. Am. Chem. Soc. 94, 3484 (1972). 15. R. Huisgen and J. Rapp, Tetrahedron 53, 939 (1997). 16. H. Staudinger, Die Ketene, Enke, Stuttgart, Germany, 1912. 17. O. Bayer, Angew. Chem. A59, 257 (1947). 18. H. Ulrich and H.R. Reymore, J. Cell. Plast. 21, 350 (1985). 19. J.C. Martin, P. Gott, V.W. Goodlett and R.H. Hasek, J. Org. Chem. 30, 4309 (1965). 20. U. Anthoni, C. Larsen and P.H. Nielsen, Acta Chem. Scand. 22, 309 (1986). 21. J. Goerdeler and H. Schenk, Angew. Chem. 75, 675 (1963). 22. W. Neumann and P. Fischer, Angew. Chem. Int. Ed. 1, 621 (1962). 23. H. Ulrich, B. Tucker, F.A. Stuber and A.A.R. Sayigh, J. Org. Chem. 34, 2250 (1969). 24. E. Schaumann, Tetrahedron 44, 1827 (1988). 25. R. Huisgen, L. Feiler and G. Binsch, Angew. Chem. Int. Ed. 3, 753 (1964). 26. T. Machiguchi, J. Okamoto, J. Takachi, T. Hasegawa, S. Yamabe and T. Minato, J. Am. Chem. Soc. 125, 14446 (2003). 27. T. Machiguchi, J. Okamoto, Y. Morita, T. Hasegawa, S. Yamabe and T. Minota, J. Am. Chem. Soc. 128, 44 (2006). 28. W.T. Brady and E.D. Dorsey, J. Org. Chem. 35, 2732 (1970). 29. H. Ulrich, Acc. Chem. Res. 2, 186 (1969). 30. H. Ulrich, R. Richter and B. Tucker, J. Heterocyclic Chem. 24, 1121 (1987). 31. E. Beckmann, Ber. Dtsch. Chem. Ges. 23, 1680 (1890).

2 1-Carbon Cumulenes 2.1 2.1.1

Sulfines, R2 C S O Introduction

Sulfines are non-linear sulfur centered heterocumulenes with the general structure RR1 C S O. Sulfines are considered to be analogs of sulfur dioxide, in which one oxygen atom is replaced by a carbon atom. Sulfines are unstable at room temperature, and they are usually generated in situ. Aromatic substituted sulfines are generally more stable than the aliphatic substituted species. For example, 9-sulfinylfluoren is obtained in 75 % yield by the dehydrochlorination of the corresponding sulfinyl chloride. In the oxidation of tropothione with m-chloroperbenzoic acid below −60 ◦ C the red tropothione S-oxide, a stable sulfine, is obtained, also in 75 % yield 1 . Some halogenated sulfines are also stable at room temperature. Review articles on sulfines were written by Opitz in 1967 2 , Zwanenburg in 1982 3 , 1985 4 , 1988 5 and 1989 6 and by Block in 1981 7 . The chemistry of thiosulfines was reviewed by Huisgen and Rapp in 1997 8 . Sulfines are usually presented by combinations of the neutral (R2 C S O), the ylene (R2 C S+ –O− ) and the ylide (R2 C–S+ O) resonance structures. The molecular structure of sulfines, particularly the non-linearity of the C S O sys˚ S-O, 1.46 A: ˚ CSO, angle tem, was established by X-ray crystallography (C–S, 1.62 A: 114◦ ). The electronic charge distribution was calculated for the parent sulfine and mono and dihalogen substituted sulfines using ab initio methods 9 . The charge on sulfur and oxygen remains almost constant (S, +0.63 0.03: O, −0.69 0.01) by varying the substituents on carbon, whereas the charge on carbon exhibits a strong influence. The non-linearity of the COS function is also deduced from the H1 NMR spectra of ortho protons in diarylsulfines syn to the COS system, which absorp at lower fields by ca. 0.6 ppm relative to the almost unperturbed anti-ortho protons 10 . The same deshielding is observed in E-phenyl(phenylthio)sulfine, whereas in the Z isomer all aromatic protons absorb at the same δ-value 11 . The infrared spectra of sulfines show two characteristic absorptions in the

Cumulenes in Click Reactions Henri Ulrich C 2009 John Wiley & Sons, Ltd

14


sulfoxide region from 1000 to 1150 cm−1 . The UV absorption of the CSO chromophore is observed at about 270 nm 12 . The stable arylsulfines have IR absorptions at 1019–1078 cm−1 and at 1093–1128 cm−1 , respectively. Historically, sulfines were first prepared in 1923 by Wedekind and coworkers 13 , who reacted campher-10-sulfonyl chloride with pyridine. The sulfine structure of the reaction product was confirmed by King and Durst in 1963 using spectroscopic evidence 14 . In 1938 Kitamura oxidized thioamides with hydrogen peroxide, but assigned an imino sulfenic acid structure to the reaction product 15 . Walter, in 1960, showed that the correct structure was that of an aminosulfine (RC(NH2 ) S O) 16 . During the reinvestigation of Wedekind’s work, King and Durst discovered that sulfines can exist as stable geometrical isomers. The assignment of the E- and Z-geometry was made by means of NMR spectroscopy 17 . Ethylsulfine (propanethial S-oxide) was spectroscopically identical to the natural onion lachrymatory factor 18 . The configuration of the natural ethylsulfine was established to be Z by the anisotropic deshielding effect of the CSO group on the C(1)–H in combination with benzene induced shifts 19 . The lachrymatory effect of sulfines diminishes when the substituent is more bulky; t-butylsulfine is devoid of lachtymatory activity. Also, 2,3dimethylbutanedithial S,S -dioxide, a disulfine, was isolated from an onion extract 20 . The click chemistry, involving sulfines, is encountered in their [3+2] and [4+2] cycloaddition reactions which afford five- and six-membered ring heterocycles, often in high yields. Examples of the [2+1] and the [2+2] cycloaddition reactions of sulfines are hardly known. Thiosulfines, R2 C S S, are also not stable and rearrangement to thiocarboxylic esters seems to be faster than reaction with alkynes or norbornadiene 21 . However, numerous [3+2] cycloaddition reactions, in which the C S S system reacts as a 1,3-dipolar species are known (see Section 2.3.2). Thione S-imides, the nitrogen homologues of sulfines, also undergo mainly [3+2] and [4+2] cycloaddition reactions (see Section 2.3.1.2). 2.1.2 Dimerization Reactions In contrast to the sulfenes, the [2+2] cycloaddition reactions of sulfines are not well known. The dimerization of ethylsulfine gives rise to a four-membered ring trans-3,4-diethyl-1,2dithietane 1,1-dioxide, which is not the result of a [2+2] cycloaddition 22 . Similarly, reaction of trimethylsilylmethanesulfinyl chloride with triethylamine affords the sulfine 1, which on standing at room temperature for several days gives 42 % of trans-3,4-bis(trimethylsilyl)1,2-dithietane 1,1-dioxide, 2 23 .

Me3SiCH2SOCI + Et3N

[Me3SiCH 1

S

O]

SO2

Me3Si Me3Si

S 2

The dimer of trifluoromethylsulfine is obtained in the thermal generation of the sulfine from the anthracene adduct 24 . Also, the cyclic dimers of γ -acetylenic-β,β-disubstituted thioaldehyde S-oxides are isolated in their generation from allenic sulfinates with vinyl magnesium bromide 25 .

1-Carbon Cumulenes

15

The mechanism of formation of the dithietane 1,1-dioxide dimers involves an opposite [3+2] cycloaddition to form 3, which subsequently rearranges to give 4 . 26

R2C

S

O

S

R2

O SO

R2

R2

S

R2

SO2

3

2.1.3 2.1.3.1

4

Cycloaddition Reactions [2+1] Cycloaddition Reactions

Diphenylsulfine reacts with dichlorocarbene to give the [2+1] cycloadduct 5 in 18 % yield 27 .

Ph2C

S

O + :CCl2

Ph Ph

S

O

Cl Cl 5

2.1.3.2

[2+2] Cycloaddition Reactions

The [2+2] cycloadditions to sulfines have not, as yet, been observed. However, singlet oxygen addition occurs across the C S bond of sulfines with formation of ketones and sulfur dioxide 28 . 2.1.3.3


Sulfines participate as dipolar species in numerous [3+2] cycloaddition reactions. Huisgen has labelled sulfines as ‘superdipolarophiles’. For example, generation of benzonitrile oxide in the presence of diarlsulfines affords the [3+2] cycloadducts in a regiospecific reaction. The formed 1,4,2-oxathiazole S-oxides 6 are obtained in 50–88 % yield 29 . O R 2C

S

O + PhC N–O

S

R R O

Ph N

6

The cycloadducts are thermally labile and, on heating in refluxing xylene, extrusion of sulfur monoxide with formation of diarylketones and benzonitrile is observed.

16


However, in the reaction of bis(trifluoromethyl)sulfine 7 with benzonitrile oxide, 3phenyl-4,4-bis(trifluoromethyl)-1,5,2-oxathiazol 5-oxide 8 is obtained in 57 % yield 30 . O (CF3)2C S

O + PhC

N–O

S

CF3 CF3

O N

Ph 7

8

The corresponding 1,5,2-oxathiazole S-oxide is also obtained in the reaction of fluorenesulfine and benzonitrile oxide 29 . In a similar manner diphenylnitrilimines, generated in situ, react with diarylsulfines to give 1,3,4-thiadiazoline S-oxides 9 in 62–85 % yield in a stereospecific reaction 31 . O R 2C

S

O + PhC

N–NPh

S

R R N

Ph N

Ph 9

The orientation in cycloaddition reactions of nitrile oxides and imines with heterodipolarophiles obeys the principle of maximum gain in σ -bond energy 32 . This means that the reactants join in such a manner that the best compensation for the π -bond energy lost is achieved in the combined energy of the two newly formed σ -bonds. The cycloaddition of diphenylsulfine with the nitrile ylide 10 affords 2 -thiazoline Soxides 11 33 . O Ph2C

S

O + PhC

Ph Ph

N–CHPhNO2-p

S

Ph N

O2N 10

11

The reactions of sulfines with C-phenyl-N-methylnitrone is more complicated 34 . For example, sulfine and this dipole react in a molar ratio of 2:1. The initially formed 1:1 adduct loses sulfur dioxide providing a dipolar species which reacts with the second molecule of the sulfine. Diphenylsulfine reacts with ammonium azide to give diphenyldiazomethane in 88 % yield 35 . Apparently the cycloadduct reverses to give the isolated product. Also, some mesoionic compounds undergo a [3+2] cycloaddition reaction with diarylor arylchlorosulfines. Münchenone, an oxazolium-5-olate 12, reacts with arylchlorosulfine

1-Carbon Cumulenes

17

to give the [3+2] cycloadduct. The cycloaddition product expels carbon dioxide to give a new dipolar species 13 which rearranges to give the heterocycle 14 (yield: 40 %) 36 . O

Me N

Ph

+ RC(Cl) O

S

S

R Cl

Ph O

R Cl

Ph NMe

O

Ph

12

Me N

Ph

S

Ph

O 13

14

Chlorophenylsulfine reacts with azlactones 15 to give the [3+2] cycloadduct, which reorganizes with loss of carbon dioxide and hydrogen chloride to give the thiazole S-oxide 16. O N

R

+ PhC(Cl)

O

S

Ph

Ph S

O

N

Ph

O

R

15

+ CO2 + HCI

16

Aromatic and aliphatic sulfines react with 2-diazopropane in a regio- and stereospecific manner to give 3 -1,3,4-thiadiazoline S-oxides 17 37,38 . O S

1

Me2C

N2 + R1R2C

S

R

O

R2

N

N

Me Me

17

R1

R2

Yield (%)

Cl 2-MeOPh α-Naphthyl

Ph Ph Ph

81 88 91

The cycloadducts are thermally rather unstable and they slowly deteriorate on storage. The reaction is best conducted to allow the reaction products to crystallize from the reaction mixture. In solution, cycloreversion is often observed. In the reaction of an arenesulfonyl substituted sulfine with diazomethane the initially formed 3 - thiadiazoline S-oxide rearranges to give a thiazole derivative 39 . In the reaction of diazomethane with arylsulfonyl substituted sulfines the initially formed cycloadduct 18 rearranges on standing or in solution to give the thiazole derivative 19. O

PhSO2(Ph)C

S

O + CH2

N2

PhSO2 Ph N 18

O

S

PhSO2 Ph N

HN 19

S N

18


Phenyldiazomethane reacts below room temperature with bis(trifluoromethyl)sulfine to give the [3+2] cycloadduct 20, which rearranges to form the isomer 21. At room temperature the reaction product decomposes 56 . O CF3 (CF3)2C

S

O + PhCH

N2

CF3

O

S N

S

CF3

Ph

CF3

N

20

HN

N

21

Also, the [3+2] cycloadducts derived from diphenyldiazomethane and p-nitrophenyldiazoethane are not stable at room temperature. The reaction of diaryldiazomethanes with dichlorosulfine affords the benzo[b]thiophene 23 (55 % yield) by loss of nitrogen from the initial cycloadduct 22 40 . O Ph2C

N2 + Cl2C

S

S

Cl Cl

O

N

Ph Ph

Ph

N

S 23

22

Cl

An exchange reaction is observed in the reaction of dichlorosulfine with diazofluorene to give the fluorenesulfine in 50 % yield 41 . The [3+2] cycloaddition reaction of sulfines with C S double bonds is also observed. For example, in the reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone S-oxide 24 with diarylthioketones the [3+2] cycloadducts 25 are obtained. These cycloadducts are in a mobile equilibrium with the starting materials 42 . S O

S

O + R2C

S

O S

24

O R2

25

The [3+2] cycloadducts of sulfines with aliphatic thiones are more stable. For example, reaction of the same sulfine with adamantanethione at 110 ◦ C for 10 min affords a 86 % yield of the [3+2] cycloadduct. A bis-spiroadamane derivative is obtained in 85 % yield from adamantanethione and adamantanethione S-oxide 43 . In contrast, aromatic sulfines react with two equivalents of the shown thione to give a spiro-1,2,4-trithiolane 26 in 86 % yield. 44 S Ph2C

S

O + 2S

O

O S

S

+ O

O

Ph2

26

When the reaction of diphenylsulfine with 2,2,4,4-tetramethyl-3-thioxocyclobutanone is conducted in the presence of trans-cyclooctene, sulfur transfer occurs with formation of the trans-episulfide 45 . Using 1-methoxycyclooctene as the sulfur acceptor results in an unexpected formation of an insertion product. 46

1-Carbon Cumulenes

19

In the reaction of tropothione S-oxide 27 with 1-morpholinocyclopentene the sulfine reacts as a 1,3-dipol to give the cycloadduct 28. 1 O O S

O

N

S

N

+

27

28

Thioketene S-oxides, which are sulfines with an extended cumulenic system, also participate in the cycloaddition reaction with 2-diazopropane. In this case, exclusive reaction across the C C bond is observed to form the cycloadduct 29 in 70 % yield 47 . O S t-Bu2C

C

S

O

+

Me2C

N2

t-Bu t-Bu N

N 29

A 95 % yield of the cycloadduct is obtained when 2,2 ,6,6 -tetramethylcyclohexylidenethioketene S-oxide is used in this reaction. In contrast, thioketene S-oxides react with azomethines via a [3+2] cycloaddition in which the C S O group participates as a 1,3-dipol to give 30 48 . S

R2C R 2C

C

O + R1N

S

CHR2

O

R1N

R2 H 30

2.1.3.4


The [4+2] cycloadditions of sulfines with 1,3-dienes to give thiacyclohexene S-oxides 31 are well known reactions. Sulfines are interesting partners in this Diels–Alder type reaction, because the stereochemistry of ring formation can be studied by comparing the cycloadducts derived from geometrical isomers. O O S 1 R R2

S

+ R1

R2 31

In contrast to the [4+2] cycloaddition reactions of sulfur dioxide with 1,3-dienes, the sulfine derived cycloadducts are stable compounds. For example, by reacting both isomers of chlorophenylsulfine with 2,3-dimethyl-1,3butadiene it is shown that the stereochemical relationship in the sulfine is predominantly retained in the cycloadducts 49 . These cyclization reactions were studied kinetically and the activation parameters were H* 18.4 kcal/mol, S* −15 cu for the E isomer, and

20


H* 18.4 kcal/mol, S* −20 cu for the Z isomer. The negative S* values are suggestive of a concerted cycloaddition process. The dienophilicity of sulfines depends on their substituents. Electron withdrawing substituents, such as Cl or RCO groups enhance the reactivity, while sterically bulky groups retard the reaction. For example, dichlorosulfine reacts readily with cyclopentadiene and anthracene. The first trapping of the parent sulfine with cyclopentadiene was accomplished in 1987. The initially formed Diels–Alder adduct 32 is unstable at room temperature and it undergoes a sigmatropic rearrangement to give 2-oxa-3-thiabicyclo[3.3.0]oct-7-ene 33 50 . [CH2

Me3SiCH2SOCI + CsF

S

O]

S

+

O

32 O + Me3SiF + CsCl

S 33

Similar [4+2] cycloadducts are obtained from ethyl- and butylsulfines and both cycloadducts undergo the same rearrangement 51 . Mono substituted sulfines also undergo thermal and Lewis acid induced [4+2] cycloaddition reactions to 2,3-dimethyl-1,3-butadiene, 1,3-butadiene and cis- and trans-penta-1,3diene to give dihydrothiopyran S-oxides 52 . Some of the [4+2] cycloadducts derived from halosulfines and dienes are listed in Table 2.1. Table 2.1 [4+2] cycloadducts from halosulfines and dienes Sulfine

Diene

CF2 Cl C(F) S O CF3 C(Cl) S O

Cyclopentadiene Cyclopentadiene 2,3-Dimethylbutadiene Cyclopentadiene Cyclopentadiene 2,3-Dimethylbutadiene Anthracene Cyclopentadiene 2,3-Dimethylbutadiene

CF3 C(Me) S O CF3 C(SCH2 Ph) S O (CF3 )2 C S O

Yield (%)

Reference

78 62 99 62 75 67 72 73 93

53 54 53 55 53 53 56 57 56

Also, trithiocarbonate S-oxides 34 undergo the [4+2] cycloaddition reaction with 2,3dimethyl-1,3-butadiene to give the corresponding [4+2] cycloadducts 35 58 . O (RS)2C 34

S

O

+

RS RS

S

35

1-Carbon Cumulenes

21

Sulfines derived from proline 36 also reacted with 2,3-dimethyl-1,3-butadiene to give the expected cycloadducts 37 59 . During the cycloaddition reactions, asymmetric induction of up to 40 % is observed. The best results are obtained when one of the sulfine substituents is a chloro group and when the reaction is performed at −78 ◦ C. All thiopyran S-oxides obtained in this manner are mixtures of diastereomers. O

O S

S NS O2

R2

+

NS O2 OR1

OR1 36

37

Vinylsulfines 38, generated in situ, also undergo a [4+2] cycloaddition reaction with 2,3-dimethylbutadiene to give the cis- and trans-cycloadducts 39 and 40 60 . O

O

S R

O S

+ H

S

+ R

R

38

39

R

40

Yield (%)

Ratio of isomers

95 93

1:1.5 1:4.5

PhCH CH– Me2 C CH–

In a similar manner the [4+2] cycloadducts from 38 (R = PhCH CH–) and cyclohexadiene are obtained as three stereoisomers in high yield. Vinylsulfines 38 (R = PhCH CH–) can also participate as dienes in the [4+2] cycloaddition reaction with norbornene to give the tricyclic adduct 41 in 90 % yield. O O

R

S

+

S H

Ph 38

41

The reaction of 38 (R = PhCH CH–) with the norbornyl derivative 42 affords products 43 (48 %) and 44 (40 %) resulting from loss of sulfur dioxide and HCl.

H

S

Cl

+

S R

O

Cl

O SO2CCl3 42

S

+ Cl

Ph 38

O

43

Cl 44

22


The cycloaddition reactions of the reactive α-oxo sulfines 45 with dienes are well investigated and [4+2] cycloadducts 46 are obtained. Benzoyl substituted thioaldehyde S-oxides already react with 2,3-dimethyl-1,3-butadiene at −78 ◦ C. O RCO(R1)C

S

O

+

R1

S

RCO 45

46

Some of the cycloadducts derived from α-oxo sulfines and 2,3-dimethyl-1,3-butadiene are shown in Table 2.2. Table 2.2 [4+2] cycloadducts derived from α-oxysulfines and 2,3-dimethy-1.3-butadiene R

R1

Reaction temperature (◦ C)

Yield (%)

Reference

EtO CH2 CH CH2 CH Ph

CN H Me H

0 0 0 −78

96 48 52 84

61 62 60 63

25

75

64

25

86

65

25

66

56

25

70

56

0

68

61

25

59

63

O

O S

O

O S S

O

O S

O

O S

O O

O S O O

S

S O

Other dienes, such as cyclohexadiene, anthracene and cyclopentadiene have also been reacted with α-oxo sulfines. The cycloaddition of α-oxo sulfines with 2-trimethylsilyloxy1,3-butadienes afford thiacyclohexane-3-one S-oxides after hydrolysis 60 .

1-Carbon Cumulenes

23

An intramolecular hetero Diels–Alder reaction of α,α-dioxosulfines with a tethered electron-rich double bond 47, generated in situ, affords the bicyclic adduct 48 66 . O

O

S

O

S

O

O

R

O

O O

47

48

R

Yield (%)

Ph 4-MeOPh

43 48

The α-oxo sulfines can also participate as dienes in cycloaddition reactions with electronrich olefins, such as vinyl ethers. For example, the stable α-oxo sulfines 49 react with ethyl vinyl ether to give the cycloadducts 50 67 . O

O S

S

+ CH CH(OEt) 2 O

O

49

OEt

50

Complete asymmetric induction is observed in the cycloaddition reaction of 2,3dimethyl-1,3-butadiene with chiral camphor or sulfoximino substituted sulfines 68 . Excellent yields are obtained for the cycloaddition reaction of sulfoximino sulfines which have the inducing chiral center in close proximity to the sulfine group. The cycloadducts derived from α-oxo sulfines can be subjected to enzymatic hydrolysis to give optically active esters 60 . Another useful synthetic method involves the transformation of the [4+2] cycloadduct 51 into thiabenzenes 52 60,69 . O S

S

R O 51

52

References 1. T. Machiguchi, T. Hasegawa, H. Otani, S. Yamabe and H. Mizuno, J. Am. Chem. Soc. 116, 407 (1994). 2. G. Opitz, Angew. Chem. 79, 161 (1967). 3. B. Zwanenburg, Recl. Trav. Chim, Pays-Bas 101, 1 (1982). 4. B. Zwanenburg and B.G. Lenz, Houben-Weyl, Vol. E11, p. 911 (1985). 5. B. Zwanenburg, Rev. Heteroatom Chem. (Tokyo) 1, 218 (1988). 6. B. Zwanenburg, Phosphorus, Sulfur 43, 1 (1989).

24


7. E. Block in Organic Sulfur Chemistry, R.Z. Freidlina and A.E. Skorova (Eds), Pergamon Press, Oxford, UK, p. 15, 1981. 8. R. Huisgen and J. Rapp, Tetrahedron 53, 939 (1997). 9. J. van Lierop, A. Van Der Avoird and B. Zwanenburg, Tetrahedron 33, 539 (1977). 10. B. Zwanenburg, L. Thijs and A. Tangerman, Tetrahedron 27, 1731 (1971). 11. B. Zwanenburg, L. Thijs and J. Strating, Recl. Trav. Chim. Pay-Bas 90, 614 (1971). 12. B. Zwanenburg, A. Wagenaar, L. Thijs and J. Strating, J. Chem. Soc., Perkin Trans. 1, 73 (1973). 13. E. Wedekind, D. Schenk and R. Stuesser, Chem. Ber. 56, 633 (1923). 14. J.F. King and T. Durst, Tetrahedron Lett. 585 (1963). 15. R. Kitamura, J. Pharm. Soc. Jpn. 58, 246 (1938). 16. W. Walter, Liebigs Ann. Chem. 633, 35 (1960). 17. J.F. King and T. Durst, J. Am. Chem. Soc. 85, 2676 (1963). 18. E. Block, Angew. Chem. Int. Ed. 31, 1135 (1992). 19. E. Block, L.K. Revelle and A.A. Bazzi, Tetrahedron Lett. 1277 (1980). 20. E. Block and T. Bayer, J. Am. Chem. Soc. 112, 4584 (1990). 21. A. Senning, Angew. Chem. 91, 1006 (1979). 22. E. Block, A.A. Bazzi and L.K. Revelle, J. Am. Chem. Soc. 102, 2490 (1980). 23. E. Block, A. Yencha, M. Aslam, V. Eswarakrishnan, J. Luo and A. Sano, J. Am. Chem. Soc. 110, 4748 (1988). 24. J. Hasserodt, H. Pritzkow and W. Sundermeyer, Liebigs Ann. 839 (1995). 25. J.B. Baudin, M.G. Commenil, S.A. Julia, L. Toupet and Y. Wang, Synlett 839 (1993). 26. E. Block, J.Z. Gillies, C.W. Gillies, A.A. Bazzi, D. Putnam, L.K. Revelle, D. Wang and X. Zhang, J. Am. Chem. Soc. 118, 7492 (1996). 27. B.F. Bonini, and G. Maccagnani, Tetrahedron Lett. 3585 (1973). 28. B. Zwanenburg, A. Wagenaer and J. Strating, Tetrahedron Lett. 11, 4683 (1970). 29. B.F. Bonini, G. Maccagnani, G. Mazzanti, L. Thijs, H.P.M.M. Ambrosius and B. Zwanenburg, J. Chem. Soc., Perkins Trans. 1, 1468 (1977). 30. M. Schwab and W. Sundermeyer, Chem. Ber. 121, 75 (1988). 31. B.F. Bonini, G. Maccagnani, G. Mazzanti, L. Thijs, G.E. Veenstra and B. Zwanenburg, J. Chem. Soc., Perkin Trans. 1, 1220 (1978). 32. R. Huisgen, Angew. Chem. 75, 604, 742 (1963). 33. B.F. Bonini, G. Maccagnani, G. Mazzanti and B. Zwanenburg, Gazz. Chim. Ital. 107, 289 (1977). 34. B.F. Bonini, G. Maccagnani, G. Mazzanti, P. Pedrini and B. Zwanenburg, Gazz. Chim. Ital. 107. 283 (1977). 35. L. Carlsen and A. Holm, Acta Chem. Scand., Ser. B 30, 997 (1976). 36. J.W.H. Handels, PhD Thesis, University of Nijmegen, The Netherlands (1979). 37. L. Thijs, A. Wagenaar, E.M.M. van Rens and B. Zwanenburg, Tetrahedron Lett. 3589, (1973). 38. B.F. Bonini, G. Maccagnani, A. Wagenaar, L. Thijs and B. Zwanenburg, J. Chem. Soc., Perkin Trans. 1, 2490 (1972). 39. B. Zwanenburg and A. Wagenaar, Tetrahedron Lett. 5009 (1973). 40. L. Thijs, J. Strating and B. Zwanenburg, Recl. Trav. Chim. Pay-Bas 91, 1345 (1972). 41. B. Zwanenburg, E. Thijs and J. Strating, Tetrahedron Lett. 4461 (1969). 42. R. Huisgen, G. Mloston and K. Polborn, J. Org. Chem. 61, 6570 (1996). 43. R. Huisgen, G. Mloston, K. Polborn, R. Sustmann and W. Sicking, Liebigs Ann. 179 (1997). 44. R. Huisgen, G. Mloston, K. Polborn and F. Palacios-Gambra, Liebigs Ann. 187 (1997). 45. W. Adam, R.M. Bargon and G. Mloston, Eur. J. Org. Chem. 4012 (2003). 46. W. Adam and B. Fröhling, Org. Lett. 4, 599 (2002). 47. E. Schaumann, H. Behr, G. Adiwidjaja, A. Tangerman, B.H.M. Lammerink and B. Zwanenburg, Tetrahedron 37, 219 (1981). 48. E. Schaumann, J. Ehlers and U. Behrens, Angew. Chem. 90, 480 (1978). 49. B. Zwanenburg, L. Thijs, J.B. Broens and J. Strating, Recl. Trav. Chim. Pay-Bas 91, 443 (1972). 50. E. Block and A. Wall, J. Org. Chem. 52, 809 (1987). 51. E. Block, A. Wall and J. Zubieta, J. Am. Chem. Soc. 107, 1783 (1985). 52. G. Barbaro, A. Battaglia, P. Giorgianni, B.F. Bonini, G. Maccagnani and P. Zaul, J. Org. Chem. 56, 2512 (1991).

1-Carbon Cumulenes 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69.

25

J. Gradel and W. Sundermeyer, Chem. Ber. 125, 1889 (1992). H. Fritz and W. Sundermeyer, Chem. Ber, 122, 1757 (1989). B. Schuler and W. Sundermeyer, Chem. Ber. 123, 177 (1990). A. Elsaesser and W. Sundermeyer, Chem. Ber. 118, 4553 (1985). M. Schwab and W. Sundermeyer, Chem. Ber. 119, 2458 (1986). I. El-Sayed, K.M.H. Hilmy, S.M. El-Kousky, A. Fischer and H.S. Slem, Phosphorus Sulfur 178, 2403 (2003). L.A.G.M. Van Den Broek, P.A.T.W. Porskamp, R.C. Haltiwanger and B. Zwanenburg, J. Org. Chem. 49, 1691 (1984). S. Braverman, D. Grinstein and H.E. Gottlieb, J. Chem. Soc., Perkin Trans. 1, 103 (1998). M.W. Wieczorek, J. Blaszczyk, B. Dziuba, P. Kielbasinski, M. Mikolajczyk, B. Zwanenburg and J.B.M. Rewinkel, J. Heteroatom Chem. 6, 631 (1995). B. Zwanenburg, Rev. Heteroatom. Chem. 218 (1988). B.G. Lenz, H. Regeling, H.L.M. van Rozendaal and B. Zwanenburg, J. Org. Chem. 50, 2930 (1985). B.G. Lenz, H. Regeling and B. Zwanenburg, Tetrahedr on Lett. 25, 5947 (1984). B.G. Lenz, R.C. Haltiwanger and B. Zwanrnburg, J. Chem. Soc. Chem. Commun. 502 (1984). G. Capozzi, S. Menichetti, C. Nativi and A. Provenzani, Eur. J. Org. Chem. 3721 (2000). B.G. Lenz, H. Regeling, H.L.M. van Rozendaal and B. Zwanenburg, J. Org. Chem. 50, 2930 (1985). P.A.T.W. Porskamp, R.C. Haltiwanger and B. Zwanenburg, Tetrahedron Lett. 24, 2035 (1983). R.C. de Laet, A.J.J.M. Breemen, A.J. Derksen, M. van Klaveren and B. Zwanenburg, Phosphorus Sulfur 74, 371 (1993).

2.2 2.2.1

Sulfenes, R2 C S(O) O Introduction

The synthesis of ketenes by Staudinger prompted others to investigate the possibility of obtaining related species by similar procedures. Wedekind and Schenk attempted in 1911 to synthesize sulfenes by dehydrochlorination of sulfonyl chlorides 1 . The name sulfene was suggested because of its analogy to ketene. The existence of sulfenes was established by King and Durst in 1964 2 . Sulfenes are usually generated in situ by either dehydrochlorination of alkanesulfonyl chlorides, using triethylamine as the hydrogen chloride scavenger, or in the reaction of diazoalkanes with carbon dioxide. Other methods of generation of sulfenes include the photolysis of cyclic sultones. While sulfenes are generally obtained as reactive intermediates, some aldo- and ketosulfenes are stable up to their melting points. The polarization of the C S double bond in sulfenes as shown in 1 and 2 account for their reactivity in cycloaddition reactions. R 2C

SO2

R2C–SO2

R2C–SO2

1

2

The recent example of the addition of dichlorosulfene to indanetrione to give a linear adduct shows that both resonance forms can be operative in sulfene reactions 3 . The switter ionic structures of sulfenes can be stabilized with tertiary amines. The coordination of the tertiary amine occurs generally on sulfur 4 . For example, from bis(bistrifluoromethyl)sulfene a stable quinucledine adduct, m.p. 181 ◦ C (dec.) is obtained in 74 % yield 5 . However, from

26


fluoro- and difluorosulfene and triethylamine stable complexes are obtained in which the tertiary amino group is coordinated with the carbon atom 6 . Cycloaddition reactions, especially [2+2] cycloadditions, are prominent in sulfene chemistry and even insertion of sulfene into metal–hydrogen bonds is observed 7 . The chemistry of sulfenes has been reviewed by Opitz 8 and by Lenz and Zwanenburg 9 . 2.2.2 Dimerization Reactions The sulfene cyclodimer 3 is obtained on treatment of methanesulfonyl chloride with triethylamine at −20 ◦ C in THF in 18 % yield 10 . SO2

2 CH3SO2CI O2S 3

Halogenation of the sulfene cyclodimer affords perhalogenated sulfene cyclodimers, which can be used as precursors of the corresponding sulfenes 11 . While thermolysis of sulfene cyclodimers affords olefins and sulfur dioxide, other chemical transformations are used to convert the cyclodimers back to the monomers. For example, treatment of tetrafluoro-1,3-dithietane-1,1,3,3-tetraoxide with triethylamine in THF at −70 ◦ C affords the inverse triethylamine stabilized difluorosulfene 12 . Perchloro- and perbromosulfenes (X3 CSO2 C(X) SO2 ) are obtained by converting the disulfenes to an intermediate sulfonyl fluoride, and treating the latter with SiF4 and quinucledine. The sulfenes thus obtained X = Cl (m.p. 169 ◦ C (dec.); 36 % yield) and X = Br (m.p. 166 ◦ C (dec.); 47 % yield) are base stabilized on the sulfonyl group 13 . Treatment of the sulfene dimers with silylating agents produces sulfoxonium ylides 14 . In the reaction of benzoylmethanesulfonyl chloride with triethylamine the α-oxo sulfene 4 is generated, which undergoes dimerization via a [4+2] cycloaddition reaction to give the cyclodimer 5. 15 Ph

SO2

O + SO2

O

Ph

O S

Ph

O Ph

S

O

O

4

O

O

5

2.2.3 Cycloaddition Reactions 2.2.3.1


Sulfene reacts with triphenylphosphine to give a quaternary phosphonium salt. The reaction seems to proceed via an initial [2+1]] cycloaddition to form 6, which rearranges to give a thiaphosphoridene dioxide intermediate 16 . O

O S

CH2

SO2 + PPh2

PPh3 6

1-Carbon Cumulenes

27

A carbene, generated from trimethylsilyldiazomethane, adds to sulfenes to give threemembered ring sulfones 7 17 . O

O S

RCH

SO2 + Me3SiCH

N2

R

SiMe3 7

Primary sulfonyl chlorides react with triethylamine at −40 ◦ C to give thiirane dioxides 18 . 2.2.3.2


Bis(trifluoromethyl)sulfene is trapped with monoalkenes, dienes and anthracene to give cycloadducts in moderate to good yields. Moderately electron-rich alkenes react regiospecifically to give the [2+2] cycloadducts. From dienes, mixtures of the corresponding [2+2] and [2+4] cycloadducts are obtained 19 . The cycloaddition reaction of sulfenes to numerous electron-rich alkenes is a general reaction. In this respect sulfenes are very similar to ketenes. An example is the reaction of sulfenes with enamines to give aminothietane sulfones 8.

NR(R)

CR1R2 + R3R4C

R3R 4 SO2

SO2 R 1R2

N H 8

The cycloaddition reaction of sulfenes to enamines occurs readily. Linear as well as cyclic enamines react well, and primary sulfonyl chlorides react better than secondary sulfonyl chlorides. However, cycloadducts from secondary sulfonyl chlorides are obtained in excellent yield if the reaction is conducted in acetonitrile at −40 ◦ C 20 . Some of the cycloadducts rearrange to linear isomers, but this tendency is not as pronounced as in other four-membered ring cycloadducts. The crystalline cycloadducts derived from mesyl chloride and enamines can be used for the identification of liquid enamines 21 . Paquette demonstrated that the cycloaddition of sulfenes to enamines derived from 5-norbornene2-carboxaldehyde and secondary amines proceeds stereoselectively 22 . Also chlorosulfene (CHCl SO2 ) reacts with morpholine enamines to give one of the possible stereoisomers 23 . Methane sulfonyl chloride reacts with triethylamine at −40 ◦ C to generate MeSO2 CH SO2 , which reacts with enamines to give the [2+2] cycloadducts 24 . This sulfene is stable for several days at −40 ◦ C, but on warming to −30 ◦ C decomposition is observed. Dialkylaminobutadiene reacts with mesyl chloride to give a mixture of the [2+2] adducts 9 and the [4+2] cycloadducts 10 25 . R2N R2NCH

CH–CH

CH2 + CH2

SO2

+ SO2 9

SO2

SO2

R2N 10

28


In the reaction of N,N,N ,N -tetramethyl-1-butene-1,3-diamine with sulfene a mixture of the linear adduct 11 and cycloadducts 12 and 13 is isolated 26 . Me2NCH

CH(Me)NMe2 + CH2

SO2

Me2NCH

CHSO2CH

CHMe +

11 Me2N

Me2N + SO2

SO2

SO2 Me2N

12

13

In my earlier book I have listed the linear and the [2+2] cycloadducts obtained from sulfenes and enamines. The yields obtained were usually very high 27 . In the reaction of the enamine derived from isobutyraldehyde and sulfene, generated from diazomethane and sulfur dioxide, the [2+2] cycloadduct 14 (9–18 %) and the [2+2+2] cycloadduct 15 (2–26 %) are obtained 28 . O NCH

CMe2 + CH2

SO2

SO2

O S O

+

N

S

N

H 14

O 15

The [2+2] cycloaddition reaction of methylsulfonylsulfene to vinyl ethers is also known. For example, methylsulfonylsulfene adds to dihydropyran to give a single diastereoisomer 16 29 .

+

MeSO2CH

SO2

O

SO2 O

H SO2Me

16

Mixtures of tautomeric [2+2] cycloadducts are obtained in the reaction of several sulfenes, generated in situ, with 1-diethylaminopropyne 30 . Ketene acetals also undergo a facile [2+2] cycloaddition reaction with sulfenes. For example, a 79 % yield of 3,3-diethoxythietane 1,1-dioxide 17 is obtained in the reaction of ketene diethylacetal with sulfene 31 . SO2 (EtO)2C

CH2 + CH2

SO2

EtO EtO 17

1-Carbon Cumulenes

29

The unsaturated sulfene, generated from 1-propenesulfonyl chloride and triethylamine, reacts with ketene diethylacetal to give the [2+2] cycloadduct 18 and a [4+2] cycloadduct 19. H CH2

CHCH

SO2 + (EtO)2C

CH2

CH2

OEt OEt

CH

+ S

O2S

O 18

O 19

Alkanesulfonyl chlorides with hydrogen atoms in the β-position do not undergo cycloaddition reactions with ketene diethylacetal 32 . Reaction of two equivalents of ketene diethylacetal with methanesulfonyl chloride in the absence of triethylamine affords a 5% yield of the [2+2+2] cycloadduct 20 33 . EtO 2 (EtO)2C

CH2 + CH2

OEt

SO2

S O

O 20

Some of the [2+2] cycloadducts 21 derived from sulfenes and ketene acetals are listed in Table 2.3. Table 2.3 [2+2] Cycloadducts from sulfenes and ketene O,O-acetals (EtO)2C CH2 + RCH SO2

SO2

R (EtO)2 21

R H CF3 Ph

Yield (%)

Reference

79 61 70

33 34 34

An iminosulfene 22, generated from the precursor with trimethylenediamine, reacts with ketene diethylacetal to give the [2+2] cycloadduct 23 35 . O Me–S–Cl + CH2 C(OEt)2 TsN 22

O S EtO EtO

NTS

23

Ketene O,N-acetals and ketene N,N-acetals (aminals) react with sulfene to give linear adducts or cyclic [2+2] adducts. However, the cycloadducts eliminate alcohol or amine to form isomeric 3-dialkylaminothiete 1,1-dioxides. The product distribution depends upon the solvent used. In chloroform, the linear adducts are formed, while in tetrahydrofuran or diethyl ether predominantly cyclic adducts are obtained 36 .

30


Lists of some of the adducts obtained from ketene O,N- and ketene N,N-acetals and sulfenes are found in my earlier book 27 . A [2+2] cycloaddition reaction across a polarized C O bond also occurs. Reaction of chloral with sulfene affords a β-sultone 24 37 . CCl3CHO + CH2

SO2

SO2

H

O CCl3 24

1,2-Thiazetidine-1,1-dioxides (β-sultames) 25 (R2 = COOMe) are obtained in the [2+2] cycloaddition of sulfenes across the C N bond in azomethines (yields: 9–93%) 38 . R2 RCH

NR1

+

R2CH

SO2

SO2

NR1

H R 25

2.2.3.3


The reaction of sulfene with C,N-diphenylnitrone generates the [2+3] cycloadduct 26, which rearranges to give the heterocyclic seven-membered ring compound 27 39 . Ph PhCH

N(Ph)

O + CH2

SO2

N S

O

H N

Ph

O

O S

O 26

Ph O O

27

Also, azomethine imines 28 react with sulfenes, generated from the corresponding sulfonyl chlorides and triethylamine, to give 1,2,3-thiadiazolidines 29 40 . + RCH N

SO2

N NX S O O

NX

28

29

R

X

H H Ph Ph

Ph 4-O2 NPh Ph 4-O2 NPh

Yield (%) 92 86 77 88

1-Carbon Cumulenes

31

In the reaction of p-nitro-α-toluenesulfonyl chloride with excess diazomethane the [3+2] cycloadduct 30 is obtained 41 .

N 4-O2NC6H4CH

SO2 + CH2

H N S O O

N2 O2N 30

2.2.3.4


Vinylogous carboxamides 31 react with sulfene via a [4+2] cycloaddition reaction to give cyclic sulfones 32 29 . The reaction occurs at 0–20 ◦ C, and the yields range from 5 to 80 %. N R2 R1

N R3

+ RCH

SO2

R1

O

R3

R2 O

S

R O O

32

31

R

R1

R2

R3

Amine component

H H H

Me CH(Me)2 Me

Me H –(CH2 )4 –

H H

Piperidine Pyrrolidine Pyrrolidine

Yield (%) 80 75 32

Similarly, dialkylaminobutadienes react with sulfene to give a low yield of the [4+2] cycloadducts 24 . Cyclopentadiene also reacts with sulfenes to give [4+2] cycloadducts. In the generation of sulfene from Me3 SiCH2 SO2 Cl in acetonitrile, the presence of CsF and cyclopentadiene, the cycloadduct 33 is obtained in 75 % yield. From ethylsulfene the cycloadduct is obtained in 76 % yield 42 . Me3SiCH2SO2Cl + CsF

[CH2

S

SO2] +

O O CH2Si Me3

33

Thermolysis of thiete 1,1-dioxide 34 in the presence of norbornene affords the [4+2] cycloadduct 36 of the generated vinyl sulfene 35 to the olefin 43 . + SO2 34

SO2 35

S O 36

O

32


[4+2] Cycloaddition reactions of sulfenes to methylcyclopentadiene and 1,2,3,4tetraphenylcyclopentadiene are also known 44 .

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44.

E. Wedeking and D. Schenk, Chem. Ber. 44, 198 (1911). J.F. King and T. Durst, J. Am. Chem. Soc. 86, 287 (1964). R. Allmann, W. Hanefeld, M. Krestel and B. Spangenberg, Angew. Chem. 99, 1175 (1987). U. Hartwig, H. Pritzkopf and W. Sundermeyer, Chem. Ber. 121, 1435 (1988). U. Hartwig, K. Rall and W. Sundermeyer, Chem. Ber. 123, 595 (1990). H. Pritzkow, K. Rall, S. Reimann-Andersen and W. Sundermeyer, Angew. Chem. 102, 80 (1990). I. Lorenz, Angew. Chem. 90, 293 (1978). G. Opitz, Angew. Chem. 79, 161 (1967). B.G. Lenz and B. Zwanenburg, Houben Weyl, Vol. E11, p. 1326 (1985). G. Opitz and H.R. Mohl, Angew. Chem. 81, 36 (1969). W. Sundermeyer, Synthesis 349, (1988). H. Pritzkow, K. Rall, S. Reimann-Andersen and W. Sundmeyer, Angew. Chem. Int. Ed. 29, 60 (1990). H. Pritzkow, K. Rall and W. Sundermeyer, Z. Naturfarsch., B 45, 1187 (1990). W. Sundermeyer and A. Walch, Chem. Ber. 129, 161 (1996). R. Fusco, S. Rossi, S. Maiorana and G. Paganzi, Gazz. Chim. Ital. 95, 774 (1965). J.F. King, E.G. Lewars and L.J. Danks, Can. J. Chem 50, 866 (1972). T. Aoyama, S. Toyama, N. Tamaki and T. Shioiri, Chem. Pharm. Bull. (Tokyo) 31, 2957 (1983). G. Opitz, T. Ehlis and K. Reith, Chem. Ber. 123, 1989 (1990). B.E. Smart and W.J. Middleton, J. Am. Chem. Soc. 109, 4982 (1987). G. Opitz and K. Rieth, Tetrahedron Lett. 3977 (1965). G. Opitz, H. Schemmp and H. Adolph, Liebigs Ann. Chem. 684, 92 (1965). L.A. Paquette, J. Org. Chem. 29, 2851 (1964). L.A. Paquette, J. Org. Chem. 29, 2854 (1964). G. Opitz, M. Kleemann, D. Buecher, G. Walz and K. Rieth, Angew. Chem. Int. Ed. 5, 594 (1966). G. Opitz and F. Schweinsberg, Angew. Chem. Int. Ed. 4, 786 (1965). L.A. Paquette and M. Rosen, Tetrahedron Lett. 311 (1966). H. Ulrich, Cycloaddition Reactions of Heterocumulenes, Academic Press, New York, pp. 299– 300, (1967). G. Opitz and K. Fischer, Z. Naturforsch., B 18, 775 (1963). B. Beagley, M.R. James, R.G. Pritchard, C.M. Raynor, C. Smith and R.J. Stoodley, J. Chem. Soc., Perkin Trans. 1, 2371 (1992). D.R. Eckroth and G.M. Love, J. Org. Chem. 34, 1136 (1969). W.E. Truce, J.J. Breiter, D.J. Abraham and J.R. Norell, J. Am. Chem. Soc. 84, 3030 (1962). W.E. Truce and J.R. Norell, J. Am. Chem. Soc. 85, 3231 (1963). W.E. Truce, D.J. Abraham and P.S. Radhakrishnamurti, Tetrahedron Lett. 1051 (1963). W.E. Truce and P.N. Son, J. Org. Chem. 30, 71 (1965). C.R. Johnson and E.U. Jonsson, J. Am. Chem. Soc. 92, 3815 (1970). R.H. Hasek, R.H. Meen, and J.C. Martin, J. Org. Chem. 30, 1495 (1965). D. Borrmann and R. Wegler, Chem. Ber. 99, 1245 (1966). M.J. Szymonifka and J.V. Heck, Tetrahedron Lett. 30, 2869 (1989). W.E. Truce, J.W. Fieldhouse, D.J. Vrencur, J.R. Norell, R.W. Campbell and D.G. Brady, J. Org. Chem. 34, 3097 (1969). W.E. Truce and J.R. Allison, J. Org. Chem. 40, 2260 (1975). S. Rossi and S. Maiorana, Tetrahedron Lett. 263 (1966). E. Block and A. Wall, J. Org. Chem. 52, 809 (1987). D.C. Dittmer, J.E. McCaskie, E. Babiarz and M.V. Ruggeri, J. Org. Chem. 42, 1910 (1977). G. Opitz, M. Deissler, T. Ehlis, H. Irngartinger, M.L. Ziegler and B. Nuber, Liebigs Ann. 2137 (1995).

1-Carbon Cumulenes

2.3

33

Other 1-Carbon Cumulenes

2.3.1 2.3.1.1

Thiocarbonyl S-Imides Introduction

Thiocarbonyl S-imides, R2 C S NR, were first synthesized as reactive intermediates by Burgess and Penton in 1973 by dehydrochlorination of N-sulfenyl chlorides 1 at −78 ◦ C in THF 1 . In the absence of dipolarophiles the red solution of the thiocarbonyl S-imide 2 undergoes cyclization at about −30 ◦ C to form the oxathiazole derivative 3.

S N

SNHCOPh

S

Cl

1

NCOPh

O

2

Ph

3

The thiocarbonyl S-imides are usually generated in situ; however, N(adamantyl)hexafluorothioacetone, (CF3 )2 C S NR (R = adamantyl), was found to be stable at room temperature 2 . Thiocarbonyl S-imides are excellent dipols in [3+2] cycloaddition reactions. Also [2+4] cycloaddition reactions of thiocarbonyl S-imides are known.

2.3.1.2


The thiocarbonyl S-imide 4, generated in the reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone with phenyl azide, is intercepted with fumarodinitrile to give the cycloadduct 5 in 25 % yield 3 .

CN O

S + PhN3

S

O

NPh

O

+ NC

4

S

NPh

CN CN 5

Other reactive olefins, such as enamines and vinyl ethers also participate as dipolarophiles in their reaction with thiocarbonyl S-imides. Even fulvenes undergo [3+2] cycloaddition reactions. For example, enamines react with fluorenethione S-benzoylimide to give [3+2] cycloadducts in good yield 4 . Likewise, vinylethers 6 participate as dienophiles in the

34


[3+2] cycloaddition reaction with 9-fluorenethione S-p-toluenesulfonimide to give 7 5 .

S S

NTs

CHOR

NTs + CH2

OR 6

7

R

Yield (%)

Et n-Bu i-Bu

94 84 95

The above tosylimide also reacts with 1-(pyrrolidinyl)-2-methyl-1-propene to give the [3+2] cycloadduct in 50 % yield. Fulvenes 8 also participate in the [3+2] cycloaddition reaction with 9-fluorenethione N-tosylimide to form 9 6 . The reaction is conducted in 1,2-dichloroethane at room temperature. R S

R

S

NTs

NTs + R

8

R 9

R

Yield (%)

Me Ph

99 87

In the reaction of the above 9-fluorenethione N-tosylimide with diphenylketene two regioisomeric [3+2] cycloadducts 10 and 11 are obtained 7 . S S

NTs + Ph2C

C

S

NTs

O

NTs

+ Ph Ph 10

O

O 11

Ph

Ph

1-Carbon Cumulenes

35

In the [3+2] cycloaddition reaction with ketenimines two isomeric adducts 12 and 13 are formed by reaction across either the C C or the C N bond of the ketenimines 6 . + NTs

S S

NTs + RN

S

NTs

C N RN

R

12

R

13

Yield of 12 (%)

Yield of 13 (%)

87 0 67 93

8 55 17 3

Ph 4-MePh 4-ClPh α-C10 H7

In the [3+2] cycloaddition reaction with carbodiimides, the initially formed cycloadducts 14 rearrange to give the heterocycles 15 7 .

S S

NTs + RN

C

S

NTs

NR

NR N

N

NR

NTs

R

R

15

14

R

Yield (%)

Et C6 H11

21 43

Similar [3+2] cycloaddition reactions are also observed with imines, oximes and diarylthiones. For example, reaction with the imines 16 afford the cycloadducts 17 in excellent yields 8 . S S

NTs +

R1

CH

N

NTs

R2 N R1 R2

16

17

36

Cumulenes in Click Reactions R1

R2

H H H Cl Cl

H Me NO2 H Cl

Yield (%) 90 91 91 90 87

In the [3+2] cycloaddition reaction with oximes 18 the cycloadducts 19 are obtained 8 .

S S

NTs +

R1R2C

NOH N

NTs R1 R2

OH 18

19

R1

R2

Me Me

Me Et –(CH2 )5 – Ph 4-ClPh

Ph Ph

Yield (%) 92 89 92 88 95

The reaction of aromatic thiones as dipolarophiles with N-(1-adamantyl) hexafluorothioacetone 20 affords the [3+2] cycloadducts 21 in good yields 9 . S (CF3)2C

S

N

+ (Ar)2C

S

N

(CF3)2 S

20

Ar2 21

Ar– –Ar

Yield (%)

73 (C6 H5 )2

76

1-Carbon Cumulenes

37

However, diarylthiones likewise undergo the [3+2] cycloaddition reaction giving the cycloadducts 23 formed by reverse addition to the 1,3-dipole in 22 7 . S S

NTs + R2C

NTs R R

S S

22

23

R

Yield (%)

Ph 4-MeOPh

73 88

The latter cycloadducts are rather unstable. The [3+2] cycloaddition reactions of 22 with dipolarophiles with C N and C P bonds have also been observed 10 . 2.3.1.3


The [4+2] cycloaddition reaction of thione S-imides with dienes results in formation of the Diels–Alder adducts 24 in good yields. The reaction proceeds across the C S bond of the thione S-imide 11 . TsN S

R1

S

R1 NTs + R3

R2

R2

R3 24

R1

R2

R3

Yield (%)

Me Me

Me H

H H

61 94

From norbornadiene and cyclopentadiene the mono [4+2] cycloadducts are obtained. 2.3.2

Thiocarbonyl S-Sulfides

Thiocarbonyl S-sulfides (thiosulfines) were postulated as intermediates and sometimes their cyclodimers, 1,2,4,5-tetrathianes, are isolated. In 1987 Huisgen and Rapp provided the first evidence for their existence 12 . The authors generated diphenylthiocarbonyl S-sulfide by heating 3,3,5,5-tetraphenyl-1,2,4-trithiolane 25, and intercepted the reactive ‘diphenylthiosulfine’ 26 with suitable dipolarophiles, such as dicyanoacetylene to give 27

38


(76 % yield), or dimethyl acetylenedicarboxylate to give 28 (83 % yield). S S

Ph2

S Ph2

Ph2 S

CN

NC

S Ph2C

S

27

S

S

25

S

Ph2

26

CO2Me

MeO2C 28

In addition, the generated diphenylsulfide was also intercepted with the same dipolarophiles to give the Diels–Alders cycloadducts 29 (R = –CN or –CO2 Me). Ph2C

S + RC

S

CR

R R 29

Adamantanethione was also used as a dipolarophile to trap 26, and the [3+2] cycloadduct is obtained in 81 % yield. Cyclooctyne is also used as a dipolarophile for trapping diphenylthiocarbonyl S-sulfide and p-chlorodiphenylthiocarbonyl S-sulfide 13 . The [3+2] cycloaddition reaction of the thiocarbonyl S-sulfide 30 with diarylsulfides affords the cycloadducts 31 14 . S S O

S

S + R2C

R2

O

S

S

30

31

In the reaction of tetraethoxyallene with disulfurchloride an 83 % yield of 1,2,4,5tetrathiane-3,3,6,6-tetracarboxylate 32, the dimer of (EtO2 C)2 C S S, is obtained 15 . (EtO2C)2C

C

C(CO2Et)2 + S2CI

S

S

S

S

(EtO2C)2

(CO2Et)2 32

The [3+2] cycloaddition of thiocarbonyl S-sulfides with maleic anhydride to give cycloadduct 33 is also observed 16 . S S

R2 O

O

O

+ R2C

S

S O

O 33

O

1-Carbon Cumulenes

39

In the reaction of the tropothione S-sulfide 34, obtained from tropone hydrazone and disulfur dichloride, at −78 ◦ C in the presence of dimethyl acetylenedicarboxylate, the [10π + π ] cycloadduct 35 was obtained in 23 % yield 17 .

S

S + MeOCOC

S

CCOOMe

S

CO2Me CO2Me

34

2.3.3 2.3.3.1

35

1-Aza-2-azoniaallene Salts Introduction

Monocations derived by replacing carbon atoms in allenes with nitrogen atoms are of recent vintage. They were synthesized by Jochims and coworkers at the University of Konstanz in Germany in the 1980s. The 1-aza-2-azoniaallenes, R2 C N+ NR, treated in this current chapter, react as 1,3-dipols in stepwise [3+2] cycloaddition reactions. 2-Azoniaallene salts, R2 C N+ CR2 , 1-oxa-3-azonia-butatriene salts, R2 C N+ C O, and 1-thia-3-azoniabutatriene salts, R2 C N+ C S, are treated in Chapter 5. The 1-aza-2-azoniaallene salts are usually generated in situ and reacted at low temperatures with numerous dipolarophiles. The initially formed cycloadducts often undergo a 1,2-shift to form isomeric heterocycles.

2.3.3.2


To carbon multiple bonds [3+2] Cycloadducts are obtained from 1-aza-2-azoniaallene salts and alkynes and olefins 18 . For example, from Me2 C N+ NR (R 2,4,6-trichlorophenyl-) and diethylacetylene an 88 % yield of the [3+2] cycloadduct 36 is obtained at 0 ◦ C.

[Me2C

N⊕

NR] AICI4 + EtC

CEt

Me2

N NR

Et Et

Me

NMe

AICI4

NR

Et

AICI4−

Et 36

In the reaction of the 1-aza-2-azoniaallene salts with (E)-3-hexene a single stereoisomer is obtained. However, in the reaction with allylcyanide, exclusive reaction of the nitrile group is observed. The [3+2] cycloaddition reaction of 1-aza-2-azoniaallene salts with alkynes to give pyrazolium salts is a general reaction. The initially formed 3H-pyrazolium

40


salts 37 rearrange to give 1H-(38) or 4H-pyrazolium salts (39) or mixtures of both 19 .

R1R2C

N⊕

NR3 + R4C

N

R1R2

CR5

R4

NR2

R1

NR3

NR3

R4

R1 + R2 R4

N NR3 AICI4−

R5

R5

R5

37

38

39

R1

R2

R3

R4

R5

Ratio 38:39

Yield (%)

Me Me Me Me

Me Et Et i-Pr

2,4,6-Cl3 Ph 2,3,6-Cl3 Ph 2,4,6-Cl3 Ph t-Bu

Et Et Me Et

Et Et Ph Et

37, 38, 39 50:50 37, 38, 39 37, 38, 39

88 — 91 100

In the case of R4 = H, cycloadduct 39 can undergo a 1,3-shift to form 40. An example is the reaction of Me2 C N+ NR (R = 2,4,6-trichlorophenyl) SbCl6 − with BuC CH, which affords the [3+2] cycloadduct 40 in quantitative yield. R1

N NR3

R2

⊕

R4

R5 39

⊕

R1

NH NR3

R2

SbCl6

R5 40

With unsymmetric acetylenes the cycloaddition proceeds with complete regioselectivity. The reaction of 1-aza-2-azoniaallene salts derived from coumarins with alkynes does not afford cycloadducts but rather leads to intramolecular cyclization. In contrast, a [3+2] cycloadduct is obtained in 92 % yield (mixture of diastereoisomes, ratio 2:1) from the same salt in the reaction with norbornene. From the camphor salt 41 (R = 2,4,6-trichlorophenyl) and phenylacetylene a 53 % yield of the cycloadduct 42 is obtained 20 .

⊕

N⊕NR SbCl6 + PhC CH 41

N

NR

SbCl6

42

Also, RCH N+ NR SbCl6 − reacts with acetylenes and olefins to give the [3+2] cycloadducts 21 . Similar cycloaddition reactions with alkynes and alkenes are also observed with 1-(chloroalkyl)-1-aza-2-azoniaallene salts to give 43; examples are shown in Table 2.4 22 .

1-Carbon Cumulenes

41

Table 2.4 [3+2] cycloaddition reactions of 1-(chloroalkyl)-1-aza-2-azoniaallene salts with olefins R1R2C

N⊕

N-C(Cl)R3R4

+

R5CH

N

R1R2 R5

CR6R7

N R6 R7

R4 C

−

R3 SbCl6

Cl

43

R1

R2

R3

R4

Olefin

Me Me Me Ph Ph

Me Me Me Ph Ph

Me Me Me C6 H11 C6 H11

Me Me Me C6 H11 C6 H11

Allylchloride Styrene Cyclopentene Isobutene Norbornene

Yield (%) 72 74 74 71 68

To carbon–nitrogen multiple bonds In the reaction of 1-aza-2-azoniaallene salts, generated in situ with nitriles at low temperatures, 1,2,4-triazolium salts 45 are obtained as the result of a 1,2-shift involving the initial cycloadduct 44 23 . R 1R 2C

N⊕

NR3 + R4CN

⊕

N

R1R2 N

NR2

R1 N

NR3 ⊕

NR3

R4

R4

44

45

R1

R2

R3

R4

Me Me Me Me Me Me

Me Me Me Me Me Me

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph

Me Et i-Pr t-Bu Ph MeS

Yield (%) 97 84 98 91 94 95

Likewise, Et(Cl)C N+ NR and R1 R2 C N+ NC(Cl)R3 R4 react with nitriles to give the [3+2] cycloadducts 23,24 . Sugar nitriles react with 1-(chloroalkyl)-1-aza-2-azoniaallene salts in the presence of Lewis acids to give the expected cycloadducts 24 . Also, cyclopropyl substituted 1-aza-2-azoniaallene salts 46 react with acetonitrile to form mixtures of [3+2] cycloadducts 47 and 48 25 .

(Me)C

N⊕

46

NAr SbCl6 + MeCN

Me N

NMe

N NAr

+

N

NAr

Me

Me

47

48

42


1-Aza-2-azoniaallene salts add across the C N double bond of 2-phenyl-3,3dimethylazirines to give the [3+2] cycloadducts 49 26 . N N⊕

R 1R 2C

N–C(CI)R2 SbCl6

N

+

N Ph

R1R2

Ph

N

49

R1 = R2 = Me R1 = Me, R2 = i-Pr

76 % 59 %

Azomethines undergo nucleophilic addition to 1-aza-2-azoniaallene salts to give linear iminium salts. Heterocumulenes, such as isocyanates 23 and carbodiimides 27 also react with 1-aza-2azoniaallenes across the C N bond to give [3+2] cycloadducts. For example, aliphatic and aromatic isocyanates add at –20 ◦ C to 1-aza-2-azoniaallene salts 50 to give 4,5-dihydro-5oxo-3H-1,2,4-triazolium salts 51 or the rearranged triazolium salts 52 28 . 1R 2C

R

N⊕

NR3

SbCl6

+

R4N

C

N

R 1R2 R4N

C

NR3

R1 R4 N

O 51

50

NR2 NR3

SbCl6

O 52

R1

R2

R3

R4

Adduct

Yield (%)

Me Me Me Me

Me Me Me Et

t-Bu t-Bu 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph

Pr Ph Pr Pr

51 51 52 52

90 82 93 93

In a recent theoretical study of the reaction of 1-aza-2-azoniaallene salts, with isocyanates it was concluded that these reactions proceed in asynchronous but concerted pathways. The presence of chloro groups in the 1-aza-2-azoniaallene salts, as well as methyl groups in the isocyanates, favor the cycloaddition reactions 29 . In contrast to the isocyanate reaction with 1-aza-2-azoniaallene salts, isothiocyanates react across their C S bond in the [3+2] cycloaddition reaction to give 1,3,4-thiadiazolium salts. The initially formed [3+2] cycloadducts 53 undergo a 1,2-shift to give the isomeric adducts 54 30 . R1R2C

N⊕

NR3 SbCl6

+ R4N

C

S

R1R2 S

N NR3 NR4 53

R1 S

NR2 NR3 SbCl6 NR4 54

1-Carbon Cumulenes

43

R1

R2

R3

R4

Yield (%)

i-Pr i-Pr Me

i-Pr i-Pr I-Pr

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph

Me Ph Ph

89 91 95

In some cases the initially formed cycloadducts undergo a Dimroth rearrangement to form 4,5-dihydro-5-thioxo-1H-1,2,4-triazole salts 55. N

R 1R 2 S

N

R 1R 2 R 4N

NR3

NR3

NR4

NR2

R1 R4N

S

NR3 SbCl6 S 55

R1

R2

R3

R4

Yield (%)

Me –(CH2 )4 – Ph

Me

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph

i-Pr Me Me

66 88 93

Et

In the reaction of 2,3,4-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanates with 1-aza2-azoniaallene salts the cycloaddition also proceeds across the C S bond 31 . Also, glycosyl isothiocyanates undergo the [3+2] cycloaddition reaction with 1-aza-2-azoniaallene hexachloroantimonates to give acylated 5-thio-β-d-glucopyranosylimino-1,3,4-thiadiazoles 32 . Carbodiimides also undergo [3+2] cycloaddition reactions with 1-aza-2-azoniaallene salts to give 4,5-dihydro-5-imino-1H-1,2,4-triazolium salts 56 25 . The reaction proceeds stepwise, but the linear intermediate cannot be detected. R 1R 2C

N

R 1R 2 R 4N

N+

R2 R 4N

NR3 NR5

R3 SbCl6

+ R4N

NR1

C

R2 R4N

NR3 NR5

NR5

NR1 NR3 SbCl6 NR5 56

R1

R2

R3

R4

R5

i-Pr –(CH2 )4 – Me Me Me

Me

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph

i-Pr i-Pr C6 H11 i-Pr Ph

i-Pr i-Pr C6 H11 Ph Ph

Me Me Me

Yield (%) 83 81 83 90 100

44


References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.

E.M. Burgess and H.R. Penton, Jr, J. Am. Chem. Soc. 95, 279 (1973). A. May, H.W. Roesky, D. Stalke, F. Pauer and G.M. Sheldrick, Chem. Ber. 123, 1475 (1990). G. Mloston, J. Romanski, A. Linden and H. Heimgartner, Helv. Chim. Acta 79, 1305 (1996). E.M. Burgess and H.R. Penton, Jr, J. Org. Chem. 39, 2885 (1974). T. Saito and S. Motoki, J. Org. Chem. 44, 2493 (1979). T. Saito, T. Musashi and S. Motoki, Bull. Chem. Soc. Jpn 53, 3377 (1980). T. Saito, I. Oikawa and S. Motoki, Bull. Chem. Soc. Jpn 53, 2582 (1980). T. Saito, I. Oikawa and S. Motoki, Bull. Chem. Soc. Jpn 53, 1023 (1980). G. Mloston, M. Celeda, H.W. Roesky, E. Parisini and J. Ahlemann, Eur. J. Org. Chem. 459 (1998). H.W. Roesky, A. May and M. Noltemeyer, J. Fluorine Chem. 62, 77 (1993). T. Saito and S. Motoki, J. Org. Chem. 44, 2493 (1979). R. Huisgen and J. Rapp, J. Am. Chem. Soc. 109, 902 (1987). R. Huisgen and J. Rapp, Tetrahedron 53, 939 (1996). G. Mloston and H. Heimgartner, Helv. Chim. Acta 78, 1298 (1995). R.W. Saalfrank and W. Rost, Angew. Chem. 97, 870 (1985). K. Okuma, M. Shimasaki, K. Kojima, H. Ohta and R. Okazaki, Chem. Lett. 1599 (1993). T. Machiguchi, M. Minoura, S. Yamabe and T. Minato, Chem. Lett. 103 (1995). Q. Wang, A. Amer, S. Mohr, E. Ertel and J.C. Jochims, Tetrahedron 49, 9973 (1993). Q. Wang, M. Al-Talib and J.C. Jochims, Chem. Ber. 127, 541 (1994). N.A. Hassan, T.K. Mohamed, O.M. Abdel Hafez, M. Lutz, C.C. Karl, W. Wirschun, Y.A. Al-Soud and J.C. Jochims, J. Prakt.Chem. 340, 151 (1998). Y. Guo, Q. Wang and J.C. Jochims, Synthesis 274 (1996). Y.A. Al-Soud, W. Wirtschun, N.A. Hassan, G. Maier and J.C. Jochims, Synthesis. 721 (1998). Q. Wang, J.C. Jochims, S. Köhlbrandt, L. Dahlenburg, M. Al-Talib, A. Hamed and A. El-Hamid Ismail, Synthesis 710, (1992). N.A. Al-Masoudi and Y.A. Al-Soud, J. Carbohydrate Chem. 23, 111 (2004). Q. Wang, A. Amer, S. Mohr, E. Ertel and J.C. Jochims, Tetrahedron 49, 9973 (1993). Y.A. Al-Soud, P.B. Shrestha-Dawadi, M. Winkler, W. Wirschun and J.C. Jochims, J.Chem. Soc., Perkin Trans. 1, 3759 (1998). Q. Wang, A. Amer, C. Troll, H. Fischer and J.C. Jochim. Chem. Ber. 126, 2519 (1993). Q. Wang, S. Mohr and J.C. Jochims, Chem. Ber. 127, 947 (1994). M. Wei, D. Fang and R. Liu, Eur. J. Org. Chem. 19, 4070 (2004). A.B.A. El-Gazzar, K. Scholten, Y. Guo, K. Weissenbach, M.G. Hitzler, G. Roth, H. Fischer and J.C. Jochims, J. Chem. Soc., Perkin Trans. 1, 1999, (1999). A.B.A. El-Gazzar, M.I. Hegab and N.A. Hassan, Sulfur Lett. 25, 161 (2002). N.A. Al-Masoudi, Y.A. Al-Soud and W.A. Al-Masoudi, Nucleosides, Nucleotides, Nucleic Acids, 23, 1739 (2005).

3 2-Carbon Cumulenes 3.1 3.1.1

Carbon Oxides, O C O, : C O Introduction

Carbon oxides are an interesting class of heterocumulenes, ranging from the stable, but relatively non-reactive carbon dioxide to the highly reactive carbon dioxides OCn O, where n = 4 or 5. Carbon suboxide, C3 O2 , takes an intermediate role because it can be readily synthesized and is a stable molecule. The interest in the higher homologs is prompted by the fact that these type of molecules could exist in interstellar space. Ethylenedione (OC2 O) has not as yet been synthesized, but the molecule should be relatively stable according to ab-initio calculations 1 . Carbon monoxide is an important industrial ‘C-1 Chemical’. The major derived products are methanol and phosgene. The synthesis of methyl methacrylate from acetylene, carbon monoxide and methanol is another industrially useful reaction. Carbon monoxide is a stable carbene, : CO, and therefore I have included many of its cycloaddition reactions. The [2+2+1] cycloaddition reaction which leads to five-membered ring carbonyl compounds is of considerable synthetic value. Copolymers of alkenes and carbon monoxide are a new class of biodegradable polyketones, which can be readily converted into functional polymers. Also copolymers of alkylene oxides and carbon monoxide are known. Carbon dioxide is the most abundant heterocumulene on earth. The total amount of carbon dioxide in the atmosphere and in the oceans is estimated to represent 1014 tons of carbon. However its industrial use is currently not extensive. Examples of its industrial use include the production of urea, the Kolbe–Schmitt synthesis of salicylic acid, methanol synthesis and the synthesis of cyclic carbonates. Future industrial uses of carbon dioxide can be anticipated because it will become readily available by sequestering from the air. The higher homologs of carbon dioxide are synthesized in the photolysis of suitable diazoketones and the reaction products are isolated in an argon matrix. For example, 1,2,3butatriene-1,4-dione (C4 O2 ) 2 is generated in the photolysis of the five- 1 and six-membered

Cumulenes in Click Reactions Henri Ulrich C 2009 John Wiley & Sons, Ltd

46


ring diazoketones 3 using a light source of 254 nm 2 . O

O

O

N2

N2 O

N2

C

C

C

C

N2

O O

O

O

O 1

2

3 -CO

hu (> 300 nm) :C

C

C

O

4

Using a light source of higher wavelength (>300 nm) generates the carbene carbon monoxide species 4, C4 O2 , can also be generated in the vapor phase 3 . 1,2,3,4-Pentatetraene-1,5-dioxide (C5 O2 ) 6 is similarly obtained in the photolysis of the six-membered ring diazoketone 5, using 254 nm light 4 . O N2

N2

O

O

O

C

C

C

C

C

O + CO + N2

N2 5

6

Photolysis, using light of >300 nm again affords the carbene monoxide :C C C C O. The yellow C5 O2 6 is stable to −90 ◦ C. At higher temperatures it polymerizes to give a black polymer, indicating its high reactivity in cycloaddition reactions. Heptahexaenedione (C7 O2 ) is obtained in the pyrolysis and matrix photolysis of mellitic acid trianhydride 5 . Carbon suboxide, C3 O2 , b.p. 6.8 ◦ C, was obtained by Diels in 1906 in the reaction of diethyl malonate with phosphorous pentoxide 6 ; however, it is best synthesized in the laboratory by thermolysis of O,O-diacetyltartaric acid anhydride (yield: 45–68 %) 7 , by thermolysis of diethyl oxalate in the presence of acetic anhydride (yield: 48 %) 8 , or by treatment of dibromomalonyl chloride with zinc in diethyl ether (yield: 80 %) 9 . Carbon suboxide can also be thermally generated from its thioamide adduct 7 10 . O RN PhC(S)NHR + C3O2

Ph

S

O

7

A review article on carbon suboxide appeared in Houben Weyl in 1968 11 , and its chemistry was summarized by Kappe and Ziegler in 1974 12 . The structure of carbon suboxide is mainly linear 13 . Carbon suboxide structurally resembles a ketene, but its chemistry is rather different although the polarization of the molecule is similar to that of ketenes. According to theoretical calculations the center carbon atom has the highest negative charge, as indicated in its resonance structure 8. O

C

C

C

O

O

C+-C− 8

C

O

2-Carbon Cumulenes

47

The stable oxocarbons 9 14 and 10 15 are also synthesized, and theoretical studies confirm the stability of the neutral oxocarbons 16 . O O

O O

O O O

O

O

O

O

O

O

O

O

O

O

O O 9

10

The polymerization of carbon suboxide can theoretically be initiated by a ketene like dimerization of the molecule 17 . However, it was shown that the polymerization is induced by trace amounts of nucleophiles, such as water, to give pyrone derivatives, which react with more carbon suboxide to form poly(α-pyrone) 18 . Although most reactions of carbon suboxide seem to be initiated by nucleophilic reactions, some cycloaddition reactions of carbon suboxide are known (see Section 3.1.2.2). The use of carbon dioxide in the synthesis of functional molecules is of considerable interest. An example is the industrially important reaction of epoxides with carbon dioxide to give cyclic carbonates. Also, functionalization of acetylenes and dienes with carbon dioxide on transition metal catalysts gives rise to the formation of cyclic lactones or dicarboxylic acids. The activation of carbon dioxide by metal complexes was reviewed in 1983 19 . Reactions of carbon dioxide with carbon–carbon bond formation catalyzed by transition metal complexes was reviewed in 1988 20 , heterogenous catalytic reactions of carbon dioxide were reviewed in 1995 21 , and the use of carbon dioxide as comonomers for functional polymers was reviewed in 2005 22 . Carbon oxides Cn O are also known. C3 O has been generated by pyrolysis. Mixtures of Cn O (n = 4–9) have been obtained from pulsed discharges through mixtures of C3 O2 and argon. FT microwave spectra of Cn O (n = 5,7,9) show that they all have singlet ground states. The molecular structure of C5 O has been determined 23 . Free Cn O (n = 4,6) molecules have been observed by ESR spectroscopy in neon or argon matrixes at 4 K as linear triplets 24 . A metal complex (CO)5 Cr C C C O has been synthesized 25 . This complex, in the form of black–violet crystals (dec. 32 ◦ C), is stable for some time at room temperature. 3.1.2 3.1.2.1

Cycloaddition Reactions [2+1] Cycloadditions

The reaction of liganded nickel 26 , molybdenum 27 and niobium 28 complexes with carbon dioxide produces [2+1] cycloadducts 11, which are relatively stable compounds. L2M + CO2

O

L 2M O 11

48


Molybdenum complexes with two side-on coordinated carbon dioxide molecules are also known 29 . Stepwise insertion of two moles of carbon dioxide into IrCl(C8 H14 )(PMe3 )3 affords the five-membered ring metallacycle 12, in which one molecule of CO2 is bonded at the carbon center, while the other molecule of CO2 is bonded to the metal at oxygen 30 . O

O

L3(Cl)Ir

IrCl(C8H14)(PMe3)3 + 2 CO2

O

O 12

The reaction of (PPh3 )2 Pt(C2 H4 ) with C3 O2 occurs by a [2+1] cycloaddition to give the platinum complex 13 in 37 % yield 31 . O (PPh3)2Pt(C2H4) + C3O2

(PPh3)2Pt O 13

The complex has a strong ketene absorption at 2080 cm−1 . A similar reaction occurs when (PPh3 )2 PtO2 is treated with carbon suboxide to give the [2+1] cycloadduct 14. O

O

O + C3O2

(PPh3)2Pt

(PPh3)2Pt

O

O

O

14

In the reaction of (C18 H14 )2 RhCl with C3 O2 only polymers are formed, which contain ketene groups in their backbone structure 32 . In contrast, reaction of the platinum carbonate 15 with tetracyanoethylene causes elimination of carbon dioxide with formation of the metallacycle 16 33 . O

LPt O

+ (NC)2C

LPt C(CN)2

(NC)2

O

O CN2

15

+ CO2

16

Decamethylsilicocene reacts with carbon dioxide under mild conditions in toluene to give a 70 % yield of the [2+1] cycloadduct 17. When the reaction is conducted in pyridine the macrocyclic products 18 and 19 are formed in 65 % yield 34 .

L2Si: + CO2

O

O L2Si

SiL2 +

L2Si O

O

O

O

L2Si O O

O 17

18

O

O

O

19

SiL2

2-Carbon Cumulenes

3.1.2.2

49

[2+2] Cycloadditions

The direct [2+2] reaction of carbon dioxide with other cumulenes or activated double bonds is rare and often these compounds are not stable. However [2+2+2] cycloaddition reactions are more often observed. The reaction of carbon dioxide with multiple bonded carbon derivatives proceeds in the presence of nickel (o) catalysts to give five-membered ring metallacycles, which on hydrolysis produce carboxylic acid derivatives. This derivatization of olefins and acetylene compounds is of considerable interest in synthetic organic chemistry. The reaction of alkynes with carbon dioxide in the presence of nickel (o) catalysts leads to the formation of metallacyclic 1:1 and 2:1 complexes. For example, the reaction of dimethylacetylene with carbon dioxide, in the presence of 1,5,9-cyclododecatrienenickel and N,N,N,N-tetramethylenediamine, affords the five-membered ring metallacycle 20 in 65 % yield 35 . Hydrolysis of the metallacycle affords 2-methylcrotonic acid.

MeC

CMe + CO2

LNi O 20

O

+ H2O

C(CH3)COOH

CH3CH

Titanium complexes of diphenylacetylene react with carbon dioxide to give similar fivemembered ring metallacycles 36 . In contrast, reaction of alkynes with carbon dioxide in the presence of Ni(COD)2 /Ph2 P(CH2 )4 PPh2 in benzene at 120 ◦ C (50 bar carbon dioxide pressure) produces pyrones 21 and acetylenic oligomers 37 .

RC

CR + CO2

+ Oligomers O

O

21

With 4-octyne a conversion of 98 % was achieved giving a 60 % yield of the corresponding pyrone. The intermediate formed in this reaction is most likely a seven-membered ring metallacycle 38 . Diynes react with carbon dioxide to give bicyclic α-pyrones 22 39 .

O EtC

C(CH2)4C

CEt + CO2

O

22

Nickel catalysts also effectively catalyze the [2+2+2] cycloaddition reactions of some diynes with carbon dioxide. For example, diynes 23 react with carbon dioxide in the presence of Ni(COD)2 and 1,3-bis-(2,6-diisopropylphenyl)imidazol at 60 ◦ C to give the

50


pyrones 24 in high yields 40 . R MeO2C MeO2C

R + CO 2 R

O

MeO2C MeO2C

O R

23

24

Similarly, asymmetrically diynes afford pyrones in a regioselective nickel(o) catalyzed cycloaddition reaction in 63–83 % yield 41 . The reaction of ethylene with carbon dioxide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and a nickel (o) catalyst affords the metallacycle 25, which on hydrolysis gives propionic acid in 85 % yield. Reaction of the metallacycle with another equivalent of ethylene affords a mixture of unsaturated C-5 carboxylic acids after hydrolysis in 79 % yield 42 . CH2 CH2 + CO2

(DBU)2Ni

O

O

25

In the reaction of the initially formed metallacycle with an acrylic acid ester a dicarboxylic acid derivative is obtained. The reaction of decamethylzirconocene bistrimethylsilylacetylene complex with carbon dioxide affords the zirconafuranone 26, which on heating rearranges to give the ketene complex 27 43 . Me3Si L L

SiMe3

Zr O

O

SiMe3 L Zr L

26

O OSiMe3 27

Conjugated dienes 44 and allene 45 react with carbon dioxide in the presence of nickel (o) catalysts to give eight- and five-membered ring metallacycles, respectively. Hydrolysis of the eight-membered ring metallacycle 28 with MeOH/HCl affords the cis-dicarboxylic acid ester 29. O O + MeOH/HCI

LNi

MeOCOCH2CH

CHCH2COOMe

O O 28

29

The cis-dicarboxylic acid is also obtained in 27 % yield from butadiene and carbon dioxide, using (η4 -butadiene)-tris(trimethylphosphane) (o)iron as the catalyst. The insertion of carbon dioxide occurs into the Fe–C σ bond of the initially formed metallacycle to give 30. Treatment of 30 with FeCl3 gives rise to an oxidative coupling reaction affording the

2-Carbon Cumulenes

51

dicarboxylic acid 31 in 93 % yield 46 . + FeCI3

L3Fe O

HOCO

COOH

O 30

31

The palladium catalyzed reaction of butadiene with carbon dioxide affords mixtures of the cyclic adducts 32 and 33 and linear adducts. The yield of the six-membered ring lactone increases when using a catalyst containing more basic phosphine ligands (PCy3 , P-i-Pr3 ) 47 . + CO2

+ O 32

+ linear adducts

O

O

O

33

Zirconium complexes of dienes react with carbon dioxide to give metallacycles, which also undergo reaction with another equivalent of carbon dioxide to give dicarboxylic acids after hydrolysis 48 . Oxidative coupling of dienes with carbon dioxide is also observed using nickel (o) catalysts 49 . Also, bis-1,3-dienes incorporate carbon dioxide in the presence of Ni(acac) and a diorganozinc reagent to afford cyclic carboxylic acids 50 . Conjugated dienemagnesium reagents react with acetone at −78 ◦ C, followed by carbon dioxide at 0 ◦ C to form the spiro-γ -lactone 34 in 68 % yield 51 . Mg + CH3COCH3 + CO2

O O 34

In contrast, reaction of allene with carbon dioxide in the presence of palladium 52 or rhodium 53 complexes affords a mixture of pyrones and esters. Electron-rich olefins, such as tetramethoxy ethylene, react with carbon suboxide to give an intermediate [2+2] cycloadduct 35, which reacts with another equivalent of the olefin to give the [4+2] cycloadduct 36, or it dimerizes and rearranges to form 37 54 . O 2 (MeO)2C

C(OMe)2 + 2 C3O2 O 35 O O

O

O O

O

36

37

O

52


Allene reacts with carbon dioxide in the presence of a ruthenium catalyst to give the [2+2] cycloadduct 38 55 . CH2

CH2 + O

C

C

O O

O 38

Dialkylketenes 39 react with carbon dioxide, catalyzed by Ph3 P, to give the six-membered ring [2+2+2] cycloadducts 40 56 . O 2 R2C

C

+ O

O

C

R2

O

O

R2 O

O 40

39

A mixed trimer of dimethylketene with carbon dioxide 41 is also obtained indirectly in the reaction of dimethylmalonic acid and acetic anhydride. O Me2

Me2

Me2C(COOH)2 + (AcO2)

O

O

O 41

Carbon dioxide also reacts with titanium cumulenes 42 to give the [2+2] cycloadducts 43 in 86 % yield 57 . [L2Ti

L2Ti

CH2] + CO2

C

O

42

O 43

This is an example of the cycloaddition of carbon dioxide to an M C bond giving rise to a stable [2+2] cycloadduct. Cyclopentenediisopropoxytitanium reacts with carbon dioxide to give the metallacycle 44 which on hydrolysis affords the cyclopentane carboxylic acid 45 58 . O Ti

OR OR

+ CO2

COOH

O Ti

OH

RO OR 44

45

The reaction of carbon suboxide with azomethines 46 was previously believed to involve a double [2+2] cycloaddition; however it was subsequently shown that the reaction product is a 1:1 adduct 47 with a switter ionic structure 59 . Ar ArCH 46

NR + C3O2

NR

O

O 47

2-Carbon Cumulenes

53

Another [2+2] cycloaddition reaction of carbon suboxide is encountered in the double Wittig reaction with the methylene phosphorane 48, which affords the 1,2,3,4-pentatetraene derivative 49 in 46 % yield 60 . 2 PhC(COOMe)

PPh3 + C3O2

MeOOCC(Ph)

C

C

48

C

C(Ph)COOMe + 2 Ph3PO

49

The cycloaddition reaction of carbon dioxide across P N bonds is likewise observed, but in these cases an exchange reaction occurs with formation of isocyanates. The [2+2] cycloaddition reaction of iminophosphoranes with carbon dioxide was already investigated by Staudinger and Hauser in 1921 61 . A mixture of isocyanates and carbodiimides was obtained, because the generated isocyanate 50 reacts with iminophosphoranes to give carbodiimides 51. Ph3P

NR + O

C

O

RN

C

O + Ph3O

50 Ph3P

NR + RN

C

O

RN

C 51

NR + Ph3O

This reaction is utilized in the catalytic conversion of isocyanates into carbodiimides using phospholene oxides as the catalyst 62 . When aliphatic diisocyanates were converted into carbodiimides using a phospholene oxide catalyst, the generated carbon dioxide was partially incorporated into six-membered ring [2+2+2] cycloadducts 63 . Phosphoramidate anions 52 also react with carbon dioxide to give carbamates 53, which on heating to 80 ◦ C afford isocyanates in good yield 64 . (EtO)2P(O)N−R + (CO)2

(EtO)2P(O)N(R)COO−

52

RNCO

53

In the reaction of the phenyl phosphoramidate anion 53 (R = Ph) with carbon dioxide only triphenyl isocyanurate is obtained because the generated phenyl isocyanate trimerizes under the reaction conditions. Also, from sodium diethyl N-alkoxy-phosphoramidate (R = OR) and carbon dioxide only 1,3,5-trialkoxyisocyanurates are obtained 65 . Also, switterionic titanium–imide complexes mediate the reaction of carbon dioxide with primary amines to give the corresponding isocyanates and symmetrical carbodiimides via a ligand metathesis reaction 66 . Titanium amidinate complexes 54 react rapidly at room temperature in toluene with carbon dioxide giving the [2+2] cycloadducts 55 67 . R N Me

Cp Ti

N R 54

NR

+ CO2

Me

R CP N O Ti N N R R 55

O

Also, the tosyl isocyanate cycloadduct of 54 undergoes an insertion with carbon dioxide 68 .

54


The iminophosphorane reacts with carbon dioxide via a [2+2] cycloaddition sequence and once again the cycloadduct 56 is not stable at room temperature and only dissociation products are isolated 69 .

RP

RP

N–N(SiMe3)2 + CO2

N–N(SiMe3)2

Me3SiNNCO + (RP

O

O)3

O 56

The phosphazene bond in a 1,2-azaphosphole also forms an unstable carbon dioxide [2+2] cycloadduct 70 . Also, aminoiminoboranes react with carbon dioxide to give [2+2] cycloadducts 71 . The [2+2] cycloaddition of carbon dioxide across a W–C bond in 57 is also observed to give 58 72 . NEt2 Ph CO P 2

Ph CO P 2 Et2N–C

+ CO2

Mo(CO)4

W

CO P Ph2

O

57

3.1.2.3

Mo(CO)4 NEt 4

W

O

CO P Ph2

58


The insertion reaction of carbon monoxide into epoxides affords β-lactones in excellent yields. For example, several epoxides 59 react with carbon monoxide in the presence of porphyrine catalysts to give the β-lactones 60 stereoselectively, usually in >99 % yield 73 . R1

R

R1

R

+ CO O

O 59

O 60

Several glycidyl esters 61 isomerize under the reaction conditions to give the γ -lactones 62 in almost quantitative yields. Ph Ph

O O

+ CO O 61

O O O

O

62

When using [(CITPP)Al(THF)2 ]+ [Co(CO)4 ]− (CITPP = meso-tetra(4-chlorophenyl) porphinato) as a catalyst in dioxane at 60 bar CO, chiral epoxides are similarly converted into β-lactones 74 . When the reaction is conducted with a second equivalent of carbon

2-Carbon Cumulenes

55

monoxide double insertion of carbon monoxide is observed with formation of succinic acid anhydrides (see also Section 3.1.2.5) 75 . When using chiral epoxides and 0.3 mol% catalyst at 50 ◦ C in dioxan, succinic acid anhydrides are obtained in 70–90 % yield (>99 % e,e) 76 . The carbonylative ring expansion of aziridines with carbon monoxide is accomplished in the presence of rhodium complexed dendrimers to afford β-lactames 63 in quantitative yields 77 . R2

R2

+ CO N R1

NR1

O 63

In the reaction of the aziridine 64 with CO in the presence of Co2 (CO)8 in DME at 100 ◦ C the β-lactame 65 is obtained in 94 % yield 78 . Et

H

Et

H

+ CO N

N

O

PhCH2CH2

CH2CH2Ph 64

65

The reaction is regiospecific with carbonyl insertion into the less substituted of the two ring carbon–nitrogen bonds. Using this reaction in the carbonylation of the cis-bicyclic aziridine 66 (R1 = adamantyl) resulted in the formation of the trans-β-lactame 67 in 80 % yield. + CO

H

H 1 R N

N R1 66

O

67

When the N-benzoyl derivative 68 is similarly reacted with CO a mixture of both stereoisomers 69 (55 % yield) and 70 (37 % yield) is obtained.

N

+

+ CO

Ph

N

N O

O Ph 68

3.1.2.4

Me

Me

Me

Ph

O

O

O 69

70


Some olefins, like 71, react with carbon dioxide (1 atm at 75 ◦ C), in the presence of (Ph3 P)4 Pd to give the [3+2] cycloadduct 72 in 63 % yield 79 . O OAC + CO2

Me3Si 71

O 72

56


Methylenecyclopropane 73 reacts with carbon dioxide in the presence of palladium (o)-phosphine catalysts to give the [3+2] cycloadduct 74 in 80 % yield 80 .

+ CO2

O 74

73

O

Higher oligomers, resulting from reaction of the cycloadduct with the olefin, are obtained as byproducts. From diphenylmethylenecyclopropane the oligomers are the major reaction products, while the [3+2] cycloadduct is only obtained in 18 % yield. From dimethylmethylenecyclopropane 75 and carbon dioxide at 126 ◦ C, in the presence of palladium (o)-phosphine catalysts, a mixture of the cycloadducts 76 and 77 is obtained 81 .

+ CO2 O 75

O

+ O 77

76

O

The reaction of carbon dioxide with epoxides affords ethylene carbonates. Recent examples include the use of Ni(cyclam)Br2 82 and Ti(O-i-Pr)4 83 . From propylene oxide 78 and carbon dioxide at room temperature and atmospheric pressure, in the presence of MoCl5 /PPh3 as the catalyst, 78 % of the cyclic carbonate 79 is obtained 84 .

+ CO2

O

O

O 78

O 79

Higher yields of cyclic carbonates are obtained using chromium (iii) bis(salicylaldimine) complexes in combination with DMPA as a catalyst 85 . Also, tetrahaloindate (iii) based ionic liquids catalyze this reaction. From chloromethyloxirane and CO2 (7 bar) at 120 ◦ C a 98 % yield of the corresponding carbonate is obtained 86 . The reaction can also be conducted in tetrabutylammonium halides as solvents and catalysts 87 . Also, [PPN]+ [Mn(CO)4 PPh3 ] is a good catalyst for the reaction of epoxides with carbon dioxide 88 . A solventless reaction of epoxides with carbon dioxide uses Re(CO)5 Br as a catalyst at 110 ◦ C 89 . Quantitative yields of propylene carbonate are also obtained when carbon dioxide is reacted with propylene oxide in the presence of NaI/PPh3 /PhOH 90 . Magnesium–aluminum mixed oxides are also excellent catalysts for the reaction of several epoxides with carbon dioxide to give the cyclic carbonates 80.

2-Carbon Cumulenes

57

R

R + CO2

O

O

O O 80

R

Yield (%) >99 >99 91 94

MeOCH2 C6 H13 Ph Bz

The [3+2] cycloaddition reaction of epoxides with carbon dioxide is also catalyzed by SnCl2 in acetone to give the cyclic carbonates 81 91 . R

R + CO2

O

O

O O 81

R

Yield (%)

CH3 (CH2 )5 CH2 CHCH2 OCH3 Ph

97 95 90

Racemic epoxides are converted into optically active carbonates using a chiral SalenCo(iii) quaternary ammonium halide catalyst system 92 . In the reaction of enantiopure amino epoxides 82 with carbon dioxide in the presence of BF3 , the corresponding carbonates 83 are obtained 93 . NBz2

R

R

+ CO2 O 82

Bz2N O

O O 83

Five-membered ring carbonates with a vinyl substituent, useful for radical polymerization to give polymers with pendant cyclic carbonate groups, have also been synthesized 94 .

58


Glycidyl acrylate 95 and glycidyl methacrylate 96 are also converted with carbon dioxide into the respective cyclic carbonate derivatives. The ring-opening reaction of aziridines with carbon dioxide, catalyzed by (Salen) Cr(III)/DMPA affords oxazolidinones 84 in high yields 97 . R1 R1 + CO2

RN

O

N R

O 84

A variety of mono-substituted N-aryl- and N-alkylaziridines, as well as 2,3-disubstituted N-alkylaziridines, react similarly. Symmetrical tetraalkyl ammonium salts promote the fixation of carbon dioxide to aziridine in the presence of iodine affording a 98 % yield within 5 min 98 . Regioselectivity and selectivity enhancement of carbon dioxide fixation to 2-substituted aziridines to give 2-oxazolidinones under supercritical conditions is also observed 99 . The 1,3-dipol 85, generated in the reaction of benzyne and imines is intercepted by carbon dioxide to form benzoxazinones 86 in high yields 100 . R N + ArCH

R N

Ar + CO2

NR

O O 86

85

3.1.2.5

Ar


The reaction of oxetane with carbon dioxide in the presence of tetraphenylstibonium iodide affords the six-membered ring [4+1] cycloadduct 87 101 . O O

+ CO2

O

O 87

The carbonylation of β-lactones with carbon monoxide (200 psi) in toluene at 80 ◦ C in the presence of an aluminum/[Co(CO)4 catalyst affords succinic anhydrides 88 in 95–> 99 % yield (95–99 % e,e) 102 . O R

O R

1

+ CO

O

O

R

O R1

88

2-Carbon Cumulenes

59

When the carbonylation is conducted in the presence of methyl iodide a double carbonylation to give 89 is observed 103 . Ph

Ph

O

R

H R H

+ 2 CO O

3.1.2.6

O

O 89


The reaction of butadiene with carbon dioxide to give a δ-lactone is not known. However, this reaction can be accomplished starting with the mono-epoxide 90 and reacting it with carbon monoxide. When the reaction is catalyzed by iron or cobalt, the shown δ-lactone 91 is formed. However, if a rhodium catalyst is used a β,γ -unsaturated lactone 92 is obtained 104 . O O

+ CO

O

+ O

90

O

91

92

In the reaction of isoprene with carbon dioxide in the presence of Pd(o) complexes mixtures of lactones are obtained. Also, teleromization of butadiene with carbon dioxide is accomplished with the same catalyst 105 . 3.1.2.7


In the reaction of oxazolines 93 with carbon monoxide and hydrogen, in the presence of [Rh(COD)Cl]2 the heterocycles 94 are obtained in 78–97 % yield 106 . Me

CO2Et R

R

N

N

+ CO + H2 O

O 94

93

O

Cyclopropyl imines 95 undergo a ruthenium catalyzed [5+1] cycloaddition reaction with CO to give the unsaturated lactames 96 in good yields 107 . R

NR1

R

+ CO

95

NR1 O 96

60


Also, 1,3-oxazin-2,4-diones 97 are obtained from epoxides (R = alkyl). These compounds are also obtained from aryl isocyanates and carbon monoxide in >97 % yields in the presence of Lewis acid/Co(CO)8 catalysts 108 . O

R

NR1

O

+ R1NCO + CO O

O

R 97

3.1.3 Insertion Reactions Numerous examples of insertion of carbon dioxide into metal to carbon bonds are known. This reaction usually affords ester products. However, treatment of liganded diphenyltitanium gives rise to the formation of the mono- 98 and the diinsertion product 99 109 . O L2TiPh2 + CO

+

L2Ti O

O L2Ti O

O

O

98

99

A similar carboxylation of the benzene ring occurs in the reaction of L2 Ti(Me)Ph with carbon dioxide 110 . The photolysis of L2 TiMe2 in the presence of carbon dioxide affords the mono insertion product 100 111 . L2TiMe2 + CO2

L2Ti(OCOMe)Me 100

Mono insertion of carbon dioxide also occurs into the intermediate 101 of the reaction between quadricyclane and [(bipy)Ni(cod)]x to give the metallacycle 102 112 .

Ni L 101

+ CO2 O

O

NiL

102

Insertion reactions of carbon dioxide into P–N, As–N, Si–N and Hg–O bonds are also reported. For example, addition of carbon dioxide to the amides of trivalent phosphorous

2-Carbon Cumulenes

61

affords 1:1 103 and 2:1 adducts 104. Likewise insertion into a trivalent arsenic amide is observed 113 . P(NMe2)3 + CO2

(Me2N)2POC(NMe2)

O

Me2NP[OCONMe2]2

103

104

Carbon dioxide reacts likewise with dialkylaminosilanes to give the insertion product. For example, the insertion product obtained from Me3 SiNEt2 can be distilled without dissociation 114 . From the diamino compound 105 and carbon dioxide the stable 1:2 adduct 106 is obtained 115 . Me2Si(NEt2)2 + 2 CO2 105

Me2Si[OCONEt2]2 106

In the reaction of the methylmercuric oxide 107 with carbon dioxide the expected insertion product 108 is obtained 116 . MeHgOHgMe + CO2 107

MeHgOC(OHgMe)

O

108

In the presence of ruthenium complexes, primary amines react with carbon dioxide at 120–140 ◦ C to give N,N -disubstituted symmetrical ureas 117 . Ruthenium complexes also catalyze the reaction of secondary amines with alkynes and carbon dioxide to give vinyl carbamates 118 .

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2-Carbon Cumulenes 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118.

63

E.O. Fischer, A.C. Filippou, H.G. Alt and U. Thewalt, Angew. Chem. Int. Ed. 24, 203 (1985). J.A.R. Schmidt, E.B. Lobkovsky and G.W. Coates, J. Am. Chem. Soc. 127, 11426 (2005). J.N. Chheda, G.W. Huber and J.A. Dumesie, Angew. Chem. 119, 7298 (2006). Y. Fukura, Y. Iizuka, K. Sekikawa and H. Ohno, Green Chem. 9, 1155 (2007). G. Imperato, B. König and C. Chiappe, Eur. J. Org. Chem. 1049 (2007). S. Lu and H. Alper, J. Org. Chem. 69, 3558 (2004). M.E. Piotti and H. Alper, J. Am. Chem. Soc. 118, 111 (1996). G.E. Greco, B.L. Gleason, T.A. Lowery, M.J. Kier, L.B. Hollander, S.A. Gibbs and A. Worthy, Org. Lett. 9, 3817 (2007). P. Binger and H.J. Weintz, Chem. Ber. 117, 654 (1984). Y. Inoue, T. Hibi, M. Satake and H. Hashimoto, J. Chem. Soc., Chem. Commun. 982 (1979). P. Tascedda and E. Dunach, J. Chem. Soc., Chem. Commun. 43 (1995). M. Brunner, L. Mussmann and D. Vogt, Synlett 69 (1994). M. Ratzenhofer and H. Kisch, Angew. Chem. 92, 303 (1980). S.T. Nguyen and R.L. Paddock, J. Am. Chem. Soc. 123, 11489 (2001). Y.J. Kim and R.S. Varma, J. Org. Chem. 70, 7882 (2005). V. Calo, A. Nacci, A. Monopoly and A. Fanizzi, Org. Lett. 4, 2561 (2002). W.N. Sit, S.M. Ng, K.Y. Kwong and C.P. Lau, J. Org. Chem. 70, 8583 (2005). J. Jiang, F. Gao, R. Hua and X. Qiu, J. Org. Chem. 70, 381 (2005). J. Huang and M. Shi, J. Org. Chem. 68, 6705 (2003). J.R. Vyvyan, J.A. Meyer and K.D. Meyer, J. Org. Chem. 68, 9144 (2003). X. Lu, B. Liang, Y. Zhang, Y. Tian, Y. Wang, C. Bai, H. Wang and R. Zhang, J. Am. Chem. Soc. 126, 3732 (2004). J.M. Concellon, V. del Solar, S. Garcia-Grande and M.R. Diaz, J. Org. Chem. 72, 7567 (2007). J.W. Huang and M. Shi, J. Org. Chem. 68, 6705 (2003). H.J. Golden, B.G.M. Chew, D.B. Zax, F.J. DiSalvo, J.M.J. Frechet and J.M. Terason, Macromolecules. 28, 3468 (1995). N. Kihara and T. Endo, Makromol. Chem. 193, 1481 (1992). A.W. Miller and S.T. Nguyen, Org. Lett. 6, 2301 (2004). H. Kawanami, H. Matsumoto and Y. Ikushima, Chem. Lett. 34, 60 (2005). H. Kawanami and Y. Ikushima, Tetrahedron Lett. 43, 3841 (2002). H. Yoshida, H. Fukushima, J. Ohshita and A. Kunai, J. Am. Chem. Soc. 128, 11040 (2006). A. Baba, H. Kashiwagi and H. Matsuda, Tetrahedron Lett. 26, 1323 (1985). Y.L. Grtzler, V. Kundnani, E.B. Lobkovsky and G. W. Coates, J. Am. Chem. Soc. 126, 6842 (2004). H. Alper, H. Arzoumanian, J.F. Petrignani and M. Saldano-Maldonado, J. Chem. Soc., Chem. Commun. 340 (1985). R. Aumann and H. Ring, Angew. Chem. 89, 47 (1977). E. Dinjus and W. Leitner, Appl. Organomet. Chem. 9. 43 (1995). M. Vasylyev and H. Alper, Org. Lett. 10, 1357 (2008). A. Kamitani, N. Chatani, T. Morimoto and S. Murai, J. Org. Chem. 65, 9230 (2000). T.L. Church, C.M. Byme, E.B. Lobkovsky and G.W. Coates, J. Am. Chem. Soc. 129, 8156 (2007). L.S. Kolomnikov, T.S. Lobeeva, V.V. Gorbachevskaya, G.G. Aleksandrov, Y.T. Struckov and M.E. Vogel, J. Chem. Soc., Chem. Commun. 972 (1971). G.A. Luinstra and J.H. Teuber, Organometallics 11, 1793 (1992). R.F. Johnston and J.C. Cooper, Organometallics. 6, 2448 (1987). A. Behr and G. Thelen, C1 Mol. Chem. 1, 137 (1989). G. Oertel, H. Malz and H. Holtschmidt, Chem. Ber. 97, 891 (1964). H. Breederveld, Recl. Trav. Chim. 79, 1126 (1960); Chem Abstr. 55, 7283 (1961). H. Breederveld, Recl. Trav. Chim. 81, 276 (1962); Chem Abstr. 57, 5946 (1962). D. Grdenic and F. Zabo, J. Chem. Soc. 521 (1962). J. Fornier, C. Bruneau, P.H. Dixneuf and S. Lecolier, J. Org. Chem. 56, 4456 (1991). R. Mahe, Y. Sasaki, C. Bruneau and P.H. Dixneuf, J. Org. Chem. 54, 1578 (1989).

