Volume 4, Compendium of Organic Synthetic Methods

Compendium of Organic Synthetic Methods Compendium of Organic Synthetic Methods Volume 4 LEROY G.WADE, Jr. DEPARTMEN...

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Compendium of Organic Synthetic Methods

Compendium of Organic Synthetic Methods Volume 4 LEROY G.WADE, Jr.

DEPARTMENT OF CHEMISTRY COLORADO STATE UNIVERSITY FORT COLLINS, COLORADO

A Wiley-lnterscience Publication

JOHN WILEY & SONS, New York

Chichester

Brisbane

Toronto

Copyright0 1980 by John Wiley 8 Sons, Inc. All rights resewed. Published simultaneously in Canada.

No part of this book may be reproduced by any means, nor transmitted, nor translated into a machine language without the written permission of the publisher. Library of Congress Catalog Card Number:71-162800 ISBN 0-471-04923-9 Printedin the United States of America. 10 9 8 7 6 5 4 3 2 1

CONTENTS ABBREVIATIONS

ix

INDEX, MONOFUNCTIONALCOMPOUNDS

xi

INDEX, DIFUNCTIONAL COMPOUNDS

xii

INTRODUCTION

xiii

1 PREPARATIONOF ACETYLENES

1

2 PREPARATIONOF CARBOXYLIC ACIDS, ACID HALIDES,

AND ANHYDRIDES

9

3 PREPARATIONOF ALCOHOLS AND PHENOLS

28

4 PREPARATIONOF ALDEHYDES

73

5 PREPARATION OF ALKYLS, METHYLENES, AND ARYLS

102

6 PREPARATION OF AMIDES

135

7 PREPARATION OF AMINES

146

8 PREPARATIONOF ESTERS

176

9 PREPARATION OF ETHERS AND EPOXIDES

198

10 PREPARATIONOF HALIDES AND SULFONATES

215

11 PREPARATIONOF HYDRIDES

235

12 PREPARATIONOF KETONES

252

13 PREPARATION OF NITRILES

297

14 PREPARATIONOF OLEFINS

309

15 PREPARATIONOF DIFUNCTIONALCOMPOUNDS

340

PREFACE By their compilation of Volumes 1 and 2 of this Compendium, Ian and Shuyen Harrison filled one of the greatest needs of the synthetic community: a method for rapidly retrieving needed information from the literature by reactiontype rather than by the author’s name or publicationdate. Compendiumof Organic Synthetic Methods, Volume 4, presents the functional group transformations and difunctional compound preparations of 1977, 1978, and 1979. We have attempted to follow as closely as possible the classificationschemes of the first three volumes; the experienced user of the Compendium will require no additional instructions on the use of this volume. Perhaps it is fitting here to echo the Harrisons’ request stated in Volume 2 of the Compendium: The synthetic literature would become more easily accessible and more useful if chemists could write well-organized, concise papers with charts and diagrams that allow the reader to assess quickly and easily the scope of the published research. In addition, the reporting of actual, isolated yields and detailed experimental conditions will save a great deal of wasted effort on the part of other chemists hoping to apply the reported reactions to their own synthetic problems. I wish to express my gratitude to the many people who helped to bring this book to completion: To Mrs. JoAnn Barley for her patience and dedication in the typing of the camera-ready copy; to Roy Smith, James McKearin, and Jon Lawson for proofreading the manuscript with great care and offering hundreds of helpful suggestions; and to my wife Betsy for her patience and moral support throughout the arduous preparation of this Compendium. Fort Collins, Colorado

LEROY G. WADE,JR.

September, 1980

V

ABBREVIATIONS An attempt has been made to use only abbreviations whose meaning will be readily apparent to the reader. Some of those more commonly used are the following: Ac Am Ar

9-BBN Bu BZ

CP DBU DCC DDQ DEAD DIBAL (DIBAH) DMAD DME DMF DMSO Et Hex HMPA, HMPT hv L LAH LDA MCPBA Me MEM Ms MVK NBS Ni @ Ph PPA

Acetyl Amy1 Awl 9-borabicyclo[3.3.1 Inonane Butyl Benzyl Cyclopentadienyl 1,5-diazabicyclo[5.4.O]undecene-5 Dicyclohexylcarbodiimide 2,3-Dichloro-5,6-dicyanobenzoquinone Diethyl azodicarboxylate Diisobutylaluminum hydride Dimethyl acetylenedicarboxylate 1,P-Dimethoxyethane Dimethylformamide Dimethyl sulfoxide Ethyl Hexyl Hexamethylphosphoramide (hexamethylphosphoric triamide) Irradiationwith light Triphenylphosphineligand (if not specified) Lithium aluminum hydride Lithium diisopropylarnide meta-Chloroperbenzoic acid Methyl p-MethoxyethoxymethyI Methanesulfonyl Methyl vinyl ketone N-bromosuccinimide Raney nickel Polymeric backbone Phenyl Polyphosphoric acid

X

PPE Pr Py, Pyr Sia Tf TFA TFAA THF THP TMEDA TMP TMS Ts

A

ABBREVIATIONS

Polyphosphate ester Propyl Pyridine secondary-isoamyl Trifluoromethanesulfonate Trifluoroacetic acid Trifluoroacetic anhydride Tetrahydrofuran Tetrahydropyranyl Tetramethylethylenediamine 2,2,6,6-Tetramethylpiperidine TrimethylsiIyl p-Toluenesulfonyl Heat

E.

