Organophosphorus Chemistry

Organophosphorus Chemistry Volume 13 A Specialist Periodical Report Organophosphorus Chemistry Volume 13 A Review o...

Author: D. W. Hutchinson

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Organophosphorus Chemistry Volume 13

A Specialist Periodical Report

Organophosphorus Chemistry Volume 13

A Review of the Literature published between July 1980 and June 1981

Senior Reporters

D. W. Hutchinson Department of Chemistry and Molecular Sciences, University of Warwick J. A. Miller Chemistry Department, University of Dundee Reporters

D. W. Allen Sheffield City Polytechnic R. S. Edmundson University of Bradford C.

D. Hall King's College, London

J. B. Hobbs The City University, London W. J. Stec Polish Academy of Sciences,*ddi

J. C . Tebby North Staffordshire Polytechnic, Stoke-on- Trent B. J. Walker Queen's University of Belfast

The Royal Society of Chemistry Burlington House, London W1 V OBN

British Library Cataloguing in Publication Data Organophosphorus chemistry.-Vol. 13.(Specialist periodical report/Royal Society of Chemistry) 1. Organophosphorus compounds - Periodicals I. Royal Society of Chemistry 11. Series 547’.07’05 QD412.Pl ISBN 0-85186-1 16-4 ISSN 0306-0713

Copyright 01982 The Royal Society of Chemistry All Rights Reserved

No part of this book may be reproduced or transmitted in any form or by any means - graphic, electronic, including photocopying, recording, taping, or information storage and retrieval systems - withour written permission from The Royal Society of Chemistry

Printed in Great Britain by Adlard and Son Ltd Bartholomew Press, Dorking

Introduction

One of the major events of 1981 was the International Conference on Phosphorus Chemistry held at Duke University, Durham, NC, and which included sessions recognizing the contributions of Professors Wittig and Westheimer to phosphorus chemistry. The manuscripts provided by those lecturing at this Conference have been published by the American Chemical Society, and give an idea of the ‘state of the art’ in phosphorus chemistry. In this volume, the occasional review concerns the important anti-cancer drug cyclophosphamide and has been contributed by Professor W. J. Stec of the Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, in €hdi, Poland. Despite many trials and tribulations, Professor Stec has completed his voluminous review with very little delay, and must be congratulated for the production of an interesting, up-to-date review. Next year, the occasional review will be devoted to the mass spectrometry of organophosphorus compounds, a field which has become increasinglyimportant with the advent of such techniques as field desorption and fast-atom bombardment, which allow the mass spectra of involatile compounds to be studied. During the past year, the use of nucleoside polyphosphates that are specifically labelled with oxygen isotopes for the investigation of enzyme mechanisms has continued to provoke considerable interest and elegant experimentation, and has afforded many new results. Significant progress has been made in the development of novel reagents and methods for use in the phosphotriester strategy of oligonucleotide synthesis, and in particular the description of increasingly, efficient solid-phase methods for this process. Reports on the simple, large-scale preparation of nicotinamide coenzymes and sugar phosphates, using immobilized enzymes, should be of considerable commercial importance, as the starting materials are cheap and the products require little or no purification. Interest in the new field of two-co-ordinate phosphorus compounds continues to grow. Monomeric trimetaphosphate, for so long an elusive species, has been prepared, and it can attack acetophenone at the carbonyl oxygen atom to give an enol phosphate. New synthetic developments include the use of palladium complexes in the synthesis of phosphonic acids and the formation of mixed phosphate esters by the stepwise replacement of triazole groups from phosphoryl tris(triazo1ide). In keeping with one of the themes of the 1981 ICPC meeting, there has been much exciting progress on several aspects of the Wittig reaction. Particularly pleasing is the degree of agreement (albeit not complete!) between MO studies, and perhaps the most thorough general experimental study of the Wittig reaction

vi

Introduction

mechanism yet published. These studies clearly indicate that betaine intermediates, so favoured for many years, must now be regarded as unlikely, at least in salt-free systems. For the more practically orientated there have also been valuable additions to our options for control of the geometry of alkenes in Wittig reaction products. Another old faithful in which some mechanistic progress has been made is the Conant reaction, between phosphorus(II1) halides and simple carbonyl compounds. Much of the new synthetic work with phosphines and derived oxides or sulphides has been devoted to new heterocyclic phosphorus compounds. Perhaps the most novel is in the medium-ring field, where, for example, the first synthesis of a phosphonin has appeared. Once again, the synthesis of new chiral di- and tri-phosphine ligands for asymmetric homogeneous hydrogenation continues to attract much attention. The phospha-alkenes are becoming increasing recognized as interesting reactive intermediates, as are the phospha-alkynes. There should be exciting times ahead as the properties of these n-bonded structures are investigated. Various aspects of the equilibria between phosphorus(Iv), phosphorus(v), and phosphorus(v1) species remain a focal point for research. Overall, one has the impression that organophosphorus chemistry remains an active field, in which there is much new fundamental work being done, and several interesting and potentially valuable applications are being examined. This provides its enthusiasts with a nice blend of consolidation in some areas, and of completely new horizons in others. April 1982

D.W.H. J.A.M.

Contents Chapter 1 Phosphines and Phosphonium Salts By D. W. Allen

1

1 Phosphines Preparation From Halogenophosphines and Organometallic Reagents From Metallated Phosphines By Addition of P-H to Unsaturated Compounds By Reduction Miscellaneous Methods of Preparation Reactions Nucleophilic Attack at Carbon Nucleophilic Attack at Halogen Nucleophilic Attack at Other Atoms Miscellaneous Reactions

1 1 1 3 6 7 9 13 13 14 17 19

2 Phosphonium Salts Preparation Reactions Alkaline Hydrolysis Additions to Unsaturated Phosphonium Salts Miscellaneous Reactions

21 21 24 24 26 27

3 Phospholes and Phosphorins

29

Chapter 2 Quinquecovalent Phosphorus Compounds By C. D. Hall

33

1 Introduction

33

2 Structure and Bonding

34

3 Phosphoranes containing a P-H Bond

34

4 Acyclic Phosphoranes

36

5 Four-membered-ring Phosphoranes

39

6 Five-membered-ring Phosphoranes

39

7 Hexaco-ordinated Phosphorus Compounds

47

vii

viii

Contents

Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller

49

1 Introduction

49

2 Halogenophosphines

49 49

Preparation Reactions with Carbonyl Compounds and Related Compounds Reactions with Group V Donors Reactions with Carbanions, Alkenes, and Aromatic Compounds Insertion Reactions of Silylphosphines Physical and Structural Aspects 3 Halogenophosphoranes Structural Preparation Reactions with Nitrogen Compounds Reactions Relevant to Organic Synthesis

Chapter 4 Phosphine Oxides and Related Compounds By J. A. Miller

51 55 55

57 57 58 58 58 59 59

62

1 Introduction

62

2 Preparation of Acyclic Oxides

62

3 Preparation of Cyclic Oxides

66

4 Structural and Physical Aspects

69

5 Reactions at Phosphorus

71

6 Reactions of the Side-Chain

72

7 Phosphine Oxide Donor-Acceptor Complexes, and Extractants

75

Chapter 5 Tervalent Phosphorus Acids By B. J. Walker

77

1 Introduction

77

2 Phosphorous Acid and its Derivatives Nucleophilic Reactions Attack on Saturated Carbon Attack on Unsaturated Carbon Attack on Nitrogen

77

77 77 79 85

Contents

ix Attack on Oxygen Attack on Halogen Electrophilic Reactions Cyclic Esters of Phosphorous Acid Miscellaneous Reactions 3 Phosphonous and Phosphinous Acids and their Derivatives

Chapter 6 Quinquevalent Phosphorus Acids By R. S. Edmundson

86 88 88 94 95 96

98 98

1 Synthetic Methods General Phosphoric Acid and its Derivatives Phosphonic and Phosphinic Acids and their Derivatives

98 100 103

2 Reactions General Phosphoric Acid and its Derivatives Phosphonic and Phosphinic Acids and their Derivatives

111 111 113 121

Chapter 7 Phosphates and Phosphonates of Biochemical Interest 131 By D. W. Hutchinson 1 Introduction

131

2 Coenzymes and Cofactors

132

3 Sugar Phosphates

134

4 Phospholipids

135

5 Phosphonates

137

6 Enzyme Mechanisms

139

7 Phosphorylated Proteins

141

8 Other Compounds of Biochemical Interest

142

Chapter 8 Cyclophosphamide and its Congeners By W. J. Stec

145

1 Introduction

145

2 The Rationale for the Synthesis of Cyclophosphamide

146

3 The Current Status of Knowledge of the Metabolism of Cyclophosphamide

146

Contents

X

4 The Synthesis of Analogues of Cyclophosphamide and their Metabolites

153

5 Biological Properties of Newly Synthesized Analogues of Cyclophosphamide

170

6 Concluding Remarks

172

Chapter 9 Nucleotides and Nucleic Acids B y J . B. Hobbs

175

1 Introduction

175

2 Mononucleotides Chemical Synthesis Cyclic Nucleotides Affinity Chromatography

175 175 182 185

3 Nucleoside Polyphosphates Chemical Synthesis Affinity Labelling

187 187 197

4 Oligo- and Poly-nucleotides Chemical Synthesis Enzymatic Synthesis Sequencing 0ther Studies

201 20 1 212 213 214

5 Analytical Techniques and Physical Methods

219

Chapter 10 Ylides and Related Compounds By B. J. Walker 1 Methylenephosphoranes

Preparation and Structure Reactions Aldehydes Ketones Miscellaneous

222 222 222 226 226 230 233

2 Reactions of Phosphonate Anions

240

3 Selected Applications in Synthesis

247 247 249

Pheromones Prostaglandins

xi

Contents Carbohydrates Carotenoids and Related Compounds /3-Lactam Antibiotics Non-benzenoid Aromatic Compounds Miscellaneous Applications