64


3.2 Carbon Sulfides, S C S, S C O 3.2.1 Introduction The sulfides derived from carbon, such as carbonyl sulfide (O C S) and carbon disulfide (S C S) are relatively inert compounds. In contrast, carbon monosulfide and the higher carbon disulfides and oxysulfides are unstable at room temperature. These species are often matrix isolated at lower temperatures. In this manner the carbon monosulfides (C)n S, which are heterocumulenes with carbene-like character, are obtained. For example, C2 S was generated by laser induced photolysis of matrix isolated C3 S2 or C3 OS 1 . The higher homolog C3 S is obtained by matrix isolation in the photolysis of 7-diazo-2-thia3,4-diazabicyclo[3,3,0]hepta-1,3-diene-6,8-dione 2 . The next higher member of this series, C4 S, is obtained by photochemical cleavage of matrix isolated C5 OS 3 . The higher carbon disulfides are also of recent vintage. For example, ethylenedithione, S C C S, is generated from 1,3,4,6-tetrathiapentalene-2,5-dione using 70 eV 4 . Several other heterocycles also generate C2 S2 upon pyrolysis 1 . The next higher homolog C3 S2 is a well known stable molecule. Butatrienedithione, C4 S2 , is also obtained by matrix isolation spectroscopy 1 , and C5 S2 was synthesized in the pyrolysis of benzotristhiadiazole 1 5 . N N S

S N

N N S 1

S

C

C

C

C

C

S

N

The next higher homolog of this series, C6 S2 , has been discovered in the gas phase 6 . While carbonyl sulfide is a well known stable molecule, the higher sulfide oxides O (C)n S are also of recent vintage, and they were obtained by matrix isolation. For example, C2 OS 2 was matrix isolated by generating it in the photochemical reaction of carbon monosulfide with carbon monoxide 7 . C

O + C

S

O

C

C

S

2

The carbon monosulfide was generated by a microwave discharge in carbon disulfide. The next higher homolog C3 OS 4 was prepared by pyrolysis of the heterocycle 3. Matrix isolation was not necessary, because the heterocumulene is stable under normal conditions, similar to carbon suboxide 8 . O

S

O

O

S

O

S 3

C

C 4

C

O

2-Carbon Cumulenes

65

The next higher homolog C4 OS 6 was isolated by matrix photolysis of 7-diazo-2-thia3,4-diazabicyclo[3,3,0]hepta-1,3-diene-6,8-dione 5 1 . O S N2

N

hu

S

C

C

C

C

O

N O 5

6

The next higher member of this series, C5 OS 8, was generated by pyrolysis of benzo-[1,2d;4,5-d]bis[1,2,3]thiadiazole-4,7-dione 7 or matrix photolysis of thiophenetetracarboxylic acid bis-thioanhydride 9 1 . O

O

N

S

S

N

N

N

S

C

C

C

C

C

O

O

S

S S

O

O 7

8

O 9

The higher carbon cumulenes are assumed to be present in interstellar regions. Thus far stable dimers of the higher carbon cumulenes have not been isolated. Recently, the spectroscopic identification of carbonyl telluride, obtained by photolysis of H2 Te in CO or 1 % CO/Ar matrices at 10 K, was reported 9 . Carbonyl selenide is readily synthesized in situ from R2 NC(O)Se− R2 NH2 + and acids, but little of its chemistry is known 10 . Poly(carbon diselenide) is obtained as a black powder by thermal polymerization or photopolymerization of carbon diselenide. The obtained polymer is highly disordered, and it has a head-to-head polymer structure 11 . 3.2.2 3.2.2.1


Liganded cobalt complexes react with carbon disulfide by addition across one of the C S bonds to give relatively stable complexes 10 12 . The same complex reacts with carbonyl sulfide to give a liganded carbonyl complex 11 and Me3 PS. In the reaction of carbon sulfoselenide at −20 ◦ C the adduct 12 as well as the thiocarbonyl complex 13 are formed, indicating that carbon sulfoselenide can be used for the synthesis of thiocarbonyl compounds. CS2

LPMe3Co

C

S

S 10 L(PMe3)Co

COS

LPMe3Co

C

O

CSSe

LPMe3Co

LPMe3Co(CO) + Me3PS 11

S C Se 12

S

LPMe3Co(CS) + Me3PS 13

66


Carbon disulfide complexes of iron 14 are obtained in the reaction of (benzylideneacetone)-tricarbonyliron (o) with P(OMe)3 in carbon disulfide 13 . The complexes react with acetylenes to form iron–carbene complexes 15 14 . Depending on the phosphorous ligands, rearrangement to give 16 is observed 15 . P(OMe)3 OC OC

Fe

S

+ RC

S

R

S

Fe

Fe

CR

S

S P(OMe)3 14

R

R

R

15

S

16

1,3-Dithiolium carbenes are also obtained in the reaction of perfluorinated acetylenes with carbon disulfide and Ph3 P 16 . Cyclopentadienyl manganese complexes CpMn(CO)2 CS2 17 and [CpMn(CO)2 ]2 CS2 18 are obtained in the photolysis of CpMn(CO)3 and subsequent reaction of the generated CpMn(CO)2 THF intermediate with carbon disulfide. The carbon disulfide is added to the metal via one C S bond 17 . In solution the monometal complex 17 converts into the dimetal complex 18. CpMn(CO)2 THF + CS2

CpMn(CO)2CS2 + [CpMn(CO)2]2CS2 17

18

In the reaction of CpMn(CO)(CS)(C8 H14 ) with carbon disulfide and Ph3 P as sulfur acceptor, di- and trithiocarbonyl complexes are obtained 18 . Platinum and palladium [2+1] cycloadducts with CS2 and CSSe are also known 19 . In the reaction of oxaziridine with carbon disulfide, addition of the generated nitrene to carbon disulfide affords isothiocyanates and sulfur 20 . 3.2.2.2


The cycloaddition reaction of carbon disulfide to a carbon–carbon double bond was first observed by Mumm and coworkers in 1939 21 . The authors obtained 1:1 adducts from enamines and carbon disulfide. The initially formed cycloadducts rearrange to form linear adducts 19 because of the availability of β-hydrogen atoms. Me2

Me2 + CS 2 N Me

N CHC(S)SH Me 19

Ketimines react with carbon disulfide similarly to afford linear 1:1 adducts 22 . When the reaction of enamines or ketimines with carbon disulfide is conducted in the presence of elementary sulfur, the five-membered ring heterocycles 20 are obtained 23 . R2 R2NC(R1)

CHR2 + CS2 + S

S

R1

S 20

S

+ R2NH

2-Carbon Cumulenes

67

The reactive peraminoethylenes 21 react with carbon disulfide to give the linear switter ionic adducts 22 24 . Et N

Et N

N Et

N Et

Et N + CS2

C(S)S N Et 22

21

The photochemical cycloaddition of carbon disulfide to 1,1-dimethyl-2,5diphenylsilapentadienes 23 leads to the formation of the isomeric [2+2] cycloadducts 24 and 25 25 . S S Si Ph Ph Me Me

+ CS2

Si Ph Ph Me Me

23

S +

S Si Ph Ph Me Me 25

24

The C C bond in ketenes also participate in cycloaddition reactions with other cumulenes. For example, [2+2+2] cycloadducts 27 are obtained from dialkylketenes 26 and carbon disulfide 26 . O 2 R2C

O + S

C

C

R2

R2

S

S 26

O

S 27

The C N double bond in azirines also undergoes [2+2] cycloaddition reactions with carbon disulfide and depending on the substituents, different different reaction products are obtained. For example, the 2-aminoazirine 28 (R1 = R2 = Me) reacts with carbon disulfide to form a linear switter ionic adduct 29 in 93 % yield 27 . However, [2+2] cycloaddition across the C N bond is also observed and the cycloadduct 30 rearranges to give the fivemembered ring switter ionic adduct 31, which is in equilibrium with the isothiocyanate 32. In solution an isothiocyanate band is observed in the infrared spectrum. R1

R1 R2

NR2 N

R2

+ CS2

NR2

NR2 R1

N

R2 S

28 NR2

R2

S

N

30 R1 SCN C 2

R S 31

N

S 29

R1

S

32

C(S)NR2

S

68


When one methyl group in 28 is replaced by a phenyl group the initially formed switter ionic adduct 33 rearranges to form the five- and six-membered ring heterocycles 34 and 35 28 . Ph Ph

NR2

Me S

+ CS2

Me N

NR2 + N −

Ph

NR2

Me

S

+

N

S

33

H

Ph NR2

S

N

S

S

34

35

In the reaction of 2-N-morpholino-3,3-diethylaziridine 36 with carbon disulfide the carbodiimide 37 is formed 29 . Et

N

O

Et

N – CC(Et)2N

O

+ CS2

N

C

NC(Et)2C– N

S

O

S

36

37

Cyclic carbodiimides 38 react with carbon disulfide to give aliphatic diisothiocyanates 39. This reaction involves an initial [2+2] cycloaddition across one of the C N groups of the carbodiimide 30 . N (CH2)n

N

+ CS2

S

C

N–(CH2)n–N

38

C

S

39

Iminophosphanes 40 also undergo a [2+2] cycloaddition reaction with carbon disulfide to give the cycloadducts 41 31 . RP

N–N(SiMe3)2 + CS2

RP S

40

N(SiMe3)2

N S 41

In the reaction of hexaphenylcarbodiphosphorane 42 with carbon disulfide, ionic linear 1:1 adducts 43 are obtained, which dissociate on heating to give 44 and Ph3 PS 32 . Ph3P Ph3P

C

PPh3 Ph3P+–C−

PPh3 + CS2 S

42

+

−

43

C

S + Ph3S

S 44

The reaction of Ph3 P C C O with carbon disulfide gives rise to the formation of Ph3 P C C S and carbonyl sulfide. This exchange reaction most likely proceeds via an initial formation of a [2+2] cycloadduct 33 . The reaction of Ph3 P C C NR with carbonyl sulfide or carbon disulfide affords [2+2] cycloadducts resulting from addition across the C C bond 34 . A similar [2+2] cycloadduct is obtained from Ph3 P C C(OEt)2 . The reaction of diphenylmethylene phosphorane with carbon disulfide affords polymeric diphenylthioketenes 35 . In a similar reaction fluorenylidene triphenylphosphorane affords the corresponding thioketene dimer 36 . An exchange reaction is observed in the reaction of

2-Carbon Cumulenes

69

triphenyliminophosphoranes 45 with carbon disulfide because the initially formed [2+2] cycloadduct 46 dissociates to give isothiocyanates and Ph3 PS 37 . Ph3P

NR + CS2

Ph3P

NR

S 45

RN

S + Ph3PS

C

S 46

The reaction of carbon disulfide with iminophosphoranes is quite general. In addition to trialkyl- and triaryliminophosphoranes also bisalkoxyalkyliminophosphoranes 38 , trialkoxyiminophosphoranes 39 , dimeric trichlorophosphazenes 40 and phosphoramidate anions 41 react similarly. Bisiminophosphoranes react with carbon disulfide to give diisothiocyanates which are used in the construction of macrocyclic carbodiimides 42 . Carbon disulfide also undergoes cycloaddition reactions with other hetero double bonds. For example, aminoiminoboranes react with CS2 , COS and CSe2 to give [2+2] cycloadducts in high yields 43 . Also, triphenylarsenic oxide undergoes an exchange reaction with carbon disulfide to give Ph3 As S and carbonyl sulfide 44 . Cyclostannacenes react with carbonyl sulfide to give isothiocyanates and [R2 Sn S]2 . This reaction is most likely initiated by dissociation of the cyclostannacene to t-Bu2 Sn NR 47, followed by [2+2] cycloaddition to form 48, which also dissociates to give the exchange products 45 . t-Bu2Sn

NR + CS2

t-Bu2Sn

NR

S

RN

C

S + [t-Bu2Sn

S]2

S

48

47

Stannathiones also undergo a [2+2] cycloaddition reaction with carbon disulfide to form 49 46 . R2Sn

S + CS2

R2Sn

S

S

S 49

The W As derivatives 50 also undergo [2+2] cycloaddition reactions with carbon disulfide to give 51 47 . L(CO)2W

As(t-Bu)2 + CS2

L(CO)2W

As(t-Bu)2

S 50

S 51

The reaction of dithiocarbonate complexes of ruthenium 52 with carbon disulfide affords trithiocarbonate complexes 53. The reaction proceeds via addition across the ruthenium–sulfur bond with generation of 54 and carbonyl sulfide 48 .

L3Ru S

+

S

S O + CS2

L3Ru

O S

S

− BPh4

L3Ru

S S

S 52

53

+

S

54

− BPh4 + COS

70


The rhodium catalyzed [2+2+2] cycloaddition of 1,6-diynes with carbon disulfide affords bicyclic dithiopyrones 55 in 74–85 % yield 49 . R1

R1 + CS2

R2

S S

R2 55

The dithiopyrones are also obtained using CpRu(COD)Cl as the catalyst but the yields are only about 50 % 50 . 3.2.2.3


Ethylene sulfide reacts with carbon disulfide in the presence of triethylamine as the catalyst to give a 63 % yield of trithiocarbonate 56 51 . S

+ CS2

S S 56

O

From ethylene oxide and carbon disulfide at 90–100 ◦ C, in the presence of tetraethylammonium bromide, a mixture of ethylene carbonate and trithiocarbonate is obtained, while propylene oxide gives the expected [3+2] cycloadducts. The reaction of alkylene oxide and carbon disulfide in the presence of LiBr in THF at room temperature affords the dithiocarbonates 57 in good yields 52 .

O

+ CS2

S S 57

O

Also, the organophosphine catalyzed reaction of chloromethyloxiran with carbon disulfide provides the corresponding [3+2] cycloadduct in 74 % yield 53 . Similarly, aziridines 58 react with carbon disulfide in the presence of Bu3 P to give the cycloadducts 59 53 . R2 R1

R1

R2 S

+ CS2

NTs

N Ts

S

58

59

R

R1

Yield (%)

Bu Ph

H H

98 98

2-Carbon Cumulenes

71

Also, the bicyclic aziridine 60 reacts with carbon disulfide to give the [3+2] cycloadduct 61 in 92 % yield.

+ CS2 S

N Ts

NTs S

60

61

Nitrile oxides react with carbon disulfide to give the [3+2] cycloadduct 62 which reacts with a second equivalent of the nitrile oxide and, with elimination of isothiocyanates gives the carbonyl sulfide cycloadduct 63 54 . Ar–C

N

N

Ar

O + CS2

O + Ar–C

N

N

Ar

O

S

O S

S

O

62

63

The reaction of the switter ion 64 with carbon disulfide in DMF in the presence of triethylamine affords the cycloadduct 65 in 70 % yield 55 . H N +

H N

−

N

N H

OSO2

+ CS2

N

N

H

S

S 64

65

Nitrile imines react similarly to form the [3+2] cycloadduct 66, which reacts with a second equivalent of nitrile imine to give the spiro compound 67 56 . PhC

N

NPh + CS2

N Ph

NPh + PhC

N N

Ph

NPh

S PhN

S S

NPh S

N 67

66

Ph

C-Aryl-N,N -dimethylazomethine imine 68 also reacts with carbon disulfide to give the [3+2] cycloadduct 69 57 .

RCH

N(Me)

NMe + CS2

Me N NMe

R S

S 68

69

72


The N-imine of quinoline 70 also reacts with carbon disulfide to give the ionic adduct 71 in 81 % yield 58 . + CS2

+

+

N

N HN

NH

S

−

S

70

−

71

The red isoquinoline N-phenylimide reacts with CS2 to give a stable [3+2] cycloadduct which can be used as a neutral source of the unstable N-phenylimide because dissociation occurs in solution 59 . Diazomethylenephosphoranes 72 also undergo the [3+2] cycloaddition reaction with carbon disulfide to give 73 60 . R2(Cl)P

C

N

N2 + CS2

R2(Cl)P

N S

S 72

73

The thioketocarbene 74, generated in the thermolysis of 1,2,3-benzothiadiazole, reacts with carbon disulfide to give the 1:1 cycloadduct 75 and the 2:2 adduct 76 61 . S

S

+

S

−

+ CS2

S

S + S

S

74

75

S 76

Similarly, aliphatic thiocarbenes react with carbon disulfide to give trithiocarbonates. For example, from 77 and carbon disulfide, 78 is obtained in 42 % yield 62 . S

S N

N + CS2

S S

77

78

The reaction of carbon disulfide with sodium azide and subsequent acidification affords the triazole derivative 79 63 . NaN3 + CS2

N N S NH S 79

The azido nickel complex 80 reacts with carbon disulfide at room temperature to give the [3+2] cycloadduct 81 64 . LNi(PBu3)2N3 + CS2

N N L(PBu3)Ni– N S S

80

81

2-Carbon Cumulenes

73

In the rhodium catalyzed decomposition of α-diazoketones 82 in the presence of carbon disulfide the [3+2] cycloadduct 83 is obtained 65 . R

O

R

O

R1

S

S

+ CS2 R

N2

1

82

83

A [3+2] cycloaddition reaction of carbon disulfide across a 1,3-dipole in the mesoionic compound 84 also affords the cycloadduct 85. Heating of 85 causes elimination of phenyl isothiocyanate and sulfur to give 2,4,5-triphenyl-2H-1,2,3-triazole 86 66 . NPh Ph

N +

NPh + CS 2 N

S

Ph

Ph Ph N N N NH S Ph Ph

84

Ph

H N

NPh + PhNCS + S N

Ph

85

86

The reaction of heterocumulenes with alkynes sometimes leads to the formation of a carbene, which undergoes dimerization. For example, from alkynes and carbon disulfide under high pressure, tetrathiofulvenes 87 are obtained 67 . R RC

CR1

+ CS2 R1

R

S S

R1

S

S

S

S

R R1

87

R

R1

Yield (%)

H Me

Me Me

96 87

The reaction of 3,3,7,7-tetramethylcycloheptyne 88 with carbon disulfide affords the corresponsing tetrathiofulvene 89 68 .

+ CS2 88

S

S

S

S 89

In the reaction of cyclooctyne with carbon diselenide the generated carbene picks up a selenium atom from carbon diselenide to give the bicyclic selenium derivative 90 in 20 %

74


yield 69 . Se

Se

Se

Se

Se

+ CSe2

90

Liganded cobalt imines 91 react with carbon disulfide to give dimetallaspiro heterocycles 92 70 . Me 2 L2CoC(Me)

NR

L2Co

NR + CS2

S

S

CoL2

RN Me

91

92

A ‘criss-cross’ [3+2] cycloaddition is observed in the reaction of the gold complex 93 with two equivalents of carbon disulfide to give 94 71 .

C6H5AuP(Ph)2CHP(Me)Ph2 + 2 CS2

Ph2 Au(C6F5)22 S S P Au P + P(Me)Ph S 2 Ph2

+

Ph2(Me)P S

94

93

3.2.2.4

−


Azomethines react with carbon disulfide to give 1,4-dipoles, which on reaction with another equivalent of azomethine affords hexahydro-1,3,5- thiadiazene derivatives 95 in high yields 72 . H MeN

NMe + CS2

2 PhCH

S

Ph NMe H Ph S 95

Heating of 95 causes dissociation with formation of the starting components. The enamine derived from styrene and morpholine reacts with CS2 to form a 1,4dipole, which is intercepted with a second equivalent of the enamine to give the [4+2] cycloadduct 96. Heating of 96 results in elimination of morpholine and formation of 4,6diphenylthiopyran-2-thione 97 73 . Ph

S

N −

S

Ph

Ph

O + Ph

N

N

O

O Ph

S

S 96

N

O

S

S 97

Ph

2-Carbon Cumulenes

3.2.3

75

Insertion Reactions

The insertion of carbon disulfide into P–N single bonds was already observed by Michaelis and Kaene in 1898, who obtained a 2:1 adduct 99 from carbon disulfide and phenyldipiperidinophosphorane 98 74 . The structure 99 of the adduct was elucidated by Vetter and Nöth in 1963 75 . PhP N

2

+ 2 CS2

PhP SC(S)N

98

2

99

Similar 2:1 and 3:1 adducts from carbon disulfide and the amides of trivalent phosphorus and arsenic are also obtained 76 . The crystal structure of the 3:1 adduct derived from P(NMe2 )3 and CS2 has been reported 77 . Polynuclear aluminum–magnesium compounds undergo insertion reactions with carbon disulfide 78 . Also, insertion into a P–P bond occurs in the reaction of carbon disulfide with the tetra-substituted diphosphine 100 to give the insertion product 101 79 . Et2P–PEt2 + CS2

Et2PSC(S)PEt2

100

101

Insertion of carbon disulfide into Mn–O and Re–O complexes of (CO)3 (P–P)MOR (where P–P is 1,2-bis(diphenylphosphinoethane) also occurs readily 80 . The insertion reaction of carbon disulfide is not limited to the amides of group V elements. Dialkylaminosilanes react with carbon disulfide at room temperature to give the silyldialkyldithiocarbamates 102, which can be distilled under vacuum without decomposition. However, at 100 ◦ C and atmospheric pressure carbon disulfide is eliminated with regeneration of the starting material 81 . Me3SiNEt2 + CS2

Me3SiSC(S)NEt2 102

Carbon disulfide also reacts with tin amides, such as Me3 SnNMe2 , to give the insertion products 82 . Tin alkoxides react similarly to give the 1:1 adducts. For example, reaction of bistributyltin oxide 103 with carbon disulfide affords bis(tributyltin)sulfide 105 with elimination of carbonyl sulfide 83 . The reaction involves the insertion product 104 as an intermediate. Bu3SnOSnBu3 + CS2 103

[Bu3SnSC(S)OBu3] 104

Bu3SnSSnBu3 + COS 105

Bis(triaryltin)oxides react with carbon disulfide and carbonyl sulfide in a similar manner to afford the corresponding sulfides in high yields. Similarly, Pb, Hg and As metal organic compounds with metal–oxygen bonds or metal–hydroxy bonds undergo this reaction.

76


Bis(2,4,6-tri-t-butylphenyl)stannylene reacts with carbon disulfide by stepwise insertion into the Sn–C bonds 84 . Also, organostannylphosphines react with carbonyl sulfide (X = O) or carbonyl disulfide (X = S) to give the insertion products 106 in good yield 85 . Ph3Sn–PPh2 + S

C

X

Ph3SnXC(S)PPh2 106

Likewise, triphenyltinlithium reacts with carbon disulfide to give the insertion product, which on reaction with alkyl iodides gives Ph3 SnC(S)SR 86 . The 1:1 adduct derived from mercury compounds and carbon disulfide is known since 1899 when Pesci reacted phenylmercuric sulfide with carbon disulfide to give 107 87 . PhHg–S–HgPh + CS2

PhHgSC(S)SHgPh 107

From methylmercuric oxide and carbon disulfide, in the presence of methanol, the adduct 108 is obtained, indicating preferential alcoholysis of the mercury–oxygen bond 88 . MeHg–O–HgMe + CS2 + MeOH

MeHgSC(S)OMe 108

From lead–sulfur compounds 109 with carbon disulfide the 2:1 adducts 110 are also obtained, which on standing dissociate to give lead sulfide, carbon disulfide and trithiocarbonate 89 . (BuS)2Pb + CS2

Pb[SC(S)SBu]2

109

PbS + CS2 + (BuS)2C

S

110

Double insertion of carbon disulfide into lead(ii)bisarenethiolates 111 to give 112 is also observed 90 . (RS)2Pb + 2 CS2 111

Pb[SC(S)SR]2 112

Insertion of carbon disulfide into platinum metal-hydrogen bonds is known 91 , and insertion of carbon disulfide into alkoxo–palladium bonds also occurs 92 . Insertion of carbon disulfide into ruthenium alkenyl bonds gives rise to the formation of an alkenedithiocarboxylate ligand 93 . Examples of the insertion of carbon disulfide into carbon–nitrogen bonds is also known. Dipiperidinomethane 113 reacts with carbon disulfide to give the insertion product 114 94 . NCH2N 113

+ CS2

NCH2SC(S)N 114

2-Carbon Cumulenes

77

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2-Carbon Cumulenes

3.3

79

Carbon Nitrides

3.3.1 3.3.1.1

Isocyanates, RN C O Introduction

Isocyanates are esters of isocyanic acid, and the first member of this class of compounds was synthesized by Wurtz in 1848. Shortly thereafter, several prominent 19th Century scientists, such as Hofmann and Curtius, systematically investigated the chemistry of isocyanates. It almost took a century to recognize that isocyanates are ideally suited to produce macromolecules by a polyaddition process. Polyurethanes, derived from diisocyanates and macroglycols were invented by Otto Bayer of IG Farben (later Bayer) and his coworkers in 1937. Polyurethanes can be considered to be formed in a click reaction at room temperature, without a solvent, and the yields are quantitative. The reactivity of the isocyanate group is caused by its heterocumulene structure R–N=C=O and the following resonance forms demonstrate that the charge density in isocyanates is greater on oxygen and lowest on carbon. RN

+

−

C–O

−

RN–C

+

O

RN

C

O

The substituent R determines the reactivity of the isocyanate. Aromatic isocyanates react faster than aliphatic isocyanates, and carbonyl and sulfonyl isocyanates are considerably more reactive than the former. Isocyanate groups attached to oxygen or nitrogen are not stable in their monomeric forms. In cycloaddition reactions, isocyanates react preferentially across their C N bonds, but additions across the C O bonds are also encountered. In this respect, isocyanates resemble ketenes (see Chapter 4, Section 4.1.). Suitable substrates for cycloaddition reactions are carbon multiple bonds (acetylenes, olefins, ketenes, etc.), C N bond-containing compounds (imines, amidines, ketenimines, azines, carbodiimides, etc.), C O bonds and C S bond-containing substrates and phosphorus multiple-bondcontaining substrates. Cycloaddition reactions of isocyanates across multiple metal bonds are also known. The most common [2+2] cycloaddition reaction of isocyanates usually affords fourmembered ring heterocycles, but rearrangement to linear products sometimes occurs. Linear polar 1:1 adducts are also known. They are often intermediates in [2+2] cycloadditions. The four-membered ring cycloadducts 2 obtained from isocyanates and other C N bondcontaining heterocumulenes 1 (X = O, S, NR) are thermally labile and heating causes dissociation into the starting materials or cycloreversion to form a new set of heterocumulenes. Sometimes the exchange reaction can be directed by removing the lower boiling reagent by distillation.

RN

C

O + R1N

C

RN C

X

NR1 X

1

2

R1N

C

O + RN

C

X

80


The reactivity of isocyanates in [2+2] cycloaddition reactions is as follows: alkyl < aryl < nitroaryl 95 95 100 100 95 91 85

123 124 125 125 125 125 124

When hydrogen is attached to the β-position in the enamine, the rearranged linear 1:1 adducts 88 are formed. Also, enamines derived from cyclic ketones undergo this type of reaction. Some examples of this reaction are shown in Table 3.9. Again, the yields obtained are very high.

98


Table 3.9 Some linear 1:1 adducts from enamines and isocyanates RNCO + R1R2C

CHR3

R1R2C

C(R)3CONHR 88

R

R1

R2

R3

Yield (%)

Reference

FSO2 ClSO2 Ph Ph Ph Ph 3,4-Cl2 Ph

Pyrrolidone-2 Pyrrolidone-2 Morpholino Morpholino Morpholino Piperidino Piperidino

H H –(CH2 )3 – –(CH2 )4 – –(CH2 )5 – Piperidino Piperidino

H H

97.5 88 92 93 92 90 94

126 126 127 127 127 128 128

H H

2-Alkyl-2 -oxazolines 89 or 2-methyl-2-thiazolines, which are in equilibrium with enamines, react with phenyl isocyanate to give the linear 2:1 adducts 90 and 91, when two equivalents of phenyl isocyanate are used 129 . O

O

O + 2 PhNCO

N

N

C(CONHPh)2

CHCONHPh N

CONHPh 89

90

91

◦

When the reaction is conducted at 150 C an oxazolo[2,3-c]pyrimidine is obtained 130 . However, in the presence of a catalytic amount of boron trifluoride etherate, complex heterocyclic spiro compounds are produced (2:2 adducts) 131 . Ketene-O,O-, N,N-, N,O-, N,S- and S,S-acetals react readily with alkyl, aryl and especially arenesulfonyl isocyanates to give 1:1 adducts. The structure of the adducts depends on the degree of substitution on the β-carbon atom. The β-disubstituted ketene acetals give [2+2] cycloadducts 132 . In the reaction of phenyl isocyanate with ketene diethylacetal, a six-membered ring 2:1 cycloadduct is obtained 133 , and mixtures of the [2+2] and the [2+2+2] are obtained from substituted keten O,O-acetals 134 . Heterocyclic ε-caprolactim ethers 92, which are in equilibrium with ketene O,N-acetals, react with aryl isocyanates at room temperature to give [2+2] cycloadducts 93 and at 150 ◦ C to produce [2+2+2] cycloadducts 94 135 . RT N

OMe NR

O

+ RNCO

93

N OMe

O

92

NR 150°C

N R

N H 94

O

2-Carbon Cumulenes

99

Heterocyclic imines with a thiomethyl group adjacent to nitrogen are in equilibrium with ketene S,N-acetals. On reaction with aryl isocyanates, linear 1:1 adducts 95 are obtained 136 . CONHR SMe

N

+ RNCO

SMe

N 95

In contrast, cyclic ketene S,N-acetals 96 (n = 2,3,4) react with two equivalents of aryl isocyanates to give bicyclic azacyccloalka[2,3-d] pyrimidines 97 137 . O (CH2)n

+ 2 RNCO N

NR

(CH2)n

SMe

N N Me R

Me 96

O

97

Ketene N,N-acetals react with alkyl and aryl isocyanates to give linear 1:1 and 1:2 adducts 138 . Tetramethoxyethylene reacts with phenyl isocyanate to give the four-membered ring [2+2] cycloadduct 98 in high yield 139 . (MeO)2C

O

PhN

C(OMe)2 + PhNCO

(MeO)2

(OMe)2 98

The [2+2] cycloaddition of isocyanates to ketenes affords the four-membered ring azetidindiones. For example, reaction of phenyl isocyanate with diphenylketene to give the [2+2] cycloadduct 99 was already observed by Staudinger and coworkers in 1914 140 . PhNCO + Ph2C

C

O

O

PhN

Ph2

O 99

Tetrakis(ethylthio)allene reacts with benzenesulfonyl isocyanate at −60 ◦ C to give the [2+2] cycloadduct 100, which exists as a switter ion 101 at room temperature 141 . (EtS)2C

C

C(SEt)2 + PhSO2NCO

PhSO2N

O

SEt SEt +

EtS

(EtS)2

SEt

SEt −

O

SEt 100

NSO2Ph

101

From chlorosulfonyl isocyanate and the same allene derivative only the switter ionic linear adduct is obtained. A five-membered ring cycloadduct 103 is obtained in the reaction of the metalorganic allene 102 and p-toluenesulfonyl isocyanate 142 . NSO2R CpFe(CO)2CH 102

C

CH2 + RSO2NCO

CpFe(CO)2 103

O

100


Across C O bonds Stable [2+2] cycloadducts 104 are often obtained from ketones with strong electron withdrawing substituents (hexafluoroacetone and other perhalogenated ketones) and alkyl isocyanates. The cycloadducts are formed in low to moderate yields 143 . R 1R 2C

O

RN

O + RNCO

R 1R2

O 104

Also, from tetrameric formaldehyde and phenyl isocyanate, in the presence of boron trifluoride etherate at 0 ◦ C, a low yield of 3-phenyl-1,3-oxazetidinone is obtained 144 . Most [2+2] cycloaddition reactions of isocyanates across the C O bond in aldehydes, ketones and N-substituted amides proceed with elimination of carbon dioxide to give imines 105. The initial cycloadducts cannot be isolated because elimination of carbon dioxide is instantaneous. The reaction of aryl isocyanates with carbonyl compounds requires higher temperatures, while sulfonyl isocyanates react at room temperature 145 . This reaction can also be catalyzed with metal carbonyls 146 and liganded nickel (o) complexes 147 . R1CH

O + R2NCO

O

R 2N Ph

R1CH

NR2 + CO2

O 105

The nickel (o) catalysis proceeds via a five-membered ring heterocycle, which is isolated and characterized. The intermediate catalyzes the reaction of phenyl isocyanate with benzaldehyde. In the reaction of chlorosulfonyl isocyanate with aldehydes, N-sulfonyl imines 106 are also generated 148 . RCHO + CISO2NCO

O

ClSO2N R

CISO2N

CHR + CO2

O 106

The reaction of tropone 107 or 2,7-diphenyltropone with arenesulfonyl isocyanates gives N-sulfonyl imines 108, which react with excess isocyanate to give the bicyclic adducts 109 149 . SO2R N O + 2 RSO2NCO

O

NSO2R

N SO2R

107

108

109

Heating phthalaldehyde with aryl isocyanates affords high yields of N-arylphthalimidines 110. The reaction involves an intramolecular redox process 150 . CHO

CHO + RNCO CHO

CH

NR

NR O 110

2-Carbon Cumulenes

101

2-Benzoylbenzaldehyde reacts similarly with aryl isocyanates 151 . Aliphatic aldehydes and ketones with a CH2 group adjacent to the carbonyl group react with aryl isocyanates at 200 ◦ C to give heterocyclic compounds 152 . Aryl isocyanates react at elevated temperatures with benzoquinone to give p-quinonebis-imides with elimination of carbon dioxide 153 . When the reaction of 2,5-dihydroxy-1,4benzoquinone with aryl isocyanates is conducted in DMSO, in the presence of triethylamine, addition across the C C bond occurs with formation of the rearrangement products, 2,5dihydroxy-3,6-bis(anilinocarbonyl)-1,4-benzoquinones in 19–68 % yields 154 . The first reaction of aryl isocyanates with amides was observed by Kühn in 1884, who obtained a 44 % yield of N,N -diphenylbenzamidine on heating of benzanilide with phenyl isocyanate at 200–220 ◦ C 155 . The general character of this reaction was recognized much later. In 1961 Weiner reported the formation of N,N -dimethyl-N-phenylformamidine in 80 % yield on refluxing phenyl isocyanate for 4 h in excess DMF 156 . Similar results were reported by Jovtscheff and Falk in 1961 157 . The complex course of the reaction of phenyl isocyanate with DMF was elucidated by Ulrich and coworkers in 1968 (see Section 3.3.1.4). Tosyl isocyanate reacts with N,N-dialkylformamides to give N-sulfonyl amidines 111. In contrast, N-monoalkyl amides react either by elimination or by substitution to give 112 158 . RSO2NCO + MeCONHR1

RSO2N

C(Me)NR1 + RSO2NHCON(R1)COMe

111

112

A similar substitution reaction is observed in the reaction of tosyl isocyanate with Nmonoalkyl formamides at 0 ◦ C 159 . Across C N bonds The cycloaddition reactions of isocyanates across C N bonds usually afford [2+2] and [2+2+2] adducts but linear 1:1 adducts are also encountered. If the reaction is concerted, as in the dimerization of isocyanates, the four-membered ring [2+2] cycloadducts are obtained. However, when the reaction proceeds stepwise, the initial acyclic polar adduct can be intercepted by either the isocyanate or the substrate to give [2+2+2] cycloadducts. If the lifetime of the initial acyclic adduct is shorter than the time for rotation around the bond formed, the process is indistinguishable from the concerted reaction 160 . An exchange reaction may proceed via the intramolecular [2+2] cycloaddition and the new set of double bonded substrates and heterocumulenes can participate in the reactions. An example is the cycloaddition reaction of arenesulfonyl isocyanates with carbodiimides 161 . The ease of adduct formation depends largely on the electron density on the N atom of the imine and the electrophilicity of the center carbon atom of the isocyanate. Most reactive are persubstituted guanidines and amidines on one side and aryl isocyanates with electron withdrawing substituents on the other side. The initial attack occurs on the more nucleophilic center. Delocalization of the developing charges favors intermolecular [2+2+2] cycloaddition over intramolecular [2+2] cycloaddition or the exchange reaction. When a hydrogen shift can occur, the intramolecular isocyanate induced enurea reaction is faster than the intermolecular [2+2+2] cycloaddition reaction. Thermodynamically controlled equilibria are established above 100 ◦ C and the thermodynamically more stable reaction product is isolated.

102


For example, heating of aryl isocyanates with benzaldehyde anils with electron donating groups in the p-position, such as 113, affords the [2+2] cycloadducts 114. O

R3N 4-R1PhCH

NR2

+

R3NCO

NR2 R1

113

R1

114

R2

R3

Yield (%) Reference

Me2 N 4-ClPh Ph Me2 N Ph CCl3 CO Et2 N 4-O2 NPh CCl3 CO

85 83 96

162 163 163

When an excess of the azomethine derivative is used the six-membered ring [2+2+2] cycloadducts, consisting of two equivalents of the azomethine and one equivalent of the isocyanate, are formed exclusively 164 . Anils derived from benzophenone 154 and Nbenzylidenealuminum amides 165 also give the six-membered ring cycloadducts. When using an excess of the isocyanate, often six-membered ring [2+2+2] cycloadducts, consisting of two equivalents of isocyanate and one equivalent of the imine, are obtained. Amidines and guanidines form switter ionic 1:1 adducts with arenesulfonyl isocyanates 166,167 . However, formation of six-membered ring [2+2+2] adducts is more common . p-Toluenesulfonyl isocyanate reacts with 2-dimethylamino-3,3-dimethylazirine to give a switter ionic adduct 115, which on heating rearranges to give the isocyanate 116 168 . Me2N

Me2N

+

N

RSO2NCO +

−

O

NSO2R

N

RSO2N

115

C(NMe2)–C(Me)2NCO

116

Some imines behave like enamines in their reactions with isocyanates. For example, the reaction of the cyclopentanone anil 117 with phenyl isocyanate gives 1anilinocyclopentene-2-carboxanilide 118 169 . NPh

NHPh + PhNCO

NHPh CONHPh

117

118

2-Methyl- and 2,6-dimethyl-1 -piperidine also react with one equivalent of aryl isocyanate to give the C-substituted product 170 . The reaction of 2-phenylimino-1,3-thiazine 119 with tosyl isocyanate proceeds via a [2+2] cycloaddition across the the C N bond to give 2-(p-toluenesulfonyl)imino-1,

2-Carbon Cumulenes

103

3-thiazine 120 with elimination of phenyl isocyanate 171 . H N

H N

Ph N

S

N

NPh + RSO2NCO

H N NSO2R + PhNCO

O

S

S

SO2R 119

120

Only enureas 122 are obtained in the reaction of N-alkyl-N-cyclohexylideneamines 121 with alkyl or aryl isocyanates 172 . NR + R1NCO 121

N(R)CONHR1 122

This reaction proceeds via attack on nitrogen. From 2-phenyl-1 -pyrrolodine 123 and phenyl isocyanate the enurea 124 is obtained, which reacts at elevated temperatures with more phenyl isocyanate to give 125 and 126 173 . CONHPh

CONHPh Ph

Ph

N

N

123

124

Ph

Ph

N

CONHPh

N

CONHPh 125

126

1-Methyl-3,4-dihydroisoquinoline 127 reacts with aryl isocyanates at room temperature to give the labile enurea 128, which on heating affords the 1:1 adducts 129 and 1:2 adducts 130, formed by substitution of the methyl group 174 .

N + RNCO

N CONHR

NH

CH3

+

NH

CHCONHR

127

128

129

130

Trimethylindolenine 131 reacts with phenyl isocyanate dimethylphenylcarbamoylmethylene-2,3-dihydroindole 132 175 .

N 131

C(CONHR)2

CH3 + PhNCO

to

give

3,3-

CHCONHPh N H 132

4,5-Dihydro-2-thiazolamine 133 reacts with phenyl isocyanate at low temperatures (0– 5 ◦ C in acetonitrile) by addition to the ring nitrogen to give 134. At room temperature, the

104


exocyclic adduct 135 is the major product 176 . S N

S NH2 + PhNCO

S NH

NCONHPh

N

N

CONHPh 134

133

135

4-Pyridone 136 reacts with excess alkyl isocyanates in the presence of tetramethylguanidine to give the 1:2 adducts 137. A two-step addition of two different isocyanates produces 1,3-dialkyl-1,3,5-triazine derivatives having different alkyl substituents 177 . O

O +

2 RNCO

N H

N

NR

O 136

O

N R 137

When C N groups are part of a heterocumulene system, as in ketenimines and carbodiimides, they readily undergo [2+2] cycloaddition reactions with isocyanates. For example, C,C-diphenyl-N-p-tolylketenimine 138 reacts with phenyl isocyanate to give the fourmembered ring cycloadduct 139 in 83 % yield. The cycloaddition proceeds exclusively across the C C bond of the ketene imine 178 . O

PhN Ph2C

C

NR + PhNCO Ph2

RN 138

139

Numerous [2+2] cycloadducts are obtained from isocyanates and linear or cyclic carbodiimides (see Section 3.3.3). Iminodihydrooxathiazole-2-ones 140 react with phenyl isocyanate with addition to the C N bond to give a polar adduct 141 which rearranges to the oxazolidineimine 142. This reaction amounts to the transformation of one heterocyclic five-membered ring compound into another one 179 . PhN RN

N O + PhNCO S CH O 3

R ⊕

N O

N O S CH O 3

NPh

O

NR NSO2CH3

140

141

142

Across other double bonds Isocyanates also undergo [2+2] cycloaddition reactions with metal/carbon double bonds. For example, liganded tungsten carbonyl complexes 143 add

2-Carbon Cumulenes

105

phenyl isocyanate across the metal/carbon double bond to give the metallacycles 144 180 . L2W(CO) + PhNCO

O

L2W

NPh

O 143

144

The reaction of liganded cobalt isonitrile complexes 145 with alkyl isocyanates affords the [2+2] cycloadducts 146 in 75–80 % yields 181 . Aromatic isocyanates also add to liganded isonitrile complexes to give the [2+2] cycloadducts 182 . L2Co

C

NMe + RNCO

NMe

L2Co

NR

O 145

146

The [2+2] cycloaddition of isocyanates across metal/oxygen double bonds is also observed. For example, complexed molybdenum oxide reacts with phenyl isocyanate to give the [2+2] cycloadduct 147 183 . L2Mo

O + PhNCO

L2Mo

O

PhN

O

147

Cycloaddition reactions across metal/nitrogen bonds are also observed. Nitrene complexes, formed in the reaction of the ruthenium complex 148 with an isocyanate, add a second molecule to give the [2+2] cycloadduct 149 184 . Ru(CO)3(PPh3)2 + 2 RNCO

(PPh3)2(CO)2Ru

NR

RN 148

O

149

Similar metallacycles are obtained from liganded rhenium, iridium, palladium and platinum complexes 185 . Also, Cp(CO)2 M PR2 (M = Mo, W) undergo [2+2] cycloaddition reactions with ethyl- and phenyl isocyanate 186 . When MeB C(SiMe3 )2 is reacted with phenyl isocyanate the [2+2] cycloaddition reaction proceeds across the C O bond of the isocyanate to give 150 187 . MeB

C(SiMe3)2 + PhNCO

MeB

(SiMe3)2

O NPh 150

Reaction of the germanium imide 151 with methyl isocyanate forms the [2+2] cycloadduct 152, which reacts with another equivalent of the isocyanate to give the [2+2+2]

106


cycloadduct 153 188 . Ph [Ph2Ge

NPh] + MeNCO

Ph2Ge

NMe

MeN 151

Ph Ge

MeN

NMe

O

O

152

O N Me 153

Isocyanates also react readily with P C, P O, P N and Si Si bond-containing substrates. However, exchange and insertion reactions, rather than cycloaddition reactions, are observed. For example, phosphonium ylides react with alkyl and aryl isocyanates to give a polar adduct, which dissociates into a ketenimine and triphenylphosphine oxide 189 . Relatively stable linear polar adducts are obtained from Ph3 P CMe2 and phenyl isocyanate 190 .The reaction of phosphor/carbon double bond substrates with isocyanates was first observed by Staudinger and Meyer in 1919 191 , who reacted phenyl isocyanate with Ph3 P CPh2, 154. This is the first example of the conversion of a carbonyl compound (phenyl isocyanate) to an olefin (triphenylketenimine, 155) via a cyclic process (Wittig reaction). Wittig gave a vivid account of the genesis of this reaction in his article ‘Variation on a Theme by Staudinger’ 192 . Ph3P

CPh2 + PhNCO

154

Ph2C

C

NPh + Ph3PO

155

Methylenetriphenylphosphorane 156 forms the linear 1:2 adduct 157 with phenyl isocyanate, and from substituted methylenetriphenylphosphoranes the corresponding linear 1:1 adducts are obtained 235 . Ph3P

CH2 + 2 PhNCO

156

Ph3P

C(CONHPh)2

157

Cyclic P O compounds, such as phospholene oxides, already react at room temperature with isocyanates to give the exchange products (iminophosphorane and carbon dioxide) 193 . Since the generated iminophosphorane reacts more readily with isocyanates to give carbodiimides with generation of the phospholene oxide, such cyclic phosphorus compounds are excellent catalysts to convert isocyanates into carbodiimides under mild conditions. Triphenylarsenic oxide and triphenylantimony oxide are also catalysts for the conversion of isocyanates to carbodiimides and a similar mechanism was postulated for this reaction 194 . The catalytic activities of the oxides of arsenic, phosphorus and antimony are in agreement with their dipole moments, i.e. Ph3 As O (5.50 D) > Ph3 P O (4.31 D) > Ph3 Sb O (2.0 D), reported for the tris o-tolyl compounds. The catalytic activity of the various phosphorus compounds seems to follow in the order of the nucleophilicity (and polarity) of the phosphoryl group, i.e. phosphine oxides > phosphinates > phosphonates >> phosphates. Arenesulfonyl isocyanates do not react with P O compounds. Also, phenylcarbonyl isocyanate reacts differently with phospholine oxides 195 . Isocyanates also undergo a slow exchange reaction with other metal oxygen double bonds. For example, the tungsten oxo-complex 158 reacts with isocyanates in hexane at

2-Carbon Cumulenes

107

140 ◦ C for one week to form the imido-complex 159 in 52 % yield.

W

W O

2NCO

O + R

C

O

NR2 + CO2

C

R1

R1

158

159

The reaction of 159 with a second equivalent of isocyanate results in complete conversion of the C O to C NR2 bonds after 20 days at 120 ◦ C 196 . The reaction of P N compounds with isocyanates to give carbodiimides is a general reaction, and it is referred to as the aza–Wittig reaction 197 . This reaction is used to synthesize numerous heterocycles when reactive groups are adjacent to the generated carbodiimide. Of course, the generated carbodiimide can be trapped with nucleophiles. When the reaction of an iminophosphorane with an aryl isocyanate is conducted in the presence of pyridine or isoquinoline, a tricyclic ring system is formed, incorporating the heterocycle 198 . Some heterocyclic iminophosphoranes, such as 160, react with isocyanates to give mesoionic fused bicyclic compounds 161. In this manner, thiadiazolotriazines are formed in the reaction shown 199 . MeN

N

Me

MeN

N

Me

N

MeN

+ RNCO S

N

O

N

PPh3

Me

+

S

O

N N

•

S −

RN

NR

N N

160

161

Trichlorophosphazenes also react with isocyanates to give carbodiimides 200 . However, when the P N bond is part of a heterocyclic system, such as in 162, a [2+2] cycloaddition across this bond is observed using methyl isocyanate to give 163 201 . O

MeN Cl2P

Cl2P N Ph + MeNCO MeO2C Ph

N Ph Ph

MeO2C

CO2Me

CO2Me

162

163

Generation of a P N bond by thermolysis of an azide in the presence of phenyl isocyanate leads to addition across this bond, but the cycloadduct 164 undergoes rearrangement to give the phosphorous isocyanate 165 202 . O

PhN (R2N)2P–N3

[(R2N)2P

N] + PhNCO

R2N

P

N

(R2N)2P(NCO)

NR2 164

165

NPh

108


A [2+2] cycloaddition reaction occurs in the reaction of di-t-butyldisilene with tris-tbutylsilyl isocyanate, but the cycloadduct rearranges to give the heterocycle 166 203 .

t-Bu2Si

Si-t-Bu2 + t-Bu3SiNCO

t-Bu3Si

Si O Si N 166

The reaction of isocyanates across C S, N O, S O and S N bonds affords exchange products. For example, reaction of thiocarbonyl compounds with phenyl isocyanate at elevated temperatures affords azomethines and COS 204 . This reaction most likely proceeds via the unstable [2+2] cycloadduct 167. R2C

S + PhNCO

O

PhN

R2C

R2

NPh + COS

S 167

1,3-Thiazine-2-thione and 1,3-oxazine-2-thione react similarly to give the corresponding exchange products. Heating of isocyanates with isothiocyanates also produces exchange products, most likely involving the [2+2] cycloadducts 168 as intermediates. RN

C

O + R1N

C

S

RN

O R1N

NR1

C

S + RN

C

S

S 168

For example, heating α-naphthyl isocyanate with phenyl isothiocyanate affords phenyl isocyanate 205 . Tolylene diisocyanate (TDI) can be used as a higher-boiling isocyanate source. Thus, heating TDI with allylisothiocyanate affords allyl isocyanate 206 . In a similar manner phenyl isocyanate reacts with nitrosobenzene to give azobenzene and carbon dioxide. Tosyl isocyanate reacts with dimethyl sulfoxide to give the expected exchange products, dimethylsulfilimine and carbon dioxides 207 . Sulfonyl diisocyanate reacts with two equivalents of dimethyl sulfoxide in acetonitrile to give sulfonyl bis(dimethylsulfilimine) 169 in 83 % yield 208 . SO2(NCO)2 + Me2SO

SO2[N

SMe2]2 + 2 CO2

169

Chlorosulfonyl isocyanate reacts similarly with dimethyl sulfoxide. Also, carbonyl isocyanates undergo an exchange reaction with dialkyl sulfoxides to give the corresponding sulfilimines 209 . In contrast, dimethyl-oxo-sulfonium-methylid 170 reacts with isocyanates to give linear adducts 171 210 . Me2S(O)

CH2 + 2 RNCO

170

Me2S(O)

C(CONHR)2

171

2-Carbon Cumulenes

109

Sulfurdiimides 172 react with sulfonyl isocyanates by an exchange reaction to give a sulfonylsulfurdiimide 173 and an alkyl isocyanate 211 . t-BuN

S

N-t-Bu + RSO2NCO

RSO2N

S

172

N-t-Bu + t-BuNCO

173

Sulfonyl diisocyanate reacts with two equivalents of di-t-butylsulfurdiimide to give the double exchange products 212 . The reaction of sulfur triimides 174 (R = t-Bu) with chlorosulfonyl isocyanate affords the four-membered ring [2+2] cycloadducts 175 213 . S(

NR)3

O

ClSO2N

+ CISO2NCO

RN

S

NR

RN 174

175

In the reaction of t-BuN Te N-t-Bu with t-butyl isocyanate, the [2+2] cycloadduct was obtained 214 . [2+2+2] Cycloadditions The reaction of isocyanates with a substrate A B often leads to ionic intermediates 176, which can react with another molecule of the isocyanate or the substrate to form [2+2+2] cycloadducts 177 or 178. RNCO

A RN

B C

O + A

B RN

O NR

O 177

A RN

B

O

A

176

A

B

B

RN

A B

O 178

The simplest [2+2+2] reaction of isocyanates is their trimerization (see Section 3.3.1.3.). Numerous triple and double bonded substrates are known to undergo this reaction. The stoichiometry of the reagents sometimes determines when 2:1 or 1:2 adducts are formed. For example, reaction of isocyanates in the presence suitable catalysts form [2+2+2] cycloadducts 179, consisting of two equivalents of the acetylene derivative and one equivalent of the isocyanate 215 . This reaction proceeds in high yield using Ni(o) or aluminum catalysts. The same cycloadducts are also obtained when the reaction is conducted in the presence of Co(acac)3 /Et3 Al catalysts 216,217 . Even better yields are obtained when a heterocyclic carbene catalyst is used in conjunction with triethylphosphine 218 . R R1 2 RC

R1

CR1 + R2NCO R

N R2 179

O

110

Cumulenes in Click Reactions R

R1

R2

Yield (%)

Reference

Me Me Me Me Et Ph

Me TMS TMS i-Pr Et Ph

Ph Et Ph Et Ph Ph

81 92 83 94 90 84

215 218 218 218 218 215

Using an excess of phenyl isocyanate in the reaction of MeC≡CTMS affords the 2:1 cycloadduct 180 in 75 % yield 219 . O Me MeC

NPh

CTMS + 2 PhNCO TMS

O

N Ph 180

Also, metallacycles 181, obtained from diphenylacetylene and a liganded Ni(o) catalyst, react with alkyl isocyanates to give [2+2+2] cycloadducts 182 220 . Ph

O Ph

L–Ni Ph

Ph

NR

+ RNCO Ph

Ph

N R

181

182

O

In the reaction of ynamines with phenyl isocyanate, 2- and 4-quinolones are formed. In these reactions the double bond of the benzene ring of phenyl isocyanate participates as an A B substrate. For example, the ynamine 183, derived from butadiyne, reacts with phenyl isocyanate to give the [2+2+2] cycloadduct 184 221 . O N-C

C-C

H N

C

C-R + PhNCO

C

N

R 183

184

In contrast, cyanoynamines react with phenyl isocyanate via an initial [2+2] cycloaddition reaction across the C O bond of the isocyanate to give a quinoline derivative 222 . Intramolecular cobalt catalyzed cyclization of alkynes and isocyanates was employed in the total synthesis of camptothein, an antitumor alkaloid. The key step of the synthesis involves the reaction of the acetylene group-containing isocyanate 185 with the acetylene derivative 186 to give 187 223 . O O

O

+

–SiMe3

O N

SiMe3

NCO 185

186

187

2-Carbon Cumulenes

111

At elevated temperatures (120–140 ◦ C) β-disubstituted enamines react with two equivalents of aryl isocyanates to give [2+2+2] cycloadducts 188 224 . O Me2C

CHR + 2 R1NCO

NR1

Me2 R

N R1

O

188

R

R1

NMe2 Piperidino Piperidino

Ph Ph 4-MePh

Yield (%) 90 80 98

Imines also undergo [2+2+2] cycloaddition reactions with isocyanates. Usually, one equivalent of the imine reacts with two equivalents of the isocyanate. For example, heating of an excess of azomethines or benzophenone anils with isocyanates affords six-membered ring [2+2+2] cycloadducts (see Section 3.3.1.4). This reaction proceeds in a stepwise manner, as indicated by the formation of different cycloadducts when different isocyanates are used. Also, reaction of N-alkyl- and N-aryl formamidines with alkyl- or aryl isocyanates on heating or in the presence of zinc chloride as the catalyst gives 2:1 (imine:isocyanate) adducts. Some examples of these reactions are listed in Table 3.10. Table 3.10 Some [2+2+2] Cycloadducts of isocyanates and C N substrates Imine

Structure H

EtCH NR

NR

NR

NR N R

Me2N

(Me2 N)2 C NR

Alkyl, Aryl

227

Alkyl, Aryl

228

O NMe2 NR

RN O

226

NMe2

RN O

Aryl

O

N R H

Me2 NCH NR

225

Ar

RN O

Aryl

O

N R H

ArCH NR

Reference

Et

RN O

Isocyanate

N R

O

112


The 2:1 (imine–isocyanate adducts) are less common. However, monomeric or oligomeric N-alkyl- and N-arylformaldimines afford the 2:1 adducts 189 with alkyl or aryl isocyanates on heating or in the presence of zinc chloride as the catalyst 229 . R1 N RNCO + 2 R1N

CH2

NR1

RN O 189

R

R1

Et n-Bu n-Bu Ph

Et n-Bu t-Bu n-Bu

Yield (%) 49 98 76 50

A 2:1 adduct is also obtained from 3,4-dihydroisoquinoline and phenyl isocyanate 230 . Caprolactim ethers, which are in equilibrium with ketene-O,N acetals also undergo [2+2+2] cycloaddition reactions with aryl isocyanates at 150 ◦ C. At room temperature, [2+2] cycloadducts are obtained (see Section 3.3.1.4). In the reaction of carbodiimides with sulfonyl isocyanates [2+2+2] cycloadducts 190 are also isolated 231 . NR RN

C

NR + R1SO2NCO

NSO2R1

RN O

O

N

SO2R1 190

N-Phenyl keteniminylidene phosphoranes 191 react with two equivalents of phenyl isocyanate to give [2+2+2] cycloadducts 192 232 . ⊕

Ph3P Ph3P

C

C

NPh + 2 PhNCO O

191

O NPh N Ph

O

192

Similar six-membered ring heterocycles are obtained from two equivalents of alkyl or aryl isocyanates and Ph3 P C C(OEt)2 233 . Two equivalents of cyanamides react with RR1 C N+ C O SbCl− 6 to give [2+2+2] cycloadducts. In this reaction addition proceeds across the C O bond of the

2-Carbon Cumulenes

113

1-oxa-3-azabutatrienium salt 193 to form 194 234 . CRR1

N RR1C

N+

C

O

O

SbCI6 + 2 R2NCN R2N

⊕

N

193

SbCI6

NR2

N 194

Another [2+2+2] cycloaddition reaction, using alkenyl isocyanates and alkynes, affords the vinyl amides 195 and 196 in good yields. The catalysts system used is [RhCl(C2 H4 )]2 and P(4-MeOPh)3 235 . R NCO

R + RC

O R

N

CR

N

+

O

R 195

196

When R = alkyl, 196 is mainly obtained, while 195 is the major product in the reaction of the alkynes with R = aryl. Terminal alkynes react similarly with alkenyl isocyanates. In the presence of chiral phosphoramidites as ligands the corresponding cycloadducts are obtained. For example, from the alkenyl isocyanate 197 and the heterocyclic alkyne 198 the cycloadducts 199 and 200 are obtained in 85 % yield (91 % e,e) 236 . R

O

NCO N

+ N

O

N

+ R

H

H

BOC 197

198

199

200

When using aliphatic alkynes the lactam products are also preferentially obtained in good yields. Through modification of the phosphoramidite ligand, high levels of enantioselectivity, regioselectivity and product selectivities are obtained 237 . The uncatalyzed reaction of heterocyclic formamidines 201 with two equivalents of phenyl isocyanate affords the [2+2+2] cycloadduct 202 in 48 % yield 238 . NBz + 2 PhNCO

NBz

N

N O

201

202

NPh N Ph

O

114


The Ni(COD)2 catalyzed reaction of dialkynes 203 with isocyanates affords the bicyclic pyridones 204 in high yields 239 . R R + R1NCO

X

NR1

X

R

O R

203

204

X

R

R1

C(COOMe)2 C(COOMe)2 C(COOMe)2 C(COOMe)2 TsN C(COOEt)2

H Me Me i-Pr Me Cl

C6 H11 C6 H11 Ph n-Bu Ph PhCH2

Yield (%) 77 91 100 85 78 99 240

In the reaction of the diyne 205 with cyclohexyl isocyanate a 99 % yield of the cycloadduct 206 is obtained 260 . Et Et

NC6H11

+ C6H11NCO

O

Et Et 205

206

Ruthenium catalysts, such as [CpRuCl(COD))], in refluxing 1,2-dichloroethane afford the [2+2+2] cycloadduct 207, when α-naphthyl isocyanate is used, in 79 % yield 241 . NCO MeO2C

MeO2C

+

MeO2C

N

MeO2C

O 207

Likewise, substituted diynes 208 (X = C(COOMe)2 , TsN or O) react with isopropyl isocyanate under similar conditions to give the cycloadducts 209 242 . + i-PrNCO

X

N-i-Pr

X

R 208

O 209

Macrocycles are also obtained in the cobalt mediated [2+2+2] cycloaddition reaction of α,ω-diynes with isocyanates 243 . For example, 2-oxopyridinophanes 210 and 211 are

2-Carbon Cumulenes

115

obtained in 68 % yield (ratio of m- to p- = 1:2). O O

O

+ RNCO

NR

+

O

O

O

NR O O

210

211

The yields from aliphatic isocyanates are usually higher than those obtained using aromatic isocyanates. Some examples of the macrocycles are listed in Table 3.11. Table 3.11 Some 2-oxopyridinophanes from α,ω-diynes and isocyanates 243 O

NR

+ RNCO

O

+

NR

O

R

O

Yield (%)

PhCH2 4-MeOPhCH2 C6 H11

64 70 60

Also [2+2+1] cycloadducts 212 are obtained in excellent yields from isocyanates, alkynes and carbon monoxide (1 atm) in refluxing mesitylene in the presence of Ru3 (CO)12 as catalyst 244 . O R1 RNCO +

R1C

CR2

RN

+ CO

R2 O 212

R

R1

R2

t-Bu C6 H13 Ph Ph

Ph Ph Ph Ph

Me Me Ph SiMe3

Yield (%) 97 95 98 96

This is the heterocyclic version of the Pauson–Khand reaction. Across single bonds (insertion reactions) The insertion reaction of isocyanates into substrates A–B seems to involve a stepwise process. The insertion product either forms a single

116


bond between the isocyanate C-atom and B to form the ionic intermediate 213 or it can be formulated as a concerted reaction. RN A–B + RNCO

O A–N(R)COB

A B

⊕

213

Metal alkoxides and metal amides undergo this reaction readily and some substrates act as catalysts for the trimerization of isocyanates. Also a stepwise conversion of different isocyanates leads to the selective formation of trimers with different substituents. A review on this reaction appeared in 1987 245 . A summary of the earlier literature appeared in my previous book 246 . The insertion reaction of isocyanates into Ti–O bonds in Ti(O-i-Pr)4 has been used to catalyze the reaction of sterically hindered isocyanates with alcohols. The reaction occurs at room temperature and the yields are very high 247 . The insertion of isocyanates into C–H bonds is also well known. Olefins, alkanes, aromatic and heteroaromatic compounds are known to react with isocyanates to give Nsubstituted carboxylic acid amides. Often the formation of the linear adduct is the result of a [2+2] cycloaddition reaction and subsequent rearrangement. Electron donating groups on the aromatic nucleus on the one side and electron withdrawing groups on the isocyanate enhance the reactivity of both components. Lewis acids, such as aluminum chloride, are supplied successfully as catalysts 248 . Aromatic isocyanates are used to acylate aromatic substrates 249 and polystyrene 250 . Reaction of trialkylstannyl substituted arenes 214 with phenyl isocyanate at 20 ◦ C in the presence of aluminum chloride affords N-substituted amides 215 251 . PhSnR3 + PhNCO 214

PhCONHPh 215

A similar reaction is observed with unsaturated stannyl derivatives 252 . Aromatic hydrocarbons and some heterocycles, such as pyrrole 253 , furane 254 and thiophene 255 , react with chlorosulfonyl isocyanate in the presence of triethylamine to give nitriles 216. + CISO2NCO S

S

CONHSO2Cl

S

CN

216

Nitriles are also obtained from some indole derivatives 256 and from N-phenyl2-pyrazolines 257 . In the reaction with hydrocarbons the initially formed Nchlorosulfonylcarboxamides 217 are treated with DMF or triethylamine to produce the aromatic nitriles 218 258 . Hydrolysis of the intermediates gives rise to the formation of

2-Carbon Cumulenes

117

carboxamides 219. CN OMF CONHSO2Cl

OMe 218 CONH2

OMe

OMe

OH

217

OMe 219

Other carboxamidation reactions involving aromatic compounds involve the generation of isocyanates from carbonyl azides. For example, thermolysis of certain carbonyl azides substituted in the α-position by vinylidene radicals, such as 220, or aryl rings undergo cyclization to the pyridones 221 or condensed pyridones 259 .

N3

•

O

N

NH

O

O

220

221

Photolysis of 2-biphenyl isocyanate 222 gives a mixture of phenanthridone 223 and carbazole 224 260 .

+ N H 223

NCO 222

O

N H 224

A related ring closure with formation of 3-phenyl isocarbostyril 226 is observed in the photolysis of β-styril isocyanate 225 261 . PH

Ph NH

NCO O 225

226

Numerous CH insertion reactions of isocyanates involve substrates with a CH2 CO group. For example, dialkyl malonates 262 , malonitrile 263 , ethyl cyanoacetate 264 and oxaloacetic esters 265 react with alkyl and aryl isocyanates at room temperature, in the presence of triethylamine, to give products resulting from insertion into the activated C–H bond as

118


shown for the reaction of dialkyl malonates 227 with isocyanates to form 228. ROOCCH2COOR + R1NCO

R1NHCOCH(COOR)2

227

228

Alkylidenemalononitriles react with phenyl isocyanate to afford 6-amino-2iminopyrones 266 . Other compounds with the general formula COCH2 CO also afford the expected insertion products. For example, the diketone 229 reacts with aryl isocyanates in the presence of triethylamine to give the insertion product 230 267 . O

O + RNCO

S

S

O

CONHR O 230

229

In the reaction of ketoglutaric acid esters with aryl isocyanates ring closure of the initiallly formed insertion products 231 occurs to produce the heterocycle 232 268 . OH CO2R

CO2R + RNCO

O CO2R

O CO2R

RNH

HO

N R

O

O 231

232

Acylation of β-amino-α,β-unsaturated ketones 233 and esters with isocyanates in the presence of montmorillonite clay produces selective C-alkylation to give 234 269 . R1NH R1NH

O

O

R

+ PhNCO R

NHPh

O

233

234

2-Pentanedione reacts with aryl isocyanates in the presence of Ni(acac)2 as the catalyst to give the amides in high yield 270 . The catalyst reacts with two equivalents of aryl isocyanate to give the expected double insertion products. A similar reaction is observed with copper and nickel β-keto imino complexes, which react with alkyl or aryl isocyanates to give the insertion products in a stepwise manner 271 . The chelated phosphino enolates 235 react with isocyanates to afford 1:1 mixtures of adducts 236 and 237 resulting from Michael addition at the C–H group of the coordinated ligand and from rearrangement of the initial adducts 272 . Ph2 H P + PhNCO

Pd N

Ph2 CONHPh P

O 235

Ph

+

Pd N

Ph2 COPh P

O 236

Ph

Pd N

NHPh

O 237

With some of the chelates, only the rearranged products are obtained 273 .

2-Carbon Cumulenes

119

α-Arylsulfonylacetophenone 238 and p-toluenesulfonylacetone react similarly with aryl isocyanates to give the insertion products 239 274 . RSO2CH2COR1 + R2NCO

RSO2CH(CONHR2)COR1

238

239

Hydrogen cyanide adds to aliphatic and even better to aromatic isocyanates, in the presence of triethylamine, to give the expected insertion product 240. Instead of the highly toxic hydrogen cyanide, aqueous potassium cyanide can be used in the reaction with phenyl isocyanate 275 . PhNCO + KCN

PhNHCOCN 240

The carbanions of dimethyl sulfoxide or dimethyl sulfone add one or two moles of aryl isocyanate to give the insertion products such as 241 (R = H, CONHR) 276. MeSOMe + RNCO

MeSOCH(R1)CONHR 241

277

Dimethylsulfonium methylide , dimethyloxosulfonium methylide 278 and other sulfur and phosphorus ylides react similarly 279 . Also, small ring molecules are known to add isocyanates across a single C–C single bond to give 1:1 adducts. For example, reaction of the tetramethylcyclobutane aluminum trichloride complex 242 with alkyl and aryl isocyanates gives the Dewar pyridones 243, which rearrange in the presence of trifluoroacetic acid to give 2-pyridones 244 280 . O ⊕

AlCl3 + RNCO

O

NR

N R 242

243

244

Insertion into O–C–O, N–C–N and C–halogen bonds is also observed. Orthoformates also form 1:1 adducts with alkyl or aryl isocyanates if the reaction is conducted at 30–70 ◦ C in the presence of a Lewis acid catalyst. An insertion reaction of isocyanate into oxetane 245, in the presence of Bu2 SnI2 and Ph3 P, to give the cyclic carbamate 246 is also observed 281 . + RNCO

O

O

NR O

245

246

Phenyl isocyanate reacts with β-propiolactone 247 in the presence of BF3 by insertion into the C–O bond to give 2,4-dioxo-3-phenyl-3,4,5,6-tetrahydro-2H-1,3-oxazine 248 282 . O NPh

+ PhNCO O 247

O

O 248

O

120


The ketene dimer, 249, reacts with isocycanates in the presence of BF3 to give the oxazinedione 250 and the amide 251. However, reaction of 249 with aryl isocyanates, in the presence of triethylamine, affords the pyridine derivatives 252 283 .

O BF3

O NR

Me

O

CONHR

N

O

Me

Me

O 251

250 + RNCO

O

OH

O 249

COCH3

Et3N Me

N R

O

252

Aminals, such as formaldehyde N,N-acetals 284 and trisaminoethanes 285 , react with aryl isocyanates to form the insertion (into the C–N bond) products 253.

R2NCH2NR2 + R1NCO

R2NCON(R1)CH2NR2 253

Insertion reactions of isocyanates into the C–NR2 bond of R2 NCH2 NHCOOR 286 and R2 NCH2 OR 287 and into the C–OR bond in R2 NCH(OR)2 288 are also known. In the reaction of (RS)2 CHNR2 with isocyanates, an insertion into the C–SR bond occurs 289 . The cyclic trimer obtained from formaldehyde and aniline 254 reacts with phenyl isocyanate at 130 ◦ C to give the 1,3,5-triphenylhexahydro-s-triazine-2-one 255. 29 The reaction most likely proceeds by dissociation of the trimer to a 1,4-dipolar intermediate which adds phenyl isocyanate.

PhN

NPh N Ph 254

PhN

CH2 + PhNCO N Ph

PhN

NPh N Ph

O

255

When the reaction is conducted at 80 ◦ C, only the cyclic tetramer of formaldehyde and aniline is obtained. Phenyl isocyanate serves merely as a solvent in the reorganization of the ring. The reaction of N-substituted small-ring heterocycles and cyclic aminals with isocyanates produce the ring-enlarged insertion products shown in Table 3.12.

2-Carbon Cumulenes

121

Table 3.12 Insertion reactions of isocyanates into N-heterocycles Substrate

Insertion product

Reference

R N

290

O

NR

N R1

R N

R

RN N

NR

O

291

O

292

N R1

R N

RN O

O

N R1

R N

R

S N

S RN R N

R N

N R

N R

293

O

N R1

RN

NR1

294

O

The insertion reaction of isocyanates into C–Cl bonds requires Lewis acids or carbon as a catalyst. For example, alkyl isocyanates react with phosgene at 150 ◦ C, in the presence of carbon, to give the insertion product 256. A better synthesis of the insertion product is the reaction of the sulfur heterocycle 257 with chlorine 295 . O RNCO + COCl2

RN(COCl)2

S

RN

S O

256

257

Carbamoyl chlorides 258 react with isocyanates, in the presence of SnCl4 , to give the allophanoyl chlorides 259 296 . RNHCOCI + RNCO

RNHCON(R)COCI

258

259

The reaction of ω-isocyanato carboxylic acid chlorides with ethyl carbamate, in the presence of zinc chloride, affords ω-isocyanatoalkyl carbamates 260 297 . OCN(CH2)5COCI + H2NCOOEt

OCN(CH2)5CONHCOOEt 260

However, N-aryl- and alkyl-S-chloroisothiocarbamoyl chlorides react with isocyanates by insertion into the S–Cl bond to give the insertion product 261 298 . RN

C(Cl)SCI + R1NCO

RN

C(Cl)SN(R1)COCI 261

122


The insertion reaction of isocyanates into numerous metalorganic compounds is well documented. For example, reactions of t-BuLi, s-BuLi and n-BuLi with carbon monoxide in the presence of alkyl isocyanates afford α-oxoamides 262 299 . BuCOC(NR)O–Li+

BuLi + CO + RNCO

BuCOCONHR 262

Alkyl and aryl magnesium halides react with isocyanates to give the substituted carboxylic acid amides 263 after hydrolysis 300 . RNCO + R1MgX

R1CON(R)MgX

R1CONHR 263

When the reaction of isocyanates with isopropyl or s-butyl magnesium chloride is conducted in the presence of Cp2 TiCl2 normal alkylamides are obtained 301 . Isocyanates also insert into Mg–C bonds of polynuclear aluminum–magnesium compounds 302 . Alkylzinc alkoxides and alkylzinc amides also undergo insertion reactions with isocyanates 303 . In the reaction of Hg(OMe)2 with isocyanates the double insertion products 264 are formed 304 . RNCO + Hg(OMe)2

Hg[N(R)COOMe]2 264

The 2:1 insertion product 265 of phenyl isocyanate into triarylboranes is obtained in high yield 305 . BR3 + 2 PhNCO

RCON(Ph)B(R)N(Ph)COR 265

The heterocyclic boron amines 266 undergo insertion of isocyanates to give the macrocycles 267 306 . R N PhB

R1 R NCON + 2 R1NCO

N R 266

PhB NCON R1 R 267

Bis(dimethylamino)phenylborane reacts with phenyl isocyanate to give a 1:1 insertion product 307 . Using excess isocyanate and heat, the 2:1 insertion product is obtained. Likewise, reaction of 268 with sulfonyl diisocyanate gives the heterocycle 269 308 . PhB[N(CH3)2]2 + SO2(NCO)2

PhB Me2NCON

268

NCONMe2 SO2

269

Trimethylborazine 270 reacts with isocyanates, not at the NH groups, but rather through cleavage of the B–N bond of the ring, giving rise to the formation of the cycloadducts 271

2-Carbon Cumulenes

123

derived from the isocyanate and the hypothetical MeB NH 334 . Me B HN NH BMe MeB N H

Me B HN NR

+ 2 RNCO

O

270

O

N R 271

Boron halides or arylchloroboranes react with isocyanates to give insertion products. BCl3 reacts with isocyanates by stepwise insertion. In contrast, BF3 fails to undergo an insertion reaction with isocyanates. Phenyldichloroborane 272 reacts with two equivalents of isocyanate with insertion into the B–Cl and the B–C bonds to give 273 328 . PhBCl2 + 2 RNCO

PhCON(R)B(Cl)N(R)COCI

272

273

Organoaluminum compounds also undergo insertion reaction with isocyanates. For example, aluminum trialkyls react with alkyl and aryl isocyanates to give carboxylic acid amides after hydrolysis 309 . Alkyl aluminum chlorides react similarly 310 . Aluminium trichloride also forms insertion products with isocyanates 311 . Diethylaluminum ethyl thiolate or dimethylamide react with equimolar amounts of alkyl or aryl isocyanates to give the expected insertion products 274 312 . Et2AISEt + RNCO

Et2AIN(R)COSEt 274

Triethylindium gives a mono insertion product 275 in the reaction with phenyl isocyanate 313 . InEt3 + PhNCO

Et2InN(Ph)COEt 275

A similar reaction is observed when triphenylthallium is reacted with phenyl isocyanate 314 . Also, Group IV elements, other than the carbon derivatives already discussed, undergo insertion reactions with isocyanates. Both Sn(ii) and Sn(iv) compounds react readily with isocyanates and insertion into Sn–C, Sn–O and Sn–N bonds are observed. Tin(ii) dimethoxide reacts with phenyl isocyanate to give the double insertion product 276 315 . Sn(OMe)2 + 2 PhNCO

Sn[N(Ph)COOMe]2 276

Tin (iv) alkoxides and oxides react similarly with alkyl and aryl isocyanates 316 . On treating bis-tributyl tin oxide with two different isocyanates, isocyanurates 277 are obtained via repeated insertion reactions 317 . (R3Sn)2O + R1NCO

R3Sn(R1)COOSnR3 O

R3Sn(R1)COOSnR3 + 2 R2NCO

NR2

R1N O

N R2 277

O

+ (R3Sn)2O

124


Depending on the structure of the isocyanate used, the insertion can take a different course to give urea derivatives 278 318 . (Bu3Sn)2O + 2 PhNCO

Bu3SnN(Ph)CON(Ph)SnBu3 + CO2 278

Halogenated tin(iv) alkoxides 279 (X = Cl, Br, I, n = 2,3) react with isocyanates to give the cyclic compounds 280 and 281 319 . [Bu3SnN(R)COO(CH2)nX]

Bu3SnO(CH2)nX + RNCO 279 (CH2)n

(CH2)n

+ Bu3SnX

+ O

O

O

NR

RN

O

280

281

The reaction of Sn–N bonds with isocyanates also gives rise to the formation of insertion products. For example, trimethyltin dimethylamine reacts with phenyl isocyanate to give the expected insertion product 282 320 . Me3SnNMe2 + PhNCO

Me3SnN(Ph)CONMe2 282

Insertion of isocyanates into R3 SnN3 affords the expected insertion product 283, which undergoes cyclization to give the heterocycle 284. O R3SnN3 +

R1NCO

R3

SnN(R1)CON

NR1

N

3

N 283

N

SnR3

284 321

Insertion of isocyanates into GeOGe, GeOSn , Sn–H and Sn–P 323 bonds are also observed. Reaction of isocyanates with silicon compounds having Si–Si, Si–OR, Si–N, Si–S, Si–P, Si–C and Si–H bonds are known. While β-haloalkoxytrimethylsilanes react with phenyl isocyanate only at 170–200 ◦ C to give a mixture of compounds 324 , the expected thiocarbamate is obtained from Me3 SiSEt and phenyl isocyanate at 80 ◦ C 325 . Reaction of (RO)2 P(S)SSiMe3 with alkyl isocyanates affords insertion products 285 that undergo a thiol–thione rearrangement to give 286 326 . (RO)2P(S)SSiMe3 + R1NCO

322

[(RO)2P(S)SC(OSiMe3)

NR1]

285 (RO)2P(S)N(R1)C(S)OSiMe3 286

The reaction of isocyanates with Si–N bonds is exothermic to give the expected insertion products. For example, bis(pyrrolidinyl)dimethylsilane 287 reacts with two equivalents of

2-Carbon Cumulenes

125

phenyl isocyanate to give a bisureidosilane 288 327 . Me N

Si

Me N

+ 2 PhNCO

NCON

Me 287

Si

NCON

Ph Me Ph 288

Cyclosilazane (R2 SiNR)n reacts with phenyl isocyanate at 60–90 ◦ C to give the sixmembered ring insertion products in high yield 328 . Silylated imines 289 react with one equivalent of isocyanate to give the insertion products 290, which on further reaction with a different isocyanate afford 5,6-dihydro-1,3,5-triazine-2,4(1H,3H)-diones 291 with two different substituents 329 . R RCH

NSiMe3 + R1NCO

RCH

NC(OSiMe3)

289

NR1

HN

NR1 + R2NCO

O

290

N R2

O

291

Insertion of phenyl isocyanate into the N–SiMe3 structure in 292 produces the insertion product 293 330 . (Me3Si)2NP

NSiMe3 + PhNCO

Me3SiOC(

NPh)–N(SiMe3)P

292

NSiMe3

293

The photolysis of silaaziridines 294 in the presence of aryl isocyanates produces 5methylene-1-sila-2,4-diaza-3-oxocyclopentanes 295 331 . R1

SiMe3 OSiMe3

(Me3Si)2Si

+ R2NCO

Me3Si

OSiMe3

Si R2N

N R

R1

NR

O 295

294

Trimethylsilyl cyanide 296 reacts with trifluoromethyl isocyanate at room temperature to give the insertion product 297 in 70 % yield 332 . Me3SiCN + CF3NCO

CF3NC(CN)–OSiMe3

296

297

In the reaction of phenylbis(trimethylsilyl)phosphine with phenyl isocyanate, the 1:1 adduct 298 is obtained 333 . PhP(SiMe3)2 + PhNCO

PhP(SiMe3)CON(SiMe3)Ph 298

Two different products are obtained in the reaction of triethylsilane with isocyanates in the presence of a palladium catalyst at 80 ◦ C. A silylformamide 299 is produced with α-naphthyl isocyanate, while the reaction with n-butyl and phenyl isocyanate affords Si–C

126


bond formation to give carbamoylsilanes 300 334 . Et3SiN(R)CHO 299

Et3SiH + RNCO

Et3SiCONHR 300

Hypervalent difunctional organosilanes react with one equivalent of isocyanate to give the mono insertion products 301, which, on reaction with carboxylic acid chlorides, afford functionalized formamides 302 335 . R2SiH2 + PhNCO

R2Si(H)N(Ph)CHO + R1COCI 301

R1CON(Ph)CHO 302

Trifluoromethyl isocyanate undergoes an insertion reaction with cyanotrimethylsilane at room temperature to give the insertion product 303 in 70 % yield 336 . CF3NCO + Me3SiCN

CF3NC(CN)OSiMe3 303

Two equivalents of the isocyanate react with cyanotrimethylsilane at 50 ◦ C to give a five-membered ring [2+2+1] cycloadduct. N,N -disubstituted 5-trimethylsilyliminoimidazolidinediones are obtained in the reaction of aryl- or arenesulfonyl isocyanates with trimethylsilyl cyanide 337 . In the reaction with arenesulfonyl isocyanates the initially formed insertion products can also be isolated. The reaction of trimethylsilylamides with phenylcarbonyl isocyanate also affords the insertion product. 338 Trimethylsilylmethylenedimethylphenylphosphorane reacts with phenyl isocyanate at −35 ◦ C in diethyl ether to give a 1:2 adduct 304, formed by insertion of the isocyanate into the C–H and C–Si bonds with subsequent migration of the SiMe3 group 339 . Ph(Me)2P

CHSiMe3 + 2 PhNCO

Ph(Me)2P

C(CONHPh)C(OSiMe3)

NHPh

304

Insertion into a Pb–OR bond is observed in the reaction of triphenyl or tributyl lead methoxide with α-naphthyl isocyanate 340 ; however, trimeyhyl lead methoxide causes trimerization of the isocyanates 341 . Careful addition of cyclohexyl- or phenyl isocyanate to tributyllead-N-diethylamine affords the insertion product 305 342 . Reverse addition leads to trimerization. Bu3PbNEt2 + RNCO

Bu3PbN(R)CONEt2 305

Triethylphenylethynyl lead reacts exothermally with phenyl isocyanate to give the double insertion product 306 which cyclizes to form a uracil derivative 307, most likely via a

2-Carbon Cumulenes

127

[2+2+2] cycloaddition reaction 343 . O Et3PbC

CR + 2 PhNCO

[Et3PbN(Ph)CON(Ph)COC

PbEt3

PhN

CR]

O

306

N Ph

R

307

Insertion of isocyanates into Ti–C, Ti–O and Ti–N bonds is also observed. For example, titanium tetraalkoxide reacts reversibly with four equivalents of isocyanates to give the tetracarbamate 308. On standing at room temperature, slow conversion into isocyanurates occurs 344 . Ti(OR)4 + R1NCO

Ti[N(R1)COOR]4 308

Liganded titanium alkoxides react with phenyl isocyanate at room temperature to give insertion products 345 . Also, trifluoroethoxytitanium chloride reacts with phenyl isocyanate by insertion into the Ti–O bond to give 309 346 . ClTi(OCH2CF3)3 + PhNCO

ClTi(OCH2CF3)2N(Ph)COOCH2CF3 309

The insertion of phenyl isocyanate into liganded titanium (iii) alkyl complexes affords the expected products 310 347 . O Cp2TiMe + PhNCO

Me

Cp2Ti N Ph 310

However, diphenyltitanocene gives the adduct 311 with phenyl isocyanate resulting from addition across the C O bond of the isocyanate 348 .

Cp2Ti

+ PhNCO

Cp2Ti O

NPh

311

Also, Cp2 Ti–C(Me) CHMe reacts at low temperature with phenyl isocyanate to give an insertion product 349 . Insertion of phenyl isocyanate into Ti(NMe2 )4 affords a product resulting from complete reaction 350 . Zirconium and hafnium amides react similarly with phenyl isocyanate. Aminoalkoxides of zirconium react with phenyl isocyanate by complete insertion into the Zr–O bond 351 . Also, liganded dimethyl - 312 or diphenyl zirconium undergo an insertion reaction with phenyl- and α-naphthyl isocyanate to give 313 352 . No

128


double insertion occurs when excess isocyanate is used. Me

O Me

Cp2Zr

Cp2ZrMe2 + RNCO

N R

312

313

Zirconium isoprene and butadiene complexes 314 undergo reaction with methyl-, t-butyland phenyl isocyanate to give 1:1 adducts 315 and 1:2 adducts 316 353 . NR1 NR1

O

O + R1NCO

L2Zr

+ R1NCO

L2Zr

L2Zr

R

R

R O NR1

314

315

316

Several phosphorus compounds react readily with isocyanates with insertion into P–H, P–O and P–N bonds. N-Phenyl diphenylphosphinous amide reacts with aryl isocyanate to give both an addition product 317 and an insertion product 318 354 . Ph2PHNPh + RNCO

Ph2PN(Ph)CONHR + Ph2PN(R)CONHPh 317

318

Four-membered ring P–N heterocycles, such as 319, also afford insertion products with isocyanates to give 320 after hydrolysis with water 355 . Cl

O MeN Cl3P

NMe

+ RNCO

MeN O

Cl P

MeN

NR Cl

N Me

Cl

O

O

O

319

P

NR

O N Me 320

Reaction of n-butyl- or phenyl isocyanate with P(OSiMe3 )3 affords the insertion products 321 356 RNCO + P(OSiMe3)3

RN

C(OSiMe3)P(O)(OSiMe3)2 321

Both alkyl- and aryl isocyanates insert readily into As–N bonds 357 . In contrast, As(NMe2 )3 reacts with fluorosulfonyl isocyanate to give a rearrangement product 322 387 . 2 As(NMe2)3 + 3 FSO2NCO

As[N(CONMe2)SO2NMe2]3 + AsF3 322

2-Carbon Cumulenes

129

In the reaction of the formaldehyde zirconium dimer 323 with t-butyl isocyanate the double insertion product 324 is isolated 358 . L2Zr O

O

L2 O Zr O + 2 t-BuNCO

t-BuN

Zr O L O 2

ZrL2

323

N-t-Bu

324

Insertion of isocyanates into Zr–M (M = Fe, Ru) bonds is also observed 359 . Some oxovanadium (v) derivatives, such as 325, react with phenyl isocyanate to give the insertion products 326 360 . V(O)(O-i-Pr)3 (OCH2CF3) + PhNCO

V(O)(O-i-Pr)3N(Ph)COOCH2CF3

325

326

Metalorganic substrates derived from niobium and tantalum also undergo insertion reactions into metal–carbon 361 and metal–hydrogen 362 bonds. Also, stepwise insertion into Nb(OR)5 is observed 363 . Similarly, chromium trialkoxides undergo insertion reactions with aryl isocyanates 364 . Dimolybdenum 365 and ditungsten hexaalkoxides (M = Mo, W) 366 react with phenyl isocyanate to give the double insertion products 327. In this reaction, migration of two alkoxy groups also occurs. Ph

OR

N M2(OR)6 + 2 PhNCO

O M(OR)2

(OR)2M O

N RO Ph 327

Insertion into a tungsten–carbon bond to give 328 is observed in the reaction of W(C-tBu)(dme)Cl3 with cyclohexyl isocyanate 367 . O W(C-t-Bu)(dme)Cl3 + RNCO

Cl3W

C-C(t-Bu)

C

O

N R 328

Alkyl isocyanates insert into tungsten and iron hydride complexes to give the insertion products resulting from insertion into the metal–hydrogen bond. For example, reaction of CpW(CO)3 H with methyl isocyanate affords the carbamate complex 368 . Likewise, CpFe(CO)2 H reacts with t-butyl isocyanate to give the carbamate complex 329 369 . CpFe(CO)2H + RNCO

CpFe(CO)2CONHR 329

Also, Os3 (H)2 (CO)9 (PMe2 Ph) reacts with p-tolyl isocyanate to give a bridged carbamate complex 370 . When Os3 (H)2 (CO)10 is used, formamide complexes and other products resulting from fragmentation reactions are obtained. For example, p-tolyl isocyanate reacts with the osmium hydride complex and ruthenium complexes to form formamido, ureylene

130


and formamidate complexes 371 . Formamido complexes are also obtained from a hydrido triosmium cluster and methyl isocyanate 372 . Heating of ortho-manganated aromatic ketones 330 with isocyanates affords 3-alkylidene phthalimidines 331 373 . COCH3 NR

+ RNCO Mn(CO)4

O

330

331

Also, insertion of isocyanates into Mo–OR and Rh–OR complexes occurs 374 . Nickel alkoxides undergo reactions with aryl isocyanates to give the expected mono- 332 and di-insertion products 333 375 . Ni(OR)2 + R1NCO

RONi[N(R1)COOR] + Ni[N(R1)COOR]2 332

333

The reaction of a liganded nickel ethynyl complex with aryl isocyanates affords the substitution products 334 376 . CpNi(PR3)C

CH + PhNCO

CpNi(PR3)C

CCONHPh

334

Likewise, substitution occurs in the reaction of a nickel–SH complex with phenyl isocyanate 377 . Trans-Pt(H2 )(PR3 )2 also undergoes an insertion reaction with phenyl isocyanate, with the hydrogen being transferred to the carbon atom of the isocyanato group 378 . Insertion into a Pt–N bond rather than into a Pt–H bond occurs with the hydrido amide complex trans-PtH(NHPh)(PEt3 )2 to give the diphenyl urea derivative transPtH(PhNHCONHPh)(PEt3)2 379 . Insertion of phenyl isocyanate into the Pt–O bond occurs in Pt(PPh3 )2 O2 380 . Insertion of phenyl isocyanate into liganded copper alkoxides to give 335 is also observed 381 . Cu(PPh3)2OEt + PhNCO

Cu(PPh3)2N(Ph)COOEt 335

◦

Insertion of phenyl isocyanate into a liganded uranium carbene complex occurs at −78 C to form 336 382 . O Cp3U

CHPR3 + R1NCO

Cp3U

CHPR3 N R1 336

[3+2] Cycloadditions The [3+2] cycloaddition reaction of isocyanates affords fivemembered ring heterocycles. The substrates include dipolarophiles or three-membered ring compounds, which undergo ring opening to generate an intermediate dipolar species. Generally, the [3+2] cycloaddition reaction occurs across the C N bond of the isocyanates;

2-Carbon Cumulenes

131

in rare cases addition across the C O bond is observed. The [3+2] cycloaddition reactions of heterocumulenes with suitable substrates became popular in the 1960s through the pioneering work of Huisgen 383 . The three-membered ring compounds that generate 1,3-dipolar intermediates with or without added catalysts include cyclopropanes, oxiranes, aziridines, oxaziridines and diaziridines. Also, an unstable iminothioaziridine derivative is trapped with an isocyanate. For example, the bicyclic cyclopropane derivative 337, having a highly strained single bond, reacts with chlorosulfonyl isocyanate by ring opening and subsequent [3+2] cycloaddition to give 2-chlorosulfonyl-2-aza-3-ketobicyclo-[2.2.1.]heptane 338 384 . O + CISO2NCO 337

NSO2Cl 338

Also, cyclopropane derivatives with substituents producing a ‘push–pull’ effect, such as 339, react with phenyl isocyanate to give the [3+2] cycloadducts 340 385 . H

Me H

(MeO)2

Me

(MeO)2 + PhNCO

CO2Et

PhN

CO2Et O

339

340

Vinyl substituted cyclopropanes 341 react with aryl isocyanates, in the presence of Pd0 complexes, to give vinyl substituted pyrazolones 342 386 . R2 R2

R1

R3

+ PhNCO

R3

R1 PhN

R4

O

341

R4

342

The [3+2] annulation of allylsilanes 343 with chlorosulfonyl isocyanate is used in the stereoselective synthesis of 2-pyrrolidinones 344 (yields: 54–75 %). The chlorosulfonyl group was removed by reduction with red aluminum 387 . Me2(Ph)Si

R2

R2

Me2(Ph)Si

+ CISO2NCO

R1 343

R1

N H

O

344

Substitution on the allylic carbon is necessary because the [2+2] cycloadduct is obtained from Me2 (Ph)SiCH2 CH CH2 and CSI in 55 % yield.

132


Allylic alkoxysilanes 345 similarly undergo a [3+2] cycloannulation with CSI in a stereoselective manner to give 346 in 51–80 % yield 388 . R1

TBOMSO

R2

Me2(Ph)Si

R3

Me2(Ph)Si + CISO2NCO

TBOMSO

R3

N H

345

346

R1 R2 O

When the protecting group on oxygen is replaced by an acetoxy group, mixtures of the [3+2] adducts resulting from addition across the C N and the C O bonds of the isocyanate are obtained. The [3+2] cycloaddition of CSI across the C O bond is utilized in the total synthesis of (+)-blasto-mycinone 389 . The more common annulation, involving the C N bond in CSI, was used in the synthesis of (+)-peduncularin 390 . Epoxides react with isocyanates at elevated temperatures to give 2-oxazolidinones 347 391 . A similar reaction is observed with phenylcarbonyl isocyanate 392 . The reaction is catalyzed by palladium (o)-triisopropyl phosphite catalysts, lithium salt–phosphine adducts, aluminum trichloride or calcium ethoxide. The reaction can formally be regarded as interception of the thermally generated 1,3-dipolar intermediates, and it was shown that the reaction does not occur, unless the catalyst initiates ring opening 393 .

O

O

RN

+ RNCO

O O 347

It was demonstrated that n-Bu3 SnI Ph3 PO causes complete reaction of aryl isocyanates with alkylene oxides at 40 ◦ C to give 2-oxazolidinones 394 . From aliphatic isocyanates and alkylene oxides, 2-dioxolanimines 348 and some 2-oxazolidinones 349 are mainly obtained.

+ RNCO

O

O

+

RN

O

O NR 348

O 349

The formation of 2-dioxolanimines is not observed using other catalyst systems. An exception is the reaction of chlorosulfonyl isocyanate with oxiranes 395 . Unsymmetrically substituted 1,2-epoxides give mixtures of isomeric oxazolidinones 396 . When the reaction is conducted in the presence of Ph4 SbI as the catalyst, selective formation of 3,4-disubstituted oxazolidinones is observed 397 . The [3+2] cycloaddition reaction of phenyl isocyanate to chloromethyloxirane is catalyzed by erbium, ytterbium and yttrium chlorides 398 . The reaction of mono substituted 1,2-epoxides can proceed stereospecifically 399 . For example, an optically active oxazolidinone is obtained from a racemic vinyloxirane and phenyl isocyanate using a chiral palladium (o) catalyst 400 . The reaction of vinyloxiranes with tosyl isocyanate in the presence of palladium (o) catalysts and triisopropyl phosphite affords oxazolidinones in a stereospecific reaction. For example, the monoepoxide of

2-Carbon Cumulenes

133

cyclohexadiene reacts with tosyl isocyanate to give the shown oxazolidin-2-one 350 401 . O O

O

+ RSO2NCO

N SO2R 350

When 2-vinyloxirans 351 are reacted with aryl isocyanates in the presence of Pd(PPh3 ) and PPh3 , 4-vinyl-1,3- oxazolidinones 352 are obtained 402 . + R1NCO

NR1

R

R O

O

351

352

R

R1

H H Me

Ph 4-ClPh 4-ClPh

O

Yield (%) 90 98 94

Similarly, vinyloxetanes 353 react with isocyanates in the presence of a Pd catalyst to give the [4+2] cycloadducts 354. 403

R

+

R NR1

R1NCO

O

O O 354

353

R

R1

H H

Ph 4-BrPh

Yield (%) 83 61

The thermal reaction in the absence of the catalyst affords a 1:2 mixture of the oxazolidinone and the isomeric dioxolanimine. When a 1:2 cis/trans mixture of the shown vinyloxirane is used, the chirality of the obtained adducts is influenced by the isocyanate used. For example, ortho substituted aryl isocyanates and naphthyl isocyanates favor formation of the cis-oxazolidin-2-ones 355 404 . Ph

H O Ph

+ RNCO

NR

O O

Ph

H +

H RN

O O

355

H

134


cis/trans Overall yield (%)

4-MePhSO2 1:3 Ph 3:1 2-MeOPh 11:1 α-C10 H7 10:1

92 88 85 75

Because of the above results, 2-methoxyphenyl isocyanate is used to achieve the highest stereoselectivity. When vinyloxiran is reacted with phenyl isocyanate in the presence of a palladium catalyst and bis-phosphine ligands, a 95 % yield of the [3+2] cycloadduct is obtained with an e,e-content of 70 % 405 . Chlorosulfonyl isocyanates react with epoxides to give a mixture of 1,3-dioxolan-2imines and 1,3-oxazolidinones 406 . Styrene oxide reacts with p-toluenesulfonyl isocyanate in the presence of n-Bu3 PO/LiBr to give a mixture of the two isomeric 2-oxazolidinones 407 . When the reaction of epoxides with isocyanates is conducted at room temperature in the presence of CO, catalyzed by [Lewis acid]+ [Co(CO)4 ]− , 1,3-oxazinone-2,4-diones 356 are obtained in >97 % yields 408 . O

R1 O

+ RNCO + CO O

NR

R1

O 356

Disubstituted oxirans react similarly again in >97 % yields. Also, thermolysis of a carbonyl azide attached to an oxirane ring generates the isocyanate 357, which undergoes an intramolecular cycloaddition to give a 3-oxazolin-2-one 358 409 . O

NCO N3

N

O

O

O

O 358

357

Also, 2-vinylthiiranes 359 react with aryl isocyanates in the presence of palladium catalysts to give the [3+2] cycloadducts 360 in 57–75 % yields 410 . NR + RNCO S 359

S

O

360

Cyclic carbonates react with isocyanates in the presence of catalysts to give oxazolidinones with elimination of carbon dioxide 411 . The catalysts sometimes cause trimerization of the isocyanate. Carbonates derived from α-hydroxy carboxylic-, α-mercapto carboxylic and α-N-substituted amino acids react with isocyanates with elimination of carbon dioxide to give five-membered ring [3+2] adducts 412 .

2-Carbon Cumulenes

135

4-Benzoyl-5-phenyl-2,3-furandiones 361 react with alkyl and aryl isocyanates to give 2,3-pyrrolodiones 362 and carbon dioxide 413 . O

O O

Ph

O

Ph

+ RNCO

+ CO2

O

O

O

N R

361

362

Several three-membered ring nitrogen heterocycles, such as azirines, aziridines, diaziridines and oxaziridines, undergo [3+2] cycloaddition reactions with isocyanates. For example, irradiation of 3-phenyl-2H-azirines 363 affords the benzonitrile ylides 364 which react with aryl isocyanates to give the oxazolines 365, resulting from addition across the C O bond of the isocyanate 414 . R R

Ph

[PhC

N

R2 O

CR2] + R1NCO

N Ph NR1

N 364

363

365

Some aziridines, such as 366, react with aryl isocyanates cyanate 416 to give the imidazolidones 367. Ph

CO2R + PhNCO

Ph PhN

415

or phenylcarbonyl iso-

NR CO2R

N R

O

366

367

In the palladium catalyzed reaction of racemic N-substituted vinylaziridines with isocyanates in the presence of chiral ligands higher e,es with benzyl- and methoxyphenyl isocyanate, as compared to phenyl isocyanate, are obtained 417 . N-substituted cis-aziridines 368 react with chlorosulfonyl isocyanate to give Nchlorosulfonylimino-1,3-oxazolidin 369 via reaction across the C O bond of the isocyanate 418 . Ph

Ph

Ph O

+ CISO2NCO

N Ph

Ph NPh NSO2Cl

368

369

Also, substituted aziridines react with phenyl or benzyl isocyanate in the presence of NiI2 to give the [3+2] cycloadducts 370 (up to 92 % yields) 419 . R2

R2 N R1

+ RNCO

NR1

O NR 370

136


Also, 2-aryl- and 2-alkyl-1-arenesulfonylaziridines react with isocyanates in the presence of sodium iodide to give the [3+2] cycloadducts 371 and 372 420 . R2

R2

R 1N

+ R1NCO

N

R2 NSO2R + R1N

NSO2R

O

O

371

372

SO2R

When R = aryl, the [3+2] adduct 371 is obtained exclusively, while in the case of R = alkyl, the [3+2] adduct 372 is formed. Ring-opening cyclization of 2-vinylaziridines 373 with aryl isocycnates in the presence of Pd catalysts affords 2H-imidazolidine-2-ones 374 in 97 % yields 421 . NR

+ RNCO Bu

N Bu

373

374

N

O

Similarly, vinylpyrrolidines react with aryl isocyanates to give 1,3-diazepin-2-ones. For example, from 375 and p-chlorophenyl isocyanate (R3 = 4-ClPh) an 82 % yield of the cycloadduct 376 is obtained 422 . R1

N R2

NR3

+ R3NCO

R1

N R2 376

375

Interception of trans,trans-1,3-diphenyl-2-azaallyllithium 377, prepared by thermal ring cleavage from N-lithio-2,3-diphenylaziridine, with phenyl isocyanate at low temperatures gives the [3+2] cycloadducts 378 423 . Ph Ph

N

Ph

+ RNCO

NH RN

Ph O 378

377

On heating the bicyclic diaziridine 379 in the presence of phenyl isocyanate, a [3+2] cycloaddition occurs across the generated 1,3-dipole 380 to give 381 424 . O

N N

H Ph

O

N N

eHPh

+ PhNCO

O

N N

H Ph NPh

O 379

380

381

2-Carbon Cumulenes

137

1-(p-Toluenesulfonyl)-2-alkyl-3,3-pentamethylenediaziridines 382 react with phenyl or phenylcarbonyl isocyanate to give the triazolidinones 383 425 . SO2R NR1

+ PhNCO

R1N

N

PhN

N

O

SO2R 382

383

Also, triisopropyldiaziridine imine 384 reacts with phenyl isocyanate at −78 ◦ C to give a 1,2,4-triazolidine derivative 385 in 82 % yield 426 . RN

NR

RN

NR + PhNCO NR

PhN

NR O 385

384

On heating of the cycloadduct with phenyl isocyanate an exchange reaction across the C N bond is observed with formation of isopropyl isocyanate. A similar reaction is observed when di-t-butyldiaziridinone 386 is treated with phenylcarbonyl isocyanate to give 387 427 . O N

N + PhCONCO

N N

PhCON

O

O 387

386

1,2,3-triethyldiaziridine 388 reacts with phenylcarbonyl isocyanate to give the [3+2] cycloadduct 389. A byproduct is N-ethyl-N -benzoylurea 428 . EtN

Et

NEt + PhCONCO

H

PhCON

Et

NEt NEt O 389

388

Alkylidenediaziridines 390 (R = H, Br, Me) react with phenyl isocyanate to give the oxazolidine imines 391 in 64–73 % yield. Also in this case the cycloaddition occurs across the C O bond of the isocyanate 429 . R

N

NSO2Me

NSO2Me + PhNCO

390

O

N NPh 391

R

138


N-Substituted oxaziridines also react with alkyl- and aryl isocyanates at elevated temperatures to give the 1,2,4-oxadiazolidin-5-ones 392 430 . NR1

+ R2NCO

NR1 O

R2N

O

O 392

Thiirans react with phenylcarbonyl isocyanate to give both cyclic [3+2] adducts 393 and linear adducts 394 431 . + PhCONCO

PhCON

S

S

+ PhCONHCOSCH2CH

O 393

CH2

394

Thermolysis of 4-benzyl-5-phenylimino-1,2,3,4-thitriazoline generates an iminothiaziridine derivative 395, which can be trapped with an isocyanate to give 5-imino-1,2,4thiadiazolidin-3-ones 396 432 . NR N N BzN

BzN

S

S + PhNCO

S

PhN

NR

NR

NBz

O 396

395

Thermolysis of 5-sulfonyliminothiatriazoles 397 proceeds similarly and trapping with phenyl isocyanate gives the 1,2,3-thiadiazolines 398 433 . N N R 1N S

NSO2R

S + R2NCO

R2N

NSO2R

NR1

O 398

397

5-Amino-1,2,3,4-thiatetrazole 434 and 5-alkyl(aryl)amino-1,2,3,4-thiatetrazoles 399 435 react with two equivalents of isocyanates to give the [3+2]cycloadducts with simultaneous elimination of nitrogen and nucleophilic substitution on the amino group to form 400. N(R)CONHR1 N N N RNH

S 399

S + 2 R1NCO

R1N

N O 400

The cycloadducts derived from the secondary amino substituted 1,2,3,4-thiatriazoles rearrange to (aminocarbonyl-imino)-3-oxo-2,3,4,5-tetrahydro-1,2,4-thiadiazoles 436 .

2-Carbon Cumulenes

139

Similarly, 5-alkylidenehydrazino-1,2,3,4-thiatriazoles 401 react with isocyanates at 20 ◦ C with elimination of nitrogen to give the [3+2] cycloadducts 402 437 . NH HN

N

N N H

R 1N

+ R1NCO

N

RR1C

CRR1

N

S N

S O 402

401

4-Methyl-5-arylamino-1,2,3,4-thiatriazolines 403 react with isocyanates at room temperature in chloroform to give the expected cycloadducts 404, which rearrange to form 4-methyl-5-arylimino-1,2,4-thiadiazolidine-3-ones 405 438 . MeN

N

PhN

NMe

S

N

1

R1N

+ R NCO

NPh

S R1N

NPh

NMe

S 403

O

O

404

405

The isomerization of 404 proceeds by formation of thia-1,3,4,6-tetraazapentalene-2,5diones 406. NMe

S R 1N

NPh

+ R1NCO

N

O

N

Ph

404

NR1

S

RN

Me

406

Reaction of benzil with phenyl isocyanate and triethyl phosphite, catalyzed by anhydrous CuSO4 , affords a [3+2] cycloadduct 408 of the isocyanate with the generated ketocarbene 407 439 . Ph

O

Ph

Ph

O

Ph

Ph ••

+ PhNCO

Ph

PhN

O

O O

407

408

On heating of 3,4,5,6-tetrachlorophenyl-2-diazo-1-oxide 409 in the presence of phenyl isocyanate nitrogen is evolved and the benzoxazolone 410 is obtained 440 . Cl

Cl Cl

N2

Cl

Cl

O

Cl

Cl 409

Cl ••

Ph N

Cl

O

+ PhNCO O

Cl

Cl

O Cl 410

Linear and cyclic N-oxides of imines (nitrones) undergo a [3+2] cycloaddition reaction with isocyanates. This reaction had already been observed in 1890, when

140


1,2,4-oxadiazolidin-5-one 412 was obtained from C-phenyl-N-benzil nitrone 411 and phenyl isocyanate 441 . Ph N(CH2Ph)–O + PhNCO

PhCH

NBz

PhN

O O

411

412

Reaction of C-phenyl-N-t-butylnitrone with phenylthiomethylmethyl isocyanate, generated in situ from the corresponding carboxylic acid azide, affords the expected oxadiazolidinone in high yield 442 . Cyclic nitrones, such as 7-chloro-2-(methylamino)-5-phenyl-3H-1,4benzodiazepine-4-oxide 443 , 5,6-dihydro-2,4,4,6-tetramethyl-1,3-oxazine N-oxide 444 and 2,4,4-trimethyloxazoline N-oxide, react with phenyl isocyanate in a similar manner to give the [3+2] cycloadducts in high yields. Also, [3+2] cycloadducts are obtained from nitrones and phenylcarbonyl isocyanate 445 . In the reaction of nitrones with phenyl thiocarbonyl isocyanate a labile [3+2] cycloadduct 413 is formed, which loses carbon dioxide on standing to give the amidine 414 446 . Ph PhCSNCO + PhCH

1

N(R )–O

NR1

PhCSN

PhCSNHC(Ph)

O

NR1 + CO2

O 413

414

The cycloaddition reaction of cyclic nitrones 415 with aryl isocyanates proceeds regioand diastereoselectively (in the case of chiral nitrones) to give the cycloadducts 416 447 . R2 RN

R2 R N RN

+ RNCO

N

N

O

R1 415

O O

R1

416

Likewise, cycloaddition of nitrones with electron donating groups with phenyl isocyanate affords 1,2,4-oxadiazolidinones in moderate yields 448 . Paracyclophanyl nitrones react with phenyl isocyanate to give oxadiazolones 449 . Some nitrones also react with isocyanates across their C O bonds to give 1,2,4-dioxazolidines 450 . N-Oxides of pyridine, isoquinoline, phenanthridine and other heteroaromatic amines react with phenyl isocyanate at 110 ◦ C with evolution of carbon dioxide to give heteroaromatic amines 418 with an anilino group adjacent to the nitrogen 451 . This reaction involves the [3+2] cycloadduct 417 as an intermediate.