Miscellaneouscompounds

Oletins

Nitriles

Ketones

Hydrides (RH)

Halides,sulfonates,sulfates

Ethers, epoxides

Esters

Amines

Amides

Alkyls, methylenes, aryls

Aldehydes

Carboxylic acids, acid halides, anhydrides Alcohols, phenols

Acetylenes

I

14 7

12 6

10 5

5

8

4 3

1 1

29 21 30 22

25 19 26 19 27 20

23 15

16 9 17 9 18 12 19 13

44 59

36 36 37 37 38 38 39 39 40 44 41 46 42 48

29

34

31 28 32 28

94

60

59 92

74 118

90 145

144

88

61 102 47 62 77 73 103 135 4 8 6 3 76 104 49 64 79 82 105 137 50 83 51 66 81 84 106 138 52 82 84 140 53 68 83 86 107 141 54 69 84 86 107 141 55 70 85 87 109 142 56 71 86 90 113 142 57 72 87 90 115 143 102 158 103 160 104 161 105 161

96 150 97 154 98 155 99 156 100 156

148

94

93 146

119 196 120 197

134 209 135 214

111 188 112 189 113 128 189 205 114 129 191 206 115 130 191 206 116 192 117 132 194 208

107 176 108 123 182 198 109 124 186 203

166 181 136 215 252 297 137 152 167 217 235 253 138 153 168 217 236 257 139 169 184 221 264 298 140 155 170 222 239 266 186 301 142 157 172 187 223 239 268 303 158 173 188 241 269 303 144 159 174 225 242 270 145 160 175 190 226 243 271 303 146 176 191 227 274 305 147 177 192 230 275 306 163 193 250 306 149 179 194 231 282 307 150 165 180 195 233 251 284 307 207 331 208 335 209 336 210 337

202 323 203 323 204 324 205 327

198 314 199 317 200 320

196 309

Sect. 15A 30A 45A 60A 90A 105A 120A 180A 210A

Blanks in the table correspondto sections for which no additional examples were found in the literature.

Acetylenes Carboxylic acids Alcohols, phenols Aldehydes Amides Amines Esters Ketones Olefins

(PROTECTION] Pg. 8 22 63 95 145 165 197 287 338

INDEX,DIFUNCTIONALCOMPOUNDS

Sections-heavy type Pages-light type

315 352

325 367

317 359 318 360

327 370 328 372

309 345 310 347

320 361

330

348

362

306 344 307

344

403

410

415

412 355 413

420 361 429

440

413

430

441

337 391

375 331 381

339 392 340 394

382

395

407

448 370 456

465 373 474

457

475

490

Blanks in the table correspondto sections for which no examples were found in the literature.

xii

493

INTRODUCTION Relationship between Volume 4 and Previous Volumes. Compendium of Organic Synthetic Methods, Volume 4 presents over 1000 examples of published methods for the preparationof monofunctional compounds, updating the 5000 in Volumes 1,2, and 3.In addition, Volume 4 contains over 1000 additional examples of preparations of difunctional compounds and various functional groups, updating these sections which were initially introduced in Volume 2. The same systems of section and chapter numbering are used in all four volumes. Classification and Organization of Reactions Forming Monofunctional Compounds. Examples of published chemical transformations are classified according to the reacting functional group of the starting material and the functional group formed. Those reactions that give products with the same functional group form a chapter. The reactions in each chapter are further classified into sections on the basis of the functional group of the starting material. Within each section reactions are listed in a somewhat arbitrary order, although an effort has been made to put similar reactions together when possible. The classification is unaffected by allylic, vinylic, or acetylenic unsaturation, which appears in both starting material and product, or increases or decreases in the length of carbon chains; for example, the reactions t-BuOH -+ t-BuCOOH, PhCH,OH + PhCOOH and PhCH=CHCH,OH + PhCH=CHCOOH would all be considered as preparations of carboxylic acids from alcohois. Entries in which conjugate reduction or alkylation of an unsaturated ketone, aldehyde, ester, acid, or nitrile occurs have generally been placed in category 74, Alkyls from Olefins. The terms hydrides, alkyls, and aryls classify compounds containing reacting hydrogens, alkyl groups, and aryl groups, respectively; for example, RCH,-H -+ RCH,COOH (carboxylic acids from hydrides), RMe -+ RCOOH (carboxylic acids from alkyls), RPh + RCOOH (carboxylic acids from aryls). Note the distinction between R,CO -+ R,CH, (methylenesfrom ketones) and RCOR’ + RH (hydrides from ketones). Alkylations which involve additions across a double bond are found in section 74, Alkyls from Olefins.

xiii

XIV

INTRODUCTION

The following examples illustrate the application of the classification scheme to some potentially confusing cases: RCH=CHCOOH +. RCH=CH, RCH=CH, -+ RCH=CHCOOH ArH + ArCOOH ArH -+ ArOAc RCHO + RH RCH=CHCHO -+ RCH=CH, RCHO + RCH, R,CH, + R,CO RCH,COR + R,CHCOR RCH=CH, -+ RCH,CH, RBr RC=CH + RC=CR