Chapter 11 Physical Methods By J. C. Tebby

249 249 25 1 252 254

259

1 Nuclear Magnetic Resonance Spectroscopy Biological Applications and Instrumental Techniques Chemical Shifts and Shielding Effects Phosphorus-31 BP of n2 compounds BP of n3 compounds BP of n4 compounds BP of n6 compounds Carbon-13 Nitrogen-15 Chlorine-35 Studies of Equilibria, Shift Reagents, and Liquid Crystals Variable-temperature Studies Pseudorotation Restricted Rotation Studies of Configuration Spin-Spin Coupling J(PP) and J(PM) J(PC) J(PH) J(PCnH) and J(PXCnH) Studies of Relaxation, CIDNP, and N.Q.R.

259 259 259 259 260 260 26 1 262 262 262 262 262 263 263 264 265 265 265 266 267 267 268

2 Electron Spin Resonance Spectroscopy

268

3 Vibrational and Rotational Spectroscopy Band Assignments and Absorptivity Bonding Stereochemistry Rotational Data

269 269 270 27 1 272

4 Electronic Spectroscopy Absorption Spectroscopy Photoelectron Spectroscopy X-Ray Fluorescence Spectroscopy

272 272 272 273

5 Diffraction X-Ray Diffraction Electron Diffraction

273 273 276

xii

Contents

6 Dipole Moments and the Kerr Effect

277

7 Mass Spectrometry

278

8 pKa and Thermochemical and Kinetic Studies

278

9 Chromatography Gas-Liquid Chromatography Thin-layer Chromatography and Paper Chromatography High-performance Liquid Chromatography Column Chromatography

280 280 280 280 280

Author Index

281

Abbreviations* AIBN CIDNP CNDO CP DAD DBN DBU DCC DIOP DMF DMSO DMTr EDTA E.H.T. ENU FID g.1.c.-m.s. HMPT HN2 h.p.1.c. 1.r. L.F.E.R. MIND0 MO MS-Cl MS-nt MS-tet NBS n.q.r. p.e. PPA SCF TBDMS TDAP TFAA Tf2O

bisazoisobutyronitrile Chemically Induced Dynamic Nuclear Polarization Complete Neglect of Differential Overlap cyclopentadienyl diethyl azodicarboxylate 1,5-diazabicyclo[4.3.O]non-5-ene 1,5-diazabicyclo[5.4.O]undec-5-ene dicyclohexylcarbodi-imide [(2,2-dimethyl-1,3-dioxolan-4,5-diyl)bis(methy1ene)lbis( diphenylphosphine) dimethylformamide dimethyl sulphoxide 4,4’-dimethoxytrityl ethylenediaminetetra-aceticacid Extended Hiickel Treatment N-ethyl-N-nitrosourea Free Induction Decay gas-liquid chromatography-mass spectrometry hexamethylphosphortriamide methylbis-(2-chloroethyl)amine high-performance liquid chromatography infrared Linear Free-Energy Relationship Modified Intermediate Neglect of Differential Overlap Molecular Orbital mesitylenesulphonyl chloride mesitylenesulphonyl-3-nitro1,2,4-triazole mesit ylenesulphonyltetrazole N- bromosuccinimide nuclear quadrupole resonance photoelectron polyphosphoric acid Self-Consistent Field t-butyldimethylsilyl tris(diethy1amino)phosphine trifluoroacetic acid trifluoromethanesulphonic anhydride

* Abbreviations used in Chapters 7-9 and 1978,171, 1.

are detailed in Biochem. J., 1970,120, 449 xiii

xiv THF t.1.c. TPS-C1 TPS-nt TPS-tet TsOH U.V.

Abbreviatiort

tetrahydrofuran thin-layer chromatography tri-isopropylbenzenesulphonylchloride tri-isopropylbenzenesulphonyl-3-nitro1,2,4-triazole tri-isopropylbenzenesulphonyltetrazole toluene-p-sulphonic acid ultraviolet

1 Phosphines and Phosphonium Salts BY D. W. ALLEN

1 Phosphines Preparation.-From Hulogenophosphines and Orgunometallic Reagents. Interest in the availability of tertiary phosphines which may form hydrocarbon-soluble transition-metal complexes (of possible importance in homogeneous catalysis) has prompted the synthesis of a series of arylphosphines (l), bearing straightchain alkyl substituents in the para-position of the benzene ring, via the reaction of phosphorus trichloride with Grignard reagents derived from the appropriate p-bromo(alky1)benzene. These phosphines are more sensitive to atmospheric oxidation than is triphenylphosphine.' The reactions of bis(dich1orophosphino)methane with Grignard reagents (or equimolar mixtures of Grignard reagents) have given the diphosphines (2), which on treatment with hydrogen chloride are converted into the corresponding bisphosphonium salts. The reaction of the bis(dich1orophosphine) with t-butylmagnesium chloride unexpectedly gives the cyclic tetraphosphine The Grignard procedure has also been used in the synthesis of the chelating diphosphine (4), which undergoes dehydration in the presence of certain rhodium(1) complexes to give (5).4 ( 3 ) . 2 9 3

(1) TI = 2-9

(2) R',Rz= alkyl or Ph

Organolithium reagents continue to be widely employed in the synthesis of tertiary phosphines. Improved routes to the (2-pyridy1)phosphines(6), involving the reactions of halogenophosphines with 2-lithiopyridine, have been de~cribed.~ S . Franks and F. R. Hartley, J . Chem. SOC.,Perkin Trans, I , 1980, 2233. A. A. Prishchenko, N. E. Nifant'ev, Z . S. Novikova and I. F. Lutsenko, Zh. Obshch. Khim., 1980, 50, 1881 (Chrm. Abstr., 1980, 93, 239 536). A. A. Prishchenko, Z . S. Novikova, and 1. F. Lutsenko, Zh. Obshch. Khim., 1980, 50, 687 (Chem Abstr., 1980, 93, 186 460). M. A. Bennett and H. Neumann, Aust. J . Chrm., 1980, 33, 1251 H. Schmidbaur and Y . Inoguchi, 2. Nuturforsch., Tril. B , 1980, 35, 1329.

1

2

Organophosphorus Chemistry

Me

( 6 ) n = 0,1, o r 2

(7) R’ = H, Me, or Pri;R2 = CH(OR),

(8)

Q\

[I”/;.;;lr..

Fe

PPh

(9) R = Me, But, o r Ph

The reactions of N-protected 2-lithio-imidazoles with phosphorus trichloride have given the (imidazoly1)phosphines(7), from which the N-protecting group can be removed on treatment with aqueous acetone.6 The potentially chelating ligand (8) is formed in the reaction of di-t-butylchlorophosphinewith a 2-lithiomethylquinoline reagent.’ The synthesis of (0-hydroxyaryljphosphines, e.g. (9), in good yield has been achieved from the reactions of halogenophosphines with the lithium reagent that is obtained on treatment of o-bromophenol with two moles of butyl-lithium.* The atropisomeric, chelating diphosphine (10) (which has been resolved via chiral palladium complexes) has been prepared from the reaction of chlorodiphenylphosphine with the dilithium reagent obtained from metallation of 2,2’-dibromo-l,l’-binaphthylwith t-butyl-lithi~m.~ A second report of the synthesis of the phosphino-[ Ilferrocenophane (1 1) has appeared.1° A wide range of chiral ferrocenyl-phosphines and -diphosphines, e.g. (12), has been prepared by previously established routes involving lithiation of the ferrocenyl nucleus ortho to the chiral aminoalkyl function, followed by reaction with

Fe

(HOOC CH,),P

n

P(CH,COOH),

PR, (12) R = Me or Ph N. J. Curtis and R. S . Brown, J . Org. Chem., 1980, 45, 4038. A. J . Deeming, 1. P. Rothwell, M. B. Hursthouse, and K. M. A. Malik, J . Chem. Soc., Dalton Trans., 1980, 1974. 8 A. Tzschach and E. Nietzschmann, Z. Cfzem., 1980, 20, 341. 9 A. Miyashita, A. Yasuda, H . Takaya, K . Toriumi, T. Ito, T. Souchi, and R. Noyori,J. Am. Chem. SOC.,1980, 102, 7932. l o A. G . Osborne, R. H. Whiteley, and R. E. Meads, J . Organonlet. Cfiem., 1980, 193, 345. 6