+ PhNCO N

+ CO2

NPh

N O

N

NHPh

O

O 417

418

2-Carbon Cumulenes

141

From 3-picoline N-oxide and phenyl isocyanate the cycloadduct can be isolated 452 . Also, nitrile oxides, generated from arylhydroxamoyl chloride and triethylamine, react with phenyl isocyanate to give 2,4-diaryl-1,2,5-oxadiazol-3-ones and nitrile oxide dimers 453 . Mesitonitrile oxide reacts with a 1-oxa-3-azonia-butatriene salt 419 (R = 2,4,6Me3 Ph) by addition across the C O bond of the isocyanate to give a 1,2,5-oxadiazole derivative 420 454 . O RC

N

O + Me2[NCH

N+

C

O] SbCl6

N

N+

Me2NCH

O 420

419

Ph SbCl6

Trichloromethylcarbonyl isocyanate reacts with nitrile oxides by addition across the C O bond with retention of the isocyanate group 455 . However, chlorocarbonyl isocyanate reacts with nitrile oxides to give the regular [3+2] cycloadducts 421 456 . R CICONCO + RC

N

N

ClCON

O

O O 421

1,1-Dichloroalkyl isocyanates react with nitrile oxides in the presence of a catalytic amount of a tertiary amine to give linear adducts 422, rather than [3+2] cycloadducts 457 . RC(Cl)2NCO + R1C

N

R1C(Cl)

O

NOCON

C(Cl)R

422

A [3+2] cycloaddition occurs in the reaction of 1-oxa-3-azoniabutatriene salts and a nitrone. N-Arylnitrilium salts undergo a [3+2] cycloaddition reaction with alkyl isocyanates to give salts of 4(3H)-quinazolidinones 423 458 . O PhC+

NR1

NR SbCl6 + R1NCO

R

N 423

Reaction of 1-oxa-3-azoniabutatriene salts with azibenzil affords the 2-azoniaallene salt 424. Me2NCH

N+

C

O SbCl6 + PhCOC(N2)Ph

Me2NCH

N+

O

Ph

O

Ph

SbCl6

C

424

Reaction of 1-aza-2-azoniaallene salts 425 with phenyl isocyanate occurs via a [3+2] cycloaddition reaction with subsequent rearrangement to give triazolium salts 426 459 . Me2C

N+

Me2 NR + PhNCO

N

PhN

NR O

425

Me

NMe NR SbCl6

PhN O 426

142


The [3+2] cycloaddition reactions of isocyanates with 1-aza-2-azoniaallene salts proceed by an asynchronous concerted mechanism 460 . Azomethine imines and aromatic nitrile imines, the nitrogen analogues of N-oxides and nitrile oxides, also react with isocyanates to give [3+2] cycloadducts. For example, isoquinoline N-phenylimine 427 reacts with phenyl isocyanate at room temperature to give the [3+2] cycloadduct 428 461 . + PhNCO

N

N NPh

Ph PhN 427

O

428

Some azomethine imines are generated in situ in the presence of excess isocyanate to give the cycloadducts 462 . Aromatic nitrile imines, generated by thermolysis of 2,5-diphenyltetrazole or by dehydrochlorination of carboxylic acid hydrazide chlorides, also add readily to isocyanates 463 . Benzonitrile N-phenylimine 429 and aryl isocyanates give mixtures of adducts 430 and 431 resulting from addition across the C N or C O bond of the isocyanate: Ph

Ph N

PhC

N

NPh + RNCO

RN

N

NPh

+

O

O 430

429

NPh NR 431

NH-Azomethine ylides 432 react with isocyanates to give 1H-imidazol-5(4H)-ones 433 464 . R2

R3 R2(OR)

NH+-C

N + R1NCO

R 1N

R3

R3 R3

O 433

432

N-metalated azomethine ylides, generated in situ, react with isocyanates to give substituted imidazolidines 465 . Triarylcyanoazomethines react with isocyanates to give 1,2,4-triazolidin-3-ones 434 as the result of a [3+2] cycloaddition reaction 466 .

R 2C

N+(Ar)–N−CN

R2 + PhNCO

NR

PhN

NCN O 434

2-Carbon Cumulenes

143

Iodonium ylides 435 also undergo a [3+2] cycloaddition reaction with phenyl isocyanate to give 436 467 . + PhNCO O

O

O

O PhN

PhI 435

O

436

Tungsten ketenimine complexes react with isocyanates to give [3+2] cycloadducts 468 (see Chapter 4, Section 4.3). The reaction of mesoionic 1,3-dithiolium-4-olates 437 with phenyl isocyanate affords another mesoionic compound 438 with elimination of COS 469 . R O

R S

O

S

+ PhNCO

PhN

O S

S

R

O S

NPh + COS

N

N

O

437

438

Also, 3-phenylsydnone reacts with phenyl isocyanate to give a [3+2] cycloadduct, which eliminates carbon dioxide with formation of a new mesoionic compound 470 . Similar reactions are observed using carbonyl isocyanates 471 . The proposed bicyclic structure for the 1:1 adducts of isocyanates with some mesoionic compounds is apparently in error 472 and the formation of acylated mesoionic adducts is postulated. The reaction involves the bicyclic compounds as intermediates. For example, the mesoionic five-membered ring compounds 439 react with phenyl isocyanate to give the acylated mesoionic adducts 440. R

O O

O

NMe

+ PhNCO

PhN

O O

PhNHCO

NMe

O O

NMe

R 440

R 439

Photolysis of aroyl azides generates an aryl nitrene, which can be intercepted with isocyanates to give [3+2] cycloadducts 441 473 . R RCON3

·· [RCON] + R1NCO ··

N R1N

O

O 441

Alkyl and aryl isocyanates react with aluminum azide, generated in situ from sodium azide, to give 1-substituted 5-hydroxy-1H-tetrazoles 442 474 . Better yields are obtained

144


using azidotrimethylsilane 475 . N RNCO + NaN3 + AlCl3

N

RN

N OH 442

Alkyl azides, on heating with aryl isocyanates for extended periods of time, afford tetrazolinones 443, formed by a [3+2] cycloaddition 403,476 . N RN3 +

R1NCO

N

R 1N

NR O 443

Also, [3+2] cycloadducts are obtained in the reaction of alkyl azides with phenylcarbonyl or ethoxycarbonyl isocyanates 403 . Several arenecarboxaldehyde azines react with aryl isocyanates in a double [3+2] cycloaddition involving both C N double bonds to afford tetrahydrotriazolotriazoles 444 477 . Ar

O N ArN

CH–CH

NAr + 2 PhNCO

PhN

NPh

N O

Ar 444

A similar reaction is observed when arylaldehyde azines are treated with phenylcarbonyl isocyanate 478 , chlorosulfonyl isocyanate 479 and arenesulfonyl isocyanates 480 . Aromatic aldazines, such as 4-methoxybenzaldazine, undergo [3+2] ‘criss-cross’ cycloaddition reactions with 4,4 -diisocyanatodiphenylether to give isocyanate terminated polymers 481 . Also, ketazines participate in this reaction 482 . Cyclopentanone, cyclohexanone and cycloheptanone azines react with KNCO in the presence of acetic acid to give the expected ‘criss-cross’ cycloadducts 445 in moderate yields 483 .

O N N-N

+ 2 HNCO

HN

N

NH O

445

In contrast, butyraldazine 446 reacts with phenyl or benzyl isocyanate, in the presence of picric acid, to give the pyrazoline derivatives 447 and 448. The isocyanate attack is

2-Carbon Cumulenes

145

preceded by an acid promoted proton shift, followed by cyclization 484 . Et PrCH

N–N

N

CHPr + RNCO

Pr

N

Pr +

N N

CONHR 446

Et

CONHR

447

448

A dipolar intermediate is also generated from trimethylsilyl diazomethane and n-butyl lithium, which on reaction with alkyl or aryl isocyanates gives rise to the formation of 1-substituted 5-hydroxy-1,2,3-triazoles 449 485 . OH

RN RNCO + Me3SiC(Li)N2

N N 449

Reaction of isonitriles with trialkylboranes gives derivatives which react with isocyanates to afford 1,4-diaza-2-boracyclopentanones 450 486 .

R1NC + R3B

[R1N+

R 2N

C–B−R3] + R2NCO

BR NR2

O 450

Mesomeric betaines 451 derived from N-heterocyclic carbenes and isocyanates undergo a [3+2] cycloaddition reaction with acetylenes (R = Me, COOMe, COOEt; R1 = Me, Et) to give spiroindazole-3,3 -pyrroles 452 in high yields 487 . Me N NMe O

+ RC

CCOOR1 O

NPh

Me N NMe COOR1 N

R

Ph 451

452

[4+1] Cycloadditions Vinyl isocyanate is exceedingly useful as a 1,4-dipolar species to undergo [4+1] cycloaddition reactions with suitable dipolarophiles. For example, reaction of the vinyl isocyanate 453 at room temperature with cyclohexyl isocyanide affords the hydroindolone derivative 454 in 84 % yield 488 . NHC6H11 + C6H11N NCO 453

O

C: N H 454

146


Likewise, 453 reacts with two equivalents of dimethoxycarbene to give the [4+1] cycloadduct 455 in 80 % yield 489 . MeO OMe O

+ 2 (MeO)2C:

N

NCO

MeO OMe 455

453

Also, bis-alkylthiocarbene undergoes the [4+1] cycloaddition reaction with a suitably substituted indol isocyanate to give the [4+1] cycloadduct in 72 % yield. This approach was utilized in the total synthesis of (+) phenserin 490 . Numerous examples of vinyl isocyanates, generated from the corresponding carbonyl azides, in the presence of bis-alkylthiocarbene precursors afford the [4+1] cycloadducts, often in high yields 491 . Likewise, an excess of bis-alkylthiocarbenes react with 453 to give the 2:1 adduct 456 in 86 % yield 492 . i-PrS SPr-i O

+ 2 (i-PrS)2C:

N

NCO

i-PrS SPr-i 456

453

However, when an excess of the bis-alkylthiocarbene precursor 457 is used in the reaction with 453 in refluxing benzene a 63 % yield of the six-membered ring heterocycle 458 is obtained 493 . N

N SPr-i O

PrS

SPr SPr-i SPr-i

+

SPr-i

NCO

457

453

N H

O

458

N-Heterocyclic carbenes also react with vinyl isocyanate via a [4+1] cycloaddition to afford functionalized hydroindolon derivatives. For example, heating of the carbene precursor 459 with 453 affords the cycloadducts 460 in 57–71 % yield 494 .

N N Ph 459

CCl3 H

N Ph

NHPh

PhN

Ph N ··

Ph

+

O NCO

N H 460

[4+2] Cycloadditions Isocyanates undergo [4+2] cycloaddition reactions with 1,3-dienes, heterodienes, conjugated azomethines and cumulenes. The reactions generally proceed by addition across the C N bond of the isocyanate, but additions across the C O bond are also known.

2-Carbon Cumulenes

147

In o-quinodimethane derivatives the dienes are in the cis-configuration, which allows ready cycloaddition reactions with phenyl isocyanate. For example, phenylimines of oquinodimethanes 461 afford the quinazolinediones 462 on reaction with phenyl isocyanate followed by hydrolysis 495 . Ph N

NPh SMe

+ PhNCO

Ph N

O NPh

Me2N SMe

NMe2

O

NPh O

461

462

A similar reaction is observed with the o-quinonedimethanes 463 and phenyl isocyanate at −40 ◦ C in DMF. In this case 2,3-dihydroisoquinolines 464 are formed 496 . CN

CN H

O + PhNCO

NPh

SMe Me2N

NMe2

463

464

Intramolecular [4+2] cycloaddition reactions of isocyanates are sometimes observed. For example, heating of 1,3-pentadienyl isocyanate 465 in o-dichlorobenzene affords 3methyl-2(1H)-pyridine-2-one 466, albeit in 17 % yield 497 . Me

Me

NCO

N

N H

O

465

O

466

Also, generation of N-arylimidoyl isocyanates 467 in situ causes intramolecular cyclization to give the heterocycle 468 498 . O

O

•

N N 467

NH

R

R

N

468

The cyclodimerization of isocyanates attached to an α-carbonyl, α-thiocarbonyl or αimidoyl group proceeds via a [4+2] cycloaddition sequence. For example, treatment of phenylcarbonyl isocyanate with a catalytic amount of triehtylamine at 50 ◦ C gives rise to the formation of the cyclodimer 469 499 . O

O N

2 PhCONCO Ph

N O

469

Ph O

148


A [4+2] cycloadduct with a similar structure, 470, is obtained in the reaction of methyl isocyanate with methylcarbonyl isocyanate 500 . O N

MeNCO + MeCONCO

NMe

Me

O

O

470

The reaction of phenyl isocyanate with t-butyl-N-(2,6-dimethylphenyl)imidoyl isocyanate proceeds similarly 424 . A double [4+2] cycloaddition occurs in the reaction of carbonyl diisocyanate with aliphatic isocyanates to give 1,3,5-triazino[2,1-b]-1,3,5-oxadiazine tetrones 471 501 . O

O RN

CO(NCO)2 + RNCO

O

N N

NR O

O

471

Similar cycloadducts are obtained from carbonyl diisocyanate and azomethines, isocyanates, carbodiimides and dimethylcyanamide. Also, aliphatic isocyanates react with chlorocarbonyl isocyanate to give the [4+2] cycloadducts 502 . The reaction of carbonyl isocyanates with silylketenes affords unstable [4+2] cycloadducts 472, which undergo a Diels–Alder reaction with enamines 503 or acetylenes 504 to give 2-pyridones 473. O RCONCO + Me3SiCH

C

O

O

+ R1C

C-COOMe

R

N

472 R1 O

R

S

O

R1

CO2Me

CO2Me

O

N H

R

473

A theoretical study of this reaction was conducted recently 505 . Phenylthiocarbonyl isocyanate dimerizes readily to give the [4+2] cyclodimer 474 506 . Heating of the cyclodimer affords 1,3,5-thiadiazin-4-one 475 with loss of COS 507 . S

O N

2 PhCSNCO Ph

N S

474

O Ph

O

N Ph

N

+ COS Ph

S

475

2-Carbon Cumulenes

149

Standing of the carbamoyl isothiocyanate 476 causes isomerization to the thiocarbonyl isocyanate 477, which undergoes dimerization to give the [4+2] cyclodimer 478 508 . S

S R2NCONCS

N

R2NCSNCO

N

R2N

476

O

O

477

NR2

478

Also, the relatively unstable imidoyl isocyanates undergo self-condensation (R2 = Ph) to give 479 or undergo cyclodimerization to give 480 509 . R1

N

NH

R1C(NCO)

O 479

NR2

NR3

O

R1

R1

N

N

O

N R2

480

In the reaction of chlorocarbonyl isocyanate with secondary amines, allophanoyl chlorides are formed, which are readily dehydrochlorinated to give dialkylaminocarbonyl isocyanate, which dimerizes by a [4+2] cycloaddition reaction to give 481 542 . O R2NH + CICONCO

[R2NCONHCOCI]

N

[R2NCONCO] R2N

O N

O

NR2 O

481

Heating of isoprene or butadiene with phenyl isocyanate in the presence of catalytic amounts of palladium catalysts produces mixtures of isomeric 2:1 (diene:isocyanate) cycloadducts 482 and 483 510 .

+ PhNCO

+ PhN O 482

H Me

PhN

Me O H 483

150


2-Vinylpyridine 484 reacts with trichloromethylcarbonyl isocyanate to give the [4+2] cycloadduct 485 511 . O N

+ CCl3CONCO

N

CCl3

N

O

484

485

In contrast, aliphatic and aromatic carbonyl isocyanates react with 2-vinylpyridine to give 2-acyl-1-oxo-2,3-dihydro-1H-pyrido[1,2c]pyrimidines 486 426 . + RCONCO

N

N

N

R O

O

486 512

Heterodienes, such as 2-isopropenyloxazoline and thiazolinylformamidine 487 513 undergo [4+2] cycloaddition reactions with aryl isocyanates to give the expected cycloadducts. In the case of 487, the [4+2] cycloadduct 488 is obtained.

NMe2 + PhNCO

N

N

S S

NMe2 NPh

H

H

O

N

487

488

2,4-Diphenyl-1,3-diazabutadienes 489 (R = MePh, Bz) react with isocyanates via a [4+2] cycloaddition reaction to give triazinones 490 514 . Ph

R N

NR N

+ R1NCO

NR1 Ph

N H

Ph 489

O

490

The α-double bond-containing isocyanates react as dienophiles with numerous unsaturated substrates to give [4+2] cycloadducts. Cabon–carbon double- and triple-bond-containing substrates sometimes react with double bond-containing isocyanates to undergo the Diels–Alder reaction. For example, phenylcarbonyl isocyanate reacts with ethoxyacetylene to give the [4+2] cycloadduct 491 515 . O N EtOC

CH + PhCONCO Ph

O

491

OEt

2-Carbon Cumulenes

151

Also, from eyhoxyacetylene and phenyl isocyanate the [4+2] cycloadduct 492 is obtained 516 . OEt EtOC

CH + PhNCO O

N H

492

Ynamines react with phenyl isocyanate to give a mixture of the 2- (493) and the 4quinolone (494). The formation of the 2-quinolone can be explained as a result of a [4+2] cycloaddition reaction in which the phenyl isocyanate reacts as the diene component 517 . NR2

O

R1

R1 1C

R

+

CNR2 + PhNCO O

N H 493

N

NR2

494

Vinyl isocyanate reacts with diethylaminopropyne to give the [4+2] cycloadduct 495 plus 496 as a byproduct. The latter is formed by a [2+2] cycloaddition, followed by rearrangement 518 .

N

NEt2

O

O

Me

HN

CMe

+ Et2NC

+

HN

NEt2

O

495

496

An internal [4+2] cycloaddition occurs in the photolysis of β-styryl isocyanate to give 497 519 . R

R

N

NH

• O

O

497

Several vinyl isocyanates undergo a [4+2] cycloaddition reaction with benzyne. For example, from benzyne and the vinyl isocyanate 498, the heterocycle 499 is obtained in 58 % yield 520 .

+

NH N O

O

• 498

499

152


Vinyl isocyanates also undergo a [2+4] cycloaddition reaction with enamines 500 to give the [4+2] cycloadduct 501 in 81 % yield 521 .

N +

O

N H 501

NCO 500

In a similar manner ketenaminals react with vinyl isocyanates to give the [4+2] cycloadducts in 55–75 % yield 522 . Phenyl isocyanate also reacts with benzyne to give 502 via a [4+2] cycloaddition sequence 523 . OH PhN

C

O

N

+

502

Also, ester enolates undergo the [4+2] cycloaddition reaction with vinyl isocyanate 503 to give the cycloadducts 504 in good yields 524 . O

O

OH

O

N H

O

OEt

+ NCO

503

504

Also, vinyl isocyanate reacts with oxovinylidenetriphenylphosphorane or Nphenylimino-vinylidenetriphenyl-phosphorane to give the [4+2] cycloadduct 505 525 . O CH2 CHN

C

O + Ph2P

C

C

PPh3

HN

O

O 505

Reaction of phenylthiocarbonyl isocyanate with norbornene produces the [4+2] cycloadduct 506 526 . O N

+ PhCSNCO S 506

Ph

2-Carbon Cumulenes

153

Norbornadiene reacts similarly. Morpholinocyclohexene also reacts with phenylthiocarbonyl isocyanate to give [4+2] cycloadducts 422 . Likewise, dihydropyrane reacts with p-chlorophenylthiocarbonyl isocyanate to give the [4+2] cycloadduct. Dimethylketene reacts with phenylcarbonyl isocyanate to give a [4+2] cycloadduct 527 . Phenylthiocarbonyl isocyanate adds across the C O bond of aromatic ketenes or the C N bond of aromatic ketenimines to give [4+2] cycloadducts 528 . N-Alkyltrichlorovinylketenimine reacts with trichlorocarbonyl isocyanate to give the [4+2] cycloadduct 507 resulting from addition across the ketenimine C C bond 529 . O Cl2C

C(Cl)–CH

C

C(Cl)

N

NR + CCl3CONCO

NR

O

CCl3

CCl2

507

Iminoketenes, 508, generated in the thermolysis of benzotriazinones or isatoic anhydride, react with aryl isocyanates to give 2-aryliminobenz-1,3-oxazin-4-ones 509 530 . O •

O N H

O

O

O

+ RNCO NH

O

N H

508

NPh

509

Phosphacumulenylidene derivatives, such as 510, react with phenylcarbonyl isocyanate to give the [4+2] cycloadducts 511 531 . O Ph3P

C

C

PPh3

N

NPh + PhCONCO Ph

510

O

NPh

511

Acylketenes, generated in the thermolysis of 4-oxo-1,3-dioxine derivatives, react with phenylcarbonyl-, methoxycarbonyl-, or phenoxycarbonyl isocyanates by a [4+2] cycloaddition reaction to give 2,4-dioxo-1,3- oxazines 532 . Trifluoromethylcarbonyl isocyanate reacts with diarylimines via a [4+2] cycloaddition reaction to give 6-trifluoro-methyl-4-oxo-2,3-dihydro-4H-1,3,5-oxadiazines 512 533 . O RCH

NR1

N

NR1 + CF3CONCO CF3

O

R

512

When this reaction is conducted in the presence of sulfur dioxide, the generated 1,4dipole is intercepted to give mixtures of 2-oxotetrahydro-1,2,4-thiadiazole-1,1-dioxides and 4-oxotetrahydro-1,2,3,5-oxathiadiazine-2-oxides 534 .

154


Cinnamylideneanilines 513 undergo a [4+2] cycloaddition reaction with phenylyhiocarbonyl isocyanate across the C N bond of the substrate to give 514 535 . O RN

CHCH

NR

N

CHPh + PhCSNCO Ph

CH

S

513

CHPh

514

Benzaldazine reacts similarly with phenylthiocarbonyl isocyanate to give the mono and bis adducts 536 . Also, benzoylhydrazones undergo this reaction with phenylthiocarbonyl isocyanate to form 515 537 .

PhCONHN

S

PhCONHN

+ PhCSNCO

O

N 515

Ph

The C N bond in 3-phenyl-2H-azirines reacts with phenylcarbonyl or phenylthiocarbonyl isocyanate to give the [4+2] cycloadduct 516 538 . Ph

O N

N

N

+ PhCONCO Ph

O 516

Aliphatic imines react with chlorocarbonyl isocyanate to give uracile derivatives 539 . Dibenzylideneethylenediamine reacts with two equivalents of phenylcarbonyl isocyanate to give the bis [4+2] cycloadducts 444 . Bis [4+2] cycloadducts are also obtained from biscyclohexylethylenediimines and phenylcarbonyl isocyanate at room temperature. However, in refluxing xylene the ‘criss-cross’ [3+2] cycloadducts are obtained (see Section 3.3.1.4) 540 . Arylaldehyde azines react with phenylcarbonyl isocyanate to give the ‘crisscross’ [3+2] cycloadduct. However, reaction with trifluoromethylcarbonyl isocyanate affords [4+2] cycloadducts resulting from addition across one of the C N bonds 541 . Also, aliphatic and aromatic aldehydes and acetone react with ethoxycarbonyl and phenylthiocarbonyl isocyanate to give [4+2] cycloadducts 542 . The reaction of arylcyanates or disubstituted cyanamides with phenylthiocarbonyl isocyanate affords 1,3,5-thiadiazinones 517 543 . O N

N

R2NCN + PhCSNCO Ph

S

NR2

517

Several liganded metal complexes react with carbonyl isocyanates to give metallacycles, in which the carbonyl group adjacent to the isocyanate group participates in the bonding. For example, reaction of Pd(bipyridine)-(dibenzylindeneacetone) with phenylcarbonyl

2-Carbon Cumulenes

155

isocyanate affords a metallacycle 518 resulting from a 1,4-dipolar addition to palladium 544 . O N

L2Pd + PhCONCO

PdL2

Ph 518

Rhenium 545 and ruthenium 546 react similarly to give five-membered ring metallacycles. Iminoketeneimines 519, which are also suitable dienes for [4+2] cycloaddition reactions, react with phenyl isocyanate to give the expected cycloadduct 520 547 .

R2

•

NR3

NR3

R2

NPh

+ PhNCO

R3

R3

NR1 519

N1 R 520

O

Ketoketenes undergo similar [4+2] cycloadditions with isocyanates 548 . Another example of the cycloaddition reaction of α-oxo ketenes is the reaction of diketene with FSO2 NCO, which is conducted in CCl4 at 50 ◦ C to give the [4+2] cycloadduct 521 in 65 % yield 549 .

O

O

•

O

O

NSO2F

+ FSO2NCO

O

O

O 521

O

Reaction of diketene with aryl isocyanates, in the presence of triethylamine, affords pyridine derivatives 550 . In the [4+1] cycloaddition of vinyl isocyanate with chiral nucleophilic carbenes an asymmetric induction is observed 551 . 2-Alkoxycarbonylazolium N-aminides, 522, generated in situ, react with phenyl isocyanate in a formal [4+2] cyclocondensation process to give the heterobetaines 523 in 70 % yield 552 . Me N

CO2Et

N

Me N + PhNCO

N

+

NH –

522

523

O NPh N

O

–

156


Benzannulated enyne isocyanates 524 undergo a cycloaromatization reaction on heating in the presence of PhMe2 SiCl to give the heterocyclic adduct 525 in 82 % yield 553 . Me2N MeN

NCO

N H

524

O 525

◦

Likewise, heating of 526 at 180 C for 36 h in the presence of one equivalent of PhMe2 SiCl affords 527 in 89 % yield. O O

NCO 526

N H 527

O

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157

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2-Carbon Cumulenes

159

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160 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210. 211. 212. 213. 214. 215. 216. 217.

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2-Carbon Cumulenes 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267.

161

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162


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2-Carbon Cumulenes 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. 331. 332. 333. 334. 335. 336. 337. 338. 339. 340. 341. 342. 343. 344. 345. 346. 347. 348. 349. 350. 351. 352. 353. 354. 355. 356. 357. 358. 359. 360. 361. 362.

163

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164


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2-Carbon Cumulenes

165

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166


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3.3.2 Isothiocyanates, RN C S 3.3.2.1

Introduction

The chemistry of isothiocyanates resembles very much the chemistry of isocyanates. In addition to the widely known nucleophilic reactions of isothiocyanates, cycloaddition reactions are also prominent. The cycloaddition reactions can occur across either the C N or the C S double bond but the latter is often preferred. The polarization of the N C S bond is shown in the following resonance forms: RN

RN−–C+

C–O

RN−

S

C+–S−

The [2+2] cycloaddition reaction can proceed as a concerted or a stepwise reaction. More evidence points to the stepwise reaction mechanism. In [4+2] cycloaddition reactions isothiocyanates can participate as dienes or as dienophiles. A review covering the synthesis and reactions of isothiocyanates was published in 1977 1 . Other isothiocyanate reviews include the 1,3-dipolar reactions of isothiocyanates, which appeared in 1974 2 , and the use of isothiocyantes in the synthesis of heterocycles, which was published in 1991 3 . The chemistry of isoselenocyanates was reviewed more recently, and their cycloaddition reactions are included in this chapter 4 . 3.3.2.2

Dimerization Reactions 5

Sulfonyl - and alkoxycarbonyl isothiocyanates 6 undergo dimerization reactions across their C S bonds to give four-membered ring cycloadducts 1. RSO2N

S

2 RSO2NCS S

NSO2R 1

Several reactive isothiocyanates undergo dimerization reactions in which one of the isothiocyanates functions as the diene and the other isothiocyanate reacts as the dienophile. These [4+2] cycloaddition reactions are very pronounced with heterocyclic isothiocyanates and isothiocyanates having carbonyl, thiocarbonyl and imidoyl substituents. For example, 2-pyridyl isothiocyanate undergoes dimerization to give the triazine derivative 2 7 . S N

2 N

NCS

N N S

N

2

Imidoyl 8 -, thiocarbamoyl 9 - and ethylmercaptothiocarbonyl isothiocyanates 10 also afford dimers formed in a [4+2]] cycloaddition reaction. Carbamoyl isothiocyanates are in equilibrium with thiocarbamoyl isocyanates; therefore on standing mixed dimers 3 of the

2-Carbon Cumulenes

169

two species are obtained 11 . O R2NCONCS

N

R2NCSNCO R2N

NCONR2 S

S 3

N-Isothiocyanatodimethylamine 4 dimerizes at room temperature in less than 1 min to form an ionic dimer 5, which rearranges in solution to give the heterocycle 6 12 . N

Me2N

Me2NNCS

S

MeN N

4

S

S

N

SMe

N

NMe2

NMe2

5

6

The trimerization of methyl isothiocyanate to give the six-membered ring isocyanurate caused by ethylene oxide in the presence of a tertiary amine is discussed in Section 3.3.2.4. 3.3.2.3

Cycloaddition Reactions

[2+1] and [1+2+2] Cycloadditions Tosyl isothiocyanate reacts with diphenylmethyldiazomethane via addition of the generated carbene to the C S bond to give a 67 % yield of the [2+1] cycloadduct 7 13 . RSO2N RSO2NCS

Ph2C

S

N2 Ph

Ph 7

The reaction of RCONCS with diphenylmethyldiazomethane is more complex, giving rise to the 1:2 adduct 8, which rearranges to give the four-membered ring compound 9 14 . Ph

Ph

S RCONCS + 2 Ph2C

N

NCOR

Ph2

Ph2

N2

O

Ph2

S

R 8

9

Liganded osmium complexes react with isothiocyanates across their C S bond to give [2+1] cycloadducts 10 15 . L L2ClOsNO + PhN

C

S

Cl ON

L 10

S

Os NPh

170


Carbenes can also participate in [1+2+2] cycloaddition reactions. In these reaction, ionic intermediates are formed, which can be intercepted by a second molecule of the isothiocyanate. For example, dimethoxycarbene, formed in the thermolysis of 1,2,3,4-tetrachloro7,7-dimethoxy-5-phenylbicyclo[2.2.1]hepta-2,5-diene 11, reacts with excess aryl isothiocyanate to give the [1+2+2] cycloadducts 12. The initial reaction of dimethoxycarbene with the aryl isothiocyanate generates a 1,3-dipole, which undergoes a [3+2] cycloaddition reaction with the second equivalent of the aryl isothiocyanate 16 . PhN

MeO OMe Cl Cl Cl

(MeO)2C: + 2 PhNCS

S

MeO MeO

NPh

S

Cl Ph 11

12

Electron-rich olefins, such as tetraaminoethylene 13, react as masked carbenes with four equivalents of isothiocyanates to give 2,4-dithiono-6,9-diphenyl-1,3,6,9tetraazaspiro[4,4]nonanes 15. An intermediate ionic 1:1 adduct 14 can be isolated when two equivalents of isothiocyanates are used 17 . Ph N

Ph N

Ph N +

N N Ph Ph 13

Ph S N

S

N Ph 14

NR

NR

N N Ph R 15

S

Stable ionic 1:1 adducts 16 are also obtained when the reaction is conducted in toluene using carbonyl isothiocyanates. Further reaction of the dipoles with phenyl isocyanate affords tetraazaspiro[4,4]nonanes 17 18 . Ph N

Ph N S : + RCONCS

N Ph

N

N Ph 16

Ph S N

O

NCOR

+ PhNCO R

N N Ph Ph 17

O

Thiazolium ylides 18 also react with isothiocyanates to give the fused spiro ring systems 20 or linear ionic 1:1 adducts 19. Electron withdrawing substituents in aryl isothiocyanates support the formation of the ionic 1:1 adducts, while electron donating substituents favor the formation of the [1+2+2] cycloadducts 19 . S NR S S

RN

NR S

RN

RN

S S

RN Me

CH2CH2OH

Me 18

CH2CH2OH

Me 19

O 20

2-Carbon Cumulenes

171

Carbamoyl isothiocyanates in their reactions with isonitriles afford iminooxazolinethiones 21 (when R = Me or Et) or they react as the rearranged thiocarbamoyl isocyanates to give iminothiazolinones 22 (when R = C6 H11 ) 20 . S N R2N

NR1

O 21

R2NCONCS + R1NC

O N R2N

NR1

S 22

Isothiocyanates also react with enamines and isonitriles in polar solvents to give the [1+2+2] cycloadducts 23 21 . N NCH

Me2

CMe2 + R1NCS + R2NC

R1N

NR2 S 23

Decamethylsilicocene reacts with isothiocyanates by an initial [2+1] cycloaddition reaction 22 . [2+2] Cycloadditions Across carbon multiple bonds The [2+2] cycloaddition reaction of isothiocyanates occurs readily with activated olefins, such as enamines and ketene acetals. For example, arenesulfonyl isothiocyanates undergo a regiospecific [2+2] cycloaddition reaction with vinyl ethers at 50 ◦ C to give 2-thietan imines 24 23 .

RSO2NCS + R1R2C

NSO2

S

CR3OR4

R3

R

R1R2

OR4 24

R

R1

R2

R3

R4

Yield (%)

Me Me

Me Me

H Me

H H

Et Et

76 69

2-Thietane imines 26 are also obtained from 2-oxetanone derivatives 25 and phenyl isothiocyanate at −78 ◦ C. This reaction is an example of the conversion of one

172


four-membered ring compound into another one 24 . O

O R

NPh

S

+ PhNCS Ph

R

Ph 26

25

R

Yield (%)

i-Pr t-Bu

41 52

Bis(trifluoromethyl)thioketene also undergoes the [2+2] cycloaddition reaction with isothiocyanates to give the four-membered ring cycloadducts 27, resulting from addition across the C S bonds of both the thioketene and the isothiocyanate 25 . NR

S (CF3)2C

C

S + RN

C

S S

CF3 CF3 27

R

Yield (%)

Ph 3,4,5-(MeO)3 Ph α-C10 H7

49 73 79

From methyl isocyanate and bis(trifluoromethyl)thioketene the initial [2+2] cycloadduct 27 reacts across its C N bond with another two equivalents of the thioketene to give the bicyclic [2+2+2] cycloadduct 28 in 52 % yield 26 . CF3 Me S N

CF3 3 (CF3)2C

C

S

S + MeNCS

S

CF3

S

CF3 CF3

CF3 28

The reaction of isothiocyanates with linear and cyclic olefins, activated with dialkylamino substituents, is generally exothermic, with only short heating in an inert solvent being necessary to produce high yields of the linear 1:1 adducts 29. The reaction proceeds via a [2+2] cycloaddition and subsequent rearrangement to give the final product. Several examples of linear products derived from enamines and isothiocyanates are listed in Table 3.13.

2-Carbon Cumulenes

173

Table 3.13 Linear adducts obtained from enamines and isothiocyanates R2NCR1

CHR2 + R3N

C

S

R2NCR1

CR2C(S)NHR3 29

R1

R2

Pr Et Ph H –(CH2 )3 – –(CH2 )4 –

R3

Amine Compound

Ph PhCO Ph Ph

Morpholine Morpholine Morpholin Morpholine

Yield (%)

Reference

100 75 93 93

27 29 29 29

Heating of the linear 1:1 adduct with phenyl isothiocyanate affords the 1:2 adduct. Also, heating of the 1:1 adduct derived from the cyclohexanone enamine and phenyl isothiocyanate with phenyl isocyanate produces a 2:1 adduct 30 derived from both reagents and the enamine 27 . Excess phenyl isocyanate effects exchange of the thioanilide function into an anilide function to give 31. O N

PhN

N

O NPh

CSNHPh

PhN

NPh

S

+ PhNCS

O + PhNCS

30

31

In the reaction of tosyl isothiocyanate with enamines, having substituents at the β-carbon, crystalline ionic 1:1 adducts 32 are obtained 28 . CMe2 R2NCR1

CMe2 + R2SO2NCS

R 2N

C(R1) NSO2R2

S 32

1-Morpholinocyclohexene reacts with phenylcarbonyl isothiocyanate to give the benzoxazine-4-thione derivative 33, via a [4+2] cycloaddition process 29 . S N

+ PhCONCS

N O

O

Ph

33

Linear 1:1 adducts are also obtained in the reaction of β-aminocrotonic acid derivatives with isothiocyanates 30 .

174


N-Substituted ketenimidylidenetriphenyl phosphoranes 34 react with isothiocyanates in a [2+2] cycloaddition reaction to give 2,4-bisiminothietanes 35 31 . Ph3P+–C−

C

NR2

S

NR1 + R2N

C

S PPh3

R1N 34

35

R1

R2

Ph Ph Ph Ph

CH2 CH CH2 C6 H11 CH2 COOMe 4-Me2 NPh

Yield (%) 89 91 93 94

In the reaction of 4-diethylamino-3-butyn-2-one 36 with isothiocyanates thiet-2(2H)imines 37 are obtained in a [2+2] cycloaddition reaction 32 . NR

S CH3CO–C

C–NEt2 + RN

C

S Et2N

COCH3

36

37

In a similar manner, aryl isoselenocyanates react with 36 to give the four-membered ring cycloadducts in moderate yields resulting from addition across the C Se bond 33 . The rhodium catalyzed [2+2+2] cycloaddition reaction of isothiocyanates with 1,6diynes 38 affords bicyclic thiopyranimines 39 in 59–98 % yield 34 . R1 R2

+ RNCS

38

NR

R1 R2

S 39

Using the (R) derivative of 40 and phenyl isothiocyanate the [2+2+2] cycloadduct 41 is obtained in 98 % yield (61 % e,e). Ph MeO2C

+ PhNCS

40

NPh

Ph MeO2C

S 41

Similarly, 1,6-diynes react with isothiocyanates in the presence of ruthenium catalysts to give the bicyclic thiopyranimines 35 . Across C N bonds The [2+2] cycloaddition reaction of isothiocyanates across C N bonds is often observed, and in addition to four-membered ring cycloadducts resulting from addition across the C S as well as the C N bond of the isothiocyanate, rearranged linear adducts, or ionic linear adducts are also isolated. Another interesting reaction of isothiocyanate is the exchange reaction with other heterocumulenes containing C N bonds. The

2-Carbon Cumulenes

175

latter reaction occurs readily with isocyanates and carbodiimides (see Sections 3.3.1 and 3.3.3) and amounts to a [2+2] cycloaddition followed by cycloreversion. The driving force of this reaction is the continuous removal of the lowest-boiling component. For example, in the heating of TDI with allyl isothiocyanate, both isocyanate groups are replaced with formation of two equivalents of allyl isocyanate and an aromatic diisothiocyanate 36 . Azomethines derived from aryl alkyl ketones react with isothiocyanates at 130–140 ◦ C to give linear 1:1 adducts 37 . The more reactive tosyl-, alkoxycarbonyl- and mercaptocarbonyl isothiocyanates undergo a [2+2] cycloaddition reaction with azomethines (R = i-Pr, C6 H11 , Ph) across their C S bonds to give 1,3-thiazetidine derivatives 42 (R = 4-MePhSO2 −, MeSCO−, EtOCO−) 22 . NR

S RN

CHPh + RNCS

Ph

NR 42

Thiocarbamoyl isoselenocyanates 43 also undergo the [2+2] cycloaddition reaction with imines to give 1,3-selenazetidines 44 38 . NCSNR2

Se R2NCSN

C

Se + RCH

NPh

R

43

NPh 44

In contrast, [2+2+2] cycloadducts 45 are obtained from from two equivalents of benzylidene methylamine and carbonyl isothiocyanates (R = COOEt, COSMe and CONPh2 ) 39 . S 2 PhCH

RN Ph

NMe + RNCS

NMe N Me 45

Ph

Azomethines derived from formaldehyde are cyclic aminals, (RN CH2 )3 , and in their reaction with alkyl isothiocyanate, [2+2+2] cycloadducts are obtained as result of an insertion into the C–N bond of the cyclic aminal 31 . N-Alkylimidocarbonates and imidothiocarbonates react with tosyl isothiocyanate to give crystalline ionic linear 1:1 adducts 46. Some of the adducts are labile and dissociate in solution back to the starting materials 40 . R1 N R1N

CR2R3 + 4-MePhSO2NCS

S

CR2R3

NSO2 46

CH3

176


R2

R3

Me Me Me

OMe OMe OMe

OMe OEt SEt

Yield (%) 89 67 60

In the reaction of MeN C(OMe)NMe2 with tosyl isothiocyanate a linear ionic 1:1 adduct is obtained, which rearranges to give 4-MePhSO2 N C(SMe)N(Me)CONMe2 in 57 % yield. When the isourea configuration is locked into the ring structure 47, [2+2] cycloaddition with phenyl isothiocyanate across the exocyclic C N bond occurs with formation of the exchange product 48 41 . Me Me

Ph Me

Ph

MeN

O

MeN

O

MeN

NPh

+ PhNCS

Ph

MeN

+ MeNCS

O NPh

MeN S

48

47

In the reaction of p-nitrophenyl isothiocyanate with N,N-tetramehtyl-N -n-butylguanidine 49 an exchange reaction with formation of n-butyl isothiocyanate 50 is observed 42 . BuN

4-O2NPh

C(NMe2)2 + 4-O2NPhNCS 49

C(NMe2)2 + BuNCS 50

Phenylcarbonyl isothiocyanate reacts with 1-azirines to give [2+2] cycloadducts 51; however, the strained bicyclic adduct undergoes rearrangement to give 4,5-disubstituted 2-benzamido-1,3-thiazoles 52 43 . R1

PhCON

R

N

+ PhCONCS R1

R

N

H

N

S

R1

R

NHCOPh

S

H 51

52

In the reaction of 3-(dialkylamino)-2H-azirines with isothiocyanates, a similar [2+2] cycloaddition across the C N bond occurs; however in this case the strained bicyclic adducts undergo further transformation to give carbodiimides 54 which are in equilibrium with the dipolar heterocycle 53 44 . N

NR1

NMe2

S + R1NCS

N

Me2N 53

Me2NCSC(Me)2N 54

C

NR1

2-Carbon Cumulenes

177

The imino heterocycle 55 reacts with benzoyl isoselenocyanate via a [2+2] cycloaddition sequence to give aryl-(4-seleno-4H-pyrido[1,2-a]pyrazin-3-yl)amines 56 45 . + PhCONCSe N

N

N RN

N

RN

NHR

N

N

Se

NHR

Se NHR

PhCON

56

55

The carbodiimide 57 undergoes a [2+2+2] cycloaddition reaction with aliphatic isothiocyanates to form six-membered ring triazine derivatives 58. 49

Me2NCSC(Me)2N

C

NR1

+ 2

R2 N

Me2NCSC(Me)2N

R2NCS

S NR2

R1N S 57

58

R1

R2

i-Pr i-Pr

Me PhCH2

Yield (%) 51 44

In the reaction of 3-(dialkylamino)-2H-azirines with trimethylsilyl isothiocyanate the initially formed [2+2] cycloadduct 59 again is transformed into the five-membered ring compound 60, which on treatment with methanol to remove the silyl group is converted into 4-(dialkylamino)imidazoline-2-thiones 61 (yield: 26–80 %) 46 . N

NR2 + Me3SiNCS

R 2N

S

Me3SiN R2N

N

SiMe3 S

N H

59

R2N N H

S

61

60

In the reaction of carbodiimides with isothiocyanates, cycloadducts resulting from addition across the C S bond to give 62 are obtained. In some cases cycloaddition across the C N bond of the isothiocyanate to give 63 also occurs 47 . The obtained [2+2] cycloadducts are listed in Section 3.3.3.

RN

C

S + R1N

C

NR

S

NR1

S

RN +

NR1

R1N 62

NR1

R1N 63

178


In the reaction of isoselenocyanates with carbodiimides, reaction occurs exclusively across the C Se bond of the isoselenocyanate to give 1,3-selenazetidine-2,4-diimines 64 48 .

R1N

C

Se +

R2N

C

NR1

Se

NR2

NR2

R2N 64

R1

R2

Cyclohexyl Ph Ph 4-ClPh 4-BrPh

Cyclohexyl i-Pr Cyclohexyl i-Pr i-Pr

Yield (%) 99 84 98 97 99

In the reaction of acyl isoselenocyanates with carbodiimides, mixtures of the [2+2] cycloadducts 65 and the [4+2] cycloadducts 66 are obtained 49 . Se NCOR

Se RCON

C

Se + RN

C

NR

N

+ NR

RN

R

65

NR O

NR

66

Across other double bonds The reaction of phenyl thiocyanate with P N compounds was first investigated by Staudinger and Meyer in 1919 50 . The reaction proceeds across the C S bond of the isothiocyanate to give fragmentation products. For example, from ethyliminotriphenylphosphorane 67 and ethyl isothiocyanate a good yield of diethylcarbodiimide and triphenylphosphine sulfide is obtained 51 . The reaction most likely proceeds via the four-membered ring intermediate 68 formed in a [2+2] cycloaddition reaction. NEt

S Ph3P

NEt + EtN

C

EtN

S NEt

Ph3P 67

C

NEt + Ph3P

S

68

This transformation, now known as the aza–Wittig reaction, is exceedingly useful in the formation of heterocyclic systems 52 and macrocyclic carbodiimides 53 . The reaction of 1,2λ5 -azaphospholes 69 with methyl isothiocyanate proceeds across the C N bond of the isothiocyanate to give the [2+2] cycloadduct 70. In contrast, phenyl isothiocyanate, Me2 P(S)NCS, Ph2 P(S)NCS and phenylcarbonyl isothiocyanate react across their C S bond to give the isomeric [2+2] cycloadducts 71 54 . S

RN N

R2P MeO2C

N

R 2P Ph2

+ RNCS

Ph2

MeO2C

NR

S or

R 2P

N Ph2

MeO2C

CO2Me

CO2Me

CO2Me

69

70

71

2-Carbon Cumulenes

179

In solution the cycloadducts resulting from addition across the C S bond isomerize to the cycloadducts derived from addition across the C N bond of the isothiocyanate. An exchange reaction is observed in the reaction of aromatic nitroso compounds 72 with isothiocyanates to give azo derivatives 73 and carbonoxy sulfide 55 . RN

C

S + R1N O 72

RN

NR1 + COS 73

The reaction of the sterically highly hindered RR1 Sn S (such as R = R1 = 2,4,6triisopropylphenyl) with phenyl isothiocyanate affords the [2+2] cycloadduct 74 56 . RR1Sn

NPh

S S + PhNCS

RR1Sn

S

74

The liganded cobalt isonitrile complexes 75 react with isothiocyanates to give the rearranged [2+2] cycloadducts 76 57 . S LCo(PMe3)C

NR

S

MeN

NMe + RNCS MeN

CoL

CoL

RN

75

76

Imido complexes of titanium, supported by cyclooctatetraene ligands, react with phenyl isothiocyanate across the C S bond via a [2+2] cycloaddition reaction to give a fourmembered ring metallacycle 58 . Diaryl silanethiones with 2,4,6-substituents on the phenyl rings react with phenyl isothiocyanate to give a 63 % yield of the [2+2] cycloadduct 77 59 . RR1Si

NPh

S S + PhN

C

S RR1Si

S 77

Cyclostannacenes react with phenyl isothiocyanate by an exchange reaction giving rise to the formation of carbodiimides 60 . A stepwise cycloaddition reaction of thioisomünchenones with aryl isothiocyanates results in the thionation of the mesoionic compound in good yield 61 . Across single bonds (insertion reactions) The addition of isothiocyanates across the polar single bond in dimethylaminobis-(trifluoromethyl)borane affords the switter ionic fourmembered ring cycloadducts 78 62 . (F3C)2B−–N+ Me2 + RNCS

NR

S

B(CF3)2

Me2N 78

180


However, the addition of isothiocyanates across single bonds generally proceeds with insertion of the C N bond of the isothiocyanate into the single bond. The insertion into a C–N single bond in formaldehyde aminals is a typical example. N,N-Dimethylformamide acetals react in a similar manner 63 . The reaction of metalorganic substrates with isothiocyanates was first observed by Bloodworth and Davies in 1963 64 . The authors obtained a 1:1 adduct 79 from tributylmethoxy tin and phenyl isothiocyanate. Bu3SnOMe + PhNCS

Bu3N(Ph)CSOMe 79

The insertion of isothiocyanates into Mg–C bonds in polynuclear aluminum–magnesium compounds 65 , into Si–S bonds in ruthenium complexes 66 , into Mo–OR and Rh–OR bonds in carbonyl complexes 67 and into diiron–hydride complexes 68 has also been observed. Also, insertion of EtOCONCS into the rhenium–rhenium bond of Re2 (CO)9 (NCMe) is observed 69 . In the reaction of the liganded zirconium formaldehyde dimer 80 with excess t-butyl isothiocyanate insertion into both of the Zr–C bonds is observed to give the double insertion product 81 in 83 % yield 70 . L2 Zr

O

+ 2 t-BuNCS

t-Bu

N-t-Bu

O S Zr L2

O

Zr L2

L2 S O Zr

80

81

In the reaction of oxalyl chloride 82 with isothiocyanates, insertion into the C Cl bond occurs with formation of 3-alkyl- or 3-aryl-2,2-dichlorothiazolidine-4,5-diones 83 71 . O ClCOCOCl + RNCS

82

O

RN

S

Cl

Cl 83

The reaction of 82 with methyl isothiocyanate is exothermic at room temperature and the yield is quantitative. Other aliphatic isothiocyanates require longer reaction times, while aromatic isothiocyanates require 25 to 40 days to reach about 25 % conversion. Benzopentathiepin reacts with isothiocyanates and isoselenocyanates in the presence of triethylamine by insertion into the S–S bond 72 . The insertion of isothuocyanates into Fe–N bonds 73 is also observed and aryl isothiocyanates insert into unsupported Zr–M (M = Fe, Ru) bonds 74 . Numerous examples of this type of reaction of isothiocyanates are known. The reaction occurs across B–Cl, B–N, Hg–O, Sn–O, Si–N, P–N, As–N and S–N bonds. [3+2] Cycloadditions The [3+2] cycloaddition reaction across three-membered rings involves initial ring opening to generate the 1,3-dipole, which adds across the C S bond of the isothiocyanate. The ring opening is often caused by the addition of a catalyst. For example, carbonyl isothiocyanates react with alkoxides to give 1,3-oxathiolane

2-Carbon Cumulenes

181

derivatives 84 75 . R1 RCONCS +

R 1C

CH2

O

S

O

NCOR 84

R

R1

Ph Ph EtO

PhOCH2 CH2 CHCH2 OCH2 CH2 ChCH2 OCH2

Yield (%) 66 62 40

The reaction of oxirans with isothiocyanates to form 1,3-oxathiolanes is catalyzed by organotin iodide in the presence of a Lewis base 76 . Similarly, [3+2] cycloaddition of alkyl isothiocyanates with ethylene sulfide affords 1,3-dithiolanes 85 77 . RNCS + CH2 CH2

S

S

S NR 85

Also, 2-vinylthiirane 86 reacts with aryl isothiocyanates in the presence of Pd catalysts to give the [3+2] cycloadducts 87 78 .

S

+ RNCS

S

S NR 87

86

R

Yield (%)

Ph 4-MeOPh

98 85

The reaction of aliphatic isothiocyanates with alkylene oxides is more complex. For example, methyl isothiocyanate reacts with ethylene oxide in the presence of a tertiary amine catalyst at 20–90 ◦ C to give trimethylthioisocyanurate. When the reaction is conducted at 90 ◦ C, in the presence of tetraethylammonium bromide, the spirotriazine derivative 88 is obtained 79 . MeNCS +

S

CH2 CH2 O

MeN S

O NMe N Me 88

S

182


At 200 ◦ C, the reaction of methyl isothiocyanate and alkylene oxide gives trimethyl isocyanurate. This reaction involves the trimerization of methyl isothiocyanate followed by stepwise replacement of the sulfur by oxygen via spiro compounds. Phenyl isothiocyanate reacts with ethylene oxide to give a mixture of triphenyl isocyanurate and 3phenyloxazolidine-2-one 90 80 . The formation of the oxazolidone is caused by the reaction of the initially formed 2-phenylimino oxathiolene 89 with ethylene oxide in the presence of the catalysts 81 . O

S

+ CH2 CH2

O

O

NPh O 90

NR 89

The reaction may involve formation of phenyl isocyanate which subsequently reacts with ethylene oxide. A 1,3-dipole, generated from the aziridine 91, also undergoes a [3+2] cycloaddition reaction with p-nitrophenyl isothiocyanate to give a thiazolidine derivative 92 82 . NR S PhCH

Ph

CHCOR + 4-O2NPhNCS

COR N R

N R 91

92

The highly substituted aziridine derivative 93 reacts with aryl isothiocyanates in the presence of bis(benzonitrile)palladium (ii) dichloride as the catalyst to give thiazolidinimines 94 83 . NR S Me

CO2R

+ RNCS

N Bu 93

NBu

RO2C

Me 94

In a similar manner, N-butyl-2-methyl-3-vinylaziridine 95 reacts with phenyl isothiocyanate in the presence of [Pd(OAc)2 ]PPh3 to give the cycloadduct 96 in 96 % yield 84 .

N Bu 95

+ PhNCS

BuN

S NPh 96

Also, N-(arylsulfonyl)aziridines 97 react with isothiocyanates to give the [3+2] cycloadducts 98. In this reaction the isothiocyanate undergoes reaction across its C S bond 85 . In contrast, substituted N-(arenesulfonyl)aziridines, in the presence of sodium iodide as the catalyst, undergo [3+2] cycloaddition reactions with aryl isothiocyanate across their C N

2-Carbon Cumulenes

183

bonds to give imidazolidinethiones 86 . NR S N SO2R

+ RNCS

NSO2R

97

98

1-Cyclohexyl-2(2 -thienyl)-3-benzoylaziridine also reacts with aryl isothiocyanates to give [3+2] cycloadducts 87 . The reaction of N-tosylaziridines with isothiocyanates in the presence of tributylphosphine affords the [3+2] cycloadducts in yields up to 78 % 88 . Phenylcarbonyl isothiocyanates react with 1,3-dipoles 99, generated in the treatment of 4-substituted 1,2,3-thiadiazoles with KOH/EtOH, to give the heterocycle 100 89 . NCOR S

C–S−

RCONCS + R1C+

S

R1

99

100

Similar dipoles are obtained by heating 1,2,3,4-thiatriazoles and their reaction with isothiocyanates with or without catalysts affords [3+2] cycloadducts. For example, reaction of 5-amino-1,2,3,4-thiatriazole 101 90 or 5-alkyl(aryl)-1,2,3,4-thiatriazoles 91 with isothiocyanates proceeds with loss of nitrogen to form 102 which reacts with two equivalents of isothiocyanate to give [3+2] cycloadducts 103.

N

N

+ 2 R1NCS

RNHC

N

S

N

NHR

S

S

R1N

S

N N(R)CSNHR1

101

102

103

Also thermolysis of 4-methyl-5-phenylimino-1,2,3,4-thiatriazoline 104 generates the corresponding dipol which reacts with phenyl isothiocyanate across the C N bond to give 105 (yield, 32 %) and the C S bond to give 106 (4 % yield) 92 . S MeN N PhN

N S 104

NPh

MeN + PhNCS

PhN

MeN NPh S

105

+

PhN

S S 106

Similar [3+2] cycloaddition products are obtained in the reaction of 104 with 4nitrophenyl isothiocyanate and phenylcarbonyl isothiocyanate.

184


The reaction of N-t-butylphenyloxaziridine 107 with phenyl isothiocyanate affords a 1:1 adduct 108, most likely formed by ring opening and subsequent [3+2] cycloaddition 93 . S PhN PhCH

N-Bu-t

+ PhNCS

Ph

O N

O

t-Bu 108

107

Nitrones undergo the [3+2] cycloaddition reaction mainly across the C N bond of the isothiocyanate. For example, C-phenyl-N-methylnitrone 109 reacts with phenyl isothiocyanate 94 and phenylcarbonyl isothiocyanate 95 to give 1,2,4-oxadiazolidine-5-thiones 110. S NR PhCH

N(Me)

O + RNCS

O N Me

109

110

While the cycloaddition reaction of phenyl isothiocyanates with nitrones proceeds across its C N bond, substituted phenyl isothiocyanates, methyl isothiocyanate and benzoyl isothiocyanate react across their C S bonds. However, these cycloadducts are not stable and they undergo fragmentation with formation of thioamides and isocyanates 96 . Cyclic aldo- and ketonitrones react similarly with phenyl isothiocyanate 67 . However, substituted phenyl isothiocyanates react with 5,5-dimethyl-1-pyrroline-1-oxide to give cycloadducts derived from addition across the C N bond as well as the C S bond of the isothiocyanates. The C S cycloadducts are unstable and undergo further transformations 97 . The [3+2] cycloaddition reaction of 3,3,5,5-tetramethylpyrroline-1-oxide with aryl- and phenylcarbonyl isocyanates also occurs exclusively by addition across the C S bond 98 . The N-oxides of isoquinoline 111 99 and 1-methylbenzimidazole 100 react with isothiocyanates across the C N bonds to give the unstable [3+2] cycloadducts 112, which lose COS to give the arylamino substituted heterocycles 113. + COS

+ PhNCS

N

N

N O

O N Ph 112

111

NHPh S 113

Isoquinoline N-imines 114 also undergo [3+2] cycloaddition reactions with formation of the stable cycloadducts 115 101 . + PhNCS

N

N NPh

NPh N 114

Ph 115

S

2-Carbon Cumulenes

185

Linear azomethine imines 117, generated in the thermolysis of N-substituted hexahydrotetrazines 116, react similarly with phenyl isothiocyanate to give the [3+2] cycloadducts 118 102 . R

H

MeN

S NR

NMe [RCH

MeN

N(Me)

NMe] + RNCS

MeN

NMe

R H 116

117

R

H N Me 118

Nitrile imines react with isothiocyanates in a similar manner. For example, diphenyl nitrile imine 119, generated in the thermolysis of 2,5-diphenyltetrazole, reacts with isothiocyanates to give a mixture of 3,5-diphenyl-2-phenylimino-2,3-dihydro-1,3,4-thiadiazole 120 and 1,3,4-triphenyl-1,2,4-triazole -5-thione 121, indicating that the reaction proceeds across both the C S and the C N bonds of the isothiocyanate group 103 . NPh

S

S PhC

N

Ph + PhNCS

NPh

Ph

119

NPh

Ph

+

NPh

N

N

120

121

When diphenyl nitrile imine 123 is formed by dehydrochlorination of the hydrazidoyl chloride 122, phenylcarbonyl- 104 and imidoyl isothyocyanates 105 add exclusively across their C S bonds to give the cycloadducts 124. NR S PhC(Cl)

NNHPh

[PhC

N

122

NPh]

NPh

Ph

N

123

124

C-Trifluoromethyl-N-phenyl nitrile imide reacts with MeNCS across its C S bond to give a 14 % yield of the [3+2] cycloadduct 106 . Nitrile ylides 125 react with phenyl isothiocyanate similarly, but the initially formed cycloadduct 126 rearranges to give the thiazole derivative 127 107 . NHPh

NPh S PhC

N–CHPh + PhNCS

S

Ph

125

Ph

Ph

Ph

N

N

126

127

The reaction of aryl isothiocyanate with sodium azide and carbon dioxide affords the 5-arylamino-1,2,3,4-thiatriazoles 128 in high yield 108 . NHR S RNCS + NaN3 + CO2

N

N N 128

186


Yield (%)

Ph 4-MePh 3-ClPh

92 92.5 87.5

When the reaction of the isothiocyanates is conducted with HN3 or Me3 SiN3 , a wide variety of 5-substituted 1,2,3,4-thiatriazoles 129 are obtained 109 . NHR S RNCS + R1N3

N

N N 129

R

R1

EtOCOCH2 PhCH2 CH(COOEt) MeSO2 PhSO2 4-MePhSO2

Me3 Si Me3 Si H H H

Yield (%) 65 80 90 88 87

Reaction of phenyl isothiocyanate with trimethylsilyl chloride and sodium azide affords 83 % of 5-phenylamino-1,2,3,4-thiatriazole 110 . Arylsulfonyl isothiocyanates react with aliphatic azides across their C S bonds to give thiatriazolines 130 111 . NSO2R1

S RN3 + R1SO2NCS

RN

N N 130

In contrast, tributyl- and triphenyltin azide react with isothiocyanates across their C N bonds to give the [3+2] cycloadducts 131 112 . S NPh R3SnN + PhNCS

R3SnN

N N 131

In the reaction of alkynyl Pd(ii) azido complexes 132 with isothiocyanates tetrazolethiolato complexes 133 are obtained 113 . N N PhC

C–Pd(L2)N3 + RNCS 132

PhC

C–Pd(L2)–S–

N N R 133

2-Carbon Cumulenes

187

From p-phenylene diisothiocyanate and two equivalents of the Pd(ii) azido complex the bis-adduct is obtained in 37 % yield. Di(azido)bis(phosphine) complexes of Ni(ii) and Pt(ii) react similarly to give the corresponding bis(isothiocyanato) complexes 114 . In the reaction of azides with one equivalent each of an isocyanate and an isothiocyanate, the [3+2] cycloadducts 135 are obtained 115 . In the initial reaction of the azide with the isothiocyanate, a 1,3-dipol is generated by thermolysis of 134, which reacts with the isocyanate to form 135. NR2

NR2

S RN3 + R1NCO + R2NCS

S

N

R1N

NR

NR

N O 135

134

R

R1

R2

Me Bu C6 H11

Bu Ph Bu

Ph 4-MePh 4-ClPh

Yield (%) 95 82 84

In the [2+2] cycloaddition reactions of isothiocyanates to diazo compounds iminothiadiazolines are formed, which rearrange into 5-substituted 1,2,3-thiadiazoles 136. This is the von Pechmann synthesis of 1,2,3-thiadiazoles. The reaction is general and some examples are listed in Table 3.14. The reactivity of the isothiocyanates increases with the electrophilicity of the carbon of the isothiocyanate group, which is enhanced by electron withdrawing groups, i.e. R = aryl < EtOCO < PhCO. Table 3.14 Some [3+2] cycloadducts of isothiocyanates to diazocompounds NHR1 S RCH

N2 + R1NCS

R

N N 136

R

R1

H H PhCO 4-MeOPhCO 4-ClPhCO 3-O2 NPhCO 4-O2 NPhCO

Ph PhCO EtOSO2 Ph EtOSO2 2-MePhCO 2-MePhCO

Yield (%)

Reference

60 60 60 70 90 90 90

116 117 118 118 118 118 118

The reaction of the lithium salt of trimethylsilyldiazomethane 137 with isothiocyanates affords 2-amino-1,3,4-thiadiazoles 119 . When the reaction product is quenched with alkyl

188


halides, 1-substituted 4-trimethylsilyl-5-alkylthio-1,2,3-triazoles 138 are formed 120 . SR2

R 1N R1NCS + Me3SiC(Li)

N2 + R2X

N

SiMe3

N 137

138

In the reaction of 4-chlorobenzoyl isoselenocyanate 139 with diazomethane a regioselective [3+2] cycloaddition occurs to give the 1,2,3-selenadiazole 140 121 . N

O + CH2N2

NCSe

N

O

N

NH Se

Cl 139

Cl

140

Aroyl isoselenocyanates also react with ethyl diazoacetate to give the [3+2] cycloadduct 141 122 . CO2Et

N ArCONCSe + N2CH2COOEt

N

NHCOAr

Se 141

The similar reaction of diethyl azodicarboxylate at room temperature with aryl isoselenocyanates in the presence of triphenylphosphine affords 4,5-dihydro-5-selenoxy-1H-1,2,4tetrazole carboxylates 142 in 78–97 % yields 123 . N RO2CN

NCO2R + ArNCSe

RO2C

CO2R

N

Se

N Ar 142

The reaction of diazaazoles 143 with phenylcarbonyl isothiocyanate affords the [3+2] cycloadducts 144 124 .

+

X N

COR

N

N

x

COR

Y

y

PhCONCS PhCON

N2

143

S

N

144

X

Y

R

N CH

CH N

OEt OEt

Yield (%) 84 88

In the [3+2] cycloaddition reactions of isothiocyanates with 1-aza-2-azoniaallene salts the reaction also proceeds across the C S bond of the isothiocyanate to give 1,3,4thiadiazolium salts in high yields 125 .

2-Carbon Cumulenes

189

1,3-Dipoles can also be generated from diazoketones. For example, thermolysis of tetrachlorobenzene-o-diazooxide 145 at 130 ◦ C in the presence of isothiocyanates affords 1,3-benzoxathiole derivatives 146 126 . Cl

Cl

O

Cl

••

Cl

Cl

⊕

Cl

S

Cl

O

NR

+ RNCS Cl

O

O

Cl

Cl

Cl

Cl

Cl N2

Cl

Cl

Cl

145

146

The reaction of the diazoketone 147 with phenylcarbonyl-(X = O) and phenylthiocarbonyl isothiocyanates (X = S) proceeds across the C S bond of the isothiocyanate, but the [3+2] cycloadduct 148 eliminates nitrogen to give the heterocycle 149 127 . CxPh PhCXN N2

O

S

O

O

S

N

+ PhCXNCS

147

N

N

149

148

The thioketocarbene 150, formed in the thermolysis of 1,2,3-benzothiadiazole, also reacts with phenyl isothiocyanate to give the [3+2] cycloadduct 151 128 . N

••

N

S

⊕

S

S

NPh S

S

150

151

N,N-Dialkylamino isocyanates 153, generated from 1,1-dimethyl-4-t-butyl-1,2,4triazolidine-3,5-dione-1,2-aminimide 152, react with aliphatic isothiocyanates to give the [3+2] cycloadducts 154 resulting from addition across the C N bond of the isothiocyanate 129 . ⊕

⊕

R 2N N O

N R 152

+ R2NN

C

O

+ MeNCS

O

R2N N S N Me 154

O 153

Some mesoionic compounds undergo a [3+2] cycloaddition reaction with isothiocyanates. For example, the thiazolium hydroxide system 155 gives a [3+2] cycloadduct 156, which eliminates COS to give the new mesoionic compound 157 130 . ⊕

C

PhN + PhNCS R

S 155

O

S NMe S NPh

⊕

PhN R

156

S N Me 157

190


In a similar manner, the dimethyl-1,2,3-triazolium hydroxide 158 reacts with phenyl isothiocyanate to give 6,7-dimethyl-5-oxo-2-phenyl-1,2,6,7-tetraazabicyclo[2.2.1.]heptane-3-thione 159 in 59 % yield 131 . N N ⊕ O + PhNCS N Me

O

S NMe NPh MeN N

158

159

The [3+2] cycloaddition reaction of imidazoline 3-oxides 160 with methyl isothiocyanate proceeds regio- and diastereoselectively to give tetrahydroimidazo[1.5b][1.2.4]oxadiazol2(1H)-thiones 161 in good yields 132 . Me N

R2 N O + MeNCS

RN R1

RN

S

N O

R1

160

161

R

R1

R2

Yield (%)

4-MePh 4-MeOPh

Ph Ph

Ph Ph

95 90

The reaction of ketazine derivatives 162 with ammonium thiocyanate in the presence of acetic acid produces the ‘criss-cross’ [3+2] cycloadduct 163 in 90 % yield 133 .

S N

+ HNCS

N

HN

N

NH

N S

162

163

The [3+2] cycloaddition reaction of 1,3,4-oxadiazol-2-ylhydrazones 164 with aryl isothiocyanates affords 1,3,4-thiadiazolines 165 134 . N N

N N Ar

O

NHN

CR2

+ RNCS

Ar

O RN

164

N NH R2 S 165

2-Carbon Cumulenes

191

The dithioles 166 undergo a [3+2] cycloaddition reaction with isoselenocyanates to give the dithia-1-selenapentalenes 167 135 . Ph CHPh

Ar S

NHR

Ar

+ RNCSe

S 166

S

S 167

Se

A similar reaction of the heterocycle 168 with two equivalents of 4-methoxyphenyl isoselenocyanate affords the tetrazathiapentalene 170. The initially formed 1:1 cycloadduct 169 eliminates methyl isothiocyanate, followed by reaction with the second equivalent of the isoselenocyanate 136 . MeN S

S

MeN

N

N

+ ArNCSe

S

168

S N

NAr N

ArN Se

Se

S N

169

NAr N

Se

170

The strained 3,3,6,6-tetramethyl-1-thia-4-cycloheptyne 171 reacts with excess methyl isothiocyanate to give the spiro compound 172 in 60 % yield 137 . S S + 3 MeNCS

S

S

171

NMe

S N N Me Me 172

A ‘criss-cross’ [3+2] cycloaddition involving isothiocyanates is observed with gold complexes 173 to give 174 138 . Ph2 C6F5AuP H Ph2(Me)P

173

+ 2 RNCS

Ph2(Me)P RN

Ph2 P S Au S P

NR Au(C6F5)2 P(Me)Ph2

174

[4+2] Cycloadditions 1- or 2-Isocyanatobutadienes undergo the Diels–Alder reaction with tetracyanoethylene and dimethyl acetylenedicarboxylate to give the expected cycloadducts 139 . The isothiocyanato groups do not participate in the reaction. Likewise, isoselenocyanato groups attached to butadienes do not participate in their Diels–Alder reactions with dimethyl acetylenedicarboxylate or maleic anhydride 140 . Carbonyl-, thiocarbonyl- and imidoyl isothiocyanates undergo [4+2] cycloaddition reactions functioning as the diene component, but examples of phenyl isothiocyanate participating as a dienophile are also known. For example, the imidoyl isothiocyanates 175 react with tertiary enamines (R2 = H, R3 = NR2 ) and ketene O,O-acetals (R2 = R3 = OEt) to

192


give [4+2] cycloadducts 176 141 . S

S RC(

NR1)NCS + CH2

CR2R3

N

N R

N R1

R2R3

R

175

N R1

R2R3

176

In a similar reaction, ethylthiocarbonyl isothiocyanate reacts with diphenylketene to give the [4+2] cycloadduct. Thiocarbamoyl isothiocyanates react with ketenes and ketenimines in a similar fashion (see Chapter 4, Sections 4.1 and 4.3) 142 . The addition of phenylcarbonyl isothiocyanate to a variety of dienes to give the 1,2,3,6tetrahydropyridine derivatives 177 occurs at room temperature over a period of 6 to 7 months – not exactly a click reaction 143 . NCOPh + PhCONCS S 177

Also, 2,4-diphenyl-1,3-diazabutadiene 178 (R = 4-MePh, Bz) reacts with isothiocyanates to give the triazinethione derivatives 179 144 . R Ph

R N

Ph

N + RNCS

N

N

S NR

Ph

Ph

178

179

The α-oxoketene 180, generated on heating a mixture of the precursor and phenyl isothiocyanate at 120 ◦ C, is intercepted by the isothiocyanate to give the oxazinone derivative 181 in 29 % yield 145 . O

R

O •

O

+

O

O

O

N NR

• S

180

S

O 181

Another example of an isothiocyanate participating in a [4+2] cycloaddition reaction as a dienophile is the formation of the tetrahydroquinazoline derivative 183 from isatoic anhydride 182 and methyl isothiocyanate 146 . O O N H 182

O

O • O

+

NMe

MeNCS N H

NH 183

S

2-Carbon Cumulenes

193

The dimerization of carbonyl-, thiocarbonyl-, imidoyl- and thiocarbamoyl isothiocyanates proceeds in a [4+2] cycloaddition reaction (see Section 3.3.2.2). Carbonyl isothiocyanates also readily undergo [4+2] cycloaddition reactions with aliphatic and aromatic azomethines, the former being considerably more reactive. For example, phenylcarbonyl isothiocyanate reacts with benzylidenemethylamine 184 to give a [4+2] cycloadduct 185 147 . S PhCONS

+

PhCH

N

NMe Ph

NMe Ph

O 185

184

This reaction proceeds especially well with azomethines having electron donating substituents in the aromatic ring. Azomethines with electron withdrawing substituents afford mixtures of 1:1 and 2:1 cycloadducts 148 . 2:1 cycloadducts are also obtained in the reaction of phenylcarbonyl-, ethoxycarbonyl-, imidoyl- and arenesulfonyl isothiocyantes with benzylidenemethylamine 149 . Carbamoyl isothiocyanates react with azomethines in the isomeric thiocarbamoyl isocyanate form 186 (X = NMe2 ) to give the [4+2] cycloadducts 187 149 . O XCONCS

XCSNCO

+

PhCH

N

NR

NR

X 186

S

Ph

187

Arylcarbonyl isothiocyanates react with N,N-disubstituted hydrazones 188 to give 1,3,5oxadiazine derivatives 189 149 . S PhCONCS

+

R2C

N–N(Me)Ph

N Ph

188

N O 189

N(Me)Ph

R2

Some monosubstituted acetone hydrazones 190 react with phenylcarbonyl isothiocyanate to give the oxatriazepine derivatives 191 150 . S PhCONCS

+

Me2C

N

N–NHR Ph

190

R N NH

O 191

Thiocarbamoyl- 151 and imidoyl isothiocyanates 77 react with phenyl isothiocyanate and carbodiimides to give the [4+2] cycloadducts. In the reaction of substituted N-(trimethylsilyl) imines with isothiocyanates an intermediate 192 is formed, which undergoes a [4+2] cycloaddition reaction with an azodicarboxylate

194


to form 1,2,3,5-thiatriazines 193 152 . R1 R1CH

NSiMe3

+

R1

N

+

PhNCS PhN

RN

NR

S

HN PhN

S

NR NR

SiMe3 192

193

Azetidines 194 react with isothiocyanates in the presence of bis(benzonitrile)-palladium to give tetrahydrothiazin-2-imines 195 in a [4+2] polar cycloaddition reaction 153 . CO2 NR1 194

R2

CO2R2 +

ArNCS

S N R1 195

NAr

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2-Carbon Cumulenes 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153.

197

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3.3.3 3.3.3.1

Carbodiimides, RN C NR Introduction

Carbodiimides are a unique class of reactive organic compounds having the heterocumulene structure R–N C N–R. They can be formally considered to be the diimides of carbon dioxide and they are closely related to the monoimides of carbon dioxide, the isocyanates. The substituent R can be alkyl, aryl, acyl, aroyl, imidoyl, or sulfonyl, but nitrogen, phosphorous and metal-substituted carbodiimides are also known. The unsubstituted carbodiimide is isomeric with cyanamide, H2 NCN. Also, monosubstituted carbodiimides exist only in the isomeric cyanamide structure. The first synthesis of carbodiimides was reported by Weith in 1873 1 . However, they were already synthesized by Hinterberger 2 and Zinin 3 in 1852. These authors did not

198


recognize their structure. Carbodiimides are exceedingly useful compounds in organic synthesis. Of particular significance is their use as dehydrating agents in the synthesis of β-lactam antibiotics, nucleotides and peptides. In 1953, Khorana and Todd 4 reported the use of carbodiimides, especially dicyclohexylcarbodiimide, in the synthesis of ortho- and pyrophosphate esters. The use of carbodiimides in the synthesis of peptides was reported by Sheehan and Hess in 1955 5 . Sheehan and Henry-Logan used dicyclohexylcarbodiimide in the total synthesis of penniciloic acid in 1957 6 . Merrifield received the Nobel Price in 1985 for the synthesis of polypeptides using polymeric substrates 7 . Dicyclohexylcarbodiimide (DCC) is used in this automated stepwise synthesis of polypeptides to activate the carboxyl group. The Merrifield method allows the synthesis of polypeptides, such as ribonuclease A, consisting of 124 amino acids. Oligonucleotides are also synthesized using a carbodiimide in the automated condensation step 8 . Another useful synthetic method for the synthesis of complex heterocyclic compounds is the aza–Wittig reaction, involving carbodiimides as intermediates 9 . Carbodiimides have also found utility as agricultural chemicals and pharmaceutical intermediates. For example, N-arenesulfonyl-N -alkylcarbodiimides are precursors of the antidiabetic sulfonyl ureas 10 . Sulfonylureas are also very potent herbicides. The chemistry of the diimides of carbon dioxide is not as well understood as the chemistry of the monoimides of carbon dioxide, the isocyanates. However, from the data available, one can conclude that carbodiimides react very much like isocyanates, especially in their cycloaddition reactions. For symmetrically substituted carbodiimides the polarity of the molecules is as shown in the following. RN−–C+

NR

RN

C

NR

RN

C+–N−R

In asymmetrically substituted carbodiimides, electronic as well as steric factors determine which of the two C N bonds becomes involved in cycloaddition reactions. In N-alkylN -arylcarbodiimides the reactions proceed across the aliphatic substituted C N bond. In N-methyl-N -t-butylcarbodiimide the cycloaddition reactions proceed across the less sterically hindered C N bond. The stability of aliphatic carbodiimides in which primary alkyl groups are attached to the nitrogen is limited; in contrast, diisopropyl-, dicyclohexyl and di-t-butylcarbodiimides are indefinitely stable. Also, N-methyl-N -t-butylcarbodiimide is a stable compound. Review articles on carbodiimides were published by Khorana in 1953 4 , by Kurzer and Douraghi-Zadeh in 1967 11 , by Mikolajczyk and Kielbasinski in 1981 12 and by Williams and Ibrahim in 1981 13 . Carbodiimides containing silicon, germanium, tin and lead substituents were reviewed by Gordetsov and coworkers in 1982 14 , N-functionalized carbodiimides by Vovk and Samarai in 1992 15 and polycarbodiimides by Pankratov in 1993 16 . My recent book describes the chemistry and technology of carbodiimides 17 . A review on the synthesis of heterocycles by the aza–Wittig reaction appeared in 1991 18 . 3.3.3.2

Dimerization Reactions

Aliphatic carbodiimides undergo rapid dimerization with tetrafluoroboric acid at room temperature to give salts of the cyclodimers 1. Neutralization with dilute sodium hydroxide or better filtration through basic Al2 O3 afford the shown 1,3-dialkyl-2,4-bisalkylimino-1,3-

2-Carbon Cumulenes

199

diazetidines 2 19 . ⊕

2 RN

C

NHR BF4

RN

NR

NR

RN

NR

RN

NR

RN

1

2

R

Yield (%)

n-Pr i-Pr C6 H11

70 90 95

Salts of aliphatic carbodiimide dimers are also obtained in the reaction of carbodiimides with dimethyl sulfate. The cyclic dimer of dibenzylcarbodiimide was isolated in low yield from the distillation residue 20 . Diazetidines 4 are also obtained in the reaction of 1,2,4triazineiminophosphoranes 3 with aryl isocyanates (yields: 55–76 %) 21 . Reaction of the diazetidines with amines affords pentasubstituted biguanides 22 . Me

Me

O

N N

N–N

+

PPh3

N N

RNCO

SMe

R N

O

N–N

N–N N R

SMe

3

Me

O

N N

MeS

4

R

Yield (%)

4-Cl-Ph 3-Me-Ph 4-MeO-Ph α-C10 H7

75 75 76 67

The dimers are found to be the Z,Z-isomers 5, but small amounts of the E,E-isomers 6 are also formed. Theoretical considerations favor the formation of the Z,Z-isomers 23 . R N

Het

N

N N R 5

Me

O where Het = N

N N

MeS

Het

Het

R N N

N N R 6

Het

200


In the mono P-substituted carbodiimide 7 the dimerization proceeds across the alkyl substituted C N bond to give 8 24 . Ph2P(O)N 2 Ph2P(O)N

C

NR

NR

RN

7

NP(O)Ph2

8

The seven-membered ring pentamethylenecarbodiimide, generated in situ, also undergoes cyclooligomerization, and the cyclodimer could be isolated 25 . Likewise, tetramethyl1,3-diazahepta-1,2-diene undergoes oligomerization on attempted synthesis 26 . The seven-membered ring tricyclic carbodiimide 9, obtained in the thermolysis of tetrazolophenanthridene, is stable up to −40 ◦ C. Above this temperature it undergoes cyclodimerization to give 10 27 .

N

N N

N

N

N • 9

10

In contrast, the cyclic iminocarbodiimide 12, generated in the thermolysis of tetrazolo[1,5-c]-quinazoline 11, forms the ‘different-type’ dimer 13 28 . N

N N

N

N

11

N

•

N

N

N

N

Ph

N

N

Ph

Ph

N

N

12

Ph 13

The [2+2] cycloadducts derived from two different linear carbodiimides (mixed dimers) were first synthesized by Ulrich and coworkers in 1987 29 . For example, N-(4-dimethylaminophenyl)-N -methylcarbodiimide, acting as a nucleophile, reacts with N-(4-nitrophenyl)-N -isopropylcarbodiimide, acting as the electrophile, to form the cycloadduct 14 in 69 % yield. The reaction proceeds across the aliphatic substituted C N bonds, most likely involving a linear dipolar intermediate. Me2N

N

•

NMe

+

O 2N

N

•

Ni-Pr

Me2N N i-PrN

14

NMe N NO2

2-Carbon Cumulenes

201

Mixed dimers derived from macrocyclic carbodiimides and diphenylcarbodiimide are also reported. For example, the unstable 1,3-diazahepta-1,2-diene 15 (n = 4) was trapped with diphenylcarbodiimide to give the [2+2] cycloadduct 16 (n = 4). The larger ring cyclic carbodiimides also afford the [2+2] cycloadducts 16. These reactions proceed in quantitative yield 25 . N

N +

•

(CH2)

n

PhN

C

NPh

(CH2)

n

NPh N

NPh

N 15

16

n

M.p. (◦ C)

4 6 7 11

103–194 107–108 135–136 158–160

Also, intramolecular dimerization reactions of carbodiimides are known. For example, the dicarbodiimide 17 (R = H, Ph), generated from the corresponding bis(iminophosphoranes) and two equivalents of an aromatic isocyanate, undergoes an intramolecular dimerization reaction to give the tricyclic cyclodimers 18 in 50–61 % yield 30 .

CO2Et

S

N

R N

N

PPh3

+

CO2Et

S

2 R1NCO

N

PPh3

•

N

R N

•

NR1 NR1

17 CO2Et

S

N

R N

N

NR1 N R1

18

Dimers and trimers of N-ary-N -trifluoromethylcarbodiimides are obtained in their attempted synthesis 31 . N-p-Toluenesulfonyl-N -butylcarbodiimide, in the presence of pyridine, affords a dimer. A similar dimer is obtained from 4-chlorophenylsulfonyl-N -propylcarbodiimide 32 . The dimerization of diphenylcarbodiimide is catalyzed by tributylphosphine. In this manner, 1,3-diphenyl-2,4-diphenylimino-1,3-diazetidine 19 is obtained in 71 % yield on heating of the carbodiimide at 90 ◦ C in the presence of tributylphosphine for 22 h 33 . Heating of diphenylcarbodiimide at 165–170 ◦ C for 16 h in the absence of the catalyst afforded 43 %

202


of the dimer, indicating that the dimerization is a thermal process. PhN 2 PhN

C

NPh

NPh PhN

NPh 19

When tetrafluoroboric acid is added to aromatic carbodiimides, quinazolium salts are obtained, which on hydrolysis afford 3-aryl-2-arylamino-4-aryliminoquinazolines 20 19 . NHPh BF4

N PhN

C NPh

NHPh

N

NPh

NPh

⊕

NPh

NHPh 20

Heterocyclic substituted carbodiimides can undergo dimerization by a [4+2] cycloaddition process. For example, di-2-pyridylcarbodimide, generated in situ in the reaction of an iminophosphorane with CS2 and an isothiocyanate, affords the cyclodimer in 94 % yield (see Section 3.3.3.4) 34 . Two dimeric switter ionic five-membered ring cycloadducts 21 and 22 are formed on standing of N-t-butyl-N -N,N-dimethylaminocarbodiimide 35 . Heating of the dimers regenerates the monomers. ⊕

⊕

Me2N N 2 Me3C–N

C

N–NMe2

N

+

N

N

Me2N N Me2N–N

N

N

NMe2 21

3.3.3.3

22

Trimerization Reactions

Heating of diphenylcarbodiimide with N-methylhexamethyldisilazane affords the diphenylcarbodiimide trimer 23 36 . NPh 3 PhN

C

NPh

PhN

NPh

PhN

N Ph 23

NPh

The more reactive N,N -dimethylcarbodiimide undergoes trimerization on standing to give the cyclotrimer 24, which on heating at 160–170 ◦ C isomerizes to give the triazine derivative 25 37 . NMe2

NMe 3 MeN

C

NMe

NMe

MeN MeN

N Me 24

NMe

N

N Me2N

N 25

NMe2

2-Carbon Cumulenes

203

Because of the tendency of isocyanate terminated polycarbodiimides to crosslink on heating, most likely due to the formation of cyclic trimers, it was of considerable interest to utilize them in the construction of thermoset polymers. Thus, reacting polymeric MDI (PMDI) with a phospholene oxide catalyst affords low-density rigid open cell polycarbodiimide foams 38 . The generated carbon dioxide is used as the ‘blowing agent’. 3.3.3.4


[2+2] Cycloadditions Across carbon multiple bonds Diisopropylcarbodiimide reacts with 1,2bis(trifluoromethyl)acetylene to give the [2+2] cycloadduct 26, which undergoes ring opening to produce the linear adduct 27 39 . N–i-Pr

Pr-i–N CF3

CCF3 +

i-Pr–N

C

N–i–Pr CF3

i-PrN–C(CF3)–C(CF3)

CF3

26

CHN–i-Pr

27

The cobalt catalyzed cycloaddition reaction of diphenylcarbodiimide with disubstituted acetylenes affords the isomeric 2-imino-1,2-dihydropyridines 28 and 29 in a [2+2+2] cycloaddition raction 40 . R1

R 1

R1

R 2 RC

CR1

+

PhN

C

NPh

R1

R

+ R

N Ph 28

NPh

R

N Ph 29

NPh

The same reaction is observed using bis(triphenylphosphan)diphenlcarbodiimide as the catalyst 41 . In contrast, phenylacetylene reacts with diphenylcarbodiimide in the presence of iron pentacarbonyl to give the imidazoline derivatives 30 and 31 42 . NPh

PhN PhC

CH

+

PhN

C

NPh

PhCH

NPh NPh 30

PhN +

NPh NPh

PhCH O 31

The CO insertion product is obtained in low yield. A similar reaction is observed with diphenylbutadiyne and diphenylcarbodiimide 43 . When the [2+2] cycloadduct derived from bis(trimethylsilyl)carbodiimide and a zirconocene imide 32 is treated with diphenylacetylene a new metallacycle 33 is produced. Reaction of 33 with diisopropylcarbodiimide affords the six-membered ring metallacycle

204


34 in a [2+2+2] cycloaddition reaction 44 . NSiMe3

Me3SiN

PhC

+

CPh

N

Cp2Zr

N

Cp2Zr +

Ph

32

i-PrN

C

N–i–Pr

Ph 33

N

Cp2Zr i-PrN

Ph Ph

N-i-Pr 34

Eneyne carbodiimides 35 on heating or photolysis undergo an intramolecular cycloaddition reaction to give 6H indolo[2,3-b]quinolines 36 45 . R1

R1

•

N

N H 36

NR

35

N

In the photocyclization at room temperature yields of 91–95 % are obtained when R1 = 4-O2 NPh or 4-NCPh) 46 . The [2+2] cycloaddition of ketenes to carbodiimides affords 4-imino-2-azetidinones (βlactames) 37 in high yield. Aliphatic carbodiimides show higher reactivity in comparison to aromatic carbodiimides and the reaction proceeds across the aliphatic C N bond in N-alkyl-N -arylcarbodiimides 47 . Some of the cycloadducts obtained in this reaction are listed in Table 3.15. Table 3.15 Some cycloadducts derived from ketenes and carbodiimides O

RR1 RR1C

C

O

+

R2N

C

NR3

NR2

R3N 37

R

R1

R2

R3

F Cl Cl Me3 Si PhC(Me)2 Ph Ph Ph Ph

H H CN Br COOEt Ph Ph Ph Ph

i-Pr i-Pr C6 H11 i-Pr —a Me Et i-Pr t-Bu

i-Pr i-Pr C6 H11 i-Pr — t-Bu t-Bu i-Pr t-Bu

a

(-) Menthylcarbodiimide.

Yield (%)

Reference

40 65 88 90 74 70 71 88 75

48 49 50 51 52 47 49 50 49

2-Carbon Cumulenes

205

In the reaction of carbodiimides with chiral substituents with prochiral ketenes, βlactames are obtained in a highly diastereoselective manner 52 . In the [2+2] cycloaddition reaction of haloketenes with N-alkyl-N -trimethylsilylcarbodiimides the reaction proceeds across the alkyl substitutef C N bond to give the cycloadduct 38 53 . NSiMe3

RN RR1C

C

+

O

RN

C

NSiMe3

RR1

O 38

The [2+2] cycloaddition reaction proceeds via an ionic linear intermediate, such as 39, which can be intercepted when the reaction is carried out in liquid sulfur dioxide. For example, to a solution of diisopropylcarbodiimide in sulfur dioxide at −78 ◦ C, diphenylcarbodiimide is added and on warming and evaporation of the sulfur dioxide a 90 % yield of 1,1-dioxo-2-(N-isopropylimino)-3-isopropyl-5,5-diphenylthiazolidine 4-one, 40 is obtained 54 . NR RN C

NR

+

Ph2C

C

RN

O

C

O

NR O

RN

⊕

+

SO2

O

S Ph Ph

CPh2 39

O

40

In the reaction of ketene with carbodiimides in sulfur dioxide the five-membered ring thiazolidine 4-ones 41 are similarly obtained 55 . CH2 C

O

+

R1N

C

NR2

+

NR2 O

R1N

SO2

S

O

O 41

R1

R2

C6 H11 4-MePh 4-ClPh 4-MeOPh

C6 H11 PhCH2 4-ClPh 4-MeOPh

Yield (%) 57 70 68 60

Cyclic carbodiimides (n = 5, 6, 11) react with phenyl-, phenethyl- and diphenylketene to give the [2+2] cycloadducts in yields of >90 % 56 . From n = 5 and two equivalents of phenethyl- or diphenylketene the bis-adducts 42 are obtained in >90 % yield. O

•

N n

+

2

RR1C

C

O

N

R R1

N

R R1

(CH2)

n

N

O

(CH2)

42

206


The reaction of 1,3-diazacycloocta-1,2-diene and diphenylketene, both generated in situ, give the [2+2] cycloadduct 43 in 20 % yield 48 . N

N •

+

Ph2C

N

C

Ph2

O N

O

43

The mesoionic oxazol-5-one 44 is in equilibrium with an acylaminoketene, which undergoes a [2+2] cycloaddition reaction with diisopropylcarbodiimide to give the cycloadduct 45 in 63 % yield 57 . O

O

O ⊕

Ph

N Me 44

Ph

+

N Me

Ph

NR

RN

O

•

RN C

NR

N(Me)COPh

O

Ph

Ph 45

The reaction of the acyloxy ketenes 46 generated from mesoionic 1.3-dioxolium olates in situ with carbodiimides affords the [2+2] cycloadducts 47 in 90–96 % yield 58 .

O

Ar1 O

O

•

O

Ar1

R1N

O Ar2

O

+

R1N

C

NR1

OCOAr2

O

Ar1

Ar2 46

NR1

47

Pentacarbonyl(hydroxymethylcarbene)chromium (o) 48 reacts with dicyclohexylcarbodiimide to give an isonitrile complex 49 and a ketenimine 59 . [Me(OH)C]Cr(CO)5

+

RN

C

RNCCr(CO)5

NR

48

+

RN

C

CH2

49

[2 + 2] Cycloadducts are also obtained in the reaction of bis(trifluoromethyl)thioketene with carbodiimides (see Chapter 4, Section 4.2.) 60 . Across C N bonds The cycloaddition reactions of heterocumulenes across C N bonds are well known reactions 61 . For example, in the reaction of N-(4-methylphenyl)diphenyl imine 50 with diphenylcarbodiimide the four-membered ring [2+2] cycloadduct 51 is obtained 62 . NPh

PhN N

CH3 50

CPh2

+

PhN

C

NPh

Ph2

N

CH3

51

The reaction of carbodiimides with alkyl- or aryl isocyanates produces exclusively the 2imino-1,3-diazetidine-4-ones 52. In the case of N-alkyl-N -arylcarbodiimides the reaction

2-Carbon Cumulenes

207

proceeds across the aliphatic C N bond. In Table 3.16. some of the [2+2] cycloadducts derived from carbodiimides and isocyanates are listed. Table 3.16 [2+2] Cycloadducts derived from carbodiimides and isocyanates RN C

O +

R1N

C

NR2

R1N

NR2

NR

O 52

R

R1

R2

Me Me Me Ph Ph Ph 4-O2 NPh 4-O2 NPh

Me Me Me Me Me Me Me i-Pr

Ph 4-MeOPh 4-(Me2 N)Ph 4-MeOPh 4-MeOPh 4-(Me2 N)Ph 4-O2 NPh 4-O2 NPh

Yield (%)

Reference

28 48 71 88 85 68 90 86

29 29 29 29 29 29 29 29

p-Substituted N-aryl-N -alkylcarbodiimides undergo the fastest reaction when the substituent is Me2 N– > Me– > H– > O2 N–. The reaction of an aryl isocyanate is fastest when the p-substituent is O2 N–. Aliphatic isocyanates react considerably slower than aromatic isocyanates. Steric hindrance can also play a role in determining which C N bond participates in the [2+2] cycloaddition reaction. For example, in N-(4-dimethylaminophenyl)-N -phenylcarbodiimide addition occurs across the phenyl substituted C N bond, while in N-(4-dimethylaminophenyl)-N -2,6-dimethylphenylcarbodiimide reaction occurs across the 4-dimethylaminophenyl substituted C N bond. The [2+2] cycloaddition reaction of carbodiimides with isocyanates follows second-order kinetics. Since aromatic carbodiimides react slower than aliphatic carbodiimides, heating at 100–125 ◦ C facilitates the reaction of the former. Cyclic carbodiimides also undergo a facile [2+2] cycloaddition reaction with alkyland aryl isocyanates to give 53. With aryl isocyanates the reaction is exothermic and is completed within several minutes.

(CH2)

•

N n

N +

RNCO

(CH2)

n

N

NR N

O

53

n

R

4 5 6 7 11

4-O2 NPh Ph Ph Ph Ph

Yield (%)

Reference

70 100 100 100 100

63 25 25 25 25

208


The 2:1 Cycloadducts 54 derived from ethyl isocyanate and diethylcarbodiimide are obtained from ethyl isocyanate using bis(acetylacetonate) tin (ii) as the catalyst 64 . O EtNCO

+

EtN

C

EtN

NEt

NEt

O

NEt

N Et 54

Reaction of DCC with N-p-toluenesulfonyl-N -cyclohexylcarbodiimide affords a sixmembered ring 1:2-adduct 55 in 99 % yield 65 . NR NSO2R1

RN RN

C

NR +

2

R1SO

2N

C

NR2

R2N

NR2

N

SO2R1 55

The polar cycloaddition reaction of arenesulfonyl isocyanates with carbodiimides gives rise to the formation of cyclic six-membered ring 2:1 adducts 56 and 57 65 . NSulfonylcarbodiimide is generated in an exchange reaction as shown in the following reaction scheme. RSO2N

O

NSO2R

RSO2N

C

NR1

R1N

NR1

C

NR1

C ⊕

RSO2N O

NR1

N

R1N

+

O

NR1

NR1 R1N

C

C

R1N

O

NSO2R

NSO2R

O

N

O

SO2R

SO2R 56

57

The reaction of dicyclohexylcarbodiimide with chlorosulfonyl isocyanate affords two products depending on the mode of addition of the reagents. When the isocyanate is added to the carbodiimide the [2+2] cycloadduct 58 is obtained while addition of the carbodiimide to the isocyanate affords the cyclic six-membered ring adduct 59 66 . NR

RN C

NR +

ClSO2NCO

ClSO2N

O NR

RN

ClSO2N +

O

NR O

N

SO2Cl 58

59

2-Carbon Cumulenes

209

In the reaction of bis(trimethylsilyl)carbodiimide with phenyl isocyanate a similar sixmembered ring [2+2+2] cycloadduct 60 is obtained 67 . NSiMe3 Me3SiN

C

NSiMe3

+

Me3SiN

2 PhNCO

O

NPh O

N Ph 60

From bis(trimethylsilyl)-, bis(triethylgermanium)- or bis(tributyltin)carbodiimides with benzenesulfonyl isocyanate, cyclic 1:1 and 1:2 adducts are produced 68 . The 2:1 Cycloadducts 61 are also obtained in the reaction of isocyanate salts with carbodiimides 69 . O RR1C

⊕

N

R 2N

O SbCl6 +

C

C

RR

NCH2R3

1CHN

R3CH2N

NR2 NCH2R3

N R2 61

The reaction of phenylcarbonyl isocyanate with carbodiimides at low temperatures affords oxazetidine imines 62 by addition across the C O bond of the isocyanate group. RCON RCONCO +

R1N

C

NR2

O

R2N

NR1

62

R

R1

R2

PhCO PhCO 4-ClPh

t-Bu C6 H11 Ph

Me C6 H11 Ph

Yield (%)

Reference

81 54 72

70 69 69

Evidence for the proposed structures of the four-membered ring [2+2] cycloadducts is provided by the retroreaction of the N-methyl-N -t-butylcarbodiimide adduct 63, which affords t-butyl isocyanate rather than methyl isocyanate expected for the isomeric structure 70 . PhCON

O t-BuNCO

MeN 63

+

MeN C

NCOPh

N–t–Bu

There is considerable discrepancy in the literature regarding the structures of the cycloadducts derived from carbonyl isocyanates and carbodiimides. For example, Arbuzov and Zobova 71 claim that a cycloadduct, m.p. 132–138 ◦ C (dec.), derived from diphenylcarbodiimide and phenylcarbonyl isocyanate at 0 ◦ C, has a diazetidinedione structure. Based on our findings an oxazetidine structure is indicated. On heating of 62 the [4+2] cycloadducts 64 are obtained.

210


Tsuge and Sakai 72 obtained [4+2] cycloadducts when the reaction of arylcarbonyl isocyanates with carbodiimides is conducted in refluxing benzene. Fom phenylcarbonyl isocyanate and N-phenyl-N -2-methylphenylcarbodiimide mixtures of [4+2] cycloadducts are obtained. O +

RCONCO

R1N

C

NR1

N

NR2 R

NR2

O 64

R

R1

R2

Ph Ph Ph Ph Ph 4-O2 NPh

Ph Ph 4-ClPh 4-MeOPh 4-O2 NPh C6 H11

Ph C6 H11 C6 H11 C6 H11 C6 H11 C6 H11

a

Yield (%) —a 75 71 66.5 75 87

No yields were reported.

Phenylthiocarbonyl isocyanate reacts with carbodiimides to give the [4+2] cycloadducts 65 57 . From N-phenyl-N -cyclohexylcarbodiimide and phenylthiocarbonyl isocyanate two isomeric [4+2] cycloadducts are obtained. Aliphatic thiocarbonyl isocyanates react similarly to give [4+2] cycloadducts 73 . O PhCSN

C

O

+

RN

C

N

NR Ph

NR S 65

NR

The formation of [2+2] cycloadducts derived from isocyanate terminated MDI carbodiimide and MDI is commercially utilized to form a liquid MDI product. These types of cycloadducts are also present in polymeric MDI. The cycloaddition reaction of 4,5,6,7-tetrahydrobenzo-1,3-diazonine with phenyl isocyanate occurs across the aliphatic C N bond 25 . Across C O bonds The reaction of carbodiimides with aromatic aldehydes 66 affords isocyanates and benzylideneamines 67 in an exchange reaction 74 . RN

C

NR

+

R1CH

RN

O

C

O

+

66

RN

CHR1 67

However, an oxazole derivative 69 is obtained in 78 % yield in the reaction of 68 with benzaldehyde 75 . TsCH2N 68

C

NCPh3 +

PhCHO

Ts Ph

N O 69

NHCPh3

2-Carbon Cumulenes

211

The reaction of 1,3-diazadeca-1,2-diene 70 with hexafluroacetone affords a sixmembered ring 1:2 cycloadduct 71 25 . N

O

N •

+

N

(CF3)2C

O

O

N

CF3 CF3

CF3 CF3

70

71

Across C S bonds The [2+2] cycloaddition reaction of isothiocyanates with carbodiimides generally proceeds across the C S bond of the isothiocyanate to give the thiazetidine derivatives 72. However, in the reaction of methyl isothiocyanate with N-(4dimethylaminophenyl)-N -methylcarbodiimide a mixture of the thiazetidine derivative 72 and the isomeric iminodiazetidinethione derivative 73 is obtained. The structure of 73 was confirmed by X-ray crystallography 76 .

RN

C

S

+

R1N

C

NR2

R1N

NR2

+

••••

S

RN 72

73

Some of the cycloadducts derived from isothiocyanates and carbodiimides are listed in Table 3.17. Table 3.17 Cycloadducts derived from isothiocyanates and carbodiimides R

R1

R2

Me Ph 4-O2 NPh Ph2 P(S) Ph2 P(S)

4-Me2 NPh C6 H11 C6 H11 i-Pr C6 H11

Me C6 H11 C6 H11 i-Pr C6 H11

a

Yield (%)

72 M.p. (◦ C)

73 M.p. (◦ C)

Reference

48a 55 92 100 100

131–132 75–76 75–76 Oil 120–122

124–125 — — — —

76 76 77 78 78

Combined yield of 72 and 73.

Heating of the cycloadduct derived from 4-nitrophenyl isothiocyanate and dicyclohexylcarbodiimide causes cycloreversion to give the starting materials 77. In the reaction of phenylcarbonyl isothiocyanate and substituted phenylcarbonyl isothiocyanates, respectively, with carbodiimides the [4+2] cycloadducts 75 are usually obtained, but the [2+2] 74 is also formed when the reaction of DCC with phenylthiocarbonyl isothiocyanate is stopped at shorter reaction times 79 .

RCONCS

+

RN

C

S

NR

RN

N

+

NR

NR

S

RCON

R 74

O 75

NR

212


1-Thia-3-azoniabutatriene salts 76 react with carbodiimides to give the corresponding [2+2] cycloadducts 77 80 . NR1

R1N Me2NRC

N

C

S

R1N

+

SbCl6

C

NR1

S

N ⊕

76

C(R)NMe2

SbCl6

77

Dialkylaminothiocarbamoyl isothiocyanate reacts with carbodiimides to give [4+2] cycloadducts 81 . The [2+2+2] cycloadducts 79 are obtained in 23–51 % yields in the reaction of carbodiimide 78 with methyl- or benzyl isothiocyanate 82 .The structure of the [2+2+2] cycloadducts was determined by X-ray crystallography 83 . S Me2C(CSNMe2)N

C

+

NR

R1N

R1 NCS

NR1

S

NC(Me2)CSNMe2

N R

79

78

Heterocyclic isothiocyanates, such as 80, react with dicyclohexylcarbodiimide to give the expected [2+2] cycloadduct 81 84 . Me

NR

RN

N NCS

+

RN

C

Me

NR

N

S

N

S

S 81

80

Reaction of isoselenocyanates with carbodiimides also proceeds across the C Se bond to give the [2+2] cycloadducts 82 in very high yields (listed in Section 3.3.2.) 85 . RNCSe

+

R1N

C

NR1

R1N

NR1

Se

RN 82

The reaction of benzoylsulfene, generated in situ, with DCC gives a mixture of the [2+2] cycloadducts 83 and the [4+2] cycloadducts 84 86 .

RN

C

NR

+

PhCOCH

SO2

O

NR

RN

+ O2S

COPh

O S NR

Ph

83

O

NR

84

A cycloreversion reaction is observed in the reaction of the N-sulfinylamines 85 wiith carbodiimides to give the exchange products 87 . RN

C

NR + R1SO2N 85

S

O

R1SO2N

C

NR + RN

S

O

2-Carbon Cumulenes

213

In the reaction of N-sulfinyl-p-toluenesulfonamide with methyl-t-butylcarbodiimide, the reaction proceeds across the less sterically hindered C N group to give Nmethylsulfinylamine and N-p-toluenesulfonyl-N -t-butylcarbodiimide 70 . Carbon disulfide reacts with carbodiimides via a [2+2] cycloaddition across the C S bond and subsequent cycloreversion to give the isothiocyanates 86 88 . NR

RN RN

C

NR

+

S

C

S

2 RN

C

S

S

S

86

The reactions of the cyclic carbodiimides 87 (n = 4,5), generated in situ, with carbon disulfide result in the formation of the diisothiocyanates 88 in 23–28 % yields 63 . N

N +

•

(CH2)

n

S

(CH2)

CS2

SCN–(CH2) –NCS

n

N

N

n

S

87

88

Across other double bonds In the reaction of iminophosphoranes with carbodiimides [2+2] addition across the P N bond also occurs with simultaneous generation of the exchange products, which can undergo a [4+2] cycloaddition with the starting carbodiimide (see below). In the reaction of the P C N derivative 89 with diphenylcarbodiimide at −70 ◦ C the cycloaddition proceeds across the C P bond rather than the C N bond to give 90 89 . N–t-Bu

t-Bu–P t-BuP

C

N-t-Bu

+

PhN

C

NPh

NPh

PhN 89

90

The reaction of bis(trimethylsilyl)carbodiimide with the P N derivative 91 gives the [2+2] cycloadduct 92, which on long standing rearranges to the carbodiimide 93 90 . Me3SiN

P(

NSiMe3)NSiMe3

+

Me3SiN

C

NSiMe3

91 Me3SiN Me3SiN

P

NSiMe3

N(SiMe3)2 92

N(SiMe3)2

NSiMe3 Me3SiN

P

N

•

NSiMe3

N(SiMe3)2 93

Iminophosphoranes, such as 94, also undergo [2+2] cycloaddition reactions with carbodiimides. For example, reaction of 94 with diisopropylcarbodiimide gives the [2+2]

214


cycloadduct 95 91 . NR

RN NR1

Cl3P

+

RN

C

NR

NR1

Cl3P

94

95

Likewise, reaction of the cyclic dimer of Cl3 P NR (R = 2-F-Ph) with diisopropylcarbodiimide affords a 50 % yield of the cycloadduct 95 (R1 = 2-F-Ph) 92 . The trichloroiminophosphoranes catalytically metathesise C N bonds of carbodiimides via an addition/ elimination process. Carbodiimides also add to the B N bond in (CF3 )2 B NMe2 to give the unstable cycloadducts 96 which rearrange at 20 ◦ C to give the metallacycle 97 93 .

(CF3)2B

NMe2

+

RN

C

NR

(CF3)2B

⊕

NR

RN

NMe2

RN NMe2(CF3)2 ⊕

NR

(CF3)2B

96

97

In the reaction of Me2 N+ SO BF4 − 98 with aliphatic carbodiimides the initial [2+2] cycloadducts rearrange to give 1,2,4-thiadiazetidine salts 99 94 .

Me2

N+

S

O BF4 +

RN

C

⊕

NRBF4

RN NR

NMe2

OS

NMe2 BF4

RN

NR

OS

⊕

98

99

In contrast, diarylcarbodiimides react with 98 to give the heterocycles 100 95 . O O

S

S Me2N+

S

O BF4 +

RN

C

NRBF4

NR N H

N H

NMe2

98

NR BF4 NMe2

⊕

100

Also, metal imides, such as the pinacolate complex of iridium 101, undergo a [2+2] cycloaddition reaction with N,N -ditolylcarbodiimide to give the metallacycle 102 96 . Llr

NR1 +

C

NR Llr

101

NR

RN RN

NR1 102

The metallacycle undergoes a carbodiimide exchange reaction with a different carbodiimide 97 . Also, imino zirconocene complexes 103 undergo the [2+2] cycloaddition reaction

2-Carbon Cumulenes

215

with carbodiimides to give the metallacycles 104. Cp2Zr(THF)

NR

RN

NR1

+

RN

C

NR

NR1

Cp2Zr

103

104

Tropon-2-ylimino arsorane 105 reacts with diphenylcarbodiimide to give 106 98 . Ph N

O

+ N

PhN

C

NPh

NPh N Ph 106

AsPh

105

In the reaction of the titanium vinylmethyl derivative 107 with carbodiimides, the [2+2] cycloadduct 108, derived from addition across the Ti C bond, is obtained in high yields 99 .