+ ROH + RCOOH + RCOOR

RCH=CHCHO + R,CHCH,CHO RCH=CHCN +. RCH,CH,CN

(hydridesfrom carboxylic acids) (carboxylicacids from hydrides) (carboxylic acids from hydrides) (esters from hydrides) (hydrides from aldehydes) (hydrides from aldehydes) (alkyls from aldehydes) (ketonesfrom methylenes) (ketones from ketones) (alkyls from olefins) (acetylenes from halides; also acetylenes from acetylenes) (esters from alcohols; also esters from carboxylic acids) (alkyls from olefins) (alkyls from olefins)

Reactions are included even when full experimental details are lacking in the given reference. In some cases the quoted reaction is a minor part of a paper or may have been investigatedfrom a purely mechanistic aspect. How to Use the Book to Locate Examples of the Preparation or Protection of Monofunctional Compounds. Examples of the preparation of one functional group from another are located via the monofunctional index on p. xi, which lists the corresponding section and page. Thus Section 1 contains examples of the preparation of acetylenes from other acetylenes; Section 2, acetylenesfrom carboxylic acids; and so forth. Sections that contain examples of the reactions of a functional group are found in the horizontal rows of the index. Thus Section 1 gives examples of the reactions of acetylenes that form other acetylenes; Section 16, reactions of acetylenes that form carboxylic acids; and Section 31, reactions of acetylenes that form alcohols. Examples of alkylation, dealkylation, homologation, isomerization, and transposition are found in Sections 1, 17, 33, and so on, which lie close to a diagonal of the index. These sections correspond to such topics as the preparation of acetylenes from acetylenes, carboxylic acids from carboxylic acids, and alcohols and phenols from alcohols and phenols. Alkyiations which involve conjugate additions across a double bond are found in section 74, Alkyls from Olefins.

INTRODUCTION

xv

Examples of name reactions can be found by first considering the nature of the starting material and product. The Wittig reaction, for instance, is in Section 199 on olefins from aldehydes and Section 207 on olefins from ketones. Examples of the protection of acetylenes, carboxylic acids, alcohols, phenols, aldehydes, amides, amines, esters, ketones, and olefins are also indexed on p. xi. The pairs of functional groups alcohol, ester; carboxylic acid, ester; amine, amide; carboxylic acid, amide can be interconvertedby quite trivial reactions. When a member of these groups is the desired product or starting material, the other member should, of course, also be consulted in the text. The original literature must be used to determine the generality of reactions. A reaction given in this book for a primary aliphatic substrate may also be applicable to tertiary or aromatic compounds. The references usually yield a further set of references to previous work. Subsequent publications can be found by consulting the Science Citation Index. Classification and Organization of Reactions forming Difunctional Compounds. This chapter considers all possible difunctional compounds formed from the groups acetylene, carboxylic acid, alcohol, aldehyde, amide, amine, ester, ether, epoxide, halide, ketone, nitrile, and olefin. Reactions that form difunctional compounds are classified into sections on the basis of the two functional groups of the product. The relative positions of the groups do not affect the classification. Thus preparations of 1,2-aminoalcohols, 1,3aminoalcohols and 1,4-aminoalcohols are included in a single section. The following examples illustrate the application of this classification system:

DifunctionalProduct

Section Title

RC=C-C=CR RCH(0H)COOH RCH=CHOMe RCHF, RCH(Br)CH,F RCH(OAc)CH,OH RCH(0H)COOMe RCH=CHCH,COOMe RCH=CHOAc

Acetylene-Acetylene Carboxylic Acid-Alcohol Ether-Olefin Halide-Halide Halide-Halide Alcohol-Ester Alcohol-Ester Ester-Olefi n Ester-Olefin

How to Use the Book to Locate Examples of the Preparation of Difunctional Compounds. The difunctional index on p. xii gives the section and page corresponding to each difunctional product. Thus Section 327

xvi

INTRODUCTION

(AlcohoCEster) contains examples of the preparation of hydroxyesters; Section 323 (Alcohoi-Alcohol) contains examples of'the preparation of di01s. Some preparations of olefinic and acetylenic compounds from olefinic and acetylenic starting materials can, in principle, be classified in either the monofunctional or difunctional sections; for example, RCH=CHBr + RCH=CHCOOH, Carboxylic acids from Halides (monofunctionalsections) or Carboxylic acid-Olefin (difunctional sections). In such cases both sections should be consulted. Reactions applicable to both aldehyde and ketone starting materials are in many cases illustrated by an example that uses only one of them. Many literature preparations of difunctional compounds are extensions of the methods applicable to monofunctional compounds. Thus the reaction RCI + ROH can clearly be extended to the preparation of diols by using the corresponding dichloro compound as a starting material. Such methods are not fully covered in the difunctional sections. The user should bear in mind that the pairs of functional groups alcohol, ester; carboxylic acid, ester; amine, amide; and carboxylic acid, amide can be interconverted by quite trivial reactions. Compounds of the type RCH(OAc)CH,OAc (Ester-Ester) would thus be of interest to anyone preparing the diol RCH(OH)CH,OH (Alcohol-Alcohol).