Phosphines and Phosphonium Salts

3

an appropriate halogenophosphine.ll9 l2 Similarly, ortho-lithiation of (hydroxymethyl)cymantrene, followed by treatment with chlorodiphenylphosphine,gives (13).13 Further studies of the synthesis of chiral phosphines via the reactions of organometallic reagents with phosphinous esters that are derived from cinchonine have been reported.14The phosphorus analogue (14) of EDTA has been prepared by alkylation of 1,2-bis(dich1orophosphino)ethane with ethyl(bromozinc)acetate, followed by hydrolysis of the resulting tetraester, and isolated as the tetrasodium ~ a 1 t . lThe ~ dimethoxyethane solvate of bis(trifluoromethy1)cadmium has been used to alkylate phosphorus tri-iodide, giving tris(trifluoromethyl)phosphine, but only in 20% yield.16 Preparation from Metallated Phosphines. The reactions of metallophosphide reagents with alkyl halides or tosylates (and related sulphonate esters) continue to be widely employed in the synthesis of phosphines, and a considerable number of new systems, many of which are chiral, have been described. This area continues to be stimulated by the great interest in the use of chiral phosphines as ligands in transition-metal complexes that are used as catalysts for asymmetric hydrogenation and related reactions; a timely review of this field has appeared.17 The reactions of sulphonate esters with lithiophosphide reagents have been employed in the synthesis of the chiral unidentate phosphines (15)'* and (16),19 and of a range of chiral bidentate phosphines,20-22e.g. (17)20 and (18).21 In the CH,PPh,

I

l1

l2

13

l4 15 l6 1' 18 l9 2O 22

K. Yamamoto, J. Wakatsuki, and R. Sugimoto, Bull. Chem. SOC. Jpn., 1980,53,1132 T. Hayashi, T. Mise, M. Ftlkushima, M. Kagotani, N. Nagashima, Y. Hamada, A. Matsumoto, S. Kawakami, M. &onishi, K. Yamamoto, and M. Kumada, Bull. Chem. SOC.Jpn., I 1980,53, 1138. N. M. Lim, P. V. Kondrar'ev, N. P. Solov'eva, V. A. Antonovjch, P. V. Petrovskii, Z. N. Parnes, and D. N. Kursaqov, J. Organomet. Chem., 1981, 209, 233. W. Chodkiewicz, J. Organomet. Chem., 1980, 194, C25. J. Podlahova and J. Podlaha, Collect. Czech. Chem. Commun., 1980, 45, 2049. L. J. Krause and J. A. Morrison, J. Chem. SOC.,Chem. Commun., 1980, 671. V. Caplar, G. Comisso, and V. SunjiC, Synthesis, 1981, 85. G. Comisso, A. Sega, and V. h n j i c , Croat. Chem. Acta, 1980, 53, 445. D. Valentine, Jr., K. K. Johnson, W. Priester, R. C. Sun, K. Toth, and G. Saucy, J . Org. Chem., 1980,45, 3698. D. P. Riley and R. E. Shumate, J. Org. Chem., 1981, 45, 5187. P. A. MacNeil, N. K. Roberts, and B. Bosnich, J. Am. Chem. SOC.,1981, 103, 2273. J. Benes and J. Hetflejs, Czech. P. 178 228 (Chem. Abstr., 1981, 94, 121 713).

4


synthesis of (18), the (d)-10-camphorsulphonate esters were employed, these having the advantage of being readily separated into internal diastereoisomers by crystallization. The reactions of alkyl halides with lithiophosphide reagents have been employed in the synthesis of a range of DIOP systems (19). Purification of these phosphines is facilitated by the preparation of the copper(1) complexes, which, following recrystallization, are decomposed with ammonia to give the free ligand.23The reactions of lithiophosphide reagents with halides or tosylates have also been used in the preparation of polymer-supported p h o s p h i n e ~ , ~ ~ - ~ ~ e.g. (20).24 Interest continues in the synthesis of macrocyclic phosphines from the reactions of lithiophosphide reagents that are derived from bis(secondary alky1)phosphines with appropriate alkyl halides, under high-dilution conditions. Among the systems reported in the past year are (21)-(23).28-30

Ph

Lithiophosphide reagents have also been used for the synthesis of a range of other systems. (Dimethylaminomethy1)ferrocene undergoes asymmetric cyclopalladiation to give the chiral complex (24), which, on treatment with lithium diphenylphosphide, gives the chiral ligand (25).31 The reaction of lithium phosphide with benzoyl chloride in dimethoxyethane has given the lithium complex (26) of the enol form of dibenz~ylphosphine.~~ The dichloro-lactone (27) is converted into the diphosphine (28) on treatment with lithium diphenylphosphide, but, in the related reaction with diphenyl(trimethylsilyl)phosphine, only one chlorine is replaced, to give (29).33 Syntheses involving reagents obtained from metallation at a carbon atom that is alpha to phosphorus have also been reported. Thus lithiomethyl(dipheny1)23 2.1 25

26 27 28 29

30 31 32 33

J. M. Townsend, J. F. Blount, R. C. Sun, S. Zawoiski, and D. Valentine, Jr., J. Org. Chem., 1980, 45, 2995. T. Hayashi, N. Nagashima, and M. Kumada, Tetrahedron Lett., 1980, 21, 4623. J. K. Stille, S. J. Fritschel, N. Takaishi, T. Masuda, H. Imai, and C. A. Bertelo, Ann. N . Y. Acacl. Sci., 1980, 333, 35 (Chenz. Abstr., 1980, 93, 185 407). V. Kavan and M. Capka, Collect. Czech. Cliem. Commun., 1980, 45, 2100. J. I. Schulman, U.S. P. 4 209 468 (Clwm. Abstr., 1980, 93, 239 644). M. Ciampolini, P. Dapporto, N. Nardi, and F. Zanobini, Znorg. Chim. Acta, 1980, 45, L239. E. P. Kyba and S-S. P. Chou, J . Org. Chetn., 1981, 46, 860. E. P. Kyba and S - S . P. Chou, J . Am. Chem. SOC.,1980, 102, 7012. V. 1. Sokolov, L. L. Troitskaya, and 0. A. Reutov, J . Organomet. Chem., 1980,202, C58. G. Becker, M. Birkhahn, W. Massa, and W. Uhl, Angew. Chem., I n t . Ed. Engl., 1980. 19, 741. D. Fenske, H. Prokscha, P. Stock, and H. J. Becher,Z. Naturforsch., Ted. B, 1980,35, 1075.

5

Phosphines and Phosphonium Salts Ph

\

phosphine has been used to prepare a range of phosphines that are based on the zirconocene nucleus, e.g. (30).34The related reagent (31), obtained from the metallation of methoxymethyl(diphenyl)phosphine, has found application for the hydroformylation of sterically hindered, enolizable Sodium diethylphosphide and potassium diphenylphosphide have been used to prepare new polydentate, tripod-like phosphines, e.g. (32).36937 The reactions of sodiophosphide reagents with chloromethyltrimethylsilanehave given a range of a-trimethylsilyl-substituted methylphosphines (33).3s The new ligand (34) is formed in the reaction of potassium diphenylphosphide with chloromethyl phenyl t h i ~ e t h e rA. ~route ~ to ethylmethylphosphine, starting from phosphine, via stepwise metallation with sodium and subsequent alkylation has also been described.40

PhP( R)CH, SiMe,

PhSCH,PPh,

(33) R = Me, Et, Pri, Ph, or CH,SiMe,

(34)

A considerable number of new heterocyclic systems have been prepared via the use of metallophosphide reagents. The reaction of dilithium methylphosphide with a,o-dichloro-polysilanes has given the permethyl-phosphacyclopolysilanes (35),41 and the addition of t-butoxyl radicals to some of these systems, giving phosphoranyl radicals, has been studied by e.s.r. spectros~opy.~~ Amongst new N . E. Schore and H. Hope, J . Am. Chem. SOC., 1980, 102,4251. E. J. Corey and M. A . Tius, Tetrahedron Lett., 1980, 21, 3535. 3 6 C. Bianchini, C. Mealli, A. Meli, and L. Sacconi, Znorg. Cliim. Acta, 1980, 43, 223. 37 C. Bianchini, A . Meli, A. Orlandini, and L. Sacconi, J . Organomet. Chem., 1981, 209, 219. 38 R. Appel, J. Peters, and R. Schmitz, Z . Anorg. Allg. Chem., 1981, 475, 18. 39 A . R. Sanger, C. G . Lobe, and J. E. Weiner-Fedorak, Inorg. Cliim. Actn, 1981, 53, L123. 4 0 J . G. Morse, Znorg. Chim. Acta, 1980, 41, 161. 41 T. H. Newman, R. West, and R . T. Oakley, J . Organomet. Chem., 1980, 197, 159. 4 2 T. H. Newman and R. West, J . Organomet. Chem., 1980, 199, C39. 34

35


6 (SiMe,), Me,Si’ ‘SiMe,

I

PhP-PPh

I

Me,SiySiMe, Me (35) n = 0, 1, or 2

I

ButP --But B ‘’ NR* (36) R = alkyl or Ph

PhP\

\

/PPh N C6Hl I (37)

But P

/ \

ButP -PBu‘

(39) R = Prior But

(38)