Cp2Ti

NR

RN

Me

[Cp2Ti

C

CH2] +

RN

C

NR Cp2Ti

107

108

Carbodiimides also add to metal–carbon bonds in metalorganic compounds. For example, cyclopentadienyl iron dicarbonyl affords the [2+2] cycloadducts 109 with diphenyl-and dicyclohexylcarbodiimide 100 .

RN

C

NR

+

NR

RN

CpFe(CO)2

Cp O

Fe

CO

109

Also, pentacarbonyl(diphenylcarbene)tungsten 110 reacts with DCC or diisopropylcarbodiimide to give metathesis products, which may involve the [2+2] cycloadducts as intermediates 101 . (CO)5W

CPh2 + RN

C

NR

(CO)5W RN

Ph2 NR

(CO)5W

C

NR + RN

CPh2

110

Across single bonds (insertion reactions) The insertion reactions of carbodiimides with metal organic compounds proceed via a [2+2] addition across a single bond with subsequent rearrangement. Also, some carbon–hydrogen bonds participate in this reaction. In general, carbodiimides react faster than isocyanates and isothiocyanates, in this order 102 . Insertion of carbodiimides into metal–hydrogen, metal–halogen, metal–nitrogen, metal–oxygen and metal–sulfur bonds is known. Also, insertion of carbodiimides into carbon–hydrogen bonds has been reported.

216


Examples of insertion reactions include Grignard or alkyl lithium compounds which react with carbodiimides to give the formamidines 111 after hydrolysis 103 . PhN

C

NPh + PhMgBr

[PhN(MgBr)C(Ph)

NPh]

PhNHC(Ph)

NPh

111

The 1:1 reaction between the magnesium amide 112 (R = i-Pr) and diisopropylcarbodiimide affords dinuclear amidinate complexes 113 104 . R N Mg(NR2)2

+

RN

C

NR

R N Mg

R2N N R

112

NR2 N R

113

Amidino bridged mixed aluminum–magnesium complexes are obtained in the reaction of Al–Mg complexes with carbodiimides 105 . The aluminum amidinate complexes 114 are synthesized by addition of aluminum alkyls to aliphatic carbodiimides. Also, alkylation of carbodiimides with MeLi, followed by reaction with AlCl3 , affords aluminum amidinate complexes 115 106 . R N RN C

+

NR

AlMe3

Me

⊕

Me

Al

N R

Me

114

R N

NR Li+

Me

+

AlCl3

⊕

Me

NR

Cl Al

N R

Cl

115

Reaction of carbodiimides with organic aluminum complexes also affords insertion products 107 , and bis(trimethylsilyl)carbodiimide reacts with AlMe3 to give the insertion product Me2 Al(NSiMe3 )2 CMe 108 . Guanidinates and mixed amido guanidates of aluminum and gallium are obtained by carbodiimide insertion into Al and Ga amido linkages 109 . Diarylcarbodiimides also insert into B–Cl, B–OR, B–SR and B–NR2 bonds. Examples include insertion into BCl3 , RBCl2 and R2 BCl 110 . Sometimes, double insertion reactions occur. BCl3 reacts with two equivalents of carbodiimide to give 116. RN C

NR

+

BCl3

CIB[NRC( 116

NR)Cl]2

2-Carbon Cumulenes

217

Thioboronites 117 react with DCC to form an insertion product, which on hydrolysis gives the S-alkylisothioureas 118 111 . RN C

NR

+

[Bu2N(R)C(SBu)

Bu2BSBu

NR]

RNHC(SBu)

117

NR

118

Hydrosilanes 119 react with carbodiimides in the presence of palladium chloride by insertion into the Si–H bond to give N-silylformamidines 120 112 . RN C

NR

+

Et3SiH

Et3SiN(R)CH

119

NR

120

A similar hydrosilylation occurs using R2 SiH2 113 . Also, reaction of trimethylcyanosilane with carbodiimides in the presence of aluminum chloride affords the insertion product 121 114 . RN C

+

NR

Me3SiCN

Me3SiN(R)C(CN)

NR

121

Insertion into a Si–P bond is also observed. Reaction of alkylbis(trimethylsilyl)phosphanes 122 with alkylarylcarbodiimides affords the insertion product 123, which, depending on the substituents, can rearrange into a P C compound 124 115 . RP(SiMe3)2

+

RN

C

RP(SiMe3)C(

NR

122

NR)N(SiMe3)R

RP

123

C[N(SiMe3)R]2 124

Insertion reactions of carbodiimides are also observed with Sn–OR or Sn–NR2 bonds. For example, reaction of tributyltinmethoxide with diarylcarbodiimides affords the expected insertion product 125 116 . Bu3SnOMe

+

RN C

NR

Bu3SnN(R)C(

NR)OMe

125

Triphenylleadmethoxide also undergoes an insertion reaction with diarylcarbodiimides to give 126 117 . Ph3PbOMe

+

RN

C

NR

Ph3N(R)C(

NR)OMe

126

Titanium amides 127 and alkoxides also produce double insertion products 128 118 . Ti(NMe2)4 127

+

RN C

NR

(Me2N2)Ti[N(R)C(

NR)NMe2]2

128

The insertion products of diphenylcarbodiimide into Ti(O-i-Pr)4 carry out metathesis reactions at elevated temperatures by insertion of an equivalent of carbodiimide in a head to head fashion followed by an extrusion reaction 119 . Also, insertion into a Ti–C bond is observed in the reaction of CpTiMe3 with carbodiimides to form CpTiMe2 [NRC(Me)NR] 120 . Insertion into Ti–C bonds is also observed in the reaction of diisopropylcarbodiimide with imido titanium cations 121 . Carbodiimides also insert into Ta–N bonds in a mixed tantalium amido/imido complex 122 .

218


Pentacoordinated phosphoranes, such as 129, react with aliphatic carbodiimides to give hexacoordinated phosphorus amidinates 130 123 .

CF3PCl4

+

RN

C

NR

CF3 R N P Cl Cl N R Cl

129

Cl

130

Several metal amides Me3 MNMe2 131 (M = Si, Ge, Sn) undergo insertion of N-benzoylN -t-butylcarbodiimide to give 132 124 . Me3MNMe2 +

PhCON

C

N–t-Bu

PhCPN(MMe3)C(NMe2)

131

N–t-Bu

132

Thermolysis of 132 affords N–t-Bu–N -metaltrimethylcarbodiimide. Insertion of carbodiimides into Zr–C bonds is also observed 125 . Zinc bis-amides insert only one equivalent of carbodiimide to give zinc guanidate complexes 126 . Ruthenium, osmium and iridium hydrides insert N,N -di-p-tolylcarbodiimide into their metal–hydrogen bonds to give N,N -p-tolylformamidinato derivatives 127 . Organomercury derivatives react with carbodiimides similarly. For example, phenyldichlorobromomethyl mercury 133 reacts with carbodiimides to give the expected insertion product 134 128 . +

PhHgCCl2Br

RN

C

NR

PhHgN(R)C(

NR)CCl2Br

133

134

Bis-trimethylsilylmercury 135 reacts with carbodiimides to give the insertion products 136 129 . Hg(SiMe3)2

+

RN

C

RN(SiMe3)C(

NR

135

NR)HgSiMe3

136

R1 N

O

R1 N

+

O N R1 O 137

RN C

NR

O

The insertion of carbodiimides into copper halides may explain the catalytic effect of the copper salts on the reaction of carbodiimides with alcohols and amines 61 . Reaction of carbodiimides with malonates or acetoacetic esters affords the insertion products. For example, reaction of barbituric acids 137 and DCC in DMSO at 150 ◦ C gives the C–H insertion products 138 130 .

O N R1 O 138

NHR NHR

2-Carbon Cumulenes

219

O

O

Likewise, the malonic acid derivative 139 reacts with DCC to give the corresponding C–H insertion product 140 131 . O

O +

RN

C

NHR

NR

NHR

O

O

O

O 139

140

Acetoacetic esters 132 , acetylacetone 72 or malonic acid esters 133 react with carbodiimides to give amidines. Insertion of carbodiimides into cyclic anhydrides 141, catalyzed by a cationic hydroxy cluster affords the seven-membered ring insertion products 142 as shown for the reaction of the five-membered ring anhydrides 134 . O

O O

+

RN C

R N

NR

O

R1

R1 O

O

141

N R

142

R

R1

Yeild (%)

i-Pr i-Pr

H Ph

70 60

In a similar manner N,N-dialkyl-1,3-diazocine-2,4,8-triones are obtained from sixmembered ring anhydrides. In the reaction of 4-ethoxycarbonyl-5-phenyl-2,3-dihydrofuran-2,3-dione 143 with diisopropylcarbodiimide, insertion into the furan ring occurs to give the oxazepin-6,7-dione derivative 144 in 68 % yield 135 . O PhCO

O +

Ph

O

O

PhCO RN

C

O

O

NR Ph

143

N R

NR

144

The addition of the N-nitrourethanes 145 to carbodiimides also affords insertion products 146 136 . RN

C

NR + O2NNHCOOEt 145

EtOOCN(R)C(

NR)NHNO2

146

Insertion of di-t-butylcarbodiimide into organolanthanide complexes (La = Er, Y, Gd) to give organolanthanide amidinates is also observed 137 . Likewise, diisopropylcarbodiimide undergoes insertion into lanthanocene amides 138 . However, diisopropylcarbodiimide does not react with lanthanocene guanidate complexes 139 . In the reaction of Et2 Y(N-i-

220


Pr2 )2 with diisopropylcarbodiimide the double insertion product undergoes rearrangement reactions. [3+2] Cycloadditions The ring opening of three-membered ring heterocycles generates 1,3-dipolar species, which can be intercepted by one of the C N groups of carbodiimides. The more nucleophilic carbodiimides can act as catalysts in the opening of the threemembered rings. For example, alkylene oxides and carbonates react with carbodiimides to give imidazolidine-2-ones 147 most likely via rearrangement of the initially formed [3+2] cycloadduct 140 . RN

C

RN

+

NR

NR

O O 147

However, using BuSnI2 /PPh3 as catalyst in this reaction, the isomeric iminooxazolidines 148 are obtained in 80–85 % yield 141 . RN

C

RN

+

NR

O

O O 148

Vinyloxirans react with carbodiimides in the presence of Pd(dba)3 to give iminooxazolidines in high yields; better yields; in this reaction are obtained by using unsymmetrical carbodiimides 142 . The [3+2] cycloaddition reaction of vinyloxiran with carbodiimides in the presence of chiral palladium catalysts affords the cycloadduct 149 in 96 % yield (83% e,e) 143 .

R

+ O

PhN

C–NPh

R PhN

O NPh 149

In a similar manner, 2-vinylaziridine reacts with carbodiimides to give the [3+2] cycloadducts 150 in good yields 144 .

+ N R1

RN

C

NR

R1N

NR NR 150

2-Carbon Cumulenes

221

Also, vinylthiirane 151 reacts with carbodiimides in the presence of a palladium catalyst to give 1,3-thiazolidine derivatives 152 145 . NR + S

RN

C

NR

NR

S

151

152

R

Yield (%)

4-ClPh 4-BrPh

97 98

Vinyloxetanes 153 also undergo the palladium catalyzed cycloaddition reaction with carbodiimides to give 4-vinyl-1,3-oxazin-2-imine derivatives 154 146 . R O

NR1

+ R1N C NR1

O

NR1

O

153

154

R

R1

H H Me

Ph 4-MePh Ph

Yield (%) 98 94 83

1,2-Disubstituted aziridines 155 react with diarylcarbodiimides in the presence of bis(benzonitrile)palladium dichloride to give the [3+2] cycloadducts 156 in a regiospecific manner and in 40–94 % yield 147 . R

R + N R1

RN

C

NR

R1N

NR NR

155

156

When R2 = vinyl, the corresponding cycloadduct is obtained in high yield, using Pd(OAc)2 as the catalyst 148 . Also, vinylpyrrolidines 157 react with diarylcarbodiimides in the presence of palladium catalysts to give the insertion products 158 149 .

+

RN

C

NR

NR

N R1

N R1

157

158

NR

222


In contrast, 2-dimethylamino-3,3-dialkylaziridines react with carbodiimides to give the ionic [3+2] cycloadduct 159 which undergoes ring opening to form a new carbodiimide 160 150 . Me2N

N

N

NR

•

NR

N RN

C

NR +

NR

Me2N

NMe2

RN

159

160

Zirconoaziridines 161 react with carbodiimides via insertion into the Zr–C bond to give the metallacycle 162 125 . R2 Cp2Zr

R3N

+

C

NR3

R3N

NR3

Cp2Zr

N R1

N R1

161

R2

162

Likewise, 1-t-butyl-2-carbomethoxyazetidine 163 reacts with p-chlorodiphenylcarbodiimide in toluene at 130 ◦ C, in the presence of bis(benzonitrile)palladium, to give the tetrahydropyrimidine derivative 164 151 . CO2Et

CO2Et NR

+

NAr ArN

C

NAr N R 164

163

NAr

Since Alper and coworkers have shown that the dipolar insertion reactions of carbodiimides into three-membered ring aziridines can be extended to four- and five-membered ring nitrogen heterocycles, one wonders if these reactions may also occur with the corresponding oxygen heterocycles. The classical stable 1,3-dipoles, such as nitrones, diazo compounds and azides react with carbodiimides to form [3+2] cycloadducts. For example, the nitrones 165 react with diphenylcarbodiimide, but the obtained oxadiazolidines 166 rearrange to give triazolidinones 167 152 . NPh PhN R 2C

N(R)

165

O + PhN C NPh

R2

N R 166

O

R2

NR

PhN

NPh O 167

The reaction of carbodiimides with diazomethane 153 and diazoalkanes 154 affords triazole derivatives. For example, metal substituted diazomethanes 168 react with carbodiimides to

2-Carbon Cumulenes

223

give 5-amino-1H-1,2,3-triazoles 169 155 . NR RN RN

NR + R1R2C

C

N2

N

168

R1 R2

N 169

R

R1

R2

4-MePh 4-MePh 4-MePh

H H SnMe3

H SiMe3 SnMe3

Yield (%) 33 19 96

Alkyl diazoacetates react with diisopropylcarbodiimide to give oxazolines 156 . In the reaction of HN3 with dibutylcarbodiimide the [3+2] cycloadduct 170 is obtained 157 . NBu BuN BuN

C

NBu + HN3

N

N

NH

170

Ketenimine complexes react with carbodiimides to give [3+2] cycloadducts 171 in low yield 158 . NR RN W(CO)5N(C6H11)

C

C(OEt)Ph

+

RN

C

NR

EtO

NC6H11

Ph

W (CO)5 171

Bis(phosphino)carbodiimide 172 reacts with dimethyl acetylenedicarboxylate as a 1,3dipol to form the cycloadduct 173 in 92 % yield 159 .

R2P–N

C

N–PR2

+

MeOOC–C

C–COOMe

R2P

N

MeO2C 172

NPR2 CO2Me

173

Unstable, 1,3-dipoles can be generated in chemical reactions or by thermolysis. When these reactions are conducted in the presence of carbodiimides the expected [3+2] cycloadducts are formed. For example, generation of the diphenylnitryl imine 174 in the presence of diphenylcarbodiimide affords a spiro compound 175 as a result of the reaction

224


of the initially formed [3+2] cycloadduct with a second equivalent of the nitrile imine 160 . Ph

PhN

C

NPh

+

2 PhC

N–NPh

PhN

N NPh

PhN

NPh

N Ph 174

175

Nitrile oxides 176 also react with carbodiimides to give the [3+2] cycloadducts 177 161 . NR RN R1C(CI)

[R1C

NOH

N

O]

R1

O N

176

177

Azoniaallene salts, such as the in situ generated 178, react with carbodiimides to give 4,5-dihydro-5-imino-1H-1,2,4-triazolium salts 179, in 65–100 % yield (for more details, see Chapter 2, Section 2.5) 162 . R2 R1R2C(CI)N

NR3

[R1R2C

NR3 SbCI6] + RN

N

C

NR1 NR3

RN

NR

SbCI6

NR 178

179

2-Azaallenium salts, such as RC(Cl) N+ C(Cl)R SbCl6 , react with carbodiimides to give labile 2,2-dichloro-1,3,5-triazinium salts 180 163 .

RC(CI)

N+

C(CI)R SbCI6

+

R1N

C

R1N Cl

NR1

R

N

R

NR1

SbCI6

Cl 180

For more details, see Chapter 5, Section 5.2. Also, 1-oxa- and 1-thia-3-azoniabutatriene salts undergo this reaction (see Chapter 5, Sections 5.3 and 5.4). Likewise, 1,3-diaza-2-azoniaallene salts 181 undergo the [3+2] cycloaddition reaction with diisopropyl and dicyclohexylcarbodiimide to give 1,3,4,5-tetrasubstituted 4,5-dihydrotetrazolium salts 182 (see also Chapter 7, Section 7.2) 164 . NR RN ArN

N

NAr SbCI6 181

+

RN

C

NR

ArN

N 182

NAr

SbCI6

2-Carbon Cumulenes

225

Generation of the dipol 183 in the presence of a carbodiimide affords thiadiazolidines 184 165 . N MeN

MeN

S

RSO2N

S

+

R 1N

NR1

C

NR1

R1N MeN

N

S

RSO2N

RSO2N

183

184

Also, mesionic compounds, such as 185, undergo the [3+2] cycloaddition reaction with carbodiimides to give the new betaine 186 in 76 % yield (R = 4-MePh) 166 . Me N

CO2Et

N_

+

RN

C

Me N

NR

NH

N

185

O NR N

NHR

186

The anionic [3+2] cycloaddition of 1,3-diphenyl-2-azaallyl lithium 187 with DCC gives the cycloadduct 188, which reacts with another equivalent of DCC to give the final product 189 167 . NR

NR Li PhCH–N–CHPh

RN

RN +

RN

C

NR

187

Ph

N Li

Ph

Ph RN

188

Ph

N

NHR 189

Also, reaction of carbodiimides with thione S-imides 190 affords the [3+2] cycloadducts 191 in moderate yields 168 .

S

NTs + RN

C

S

S

NR

NR

NTs RN

RN

NTs

NR 190

191

[4+2] Cycloadditions The [4+2] cycloaddition reactions of carbodiimides with phenylcarbonyl isocyanate, phenylcarbonyl isothiocyanate and thiocarbamoyl isothiocyanate have been discussed above. In the dimerization reactions the functional carbodiimides react as both the diene and the dienophile. Unsaturated carbodiimides, generated in situ, can be trapped with N N bond- or C N bond-containing substrates. An example of carbodiimides reacting as azadienes in a [4+2] cycloaddition reaction is the intramolecular cyclization of 192, which forms the cycloadduct 193. The latter

226


rearomatized to give the isolated 1-amino isoquinoline derivatives 194 169 . NR1

NR1

•

R2

N Ph

NHR1 R2

N Ph

192

R2

N Ph

193

194

Several intramolecular cyclization reactions of unsaturated carbodiimides are known and examples are listed in Table 3.18. Table 3.18 Intramolecular cyclization reactions of unsaturated carbodiimides Carbodiimide

Cycloadduct

Reference

Ph EtO2C

•

N

RHN

NR

CO2Et

N

N

•

170

CO2R

CO2R NR

NHR

N

171 R

N

•

N

Me

NO2 N

N Ph

•

N

N H

R

172

Me

NO2 N

NR

N Ph

N

NHR

170

O

O NO2

MeN O

N

N Me

N

•

NR

NO2

MeN O

N Me

NHR

N

173

Me CO2Et N

Me

N

CO2Et N • NR • NR

N

NHR CO2Et

CO2Et CH

C

N

•

NR

174

N

NR

NHR N

N

175

2-Carbon Cumulenes

227

When the vinyl group on the aryl ring is separated by a methylene group, as in 195, rearrangement of the allyl to the vinyl group occurs to give 196, followed by electrocyclic ring closure reaction which produces 197 176 .

•

N

NAr

N

195

•

NAr

N

196

NHAr

197

The intermolecular version of the above reaction is the [4+2] cycloaddition of the metalsubstituted acetylene derivative 198 with diphenylcarbodiimide which affords 199 177 . PhNH PhN

C

NPh + Me3SnC

N

CN(Ph)Me Me3Sn

198

199

Also, vinyl carbodiimides react as azadienes in the [4+2] cycloaddition reaction. For example, reaction of the vinyl carbodiimide 200 with tetracyanoethylene affords the [4+2] cycloadduct 201 178 . NR

NR

•

N

N H

Ph

+ (NC)2C

C(CN)2

(CN)2 (CN)2

Ph Ar

H

Ar 200

201

Also, N-vinyl-N -phenylcarbodiimide reacts with dimethyl acetylenedicarboxylate to give the [4+2] cycloadduct, albeit only in 20 % yield 179 . Likewise, 202 undergoes the [4+2] cycloaddition reaction with ynamines at 0 ◦ C to give the [4+2] cycloadducts 203 in high yield 180 . NPh

• N

+ Me-C Ph

MeO2C

N

C-NEt2

NHPh Me

MeO2C

H

NEt2 Ph

202

203

The reaction of thiosalicylic acid 204 with two equivalents of carbodiimides may also involve a thioacylketene intermediate, which undergoes a [4+2] cycloaddition reaction with the second equivalent of the carbodiimide to give 205 181 . O + 2 RN SH 204

O

•

COOH C

NR

NR S

S 205

NR

228


o-Thiobenzoquinone methide 207, generated in the thermal ring opening of 206, react with diisopropyl- or dicyclohexylcarbodiimide to give the [4+2] cycloadducts 208 in 24–72 % yield 182 .

+ RN

S

C

NR

NR

S

206

NR

S 208

207

Also, reaction of 1,4-dipoles, such as 209, react with diphenylcarbodiimide to give the [4+2] cycloadduct 210 183 . S

S SMe + PhN

C

S

NPh N Me

N SMe Me 209

N Ph

NPh

210

Another example of an in situ generated 1,4-dipol is the reaction of 2,4-bis(diethylamino)cyclobutadiene 211 with diphenylcarbodiimide which affords the pyridine derivative 212 184 . NEt2 NEt2

EtO2C Et2N

CO2Et

EtO2C + PhN

C

NPh Et2N

CO2Et 211

N Ph

NPh

212

In numerous [4+2] cycloaddition reactions the diene, such as an α-oxoketene, is generated in situ and trapped by the carbodiimide. The functional ketenes are generated from diketene or from masked heterocyclic precursors. Also, o-substituted aromatic carboxylic acids are used as precursors for the functional ketenes. Diketene 213 reacts with carbodiimides to give 2,3-dihydro-2-imino-4-oxo-1,3-oxazines 214, most likely via a [4+2] cycloaddition sequence 185 . O

O

• + RN O 213

Me

O

C

NR

NR Me

O

NR

214

The masked α-oxoketene 215 reacts with carbodiimides via a [4+2] cycloaddition reaction to give 216. The reaction is conducted by heating the reagents at 120–130 ◦ C for

2-Carbon Cumulenes

229

10 min. At that temperature the α-oxoketene is generated. O R

O O

R1

+ R2N

C

R

NR2

NR2

R1

O

NR2

O

215

216

R

R1

R2

H H –(CH2 )3 –(CH2 )3

H Ph

C6 H11 C6 H11 i-Pr Ph

Yield (%)

Reference

81 86 76 92

186 183 187 187

In the reaction of the isonitroso Meldrum’s acid with carbodiimides only cyanoformamidines are obtained in quantitative yields 188 . However, ethyl 2-methylmalonate 217 on treatment with DCC generates the ketene intermediate which is simultaneously trapped with DCC to give the [4+2] cycloadduct 218 189 . O Me

EtOCOCH(Me)COOH + DCC

NC6H11

EtO

NC6H11

O 218

217

Acylketenes, 219, also react with two equivalents of carbodiimides to give the cycloadducts 220 190 . O

O

•

R

+ R2N

C

R

NR2

Cl

O

Cl

NR2 NR2

O

219

220

The reaction of dipivaloylketene 221 with diisopropyl- and phenylisopropylcarbodiimide in n-hexane affords solutions of the [4+2] cycloadducts 222 191 . O

•

R R

O

O

+ R1N

C

O NR1

R

NR2

R

O

O

NR2

222

221

R

R1

R2

Yield (%)

t-Bu t-Bu

i-Pr i-Pr

i-Pr Ph

98 50

230


In the absence of solvents, 2:1 spiroadducts 223 are obtained. O

•

2

R

+ R1N

C

NR1 O

R

NR2

R

O

R

O

O

O

R

O R2N

R O

O

223

R

R1

R2

Yield (%)

t-Bu t-Bu

Me i-Pr

Me Ph

76 45

In contrast, the dimer of dipivaloylketene 224 reacts with carbodiimides to give the [2+2] cycloadducts 225. A mixed dimer, obtained in the thermolysis of 4-pivaloyl- and 4-methoxycarbonyl-5-t-butylfuran-2,3-dione, also undergoes the [2+2] cycloaddition with dialkylcarbodiimides. O

O O

R O

R1

O

O

•

O

R2

3N

+ R

C

3

NR

O

R

R1

O R2OC R3N

O

224

O NR3

225 1

R

R

t-Bu t-Bu

t-Bu t-Bu

R

2

Me t-Bu

R3

Yield (%)

Me i-Pr

76 58

1-Aryl-2-quinoxalinyl(aroyl)ketenes 226, generated in the thermolysis of 3-aroyl-2-(2aryl-4,5-dioxo-4,5-dihydro-3-furyl)quinoxalins, react with DCC to give the [4+2] cycloadducts 227 in 92 % yield 192 . N

N

Ar

N

O

+ DCC

NC6H11

N

•

O

NC6H11

O O 227

226

N-acylketene imines 228 also react with carbodiimides to give the [4+2] cycloadducts 229 in good yields 193 . NCOR Me EtOOCC(Me)

C

EtO 228

NC6H11

NCOR + DCC O 229

NC6H11

2-Carbon Cumulenes

231

The 2,3-furanedione derivative 230 reacts with diisopropylcarbodiimide to give the [4+2] cycloadducts 231 derived from a rearranged imino derivative 194 . Ph

O O

Ph Ph

C

+ RN O

O

O

NR

O

N O R Ph

RN

O

230 Ph

NR O

Ph Ph

O

O

O

RN N N R Ph H 231

RN

O

Similar adducts are produced from other cyclic diketones (see Table 3.19). Table 3.19 [4+2] Cycloadducts derived from carbodiimides and cyclic diketones Dione

Carbodiimide

Cycloadduct

Reference

Ph O

Ph

O

O

O

O

O

Ph

MeN

N N O MePhMe

MeN C NMe

195

Ph

O

Ph Ph

O

O

N

i-PrN

Ph

O

RSO2N O

Ph O

O

Ph

O

O

i-Pr

i-PrN C N-i-Pr

RSO2N

Ph

O

i-PrN

O

196 O O

N

i-PrN

i-Pr

i-PrN C N-i-Pr

196

Ph O

Ph

S

O

Ph S

O

MeN

MeN C NMe

O N N O MePhMe

196

Unsaturated carbodiimides 232, generated in situ, can be trapped via an intermolecular [4+2] cycloaddition reaction using azo esters or imines to form 233 and 234,

232


respectively 197 . CO2Et

O

N

MeN O

O

MeN

N Me

N

NCO2Et NHR

233

O

N Me

N

•

NR O H

232

Ph

MeN O

NPh N Me

N

NHR

234

Also, -2-amenates are obtained by cyclization of the carbodiimides generated in situ, from a thiourea 198 .

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25.

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2-Carbon Cumulenes 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174.

235

D.K. Kennepohl, B.D. Santarsiero and R.G. Cavell, Inorg. Chem. 29, 5081 (1990). S. Matsuda, K. Itoh and Y. Ishii, J. Organomet. Chem. 69, 353 (1974). J.A. Tunge, C.J. Czerwinski, D.A. Gately and J.A. Norton, Organometallics 20, 254 (2001). M.P. Coles and P.B. Hitchcock, Eur. J. Inorg. Chem. 2662 (2004). L.D. Brown, S.D. Robinson, A. Sahajpal and J.A. Ibers, Inorg. Chem. 16, 2728 (1977). D. Seyferth and R. Damrauer, Tetrahedron Lett. 189 (1966). G. Neumann and W.P. Neumannn, J. Organomet. Chem. 42, 293 (1972). B.S. Jursic, F. Douelle and E.D. Stevens, Tetrahedron 59, 3427 (2003). A. Stephan, Monatsh. Chem. 97, 695 (1966). W. Traube and A. Eyme, Chem. Ber. 32, 3176 (1899). W.E. Tischtschenko and N.V. Koshin, Zh. Obshch. Khim. 4, 1021 (1934). F. Cherioux and G. Süss-Fink, Tetrahedron Lett. 43, 6653 (2002). H.A.A. El-Nabi and G. Kollenz, Monatsh. Chem. 128, 381 (1997). H.M. Yusuf, Karachi Univ. J. Sci. 5, 59 (1977); Chem. Abstr. 89, 107 936 (1978). J. Zhang, R.Y. Ruan, Z.H. Shao, R.F. Cai, L.H. Weng and X. Zhou, Organometallics 21, 1420 (2002). J. Zhang, R. Cai, L. Weng and X. Zhou, Organometallics 23, 3303 (2004). J. Zhang, X. Zhou, R. Cai and L. Weng, Inorg. Chem. ASAP, Article 10, 1021 (2005). K. Gulbins and K. Hamann, Chem. Ber. 94, 3287 (1961). A. Baba, I. Shibata, K. Masuda and R.H. Matsuda, Synthesis 1144 (1985). C. Larksarp and H. Alper, J. Org. Chem. 63, 6229 (1998). M. Ragunath and X. Zhang, Tetrahedron Lett. 46, 8213 (2005). D.C.D. Butler, G.A. Inman and H. Alper, J. Org. Chem. 65, 5887 (2000). C. Larksarp, O. Sellier and H. Alper, J. Org. Chem. 66, 3502 (2001). C. Larksarp and H. Alper, J. Org. Chem. 64, 4152 (1999). J.O. Baeg and H. Alper, J. Org. Chem. 57, 157 (1992). D.C.D. Butler, G.A. Inman and H. Alper, J. Org. Chem. 65, 5887 (2000). H.B. Zhou and H. Alper, Tetrahedron 60, 73 (2004). E. Schaumann and S. Grabley, Liebigs Ann. Chem. 290 (1981). J.O. Baeg, C. Bensimon and H. Alper, J. Org. Chem. 60, 253 (1995). M. Komatsu, Y. Ohshiro and T. Agawa, J. Org. Chem. 37, 3192 (1972). R. Rotter and E. Schandy, Monatsh. Chem. 58, 245 (1931). P.K. Kadaba, B. Stanovnik and H. Tisler, Adv. Heterocyclic Chem. 37, 304 (1984). M.F. Lappert and J.S. Poland, J. Chem. Soc. (C) 3910 (1971). J. Drapier, A. Feron, R. Warin, A.J. Hubert and P. Teyssie, Tetrahedron Lett. 559 (1979). R. Stolle, Chem. Ber. B 55, 1289 (1922). R. Aumann, E. Kuckert and H. Heinen, Angew. Chem. 97, 960 (1985). G. Veneziani, R. Reau, F. Dahan and G. Bertrand, J. Org. Chem. 59, 5927 (1994). R. Huisgen, R. Grashey, R. Kunz, G. Wallbillich and E. Aufderhaar, Chem. Ber. 98, 2174 (1965). T. Sasaki and T. Yoshioka, Bull. Chem. Soc. Jpn 42, 258 (1969). Q. Wang, A. Amer, S. Mohr, E. Ertl and J.C. Jochims, Tetrahedron 49, 9973 (1993). A. Ismail, A. Hamed, M.G. Hitzler, C. Troll and J.C. Jochims, Synthesis 820 (1995). W. Wirschun, M. Winkler, K. Lutz and J.C. Jochims, J. Chem. Soc., Perkin Trans. 1 1755 (1998). R. Neidlein and K. Salzmann, Synthesis 52 (1975). J. Valenciano, E. Sanchez-Pavan, A.M. Cuadro, J.J. Vaquero and J. Alvarez-Builla, J. Org. Chem. 66, 8528 (2001). I. Kaufmann and R. Eidenschink, Chem. Ber. 110, 651 (1977). T. Saito, I. Oikawa and S. Motoki, Bull. Chem. Soc. Jpn 53, 2582 (1980). P. Molina, M. Aljarin and A. Vidal, J. Org. Chem. 55, 6140 (1990). P. Molina, P.M. Fresneda and A. Alacorn, Tetrahedron Lett. 29. 379 (1988); P. Molina, A. Arques, P.M. Fresneda, M.V. Vinader, M. De la Concepcion Foces-Foces and F.H. Cano, Chem. Ber. 122, 307 (1989). T. Saito, H. Ohmori, E. Firuno and S. Motoki, J. Chem. Soc. Chem. Commun. 22 (1992). P. Molima, M. Alajarin and A. Vidal, J. Chem. Soc. Chem. Commun. 1277 (1990). P. Molina and M.J. Vilaplana, Synthesis 474 (1990). P. Molina, M. Alajarin and A. Vidal, Tetrahedron Lett. 32, 5379 (1991).

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3.4 Center Carbon Phosphorallenes, P C P 3.4.1 Introduction The first pentavalent center carbon phosphorallene, hexaphenylcarbodiphosphorane (Ph3 P C PPh3 ), was synthesized by Ramirez and coworkers in 1961 1 . The trivalent center carbon phosphorallenes, RP C PR, were first synthesized in 1984 2 . Even carbodiphosphoranes with heterosubstituents have been synthesized recently 3 . Cyclic tetraphenylcarbodiphosphorane derivatives have also been synthesized, but only the seven-membered ring is stable at room temperature 4 . A phosphaketene RP C O (R = 2,4,6-tris-t-butylphenyl) 5 and a 1,3-phosphaazaallene RP C N-t-Bu 6 are stable compounds, while the phosphathioketenes, RP C S (R = t-butyl or tris-t-butylphenyl) are only obtained as dimers. Phosphoarsaallenes, P C As and diarsaallenes, As C As, are also known 7 . 3.4.2 Dimerization Reactions The trivalent phosphaketenes and phosphathioketenes are usually not stable as monomers because they undergo rapid dimerization, even at low temperatures. For example, t-butylphosphaketene, t-BuP C O, is only stable below −60 ◦ C. Above this temperature,

2-Carbon Cumulenes

237

dimerization to form symmetric dimers occurs. The addition proceeds across the P C bond 8 . In contrast, 2,4,6-tris-t-butylphenylphosphaketene 1, is stable at room temperature. 2,4,6-Tris-t-butlyphenylphosphathioketene dimerizes across the C S and the P C bonds to give an unsymmetrical cyclodimer 2 9 . RP RP(SiMe)2 + Cl2C

S

[RP

C

S]

S

RP S

1

2

In contrast, the metal thioketene 3,[M] = η5 -C5 Me5 (CO)2 Fe, generated in situ, undergoes dimerization by a [3+2] sequence to form the five-membered heterocycle 4 10 . P [M]- C

S

C

[M]P(SiMe3)2 + CS2 [M]P

P C-S[M] S

3

4

Photolysis of 5 is a convenient synthetic method to generate the 1.3-diphosphaallenes 6, which undergo dimerization across two P C bonds to give the cyclodimer 7 14 . PR

RP

RP RP

S

PR

C

PR

RP

S

PR 5

6

7

Sterically hindered 1,3-diphosphaallenes, such as 6, are air- and moisture-stable and can be purified by column chromatography. Less hindered 1,3-diphosphaallenes are isolated as the ‘head-to-tail’ dimers. The 1,3-phosphaazaallenes, PhP C NR, 8 (R = 2-FPh, 2-ClPh, 2,3-Cl2 Ph) generated fom PhP(SiMe)2 and isocyanide dichlorides, undergo dimerization across the P C bond to give the four-membered ring diphosphetanes 11 . A mixture of E- and Z-isomers 9 and 10 is usually obtained. R N PhP(SiMe)2 + RN

CCl2

[PhP

C

NR]

+

PhP N

8

R

PPh

9

R

N

PPh

PhP N

R

10

When the group on phosphorus is the small ethyl group, two trimers are also obtained 12 . In the presence of (Ph3 P)4 Pd as the catalyst the dimerization proceeds across both the P C and the N C bonds 13 . Some highly sterically hindered 1,3-phosphaazaallenes are stable as monomers 14 . 1,3-Germaphosphaallenes, Mes2 Ge C PAr,11, dimerize above −40 ◦ C to give cyclodimers resulting from addition across the Ge C bonds, 12 and 13, and across the

238


Ge C and the P C bond, 14, in a ratio of 12:88 15 .

Mes2Ge

C

PAr

Mes2Ge

PAr

Ar

GeMes2

P

PAr

+ Mes2Ge

Mes2Ge +

GeMes2

P

PAr

Mes2Ge PAr

Ar

11

13

12

14

Immediately after reaction, only dimer 12 is obtained. After one week at room temperature in solution a mixture of 12 and 13 (ratio: 48:52) is formed, corresponding to the thermodynamic equilibrium 16 . 1,3-Phosphasilaallenes, Tip(Ph)Si C PAr, 15, similarly afford the head-to-tail dimers 16 and the dimer resulting from addition across one Si C and one P C bond, 17.

Tip(Ph)Si

C

Si

PAr

Si

PAr

PAr

+

Si

Si

ArP

PAr

16

15

17

In 17, the Tip groups are in the cis-position of the four-membered ring. 3.4.3 Cycloaddition Reactions 3.4.3.1


In the reaction of 1,3-diphosphaallenes 18 with dichlorocarbene the initial [2+1] cycloadduct 19 rearranges to give the final product 20 17 . Cl

ArP

C

Cl

Cl

P

P

PAr + :CCl2

Ar ArP

PAr Ar

19

18

3.4.3.2

Cl

20


The reaction of phosphaketene with styrene proceeds across the P C bond to give the [2+2] cycloadduct 21. In contrast, reaction of phosphaketene with diphenylacetylene proceeds across the C O bond to form the [2+2] cycloadduct 22 20 . PhCH

CH2

O

RP

Ph

21 RP

C

O RP

PhC

CPh

O

Ph

Ph

22

2-Carbon Cumulenes

239

The phosphaketenes 23 (R = 2,4,6-tris-t-BuPh), react with diphenylmethylenetriphenylphosphorane to give a 1-phosphaallene 24 in 30 % yield 18 . O + Ph3P

C

RP

CPh2

RP

CPh2 + Ph3PO

C 24

23

In the reaction of ArP C O with platinum and 26, respectively, are obtained.

19

or iridium 13 compounds, cycloadducts 25 PAr

LnPt

PtLn

ArP O

25 ArP

C

O PAr

LnIr

IrLn

ArP O

26

The [2+2] cycloaddition of 1,3-phosphaazaallenes with phosphaalkenes proceeds across the C N double bond of the 1,3-phosphaazaallene to give the [2+2] cycloadduct 27 20 . ArP ArP

C

NPh + Me3P

CHNMe2

NPh

Me3P

NMe2

27

The 1,3-phosphaazaallene 28 undergoes a [2+2] cycloaddition reaction with phenyl isocyanate and diphenylcarbodiimide to form the cycloadducts 29 6 . N–t-Bu

t-BuP t-BuP

C

N-t-Bu + RN

C

X

NR X 29

28

X

Yield (%)

O NPh

55 50

Also, a [2+2] cycloadduct of 1,3-phosphaazaallene with diphenylketene is obtained. The reaction proceeds across the P C bond of the 1,3-phosphaazaallene and the C C bond of the diphenylketene to give 30 21 . N–t-Bu

t-Bu t-BuP

C

N–t-Bu + Ph2C

C

O

Ph2

O 30

240


The phosphagermaallene 31 undergoes a [2+2] cycloaddition reaction with benzaldehyde to give 32. Benzophenone and fluorenone react similarly 22 . ArP ArP

C

Ge(t-Bu)Tip + PhCHO

Ge

Ph

O

Tip t-Bu

32

31

The addition of carbon dioxide to hexaphenylcarbodiphosphorane gives the switter ionic adduct 33, which produces Ph3 P C C O and Ph3 PO on heating 23 . Ph3P

Ph3P

C

O

C

PPh3 + O

PPh3

Ph3P O

C

C

O + Ph3PO

O

33

The addition of hexafluoroacetone to hexaphenylcarbodiphosphorane likewise affords the [2+2] cycloadduct 34 24 . PPh3

Ph3P PPh3 + CF3COCF3

C

Ph3P

(CF3)2

O 34

Hexaphenylcarbodiphosphorane reacts with carbon disulfide to give a switter ionic adduct 35, which on heating undergoes the Wittig reaction with formation of Ph3 P C C S 25 . Ph3P

Ph3P

C

C

PPh3 + S

PPh3

S

Ph3P S

C

C

S + Ph3PS

S

35

Pseudo-Wittig reactions are also observed with metal carbonyl complexes. For example, reaction of W(CO)6 with hexaphenylcarbodiphosphorane affords the metal cumulene 36 with elimination of Ph3 PO 26 . Ph3P

C

PPh3 + W(CO)6

(CO)5W

C

C

PPh3 + Ph3PO

36

In a similar manner, metal carbonyl bromides (M = Mn, Re) react with hexaphenylcarbodiphosphorane to give the metal cumulenes 37 27 . Ph3P

C

PPh3 + (CO)5MBr

Br(CO)4M

C 37

C

PPh3

2-Carbon Cumulenes

3.4.3.3

241


In the reaction of phosphaketene with 2,3-dimethylbutadiene the [4+2] cycloadduct 38 is obtained 20 . O + RP

C

O

PR 38

1,3-Phosphaazaallenes with a CF3 group attached to phosphorus, i.e. CF3 P C N-t-Bu, undergo a [4+2] cycloaddition reaction with 2,3-dimethylbutadiene. The reaction proceeds after elimination of t-BuNC to form CF3 P PCF3 which acts as the dienophile 28 .

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.

F. Ramirez, N.B. Desai, B. Hansen and N. McKelvie, J. Am. Chem. Soc. 83, 3539 (1961). H. Karsch, F.H. Köhler and H.U. Reisacher, Tetrahedron Lett. 25, 3687 (1984). I. Shevchenko, J. Chem. Soc., Chem. Commun. 1203 (1998). H. Schmidbaur, T. Costa, B. Milewski-Mahrla and U. Schubert, Angew. Chem. 92, 557 (1980). R. Appel and W. Paulsen, Angew. Chem. 95, 807 (1983). O.J. Kolodiazhnyi, Tetrahedron Lett. 24, 4933 (1982). J. Escudie, H. Ranaivonjatovo, M. Bouslikhane, Y. El Harouch, L. Baiget and G. Cretiu Nemes, Russ. Chem. Bull. Int. Ed. 53, 1020 (2004). R. Appel and W. Paulsen, Tetrahedron Lett. 24, 2639 (1983). R. Appel, P. Fölling, L. Krieger, M. Stray and F. Knoch, Angew. Chem. 96, 981 (1984). L. Weber, S. Uhtmann, B. Torwiehe, R. Kirchhoff, R. Boese and D. Bläser, Organometallics 16, 3188 (1997). R. Appel and R. Laubach, Tetrahedron Lett. 2497 (1980). G. Becker, H. Riffel, W. Uhl and H.J. Wessely, Z. Anorg. Allg. Chem. 534, 31 (1986). M.A. David, J.B. Alexander, D.S. Glueck, G.P.A. Yap, L.M. Liable-Sands and A.L. Rheingold, Organometallics 16, 378 (1997). T. Wegmann, M. Hafner and M. Regitz, Chem. Ber. 126, 2525 (1993). H. Ramdane, H. Ranaivonjatovo, J. Escudie, S. Mathieau and N. Knouzi, Organometallics 15, 3070 (1996). L. Rigon, H. Ranaivonjatovo, J. Escudie, A. Dubourg and J.P. DeClercq, Chem. Eur. J. 5, 774 (1999). M. Yoshifuji, K. Toyota, H. Yoshimura, K. Hirotsu and A. Okamoto, J. Chem. Soc., Chem. Commun. 124 (1991). M. Ishikawa, K. Nishimura, H. Ochiai and M. Kumada, J. Organomet. Chem. 7, 236 (1982). M.A. David, D.S. Glueck C.P.A. Yap and A.L. Rheingold, Organometallics 14, 4040 (1995). R. Appel, Multiple Bonds and Low Coordination in Phosphorus Chemistry, M. Regitz and O.J. Scherer (Eds) Thieme, Stuttgart, Germany, 1990. O.I. Kolodiazhny, Zh. Obshch. Khim. 53, 1226 (1983). Y. El Harouch, H. Gornitzka, H. Ranaivonjatovo and J. Escudie, J. Organomet. Chem. 643–644, 202 (2002). C.N. Matthews and G.H. Birum, Tetrahedron Lett. 5707 (1966). G.H. Birum and C.N. Matthews, J. Chem. Soc., Chem. Commun. 137 (1967). C.N. Matthews, J.S. Driscol and G.H. Birum, J. Chem. Soc., Chem. Commun. 736 (1966). C. Creaser and W.C. Kaska, Transitition Met. Chem. 3, 360 (1978). W.C. Kaska, D.K. Mitchell, R.F. Reichelderfer and W.D. Korte, J. Am. Chem. Soc. 96, 2847 (1974). J. Grobe, D. Le Van, B. Luth and M. Hegemann, Chem. Ber. 123, 2317 (1990).

4 1,2-Dicarbon Cumulenes 4.1 4.1.1

Ketenes, R2 C C O Introduction

The pioneering work on ketenes was done in the early years of the 20th century by two groups, Wilsmore and his coworkers in England, and Staudinger and his colleagues at the TH Karlsruhe in Germany. The first comprehensive review of ketenes was published by Staudinger in 1912 1 . Other ketene review articles appeared in 1978 2 , 1986 3 and in 1993 4 . A review article on the synthesis and reactions of α-oxoketenes was published in 1994 5 . Ketenes 2 are generally synthesized by dehydrochlorination of carboxylic acid chlorides 1, which is best conducted using a hydrogen chloride scavenger, such as triethylamine. Mono substituted ketenes (RCH C O) are less stable than disubstituted ketenes (R2 C C O). R2CHCOCI + Et3N 1

R2 C

C

O + Et3NH+Cl−

2

The most characteristic reactions of ketenes involve [2+2] cycloaddition reactions to numerous double bonds. The rapid dimerization of ketene and mono substituted ketenes is perhaps the best known example of these type of reactions. In [2+2] cycloaddition reactions ketenes react across their C C and their C O bonds. However, a stepwise reaction leading to an ionic 1:1 adduct and subseqent reaction of this dipole with a second molecule of ketene to give six-membered ring [2+2+2] cycloadducts can also occur. Because of the tendency of ketenes to undergo cyclodimerization reactions, difunctional ketenes never became useful as monomers for addition polymers. The [2+2] cycloaddition reaction of ketenes with alkenes gives cyclobutanones, usually with a high degree of stereoselectivity, and the reaction with imines affords β-lactames useful in the synthesis of penicillin and cephalosporin antibiotics. The [2+2] cycloaddition reactions of ketenes to other double bonded substrates, such as C O, C S, N O and N N compounds, are also well investigated. Cumulenes in Click Reactions Henri Ulrich C 2009 John Wiley & Sons, Ltd

244


α-Oxoketenes became available more recently, and their reactions are also well investigated. α-Oxoketenes are usually highly reactive molecules, which cannot be isolated or observed under ordinary reaction conditions. However, some ketene carboxylic acid derivatives, such as bis(ethoxycarbonyl)ketene and ketene acid chlorides, RC(COCl) C O, where R = Ph, PhCH2 and PhCH2 CH2 , are distillable compounds. Sterically hindered αoxoketenes, such as dipivaloylketene (see Section 4.1.2), and perfluorinated α-oxoketenes 6 are also relatively stable. Interestingly, trapping of the unstable α-oxoketenes with suitable dienophiles affords the [4+2] cycloadducts, often in very high yields (see Section 4.1.4.4). Thioacylketenes are only stable at very low temperatures and even at −196 ◦ C only thietons, their rearrangement products, can be detected by infrared spectroscopy (band at 1790 cm−1 ) 7 . α-Imidoylketenes are obtained by flash vacuum pyrolysis of Meldrum’s acid derivatives, but only an oxoketenimine (band at 2076 cm−1 ) rearrangement product is detected at −77 K 8 . Also, the unstable methyleneketenes (R2 C C C O) are obtained from suitable precursors. In the absence of trapping agents their cyclodimers are isolated (see Section 4.1.2). α-Oxoketenes often participate as dienes in [4+2] cycloaddition reactions. Also, tandem [2+2+2] cycloadditions are observed. The cycloaddition reactions of ketenes are readily monitored by infrared spectroscopy, because ketenes have a characteristic absorption at 2150 cm−1 . 4.1.2 Dimerization Reactions The tendency of ketene to undergo cyclodimerization reactions was noted as early as 1908 by Chick and Wilsmore 9 , and by Staudinger and Klever 10 . The unsymmetrical structure of the ketene dimer 3 was established by spectroscopical methods 11 . The mechanism of this cycloaddition reaction was studied recently 12 , and the chemistry of diketene was reviewed in 1986 13 . O 2 CH2

C

O O 3

Mixtures of β-lactone dimers and the symmetrical dimers, resulting from dimerization across the C C bond, are also obtained from mono substituted ketenes. In the generation of these ketenes by dehydrochlorination of mono substituted carboxylic acid chlorides the β-lactone dimers 4 are formed, while non-catalyzed dimerization from dilute solutions produces mainly the symmetrical dimers 5 14 . The latter are in equilibrium with their enolate structure 6. RCH 2 RCH

C

O

O

O +

R O 4

O R

R

R

R HO

O 5

6

In the dimerization of mono substituted ketenes in the presence of a cinchona alkaloid catalyst the symmetric dimers are obtained with an e,e of 91–97 % 15 .

1,2-Dicarbon Cumulenes

245

The dimerization of dimethylketene usually produces the symmetrical dimer 7. However, the lactone dimer 8 can be generated from 7 by heating in DMF at 180 ◦ C for 1 to 3 min (yield 61 %) 22 . O

O

O

O 7

8

The symmetric dimers are also obtained in the generation of cyclopropaneketenes from 1-bromocyclopropane carboxylic acid chlorides with Zn in THF or acetonitrile 16 . In this reaction, cyclohexanetrione trimers are also obtained 17 . When 1-bromocyclopropane-1carboxylic acid chloride is treated with Zn/Cu at 15 ◦ C in acetonitrile with ultrasound a mixture of the symmetric dimer 9 (27–37 %), the unsymmetric dimer 10 (27–33 %) and the symmetric trimer 11 are obtained 18 . O

O Br +

O

COCl

+ O

O

O

O

10

9

11

The dimerization of dimethylcyclopropaneketene 12 proceeds to give syn-cyclodimers 13 and anti-cyclodimers 14 in a ratio of 1:5 19 . O

O •

+

O

12

O

O

13

14

The anti-dimer 16 is also formed in the dimerization of the bicyclic ketene 15 20 . O •

O O

15

16

The β-lactone dimer reacts with triethylamine in diethylether to give a mixture of the symmetric dimer and the dimer formed by [4+2] cycloaddition. It is advantageous to add the triethylamine dropwise to phenacetyl chloride. In this manner a 65 % yield of the β-lactone dimer is obtained.

246


The unsaturated ketene dimer 17 is obtained from the corresponding acid chloride and triethylamine in THF in 70 % yield 21 . O COCl + Et3N H O 17

A mixed dimerization to give 20 occurs when the cyclopentane-substituted α-bromoacyl halide 18 is treated with nitrosyltetracarbonyl–chromium (ii), followed by addition of the dialkyl α-bromoacyl halide 19. The yield of the shown mixed dimer is 78 % 22 . O CBrCOCl + Me2CBrCOCl O

18

19

20

Mixed ketene dimers are also obtained by generating haloketenes in the presence of dimethylketene, by mixing of solutions of two different ketenes, and by cogeneration of two different ketenes from the carboxylic acid precursors 23 . Bis(trifluoromethyl)ketene does not dimerize thermally, but it reacts with Me2 C C O to form cyclobutanone and β-propiolactone-type dimers 24 . The cycloaddition always proceeds across the C C bond in the dimethylketene. In the reaction with ketene and methylketene, only the β-propiolactone-type mixed dimers are formed. Disubstituted ketenes usually form the symmetric dimers. However, Staudinger and Klever 10 also obtained a small amount of the β-lactone dimers. This dimer is the only reaction product if the dimerization of dimethylketene is conducted in the presence of aluminum chloride as the catalyst 25 . Diphenylketene produces the β-lactone dimer on addition of a catalytic amount of sodium methoxide 26 . In the reaction of ω-isocyanatoalkanoyl chlorides with triethylamine, the corresponding ketenes are generated. They undergo immediate dimerization to give the unsymmetric ketene dimers 21 (where n = 3,4,5,9,10) 27 . OCN(CH2)nCH2COCl + Et3N

[OCN(CH2)nCH

C

O]

O

OCN(CH2)n

OCN(CH2)nCH

O

21

The obtained diisocyanates undergo addition polymerization reactions with suitable monomers, and the linear polymers can undergo ring opening or crosslinking reactions with nucleophiles.


247

When 4-MeOPhC(Et) C O is generated at −78 ◦ C from a pseudo-C2 -symmetric chiral phosphorous ylide it undergoes a [2+2] cycloaddition, followed by carbon dioxide evolution to give allenic derivatives in 80 % yield with a 92 % e,e 28 . The cyclodimer 22 of diphenylketene, formed by a [4+2] cycloaddition sequence, is also obtained. This dimer reacts with diphenylketene at 100 ◦ C, in the presence of a catalytic amount of quinoline to give the trimer 23 29 . O

O

O

Ph2 2 Ph2C

C

Ph2

Ph2

O O

OCOCHPh2

OH

Ph 22

Ph

Ph

23

Vinylketene dimerizes by a [4+2] cycloaddition sequence in which the ketene acts as both the diene and the dienophile to give 24 30 . O

O

O

•

+

•

O

24

α-Oxoketenes usually undergo a [4+2] cyclodimerization reaction to give α-pyrone derivatives 25. Some examples of this reaction are listed in Table 4.1. Table 4.1 Some [4+2] cyclodimers of α-oxoketenes O

•

O

2 R1

R1

R2

O

R2

R1 R2 O 25

R1

R2

Yield (%)

Reference

Me t-Bu Ph 4-BrPh 4-MePh

H H H H H

80 83 95 86 90

31 32 36 36 36

The dimerization to α-pyrones is reversible in ether solution at room temperature in the sterically hindered mesityl derivative. When dibenzoylketene 26 is generated by thermolysis of a furanedione derivative, it dimerizes to give the [4+2] cycloadduct 27, which rearranges to the pyrone derivative 28 33 . O

O

O

O

O Ph

[(PhCO)2C Ph

O

C

O]

(COPh)2

Ph Ph

O 26

O 27

O

Ph Ph

OCOPh COPh O 28

O

248


When the thermolysis is conducted at 138–140 ◦ C, the intermediates 29 (R = Ph, 4MePh) are obtained in 55–65 % yield. Conducting the thermolysis at 160–165 ◦ C affords 30 (R = Ph, 4-MePh, 2,5-Me2 Ph) in 85–96 % yields 34 .

Ar

O

OCOAr

O

O

O

Ph

•

Ph

Ph

O

Ar

O

Ar

O

COAr Ph

Ph

O

Ar

29

Ph O

O

30

The stable dipivaloylketene 31 dimerizes slowly at room temperature to give the cyclodimer 32, which contains a stable oxoketene moiety in its structure. In this dimerization, the C O group of the pivaloyl moiety participates as a dienophile 35 . When the dimerization is conducted in the presence of one equivalent of pyridine or tributyl phosphine, or using DMSO as a solvent, a different dimer 33, resulting from addition across the C O bond of the ketene as the dienophile, is obtained 36 . Both dimers serve as precursors for the monomers. O

O

O

O O •

O

O

O

•

32

O 31

O

O O

O O O 33

The phosphorous (iii) substituted ketene 34, generated in situ from Me3 CCOC COEt and Ph2 PCl, dimerizes to give the cyclodimer 35 having pentavalent phosphorous atoms in its structure 37 . O 2 Me3COC(PPh2)

C

O PPh2

O

Ph2P O

34

O

35

Benzoylthiobenzoylketene 37, generated by thermolysis of the thiophenedione 36, undergoes an intramolecular addition across the C S bond to give the thietone derivative 38 7 . O

O O

Ph

[(PhCOPhCSC Ph

S 36

C

O)]

Ph Ph

O 37

38

S


249

α-Imidoylketenes, such as 39, generated in situ, undergo a [4+2] dimerization across their C C bond to give the cyclodimer 40 in 30 % yield 38 . O

O

O

•

N

N

N

O

O

N

39

N H

40

However, N-unsubstituted ketenimines 41 undergo [4+2] cycloadditions across their C O bonds to give the cycloadduct 42 in low yield. O

O

O

•

O

NH

O

N H

N H

NH

NH2

41

42

The α-iminoketene 43, generated in the thermolysis of either isatoic anhydride or benzotriazinone, also undergoes dimerization via a [4+2] cycloaddition across the C O bond to give 44 39 . •

O

O

O

2 NH

N H 2N

43

44

In contrast, the N-substituted ketenimine 45 undergoes a [4+1] cyclodimerization reaction to give 46 in 42 % yield 38 . O •

O O N Me

Me

O

O

N

NMe 45

N O Me 46

The intramolecular cyclization of the imidoylketene 48 (R = adamantyl) to give the azetin-2-one 49 has been observed in the flash vacuum thermolysis of the dione 47 40 . Me Ph

N R 47

O

Me

O

Ph

O

Me

NR

Ph

•

48

O NR 49

250


In contrast, the imidoylketene 50 undergoes an intramolecular [4+2] cycloaddition reaction to give the quinolone derivative 51 41 . The mechanism of this reaction was verified as a 1,3-shift by labelling experiments 42 . O

O O

Ph

Ph Ph

O

N Ph

O

• Ph

O

O

Ph

N H 51

Ph

N 50

Aryl(quinoxalinyl)ketenes 53, generated in the thermolysis of the corresponding hydro2,3-furandiones 52, undergo [4+2] cyclodimerizations across the α-imidoylketene configuration with the ketene C C bond as the dienophile to give the cyclodimers 54, in 74–80 % yield 43 . ArOC Ar Ar

N N

O

Ar

Ar

N O

OCOAr N

Ar

N

N

N O Ar

O

N • O

O

52

53

54

In a similar manner, imidoylketenes 56, generated from the tricyclic trione 55, undergo cyclodimerizations to give the cyclodimers 57 in 68–72 % yields 44 . ROC Ph N

N

O COR

N O

O

PhN

N O

• O 56

55

OCOR N

R O

N

O

O

O

O

N Ph

57

When R = 2-(5-methylfuranyl), the yield of the cyclodimer is 72 % . Similarly, cyclodimerization is observed in the generation of 56 (R = OEt) but the yield of the cyclodimer is only 40 % 46 . Also, lower yields of the cyclodimers 59 (40–52 %) are obtained in the thermolysis of the trione 58 47 . 45

RO2C Ph N

Ph N

O CO2R

N O

O 58

O

O O

OR O

N • O

OCO2R N

PhN

N O O

N Ph

59

In the flash vacuum thermolysis (FVT) or photolysis of 3-acyltriazolo[1.5a]pyridines 60, the corresponding phenyl(pyridyl)ketenes 61 are generated at low temperatures, and they undergo rapid dimerization to give the quinolizine-2,4-diones 62. The dimers, upon


251

heating, regenerate the monomeric imidoylketene 48 .

N

O N N

R

N

R

O

• O

N 60

O

R

N

61

62

The cyclodimers 63 and 64 are also generated by FVT and observed at 47 K and 40 K, respectively 49 . O •

N

O

N

N

O 63

O N •

O

N

N

O 64

The cyclic α-oxo ketene 65, generated in the thermolysis of 2-diazodihydroresorcinol, undergoes dimerization by a [4+2] cycloaddition to give the tricyclic ketone 66 50 . O N2

O

• O 65

O O

O

O

66

Matrix photolysis or flash vacuum thermolysis of the diazodiketone 67 generates the heterocyclic α-oxo ketene 68, which undergoes dimerization via the [4+2] cycloaddition reaction to give the dimer 69 in 74 % yield 51 . Me O

OO

O N2

O N Me 67

N

• O N Me 68

N Me

O

O

69

Methyleneketenes 71, generated in the flash vacuum pyrolysis of the corresponding 1,3-dioxinones 70, also undergo cyclodimerization to give 72. For example, 2,4bis(cyclopentylidene)cyclobutane-1,3-dione is obtained in 31 % yield from cyclopentyl-

252


ideneketene above −100 ◦ C 52 . O

O C

C

O

O

O

70

71

72

Methylmethoxymethyleneketene is stable for a few hours at room temperature, but undergoes subsequent dimerization 53 . Cyclic nitrogen-substituted methyleneketenes 73 also undergo intramolecular cyclization to give bicyclic lactams 74 after trapping with acetic anhydride 54 . O • N

•

O

N

O

N

R

R

R

OAc 74

73

In the reaction of cyanogen with oxalyl chloride the heterocycle 76 is obtained, which is the dimer of the unusual heterocyclic ketene 75 55 . O

Cl Cl

N •

2 CN + 4 ClCOCOCl Cl

N

N

Cl

O

N

N

O 75

Cl

N Cl

76

4.1.3 Trimerization Reactions The symmetrical trimers of disubstituted ketenes are obtained by heating the corresponding dimers with a catalytic amount of base. For example, heating of the symmetrical dimer of dimethylketene 77 with sodium methoxide at 100 ◦ C affords a 97 % yield of the trimer 78 56 . In a similar manner, 78 is obtained from the unsymmetrical dimethylketene dimer 79 in high yield. The symmetrical trimer of diphenylketene was similarly obtained 57 . O

O

O 77 O O

78 O

79

O


253

Heating of 77 in toluene for 2 h affords mixtures of 78 (40 %) and the unsymmetrical trimer 80 (48 %) 21 . O O O

+ O

O 77

O

O

O

78

80

However, heating of the dimer 81 with base affords the symmetrical trimer 82 in only 33 % yield 21 . O O

O

O

O

81

82

Cyclopropane ketenes undergo trimerization to give symmetrical trimers resulting from cycloaddition across the C C bond under some conditions (see Section 4.1.2). The symmetrical trimer 84 is also obtained by heating the symmetric ketene dimer 83 in the presence of sodium methoxide 58 .

O O

O

O

O

83

84

Unsymmetric trimeric aldoketenes were already obtained by Wedekind in 1902 59 . Trimers with a cyclobutenone structure 85 are obtained in the continuous formation of aldoketenes by dehydration of the corresponding carboxylic acids 60 . R 3 RCH

C

O

OH

OCOCH2R

R

R

R O

O 85

A trimer of methylketene with the cyclobutenone structure 85 is obtained in high yield when methylketene is generated from the corresponding carboxylic acid bromide with diisopropylethylamine on attempted [2+2] cycloaddition reaction with aldehydes 61 . This reaction presumably proceeds via the symmetrical dimer as the intermediate.

254




Ketene reacts with SO2 to form a [2+1] cycloadduct 86, which is in equilibrium with the 1,3-dipole 87. O CH2

C

O + SO2

O S O

C+–CH2SO2−

O 86

87

The 1,3-dipole can be intercepted with C C and C N bonded substrates to form [1+2+2] cycloadducts. Examples include azomethines 62 , p-toluenesulfonyl isocyanate and ketenimines 63 . Examples of the interception with ketenimines to form 88 are shown in the following. NR Ph2 CH2

C

O + Ph2C

C

NR + SO2

O S

O

O 88

R

Yield (%)

4-BrPh 4-MePh 4-MeSO2 Ph

64 57 57

When a mixture of ketene and sulfur dioxide is irradiated at 10–20 K, the four-membered ring [2+2] cycloadduct 89 is formed 64 . O CH2

C

O + SO2

O

SO 89

The vinyl ketenes 90 undergo a [4+1] cycloaddition with a variety of nucleophilic carbenes to give highly substituted cyclopentenones 91 65 . O

O

R1

•

R1

+ R2

R3 90

OMe OMe

:C(OMe)2 R2 R3 91


255

Similarly, 90 undergoes a [4+1] cycloaddition reaction with nucleophilic carbenes to give 92 66 . O

R1

•

R1

+ R2

X X

:CX2 R2

R3

R3 92

90

R1

R2

R3

X

Tip Tip

Me Me

Me Me

SPr OMe

Yield (%) 96 80

Likewise, vinyl ketenes react with sulfur ylides or trimethylsilyldiazomethane to give the corresponding cyclopentenones 67 . Also, the nucleophilic carbene 93 reacts with ketenes and alkynes at −75 ◦ C in a threecomponent reaction to give the 1,4-thiazepines 94 in high yields 68 . CO2R

R1

S

R2

N3 R

:

+

R 4R 5C

C

R1

O +

R4 R5 O S N R 2 R3

CO2R

93

4.1.4.2

CO2R

CO2R 94


Across carbon multiple bonds Ketenes are very reactive in [2+2] cycloaddition reactions to numerous double-bonded substrates. They form four-membered ring cycloadducts, even with regular olefins. In the reaction of ketenes with acetylene derivatives sometimes also four-membered ring [2+2] cycloadducts are obtained. The isolation of ethoxycyclobutenones in the thermolysis of ethoxyacetylenes was interpreted by Nieuwenhuis and Arens 69 to occur via a [2+2] cycloaddition reaction of the generated ketene with the starting material. This type of reaction is also observed when dimethylketene is reacted with ethoxyacetylene to give a 83 % yield of the cyclobutenone 70 . The ketene also reacts with ethoxyacetylene to give the cyclobutenone derivative 95 71 . O CH2

C

O + HC

COEt EtO 95

256


Interestingly, 1-buten-3-ynyl methyl ether 96 reacts with dimethylketene exclusively across the carbon–carbon triple bond to give the cyclobutenone derivative 97 72 . O MeOCH

CH-C

CH + Me2C

C

O MeOCH

96

CH

97

Vinylketenes also undergo [2+2] cycloaddition reactions with ethoxyacetylene 72 . Diphenylketenes with a substituent on one ring, such as 98 (X = Me, OMe), react with ethoxyacetylene by a [4+2] cycloaddition sequence to form norcaradiene derivatives 99, which rearrange to give azulenes 100 73 . Ph

Ph O

O X–

–C(Ph)

C

O + HC

X–

COEt

X– OEt

OEt 98

99

100

Some [2+2] cycloadducts 101, derived from ketenes and acetylene derivatives, are listed in Table 4.2. Table 4.2 Some [2+2] cycloadducts from ketenes and acetylenes O

RR1 RR1C

C

O + R2C

CH R2 101

R

R1

R2

Me Et

Me n-Bu

OEt OEt

Yield (%)

Reference

83 51

70 70

t-Butylcyanoketene also reacts with a variety of alkyl- and arylalkynes to give cyclobutenones 74 . Dichloroketene reacts with 2-butyne, 3-hexyne or 1-hexyne to form the [2+2] cycloadducts 102, which isomerize in situ by ZnCl2 , formed in the generation of the ketene, to form the isomer 103 75 . O

R CCl2

C

O + RC

CR1

R1

Cl2 102

R Cl R1

O Cl

103


257

With trimethylsilylacetylene, the same ketene forms the [2+2] cycloadduct 104, resulting from initial attack on the non-silicon substituted carbon of the alkyne 76 . In contrast, PhC CSiMe3 reacts with dichloroketene by initial attack at the silylated carbon atom to give 105 77 . Me3SiC

CCl2

C

CH

O Cl2 Me3Si 104

O

O Me3SiC

CPh SiMe3

Ph 105

Ketene reacts with 1-triisopropylsilyloxyheptyne to give 3-silyloxycyclobutenone 106 72 . O CH2

C

O + RC

COSiR1

3

R13SiO

R 106

Some ketenes react with ynamines to form the [2+2] cycloadducts 107 78 .

R2C

C

O +

R1C

CNEt2

O

R2

R1

Et2N 107

R

R1

Ph Ph

Ph NEt2

Yield (%) 95 94

However, the [2+2] cycloadducts 107 obtained from MeC≡CNEt2 rearrange to form the linear alleneamides R2 C C C(Me)COEt2 (R = H, 83 % yield; R = Ph, 96 % yield) 90 . In the reaction of carboxyethylphenylketene with PhC≡CNEt2 , the [2+2] cycloadduct 108 is obtained in 65 % yield 79 . Ph EtOCO(Ph)C

C

O + PhC

CNEt2

EtO2C

O Ph

Et2N 108

258


In contrast, the carboxamidophenyl ketene 109 reacts with ynamines to form only the [4+2] cycloadducts 110. O Ph Et2NCOC(Ph)

C

O + Et2NC

Me

CMe Et2N O

109

NEt2

110

In the generation of thioaryl substituted ketenes 111 from α-diazo esters in the presence of 3.5–5.0 equivalents of MeC≡COMe, the [2+2] cycloadducts 112 are obtained in 71–92 % yields 80 . Me ArSCH

C

O + MeC

O

COMe SAr

MeO 111

112

In the reaction of the vinyl ketene 113 (R = 4-CF3 Ph, R1 = SiMe3 ) with 1diethylaminopropyne in hexane at room temperature, the initially formed [2+2] cycloadduct rearranges to give bicyclo[3.1.0.]hex-3-en-2-one 114 in 38 % yield 81 . R OMe

Et2N R(MeO)C

CR1–C(R1)

C

O + MeC

R1

C–NEt2

R1

Me O 114

113

N,N-Bis(trimethylsilyl) ynamines 115 react with ethylphenyl- and diphenylketene to give the cyclobutenone adducts 116 82 . O (Me3Si)2N-C

C-R + R1R2C

C

O

(Me3Si)2N

115

R 116

R

R1

R2

Yield (%)

Ph Ph

Et Ph

Ph Ph

86 64

The [2+2] cycloaddition reaction of ketenes with olefins was already observed by Staudinger and his coworkers, who postulated the four-membered ring structure for the cycloadducts. The rate of reaction of ketenes with olefins is as follows: diphenylketene > dimethylketene > butylethylketene > ketene. Because of its slow rate of dimerization butylethylketene is an especially useful reagent and its cycloaddition to slow reacting olefins can be forced by using elevated temperatures.


259

The reaction generally proceeds across the C C bond of the ketene, but in the reaction of bis-(trifluoromethyl)ketene with vinyl benzoate, mixtures of the products resulting from addition across the C O bond 117 (34 % yield) and the C C bond 118 (42 % yield) are obtained 83 . (CF3)2C (CF3)2C

C

O + PhCOOCH

O

(CF3)2

O

+

CH2

PhCOO

OCOPh 117

118

Diphenylketene reacts with ethylene, propylene and 1-hexene at 85–115 ◦ C to give cycloadducts with retention of the alkene stereochemistry 84 . The cycloaddition of t-BuC(CN) C O with 2-methyl-2-butene proceeds regio- and stereoselectively to give 119 85 . O

NC t-BuC(CN)

C

O + Me2C

CHMe

119

In the reaction of t-BuC(CN) C O with Me2 C CHCH CMe2 , the isomeric [2+2] cycloadducts 120 and 121 are formed, and on heating in benzene containing 7 % EtOH the proportion of 121 is increased from 67 to 85 % 86 . CN t-BuC(CN)

C

O + Me2C

CHCH

CN

O

t-Bu

t-Bu

O

+

CMe2

121

120

Dienes, such as cyclopentadiene, are often used to trap the more reactive ketenes, which otherwise would undergo oligomerization or polymerization reactions. In the reactions of monoketenes with cyclopentadiene endo cycloaddition products are usually obtained, with the exception of t-butylketene, where the exo adduct is predominantly formed 87 . In the reaction of MeC(X) C O (X = Cl, Br) with cyclopentadiene, a strong solvent effect on the exo/endo ratio is observed 88 . The more polar solvents favor the exo isomer, indicating the presence of a polar intermediate. In the reaction of the thiophenylketene 122 with the relatively unreactive methylene cyclohexane, the [2+2] cycloadduct 123 is obtained in 78 % yield. 92 PhSCH

C

122

O

O + SPh 123

From the reactive cyclohexadiene, the [2+2] cycloadduct is obtained in 96 % yield.

260


In the thermal reaction of pentamethylcyclopentadiene with ketenes, the [2+2] cycloadducts 124 and 125 are generally obtained 108 .

R(Me)C

C

R

O +

+ R

O 124

O 125

However, when the reaction of methylarylketenes with pentamethylcyclopentadiene is conducted at 0 ◦ C in acetonitrile, in the presence of tris(p-tolyl)ammonium hexafluoroantimonate as the catalyst, the major reaction products are the [4+2] cycloadducts 126 and 127 89 . H

H R R(Me)C

C

R

+

O +

O

O 126

127

126 R

Yield (%) 127 R

4-MePh 4-MeOPh

30 31

4-MePh 4-MeOPh

Yield (%) 9 11

A third type of cycloaddition is also encountered in the catalyzed reaction to give cycloheptadienones. They become major products if the reaction is conducted in the presence of CF3 SO3 H 90 . The tungsten complexes 128 react with chloro- and arylketenes to give the [2+2] cycloadducts 129 in 57–92 % yield. This reaction allows the cycloaddition of ketenes to phenolic double bonds 91 . H Ph3P

Ph3P

NO W

+ CICH

C

O

NO

Cl O

W Tp

Tp O

O

128

129

Some of the [2+2] cycloadducts 130 formed in the thermal reaction of olefins with ketenes are listed in Table 4.3.


261

Table 4.3 [2+2] Cycloadducts derived from ketenes and olefins O

RR1 C

RR1C

C +

C

O 130

R

R1

Olefin

Cl Cl Cl Me Et Et Et Et Ph Ph Ph Ph Ph Ph Ph

H Cl Cl Me n-Bu n-Bu n-Bu n-Bu Ph Ph Ph Ph Ph Ph Ph

Bicyclopropylidenea Cyclopentene Cyclopentadiene Cyclopentadiene Hexadecene-1 Vinylcyclohexane 1,3-Pentadiene Cyclopentadiene Styrene 4-Methylstyrene 4-Methoxystyrene Cyclohexene Cyclopentadiene 1,3-Cyclohexadiene Tropone

a

Yield (%)

Reference

63 67 75 82 66 65 64 82 93 81 84 60 92 96 100

92 93 93 94 94 94 94 94 95 95 95 96 100 100 97

.

The initial reaction of diphenylketene with cyclopentadiene at low temperatures affords the [4+2] cycloadduct 131, which subsequently undergoes a [3,3] sigmatropic (Claisen) rearrangement to give the isolated Staudinger reaction product 132 98 . O

O

• Ph

O

+ Ph2C

Ph

131

132

Heating of 132 with diphenylketene at 110 ◦ C for nine days affords the bis-cycloadduct 98 . Thermolysis of the furane derivative 133 generates the allene substituted ketene 134, which cyclizes to form the cyclobutenone derivative 135 in 40 % yield 99 . O • O 133

CH2OCOPh

•

O

CH2 134

135

Also, in the reaction of linear 1,3-dienes, the initial reaction products, isolated at low temperatures, are the [4+2] cycloadducts. For example, the reaction of trans-methoxybutadiene and diphenylketene in benzene at room temperature for 24 days gives a 92 % yield of the [4+2] cycloadduct 136. The latter, after 5 days at 0 ◦ C in chloroform, rearranges to the

262


cyclobutanone 137 (62 % yield) 98 . OMe

OMe

O + Ph2C

C

O

O

Ph2

Ph2C

MeO 136

137

2-Methoxybutadiene reacts with diphenyl- and butylethylketene to give the [4+2] cycloadducts 94 . Monoolefins react with ketenes in accordance with the polarization of the double bond. For example, the cycloadduct obtained from diphenylketene and styrene has the structure 138.

Ph2C

C

O + PhCH

O

Ph2

CH2

Ph 138

In the generation of diphenylketene from phenylbenzoyldiazomethane in the presence of styrene, both the cycloadduct and the linear adduct, Ph2 CHCOCH CHPh, are obtained 100 . Intramolecular cycloaddition of ketenes, generated by photolysis or thermolysis of diazoketones, to C C bonds are also known. For example, photolysis of the bicyclic diazoketone 139 affords the bicyclic ketone 143, resulting from intramolecular cycloaddition of the ketene intermediate 141. As a byproduct, the tetracyclic ketone 142 is formed by addition of the ketocarbene 140, prior to the Wolf rearrangement 101 . O

O CH2N2

CH

CH:

•

O

+

139

140

141

O O 142

143

In the photolysis of the diazoketone 144, in the presence of an acetylene derivative, a similar intramolecular cycloaddition reaction affords a cyclobutenone derivative 145, which undergoes a retroreaction to form the ketene 146. The new unsaturated ketene cyclizes in


263

an intramolecular [4+2] cycloaddition to form the phenol derivative 147 102 . CHCOC(R1)

RCH

N2

CH–C(R1)

RCH

C

O + XC

CY

144 O O RCH

X

X

HO

R

•

CHC(R1)

X

R1

R1

Y

Y

146

147

Y 145

R

An intermediate dienylketene 149 is also generated in the reaction of the trisubstituted vinyl ketene 148 with lithium enolates, and subsequent 6 π -electrocyclization followed by tautomerization to give the highly substituted resorcinol monosilyl ethers 150 in good yields 103 . OSiMe3

OLi R3Si

•

O

R1 + R1CH

•

COLi

R2

O R3 148

R1

SiMe3 R2

R2

HO

R3 149

150

Another intramolecular cycloaddition is observed when o-toluenecarboxylic acid chlorides 151 are thermolyzed in the vapor phase at 400–600 ◦ C to give benzocyclobutenones 152 104 . COCl

•

O

O

CH3 151

152

R1

R2

R3

R4

Yield (%)

H Me H H

H H Me H

H H H –CH CHCH CH–

H H Me

28 61 72 73

Vinylketenes, generated from diazoketenes or acid chlorides, undergo an intramolecular [2+2] cycloaddition reaction to give cyclobutenone or cyclobutanones, depending on the precursors. For example, generation of vinylketene 153 affords the cyclobutenone 154 105 . N2 O O MeO

P(OMe)2

O (MeO)2P MeO 153

O •

O

O

(MeO)2P MeO 154

264


When the ketene is held in close proximity by a rigid tether, good yields of the intramolecular [2+2] cycloadducts are obtained from aldoketenes. Optimal yields are achieved by using higher dilutions. Sometimes, higher reaction temperatures are also favorable. Often, better yields are obtained by using arylketenes or α,β-unsaturated ketenes. The thermal intramolecular [2+2] cycloaddition of olefin-tethered ketenes affords bicyclic ketones. For example, from 155 the cycloadduct 156 is obtained in 70 % yield (mixture of stereoisomers) 106 . O

O

• O

O 155

156

More complex intramolecular cycloaddition reactions of aldoketenes are also observed. For example, from 157, generated in situ, the expected cyclobutanone derivative 158 is obtained in 76 % yield 107 . O O

• CH

157

158

In the photolysis of ketone 159 (R = Me) the cyclobutanone derivative 160 is obtained in quantitative yield 108 . O

O R

R

O

•

R

R

R

R 160

159

Also, the unsaturated ketene 161, generated from the corresponding acid chloride, undergoes intramolecular [2+2] cycloaddition to give 162 in 84 % yield 116 . H O

O

• H 161

162

A similar reaction occurs in the generation of vinylketenes from acyl chlorides to give cyclobutanone derivatives 163 109 . O

O

O

•

Cl + Et3N

H 163


265

The photolysis of the unsaturated ketone 164 (R = H) in a 1 % solution generates the ketene intermediate which undergoes intramolecular cyclization to give 165 in quantitative yield 110 . O

O

R

• R

O

R

164

165

When R = Cl in 164, a quantitative yield of the cycloadduct is also obtained. Chloroketenes with tethered olefins also undergo the intramolecular cycloaddition reaction with alkenes, as shown in Table 4.4 117 . Table 4.4 Intramolecular [2+2] cycloaddition of unsaturated chloroketenes Ketene

Cyclobutanone Cl

Cl

O

Yield (%)

O

• H

Cl

O

Cl

•

O

Me

Me Cl

66

O

Cl

•

64 O

H

Me

65

The intramolecular cycloaddition of unsaturated ketenes is a general reaction and from olefin-tethered disubstituted precursors (instead of Cl in Table 4.4 an aryl group is attached to the precursor) the bicyclic ketones are obtained in 80–90 % yield. Numerous examples are reported 111 . The vinylketene 166 also undergoes the intramolecular [2+2] cycloaddition to give 167 in 83 % yield 112 . O • O 166

167

Competition experiments indicate that when ketenes are substituted with two identical alkenes having different tether lengths, ring size is the determining factor. Five-membered rings are exclusively formed when competing with six-membered rings. Also, electron

266


donating groups on a styrene substituent favor ring closure. For example, from the ketene 168 the cycloadduct 169 is obtained in 82 % yield 113 . O

O

•

168

169

Alkoxyketenes are also very reactive in intramolecular [2+2] cycloaddition reactions, as shown in Table 4.5 114 . Table 4.5 Intramolecular [2+2] cycloaddition reactions of alkoxyketenes Ketene

Cycloadduct

O

•

O

72 O

O

H O

•

O

O

O

H

Yield (%)

66

H •

O

O

O

O

62

Also, phenoxyketenes undergo the intramolecular [2+2] cycloaddition reaction, as shown in Table 4.6 115 . Table 4.6 Intramolecular [2+2] cycloaddition of phenoxyketenes Ketene

Cycloadduct

O

•

O

•

Yield (%)

O

O

O

60

O

O

O

76

O

85

O

86

O

84

Ph •

O

O

O

Ph Ph

Ph H O

•

O

O

Ph

O

Ph

•

O

O


267

Even sulfonylketenes 170 undergo this reaction to give the cyclobutenone derivative 171 in 31 % yield 116 . SO2Ph O

SO2Ph • O

170

171

Also, iminoketenes 173, generated in the thermolysis of N-allyleneamino esters 172, undergo the intramolecular cyclization to give the cyclobutanone derivatives 174 in 33–62 % yield 117 . HN

N CO2Et

R

N

• R

172

O

O

R

173

174

Also, generation of the α-oxoketene 175 results in intramolecular [2+2] cycloaddition to give the diketone 176 118 . O

O CO2Et

O

O

•

175

O

176

The stereospecific [2+2] cycloaddition of the unsaturated vinylketene 177 affords the bicyclic ketone 178 (43 % yield), used to synthesize racemic chrysanthenone 119 .

• O

O 177

178

Acylimidoylketenes 179 undergo an intramolecular [4+2] cycloaddition reaction, followed by a 1,3-shift to give the tricyclic lactone 180 in low yield 120 . H N N

H N

O CO2Et

O

N •

O

O

N

O OEt

N H

O O

O 179

180

The [2+2] cycloaddition reaction of dimethyl- and diphenylketene to tetramethylallene is another example of the addition of the ketene C C bonds across the cumulative C C

268


bond to give the cyclobutanone 181 103 . O

R2 R2C

C

O + Me2C

C

CMe2

Me2 181

From 1,1-dimethylallene and t-butylcyanoketene the two isomeric [2+2] cycloadducts 182 and 183 are formed in 65 % and 35 % yields, respectively 121 . CN t-BuC(CN)

C

O + Me2C

C

CN

O

t-Bu

O

t-Bu +

CH2 182

183

The cycloaddition reaction of 1,1-dimethylallene and phenylchloroketene similarly produces the two cycloadducts, but in this case the propylidenecyclobutanone is the predominant cycloadduct 122 . In the reaction of the same ketene with optically active 1,3-dimethylallene, optically active and racemic [2+2] cycloadducts are obtained, indicating that the reaction is a stepwise process 123 . Optically active 1,3-diphenylallene reacts with t-butylcyanoketene to give cyclobutanones with the E-configuration 124 . In contrast, reaction of the same ketene with optically active 1,2-cyclononadiene gives a 2:3 mixture of the E:Z stereoisomeric cycloadducts 125 . The polarization of the allene system is similar to that of olefins, as indicated by the structure of the cycloadducts. The center carbon atom in the allene is nucleophilic, rather than electrophilic, as in the heterocumulene system. Activated olefins, such as enamines, react very readily with ketenes to give [2+2] and [2+2+2] cycloadducts. For example, from dimethylketene and N,Ndimethylisobutenylamine the [2+2] cycloadduct 184 is obtained in high yield. When the reaction is conducted in a polar solvent, the [2+2+2] cycloadduct 185 is also obtained 126 . H

O Me2C

C

O + Me2NCH

CMe2

NMe2

+

Me2N

O

O 185

184

In the reaction of silylketenes 186 with excess enamines, six-membered ring [2+2+2] cycloadducts 187 are formed, which eliminate the amines to give the resorcinol derivatives 188 127 . Me2N

NMe2 R3SiCH

C

R2

O + R1

186

SiR3 O

R1 R2

R1

OSiR3

R2 O

OSiR3

187

188


269

From ketene itself and N,N-dimethylisobutenylamine the linear adduct, Me2 NCH CHCOCH(Me)2 , is obtained. The formation of the cycloadduct is observed when the reaction is conducted at −20 ◦ C 128 . It is not necessary to use ketenes themselves in the cycloaddition reaction with enamines. Opitz and coworkers have demonstrated that the adducts can be obtained in good yield from carboxylic acid chlorides and enamines in the presence of a tertiary amine as the hydrogen chloride scavenger 129 . Some of the the [2+2] cycloadducts 189 derived from ketenes and enamines are listed in Table 4.7. Table 4.7 [2+2] Cycloadducts from ketenes and enamines O

RR1 RR1C

C

O +

NCH

CR2R3

R 2R3

N H 189

R

R1

R2

R3

Amine component Yield (%) Reference

H H H H H Me Et Et –(CH2 )5 –

H Me OPh OCOOMe OCOOMe Me Et n-Bu

Me Me Me Me Me Me Me Me Me

Me Me Me Me Me Me Me Me Me

Morpholine Piperidino Piperidino Piperidino Morpholino Piperidino Pyrrolidino Pyrrolidino Pyrrolidino

75 60 77 77 60 76 75 70 72

130 129 129 129 129 129 129 129 129

The cyclobutanone derivatives rearrange to linear isomers on heating. Therefore, good yields are only obtained when the products can be purified by recrystallization below 80–100 ◦ C 132 . The reaction of the eneamides 190 (R = alkyl) and enecarbamates 190 (R = OR) with a variety of monoketenes and dichloroketene produces the expected [2+2] cycloadducts O 191 131 . +

RCH

C

R

O

N O

N R

O

190

R 191

Likewise, reaction of the enecarbamate 192 with dichloroketene affords the [2+2] cycloadduct 193 in very high diastereoselectivity 132 . O t-BuO2C

+ N BOC

192

Cl2C

C

O

Cl t-BuO2C

N BOC 193

Cl

270


Reduction of 193 with Zn–Cu in methanol affords the cyclobutanone derivative in 83 % yield. The [2+2] cycloaddition reaction of 4-aryl endocyclic enecarbamates 194 with 2-chloroethylketene, generated in situ, affords exclusively endo-(2-chloroethyl)cyclobutanones 195 133 . Ar

O

Ar + N

ClCH2CH2CH

C

O

Cl

N BOC

BOC 194

195

Ar

Yield (%)

4-ClPh 2-MeOPh

67 65

The intraconversion of the endo adduct into the exo adduct can be carried out in the presence of ammonium chloride. The endoselectivity in the formation of 195 is significantly higher than that observed for the reaction of the unsubstituted endocyclic enecarbamates with mono substituted ketenes. When alkylketenes are used in the reaction of substituted endocyclic enecarbamates high stereoselectivity is also observed 134 . The reaction of the four-membered ring eneamide 196 with dichloroketene provides the unstable [2+2] cycloadduct 197, which on reduction with NaBH4 in THF affords the cyclobutanol derivative 198 in a combined yield of 54 % 135 .

+ N O

Cl2C

C

Cl2

O N O

196

N

O

OH

O 197

198

The [2+2] cycloaddition reaction of ketenes with vinyl ethers and thioethers also occurs very readily. Even allyl ethers undergo this reaction. The reaction of diphenylketene with vinyl ethers is stereospecific, indicating a concerted one-step process 136 . Also, dimethylketene and E-MeOCH CHMe affords a cycloadduct in which the alkene stereochemistry is maintained 137 . In contrast, the [2+2] cycloadduct obtained from t-butylcyanoketene and CH2 CHOEt or CH2 CHOAc did not give a 100 % stereoselectivity and linear products are often also obtained, indicating the formation of a switter ionic intermediate 138 . The latter are detected in the reaction of bis(trifluoromethyl)ketene with ethyl vinyl ether (see the ‘General Introduction’). The initial reaction occurs across the C O bond of the ketene, which rearranges via switter ionic intermediates to form the cyclobutanone reaction product 139 .


271

Using propenylpropylether as the substrate, the cis-isomer reacts 170 times faster than the trans isomer. Heating of the cycloadducts from both isomers results in the formation of the isomeric linear adduct. An efficient one-pot synthesis of cyclobutanones from chiral enol ethers, which uses Zn/Cu in diethyl ether to achieve the dechlorination, affords the cyclobutanones in >90 % yield and 100 % stereoselectivity 140 . The [2+2] cycloaddition of dichloroketene with chiral enol ethers is the key step in the synthesis of natural pyrrolizidines 141 . Some of the [2+2] cycloadducts 199 derived from vinyl ethers and vinyl thioethers are listed in Table 4.8. Table 4.8 [2+2] Cycloadducts of ketenes with vinyl ethers and vinyl thioethers RR

1C

C

O +

R2CH

CHR3

RR1

O

R2

R3 199

R

R1

R2

R3

Yield (%)

Reference

Me Me Me Me Me Me Et Et Ph Ph Ph Ph

Me Me Me Me Me Me n-Bu n-Bu Ph Ph Ph Ph

OEt OEt OCH2 CH2 Cl OCH(Et)Bu O(CH2 )2 NHCOCH(Me)2 –OCH2 CH2 CH2 – OEt OCOMe OPr –OCH2 CH2 CH2 – OCH CH2 S(CH2 )2 OCOMe

H Me H H H

80 64 70 84 80 80 81 30 86 88 75 87

142 142 143 143 142 142 142 142 142 143 143 142

H H Me H H

The reaction of dichloroketene with ethyl vinyl ether affords the [2+2] cycloadduct which reacts with a second equivalent of dichloroketene to give the cyclobutenone ester 200 144 . OCOCHCl2

Cl2 2 Cl2C

C

O + EtOCH

CH2

EtO 200

However, in the regiospecific reaction of trimethylsilyl enol ethers with dichloroketene the expected [2+2] cycloadducts are obtained in high yields 145 . The reaction of diphenylketene with CH2 CHOSi(t-Bu)Me2 also affords an 86 % yield of the [2+2] cyclobutanone cycloadduct 146 . The reaction of phenylchloroketene with 4,5-dihydrofuran affords the [2+2] cycloadduct 201 in 75 % yield. The linear product 202 is also formed in 15 % yield 147 . O PhC(Cl)

C

CO CH (Cl) Ph Cl

O + O

Ph

O 201

+ O 202

272


When the [2+2] cycloadducts derived from ketenes and vinyl ethers are treated with basic or neutral Al2 O3 , the cyclobutenones 203 are obtained in high yields 148 . Heating of 203 affords the naphthalene derivatives 205 in quantitative yields via the vinyl ketene intermediate 204 149 .

Ph2 EtO

O Me

+ Al2O3

OH

O

O

Ph2

•

Me

Me

Me Ph 204

203

Ph 205

Mesoionic 1,3-oxazinium 4-olates 206 undergo ring-opening to give ketenes 207 which undergo an intramolecular ‘criss-cross’ [2+2] cycloaddition reaction to afford 3-azabicyclo[3.1.1]heptanetriones 208 in 75–85 % yields 150 . O

O O R1

O

R3 N

O

O

•

N

R1

R2

O

O

N

O

R2

R2

206

R1 R3

R3

207

208

Cycloadducts and linear adducts derived from ketenes and ketene O,O, O,N, N,N and S,S -acetals are also known. However, four-membered ring [2+2] cycloadducts are only obtained in the reaction of diphenylketene with dialkylketene acetals 151 . An example is the reaction of the heterocyclic O,N-acetal 209 with diphenyl- and chlorophenylketene to give mixtures of the cycloadducts 210 and 211 152 . O t-Bu

O •

+ N

Ph

R

O

Ph

t-Bu N

R

CO2R1 209

O

t-Bu N

CO2R1

CO2R1

210

211

R

R1

Cl Cl Ph

Me t-Bu Me

O

O +

Yield (%)

Ratio 210:211

87 60 80

10:1 6:1 5:1

Ph R

The cycloaddition of ketene with tetramethoxyethylene affords a mixture of an oxetane cycloadduct 212 and a cyclobutanone cycloadduct 213. From diphenylketene and


273

tetramethoxyethylene, only the oxetane is obtained 153 . (MeO)2C

C(MeO)2 + CH2

C

O

(MeO)2

O

O + (OMe)2 (MeO)2 212

(OMe)2 213

A 57 % yield of 213 was reported by Bellus and coworkers 154 . Addition of zinc chloride as the catalyst favors the formation of cyclobutanones 155 . In the reaction of dichloroketene with tetramethoxyethylene, the cyclobutanone cycloadduct is obtained; however, the reaction of methylchloroketene with tetraethoxyethylene afforded the linear adduct, MeCH(Cl)COCH C(OEt)2 156 . In contrast, reaction of methylchloroketene and phenylchloroketene with tetramethoxyethylene again affords the cycloadducts in high yields 157 . Across C O bonds The [2+2] cycloaddition of ketenes across C O bonds to give βlactones was extensively investigated by Staudinger and his coworkers. The reaction often proceeds without a catalyst, but added catalysts sometimes alter the course of the reaction. The reaction involves the C C bond of the ketene, which adds across the C O bond of the carbonyl compound. At elevated temperatures, the cycloadducts eliminate carbon dioxide to give olefins. Trihaloaldehydes react especially well to produce the four-membered ring cycloadducts 158 . The thus obtained β-lactones can be converted in a one-pot (two steps) reaction into β-lactames 159 . Also, methyleneketenes 214 undergo a [2+2] cycloaddition reaction with chloral to give the expected adducts 215 160 . R1

O

R2

O

R1

R 1R 2C

R2

C

C

O

O O

+

CCl3CHO

CCl3

214

O O

215

R1

R2

Yield (%)

OMe OMe –SCH2 CH2 S–

H Me

74 81 68

When R1 = OMe and R2 = H, a low yield of a six-membered ring 1:2 cycloadduct is also obtained. The reaction of ketene with chloral at −50 ◦ C gives an 89 % yield of the cycloadduct 216 161 . O

CCl3CHO + CH2

C

O

CCl3

O

216

The catalytic (Al(iii) triamine catalyst) asymmetric [2+2] cycloaddition reaction of monoalkyl ketenes with aldehydes in benzotrifluoride at −20 ◦ C affords the β-lactones 217

274


in high yields 61 . O RCH

C

O

+

R

R1CHO

R1

O 217

R

R1

Me Et n-Pr

Ph PhCH2 CH2 CH2 CH2 OBz

Yield (%) 80 81 88

When the cycloaddition of methylketene and unsaturated aldehydes is conducted in the presence of a chiral Al(iii)-triamine complex the expected β-lactones 218 are obtained in 78–90 % chemical yields and an enantoselectivity of 90–98 % e,e 162 . O

RCHO

+

MeCH

C

Me

O

R

O

218

R

Yield (%)

PhC C– t-BuC C– Me3 SiC C–

83 90 90

The reaction of the aldehyde 219 with ketene, generated from acetyl chloride and i-Pr2 NEt in the presence of a chiral quinidine catalyst, affords the β-lactone 220 in 85 % yield (94 % e,e) 163 . O

O H +

Ph Cl

CH2

C

O

O

Ph

Cl

Cl

Cl

219

220

Also, reaction of ketene with 4-nitrophenyl trichloroacetophenone at −25 ◦ C in the presence of a quinidine catalyst gives the corresponding β-lactone in 95 % yield (89 % e,e). 164 Ketene reacts with aldehydes in the presence of oxazaborolidine catalysts to give the β-lactones in an enantioselective manner 165 . The enantioselective [2+2] cycloaddition of silylketenes 221 with α-ketoesters affords the cycloadducts 222 in 86–99 % yield (high e,es) 166 . O

O OR

Me3SiCH

C

221

O

+

R1

O

1

R

O

RO2C

222


275

Likewise, chiral N-heterocyclic carbenes are efficient catalysts for the enantioselective [2+2] cycloaddition reaction of disubstituted ketenes with oxoaldehydes, and yields of up to 99 % are achieved with enantioselectivities of up to 99 % 167 . In the cycloaddition reaction of mono substituted ketenes (R = Cl, Me, i-Pr and PhO) with chloral, mixtures of cis- 223 and trans-2-oxetanones 224 are obtained in about equal amounts 168 . O H RCH

C

O

+

CCI3CHO

H H O +

R

CCl3 O

R CCl3

H

223

224

When trimethylsilylketene is reacted with chloral in the presence of BF3 Et2 O, cisand trans-oxetanones are also obtained. Using α,β-unsaturated aldehydes the initial cycloadducts undergo a silicon and ring opening reaction to give trimethylsilyldienoate esters. The 2-oxetanones derived from dichloroketene or diphenylketene and cinnamaldehyde underwent decarboxylation to give substituted 1,3-butadienes 169 . However, trimethylsilylketene reacts with aldehydes in the presence of methylaluminum–bis(4-bromo-2,6-di-t-butylphenoxide), to give the [2+2] cycloadducts 225 in a steriocontrolled manner 170 . O

Me3SiCH

C

O + RCHO

Me3Si R

O 225

The reaction of trimethylsilylketene with hexafluoroacetone similarly produces the fourmembered ring [2+2] cycloadducts 171 . Similar [2+2] cycloadducts are obtained from trimethylsilylketene and BzOCH2 CHO (90 %) and from benzylketene and Me3 SiC C– CHO (86 %). Even disubstituted ketenes undergo the cycloaddition reaction with aldehydes in the presence of planar chiral catalysts at −78 ◦ C in THF to give the [2+2] cycloadducts 226 in high yields and good stereoselectivity 172 . RR1C

C

O

+

O

RR1

R2CHO

R2

O 226

R

R1

R2

Me Et Et

Me Et Et

Ph Ph 2-Naphthyl

Yield (%)

e,e%

68 92 77

76 91 89

Aromatic aldehydes and ketones react with diphenylketene at 120–160 ◦ C to form aromatic olefins 227 173 . In these reactions, diphenylketene can be generated in situ from its 2:1 cycloadduct with quinoline, because cycloreversion occurs above its melting point (121 ◦ C).

276


The released quinoline is a mild catalyst for the fragmentation reactions. Many carbonyl compounds, such as PhC(CN)C O, pyranones and unsaturated ketones, react similarly. In the reaction of diphenylketene with α-diketones and α-ketoesters, only one carbonyl group participates in this reaction. In contrast, acetoacetic esters and β-diketones do not react with diphenylketene 1 . O

Ph2C

C

O

+

R2C

Ph2

O

R2

Ph2C

CR2

+

CO2

O

227

Dicyanoketene, generated in situ from 2,5-dicyano-3,6-diazido-1,4-benzoquinone in benzene under nitrogen, reacts with ketones across their C O bonds to give olefins 174 . In this manner, dicyanofulvene 229 is obtained in 26 % yield from diphenylcyclopropenone 228, and similarly dicyanoolefins are formed from tropolone (20 % yield) and from thiapseudo-phenalenone (37 % yield). Ph

Ph

CN + (NC)2C

O

C

O

+ Ph

Ph

CO2

CN

228

229

In the reaction of the furandione 230 with diphenylketene, reaction across the C O bond of 230 occurs with formation of the five-membered ring lactone 231 and carbon dioxide 175 . O

O O

Ph

+ Ph

O

Ph2C

C

CPh2

Ph

O

+ Ph

O

230

O

CO2

O

231

Diketene reacts with aliphatic aldehydes in its ring-opened acetylketene form to give the unsaturated ketones 232 176 . O

RCHO

+

MeCOCH

C

O

MeCO R

RCH

CHCOMe

O

+

CO2

232

However, more often α-oxyketenes undergo the [4+2] cycloaddition reaction of aldehydes and ketones (see Section 4.1.4.4). In the reaction of diphenlketene with quinones, a [2+2] mono cycloadduct 233 is formed, which eliminates carbon dioxide on careful heating below its melting point to form the quinonemethide 234. When the β-lactone is heated to its melting point or in a high-boiling


277

solvent, the quinodimethanes 235 are formed 177 . O O

O +

Ph2C

C

CPh2

CPh2

O

O

CPh2

233

234

O

O

235

The reaction proceeds with 1,4-benzoquinone, alkyl-1,4,benzoquinones, halo-1,4benzoquinone and naphthoquinone, but tetramethyl- and tetrachloro-1,4-benzoquinone fail to react. In contrast, bis-trifluoromethylketene reacts with 1,4-benzoquinone to form 5-hydroxy2-oxo-3,3-bis(trifluoromethyl)-2,3-dihydro- 236 in 60 % yield 178 .

(CF3)2C

C

O

O

O

O

O

O (CF3)2

+

236

An intramolecular cycloaddition is observed in the generation of α-ketenylcyclobutanones 237, giving rise to the formation of 5-spirocyclopropyl- α,β -butenolids 238 179 . O

O

COC(R1)N2

O

C(R1)

•

O

O

R

R

237

238

The ketene 239 also undergoes an intramolecular cycloaddition reaction to give the cyclubutane-fused lactone 240 180 . Ph

Ph

O

• O CO2Et

O CO2Me

O

239

240

Intramolecular [4+2] cycloaddition reactions of the imidoyl ketene 241, giving rise to the formation of the heterocyclic compound 242, is also observed 181 . H O

• O

N

241

O

N

O

242

278


The ketene 243, generated by a Wolff rearrangement, undergoes cycloaddition across the ester C O group to give 244 182 . H

CO CH2N2

O

• O

O

O

O O

O

O

243

244

The racemic bicyclic β-lactone 246 is obtained in 68 % yield on treatment of the acid chloride 245 with three equivalents of N-methyl-2-chloropyridine (Mukaiyama reagent) and four equivalents of triethylamine at room temperature 183 . COCl

O O

CHO 245

246

Across C N bonds The addition of ketenes to isolated C N bond-containing compounds has been investigated by Staudinger and his coworkers. Depending on the nucleophilicity of the nitrogen, four-membered ring [2+2] cycloadducts or six-membered ring [2+2+2] cycloadducts are formed. The less basic N-arylazomethines produce β-lactams. The reactivity of the ketenes with benzophenone anil, according to Staudinger 1 is biphenylene > diphenyl > methylphenyl > dimethylketene. Ketene itself reacts with benzylidenaniline only at 200 ◦ C 184 . The Staudinger reaction is the most important synthetic procedure for the synthesis of β-lactames, encountered in penicillin and cephalosporin antibiotics. The β-lactam antibiotics are the most widely employed antimicrobial agents to date, accounting for 50 % of the world’s total antibiotic market. The β-lactam synthesis was utilized in the modification of the naturally occuring compounds and in the formation of novel β-lactam structures by ‘total synthesis’. Other β-lactames with antibiotic properties include the fused β-lactame thienamycin, the penicillinase inhibitor clavulanic acid and norcardicin. The β-lactam ring can be constructed by reacting a ketene with a suitable imine. However, it is often advantageous to generate the ketene in situ, by reacting the imine with a carboxylic acid chloride in the presence of a tertiary amine. For example, α-alkoxyketenes, generated in this manner, react with chiral imines to give the β-lactams in 50–78 % yield 185 . From the kinetic data of the latter reaction it was concluded that the azetidinone arises completely from the ketene intermediate and not via direct acylation of the imine 186 . Calculations of the reaction of MeOCH C O with a chiral imine 247, using AM 1, indicate formation of an intermediate switter ion 248 which predicts the diastereoselectivity in the formation of the β-lactam 249 187 . O C

NH

+

MeOCH

C

MeO

O

NH

MeO 247

O

NH

248

249


279

The switter ionic intermediate 248 undergoes an electrocyclic conrotatory ring closure to form the β-lactam. Extension of these calculations to several substituted ketenes and other imines correctly predicted the observed stereoselectivity of these reactions 188 . These calculations are consistent with the experimental observation of the switter ion intermediate by IR spectroscopy. 189 An overview of the advances in catalytic asymmetric synthesis of β-lactams was published by Lectka in 2004 190 , the diastereoselective formation of β-lactams from acyl chlorides and imines is discussed by Palomo in 1999 191 , and the influence of solvents in these reactions is summarized by Xu in 2006 192 . Diketene can be used as a masked acetylketene, and reaction with chiral imines, in the presence of imidazole as the catalyst, gives rise to the formation of acetyl substituted azetidinones 250 193 O O

O

+ R1N

R2

CR2 O

NR1 250

In the reaction of diketene with N-di-p-anisylmethyl substituted imine mixtures of the two 3-acetyl-β-lactams are formed in a ratio of 7:1 194 . Haloketenes, generated in situ, react with imines to afford halogenated β-lactams. For example, reaction of chloroacetyl chloride or dichloroacetyl chloride with benzophenone anil in the presence of triethylamine at room temperature affords high yields of the cycloadducts 195 . The stereochemistry of the [2+2] cycloaddition of chloroketene to substituted benzalaniline was investigated by Nelson 196 , who found that substituents in the o-position of the phenylring on carbon enhanced the formation of the cis isomers, while para substituted derivatives afforded exclusively the trans products. A two step cycloaddition process was also postulated for this reaction. Fluoroketenes, PhC(F) C CO and CHF C O, react with imines R1 CH NR (R1 = Ar, Et, Me) to give [2+2] cycloadducts having cis stereochemistry 197 . Trimethylsilylbromoketene, generated in situ, reacts with N-t-butylbenzylimine to give a 56 % yield of the cycloadduct 198 . Attachment of a trimethylsilyl group to the imine nitrogen allows formation of azetidinones with no substituents on nitrogen, but the yields of the cycloadducts are low 199 . MeO, Ph, A comparison of the reaction products obtained from RCH NPh (R PhCH CH) and two heterocyclic imines with ketenes, generated by photolysis of oxazolidine– and oxazolidinone–chromium carbene complexes and from the oxazolidinone carboxylic acid chlorides, indicated high yields and high diastereoselectivities in some of these reactions 200 . Photolysis of the chromium carbene complexes 251 in the presence of iminodithiocarbonates affords the expected β-lactams 252 201 .