Compendium of Organic Synthetic Methods, Volume4 Edited by Leroy G. Wade, Jr. Copyright 0 1980 by John Wiley & Sons, Inc.

CHAPTER 1

PREPARATION OF ACETYLENES Section 1 Acetylenes from Acetylenes

B + 3 Ph-C-CH

electrolysis

TH F

3

C-C-Ph

70%

Chem Lett, 999 (1977)

i-Bu3A1

+

*-.

N i (Mesal)2

n-Bu-CXBr

pentane

1-B u - C=.C --n- Bu

70%

Tetr Lett, 2831 (1978) C5H1 CECZnCl 93%

NC

--@ 0r

JOC 1

43,

358 (1978)

2

SECTION 2

COMPENDIUM OF ORGANIC SYNTHETIC METHODS VOL 4

1) BuBr

*

LiCH2C-C-Li

BuCH2CzCBu

30%

2 ) BuBr/HMPT JCS Perkin I,1218 (1979)

NaNH2

Bu-CX-CH2CH20H

91%

H C X ( CH2) 60H

H2N( CH2 13NH2

Rec Trav Chim 96, 160 (1977) L

Me

-

Me

PdCl 2L2

CuI, E t 3 N

Me

Me

+ Ph-CECH

Section 2

Chem Pharm B u l l

Acetylenes from Carboxylic Acids

No a d d i t i o n a l examples

26,

3843 (1978)

SECTION 4

Section 3

3

ACETYLENES FROM ALDEHYDES

Acetylenes from Alcohols

No a d d i t i o n a l examples Section 4 Acetylenes. from Aldehydes

Ar-CHO 2)

*

*

Ar-C-CH

up t o 90%

Ar = p y r r o l e , furan, azulene, e t c . Angew I n t Ed 17, 609 (1978) c

8

t-BuOK, (Me0)2PCHN2

*

Ph-CH2 CHO

Ph-CH2-C-CH

TH F JOC 44, 4997 (1979)

80%

4


Section 5

_Acetylenes from A l k y l s . Methylenes and A r y l s

No Examples Section 6

Acetylenes from Amides

No add: ti onal examples Section 7

SECTION 7

AcetYlenes from Amines


SECTION 10

Section 8

ACETYLENES FROM HALIDES

5

Acetylenes from Esters

1 ) BuLi COOMe 54%

2) C1 P03Ph2 base 3 ) Nay NH3

JACS Section 9

100,4852

(1978)

Acetylenes from Ethers

No examples S e c t i o n 10

Acetylenes from Hal i d e s

C5H1 C-CZnC1

t

PdL4 NC@ -

c5H1 cx+N

r JOC

43,

358 (1978)

93%

6

COMPENDIUM

OF ORGANIC SYNTHETIC METHODS VOL 4

SECTION 12

1) BuLi

I

LiCHC12

\

Ph

CH2Br

-

Synthesis, 502 (1979)

BuLi

Et-CH2CF3

Et-C-C-Bu

73%

T e t r L e t t , 3103 (1978)

Section 11

Acetylenes from Hydrides

No examples For examples o f t h e r e a c t i o n RCzCH (Acetylene

-

Section 12

+

RCEC-CzCR'

see s e c t i o n 300

Acetyl ene) Acetylenes from Ketones

0

II

*

Ph-C-CH2Et

Ph-C-C-Et

Et3N, CH2C12 Chem L e t t , 481 (1979)

50%

ACETYLENES FROM OLEFINS

SECTION 14

-

fi

7

Me3Si CHN2

/"\ Ph Ph

Ph-CEC-Ph

80%

BuLi

JCS P e r k i n I , 869 (1977)

CEC-

65%

pyr, r e f l u x JOC 44, 4116 (1979)

8 Ph-C-CH-SMe I

Me

1 ) H2NNHTs

P h- CX-Me

90%

2) MeLi


S e c t i o n 13

Acet.ylenes from N i t r i l e s


Acetylenes from O l e f i n s 1 ) LiA1H4, TiC14 t

HCzC

2 ) CH2=C=CHBr, CuCl Chem L e t t , 789 (1978)

54%

8


S e c t i o n 15

SECTION 15A

Acetylenes f r o m M i scell.aneous Compounds

No a d d i t i o n a l examples S e c t i o n 15A

P r o t e c t i o n o f Acetvlenes

Use o f t h e T r i m e t h y l s i l y l group t o t e r m i n a t e polyeneynes of t h e f o r m -(CH=CH)nrCzC-TMS.