(40) R = Prior But

systems that have been reported in the past by Baudler’s group are (36)43 and (37),44Of particular interest is the cyclopropane-like ring-closure with lithium hydride, giving reaction of 1,3-di-iod0-1,2,3-tri-t-butyltriphosphane (38).4sThe related reactions of bis(monoha1ogenophosphino)methanes with alkali metals have given the diphosphacyclopropanes (39), which dimerize readily to give (40).49 Preparation of Phosphines by Addition of P-H to Unsaturated Compounds. A procedure for the continuous production of (secondary alky1)phosphines by the free-radical-catalysed addition of phosphine to alkenes at high temperature and pressure, in an inert solvent, has been described. The bicyclic secondary phosphines (41) have also been prepared by this method.50 Free-radical-catalysed procedures continue to be, employed in the synthesis of polydentate phosphine ligands. Thus, e.g., the addition of cyclohexylphosphine to vinyldiphenylphosphine has given (42), and addition of dicyclohexylphosphine to phenyldivinylphosphine gives (43).51Secondary phosphines also undergo free-radical-catalysed

rr\

Cy P(CH,CH,PPh,),

(R’HC) PH(CHR2),

QJ

(41) n , m = 1 - 3 (n + rn R’, R2= H or alkyl

< 5)

R10SO2NHCH(Ph)PR2,

(42)

CyP [ C( X)NHPh ] ,

(45) X = 0 or S (44) R’ = H or Me R 2 = P h o r Cy

PhP(CH,CH,PC y 3,

(43)

k k Ph

(46)

50

Baudler and A. Marx, Z. Anorg. Allg. Chem., 1981, 474, 18. Baudler and P. Lutkecosmann, Z . Anorg. Allg. Chem., 1981, 472, 38. Baudler, Y . Aktalay, J. Hahn, and E. Di rr, Z . Anorg. AIIg. Chem., 1981, 473, ?.0. Baudler, W. Fa5er, and J. Hahn, Z . Anorg. Allg. Chem., 1980, 469, 15. Baudler and S. Klautke, Z . Nuturforsch., Teil. B , 1981, 36, 527. Baudler and J. Hellmann, Z . Nrrturforsch., Teil. B , 1981, 36, 266. A. A. Prishchenko, Z . S. Novikova, and 1. F . Lutsenko, Zh. Obshch. Khirn., 1980, 50, 689 (Chem. Ahstr., 1980, 93, 168 342). G. Elmer, G . Heymer, and H . W. Stephan, Br. P . 1 5 6 1 874 (Cham. Abstr., 1981, 94, 8 4

51

294). G. Miihlbach, B. Rausch, and D. Rehder, J . Organornet. Chem., 1981, 205, 343.

43 4-1 45

46 47

-18 49

M. M. M. M. M. M.

7


addition to N-(arylsulphony1)benzaldimines to give the a-(arylsu1phonamido)benzylphosphines (44).52 Further studies have been made of the addition of primary and secondary phosphines to hetero-allenes. Amongst new products of such reactions are the phosphino-amides (43, which arise from the addition of cyclohexylphosphine to phenyl isocyanate and phenyl is~thiocyanate.~~ Various substituted 4-phosphorinanones, e.g. (46), have been prepared by the addition of phenylphosphine to appropriately substituted penta-l,4-dien-355

Preparation qf Phosphines by Reduction. The reduction of phosphine oxides and phosphine sulphides continues to be a major route to phosphines, and the past year has seen the use of a wide range of reagents. The complex that is formed when titanium tetrachloride is reduced with four equivalents of lithium hydride in THF is capable of reducing phosphine oxides in high yield.56The most commonly used reagent has been trichlorosilane, which has been employed for the reduction of phosphine oxides to give both chiral forms of the chelating diphosphine (47),57 the substituted phospholans (48) and (49), and the bicyclic system (50), as a mixture of It has also found use in the synthesis of the novel bicyclic heterocyclic phosphines (51) and (52), designed to explore the possibility of forcing the lone pair on phosphorus into n-p, conjugation with the aromatic ring as a result of the steric constraints that are imposed by the ring system. Alas, electrochemical and spectroscopic data suggest that in neither of these compounds does this interaction occur to any significant extent, and both systems behave normally in reactions with oxygen and i ~ d o m e t h a n e . ~ ~

0:

QPPh2

d3 s

PPh,

Me (49)

(47)

(50) 52 53 54 55 56 57

58 59

(51)

( 5 2)

K. Kellner, H-J. Schultz, and A. Tzschach, Z . Chem., 1980, 20, 152. D. H. M. W. Thewissen and H. P. M. M. Ambrosius, R e d . Trar. Cliiiii. Puys-Bas, 1980,99, 344. J. B. Rampal, G. C . Macdonnell, J. P. Edasery, K. D. Berlin, A. Rahman, D. van der Helm, and K. M. Pietrusiewicz, J. Org. Chem., 1981, 46, 1156. J. B. Rampal, K. D. Berlin, J. P. Edasery, N. Satyamurthy, and D. van der Helm, J . Org. Chem., 198 1,46, 1166. U. M. Dzhemilev, L. Yu. Gubaidullin, G . A. Tolstikov, and L. M. Zelenova, Izzo. Akutl. Nauk SSSR, Ser. Khim., 1980, 734 (Chem. Abstr., 1980, 93, 25 841). H. Brunner, W. Pieronczyk, B. Schonhammer, K . Streng, I. Bernal, and J. Korp, Chem. Ber., 1981, 114, 1137. J. E. MacDiarmid and L. D. Quin, J . Orp. Chem., 1981, 46, 1451. C . H. Chen, K. E. Brighty, and F. M. Michaels,J. Org. Chem., 1981, 46, 361.

8

Organophosphorus Chemistry R' \P

R' = M e or Ph

( 5 3)

(54)

( RZ,R3 = H or Me)

(55)

Trichlorosilane in the presence of pyridine, in benzene solution, has been used in the reduction of the phosphine oxide of the first dibenzophosphonin system (53). This potentially aromatic lor-electron system is found to be highly puckered and non-aromatic as a result of the unfavourable orientation of p-orbitals, preventing extended pn-p,, overlap.6o A combination of trichlorosilane with triethylamine in benzene solution is effective for the reduction of phosphole oxide dimers (54) to the syn-7-phosphanorbornenes (55), which have the most deshielded 31Pn.m.r. shifts ever reported for tertiary phosphines. Attempted reduction of (54) with trichlorosilane in the absence of triethylamine leads to a retro-McCormack cycloaddition, with loss of the phosphorus bridge.s1 The 7-phosphanorbornene system (56) has been obtained by reduction of the corresponding phosphine sulphide, using the nickelocene-ally1 iodide reagent that has been developed by Mathey's group in the past few yearss2 This reagent has also found application in the synthesis of the (E)-l,3-butadienyl-phosphines (57).63Reduction of phosphine sulphides has also been achieved, using sodium, in the preparation of chiral diphosphines, e.g. (58),64 and by the use of hexachlorodisilane in the preparation of chelating diphosphinomethanes, e.g. (59).65-67 Ph

Ph,PCH,PBu',

Ph,P(CH,).CN

(5 9)

(60) n = 3 or 4

0 'Me

(61) 60

61 62

63 64

65 66 67

E. D. Middlemas and L. D. Quin, J . Am. Chem. SOC.,1980, 102, 4838. L. D. Quin and K. A. Mesch, J . Chem. SOC.,Chem. Commun., 1980, 959. F. Mathey and F. Mercier, Tetrahedron Lett., 1981, 22, 319. F. Mathey, F. Mercier, and C. Santini, Inorg. Chem., 1980, 19, 1813. 0. Samuel, R. Couffignal, M. Lauer, S . Y. Zhang, and H. B. Kagan, Nouu. J . Chim., 1981, 5 , 15. S. 0. Grim, P. H. Smith, I. J. Colquhoun, and W. McFarlane, Inorg. Chem., 1980,19, 3195. S. 0. Grim, L. C. Satek, and J. D. Mitchell, Z. Naturforsch., Teif. B, 1980, 35, 832. S. 0. Grim and E. D. Walton, Phosphorus Sulfur, 1980, 9, 123.


9

Diphenylsilane has found use for the selective reduction of (w-cyanoalky1)phosphine oxides to give (60).ss Full details have now appeared of the use of phenylsilane in the selective reduction (with retention of configuration at phosphorus) of epoxyphosphine oxides to give, e.g., (61).s9 Several patents have appeared, describing conditions for the reduction of dichlorophosphoranes to phosphines by hydrogen under pressure, either in the presence or absence of a transition-metal c a t a l y ~ t . ~ ~ - ~ ~ Miscellaneous Methods of Preparation of Phosphines. The synthesis of the diphospheten system (62) by the reactions of substituted acetylenes with cyclopolyphosphines has been re-investigated, and improved routes have been d e ~ e l o p e d . ~ ~ Treatment of the phosphonium salt (63) with butyl-lithium generates an ylide which rearranges over the course of 2-3 days to form the bicyclic phosphine (64), the structure of which was proved by X-ray Tris(trimethylsiloxymethy1)phosphine is converted into the bicyclic phosphine (65) on treatment with trimethyl orthoacetate in the presence of toluene-p-sulphonic An interesting ring-contraction occurs, on treatment of the perhydrodiazaphosphorine(66) with p-toluidine, to give the azaphosphetidine (67).76 A number of other (aminomethyl)phosphines, some of them chiral, have been prepared by the reactions of (hydroxymethy1)phosphines with amines or with

I

I

RZC=CR2 RIP-PR'

[a C/ H!(NMe2)R

c1 OP(0Et)R

“aa >/P O E t

+ RCH=kMe,

Cl-

(15) 5 6

7

J. Rachon and U. Schollkopf, Liebigs Ann. Chem., 1981, 99. J. Rachon, U. Schollkopf, and T. Wintel, Liebigs Ann. Chem., 1981, 709. B. Costisella and H. Gross, Phosphorus Suvur, 1980, 8, 99.