R1C(R)

Cr(CO)5

251

R1C(R)

C

O

+

(MeS)2C

NR2

O

RR1

NR2

(MeS)2 252

280


Generation of asymmetric ketenes in the photolysis of the chromium aminocarbene complex 253, in the presence of acetone benzyl imine, afforded the β-lactames 254 with a modest level of asymmetric induction (70 % de) 202 .

O

+ N

Ph

BzN

Me Me

N

O

CMe2

Ph O

H

NBz

Cr (CO)5 253

254

Similar cycloadducts are also obtained from the corresponding carboxylic acid chlorides and triethylamine 203 . Other functional groups in ketenes, generated in situ from the carboxylic acid chloride precursors, include isocyanoketene 204 , azidoketene 205 and alkylcyanoketenes and halocyanoketenes 206 , which are generated in the thermolysis of an azidobutenolide 255 or 2,5-diazido-3,6-dialkylquinones 256. The cycloaddition reaction of halocyanoketenes with formimidates and thioformimidates to give the cycloadducts 257 is stereospecific 207 . O

O

X O

N3

H

255

OMe

O

X

N3

N3

X

or

X NC(X)C

C

O

+

R1N

H NR1

CHR2 NC

O

R2 257

256

X

R1

R2

Cl Br Cl Me

C6 H11 C6 H11 C6 H11 Ph

OEt OEt SMe SEt

Yield (%) 94 85 85 80

In the reaction of cyano-t-butylketene, generated from 256, with benzylidenemethylamine, a 75 % yield of the [2+2] cycloadduct is obtained. However, conducting the reaction at −78 ◦ C in liquid sulfur dioxide, six-membered ring 1:2 adducts are obtained 208 . The [2+2+2] cycloadducts are also obtained if one equivalent of the ketene is reacted with three equivalents of benzylidenemethylamine at −17 ◦ C in toluene 209 . Alkylthioimidates also react with ketenes, generated from the corresponding carboxylic acid chlorides and triethylamine, to give trans-β-lactams 210 . Thioalkyl substituted ketenes 258, generated in the photolysis of a diazomalonate precursor, react with N-benzylidene-aniline to give a quantitative yield of the [2+2]


281

cycloadduct 259 211 . SR MeOCOC(COSR)

N2

[MeOCOC(SR)

C

O]

+

PhCH

MeO2C

NPh

Ph

258

O

NPh 259

Dehydrochlorination of α-(phenylthio)alkanoyl chlorides with triethylamine in the presence of imines derived from cinnamaldehyde and p-anisidine give high yields of α-phenylthio-β-lactams. α-Haloalkanoyl chlorides react with the same imines to give [4+2] cycloadducts 212 . In order to convert the substituent on the azetidinone into a functional group, which can be derivatized, several strategies were developed. Sheehan and Ryan 213 reacted phthalimidylacetyl chloride 260 with imines in the presence of triethylamine. Acidcatalyzed removal of the phthalimide afforded an amino group for further functionalization. For example, nocardicin A is constructed by reacting 260 with a masked methylene imino derivative to form the [2+2] cycloadduct 261 in the key step of the synthesis 214 . R

O NCH2COCI

N

+ R

O H

N O

+

Et3N

H

N

H

R O

O

NR O

261

260

In the reaction of phthalimidylacetyl chloride with the chiral imines 262, the two isomeric cycloadducts 263 and 264 are obtained. The ratio of the stereoisomers depends on the solvent used in the cycloaddition reaction 215 . O

O O

N NCH2COCI + BzCH2N

CH2X

+ O

NBz O

X

N

X O

NBz O

O

262

Solvent CH2 Cl2 CHCl3 CCl4 CCl2 CHCl PhMe

263

264

Ratio of 263:264 65:35 90:10 80:20 75:25 70:30

N-Alkyl-N-phenylglycine hydrochloride reacts with tosylchloride and five equivalents of triethylamine, in the presence of imines, to give the β-lactams 265. One isomer is formed

282


in all cases, and the substitution in the imine influences the stereochemistry 216 . H

RN(Ph)CH

C

O

R1CH

+

NR2

R1

RN(Ph)

NR2 O

265

R

R1

R2

Me Me Me Me

Ph Ph 4-MeOPh 4-ClPh

PhCH2 2-MeOPh PhCH2 α-C10 H7

Yield (%) 66 57 86 73

Isomer cis trans cis trans

Imines derived from chiral α,β-epoxyaldehydes give enantiomerically pure cis-substituted 3-amino-4-alkylazetidinones, when the reaction with the substituted acetyl chloride and triethylamine is conducted at −78◦ C (yield: 84 %) 217 . Chiral imines, RN CHCH CHPh, derived from 3,4;5,6-di-O-isopropylidene-d-glucosamine propanedithioacetal and cinnamaldehyde, afford a 92 % yield of the cis-β-lactam 218 . Because of the harsh conditions required in the removal of the protecting group, it was necessary to find better ‘masking groups’ for the Staudinger reaction. Azidoacetyl chloride was found to be the most useful reagent for the generation of an amino group 219 . Bose and coworkers pursued the azidoacetyl chloride reaction with cyclic azomethines in order to develop analogues of penicillin and cephalosporin 220 . Penicillin G was synthesized in this manner by Firestone and coworkers 221 . By using a six-membered ring thiazine derivative in this reaction, cephems are readily obtained 222 . Using a furanothiazine as the substrate in the [2+2] cycloaddition reaction, the cephalothin lactone is obtained 223 . The reaction of azidoacetyl chloride with imines is also used to construct oligopeptides 224 . The stereochemistry of this reaction is influenced by altering the experimental conditions. When azidoacetyl chloride 266 is added to triethylamine and the azomethine, the formation of the cis-cycloadduct 267 is favored over the trans-isomer 268 by a ratio of 3:1. Conversely, when the azomethine and the triethylamine is added to the azidoacetyl chloride, the ratio of the cis- to trans-cycloadducts is 1:3 225 . However, the yields of the cycloadducts obtained are on the low side. O

O

N3 N3C(R)HCOCI

+

R1R2C

R R1 NR3

NR3 R

R2 266

267

R1 NR3

+ N3

R2 268

Trifluoromethyl substituted aldimines react with α-benzyloxyacetyl chloride in the presence of triethylamine to give the CF3 substituted azetidinones in 50 % yields 226 . Also, N-α-(trimethylsilyl)methyl imines undergo cycloaddition with the oxazolidinone substituted ketene 269 to give the [2+2] cycloadducts 270 with excellent diastereomeric


283

selectivities. The oxazolidinone group is easily cleaved after the reaction 227 . O

O

O H

N

+ RCH

O

NCH(SiMe3)2

H R

N

•

NCH(SiMe3)2

O

O

269

270

R Me Et PhCH2 PhCH2 CH2

Yield (%)

cis:trans ratio

70 60 55 82

70:30 >98:2 >98:2 92:2

The relative basicity of the nitrogen atom of the imine seems to determine the stereochemistry of the azetidinones. If the pka of the nitrogen is greater than 2.05, cis-azetidinones are formed exclusively while at lower pK a values, mixtures of both isomers are formed 228 . Instead of the azidoacetyl chloride, the anhydride, derived from azidoacetic acid and trifluoroaceticanhydride, can be used in the [2+2] cycloaddition reaction to give the β-lactames 271 229 . H

N3CH2COOCOCF3

+

PhCH

O

N3

NPh

Ph

NPh

271

A mild phosphorylation reaction is the reaction of imines with carboxylic acids, triphenylphosphine, carbontetrabromide and triethylamine at −78 ◦ C to form the cycloadducts 272 230 . O

RCH2COOH

+

PH3P

+

CBr4

+

Et3N

+

R1CH

NR2

R R1

NR2

272

R

R1

R2

MeO PhO PhCH2 O

Ph 4-MePh Ph

Ph 4-MeOPh 4-MePh

Yield (%) 85 70 85

Also, activation of carboxylic acids with 2-chloro-N-methylpyridinium iodide 273 is used to generate the ketenes in the presence of three equivalents of tripropylamine to give

284


the β-lactams 274 in good yields and with high stereoselectivity 231 . O

I− R1CH2COO

N

+

Pr3N

R2CH

+

R1 R2

NR3

Cl

273

NR3

274

R1

R2

R3

CH2 CH PhO PhO N3

Ph Ph 4-MeOPh 4-MeOPh

4-MeOPh 4-MeOPh 4-MePh 4-MePh

Yield (%)

cis:trans ratio

70 84 81 88

trans 15:1 2.2:1 10:1

Ketenes are also easily generated using an anhydride derived from the corresponding carboxylic acid and N-[(chlorosulfinyl)oxy]methylene-N-methyl methanaminium chloride 275. In the cycloaddition of diphenylketene, generated in this manner with 1,3-diaza-1,3butadiene, the [2+2] cycloadduct 276 is obtained 232 . R 2N [RR1CHCOOS(O)OCH

NMe2]CI−

Ph2C

C

O +

O

RR1

Ph

NR2

N

Ph

NMe2

Me2N

275

276

R

R1

R2

Yield (%)

Ph Ph Ph Ph

Ph Ph Ph Ph

H Cl Br Me

85 82 86 80

The substituents attached to the 1,3-diaza-1,3-butadiene system determine the course of the reaction and usually a [2+2] cycloadduct is mainly obtained in the above reaction, while [4+2] cycloadducts are obtained with other substituents (see Section 4.1.4.4). The reaction of phenylketene, generated similarly, with the diazabutadiene affords the [4+2] cycloadduct. Bulky substituents favor the [2+2] cycloaddition 233 . Phenylmalonyl chloride 277 is also used in the synthesis of azetidinones. The obtained cycloadducts 278 have the reactive COCl group for further transformations 234 . ClCO−

CICOCHPhCOCI 277

+

Et3N

+

RCH

NR1

Ph

R

O NR1

278


285

In the reaction of the unsaturated imine 279 with acid chlorides in the presence of triethylamine, the N-alkenyl-β-lactams 280 with the indicated stereochemistries are formed 235 .

RR1CCOCI

+

R2CH

N-CH

CHR3

O

RR1

+ Et3N

R2

N R

279

280

R

R1

R2

R3

PhO PhO PhO

H H H

Ph PhCH CH PhCH CH

H H Me

E:Z ratio

cis:trans ratio

Yield (%)

7.5:1

31:1 cis cis

96 86 88

In the reaction of R1 C(CN) C O with PhCH CH-CH NR, predominantly the cycloadducts 281 are formed, except in the case of R1 = t-butyl, where the cycloadduct 282 is mainly formed 236 . CN

R1C(CN)

C

O

+

PhCH

CH-CH

NR

R1

O

R1

+

NR

H CH

O

NC

NR

H

CHPh

CH

281

CHPh

282

The structure of the imine sometimes determines the product formation. In the reaction of PhSC(Me) C O, 283, with PhCH C(Me)–CH NAr the cis-[2+2] cycloadducts 284 are formed, while the reaction of the same ketene with PhCH C(Ph)–CH NAr affords the [4+2] cycloadducts 285 237 . Me

PhCH

C(Me)CH

O

PhS

NAr

Me

NAr

Ph

284

PhSC(Me)

C

O

283 Me

PhCH

C(Ph)CH

NAr

Ph

SPh O

Ph

NAr

285

286


In the reaction of diphenylvinylimine 286 with dichloroketene the [2+2] cycloadduct 287 is produced exclusively 238 . O Cl2

Cl 2C

C

O

+

Ph 2C

CH–CH

Ph

NPh

NPh

Ph

286

287

Sometimes, different stereoisomers are obtained in the [2+2] cycloaddition reaction of ketenes with imines depending on the structure of the imine. As an example, ethylketene reacts with alkylarylimines to give cis-β-lactams, while diarylimines give the trans-βlactams. When phenoxyketenes are reacted with diarylimines, the cis-β-lactams are formed. N-Aminosubstituted imines react with PhOCH2 COCl/Et3 N to give the corresponding cis-β-lactam 288 239 . O PhO

PhOCH 2COCI

+

PhN(R)–N

CR1R2

R1R2

N–N(R)Ph

288

1,4-Diaza-1,3-dienes are used as the imine component in this reaction in order to provide a precursor for cis-4-formylazetidin-2-ones 240 . The reaction of 1,4-diaza-1,3-butadienes with ketenes, generated from carboxylic acid chlorides, affords the mono cycloadducts 289 and the bis-[2+2] cycloadducts 290, by either one-pot or two-stage reactions 241 . H

MeOCH

C

O

+

RN

CH–CH

NR

MeO

O NR

RN

H

289

NR

RN + O

MeO

OMe

O

290

Chiral carbohydrate-based ketenes also undergo the [2+2] cycloaddition with imines to give cis-3-hyroxy-β-lactams after removal of the sugar 242 . In recent years considerable efforts were made to synthesize asymmetric β-lactams using chiral ketenes, chiral imines or chiral catalysts. For example, catalysis of the Staudinger reaction, using a chiral DMAP and a PPY catalyst system affords the β-lactams with good enantioselectivity (76–98 % yield, 81–98 % e,e) 243 . When the N-group is substituted with a triflyl group, preferentially trans-β-lactams are obtained. In contrast, when the N-protecting group is a p-toluenesulfonyl group, the cis-β-lactams are formed 244 . When a chiral bifunctional amine catalyst (benzoylquinine) and a proton ‘sponge’ is used in the reaction of methylphenlketene with RCH NCOOEt a mixture of two diastereomeric β-lactams with a ratio of trans:cis of 97:3 is obtained 245 . In the absence of the catalyst, using only triethylamine, a 1:1 mixture of the stereoisomers is obtained.


287

Examples of this reaction, conducted at −78 ◦ C afford the β-lactams 291 246 . CO2Et

R

RCH2COCI

+

TosN

CHCOOEt

NTos O

291

R

Yield (%)

e,e %

65 61 61

99 98 96

Ph OAc Br

Higher yields (77–85 %) of the [2+2] cycloadducts are obtained when pnitrophenylsulfonylimines are reacted with dichloroacetyl chloride in the presence of ethyldiisopropylamine in methylene chloride 247 . The [2+2] cycloaddition reaction of N-silylimines proceeds in a stepwise fashion, because the linear intermediate 292 could be isolated 248 . O +

• R1

R2

H

R2

H H

R1

N SiR3

H

R1

R2

N

N

O

H

O

R3SiO

SiR3

R2

R1

H

H NSiR3

292

When the chiral imines 293 are used in the [2+2] cycloaddition reaction with ketenes, only one β-lactam 294 is obtained 249 . R2 OSi(t-Bu)Me2

R1R2C

C

O +

R3

R3 OSi(t-Bu)Me 2

1

R

R4

4

R

5

NR

NR5

O

293

294

R1

R2

R3

R4

R5

Yield (%)

BzO BzO

H H

Me Me

Me Bz

Bz Bz

70 70

Using a chiral ketene 295 with the imine 296, and conducting the reaction in refluxing chloroform, again one β-lactam 297 is obtained. O

O

O + Et3N + R1R2C

N Ph

H

N Ph O

COCl

295

NCH(SiMe3)2

O

296

NCH(SiMe3)2

297

288

Cumulenes in Click Reactions R1 = R2

Yield (%)

Me Et i-Pr

70 69 70

When the imine R1 = Me and R2 = Et is used in this reaction, a diastereoisomeric pair of β-lactams is obtained in 65 % yield in a ratio of 70:30. In the [2+2] cycloaddition reaction of the unsymmetrical cyclic ketenes 298 with PhCH NPMP, spiro-β-lactams 299 and 300, with a cis-relative disposition of the substituents at the imine C carbon and the proline nitrogen, are obtained in 60–70 % yields 250 . R

N–Cbz

R •

O

+

PhCH

Ph

NPMP

N

N–Cbz

R

Ph

+

NPMP

NPMP O

O

Cbz 298

299

300

The asymmetric synthesis of haloazetidine-2-ones 302 is conducted by reacting the corresponding acid chlorides with the imines 301 (n = 1 or 2) in methylene chloride in the presence of triethylamine 251 . O

H

ROCH2COCI

+

H O

H CHO

RO

N N O

( )n

( )n

Cl

Cl

301

302

The reaction of diazothioesters 303 with imines 304 in the presence of Rh2 (OAc)4 affords the β-lactams 305 in high yields 252 . SPh H

O O EtO2C

+

• SPh

N2

R2

EtO2C

N

SPh

303

NR1

R1

O

304

R

1

R2

EtO2C

305

R

2

Ph

Ph

4-MeOPh 4-MeOPh

CH CHPh

O

Yield (%) 89 85 96

The [2+2] cycloaddition reactions of ketenes with C N group-containing heterocumulenes such as isocyanates (Chapter 3, Section 3.3.1) and carbodiimides (Chapter 3, Section


289

3.3.3) are discussed in the previous chapter. The cycloaddition reaction of ketenes with isothiocyanates should proceed across the C S bond of the isothiocyanate but examples are not known. Across C S bonds From thiobenzophenone and diphenylketene, a [2+2] cycloadduct (m.p. 180–181 ◦ C), is obtained at room temperature. Because of the generation of the starting materials on heating above the melting point, Staudinger suggested that the reaction proceeded as shown to give the [2+2] cycloadduct. 306. O

Ph2

Ph2C

C

O

+

Ph2C

S

Ph2

S

306

However, the [2+2] cycloadducts are not often isolated but rather the thermolysis products are isolated, often in good yields. From the p-dimethylamino substituted thiabenzophenone, presumably a β-thiolactone 307 is initially formed because of formation of tetramethyldiaminotetraphenylethylene and carbonyl sulfide 1 . O

Ph2

Ph2C

C

O

+

R2C

S

R2

Ph2C

S

CR2

+

COS

307

In the reaction of the C S heterocycle 308 with diphenylketene, reaction proceeds across the C S bond with formation of COS and 309 253 . O

O

Ar

Ar NPh

+

Ph2C

C

O

NPh

S

CPh2

308

309

+

COS

The reaction of several other heterocyclic C S bonds with ketene, bis(trifluoromethyl)and diphenylketene proceeds in a similar manner. For example, from 310 and bis(trifluoromethyl)ketene the exchange product 311 is obtained in quantitative yield 254 . CO2Me

CO2Me

N

N

CF3

N

N

CF3

CO2Me

CO2Me

310

311

S

+

(CF3)2C

C

O

+

COS

Across N O bonds The [2+2] cycloaddition reaction of ketenes with nitroso compounds affords the four-membered ring cycloadducts. For example, diphenylketene reacts with nitrosobenzene to give the cycloadduct 312. On heating of the cycloadduct, dissociation

290


with formation of benzophenone and phenyl isocyanate is observed, which is in agreement with the proposed structure 255 .

Ph2C

C

O

+

PhN

O

Ph2

O

O

Ph2CO

NPh

+

PhN

C

O

312

Electron donating groups, such as 4-alkoxy, or 4-dimethylamino groups in the nitroso compound favor the reverse type of addition giving an unstable β-lactone 256 . Some of the [2+2] cycloadducts 313 obtained in the reaction of ketenes with nitroso compounds are listed in Table 4.9. Table 4.9 [2+2] Cycloadducts of ketenes and nitrosobenzenes RR1C

C

O

+

R2N

O

RR1

O

NR2

O

313

R

R1

R2

Ph Ph Ph

Ph Ph 4-ClPh

Ph 4-ClPh Ph

Yield (%)

Reference

65 48 52

255 256 256

Across N N bonds Trans-azobenzenes do not react with diphenylketene, but the cisisomers, generated by irradiation of the azobenzene derivatives, react exothermally to give the expected [2+2] cycloadducts 314. Some of the 1,2,3,3-tetrasubstituted-1,2diazetidinediones obtained in this manner are listed in Table 4.10. Table 4.10 [2+2] Cycloadducts from ketenes and azobenzenes RR1C

C

O

+

R2N

O

RR1

NR3

NR3

R2N

314

R

R1

R2

R3

H H Me Ph Ph Ph Ph Ph

H 3-MeOPh Me Ph Ph Ph Ph Ph

Ph Ph Ph CN CN CN 2-MePh 4-MeOPh

Ph Ph COOEt 2-ClPh 3-ClPh 4-BrPh 2-MePh 4-MeOPh

Yield (%)

Reference

68 57 70 87 80 92 91 71

257 258 259 260 260 260 261 261


291

Di-p-nitroazobenzene does not form a cycloadduct, apparently due to the fact that only small amounts of the cis-isomer are formed during irradiation. In contrast, irradiation of 4,4 -bis-dimethylaminoazobenzene, in the presence of diphenylketene, gives only the retroproducts, p-dimethylaminoisocyanate and N-p-dimethylaminophenylbenzo-phenone. Heating of the [2+2] cycloadducts at 220 ◦ C gives the same fragments. An exception are the cyano substituted diazetidinones, which undergo a thermal rearrangement to give imidazo[1,2-a]benzimidazoles 260 . Azo derivatives of some heterocycles also undergo the [2+2] cycloaddition reaction with diphenylketene, generated in situ, from azobenzil 262 . In the reaction of ketene or diphenylketene with asymmetrically substituted azobenzenes, mixtures of the two regioisomeric [2+2] cycloadducts 315 and 316 are obtained. However, one of the isomers predominates, as shown in Table 4.11. Table 4.11 [2+2] Cycloadducts of ketenes and asmmetrically substituted azobenzenes RR1C

C

O

+

PhN

O

RR1

NR2

O

RR1 +

R2N

NPh

315

R

R1

R2

H H Ph Ph Ph Ph

H H Ph Ph Ph Ph

3-MePh 2-MeOPh COMe 4-MePh 4-MeOPh 4-NCPh

NR2

PhN

316

315 (%)

316 (%)

Reference

29 81 60 54 64 64

36 — 26 46 36 36

263 263 264 264 264 264

Arylazoalkenes react with diphenylketene to give both the [2+2] cycloadduct 317 and the [4+2] cycloadduct 318 265 .

RN

N–CHR1

CR2R3

+ Ph2C

C

Ph2

O

3R2C

R

R1

O +

1N

CHCR

NR

317

R

R1

R2

R3

Ph Ph Ph 4-ClPh 4-ClPh

H H –(CH2 )4 – Me Me

PhCO H COOMe H H CN H H CN

R2 N

R3 Ph2 N R

O

318

317 (%) 318 (%) 86 85 — 75 89

— — 72 10 —

The thus obtained [2+2] cycloadducts are converted into the [4+2] cycloadducts by treating a solution in dichloromethane with a catalytic amount of trifluoroacetic acid.

292


Also, azodicarboxylates react with diphenylketene to form mixtures of the [2+2] cycloadducts 319 and 1:2 adducts formed in an initial [4+2] cycloaddition reaction, followed by another [2+2] cycloaddition across the generated C N bond to give 320 266 .

Ph2C

C

O

+

EtOCON

NCOOEt

O

O

Ph2

Ph2

+ NCO2Et

EtO2CN

N

O

N O

Ph

319

Ph

320

A similar 1:2 adduct is obtained from azodibenzoyl and diphenylketene. Heating of 320 causes elimination of diphenylketene with regeneration of the 1:1 adduct. Compounds that contain an azo group locked into the cis-configuration react rapidly at room temperature with ketenes to give the [2+2] cycloadducts. For example, 3H-4,1,2benzoxadiazines react with diphenylketene to give either one of the two stereoisomers 321 or 322 267 . R2

R1

R2

O N

+

Ph2C

C

N

R3 R4

4

R

R2

O

O

N

R3

R1

Ph

R1

O

+

N

N

R3

O

N

R4

Ph

Ph Ph

O

321

322

R1

R2

R3

R4

Yield (%)

t-Bu H Cl Br

H H H H

t-Bu Cl Cl Br

H H H H

51 92 90 85

Also, dimethyl-5-carbomethoxy-3H-pyrazole reacts readily with diphenylketene to give the [2+2] cycloadduct 268 . In a similar manner, the [2+2] cycloadduct is obtained from 2,7-dimethyl-4,7a-diphenyl-3-acetyl-7,7a-dihydrofuro-[2,3-d]pyridazine and diphenylketene 269 . Diazaspiro[2,3]hexane 324 is obtained in the reaction of the ketene 323 with azobenzene 270 . Ph

Ph

Ph

Ph N

Ph •

Ph

O

+

PhN

NPh

NPh Ph

Ph 323

O

Ph 324

A double cycloaddition is encountered in the reaction of o-diazo oxides and dimethylor diphenylketene. The first step is an addition of the ketene to the diazo oxide to give 325,


293

which is in a thermodynamic equilibrium with the starting materials. In the second step, the generated azo compound undergoes the [2+2] cycloaddition with a second equivalent of the ketene to form the four-membered ring compounds 326 271 . O

O

O +

R2C

N2

C

O N

N

O

O R R

+

R2C

C

R R

O N Ph2

325

N

O

326

Across other double bonds The reactions of ketenes with compounds containing P C, P N and P S bonds were investigated by Staudinger and his coworkers. For example, tetraphenylphosphorus imine reacts with diphenylketene to give a quantitative yield of the triphenylketene imine 327. Ph3P

Ph2C

C

O

+

Ph3P

NPh

NPh

Ph2C

O

C

NPh

+

Ph3P

O

CPh2

327

The reaction of bis-iminophosphoranes 328 with diphenylketene affords the bisketenimines 329 in high yields via [2+2] cycloaddition and cycloreversion processes 272 . Ph3P

N

•

Ph2C + N

2 Ph2C

C

N

O

PPh3

N

328

•

CPh2

329

The [2+2] cycloaddition reaction of ketenes with N-sulfinylamines and N-sulfinylsulfonamides is discussed in Chapter 7, Section 7.3.1. Tetramesityldisilene 330 reacts with dimethyl- and diphenylketenes across their C O bonds to give the [2+2] cycloadducts 331 273 . SiMes2

Mes2Si

Mes2Si

SiMes2

+

R2C

C

O

O R2C

330

331

In the reaction of the rhodium ketene complex 332 with t-BuC P the cycloadduct 333 is obtained in 79 % yield 274 . PR3

Cl

Rh PR3

332

•

H H

R3P +

t-BuC

P

Cl

P Rh

R3P

333

294


The reaction of ketenes with ketenimines in anhydrous liquid sulfur dioxide affords 1,2-oxathiane-4-one 2-oxides 275 .

Across single bonds (insertion reactions) Ketenes participate in insertion reactions into many single-bonded substrates. The mechanism of this interesting reaction is not known. The reaction often is quantitative, and, depending upon reactive sites, either mono or oligo adducts are formed. Early examples include the reaction of diphenylketene with phenylmagnesium bromide 1 and ketene with methylmagnesium iodide 276 . Ketones are the hydrolysis products derived from the insertion reaction of ketenes with phenylmagnesium bromide, dimethylzinc and organic mercury compounds. From dimethoxymercury 334 and two equivalents of ketene, the esters 335, formed by insertion into the Hg–O bond, are obtained 277 . Hg(OMe)2

+

2 CH2C

C

O

Hg(CH2COOMe)2

334

335

The formation of an insertion product of diphenylketene into the B–S bond in trimethyl thioborate is evidenced by the isolation of Ph2 CHCOSMe after hydrolysis 278 . Insertion of ketene into C–H, C–O and C–Cl bonds is also encountered. For example, reaction of triphenylmethyl chloride with ketene in a nonpolar solvent, in the presence of aluminum chloride, affords the insertion product 336. In nitrobenzene, the reaction proceeds without the added catalyst 279 . Ph3CCI

+

CH2C

C

O

Ph3CCH2COCI 336

Ortho esters and acetals react similarly, to give the mono adducts 280 , and from tetrahydrofuran and ketene, in the presence of borontrifluoride, e-caprolactone is obtained 281 . Cyclic ethers and thioethers react with dichloroketene in the presence of ZnCl2 to give insertion products. For example, from 2-phenyl-1,3-dithiane 337 the insertion product 338 is obtained 282 . S

Ph

+ S

CCI2

C

S

O

S

Ph Cl

337

Cl O

338

The insertion reaction of ketenes into single bonds usually occurs across the C C bonds of the ketenes. An exception is the addition of ketenes to trimethylsilylcyanide, which occurs across the C O bond to give 2-trimethylsilyloxyacrylonitriles 339 283 . The insertion reaction into the Si–C bond is faster than the dimerization of the ketenes, as evidenced in the generation of the ketenes from the carboxylic acid chloride precursor with triethylamine, where dimerization can occur. Even from dichloroketene, which is known to undergo a fast


295

dimerization reaction, the insertion product is obtained in 60 % yield. R1R

C

C

RR1C

O + Me3SiCN

C(CN)OSiMe3 339

R

R1

Yield (%)

H Me n-C16 H35 CF3 –(CH2 )5 – Ph

H Me H CF3

96 85 95 90 82 90

H

Also, liganded 2-methylidenetitanacyclobutane 340 reacts with diphenylketene at room temperature to give the insertion product 341, resulting from insertion into the C O bond of the diphenylketene, in 59 % yield 284 . +

Li2Ti

Ph2C

C

O

L2Ti O CPh2

340

341

A similar insertion into a Si–P bond to give 343 occurs in the reaction of diphenylketene with the heterocyclic compound 342 285 . OSiMe3 P

PSiMe3

Ph2C

C

O

+

Si–SiMe3

Ph

Si–SiMe3

Ph

SiMe3

342

CPh2

SiMe3

343

In contrast, insertion of a ketene into the Si–N bond in hexamethyldisilazane proceeded across the C C bond 286 . Trialkyltin alkoxides also react with ketene with formation of the normal insertion product 287 , antimony tris-alkoxides react with ketene to give a tris ester 288 and triphenyllead acetate reacts with ketene in ethanol to give ethyl (triphenyllead)acetate 289 . Halides of nitrogen and sulfur also form insertion products with ketenes. For example, nitrosyl chloride reacts with ketene to give the insertion product 344 290 . CH2C

C

O

+

O2NCI

O2NCH2COCI 344

In contrast, ketenes insert into chloramines to give amides 291 . From sulfur dichloride and disulfur monochloride, respectively, the acid chloride insertion products are formed 292 . Arylsulfenyl chlorides 293 and acetylsulfenyl chloride 294 react similarly with ketene.

296


4.1.4.3


In the reaction of substituted oxirans with diphenyl- or ethylphenylketene in the presence of Ph4 SbI as the catalyst, 4-substituted lactones 345 are formed exclusively, indicating that stereoselective α-cleavage of the oxiran occurs 295 . R

R

Ph2C

+

C

O

Ph2

O

O

O 345

Also, dichlorocarbene undergoes a [3+2] cycloaddition to phenyloxiran 346 to give the cycloadduct 347 295 . Ph

Ph

+

CCI2

C

O

O

Cl2

O

O 346

347

2-Vinylthiiran 348 reacts with diphenylketene in the presence of palladium catalysts to give the 1,3-oxathiolane 349 in 59 % yield 296 . Ph2C

+

C

O

Ph2

S

S

O 348

349

Some azirines react with ketenes via a [3+2] cycloaddition reaction. For example, the substituted 2-aminoazirine 350 reacts with ketenes to give the 2,5-dihydro-1,3-oxazines 351 and 352 and the linear adduct 353 297 . Me2N N

CR2

O

R2C

+

C

O

N

+

O

R2

N

NMe2 351

350 +

Me2C

C(Me)C(NMe2)

NMe2 352 NCOCHR2

353

The mesoionic compound 354, which is in equilibrium with the ketene 355, undergoes a [3+2] cycloaddition reaction with azirines to give the cycloadduct 356 in good yield 298 . Ph

O

O

O N Me

354

O

•

⊕

Ph

Me2N

Ph

Ph

N Me

355

+ Ph

N

O

N (Me) COPh N

NMe2 356


297

From 3-dimethylamino-2,2-dimethylazirine and diphenylketene, the [3+2] cycloadduct, resulting from addition across the C O bond of the ketene, is obtained in 60 % yield 299 . In contrast, some substituted azirines 357 react with diphenylketene to give 5-pyrrolin2-ones 358 via the [3+2] cycloaddition reaction 300 . Ph

N

O

N

+

Ph2C

O

C

Me

Ph2

Me

O

O

R

R

357

358

R

Yield (%)

H Me Ph OMe

50 77 55 70

Vinyl sulfilimines 359 react with dichloroketene via a [3+2] cycloaddition reaction to give α-dichloro-γ -butyrolactams 360 301 . R2N S R1

R4

R5 R4

R5

+

Cl2C

C

O

R3 R1S

R3

359

Cl2 N R2

O

360

The nitrosoketene 362, generated from the Meldrums acid 361, undergoes a [3+2] cycloaddition reaction with ketones to give 3-oxazolin-5-one 3-oxides 363 302 . O

O

O

•

O

O

O

O

•

ON

N

N

+

R2C

O

O N

O

O

R2

O 361

362

363

An ab initio calculation showed that [3+2] cycloaddition reactions are preferred over [4+2] cycloaddition reactions in nitrosoketene 303 . Chiral cyclic ketones react similarly with nitrosoketene to give spiro 3-oxazolin-5-one 3-oxides 304 . Ketenes also undergo [3+2] cycloaddition reactions with typical 1,3-dipoles, such as nitrones and nitrile oxides. For example, t-butylcyanide N-oxide reacts with diphenylketene

298


to give the heterocyclic adduct 364, most likely via a stepwise process 305 . O

Ph2 Ph2C

C

O

+

Me3 C–C

N

O

N

O

364

The reaction of benzonitrile N-oxide and its derivatives with several ketenes proceeds in a similar manner 306 . From trimethylbenzonitrile oxide and several ketenes, similar [3+2] cycloadducts are obtained 307 . The reaction of pyridine N-oxides with dichloroketene affords a mixture of the [3+2] cycloadduct 365 and the bicyclic lactone 366 308 . Cl2 +

C

O

+ Cl Cl

N

–

N

Cl2C

O

O

N

O

O

O

365

366

Thermolysis of the heterocycle 367 affords a thiocarbonyl ylide, which reacts with diphenylketene in a stereospecific [3+2] cycloaddition reaction to give the adducts 368 309 . R

N N R

S

H

R1

H S

R1

Ph2C +

Ph2C

C

O

O R

367

S

R1

368

Arylnitrones react with diphenylketene to give [3+2] cycloadducts, which lose carbon dioxide to give ortho-substituted imines 310 . From pyridine N-oxide and diphenylketene 311 or dichloroketene 312 , similar reactions are observed. Diphenylketene also reacts with diphenyldiazomethane to form the [3+2] cycloadduct 369 313 . In this reaction, the C O bond of the ketene participates in the cycloaddition reaction.

Ph2C

C

O

+

Ph2C

N2

CPh2

O Ph2

N N 369

In the reaction of ketene with diazomethane, cyclopropanone is initially formed, which reacts with another equivalent of diazomethane to give cyclobutanone 314 . Diazoketones react with ketenes by addition to the diazo compound. The cycloadduct eliminates nitrogen to produce butenolides 315 . However, the ketocarbene 370, generated from


naphthalene-1,2-diazo cycloadduct 371 316 .

oxide,

O

reacts

with

diphenylketene

to

give

[3+2]

CPh2

O

O

O

••

N2

the

299

+

Ph2C

C

O

370

371

Benzoylketene 372 undergoes a [3+2] cycloaddition reaction to the isoquinolinium ylide 373 to afford pyrrolo[2.1-a]-isoquinoline derivative 374 317 . O

O

•

O Ph

Ph

O

+

NCHCOPh

N

COPh

O PhCO 372

373

OH 374

In the reaction of diphenylketene with isonitriles, initially a 1,3-dipole 375 is generated, which reacts with another equivalent of diphenylketene to give the [3+2] cycloadduct 376 318 . O

Ph2 Ph2C

C

O

+

RNC

RN

C+–COC−Ph2

Ph2

O NR

375

4.1.4.4

376


Ketenes participate as dienes as well as dienophiles in [4+2] cycloaddition reactions. For example, several ketenes with a suitable substituent in the α-positions readily participate in [4+2] cycloaddition reactions. The substituents include unsaturated groups, α-oxo, αthio or α-imino groups. In their role as dienophiles, ketenes participate in the reaction with dienes, azadienes, diimines and o-quinones by addition across the C C bonds, and sometimes the C O bonds. The [2+2+2] adducts obtained in the reaction of ketenes with C N double-bonded substrates (see Section 4.1.4.2) are another example of [4+2] cycloaddition reactions of ketenes. In the catalyzed thermal reaction of alkylarylketenes with cyclopentadiene [4+2] cycloadducts are obtained (see Section 4.1.4.2). In this reaction, the ketene undergoes the reaction across its C O bond initially, but the isolated cycloadducts derive from addition across the C C bond. In contrast, olates, such 6-oxo-3,6-dihydro-1-pyrimidinium-4-olates 377, react with dimethyl- and diphenylketene across the C O bonds to give the stable

300


[4+2] cycloadducts 378 319 . CR2

R2 R2C

C

O

+

O

O

O O

NPh

PhN

NPh

PhN

R1 377

378

R

R1

R2

Yield (%)

Me Ph

Ph Ph

H H

93 88

The diene 379 with a cis-fixed configuration reacts with diphenylketene at 55 ◦ C for 15 days to give a 1:1 mixture of the two [4+2] cycloadducts 380 and 381, resulting from addition across the C C as well as the C O bonds of the ketene, respectively, in 70 % yield 320 . Ph2C +

Ph2C

C

O

O

Ph2

O +

379

380

381

When the reaction is conducted in the presence of ZnCl2 , two equivalents of diphenylketene react with the diene to form a bicyclic lactone. Silylketenes undergo a [4+2] cycloaddition reaction with 1,3-dienes and o-quinodimethanes to give 2-pyranones and isochromenes, respectively. For example, from 382 and silylketene 383 the [4+2] cycloadduct 384 is obtained 321 . OR + 382

t-BuMe2SiCH 383

C

Si(t-Bu)Me2

O

O

384

Trimethylsilylketene reacts similarly with carbonyl isocyanates to give [4+2] cycloadducts, which undergo a Diels–Alder reaction with acetylenes 322 or enamines 323 to give 2-pyridones. A theoretical study of the reaction of silylketenes with carbonyl isocyanates and subsequent Diels–Alder reaction with ynamines was conducted recently 324 . The dienes 385 undergo [2+2] and [4+2] cycloaddition reactions to give mixtures of adducts 386 and 387. In the case of R = H, the ratio is 56:44, while R = F gave mainly the [4+2] cycloadduct 325 . Heating of the [4+2] cycloadduct caused partial isomerization to


301

give the [2+2] cycloadduct, indicating that the [4+2] cycloadduct is a kinetic product 326 . R

R

R O

+

Ph2C

C

O

O Ph

O

O

O

+

O

O

Ph2C

Ph O 386

385

387

Silyloxydienes 388 react with dichloroketene to give mixtures of [2+2] cycloadducts 389 and [4+2] cycloadducts 390, most likely formed in a stepwise process 327 . OSiMe3 OSiMe3 +

Cl2C

C

O

Me3SiO

O

Cl2 Me

+

O

CCl2

Me3SiO

388

OSiMe3 OSiMe3

389

390

The vinylketene 391 reacts with the acetylene derivative 392 to give the phenol derivative 393 in 71 % yield 328 . O

(i-Pr)3Si

OSi(i-Pr)3

C6H11

•

C6H11

+ HO OSiR3

391

392

393

Vinylmethyl ketenes react as dienes in cycloaddition reactions with cyanoethylene 329 , eneamines 330 and 4-phenyl-4H-1,2,4-triazole-3,5-dione. In the latter reaction, the [4+2] cycloadduct 394 is obtained 331 . O

O

•

O

N

+

O N

NPh

N

N

O

NPh

O 394

The reaction of α-oxoketene with ketene acetals 395 affords the [4+2] cycloadducts 396 in 98 % yields 332 . O O O

O

O • +

MeCH

C(OR)2 O

O 395

396

Me (OR)2

302


Dipivaloylketene 397 reacts with ethoxyacetylene to give the [4+2] cycloadduct 398 in 88 % yield 333 . O

O

O

O

• +

EtOC

CH O

O 397

OEt

398

A similar reaction is observed with ethoxyethylene to produce the [4+2] cycloadduct in 81 % yield. Also, n-butoxyethylene undergoes the [4+2] cycloaddition to the unsubstituted α-oxoketene to give the cycloadduct in 70 % yield 334 . Ketene O,O-acetals react with α-oxoketenes to give the [2+2] cycloadducts in high yields 335 . Acyl ketene, generated from diketene, undergoes a [2+2] cycloaddition reaction with imines (see Chapter 4, Section 4.1.4.2). However, α-oxoketenes, generated in situ, are usually intercepted with dienophiles to form the [4+2] cycloadducts. The dimerization of the cyclic α-oxoketenes is an example of this reaction (see Section 4.1.2). When diphenylketene is used as the dienophile it competes with the dimerization to give the [4+2] cycloadduct 399 336 . O

O • +

Ph2C

C

Ph2

O O

O

O

399

A similar [4+2] cycloadduct is obtained from dipivaloylketene and diphenylketene in 77 % yield 333 . The [4+2] cycloaddition reactions of linear and cyclic acylketenes proceed with doublebonded substrates, such as aldehydes, ketones and azomethines, with triple-bonded substrates, such as nitriles, and with heterocumulenes, such as ketenes, isocyanates, isothiocyanates and carbodiimides and numerous examples are reported 337 . In the thermolysis of heterocyclic furandiones 400, an α-oxoketene is generated, which can be trapped with cyclopentanone, to give the [4+2] cycloadduct 401 in 81 % yield 338 . N

Ph O

N

Ph 400

N

O

O

Ph Ph

N

O

O

Ph O

N

+ N

O

• O

Ph

O

401

When adamantanone is used to trap the α-oxoketene, the [4+2] cycloadduct is obtained in 92 % yield. It is interesting to note that the [4+2] cycloaddition proceeds across the


303

α-oxoketene, while the dimerization of these types of ‘dual-reactive’ ketenes proceeds across the α-imidoylketene configuration. However, [4+2] cycloaddition of pbromobenzaldehyde across the α-imidoylketene configuration was also observed 339 . Likewise, thermolysis of the benzoxazinetrione 402 generates the α-oxoketene which on trapping with p-bromobenzaldehyde affords the cycloadduct 403 in 60 % yield 340 . O

O

O R

O

R

N

N

4-BrPhCHO

O

R

N

O H 4-BrPh

• O

O

O

+

O

O

402

O

403

The ortho-quinoid vinylketene 404, generated from benzocyclobutenone on heating, undergoes a [4+2] cycloaddition reaction with chloral to give a 92 % yield of the cycloadduct 405 341 . O

O O

•

+

O

CCl3CHO

CCl3

404

405

The cycloadditions of acetylketene with α-chiral aldehydes or ketones is diastereoselective, forming tertiary or quaternary chiral centers at an acetal or ketal carbon with good stereocontrol 342 . Dimethylcyanamide also undergoes a [4+2] cycloaddition reaction with α-oxoketenes to give the adducts 406 343 . O

CF3 R

O O

CF3

O

O

CF3

• +

R

Me2NCN

R

O

N

NMe2

O

406

R H Me Ph

Yield (%) 91 81 93

304


From dipivaloylketene and diethylcyanamide, an 82 % yield of the corresponding cycloadduct is also obtained. Also, dimethylurea 407 (X = O) or dimethylthiourea 407 (X = S) are used to trap α-oxoketenes to give the [4+2] cycloadducts 408 in 60–85 % yields 344 .

O

CF3 R

O

O

O

CF3

CF3

• +

O

R

O

R

NMe

MeNHC(X)NHMe

407

N Me

X

408

The trapping of α-oxoketenes with alkylnitriles affords the [4+2] cycloadducts 409 in 80–85 % yields 345 .

O

O O

Ph Ph

O

Ph

O

O

O •

Ph +

Ph

O N

RCN Ph

O

O

R

409

Benzonitrile reacts similarly with α-oxoketenes to give the [4+2] cycloadducts 346 . Linear and cyclic azomethines also form 1:2 cycloadducts with ketenes. The initially formed ionic 1:1 adduct reacts with another equivalent of the ketene to give the [4+2] cycloadduct. The total reaction is a [2+2+2] cycloaddition reaction. The [2+2+2] cycloadducts derived from azomethines and ketenes are listed in Table 4.12. In the reaction of ketene or diketene with heterocyclic compounds the so-called Wollenberg compounds are obtained. For example, from quinoline and ketene the tricyclic compound 410 is obtained (see Table 4.12).

N +

CH2

C

O

O

O

N O 410

CH3


305

Table 4.12 [2+2+2] cycloadducts 411 or 412 from ketenes and azomethines R R1

RR1C RR1C

C

O

+ –CH

N–

O

O

+

RR1

N

O

O

RR1

N

H

H

411

R

R1

Azomethine

H Me Me Me Ph Ph Ph Ph Ph

H Me Me Me Ph Ph Ph Ph Ph

3,4-Dihydroisoquinoline PhCH NEt Quinoline Acridine EtOCH NPh Benzoxazole Benzothiazole Benzimidazole N-Methylbenzimidazole

412

Yield (%)

Reference

74.5 95 92 78 60 88 86 81 85

347 348 348 349 350 350 350 350 350

When diazabutadienes are used as the diene component, either [2+2] or [4+2] cycloadducts are obtained with phenyl- or in some cases with diphenylketene. In this manner, six-membered ring heterocycles are readily obtained. In the reaction of diazadienes with R3 = NMe2 , elimination of dimethylamine occurs in the cycloaddition reaction. Some of the [4+2] cycloadducts 413 derived from diazabutadienes and phenylketene are listed in Table 4.13. Table 4.13 [4+2] Cycloadducts derived from diazadienes and phenylketenea R1

R1

N

R

+

PhCH

C

N

N

R

O

R2

N

R3

O Ph

R3 413

R

R1

R2

R3

MeS MeS MeS MeS

H Cl Me OMe

H H H H

NMe2 NMe2 NMe2 NMe2

a

Yield (%)

Reference

95 93 95 90

351 351 351 351

When R2 = SMe, elimination of MeSH occurs in the cycloaddition reaction.

306


In the reaction of some 1,3-diazabutadienes with diphenylketene, [4+2] cycloadducts are also obtained (for [2+2] cycloadducts, see Section 4.1.4). The [4+2] cycloadducts derived from 1,3-diazabutadienes and diphenylketene 414 are listed in Table 4.14. Ab initio and density functional studies found that the vinylic C C and the carbonyl C O group of the ketenes are found to participate in this concerted asynchronous [4+2] cycloaddition 352 . Table 4.14 [4+2] Cycloadducts derived from 1,3-diazabutadienes and diphenylketene R1

R1

N

R N

+

Ph2C

C

N

R

O

O Ph2

N

H R2

R2 414

R

R1

R2

Ph Ph Ph Ph

H Cl Br Me

NMe2 NMe2 NMe2 NMe2

Yield (%)

Reference

91 85 96 95

353 353 353 353

Sometimes, mixtures of [2+2] cycloadducts 415 and [4+2] cycloadducts 416 are obtained from 1,3-diazabutadienes 354 . R1

R1 R2

N N

O +

R4

R1N R2 N

• R

Ph R3

R3

O

+ R Ph

R4

415

R2

N N R3 R 4

416

R

R1

R2

R3

R4

Product

Yield (%)

H H H H Ph Ph

Ar 1-Naphthyl 2-MePh Ar Me 1-Naphthyl

Ph Ph Ph SMe Ph Ph

NMe2 NMe2 NMe2 NMe2 Ph NMe2

H H H H Ph H

415 415 416 416 415 416

92 84 90 95 82 85

O R Ph


307

The reactions of 4-dialkylamino substituted 1,3-butadienes with the dienylketene 417 affords the [4+2] cycloadducts 418 and 419 355 . R N

Ph N

+ SMe

R

O

N

Ph

•

R O

N

H

N

+ Ph

Me H SMe

N

R1

R1 417

O

R1

418

419

Similarly, the cyclic dienes 420 react with diphenylketene via a [4+2] cycloaddition to give the heterocycle 421 356 . COPh NCOPh + Ph C 2

NCOPh

C

N

O

N

Ph2

O

COPh 420

421

Diphenylketene also forms [4+2] cycloadducts 422 in the reaction with a conjugated azine (1,4-diazabutadiene) 357 . Ph N

NPh NPh

+ Ph C 2

C

O N Ph

O Ph2

422

A catalytic asymmetric [4+2] cycloaddition of ketenes and N-thioacylimines 423, in the presence of a cinchona alkaloid catalyst, affords the cycloadduct 424 in 51–76 % yield (>95 % e,e) 358 . SR1 C

O

S

N

S RCH

SR1

+ H

R2

N R2

O R

423

424

308


N-Sulfinylamines also undergo the [4+2] cycloaddition reaction with α-oxoketenes to give the cycloadducts 425 in 80 % yield 359 .

+ •

O O

O

O

RNSO

O

O

O

S

NR

O 425

Likewise, diaryl α-oxoketenes are trapped with N-sulfinylamines to give the [4+2] cyclo-adducts 360 . Diaryl α-oxoketenes are also trapped with Ph3 P C C O to give the [4+2] cycloadduct 426, in 86 % yield 361 . O O + Ph3P Ph

PPh3

Ph

•

Ph

C

C

O Ph

O

O

O

426

Tetrahalo o-quinones also undergo a [4+2] cycloaddition reaction with ketenes, generated in the thermolysis of diazoketones, to give the bicyclic adducts 427 (see Table 4.15). Table 4.15 Some [4+2] cycloadducts of o-quinones and ketenes X

X O

X

+ RR1C

X

C

X

O

X

O

O

O

O X

RR1

X 427

R

R1

X

Yield (%)

Reference

H Et Ph 3-MePh 4-MeOPh 4-MeOPh β-C10 H7

Et H H H H H H

Cl Br Cl Cl Cl Br Cl

91 90 90 62 64 73 59

362 362 362 363 363 364 364

Also, silylketenes react with o-quinodimethanes to give [4+2] cycloadducts 364 .


309

The electron-rich unsaturated ketones 428 react with diphenylketene to give the [4+2] cycloadducts 429 in a stepwise process 365 . O

O +

Ph2C

C

O

O Ph2

CHR R 428

429

Chalcones react similarly to give the expected lactones. The ketene 430 undergoes an intramolecular [4+2] cycloaddition on heating to give the bicyclic lactone 431 366 . O O

•

O

O 430

431

Photolysis of trans-dibenzoylstilbene 432 produces an unsaturated ketene 433, which undergoes an intramolecular [4+2] cycloaddition to give the naphthol derivative 434 367 . COPh Ph PhCOC(Ph)

COPh

Ph

Ph

Ph

C(Ph)COPh Ph •

OH

O 433

432

434

The dienylketenes 435 undergo an intramolecular cyclization to give the cyclohexadienones 436, which on irradiation regenerate the dienylketenes 368 . O

•

O

435

436

The vinylketenes 438, generated from the alkinylcyclobutenones 437, undergo an intramolecular [4+2] cycloaddition reaction to give the 1,4-quinone derivative 439 369 .

MeO

C OH 437

MeO CR

MeO

•

MeO

O

O

O

R

R

MeO

MeO OH 438

O 439

Alkyne-tethered vinyl ketenes 441, generated in the thermolysis of propargyloxocyclobutenones 440, undergo an intramolecular [4+2] cycloaddition reaction, followed

310


by a rearrangement to give the benzoquinone derivative 442 in 76 % yield 370 .

O

MeO

•

MeO

O

O

MeO

Ph

Ph

MeO

MeO

MeO

Ph

O 440

O

O

441

442

In contrast, thermolysis of the ethoxy substituted cyclobutenone 443 in refluxing xylene affords the spiroepoxide 444, also in 76 % yield. A radical mechanism accounts for the formation of the rearranged products. A cyclic strained allene was recently proposed as the intermediate in these reactions 371 . O• O

MeO

O

MeO Ph

MeO

Ph

MeO

MeO

MeO

O

Ph

EtO

H CH3

O

• CH3

444

443

The thermolysis of phenyl substituted cyclobutenones affords a dienyl ketene 445, which undergoes cyclization and taitomerization to give the phenol derivative 446 372 . OH O

Me

Ph

Me

•

Me

O

Ph

Ph 445

446

The bicyclic cyclobutenone 447 also forms the vinylketene 448 on thermolysis. 448 also undergoes the intramolecular cyclization reaction to form the 1,4-quinone derivative 449 373 .

N Bz 447

Ph OH

O

O

•

O N

N

Bz 448

OH

Bz

O 449


311

The cyclization of the vinylketene 450 with a pendant naphthyl group to form 451 was a key step in the synthesis of diterpinoid quinones 374 . O

R

R

•

R3SiO

O

O

R R3SiO

CH3

R3SiO CH3

CH3 450

451

Vinyl ketenes derived from Fischer carbene complexes react with carbenoid reagents to give the [4+1] cycloadducts in high yields. For example, from the vinyl ketene 452 and Me3 SiCH2 N2 , the cycloadduct 453 is obtained in 93 % yield 375 . O

O

i-PrSi

•

i-Pr3Si

+

(CO)5Cr

Me3SiCH2N2

SiMe3 OMe

(CO)5Cr

OMe 452

453

Similarly, from 454 and Me3 SiCHN2 a 95 % yield of the cycloadduct 455 is obtained 376 . O

O

•

Et3Si

+

Me3SiCH2N2

Et3Si SiMe3

454

455

2-Indanones are also obtained in a [4+1] cycloaddition reaction of silylarylketenes and trimethylsilyldiazomethane 377 . The cyclopentenones 457 are also obtained via a [4+1] reaction of the vinylketenes 456 with t-butylisocyanide in very high yields 378 . O

O

•

TIP

R2

R1

+

t-BuNC

TIP N–t-Bu R1

OMe

R2

MeO

456

457

Pyrolysis of the Meldrum acid derivative 458 produces the methylene ketene 459, which rearranges to the dienylketene 460 while the latter undergoes cyclization to give the βnaphthol 461 379 . O

O

O

H •

H

O O CH3 458

•

Me 459

OH

O 460

461

312


In the generation of the N-substituted ketene 463 in the thermolysis of the precursor 462 at 500 ◦ C, the pyrazolotriaziniumolate 463 is mainly obtained. When the thermolysis is conducted at 700 ◦ C the pyrazolopyridazinone 464 is the major product 380 . O O O

NH O

O

• H

O N N

⊕

NH N

462

N N

N

463

O +

N

N N N

464

465

An intramolecular ketene electrocyclization also seems to occur in the Conrad–Limpach quinoline synthesis. In the heating of the b-anilinocrotonic acid ester in a high-boiling solvent at 240–250 ◦ C, the ketene 466 is generated, which undergoes intramolecular cyclization to form a quinoline derivative 467 381 . OH

O

N H

Me

•

Eto

O

H

H

N

Me

Me

N

466

467

The bis-ketene 469, generated in the photolysis of the cyclobutenedione 468, can be trapped with dimethylphenylisocyanide to give the cycloadduct 470 via a [4+1] cycloaddition (yield: 82 %) 382 . Ph

O

O

Ph

•

O

Ph

+ O

468

NR

RNC Ph

•

Ph

Ph

O

469

O 470

References 1. 2. 3. 4. 5. 6. 7. 8. 9.

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1,2-Dicarbon Cumulenes 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210. 211. 212. 213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240.

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1,2-Dicarbon Cumulenes 287. 288. 289. 290. 291. 292. 293. 294. 295. 296. 297. 298. 299. 300. 301. 302. 303. 304. 305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. 331. 332. 333. 334. 335. 336.

319

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4.2 4.2.1

321

Thioketenes, R2 C C S Introduction

Thioketenes (R2 C C S), selenoketenes (R2 C C Se) and telluroketenes (R2 C C Te) are less stable than ketenes. The latter have not as yet been synthesized, but their metal complexes are known. A theoretical comparison of ketenes, thioketenes and selenoketenes indicates that thioketenes and selenoketenes are more reactive than ketenes and that thioketenes resemble selenoketenes more than ketenes 1 . Selenoketenes are often encountered as intermediates in chemical reactions, but highly sterically hindered derivatives are also known. The unstable thioketenes were obtained by thermolysis of 1,2,3-thiadiazole 2 , and the unstable selenoketenes were similarly generated and characterized in the vapor phase 3 . The highly reactive fulvene substituted selenoketene 2 was also obtained in the thermolysis of benzo-1,2,3-selenadiazole 1, and the red precipitate collected at −196 ◦ C polymerizes violently on warming 4 . N N

•

Se

Se 1

2

The cycloaddition reactions of thio- and selenoketenes are similar to ketenes, but some exceptions are observed. For example, the dimerization of thioketenes occurs across the C S double bonds, while in ketenes, dimers resulting from addition across the C C bonds and unsymmetrical dimers, resulting from addition across both the C C and the C O bonds are obtained. The [2+2] cycloaddition reactions of thioketenes can involve the C S or the C C bonds, and additions across either one of these groups occurs. In their additions across C N bonds both types of additions are also encountered. The progress of these reactions is monitored by the disappearance of their intensive color. Diarylthioketenes are blue, dialkyl derivatives are purple and monosilylthioketenes are red 6 . The half-life of diarylthioketenes at room temperature in a 0.01 M solution is about 6 h, while that of t-butylthioketene at 22 ◦ C is less than 1 h 5 . t-Butyl(methyl)thioketene is stable in solution at −78 ◦ C, but t-butyl(allyl)thioketene can be distilled in vacuum and stored at 0 ◦ C for one week, while phenyl(trimethylsilyl)thioketene is stable at 20 ◦ C. Thioketenes show a characteristic IR absorption at 1725–1758 cm−1 and a UV absorption at an λmax of 575–627 nm. The crystal structure of the stable 2,2,4,4tetramethylcyclohexylidenethioketene (m.p. 37 ◦ C) showed a linear configuration for the cumulative double bonds 6 . Rhodium complexes of unsubstituted thio-, seleno- and telluroketenes are also known 7 . The high reactivities of thioketenes prompted the synthesis of sterically hindered thioketenes which undergo [2+1], [2+2], [3+2] and [4+2] cycloaddition reactions similar to other heterocumulenes. Review articles on thioketenes were written by Schaumann in 1985 8 and in 1987 9 . Oxidation of thioketenes with peracids affords thioketene S-oxides (R2 C C S O) 10 , a class of heterocumulenes also treated in this chapter. A review of thioketene S-oxides was published in 1985 11 . Also, alkylidenethioketenes (R2 C C C S) 11 and thiocarbonyl-Ssulfides (R2 C S S) 12 are known. The higher homologue, CH2 C C C S, is generated by irradiation of matrix isolated 2,5-diiodothiophene 13 .

322


Alkylidenethioketenes and thioketene S-ylides (R2 C C S CH2 ) are also described in this chapter. The latter were trapped by an intramolecular cycloaddition reaction to give dithiolanes. Also, propadieneselon, CH2 C C Se, is described in this chapter. The unusual extended system, ArN C C C S, was recently generated by flash vacuum thermolysis 14 . Thiocarbonyl-S-sulfides are treated as ‘Thiosulfines’ in Section 4.2.2.

4.2.2 Dimerization Reactions In the attempted thioketene trapping experiments, sometimes dimerization of the generated thioketenes is observed. The dimerization occurs by a [2+2] cycloaddition reaction across the C S bond to give the 1,3-dithietane derivatives 3 6 . A similar dimer is isolated in the thermal generation of MeCOCH C S 15 . R 2C 2 R2C

C

S

S S

CR2 3

In contrast, dimerization of monoalkyl thioketenes affords 2-alkylidene-1,3-thiols 4 16 . R 2 RCH

C

S CHR

S S 4

The symmetrical dimer 5, formed by addition across the C C bonds, or the unsymmetrical dimer 6, obtained by addition across both cumulative double bonds, are not observed. S S S

S

5

6

Cyclodimer 5, derived from dimethylthioketene, is synthesized independently, and on pyrolysis at 940 ◦ C generates dimethylthioketene in 62 % yield 17 . Flash vacuum thermolysis at 800 ◦ C of the dimer of diphenylthioketene, synthesized by a different route, was also used to produce diphenylthioketene 18 . Similarly, the dimer of the exceedingly reactive dichlorothioketene was pyrolyzed at 880 ◦ C to give dichlorothioketene, which was trapped with cyclopentadiene at −196 ◦ C to give the [4+2] cycloadduct 19 . The stable bis-trifluoromethylthioketene (b.p. 52–53 ◦ C) is similarly obtained in the pyrolysis of its cyclic dimer.


323

In the generation of the unstable phosphathioketene 7 (R = 2,4,6-tributylphenyl) dimerization occurs to give the unsymmetrical dimer 8 as red crystals. 20 RP 2 RP

C

S

RP

S S 8

7

When thioketenes are generated by thermolysis or photolysis of 1,2,3-thiadiazoles, the initially formed 1,3-diradical undergoes a [3+3] cycloaddition to form a 1,4-dithiine derivative 9, which can extrude sulfur to produce a thiophene derivative 10. When the initially formed diradical rearranges to the thioketene it can react via a [3+2] cycloaddition across the 1,3-diradical to give the 1,3-dithiol derivative 11. R1 R2

N

R1

R1

S

R1

R2

R2

S

R2

N S

S

R1 R2

S

S

+

RC+

R2

S

9

R 2C

R1

10

R

S

R

S

CR–S

CR2 11

Heating of 4,5-diphenyl-1,2,3-thiadiazole in naphthaline at 218 ◦ C affords tetraphenylthiophene in 90% yield 21 . In contrast, heating in bis(2-hydroxyethyl)ether, a more polar solvent, at 230 ◦ C affords a 79 % yield of 11 22 . Heating in the melt at 210–220 ◦ C gives 80 % of the thiophene 10 and 6 % of 11 23 . In the photolysis, a small amount of 10 and 18 % of 11 is formed 24 . Generation of 11 in the reaction of 4-substituted 1,2,3-thiadiazoles with KOH/EtOH occurs in a stereoselective manner to give the (Z)-configuration 25 . 4.2.3 4.2.3.1


Carbenes, generated from diazo compounds using copper sulfate or rhodium acetate as catalysts, react with thioketenes by a [2+1] cycloaddition reaction across the C S bond to give the cycloadducts 12 26 . RR1C 1

RR C

C

S

+

2 3

R R C

S

N2 R2 12

R3

324


R

R1

R2

R3

Yield (%)

t-Bu

t-Bu

Ph

Ph

85

t-Bu

t-Bu

85

–CMe2 –(CH2 )3 –CMe2 –

93

–CMe2 –CH2 SCH2 –CMe2 –

53

The germanium analogue R2 Ge: adds to di-t-butylthioketene to give a [2+1+1] cycloadduct 27 . t-Bu2C t-Bu2C

C

S

+

2 R2Ge:

S

R2Ge GeR2 13

R

Yield (%)

Me Ph

51 32

However, R2 Ge: desulfurizes bis(trimethylsilyl)thioketene, rather than form the cycloadduct. In the reaction of the sterically hindered thioketenes with benzyl nitrene, [2+1] cycloadducts 14 are also formed, which rearrange to give S-vinyl thiooximes 15 28 . The thioketenes, dissolved in benzyl azide, are heated at 135 ◦ C for 20 h. R2C R2C

C

S +

S

PhCH2N2

R2C

CH–S–N

CHPh

N Bz 14

15

The [2+1] cycloadducts 16 are also obtained in quantitative yield in the reaction of liganded cobalt and rhodium complexes with 2,2,4,4,-tetramethylcyclohexylidenethioketene 29 . L(PMe3)2Co +

C

S

L(PMe3)2 Co S 16


325

Similar [2+1] cycloadducts are obtained from rhodium complexes and sterically hindered thioketenes. The [2+1] cycloadduct of the parent thioketene to the rhodium complex 18 was synthesized independently in the reaction of 17 with elemental sulfur 7 . L(i-Pr3P)Rh

C

CH2

+

S

L(i-Pr3P) Rh S

17

18

The same reaction, using elemental selenium or tellurium, gives the corresponding rhodium complexes. The reaction of carbomethoxycyanothioketene 19 with t-butylisonitrile gives rise to the formation of the cycloadducts 20 30 . N–t-Bu

MeO2C 2 MeOCO(CN)C

C

S

+

NC

RNC

S S

19

4.2.3.2

CO2Me CN

20


Bis-trifluoromethylthioketene 21 undergoes [2+2] cycloaddition reactions with olefins, vinyl ethers, vinyl thioethers and ketene acetals 18 . The reaction always proceeds across the C S bond to give the thiethane derivatives 22 . Some of the the cycloadducts are listed in Table 4.16. Table 4.16 [2+2] Cycloadducts of bis-trifluoromethylthioketene with C C bond-containing substrates CF3 (CF)2C

C

S

+

RR1CH

CF3 S

CH2

21

RR1 22

R

R1

OEt OEt OCH2 CF3 S-t-Bu SPh Vinylcarbazole

H OEt H H H

Yield (%) 90 81 80 61 81 80

From cis-1,2-dimethoxyethylene a 94 % yield of the [2+2] cycloadduct is obtained 18 .

326


The nucleophilic ynamines also undergo a [2+2] cycloaddition reaction with thioketenes. The initially produced cycloadducts 23 rearrange to give allene thiocarboxamides 24 22 . R 1R 2C

C

S

+

R3C

S

R1 CNR2

R1R2C

NR2

R2

C

C(R3)CSNR2

R3 23

24

Triphenylphosphoralkylidene thioketenes 25 (X = S) or -ketenimines (X = NR) react with dimethyl acetylenedicarboxylate via a [2+2] cycloaddition across the P C bond to give the cycloadduct 26, which undergoes an electrocyclic ring opening reaction to give the thioketene 27 (X = S, 74 % yield) or the ketenimine 27 (X = NR, 70 % yield) 31 . X CO2Me Ph3P

C

C

X

•

Ph3P

+

Ph3PCH(COOMe)C MeO2C

CO2Me 25

CO2Me

C

X

CO2Me

26

27

The [2+2] cycloaddition of bis-trifluoromethylthioketene with ketenes proceeds similarly to give the four-membered ring cycloadducts 28 18 . (CF3)2C (CF3)2C

C

S

+

RR1C

C

O

S

RR1 O 28

R

R1

Yield (%)

H Me

H H

44 33

The [2+2] cycloaddition of thioketenes to the C N bond in azomethines is also observed 9 . In this reaction β-thiolactam, resulting from addition across the C C bond of the thioketene group, is obtained. For example, from 29 and 30 the [2+2] cycloadduct 31 is obtained in 43 % yield 32 . CN

S

t-Bu t-Bu(CN)C

C

S

+

4MeOPhCH

NMe NMe

29

30

31

The fact that also 19 % 2-cyano-3,3,N-trimethylbutanethioamide is isolated indicates that addition across the C S bond also occurs.


327

Often, the [2+2] cycloadducts 32 are obtained as a mixture of diastereoisomers in good yields 33 . R1 2

R C

C

S

+

3 4

5

R R C

NR

S

R1R2 R3R4

NR5 32

R1

R2

R3

R4

R5

i-Pr i-Pr

t-Bu t-Bu

Ph 2-MePh

H H

Me CH2 Ph

72 62

Ph

H

Me

84

Yield (%)

Switter ionic intermediates play a role in the mechanism of this cycloaddition reaction and electronic effects are more important than steric considerations. The reaction of sterically hindered thioketenes with 3,4-dihydroisoquinoline 33 affords the cycloadducts 34 in excellent yields 33 . R1R2C

C

S

+

N

N S R1

33

R2 34

R1 I-Pr t-Bu

R2

Yield (%)

t-Bu t-Bu

91 73

99

The cycloaddition reaction of the allenylselenoketene 35 with 3,4-dihydroisoquinoline affords a mixture of the [2+2] cycloadduct 36 (32 % yield) and the [2+2+2] cycloadduct 37 (19 % yield). 34 •

Se

+

N

N

N

Se

Se C(Me)2CH

35

36

N

CH2

37

C(Me)2CH

CH2

328


Seleno-β-lactams 39 are obtained from lithium alkyne selenoates 38 and azomethines. The reaction most likely proceeds via a [2+2] cycloaddition because 38 is in equilibrium with PhHC C Se 35 . Se PhC

C–Se+

Li

−

+

RCH

NR

Ph

1

R

NR1 39

38

When aldothioketenes are generated in the thermolysis of 4-mono substituted 1,2,3thiadiazoles in excess of the imines β-thiolactams are also obtained in 37–79 % yields 36 . In the generation of t-butyl(cyano)thioketene at low temperature in the presence of imines, addition across the C S bond occurs to give thiazetidine derivatives, while at higher temperatures β-thiolactams are obtained 9 . Thioketenes with electron withdrawing substituents, such as bis-trifluoromethylthioketene 18 and thioketenes with CN and alkoxycarbonyl groups 37 , react with C N bond containing substrates by addition across the C S bond in the thioketene. For example, a [2+2] cycloadduct is obtained in 79 % yield from bis-trifluoromethylthioketene and C-pentafluorophenyl-N-methylimine. However, [2+2+2] cycloadducts 40 are more common 18 . CF3 2 (CF3)2C

C

S

+

R-CH

CF3

NR1

R 1N R

CF3 CF3

S

S H

40

R

R1

H Cl OMe

Me Me 4-MeOPh

Yield (%) 78 60 62

In the reaction of cyclic C N group-containing substrates, an initial [2+2] cycloaddition is also observed. For example, reaction of thioketenes with cyclic amidines 41 occurs by initial reaction across the C S bond of the thioketene, but the strained bicyclic adduct 42 undergoes subsequent reactions to give an ionic five-membered ring compound 43 38 . R

R2 N R 2C

C

N

S +

R R

N S

N

R S

R2N 41

42

NR2

43

An initial linear switter ionic 1:1 adduct is obtained in 93 % yield in the reaction of dicyanothioketene with 2-dimethylamino-3-dimethylazirine 39 .


329

With linear amidines, t-buty(i-propyl)thioketene reacts across its C N bond to give βthiolactams 9 . Also, α,β-unsaturated imines 44 react with thioketenes to give the β-lactam cycloadducts 45 40 . S R 2C

C

S

1

+

R CH

C-CH

R2

2

NR

NR2 R1 45

44

Azines undergo the [2+2] cycloaddition reaction with thioketenes across one of their C N bonds to give the β-lactam adducts 9 . The [2+2] cycloaddition reaction of thioketenes with reactive isocyanates, such as nitrophenyl or sulfonyl isocyanates, proceeds similarly to give 4-thioxo-2-azetidinones 46 41 . The reactivity of the isocyanates is as follows: ClSO2 NCO > PhOSO2 NCO > 4-MePhSO2 NCO > MeSO2 NCO > 4-O2 NPhNCO. S

RR1 RR1C

C

S

+

R2N

C

O

NR2 O 46

R1

R

R2

t-Bu i-Pr t-Bu t-Bu t-Bu C6 H11 –CMe2 (CH2 )3 CMe2 –

Yield (%)

PhOSO2 PhOSO2 PhOSO2 PhOSO2

83 71 84 76

In the [2+2] cycloaddition reaction of thioketenes with chloro- and fluorosulfonyl isocyanates the [2+2] cycloadducts are not isolated, but β-thiolactams resulting from the hydrolysis of the halosulfonyl groups are obtained. Carbodiimides react with bis-trifluoromethylthioketene to give the β-thiolactam cycloadducts 47 18 . CF3 CF3 (CF3)2C

C

S

+

RN

C

NR

S RN NR 47

R i-Pr C6 H11 4-MePh

Yield (%) 88 92 85

330


A [2+2] cycloaddition reaction of bis(trimethylsilyl)thioketene across the C O bond in acid amides is also observed. The initial cycloadduct 48 rearranges to an intermediate new thioketene 49, which undergoes further transformation to give the isolated products 50 42 . S (Me3Si)2C

C

S

+

(Me3Si)2

R1R2NCOR3

R3

O

R 1R 2 N 48 R1R2NC(R3)(OSlMe3)C(SiMe3)C

C

R1R2NC(S)C(SiMe3)

S

49

C(OSiMe3)R3

50

The [2+2] cycloaddition reaction of thioketenes across C S bonds is also observed. For example bis-trifluoromethylthioketene reacts with C S bond-containing substrates to give the four-membered ring dithietane derivatives 51 37 . CF3 CF3 (CF3)2C

C

S

+

RR1C

S

S RR1

S 51

R

R1

Me OMe OMe Ph –SCH2 CH2 S–

SEt SMe OMe Ph

Yield (%) 95 high 73 77 87

Sterically hindered thioketenes also react across C S bond-containing substrates 43 . For example, t-butyl(isopropyl)thioketene reacts with thiobenzophenone to give the [2+2] cycloadduct in 41 % yield. In the reaction of bis-trifluoromethylthioketene with sulfurdiimides an exchange reaction occurs, resulting in the formation of ketenimines in 20–48 % yields 44 . The [2+2] cycloaddition reaction of bis-trifluoromethylthioketene also occurs across the C S bond in isothiocyanates to give the four-membered ring cycloadducts 37 . In the reaction of bis-trifluoromethylthioketene with methyl isothiocyanate the initial cycloadduct 52 reacts with another two molecules of the thioketene to give the 3:1 cycloadduct 53. CF3 CF3

S + 2 (CF3)2C

S NMe

C

S

CF3

S

CF3

S

CF3 CF3 Me N S S CF3 CF3

52

53


4.2.3.3

331


Dialkylthioketenes undergo [3+2] cycloaddition reaction with tetracyanoethylene oxide. However, the cycloadducts 54 undergo cycloreversion and rearrangement to give allene episulfides 55 45 . R CN R2C

C

S +

R1

CN CN

NC

NC

O

CN

S O CN

CN

R

CN

R1

CN

S

54

55

R

R1

i-Pr t-Bu

t-Bu t-Bu

Yield (%) 40 61

Bis(trifluoromethyl)thioketene 18 and carbometoxycyanothioketene 46 undergo [3+2] cycloaddition reactions with nitrones 56 (X = O) and nitrilimines 56 (X = NR) to give the cycloadducts 57. X

R 2C R2C

C

S +

CR1

X-N

N S

56

R1 57

Likewise, mono substituted thioketenes, generated in situ, undergo [3+2] cycloaddition reactions with nitrile oxides and nitrileimines 47 . In the reaction of bis-trifluoromethylthioketene with diazomethane, two isomeric heterocyclic adducts 58 (59 %) and 59 (41 %) are obtained, resulting from rearrangement of the initially formed [3+2] cycloadducts 37 .

(CF3)2C

C

S +

CF3

CH2N2

CF3 S

+

CF3

CF3 S

N

N

N N 58

59

In the reaction of sterically hindered thioketenes with diazopropane and di-tbutyldiazomethane the [3+2] cycloadducts 60 are also obtained 48 .

RR1C

C

S +

N−

RR1C N+

CR2R3

S N N 60

R2 R3

332


Bis-trifluoromethylthioketene reacts with bis-trifluoromethyl diazomethane to give two isomeric [3+2] cycloadducts 61 and 62 49 . CF3 (CF3)2C

C

S +

(CF3)2C

N2

CF3

CF3

S

CF3 +

N N

CF3

CF3 S

61

N N

(CF3)2 62

Reaction of the same thioketene with HN3 affords the 5-substituted-1,2,3,4-thiatriazole 63 in quantitative yield 18 . CF3 (CF3)2C

C

S +

S

CF3

HN3

N

N N 63

Arylazides react with bis-trifluoromethylthioketene to give the [3+2] cycloadducts 64 in moderate yields 18 .

(CF3)2C

C

S +

R1

CF3

N3

CF3 S

R1

N N N

R2

R2 64

R1

R2

Yield (%)

H Me OMe

H H H

26 35 57

The 1,3-dipole, obtained in the thermolysis of 1,2,3-thiadiazole, reacts with thioketenes to give the [3+2] cycloadducts 65 50 . R2C

C

S +

RC+

R

S

R

S

CR–S−

CR2

65

The reaction of the phosphorus ylide 66 with dimethyl thioketene, generated in situ, affords a [3+2] cycloadduct 67 in 60 % yield 51 . Ph3P+C(Me)2C(S)S− 66

S +

Me2C

C

S S S 67


333

Thioketene S-oxides are excellent 1,3-dipoles. For example, reaction with azomethines proceeds via a [3+2] cycloaddition to give the oxazolidinethiones 69 in 48–72 % yields 52 . The cycloadducts 68 readily rearrange to give 69. S R2C

C

S

O +

R1CH

NR2

R2C

O N R2

O

R2

R1 H

S

N R2

68

R1 H

69

When the thioketene S-oxide 70 is reacted with the Lawesson Reagent, an isolable thiirane 2-thione 71 is obtained, which is also an excellent 1,3-dipole because a quantitative yield of the cycloadduct 72 is obtained on reaction with dimethyl acetylenedicarboxylate 53 . t-Bu2C

C

S

S

t-Bu2

O

+

RC

S 71

70

R

S

R

S

C(t-Bu)2

CR 72

When the C N bond is part of a three-membered ring, a similar [3+2] cycloaddition is observed but the cycloadducts 73 also rearrange to give the thiiranimines 74 54 . Me2N RR1C

C

S

O

R2 R3

N

+

O

Me2N

R2 R3

R2

CRR1

N

R3

73

R1 S 74

R1

R

R

Me2NCOCN

S

i-Pr i-Pr t-Bu t-Bu –CMe2 –(CH2 )3 – CMe2 –

R2

R3

Yield (%)

Me Me Me

Me Me Me

96 91 93

In the reaction of thioketene S-oxides with diazo compounds also [3+2] cycloadducts 75 are obtained in 13–95 % yields 55 . O S 1 2

R R C

C

S

O

+

R1 R2

R2N2

N

N

R R

75

Also, a [3+2] cycloaddition reaction of thioketene S-oxides with 2-azaallyl anions 76 affords ionic cycloadducts, which after acidification give the heterocycle 77 56 . R 2C

C

S

O

+

Ph

N

Ph

R2CH

S

Ph 76

Ph N

77

334


The highly reactive allenylthioketene S-dioxides 79, generated through [3,3] sigmatropic rearrangement from alkynyl propargylsulfones 78, can be trapped with cyclohexene to give the [2+2] cycloadduct 80 resulting from addition across the C SO2 bond 57 .

•

H

O

SO2 +

O

•

S

Me3Si

SiMe3 78

O

•

O

S

79

80

Cycloaddition of thioketene S-ylides 81 with carbonyl compounds affords oxathiolanes 82 58 . O

O O C

S

CH2

RR1C

+

O

R R1

S

O

O 82

81

A 1,3-dipole, generated in the reaction of 4-substituted 1,2,3-thiadiazoles with KOH/EtOH, can be intercepted with carbon disulfide to give the [3+2] cycloadduct 59 . 4.2.3.4


The Diels–Alder reaction of thioketenes with cyclopentadiene and 2,3-dimethylbutadiene proceeds across the C S bond of the thioketene to give the adducts in high yields. For example, trapping of dichlorothioketene, obtained in the flash vacuum pyrolysis of its dimer, with cyclopentadiene in an argon matrix at −196 ◦ C, affords the [4+2] cycloadduct 14 . Also, pyrolysis of 5-isopropyl-4-phenyl-1,2,3-thiadiazole at 530 ◦ C and trapping of the thioketene 83 with cyclopentadiene gives a quantitative yield of the [4+2] cycloadduct 84 60 . Ph i-Pr i-PrPhC

C

S

+ S

83

84

Bis-trifluoromethylthioketene undergoes a similar [4+2] cycloaddition reaction with 2,3-dimethylbutadiene. The cycloadduct 85 is obtained in 84 % yield. From 2,3dichlorobutadiene the [4+2] cycloadduct is obtained in 72 % yield 18 . (CF3)2C

C

S

S

+ (CF3)2C 85

Similar cycloadducts are isolated using 1,3-cyclohexadiene (yield, 55 %), 1,3diphenylisobenzofurane (yield, 83 %) and cyclooctatetraene. The latter forms a bicyclic cycloadduct.


335

α-Oxothioketenes 86 react with azomethines via a [4+2] cycloaddition sequence to give 1,3-oxazines 87 6 . S RCOCH

C

S

+

R1CH

NR2 R1

NR2 R

O

86

87

Also, azadienes react with t-butylisopropylthioketene to give a mixture of the [4+2] cycloadduct 88 and the [2+2] cycloadduct 89, both in about 25 % yield 61 . PhN R2C

C

S

+

S

Ph N

S +

R2 NMe2

R2

NMe2

NPh O

88

H 89

In the [2+2] cycloadduct the enamine function is hydrolysed. In the reaction of alkenyl silyl sulfides with ynamines, the thioketenes 90 are generated as intermediates which undergo electrocyclization to give the four-membered ring compounds 91 62 . R1 R 1C

CSSiMe3

+

R2NC

•

CR2

S SiMe3

R2N R

S

R1 R2N

SiMe3 R2

2

90

91

R

R1

R2

Yield (%)

Et Et Et

t-Bu Ph Ph

Me Me Ph

42 94 45

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

N.L. Mah and M. Wong, Eur. J. Org. Chem. 1411 (2000). H. Bock, B. Solouki, G. Bert and P. Rosmus, J. Am. Chem. Soc. 99, 1663 (1977). A. Holm, C. Berg, C. Bjerre, B. Bak and H. Svanholt, J. Chem. Soc., Chem. Commun. 99 (1979). R. Schulz and A. Schweig, Angew. Chem. Int. Ed. 19, 69 (1980). G. Seybold and C. Heibl, Angew. Chem. 87, 171 (1975). E. Schaumann, S, Harto and G. Adiwidjaja, Angew. Chem. 88, 25 (1976). H. Werner, J. Wolf, R. Zolk and U. Schubert, Angew. Chem. 95, 1022 (1983). E. Schaumann, Houben Weyl, Vol. E11, p. 233, 1985. E. Schaumann, Tetrahedron 44, 1827 (1988). E. Schaumann and W.R. Klein, Tetrahedron Lett. 3457 (1977). M. Parmantier, J. Galloy, M. van Meersche and H.G. Viehe, Angew. Chem. 87, 33 (1975). T. Saito, Y. Shundo, S. Kitazawa and S. Motoki, J. Chem. Soc., Chem. Commun. 600 (1992). Y.S. Kim, H. Inui and R.J. McMahon, J. Org. Chem. 71, 9602 (2006). C. Oliver Kappe, D. Kvaskoff, D.J. Moloney, R. Flammang and C. Wentrup, J. Org. Chem. 66, 1827 (2001). 15. M. Sato, H. Ban, F. Uehara and C. Kaneko, J. Chem. Soc., Chem. Commun. 775 (1996).

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16. R.L.P. de Jong, J. Meijer, R.S. Sukhai and L. Brandsma, Rec. Trav. Chim. Pay-Bas 101, 310 (1982). 17. G. Seybold, Tetrahedron Lett. 555 (1974). 18. M.S. Raasch, J. Org. Chem. 35, 3470 (1970). 19. G. Adiwidjaja, C. Kirsch, F. Pedersen, E. Schaumann, G.C. Schmerse and A. Senning, Chem. Ber. 124, 1485 (1991). 20. R. Appel, P. Fölling, L. Krieger, M. Siray and F. Knoch, Angew. Chem. 96, 981 (1984). 21. H. Staudinger and J. Siegwart, Ber. Dtsch. Chem. Ges. 49, 1918 (1916). 22. H. Bühl, B. Seitz and H. Meier, Tetrahedron 33, 449 (1977). 23. K.P. Zeller, H. Meier and E. Mueller, Liebigs Ann. Chem. 766, 32 (1972). 24. W. Kirmse and L. Horner, Liebigs Ann. Chem. 614, 4 (1958). 25. A. Shafiee and I. Lalezari, J. Heterocyclic Chem. 10, 11 (1973). 26. H. Behr, O. Bolte, G. Dräger, M. Ries and E. Schaumann, Ann. Chem. 1295 (1996). 27. W. Ando, T. Tsumuraya and M. Goto, Tetrahedron Lett. 27, 5105 (1986). 28. E. Schaumann, O. Bolte and H. Behr, J. Chem. Soc., Perkin Trans. 1 182 (1990). 29. H. Werner, O. Kolb, U. Schubert and K. Ackermann, Angew. Chem. 93, 583 (1981). 30. G. L’abbe, P. Vangeluwe, S. Toppet, G.S.D. King and L. van Meervelt, Bull. Soc. Chim. Belg. 93, 405 (1984). 31. H.J. Bestmann, G. Schmid and D. Sandmeyer, Angew. Chem. 87, 34 (1975). 32. E. Schaumann, U. Wriede and G. Rüther, Angew. Chem. 95, 52 (1983). 33. E. Schaumann, Chem. Ber. 109, 906 (1976). 34. E. Schaumann and F. Grabley, Tetrahedron Lett. 21, 4251 (1980). 35. H. Ishihara, M. Yoshimi and S. Kato, Angew. Chem. 102, 572 (1990). 36. E. Schaumann, J. Ehlers and F. Grabley, Chem. Ber. 113, 3010 (1980). 37. M.S. Raasch, J. Org. Chem. 43, 2500 (1978). 38. E. Schaumann, S. Grabley, F.F. Grabley, E. Kausch and G. Adiwidjaja, Liebigs Ann. Chem. 277 (1981). 39. E. Schaumann, E. Kausch and W. Walter, Chem. Ber. 107, 3574 (1974). 40. K.L. Mok and M.J. Nye, J. Chem. Soc., Perkin Trans. 1 1810 (1975). 41. E. Schaumann, M. Möller and G. Adiwidjaja, Chem. Ber. 121, 689 (1988). 42. T. Tsuchiya, A. Oishi, I. Shibuya, Y. Taguchi and K. Honda, J. Chem. Soc., Chem. Commun. 1621 (1996). 43. E. Schaumann, Chem. Ber. 109, 906 (1976). 44. M.S. Raasch, J. Org. Chem. 37, 1347 (1972). 45. G. Adiwidjaja, O. Bolte, B. Dietz and E. Schaumann, J. Chem. Soc., Perkin Trans. 1 2385 (1993). 46. K. Dickore and R. Wegler, Angew. Chem. 78, 1023 (1966). 47. A. Corsaro, U. Chiacchio, G. Alberghina and G. Purello, J. Chem. Res. Synop. 370 (1984). 48. E. Schaumann, H. Behr and J. Lindstaedt, Chem. Ber. 116, 509 (1983). 49. W.J. Middleton, J. Org. Chem. 34, 3201 (1969). 50. U. Timm, H. Bühl and H. Meier, J. Heterocyclic Chem. 15, 697 (1978). 51. U. Kunze, R. Merkel and W. Winter, Angew. Chem. 94, 301 (1982). 52. E. Schaumann, J. Ehlers and U. Behrens, Angew. Chem. 90, 480 (1978). 53. K. Okuma, T. Shigetomi, Y. Nibu, K. Shioji, M. Yoshida and Y. Yokomon, J. Am. Chem. Soc. 126, 9508 (2004). 54. E. Schaumann, H. Nimmesgern and G. Adiwidjaja, Angew. Chem. 94, 706 (1982). 55. E. Schaumann, H. Behr, G. Adiwidjaja, A. Tangerman, B.H.M. Lammerinkand and B. Zwanenburg, Tetrahedron 37, 219 (1981). 56. E. Schaumann, H. Behr and A. Adiwidjaja, Heterocycles 24, 1237 (1986). 57. S. Aoyagi, M. Koyanagi, M. Takahashi, K. Shimada and Y. Takikawa, Tetrahedron Lett. 48, 1915 (2007). 58. Y. Tominaga, S. Takada and S. Kohra, Tetrahedron Lett. 35, 3555 (1994). 59. A. Shafiee and F. Assadi, J. Heterocyclic Chem. 17, 549 (1980). 60. E. Schaumann, J. Ehlers and H. Mrotzek, Liebigs Ann. Chem. 1734 (1979). 61. U. Timm, H. Bühl and H. Meier, J. Heterocyclic Chem. 15, 697 (1978). 62. M. Mueller, W.R. Foerster, A. Holst, A.J. Kingma, E. Schaumann and G. Adiwidjaja, Chem. Eur. J. 949 (1996).


4.3 4.3.1

337

Ketenimines, R2 C C NR Introduction

Ketenimines were first synthesized by Staudinger and Meyer in 1919 1 . The various methods of synthesis of ketenimines are summarized in a review article by Krow in 1971 2 . A more recent review on ketenimines in the synthesis of heterocyclic systems appeared in 2000 3 . Silaketenimines (R2 Si C NR1 ) as well as extended heterocumulene systems with a ketenimine configuration, such as Ph3 P C C NR, Ph2 C C C C NMe and RN C C NR, are also known. The configuration CF3 N C C NCF3 is observed as ligand in a dimolybdenum complex 4 . The following resonance forms describe Keteneimines: R 2C

C

R2C−–C

NR1

N+R1

R2C

C+–N−R1

Oxoketenimines (IR, 2076 cm−1 ) are formed in a thermal rarrangement from imidoyl ketenes 5 . The oxoketenimines are stable up to 0 ◦ C. N-2-carbonylphenyl ketenimines undergo a [1,5] migration to produce vinylimino ketenes (see Section 4.1) 6 . In ketenimines, the cumulative double bond system absorbs in the infrared region at 2000–2050 cm−1 . In cycloaddition reactions, ketenimines are less reactive than ketenes, and N-arylketenimines react faster than N-alkylketenimines. These reactions most likely proceed via a linear ionic intermediate, which can cyclize to give four-membered ring or six-membered ring cycloadducts, or react with a second mole of ketenimine to give a [2+2+2] cycloadduct. Generally, ketenimines undergo inter- and intramolecular [2+2] cycloaddition reactions across their C C bonds. In [4+2] cycloaddition reactions, ketenimines can participate as dienophiles via their C C or C N bonds or they react as azadienes. The [3+2] cycloaddition reactions are also known but they are less prominent. Also, many electrocyclization reactions are reported. 4.3.2


In the reaction of perfluoroisobutylene with N-phenylbis(trifluoromethyl)ketenimine, a mixture of the unsymmetrical cyclodimer of the ketenimine and the expected [2+2] cycloadduct are obtained 7 . Unsymmetrical ketenimine dimers 1 are also obtained in a slow thermal reaction 8 or in an AlCl3 -catalyzed reaction at −20 ◦ C (50 % yield) 9 . NR1 2 R2C

C

R2

NR1

NR1 R 2C 1

In contrast, the symmetrical ketenimine dimer 2, is obtained in the in situ generation of diphenyl-N-allylketenimines 10 . The dimerization proceeds across the C C bonds. Ph2C

C

NCH2CH

NCH2CH

Ph2

CH2 CH2

Ph2

CHCH2N 2

CH2

338


Ketenimine complexes, such as R(OMe)C C N(R1 ):Cr(CO)5 , 3, which can be generated from a carbene complex and an isonitrile, dimerize in the metal template to form the blue dimer complexes 4. The formation of the unexpected dimer is caused by the metal template 11 . OMe R

N 2 R(OMe)C

NR1:Cr(CO)5

C

(CO)4Cr

+

Cr(CO)6

R

N

OMe 3

4

Similar ketenimine dimer complexes are also obtained from molybdenum and tungsten ketenimine complexes. In the reaction of Ph3 P C C NPh with phenyl isocyanate a Wittig-type reaction is observed, generating a new heterocumulene, which dimerizes under the reaction conditions to form the four-membered ring dimer 5 in 53 % yield 12 .

Ph3P

C

C

NPh + PhNCO

[PhN

C

C

PhN

NPh

PhN

NPh

NPh]

5

The bis-t-butylsilaketenimine 6, generated from di-t-butylsilene and phenylisonitrile, undergoes dimerization to give the red dimer 7 in 65 % yield 13 . NPh

t-Bu–Si t-Bu2 Si: + CNPh

[t-Bu2 Si

C

NPh]

Si–t-Bu PhN

6

7

In the reaction of Ph3 P C C NPh with methyl iodide, a cyclodimer salt 8 of the phosphoruscumulene is obtained 14 . Me

⊕

Ph3P

C

C

NPh + Mel

NPh

Ph3P

I

PhN

PPh3 8

N-Aryldiphosphanyl ketenimines 9 undergo a [3+2] cyclodimerization reaction to give the cyclodimer 10 in 70 % yield 15 . Ph

Ph P

2 (PPh2)2C 9

C

NPh

(PPh2)2C

N 10

Ph P Ph NPh


339

When the substituent on nitrogen is a xylyl- or t-butyl group, no dimerization is observed. The cyclodimer can serve as a source for the monomer because the dimerization is reversible. 4.3.3 4.3.3.1


The ketenimines 11 react with methylsulfonyl nitrene via a [2+1] cycloaddition reaction to give the diaziridines 12 16 . Me2C

C

RN

NR + MeSO2N3

C CMe2 N SO2Me

11

12

R

Yield (%)

Ph 4-MePh 4-BrPh

4.3.3.2

42 56 74


Across carbon-carbon multiple bonds The [2+2] cycloaddition reaction of ketenimines to acetylenic compounds affords 2-azetines and six-membered ring 2iminotetrahydropyridine derivatives. For example, reaction of 1-diethylamino-1-propyne with N-methyldiphenylketenimine in acetonitrile for seven days gives an equimolar mixture of the [2+2] cycloadduct 13 and the [2+2+2] cycloadduct 14 17 .

Ph2C

C

NMe + Et2NC

CPh2

MeN

CMe

Et2N

Me

Ph2C

Me NMe N

+

Ph2

Me

NEt2 13

14

From N-phenyl substituted ketenimines 15 and ynamines the linear 1:1 adducts 16 are formed, which undergo an intramolecular cyclization reaction to give 4-aminoquinoline derivatives 17. R2C

C

NPh + Et2NC

15

CR1

R2C

N

R1

•

R2CH NEt2

N

R1

⊕

NEt2

16

17

340


R1

Yield (%)

Me Ph Ph

Me Me Ph

85 67 61

N-Phenylsulfonyl-bis-trifluoromethylketenimine 18 reacts with phenylacetylene to give a mixture of the 2-azetine 19 (11 %) and the iminocyclobutene cycloadduct 20 (5.5 %), indicating that the cycloaddition across the C N bond is somewhat favored in this reaction 18 .

(CF3)2C

C

NSO2Ph + HC

C(CF3)2

PhSO2N

CPh

+

Ph

18

NSO2Ph

(CF3)2

Ph

19

20

Keteniminium salts undergo [2+2] cycloaddition reactions with unreactive olefins, such as ethylene, cyclopentene, cyclohexene and styrol to give cyclobutane ammonium salts 23, which are readily hydrolyzed to give cyclobutanones 24. Likewise, reaction with acetylene derivatives affords cyclobutenylidene ammonium salts 25, which are also readily hydrolyzed to give the cyclobutenones 26. Some of the [2+2] cycloadducts obtained from keteniminium salts and olefines are shown in Table 4.17. The keteniminium salts are easily synthesized from suitable dimethylamides and phosgene, or trifluoromethanesulfonic acid anhydride. The reaction of the amide with phosgene generates a chloro compound 21, which is in equilibrium with the ketenimine salt 22. R2CHCONMe2 + COCl2

R2C

C(Cl)NMe2

R 2C

N+Me2 Cl−

C

21

22

Table 4.17 Cyclobutanones by [2+2] cycloaddition of keteniminium salts to olefins ⊕

RR1C

C

N+

Me2

X−

+

R2CH

NMe2X

RR1

CHR3

R2

O RR1

R3

R2

23

R

R1

R2

R3

Lewis acid

Me H Me Me Ph Me Me

Me H H H H Me Me

H Ph Ph –(CH2 )3 –(CH2 )3 –(CH2 )4 – –(CH2 )6 –

H H H

ZnCl3 CF3 SO3 CF3 SO3 CF3 SO3 CF3 SO3 ZnCl3 ZnCl3

R3 24

Yield (%)

Reference

68 77 60 72 80 88 86

19 20 20 20 20 20 20


341

Theoretical studies of this reaction show that electron-attracting substituents on ketiminium cations favor this reaction 21 . Some of the cyclobutenones obtained in the [2+2] cycloaddition reaction of keteniminium salts with acetylenes are listed in Table 4.18. Table 4.18 Cyclobutenones by [2+2] cycloaddition of keteniminium salts and acetylenes ⊕

RR1C

N+

C

Me2

X−

+

R2C

NMe2X

RR1

CR3

R2

O RR1

R3

R2

25

R

R1

R2

Me Me Me Me Me

Me Me Me Me H

H H Et Et

R3

H H Et Et −(CH2 )4 –

R3 26

Lewis acid BF4 ZnCl3 BF4 ZnCl3 CF3 SO3

Yield (%)

Reference

77 80 80 100 80

106 22 23 23 20

The intramolecular cycloaddition reaction of aldo- and keto-keteniminium salts was explored by Ghosez and coworkers 23 and some examples are shown in Table 4.19. The intramolecular cycloadducts were hydrolyzed to give the shown cyclobutanone derivatives. Table 4.19 Intramolecular cycloaddition of keteniminium salts Keteniminium salt

Cyclobutanone

Yield (%)

H O

• N ⊕

75 O

•

N ⊕

89 •

N

O

78 H O

• N ⊕

72

This reaction was utilized in the synthesis of prostaglandin intermediates 24 . Extension of the intramolecular [2+2] cycloaddition of keteniminium salts to alkenyloxyketeniminium salts has provided numerous bi- and tricyclic cyclobutanone

342


derivatives 25 . Some examples of the reactions of the related phenoxyketeniminium salts are listed in Table 4.20 26 . The yields decreases with extended tether length. Table 4.20 Intramolecular [2+2] cycloaddition reactions of phenoxyketeniminium salts Keteniminium salt

Cyclobutanone

Ph

Yield (%)

Ph Me

O

•

+ NEt2

O

Me O

O

•

+ NEt2

O

O

70

44

O • O

+ NEt2

O

18 O

•

O

+ NEt2

O

10

N-Sulfonylketenimines 27 undergo a [2+2] cycloaddition reaction with vinylethers and ketene-O,O-acetals to give the corresponding cycloadduct. An example is the formation of 28 27 .

(CF3)2C

C

NSO2Ph + CH2

CHOEt

C(CF3)2

PhSO2N EtO

27

28

Likewise, (CF3 )2 C C NPh reacts with ketene O,O-acetals to give the [2+2] cycloadducts, which readily undergo ring opening. Also, the highly strained seven-membered ring ketenimine 29 adds the vinyl ether at room temperature to give the bicyclic adduct 30 in 81 % yield (two diastereoisomers, ratio 57:43) 28 . S O N

29

CF3 CN CF3

S + CH2

CHOEt

O N H EtO 30

CF3 CN CF3

Across C O Bonds The [2+2] cycloaddition reaction of ketenimines with C O bonds to give iminooxetanes is also known. For example, a [2+2] cycloadduct 31 is obtained in the


343

reaction of N-p-tolyldiphenylketenimine with hexafluoroacetone at 110◦ C 29 . Ph2C

C

NR + (CF3)2C

NR

Ph2

O

(CF3)2

O 31

Ketenmines also react with aromatic carbonyl compounds under UV irradiation to give the iminooxetans 32 and 33. In Table 4.21, some examples of the formation of the photocyclization products are listed. Table 4.21 Photocyclization of aromatic carbonyl compounds with ketenimines

RR1C

C

NR2

+

R3R4C

NR2

RR1 O

+

R3R4

NR2

RR1

O

R3R4

O

32

33

R

R1

R2

R3

R4

32 Yield (%)

33 Yield (%)

Reference

Me Me Me Ph

Me Me Me Ph

C(Me)2 CN C6 H11 Ph C6 H11

Ph Ph Ph Ph

H Ph Ph Ph

— 100 40 100

50 — 60 —

30 31 27 27

From fluorenone and several ketenimines, formation of 32 is initially observed but the latter rearranges to 33 32 . The [2+2] cycloaddition reaction between ketenimines and aldehydes is also catalyzed by Y+3 and Eu+3 shift reagents 33 . Heating of the respective iminooxetanes in the presence of the same catalysts causes formation of the isomeric β-lactams 34 . Also, duroquinone reacts photochemically with Ph2 C C NPh to give the isomeric imino oxethanes 34 and 35 35 . NPh O

O

O

PhN Ph2

+ Ph2C

C

Ph2 +

NPh

O

O 34

O 35

From benzoquinone the shown rearranged product 36 is isolated 36 . OH

O + Me2C

C

NPh NPh

O

O 36

344


Across C N bonds The addition of ketenimines to C N bonds is a general reaction, and again the keteniminium salts undergo this reaction especially well 37 . In the reaction of N,Ndimethyl-1chloro-2-methyl-1-propenylamine with the azomethines at room temperature the cycloadducts 37 are obtained.

R1

R2 C

C

N+Me

2

X−

+

R3R4C

NR5

NMe2

R1R2 R3R4

X

NR5 37

R1

R2

R3

R4

R5

Me Me Me t-Bu

Me Me Me H

Ph PhCH2 S Ph Ph

H H Ph H

Me t-Bu Ph Ph

Yield (%) 74 60 65 80

However, the cycloaddition of ketenimines to azomethines is also catalyzed by zinc chloride and yields of 14–57 % of the [2+2] cycloadducts are obtained 38 . Prochiral α-chloroiminium chlorides react with imines having chiral substituents to give β-lactams 39 . The photochemically generated ketenimine 38 is trapped with benzylideneaniline to give a 46 % yield of the [2+2] cycloadduct 39 40 . The hydrogens in the four-membered ring have a cis-configuration.

R2NC(

NCN)CH

N2

[R2NCH

C

N-CN] + PhCH

NCN

R2N

NPh

Ph

38

NPh 39

Higher yields (86 %) are obtained in the reaction of N-tosyldimethylketenimine 40 with PhCH NPh to give the cycloadduct 41 41 .

Me2C

C 40

NTs + PhCH

NPh

NTS

Me2 Ph

NPh 41


345

An intramolecular cycloaddition reaction involving a ketenimine with two different substituents on its sp2 carbon terminus 42 affords a mixture of mainly cis-azeto[2,1b]quinazoline 43 and the trans- isomer 44 in total yields of 29–84 % 42 . H N •

N

R R R1

N N

Ph

42

R H R1

N

+ N

Ph

43

H Ph R1

44

The ketenimine 42 is generated in situ in an aza-Wittig reaction of an iminophosphorane with a disubstituted ketene. When chiral induction is achieved with amines or aldehydes bearing an asymmetric center in the preparation of the imine fragment, a mixture of diastereoisomeric transand cis-cycloadducts 45 and 46 are obtained in which the trans-isomers 45 are the major products (total overall yields, 26–82 %) 43 . HH N R1

R

N

•

R

CPh2

N

H R1 N H Ph

R + N

Ph

45

H H R1 N Ph Ph

46

The chiral imino ketenimine 47 is similarly converted to a single intramolecular cycloadduct 48 with a syn-relative configuration between two adjacent stereo centers 43 . H

BOC H

N O CPh2

N •

N

BOC N Ph2

N

47

N O

48

When the ketenimines 49 are generated in situ at room temperature in toluene, cyclization occurs to give the cycloadducts 50 in 36–91 % yields 44 . R2 R1

R3

N N

•

R1

N

R2R3 R4R 5

CR4R5

N

49

50

Likewise, the imino(acylimino)ketenimines 51, generated in situ, undergo an intramolecular cycloaddition reaction to give 52 45 . R1

O N N 51

•

O R2 R3 Ph

N N 52

R 1R2 R3 Ph

346

Cumulenes in Click Reactions R1 Ph Ph 4-MePh

R2

R3

Yield (%)

Ph Me 4-MePh

Ph Ph Ph

65 58 67

The intramolecular [2+2] cycloaddition of the imine-tethered ketenimine 53 affords the tricyclic cycloadducts 54 in a highly stereocontrolled manner 46 . R1

R2 R3

N N

R1 Me Ph

•

R 2R3 Me Ph

N N

53

54

R1

R2

Yield (%)

Me Ph Ph

MeS MeS Ph

85 86 51

Azeto[1,2]imidazoles 56 are also obtained in low yields by a formal intramolecular [2+2] cycloaddition reaction of the imino ketenimines 55. 47 H

Ar

N N

Me Ph

•

Ar

N

Me

N

55

Ph 56

An intramolecular ketenimin–ketenimine [2+2] cycloaddition reaction has also been observed. The bis-ketenimine 57 was generated in situ by the aza-Wittig reaction and intramolecular cyclization afforded azeto[2,1-b]quinazolines 58 in moderate to good yields. 48 R1

N

R2

N

•

CPh2

•

N

CPh2

N

CPh2 Ph2

R3 57

58

R1

R2

R3

Yield (%)

H Br Cl

H H H

Me H H

77 78 76


347

The [2+2] cycloaddition reaction of N-arylketenimines with isocyanates proceeds across the C N bond of the isocyanate to give 4-iminoazetidine-2-ones 59 in 72–83 % yields 49 . R 2C

C

NAr

R2

NAr + RNCO

NR

O 59

In a similar manner, carbodiimides undergo the [2+2] cycloaddition reaction across the C C bond of the N-tosylketenimine 60 to give the 2,4-bis(imino)azetidines 61 in low yields 50 . R2C

C

NTs +

R1N

C

NTs

R2

NR1

NR1

R 1N 60

61

Across N N bonds Another pronounced [2+2] cycloaddition reaction of ketenimines is their addition to the N N bond in cis-azomethines to give the imino-1,2-diazetidines 62 and 63. This reaction is conducted with UV irradiation to convert the unreactive transazobenzenes into the reactive cis-cis compounds. Asymmetrically substituted azobenzenes afford mixtures of the two regio isomers. Electron donating substituents on the azobenzenes increase the rate of addition. Some of the [2+2] cycloadducts obtained in the reaction of ketenimines with azo compounds are listed in Table 4.22. Table 4.22 Imino-1,2-diazetidines by [2+2] cycloaddition of cis-azobenzenes to ketenimines Ph2C

C

NR +

R1N

NR

Ph2

NR2

+

R1N

NR2

NR

Ph2 R2N

62

NR1 63

Isomers yield (%) R

R1

R2

62

63

Reference

4-MePh 4-MePh 4-MePh 4-MePh 4-MePh 4–MePh 4-MePh

Ph Ph Ph Ph Ph Ph Ph

Ph 4-MePh 3-MePh 4-ClPh 4-BrPh 4-Me2 NPh 4-Et2 NPh

—a 60 60 60 60 59 59

83 35 28 29 23(92)b 100(74)b 100(62)b

51 52 50 50 50 50 50

a b

Only one adduct is obtained. Total crude yield of both adducts.