S t a b l e t o G r i g n a r d reagents e t c . , b u t

removed by aqueous base. 34, 1037 (1978) Tetrahedron -


CHAPTER 2

PREPARATION OF CARBOXYLIC ACIDS, ACID HALIDES, AND ANHYDRIDES Sec t i on 16

Carboxyl ic Acids f r o m Ace t y l enes

KMn04, H20 BuCX-H

CH2C1

Bu-COOH

, Adogen

61 %

Synthesis , 462 (1978) S e c t i o n 17

Carboxylic Acids and Acid Halides f r o m Carboxyl i c Acids

96% ee

JOC 44, 2250 (1979) 9

10


COOH

SECTION 17

m o d i f i e d Arndt-Ei s t e r t

COOH 94%

T e t r L e t t , 2667 (1979)

R-CH2COOH fatty

acid

1 )LDA,THF

I

R-CH -COOH

bH

2)02 ,HMPA

Cr03,NaI04 AcOH/H20

-58%

R-COOH

Synth Comm

2,

63 (1979)

Review: "Synthesis o f Aldehydes, Ketones, and Carboxylic Acids from Lower Carbonyl Compounds by C-C Coupling Reactions" Synthesis, 633 (1979) Carboxylic Acids may be a l k y l a t e d and homologated v i a ketoacid, k e t o e s t e r and o l e f i n i c a c i d intermediates.

See s e c t i o n 320

( C a r b o x y l i c Acid - Ketone), s e c t i o n 360 ( E s t e r Section 322 (Carboxylic Acid

-

Olefin).

-

Ketone) and

Conjugate reductions o f

unsaturated acids are l i s t e d i n Section 74 ( A l k y l s from O l e f i n s ) .

SECTION 17

11

CARBOXYLIC ACIDS AND A C I D HALIDES FROM CARBOXYLIC ACIDS C1\NpN/C1

kB

R-COOH

N I c1

18

R-C-C1

Et3N

T e t r L e t t , 3037 (1979)

-A F'

Me2C=CNMe2

R-COOH

100%

R-C-C1

R = C13C, t-Buy HCO, furan-2-yl, e t c . Chem Corn, 1180 (1979)

0

CF3CF2CF=0

R J - OH

0 RJ-F

*

80-90%

Chem L e t t , 483 (1977)

il Ph-C-C1

polyethylene g l y c o l KF, CH3CN

*

PI

Ph-C-F

Chem L e t t , 283 (1978) Review:

" A c t i v a t i o n and P r o t e c t i o n o f t h e Carboxyl Group" Chem & Ind, 610 (1979)

98%

12


S e c t i o n 18

SECTION 18

C a r b o x y l i c Acids f r o m A l c o h o l s

K2 (Ru 04 )

86%

persulfate JCS Chem Comm, 58 (1979)

Pr-CH20H

electrolysis

N i (OH)2anode

+

Pr-COOH

92%

Synthesi s , 513 ( 1 979)

Bu4NMn04 p y r i d i ne

*

6

JCS Chem Corn, 253 (1978)

98%

SECTION 19

CARBOXYLIC A C I D S AND A C I D HALIDES FROM ALDEHYDES

S e c t i o n 19

C a r b o x y l i c Acids and A c i d H a l i d e s f r o m Aldehydes

13

0

II

1 )NaH ,( E t O)*PCH (CN)O-t-Bu -

C6Hl 3CH0

2)ZnC12,Ac20

e

C6H13CH2COOH

95%

0

3) OH JACS 99, 182 (1977)

n-C5H, CHO

e Q BzEt3NMn04 CH2C1

*

89 %

C5H,,COOH

Monatsh Chem 110, 1471 (1979)

00

Bu4NMn04

99%

c1

c1

*$


N i c k,NaOH H20 el peroxide

N02

96%

N02 Chem Pharm B u l l 26, 299 (1978)

14


'sHl

3-\ 90%

64


R-OH

SECTION 4 5 A

q-J 7 0-CCH2 Ph

\/ o r MeOH

Rec T r a v C h i m 98, 371 (1979)

R-0-THP

a c i d - w a s h e d Dowex r e s i n MeOH Synth

+

R-OH

Corn 9, 271 (1979)

JOC 43, 3548 (1978)

>97%

SECTION 45A

PROTECTION

+

OF ALCOHOLS AND PHENOLS

Can J Chem

55,

CH20Ac

OMe

65

3351 (1977)

CH20Ac NaBH4

OAc

DME

87%

*

$OH

OMe

Benzyl e s t e r s , benzoates, and cinnamates are unaffected. JOC 43, 155 (1978)

1) AgC104, c o l l i d i n e 2) morphol i n e

R-O-!*

R-OH

Br2CH

JCS Chem Comm, 987 (1979)

66


10% Pd/C

cycl ohexene or NaH2P02

0

*

SECTION 45A

R-OH

Tetr Lett, 555 (1979)

c1 -c-0

R-OH

\

0

!-

R- 0- 0-

H 2 0, dioxane Tetr Lett, 1571 (1977)

Boc-Val-Tyr(Bzl).OMe

Me3Si I

Boc-Val -Tyr.OMe


%I100%

SECTION 4 5 A

PROTECTION OF ALCOHOLS AND PHENOLS

67

Me3COCH C1, E t 3 N

R-OH

Me3COCH20R

TFA, H20

-

JOC 4 3 , 3964 (1978)

R-OH

Me2S0 t Me S i c 1

+

R-O-CH2-O-R

-

JOC 44, 3727 (1979)

1 ) BrZnCH2COOEt Ph-OH

*

PhOCH20CH3

2) C H * ( 0 W 2 S y n t h e s i s , 567 (1977)