+ EtCl

Tervalent Phosphorus Acids

79

Stable Arbusov intermediates continue to be of interest. Those formed from the cyclic phosphinite (16), i.e. (17), are thought to be on the borderline between phosphonium salts and phosphoranes, on the basis of n.m.r. and dipole-moment evidence.8

(17a) R = Me, X = I (17b) R = PhCH,, X = Br

R'

\

Cl'

0

R2

+ (R*O),P

C-C' 0 ''

+

II

R'COCR2R3P(0R1),+ R'CI

'R-?

(1 8)

b-Ketophosphonic esters (18) have been prepared by the reaction of or-chloroepoxides with trialkyl pho~phites.~ The new route overcomes the problem of the Perkow reaction (leading to enol phosphates) which is associated with similar reactions of or-halogeno-ketones. Attack on Unsaturated Carbon. Arbusov reactions with vinyl halides have been used to prepare a variety of vinylphosphonates, e.g. (19) and (20).1° Variations include the use of catalysis by palladium of the addition of a secondary phosphite, which provides a stereoselective route to vinylphosphonates,ll and the photostimulated reaction of diethyl phosphite anion with vinylmercurials.12 In the latter case, the reaction appears to take place by a free-radical mechanism. 0

F 2 C = = C F X+ (ROXP

I1 + (RO)2PCF=CFX

0

0

I1 ll + (RO)2PCF=CFP(ORX

The numerous reports of the addition of tervalent phosphorus to alkenes and related compounds include reactions with p-benzoquinone dibenzenesulphonimide,13 quinone mono xi me^,^^ and fuch~0ne.l~ Treatment of the azoalkene (21) with phosphites gives mixtures of diazaphsspholes (22) and the derived acyclic compounds (23), depending on the tervalent phosphorus compound.16 I. Granoth and J. C. Martin, J. Am. Chem. Soc., 1981, 103, 2711. J. Gasteiger and C. Herzig, Tetrahedron Lett., 1980, 21,2687. l o R. Dittrich and G . Hagele, Phosphorus Sulfur,1981, 10, 127. l1 T. Hirao, T. Masunaga, Y.Ohshiro, and T. Agawa, Tetrahedron Lett., 1980, 21, 3595. 1 2 G. A. Russell and J. Hershberger, J. Am. Chem. SOC.,1980, 102, 7603. 13 M. M. Sidky, M. R. Mahrau, and M. F. Zayed, Phosphorus Sulfur,1980, 9, 337. 14 M. M. Sidky, M. F. Zayed, A. A. El-Kateb, and I. T. Hennawy, Phosphorus Sulfur, 1980, 9, 343. 15 Yu. G. Shermolovich, L. N. Markovskii, Yu. A. Kopel'tsiv, and V. T. Kolesnikov, Zh. Obshch. Khim, 1980, 50, 811 (Chem. Abstr., 1980, 93, 95 344). l6 G. Baccolini, P. Todesco, and G. Bartolli, Phosphorus Sulfur, 1980, 9, 203. 8

80


0

Examples of the nickel(@-chloride-catalysed reaction of tervalent phosphorus with aromatic halides include the synthesis of the phosphonate (24), en route to phosphindolin-3-one (25).17 The mechanism of this general reaction has been investigated.ls In the absence of the aromatic halide, triethyl phosphite and nickel(@ chloride form tetrakis(triethy1 phosphite)nickel(o), and this compound is an effective catalyst for the conversion of iodobenzene into the phosphonate (26). On the basis of this observation and a competitive kinetic study of three para-substituted iodobenzenes, the mechanism shown in Scheme 2 has been suggested. Dialkyl pyridin-4-yl- (27), quinolin-4-yl-, and isoquinolin-1-yl4(EtOXP + NiCI, -+ [(EtOXP],Ni

5

ArNi[(EtO),P],I

I

(Slow) (- Ni")

0

II ArP(OEt), + EtI

+-

Ar$(OEt), 1-

(26) Scheme 2

$%b 0

\\P(OR),

H

+ (RO),P

.:-/. 0 17

1.9

0

\\

€'(OR), +

A H

(27) 0

T. M. Balthazor, J. Org. Chem., 1980, 45, 2520. T. M. Balthazor and R. C. Grabiak, J. Org. Chem., 1980, 45, 5425.


81

phosphonates have been synthesized regiospecifically by the reaction of trialkyl phosphites with the corresponding N-(2,6-dimethyl-4-oxopyridin-l-yl)-heterocycle in the presence of sodium iodide.ls Similar reactions are successful with acridinium and xanthylium ions, but not with the 2,6-diphenylpyrylium salt (28), and the synthesis of the phosphonate (29)20 and of the thio-analogue (30)2f requires the use of sodium diethyl phosphonate. On the other hand, even nitrogroups can be replaced by secondary phosphites if the aromatic ring is sufficiently activated and the conditions are sufficiently severe.22

Cl0,-

(29) X = 0 (30) X = S

(28)X = 0 or S

The widely studied reactions of phosphines with electrophilic acetylenes have been extended to p h ~ s p h i t e sIn . ~these ~ cases the intermediates appear to be more stable, and a series of compounds can be detected by careful control of the reaction temperature. Structures have been suggested for these on the basis of 31P, 13C, and lH n.m.r. spectroscopic evidence and the isolation of the Arbusov product (31) on treatment with hydrogen bromide at - 10°C (Scheme 3).

/x \c/x

(ROhP-C

(ROXP + XC-CX

(at -50°C)

(X = C0,Me)

X L X h t - 10°C)

JX'J3

RO'

'OR

Scheme 3

The reactions of phosphites with imino-groups continue to be reported. This year, oximes appear to be popular substrates; for example, acetone oxime gives the 0-methylhydroxylamine phosphonate (32) with trimethyl phosphite2* and l9 20 21

22 23 24

A. R. Katritzky, J. G . Keay, and M. P. Sammes, J. Chem. Soc., Perkin Trans. I , 1981, 668. C. H. Chen and G . A. Reynolds, J. Org. Chem., 1980,45,2449. C. H. Chen and G . A. Reynolds, J. Org. Chem., 1980,45,2453. G . L. Matevozyan, S. N. Vodovatova, and P. M. Zavlin, Zh. Obshch. Khim, 1980,50,2803. J. C. Tebby, S. E. Willetts, and D. V. Griffiths, J. Chem. SOC.,Chem. Commun., 1981, 420. M. P. Osipova, P. M. Lukin, and V. A. Kukhtin, Zh. Obshch. Khim., 1980, 50, 1887 (Chem. Absrr., 1980, 93, 220 863).


82

0

II

(MeOXPCMe2NHOMe

(MeO),P

Me,C=NOH

(32)

( R O ) , F O Nat

,NHP(OR),

Me2C

\

0

(R'O)2PNC0

(34)

the diphosphonate (33) with sodium dialkyl p h o s p h i t e ~ .The ~ ~ reaction of isocyanatophosphites (34) with various trichloroethylideniminesleads to cyclic products (35).26 Full details have appeared of the synthesis of stilbenes by the reaction of sodium diethyl phosphite with aromatic aldehyde^.^' The suggested mechanism involves the formation of oxiran intermediates (36), followed by further attack of phosphite anion to give the Wadsworth-Emmons intermediate (37), and hence

0

/

/"\

+ ArHC-CHAr

(EtOhPt;

0

Ar

Ar

C=C

H

'

+(EtO)2P---0 \Ar

f-

(34)

\

/

/

\

HC-CH

-0

Ar

(37) 25

26 27

M. G . Zimin, A. R. Burilov, and A. N. Pudovik, Zh. Obshch. Khim., 1980,50,751 (Chem. Absrr., 1980, 93, 71 873). I. V. Konovalova, R. D. Gareev, L. A. Burnaeva, M. V. Cherkina, A. Khayarov, and A. N. Pudovik, Zh. Obshch. Khim., 1980, 50, 1446 (Chem. Abstr., 1980, 93, 220 847). T. Minami, N. Matsuzaki, Y . Ohshiro, and T. Agawa J. Chem. SOC., Perkin Trans. I , 1980, 1731.