A substituent in the 2-position of one of the aryl groups in the azobenzene gives rise to the formation of only the isomer 62 due to steric hinderance; also, a p-dialkylamino group favors the formation of 62 due to the electronic effects. Bis-ketenimines form

348


similar cycloadducts with azobenzenes 53 . Also in this reaction, asymmetrically substituted azobenzenes give rise to the formation of mixtures of isomers. However, from N-phenylN -2-chlorophenylazobenzene only one isomer is produced because of steric hindrance. Dibenzo[c,f]diazepine, which contains an azo group ‘locked’ in the cis-configuration reacts in the dark with N-p-tolyldiphenylketenimine to give a 68 % yield of the [2+2] cycloadduct 27 . Across other double bonds Triarylketenimines react with nitrosoarenes via a [2+2] cycloaddition reaction across the N O bond to give the four-membered ring cycloadduct 64 54 . Some cycloadducts are only stable in solution and they rapidly undergo a cycloreversion reaction to form diphenylcarbodiimide and diphenylketone. Ph2C

C

NPh + PhN

NPh

Ph2

O

PhN

O

C

NPh + Ph2C

NPh

O

64

Singlet oxygen also adds across the C C bond in C,N-di-t-butylketenimine at −78 ◦ C to give 65, but the cycloadducts undergo cycloreversion to give a mixture of the corresponding aldehyde and t-butyl isocyanate 55 . N–t-Bu

t-Bu t-BuCH

C

N–t-Bu + O2

t-BuCHO + t-BuNCO O

O 65

In a similar manner the dioxetanimine 67 is obtained in the reaction of the ketenimine 66 with singlet oxygen at −45 ◦ C, but the cycloadduct is unstable and dissociates into N-methylacridine and t-butyl isocyanate 56 .

O •

MeN

N–t-Bu + O2

MeN

O N–t-Bu

66

67 ◦

The reaction of ketenimines with sulfur dioxide at −78 C affords the [2+2] cycloadducts, 68, which rearrange to give the heterocycles 69 in about 90 % yield 57 . Me2C

C

NR + SO2

NR

Me2 O

SO 68

O

Me2 OS

NR 69

Thiobenzophenones react with ketenimines to give a mixture of the [2+2] cycloadducts 70, resulting from addition across the C C bond of the ketenimine, or [4+2] cycloadducts 71, resulting from addition across the heterodiene system 58 . For example, reaction of several ketenimines, having highly substituted N-aryl groups, with thiobenzophenone afford the


349

[2+2] cycloadducts.

RR1C

C

NR2

NR2

RR1 + Ph2C

S

Ph2

S 70

R

R1

R2

Yield (%)

Me Me Ph

Me Me Ph

2,6-Me2 Ph 2,4,6-Me3 Ph Me

30 55 50

In contrast, several N-arylketenimines undergo the [4+2] cycloaddition reaction with thiobenzophenone to give 3,1-benzothiazines 71 in high yields. N RR1C

C

NR2 + Ph2C

S

CH RR1 S

Ph Ph 71

R

R1

R2

Yield (%)

Me Me Me Ph Ph

Me Me Me Ph Ph

Ph 4-MePh 4-MeOPh 4-MePh 4-ClPh

80 80 80 85 85

From thiobenzophenone N-phenylmethylketenimine, a mixture of the two cycloadducts is obtained. The photochemical reaction of N-aryldiphenylketenimine with the cyclic thiones 72 (X = O, S) affords the spiro 2-iminothietanes 73 in 80–90 % yields 59 . S Me2C

C

NAr +

X

S

72

NAr

X

73

The [2+2] cycloaddition reaction of isothiocyanates with ketenimines proceeds at room temperature across the C S bond of the isothiocyanates and the C C bond of the ketenimines to give 2,4-bis(imino)thietanes. However, only reactive isothiocyanates, such as arenesulfonyl isothiocyanates (48–54 % yield) 60 or phenylcarbonyl isothiocyanate (44 % yield), undergo this reaction 61 .

350


Also, the [2+2] cycloaducts 74 are obtained from ketenimines and tosylsulfinylamines at room temperature in 90 % yield 62 .

Me2C

C

NPh + TsN

S

NTs

Me2

O

OS

NPh 74

In a similar reaction, the cationic sulfinylamines 75 react with ketenimines to give the [2+2] cycloadducts 76 in 52–88 % yield 63 .

R2C

C

NPh + Me2N+

S

O

NMe2BF4

R2

BF4

OS

75

NPh 76

Hexa-t-butylcyclotrisilane reacts with dimethyl-N-phenylketenimine to give an intermediate cycloadduct 77, which rearranges to form the tricyclic heterocycle 78 64 . PhN (t-Bu2Si)3 + Me2C

C

Si–t-Bu Si–t-Bu

NPh t-Bu–Si

Si–t-Bu

77

78

The W C group in pentacarbonylbenzylidenetungsten 79 adds triphenylketenimine to give, after rearrangement, a linear adduct, which on thermolysis gives (CO)5 W C CPh2 and the the heterocycle 80 65 . Ph (CO)5W

C(H)Ph + Ph2C

C

NPh

(CO)5W

C

Ph

CPh2 + (CO)5W N Ph 80

79

4.3.3.3

Ph H


Diphenyl-N-p-tolylketenimine reacts with 2-dimethylamino-3-(methyl)phenylazirine 81 to give 2-dimethylamino-3-methyl-3,4,4-triphenyl-5-p-tolylimino-1-pyrroline 82 in 57 % yield 66 . Me2N Ph2C

C

N

NR + Me 81

Ph

NR

Ph2 Me

N

Ph

NMe2 82


351

Aziridines 83 react with dicarbethoxyketenimines 84 in the presence of Lewis acid catalysts to give the [3+2] cycloadducts 85 in high yields 67 . R2

NAr

(EtO2C)2 + (EtOCO)2C

N R1 83

C

NAr

NR1

R2

84

85

2-Vinylthiiran 86 reacts similarly with ketenimines in the presence of palladium catalysts to give 1,3-thiazolidines 87 68 . Cl R

+ 4-ClPhN

C

N

R

C(Me)COOEt

Me

S

S

86

87

R

CO2Et

Yield (%)

H Me

73 81

When 4-benzyl-5-tosylimino-1,2,3,4-thiatriazole 88 is heated in solution (chloroform at 60 ◦ C) in the presence of ketenimines the [3+2] cycloadducts 89 are obtained in 51–70 % yields 69 . N

BzN

N S

BzN

R2C

S NTs

+ R2C

C

NAr

N Ar

BzN

S

NTs

NTs

88

89

In the reaction of N-aryldiphenylketenimine with diazomethane at room temperature, the [3+2] cycloadducts 90 are obtained in 31–43 % yields 70 . Ph2CH

Ph2C

C

NAr

NAr + CH2N2

N N 90

352


The [3+2] cycloaddition reaction of the highly strained seven-membered ring ketenimine 91 with diazomethane at room temperature affords the bicyclic adduct 92 in 80 % yield 28 . S N

CF3 CN

+ CH2N2

CF3

S

CF3 CN

S

CF3 CN

N N

CF3

N N

CF2

N

N 92

91

Trimethylsilyldiazomethane reacts with n-butyl lithium to give Me3 SiC(Li)N2 , which undergoes a [3+2] cycloaddition reaction with ketenimines to give the 1,2,3-triazoles 93 in 67–82 % yields 71 . R1R2CH

R 1R 2C

C

NR3 + Me3SiC(Li)N2

NR3 N

Me3Si

N 93

When an electron withdrawing group is attached to the sp2 carbon terminus, 4-amino-3trimethylsilylpyrazoles are obtained 72 . Hydrazoic acid reacts with diphenylketenimines in benzene at room temperature to give the [3+2] cycloadducts 94 73 . Ph2CH

Ph2C

C

NR + HN3

NR

N

N N 94

Likewise, N-p-tolyldimethylketenimine reacts with HN3 to give a 57 % yield of 1-ptolyl-5-isopropyl-1H-tetrazole 95 74 . Me2CH

Me2C

C

NR + HN3

NR

N

N N 95

Diphenyl-N-p-bromophenylketenimine reacts with nitrones by a [3+2] cycloaddition reaction to give the iminoisoxazolidines 96 75 . NR

Ph2

Ph2C

C

NR + PhCH

N(R1)

O

Ph

O N R1 96


353

The thione-S-imides 97 react with ketenimines to give the [3+2] cycloadducts 98 and 99 76 . S C

NR +

S

S NTs

NTs

NTs

+ RN

RN

97

98

R

99

Yield of 98 (%)

Yield of 99 (%)

87 — 67 93

8 55 17 3

Ph 4-MePh 4-ClPh α-C10 H10

The ketenimine complexes 100 react with aldehydes, isocyanates and carbodiimides to give the [3+2] cycloadducts 101 77 .

(CO)5W(C6H11)N

C

C(OEt)Ph + X

C

Ph OEt X (CO)5W C N y

Y

C6H11 100

101

X

Y

Yield (%)

O O O NMe NBu NPh

Me,H Et,H Ph,H O O NPh

75 70 78 66 63 7

Diphosphanylketenimines 102 are excellent 1,3-dipoles, which readily undergo regiospecific [3+2] cycloaddition reactions with suitable dipolarophiles, such as acetylenes, phenyl isocyanate and ethyl isothiocyanate. For example, reaction of 102 with two equivalents of acetylene derivatives form the cycloadducts 103 78 . Ph

Ph

NPh

P

(Ph2P)2C

C

NPh + RC

102

CR1

R1

R

P R Ph Ph 103

R1

354


R1

H OCOMe

OCOMe OCOMe

Yield (%) 80 85

In a similar manner, the partially oxidized ketenimine 104 reacts with alkynes to give the [3+2] cycloadduct 105 (80–85 % yield), with phenyl isocyanate to give 106 (75 % yield) and with ethyl isothiocyanate to give 107 (70 % yield). O NPh

Ph2P Ph2P

R R1

105 O

Ph2PO(Ph2P)C

C

NPh

Ph2P

NPh

Ph2P

NPh

104

O 106 O Ph2P

NPh

Ph2P

NEt

S 107

In contrast, 104 reacts with HC≡CCH2 NHMe in a nucleophilic reaction to give the azaphosphaheterocycle 108. O

NPh

Ph2P Ph2PO(Ph2P)C

C

NPh + HC

CCH2NHMe

NMe

Ph2P Me 108

104

Ketenimines also react as dipolarophiles in their reactions with ethoxycarbonyl nitrene, generated from the corresponding azide at 100 ◦ C to give 109 79 . R2 R 2C

C

N–p-tolyl + EtOCON3

O

N– N OEt 109

–CH3


4.3.3.4

355


One of the earlier [4+2] cycloaddition reactions, involving ketenimines as dienophiles, is the reaction of trichloroacetyl isocyanate with the ketenimines 110 to give the cycloadducts 111 in 91–93 % yields. In this reaction, the C C bond of the ketenimine participates 80 .

N

Cl3C

•

O

O + Cl2C

O

C(Cl)CH

C

C(Cl)

N

NR

O

Cl3C

110

CCl2

NHR

111

The vinyl aldehyde 112 also reacts with N-benzylmethylketenimine across the C C bond of the ketenimine to give the unstable pyran derivative 113, which converts upon heating to give 114 81 . H

O

O + MeCH

C

Bz N

NBz

O

NBz Me

Me

113

112

114

In contrast, the C N bond of the ketenimine 115 undergoes the [4+2] cycloaddition reaction with benzoyl sulfene to give the cycloadducts 116 in 48–74 % yield 82 . O

O

SO2 Ph

O

S

+ R2C

C

NR1

NR1 Ph

CR2

O

116

115

The [4+2] cycloaddition reaction of dipivaloylketene 117 (R = t-Bu) with Ph2 C C NR1 (R1 = p-tolyl) also proceeds across the C N bond of the ketenimine to give the cycloadduct 118 in 82 % yield 83 . O

•

R R

117

O

O

O + Ph2C

C

NR1

O NR1

R R

O

CPh2

118

Also, in the thermal reaction of the furan-2,3-diones 119 α-oxoketenes are generated, which can be trapped with diphenyl-N-(4-methylphenyl)imine to give the [4+2]

356


cycloadducts 120. O

O O

R R1

R R1

O

O

•

O

O + Ph2C

O

NR2

R

NR2

C

O

R1

CPh2

O

119

120

R

R1

R2

R3

Et Me

Ph t-Bu

4-MePh 4-MePh

Ph MeO

Yield (%)

Reference

35 32

84 85

However, reaction of 4-benzoyl-furan-2,3-diones 121 with diphenyl-N-(4methylphenyl)-imine proceeds via initial [4+2] cycloaddition across the enone system to give the intermediate 122, which undergoes novel furandione rearrangements to give 123 in 55 % yield 86 . Ph

O O

Ph

+ Ph2C Ph

O

C

Ph

O

NR R2C

O

121

O N R Ph

Ph

O

O

O O

RN

O

Ph 123

122

O

The mechanisms of these rearrangements were established by O 17 labelling experiments 87 . Interestingly, irradiation of the 2,3-diones 124 at 7–15 ◦ C in the presence of diphenylketen-N-(4-methylphenyl)imine causes reaction via a [2+2] cycloaddition across the 3-ene-one configuration, followed by elimination of tolyl isocyanate to give 125 85 . O

O O

Ph

+ Ph2C Ph

X

C

CPh2

Ph

NR

Ph

O

X

O

125

124

X O NPh S

Yield (%) 60 49 10


357

The [4+2] cycloaddition reaction of of perhalo-o-quinones 126 with triarylketenimines gives rise to the formation of the heterocycles 127 88 . X

Ph2C

C

X O

X

O

X

NR + X

X

O

O

NR Ph2

X

X 126

127

R

X

Yield (%)

Ph Ph 4-MePh 4–MePh

Cl Br Cl Br

78 69 89 96

The vinyl ketenimines 128 react as azadienes in [4+2] cycloaddition reactions. For example, reaction with isocyanates gives the cycloadducts 129 (38–54 %), with diaryl sulfides the cycloadducts 130 (29–33 %) and with diphenylketene the cycloadducts 131 (47–53 %) 89 . Ph Ar

O

HN

NR CR2

129

N

•

CR2 Ph

Ar

Ph

H

Ar

Ar2 S

HN

H 128

CR2

130 Ph

H

Ar

CPh

N

O CR2

131

The vinyl ketenimines 132 react with ynamines at 0 ◦ C by a [2+2] cycloaddition across the C N bond to generate the allene 133, which undergoes electrocyclic ring closure to

358


give 134 in 89 % yield. 90

•

N

CPh2 Ph

MeO2C

CH3

Et2N + MeC

CNEt2

• N

MeO2C

H 132

NEt2 CH3

N

CPh2 MeO2C

Ph

CHPh2 Ph

H 133

134

When the reaction is conducted at 25 ◦ C a [4+2] cycloaddition reaction with formation of 135 occurs (yield, 87 %) 91 .

N

•

CPh2 + MeC

Ph MeO2C

N

CNEt2

CHPh2 Me NEt2

MeO2C

H

Ph

135

In contrast, intramolecular cycloaddition of the dienylketenimines 136 (R = Me, OMe, OCOMe; R1 = Me, i-Pr), generated in situ, gives rise to the formation of the cyclohexadiene imines 137 92 . Ph Ph Ph R1

R1 •

Ph

Ph Ph

NR2

NR2

136

137

The vinyl ketenimine CH2 CH(Me)C C NTs also reacts as a diene with tetracyanoethylene (77 % yield), maleic anhydride (88 % yield), dimethyl acetylenedicarboxylate (40 % yield) and PhC C(CN)2 (100 % yield). Also, the vinylketenimine 138 reacts with diethyl azodicarboxylate to give a 94 % yield of the cyloadduct 139 and with 4-phenyl-4H1,2,4-triazole-3,5-dione to give the cycloadduct 140 in 53 % yield 93 . NR1 R

R

138

•

NCO2Et NCO2Et

NR1

139 R

O N N

NPh O

140


359

In contrast, the vinylketenimine generated from 141 and methylsilylketene undergoes an intramolecular [4+2] cycloaddition to give the isoquinoline derivative 142 94 . CO2Et

MeO MeO

N

PPh3

CO2Et

MeO

+ Me3SiCH

C

O

N

MeO

NO2

NO2 CH2SiMe3

141

142

Heating of the ketenimines 143 causes electrocyclic ring closure to give the quinoline derivatives 144 95 . R1

R1 R2

N

R2

Ph C R3

•

N

143

CH(Ph)R3

144

However, heating of the ketenimine 145 in toluene in a sealed tube for 16 h, gives rise to the formation of a tetrahydrobenzo[b]acridine derivative 146.

N

•

CPh2

N H

145

Ph

146

The benzocarbazoles 148 are obtained in 12–73 % yields in the intramolecular cyclization of the ketenimines 147 86 .

N

•

R C Ph

N H

147

R

148

The enyne ketenimines 149 also cyclize intramolecularly to produce the benzo[b] carbazoles 150 96 . R2

R1 N

149

•

R2 •

R1

R3

N

R2 R1

•

N H

R3

150

R3

360


Similarly, intramolecular cyclization of the C-vinylketenimines 151 occurs to give the intramolecular cycloadducts 152 in 42–98 % yields 97 . CO2Me

CO2Me

R N

R1

• R2

R3

R

R3

R2

N H

151

R1

152

Likewise, imidoyl ketenimines 153 react as 1-aza-1,3-dienes in [4+2] cycloaddition reactions with phenyl isocyanate to give the cycloadducts 154 (62–67 % yields) or with tosyl isothiocyanate to give the cycloadducts 155 (62–69 % yields) 98 . NAr

EtO2C

EtO2C

Me

NAr

•

NAr1

Me 153

NPh O N Ar1 154 NAr

EtO2C Me

S NTs N Ar1 155

Also, upon refluxing in benzene, the imidoyl ketenimine 156 undergoes intramolecular cyclization to give 157 in 71–82 % yield 99 . Ph

•

Ph COPh N N

NAr Me

Me

N–N

C(Ph)COPh Ph 157

156

N H

Similarly, the imidoyl ketenimine 158 undergoes an intramolecular [4+2] cycloaddition to give the quinazoline derivative 159 in 65 % yield 100 . •

NPh Me

Me

N–N 158

Ph H N N

CPh2

N Ph

159

N-Acyl ketenimines react with carbodiimides via a [4+2] cycloaddition reaction to give the expected [4+2] cycloadducts 101 .


361

Also, the intramolecular [4+2] cycloaddition of the ketenimine 160 to give the benzimidazo[1,2-b]isoquinolines 161 in 84–92 % yields is observed 102 . CPh2

•

M

Ar

H N

Ar H

N

N

Ph 161

160

H

Likewise, the N-alkenyl substituted C-aryl ketenimines 162 undergo cyclization to give the benzo[f]indoles 163 in 21–55 % yields. The oxidation of the intermediate cycloadduct was caused by adding MnO2 103 . R X

R X

C(Ar)

N

•

Ar 162

N H

163

When the aza-Wittig reaction is first conducted with diphenylketene, followed by an aryl isocyanate, an intermediate carbodiimide can be generated in the presence of a ketenimine, as in 164, which, on heating at 160 ◦ C in toluene, undergoes cyclization to give pyrido[2,3,4de]quinazolines 165 in 69–70 % yields 104 . CH3

CH3 CO2Et

CO2Et

N

N

N

•

•

NAr

N

NAr

CHPh2

CPh2 164

165

The imine-tethered ketenimine 166 undergoes intramolecular [4+2] cycloaddition on heating in toluene to form the heterocycle 167 105 .

N

CR1R2

N

• 166

CPh2

R1 R2 N N

Ph Ph 167

362


Diazoketones react with N-p-tolyldimethylketenimines to give the shown [6+2] cycloadducts 168 106 .

+ Me2C O2N

NR

O

O C

NR

N2

O 2N

N 168

Some ketenimines, such as 169, undergo a thermal rearrangement to produce the isomeric imidoyl ketenes 170, which undergo intramolecular cyclization to give the quinolones 171. O R1

R1 X

•

R2

N •

O X

O R1 R2

N

Ph

N

R2 Ph X

Ph

169

170

R1

R2

X

H H H H H H Cl Cl

Ph Ph Ph Ph Ph Ph Ph Ph

PhSe 4-MeOPhS 4-MeOPhCH2 S 4-MeOPh PhCH2 CH2 2-IPhCH2 CH2 4-MeOPh 4-MePhS

171

Yield (%)

Reference

62 89 83 95 85 90 95 97

107 105 105 108 106 106 106 105

An intramolecular [4+2] cycloaddition reaction is also observed when the naphthyl derivative 172 is generated in situ. The cycloadduct 173 is obtained in 40 % yield. As a byproduct the acridine derivative 174 is obtained in 37 % yield. The formation of 174 is the result of a [1,5]H shift followed by a 6π electrocyclization reaction 109 .

N

•

CPh2

Ph N HN

172

+

173

174


363

Also, an intramolecular ketenimine–ketenimine [4+2] cycloaddition reaction is observed on heating the bis-ketenimine 175, generated in situ, to give the tetracyclic compound 176 in 64 % yield 44 . Ph2C

•

N

N

•

N

N H Ph

CPh2

175

176

In a similar manner, the heterocyclic ketenimines 177 (X = SR, OR or NR2 ) undergo the 6π electrocyclization to give the 6H-thieno[3,2b]pyrydine-7-ones 178 in 31–73 % yields 110 . Ph

N

• X

S

N

R1

O 177

Ph R1

S

O 178

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

H. Staudinger and J. Meyer, Helv. Chim. Acta 2, 619, 635 (1919). G.R. Krow, Angew. Chem. 83, 455 (1971). M. Alajarin, A. Vidal and F. Tovar, Targets Heterocyclic Syst. 4, 293 (2000). D. Lentz, I. Brüdgam and H. Hartl, Angew. Chem. 96, 511 (1984). C.O. Kappe, G. Kollenz, R. Leung-Toung and C. Wentrup, J. Chem. Soc., Chem. Commun. 487 (1992). M. Alajarin, M.M. Ortin, P. Sanchez-Andrada and A. Vidal, J. Org. Chem. 71, 8126 (2006). Y.V. Zeifman, E.G. Ter Gabrielyan, L.A. Simonyan, N.P. Gambaryan and I.L. Knunyants, Izv. Akad. Nauk SSSR, Ser. Khim. 1813 (1976); Chem. Abstr. 86, 16466 (1977). M.W. Barker and J. Rosamond, J. Heterocyclic Chem. 9, 1147 (1972). A. Dondoni, G. Barbero, A. Battiglia, V. Bertolasi and P. Georgianni, J. Org. Chem. 49, 2200 (1984). H.J. Christan, I. Jonanin and M. Taillefer, J. Organomet. Chem. 589, 68 (1999). R. Aumann, H. Heinen and C. Krueger, Angew. Chem. 96, 234 (1984). H.J. Bestmann, G. Schmid and E. Wilhelm, Angew. Chem. 92, 134 (1980). M. Weidenbruch, B. Brand-Roth, S. Pohl and W. Saak, Angew. Chem. 102, 93 (1990). G. Birum and C. Mathews, Chem. Ind. (London) 653 (1968). J. Ruiz, F. Marquinez, V. Rieva, M. Vivanco, S. Garcia-Granada and M.R. Diaz, Angew. Chem. 112, 1891 (2000). G. L’abbe, C.C. Yu and S. Toppet, Angew. Chem. 89, 492 (1977). L. Ghosez and C de Perez, Angew. Chem. 83, 171 (1971). D.P. Deltsova and N.P. Gambaryan, Izv. Akad. Nauk SSSR, Ser. Khim. 880 (1979); Chem. Abstr. 89, 42660 (1978).

364 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63.

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365

64. M. Weidenbruch, A. Lesch, K. Peters and H.G. von Schnering, J. Organomet. Chem. 423, 329 (1992). 65. H. Fischer, A. Schlageter, W. Bidell and A. Früh, Organometallics 10, 389 (1991). 66. E. Schaumann and S. Grabley, Liebigs Ann. Chem. 290 (1981). 67. H. Maas, C. Bensimon and H. Alper, J. Org. Chem. 63, 17 (1998). 68. C. Larksarp, O. Sellier and H. Alper, J. Org. Chem. 66, 3502 (2001). 69. G. L’abbe and C.C. Yu, Chem. Ind. (London) 312 (1977). 70. M.W. Barker and J.H. Gardner, J. Heterocyclic Chem. 6, 251 (1969). 71. T. Aoyama, S. Katsuta and T. Shiorii, Heterocycles 28, 133 (1989). 72. T. Aoyama, T. Nakano, K. Marumo, Y. Uno and T. Shiori, Synthesis 1163 (1991). 73. J. Svetlik and A. Martvon, Coll. Czech. Chem. Commun. 44, 2421 (1979). 74. G. L’abbe, J.P. Dekerk, A. Verbruggen, S. Toppet, J.P. Declercq, G. Germain and M. van Meerssche, J. Org. Chem. 43, 3042 (1978). 75. M.W. Barker and J.H. Gardner, J. Heterocyclic Chem. 5, 881 (1968). 76. T. Saito, I. Oikawa, and S. Motoki, Bull. Chem. Soc. Jpn 53, 2582 (1980). 77. R. Aumann, E. Kuckert and H. Heinen, Angew. Chem. 97, 960 (1985). 78. J. Ruiz, F. Marquinez, V. Riera, M. Vivanco, S. Garcia-Granda and R. Diaz, Chem. Eur. J. 8, 3872 (2002). 79. W.J. Kauffman, J. Org. Chem. 35, 4244 (1970). 80. A. Roedig, W. Ritschel and M. Foure, Chem. Ber. 113, 811 (1980). 81. G. Barbaro, A. Battaglia and P. Giorgianni, J. Org. Chem. 53, 5501 (1988). 82. O. Tsuge and S. Iwanami, Org. Prep. Proc. Int. 3, 283 (1971). 83. C.O. Kappe, G. Färber, C. Wentrup and G. Kollenz, J. Org. Chem. 57, 7078 (1992). 84. H.A.A. El-Nabi and G. Kollenz, Monatsh. Chem. 128, 381 (1997). 85. A. Stadler, K. Zangger, F. Belaj and G. Kollenz, Tetrahedron 57, 6757 (2001). 86. G. Kollenz, G. Penn, W. Ott, K. Peters, E. Peters and H.G. von Schnering, Heterocycles 26, 625 (1987). 87. G. Kollenz, H. Sterk and G. Hutter, J. Org. Chem. 56, 235 (1991). 88. W. Ried and W. Radt, Liebigs Ann. Chem. 688, 174 (1965). 89. L. Capuano, C. Braun and F. Kühn, Liebigs Ann. Chem. 15 (1992). 90. J. Barluenga, M. Ferrero and F. Palacios, Tetrahedron 53, 4521 (1997). 91. J. Barluenga, M. Ferrero and F. Palacios, Tetrahedron 53, 4521 (1997). 92. H.E. Eckhardt and H. Prest, Angew. Chem. 90, 497 (1978). 93. G. Barbaro, A. Battaglia and P, Giorgianni, J. Org. Chem. 52, 3289 (1987). 94. P. Molina, A. Vidal and I. Barquero, Synthesis 1199 (1996). 95. P. Molina, M. Alajarin and P. Sanchez-Andrada, J. Org. Chem. 57, 929 (1992). 96. M. Schmittel, J.P. Stellen, M.A.W. Angel, B. Engels, C. Lennartz and M. Hanrath, Angew. Chem. Int. Ed. 37, 1562 (1998). 97. E. Differding and L. Ghosez, Tetrahedron Lett. 26, 1647 (1985). 98. J. Goerdeler, A. Laqua and C. Lindner, Chem. Ber. 113, 2509 (1980). 99. E.E. Schweizer and J.E. Hayes, J. Org. Chem. 53, 5562 (1988). 100. K. Lee, H. Kwon and B.G. Kim, J. Heterocyclic Chem. 34, 1795 (1997). 101. L. Capuano and K. Djokar, Chem. Ber. 114, 1976 (1981). 102. M. Alajarin, A. Vidal, F. Tovar and C. Conesa, Tetrahedron Lett. 40, 6127 (1999). 103. P. Molina, C. Lopez-Leonarda and C. Alcantara, Tetrahedron 50, 5027 (1994). 104. P. Molina, M. Alajarin and A. Vidal, J. Org. Chem. 57, 6703 (1992). 105. M. Alajarin, P. Sanchez-Andrada, A. Vidal and F. Tovar, Eur. J. Org. Chem. 2636 (2004). 106. W. Ried and R. Junker, Liebigs Ann. Chem. 696, 101 (1966). 107. M. Alajarin, M. Ortin, P. Sanchez-Andrada and A. Vidal, J. Org. Chem. 71, 8126 (2006). 108. M. Alajarin, M. Ortin, P. Sanchez-Andrada, A. Vidal and D. Bautista, Org. Lett. 7, 5281 (2005). 109. M. Alajarin, A. Vidal and M. Ortin, Tetrahedron 61, 7613 (2005). 110. M. Alajarin, A. Vidal and M. Ortin, Synthesis 590 (2007).

366


4.4 1-Silaallenes, R2 C C Si 4.4.1 Introduction Silaallenes are of recent vintage. While 2-silaallenes and silazaallenes have only been encountered as intermediates, stable 1-silaallenes with 2,4,6-triisopropylphenyl substituents on silicon have been synthesized recently 1 . While 1-silaallenes with highly sterically hindered substituents are stable at room temperature, Me2 Si C C(SiMe3 )Ph exhibits a lifetime of about 25 µs at room temperature in nitrogen-saturated hexane solution 2 . Also, the first stable allenes with double-bonded phosphorous with one 2,4,6-triisopropylbenzene substituent on silicon have been synthesized 3 . In view of the instability of silaallenes, their dimerization reactions are mainly observed. 4.4.2 Dimerization Reactions In the photolysis reaction of the alkynyldisilanes 1, about 20 % of the head-to-head cyclodimer 3 of the intermediate silaallene 2 is obtained 4 . (Me3Si)2C Me3Si–SiR2–C CSiMe3

[R2Si

C

1

C(SiMe3)2]

C(SiMe3)2

R2Si

2

SiR2 3

In contrast, Me2 Si C C(Ph)SiMe3 , complexed by nickel, leads to a head-to-tail cyclodimer 4 in 64–78 % yield 5 . C –

Me2Si

C(Ph)SiMe3

Me2Si

C(Ph)SiMe3

SiMe2

Me3Si(Ph)C

Ni(PEt3)2

4

Also, the 1-silabutatrienes 6 generated in the photolysis or thermolysis of 5 undergo dimerization across the Si C bonds to form the cyclodimer 7 6 . (Me3Si)2C

C(SiMe3)2 SiAr2

Ar2Si

[Ar2Si

C

C

•

Ar2Si

CR2]

CR2

SiAr2

• R2C

5

6

7

The silabutatriene can also be trapped with anthracene to give the [4+2] cycloadduct 6 . The dimerization of the sterically hindered phosphasilaallenes (R = aryl, R1 = 2,4,6triisopropylbenzene) occurs across the P C and the Si C bonds, as well as across the Si C bonds only. The cyclodimers 8 and 9 were isolated in a ratio of 60:40 3 . R1(Ph)Si 2 RP

C

Si(Ph)R1

RP

PR +

R1(Ph)Si

PR

8

Si(Ph)R1

R1(Ph)Si

PR

9


367

Transient silaketenimine species are obtained in the photolysis of hexa-tbutylcyclotrisilane in the presence of arylisocyanides as evidenced by the isolation of the cyclodimers 10 and 11. For example, the [2+2] cyclodimer 10 (R = Ph) is isolated as ruby-red crystals in 65 % yield. In the case of R = 2,6-diisopropylphenyl, a small amount of the head-to-head cyclodimer 11 is also isolated 7 .

2 RN

C

NR

(t-Bu)2Si

Si(t-Bu)2

RN

NR

(t-Bu)2Si

Si(t-Bu)2

+ Si(t-Bu)2

RN

10

11

The dialkylsilaketenimines 12 are stable below room temperature but dissociate in solution to the silylene 13 and the corresponding isocyanides 8 . Me3Si

Si

4.4.3

Me3Si

SiMe3

•

SiMe3 Si :

NR

+

Me3Si SiMe3

Me3Si SiMe3

12

13

RNC


The dimesitylsilylene 15 adds to the 1-silaallene 14 to give the [2+1] cycloadduct 16 9 . Mes Mes2Si

C

C(SiMe3)R

+

:SiMes2

Si

Mes

C(SiMe3)R

Si

Mes 14

15

Mes 16

The [2+2] cycloaddition reaction of a 1-silaallene 17 (R = 2,4,6-triisopropylbenzene) with benzophenone gives the cycloadduct 18 resulting from addition of the carbonyl group across the Si C bond 1 .

R2Si

C

C(t-Bu)Ph + Ph2C

O

C(Ph)t-Bu

R2Si O

Ph2

17

18

Also, silaallenes, generated in the photolysis of ethynyldisilanes, are trapped with acetone to give a transient [2+2] cycloadduct, which decomposes to polysiloxanes and the corresponding allenes 10 .

368


References 1. M. Trommer, G.E. Miracle, B.E. Eichler, D.R. Powell and R. West, Organometallics 16, 5737 (1997). 2. C. Kerst, R. Ruffolo and W. Leigh, J. Organomet. 16, 5804 (1997). 3. L. Rigon, H. Ranaivonjatovo, J. Escudie, A. Dubourg and J.P. Declercq, Chem. Eur. J. 5, 774 (1999). 4. M. Ishikawa, K. Nishimura, H. Ochiai and M. Kumada, J. Organomet. Chem. 7, 236 (1982). 5. M. Ishikawa, S. Matsuzawa, T. Higuchi, S. Kamitori and K. Hirotsu, Organometallics 4, 2040 (1985). 6. C. Kerst, C.W. Rogers, R. Ruffolo and W.J. Leigh, J. Am. Chem. Soc. 119, 466 (1997). 7. M. Weidenbruch, B. Brand-Roth, S. Pohl and W. Saak, Angew. Chem. Int. Ed. 29, 90 (1990); M. Weidenbruch, B. Brand-Roth, S. Pohl and W. Saak, Polyhedron 10, 1147 (1991). 8. T. Abe, T. Iwamoto, C. Kabuto and M. Kira, J. Am. Chem. Soc. 128, 4228 (2006). 9. M. Ishikawa, S. Matsuzawa, H. Sugisawa, F. Yano, S. Kamitori and T. Higuchi, J. Am. Chem. Soc. 104, 7706 (1082). 10. M. Ishikawa, H. Sugisawa, T. Fuchikami, M. Kumada, T. Yamabe, H. Kawakami, K. Fukui and H. Shizuka, J. Am. Chem. Soc. 104, 2872 (1982).

4.5

1-Phosphaallenes, R2 C C P

4.5.1 Introduction Sterically hindered 1-phosphaallenes, such as RP C CPh2 (R = 2,4,6-tris-t-butyl-phenyl) are stable at room temperature 1 . The resonance structure 1 indicates the polarity of the cumulative double-bond systems in 1-phosphaallenes. RP

C

RP+

CR2

C–C–R2

1

Contrasting with other cumulenes, the 1-phosphaallenes show no significant infrared absorption bands in the 1600–2300 cm−1 region. Extension of the cumulative system produces phosphabutatrienes (Ph3 P C C CPh2 ). Many variations of the structure Ph3 P C C X, where X = O, S and NR, are also encountered 2 . The resonance structures 2 and 3 of the phosphabutatrienes are as follows.

Ph3P

C

C

X

Ph3P+–C– 2

C

X

Ph3P+–C

C–X–

3

The reaction of hexaphenylcarbodiphosphorane with carbon dioxide, carbon disulfide or isothiocyanates gives switter ionic adducts, which undergo a Wittig reaction on heating to give Ph3 P C C X. These reactions are described by Matthews and Birum 2 and by Bestmann 3 . Several other phosphorus cumulenes, such as


369

1,4-diphosphabutatrienes, RP C C PR (R tris-t-butylphenyl) 4 , and 1,6-di-phospha1,2,4,5-tetraene, RP C C C(SiMe3 )C(SiMe3 ) C C PR (R = tris-t-butylphenyl) 5 , are also known. A recent review article describes the synthesis and reactions of 1phosphaallenes 1-phosphabutatrienes and 1,4-diphosphabutatrienes 6 . Phosphacumulenes can be subdivided into compounds with uneven numbers of carbon atoms in the polyene chain (4) and compounds with even number of carbon atoms (5). RP

CR1R2]n

[C

4 (n

RP

C

5 (n

1,3,5)

CR1R2]n

[C

1,2,3)

In 4, chiral compounds are possible when R1 = R2 . Compounds 5 can form E/Z isomers. Optical antipodes of 4 (n = 1) were separated sometime ago 7 . Phosphabutatrienes were first synthesized in 1986 8 . 4.5.2


Head-to-tail dimers 7 are obtained from phosphaallenes, RP C CR1 2 6 9,10 .

2 RP

C

CR12

RP

CR12

PR

R12C

6

7

The 1-phosphabutatrienes 8 undergo dimerization across the P C bonds to give the cyclodimers 9 or across the terminal C C bonds (when R = H, Me or C6 H11 ) to give 10 11 . CR1R2 ArP

C

C

CR1R2

ArP

R1R2C

8

• + PAr

•

PAr

•

R1R2 R1R2

• PAr

9

10

When the aryl groups have electron withdrawing substituents, such as halogens, the diphosphetan dimers 9 are obtained. With less electron withdrawing groups attached to the substituents, only the cyclobutanes 10 are formed. The diphosphacyclobutadiene derivative 11 is obtained in the dimerization of Ph3 P C(Cl)PPh2 12 . Ph3P 2 Ph3P

C(Cl)PPh2

2+ Ph2P

PPh2 PPh3

11

2 Cl–

370


Treatment of Ph3 P C C X with hydrochloric acid causes dimerization to give the four-membered ring cyclodimers 12 13 . Ph3P Ph3P

C

C

[Ph3

X + HCl

P+

CH

C

X]+

Cl–

+ Ph3P

C

C

X

X PPh3

X

12

X

Yield (%)

O NPh

83 63

In the generation of the 1-phosphaallene 13, the 1,4-diphosphafulvene derivative 14 is obtained in 37 % yield 14 . Ph

RP

C

PR

RP

CHP

Ph

13

14



1-Phosphabutatrienes react with dichlorocarbene and the initial cycloadducts 15 rearrange to give the isolated phospha[3]radialenes 16 15 . Ar Cl

Cl P

ArP

C

C

CPh2 + :CCl2

C

ArP

C

CPh2

Cl2C

15

4.5.3.2

C

C

CPh2

16


The reaction of 1-phosphaallene with tetracyanoethylene affords the [2+2] cycloadduct 17 with the reaction proceeding across the P C bond 16 . ArP

C

CPh2 + (NC)2C

ArP

CPh2

(NC)2

(CN)2

C(CN)2

17


371

The imide, Ph3 P C C NPh, 18, undergoes a [2+2] cycloaddition reaction across the C C bond in N-methylmaleimide to form the cycloadduct 19 3 . O

O Ph3P

Ph3P

C

C

NPh +

NMe

NMe PhN

O

O

18

19

In the reaction of diphenylketene with Ph3 P C C(OEt)2 , the linear switter ionic adduct 20 is obtained 3 . Ph3P

C

C(OEt)2 + Ph2C

C

Ph3P

+

C(CO2Et)2

O

–

CPh2

O

20

In contrast, reaction of N-phenyldiphenylketenimine with Ph3 P C C NPh gives the [2+2] cycloadduct. Four-membered ring cycloadducts are also obtained from Ph3 P C C O and diphenylketene 17 . The reaction of Ph3 P C C X (X NPh, S) 21 with dimethyl acetylenedicarboxylate proceeds via a [2+2] cycloaddition reaction and subsequent ring opening to give the alkylideneketenimines and alkylidenethioketenes 22, respectively 18 . MeO2C

Ph3P

C

C

X + MeOOCC

CO2Me

CCOOMe Ph3P

• X

21 Ph3P+C–(COOMe)

C(COOMe)C

C

X

22

The ketenimine derivative 21 (X = NPh) undergoes a [2+2] cycloaddition reaction with 3,4-dichlorophenyl isocyanate. The 1,6-diphospha-1,2,4,5-hexatetraene 23 (R = 2,4,6-tri-t-butylphenyl) undergoes slow cyclization in solution to form the bis(arylphosphanediyl)cyclobutenes 24 (25 % yield) and 25 (19 % yield) 5 . R Me3Si RP

C

C(SiMe3)–C(SiMe3)

C

R

P

Me3Si

P

Me3Si

P

+

PR

R P

Me3Si

R 23

24

25

The cyclobutene 24 forms yellow crystals (m.p. 145–147◦ C (dec.)) which undergo ring opening at 120 ◦ C to regenerate the linear compound. In contrast, 25 forms red crystals (m.p. 187 ◦ C), which are stable up to 150 ◦ C.

372


The reaction of N-phenylketeniminylidenephosphorane with carbon dioxide also proceeds via a [2+2] cycloaddition, followed by rearrangement to give the isomeric cycloadduct 26 3 . ⊕

Ph3P Ph3P

C

C

NR + O

C

O

⊕

Ph3P

NR

O

O

NR

O

O 26

The addition of ketones and aldehydes to Ph3 P C C X occurs across the ylide P–C bond to give [2+2] cycloadducts which react like other ketenes by addition of Ph3 P C C X across the C C bond and loss of Ph3 PO to give four-membered ring adducts 27 3 . Ph3P Ph3P

C

C

O + R1R2C

O

O O

PPh3 27

R1

R2

H CF3 Ph

4-NCPh 4-ClPh CN

Yield (%) 78 26 27

Similar reactions are observed with the phenylimide derivatives 28 to give the rearranged cycloadducts 29 19 . R1R2C Ph3P

C

C

NPh + R1R2C

NPh

O PhN

28

PPh3 29

R1

R2

H Ph C13 H18 a

4-O2 NPh PhCO —

a

Yield (%) 64 58 75

Fluorenylidene.

The adducts could also derive from loss of Ph3 PO from the initially formed cycloadducts and subsequent addition of the starting Ph3 P C C X. Also, the diethyl acetal of the cumulene system, Ph3 P C C(OEt)2 , undergoes the [2+2] cycloaddition reaction with hexafluoroacetone to give a 92 % yield of the cycloadduct 30 20 .


373

On heating, the cycloadduct gives an allene derivative, which can be trapped by phenyl isocyanate to give the corresponding cycloadduct 31 in 64 % yield. (EtO)2C Ph3P

C

C(OEt)2 + (CF3)2CO

PPh3

(CF3)2

(CF3)2C

O

C

C(OEt)2 + Ph3PO

30 CF3 CF3 (CF3)2C

C

C(OEt)2 + PhN

C

(OEt)2

O

NPh O 31

With carbon dioxide a switter ionic 1:1 adduct is formed from Ph3 P C C(OEt)2 . Phosphaallenylides react with carbonyl compounds via a Wittig reaction to give the butatrienes 32 3 . Ph3P

C

CR1R2 + R3R4CO

C

R1R2C

C

C

CR3R4 + Ph3PO

32

R1

R2

R3

R4

Yield (%)

Ph Ph

Ph Ph

4-O2 NPh 3,4-Cl2 Ph

H H

69 80

Azomethines do not react with phosphacumulenes. An exception is the reaction of N-4nitrobenzylidene-4-nitroaniline, which reacts with Ph3 P C C NPh across its C C bond to give a [2+2] cycloadduct 33 3 . Ph3P Ph3P

C

C

NPh + 4-O2NPh N

NPh

CH-4-O2NPh N O2N

NO2 33

The reaction of Ph3 P C C NPh with phenyl isocyanate affords the expected [2+2] cycloadduct. Similarly, benzenesulfonyl isocyanate reacts with Ph3 P C C O to give the shown azetidinedione derivative 34 3 . Ph3P Ph3P

C

C

O + PhSO2N

C

O

O NSO2Ph

O 34

In contrast, Ph3 P C C O and Ph3 P C C(OEt)2 react with two equivalents of phenyl isocyanate to give six-membered ring [2+2+2] cycloadducts (see Section 4.5.3.4). The six-membered ring [2+2+2] cycloadduct 35 is also obtained from Ph3 P C C(OEt)2 and

374


phenyl isothiocyanate. In this reaction, addition across the C N bond of the isothiocyanate is observed 3 .

Ph3P

C

(COEt)2 + 2 RN

C

EtO Ph3P

S

OEt NR

S

S

N R 35

The reaction of Ph3 P C C NPh with Ph2 C C NPh also produces the [2+2] cycloadduct resulting from addition across the C C bond of the ketenimine 3 . In the reaction of Ph3 P C C O with carbon disulfide the initially formed fourmembered ring cycloadduct 36 undergoes cycloreversion with elimination of carbonyl sulfide 3 . ⊕

O

Ph3P Ph3P

C

C

O+S

C

S

Ph3P

S

C

C

S+O

C

S

S 36

In the reaction of Ph3 P C C NPh with carbon disulfide and carbonyl sulfide the [2+2] cycloadducts are also formed 3 . The polar linear adduct 37, obtained from Ph3 P C C(OEt)2 and carbon disulfide, upon heating, undergoes rearrangement to form the linear adduct 38. Ph3P Ph3P

C

C(OEt)2 + S

C

⊕

C(OEt)2 Ph3P+–C–(COOET)C(S)SEt

S S

S 37

38

Also, four-membered ring cycloadducts resulting from addition across the C S bond are obtained in the reaction of Ph3 P C C S with aromatic isothiocyanates. Likewise, in the reaction of Ph3 P C C NR with isothiocyanates the cycloadducts 39 are obtained 3 . NR

Ph3P Ph3P

C

C

NR +

R1N

C

S S

R1N 39

R

R1

Ph Ph Ph

Me Ph 4-Me2 NPh

Yield (%) 71 73 68


375

In the reaction of Ph3 P C C O with two equivalents of phenyl isothiocyanates, sixmembered ring [2+2+2] cycloadducts 40 are formed 3 . In this reaction, the cycloaddition proceeds across the C S bond of the isothiocyanate. O

⊕

Ph3P

C

C

C

Ph3P

O + 2 RNCS

S

RN

NR

S 40

4.5.3.3

[3 + 2] Cycloadditions

In the reaction of Ph3 P C C X with tosyl azide, [3 + 2] cycloadducts are obtained. In a similar manner ethyl diazoacetate reacts with Ph3 P C C NPh to give the mesoionic [3 +2] cycloadduct 41 3 . ⊕

Ph3P Ph3P

C

C

NPh + EtOCOCH

N2

NHPh

N

CO2Et

N 41

The phosphorous cumulene acetal 42 reacts with phenyl nitrile oxide to give the expected isoxazole derivative 43. ⊕

Ph3P Ph3P

C

C(OEt)2 + PhC

N

(OEt)2

O

O

Ph

N 43

42

Bis(diisopropylamino)chlorodiazomethylenephosphorane, upon reaction with BF3 , forms a 1,3-dipole, which reacts with methyl acrylate to form the [3 +2] cycloadduct in 70 % yield 44 21 . ⊕

ClR2P

⊕

CIR2P

C

N2 + BF3

CIR2P

C

N2 + CH2

CHCOOMe

N

BF3

N CO2Et

BF3 44

4.5.3.4


The reaction of Ph3 P C C NPh with α,β-unsaturated ketones gives [4 +2] cycloadducts 45 3 . ⊕

Ph3P

C

C

NPh + RCH

CHCOR1

NPh

PH3P

O R1

R 45

376


Ketenylidenetriphenylphosphorane undergoes a [4+2] cycloaddition reaction with phenylbenzoylketene, generated in the photolysis of azo-1,3-diketones, to form the cycloadduct 46 22 . O Ph PhCO(Ph)C

C

O + Ph3P

C

C

PPh3

O Ph

O

O

46

Also, methylenephosphine oxides undergo [4 +2] cycloaddition reactions with phenylbenzoylketene to give the cycloadducts 47 23 . O Ph PhCO(Ph)C

C

O + Ph2C

P(Ph)

O Ph

P O 47

O Ph

References 1. R. Appel, P. Fölling, B. Josten, M. Siray, V. Winkhaus and F. Knoch, Angew. Chem. 96, 620 (1984). 2. C.N. Matthews and G.H. Birum, Acc. Chem. Res. 2, 373 (1969). 3. H.J. Bestmann, Angew. Chem. 89, 361 (1977). 4. G. Märkl and P. Kreitmeier, Angew. Chem. 100, 1411 (1988). 5. G. Märkl, P. Kreitmeier, H. Nöth and K. Polborn, Angew. Chem. 102, 958 (1990). 6. J. Escudie, H. Ranaivonjatovo and L. Rigon, Chem. Rev. 100, 3639 (2000). 7. M. Yoshifuji, K. Toyota, T. Niitsu, Y. Okamoto and R. Aburatani, J. Chem. Soc., Chem. Commun. 1550 (1986). 8. G. Märkl, H. Sejpka, S. Dietl, B. Nuber and M.L. Ziegler, Angew. Chem. 98, 1020 (1986). 9. R. Appel, V. Winkhaus and F. Knoch, Chem. Ber. 119, 2466 (1986). 10. M. Hafner, T. Wegemann and M. Regitz, Synthesis 1247, (1993). 11. G. Märkl, P. Kreitmeier, H. Nöht and K. Polborn, Tetrahedron Lett. 31, 4429 (1990). 12. R. Appel, F. Knoll and H. Whiler, Angew. Chem. 89, 415 (1977). 13. H.J. Bestmann, G. Schmid, D. Sandmeier and L. Kisielowski, Angew. Chem. 89, 275 (1977). 14. S. Ito, S. Sekiguchi and M. Yoshifuji, J. Org. Chem. 69, 4181 (2004). 15. K. Toyota, H. Yoshimura, T. Uesugi and M. Yoshifuji, Tetrahedron Lett. 32, 6879 (1991). 16. R. Appel, Multiple Bonds and Low Coordination in Phosphorus Chemistry, M. Regitz and O.J. Scherer (Eds), Thiene, Stuttgart, Germany, 1990. 17. G.H. Birum and C.N. Matthews, J. Am. Chem. Soc. 90, 3842 (1968). 18. H.J. Bestmann, G. Schmidt and D. Sandmeier, Angew. Chem. 87, 34 (1975). 19. H.J. Bestmann and G. Schmidt, Angew. Chem. 86, 479 (1974). 20. R.W. Saalfrank, W. Paul and H. Liebenow, Angew. Chem. 92, 740 (1980). 21. J. Sotiropoulos, A. Baceiredo, K. Horchler von Locquenghien, F. Dahan and G. Bertrand, Angew. Chem. 103, 1174 (1991). 22. H.J. Bestmann, G. Schmid, D. Sandmeier and C. Geismann, Tetrahedron Lett. 2401 (1980). 23. L. Capuano and T. Tammer, Chem. Ber. 114, 456 (1981).


4.6 4.6.1

377

Other Metal Allenes Introduction

Cumulenes with metal atoms in the cumulative system are of recent vintage. Although the well known carbonyl and isonitrile complexes can be written as metal cumulenes, i.e. Ln M C X, where M = metal and X = O or NR, they are only included in this book if they are involved in reactions with other cumulenes. However, metal cumulenes with one or several metal atoms in the cumulative arrangement are treated in this chapter. Examples of the ‘one-metal’ complexes are listed in Table 4.23.

Table 4.23 One-metal cumulene complexes Name

Structure

Metals

Vinylidene Allenylidene Butatrienylidene Pentatetranylidene

M M M M

Ge, Ti, Co, Rh, Re, Mn Ti, Cr, W, Mn, Fe, Ru, Os, Rh, Ir As, Ru Cr, W., Ru, Rh, Ir

C C C C

CR2 C CR2 C C CR2 C C C CR2

Also, bi- and trimetallic cumulene complexes, such as M C M, M M C, M M M and M C C M 1 are known. Cationic ruthenium allenylidene complexes are used as catalysts for ring closing metathesis reactions 1 . Nonlinear optical properties have been measured for the Group 6 cumulenylidene complexes 2 . Also, cationic chromium or iron vinylidene complexes undergo [2+2] cycloaddition reactions across imines to give βlactams. This reaction is useful for the synthesis of β-lactam antibiotics 3 . Some of the vinylidene complexes include cobalt, rhodium and rhenium in ‘halfsandwich’ complexes, which are synthesized from acetylene complexes 4 . This reaction involves an intermediate alkinyl(hydrido) complex, which can sometimes be isolated 5 . The bonding between the metal and the α-carbon atom in vinylidene rhodium complexes is shorter than in carbene rhodium complexes, which indicates a high electron density on the center atom. The titanium vinylidene species, Cp2 Ti C CH2 , is generated in situ from methylenetitanacyclobutane at 80 ◦ C via a [2+2] cycloreversion reaction, or from Cp2 Ti(Me)CH CH2 by α-elimination of methane, which occurs at room temperature. The generated vinylidene species is trapped with acetylenes, heterocumulenes, transition metal carbonyls, nitriles and phosphaalkynes to give [2+2] cycloadducts 6 . Review articles on metal cumulenes appeared in 1983 7 , in 1991 8 and in 1998 9 , while molecules with multiple bonds between transition metals and ‘naked’ main group elements were reviewed in 1986 10 . Some of these molecules have a linear structure with cumulative double bonds as evidenced by X-ray crystallography. However, some triple–single bond character is also indicated. M

C

CR2

M–C

C–CR2

378




The stable germaallene 1 reacts with (Me2 N)P Te across its Ge C bond to give the 1,2-cycloadduct 2 11 . Te Tbt(Mes)Ge

C

CR2 + (Me2N)3P

Te

Tbt(Mes)Ge

1

C

CR2

2

Similarly, sulfur and selenium add to the G C bond to give the corresponding 1,2cycloadducts. The reaction of rhodium vinylidene metal complexes 3 with sulfur, selenium and tellurium affords complexes of metal substituted thio-, seleno- and telluroketenes 4 12 . L2Rh

C

CH2 + En

L2Rh

C

CH2

E 4

3

The germanium–manganese complex 5 reacts with diazomethane to give the [2+1] cycloadduct 6 13 . M M

M

Ge M

+ CH2

N2

M

Ge M 6

5

The tellurium–manganese complex reacts similarly with diazomethane. In the reaction of the rhodium alkynyl complexes 7 with excess carbon monoxide at room temperature, the cyclobutenone 8 is isolated in 90 % yield 14 . Ph

PhC

CRh(L2)

C

C

C(Ph)t-Bu

+

•

(CO)RhL2

CO

Ph

Ph O 7

8

The metal cumulene complex 9 reacts with diazomethane and carbon monoxide to give 1,1-disubstituted butatrienes 10 15 . L2ClRh

C

C

C(t-Bu)Ph + CH2N2 + CO

9

CH2

C

C

C(t-Bu)Ph + L2CIRhCO

10

Niobium ketene hydrides 11 react with t-butyl isocyanide to give t-butyl isocyanate and L2 Nb(H) C CPh2 . An intermediate 12 in this reaction is most likely formed via a [2+1] cycloaddition reaction 16 . H L2Nb(H)

C

O + t-BuNC

L2Nb

O + t-BuNC CPh2

11

12

t-BuN

C

O + L2Nb(H)

C

CPh2


379

The reaction of the titanaallene 13 with excess cyclohexylisocyanide affords a 1:3 cycloadduct 15 via initial formation of the [2+1] cycloadduct 14 6 . NR [L2Ti

C

RN

L2Ti

CH2] + RNC

L2Ti

+ 2 RNC

NR NR

13

14

15

The intermediate [2+1] cycloadduct can also be trapped with W(CO)6 to give a fivemembered ring metallacycle. Also, reaction of the rhenium vinylidene complexes 16, generated in situ, with Cp(CO)2 Re, affords the [2+1] cycloadduct 17 17 . L L(CO)2Re

C

CH2 + :Re(CO)2L

(CO)2Re

16

4.6.2.2

L Re(CO)2

17


1-Arsabutatrienes 18 undergo dimerization across the As C double bond to form the head-to tail-dimer 19 18 .

[TsiAs

C

C

•

As

CPh2]

CPh2

As • Ph2C

18

19

The titanaallene complex, L2 Ti C CH2 , 20, generated in situ, reacts with symmetrical substituted acetylenes at 80 ◦ C to give the highly colored metalacyclobutenes 21 in good yields 19 . [L2Ti

C

CH2] + RC

L2Ti

CR

R

20

R 21

R H Me SiMe3 SnBu3

Yield (%) 94 93 95 94

380


Asymmetrically substituted alkynes usually afford mixtures of stereoisomers. From the butadyines 22 red to purple colored [2+2] cycloadducts 23 with the acetylide substituent in the α-position are formed 20 . L2Ti [L2TiC

C

CH2] + RC

C-C

CR1

R1

R R

22

23

R

R1

Me CMe3 CMe3 Ph SiMe3

Me CMe3 SiMe3 Ph SiMe3

a

Yield (%) 68 83 76a 86 79

Ratio of isomers, 90:10.

A stepwise generation of (CO)5 W C CHR at low temperatures, and addition of MeC CNEt2 affords the [2+2] cycloadducts 24 in moderate yields. The initially formed cycloadducts 24 undergo tautomerization to form 25 21 . W(CO)6 + CH2Cl2

(CO)5W

C

(CO)5W[CH2Cl2] + RC

CHR + MeC

CNEt2

CH

(CO)5W Me

(CO)5W

C

CHR

(CO)5W

R NEt2

Me

24

R NEt2

25

R

Yield (%)

Bu C6 H11 Ph COOMe

34 37 32 37

When 1-ethenylcyclohexene is used as the initial acetylene compound, the [2+2] cycloadduct 26 is obtained in 28 % yield.

(CO)5W (CO)5W

C

CH–

+ MeC

CNEt2

NEt2

Me 26

The reaction of the chromium vinylidene complex 27 with 1-methyl-2thiomethylacetylene at −25 ◦ C gives rise to the formation of the four-membered ring


381

cycloadduct 28 (10 % yield), resulting from cycloaddition across the C C bond of the metal cumulene 22 . (CO)5Cr (CO)5Cr

C

CPh5 + MeC

CSMe

Ph2

Me

27

SMe 28

Likewise, [2+2] cycloadducts are obtained from pentacarbonylpentamethylene vinylidene chromium and 1-methylhio-1-propyne and N-(1-propynyl)phenothiazine. The adducts undergo subsequent thermally initiated ring expansion reactions. In the reaction of the chromium vinylidene complexes 29 with ynamines or ethoxypropyne, also [2+2] cycloadducts 30 are formed in moderate yields 23 . (CO)5Cr (CO)5Cr

C

1

CRR + MeC

CNEt2

RR1 NEt2

Me

29

30

R

R1

Yield (%)

H Me –(CH2 )5 – Ph

Me Me

12 47 50 34

Ph

In the addition of (S)-2-methoxymethyl(N-1-propynyl)pyrrolidine or (R)–methyl-1propinyl-1-phenylethylamine to the same chromium complexes mixtures of E-and Zisomers are formed. In the latter reaction the Z-isomers are predominantly formed, while in the reaction of the ynamine with the heterocyclic amino substituent predominantly the E-isomers are produced. Also, the chromium and tungsten vinylidene complexes 31 react with the alkynyl complexes 32 to give heterobimetallic cyclobutenylidene complexes 33, which are yellow or red crystalline compounds 24 . (CO)5Cr (CO)5Cr

C 31

CMe2 + RC

CFe(CO)2Cp

Fe(CO)2Cp

R

32

33

R n-Bu Ph 4-O2 NPh COOMe

Yield (%) 40 35 40 30

Pentacarbonyl(dimethylvinylidene) chromium, generated in situ, also reacts with the butadiynyl complexes 34 at −60 ◦ C by regiospecific cycloaddition of the C C bond of the

382


butadiynyl complexes to the C C bond in the chromium vinylidene complex to form the cycloadducts 35 25 . (CO)5Cr (CO)5Cr

C

CMe2 + L(CO)CpFeC

C–C

CR

Fe(CO)CpL R

34

35

R

L

Yield (%)

n-Bu Ph SiMe3 SiMe3

CO CO CO PPh3

45 60 65 65

Also, reaction of (CO)5 Cr C CMe2 with n-BuC CNi(PEt3 )Cp affords the [2+2] cycloadduct in 27 % yield. Allenylidene complexes also undergo [2+2] cycloaddition reactions with alkynes, but in addition to the cycloadducts linear insertion products are also obtained. For example, diarylallenylidene complexes of chromium and tungsten react with MeC CNEth2 or PhC CNEt2 to give both linear adducts 36 and cycloadducts 37. The linear adducts are formed via an initial cycloaddition of the ynamine to the C2 C3 bond in the allenylidene complex, followed by cycloreversion. The cyclobutenylidene complexes are formed by [2+2] cycloaddition of the ynamine to the C1 C2 double bond 26 . (CO)5M

C

C

CR2 + R1C

CNEt2 R (CO)5M

(CO)5M

C

C

C(NEt2)–C(Me)

CR2 +

R NEt2

Me

36

37

M

R

R1

Yield of linear adducts (%)

Yield of cycloadducts (%)

Cr Cr Cr

H 4-MePh 4-Me2 NPh

Me Me Me

39 35 87a

24 11

W W

4-MeOPh 4-Me2 NPh

Me Me

51 53

a b

Reaction in CH2 Cl2 . Reaction in pentane.

76b 7 42


383

In the reaction of chromium and tungsten allenylidene complexes with the alkyynyl complexes Cp(CO)2 FeC CR1 , only the [2+2] cycloadducts 38 are obtained 27 . (CO)5M (CO)5M

C

C

CR2 +

R1C

CFe(CO)2Cp

CR2

R1

Fe(CO)2Cp 38

M

R1

R

Yield (%)

Cr 4-MePh n-Bu Cr 4-MeOPh n-Bu W 4-MePh n-Bu

33 32 39

Similar cycloadducts are also obtained in the reaction of the allenylidene complexes with n-BuC CFeL3 or n-BuC CNi(PPh3 )Cp. These heterobimetallic cycloadducts are formed in lower yields (13–27 %). In the reaction of diarylosmium allenylidene complexes with dimethyl acetylenedicarboxylate the ‘ring-opened’ products 39 are formed 28 . Cp(Pr3P)CIOs

C

C

CPh2 + MeO2C-C

Cp(Pr3P)CIOs

C

C(COOMe)–C(COOMe)

C-CO2Me C

CPh2

39

The reaction of the osmium complex 40 (R = Ph, C6 H11 ) with acetonitrile affords the osmacyclopentapyrroles 41 in 83 % and 79 % yields, respectively 29 . R H R i-Pr3P MeCN BF4 + MeCN Os • MeCN • i-Pr3P CPh2 40

Ph Ph

i-Pr3 MeCN MeCN

Os i-Pr3

⊕

Me BF4

N H 41

The reactions of the pentatetraenylidene complexes of chromium and tungsten with ynamines at room temperature afford heptapentaenylidene complexes by formal insertion of the electron-rich alkyne into the terminal C C bonds of the pentatetraenylidene complexes. Most likely, the initial reactions produce the [2+2] cycloadducts 42 of the

384


ynamine to the terminal C C bond which undergo ring opening to give the isolated products 43 2 . NEt2 (CO)5M

C

C

C

C

C (NMe2)2 + MeC

CNEt2

[(CO)5M

C

C

C

C

CMe]

NMe2 NMe2 (CO)5M

C

C

C

C

C(NEt2)–C(Me)

42

C(NMe2)2

43

M

Yield (%)

Cr W

65 61

Titanium vinylidene complexes also react with olefins to give four-membered ring metallacycles 30 . The reaction of the 1-germaallene 44 with benzaldehyde affords the [2+2] cycloadduct 45 via addition across the Ge C bond 31 . t-Bu(Ph)C Tip2Ge

C

C(Ph)–t-Bu + PhCHO

GeTiP2

Ph

44

O 45

Also, in the germaphosphaallenes 46 the [2+2] cycloaddition with benzaldehyde proceeds across the Ge C bonds to give 47 32 . ArP Tip(t-Bu)Ge

C

PAr

+

PhCHO

Ge(Tip)–t-Bu

Ph

46

O 47

Similar [2+2] cycloadducts are also obtained from 46 and benzophenone and fluorenone. The reaction of titana allenes with carbon dioxide, ketenes and isocyanates proceeds across the C O bonds of the heterocumulenes to give the [2+2] cycloadducts 48 33 . [L2Ti

C

CH2] + O

C

X

L2Ti O X 48

X O C(t-Bu)2 NC6 H11

Yield (%) 86 65 75


385

Reaction of the titana allenes with diphenylketene in n-hexane at −30 ◦ C also produces the [2+2] cycloadducts as black crystals in 48 % yields 34 . Similarly, transition metal carbonyls also react with the titana allene complex to give the four-membered ring cycloadducts 49 35 .

[L2Ti

C

CH2] + LnM

C

L2Ti

O

O MLn 49

MLn

Yield (%)

Mo(CO)5 W(CO)5 LRe(CO)2 Mn2 (CO)9 Re2 (CO)9 Fe(CO)4

32 38 45 56 38 37

A variety of enolyzable ketones react with the titanocene vinylidene intermediate to give vinyltitanium enolates, which are formed via an initial [2+2] cycloaddition 36 . The titanium vinylidene complexes 50 react with ketones via a cycloaddition reaction to give the allenes 51 and [L2 Ti O] 37 . L2Ti

C

CRR1 + R2R3C

RR1C

O

50

C

CR2R3 + [L2Ti

O]n

51

Vinylidene complexes of manganese and rhenium, generated in situ, undergo [2+2] cycloaddition reactions with imines to form 52 17 . L(CO)2Mn L(CO)2Mn

C

CHR + PhN

CHPh

CHR Ph

PhN 52

R H Me Ph

Yield (%) 85 62 58

Reaction of the cycloadducts with potassium permanganate leads to formation of βlactams in excellent yields.

386


Similarly, L(CO)2 Re C CH2 reacts with imines to give the [2+2] cycloadducts 53 17 . L(CO)2Re L(CO)2ReC

C

CH2 + RN

CHPh

Ph

PhN 53

R

Yield (%)

Me Ph

45 39

The reaction of the manganese vinylidene complex 54 with HN CPh2 affords the linear adducts 55 17 . L(CO)2Mn

C

CHCH2Ph

+

HN

CPh2

L(CO)2Mn

54

C(CH2Ph)N

CPh2

55

The vinylidene complexes (CO)5 W C CPh2 react with imines and triphenylketenimines to give [2+2] cycloadducts 38 . Allenylidene complexes of chromium 56 also undergo [2+2] cycloaddition reactions with azomethines at the center C C bond to give the cycloadducts 57 39 . (CO)5Cr (CO)5Cr

C

C

CR2 + i-PrN

CHPh

CR2 Ph

i-PrN

56

57

Also, unsubstituted ruthenium butatrienyl complexes react with azomethines to give [2+2] cycloadducts 40 . Rhenium or manganese vinylidene complexes 58 react with benzalazines to give the ‘criss-cross’ [3+2] cycloadducts 59 in good yields17 .

2 L(CO)5M

C

CH2 + PhCH

N-N

CHPh

Ph H

L(CO)2M N N

Ph H

M(CO)2L

58

59

The chromium vinylidene complex, (CO)5 Cr C CH2, reacts with dicyclohexylcarbodiimide to give the [2+2] cycloadduct 60 41 . (CO)5Cr [(CO)5Cr

C

CH2 + RN

C

NR

NR RN 60


387

From titanaallenes and carbodiimides, [2+2] cycloadducts are also obtained. The azatitanacyclubutanes are thermally stable up to 150 ◦ C 42 . Some rhenium and manganese vinylidene complexes react with carbodiimides to give isocyanate complexes rather than the expected [2+2] cycloadducts 17 . A three-component reaction of 61 with cyclohexyl isocyanide and isocyanates affords the imidazolidinone complexes 62 in yields of 63–69 % 43 . Ph (CO)5W

R1NCO

C(OEt)Ph + RNC +

(CO)5W

OEt NR1 N R

61

O 62

A similar reaction occurs when carbodiimides are used instead of the isocyanates. Some metal carbonyl or metal isonitrile complexes react with isocyanates via [2+2] cycloaddition sequences to cause exchange reactions. In the first step, the carbonyl complex reacts with the isocyanate to give an isonitrile complex 63 and carbon dioxide. The generated isonitrile complex reacts subsequently with a second molecule of the isocyanate to give a carbodiimide 64 with generation of the original complex 44 . Me

C

O + RN

C

O

Me

C

NR + O

C

O

63 Me

C

NR + RN

C

O

RN

C

NR + M

C

O

64

This reaction was utilized in the catalytic conversion of isocyanates into carbodiimides. The order of catalytic activity is Fe(CO)4 CNPh > Fe(CO)5 > Fe2 (CO)9 > W(CO)6 > Mo(CO)6 . The [2+2] cycloaddition of the titana allene complex 65 with isothiocyanates proceeds exclusively across the C S bond to give the four-membered ring cycloadducts 66 45 . [L2Ti

C

CH2] + RN

C

L2Ti

S

S NR

65

66

R

Yield (%)

t-Bu C6 H11 Ph

73 54 86

Heating of the cycloadduct (R = C6 H11 ) in pyridine causes formation of an isomeric cyloadduct resulting from addition across the C N bond. A small amount of this isomer is also formed in the reaction with of the titana allene with t-butyl isocyanate. The liganded titana allene, L2 Ti C CH2, also reacts with nitriles via a [2+2] cycloaddition reaction across the C N bond to give the four-membered ring cycloadducts 67 46 . [L2Ti

C

CH2] + RCN

L2Ti R

N 67

388


R

Yield (%)

t-Bu trans-CH CHPh

53 38

An excess of nitrile and higher temperatures favor the insertion of a second nitrile molecule into the cycloadducts to give six-membered ring metallacycles. The rhodium complex 68 reacts with 2-t-butyl-1-phosphaacetylene via a [2+2] cycloaddition reaction across the Rh C bond to give the cycloadduct 69 in 79 % yield 47 . i-Pr3P

i-Pr3P CIRh

C

CH2 + P

C–t-Bu

Cl

i-Pr3P

P

Rh

i-Pr3P 68

69

Reaction of the titanaallene with 2-t-butyl-1-phosphaacetylene affords mixtures of the two isomeric cycloadducts 70 and 71. The cycloadduct with P across from Ti is isolated in 35 % yield. The other isomer is only detected in solution 6 .

[L2Ti

C

CH2] + P

L2Ti

C–t-Bu

+

L2Ti

P

P 71

70

4.6.2.3


The reaction of the 1-germaallene 72 with mesitylnitrile oxide gives rise to the formation of the [3+2] cycloadduct 73 11 .

Tbf(Mes)Ge

72

C

CR2 + R1C

Tbf N

O

Mes

Ge O

CR2 N

R1

73

The rhenium complex, LnRe C C CPh2 ]+ , reacts as a 1,3-dipole with N-heterocycles, such as 1H-benzotriazole, 2-aminopyridine and 2-aminothiazole, to give the [3+2] cycloadducts 48 .


389

References 1. A. Fürstner, M. Piquet, C. Bruneau and P.H. Dixneuf, J. Chem. Soc., Chem. Commun. 1315 (1998). 2. G. Roth, H. Fischer, T. Meyer-Friedrichsen, J. Heck, S. Houbrechts and S. Persoons, Organometallics 17, 1511 (1998). 3. A.G.M. Barrett and M.A. Sturgess, J. Org. Chem. 52, 3940 (1987). 4. H. Werner, Angew. Chem. 95, 932 (1983). 5. J. Wolf, H. Werner, D. Serhadli and M.L. Ziegler, Angew. Chem. 95, 428 (1983). 6. R. Beckhaus, Angew. Chem. Int. Ed. 36, 686 (1997). 7. M.J. Bruce and A.G. Swincer, Adv. Organomet. Chem. 22, 59 (1983). 8. M.J. Bruce, Chem. Rev. 91, 197 (1991). 9. M.J. Bruce, Chem. Rev. 98, 2797 (1998). 10. W.A. Herrmann, Angew. Chem. 98, 57 (1986). 11. N. Tokitoh, K. Kishikawa and R. Okazaki, Chem. Lett. 1811 (1998). 12. H. Werner, J. Wolf, R. Zolk and U. Schubert, Angew. Chem. 95, 1022 (1983). 13. W.A. Herrmann, J. Weichmann, U. Kusthardt, A. Schäfer, R. Hörlein, C. Hecht, E. Voss and R. Serrano, Angew. Chem. 95, 1019 (1983). 14. J. Gil-Rubido, B. Weberndörfer and H. Werner, Angew. Chem. Int. Ed. 39, 786 (2000). 15. H. Werner, M. Laubender, R. Wiedemann and B. Windmüller, Angew. Chem. Int. Ed. 35, 1237 (1996). 16. M.C. Fermin and J.W. Bruno, J. Am. Chem. Soc. 115, 7511 (1993). 17. M.R. Terry, L.A. Mercando, C. Kelley, G.L. Geoffroy, P. Nombel, N. Lugan, R. Mathieu, R.L. Ostrander, B.E. Owens-Waltermire and A.L. Rheingold, Organometallics 13, 843 (1994). 18. C. Märkl and S. Reithinger, Tetrahedron Lett. 31, 6331 (1990). 19. R. Beckhaus, J. Sang, T. Wagner and B. Gantner, Organometallics 15, 1176 (1996). 20. R. Beckhaus, J. Sang, U. Englert and U. Böhme, Organometallics 15, 4791 (1996). 21. H. Fischer, H. Volkland, A. Früh and R. Stumpf, J. Organomet. Chem. 491, 267 (1995). 22. H. Fischer, C.C. Karl and G. Roth, Chem. Ber. 129, 615 (1996). 23. H. Fischer, O. Podschadly, G. Roth, S. Herminghaus, S. Klewitz, J. Heck, S. Houbrechts and T. Myer, J. Organomet. Chem. 541, 321 (1997). 24. H. Fischer, F. Leroux, G. Roth and R. Stumpf, Organometallics 15, 3723 (1996). 25. F. Leroux, R. Stumpf and H. Fischer, Eur. J. Inorg. Chem. 1225 (1998). 26. G. Roth, D. Reindl, M. Gockel, C. Troll and H. Fischer, Organometallics 17, 1393 (1998). 27. H. Fischer, F. Leroux, R. Stumpf and G. Roth, Chem. Ber. 129, 1475 (1996). 28. M.A. Jimenez Tenorio, M. Jimenez Tenorio, M.C. Puerta and P. Valerga, Organometallics 16, 5528 (1997). 29. T. Bolano, R. Castalenas, M.A. Esteruelas and E. Ohata, J. Am. Chem. Soc. 128, 3965 (2006). 30. G.A. Luinstra and J.H. Teuben, Organometallics 11, 1793 (1992). 31. B.E. Eichler, D.R. Powell and R. West, Organometallics 18, 540 (1999). 32. Y. El Harouch, H. Gornitzka, H. Ranaivonjatovo and J. Escudie, J. Organomet. Chem. 643–644, 202 (2002). 33. R. Beckhaus, I. Strauss, T. Wagner and P. Kiprof, Angew. Chem. 105, 281 (1993). 34. R. Beckhaus, I. Strauss and T. Wagner, Zeitschr, Anorg. Allg. Chem. 623, 654 (1997). 35. R. Beckhaus, J. Oster and T. Wagner, Chem. Ber. 127, 1003 (1994). 36. R. Beckhaus, I. Strauss and T. Wagner, J. Organomet. Chem. 464, 155 (1994). 37. S.L. Buchwald and R.H. Grubbs, J. Am. Chem. Soc. 105, 5490 (1983). 38. H. Fischer, A. Schlageter, W. Bidell and A. Früh, Organometallics 10, 389 (1991). 39. H. Fischer, G. Roth, D. Reindl and C. Troll, J. Organomet. Chem. 454, 133 (1993). 40. M.I. Bruce, P. Hinterding, M. Ke, P.J. Low, B.W. Shelton and B.W. White, J. Chem. Soc., Chem. Commun. 715 (1997). 41. K. Weiss, E.O. Fischer and J. Müller, Chem. Ber. 107, 3548 (1974). 42. R. Beckhaus, J. Oster, J. Sang, I. Strauss and M. Wagner, Synlett 241 (1997). 43. R. Auman, E. Kuckert and H. Heinen, Angew. Chem. 97, 960 (1985).

390 44. 45. 46. 47. 48.

Cumulenes in Click Reactions H. Ulrich, B. Tucker and A.A.R. Sayigh, Tetrahedron Lett. 1731 (1967). R. Beckhaus, J. Sang, T. Wagner and U. Böhme, J. Chem. Soc., Dalton Trans. 2249 (1997). R. Beckhaus, I. Strauss and T. Wagner, Angew. Chem. Int. Ed. 34, 688 (1995). P. Binger, J. Haas, A.T. Herrmann, F. Langhauser and C. Krüger, Angew. Chem. 103, 316 (1991). N. Mantovani, P. Bergamini, A. Marchi, L. Marvelli, R. Rossi, V. Berttolasi, V. Ferreti, I. de los Rios and M. Perruzini, Organometallics 25, 416 (2006).

5 1,3-Dicarbon Cumulenes 5.1

Thiocarbonyl S-ylides, R2 C S CH2

Thiocarbonyl S-ylides, R2 C S CH2 , were generated in situ from 1,3,4-thiadiazoline precursors by Huisgen and his coworkers in the 1980s. For example, reaction of the 1,3,4thiadiazoline precursor 1 at 65 ◦ C in the presence of dipolarophiles, listed in Table 5.1, affords the [3+2] cycloadducts 2 in a non-stereospecific cycloaddition reaction, often in high yields 1 . iPr2

S

[iPr2

S

CH2]

N N 1

+

a–b

S

iPr2 a

b 2

Table 5.1 [3+2] Cycloadducts derived from diisopropylthiocarbonyl S-methylide Dipolarophiles, a–b Tetracyanoethylene Dimethyl fumarate Fumaronitrile Dimethyl 2,3-dicyanofumarate 2,3-Bis(trifluoromethyl)fumaronitrile Benzylidene malononitrile Methyl α-cyanocinnamate

Yield (%) 82 90 70 89 98 90 96

In a similar manner, 2,2,4,4-tetramethylcyclobutane-1-one-3-thione S-methylide 4 is obtained from the corresponding thiadiazoline precursor 3 at 40 ◦ C and trapped with the dipolarophiles a–b to give the [3+2] cycloadducts 5 listed in Table 5.2 2 . Cumulenes in Click Reactions Henri Ulrich C 2009 John Wiley & Sons, Ltd

392

Cumulenes in Click Reactions S

O

O

CH2

S

+ a–b

S

O a

N N 3

4

b

5

Table 5.2 [3+2] Cycloadducts derived from 2,2,4,4tetramethylcyclobutane-1-one-3-thione S-methylide Dipolarophiles, a–b

Yield (%)

Dimethyl acetylenedicarboxylate Fumaronitrile Tetracyanoethylene Thioxanthione Adamantanethione Chloral

87 93 73 95 88 95

In the reaction of 4 with dimethyl 2,3-dicyanoethylene, two isomeric [3+2] cycloadducts are obtained in 94 % yield, with a cis/trans ratio of 48:52 % indicating that the reaction is nonstereospecific 3 . Also, in the reaction of 4 with tetracyanoethylene, in addition to the [3+2] cycloadduct 7, the cyclic ketenimine 8, a [4+3] cycloadduct, is obtained as the major product indicating the presence of the switter ionic intermediate 6 4 . S

O

N N

+ (CH) C 2

⊕

O

C(CN)2

S (CN)2 NC

CN 6

3 S

O

(CN)2

+

S O N

NC CN 7

(CN)2 CN

8

Also, in the reaction of 4 with 2,3-bis(trifluoromethyl) fumaronitrile a mixture of the corresponding [3+2] cycloadduct and the cyclic ketenimine is obtained 5 . In the reaction of 4 with electron deficient acetylenes, 2,5-dihydrothiophene derivatives 9 are obtained. O

S

CH2

+

RC CR

S

O R

4

R

9

R COOMe PhCO

Yield (%) 65 63


393

In contrast, propiolates afford mixtures of stereoisomers 6 . In the reaction of 2,2,4,4-tetramethylcyclobutan-1-one-3-thiocarbonyl S-dimethylmethylide with suitable dipolarophiles, [3+2] cycloadducts are similarly obtained in high yields 7 . For example, reaction with tetracyanoethylene affords the [3+2] cycloadduct in 58 % yield 8 . Likewise, the thiocarbonyl S-methylide derived from spiro[fenchane-2,2 (1,3,4-thiadiazoline)] is trapped with dipolarophiles to give the corresponding [3+2] cycloadducts 9 . The adamantane S-methylide 10 reacts with C S dipolarophiles to give the [3+2] cycloadducts. For example, from 10 and thiobenzophenone, the isomeric [3+2] cycloadducts 11 and 12 are obtained in 50 % and 42 % yields, respectively 10 . Ph Ph S

CH2

S

S

+ Ph2C S

S

10

+

Ph Ph

S

11

12

The [3+2] cycloadducts from 10 and other C S dipolarophiles are listed in Table 5.3. Table 5.3 [3+2] Cycloadducts derived from adamantane S-methylide and C S dipolarophiles Dipolarophile

Yield of 11 (%) Yield of 12 (%)

Thioxanthione Thiofluorenone 2,2,4,4-Tetramethylcyclobutane-1-one-3-thione Methyl dithiobenzoate Carbon disulfide Phenyl isothiocyanate

41 60 — 51 — 90

34 18 80 45 89 —

In the reaction of thiocarbonyl S-ylides with aliphatic- or alicyclic thiones, the 2,2,4,4tetrasubstituted 1,3-dithiolanes (similar to 12) are formed exclusively, while the presence of aryl groups in either one of the reagents prompts the formation of the 4,4,5,5-tetrasubstituted 1,3-dithiolanes (similar to 11) 11 . The 1,3-dipolar cycloadditions of aliphatic or alicyclic thiocarbonyl ylides, sterically hindered on one of the termini with thiobenzophenone, also produce both the regioisomeric 1,3-dithiolanes. According to quantum chemical calculations, a concerted cycloaddition furnishes the 2,2,4,4-tetrasubstituted 1,3-dithiolanes, while a biradical intermediate is involved in the formation of the 4,4,5,5-tetrasubstituted 1,3-dithiolanes 12 . Tropothione S-methylide 13 also undergoes a [3+2] cycloaddition reaction with tropothione to give a 40 % yield of the [3+2] cycloadduct 14 13 . S S

CH2

13

+

S

S

14

394


A regioselective [3+2] cycloaddition of thiocarbonyl S-methylides with 1,3-thiazol5(4H)thiones as the dipolarophiles has also been observed 14 . The relative rate constants for cycloaddition of thiocarbonyl S-methylides with dipolarophiles show that C S dipolarophiles are very efficient. For example, thiofluorenone exceeds tetracyanoethylene and thiobenzophenone reacts 3000 times faster than dimethyl acetylene-dicarboxylate 15 .

5.2 2-Azaallenium Salts, R2 C N+ CR2 The linear 2-azaallenium salts, C N+ C, have electronic structures similar to cumulenes and their infrared spectra show the typical cumulene bands at 1870–1910 cm−1 16 . One example of the cycloaddition of a 2-azaallenium salt 15 with diphenylacetylene is known, and the cycloadduct, 11H-indeno[1,2-c]isoquinoline salt 16, is obtained in 37 % yield 17 .

H N ArC(Cl)

N+

C(Cl)Ar SbCl6 +

PhC

CPh

SbCl6 Ph

15

Cl 16

The cycloaddition reaction proceeds stepwise, involving cationic intermediates. The vinyl substituted 1,3-dichloro-2-azaallenium salt 17 undergoes cyclization on heating to give the thiazinium salt 18 in 90 % yield 18 . N

Cl Cl2C

C(Cl)–C(Cl)

N+

C(Cl)SMe SbCl6

SbCl6

Me S

Cl

Cl 17

Cl

Cl

18

When the 2-azaallenium salts 20 are generated from the N-alkylnitrilium salts 19 and dithiomethylacetylene they undergo cyclization to give the 2H-pyrrolium salts 21 19 . R1C N+

CMe 2 SbCl6 + MeSC

CSMe

19 MeSC(H)

R1 C(SMe)–C(R1) 20

N+

CMe2 SbCl6

NH

MeS SMe 21


395

When the 2-azaallenium radical cations 22 are generated in the photochemical reaction of azirines, in the presence of 1,4-naphthalenedicarbonitrile and acrylonitrile, a [2+3] cycloaddition is observed to give 23 20 . Ph

CN

N PhC Ph

N–CHPh + CH2

CHCN

Ph

Ph

N

22

23

In the presence of imines, the 1,3-dipole is also intercepted to form the N-substituted imidazoles 24. R1

R3

N PhC

N–CPh + R3CH

NR 4

R1

NR4 R2

N

R2 24

R1

R2

R3

R4

Ph Ph n-Bu

Ph H H

Ph n-Pr n-Pr

n-Pr n-Pr n-Pr

Yield (%) 87 35 40

The initially generated cycloadduct undergoes rearrangement to give 24. The relatively low yields obtained in three of the above reactions are caused by the fact that the starting azirine competes with the substrate as the dipolarophile. In the absence of acrylonitrile the generated 2-azaallenium radical cations undergo a [3+2] dimerization reaction to give 25 in 85 % yield. N

Ph N

Ph

N 25

5.3 1-Oxa-3-azabutatriene Salts, R2 C N+ C O Antimony pentachloride reacts with α-chloro isocyanates to form 1-oxa-3-azabutatriene salts, R2 C N+ C O SbCl6 , 26, which undergo [2+2+2] cycloaddition reactions with disubstituted cyanamides to give 1,3,5-oxadiazinium salts 27 21 . N CR2 R2C(Cl)NCO + SbCl5

O

−

R2C N+ C O SbCl6 + R2NCN

SbCl6 R2N

26

N N 27

NR2

396


In a similar manner, [2+2+2] cycloadducts are obtained from 26 and carbodiimides. The infrared absorption of the cumulative system C N C O is at 2220 cm−1 . In the reaction of 1-oxa-3-azabutatriene salts with ketones and aldehydes, 2-azaallenium salts and carbon dioxide are obtained 22 . 1-Oxa-3-azabutatriene salts also undergo [3+2] cycloaddition reactions as dipolarophiles at low temperatures (−50 to −78 ◦ C) with 1,3-dipoles. In these reactions the C O bond acts as the dipolarophile. For example, from mesitonitril oxide 29 and 1-oxa-3-azabutatriene salts 28 the heterocyclic salts 30 are obtained 23 . R1R2C

N+

C O SbCl6 + 2,4,6-MePhC

N

O

O 1 2

N

SbCl6

O

R R C 29

28

N

30

R1

R2

Yield (%)

NMe2 NMe2 N(Me)Ph

H Ph Ph

76 40 67

Also, ketocarbenes react with 28 at −78 ◦ C to give the [3+2] cycloadducts 31. R1R2C

N+

C

O SbCl6 + PhC(

O)C(

O

Ph

O

Ph

RR1C

N2)Ph

28

31

R1

R2

Yield (%)

NMe2 Ph

H Ph

51 86

5.4 1-Thia-3-azabutatriene Salts, R2 C N+ C S 1-Thia-3-azabutatriene salts 32 undergo [2+2] cycloaddition reactions with azomethines, carbodiimides and ketenimines across their C S bonds 24 . For example, from 32 and azomethines the [2+2] cycloadducts 33 are obtained in high yields.

Me2NC(R1)

N+

C

S SbCl6

+

R2N

CHPh

Me2N(R1)

R2 N N S

32

33

H SbCl6 Ph

1,3-Dicarbon Cumulenes R1

R2

Ph Ph Ph Ph

t-Bu PhCH2 Ph 4-MePh

397

Yield (%) 82 83 88 83

In the reaction of 32 with carbodiimides the [2+2] cycloadducts 34 are obtained.

Me2NC(R1)

N+

C

S SbCl6

+

R2N

C

NR2

R2 N

Me2NC(R1)

N

NR2

S 34

32

R1

R2

H H Ph Ph

4-MePh 2-Naphthyl i-Pr 4-Me2 NPh

Yield (%) 75 69 81 85

In the reaction of 32 with the ketenimine Ph2 C C NBu, the expected [2+2] cycloadduct 35 is obtained in 84 % yield. N+

Me2NC(Ph)

C

S SbCl6

32

5.5

+

Ph2C

C

NBu

Me2NC(Ph)

N

Bu N S

CPh2 SbCl6

35

Phosphorus Ylides

The bis(methylene)phosphorans (Me3 Si)2 C P(R) C(SiMe3 )2 (R = Me2 N, C6 H11 , Ph) were synthesized by Appel and coworkers in 1982 25 . The compounds can be purified by vacuum distillation, but little about their reactions is known. A metallobis(methylene)phosphorane, CH2 P(LFe(CO)2 CH2 , has also been synthesized 26 .

References 1. 2. 3. 4. 5. 6.

R. Huisgen and G. Mloston, Tetrahedron Lett. 30, 7041 (1989). R. Huisgen, G. Mloston and C. Fulca, Heterocycles 23, 2207 (1985). R. Huisgen, G. Mloston and E. Langhals, J. Am. Chem. Soc. 108, 6401 (1986). R. Huisgen, G. Mloston and E. Langhals, J. Org. Chem. 51, 4085 (1986). R. Huisgen, E. Langhals, G. Mloston and T. Oshima, Heterocycles 29, 2069 (1989). T. Gendek, G. Mloston, A. Linden and H. Heimgartner, Helv. Chim. Acta 85, 451 (2002).

398


7. R. Huisgen, C. Fulka, I. Kalvinsch, X. Li, G. Mloston, J.R, Moran and A. Pröbst, Bull. Soc. Chim. Belg. 93, 511 (1984). 8. R. Huisgen and G. Mloston, Heterocycles 30, 737 (1990). 9. R. Huisgen, G. Mloston and A. Pröbst, Heteroatom Chem. 12, 136 (2001). 10. G. Mloston and R. Huisgen, Heterocycles 23, 2201 (1985). 11. R. Huisgen, G. Mloston, K. Pollborn and R. Sustmann, Chem. Eur. J. 9, 2256 (2003). 12. R. Huisgen, G. Mloston, H. Giera, E. Langhals, K. Polborn and R. Sustmann, Eur. J. Org. Chem. 8, 1519 (2005). 13. R. Huisgen and J.R. Moran, Tetrahedron Lett. 26, 1057 (1985). 14. G. Mloston, A. Linden and H. Heimgartner, Helv. Chim. Acta 74, 1386 (1991). 15. L. Fisera, R. Huisgen, I. Kalwinsch, E. Langhals, X. Li, G. Mloston, K. Polborn, J. Rapp, W. Sicking and R. Sustmann, Pure Appl. Chem. 68, 789 (1996). 16. E. Würthwein, Angew. Chem. 93, 110 (1987). 17. M.G. Hitzler, C.C. Freyhardt and J.C. Jochims, Synthesis 509 (1994). 18. A. Hamed, M. Sedeak, A.H. Ismail, R. Stumpf, H. Fischer and J.C. Jochims, J. Prakt. Chem. 337, 274 (1995). 19. R. Abu-El-Halawa and J.C. Jochims, Synthesis 871 (1992). 20. F. Müller and J. Mattay, Angew. Chem. 103, 1352 (1991). 21. M. Al-Talib, J.C. Jochims, L. Zsolnai and G. Hüttner, Chem. Ber. 118, 1887 (1985). 22. E. Müller and J.C. Jochims, Synthesis 465 (1986). 23. A. Hamed, E. Müller, J.C. Jochims, L. Zsolnai and G. Hüttner, Tetrahedron 45, 5825 (1989). 24. J.C. Jochims, H. Lubberger and L. Dahlenburg, Chem. Ber. 123, 499 (1990). 25. R. Appel, J. Peters and A. Westerhaus, Angew. Chem. 94, 76 (1982). 26. H.J. Metternich and E. Niecke, Angew. Chem. 103, 336 (1991).

6 1,2,3-Tricarbon Cumulenes 6.1 6.1.1

Allenes, R2 C C CR2 Introduction

Allenes represent the lowest member of the class of carbon cumulenes with two adjacent double bonds. Their dimerization and [2+2] cycloaddition reaction with olefins and ketenes provide useful methods of synthesis of cyclobutanes, because often only one reaction product is obtained in high yield. The [2+2] cycloaddition reaction of allenes with olefins proceeds thermally, photochemically and by using Lewis acids as catalysts. Cyclic allenes, generated in situ, are often trapped with olefins to form stable cycloadducts. The [2+2] cycloaddition reactions of allenes with C O double bond-containing substrates proceed similarly. For example, from ketones and allenes oxetanes are isolated, but often a second ketone molecule adds across the generated double bond to give dioxaspiro compounds. Cycloaddition reactions across C S and C N bonds proceed similarly to give the corresponding four-membered ring heterocycles. Other bonds involved in [2+2] cycloaddition reactions with allenes include carbon/metal double bonds and N N and S O bonds. Allenes also undergo [3+2] cycloaddition reactions with diazo compounds and nitrones and [4+2] cycloaddition reactions with diolefins. In the latter reaction, allenes act as dienophiles. In the case of allenes with attached double bonds, such as divinylallene, one of the allene double bonds participates in the Diels–Alder reaction. In the reaction of divinylallene 1 with maleic anhydride at 65 ◦ C in benzene a monoadduct 2 is formed. O

O +

O

O O O

1 Cumulenes in Click Reactions Henri Ulrich C 2009 John Wiley & Sons, Ltd

2

400


In contrast, divinylallene reacts with N-phenyltriazolidenedione at room temperature to form a bis-adduct 3 involving both of the allene and the vinyl groups 1 . O N

O +

O O

N

O

N O

N

N N

O O O

3

•

Fulvenallenes 4 react with dienophiles, such as tetrafluoroethylene 2 or N-Nphenylmaleic acid imide 3 , across their cyclopentadiene double bonds to give [4+2] cycloadducts 5.

C CH 2 + (NC)2C

(CN)2

C(CN)2

(CN)2

4

5

Also, numerous intramolecular cycloaddition reactions of allenes are known. The most important of the intramolecular cycloaddition reactions involves the aromatization of ynallenes, which proceed via diradical intermediates. The diradical can be stabilized by abstraction of hydrogen from DNA, thereby cleaving DNA chains. Examples of natural products of bacterial origin having such structures include the endiyne cytostatic antibiotica 4 . The intramolecular cycloaddition reactions of allenes are also used in the construction of steroidal compounds, prostaglandine derivatives and numerous other natural products. Thermal or photochemical intramolecular cycloaddition reactions of diallenes afford cyclobutenes. Heating of vinylallene at 170 ◦ C affords 10 % of methylenecyclobutene and mixtures of C10 H12 dimers 5 . The thermal reaction of bisallenyl 6 (1,2,4,5-hexatetraene) at 200 ◦ C/35–65 torr affords a quantitative yield of 3,4-dimethylenecyclobutene 7 6 . • •

6

7

Likewise, the diallene 8 on distillation affords the [2+2] cycloadduct 9 7 . O

O

(EtO) 2 P

(EtO) 2 P

(EtO)2 P O 8

•

•

(EtO)2 P O 9

1,2,3-Tricarbon Cumulenes

401

On heating of the vinyl allene 10 at 360 ◦ C an equilibrium mixture of 10 and 11 is established in a ratio of 19:81 8 . • Ph

Ph 10

11

When a TMS substituent is attached to the vinyl group complete electrocyclization occurs in refluxing toluene to give the alkylidenecyclobutenes 12 in 85-99% yields 9 . R1

R1

R1

R1

•

R2

R2

TMS

TMS 12

The thermal conversion of 3,4-dibromo-1,1,6,6-tetraphenyl-1,2,4,5-hexatriene 13 to 1,2dibromo-3,4-bis(diphenylmethylene)cyclobutene 14 also occurs in the crystalline state. The reaction is stereoselective and proceeds from the s-trans diallene via the s-cis diallene to give the final product 10 . Ph

Ph Br Br

Ph

• •

Ph

Br

Ph Ph

Br Ph

Ph 14

13

Heating of the 1,6-diethynyldiallene derivative 15 in benzene affords benzodicyclobutadiene 16 in quantitative yield 11 . • •

C C CPh

Ph Ph

Ph Ph

C C CPh 15

16

Generation of the 1,2-diallenylbenzene derivative 17 (X = Cl, Br ) in situ, affords naphthocyclobutene 18 10 . X C(X)

•

CPh2 Ph2

C(X)

•

Ph2

CPh2 X

17

18

402


Heating of the stable 1,2,4,5-tetraallenyl derivative 19 in the solid state affords the anthrocyclobutene derivative 20 10 . Cl

Ph2C

Cl

Cl

•

CPh2

• Cl

Cl

CPh2

•

•

Ph2C

Ph2

Ph2

Ph2

Ph2

Cl

Cl

Cl

19

20

In a similar manner, heating of the 1,2,3,4-tetraallenylbenzene derivative 21, generated in situ, affords the phenanthrodicyclobutene derivative 22 12 . Cl

Cl

•

Ph2C

Ph2 Ph2C

•

• Cl

•

Ph 2C

Cl

Cl

Ph2

CPh2

Cl

Cl Cl

Ph2 Ph2 22

21

Mercury (II) triflate catalyzes the cycloisomerization of the allenynes 23 (X = N–Ts) to the vinyl allenes 24 in high yields 13 . •

• X

X 23

24

This reaction is also catalyzed by GaCl3 and the cycloisomerization products are obtained in 53–87 % yields 14 . Recent advances in the synthetic applications of allenes, including gold catalyzed reactions, were reviewed recently 15 . 6.1.2 Dimerization Reactions The thermal cyclodimerization of allenes proceeds via a stepwise [2+2] cycloaddition reaction, the intermediate being a diradical. From allene, in a flow reactor, a mixture of the head-to-head dimer 25 and the head-to-tail dimer 26 are obtained. At 500 ◦ C (9 % conversion) a mixture of 34 % of 25 and 13 % of 26 are formed. The formation of the cyclodimer 26 is unusual, because substituted allenes afford only the head-to-head dimers. +

CH2 C CH2 25

26

In the dimerization of 1,1-difluoroallene an asymmetric head-to-tail dimer 27 is isolated because the also formed head-to-head dimer undergoes simultaneous oligomerization


403

reactions 16 . F2 CF2 C CH2 F F 27

Tetrafluoroallene dimerizes slowly at 20 ◦ C 17 , while tetrachloro- and tetrabromoallene dimerize rapidly at or below ambient temperature 18 . For example, a 63 % yield of the headto-head cyclodimer of tetrachloroallene is obtained at room temperature 19 . Tetraiodoallene does not dimerize rapidly. Thermal dimerization of methylallene gives a mixture of all seven head-to-head dimers 20 . The dimerization of t-butylallene at 220 ◦ C for 72 h gives a mixture of the head-to-head dimers 28 and 29 21 . At more elevated temperatures, in addition to the two cyclodimers, aromatic trimerization products are formed (see Section 6.1.3.).

t-BuCH

C

CH2

+ 28

29

Using Ni(o) catalysts in the dimerization of electron deficient mono substituted allenes 30 affords the head-to-head dimers 31 22 . R RCH

C

CH2 R

30

31

R

Yield (%)

C6 F13 C6 F5 COOEt

79 81 71

The dimerization of phenylallene in the presence of a ruthenium catalyst affords a 44 % yield of the cyclodimer 32 23 . PhCH

C

CH2

Ph Ph 32

404


In the palladium catalyzed dimerization of mono substituted allenes in DMF a mixture of the linear dimers 33 and 34 is obtained in 39–83 % yields 24 .

RCH

C

R

CH2

R

+

R

R

33

34

In the thermal dimerization of 1,1-dimethylallene in triglyme at 157 ◦ C the three isomeric cyclodimers 35 (48 %), 36 (36 %) and 37 (18 %) are obtained. Most likely, steric effects determine the distribution of the cyclodimers 25 .

(Me)2C

C

CH 2

+

+

35

36

37

1,1-Dicyclopropylallene dimerizes at 200 ◦ C to form the cyclodimers 38, 39 and 40 in 35 % yields. The spiro compound 40 results from rearrangement of the head-to-tail dimer (ratio 1.8:1.7:1) 26 .

C

C

CH 2

+

+

38

39

40

The dimerization of 1,1,3-trichloroallene occurs already in petroleum ether at room temperature (3 days) to give a mixture of the two shown isomers 41 and 42 in quantitative yields 27 . The undiluted 1,1,3-trichloroallene decomposes violently at room temperature. H

Cl CCl2

C

CHCl

Cl

Cl

+

Cl

Cl Cl 41

Cl

Cl2 Cl2

Cl H 42

Dimethylchloroallene dimerizes to give both symmetrical and dissymmetrical cycloadducts 28 .


405

Trisubstituted allenes with an amide substituent form the expected cyclic dimers 43 29 . R1

H R1R2C

C

R2

R2NCO R2NCO

CHCONR 2

R2 H

R

1

43

R

R1

R2

Yield (%)

i-Pr Ph 2,3,5-Me3 Ph

Cl Cl Cl

Cl Cl Cl

77 72 85

Likewise, 1,1-dimethyl-3-cyanoallene forms isomeric cyclodimers 44 and 45 in 74 % yield 30 . H

CN H

CN Me2C

C

CHCN

+

NC

NC H

H

44

45

From the trisubstituted allene 46 ( R = Br) the head-to-tail dimer 47 is obtained in 80 % yield 31 .

C

R

H

R

H

C(R)H

46

47

A similar head-to-tail dimer is obtained in 64 % yield from the trimethylsilyl derivative of 46 (R = TMS) at 110 ◦ C. From 46 (R = Ph), a sequential formation of four stereo-isomeric dimers is observed. The cyclodimer 47 isomerizes to the tail-to-tail dimer 48, which is obtained in 58 % yield 32 . TMS H H TMS

H TMS TMS H

47

48

406


Heating of the initially formed cyclodimer 49 in DMSO at 180 ◦ C affords the blue tetraene 50 33 .

H Ph

Ph

Ph

Ph

H

49

50

The dimerization of tetra substituted allenes containing polar substituents occurs randomly across either one of the double bonds (see Table 6.1). The rate of dimerization of allenes to give 1,2-dimethylenecyclobutane derivatives depends on the substituents (R = CN > COOEt > Cl > Ph > Br > H) 7 . Table 6.1 Dimerization of some tetrasubstituted allenes with polar substituents Allene

Reaction conditions

Cyclodimer

Yield (%) Reference

CO2Et Cl2 Cl2

Cl Cl CO2Et

CCl2 C C(Cl)COOEt Room temperature, 20 h (EtO)2

100

34

85

35

65

36

C(CF3)2

(EtO)2

(CF3 )2 C C C(OEt)2

C(CF3)2

Room temperature, 5 min

(EtO)2 C

C(OEt)2

OEt OEt

—

The dimerization of several highly strained cyclic allenes, generated in situ, also affords mixtures of head-to-head cyclodimers. For example, from 1,2-cyclononadiene at 125 ◦ C mixtures of the dimers 51 (62.5 % yield), 52(31.2 % yield) and 53 (6.3 % yield) are


407

obtained 37 . +

51

+

52

53

Lower yields of cyclodimers are obtained in the thermolysis of 1,2,6-cyclononatriene at 130 ◦ C 38 . 1,2-Cyclononadiene is a distillable liquid, and its dimerization requires heating to 138 ◦ C 39 . In contrast, 1,2-cyclooctadiene is only observed at −60 ◦ C because of rapid dimerization at room temperature. 1,2-Cyclooctadiene has a half-life of 10 min at 0 ◦ C 40 . The more strained cycloocta-1,2,4,6-tetraene 54 is only obtained as the cyclodimer 55 41 .

54

55

Attaching substituents to the cumulative system reduces the tendency of dimerization. 1-Methyl-1,2-cyclooctadiene has a half-life of 10–15 min at ambient temperature, while 1-t-butyl-1,2-cyclooctadiene does not dimerize on standing 42 . In the trapping of strained cyclic allenes, in addition to the cycloadducts the expected cyclodimers are also formed. The dimers are sometimes the only isolated products. In Table 6.2, some head-to-head dimers obtained from several strained cyclic allenes are listed. Table 6.2 Head-to-head dimers from strained cyclic allenes Strained allene

OMe

• a

No yield reported.

Cyclodimer

OMe

OMe

Yield (%) Reference

55

43

85

44

—a

45

85

46

408


The generation of 1-cyclohept-1,2-dien-1-yl 56 in situ results in the formation of the [4+2] cyclodimer 57 (52 %) and the [2+2] cyclodimer 58 (9 %) 47 .

Ph +

Ph

Ph Ph 56

57

58

The dimerization of allenyl ketones 59, catalyzed by triphenylphosphine, affords the cyclodimers 60 formed by a [4+2] cycloaddition reaction in moderate yields 48 . •

2

O R

O

O

59

R

60

R

Yield (%)

4-BrPh 2,4,6-Me3 Ph 2,6-MeOPh

48 54 44

In contrast, the cyclodimerization of allenyl ketones 61 in the presence of [PdCl2 (MeCN)2 ] affords the 2,4-disubstituted furanes 62 in high yields 49 . O RCOCH

C

R

CH 2 R O 62

61

Depending on the substituents, the Pd catalyzed cyclization of terminal α-allenones 63 affords the cyclodimers 64 or the cycloisomerization products 65 50 . R

Ar

R ArCOC(R)

C

R +

CH2 Ar

63

O

Ar

O 64

O

65

R H Me Ph

Yield of 64 (%)

Yield of 65 (%)

60 6 —

— 63 76


409

In contrast, treatment of allenyl ketones with AgNO3 in aqueous acetone causes cyclization to give substituted furans 66 51 . R2 R3COCH(R2)

CHR1

C

R1

R3 O 66

The dimerization of allenes is facilitated by using nickel (o) catalysts. Intermediates in this reaction are five-membered ring metallacycles. For example, dimerization of allene in the vapor phase in the presence of a phosphine modified Ni(CO)4 catalyst gives 30 % of the head-to-tail dimer, 8 % of the head-to-head dimer and 42 % of the cyclotrimer (1,2,4-trimethylenecyclohexane) 52 . A mixed dimer 68 from cyclonona-1,2-diene 67 and allene is obtained in 60 % yield 53 . +

•

CH2

C

CH2

67

68

A [4+2] cyclodimer 69 is also obtained in the palladium catalyzed cyclodimerization of vinyl allene in 81 % yield 54 . + •

•

• 69

The [4+2[ cyclodimerization of the phenylvinyl allene 70 to give the cyclodimer 71 even occurs at −30 ◦ C 55 . Ph

Ph 2

Ph • • 70

71

Sometimes, different cyclodimers are formed in the dimerization of tetrasubstituted allenes. For example, from the allene 72 cyclodimers are formed by a 1,4-dipolar addition of the mesomeric form of the allene to the ketenacetal-like double bond in the second molecule, followed by an electrocyclic reaction to give the cyclodimers 73 56 . X

OEt OEt

OEt

X

O

•

O

OEt

EtO OEt

O 72

X

73

X O CH2

Yield % 48 45

410


‘Push-pull’ allenes, such as the shown cyclopentadienylidene allenes 74, dimerize in solution on attempted synthesis to give two major dimers 75 and 76 57 and one minor dimer 77 58 . In contrast, fulvenallenes do not undergo a dimerization reaction. H •

H

H

R

R

R

+

+

R

H 74

R R

R

H

75

76

77

1,2,4,6-Cycloheptatetraene 78 dimerizes through the isomeric carbene structure 79 to form the dimer 80 59 . ••

78

79

80

1,3-Di-t-butyl-5-vinylidenecyclopentadiene 81 undergoes a [6+2] cyclodimerization in the solid state (10 ◦ C, 14 days) to give 1,3,5,7-tetra-t-butyl-4,4a,8,8a-tetrahydrodicyclopenta[a,e]pentalene 82 in 35 % yield 60 .