72%

68


SECTION 4 5 A

CH2C1 2, C1 CH20Me Ar-OH

b

H20, NaOH, A d o g e n 464

Ar-OCH20Me

79-95%

T e t r L e t t , 661 (1978)

S y n t h Comm

9, 57

(1979)

1 DMSO, A c 2 0

R-OH

acetone

A u s t J Chem

2, 1031

(1978)

SECTION 45A

PROTECTION OF ALCOHOLS AND PHENOLS C1 CH2SCH3, AgN03

69

* R-OCH2SCH3

R-OH

Et3N, benzene Chem L e t t , 1277 (1979)

1) NaOH 2) MeSCH2C1, HMPA

Ar-OH

Ar-OCH2SCH3

T e t r L e t t , 533 (1977)

Me

\a3

R-OH

Me-

H


0""

7) N H p ,

8~

*

2 ) VO(acac)2, A

J P r a k t Chern 319, 274 (1977)

88%

144


SECTION 8 9

Bull Chem SOC Japan 52, 3381 (1979)

Section 88

Amides from N i t r i l e s 0 C-NH2

Na02, Me2S0 w

0"

44, 4727 (1979) JOC 1 ) KOH, t-BuOH Ph-CN

0 II

+ Ph-C-NH-C6H1

2 ) tl--CsH13-I S y n t h e s i s , 303 (1978)

Section 89

Amides from Olefins


85%

94%

Section 90

145

PROTECTION OF AMIDES

SECTION 90A

Amides from Miscellaneous Compounds

Fe, CH3COOH

tvleONH!-CH3

97%


Ph-N02

Pr-COOH

Mo(c0)6

8

63%

Ph-NH-C-Pr

JOC

2,3755

-0

A1 (Hg ) , THF/H20

'COPh

PH

100%

kHCOPh

Synth Comm

Section 90A

(1977)

2,

281 (1979)

P r o t e c t i o n o f Amides

Review: "Advances i n t h e Chemistry of t h e Acetals o f Acid Amides and Lactams" Russ Chem Rev

46,

361 (1977)


CHAPTER 7

PREPARATION OF AMINES Section 91

Amines from Acetylenes


Section 92

Amines from Carboxylic Acids and Acid Halides


Section 93

Amines from Alcohols

HNMe2, 230’ ‘gH1 70H

CuO, Cr203, Na20

* C8H17NMe2

T e t r L e t t , 1937 (1977)

146

97%

SECTION 93

Ph(CH2l30H

147

AMINES FROM ALCOHOLS

HNMe2, H2

Ph(CH2)3NMe2

CuO, 240'

90%

Synth Comm 8, 27 (1978)

1

79%


(R)-2-octanol

1. Pyridinium salt, Et3N 2) L i N 3 , HMPA

3) LiA1H4

Pyridinium salt =

(S)-2-aminooctane

0

@OTs F

t

Y

Me Chem Lett, 635 (1977)

77%

148


S e c t i o n 94

SECTION 94

Mines from Aldehydes

CH=NNHPh

6

-

CH2-NHNHPh

H p 3 Pd/C

E t O H , NH3

OH

$OH OH

P

OH

S y n t h Comm 7 , 71 (1977)

El

NH

I

Mg++, THF, A

m

EtOOC

COOEt

I

H

Tetr Lett, 913 (1977)

100%

SECTION 94

AMINES FROM ALDEHYDES

HC=NPh

8

149

CH2NHPh

1) C8K, THF

*

OMe

90%

OMe

Synthesis , 30 (1 979) NaBH3( OcOcF3)

*

P hCH=NOMe

90%

PhCH2-NH2

THF Chem Pharm 26, 2897 (1978) NaBH4

P h-CH=NOH

*

OH

I Ph-CH2-N-CH2-i-Pr

65%

i-Pr-COOH


NaBH4

Me2C I c1

H

Y

EtOH

Rec Trav Chim 96, 242 (1977) Related methods:

Amines from Ketones (Section 102)

98%

150


S e c t i o n 95

SECTION 96

Amines f r o m A l k y l s , Methylenes and A r y l s

No Examples

S e c t i o n 96

Amines f r o m Amides

19

1 ) KH, THF

6

*

23)) Me1 18-crown-6

4) KOH, MeOH

84%

T e t r L e t t , 4987 (1978) 0 II Ph-C-NHPh

1) t-BuOK, e t h e r 18-crown-6

HN/Ph

\

%75%

Pr

2) P r B r

3 ) H20 Synth Corn 9, 757 (1979)

0 I1

C

Ph’

‘NH2

1) P0Cl3

PhCH2NH2

2) Zn, E t O H

Experientia 33, 101 (1977)

%go%

SECTION 96

AMINES FROM

AMIDES

151

JOC 42, 2082 (1977)

eo

1 ) Et30BF4 H N WO ‘

“M e 0

0

* 2 ) NaBH4, SnC14

M e Me0

o

m

H

80%

II S

Me-C-NHPh

-

S y n t h e s i s , 652 (1977)

Fe(C0)5

Me-CH2-NHPh

KOH

JOC 42, 3522 (1977)

JOC 42, 3522 (1977)

51 %

152


SECTION 96

Go -(3-cH2cH 1) LiA1H4

72%

8

T e t r L e t t , 3395 (1979)