83

stilbene. In most cases, similar reactions with aromatic ketones did not give any alkene; however, the sterically less hindered compound fluorenone gave 9,9’bifluorenylidene (38) and the spiro-ketone (39). A similar reaction of diethyl 1-[(N-sodio)anilino]cyclohexylphosphonate (40) with aromatic aldehydes provides a route to the isomeric oxirans (41). Amides of tervalent phosphorus acids generally undergo a reaction with aldehydes which involves a rearrangement; for example, the 2-anilidophospholan (42) reacts with benzaldehyde to give (43) and (44),28and the accompanying ring-opened product (45) is presumably the result of hydrolysis.

k B==8 +

0 + (EtOXP=O

\ /

\

/

I@h Na’

(>
PNPri, \ P-0 PI ',N (85)

(84)

Iminophosphines have also been reported to undergo the equivalent for tervalent phosphorus of the Wittig reaction.53Di-isopropylamino-t-butyliminophosphine (82) reacts with sulphur dioxide at low temperature to give t-butyliminosulphur oxide (83) and the novel heterocycle (85). The authors suggest that an initial [2 21 cycloaddition is followed by elimination of the so far unknown phosphinidene oxide (84), which trimerizes.

+

@CHR2 R',N-P %HRI

Y

R2 /CH\N

R'CHN?

R',N-P=CHR'

'CH-" R' (88)

-

ACHR'

(GNJ

II

R',W

R'ZNp\

/

CHR' (89)

Reactions of two-co-ordinate phosphorus compounds also provide insight into the relative stabilities of the acyclic and cyclic tautomers (86). For example, attempts to generate the unknown bis(methy1ene)phosphorane (87) from the 1,2,4A3-diazaphospholine(88) gave the isomeric A3-phosphiran(89).54 However, [bis(trimethylsilyl)amino]trimethylsilylmethylenephosphine (90) reacts with sulphur to give the methylene(thioxo)phosphorane (91) and its sulphur-addition product (92).5s The cyclic tautomer (93) was not observed. Further studies of

54

E. Niecke, H. Zorn, B. Krebs, and G. Henkel, Angew. Chem., Znr. Ed. Engl., 1980, 19, 709. E. Niecke, W. W. Schoeller, and D.-A. Wildbredt, Angew. Chem., Inr. Ed. Engl., 1981, 20,

55

E. Niecke and D.-A. Wildbredt, J. Chem. Soc., Chem. Commun., 1981, 72.

53

131.


91

three-membered phosphorus-containing heterocyclic rings have involved the synthesis of 1,2A3,3A3-azadiphosphiridines(94).66 These compounds prefer the cyclic rather than the alternative acyclic form (99, although cycloreversion occurs above 50 "C in the case of (94; R2= Pri) (Scheme 9).

R',N-P-NHR' H

i, ii

H R',N-P-NR

I R2,NPF

(R' = SiMe,)

NR'

I

5 R1,M'

'PNRZ,

(94)R2= SiMe, or Pri [ R' = Pri]

R' ,N-P=NR1

R~,N--P=NR'

+

+

+ [ Rz,NP:]

[R',NP:]

(95)

Reagents: i, BunLi; ii, R22NPFz; iii, MeLi

Scheme 9

Although frequently suggested as reaction intermediate^,^^ phosphinidene oxides have not so far been isolated. However, the amino-substituted example (97) can be stabilized by complexation through treatment of the iminophosphine complex (96) with sulphur dio~ide.~'

N (98)

(99)

H N-

1

4 N\p,NH

NMe,

7

(100)

2M(CO), + (CO),M\I (M = Mo, W,or Cr) HN/'~_/N,N

+

Me,,NL;

LdNMe, H (101)

56 57

E. Niecke, N. Nickloweit-Luke, and R. Ruger, Angew. Chem., Int. Ed. Engl., 1981,20, 385. E. Niecke, M. Engelmann, H. Zorn, B. Krebs, and G. Henkel, Angew. Chem., Int. Ed. Engf., 1980, 19, 710.

92


The ligand properties of 1,2,4,3-triazaphospholes have been inve~tigated.~~ While compounds (98) and (99) form 1 :1 complexes with transition-metal pentacarbonyls, 5-dimethylamino-l,2,4,3-triazaphosphole (100) forms the coordinated tetramer (101). Attempts to displace the tetramer from the metals A3-triazaphosphole (102) have led to the monomer. 2-Methyl-5-phenyl-2H-1,2,4,3 undergoes [4+ 11 cycloaddition at the a2-phosphorus with azodicarboxylic esters, followed by [2+ 21 dimerization of the initial product to give the diphosphoranes (103).59

2H-1,2,3 a2-Diazaphospholes (106) have been prepared from acetone hydrazones;6othe initially formed hydrogen chloride adducts can be ionic, e.g. (104), or covalent, e.g. (105), depending on the N-substituents. Methylation of (106) occurs at nitrogen to give (107) and phosphorylation at the carbon atom adjacent to phosphorus to give (108). c1-

RNHN=CMe,+

PC1,

Mef17Me

(105)

The phosphite coupling approach to oligonucleotide synthesis continues to be of interest. The bis-triazolyl(lO9) and bis-tetrazolyl(ll0) derivatives of tervalent phosphorus show much greater selectivity than the dichloro-compound (1 11) in phosphorylation of nucleosides,61and a new experimental procedure apparently 58 59 60

61

A. Schmidpeter, H. Tautz, J. Von Seyerl, and G. Huttner, Angew. Chem., Int. Ed. Engl., 1981,20,408. H. Tautz and A. Schmidpeter, Chem. Ber., 1981, 114, 825. J. H. Weinmaier, G. Brunnhuber, and A. Schmidpeter, Chem. Ber., 1980, 113, 2278. J. L. Fourrey and D. J. Shire, Tetrahedron Lett., 1981, 22, 729.

93

Tervalent Phosphorus Acids ROPX,

N (109) X

=

-N/ \-N

9

AN

(110) X = -N

L A (111)

x = c1

allows the use of tris(imidazo1-1-yl)phosphine, which had previously proved too unstable.62 The inconvenience caused by the instability of the generally used mononucleoside phosphite derivatives (1 14) has been overcome by replacing them with NN-dimethylaminophosphoramidites(113), which are readily available from chloro(NN-dimethy1amino)methoxyphosphine (112).s3

MeOP,

/NMe2 c1

(1 12)

+

Roc@ OH

Pri2NEt+

pB pB ROCH,

ROCH,

0

0

I

I

ROPX

MqNPOMe

(113)

N (114)

x = c1 or N4 \

‘N/ I

N=N (B = base)

(1 15)

Me

(117)

Both cis- and trans-NN-dimethylphosphoramidate(1 16)64 and phosphonate (1 17)65 analogues of thymidine 3’,5’-phosphate have been prepared by the reaction of the phosphite (1 15) with N-chlorodimethylamine and methyl iodide, respectively. Phosphite analogues (1 18) of ribonucleotides have been prepared66 and used in the synthesiss7 of a variety of analogues of diribonucleoside monophosphates, e.g. (1 19). 62

64 65 66

T. Shimidzu, K. Yamana, A. Murakami, and K. Nakamichi, Tetrahedron Lett., 1980, 21, 2717. S. L. Beaucage and M. H. Caruthers, Tetrahedron Lett., 1981, 22, 1859. A. E. Sopchik and W. G. Bentrude, Tetrahedron Lett., 1980, 21, 4679. G. S. Bajwa and W. G . Bentrude, Tetrahedron Lett., 1980, 21, 4683. B. P. Melnick, J. L. Funnun, and R. L. Letsinger, J. Org. Chem., 1980, 45, 2715; K. K. Ogilvie and M. J. Nemer, Tetrahedron Lett., 1980, 21, 4145. K. K. Ogilvie and M. J. Nerner, Tetrahedron Lett., 1980, 21, 4153.

94


R3si0T7 0 OSIR,

I

P-x

I I

EGNP-0

I

"TiUKd

o%urd R,SiO

HO OH

(118) X = OR, N k , or OCH$Cl,

OSiR,

(1 19)

Cyclic Esters of Phosphorous Acid.-The reactions of the isomeric pairs of phosphites (120) and (121), and (122) and (123), with ozone give the corresponding phosphates with a very high degree of retention of configuration.ss The results show that the intermediate ozonides, e.g. (124), do not undergo inversion. Similar reactions of the phosphites with neopentyl and t-butyl hypochlorites give close to 1 :1 ratios of the isomeric phosphates in all cases, and so probably involve equilibration of pentaco-ordinated intermediates.

MeXMe d o 'P'I

&qp\0M 0e

OMe

MeN-P

Me

Me

-NMe

(125)

Me

Me (1 26)

The bicyclic aminophosphines (125) and (126) have been prepared and their reactions with a-diketones to give phosphoranes investigated; (126), unlike (125), is relatively stable to polymerizati~n.~~ Full details of the synthesis of a series of 68 69

D. B. Denney, D. Z. Denney, and S. G. Schutzbank, Phosphorus Sulfur, 1980, 8, 369. D. B. Denney, D. Z. Denney, D. M. Gavrilovic, P. J. Hammond, C. Huang, and K.-S. Tseng, J. Am. Chem. SOC.,1980, 102, 7072.


95

diastereomerically pure 2,8-dioxa-5-aza-l-phospha(111)bicyclo[3.3.O]octanes (127) have been Two methods of synthesis are used, as shown in Scheme 10, and that from tris(dimethy1amino)phosphine also gives the phosphorane (128) through addition of dimethylamine to (127). Compounds (127) tend to oligomerize,’l and in one case a dimer was isolated and identified as (129).