•

81

82

6.1.3 Oligomerization Reactions The cyclotrimerization of allene in the vapor phase, in the presence of a nickel (o) catalyst, gives a mixture of the shown cyclotrimers 83 and 84 (35 % yield) and the cyclotetramer 85 in 7 % yield 61 . Also, the pentamer 86 is isolated in the oligomerization of allene 62 .

CH2

C

CH2

+

83

+

84

+

85

86

The complexes formed in the reaction of allene with a stoichiometric amount of nickel (o) catalysts readily add another molecule of allene to give trimer complexes, from which a quantitative yield of 1,2,4-trimethylenecyclohexane is obtained 63 . In the oligomerization of allene, mixtures of higher oligomers are often formed, from which the oligomers listed in Table 6.3 were isolated.


411

Table 6.3 Some allene oligomers Number of allene Units

Conditions

Reference

3

Thermolysis

64

3

Photolysis

65

Liquid phase, Ph3 P)3 RhCl Catalysis

66

4

Thermolysis

67

4

Cyclotetramization

68

5

Thermolysis

69

Liquid phase, Ph3 PRh(CO)2 Cl2 catalysis

70

4

6

Structure

—

—

Also, from the nickel (o) complex of 1,2-cyclononadiene upon heating to 60 ◦ C mixtures of trimers and oligomers are formed. From t-butylallene at 290 ◦ C, a mixture of the two aromatic trimers 87 and 88 are formed (see also Section 6.1.2.) 21 .

t-BuCH

C

CH2

+

87

88

412




The reaction of tetramethylallene with isopropylidene carbene affords the [2+1] cycloadduct in 12 % yield. Likewise, reaction with dimethylvinylidene carbene 89 affords the [2+1] cycloadduct 90 in 35 % yield 71 .

Me2C

C

CMe2 + Me2C

C

C: •

89

90

The allene 91 reacts with diazomethane in the presence of CuCl to give the mono adduct 92 (50 % yield) and the bis-adduct 93 (30 % yield) 72 .

+ CH2N2

•

+

91

92

93

Halocarbenes undergo this reaction very well and usually in high yields. For example, the cyclopropanation of the diaryl vinylidene cyclopropanes 94 with dihalocarbenes (X = Cl, Br) affords the 1-dihalomethylenespiropentanes 95 73 .

R1 R2

+

•

X

X

R1

R2

X X

:CX2 R1

94

R2 95

R

R1

X

Yield (%)

Ph Ph

Ph Ph

Cl Br

99 73

A concerted reaction occurs at the π 1,2 bond in 1,1-dimethylallene with dibromocarbene which affords the cycloadduct 96 74 .

(Me)2C

C

CH2

+

:CBr2 Br

Br 96


413

The addition of difluoro- and dichlorocarbene to perfluoro-1,1-dimethylallene in the gas phase produces the rearranged [2+1] cycloadducts 97 75 . CF3 (CF3)2C

C

CF2

+

CF3

X F2

:CX2 X

X

(CF3)2 F

X

F 97

Often bis-adducts 98 are obtained in good yields in the addition of halocarbenes to allenes 76 . X X R1R2C

C

CR3R4

+

X X

:CX2 R1

R1

R2

R2 R3 98

R3

R4

R4

X

H H Me Me Cl Me Me Me Me Cl –(CH2 )3 – –(CH2 )3 – Br

Yield (%) 70 90 89

Phenyl substituted carbenes are added to 1,2-dimethylallene to give the [2+1] cycloadducts. All singlet carbenes add across the π 1,2 bond, while triplet carbenes add predominantly across the π 2,3 bond 77 . Also nitrenes, generated from the allenyl azides 99, undergo the [2+1] cycloaddition reaction to give the annelated indole derivatives 100 78 . • N3

R1

R1R3

R2

R2

N

99

6.1.4.2

R3

100


Across ca rbon–carbon multiple bonds The reaction of allenes with electron deficient acetylenes affords [2+2] cycloadducts or cross-conjugated trienes resulting from an ‘ene reaction’. From tetrafluoroallene and bis-trifluoromethylacetylene, the expected [2+2] cycloadduct 101 is obtained 79 . F CF2

C

CF2 + CF3C

CCF3

F

F2

CF3

F3C 101

However, from tetramethylallene and bis-trifluoromethylacetylene mainly crossconjugated trienes 102 (78 %) and 103 (18 %) and the [2+2] cycloadduct 104 (11 %)

414


are isolated 80 . CF3 Me2C C CMe2

+

CF3

+

CF3C CCF3 CF3

F3C

102

+ F3C

103

CF3 104

Also, benzyne undergoes a [2+2] cycloaddition reaction with several allenes, as shown in Table 6.4 81 . Table 6.4 [2+2] Cycloadducts derived from allenes and benzyne Allene

Cycloadduct

Yield (%)

H Cl

CH2 C CHCl

12 H OMe

CH2 C CHOMe

17 H OMe

t-BuCH C CHOMe

25

Two equivalents of allenes and two equivalents of acetylene dicarboxylate, in the presence of diazadiene-stabilized palladacyclopentadiene as the catalyst, afford high yields of the hydronaphthalene intermediates 105, which are readily oxidized with DDQ to give tetrasubstituted-naphthalene esters 106 useful for the preparation of polyimides 82 . R 2

CH2

C

CH2

+

2

RC

R

R

R

R

R

CR R 105

R 106

Apparently the allene dimer intermediate diradical is trapped by the acetylene dicarboxylates. Allenes with tethered alkyne groups undergo intramolecular [2+2] cycloaddition reactions or ‘ene cyclyzations’. For example, an intramolecular [2+2] cycloaddition of the allene 107 occurs on refluxing in mesitylene to give the bicyclic adduct 108 in 91 % yield 83 . SO2Ph

PhSO2 • O 107

Ph

O

Ph 108

When O in 107 is replaced by NTs the cycloadduct is also obtained in 91 % yield.


415

Similarly, the allenes 109 undergo intramolecular [2+2] cycloaddition reactions to give the expected cycloadducts in excellent yields. SO2Ph

PhSO2 • X

R

X CH2

R

109

R

X

Yield (%)

Me TMS Pr Bu

O O NTs C(COOMe)2

98 94 100 94

The allenyl sulfone 110, generated on heating, undergoes an intramolecular [2+2] cycloaddition reaction to give 111 in 62 % yield. SO2Ph

H

H

PhSO2

•

H

H H 110

111

Likewise, the allene 112 with the unsaturated ether tether affords the cycloadduct 113 in 92 % yield. PhSO2

H

SO2Ph

•

H

H

H O

O CH3

CH3 112

113

Also, the phenylsulfonylallenes 114 (E = SO2 Ph) undergo the intramolecular [2+2] cycloaddition reaction at 80 ◦ C to give the cycloadducts 115 in 80–98 % yields 84 . PhSO2

SO2Ph • R1

E E 114

R2

E E

R1 R2 115

The olefin-tethered arylallene 116 is stable at −78 ◦ C and at 0 ◦ C, in the presence of MeOH, it undergoes the intramolecular [2+2] cycloaddition reaction across its

416


unsubstituted C C bond to give the cycloadducts 117 85 . H

SO2Ph H

SO2Ph

H R3 R2

• R1 H R3

SO2Ph

H

R3 R1

R2

R1

R2 116

117

R

R1

R2

Yield (%)

H Me

H H

H H

92 59

Thermolysis of the sulfones 118 (R = COOMe) produces the eight-membered 3methylene cyclooctenes 119 in 80 % yield. SO2Ph

PhSO2 • R

SO2Ph R

R

R

R

R 118

119

Also, the fluoroallenes 120 participate in intramolecular [2+2] cycloaddition reactions to tethered alkyne chains in the presence of Mo(CO)6 to give the cycloadducts 121 86 . TIP

TIP

F

•

F2

F

X

X

Ph 120

121

X

Yield (%)

C(COOMe)2 NTs

88 92

Allene esters with tethered alkyne groups, such as 122, undergo intramolecular cyclization in the presence of trans-RhCl(CO)(PPh3 )2 to give the adduct 123 in 87 % yield 87 . O

• O O

Pr

Ph

Pr

Ph 122

Ph Ph

O 123


417

Microwave irradiation at 250 ◦ C of the allene ketones 124 (n = 1,2) causes cyclization to give the expected adducts 125 88 . O

R2 nO

•

R1 R2

H R1

n

124

125

Also, the amide allenes 126 undergo carbocyclization reactions in the presence of [Rh(CO)2 Cl]2 in toluene at 90 ◦ C to give the ε-lactames 127 in good yields 89 . O

R1

MeO2C

•

HN

R1

R2

R2

HN

MeO2C

O 126

127

In contrast, the alkyne-tethered allenes 128, in the presence of [Rh(CO)2 Cl]2 , undergo ‘cyclic ene’ reactions to give the cross-conjugated trienes 129 in high yields 90 . R1

R •

X

H

X

H

R1

H

128

R

129

R

R1

X

CH2 C7 H15 H C5 H11 C6 H13

TMS H H Me

CH2 C(COOMe)2 C(COOMe)2 O

Yield (%) 72 74 80 74

Cross-conjugated trienes are also obtained in the cyclization of allene esters 130 in the presence of rhodium catalysts to give 131 91 . R1

R4 • O O

R R3

O R3 2

O R5 131

R2 R3

H H –(CH2 )5 –

R1 R4

R5 130

R1

R2

R4 R5

Me Bn Ph H H TMS

Yield (%) 67 78

418


Likewise, the cross-conjugated trienes 133 are obtained from the allenes 132 (X = O, NTs or C(COOEt)2 , n = 1,2 ) in the presence of RhCl(PPh3 )3 in 41–81 % yields 92 . R X

n

•

H

X

R

n

132

133

Also, PtCl2 catalyzes the cyclization of the ynallenes 135 to give the 3allenylcyclohexenes 136 in 71–84 % yields 93 . R1

Me •

MeO

Me

MeO

Me

Me

MeO

•

CH2R2

MeO

R2 135

H

136

In a similar manner, the terminal ynallene 137 affords the bicyclic adducts 138 in high yields. Me

Me

Me R2

•

Me

Me

R2 R1

R1 137

138

The cycloaddition of the 1,2-diene-7-yne 139 in the presence of a titanium complex affords the cyclodentane derivative 140 in 98 % yield (mixture of isomers 82:18; the major isomer is shown) 94 . C5H11 •

BzO

C5H11

BzO

H BzO

SiMe3

BzO

SiMe3

139

140

The cyclization reaction of the ynallene 141 in the presence of Pd2 (dba)3 /P(C6 F5 )5 , mediated by Ph3 SnSiMe2 –t-Bu, affords a 78 % yield of the two indolizidine isomers 142 and 143 (ratio 60:40) 95 . H

H

H

Ph3Sn

•

N

+ N

t-Bu(Me)2Si

N

t-Bu(Me)2Si O

O 141

H

Ph3Sn

142

O 143


419

Allenes and cumulenes in general are more reactive than alkenes in undergoing cycloaddition reactions with isolated non-activated double bonds. The stereochemistry of the major cycloadducts can be predicted from the most stable diradicals formed upon initial bonding of the sp carbon to the allene. The [2+2] cycloaddition reaction of allenes to olefins proceeds thermally, photochemically and at room temperature, using a Lewis acid catalyst. The mechanism of these reactions are considered to be stepwise processes, with radical or ionic intermediates. The thermal reaction of allene with acrylonitrile at 210 ◦ C gives a 60 % yield of the [2+2] cycloadduct 144 96 . CN CH2

C

CH2

+

CH2

CHCN 144

1,3-Dimethylallene reacts with acrylonitrile at 150 ◦ C for 5 days to give the [2+2] cycloadduct 145 in >90 % yield 97 . CN MeCH

C

CHMe

+

CH2

CHCN 145

Methyl acrylate reacts analogously to give the [2+2] cycloadduct in high yield. Methoxyallene reacts with 1,1-bis-trifluoromethyl-2,2-dicyanoethylene to give an 81 % yield of the expected cycloadduct 146 98 . CH2

C

CHOMe

+

(CF3)2C

(CF3)2

C(CN)2

(CN)2 OMe 146

From 1,1-dicyclopropylallene and activated olefins at 200 ◦ C, [2+2] cycloadducts are obtained in good yields. For example, 1,1-dicyclopropylallene reacts with diethyl methylenemalonate to give an 81 % yield of the two cycloadducts 147 and 148 in a ratio of 73:27. The major dimer was exclusively formed when AlCl3 was used as the catalyst 99 .

C

C

CH2

+

CH2

C(CO2Et)2

+ (EtO2C)2 147

(EtO2C)2 148

Similar thermal reactions are observed with other activated olefins to give the cycloadducts 149 and 150 as shown in Table 6.5 100 .

420

Cumulenes in Click Reactions Table 6.5 Thermal reaction of 1,1-dicyclopropylallenes with activated olefins C

C

CH2

+

R1R2C

CR3R4

+ 150

149

R1

R2

R3

R4

Ratio, 149:150

Yield (%)

CO2 Me CO2 Me CN

H CO2 Me CN

H H CN

H H CN

11:89 5:95 99: —a

68 84 71

a

Not detectable.

Also, thermal reactions of unsaturated ketones, acrylonitrile and methyl methacrylate with CH2 C C(SMe)SiMe3 afford the [2+2] cycloadducts in high yield as shown in Table 6.6 101 . The asymmetric [2+2] cycloaddition reactions of allenylsulfides also proceed in high enantioselectivity by the use of chiral titanium reagents 102 . Table 6.6 Thermal [2+2] cycloaddition reactions of CH2 C C(SMe)SiMe3 Olefin

Cycloadduct Me

COPh SMe SiMe3

PhCOCH CHCH3 Ph

PhCOCH CHPh

a

81

COPh SMe SiMe3

92 CO2Me

CO2Me

CH2 C(Me)CO2 Me

Yield (%)

SMe SiMe3

+

SiMe3 SiMe

91a

Ratio: 85:15.

Lewis acids, such as EtAlCl2 , GaCl3 and AlBr3 , catalyze the cycloaddition of allenes to alkenes to give methylenecyclobutanes 151. 1-Alkenes and sterically hindered olefins, such as 4,4-dimethyl-2-pentene, do not react, and from butadiene only polymeric products are obtained. Substituted olefins react more readily, i.e. 1,1,2,2-tetraalkylethylene > 1,1,2trialkylethylene > 1,2-dialkylethylene. The acid catalyzed [2+2] cycloaddition reaction most likely proceeds via a vinyl cation. The slightly exothermic reaction proceeds at room temperature in chlorobenzene and EtAlCl2 was used as a catalyst in the examples listed in Table 6.7 103 .


421

Table 6.7 Lewis acid catalyzed [2+2] cycloaddition reaction of allenes to olefins R1

R4

R1R3 +

•

R2

R5

R5

R3

R2R4 151

R6

R6

R1

R2

R3

R4

R5

R6

Yield (%)

Me Me i-Pr Me

Me Me Me Me

H Me Me H

H Me Me H

H H H H

H H H Me

40 >90 >90 90

Carbomethoxyallene 152 also undergoes the [2+2] cycloaddition reaction with olefins in the presence of EtAlCl2 . From 152 and cis-1,2-dimethylethylene, the [2+2] cycloadducts 153 (65 %) and 154 (5 %) are obtained. Trans-1,2-dimethylethylene reacts with 152 to give the cycloadducts 155 (45 %) and 156 (35 %) 104 .

+

CO2Me

CO2Me CH2

C

CHCO2Me

154

153

152 +

CO2Me

CO2Me 155

156

In a similar manner, [2+2] cycloadducts are obtained from 1-methyl-3-carbomethoxy, 1,1-dimethyl-3-carbomethoxy and 3-methyl-3-carbomethoxyallenes using EtAlCl2 as the catalyst 105 . Also, CH2 C CHSO2 Ph reacts with methylenecyclohexane in the presence of EtAlCl2 across the terminal C C bond to give the expected cycloadduct 157 117 . SO2Ph CH2

C

CHSO2Ph

+ 157

In a similar manner AlCl3 is used as the catalyst in the cycloaddition of CH2 C CHCO2 Et with some cyclic olefins, as shown in Table 6.8 106 . From cyclopentadiene only the [4+2] cycloadduct (ratio of endo:exo cycloadduct, 86:14) was obtained.

422

Cumulenes in Click Reactions Table 6.8 [2+2] Cycloaddition of carboethoxyallene with olefins in the presence of AlCl3 Olefin

Cycloadducts

Ratio E:Z

Yield (%)

92:7

50

—

77

H

CO2Et

CO2Et

H Me3Si CO2Et SiMe3

H

Lewis acids also catalyze the rearrangement of the arylvinylidenecyclopropanes 158 to aromatic hydrocarbons. In 158 (R1 , R2 , R3 = aryl, R4 = H and R5 , R5 = alkyl) the cyclization affords the naphthaline derivatives 159 using Eu(OTf)3 as the catalyst in high yields. While in 158 (R1 , R2 , R3 , R4 = aryl, R5 = alkyl or H and R6 = H) the cyclization in the presence of Zr(OTf)4 affords the indene derivatives 160 in 88–97 % yields 107 . R2

R5 R1

R3

R4

R6

R5

R6

R3

159

• R2

R1

R4

R2

158

160

When the vinylydenecyclopropanes have three substituents at the 1,2-positions of the cyclopropane ring, as in 161, rearrangement in the presence of Sn(Otf)3 in DCE at 80 ◦ C, affords the benzofluorene derivative 162 in 97 % yield (Z:E ratio, 1:2) 108 . Br Ph

Me

Me •

Ph

H 161

Me

H Me 162

Likewise, cyclization reactions of vinylidenecyclopropanes with activated C O bonds, such as in HCOCOOEt in the presence of BF3 • Et2 O, afford the tetrahydrofuran


423

derivatives 163 109 . R1 R2 R1 R2

+

•

HCOCOOEt

EtO2

O 163

R1

R2

Ph 4-MePh

Ph 4-MePh

Yield (%) 99 98

Activated olefins, such as enamines or vinyl ethers, undergo [2+2] cycloaddition reactions with allenes in the absence of a catalyst. For example, the addition of 1-dimethylamino2-methylpropane 164 occurs across the substituted C C bond in phenylsulfonylallene to give the [2+2] cycloadduct 165 110 .

Me2C

CHNMe2

+

CH2

C

NMe2

CHSO2Ph

SO2Ph 165

164

Phenylsulfonylallene also reacts with vinyl ethers under high pressure across its terminal C C bond to give the [2+2] cycloadducts in 44–74 % yields 111 . The photochemical [2+2] cycloaddition reaction of cyclopentenone with allene affords a mixture of the two isomeric adducts 166 and 167 112 .

CH2

C

CH2

+

+ O

O 166

O 167

Similarly, substituted cyclohexenones undergo the light-induced [2+2] cycloaddition reaction to afford the bicyclic adduct 168 113 . R

R CH2

C

CH2

+ O

O 168

Interestingly, the [2+2] cycloaddition reaction of olefins to the heterocyclic allene 169 (R = Ts, Bn or SO3 CH2 CCl3 ) occurs across the terminal C C bond rather than the enamide

424


double bond to give the adducts 170. The yields in this reaction range from 55 to 98 % 114 . R1

•

•

R2 +

NR

O

CR1CR2

CH

NR

O

O

O

169

170

Intramolecular [2+2] cycloadditions are also observed with allenes, having a tethered olefinic double bond. For example, heating of the allene 171, in the presence of EtAlCl2 , gives a mixture of the two isomeric intramolecular cyloadducts 172 (63 %) and 173 (32 %) 115 . MeO2C

CO2Me •

CO2Me

+ 171

172

173

The thermal intramolecular [2+2] cycloaddition reaction of the azetidinone-tethered enallene 174 affords the tricyclic β-lactam 175 116 . OH

H H R

1

N

R

2

OH •

R2

R1 N

O

O 174

175

The gold-catalyzed intramolecular cyclization of the allene 176 (E COOMe) at −10 ◦ C affords the cycloadduct 177 (88 % yield, e,e = 92 %) 117 . Me

•

E E

N E E

N Me 176

177

Likewise, light-induced intramolecular [2+2] cycloaddition is observed upon irradiation of the allene 178. The intramolecular cycloadducts 179 are obtained in 50–100 % yields 118 . RN • H O 178

O

R1

RN

H

R1 O 179

O


425

The thermal intramolecular [2+2] cycloaddition reaction of allenes 180 (R = Me3 PhSO2 ) affords the cycloadducts 181 and 182 (ratio, 99:1) in 88 % yield 119 . H •

Bu

Bu Ph

RN

RN

180

Bu +

RN

Ph

Ph 182

181

An efficient stereodivergent entry to (−) α-kainic acid derivatives involves the intramolecular cyclization of the allene 183 to give the cycloadduct 184 in 57 % yield 120 . O

O

O

N

O

O

O N

•

N

N

O

O

O

O 183

184

Several complex light-induced intramolecular cycloaddition reactions are also observed. For example, the unsaturated ketone 185, tethered to an allene group, upon irradiation at −70 ◦ C, affords a 60 % yield of the cycloadduct 186 121 . HO

OH

O • 185

186

In the photocyclization of the allene 187, the bicyclic [2+2] cycloadduct 188 is formed 122 .

•

Ph Ph 187

188

The 2,3-dihydro-4-H-pyran-4-ones 189 react with allene stereospecifically to give two isomeric cycloadducts 190 and 191 123 . O

O

O + O

O 189

O

O CH2

C

CH2

O +

O

O 190

O

O 191

426


Likewise, the photochemical reaction of duroquinone 192 with 1,1-dimethylallene gives a 87 % yield of the [2+2] cycloadduct 193 124 . O

O Me2C

+

C

CH2

O

O

192

193

Also, the 1,2-dichloro-1,4-naphthoquinone reacts with phenylallene under photolytic conditions to give a 74 % yield of the [2+2] cycloadduct 125 . In contrast, 1,4-benzoquinone (87 % yield) and 1,4-naphthoquinone (40 % yield) react with tetramethylallene in the presence of light to give the cyclic ketones 194 126 . O

O +

Me2C

C

OH

CMe2 •

O

O• O 194

Photocyclization of 4-methoxyquinolin-2(1H)-one 195 with allene affords two isomeric cycloadducts 196 (53 %) and 197 (9.7 %), respectively 127 . OMe

MeO +

N Me 195

O

CH2

C

MeO

CH2

+ N Me 196

O

N

O

Me 197

In the reaction of 1,1-dimethylallene with diethylfumarate the [2+2] cycloadducts retain the trans-diester stereochemistry. In contrast, in the reaction of 1,1-dimethylallene with diethylmaleate, in addition to the cycloadducts having the expected cis-ester configuration, cycloadducts with the trans-ester configuration are also formed indicating that internal rotation in the reaction occurs. In the reaction of t-butylallene with diethylfumarate and diethylmaleate only cycloadducts having the trans-ester configuration are formed, indicating that diethylmaleate isomerizes under the reaction conditions. Methoxyallene reacts 100 times faster than 1,1-dimethylallene, giving only the trans-diester cycloadducts 128 .


427

Tetrasubstituted allenes with cyclopropane substituents, such as 198, react with CF2 CCl2 across the three-membered ring-substituted double bond to give the cycloadduct 199 129 .

C

C

CMe2

+

CF2

CCl2 Cl2

F2 198

199

The reaction of cyclopropane-substituted allenes with tetracyanoethylene or bistrifluoromethyldicyanoethylene proceeds similarly to give the [2+2] cycloadducts 200 130 .

C

C

CMe2

+

R2C

C(CN)2

(CN)2

(NC)2

200

Allenes with polar substituents also undergo a [2+2] cycloaddition reaction with olefins. For example, 1,1-3,3-tetrathioethylallene reacts with tetracyanoethylene to give the [2+2] cycloadduct 131 . In contrast, 1,1,3,3-tetramethoxyallene affords a linear switter ionic 1:1 adduct in its reaction with tetracyanoethylene 132 . The cycloaddition reaction of polar allenes with enamines also affords [2+2] cycloadducts. These reactions also proceed via intermediate switter ionic adducts. For example, Me2 C C(H)NR2 (R = Me, –(CH2 )4 ) reacts with 1,1-dimethyl-3,3-dicyanoallene to give the cycloadducts 201 and 202, resulting from addition across the polar substituted double bond of the allene. Upon long standing or heating of the initially formed cycloadducts a new cycloadduct 204 is obtained, most likely formed via the linear intermediate 203 133 . Me2 C

C(H)NR2

+

Me2C

C

C(CN)2 CN

CN NC (NC)2

+ H NR2

(NC)2

NR2

NC NR2

NR2

+

H

201

-

H

H

202

203

204

From 1-benzenesulfonylallene and Me2 C C(H)NR2 , a [2+2] cycloadduct, also resulting from addition across the polar substituted double bond, is obtained. Morpholinocyclohexane and cyanoallene form a cycloadduct in 50 % yield, resulting from addition across the unsubstituted double bond 134 . Reaction of CH2 C C(H)NMe2 with acrylonitrile gives a 97 % yield of the [2+2] cycloadduct 205 135 . H NMe2 CH2

C

C(H)NMe2

+

CH2

CHCN CN 205

428


In the cycloaddition reaction of R1 R2 C C CH2 (R1 = EtO, R2 = H and R1 = MeO, R = Me3 Si) with unsaturated ketones, mixtures of the [2+2] 206 and the [4+2] cycloadducts 207 are obtained 136 . The [4+2] cycloadducts are preferentially formed. 2

R3

R1 R2

O +

R1R2C

C

CH2

O

R3

R1R2

+ R3

O 206

207

Strained cyclic allenes, generated in situ are often trapped as [2+2] cycloadducts with olefins. The reactive species are best generated by using the trapping agent as the solvent. Generally, styrene, butadiene, isoprene and 2,3-dimethylbutadiene are used and in the case of the diolefin, mixtures of the [2+2] and the [4+2] cycloadducts are often formed. The [2+2] cycloadducts resulting from diolefins are thermally converted into the [4+2] cycloadducts. Deuterium addition in the generation of the [2+2] cycloadduct derived from 1,2-cyclohexadiene and styrene shows that the addition proceeds in a stepwise fashion 137 . The chemistry of the strained allenes is described in a recent review article 138 . For example, trapping of the strained allene 208 with the dienes 209 used as solvent affords mainly the [2+2] cycloadducts 210 and 211 and a small amount of the [4+2] cycloadducts 212 139 . R2 + R

R4

R3 R2

R3

1

208

R 209

R2

R4

1

+

R3 +

R3 R

210

R4

R4

R2

1

R

211

1

212

The [2+2] cycloadducts are also obtained when cis-1,3-pentadiene, trans, trans-2,4hexadiene, 2,3-dimethylbutadiene and vinylbicyclo[4.2.0]oct-1-ene, styrene and furan are used to trap the strained allene 208 (R = H). Trapping the bicyclic allene 213 with styrene, 1,1-diphenylethylene, furan and several 1,3-dienes also affords [2+2] cycloadducts, such as 214 140 . Ph2C

+

CH2 Ph Ph

213

214

Trapping cyclohexa-1,2,4-triene 215 with styrene to give the [2+2] cycloadduct is not observed. However, by generating 215 in furan a 30 % yield of the Diels–Alder adduct 216 is obtained 141 . + 215

O

O 216


429

Also, generation of the heterocyclic strained allene 217 in diolefins 218 used as solvents affords the cycloadducts 219 and 220 142 . R1 O

R1

O

+ 217

R2 R2

+

R1

O

R2

218

219

220

R1

R2

Yield of 219 (%)

Yield of 220 (%)

H Me Me

H H Me

60 42 52

18 2 —

Using styrene to trap the strained allene 217 produces a 10:1 mixture of exo and endo8-phenyl-3-oxabicyclo[4.2.0]oct-5-ene in 53 % yield. The cycloadduct of 217 and furan is obtained in 21 % yield. An isomeric strained heterocyclic allene is also trapped with olefins 143 . The nitrogen-containing strained heterocyclic allene 223 is similarly trapped with styrene, 1,3-butadiene, furan, cyclopentadiene and cyclohexa-1,3-diene to give [2+2] cycloadducts, such as 224 144 . +

RN

PhCH

Ph

CH2

RN

223

224

1-Methyl-1-azacyclohexa-2,3-diene is also trapped with styrene to give three isomeric [2+2] cycloadducts 145 . 1-Azacyclohexane-2,3.5-trienes and thiacyclohexane-2,3,5-triene are also generated in situ, but olefin trapping experiments were not conducted 146 . In a similar manner, strained cyclic allenes with another double bond adjacent to the cumulene system are also generated in situ. In this manner, isobenzene and isonaphthalene are generated and trapped with olefins to give [2+2] or [4+2] cycloadducts 147 . The [2+2] cycloaddition reaction of ketenes with allenes usually proceeds across both of the allene double bonds in substituted allenes and the C C bond of the ketenes (see Chapter 4, Section 4.1).

Across C O Bonds The photochemical [2+2] cycloaddition reactions of allenes with aldehydes and ketones respectively, afford the four-membered ring cycloadducts, which usually add a second equivalent of the ketone to give dioxaspiro[3,3]heptanes. For example, from tetramethylallene and acetone, the [2+2] cycloadduct 225 (8 %) and the spiro compounds 226 (57 %) and 227 (27 %) are obtained 148 . O Me2C

C

CM2

+

MeCOMe

+ O 225

O +

O 226

O 227

430


In the reaction of the allenoates 228 with aryl aldehydes, the [2+2+2] cycloadducts 229 are obtained in 47–99 % yields 149 . Ar CH2

C

CHCOO-i-Pr

+

2

O

ArCHO

O

Ar CO2i-Pr 228

229

In contrast, reaction of allenoates with aryl aldehydes, in the presence of PMe3 and MeOH, affords the cycloadducts 230 150 . O C

CH2

CHCOOMe

+

ArCHO

+

O

MeOH

OMe

Ar 230

The reaction of ethyl allenoate 231 with the enone 232 in the presence of 2-phospha-[3]ferrocenophanes affords the [3+2] annulation product 233 in 85 % yield (80 % ee) 151 . EtO2C

O CH2

C

CHCOOEt

O

+ Ph

Br

Br Ph

231

232

233

The gold-catalyzed cyclization of malonates 234 affords the δ-lactones 235 in 61–99 % yields 152 . MeO MeO2C R1

O O

MeO2C

R2 •

O

R1

R3

234

R2 R3

235

The intramolecular photocyclization of the cyclic ketones 236 gives rise to the formation of the bicyclic adduct 237 in 90 % yield. The reaction most likely proceeds via an intermediate diradical 153 .

O • 236

O

• O • 237


431

In the presence of TiCl4 , the silylallenes 238 react at −78 ◦ C with unsaturated ketones to give the annulated adducts 239 in 67–78 % yields 154 .

Me3SiC(R1)

C(R2)R3

C

O

OTiCl4

O

R1

R1 SiMe3

+

SiMe3

R

R R2

R3

2

R

238

3

R

239

The polar allenes 1,1,3,3-tetradimethylamino- 240 (R = R1 = NMe2 ) and 1,3dimethylamino-1,3-diethoxyallene 240 (R = NMe2 , R1 = EtO) react with carbon dioxide to give the switter ionic 1:1 adducts 241 155 . R

+

R1 RR1

C

1

C

CRR

+

R R1

CO2 O

240

O 241

In contrast, allene reacts with carbon dioxide, in the presence of palladium complexes, to give mixtures of the lactone 242 and the esters 243 and 244 156 . O CH2

C

CH2

+

CO2

+

O

+

O

O

O 242

O

O

243

244

However, in the reaction of allene with carbon dioxide in the presence of [RhCl(C2 H4 )– (i-Pr)2 ] the [2+2] cycloadduct 245 is obtained 157 . CH2-C

CH2

+

O

C

O O

O

245

Across C S bonds Allenes undergo a thermal and a photochemical [2+2] cycloaddition reaction with thioketones to give four-membered ring heterocycles. For example, irradiation of tetramethylallene and thiobenzophenone in benzene affords the [2+2] cycloadduct 246 in 64 % yield. As the result of the thermal reaction the linear adduct 247 was formed in 36 % yield 158 . Me2C

C

Me2

+

Ph2C

S

+ S 246

Ph2

CH2

C(CH3)C(SCHPh2)

CMe2

247

From xanthione and tetramethylallene two isomeric [2+2] cycloadducts are obtained in 68 % yield. The photochemical reaction of methoxyallene with thiobenzophenone affords a mixture of the [2+2] cycloadduct 248 and the cycloadduct 249, involving one of the aromatic rings of thiobenzophenone. Both products are formed in about 15–20 % yields.

432


From xanthene-2-thione the [2+2] cycloadduct is obtained in 34 % yields 159 .

H OMe MeOCH

C

CH2

+

Ph2C

S

S

+ S

OMe

Ph2 H

248

249

Mixtures of the two [2+2] cycloadducts 250 and 251 and the two cycloadducts 252 and 253 are obtained from arylallenes 160 . H

H

Ar

Ar + S

Ph2

S

250 ArCH

C

CH2

+

Ph2C

Ph2

251

S + S

S Ar H

Ar 252

253

In the thermal reactions of xanthenethione with allenes, CH2 C C(X)R (X = NMe2 , t-BuO, t-BuS, Ph; R = H, D) at 25 ◦ C, [2+2] and [4+2] cycloadducts are obtained in yields of 80–95 % 161 . Across C N bonds The [2+2] cycloaddition reaction of 1,3-di-t-butyl-1,3-dicyanoallene with the azomethine PhCH NR affords 254 in 60 % yield. From the same allene and Me2 NCH NMe the cycloadduct 255 is obtained in 58 % yield 162 . CN

NC Ph t-Bu(CN)C

C

NR 254

C(CN)–t-Bu CN

NC Me2N

NMe 255


433

Similarly, reaction of the allene 256 with the tosylimine 257 in the presence of a Cu (i) catalyst affords the cycloadduct 258 in 90 % yield with a 97 % ee 163 .

Me3Si(OMe)C

C

CH2

+

TsN

OMe SiMe3

CHCOOEt

NTs EtO2C

256

257

258

In the reaction of allenes with C N heterocumulenes, such as isocyanates, isothiocyanates and carbodiimides, [2+2] cycloadducts or switter ionic linear 1:1 adducts are also formed. For example, from tetramethoxyallene and phenyl isocyanate the [2+2] cycloadduct is obtained 101 . Also, from tetrathiethylallene and p-toluenesulfonyl isothiocyanate the four-membered ring cycloadduct is formed 145 . In contrast, the same allene reacts with p-toluenesulfonyl isocyanate to give a [2+2] cycloadduct, which is in equilibrium with the linear switter ionic adduct. Using chlorosulfonyl isocyanate as the reagent, only a switter ionic product is formed 145 . Some [2+2] cycloadducts derived from allenes and isocyanates are listed in Chapter 3, Section 3.3.1. In the reaction of allene with phenyl isocyanate in the presence of a nickel (o) compound, the five-membered ring metallacycle 259 is obtained, which on treatment with FeCl3 affords the diamide 260, formed by an oxidative coupling reaction 164 . O NHPh CH2

C

CH2

+

PhNCO

PhNH

Ni N Ph 259

O O 260

Across carbon–metal bonds The reaction of the titanocene aluminum complex 261 with hexamethylphosphoramide gives rise to an intramolecular cyclization involving an intermediate titanoallene to give the metallacycle 262 165 . Ti(L)2Cl

•

AlMe2

TiL2

TiL2

261

262

The formation of a titanoallene as an intermediate is also observed in the reaction of the metallacycle 263 with ketones, involving a [2+2] cycloaddition reaction across the Ti C bond to give the substituted allenes 264 166 .

L2Ti +

R3R4C

O

L2Ti O

R1 R2 263

R1 R2 R 3R4

R1R2C

C

264

CR3R

+

[L2Ti

O]

434


In the reactions of the carbene complexes (CO)5 M C(OEt)Ph (M = Cr, Mo, W) with phenylallene, the [2+2] cycloadduct 265 is formed, which rearranges to give the two trimethylenemethane complexes 266 and 267 167 . OMe (CO)5M=C(OEt)Ph

+

Ph

(CO)5M

PhCH=C=CH2

Ph H 265 Ph

Ph OEt M(CO)4

+

Ph

266

OEt Ph M(CO)4 267

Reaction of either 266 or 267 with two equivalents of phenylallene gives the [3+2] cycloadduct 268. Ph 2 PhCH=C=CH2

+

OEt

266 or 267

Cr(CO)3 Ph 268

1,1-Disubstituted allenes undergo a [2+2] cycloaddition reaction across the Cr C bonds in the alkenylchromium complexes 269 to give 270, followed by a retro-reaction to give the α,β-unsaturated ketones 271 in 75–93 % yields 168 .

(CO)5Cr=C(OMe)–CH=CHPh +

R2C=C=CH2

MeO (CO)5Cr

O

Ph

R Ph

R 269

271

270

In contrast, using a rhodium complex as the catalyst, a [4+2] cycloaddition occurs with formation of the pentenyl ethers 272 in 92–93 % yields as a result of a reductive elimination. (CO)5 MeO

Cr(CO)5 + R1

R2C=C=CH2

MeO

OMe

Cr R2 R1

R1 272

R2


435

Using two equivalents of the allenes in the presence of [Rh(COD)Cl]2 , a [3+2+2] cycloaddition occurs with formation of the seven-membered ring cycloadducts 273 169 . R4

MeO (CO)5Cr=C(OMe)–CH=CR1R2

+ 2 R3R4C=C=CH2

R3

R1 R4

R2 R3 273

Across other double bonds Allenes undergo [2+2] cycloaddition reactions with azo compounds. For example, reaction of difluoroallene with diethyl azodicarboxylate affords a low yield of the [2+2] cycloadduct 274 170 . CF2

C

CH2 + EtOOCN

NCO2Et

NCOOEt

NCO2Et

F F

274

A higher yield of the [2+2] cycloadducts is obtained from tetramethoxyallene and diethyl azodicarboxylate (43 %) 171 . Reaction of the cis-like azo compound 275 with tetramethoxyallene affords the [2+2] cycloadduct 276 in 69 % yield. OMe

O (MeO)2C=C=C(OMe)2

+

N N

MeO NPh

(MeO)2

O N N

NPh

O

O 276

275

The reaction of tetramethylallene with EtOCON SO2 affords the [2+2] cycloadduct 277 and the [4+2] cycloadduct 278 172 . Me2C=C=CMe2 +

NCO2Et

EtOCON=SO2

+

O

Me2

SO2

277

N

O

O

S

OEt

278

The [2+2] cycloadduct 279 is obtained in the reaction of tetramethylallene with sulfur trioxide 173 . In contrast, a switter ionic 1:1 adduct is produced in the reaction of polar allenes with sulfur dioxide. Me2C=C=CMe2 +

SO3

O2S 279

O

436


The reaction of tetraethoxyallene with thionyl chloride proceeds with elimination of ethylchloride to give diethylthioxomalonate-S-oxide, (EtO2 C)2 C S O 174 . Allene reacts with L2 Ti O to give the [2+2] cycloadduct 280 in 58 % yield. The isolated dark green–brown crystals are stable at room temperature, but unstable in solution 175 . CH2

C CH2

+

L2Ti

L2TiO

O

280

The reaction of racemic zirconocenes 281 with racemic allenes provides the single diastereomeric products 282 176 . L Zr L Zr

NAr + RCH C

CHR1

NAr

R

R1 H

H

THF 282

281

6.1.4.3

[2+2+2] Cycloadditions

The nickel catalyzed cyclotrimerization of two equivalents of propiolates with allenes affords the [2+2+2] cycloadducts 283 in 69–86 % yields 177 . R2 MeO2C R1CH

C CH2

+

R2C

R1

CCOOMe MeO2C R2 283

The mixed oligomerization of allene and butadiene (1:10) in the presence of nickel(o) tris(2-biphenylyl) phosphite affords the ten-membered ring [2+2+2] cycloadducts 284 and 285 in a combined yield of 69 %. Heating of the cycloadducts at 150 ◦ C gives 4-methylenecis-divinylcyclohexane 286 as the result of a thermal Cope rearrangement 178 . CH2

C CH2 +

+

2

284

285

286

Similarly, 1,1-dimethylallene or methoxyallene react with excess butadiene in the presence of the Ni(o) catalyst to give the ten-membered ring cycloadducts, which were isolated as the thermal rearrangement products in about 40 % yield. A highly regio- and chemoselective [2+2+2] cycloaddition of 1,6-heptadiynes 287 with allenes in the presence of CoI2 (PPh3 )2 /Zn affords the cycloadducts 288 (X = O, CH2 ) in


437

63–90 % yields 179 . CO2Me CO2Me X

+

RCH = C = CH2

R

X

CO2Me CO2Me 287

288

Likewise, the electron deficient diyne 289 reacts with phenylallene in the presence of Ni(dppe)Br2 /Zn to give the [2+2+2] cycloadduct 290 in 90 % yield. CO2Me

Ph CO2Me

Ph

•

+

CO2Me CO2Me 289

290

Also, 1,6-heptadiynes 291 react with allenes to give the [2+2+2] cycloadducts 292 180 . R •

+

X

X

R

R

X

291

292

R1

X

Yield (%)

C6 H11 O C6 H11 C(COOMe)2

84 95

The same reaction with unsymmetrically substituted diynes produces mixtures of stereoisomers. Likewise, intramolecular cyclization of 293, using CpCo(CO)2 as the catalyst, affords the steroid skeleton 294 in 48 % yield 181 . O

Ph

O

Ph

• X 293

294

The light-induced intramolecular [2+2+2] cycloaddition reaction of the allendiynes 295, catalyzed by CpCo(CO)2 , affords mixtures of the endo adduct 296 and the exo adduct 297

438


in good yields 182 . R1

R1

R1

• +

R2 R2

R2

CoCp

295

CoCp

296

297

Similarly, the allendiyne 298 cyclizes to give the [2+2+2] cycloadduct 299 in 98 % yield (ee > 95 %). R

CoCp

• H R

P(O)Ph2

Ph2P = O

298

6.1.4.4

299


Electron deficient allenes 300 ( R = R1 = CN or COOEt) react with alkenes (R3 = R4 = CN or PhSO2 ) in the presence of a palladium catalyst as 1,3-dipoles to give the cyclopentanes 301 183 . CH2 C =C = CHCHR1R2

+

RCH = CR3R4

R3R4 1R2

R

R 300

301

R

R1

R2

R3

R4

Yield (%)

H PhSO2 PhSO2 CN CN Ph CN CN CN CN

70 71

When malononitrile is reacted with allenes in the presence of palladium catalysts, insertion into the C–H bond is observed with formation of a linear adduct 184 . Also, phosphine catalysts are used in an asymmetric [3+2] cycloaddition of carboethoxyallene 302 with enones to give the isomeric cycloadducts 303 and 304 in 54–87 % yield (% ee in 303, the major product, 87–89 %) 185 . CO2Et CH2 = C =CHCOOEt

+

COAr

RCH = CHCOAr

CO2Et R

+

R 302

303

COAr 304


439

In the reaction of allenes with diazo compounds, nitrones and nitrile oxides, typical [3+2] cycloadducts are obtained. For example, from allene and diazomethane at room temperature a mixture of 305 and 306 is obtained in 65 % yield (ratio of the isomers, 93:7) 186 . CH2 = C = CH2

+

N

CH2N2

N

+

N

N 306

305

The reaction seems to proceed in a stepwise manner as indicated by a density functional study 187 . From CD2 N2 and fluoroallene at 25 ◦ C a 54 % yield of the expected [3+2] cycloadducts is obtained in a ratio of 88:12 188 . A 95 % yield of the [3+2] cycloadducts 307 and 308 from difluoroallene and CD2 N2 was obtained. D D CF 2 = C = CH2 + CD2N2

D D F

N

N

+

N

N 307

F

308

The [3+2] cycloaddition reactions of fluoro- and 1,1-difluoroallenes with diazoalkanes also afford the cycloadducts resulting from addition across the non-substituted double bonds in high yields 189 . Likewise, allenic esters undergo cycloaddition reactions with diazoalkanes, mainly across the double bond containing the ester substituent 190 . Also, methyl- and 1,1-dimethylallenes react with diazomethane across the unsubstituted double bonds to give the expected [3+2] cycloadducts 191 . From fluoroallene and N-t-butylnitrone at room temperature (5 days) a mixture of the [3+2] cycloadducts 309 and 310 is obtained in 83 % yield (ratio of isomers 3.6:1) 214 . F N = CHPh

+ CHF = C =CH2

F

Ph

Ph

+

N O

N O

O 309

310

In the reaction of difluoroallene with the same nitrone a 95 % yield of only one [3+2] cycloadduct 311 is obtained 214 . F N = CHPh +

CF2 = C =CH2

F

N O

O 311

440


From phenyl- (75 % yield) and mesitylnitrile oxide (94 % yield) and difluoroallene, mixtures of the isomeric [3+2] cycloadducts 312 and 313 are isolated 214 . F RC

O +

N

CF2= C = CH2

F

F +

R

F O N

N O R 312

313

In all the cycloaddition reactions of fluoroallene and difluoroallene, such reactions occur across the unsubstituted C C bond. Also, dichloromesitonitrile oxide undergoes a [3+2] cycloaddition reaction with the substituted allene 314 to form the cycloadduct 315 192 . RC

O +

N

Ph2NCH = C= CH2

R N O

314

H NPh2

315

The strained allene 316, generated in situ at −78 ◦ C, reacts with 2,4,6trimethylbenzonitrile oxide across the C P bond to give the cycloadduct 317 in 72 % yield 193 . P P

P

O +

RN

N

O

N

P R

316

317

A nitrile oxide tethered to an allene, generated in situ, undergoes an intramolecular cycloaddition reaction to generate a key intermediate in the synthesis of hyperforins 194 . The intramolecular cycloaddition of allenylazides affords pyrrolidine-containing bicycles and tricycles in good yields 195 . The [3+2] cycloaddition of the alkenyl Fischer carbene complexes 318 with the allenes 319, catalyzed by a Rh(i) catalyst, affords the alkylidenecyclopentanones 320 in 47–99 % yields in a stereoselective manner 196 . (CO)5Cr = C(OMe)–CH = CHR + CH2 = C = CHNR1R2 NR1R2

R 318

319

320

Also, spirocycles are obtained in the phosphine-catalyzed [3+2] cycloaddition of cyclohexenone derivatives with allenoates. This reaction is utilized in the total synthesis of (−) hinesol 197 .


441

A highly diastereoselective [3+2] cycloaddition reaction of the enoates 321, catalyzed by PBu3 , with N-tosylimines affords the pyrroline derivatives 322 in 95– > 99 % yields 198 . Ts N

R +

RCH C CHCOOEt

Ar

CHAr

TsN

CO2Et 321

322

However, from the allenoate 323 the six-membered ring [4+2] cycloadduct 324 is obtained in very high yield 199 . Ts N

R CH2

C C (Me)COOEt +

TsN CHR CO2Et

323

324

In the Cu(i) catalyzed reaction of the 1-alkyl substituted allenylsilane 325 with tosyl imines in refluxing benzene a 92 % yield of the [3+2] cycloadduct 326 is obtained 200 . Me Pr3Si(Me)C C CH2

+

Ts N

TsN CHCOOEt

CO2Et

i-Pr3Si 325

326

Intramolecular palladium-catalyzed [3+2] cycloaddition reactions of the allenes 327 across the cyclopropyl substituted double bonds afford two isomeric cycloadducts 328 and 329 in high combined yields 201 . R1 • X

H

R2

H

X

+ H R2

327

R1

328

R

R1

X

Me H H

Me Me Me

C(COOEt)2 C(COOEt)2 NCHPh2

X H R2

R1

329

Ratio, 328:329

Yield (%)

6:1 14:1 20:1

80 90 77

Interestingly, the cyclopropyl ketones 330 react with the silylallenes 331 in the presence of Lewis acid catalysts to give the [3+2] cycloadducts 332 and the [3+3]

442


cycloadducts 333 202 . SiR 3 O

R2

R1

TBDPS

R3Si(R2)C C CH2

+

R1 O

330

TBDPS

331

332 SiR 3 R2 +

R1

TBDPS O 333

A [3+2] cycloaddition reaction of the vinylidene cyclopropanes 334 with MeCN does not proceed across either one of the C C bonds, but occured via ring opening to form the cycloadduct 335 203 . R2C C C

+

MeCN

•

R2C

N Me 334

335

The triphenylphosphine-catalyzed [3+2] cycloaddition reaction of allenyl ketones to cyclic enones affords spirocyclic adducts. For example, from 336 and the allenyl methyl ketone 337 the cycloadducts 338 and 339 (ratio 55:45) are obtained in 84 % yields 51 . Using chiral phosphines, ees of 53–71 % are observed. O O

O +

BzO

MeCOCH

C CH2

O

BzO

336

O

337

338 O + BzO

O

O

339

Some spirocyclic compounds obtained in the reaction of exo-methylenecycles and allenoates are shown in Table 6.9 204 . Also, a cobalt-catalyzed diastereoselective reductive [3+2] cycloaddition of allenes to enones is observed. Thus phenylallene reacts with methyl vinylketone 340 in the presence of CoI2 (dppe)/Zn and ZnI2 , to give the cyclopentane derivative 341 in 88 % yield 205 . OH

O H PhCH C CH2

+

Ph 340

341


443

Table 6.9 [3+2] Cycloadducts from exo-methylenecycles and allenoates Substrate

Cycloadducts

O

Yield (%)

Ratio

93

79:21

98

84:16

94

82:18

96

65:35

O

O CO2Et

CO2Et O

O

O CO2Et

CO2Et O

O

O TsN O BzN O

TsN

TsN

CO2Et O

BzN NBz

CO2Et

O

O

CO2Et

NBz

BzN O

NBz CO2Et

The two-step formal [3+2] cycloaddition reactions of enones or enals with allenylethers afford cyclopentenone derivatives. For example, reaction of the masked enalallene 342 at room temperature in the presence of a gold catalyst affords the bicyclic aldehyde 343 in 90 % yield 206 . OTMS OMOM

O

H

• H 342

343

The photocycloaddition of allene-tethered enones, like 344, affords the expected adducts 345 in 67–90 % yields. The reaction proceeds with an enantioselectivity of > 99 % 207 . SiMe3 •

H O

O H

SiMe3 H

O 344

O 345

In the intramolecular [3+2] cycloadditions of enones and benzyl allenyl ethers in the presence of AuCl, benzyl protected phenols are formed. For example, from 346, generated

444


in situ, the phenol ether 347 is obtained in 99 % yield 208 . O OBz

OBz

• 346

347

The gold-catalyzed cyclization of the N-allenylanilines 348 at room temperature affords the hydroquinoline derivatives 349 in 92 % yields 209 . OMe

OMe •

MeO

N

MeO

N

CO2Me

CO2Me

348

349

The 2-styryl allenoates 350 undergo an intramolecular stereoselective [3+2] cycloaddition in the presence of phosphine catalysts to give cyclopentene-fused dihydrocoumarins 351 210 . EtO2C CO2Et •

R

350

O

H O

O

O

351

R

Yield (%)

H 3-Me 4-MeO

96 98 94

Also, the allenoates 352 react with diketones in refluxing toluene in the presence of PPh3 to give the cycloadducts 353 in 84 % yields 211 .

CH2

C CHCOOMe

+ O

O

O

O CO2Me

352

353

The intramolecular version of this reaction is also known. The allene 354, generated in situ, undergoes cyclization in the presence of PPh3 to give the furan derivatives 355 in


445

60–86 % yield 212 . R2

CO2Et

O

H •

R1

R1

EtO2C

354

R2 O 355

The [3+2] cycloaddition reactions of the allenes CH2 C CHR3 (R3 = CN, COOEt) with 3,4-dihydroisoquinoline-N-oxides 356 give the cycloadducts 357 and 358 213 . MeO

MeO N

R1 R

O +

CH2 C CHR3

N

R1

O

R2 R3

2

356

357 MeO +

N

R1

O

R2 R3 358

+

Tetraphenylallene reacts with RN N [3+2] cycloadduct 359 in high yield 214 .

NR (R = 2,4,6-trichlorophenyl) to give the N RN

Ph2C C Ph2 +

RN N+

NR

Ph

SbCl6 NR Ph2

Ph 359

Generation of the allenes 360 in situ affords the benzoazepinones 361 in good yields via intramolecular cycloadditions 215 . R H

N

R O

H

N

R O

N O

H R1

360

6.1.4.5

•

R1

R1 361


In the reaction of allenes with dienes, such as cyclopentadiene, [4+2] cycloadducts are obtained. From allene at 200–230 ◦ C only a 49 % yield of the [4+2] cycloadduct is obtained, while fluoroallene reacts at 0 ◦ C for 4 days to give a 99 % yield of a mixture of two isomeric cycloadducts in a ratio of 1:1. In contrast, difluoroallene reacts even faster with cyclopentadiene (1 min at −20 ◦ C) to give the [4+2] cycloadduct in 99 % yield. In contrast, 1,3-butadiene, on reaction with difluoroallene at 110 ◦ C, affords mixtures of the [4+2]

446


cycloadduct 362 (63 %) and the [2+2] cycloadducts 363 (37 %) and 364 (< 2 %) 204 . F

F CF2 C CH2

+

+

F

F

+ F2 363

362

364

Some other cycloaddition reactions obtained from allenes and dienes are listed in Table 6.10. Vinylallene reacts with 1,3-dienes in the presence of Pd(PPh3 ) to give high yields of the [4+2] cycloadducts 365 221 . R

•

+

R 365

In vinylallenes with a pendant phenyl or vinyl substituent eight-membered ring carbocyclic byproducts are formed by a head-to-head [4+4] cycloaddition 222 . From 1,2,4-cyclohexatriene and 2,5-dimethylfuran or furan, [4+2] cycloadducts are also obtained. Similarly, trapping of the strained allene 366 with diphenylbenzofuran affords the two isomeric [4+2] cycloadducts 367 and 368 in low yields 223 .

Ph

Ph

O

Ph +

+

O O

Ph

Ph Ph

366

367

368

Trapping of isonaphthalene 369 with furan also affords two isomeric cycloadducts 370 (11 % yield) and 371 (8 % yield) 224 .

O +

+

O

O 369

370

371


447

Table 6.10 [4+2] Cycloadducts derived from dienes and allenes Diene

Allene

Adduct

Yield (%)

Reference

80

216

58, 36

216

87

220

100

217

86 (9:1)

218

74

219

82

220

H CO2Et CO2Et

EtO2 CCH C CHCO2 Et

+ H NCS

CH2 C CHN C S

NCS

H CO2Et

O O

CO2Et

EtO2 CCH C CHCO2 Et

O O

SO2CCl3

CCl3 SO2 CH C CH2 O

O

O O

O

NC

•

CO2Et

MeOCH C CH2

O

O

OMe

CO2Et

SO

S O

O

NC

O

O +

CH2 C CH CO2 Et

CO2Et

While numerous other strained allenes are similarly trapped, they are not treated here because the yieds are usually rather low. Allenyl ions 372 undergo [4+2] cycloaddition reactions. For example, from allenyl cations, formed in the reaction of propargyl halides with zinc chloride at −30 to −50 ◦ C and cyclopentadiene the [4+2] cycloadducts 373 (R1 = alkyl) or the [4+2] cycloadducts

448


374 (R1 = aryl) are formed 225 .

R1-C C+–CR22

X–

R2 R2 X

+

+

R22

X 1

CR R1 373

372

374

R1

R2

X

Yield of 373 (%)

Yield of 374 (%)

Me Et Ph

Me Me Me

Cl Cl Cl

36 28 —

— — 65

The [4+2] cycloadducts are also obtained in the reaction of propargyl halides and cyclopentadiene in the presence of silver trifluoroacetate 226 . The [4+2] cycloadduct 375 is also obtained in 91 % yield in the reaction of trichloroallenyl lithium with carbon dioxide at –90 ◦ C, followed by quenching with cyclopentadiene, and hydrolysis at ambient temperature 227 .

Cl CCl2 C CClLi

+

CO2

Cl Cl

[CCl2 C C(Cl)COOLi]

COOH 375

Electron-poor dienes, such as 376, react with 1,1-dimethylallene across the substituted double bond of the allene to give the [4+2] cycloadduct 377, which loses carbon monoxide to form the cyclohexadiene derivative 378 228 .

Ph Ph

Ph +

Ph

O 376

Ph

Ph

Ph

Ph O

Me2C C CH2 Ph

Ph Ph

Ph

377

378


449

An intramolecular [4+2] cycloaddition is observed on heating of the allenecarboxamides 379 to give the Diels–Alder adducts 380 229 . R2

R2

R3

•

H

O

R3

O

N

R1

N

1

R

379

380

R1

R2

R3

Yield (%)

Me Me

H Me

H H

90 87

Intramolecular [4+2] cycloadditions of the allenamides 381 (X = CH2 , NMe and O) with α,β-unsaturated enones in the presence of ZnCl2 afford the [4+2] cycloadducts 382 in 40–62 % yields 230 . O O

R N

R

O

O

N

X

+

•

X

381

382

Likewise, the allenamides 383 react with vinylketones or propenals to give the [3+2] cycloadducts 384 in good yields 231 . O N O

R Ph

N

O

+

N

N

Ph

•

H

R

O

383

384

N-(2-Thienyl)allene carboxamides 385 also undergo intramolecular Diels–Alder reactions to produce the 2-indoline derivatives 386 in 73 % yields 232 . O Ph Ph

N S • 385

O

Ph

S

N

O N

Ph Ph

Ph 386

The intramolecular variant of the Diels–Alder reaction of tethered furans with allenylsulfones 388 is also known. For example, treatment of furfurylpropynyl sulfone 387 with

450


a catalytic amount of aluminum oxide resulted in rearrangement to 388 which forms the cycloadduct 389 in 89 % yield. 233

O

O

R

R O

SO2

SO2

•

387

S

O

O 389

388

In a similar manner, the carbomethoxyallene 390 undergoes the intramolecular cycloaddition reaction at room temperature to form the cycloadduct 391 as a single diastereomer 234 . OH

OH O

O OH

•

OH CO2Et

CO2Et

390

391

Furanoketoallenes 392 on heating in benzene, afford a 5:4 mixture of the isomers 393 and 394 235 . O •

O

+

O O

H O

O 392

H

393

394

The optically active allene 395 undergoes the intramolecular [4+2] cycloaddition under basic conditions to give 396 in 98 % yield 236 . O S

S

S O

S

HO

O •

395

396

When a nitrogen atom is present on the tether, a furan–pyrrole exchange reaction can occur. For example, the furfuryl allene 397 cyclizes at 40 ◦ C under basic conditions to form the hydroisoindole 398 237 . BOC

BOC

N •

BzO

N BzO

O Me 396

Me 398

OH


451

Also, double-furan-transfer reactions occur in the sequential cycloaddition of 399 to give 401 via the intermediate allene 400 238 . O

O

O

O

•

O O

O

HO

HO OH

399

OH

400

401

This type of chemistry was applied to the synthesis of euryfuran 239 and xestoquinone 240 , as well as spongiaditerpenoids. The optically active allenic ketone 402, in the presence of Me2 AlCl, undergoes cyclization to afford the cyloadduct 403 in 91% yield 241 . O

O Me Me

•

Me

O

O Me

Me

Me

Me

Me

402

403

Transition metal catalyzed intramolecular [4+2] diene–allene cycloadditions provide 6,6- and 6,5-fused ring systems in good yields under mild conditions. 242 For example, from the tethered allene 404 in the presence of Ni(COD)2 as the catalyst a 97 % yield of the cycloadduct 405 is obtained resulting from addition to the terminal allene double bond. From the same substrate, using [Rh(COD)Cl]2 as the catalyst, the hydrindane derivative 406 is obtained in 90 % yield. OTs

OTs

OTs or

•

404

405

406

The reaction proceeds with numerous unactivated tethered allenes as demonstrated by the examples shown in Table 6.11. In these examples some of the reactions proceed across the substituted allene double bonds. A regioselective hetero Diels–Alder reaction occurs in the generation of the nitrosoalkenes 407 in situ in the presence of the allenes, RC(MeO) C CH2 (R = H, CF3 , COOEt, Ph), at 20 ◦ C. The initially formed [4+2] cycloadducts 408 isomerize in the presence of triethylamines to give the 6H-1,2-oxazines 409 243 . N

O

N +

RC(OMe)

C

O

CH2 R

R 407

R OMe

N

O

R 408

409

R OMe

452


Table 6.11 Transition metal catalyzed intramolecular [4+2] cycloadditions Diene–allenea

Cycloadduct

Catalyst

O

Yield (%)

O

• O

•

O

O

[Rh(COD)Cl]2

98

[Rh(COD)Cl]2

94

O

•

•

• a

O

O

E E

E E

Rh(CH2 CH2 )2 Cl

87

E E

E E

Rh(CH2 CH2 )2 Cl

87

Rh(CH2 CH2 )2 Cl

89

E E

E E

E = CO2 Me.

The thermal intramolecular cycloaddition of the allene 1,3-dicarboxylate 410 affords the [4+2] cycloadducts 411 in 95 % yields 244 .

O

O H

O

• R1

R R

O

CO2Me

R1

CO2Me

R R 410

411

Likewise, the base-catalyzed intramolecular cycloaddition reaction of the allene 412, generated in situ, affords the [4+2] cycloadduct 413 when R = H. When R is not H, an intramolecular [2+2] cycloaddition occurs, followed by a [3,3] sigmatropic rearrangement


453

to give 414 245 . •

O

O

O

R

or

R

412

R

413

414

Likewise, the intramolecular [4+2] cycloaddition reaction of S-cis 415 (R = H) affords the tricyclic adduct 416, while the S-trans 415 (R = Me) affords the [2+2] cycloadducts 417 (44 % yield) and the [4+2] cycloadduct 418 (24% yield) 246 . O2S •

O2S

R

R 416

415 O2S

O2S

Me

Me

+

417

418

The allenyldiene 419 also undergoes an intramolecular Diels–Alder reaction to give the tricyclic adduct 420 247 . • H

CO2Et H

CO2Et H

420

419

The [4+2] cycloaddition reacton of vinyl allenes and aldehydes is catalyzed by BF3 . For example, from the vinyl allene 421 and benzaldehyde a 74 % yield of 422 is obtained 248 . H

H • Ph

Ph +

421

PhCHO O

Ph

422

The intramolecular version of this reaction is also known. The vinyl allenes 423, with tethered aldehyde groups, in the presence of a Lewis acid catalyst, afford the cycloadducts

454


424 249 . R

R • 423

(CH2)n

(CH2)n

O

O

H

424

The methanol-assisted reactions of allenoates with aromatic aldehydes in the presence of phosphine catalysts afford the dihydropyrones 425 in 36–83 % yields 250 . O O CH2 C CHCOOMe +

ArCHO

+

MeOH

OMe

Ar 425

When the reaction is catalyzed by tricyclopentylphosphine the annulation products 426 are obtained in moderate to excellent yields 251 . R CH2 C

O

O

CHCOOEt + RCHO 426

R

Yield (%)

3-ClPh 4-CF3 Ph 3-MeOPh

91 82 69

The phosphine-catalyzed [4+2] annulation of allenoates with activated olefins 427 affords the annulation products 428 or 429 depending on the phosphine catalyst being used 252 . R

NC CN NC

R CH2

C

CHCOOEt

+

RCH

C(CN)2

+

NC

CO2Et 427

CO2Et

428

R Ph 4-MeOPh 4-MeOPh 4-BrPh

429

Yield of 428 (%) Yield of 429 (%) 98 94 — —

— — 90 84

From the vinyl allene 430 and diethyl azodicarboxylate the [4+2] cycloadduct 431 is also obtained in 60 % yield. H •

+

EtOOC–N

N–COOEt N

N CO2Et

CO2Et 430

431


455

Likewise, vinyl allenes 432 react with imines in the presence of Lewis acids to give the [4+2] cycloadducts 433 in good yields and as single isomers 253 . R1

R1

R2

2

R

•

+

R3

R3

R4CN

NBz R4

N Bz 432

433

Likewise, the allenoates 434 react with N-tosylaldimines to afford the tetrahydropyrimidines 435 254 . Ts N

R CH2

C

C(CH2R)COOEt

+

R1CH

NTs CO2Et

434

435

R1

R

Yield (%)

Ph Ph 4-MePh 3-MeOPh

99 99

Diels–Alder cycloadditions are also obtained when vinylallenes are reacted with maleic anhydride. For example, from 436 and maleic anhydride, in the presence of Lewis acids at room temperature, the cycloaducts 437 are obtained in 75–94 % yields. R1

R1

O

R2

R2

•

R

3

R3 +

O O O O

436

O

437

The azadiene 438 reacts with allenoates on refluxing in benzene to produce the Diels–Alder products 439 in 78–97 % yields. However, on standing at room temperature for over 40 days the [2+2] cycloadducts 440 are also obtained 255 . Ph

Ph +

RCH

C

CO2Et

CHCOOEt

N

N

Ar

Ar 439

438

Ph

NAr

or

CH2R

CO2Et H 440

456


Likewise, the 1-thia-3-azabutadiene 441 underwent stereoselective [4+2] cycloaddition reactions with allenoates to produce the heterocycles 442 256 . Ph

S

S

Ph +

CH2

C

CHCOOEt

N

CO2Et

N

N

441

442

Cycloaddition reactions of dienes with allenes are used in the synthesis of natural products. For example, the [4+2] cycloaddition reaction of the furan-tethered diene 443 with the allene 444 affords the carbon framework of the eleutherobin aglycone 445 257 . H +

i-PrCH

CHCOC(CH2OTBS)

C

CH2

O

O

H i-Pr O 444

443

OTBS

445

Also, cycloaddition of the diene 446 with 3-methylallenoate affords 447, which is used in a key step in the synthesis of (−) dysidiolide 258 . O TBS

OTBS

OBz +

CH2

C

OBz

C(Me)COOEt EtO2C

446

Me

447

The heterocyclic allenyldienes 448 react similarly to form the intramolecular Diels–Alder adducts 449 259 . O

O N

O • 448

N 449

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460 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210. 211.

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1,2,3-Tricarbon Cumulenes 212. 213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259.

461

C. Jung, J. Wang and M.J. Krische, J. Am. Chem. Soc. 126, 4118 (2004). Bao-Xiang Zhao and S. Eguchi, Tetrahedron 53, 9575 (1997). W. Wirschun, G. Maier and J.C. Jochims, Tetrahedron 53, 5755 (1997). K. Knobloch, M. Keller and W. Eberbach, Eur. J. Org. Chem. 3313 (2001). K. Bauert, Ann. Chem. 2005 (1997). S. Braverman and Z. Lior, Tetrahedron Lett. 35, 6725 (1994). F. Fotiadu, A. Archarlis and G. Buono, Tetrahedron Lett. 31, 4859 (1990). N.P. Parri and M.L. Trudell, Tetrahedron Lett. 38, 7893 (1997). T. Thiemann, H. Fujii, D. Ohira, K. Arima, Y. Li and M. Mataka, New. J. Chem. 27, 1377 (2003). M. Murakami, K. Itami and Y. Ito, J. Am. Chem. Soc. 119, 7163 (1997). M. Murakami, K. Itami and Y. Ito, Synlett 951 (1999). B. Miller and X. Shi, J. Am. Chem. Soc. 109, 578 (1987). S. Groetsch, J. Spuziak and M. Christl, Tetrahedron 56, 4163 (2000). H. Mayr and I.K. Halberstadt, Angew. Chem. 92, 840 (1980). H. Mayr and B. Grubmüller, Angew. Chem. 90, 129 (1978). G. Köbrich and E. Wagner, Angew. Chem. 80, 481 (1968). D.J. Pasto, Tetrahedron Lett. 21, 4787 (1980). G. Himbert and L. Henn, Angew. Chem. 94, 631 (1982). L.L. Wei, H. Xong, C. Douglas and R.P. Hsung, Tetrahedron Lett. 42, 6903 (1999). L.L. Wei, R.P. Hsung H. Xiong, J.A. Mulder and N.T. Nkausah, Org. Lett. 1, 2145 (1999). G. Himbert, H.J. Schlindwein and G. Ma, J. Chem. Soc., Chem. Commun. 405 (1990). K. Kanematsu and I. Kinoyama, J. Chem. Soc., Chem. Commun. 735 (1992). G. Appendino, J. Hoflack, P.J. De Clercq, G. Chiari and M. Calleri, Tetrahedron 44, 4605 (1988). S.G. Cauwberghs and P.J. De Clercq, Tetrahedron Lett. 29, 6501 (1988). K. Kanematsu, A. Nishizaki, Y. Sato and M. Shiro, Tetrahedron Lett. 33, 4967 (1992). M. Lee, H. Moritomo and K. Kanematsu, Tetrahedron 52, 8169 (1996). Y. Yamaguchi, H. Yamada, K. Hayakawa and K. Kanematsu, J. Org. Chem. 52, 2040 (1987). K. Kanematsu, S. Soejima and G. Wang, Tetrahedron Lett. 32, 4761 (1991). Y. Baba, T. Sakamoto and K. Kanematsu, Tetrahedron Lett. 35, 5677 (1994). M.E. Jung and S. Min, J. Am. Chem. Soc. 127, 10834 (2005). P.A. Wender, T.E. Jenkins and S. Suzuki, J. Am. Chem. Soc. 117, 1843 (1995). R. Zimmer and H.U. Reissig, Angew. Chem. 100, 1576 (1988). M. Yoshida, Y. Hidaka, Y. Nawata J.M. Rudzinski, E. Osawa and K. Kanematsu, J. Am. Chem. Soc. 110, 1232 (1988). K. Hayakawa, K. Aso, M. Shiro and K. Kanematsu, J. Am. Chem. Soc. 111, 5312 (1989). S. Yeo, M. Shiro and K. Kanematsu, J. Org. Chem. 59, 1621 (1994). N. Khan, L. Larsen and J.K. Sutherland, Tetrahedron 49, 8233 (1993). D. Regas, J.M. Ruiz, M.M. Alfonso and A.J. Palenzuela, J. Org. Chem. 71, 9153 (2006). D. Regas, J.M. Ruiz, M.M. Alfonso, A. Galindo and J.A. Palenzuela, Tetrahedron Lett. 44, 8471 (2003). G.S. Creech and O. Kwon, Org. Lett. 10, 429 (2008). X. Zhu, A, Schaffner, R.C. Li and O. Kwon, Org. Lett. 7, 2977 (2005). Y.S. Tran and O. Kwon, J. Am. Chem. Soc. 129, 12632 (2007). D. Regas, M.M. Alfonso, M.L. Rodriguez and J.A. Palenzuela, J. Org. Chem. 68, 7845 (2003). X. Zhu, J. Lan and O. Kwon, J. Am. Chem. Soc. 125, 4716 (2003). M.P.S. Ishar, K. Kumar, S. Kaur, S. Kumar, N.K. Girdhar, S. Sachar, A. Marwaha and A. Kapoor, Org. Lett. 3, 2133 (2001). M.P.S. Ishar, A. Kapur, T. Raj, N.K. Girdhar and A. Kaur, Synlett 775 (2004). J.D. Winkler, K.J. Quinn, C.H. MacKinnon, S.D. Hiscock and E.C. McLaughlin, Org. Lett. 5, 1805 (2003). M.E. Jung and N. Nishimura, Org. Lett. 3, 2113 (2001). P. Magnus, J. Rodriguez-Lopez, K. Muhlholland and I. Matthews, Tetrahedron 49, 8059 (1993).

462


6.2

[3] Cumulenes, R2 C C C CR2

6.2.1 Introduction ˚ The [3] and [5] cumulenes have a linear structure 1 . Their terminal double bonds are 0.02 A shorter than in cumulenes with straight numbered carbon atoms. Therefore the shown mesomeric structures can contribute to the observed reactions. C–C+

C C C C

C–C

C–C

C–C+

1,2,3-Cyclooctatriene is the first stable strained butatriene generated in situ and trapped with 2,5-dimethylfurane 2 . The instability of the butatrienes is evidenced by the free radical polymerization of bis(pentamethylene)butatriene on heating in THF in the absence of air or light 3 . The cyclodimerization of butatrienes, [3]cumulenes, usually affords tetramethylenecyclobutanes (radialenes). In contrast, [5]cumulenes afford head-to-tail dimers. In [2+2] cycloaddition reactions of the higher cumulenes, reaction usually occurs across one of the double bonds. In the reaction of hexapentaenes with fluorinated olefins the center C C bond is involved, while C S double bond-containing substrates add across the substituted double bonds. Linear and macrocyclic butatrienes also undergo cycloaromatization via diradicals, i.e. they undergo DNA cleavage reactions similar to allenes. Strained butatrienes are trapped with dienes to give [4+2] cycloadducts. The ring strains in cyclic butatrienes decrease with ring size 4 . 6.2.2 Dimerization Reactions The dimerization of butatrienes often proceeds across the center double bonds to give tetramethylenecyclobutanes (radialenes). The unsubstituted butatriene is unstable and already below 0 ◦ C a violent reaction occurs with formation of oligomeric products. From the reaction mixture a [4+4] cyclodimer is isolated in 2 % yield 5 . Perfluorobutatriene also undergoes violent decomposition above −5 ◦ C 6 . In contrast, perchlorobutatriene and substituted butatrienes afford radialene dimers, often in good yields (see Table 6.12). The oldest example of this reaction is the dimerization of tetraphenylbutatriene 1, which occurs in the solid state upon exposure to sunlight to give the cyclodimer 2 7 . Ph

Ph Ph

Ph Ph2C

C

C

CPh2 Ph

Ph Ph

Ph 1

2

The radialene structure of this cyclodimer was elucidated in 1974 11 . The photo dimer derived from Ph2 C C C C(CF3 )2 has a different structure 3, as evidenced by C13 -NMR spectroscopy 8 .


463

Table 6.12 Several [4] Radialenes obtained from Substituted Butatrienes Butatriene

[4] Radialene Cl

Reference

50

12

94a

8

62

8

75b

13

32

14

Cl

Cl

Cl Cl

Cl Cl

Cl2 C C C CCl2

Yield (%)

Cl

Me2 C C C CMe2

C C

Ph

Ph

EtO2C Ph

Ph C

EtO2C

a b

C C

CO2Et CO2Et

EtO2C

C CO2Et

Ph

Ph

Crude yield. When the dimerization was conducted at 100 ◦ C for 5 days, in refluxing toluene only 32 % of the radialene is obtained.

Ph2C

C

C

•

Ph2

C(CF3)2 CF3

CF3 CF3

Ph2

•

CF3 3

The tetramethyl [3] cumulene, generated in situ, undergoes oligomerization in the presence of Ni(PPh3 ) to give the [4] radialene, in 6.5 % yield, in addition to the cyclotrimer, which is formed in 38 % yield 9 . The same [4] radialene dimer is also obtained in high yield, when 2,5-dimethyl-2,3,4-hexatriene is reacted in THF in the presence of

464


2,2 -bipyridyl-1,5-cyclooctadienyl-nickel (o). In this reaction an intermediate nickel complex 4 is obtained in 80 % yield. Treatment of 4 with maleic anhydride gives rise to the formation of the [4] radialene 5 in 94 % yield 10 .

N Me2C

C

C

CMe2

Ni N 4

5

A [2+2] cycloreversion of the radialene dimer, obtained from tetraphenylbutatriene, is observed upon irradiation at −190 ◦ C 11 . The conjugated butatriene 6, in the presence of Ni(CO)2 (PPh3 )2 , gives the radialene 7 in 67 % yield 15 .

C

C

6

7

In the thermal dimerization of the conjugated butatriene 8, the corresponding radialene 9 is obtained in 25 % yield. In the presence of the nickel catalyst, the yield increased to 95 % 16 . O

O

C

O

O

C

O

O

8

9

6.2.3 Trimerization Reactions In the oligomerization of tetramethylbutatriene, in the presence of Ni(CO)2 (PPh3 )2 , a 38 % yield of the 6-radialene 10 is obtained 8 .

Me2C

C

C

CMe2

10


465

The yield of the [6] radialene trimer of tetramethylbutatriene, generated in situ from dibromohexadiene in DMF, increases to 63 % 8 . 6.2.4 6.2.4.1


Dichlorocarbene adds to the butatriene derivative 11 under phase-transfer conditions to give the [2+1] cycloadduct 12, which rearranges in the presence of water to give the unsaturated alcohol 13 17 . Cl Cl Cl C

C

+

:CCl2

• OH

11

12

13

Tetraphenylbutatriene reacts with dichlorocarbene across two adjacent double bonds to give a 24 % yield of the bis-adduct 14 18 . Cl

Cl Ph Ph

Ph 2C

C

C

CPh + 2 :CCl2

Ph2 Cl

6.2.4.2

Cl 14


Across carbon multiple bonds In the reaction of [3] cumulenes with cyclopentadiene, the [2+2] cycloadducts resulting from additions across the center double bonds are obtained 19 . 1,1-Bis-diphenyl-4,4-bis(trifluoromethyl)butatriene 15 also reacts with activated olefins across the center C C bond to give the [2+2] cycloadducts 16 in good yields 20 . Ph

CF3 CF3

R1

R 2R3

Ph Ph2C

C

C

C(CF3)2

+

R2R3C

CHR1

15

16

R1

R2

H H

OMe OMe NMe2 NMe2 –(CH2 )3 – –(CH2 )4 –

R3

Yield (%) 83 54

N

O

N

O

64 68

Some didehydroheterocycles, generated in situ, undergo [2+2] and [4+2] cycloaddition reactions with suitable substrates. For example, 3,4-didehydrothiophene 17 can be trapped

466


with acrylonitrile to give a 13 % yield of the [2+2] cycloadduct 18 21 . CN

+

CH2

CHCN

S

S

17

18

Also, 1-t-butoxycarbonyl-3,4-didehydro-1H-pyrrole 19 is trapped with acrylonitrile, but the yield of 20 is only 1.4 % 22 . CN

+

CH2

CHCN

N O

N O

O–t-Bu 19

O–t-Bu 20

An intramolecular [2+2] cycloaddition reaction of the enyne [3] cumulene 21 affords the tricyclic aldehyde 22 23 . SiMe3 •

•

Ph

SiMe3

Me CHO

Me CHO

Ph 21

22

Across C S bonds Irradiation of thioxanthenethione 23 in the presence of alkyl- and alkoxy substituted butatrienes (R1 = H; R2 = MeO, t-BuO, PhO, or R1 = R2 = Me) gives the [2+2] cycloadducts 24 in over 90 % yields 24 . Apparently, the triplet thione attacks the end of the triene system and the generated diradical cyclizes to give the cycloadducts.

S S

S

+

Me2C

C

C

CR1R2

S

R1 R2

• 23

24

Across other double bonds The light-induced addition of oxygen to tetramethylbutatriene in an argon/oxygen matrix at 10–40 K produces the dioxethanes 25– 27 via addition of oxygen across the double bonds 25 . O C

C

CMe2

+

O2

O

•

Me2C

O 25

+ O

O

O + O

O 26

O

O

O 27

O


6.2.4.3

467


The [3+2] cycloaddition reaction of the 1,3-diaza-2-azoniaallene salts 28 with 1,4-bis(4bromophenyl)-1,4-di-t-butylbutatriene affords the cycloadduct 29, resulting from addition across the terminal double bond 26 . RR1C

C

CRR1

C

+

R2N

N+

R2N

NR2

N

NR2 RR1

•

R

R1 28

6.2.4.4

29


Tetraarylbutatrienes react with cyclopentadienone across its center double bond to form the Diels–Alder adducts 27 . In contrast, the butatrienylsulfonium salts 30 (R = Me, Et; X = Cl, Br, PF6 ) react with cyclopentadiene to give 1:1 mixtures of the isomeric cycloadducts 31 and 32 in high yields. In these reactions the terminal double bonds are involved in adduct formation 28 . R2S+(H)C

C

C

CH2

X−

+

+

•

SR2 H

30

31

•

H R2 S

32

The strained 1,2,3-cycloheptatriene 33, generated in situ, can be trapped as the [4+2] cycloadducts 34 and 35 using tetraphenylcyclopentadienone (yield, 30 %) or 2,5dimethylfurane (yield, 38 %), respectively 29 . The reaction is conducted at 100 ◦ C in DMSO in the presence of KF. Ph

Ph Ph

Ph

O

Ph

Ph O

Ph

Ph 34

O O

33

35

The six-membered ring strained butatriene 36 is also trapped with diphenylisobenzofuran to give the [4+2] cycloadduct 37 in 29 % yield 30 . Ph +

O Ph

36

Ph O Ph 37

468


3,4-Didehydrothiophene 38 is similarly trapped with furan to give a 31 % yield of the [4+2] cycloadduct 39 21 . +

O

O

S S 39

38

Vinylbutatriene 40 reacts at −78 ◦ C as diene in the Diels–Alder reaction with tetracyanoethylene to form the cycloadduct 41 31 . • CH2

CHCH 40

C

C

CH2

+

(NC)2C

(CN)2 (CN)2

C(CN)2 41

References 1. H. Irngartinger and H.U. Jäger, Angew. Chem. 88, 615 (1976). 2. S. Hernandez, M.M. Kirchhoff, S.G. Swartz, Jr and R.P. Johnson, Tetrahedron Lett. 37, 4907 (1996). 3. S.K. Pollack, B. Narayanswamy, R.S. Macomber, D.E. Rardon and I. Constantinides, Macromolecules 26, 856 (1993). 4. K.J. Daoust, S.M. Hernandez, K.M. Konrad, I.D. Mackie, J. Winstanley and R.P. Johnson, J. Org. Chem. 71, 5708 (2006). 5. E. Kloster-Jensen and J. Wirz, Helv. Chim. Acta 58, 162 (1975). 6. E.L. Martin and W.H. Sharkey, J. Am. Chem. Soc. 81, 5256 (1957). 7. K. Brand, Chem. Ber. 54, 1987 (1921). 8. J. Buddrus and H. Bauer, Angew. Chem. 99, 642 (1987). 9. M. Iyoda, S. Tanaka, M. Nose and M. Oda, J. Chem. Soc. 1058 (1983). 10. L. Stehling and G. Wilke, Angew. Chem. 97, 505 (1985). 11. Z. Berkovitch-Yellin, M. Lahar and L. Leiserowitz, J. Am. Chem. Soc. 96, 918 (1974). 12. B. Heinrich and A. Roedig, Angew. Chem. 80, 367 (1968). 13. F.W. Nader, C.D. Wacker, H. Irngartinger, U. Huber-Patz, R. Jahn, and H. Rodenwald, Angew. Chem. 97, 877 (1985). 14. S. Hashmi, K. Polborn and G. Szeimies, Chem. Ber. 122, 2399 (1989). 15. B. Hagenbruch, K. Hesse, S. Hünig and G. King, Liebigs Ann. Chem. 256 (1981). 16. R.O. Uhler, H. Shechter and G.V.D. Tiers, J. Am. Chem. Soc. 84, 3397 (1962). 17. H. Irngartinger and W. Götzmann, Angew. Chem. 98, 359 (1986). 18. E.V. Dehmlow and J. Schönfeld, Liebigs Ann. Chem. 744, 42 (1971). 19. T. Asakawa, M. Iinuma, T. Furuta, S. Fujii, T. Kan and K. Tanaka, Chem. Lett. 35, 512 (2006). 20. H. Gotthard and R. Jung, Tetrahedron Lett. 25, 4217 (1984). 21. X.S. Ye and H.N.C. Wang, J. Org. Chem. 62, 1940 (1997). 22. J. Liu, H. Chan, F. Xue, Q. Wang, T.C.W. Mak and H.N.C. Wong, J. Org. Chem. 64, 1630 (1999). 23. J.G. Garcia, B. Ramos, L.M. Pratt and A. Rodriguez, Tetrahedron Lett. 41, 7391 (1995). 24. R.G. Visser and H.J.T. Bos, Tetrahedron Lett. 4857 (1979). 25. W. Sander and A. Putyk, Angew.Chem. 99, 485 (1987). 26. W. Wirschun, G. Maier and J.C. Jochims, Tetrahedron 53, 5755 (1997). 27. W. Ried and R. Neidhardt, Liebigs Ann. Chem. 739, 155 (1970).

1,2,3-Tricarbon Cumulenes 28. 29. 30. 31.

469

H. Braun and G. Strobl, Angew. Chem. 86, 477 (1974). H.G. Zoch, G. Szeimies, R. Römer and R. Schmitt, Angew. Chem. 93, 894 (1981). W.C. Shakespeare and P.J. Johnson, J. Am. Chem. Soc. 112, 8578 (1990). H. Maurer and H. Hopf, Angew. Chem. 88, 687 (1976).

6.3 6.3.1

[4] Cumulenes, R2 C C C C CR2 Introduction

The [4] cumulenes or pentatetraenes are not well investigated. However, a few of their dimerization and cycloaddition reactions are reported. Some pentatetraenes, such as tetraphenyl- 1 , bis-cyclohexylidene- 2 and tetraferrocenylpentatetraene 3 are stable at room temperature. 6.3.2


The pentatetraene 1, on standing for several days at room temperature or heating for several hours, forms the [4] radialene cyclodimer 2 in quantitative yield 4 . t-Bu t-Bu C

C

C

1

•

•

t-Bu2C

t-Bu t-Bu

2

In contrast, the less stable pentatetraene 3, generated in situ, could only be isolated as the cyclodimer 4. In this example the dimerization proceeds across the cyclopropenyl substituted double bond 5 . •

•

C

C

C

C

C

3

4

The pentatetraene 5, obtained in the reaction of carbon suboxide with Ph3 P C(Ph)COOEt, is stable for some time at −20 ◦ C in the absence of air. However, at room temperature it undergoes di- and oligomerization reactions. The cyclodimer could not be isolated 6 . EtOOC(Ph)C

C

C 5

C

C(Ph)COOEt

di- or oligomers

470


The quinocumulene 6, generated in situ, underwent cyclotrimerization to give the highly symmetrical cyclotrimer 7 in almost quantitative yield 7 . O O

O

•

•

•

O

O O

O 6

6.3.3 Cycloaddition Reactions The photochemical [2+2] cycloaddition reaction of thioxanthenethione 8 with Me2 C C C C C(H)-t-Bu at −70 ◦ C affords a mixture of the three isomeric [2+2] cycloadducts 9–11 8 .

S

S

• • •

+ H

8

S

S

S

+

+

H •

•

• H

9

10

H 11

References 1. R. Kuhn, H. Fischer and H. Fischer, Chem. Ber. 97, 1760 (1964). 2. H. Irngartinger and W. Götzmann, Angew. Chem. 98, 359 (1986). 3. B. Bildstein, M. Schweiger, H. Kopacka, K. Ongania and K. Wurst, Organometallics 17, 2414 (1998). 4. A.E. Learned, A.M. Arif and P.J. Stang, J. Org. Chem. 53, 3122 (1988). 5. W.J. Le Noble, S. Basak and S. Srivastava, J. Am. Chem. Soc. 103, 4368 (1981). 6. F.W. Nader and A. Brecht, Angew. Chem. 98, 105 (1986). 7. T. Kawase, Y. Minami, N. Nishigaki, S. Okano, H. Kurata and M. Oda, Angew. Chem. Int. Ed. 44, 316 (2005). 8. R.G. Visser, E.A. Oostveen and H.J.T. Bos, Tetrahedron Lett. 22, 1139 (1981).

6.4

[5] Cumulenes, R2 C C C C CR2

6.4.1 Introduction In this section the [5] cumulenes or hexapentaenes are highlighted, but the less investigated higher cumulenes are included. The [5] cumulenes, like the [3] cumulenes, have linear structures, and therefore they ought to be more stable than the [4] and [6] cumulenes 1 . However, tetramethylhexapentaene is only stable in dilute solution 2 .


471

Hexapentatetraenes, generated in situ, can also be trapped with [Fe(CO)12 ] to give two isomeric iron carbonyl complexes in low yields 3 . Also, a [7] cumulene, tetraferrocenylheptahexaene, can be generated in situ 4 . 6.4.2


Tetra-t-butyl [5] cumulene 1 undergoes thermal dimerization to give the cyclodimer 2 in 85 % yield 5 . •

•

C

C

C

C

C–t-Bu2

1

•

•

t-Bu2C

2

The tetraaryl [5] cumulenes 3 react in the presence of stoichiometric amounts of Ni(CO)2 PPh3 in benzene to give the cyclodimers 4 resulting from addition across the second C=C bond 6 . R R

•

R R2C

C

C

C

C

CR2

•

R R

•

3

•

R 4

R

R R

Yield (%)

Ph 4-MePh

64 57

Similarly, heating of the [5] cumulene 5 in benzene (using half an equivalent of the Ni catalyst) affords the head-to-tail dimer 6 (similar in structure to the tetraaryl [5] cumulene dimers) in 82 % yield 7 . However, in the thermal dimerization of 5 (270 ◦ C, 5 min) the [4] radialene dimer 7 is obtained in 64 % yield 8 .

C

or •

•

•

C

•

•

C

•

•

C

•

5

6

7

Also, reaction of the benzo derivative of 5, in the presence of the Ni(o) catalyst affords the head-to-tail cyclodimer 7 .

472


C

C

C

•

•

C

•

•

The formation of the symmetric dimer 9 is also observed in the generation of the [5] cumulene 8 9 .

9

8

Heating of the slower reacting [5] cumulenes, in the presence of the Ni(o) catalyst, affords mixtures of the [4] radialenes 10 and [5] radialenones 11, as shown in Table 6.13.

•

•

•

•

Table 6.13 [4] Radialenes and [5] radialenones from [5] cumulenes

•

•

•

• O 10

11

[5] Cumulenes C

C

C

C

C

C

C

C

C

C

Yield of 10 (%)

Yield of 11 (%)

Reference

6

74

10

36

32

9

64

—

7

C

C

C

C

6.4.3 Cycloaddition Reactions The reaction of tetra-t-butylhexapentaene with bis(trifluoromethyl)acetylene at 190 ◦ C affords a low yield of the [2+2] cycloadduct 12. However, in the reaction of


473

•

•

tetra-t-butylhexapentaene, with tetrafluoroethylene, the [2+2] cycloadduct 13 is obtained in 70 % yield 5 .

CF3C CCF3 F3C

CF3 12

C

C

C

C

C –t-Bu2

CF2

•

•

t-Bu2C

CF2 F2

F2 13

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

H. Irngartner and H.U. Jäger, Angew. Chem. 88, 615 (1976). L.T. Scott and G.J. DeCicco, J. Org. Chem. 45, 4055 (1980). M. Iyoda, M. Kuwatani, M. Osa, K. Tatsumi and A. Nakamuro, Angew. Chem. 103, 1697 (1991). B. Bildstein, W. Skibar, M. Schweiger, H. Kopacka and K. Wurst, J. Organomet. Chem. 622, 135 (2001). H.D. Hartzler, J. Am. Chem. Soc. 88, 3155 (1966). M. Iyoda, Y. Kuwatani and M. Oda, J. Am. Chem. Soc. 111, 3761 (1989). M. Iyoda, Y. Kuwatani, M. Oda, Y. Kai, N. Kanehisa and N. Kasai, Chem. Lett. 2149 (1990). Y. Kuwatani, G. Yamamoto, M. Oda and M. Iyoda, Bull. Chem. Soc. Jpn. 78, 2188 (2005). M. Kaftory, I Agmon, M. Ladika and P.J. Stang, J. Am. Chem. Soc. 109, 782 (1987). M. Iyoda, Y. Kuwatani, M. Oda, Y. Kai, N. Kanehisa and N. Kasai, Angew. Chem. 102, 1077 (1990).

7 Noncarbon Cumulenes 7.1 7.1.1

Azides, RN N N Introduction

The [3+2] cycloaddition reaction of azides to numerous dipolarophiles is a standard Huisgen type cycloaddition reaction 1 . The reaction usually proceeds via a concerted reaction of the HOMO orbitals of the 1,3-dipole with the LUMO orbitals of the dipolarophile. However, switter ionic intermediates are observed in the cycloaddition reaction of ketene-N,N acetals with nitroarylazides 2 . In the reaction of picrylazide with one of the ketene-N,N-acetals a 90 % yield of the stable switterionic linear adduct is obtained. Electron withdrawing groups on the dipolarophile normally favor the concerted formation of cycloadducts, while electron donating groups on the dipolarophile favor the formation of switterionic intermediates. The dipolar character of the azides is demonstrated by their mesomeric structures. RN

N+

N−

RN-N

N

The [3+2] cycloaddition reaction of azides with terminal olefins is of considerable interest in the modification of biomolecules, because the azide group is abiotic in animals. Especially, the Cu(i) catalyzed cycloaddition reaction of azides with terminal alkynes achieves regioselective formation of 1,4-disubstituted 1,2,3-triazoles and this reaction is currently referred to as ‘click chemistry’ 3 . In the thermal reaction of azides with terminal alkynes, about 1:1 mixtures of 1,4- and 1,5-disubstituted 1,2,3-triazoles are obtained. Likewise, disubstituted alkynes afford mixtures of the stereoisomers. In order to avoid the cellular toxicity caused by the copper catalyst, Cu-free click chemistry is of considerable interest. The use of strained cyclooctyne derivatives as dipolarophiles was proposed recently. In this manner a novel 6,7-dimethoxyazacyclooct-4-yne was constructed from a glucose analogue 4 . The disadvantage of this reaction is its significantly slower reaction rate but introduction of fluoro groups adjacent to the triple bond achieves some rate enhancement 5 . Cumulenes in Click Reactions Henri Ulrich C 2009 John Wiley & Sons, Ltd

476


The 1,3-dipolarophiles participating in the [3+2] cycloaddition reaction with azides include carbon–carbon multiple bonds, such as alkynes, olefins, vinyl ethers and ketene acetals, but addition across C N multiple bonds, such as in nitriles and isocyanates, C S and P C bonds is also observed. The yields observed for many of these reactions approach quantitative. Review articles on the application of the [3+2] cycloaddition reaction of azides to alkynes as a tool in polymer chemistry and material science appeared in 2007 6,7 and 2008 8 and on bioconjugates and biomaterials in 2008 9 . Considerable precautions have to be taken in the thermal reaction of the lower alkyl azides as well as the higher functional azides because explosions may occur. 7.1.2 Oligomers The reaction of 4-chlorosulfonylbenzene isocyanate 1 with sodium azide affords the trifunctional sulfonyl azide 2 in 89 % yield, useful as a thermal or photocrosslinker 10 . O 4-CISO2PhNCO

NaN3

+

N3SO2

N O

SO2N3

N O

N

SO2N3 1

2

Triazides, such as 3, are also used in the construction of nanosize cages by reacting them with the trialkyne 4 to give the cage compound 5 in 92 % yield 11 . O

N N O

O(CH2)2N3

O N

N

O N

N N3(CH2)2O

N

N

+ O

O(CH2)2N3

O

N

N

O

N

N

N

O

N N O 3

4

5

The triazolylamine 6 is obtained in the reaction of tripropargylamine with benzyl azide 12 . The triazolylamine is used as a stabilizing ligand and rate enhancement agent for the copper catalyzed [3+2] cycloaddition of azides with terminal alkynes and yields of >99 % of the cycloadducts can be obtained using 6 in addition to the copper catalyst. N(CH2C

CH)3

+

3 PhCH2N3

N(CH2-C N

CH)3 N

6

NBz

Noncarbon Cumulenes

477

Tripropargylamine is also used in the construction of triazole dendrimers 13 . Oligotriazoles 9 are obtained from the diyne salts 7 and diazide salts 8, using cucurbituril (a macrocyclic host molecule consisting of glycouril repeat units) as the catalyst 14 .

HC

CCH2NH2CH2C

+

CH

N3(CH2)2NH2(CH2)2

7

N H

8

N N

H N

N

N N

N 9

N H

N N

H N

N3

N

n

Upper rim appended hybrid calixarenes are obtained from azide terminated calixarenes and alkyne terminated polymers 15 . The construction of oligomers is also possible by reacting trialkylsilylpropargyl azides with propargyl alcohol to give the corresponding 1,2,3-triazoles, which can be extended by subsequent click reactions or via the alcohol group 16 . Furanotriazole macrocycles can be constructed using furan derivatives with both an azido and an alkyne side chain 17 . A series of mono- and bis-metallated [2] rotaxanes are also produced using CuAAC chemistry 18 . Linear oligomers are formed in the reaction of an ethynyl α-C-mannoside and 6-azido-α-Cmannoside to give alternating mannose and triazole fragments up to a triazolopentamannose derivative in 80–90 % yield 19 . A combination of perfluoroalkyl and triazole moeties are used to promote emulsion formation in dichloromethane/water and to stabilize TEMPO (2,2,6,6-tetramethylpiperidine1-oxyl) used in the oxidation of alcohols to aldehydes 20 .

7.1.3 7.1.3.1

[3+2] Cycloaddition Reactions Across Carbon–Carbon Multiple Bonds

The [3+2] cycloaddition reaction of azides to alkynes is a useful synthetic method to produce 1,2,3-triazoles. When terminal alkynes are used in the non-catalyzed reaction, mixtures of two stereoisomers are usually obtained in high yields. However, in the reaction of benzyl azides with ethyl propiolate in refluxing ethanol the 1,4-disubstituted 1,2,3triazoles are obtained exclusively in higher than 80 % yields 21 . The regioselectivity in this reaction is sometimes achieved using suitable substituents. For example, the sulfone group in the reaction of N-(azidomethyl)benzoisothiazolone-derived azides with terminal alkynes afforded only the 1,5-disubstituted isomer 22 . The reaction times can be shortened, from 24 to 48 h to 30 to 60 min, by running the reaction in a microwave reactor at 80 ◦ C 23 . The reaction of dibenzylazides with dialkyl acetylenedicarboxylates affords quantitative yields of the dicycloadducts 24 . In the reaction of acetylene with cyanogen azide at 45 ◦ C a 75 % yield of 1-cyano-1,2,3-triazole 10 is obtained, which is in equilibrium with

478


α-diazo-N-cyanoethylidenimine 11 25 . +

HC

NCN

CH

N2

NCN

N N3CN

N H

10

H 11

The Cu(i) catalyzed stepwise cycloaddition of azides to terminal alkynes affords 1,4disubstituted 1,2,3-triazoles in excellent yields and high stereoselectivity. The reaction is conducted at room temperature in water/t-butanol (1:1) using CuSO4 and sodium ascorbate as a reducing agent 26 . Also, Cu(i) generated in situ from a nanosized activated powder in the presence of triethylamine hydrochloride 27 , as well as Cu/CuO nanoparticles 28 , are used to catalyze the reaction. Air-stable copper nanoclusters are also used and no additional base or reducing agent is required 29 . Copper nanoparticles, mounted within the pores of activated charcoal, are also used in combination with triethylamine to accelerate the reaction 30 , and high pressure also increases the reaction rate 31 . The reaction times are also significantly shortened by using organic-soluble copper complexes, such as (Ph3 P)3 CuBr or (EtO)3 CuI, and microwave irradiation 32 . The recyclable copper complex [Cu (186 -tris(2octadecylaminoethyl)) amine] can also be used effectively in this reaction 33 . Also, ionic liquids and a 1:1 mixture of water and methylenechloride accelerate the reaction 34 . The reaction of water-insoluble azides with water-insoluble alkynes can be conducted ‘on water’ using 10 mol% CuBr and 50 mol% PhSMe as the ligand 35 . A molecularly imprinted nanoreactor, constructed by click chemistry, is capable of providing a template for the reaction of 2-aminobenzyl azide with ethyl propiolate 36 . Also, selectivity could be accomplished using a self-assembled capsule 37 . Using a Cu(i) exchanged solid catalyst, based on zeolites as a reusable catalyst, at room temperature affords the 1,2,3-triazoles 12 from benzylazide and terminal alkynes 38 . N PhCH2N3

+

RC

PhCH2N

CH

N R

12

R Pr Ph PhNHCO

Yield (%) 85 83 87

Perfluoroalkylated 1,2,3-triazoles are similarly obtained from the fluorinated azides Rf CH2 N3 and terminal alkynes in the presence of Cu(i)/Et3 N at room temperature 39 . The copper-catalyzed reaction of propargyl carbamate with azides to give the corresponding triazoles is best conducted in pyridine as the solvent, and high yields were obtained 40 . The reaction of N-protected organic azides, such as azidomethyl pivalate or azidomethyl N,Ndiethylcarbamate, with alkynes affords 1,2,3-triazoles with base labile protecting groups 41 . Even steroidal alkynes react with 3,4-dihydroxypropyl azide in water/BuOH to give the [3+2] cycloadduct in 94 % yield 42 .

Noncarbon Cumulenes

479

The reaction of N-arylsulfonyl azides with terminal alkynes often leads to the formation of products resulting from rearrangement or loss of nitrogen, However, using copper iodide and 2,6-lutidine (1.2 equivalents) in chloroform at 0 ◦ C affords the 1-arenesulfonyl-1,2,3triazoles 13 43 . N R1C

+

RSO2N3

RSO2N

CH

N R1

13

R

R1

4-MePh 4-MePh Me3 Si(CH2 )2

4-BrPh 3-Thiophenyl Ph

Yield (%) 95 90 84

3-Azidocoumarins 14 react with terminal arylalkynes in the presence of Cu(i) catalysts to produce intensely fluorescent 1,2,3-triazoles 15, useful in bioimaging applications 44 . O

O

O

+

ArC

O

CH

N

N3

N

N Ar

14

15

Ar

Yield (%) 81a 86 84

Ph 4-MeOPh 4-CF3 Ph a

Crude yield (100 %).

A fluorogenic probe is also constructed by reacting the low-fluorescent coumarin 16 with benzylazide to give the highly fluorescent cycloadduct 17 45 . O

O

O OH

O

+

N3

HO

O

O

16 N N

HO

N O

O

O

O OH

O

O 17

480


The [3+2] cycloaddition reaction of 4-hydroxyphenyl azide with 2-ethynylpyridine affords the non-fluorescent cycloadduct 18, which displays ‘turn-on’ fluorescence upon addition of Zn(OTf)2 46 . N BzO

N3

BzO

+

N

N

N

N

18

The scope of the reaction can be extended to a three-component reaction by reacting azides with propargyl bromide in the presence of secondary amines to give the 1-substituted 1H-1,2,3-tetrazol-4-ylmethyl)dialkylamines 19 in good yields 47 .

R 1N3

R1N

BrCH2C CH

+

N N NR2 19

1,4-Disubstituted 1,2,3-triazoles are also formed from terminal alkynes and in situgenerated azides. For example, reactions of sodium azide, alkynes and aryl iodides in the presence of Cu(i) in a mixture of ionic liquids and water afford 1,4-disubstituted 1,2,3triazoles 48 . Likewise, reaction of terminal alkynes with sodium azide and formaldehyde affords 2-hydroxymethyl-2H-1,2,3-triazoles 20 (major isomer) in high yields 49 . RC

CH

+

+

NaN3

HCHO N

N N OH 20

Also, reactions of terminal alkynes with sodium azide and aryl iodide afford 5-aryl-1,4disubstituted 1,2,3-triazoles 50 . In the reaction of α,β-acetylenic aldehydes with sodium azide in DMSO at room temperature, 5-substituted-4-carbaldehyde-1,2,3-triazoles are obtained in quantitative yields 51 . Likewise, EtOCOCH2 Br can be used in the one-pot reaction as the azide precursor 52 . 1,2,3-Triazoles 21 are also obtained in the three-component reaction of trimethylsilylazide, allylcarbonate and alkynes in the presence of Pd(o) and Cu(i) catalysts 53 . Me3SiN3

+

RC

CH

+

CH2

CHOCO2Me

N

N N

21

Noncarbon Cumulenes

481

A three-component regioselective synthesis of β-hydroxy-1,2,3-triazole 23 uses the epoxide 22, phenylacetylene and sodium azide in water at room temperature 54 . OH +

O

PhC

+

CH

NaN3

N N

22

N Ph

23

The tandem Cu(i)-catalyzed reaction of the ynamide 24 with PhI and NaN3 affords the cycloadduct 25 in 75 % yield 55 .