LiA1H4

MeOOC

THF

0

II

’H

C

‘NH-peptide

BH3

91%

T e t r L e t t , 1077 (1978)

38-53%

CH3-NH-peptide

TH F

JOC 42, 4148 (1977) NaBH4, BF3* Et20

I

Ar

diglyme

+

~80% 1

Ar

L i e b i g s Ann Chem, 461 (1979)

153

AMINES FROM AMIDES

SECTION 96

1) 2 EtMgBr

*

HC ( OMe )

I

NBu2

HCEt,

I

2 ) H20, NH4C1

NBu2

S y n t h e s i s , 757 (1978)

1) BuBr, NaOH

Me

Me I

I

PhCH-NH,BU

PhCH-NHCHO

91 %

2 ) H2S04 3) NaOH 4 ) HC1 gas S y n t h e s i s , 549 (1979)

; C6H51 (OCOCF,),

H2° JOC

Related methods:

44,

6

1746 (1979)

P r o t e c t i o n o f Amines ( S e c t i o n 105A)

96%

154


Section 97

SECTION 97

Amines from Amines

i -PrOH, Ra-Ni

H

*

94%

(t-BuO)3Al

A Synthesis, 722 (1 977)

2C6H13-NH2

Raney-N i xyl ene , ref1 ux

* (C6H13)2NH

75%


steroid-NH2

1 ) CH20, MeOH

2) NaCNBH3

*

steroid-NMe2

.go%

Tetr Lett, 3469 (1977)

8

Ph-NH2

1) (Et0)2PH

*

2) BuBr, NaOH Bu NHA04

Ph-NH-BU

43

3) HC1

16, 107 (1977) Angew Int Ed -

83%

SECTION 98

AMINES FROM ESTERS

155

H2NPNH Me2CHBr

Me2CHNH

EtOH

J Prakt Chem 321, 680 (1979)

0 NI

Et

0 II 1 ) CH2=CH-O-C-C1

*

2 ) HC1

Tetr Lett,

Section 98

0 k

90%

567 (1977

Amines f r o m Esters

%60%

2 ) HCOOH

JOC 44, 3451 (1979)

156

COMPENDIUM OF ORGANIC SYNDTHETIC METHODS

Section 99

VOL 4 SECTION 100

Amines from Ethers

*

LiNH(t-Bu) -

@?

41%

NH(t-BU)

OMe

OMe

JOC 42, 2653 (1977)

S e c t i o n 100

Mines f r o m Halides

H2N-CN

NaOH, H20 2 BuBr

*

hydrolysis Bu2N-CN -Bu2NH

80%

A l i q u a t 336


1) + @ - - o y l : c H 2 ! - i 0

n-C8H,71

n-C H NMe2 * 817

2) LiA1H4, dioxane Angew I n t Ed 17, 274 (1978)

~50%

SECTION 100

157

AMINES FROM HALIDES

$

0

Me2N=CH2 OCOCF3 ~

~

BuLi

*

72%

BuCH2NMe2 Synth Comm

5,

539 (1976)

1) PhCH,NHOH

I

Me

PhOCH2CH2Br

*

PhOCH2CH2NH2

60%

3 ) HC1

0 P h2II P -N= CH -0E t

1 ) 3 BuMgBr w

8

Bu2CHNH3

80%

2 ) aq. NH4C1 3) HCl/THF S y n t h e s i s , 691 (1979)

0

II

n-PrBr,

E t B r , NaOH

t

P h2P-NH2 P-

NaOH

76%

II

P h2PNEt P r

phase-trans ,

Et-NH2

0

1:;

Et-NH-Pr 88% 16, 702 (1977) Angew I n t Ed -


158

S e c t i o n 101

SECTION 102

Amines from Hydrides


Section 102

Amines from Ketones

Ph

BH3.pyridine

C =,\ NNHTs

*

Et

Ph

\ ,CH-NHNHTs

95%

Et Synth Corn 9, 49 (1979)

P h - CH2NH2

1) NaBH4, AcOH

Et I

*

t

2)

82%

Ph-CH2-N-CHMe2

50'

CH3-C-CH 3

8


Ph-CH-C 6H

-

NNNHTS NaBH3CN \Ph

tPITHF

NHNHTs I

85%

Ph-CH-CHPh

I OH

Synthesis

, 789

(1979)

SECTION 102

d

AMINES FROM KETONES

159

O ,Me

NaBH3( OCOCF,)

90%

TH F Chem Pharm

-

26, 2897

(1978)

HO-N-CH2CH2CH3

NaBH4

87%

CH3CH2COOH


1 ) LiA1H4

83%

T e t r L e t t , 2737 (1977)

Me

/ +M!*e

A Me Ph

1) LiA1H4

H-

* IC - NH2 I

I

2 ) H',

MeOH

Ph 78%ee


~50%

160


SECTION 103

Related methods: Amines from Aldehydes (Section 94)

S e c t i o n 103

Amines from N i t r i l e s

9

BH30H

Ph-CN

89%

Ph-CH2NH2 JOC 42, 3963 (1977)

H2 Y [RhH(L-Pr3P)31

*

Me ( CH2)4CN

Me( CH2)4CH2NH2

100%

TH F JCS Chem Comm, 870 (1979)