HN

/cR 2CHR2

-

‘CR3 ,CH R40H

R

2

FR’ 7R35

R

4

0-P-0 (127)

Reagents: i, 3Et3N, PCh; ii, (Me2N)zP

Scheme 10

Examples of donor-acceptor adducts of aminophosphines in which both phosphorus and nitrogen are co-ordinated are rare, and the adducts are usually unstable when this does occur. However, the bicyclic aminophosphines (130) and (131) form, successively, mono- and di-adducts with diborane, all of which are remarkably Although (131) is a mixture of diastereoisomers, only adducts of the meso-form have been isolated. P-N\

Me’

‘R

(130) R = H (131) R = Me

Miscellaneous Reactions.-A kinetic study of the AIBN-initiated autoxidations of triethyl phosphite, diethyl ethylphosphonite, and ethyl diethylphosphinitehas been The results of electrochemical oxidation of the cis- and trans70

71 72

’3

C. Bonningue, D. Houalla, M. Sanchez, R. Wolf, and F. H. Osman, J . Chem. SOC.,Perkin Trans. 2, 1981, 19; see also D. B. Denney, D. Z. Denney, P. J. Hammond, C. Huang, and K . 4 . Tseng, J. Am. Chem. SOC., 1980, 102, 5073. B. J. Walker, in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1976, Vol. 7, p. 102. D. Grec, L. G. Hubert-Pfalzgraf, J. G. Riess, and A. Grand. J. Am. Chem. SOC.,1980,102, 71 33. W.-S. Hwang and J. T. Yoke, J. Org. Chem., 1980,4S, 2088.


96 R

R

trans-(1,32)

cis-(132)

isomers of 1,3-di-isopropy1-2,4-bis( di-isopropylamino)cyclodiphosph(~~~)azine (1 32) are quite different ;74 only the trans-isomer produces a stable radical cation. Isomeric mixtures of phosphole complexes (133) are formed in the reaction of cobaltacyclopentadienes with phosphites and with pho~phonites.~~ The free R'

Ph,P

(133)

phosphole can be obtained, in most cases, by oxidation with Ce4+ion. Phenylthiocopper is an insoluble polymer; however, it can be depolymerized in the presence of trimethyl phosphite to give the complex (134).76 This complex acts as a useful source of phenylthiocopper, converting alkyl halides into the corresponding thioethers and propargyl halides into allenyl thioethers. PhSCuP(OMe)3

(134)

3 Phosphonous and Phosphinous Acids and their Derivatives The barrier to inversion at phosphorus in phosphinous acid derivatives (136) has been suggested to be small on the basis of the results obtained from the S

II

,P X" M '\e Ph (135) X = OR or SR 74

75 '6

-

P

X

A\

/

Ph

Me

(136) X = OR or SR

A. F. Diaz, 0. J. Scherer, and K. Andres, J. Chem. SOC.,Chem. Commun., 1980, 982. K. Yasufuku, A. Hamada, K. Aoki, and H. Yamazaki, J. Am. Chem. SOC.,1980,102,4363. A. J. Bridges, Tetrahedron Lett., 1980, 21, 4401.


97

NR',

+ PhCH, R3

(137)

reduction of optically active thiophosphinic acid esters (135) by a variety of However, optically active amides of phosphinousacidscan be obtained in high yield from the corresponding chiral aminophosphonium salt (137) by electrochemical reduction or by cyanolysis; both reactions occur with retention of configuration at pho~phorus.~~

'7 78

L. Horner and M. Jordan, Phosphorus Sulfur, 1980,8,221. L. Horner and M. Jordan, Phosphorus Suljiur, 1980, 8, 227.

6 Quinquevalent Phosphorus Acids BY

R. S. EDMUNDSON

The chemistry of organophosphorus compounds that possess peroxide bonds1 and that of l-oxophosphonic acids2 have been reviewed. Mechanistic aspects of organophosphorus chemistry have been discussed in two Two further articles describe our current knowledge of the chemistry and biological evaluation of anti-cancer perhydro-1,3,2-0xazaphosphorines,~~ and the chemistry of compounds possessing a single P-N bond has been summarized.’ As in the Reports for previous years, the sections headed ‘General’ cover papers which describe work on phosphonic or phosphinic acid derivatives as well as on those of phosphoric acid, or which describe compounds having more than one type of ‘phosphyl’ function within the molecule. 1 Synthetic Methods General.-Although dimeric molecules may result from condensation reactions between formaldehyde and dihydrazides derived from phosphoric or phosphonic acids, the monomeric compound (1) has been isolated8 and its structure confirmed by X-ray analysis. The reaction between dialkyl phosphoroisothiocyanatidite and dialkyl trichloroacetylphosphonates yields the compounds (2), which are not isolable in pure form since, when heated, they afford the 1,3,2,4-dioxadiphospholans (3).1° Further compounds that possess this ring system have been obtained by the reaction between the phosphinates (4) and phosphorus trich1oride.l’ The treatment of dialkyl l-oxophosphonates with sulphur ylides yields, inter alia, the compounds (7), probably via the postulated intermediate (5). The enol phosphates (8) are also formed, through either a modified intermediate or a transition state of the type (6).12 M. Konieczny and G. Sosnovsky, Chem. Rev., 1981, 49. Yu. A. Zhdanov, L. A. Uzleva, and Z. I. Glebova, Usp. Khim., 1980,49, 1730. H. M. Buck, Recl. Trav. Chim. Pays-Bas, 1981, 100, 217. F. Ramirez, Pure Appl. Chem., 1980, 52, 1021. 5 W. J. Stec, Phosphorus Chem. Directed Biol., Lect. Int. Syrnp., 1979 (publ. 1980), p. 95. T. Kawashima, Kagaku No Ryoiki, 1979, 33, 1026 (Chem. Absfr., 1980, 93, 71 582). V. P. Kukhar and V. A. Gilyarov, Pure Appl. Chem., 1980, 52, 891. J. P. Majoral, M. Revel, and J. Navech, J . Chem. Res. ( S ) , 1980, 129. 9 J. Jaud, J. Galy, R. Kraemer, J. P. Majoral, and J. Navech, Acta Crystallogr., Sect. B, 1980, 36, 869. l o I. V. Konovalova, R. D. Gareev, L. A. Burnaeva, N. K. Novikova, T. A. Faskhutdinova, and A. N. Pudovik, Zh. Obshch. Khim., 1980, 50, 1451 (Chem. Abstr., 1981, 94, 15 808). 11 M. B. Gazizov, R. A. Khairullin, and A. I. Razumov, Zh. Obshch. Khim., 1980, 50, 1882 (Chem. Absrr., 1980, 93, 239 537). 12 F. Hammerschmidt and E. Zbiral, Monatsh. Chem., 1980, 111, 1015. 1

98

Quinquevalent Phosphorus Acids

99 R' 0 \

0

II

'PC HM eOCH( OE t )Me

R'

/

(4) R20 0

0

(R'O),PNCS

(R'O),PC II (O)CCI,

CCl,

II I1

(R20),P-C

OR'

I / 0-P=O

''eat

I

NCS (2)

\\

R'O

(3)

J [ (R'O),P(O)-, R2COR3]

(R2= Me or Ar, R 3 = Me,i(X)CH,; X is a lone pair or =O) Spectroscopic properties of 5-bromo-5-nitro-l,3,2-dioxaphosphorinans have been recorded, and some compounds exemplifying this system have been dehydrobrominated by the action of trieth~1amine.l~ Several derivatives of the 3,5-di-t-butyl-l,3,2-oxazaphospholinesystem (9) have been prepared, by standard procedures, and their n.m.r. spectra recorded; in one case, i.e. (9; X = 0, R = Me), a crystal structure was also determined.14 In the reactions between dialkyl phosphoroisocyanatidites and dialkyl aroylphosphonates, many related examples of which have been recorded in

But (9) X is a lone pair, =0, or =S 13

l4

R. Valceanu and I. Neda, Rev. Chirn. (Bucharest), 1980, 31, 964 (Chem. Abstr., 1981, 94, 208 253) ; Phosphorus Sulfur, 1980, 8 , 13 1. Yu. V. Balitskii, Yu. G. Gololobov, V. M. Yurchenko, M. Yu. Antipin, Yu. T. Struchkov, and I. E. Boldeskul, Zh. Obshch. Khim., 1980, 50, 291 (Chem. Abstr., 1980, 93, 26 506).