Ph

N

O

O

O

Ph +

O

+

PhI

N

NaN3

N N N Ph

24

25

Optically pure (S) 2-azido-1-(p-chlorophenyl)ethanol reacts with terminal alkynes to give optically pure triazole containing β-adrenergic receptor blocker analogues 56 . Interestingly, the stereoselectivity is reversed using ruthenium catalysts, such as Cp(RuCl)(PPh3 )2 , to give 1,5-disubstituted 1,2,3-triazoles 26 57 . RN3

+

R 1C

N CH

RN

N

R1 26

R

R1

Bz Bz PhCH2 CH2 –

2-Naphthyl C(Me)2 OH Ph

Yield (%) 93 94 89

In a similar manner, reaction of 1-(4-chlorophenyl)-4-methylazido piperidine with terminal alkynes in DMF affords 1,5-disubstituted 1,2,3-triazoles 58 . A ruthenium-catalyzed reaction of azides with ynamines 27 (EWG = electron withdrawing group) affords the triazoles 28 59 . RN3

+

R1C

N

C–N(EWG)R2

RN

N R1

N 2

EWG 27

R 28

482


The ruthenium-catalyzed reaction of unsymmetrically substituted internal alkynes affords mixtures of the stereoisomers 29 and 30 60 . BzN3

+

RC

N

CR1

BzN

N

+

N

BzN

R1

R

N

R1

29

R 30

R

R1

Me Me Bu Ph Ph

CH2 NEt2 CH2 CH2 OH CO2 Me Me COMe

Yield (%)

Ratio, 29:30

70 90 90 95 100

0:100 23:77 100:0 38:62 100:0

In the [3+2] cycloaddition reactions of azides with disubstituted alkynes no catalyst is required and the corresponding 1,2,3-triazoles are usually obtained in high yields. High yields are even obtained in the reaction of benzynes, generated from 31 and CsF, and azides to give the benzotriazoles 32 61 . N

TMS

+

+

CsF

N

RN3

OTF

N R

31

32

R

Yield (%)

EtO2 CCH2 Ph 2-IPh 4-EtO2 CPh 4-MeOPhC CCH2 CH2 –

100 87 100 90 93

The reaction of trimethylsilylmethylazide with 1-phenylseleno-2-(p-toluenesulfonyl) ethyne 33 affords a mixture of the cycloadducts 34 (58 %) and 35 (18 %) 62 . N Me3SiCH2N3 +

RSO2C

33

CSePh

Me3Si

N RSO2 34

N N SePh

+

Me3Si

N PhSe 35

N SO2R

Some slower reacting alkynes are reacted with azides using microwave irradiation. In this manner, acetylenic amides 63 and phosphonate azides 64 are converted into 1,2,3-triazoles in good yields. Also, the use of ionic liquids can be advantageous and may lead to a greater stereoselectivity. For example, reaction of the heterocyclic azides 36 with alkynes led to

Noncarbon Cumulenes

483

the formation of the two stereoisomeric 1,2,3-triazoles 37 and 38 65 . Cl

Cl

R R 1C

+ N

R

CR2

N3

N

R

+

R1

N

N N

36

Cl

R2

R1

N

N

37

R2

N N

38

R

R1

R2

Yield (%)

Ratio, 37:38

Cl F Cl

nC5 H11 Ph Ph

H H H

62 70 65

80:20 99:1 98:2

The reaction of 2,3-diazidobutadiene with dimethyl acetylenedicarboxylate affords the expected bis-1,2,3-triazole cycloadducts. In contrast, reaction of 2-azidobutadiene with the alkyne affords the [3+2] and Diels–Alder adduct 39, but only in 28 % yield 66 . CO2Me + N3

2 MeO2CC

CCO2Me

N N MeO2C

CO2Me

N CO2Me 39

The intramolecular cycloaddition reaction of the alkyne-tethered aryl azide 40 (R = CH2 C CH) leads to the fused ring triazole 41 in good yield 67 . N N

N3 OR

N

O

40

41

From 40 (R = CH2 CN) the fused 1,2,3,4-tetrazoles are similarly obtained. Also, triazolobenzoazepines 42 are obtained in high yields in a one-pot azide/alkyne cycloaddition reaction, using 2-azidobenzoic acid and propargylamines 68 . N N

N3 +

N RNHCH2C

CH

COOH

NR 42

484


An intramolecular azide/alkyne cycloaddition reaction to give the fused triazoloimidazoles 44 is also observed using 43 69 .

R1

R1 N

N

N3

N

N

–R2

N

N

N R2

43

44

Fused triazole derivatives are also obtained in the reaction of azido/alkynes 45 to form 46 in excellent yields 70 . R1 RNH

R1

O N

N3

O

RNH

N

O

N

O

N N

45

46

The solid phase azide/alkyne cycloaddition is used as an efficient macrocyclization tool in the synthesis of jasplakinolide analogues 47 (57–92 % yields) 71 . R

R H N HN O

Me

H N

R2

NH

O

Me

O

O

R2

HN

O

O NH

X

X

O

O R3

N

N3

R3

N

N

47

Furanotriazole macrocycles 49 are similarly obtained from the AB monomer 48 72 . O O

O

N N O O

O N3 48

N

N O O

O O O

O

O O

N N

O 49

A [3+2] cycloaddition/elimination procedure to 1H-1,2,3-triazoles involves the solventfree reaction of trimethylsilylazide with nitroethenes 50 in the presence of TBAF

Noncarbon Cumulenes

485

(tetrabutylammonium fluoride) to give 4-aryl-1H-1,2,3-triazoles 51 73 . Me3SiN3

+

RCH

N

N

C(NO2)R1

NH

R R1 50

51

R

R1

Ph 4-ClPh 4-ClPh

CN CN CO2 Et

Yield (%) 85 90 85

Solid PEG-bonded azides also undergo the [3+2] cycloaddition reaction with alkynes to give polymer-bound 1,2,3-triazoles, and with nitriles to form the polymer-bound tetrazoles, both in high yields 74 . Also, a water-soluble PEG-bonded alkyne was used to synthesize sugar-derived triazoles 75 . Resin-bound azido esters are stereoselectively reacted with methyl propiolate to give 1,4-disubstituted 1,2,3-triazoles 76 . The cleavage of the resinbound triazoles is accomplished using trifluoroacetic acid 77 . The reaction is also conducted in pre-packed glass tubes containing immobilized reagents and scavengers in a modular flow reactor 78 . Also, a reusable polymer-supported catalyst was prepared from Cu(i) and Amberlist A21. This catalyst was used in the automated synthesis of 1,4-disubstituted 1,2,3triazoles 79 . Abnormal carbene complexes are obtained in the reaction of 1,2,3-triazoles with Pd(ii), Ru(ii), Rh(i) and Ir(i) compounds 80 . The [3+2] cycloaddition reaction of azides with alkenes affords 1,2,3-triazolines 81 . Even electron-poor olefins react with butyl- and phenyl azide to give 1,2,3-triazolines 82 . Better yields are obtained when the reaction of these olefins is conducted under high pressure (12 Kbar, room temperature, 24 h). In this manner, the cycloadducts 52 and 53 are obtained in high yields 83 . N RN3

+

CH2

C(Me)EWG

N

N

+

NR

RN

N

Me

Me

EWG 52

R

EWG

n-Bu Bz Ph

COMe COOMe COMe

EWG 53

Yield (%)

Ratio, 52:53

95 95 93

82:18 92:8 55:45

The cycloaddition of CH2 C(CH2 OMe)2 with benzyl azide (12 Kbar, room temperature) affords the cycloadduct 54 in 83 % yield. BzN3

+

CH2

C(CH2OMe)

N BzN

N CH2OMe

MeOCH2 54

486


Perfluoropropene and perfluorobutene-2 react with benzyl azide at 150 ◦ C to give the [3+2] cycloadducts in 85 % and 65 % yields, respectively 84 . Trimethylvinylsilane also undergoes the [3+2] cycloaddition reaction with 4-nitrophenyl- and 4-cyanophenyl azide to give the triazolines in high yields 85 . Also, N-alkylmaleimides react with trimethylsilyl azide to give the corresponding [3+2] cycloadduct 86 . The reaction of maleimide N-proponic acid and a heterocyclic azide is accelerated by molecular recognition 87 . The palladiumcatalyzed reaction of alkenyl bromides with sodium azide in dioxane at 90 ◦ C or DMSO at 110 ◦ C affords the 4-substituted 1,2,3-triazoles 55 88 . RCH

CHBr

N

+

NaN3

HN

N

R 55

However, reaction of azides with vinyl ethers often leads to loss of nitrogen with formation of linear products. For example, reaction of fluoroalkanesulfonyl azide with EtOCH CH2 at room temperature affords the expected [3+2] cycloadduct 56, which decomposes slowly at room temperature 89 . +

RfSO2N3

EtOCH

CH2

N RfSO2N

N

EtO 56

However, reaction of fluoroalkanesulfonyl azide with cycloalkenylethers proceeds with loss of nitrogen to give linear products 90 . When the reaction is conducted neat at 200 ◦ C, elimination of alcohol with formation of 1,2,3-triazoles in good yields is observed 91 . In contrast, a [3+2] cycloadduct is obtained from from 2,3-dihydropyran and 4-nitrophenyl azide 92 . Also, the reaction of 1,1,1-trifluoro-4-ethoxy-3-butene-2-one 57 with aryl- or benzyl azide at 80 ◦ C for several days affords 1,2,3-triazoles 58 stereoselectively and in good yields 93 . +

RN3

EtOCH

CHCOCF3

N RN

N COF

57

58

The reaction of enamines with azides usually proceeds with the loss of nitrogen to give linear reaction products. However, the [3+2] cycloadduct 60 is obtained in the reaction of 59 with phenylazide 94 . N PhN3

CHCO2Et

+

N PhN

Rf

N CO2Et

Rf 59

60

Noncarbon Cumulenes

487

Also, [3+2] cycloadducts are obtained in the reaction of phenyl azide to piperidine enamines derived from acetophenone and phenylacetaldehyde, respectively 95 . Enamides react similarly with aryl azides to give 1-aryl-5-amido-1,2,3-triazolines 96 . The [3+2] cycloaddition reaction of azides to ketene N,N or N,O-acetals also affords the expected cycloadducts. For example, reaction of alkyl- and aryl azides to the ketene N,N acetals 61 affords the cycloadducts 62 2 . Me

Me R 1N3

+

N N

R2

N N

N N

R3

N N

N

R R4

R4 61

R1 N N 2

R3

62

R1

R2

R3

R4

Yield (%)

t-Bu t-BuCH2 Ph 2-O2 NPh

Me Me Me Me

Me Me Me Me

Me Me Me Me

80 90 86 90

Picryl azide and sulfonyl azides react with ketene N,N-acetals to give switter ionic linear adducts. The intramolecular cycloaddition reaction of azides to ketene S,S-acetals at 130 ◦ C proceeds with loss of nitrogen to produce cyclic imines 97 . The addition of azides to strained bicyclic olefins also affords the expected [3+2] cycloadducts. For example, the addition of phenyl azide to norbornene is remarkably accelerated in water 98 . Also, addition of azides to bicyclic nitroso Diels–Alder adducts 63 affords the [3+2] cycloadducts as a mixture of the two stereoisomers 64 and 65 (about 1:1) in virtually quantitative yields 99 . BOC

BOC

BOC N O

RN3

+

N

N O

63

N

R N

N O

+

N R 64

N N 65

R

Yield (%)

n-octyl Bz Ph

99 99 99

Also, benzyl azide reacts with 66 to give a mixture of the stereoisomers 67 and 68 (1.6:1) in 62 % yield.

BzN3

+

O

O

N

N BOC

BOC 66

67

N N N Bz

Bz N

O

+

N

N

N

BOC 68

488


Even heterocyclic carbon–carbon double bonds undergo the [3+2] cycloaddition reaction with azides, as exemplified by the reaction of isothiazol-1,1-dioxides with aryl- and benzyl azides 100 . The intramolecular [3+2] cycloaddition reaction of azides to olefin tethers is also observed. For example, vinyl-substituted biphenyl azide 69 undergoes the reaction on standing at room temperature to give the 1,2,3-triazoline 70 in quantitative yield 101 .

N

N N3

N

69

70

Likewise, the allyl azide 71 undergoes the intramolecular [3+2] cycloaddition reaction to give the hexahydro[1,2,3-triazolo[1,5a]pyrazines 72 102 . NR N3

NR

N N

71

N 72

Also, the ortho-substituted benzene derivatives 73 undergo the intramolecular [3+2] cycloaddition reaction to give the tricyclic adducts 74 103 . O

O N3 73

N 74

N

N

Intramolecular cycloadditions of the N-alkenoylaryl azides 75 afford the 1,2,3triazolobenzodiazepines 76 104 . N N

N3

O

N

N

Bz 75

N

Bz

76

Allenes react with azides across one of their C C bonds to give a mixture of the expected stereoisomeric 1,2,3-triazolines. For example, from 1,2-nonadiene and phenyland 4-bromo-phenyl azide mixtures of the two stereoisomeric cycloadducts are obtained 105 . Also, picryl azide adds to tetramethylallene to give 4-isopropylidene-5,5-dimethyl-1-picryl1,2,3-triazoline 106 . In contrast, heating of the allenyl azides 77 at 100 ◦ C leads to the formation of tricyclic imines, formed by loss of nitrogen from the initial cycloadducts,

Noncarbon Cumulenes

489

which, on reaction with trimethylsilyl cyanide, afford the nitriles 78 in 84–96 % yields 107 . N

N

NH

N Me

•

+

Me3SiCN

CN

R R 77

78

Heating of the 2-(allenyl)phenyl azides 79 at 110 ◦ C gave a mixture of the cyclopentannelated indoles 80 and 81 108 . R1 H

R2 •

R R1 N H

R

N3

R2

+

R2

N R1

79

80

R

81

From the azido allenes 82, the azacycles 83 (87 % yields) are obtained when the reaction is conducted in the presence of Bu3 SnH at room temperature. When the reaction is conducted in THF at 50 ◦ C the bicyclic adducts 84, resulting from intramolecular cycloaddition, are obtained (n = 2, 90 %; n = 3, 62 %) 109 .

( )n

( )n

N3

N

or

•

N

RSO2 82

7.1.3.2

SO2R

SO2R

N 83

N

( )n

84

Across Carbon–Nitrogen Multiple Bonds

The [3+2] cycloaddition reaction of alkyl- and aryl azides with electronegative nitriles at 130–150 ◦ C affords the 1,5-disubstituted tetrazoles 85 110 . N RN3

+

RN

R1CN

N N

R1 85

R

R1

n-C8 H17 n-C8 H17

CF3 CCl3

Yield (%) 96 69

Of course, the formation of 1H-tetrazoles is more easily accomplished by reacting nitriles with sodium azide in the presence of ZnBr2 in water (refluxing for several days) to afford

490


the cycloadducts 86 111 . N +

RCN

N

NaN3

NH N

R

86

R

Yield (%)

4-O2 NPh 4-MeOPh 4-HOPh

94 86 96

Using 2-cyanopyridine or cyanopyrazine, the reaction is complete within several hours 112 . The intramolecular [3+2] cycloaddition reaction of 4-cyanobutyl azide affords the bicyclic tetrazole 87 113 . N

N N

NC(CH2)4N3

N

87

When the reaction of nitriles is conducted with (C6 F13 CH2 CH2 )3 SnN3 , followed with HCl, mono substituted tetrazoles are obtained 114 . The cycloaddition of nitriles with trimethylsilyl azides, under solventless conditions, is catalyzed by tetrabutylammonium fluoride. In this manner, 5-substituted 1H tetrazoles 88 are obtained 115 . N Me3SiN3

+

HN

RCN

N N

R 88

R n-Bu Ph 4-O2 NPh

Yield (%) 80 86 96

Nitriles, generated in situ from primary alcohols or aldehydes, are reacted with sodium azide and ZnBr2 at 80 ◦ C, assisted by microwave irradiation, to give 5-substituted 1Htetrazoles in high yields 116 . Tetrazoles derived from sulfonyl cyanides 117 or acyl cyanides 118 are useful in the construction of tetrazole scaffolds by reacting them with hydroxyl groupcontaining templates. The reaction of azides with cyanates at 5–10 kbar affords high yields of 5-substituted tetrazoles 119 . 1-Substituted tetrazoles are also obtained in high yields in the reaction of trimethylsilyl azide with isocyanides in the presence of catalytic amounts of HCl 120 .

Noncarbon Cumulenes

491

The cycloaddition reaction of azides across C N bonds is also observed. For example, reaction of alkyl azides with aryl isocyanates affords 1,4-disubstituted tetrazolidinones 89 121 . N +

RN3

RN

R1NCO

N NR1

O 89

R

R1

n-Bu C6 H11

Ph 4-O2 NPh

Yield (%) 80 86

Similar cycloadducts are obtained from alkyl azides and chlorosulfonyl isocyanates 122 and from alkyl- or aryl azides and arenesulfonyl isocyanates 123 . Similarly, trimethylsilyl azide reacts with aryl isocyanates to give the [3+2] cycloadducts 124 . 7.1.3.3

Across C S Bonds

The reaction of alkyl azides with sulfonyl isothiocyanates at room temperature affords the [3+2] cycloadducts 90 in 50–75 % yields 125 . N RN3

RN

R1SO2NCS

+

N S

R1SO2N 90

7.1.3.4

Across Other Double Bonds

The [3+2] cycloaddition reaction of trimethylsilyl azide across the P C bond in the diphosphaallenes 91 results in the formation of 92 via subsequent reactions of the cycloadduct 126 . N Me3SiN3

+

Ph3P

C

PN–i-Pr2

N

Ph2(i-Pr2N)P

P(N–i-Pr2)Ph2 P 92

91

In contrast, trimethylsilyl azide reacts with MesN AsCl in the presence of gallium trichloride to give the five-membered ring heterocycle 93 in 98 % yield 127 . Mes N Me3SiN3

+

MesN

AsCl

+

GaCl3

N N

AS N GaCl3 93

492


The GaCl3 -assisted [3+2] cycloaddition of MesN PCl with trimethylsilyl azide affords 94 in >96 % yield 128 . Mes N Me3SiN3

+

MesN

+

PCl

N

GaCl3

P N GaCl3 94

Also, the imidozirconium complexes 95 react with azides to give the corresponding [3+2] cycloadducts 96 129 . N RN3

+

Cp2Zr 95

NR1

RN

N

Cp2Zr

NR1

96

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Noncarbon Cumulenes 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65.

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494 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110.

Cumulenes in Click Reactions H. Priebe, Angew. Chem. 96, 728 (1984). R. Fusco, L. Garanti and G. Zeechi, J. Org. Chem. 40, 1906 (1975). A.W. Thomas, Bioorg. Med. Chem. Lett. 12, 1881 (2002). V. Gracias, D. Darczak, A.F. Gasiecki and S.W. Djuric, Tetrahedron Lett. 46, 9053 (2005). I. Akritopoulou-Zahze, V. Gracias and S.W. Djuric, Tetrahedron Lett. 45, 8439 (2004). T. Hu, R. Tannert, H. Arndt and H. Waldmann, J. Chem. Soc. Chem. Commun. 3942 (2007). S. Chandrasekhar, C.L. Rao, C. Nagesh, C.R. Reddy and B. Sridhar, Tetrahedron Lett. 48, 5869 (2007). D. Amantini, F. Fringuelli, C. Piermatti, F. Pizzo, E. Zunino and L. Vaccaro, J. Org. Chem. 70, 6526 (2005). G. Molteni and P. Del Buttero, Tetrahedron 61, 4983 (2005). M. Moore and P. Norris, Tetrahedron Lett. 39, 7027 (1998). B.E. Blass, K.R. Coburn, A.L. Faulkner, C.L. Hunn, M.G. Natchus, M.S. Parker, D.E. Portlock, J.S. Tullis and R. Wood, Tetrahedron Lett. 43, 4059 (2002). K. Harju, M. Vahermo, I. Mutikainen and J. Yli-Kauhaluoma, J. Combinator. Chem. 5, 826 (2003). C.D. Smith, I.R. Baxendale, S. Lanners, J.J. Hayward, S.C. Smith and S.V. Ley, Org. Biomol. Chem. 5, 1559 (2007). ¨ C. Girard, E. Onen, M. Aufort, S. Beauviere, E. Samson and J. Herscovici, Org. Lett. 8, 1689 (2006). P. Matthew, A. Neels and M. Albrecht, J. Am. Chem. Soc. 130, 13534 (2008). R. Huisgen, R. Knorr, L. Möbius and G. Szeimies, Chem. Ber. 98, 4014 (1965). W. Broeckx, N. Overbergh, C. Samyn, G. Smets and G. L’Abbe, Tetrahedron 27, 3527 (1971). G.T. Anderson, J.R. Henry and S.M. Weinreb, J. Org. Chem. 56, 6946 (1991). W. Carpenter, A. Haymaker and D.W. Moore, J. Org. Chem. 31, 789 (1966). P, Zanirato, J. Chem. Soc. Perkin Trans. 1 2789 (1991). S.S. Washburne, W.R. Peterson, Jr and D.A. Berman, J. Org. Chem. 37, 1738 (1972). C.A. Booth and D. Philip, Tetrahedron Lett. 39, 6987 (1998). J. Barluenga, C. Valdes, G. Beltran, M. Escribano and F. Aznar, Angew. Chem. Int. Ed. 45, 6893 (2006). S. Zhu, P. He, J. Zhao, and X. Cai, J. Fluor. Chem. 125, 445 (2004). P. He and S. Zhu, Tetrahedron 62, 549 (2006). D.R. Rogue, J.L. Neill, J.W. Antoon and E.P. Osuch, Synthesis 2497 (2005). R. Huisgen, Angew. Chem. 75, 604 (1963). W. Peng and S. Zhu, J. Fluor. Chem. 116, 81 (2002). W. Peng and S. Zhu, Tetrahedron 59, 4395 (2003). M.E. Munk and Y.K. Kim, J. Org. Chem. 29, 2213 (1964). P.K. Kadaba, J. Org. Chem. 57, 3075 (1992). W.O. Moss, E. Wakefield, M.F. Mahon, K.C. Molloy, R.H. Bradbury, N.J. Hales and T. Gallagher, Tetrahedron 48, 7551 (1992). J.W. Wijnen, R.A. Steiner and J.B.F.N. Engberts, Tetrahedron Lett. 36, 5389 (1995). B.S. Bodnar and M.J. Miller, J. Org. Chem. 72, 3929 (2007). F. Clerici, F. Galletti and D. Pocar, Tetrahedron 52, 7183 (1996). A. Padwa, A. Ku, H. Ku and A. Mazzu, J. Org. Chem. 43, 66 (1978). T.V. Lukina, S.I. Sviridov, S.V. Shorshnev, G.G. Alexandrov and A.E. Stepanov, Tetrahedron Lett. 46, 1205 (2005). B.S. Orlek, P.G. Sammes and D.J. Weller, Tetrahedron 49, 8179 (1993) . L. Garanti, G. Molteni and G. Broggini, J. Chem. Soc., Perkin Trans. 1 1816 (2001). D.K. Wedegaertner, R.K. Kattak, I. Harrison and S.K. Christie, J. Org. Chem. 56, 4465 (1991). R.F. Bleiholder and H. Shechter, J. Org. Chem. 33, 2131 (1968). K.S. Feldman and M.R. Iyer, J. Am. Chem. Soc. 127, 4590 (2005). K.S. Feldman, M.R. Iyer and D.K. Hester, Org. Lett. 8, 3113 (2006). C. Mukai, M. Kobayashi, S. Kubota, Y. Takahashi and S. Kitagaki, J. Org. Chem. 69, 2128 (2004). W.R. Carpenter, J. Org. Chem. 27, 2085 (1962).

Noncarbon Cumulenes 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129.

495

Z.P. Demko and K.B. Sharpless, J. Org. Chem. 66, 7945 (2001). F. Himo, Z.P. Demko, L. Noodleman and K.B. Sharpless, J. Am. Chem. Soc. 125, 9983 (2003) . Z.P. Demko and K.B. Sharpless, Org. Lett. 3, 4091 (2001). D.P. Curran, S. Hadida and S. Kim, Tetrahedron 55, 8997 (1999). D. Amantini, R. Beleggia, F. Fringuelli, F. Pizzo and L. Vaccaro, J. Org. Chem. 69, 2896 (2004). J. Shie and J. Fang, J. Org. Chem. 72, 3141 (2007). P.D. Zachary and K.B. Sharpless, Angew. Chem. Int. Ed. 41, 2110 (2002). P.D. Zachary and K.B. Sharpless, Angew. Chem. Int. Ed. 41, 2113 (2002). M.M. Krayushkin, A.M. Beskopylnyi, S.G. Ziotin, V.V. Son, N.N. Vainberg, O.K. Lukyanov and V.M. Zhulin, Russ. Chem. Bull. 31, 567 (1982). T. Jin, S. Kamijo and Y. Yamamoto, Tetrahedron Lett. 45, 9435 (2004). J.-M. Vandensavel, G. Smets and G. L’Abbe, J. Org. Chem. 38, 675 (1973). E.J. Moriconi and C.P. Datta, J. Org. Chem. 35, 2448 (1970). G. Denecker, G. Smets and G. L’Abbe, Tetrahedron 31, 765 (1975). O. Tsuge, S. Urano and K. Oe, J. Org. Chem. 45, 5130 (1980). E. van Loock, J.M. Vandensavel, G. L’Abbe and G. Smets, J. Org. Chem. 38, 2916 (1973). D. Martin, H. Gronitzka, A. Baceiredo and G. Bertrand, Eur. J. Inorg. Chem. 2619 (2005). A. Schulz and A. Villinger, Angew. Chem. 120, 614 (2008). A. Villinger, P. Mayer and A. Schulz, J. Chem. Soc. Chem. Commun. 1236 (2006). K.E. Meyer, P.J. Walsh and R.G. Bergman, J. Am. Chem. Soc. 117, 974 (1995).

7.1.4 7.1.4.1

Some Applications in Modification of Biopolymers Modification of Peptides and Enzymes

The use of click chemistry in the modification of biopolymers was proposed by Sharpless and coworkers and simultaneously by Meldal and coworkers. For example, the cowpea mosaic virus was used as a protein component and labeled with azides or alkynes of either reactive lysine or cysteine residues. The efficiency of coupling to the virus–azide or virus–alkyne groups was assayed with fluoresceine derivatives containing complimentary groups for coupling 1 . Proteins labeled with homopropargylglycine or ethynylphenylalanine were also reacted with fluorogenic coumarine azides 2 . Peptide-based linear or medium ringsize polymers were also prepared by the microwave-assisted CuAAC reaction 3 . Meldal and coworkers used polymer supported alkynes and azides, fully compatible with solid-phase peptide synthesis 4 . In situ click chemistry was used to assemble inhibitors for acetylcholinesterase derived from tacrine and phenylphenanthridinium azides. The in situ generated inhibitors were extremely potent acetylcholinesterase inhibitors and care should be observed in handling these neurotoxic compounds 5 . A potent inhibitor of human α-1,3-fucosyltransferase was similarly identified from a 1,2,3-triazole library of 85 compounds prepared by the [3+2] cycloaddition reaction of azides with terminal alkynes 6 . Also, protein tyrosine phosphatase inhibitors are synthesized in a similar manner 7 . Scaffolded peptides are also generated through site-selective ligation of three azidoacetylated peptides to different sites of a scaffolded molecule 8 . For anchoring of peripheral proteins onto cellular membranes an azide labeled diacyl glycerol analogue was reacted with protein kinase C 9 . Click chemistry is also used to produce a monofunctionalized enzyme which retained its reactivity 10 .

496


The attachment of alkyne or azide anchors to peptides can be achieved via a nucleophilic reaction using HC≡C–(CH2 )n OSO2 Ph or N3 (CH2 )n OSO2 Ph. The labels are than attached at room temperature by complimentary click chemistry. For example, 18 F-radio labeled peptides are readily obtained by attaching [18 F]fluoroalkynes to azide labeled peptides 11 . Also, 18 F-labeled 1,4-diphenyltriazole probes are used to target β-amyloid aggregates in Alzheimer disease 12 . The RAFT polymerization of α-azido-ω-dithiopyridine affords azide-terminated heterotelechelic polymers which were reacted with biotin/avidine glutathion and bovin serum albumine via click and thiol–disulfide exchange reactions 13 . Virus–glycopolymer conjugates are constructed from azide-modified viral protein scaffolds with alkynes to provide the end-functionalized products 14 . Icosahedral virus particles are decorated with a Gd(DOTA) complex using click chemistry 15 . In vitro and in vivo labeling of enzymes with an azido ABPP (activity-based protein profiling) probe and detecting the azide-labeled proteins with a rhodamin–alkyne reagent is also accomplished 16 . In the reaction of biotin–PEO–propargyl–amide to azide-labeled E. Coli cell surfaces, highly pure CuBr is used as the catalyst 17 . Liposome surfaces are also modified using CuAAC chemistry, allowing colorimetric assay of the process 18 . Triazide-based peptide dendrimers with a variety of cores, such as triazole, cystine and Lys–Asp dipeptide are also constructed 19 . Backbone modification in an α-helical coiled peptide cluster is also accomplished with click chemistry. The 1,2,3-triazole spacers contribute via hydrogen bonding in the reconstruction of the biomolecule 20 . The CuAAC reaction also allows the mimicking of a β-turn in the reaction between two peptide strands derivatized with terminal azide and alkyne groups, respectively 21 . Peptido triazoles with alternating amide and triazole linkages are also synthesized on a solid support 22 . Rigid rod polyisocyanopeptides containing alkyne groups on the side arms are functionalized further with C12 H25 N3 using click chemistry 23 .

7.1.4.2

Modifications of Nucleotides

The introduction of functional groups to DNA can be accomplished under biological conditions without a catalyst when an electron deficient alkyne, such as HC≡COCOEt, is added to azide-modified DNA 24 . Oligonucleotides, labeled with an azido group, were reacted with an alkyne-substituted fluoresceine molecule to construct fluorescent oligonucleotides for DNA sequencing 25 . Similarly, alkyne-modified DNA is tagged with fluorescent azides. For a high density functionalization of DNA, the Cu(i)-stabilizing ligand tris(benzyltriazolylmethyl)amine 26 was necessary to affect complete conversion. In this manner an azido sugar for selective Ag staining, a coumarine azide, which fluoresces only after 1,2,3-triazole formation and a fluoresceine azide are incorporated into the alkynemodified DNA molecules 27 . Also, the terminal alkyne groups in octa-1,7-diynylnucleotides were selectively reacted with the non-fluorescent 3-azido-7-hydroxycoumarin to provide strongly fluorescent 1,2,3-triazole conjugates. For example, the non-fluorescent alkynyl functionalized nucleotide 1 on reaction with the coumarine azide 2 affords the highly fluorescent conjugate 3 28 . The location of the 1,2,3-triazole moiety in 3 does not interfere with

Noncarbon Cumulenes

497

the macromolecular structure of the biomolecule. OH

O O N

NH2

OH

O

N

N

NH2

O

N

N

+ N

N

N

N3

O

N O

RO

RO

OR1 1

OR1 3

2

The synthesis of octadiynyl side-chain functionalized 2-deoxyuridine 29 and the alkynylated pyrimidines and 7-deazapurines 30 are also accomplished using click chemistry. The octa-1,7-diynyl substituents in 5-(octa-1,7-diynyl-2-deoyuridine) can be converted into pyrrolo-dC-oligonucleotides, thereby eliminating the alkyne group adjacent to the nucleoside. Oligonucleotides with one triple-bonded nucleoside have a more stabilizing effect on the molecule 31 . Also, 5-tripropargylamine-2 -deoxyuridine 4 has been synthesized to provite sites for the attachment of two reporter units to afford the highly fluorescent 5, where R = 3-azido-7-hydroxycoumarin and R1 = the antiviral nucleoside AZT 32 . N N O

N

N O O

O

N

N

N

NR

N O

N

HO

O

NR1 N

HO

HO

HO 4

5

Also, azido-substituted nucleosides are reacted with alkyne-substituted coumarins to give fluorescent conjugates 33 . Template-directed ligation of oligonucleotides is accomplished using nucleotide strands with 5 -alkyne and 3 -azide strands to produce DNA strands with an unnatural backbone at the ligation point 34 . 2-Propynyl substituted hemicyanine dyes are attached to azidecontaining virus molecules 35 .

498


Self-organizing oligothiophene–nucleoside conjugates were constructed from azidecontaining nucleotides and alkyne-containing oligothiophenes 36 . Also, a rapid (18 min) microwave-assisted synthesis of 3 ,5 -pentathymidine is accomplished starting with 5 -Otosylthymidine by sequential azide formation and Cu(i) catalyzed-azide/alkyne cycloadditions 37 . Functionalized thymidines are also obtained in the [3+2] cycloaddition reaction of thymidine azides with propargyl alcohol in water using click chemistry. The thus obtained 1,2,3-triazole-substituted nucleotides were devoid of significant activity against a battery of viruses 38 . Ribavirin analogs are also prepared using microwave-assisted copper or ruthenium-catalyzed click chemistry 39 . Alkyne groups bearing oligonucleotides were reacted with azide functionalized selfassembled monolayers on gold. This strategy may become useful in the formation of diagnostic microarrays 40 . Similarly, aliphatic long-chain azido alkanethiols attached to a gold surface were reacted with alkynes possessing redox-active ferrocene substituents. Electrochemical measurements of the ferrocene modified electrodes are used to quantify the redox centers attached to the platform 41 . Cyclization and bicyclization of oligonucleotides is also accomplished using CuAAC chemistry assisted by microwave irradiation 42 .

7.1.4.3

Modification of Carbohydrates

A series of ‘comb’ sugar polymers are constructed using the [3+2] cycloaddition reaction of appropriate sugar azides with poly(methacrylates) bearing terminal alkyne functionalities. In this manner a number of mannose- and galactose-containing multidentate ligands are prepared by reacting different sugar azides onto the polyalkynemethacrylate backbone 43 . Other examples include sugar heterodimers, glycoclusters, calix sugars and glycocyclodextrins 44 . In the construction of multivalent neoglycoconjugates from azide cores and alkyne-substituted sugars microwave irradiation and organic-soluble copper complexes are used as catalysts 45 . Likewise, bis-calixarenes and anthracenyl- and ferrocenylcalix[4]arenes are constructed 46 . A calix[4]arene platform is also constructed by reacting sugar tetrazols, obtained from from the corresponding azides and p-toluenesulfonyl cyanide, with a calix[4]arene tetrol 47 . Also, ionic liquids are used in the reaction of sugar azides with sugar alkynes 48 . This method is very efficient in constructing C-glycoside clusters on calix[4]arene, adamantane and benzene scaffolds through 1,2,3-triazole linkers 49 . Glycosyl azides are also prepared in situ from glucal and trimethylsilyl azide and reacted with phenylacetylene under CuAAC conditions to form 1,2,3-triazole conjugates 50 . It has been demonstrated that slightly elevated temperatures increase the rate of these reactions significantly 51 . Also, oligomannoside clusters with high affinities toward E. Coli are synthesized from pentaerythritol scaffolds bearing alkyne or azide functionalities 52 . Fullerene–carbohydrate conjugates are also constructed using azide chemistry 53 . Ligation of oligosaccharides to oligosaccharide/peptides, as well as ligation of oligosaccharides to amino acid glycoconjugates under neutral conditions, is also accomplished using click chemistry 54 . Glycoproteomic probes are constructed by reacting the non-fluorescent precursor 4-ethynylN-ethyl-1,8-naphthalimid with acid-modified sugars to form fluorescent 1,2,3-triazoles 55 . The one-pot synthesis of triazole-linked glycoconjugates uses sodium azide and alkynes to

Noncarbon Cumulenes

499

construct the 1,2,3-triazoles from unprotected sugars 56 . A review of the CuAAC reactions in carbohydrate chemistry appeared in 2007 57 . Carbohydrate-based anticancer vaccines are also constructed by reacting azido oligosaccharides with polypeptides with pendant alkyne groups 58 . The cycloadducts formed from 4-azidobenzenesulfonamides and O-propynyl glycosides are carbonic anhydrase inhibitors 59 . Also, diazidotrehalose monomers are reacted with dialkyne comonomers to produce trehalose polymers, which inhibit nanoparticle aggregation and promote DNA delivery in serum 60 . 2-Pyridyl triazole-substituted β-cyclodextrins are constructed by reacting 6-azido-β-cyclodextrin with 2-ethynylpyridine. These functionalized β-cyclodextrins are useful as Zn2+ -sensitive chelating agents 61 . Even stable cellulose derivatives, soluble in organic solvents, are prepared using CuAAC chemistry 62 .

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26. T.R. Chan, R. Hilgraf, K.B. Sharpless and V.V. Fokin, Org. Lett. 6, 2853 (2004). 27. J. Gierlich, G.A. Burley, P.M.E. Gramlich, D.M. Hammond and T. Carell, Org. Lett. 8, 3639 (2006). 28. F. Seela, V.R. Sirivolu and P. Chittepu, Bioconjugate Chem. 19, 211 (2008). 29. F. Seela and V.R. Sirivolu, Helv. Chim. Acta 90, 535 (2007). 30. F. Seela and V.R. Sirivolu, Chem. Biodiversity 3, 509 (2006). 31. F. Seela and V,R, Sirivolu, Org. Biomol. Chem. 6, 1674 (2008). 32. V.R. Sirivolu, P. Chittepu and F. Seela, Chem. Biochem. 9, 2305 (2008). 33. I. Kosiova, S. Kovackova and P. Kois, Tetrahedron 63, 312 (2007). 34. R. Kumar, A. El-Sagheer, J. Tumpane, P. Lincoln, L.M. Wilhelmsson and T. Brown, J. Am. Chem. Soc. 129, 6859 (2007). 35. W. Zhan, H.N. Barnhill, K. Sivakumar, H. Tian and Q. Wang, Tetrahedron Lett. 46, 1691 (2005). 36. A. Jatsch, A. Kopyshev, E. Mena-Osteritz and P. Bäuerle, Org. Lett. 10, 961 (2008). 37. R. Lucas, R. Zerrouki, R. Granet, P. Krausz and Y. Champavier, Tetrahedron 64, 5467 (2008). 38. L. Zhou, A. Amer, M. Koru, R. Burda, J. Balzarin, E. De Clercq, E.R. Kern and P.F. Torrence, Antivir. Chem. Chemoth. 16, 375 (2005). 39. U. Pradere, V. Roy, T.R. McBrayer, R.F. Schinazi and L.A. Agrofoglio, Tetrahedron 64, 9044 (2008). 40. N.K. Devaraj, G.P. Miller, W. Ebina, B. Kakaradov, J.P. Collman, E.T. Kool and C.E.D. Chidsey, J. Am. Chem. Soc. 127, 8600 (2005). 41. J.P. Collman, N.K. Devaraj, T.P.A. Eberspacher and C.E.D. Chidsey, Langmuir 22, 2457 (2006). 42. J. Lietard, A. Meyer, J. Vasseur, and F. Morvan, J. Org. Chem. 73, 191 (2008). 43. V. Ladmiral, G. Mantovani, G.J. Clarkson, S Cauet, J.L. Irwin and D.M. Haddleton, J. Am. Chem. Soc. 128, 4823 (2006). 44. F.G. Calvo-Flores, J. Isac-Garcia, F. Hernandez-Mateo, F. Peres-Balderas, J.A. Calvo-Asin, E. Sanchez-Vaquero and F. Santoyo-Gonzales, Org. Lett. 2, 2499 (2000). 45. F. Perz-Balderas, M. Ortega-Munoz, J. Morales-Sanfrutos, F. Hernandez-Mateo, F.G. CalvoFlores, J.A. Calvo-Asin, J. Isac-Garcia and F. Santoyo-Gonzales, Org. Lett. 3, 1951 (2003). 46. J. Morales-Sanfrutos, M. Ortega-Munoz, J. Lopez-Jaramillo, F. Hernandez-Mateo and F. SantoyoGonzales, J. Org. Chem. 73, 7772 (2008). 47. A. Dondoni and A. Marra, Tetrahedron 63, 6339 (2007). 48. A. Marra, A. Vecchi, C. Chiappe, B. Melai and A. Dondoni, J. Org. Chem. 73, 2458 (2008). 49. A. Dondoni and A. Marra, J.Org.Chem. 71, 7546 (2006). 50. J.S. Yadav, B.V.S. Reddy, D.N. Chary and C.S. Reddy, Tetrahedron Lett. 49, 2649 (2008). 51. B.L. Wilkinson, L.F. Bornaghi, S. Poulsen and T.A. Houston, Tetrahedron 62, 8115 (2006). 52. M. Tonaibia, T.C. Shiao, A. Papadopoulos, J. Vaucher, Q. Wang, K. Benhamioud and R. Roy, J. Chem. Soc. Chem. Commun. 380 (2007). 53. H. Isobe, K. Cho, N. Sodin, D.B. Werz, P.H. Seeberger and E. Nacamura, Org. Lett. 9, 4611 (2007). 54. S. Hotha and S. Kashyap, J. Org. Chem. 71, 364 (2006). 55. M. Sawa, T. Hsu, T. Itoh, M. Sugiyama, S.R. Hanson, P.K. Vogt and C. Wong, Proc. Natl. Acad. Sci. USA 103, 12371 (2006). 56. S. Chittaboina, F. Xie and Q. Wang, Tetrahedron Lett. 46, 2331 (2005). 57. S. Dedola, S.A. Nepogodiev and A.R. Fields, Org. Biomol. Chem. 5, 1006 (2007). 58. Q. Wan, J. Chen, G. Chen and S.J. Danishefsky, J. Org. Chem. 71, 8244 (2006). 59. B.L. Wilkinson, L.F. Bornaghi, T.A. Houston, A. Innocenti, D. Vullo, C.T. Supuran and S. Poulsen, J. Med. Chem. 50, 1651 (2007). 60. S. Srinivasachari, Y. Liu, G. Zhang, L. Prevette and T.M. Reineke, J. Am. Chem. Soc. 128, 8176 (2006). 61. O. David, S. Maisonneuve and J. Xie, Tetrahedron Lett. 48, 6527 (2007). 62. T. Liebert, C. Hänsch and T. Heinze, Macromol. Rapid Commun. 27, 208 (2006).

Noncarbon Cumulenes

501

7.2 Triazaallenium Salts, RN N+ NR 7.2.1

Introduction

The 1,3-dipolar character of triazaallenium salts, from now on referred to as 1,3-diaza-2azoniaallene salts, is evidenced by the many [3+2] cycloaddition reactions these types of compounds can participate in. The 1,3-diaza-2-azoniaallene salts are generated in situ and trapped with suitable dipolarophiles. For example, 1,3-diaza-2-azoniaallene salts undergo stereospecific [3+2] cycloaddition reactions with alkynes and olefins. However, they fail to react with isocyanates, isothiocyanates and azo compounds. Also, [3+2] cycloadditions to carbodiimides and cyanamides are observed. In contrast, nitriles fail to react. 1,3Diaza-2-azoniaallene salts are obtained in the oxidation of 1,3-disubstituted triazenes with t-butyl hypochlorite. The resultant N-chlorotriazenes react with antimony pentachloride to form the salts as reactive intermediates. Above −25 ◦ C, 1,3-diaza-2-azoniaallene salts disproportionate into diazonium salts and azo compounds. 7.2.2


The reactions of 1,3-diaza-2-azoniaallene salts 1, generated in situ, with alkynes at low temperatures, afford the [3+2] cycloadducts 2 as shown in Table 7.1 1 . Table 7.1 Cycloaddition reactions of 1,3-diaza-2-azoniaallene salts with alkynes N R 1N

N+

NR2 X– + R3C

R1N

CR4

NR2 X–

R3 1

R4 2

R1

R2

R3

R4

X

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 4-ClPh 4-MePh

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 4-ClPh Me

H CH2 OH Ph CO2 Me Et Et

H H Ph CO2 Me Et Et

SbCl6 SbCl6 SbCl6 SbCl6 PF6 PF6

Yield (%) 83 77 66 62 64 81

1,3-Diaza-2-azoniaallene salts also undergo a [3+2] cycloaddition reaction with olefins to give the cycloadducts 3 as shown in Table 7.2. In the reaction of 1,3-diaza-2-azoniaallene salts, R1 N=N+ =NR2 , with dienes, such as butadiene and 2,3-dimethylbutadiene, mono [3+2] cycloadducts are obtained. From cyclooctatetraene a bis-cycloadduct was isolated. Also, allenes and higher cumulenes undergo [3+2] cycloaddition reactions with the same salts 2 . With butatrienes, reaction proceeds across the terminal double bonds, while pentatetraenes react across the center double bonds.

502


Table 7.2 [3+2] Cycloaddition reactions of 1,3-diaza-2-azoniaallene salts with olefins N ArN

N+

NR

+

R1R4C

ArN

CR2R3

NR

R 1R4

SbCl6

R2R 3 3

Ar

R

R1

R2

R3

R4

Yield (%)

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Me3 Ph 4-O2 NPh

2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Cl3 Ph 2,4,6-Me3 Ph 4-O2 NPh

H Me CH2 Cl CO2 Bu Ph –(CH2 )3– CH2 Cl

H H H H H

H H CH2 Cl CO2 Bu H H H

H Me H H Ph H H

72 81 87 82 71 70 72

H

Also, reaction of 1,3-diaza-2-azoniaallene salts (Ar = 2,4,6-Cl3 Ph) with cyanamides gives the [3+2] cycloadducts 4. ArN

N+

−

NAr SbCl6

N +

ArN

R1R2NCN

NAr

N 4

SbCl6

NR1R2

R1

R2

Yield (%)

Me Me i-Pr

Me i-Pr i-Pr

73 82 88

Likewise, 1,3-diaza-2-azoniaallene salts (Ar = 2,4,6-Cl3 Ph) react with carbodiimides at −60 ◦ C to give the [3+2] cycloadducts 52 . ArN

N+

−

NAr SbCl6

N +

RN

C

ArN

NR

NAr

SbCl6

RN NR 5

R i-Pr C6 H11

Yield (%) 57 53

References 1. W. Wirschun, M. Winkler, K. Lutz and J.C. Jochims, J. Chem. Soc. Perkin Trans. 1, 1755 (1998). 2. W. Wirschun, G. Maier and J.C. Jochims, Tetrahedron 53, 5755 (1997).

Noncarbon Cumulenes

503

7.3 Sulfur Oxides 7.3.1

Introduction

The common sulfur oxides, sulfur dioxides and sulfur trioxides are heterocumulenes capable of undergoing many of the reactions observed with other heterocumulenes. The more useful click reaction of sulfur dioxides is their chelotropic addition to 1,3-dienes to produce sulfolenes, often in quantitative yields, while the [2+2] cycloaddition reactions of sulfur trioxide to olefins afford the four-membered ring cycloadducts, usually in high yields. The reaction of sulfur trioxide with olefins was already investigated in the last century. However, well characterized cycloadducts are of recent vintage, because under most reaction conditions the [2+2] cycloadducts are unstable, short-lived species, which undergo secondary reactions. The stereospecific nature of the cycloaddition of SO3 to olefins was demonstrated by the fact that the respective cycloadducts were obtained from cis- and trans-butene-2 1 , and from cis- and trans-octene-4 2 . Sulfur monoxide is not stable in its free form, but stabilization in metal complexes 3 , metal clusters 4 and in complexes containing S O as bridging ligands are known 5 . Free S O is generated by thermolysis of thiiran-S-oxides 1 6 . CH2

S

CH2

+

S

O

O 1

Disulfuroxide (S S O) and disulfurdioxide (O S S O) are unstable, and they polymerize to give polysulfur oxides. In disulfuroxide, the S S bond is weaker and more polarized than the S O bond 7 . Disulfur oxide is conveniently generated in the thermolysis of 4,5-diphenyl-3,6-dihydro-1,2-dithiin-1-oxide 2 8 . O

Ph S S

CH2

C(Ph)C(Ph)

CH2

+

S

S

O

Ph 2

Metal complexes of S2 O and S2 O2 are obtained in the oxidation of iridium-bonded S2 complexes 9 . Likewise, manganese sulfur complexes are oxidized to give L(CO)2 MnS2 O 10 . A Se2 O complex was obtained similarly 11 . In one example, L2 Pt(C2 H4 ) reacts with thiiran S-oxide to give an intermediate complex, which on heating produces a liganded S2 O2 complex 12 . The coordination chemistry of the sulfur oxides was reviewed by Schenk in 1987 13 . Review articles on the cycloaddition of SO3 to olefins were published by Gilbert in 1962 14 , and on the cycloaddition of SO3 to fluoroolefins by Knunyants and Sokolskii in 1972 15 and by Mothasham and Gard in 1992 16 . Perhaps one of the most important reactions involving sulfur dioxide is the retro-reaction, which affords olefins and sulfur dioxide. A review article on the formation of olefins from sulfenes, generated from diazo compounds and SO2 , was published by Fischer in 1970 17 . Sulfur dioxide is used extensively as a beverage and food preservative, but recently it has gained more prominence in organic synthesis 18 .

504


7.3.2 Sulfur Dioxide, O S O 7.3.2.1


[2+1] Cycloadditions The [2+1] cycloaddition of sulfur dioxide to ketenes affords an unstable [2+1] cycloadduct, which is in equilibrium with the linear 1,3-dipole. The intermediate can be trapped with C N double bond-containing substrates, such as azomethines, ketenimines and isocyanates 19 . Diphenyldiazomethane reacts with sulfur dioxide to give thiirane dioxide 3, which loses sulfur dioxide above its melting point to give tetraphenylethylene 20 . Ph2 Ph2C

N2

+

SO2

[Ph2C

SO2]

Ph2 Ph2C

S O

CPh2

O 3

[2+2] Cycloadditions [2+2] Cycloaddition reactions of sulfur dioxide to double-bonded substrates are rare. An example is the addition to the C S bond in sulfenes, generated in situ. However, the cycloadduct 4 loses S2 O3 to form a ketone 21 .

R2C

+

SO2

SO2

SO2 O

+

R2CO

S2O3

SO 4

The [2+2] cycloaddition reaction across a P N bond in 5 already occurs at −25 ◦ C to give products resulting from the retro-reaction 22 . (i-Pr)2N–P

N–t-Bu

+

O

S

O

[(i-Pr)2NPO]3

+

t-BuNSO

5

A similar [2+2] cycloaddition reaction occurs with iminophosphane complexes 23 . The [2+2] cycloaddition reaction of SO2 to an osmium carbon double bond in 6 affords the cycloadduct 7 24 . Cl PPh3 Os

Cl PPh3 CH2

+

SO2

SO

Os

O

ON PPh 3

ON PPh 3

6

7

Manganese and rhenium carbonyl compounds, such as 8, react with AgAsF6 in liquid SO2 to give the carbonyl complexes 9 incorporating the sulfur dioxide 25 . Rh(CO)5Br 8

+

AgAsF6

+

SO2

[Rh(CO)5SO2]+AsF6 9

+

AgBr

Noncarbon Cumulenes

505

An insertion of sulfur dioxide into a cobalt–cobalt bond in the liganded dicobalt complexes 10 has also been observed. The insertion product 11 is obtained in 75 % yields 26 . O

O S

L

Co

Co

Me

P

Me

P 10

+

L

SO2

Me Me

L

Co

Co

L

Me

P

Me

Me

P 11

Me

An interesting insertion reaction of sulfur dioxide with boraene 12 at −20 ◦ C affords the insertion product 13 in quantitative yield 27 . O O

+

B

S

SO2

O 12

O O

B O

13

In the reaction of the silylalkenes 14 with sulfur dioxide in acetonitrile at −40 ◦ C, insertion also occurs to give the silyl methallylsulfinates 15 in 46–54 % yields 28 . O +

SiR3

S

SO2

14

OSiR3

15

Also, insertion of sulfur dioxide into the Co–C bond of organocobaltoximes is observed 29 . The insertion of sulfur dioxide into a C–H bond in alkenes leads to their isomerization via a retro-reaction sequence 30 . Selenium dioxide also undergoes an insertion reaction with excess triethylborane to give an eight-membered ring heterocycle 16 31 . Et O Se O

Se

O

+

BEt3

Et2B

O BEt2

O Se O Et 16

The [2+2] cycloaddition reactions of ketenes and ketenimines with sulfur dioxide are discussed in chapter 4, Sections 4.1 and 4.3, respectively. [3+2] Cycloadditions The photochemical reaction of arylcyclopropanes with SO2 affords the [3+2] cycloadducts as a result of ring opening. 4-Cyanophenylcyclopropane 17 produces the [3+2] cycloadduct 18 (36 % conversion) 32 . O +

NC 17

SO2

SO

NC 18

506


The reaction of sulfur dioxide with cyclopropanes in trifluoroacetic acid at 20 ◦ C affords mixtures of isomeric 1,2-oxathiolane 2-oxides (γ -sultines). From cis-1,2diphenylcyclopropane a mixture of the (2,3-cis)-2-oxide 19 (yield, 52 %) and the (2,3trans)-2-oxide 20 (yield, 18 %) is obtained 33 . O H Ph

+

H Ph

OS Ph H

SO2

O

Ph H

OS H Ph

+

19

Ph H

20

In the reaction of trans-diarylcyclopropanes and SO2 four diastereoisomers are obtained 34 . From phenylcyclopropane, the diastereoisomers of 5-phenyl-1,2-oxathiolane 2-oxide are obtained in 66 % yields. Similarly, diarylcyclopropanes react with sulfur dioxide to give the five-membered ring [3+2] cycloadducts 35 . From 1-methyl-2phenylcyclopropane a mixture of mainly three isomeric γ -sultines are obtained 36 . In Table 7.3 some γ -sultines 21, obtained in this manner, are listed. Table 7.3 γ -Sultines from arylcyclopropanes and sulfur dioxide 37 R2 O + R1

R2

SO

SO2 1

R3

R

R3 21

Isomer distributiona R1

R2

R3

Yield (%)

A

B

H 4-I 4-Me 4-MeO H

H H H H Ph

H H H H Ph

76 93 88 92 95

60 55 60 60 100

40 45 40 40 —

O O a

Stereoisomer structure:

R H

S O

H R

R H

S O R B

A

H

Also, the liganded cyclopropane complexes 22 react with SO2 to give the [3+2] cycloadducts 23 38 . O LFe(CO)2 22

+

SO2

SO

LFe 23

Noncarbon Cumulenes

507

Some metal alkyne complexes react with SO2 by insertion into the metal–carbon bond to give 24 39 . O

MO

O

S M-CH2–C

C-R

+

SO

SO2 •

M

R

R 24

[4+2] Cycloadditions Interestingly, sulfur dioxide participated as a dienophile in the [4+2] cycloaddition reaction with 1,3-dienes. In this manner, sulfur dioxide reacts similarly to the related selenium dioxide and the other sulfur dienophiles RN S O, RN S NR and R2 C S O (sulfines). However, the [4+2] cycloadducts derived from 1,3-dienes and sulfur dioxide are only obtained at low temperatures (−80 ◦ C) in a kinetically controlled reaction and the cycloaddition reactions often require the presence of a Lewis acid (CF3 COOH or BF3 ). Above −50 ◦ C the Diels–Alder adducts undergo a cycloreversion and a cheletropic addition of the generated sulfur dioxide to the diene occurs with formation of the corresponding 2,5-dihydrothiophene-1,1-dioxides (sulfolenes). According to ab-initio computations, electrostatic solvent effects are predicted to be of importance in the control of the selectivities in this reaction 40 . From linear dienes, the [4+1] cycloadducts are usually obtained. For example, from 1,3-butadiene and SO2 at −20 ◦ C, the cyclic sulfone 25 is obtained in 95 % yield 41 . +

O

SO2

S O 25

Detailed investigation into the reaction of 1-substituted 1,3-butadienes demonstrated the intermediacy of the Diels–Alder adducts 26 and 27 at low temperatures, but the isolated products are the sulfolenes 28 42 . R

R +

SO2

R

R O S

S

S O

26

O

O

O

O 27

28

R

Yield (%)

t-Bu Cyclopropyl 4-ClPhS

59 99 60

Several sulfolenes, such as R = PhO, MeS, are unstable at room temperature. Also, 2-benzyloxy-3,5-dimethyldihydrothiophene-1,1-dioxide and 3,5-dimethyl-2-[2(trimethylsilyl)ethoxy]dihydrothiophene-1,1-dioxide are unstable above −20 ◦ C 43 . Some 1-substituted 1,3-butatrienes, more electron-rich than the (E) 1-alkyl or (E)

508


1-acyloxybutadiene do not form the Diels–Alder cycloadducts even in the presence of Lewis acids 44 . Isoprene (2-methylbutadiene) reacts with excess sulfur dioxide in the presence of a Lewis acid to give the Diels–Alders cycloadducts 29. The formation of the isomeric cycloadduct 30 was not observed. In contrast, 2-chloro- (R = Cl), 2-methoxy (R = MeO) 2-acetoxy (R = OAc) and 2-phenylselenobutadiene (R = PhSe) also did not add sulfur dioxide in the Diels–Alder mode 52 . However, 2-(triethylsilyl)- and 2-phenylbutadiene form mixtures of the isomeric sultines and again the isomeric sulfolenes 31 are the only products isolated at room temperature 45 . O +

SO2

S

O

S R

R

O

S

O R

O

O

R

29

30

31

R

Yield (%)

Et3 Si Ph 2-Naphthyl

77 68 73

2-Fluorobutadiene reacts with sulfur dioxide to give only polymeric products, while1fluorobutadiene formed the expected Diels–Alder cycloadducts 46 . 2,4-Hexadiene reacts with SO2 to give two isomeric sulfones 32 and 33 47 . O +

SO2

O +

S

S

O 32

O 33

Exocyclic conjugated dienes 34, such as 1,2-dimethylidenecyclopentane (n = 1), -cyclohexane (n = 2), -cycloheptane (n = 3) and -cyclooctane (n = 4), add to sulfur dioxide below −60 ◦ C to give the Diels–Alder cycloadducts 35. On heating above −40 ◦ C the corresponding sulfolenes 36 are obtained 48 .

( )n

+

SO2

O

O

( )n

( )n

S

S O

O 34

35

36

In the reaction of 1,2,3,4-tetrahydro-1,2-dimethylidenenaphthalene 37, generated in situ with sulfur dioxide at −80 ◦ C, a mixture of the cycloadducts 38 and 39 and the cyclodimer

Noncarbon Cumulenes

509

of 37 are obtained in a ratio of 1.0:0.15:0.4 (total yield, 37 %) 49 . O S

+

O

O S

O

SO2

+

37

38

39

Norbornadiene reacts with sulfur dioxide in the presence of 2,6-di-t-butyl-p-cresol to give a 33 % yield of the cycloadduct 40 after two days at room temperature 58 .

+

SO2 S O

O 40

In a similar manner, an 81 % yield of the sulfolane 42 is obtained in the reaction of 3,3-dimethyl-1,4-pentadiene 41 with sulfur dioxide (8 days at 23 ◦ C). Me

Me

Me +

Me

SO2 S O 42

41

O

In contrast, when 2,3,5,6-tetramethylidenebicyclo[2.2.1]heptane 43 (X = CH2 ) is reacted with sulfur dioxide the sulfolane 44 (X = CH2 ) is only observed at −20 ◦ C. At 0 ◦ C, 44 underwent a slow cycloreversion into the starting materials, which reform to give the sulfolene 45. When X = O, the corresponding sulfolene is similarly obtained 50 . X

X

X +

O

SO2

S

S O 43

O

O

44

45

When X = CH2 CH2 in 43, the corresponding bis-sulfolene is obtained. Dimethylbutadiene reacts with SeO2 to give the [4+2] cycloadduct 46 51 . O +

Se

SeO2

O 46

510


In the photochemical reaction of o-quinonemethides and SO2 a mixture of the [4+2] cycloadduct 47 and the [4+1] cycloadducts 48 (ratio 90:10) is obtained in 45 % yield 52 . O +

S

SO2

O

+

S

O

O

47

48

Substituted o-quinonemethides react similarly and high yields of the [4+2] cycloadducts are obtained in some cases, while with other substituents the [4+1] cycloadducts are produced 53 . Also, the highly reactive diene 49 reacts with sulfur dioxide below room temperature to give the rearranged cycloadduct 50 (90 % yield). Again, 50 is not stable at room temperature and it thermally reformed the sulfolene 51 (isolated in 98 % yield) 54 . O +

O

S

SO2

S

O 49

O

50

51

While the [4+2] cycloadducts of sulfur dioxide and 1,3-dienes are not stable at room temperature it is noteworthy that rotaxenes with a sultine end group, which are synthesized independently, are stable at room temperature and that they are used as a diene precursor to generate C60 -terminated rotaxenes 55 . Quinoxalinosultines and pyrazolinosultines, synthesized independently, are also stable entities and they are used to attach [60] fullarenes to the generated heterocyclic o-quinodimethanes. As expected, when 52 is heated in toluene in the absence of a dienophile the corresponding sulfolane 53 is obtained in 73 % yield 56 . N N 52

O S O

N

O S O

N 53

7.3.3 Sulfur Trioxide, O SO2 7.3.3.1


[2+2] Cycloadditions Across carbon multiple bonds The addition of SO3 to olefins under controlled conditions often results in the isolation of the [2+2] cycloadducts, especially with fluorinated olefins. The reaction initially produces a linear dipolar adduct 54, which can undergo ring closure to produce the cycloadduct 55, dimerization of 55 forms an eight-membered ring cyclic

Noncarbon Cumulenes

511

dimer 56, or it can undergo insertion of SO3 to give the six-membered ring carbyl sulfates 57, especially if an excess of SO3 is used 57 .

O

O S O

O S O O 56 C C

+

C+–C–SO3–

SO3

54

+ O

SO2 55 O S O

O S O O

O 57

The isolation of the eight-membered ring dimer in the reaction of tetrafluoroethylene 58 or styrene 59 with SO3 is an indication that the ionic intermediate is formed. The formation of only one [2+2] cycloadduct, depending on the polarity of the olefin, is another indication for the formation of an ionic intermediate. The intermediate in the styrene reaction with sulfur trioxide 58 is intercepted with another equivalent of styrene to give the six-membered ring [2+2+2] cycloadduct 59 49 .

Ph

O2S

O 58

Ph +

PhCh

CH2

O2S

O 59

Ph

The reaction of olefins with SO3 is exothermic, and often only secondary reaction products are isolated. Attempts to control the cycloaddition reaction involve the use of dioxane– or pyridine–SO3 complexes. However, to generate the monomer from the cyclic trimer, freshly distilled SO3 at low temperatures is more effective. Also, oleum seem to have an advantage over the pure sulfur trioxide in [2+2] cycloaddition reactions 60 . The reaction of terminal fluoro olefins with SO3 at low temperatures affords the [2+2] cycloadducts in good yields. Examples of this type of reaction are listed in Table 7.4. However, insertion of sulfur trioxide into allylic C–F bonds often occurs simultaneously 61 .

512


Table 7.4 1,2-Oxathietanes obtained from fluoroolefins and SO3 Substrate

Cycloadduct F2

Reference

93

62

85

63

61

63

80

63

90

63

90

63

69–72

63

63

64

80

65

F2

O2S

CF2 CF2

Yield (%)

O

F Cl

F2

O2S

CF2 CFCl

O

F H

F2

O2S

CF2 CHF

O

Cl2

F2

O2S

CF2 CCl2

O F

HCF2CF2

F2

O2S

CF2 C(F)CF2 CF2 H

O

F H(CF2)6

F2

O2S

CF2 C(F)(CF2 )6 H

O

F CF3OCF2

F2

O2S

CF2 C(F)CF2 OCF3

O

CF3 CF3

F2

O2S

CF2 C(CF3 )2

O F

(CF3)2N O2S

CF2 C(F)N(CF3 )2

F2 O

Hexafluorocyclobutene 60 reacts with sulfur trioxide at room temperature to give a mixture of the insertion products 61 (63 %) and 62 (32 %) 66 .

F

F2

F2 +

F2

F 60

SO3

F

F2

OSO2F

+ FSO2O F 61

F

FSO2O

F F 62

Noncarbon Cumulenes

513

Acetylene reacts with two equivalents of SO3 at 40 ◦ C to give a [2+2+2] cycloadduct 63 67 . O HC

CH

2 SO3

+

S O

O S O O

O 63

When the reaction is conducted with four equivalents of SO3 in liquid SO2 , the bicyclic 1:4 adduct 64 is obtained 68 . O O HC

CH

+

S O O

4 SO3

O

O S

O S O 64

O O S O O

The reaction of aryl cyanates with SO3 proceeds via an initial [2+2] cycloaddition to give 65. However, the cycloadduct rearranges to a linear 1,4-dipole, which reacts with another equivalent of aryl cyanate to form 1,4,3,5-oxothiadiazine-4,4-dioxide 66 69 . RO

RO

N ROCN

+ SO3

RO

O

OR

O

+ ROCN O

SO2

N

N

SO2

S

O 65

N O

66

Across other double bonds In the reaction of fluorosulfonyl-N-sulfinylamine with sulfur trioxide an initial reaction across the N S bond occurs to form the [2+2] cycloadduct 67, which disproportionates to give sulfur dioxide and FSO2 N SO2 . The latter dimerizes via a [2+2] cycloaddition across the S N bond to give a symmetrical dimer 68. O FSO2NSO

+

SO3

FSO2N

S

O2S

O

FSO2N

SO2

FSO2N

SO2

O2S

67

NSO2F 68

A [2+2] cycloaddition reaction of FCON SF2 with SO3 affords the four-membered ring cycloadduct 69 70 . FCON FCON

SF2

+

SO3

O2S 69

SF2 O

514


[3+2] Cycloadditions The perfluorinated oxiran 70 reacts with sulfur trioxide at 150 ◦ C to give the [3+2] cycloadduct 71 71 . F

CF3

CF3

F2

F

+

SO3

F2 O

O S

O O 71

70

O

Methylenecyclopropane 72 reacts with SO3 at −50 ◦ C to give 2-methylene-1,3propanesultone 73 in 97 % yield 72 . From diphenylmethylenecyclopropane and SO3 1-(diphenylmethylene)-1,3-propanesultone is obtained, and a similar reaction is observed with adamantylidenealkanes. +

SO3

O

Ph

S O

Ph Ph 72

O

Ph

73

1-Methoxytrifluorocyclopropene 74 reacts with SO3 at −50 ◦ C to give the γ -sultone 75 in 67 % yield 73 . O

F2 OMe

+

SO3

F

O

F2

F

S O 74

O 75

Beware though that 74 on treatment with sulfur trioxide at room temperature explodes! A criss-cross [3+2] cycloaddition to give 1,2,3-oxathiazolo[4,5-d][1,2,3]oxathiazole2,2,5,5-tetroxide 77 in 83 % yield is observed in the reaction of sulfur trioxide with dicyanogen 76 74 . +

SO3

N

O

O NC–CN

S O

O S

O

N

76

O

77

[4+2] Cycloadditions The [2+2+2] cycloaddition reaction of olefins with SO3 occurs via a [4+2] cycloaddition of an intermediate dipole with another equivalent of SO3 . Benzonitrile also reacts with SO3 at 0 ◦ C to form an ionic intermediate 78, which reacts with another equivalent of benzonitrile to form 4,6-diphenyl-1,2,3,5-oxathiadiazine-2,2-dioxide 79 75 . Ph PhC

N

+

SO3

PhC

NSO2O 78

+

PhC

N

N O2S

N O 79

Ph

Noncarbon Cumulenes

515

Cyanogen chloride forms a similar dipole 80 with SO3 , which rearranges via an isomeric switter ion 81 to give chlorosulfonyl isocyanate 82 or it reacts with another equivalent of cyanogen chloride to give the [4+2] cycloadduct 83 76 . CISO2N

C

O

82 CIC

N

+

SO3

CIC

NSO2O

O2SN

80

C(Cl)O– 81

O N Cl

O S O

N Cl

83

A 1,4-dipole 84 is also obtained from azomethines and SO3 . Reaction of the dipole with ethylvinyl ether affords the [4+2] cycloadduct 85 77 . Ph

Me N O2S

Ph O

84

+

EtOCH

CH2

H

MeN O2S

OEt O

H

85

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

M. Nagayama, O. Okumura, S. Noda and A. Mori, J. Chem. Soc., Chem. Commun. 841 (1973). B.H. Bakker and H. Cerfontain, Tetrahedron Lett. 28, 1699 (1987) . G. Schmid, G. Ritter and T. Debaerdemaker, Chem. Ber. 108, 3008 (1975). L. Marko, B. Marko-Monostory, T. Madcich and H. Vahrankamp, Angew. Chem. 92, 225 (1980). I. Lorenz, J. Messelhäuser, W. Hiller and K. Haug, Angew. Chem. 97, 234 (1985). B. Bonini, G. Macagnani and G. Mazzanti, J. Chem. Soc., Chem. Commun. 431 (1976). H. Bock, B. Solouki, P. Rosmus and R. Steudel, Angew. Chem. 85, 987 (1973). M.E. Welker, Chem. Rev. 92, 97 (1992). G. Schmid and G. Ritter, Angew. Chem. 87, 673 (1975). M. Herberhold, B. Schmidkonz, M.L. Ziegler and T. Zahn, Angew. Chem. 97, 517 (1985). J.E. Hoots, D.A. Lesch and T.B. Rauchfuss, Inorg. Chem. 23, 3130 (1984). I. Lorenz and J. Kull, Angew. Chem. 98, 276 (1986). W.A. Schenk, Angew. Chem. 99, 101 (1987). E.E. Gilbert, Chem. Rev. 62, 549 (1962). I.L. Knunyants and G.A. Sokolskii, Angew. Chem. 84, 623 (1972). J. Mohtasham and G.L. Gard, Coord. Chem. Rev. 112, 47 (1992). N.H. Fischer, Synthesis 393 (1970). P. Vogel, M. Turks, L. Bouchez, D. Markovic, A. Varela-Alvarez and J.A. Sordo, Acc. Chem. Res. 40, 931 (2007). J.M. Bohen and M.M. Joullie, J. Org. Chem. 38, 2652 (1973). H. Staudinger and F. Pfenninger, Chem. Ber. 49, 1941 (1916). N. Tokura, T. Nagai and S. Matsumura, J. Org. Chem. 31, 349 (1966). E. Niecke, H. Zorn, B. Krebs and G. Henkel, Angew. Chem. 92, 737 (1980). E. Niecke, M. Engelmann, H. Zorn, B. Krebs and G. Henkel, Angew. Chem. 92, 738 (1980). W.R. Roper, J.M. Waters and A.H. Wright, Organomet. Chem. 276, C13 (1984).

516 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67.

Cumulenes in Click Reactions R. Mews, Angew. Chem. 87, 669 (1975). W. Hoffmann and H. Werner, Angew. Chem. 93, 1088 (1981). M. Turks, A.K. Lawrence and P. Vogel, Tetrahedron Lett. 47, 2783 (2006). X.G. Huang, C. Craita, L. Awad and P. Vogel, J. Chem. Soc., Chem. Commun. 1297 (2005). P. Chadha, B.D. Gupta and K. Mahata, Organometallics 25, 92 (2006). D. Markovic, A.V. Alvarez, J.A. Sordo and P. Vogel, J. Am. Chem. Soc. 128, 7782 (2006). R. Köster, W. Schüssler, R. Boese, M. Herberhold, S. Gerstmann and B. Wrackmeyer, Chem. Ber. 129, 503 (1996). D.E. Applequist and L.F. McKenzie, J. Org. Chem. 42, 1251 (1977). O.B. Bondarenko, T.I. Voevodskaya, L.G. Saginova, V.A. Tafeenko and Y.S. Shabarov, Zh. Org. Khim. 23, 1736 (1987). O.B. Bondarenko, A.V. Buevich, T.I. Voevodskaya, L.G. Saginova and Y.S. Shabarov, Zh. Org. Khim. 24, 1937 (1988). E.V. Grigoriev, A.V. Yatsenko, N.V. Novozhilov, L.G. Saginova and V.S. Petrosyan, Vestn. Mosk. Univ., Ser. 2, Khim. 34, 87 (1993); Chem. Abstr. 119, 72527 (1993). O. Bondarenko, L.G. Saginova, T.I. Voevodskaya, A.V. Buerich, D.S. Yufit, Y.T. Struchkov and Y.S. Shabanov, Zh. Org. Khim. 26, 281 (1990). O.B. Bondarenko, L.G. Saginova and N.V. Zyk, Russ. Chem. Rev. 65, 147 (1996). A. Cutler, R.W. Fisch, W.P. Giering and M. Rosenblum, J. Am. Chem. Soc. 94, 4354 (1972). J.E. Thomasson, P.W. Robinson, D. A. Ross and A. Wojcicki, Inorg. Chem. 10, 2130 (1971). D. Suarez, X. Assfeld, J. Gonzales, M.F. Ruiz-Lopez, T.L. Sordo and J.A. Sordo, J. Chem. Soc., Chem. Commun. 1683 (1994). A. Schoeberl and A. Wagner, Houben Weyl, 9, 237 (2000). E. Roversi, F. Monnat, P. Vogel, K. Schenk and P. Roversi, Helv. Chim. Acta 85, 733 (2002). V. Narkevich, S. Megevand, K. Schenk and P. Vogel, J. Org. Chem. 66, 5080 (2001). E. Roversi, F. Monnat, K. Schenk, P. Vogrl, P. Braun and J.A. Sordo, Chem. Eur. J. 6, 1858 (2000). E. Roversi and P. Vogel, Helv. Chim. Acta 85, 761 (2002). E. Roversi, R. Scopelliti, E Solari, R. Estoppey, P. Vogel, P. Brana, B. Menendez and J.A. Sordo, Chem. Eur. J. 8, 1336 (2002). W.L. Mock, J. Am. Chem. Soc. 88, 2857 (1966). F. Monnat, P. Vogel and J.A. Sordo, Helv. Chim. Acta 85, 712 (2002). E. Roversi, P. Vogel and K. Schenk, Helv. Chim. Acta 85, 1390 (2002). J. Roulet, B. Deguin and P. Vogel, J. Am. Chem. Soc. 116, 3639 (1994). W.L. Mock and J.H. McCausland, Tetrahedron Lett. 391 (1968). T. Durst and L. Tetreault-Ryan, Tetrahedron Lett. 2353 (1978). G. Attardo, W. Wang, J. Kraus and B. Belleau, Tetrahedron Lett. 35, 4743 (1994). R.F. Heldeweg and H. Hogeveen, J. Am. Chem. Soc. 98, 2341 (1976). H. Sasabe, N. Kihara, Y. Furusho, K. Mizuno, A. Ogawa and T. Takata, Org. Lett. 6, 3957 (2004). J. Liu, A. Wu, M. Huang, C. Wu and W. Chung, J. Org. Chem. 65, 3395 (2000). B.H. Bakker and H. Cerfontain, Tetrahedron Lett. 28, 1703 (1987). G.A. Sokolskii, M.A. Dimitrijev and I.L. Knunyants, Izv. Acad. Nauk SSSR, Ser. Khim. 1231 (1968). F.G. Bordwell, M.L. Peterson and C.S. Rondestvedt, J. Am. Chem. Soc. 76, 3945 (1954). Y. Cheburkov and W.M. Lamanna, J. Fluor. Chem. 121, 147 (2003). F.E. Behr, R.J. Terjeson, J. Mohtasham and G.L. Gard, J. Fluor. Chem. 105, 137 (2000). D.C. England, M.A. Dietrich and R.V. Lindsey, J. Am. Chem. Soc. 82, 618 (1960). F. Forohar and D.D. DesMarteau, J. Fluor. Chem. 66, 101 (1994). M.A. Belaventsev, L.L. Mikheev, V.M. Pavlov, G.A. Sokolskii and I.L. Knunyant, Izv. Akad. Nauk SSSR, Ser. Khim. 2510 (1972). A. Vij, R.L. Kirchmeier, J.M. Shreeve, T. Abe, H. Fukaya, E. Hayashi, Y. Hayakawa and T. Ono, Inorg. Chem. 33, 628 (1994). B.E. Smart, J. Org. Chem. 41, 2353 (1976). A.V. Dombrovskii and G.M. Prilutskii, Zh. Obshch. Khim. 25, 1943 (1955); Chem. Abstr. 50, 8450 (1956).

Noncarbon Cumulenes

517

68. 69. 70. 71. 72. 73. 74.

E.E. Gilbert, J.A. Otto and C.J. McGough, Ind. Eng. Chem. 51, 349 (1966). E. Grigat, Angew. Chem. 84, 1008 (1972). K.D. Schmidt, Diplomarbeit, University of Göttingen, The Netherlands, 1973. I.L. Knunyants, V.V. Shokina and E. I. Mysov, Izv. Akad. Nauk SSSR, Ser. Khim. 2725 (1973). B.H. Bakker, H. Cerfontain and H.P. Tomassen, J. Org. Chem. 54, 1680 (1989). B.E. Smart and C.G. Krespan, J. Am. Chem. Soc. 99, 1218 (1977). H.W. Roesky, N. Amin, G. Remmers, A. Gieren, U. Riemann and B. Dederen, Angew. Chem. 91, 243 (1979). 75. H. Weidinger and J. Krauz, Chem. Ber. 96, 2070 (1963). 76. R. Graf, Chem. Ber. 89, 1071 (1956). 77. R. Huisgen, Z. Chem. 290 (1968).

7.4 Sulfur Nitrides 7.4.1 7.4.1.1

N-Sulfinylamines, RN S O and N-Thiosulfinylamines, RN S S Introduction

The nitrogen analogs of sulfines, N-sulfinylamines (RN S O) and N-sulfinylsulfonamides (RSO2 N S O) are well known compounds. Likewise, sulfurdiimides (RN S NR) and the corresponding sulfones have been thorougly investigated. The sulfurdiimide structure is also encountered in heterocyclic N–S compounds 1 . The seleniumdiimide structure (RN Se NR) occurs likewise in heterocycles 2 , and arsenic-substituted linear (R2 AsN S NAsR2 ) and arsenic-substituted cyclic sulfurdiimides are also known 3 . Aromatic N-thiosulfinylamines (RN S S) are also described in the literature 4 . The latter compounds react as 1,3-dipoles in [3+2] cycloaddition reactions and they are also referred to as thionitroso S-sulfides. N-sulfonylaniline, the reaction product derived from aniline and thionyl chloride, was first synthesized by Boettinger in 1878 5 . Much of the chemistry of N-sulfinylamines was investigated by Kresze and his coworkers in Germany in the 1960s. N-Sulfinylamines are typical heterocumulenes and the molecules are polarized as shown below. RN

S

O

RN−–S+

O

RN−–S+–O−

N-Sulfinylsulfonamides (RSO2 N S O) are considerably more reactive than Nsulfinylamines. N-Sulfonylamines and sulfurdiimides undergo [2+2] cycloaddition reactions with C C, C O, C N, C S, S O and P S double-bonded compounds. Sometimes, the cycloadducts are isolated but more often elimination of SO2 or S2 O, or fragmentation of the initial cycloadducts is observed. The [3+2] and [4+2] cycloaddition reactions of N-sulfinylamines are also well investigated. High pressure is used to assist the cycloaddition reactions of azulene-substituted N-sulfinylamines 6 . The [4+2] cycloaddition reaction of MeCONSO with pentacene (yield >90 %) is used to synthesize a solution-processable organic thin film transistor 7 . 7.4.1.2


The unsymmetrical cyclodimers of the N-sulfinylsulfonamides 1 are postulated as intermediates in the disproportionation of N-sulfinylsulfonamides to give sulfurdiimides and sulfur

518


dioxide 8 . RSO2N 2 RSO2N

S

S

O

RSO2N

O

RSO2N

S

NSO2R

+

SO2

SO

1

7.4.1.3


[2+2] Cycloadditions Across carbon multiple bonds Highly strained carbon to carbon bonds, such as quadricyclane 2, react with aryl-N-sulfinylamines to give the fused 1,2-thiazetidine-1-oxides 3 9 . +

RN

S

SO NR

O

2

3

R

Yield (%)

Ph 4-MePh 4-O2 NPh

90 78 80

The ynamines 4 react with p-toluenesulfinylsulfonamide 5 at 0 ◦ C to give the cycloadducts 6, which undergo cycloreversion to give the sulfines 7, isolated in 66–90 % yields 10 . R2

RR1N RR1NC

CR2

+

TsN

S

RR1NC(

O TsN

4

5

NTs)C(R2)

S

O

SO 6

7

The C C bond in 1,4-quinones reacts with aromatic sulfinylamines by an initial [2+2] cycloaddition reaction. However, the cycloadducts rearrange to form arylsulfinamoyl-1,4quinones 11 . For example, 1,4-naphthoquinone gives the rearranged products 8. O

O +

O

RN

S

O

S

SO NR

O

O NHR

O

O 8

R Ph 4-MePh β-C10 H7

Yield (%) 62 68 72

Noncarbon Cumulenes

519

In the reaction of 5-hydroxy-1,4-naphthoquinone with aryl N-sulfinylamines 3substituted products are formed exclusively in 70–76 % yields. In the reaction of 1,4benzoquinone with three eqivalents of N-sulfinylamines products 9, resulting from addition across the C C bonds as well as one C O bond, are formed. O

O

O

O

S + 3 RN

S

S

RNH

O

O

NHR NR 9

The reaction of vinyl ethers with N-sulfinylsulfonamides affords the four-membered ring [2+2] cycloadducts 10 12 . RSO2N

S

O

+

R1OCH

SO

RSO2N

CH2

R1O 10

Some of the stable [2+2] cycloadducts 11, obtained from N-sulfinylamines and ketenes, are listed in Table 7.5. The reaction proceeds rapidly at room temperature and can be followed by the discoloration of the reaction mixture. Aliphatic N-sulfinylamines react considerably faster than the aromatic N-sulfinylamines. Table 7.5 [2+2] Cycloadducts from N-sulfinylamines and ketenes RR1C

C

O

+

R2N

S

R2N

O

SO RR1

O 11

R

R1

R2

CF3 CF3 Ph Ph Ph Ph Ph Biphenylene

CF3 CF3 Ph Ph Ph Ph Ph

Me C6 H11 C6 H11 Ph 2-ClPh 4-ClPh 4-O2 NPh Ph

Yield (%)

Reference

83 86 99 95 93 99 86 96

13 12 14 14 14 14 14 14

Across C O bonds Aldehydes and ketones react with N-sulfinylamines to form the [2+2] cycloadducts 12, which instantly undergo fragmentation to form imines and sulfur dioxide. RCH

O

+

R 1N

S

O

R1N R

SO O

12

R 1N

CHR

+

SO2

520


α-Diketones react with N-sulfinylaniline and N-sulfinylsulfonamides across one C O bond to give keto imines, azomethines and N-sulfonyl imides, respectively, with elimination of sulfur dioxide 15 . From enolizable alkanones and cycloalkanones and Nsulfinylnonafluorobutanesulfonamide an oxa–ene reaction is observed 16 . The aldehydic group in the glyoxylic ester 13 reacts with N-sulfinylsulfonamides in the presence of AlCl3 as the catalyst to give the N-sulfonylimide 14 and sulfur dioxide 17 . BuOCOCH 13

+

O

RSO2N

S

O

BuOCOCH NSO2R 14

+

SO2

Hexafluoroacetone reacts similarly with N-sulfinylaniline to give PhN C(CF3 )2 18 . Some heterocyclic ketones also react with N-sulfinylsulfonamides to give the corresponding imines. For example, from 15 and RSO2 N S O the imine 16 is obtained 19 . O

RSO2N Ph

Ph +

S

RSO2N

S

O

+

S

15

SO2

16

N-Sulfinylammonium salts react with aldehydes in a similar manner to give immonium salts 20 . Dialkylformamides react with N-sulfinylsulfonamides to give amidines and sulfur dioxide in almost quantitative yields 21 . Across C N bonds The reaction of N-sulfinylsulfonamides across the C N bond in the aldazines 17 produces the cycloreversion products 18 and 19 22 . +

PhCH NPh 17

PhSO2N

S

O

PhCH

NSO2Ph 18

+

PhN

S 19

O

Carbodiimides 20 react with N-sulfinylamines in a similar manner to produce the cycloreversion products 21 and 22 23 . RN

R1SO2N

+

C NR 20

S

R1SO2N C 21

O

NR

+

RN

S 22

O

In the reaction of N-sulfinyl-p-toluenesulfonamide with methyl-t-butylcarbodiimide, the reaction proceeds across the less sterically hindered C N bond to give methyl N-sulfinylamine and N-p-toluenesulfonyl-N’-t-butylcarbodiimide 24 . Across S O bonds Sulfoxides react with N-sulfinylsulfonamides to give sulfilimine derivatives 23 and sulfur dioxide. The aliphatic sulfoxides react at room temperature, while heating at 80–100 ◦ C is required for aromatic sulfoxides 25 . R 2S

O

+

R1SO2N

S

O

R1SO2N SR2 23

+

SO2

In the reaction of sulfoxides with N-sulfinylammonium salts the corresponding aminosulfonium salts are obtained via a [2+2] cycloaddition sequence 26 . Thioamides and thioureas react with N-sulfinylsulfonamides across the C S bonds to give amidines and guanidines, respectively. Sulfur and sulfur dioxide are formed as byproducts. An example is

Noncarbon Cumulenes

521

the reaction of tosyl-N-sulfinylamine with tetramethylthiourea which affords the expected guanidine derivative in 65 % yield 27 . Across other double bonds Nitrosobenzenes react with N-sulfinylaniline to give low yields of azobenzenes 24. The reaction proceeds via a [2+2] cycloreversion 28 . PhN RN

O

+

PhN

S

SO

O

RN

NPh

+

SO2

O

RN 24

The P S bond in triphenylphosphorous sulfide reacts with N-sulfinylsulfonamides to give a phosphine imine and S2 O 29 . Reaction of perfluoroalkyl N-sulfinylsulfonamides with POCl3 proceeds by addition across the P O bond to give RSO2 N PCl3 . The same N-sulfinylsulfonamide reacts with aldehydes, ketones and sulfoxides via [2+2] cycloadditions across the respective double bonds with subsequent cycloreversions 30 . A [2+2] cycloaddition of t-butyl N-sulfinylamine across the Re O bond in 25 to give 26 and sulfur dioxide has also been observed 31 . t-BuN Cl3(PPh3)Re

O

+

t-BuN

S

SO

O Re

O

Cl3(PPh3)Re

25

N–t-Bu

+

SO2

26 PPh3

[3+2] Cycloadditions The first example of a [3+2] cycloaddition reaction involving a N-sulfinylamine was reported by Huisgen and coworkers in 1962 32 . The authors added N-sulfinylaniline to diphenylnitrile imine 27 and they isolated the [3+2] cycloadduct 28 in 87 % yield. O PhC

N

NPh

+

PhN

S

PhN

O

S NPh

Ph

N 28

27

A stable [3+2] cycloadduct 29 is also obtained from benzonitrile oxide and N-sulfonylaniline. On heating, the cycloadduct forms diphenylcarbodiimide and sulfur dioxide 33 . This reaction is general and several 4,5-disubstituted 1,2,3,5-thiaoxadiazole 1-oxides 29 are obtained from N-sulfonylaryl- 34 and N-sulfinyl-alkylamines 35 . O RC

N

O

+

R 1N

S

O

R1N Ph

S O

N 29

Also, nitrones react with N-sulfinylbenzenesulfonamide by a [3+2] cycloaddition sequence but the initially formed cycloadducts eliminate sulfur dioxide at room temperature 36 . Pyridine N-oxides react with N-sulfinylamines to give linear betains.

522


Thiobenzophenone S-methylide 30 reacts with PhNSO to give the [3+2] cycloadduct 31 37 . O Ph2C

S

CH2

+

PhN

PhNSO

Ph2

S

S 31

30

However, TsNSO reacts across the S O bond to give 32. NTs Ph2C

S

CH2

+

O

RSO2NSO Ph2

S S 32

A [3+2] cycloaddition reaction of an aromatic N-sulfinylamine to a heterocyclic ylide is also observed. The initially generated cycloadduct 33 eliminates a different N-sulfinylamine to give the heterocycle 34 38 . R R

N

+ N

ArN

N

R1NSO R 1N

N N

R

NAr

R

NAr

R

S

Ar

O 33

Ar

N

N NAr

+

ArNSO

34

Some N-thiosulfinylaniline derivatives undergo [3+2] cycloaddition reactions across olefins and aromatic C C bonds to give heterocyclyc adducts. For example, reaction of 2,4,6-tris-t-butylaniline 35 with S2 Cl2 in the presence of triethylamine gives cycloadduct 36 in 70 % yield. In solution, 36 is in equilibrium with the N-thiosulfinylaniline 37 39 . N

NH2

S

NSO

S +

35

S2Cl2 36

37

A similar cycloadduct is obtained from 2,4-di-t-butyl-6-methylaniline (yield, 81 %). A relatively unknown class of noncarbon cumulenes are the highly colored thionitroso S-sulfides, RN S S. They are also 1,3-dipolar species, which undergo [3+2] cycloaddition reactions. Huisgen and Peng 40 have studied the reaction of 2-methyl-4,6-di-t-butylphenylthionitroso S-sulfide with cyclooctene and obtained the [3+2] cycloadduct in 50 % yield. In a similar manner, reaction with cyclooctadiene afforded the mono cycloadduct in 83 % yield.

Noncarbon Cumulenes

523

Also, 4-dimethylaminophenylthionitroso S-sulfide 38 reacts with norbornadiene to give the mono cycloadduct 39 41 . S Me2N

N

S

+

S

S N

NMe2 38

39

[4+2] Cycloadditions The facile [4+2] cycloaddition reaction of N-sulfinylamines as dienophiles with 1,3-dienes to give the six-membered ring cycloadducts 40 was first observed by Wichterle and Rocek in 1953 42 . Subsequent work by many investigators demonstrated the general nature of this reaction and butadiene and its methyl- and dimethyl derivatives react readily, and the yields are normally very high as shown in Table 7.6. Table 7.6 [4+2] Cycloadducts of N-sulfinyl derivatives and 1,3-dienes R1

R1 R2

RN

S

O

R2 OS

+

RN

R3 R4

R3 R4

40

R

R1

R2

R3

R4

Yield (%)

Reference

CF3 Ph 4-MeOPh 4-MeOCOPh α-C10 H7 PhSO2 PhSO2 4-MePhSO2 4-MePhSO2 4-ClPhSO2 4-O2 NPh

H H H H H H H H H H H

Me H Me Me Me H Me H Me H H

Me Me Me Me Me H Me H Me H H

H H H H H H H H H H H

90 85 88 87 70 95 93 95 90 95 95

43 44 43 43 43 14 14 14 14 14 14

The direction of addition of unsymmetrical dienes depends on the polarization of the double bonds. For example, from 1-methylbutadiene and N-sulfinyl-p-toluenesulfonamide only the cycloadduct 41 is obtained 14 . d

O

O

S

S

NSO2R

+ d Me

N SO2R 41

524


In the reaction of the three isomeric hexadienes with TsNSO, stereospecific nonconcerted [4+2] cycloaddition is observed. For example, from trans-hexadiene the diastereomeric suprafacial adducts 42 and 43 are obtained 45 . Me

Me O

+

O

S

TsNSO

S

+

NTs

NTs

Me 42

Me 43

From cis-trans hexadiene and TsNSO the expected cycloadduct is obtained, while from cis–cis hexadiene the antarafacial adduct 44 is obtained. Me O +

S

TsNSO

NTs Me 44

In the reaction of pentacene 45 with N-sulfinylacetamide the [4+2] cycloaddition proceeds across the center diene system to give 46 in yields of >90 % 7 . COMe O

N S

+

MeCONSO

45

46

Several perfluoro sulfinylamines also undergo [4+2] cycloaddition reactions with 1,3dienes 46 . The asymmetric Diels–Alder reaction of TsNSO with acyclic dienes in the presence of stoichiometric amounts of chiral bis-oxazoline Cu(ii) or Zn(ii) triflates affords mainly the cis-adducts 47 in 60–85 % yields 47 . R

R +

R

O S

TsNSO

NTs R 47

From cyclic dienes the endo products are obtained as major products. A copper catalyst was found to be more efficient with 10 mol% loading 48 . The preferential formation of endo products also follows from a theoretical study 49 .

Noncarbon Cumulenes

525

The cycloaddition of N-sulfinylphosphoramidiates with cyclohexadiene showed stereoselectivity at sulfur under thermal or Lewis acid conditions. For example, from 48 (R = Et or Me) the [4+2] cycloadducts 49 are obtained in 83 % and 80 % yields, respectively, with an endo:exo ratio of >95:5 % 50 . O O

O

(RO)2P

S N

S +

O

N P RO

OR 48

49

Diphenylbenzofuran 50 reacts with N-sulfinylaniline by addition and subsequent elimination to give 1,2,3-triphenylisoindole 51 51 . Ph O

PhN

+

S

O

O

O S NPh

SO2 NPh

Ph 50 NPh

SO2

+

51

The immonium salts 52, derived from the reaction of aliphatic N-sulfinylamines with tritrialkoxonium tetrafluoroborate, also undergo a cycloaddition reaction with 2,3-dimethyl1,3-butadiene to give the cycloadducts 53 52 . O +

Me2N+

S

SO BF4–

BF4

NMe2 52

53

The reaction of α-oxoketenes, generated in situ, with N-sulfinylamines affords mixtures of [2+2] and [4+2] cycloadducts in 9–54 % yields, but more often the [4+2] cycloadducts are obtained in high yields (Chapter 4, Section 4.1.4.4) 53 . The α-oxo N-sulfinylamine EtOCONSO reacts with norbornene to give the [4+2] cycloadduct 54 in 80 % yield. 54 OEt

O +

EtOCONSO S O 54

N

526


In contrast, reaction with 2,3-dichlorobutadiene affords the regular Diels–Alder adduct in 70 % yield. N-Sulfinylaniline can also participate in a [4+2] cycloaddition reaction as a diene. For example, norbornene or dicyclopentadiene react with N-sulfinylaniline to give the cycloadduct 55 55 . O

O S

S N

+

N

55

Also, benzalaniline 56 reacts with N-sulfinylanilines to give the [4+2] cycloadducts 57 in high yields 56 . H N PhNSO

+

R2CH

56

NR1

O S NR1

R R 57

7.4.2 Sulfurdiimides, RN S NR 7.4.2.1

Introduction

Sulfurdiimides are obtained from aromatic amines and sulfur tetrafluoride. Heating of N-arylsulfonylimido dichlorides with aromatic amines affords N-aryl-N’sulfonylarylsulfurdiimides. The latter compounds are also formed in the stepwise replacement of the arylsulfonyl moiety in bis-arylsulfonylsulfurdiimides with aromatic amines. The [4+2] cycloaddition reactions of sulfurdiimides, which proceed in high yields, were extensively investigated. Sulfurdiimides containing metal substituents are used in the construction of cyclic and bicyclic N S N compounds.

7.4.2.2


[2+2] Cycloadditions The [2+2] cycloadducts derived from sulfurdiimides are seldom isolated but exchange reactions with heterocumulenes, proceeding via a [2+2] cycloaddition sequence, are often observed. In the reaction of diphenylketene with ditosylsulfurdiimide at −15 ◦ C the [2+2] cycloadduct 58 is formed, while at 70 ◦ C the [3+2]

Noncarbon Cumulenes

527

cycloadduct 59 is obtained 57 . NTs TsN Ph2C

C

O

+

TsN

S

NTs

or

Ph2

O

O

Ph2

S

TsN

NTs S

58

59

In contrast, the reaction of di-t-butylsulfurdiimides 60 with phenyl isocyanate proceeds across the C N bond of the isocyanate to give the expected exchange products t-butyl isocyanate 61 and t-butylphenylsulfurdiimide 62 58 . PhN

C

O

+

t-BuN

S N–t-Bu 60

t-BuN

C 61

O

+

t-BuN

S 62

NPh

With two equivalents of p-chlorophenyl isocyanate, complete exchange with formation of di-p-chloro-phenylsulfurdiimide and two equivalents of t-butyl isocyanate is observed. Removal of the volatile t-butyl isocyanate is the driving force for the completion of the exchange reaction. The reaction of phenyl isothiocyanate and di-t-butylsulfurdiimide gives rise to the formation of N-phenyl-N’-t-butylsulfurdiimide and sulfur, indicating that the exchange reaction proceeds across the C S bond in the isothiocyanate. With two equivalents of phenyl isothiocyanate, 60 affords N-phenyl-t-butylcarbodiimide 64. The reaction proceeds via the four-membered ring intermediate 63. N N 2 PhN

C

S + t-BuN

S

S

N–t-Bu

PhN

N–t-Bu + PhN

C

S+–S–

S PhN 60

63

64

Insertion reactions of selenium- and sulfurdiimides are also pronounced. Selenium bis(t-butylimide) reacts with triethylborane to give a four-membered ring insertion product 65 59 . N t-BuN

Se

N–t-Bu

+

BEt3

SeEt N

Et2B 65

[3+2] Cycloadditions The reaction of the aziridine derivative 66 with diarylsulfurdiimides, in the presence of a palladium catalyst, affords the imidazolidinethiones 67 in 52–70 % yields 60 . R

R

RN + N R1 66

RN

S

NR S

N R1 67

[4+2] Cycloadditions The [4+2] cycloaddition of sulfurdiimides with dienes is a well known reaction and the cycloadducts 68 are often obtained in good yields (see Table 7.7).

528


Table 7.7 [4+2] Cycloadducts of sulfurdiimides and 1,3-dienes R2

R2

R3 + R4

NSO2R

R3 RSO2N

S

S

NR1

NR1

R4 R5

R5 68

R

R1

R2

R3

R4

R5

Yield (%)

Reference

Ph Ph Ph Ph 4-MePh 4-ClPh 4-ClPh 4-O2 NPh

Ph 4-MePh 4-O2 NPh 4-Me2 NSO2 Ph 4-MePh 4-ClPh 4-ClPh 4-O2 NPh

H H H H H H H H

Me Me OEt Me H H Me H

Me Me H Me H H H H

H H H H Me Me H Me

87 90 92 89 —a —a —a —a

58 58 58 58 59 59 59 59

a

¨ The yields of the isolated cycloadducts (Koster et al., 1996 59 ) are 85–90 %.

The Diels–Alder reaction of sulfurdiimide 69 with cyclohexadiene affords the cis-vicinal carbamate 70 in good yield 61 . H +

MeO2C–N

S

NCO2Me S

N–CO2Me

NCO2Me H

69

70

In the reaction of ditosylseleniumdiimides with 1,3-dienes, instead of the expected [4+2] cycloadducts only the 1,2-disulfonamides are obtained. 62 Also, disulfonylsulfurdiimides undergo the [4+2] cycloaddition reaction and the obtained yields are very high 58 . An intramolecular [4+2] cycloaddition reaction occurs in imidoylsulfurdiimides 71, which are generated in situ from arylamidines and N-sulfinylarylsulfonamides to give 72 63 . R3 R2

N

R1 NH2

R3

R1

N

+ RSO2NSO

N

R2

S

R3

S

R2

NH

NSO2R

RSO2N 71

R1

N

72

Noncarbon Cumulenes

7.4.3 7.4.3.1

R

R1

R2

R3

Yield (%)

Me 4-MePh 4-MePh 4-MePh

Ph Ph 4-ClPh PhNH

H H H H

H H H H

86 95 96 90

529

N-Sulfonylamines, RN SO2 and Hexavalent Sulfurdiimides Introduction

Derivatives of hexavalent sulfur are also known. The aliphatic N-sulfonylamines (RN SO2 ) are well known. Lwowski and Scheiffele 64 suggested that N-sulfurylaniline is formed as a reactive intermediate in the base-catalyzed decomposition of N(p-nitrobenzenesulfonoxy)benzenesulfonamide. The alkyl-N-sulfonylamines participate in cycloaddition reactions. From FSO2 N SO2 only a four-membered ring dimer is obtained 65 . Tris-imidosulfur derivatives (RN )3 S and sulfur diimides containing hexavalent sulfur are also known 66 . Other hexavalent sulfur-containing linear heterocumulenes include (R3 SiN )2 S O, (R3 CN )2 S NX (where X = Rf , R1 SO2 , SF5 and POF2 ) and RN S(F2 ) NR. 7.4.3.2


In the reaction of (Me3 SiN )3 with perfluoropropyl N-sulfinylamine an exchange reaction occurs with formation of Me3 SiN S NC3 F7 and Me3 SiN S(O) NSiMe3 . The latter undergoes cyclodimerization to give 73 67 . Me3SiN 2 Me3SiN

S(O)

NSiMe3

S O Me3SiN

NSiMe3 O S NSiMe3 73

In the reaction of FSO2 NSO with sulfur trioxide an initial reaction across the N S bond occurs with formation of sulfur dioxide and FSO2 N SO2 . The latter dimerizes via a [2+2] cycloaddition reaction across the S N bond to give 1,1,3,3-tetraoxo-2,4difluorosulfonylcyclodiaza-λ6 -thian 74 (yield, 80 %) 67 . O2S 2 FSO2N

SO2

NSO2F

FSO2N

SO2 74

The monomeric FSO2 N SO2 is obtained from the dimer as a 1:1 complex with N4 S4 or pyridine 68 .

530


7.4.3.3


[2+1] Cycloadditions t-Butylsulfonylamine 75 reacts with the diazoalkane derivative 76 at −78 ◦ C to give 2,3-di-t-butylaziridine 1,1-dioxide 77 in 43 % yield 69 . SO2

t-BuN t-BuN

SO2

+

Me3CH

N2

H CMe3

75

76

77

On heating, 77 eliminates sulfur dioxide to give an azomethine in quantitative yield.

[2+2] Cycloadditions N-Sulfonylurethane, MeOOC–N SO2 78, which is obtained in a [4+2] cycloreversion reaction from 1,4,3,5-oxathiadiazines, reacts with olefins, like styrene and 1,1-diphenylethylene, to give a mixture of [2+2] cycloadducts 79 and [4+2] cycloadducts 80 70 .

RR1C

MeOCON CH2

+

MeOCON

SO2

SO2

+

RR1

RR1

S O

78

79

OMe

O N

O 80

In the reaction of N-sulfonylurethane with styrene, the ratio of 79:80 = 1:4, while from 1,1-diphenylethylene and trimethylethylene only the [2+2] cycloadducts are isolated. From phenylcarbonyl-N-sulfonylamine 81 and EtOCH CH2 at 30 ◦ C, the [2+2] cycloadduct 82 is obtained in 71 % yield 71 . SO2

PhCON PhCON

SO2 + EtOCH

CH2

EtO

81

82

Tetramethylallene also reacts with EtOCON SO2 to give a mixture of the [2+2] and the [4+2] cycloadducts in a combined yield of 60 % 72 . The [2+2] cycloaddition reaction of N-sulfonylamines across C O and S O double bonds results in exchange reactions. For example, reaction of MeOCON SO2 with diphenylcyclopropenone affords the corresponding imine in quantitative yield, while dimethylsulfoxide affords Me2 S NCOOMe 70 . Ethyl-N-sulfonylamine reacts with the enamine 83 to give the [2+2] cycloadduct 84 in good yield 73 . EtN EtN

SO2 + Me2C

CH-N

SO2

N H

83

84

Noncarbon Cumulenes

531

Likewise, reaction of the activated olefin 85 with EtN SO2 gives a 85 % yield of the cycloadduct 86. O EtN

SO2 + Cl2C

EtN

C

SO2

O

O

Cl2

O

85

86

The reaction of sulfur t-butyltriimides 87 with fluoro- or chlorosulfonyl isocyanate results in an exchange reaction giving rise to the formation of t-butyl isocyanate and another sulfur triimide 88 74 . t-BuN (Me3CN

S

t-BuN

)3S + RSO2NCO

N RSO2

N–t-Bu O

87 (Me3CNCO + (Me3CN

)2S

NSO2R

88

When the reaction is conducted using excess sulfonyl isocyanate, the [2+2] cycloadducts 89, derived from a different sulfur triimide and t-butyl isocyanate, are isolated. RSO2N (Me3CN

)2S

NSO2R + RSO2NCO + Me3CNCO

S

RSO2N

N–t-Bu

N

O

t-Bu 89

R

Yield (%)

F CF3

85 34.5

A similar exchange reaction is observed in the reaction of tris-trimethylsilylsulfur triimide with perfluoroisopropyl isocyanate, giving rise to the formation of N-trimethylsilyl-N’perfluoroisopropylsulfurdiimide 90 and (Me3 SiN )2 S O 69 . (Me3SiN

)3S + C3F7NCO

Me3SiN

S

NC3F7 + (Me3SiN

)2S

O

90

Cycloaddition across the S N bonds in perfluorosulfinylamines and in sulfur triimides to give cyclodiaza-λ6 -thianes 91 is also observed. t-BuN (C2F5CN

)2S

NCMe3 + (Me3CN

)2S

NC3F7

C3F7N

S N

t-Bu

N–t-Bu N–t-Bu S NC3F7 91

532


The parent sulfonylamine 92, generated in situ from HN3 and SO3 , undergoes trimerization to give the six-membered ring heterocycle 93 75 . O

O S

HN3 + SO3

[HN

NH O O HN S S N O O H

SO2]

92

93

In the reaction of CF3 SO2 N SO2 with arylnitriles [2+2+2], the cycloadduct 94 is obtained 76 . From benzonitrile and FSO2 N SO2 the corresponding [2+2+2] cycloadduct also is obtained in 60 % yield 77 . O CF3SO2N

O

N

SO2 + 2 RCN

S

NSO2CF3

N 94

[3+2] Cycloadditions Aliphatic N-sulfonylamines react with aziridines with ring-opening and formation of the [3+2] cycloadducts 95 78 . Ph RN

SO2 + N

Ph

Ph

Ph

Me2N

C

NR SO2

N

NMe2

95

[4+2] Cycloadditions The reaction of MeOCON SO2 with dimethylaminoacetylene gives the [4+2] cycloadduct 96 in 40 % yield 79 . O

MeO MeOCON

SO2 + PhC

CNMe2

N

NMe2 Ph

S

O

1-phenyl-2-

O 96

N-Sulfonylamines undergo [4+2] cycloaddition reactions with some dienes to give 1,2thiazin-5-one 1,1-dioxides 97. O RN

SO2 + CH2 C(OSiMe3)CH

SO2 NR

CHR1 97

R

R1

Et i-Pr i-Pr

OMe OMe H

Yield (%)

Reference

60 71 14

80 82 83

Noncarbon Cumulenes

533

Some 2-azabutadienes also undergo [4+2] cycloaddition reactions with alkyl Nsulfonylamines, but linear adducts are also obtained 81 . 7.4.4 7.4.4.1

Dithionitronium Salts, S N+ N Introduction

Dithionitromium salts have the structure − S N+ S− , which is an unusual cumulative system. The bonding in the SNS+ compounds is represented by the following valence structures, indicating that the sulfur and nitrogen atoms carry positive and negative charges. –S

N+

S+–N––S+

S–

N–S+

S

An example of the dithionitronium salts is dithionitronium hexafluoroarsenate SNS+ AsF− 6 , which in liquid sulfur dioxide reacts with numerous double- and triple-bonded substrates to form the [3+2] cycloadducts 98 in virtually quantitative yields. SNS+AsF6− + A

N S + S A B 98

B

AsF6

This type of reaction was discovered when a sample of the salt was dissolved in acetonitrile. From this solution, a 1:1 cycloadduct was isolated in quantitative yield. The dichlorodithionitronium cation ClSNSCl+ also serves as a masked SNS+ species because it undergoes cycloaddition reactions with alkynes and olefins 82 . For example, reaction of the dichlorodithionitronium salt with ethyne and propyne in sulfur dioxide below room temperature affords the expected [3+2] cycloadducts 100. Most likely, an intermediate dichloro cycloadduct 99 is formed, which loses chlorine to form the isolated cycloadduct. ClSNSCl+ AsF6− + RC

N

Cl

S

CH

S

N S + S

Cl

AsF 6 + Cl2

R

R 99

100

In the reaction of ClSNSCl+ AsF− 6 with olefins the initially formed dichloro cycloadducts are stable. However, dichlorodithionitronium salts do not form cycloadducts with nitriles. 7.4.4.2


Across carbon multiple bonds The reaction of SNS+ AsF− 6 with alkynes proceeds in sulfur dioxide as the solvent to give the [3+2] cycloadducts 101 in almost quantitative yields. R 1C

CR2 + SNS+ AsF6−

N S + S R1

R2 101

AsF6

534


R2

Reaction time

H CN Me CF3 CF3 COOMe Ph Me3 Si

H H H H CF3 COOMe Ph Me3 Si

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