100

previous Reports, the formation of stereoisomeric mixtures of either 2-0x01,3,4-oxazaphospholidine derivatives or of 4-0~0-1,3,2-oxazaphospholidine derivatives (Scheme l), or indeed of O-alkylated products, depends on the nature of the substituent R2, and to a lesser extent on the nature of the alkyl groups.15 (MeO)?PNCO + (R'0)2P(0)COC,H,R2-4

1 dipolar ion I jj&$-i+

dipolar ion I1

/

[ R' = H. 'vie. or Me01

-

(MeO) P-N

0 '

\

>O

XP(O)(OR'),

Ar

Scheme 1

Synthesis of Phosphoric Acid and its Derivatives.-Aryl phosphorodifluoridates are conveniently obtained from the corresponding chlorides by the action of sodium fluoride in the presence of a crown ether.16 Aroyloxy phosphoro-dichloridates and -difluoridates are isolable from mixtures of a carboxylic acid anhydride and pyrophosphoryl ch10ride.l~ The mass spectra of the l-phosphabicyclo[2.2.2]octanes(10; R = Me, Et, or Pri; X=lone pair, 0, S, or Se)lS and (10; R=But; X=lone pair or 0)l9 have been recorded. Unlike the 4-methyl and 4-ethyl compounds, the 4-t-butyl bicyclic phosphite does not undergo ring-opening when chlorinated with sulphuryl chloride but is, instead, merely 0 ~ i d i z e d . l ~ 2-Hydroxyethyl phosphates have been described; not surprisingly, they polymerize when heated.20 Tris(tetrabuty1ammonium) hydrogen pyrophosphate has been described as a new reagent for the preparation of monosubstituted pyrophosphates from reactive (e.g. allylic) halides.21 Mixed disubstituted dihydrogen pyrophosphates have been prepared by the reaction between aryl dihydrogen phosphates and 4-methoxyphenyl hydrogen N-(2-aminophenyl)phosphoramidate in the presence of copper(r1) chloride.22 V. V. Konovalova, R. D . Gareev, L. A. Burnaeva, N. V. Mikhailova, and A. N. Pudovik, Zh. Obshch. Khim., 1980, 50, 285 (Chem. Abstr., 1980, 93, 114 399). l 6 F. Effenberger, G. Konig, and H. Klenk, Synthesis, 1981, 70. l7 F. Effenberger and G . Konig, Chem. Ber., 1981, 114, 916. l8 H. Kentamaa and J. Enqvist, Org. Mass Spectrom., 1980, 15, 520. l9 R. S. Edmundson and C. I. Forth, Phosphorus Sulfur, 1980, 8, 315. 20 K.-Y. Choi and S.-K. Choi, Taehan Hwahakhoe Chi, 1 9 8 0 , 2 4 , 4 6 3 (Chem. Abstr., 1981,94, 191 633). 21 V. M. Dixit, F. M. Laskovics, W. I. Noall, and C. D . Poulter,J. Org. Chem., 1981,46, 1967. 2 2 H. Takaku, K. Tsubuhari, and Y. Nakajima, Chem. Pharm. Bull., 1980,28, 1626. 15


101

The synthetic value of acylphosphonates as sources of enol phosphates and related compounds has been explored. An intermediate of the form ( 6 ) is consistent with the formation of enol phosphates (8) when acylphosphonates react with sulphur-containing ylides. A factor which contributes towards the control of the product ratio of (7) to (8) is the electron-withdrawing power of the group R2.l2 Reactions of the same phosphonates with the alkynes R4C=CH in toluene give the expected (a-hydroxya1kyl)phosphonates (1 1); these, when treated with base, afford either or both of the products (12) and (13). Here the relative proportions of products, (12) and (13), depend on the nature of the base; (13) is the principal product when the base is (Me,Si),NNa in DMS0.23 0 R<JP=X

(R'O),P(0)C(OH)RT'CR4

L0' (10) ( R'O),P(O)OCR2=C

=CH R4

( R1O)?P(0)OC H RZC-

C R4

(13)

(1 2)

Fresh evidence should help to dispel lingering doubts one might have concerning the existence of monomeric metaphosphate species. Fragmentation of either threo- or erythro-( 1,2-dibromo-l-phenylpropyl)phosphonicacid (14; R1= H) by a hindered base in the presence of acetophenone (Scheme 2) yields the enol phosphate; with ethyl acetate, in the presence of aniline, N-phenylacetimino ethyl ether is rapidly formed. These and other results are consistent with the rapid formation of a metaphosphate anion, capable of reacting at a carbonyl .~~ oxygen and so activating the group towards the nucleophilic a ~ n i n e Related reactions, using the methyl ester (14; R1= Me), suggest that the methyl metaphosphate anion is formed.25 Oxetans behave like oxirans in their reactions with cyclic hydrogen phosphorothioates ; the 2-(o-hydroxyalkylthio)-esters that are initially produced undergo 0

\/

CBrPhCHBrMe (-

'0-

MeC -R2

28- [R'= H] Br-,

- PhCBr=CHMe,

-2BH)

*

[Po;-]

'OR1 (14)

MeCR'

11

NPh

B-

II

+o-PO,

opo; Me-L-R'

I

+NH,Ph

Reagents: i, MeCOR2 (R2=Ph or OEt); ii, PhNHz

Scheme 2 23 24

25

F. Hammerschmidt, E. Schneyder, and E. Zbiral, Chem. Ber., 1980, 113, 3891. A. C. Satterthwait and F. H. Westheimer, J . Am. Chem. SOC.,1981, 103, 1177 A. C. Satterthwait and F. H. Westheimer, J. Am. Chem. SOC.,1980, 102,4464; Phosphorus Chem. Directed Biol., Lect. Int. Symp., 1979 (publ. 1980), p. 117.


102

(15)

isomerization to the 2-(co-mercaptoalkoxy)-esters.2sThe dihydropyranyl esters (15) are formed by addition of dialkyl oxyphosphoranesulphenyl chlorides to dihydropyran and subsequent dehydrochlorination with triethylamine or triethyl p h o ~ p h i t e .A ~ ~synthesis of chiral OSS-trialkyl phosphorodithioates utilizes the resolved diastereoisomeric amides (16) (see Scheme 3) and the removal of the amide function with retention of configuration, by a well-established procedure.28 R’O (R’O),P

‘a

A R2S’

‘NHtHMePh

0

R’0

/ \-

R2S

S M

Reagents: i, (+)- or (-)-PhMeCHNHz; ii, NaH, CS2; iii, R31

Scheme 3

Many of this year’s reports on the chemistry of the P-N bond concern new nitrogen-containing ring systems and their reactions. Phenyl phosphorodichloridate reacts with S-methylisothiouronium sulphate to give the expected product (17); on the other hand, ethyl phosphorodichloridate behaved unexpectedly, the product being the dihydro-l,3,2-diazaphosphorine(18).29 40x0perhydro-l,3,2-diazaphosphorineshave been prepared via the PII1 The 1,3,2-diazaphospholines (19) are obtained conventionally from NN’dib~tylbutane-2,3-di-imine.~l The 1,3,2-oxazaphospholine (20) is transformed into the 1,3,2-thiazaphosphoIine(21) by the action of phosphorus pentasulphide in the presence of aluminium chloride.32Phosphorus pentasulphide itself converts into the 1,3,2-oxazaphosphorine-4-thiones 4-hydroxy-1,3-diazole-5-carboxamides (22).33Other 1,3,2-oxazaphospholines(23) can be obtained by the cyclization of N-phosphorylated a-bromo-amidines by means of t-butoxide anion.34 The 26 27

28 29

30 31 32

33 34

0. N. Nuretdinova, Izv. Akad. Nauk SSSR, Ser. Khim., 1980, 477 (Chem. Absrr., 1980,93, 8098); 0 .N. Nuretdinova and F. F. Guseva, ibid., p. 2594 (Chem. Absrr., 1981,94,103 317). M. B. Gazizov, A. I. Razumova, and 1. Kh. Gizatullina, Zh. Obshch. Khim., 1980,50, 2386 (Chem. Absrr., 1981, 94, 139 552). A. Kotynski, K. Lesiak, and W. Stec, Pol. J. Chem., 1979,53,2403 (Chem. Abstr., 1980,93, 45 887). V.-S. Li and L. A. Cates, J . Heterocycl. Chem., 1981, 18, 503. E. E. Nifant’ev, A. I. Zavalishina, E. I. Smirnova, and M. M. Vlasova, Zh. Obshch. Khim., 1980, 50, 459 (Chem. Absrr., 1980, 93, 8151). A. M. Kibardin, T. Kh. Gazizov, and A. N. Pudovik, Izv. Akad. Nauk SSSR, Ser. Khim., 1980, 1452 (Chem. Abstr., 1980, 93, 168 203). Yu. V. Balitskii and Yu. G. Gololobov, Zh. Obshch. Khim., 1980, 50, 1204 (Chem. Abstr., 1980, 93, 114 409). Sumitomo Chemical Co., Ltd, Jpn. Kokai Tokkyo Koho 80 89267 (Chem. Absfr., 1981, 94, 65 682). G. L‘abbe, A. Verbruggen, and S. Toppet, Bull. Soc. Chim. Belg., 1981, 90, 99 (Chem. Abstr., 1981, 94, 192 203).


103

1,3,2-0xazaphospholidines (24) are the minor products from the reactions between ethyl bromopyruvate and dialkyl phosphoroisocyanatidites, the major products being the enol phosphates (25).35 The n.m.r. and mass-spectrometric properties of several (4s)- and (4R)-2alkoxy-4-alkyl-l,3,2-oxazaphospholidine 2-sulphides (26), prepared from optically active amino-alcohols by using standard procedures, have been An interesting route to good yields of 2-amino-l,3,2-oxazaphospholidine 2-oxides and 2-amino-perhydro-l,3,2-oxazaphosphorine 2-oxides is provided by the rearrangement of the phenylimino-compounds (27),37which is catalysed by boron trifluoride etherate. Bu

PhOP-(N=C

Organophosphorus Chemistry

Organophosphorus Chemistry

Organophosphorus Chemistry