1 ) MeMgI CN

2)

e M g B r

Me

3) H20 T e t r L e t t , 23 (1977)

NC

I

R- C-H

I

H

1 ) BuLi

2 ) BzBr

R- C-BZ

I

H


61%

SECTION 105

Section 104

AMINES FROM MISCELLANEOUS COMPOUNDS

161

Amines from O l e f i n s 1 ) PdCl ( PhCN)2 2 ) Me2NH

*

C8H1 7-CH=CH2

81 %

C 8H 17-CH-NMe2 I

3) MCPBA 4) KBH4

CH2NMe2

T e t r L e t t , 163 (1978)

A -

Me

i

MeNHCl

Ph

51 %

Me-#\ Ph

J P r a k t Chem 320, 413 (1978) 1 ) MeNH2, PdC12(PhCN)2

*

C8H1 7-CH=CH2

43%

2) Br2 ‘gH1 7 JCS Chem Comm, 413 (1977) S e c t i o n 105

Amines from Miscellaneous Compounds

92%

OMe

OMe JACS 99, 98 (1977)

162


SECTION 105

H20, CO, Fe(CO)5 Ph-N02

w

Ph-NH2

JACS

100,3969

100%

glyrne, E t 3 N (1978)

Cl

c1

Angew I n t Ed 16, 41 (1977) NH,

Fe(II1) oxide 92% N2H4, YeOH

Me

Me Synthesis, 834 (1978)

bC1bcl N2H4, Pd-C

100%

CH3

THF/ ethanol

*

CH3


SECTION 105

AMINES FROM MISCELLANEOUS COMPOUNDS

-

163

Et3N*HCOOH

Ph-NOZ

Ph-NH2

100%

Pt/C

JOC 42, 3491 (1977)

H2

hC

100%

Ru c a t a l y s t

IEC

I CMe2 I OH

I

4

JOC

H2, Ra-Ni CH20 MeOH,

44,

1233 (1979)

60%

COOMe

Q

CH2CH2N3

N02

I n d i a n J Chem 148, 904 (1976)

c:: Et3N, MeOH

Q

CH2CH2NH2

N02

T e t r L e t t , 3633 (1978)

95%

164

CONPENDIUM OF ORGANIC SYNTHETIC METHODS VOL 4

-

SECTION 105

CrCl

Ph-N02

97%

Ph-NH2

CH30H

S y n t h e s i s , 792 (1977)

Y

CrCH

C-CH

cosx

90%

NH2 JOC

L

5, 3671

(1979)

paraffin 78% 4COo

C@CH3

COCH3 S y n t h e s i s , 23 (1 978)

6

N 13 TMSO-CH

CH NH

l 2

93%

T e t r L e t t , 2737 (1977) Review: "0-Mesi t y l e n e s u l f o n y l hydroxylamine and R e l a t e d Compounds-Powerful G i n a t i n g Reagents" S y n t h e s i s , 1 (1977)

SECTION 105A

PROTECTION OF AMINES

165

Review: "General Methods o f A1 k a l o i d S y n t h e s i s " Accounts Chem Res

S e c t i o n 105A

2,193

P r o t e c t i o n of M i n e s

R e l a t e d methods: h i d e s f r o m Amines ( S e c t i o n 82); h i d e s ( S e c t i o n 96)

CH 1 2 CHMe2

(1977)

HCOOH

~ ~ ~ - c H -coo-t-~~

Amines f r o m

R I

CH2 CHMe2

H-C-NH-CH-COO-t-Bu -

DCC

87%

JOC 42, 2019 (1977) R I

H2N-CH-COOR'

0 1 I1 [H-C-0-C-H]

in situ +

OT\NMe/CH2Cl

w

if:

H-C-N-CH-COOR' 1 H

S y n t h e s i s , 709 (1979)

1w c H 2 i + N o 2 2 ) PhCOCl H2N( CH2)aNH2

*

1

81 %

H2N( CH2)8NHCPh

3 ) TFA I s r a e l J Chem

lJ,

248 (1979)

166


R

I

H2N-CH-COOH

0

It

EtO-C-CF3

O R II 1 F3C-C-NH-CH-COOH

SECTION 105A

~80-90%

E t 3 N , MeOH

JOC 44, 2805 (1979)

Use of t h e p-hydroxybenzyloxycarbonyl p r o t e c t i n g group i n p e p t i d e s y n t h e s i s . Removed by H202/NH3. Tetrahedron 34 31 05 (1 978)

0 R-NH-C-O-C(Me2)CC1 II

R-NH2 Zn/HOAc

Angew I n t Ed 17, 361 (1978)

8 / Use o f t-BuO-C-N=C,

\

Ph as a t-butyloxycarbonylating reagent.

COOE t BCS Japan 50, 718 (1977)

Z-peptide

-

H2N-peptide

Pd/C

JCS P e r k i n I

490 (1977)


SECTION 105A

BOC- Gly-OBZl

1) Me3SiSiMe3/12

*

167

glycine

100%

2 ) H20

Angew Int Ed 18, 612 (1979) TsOH

Boc-Trp-OH

*

dioxane/anisole

H2N-Trp-OH

Chem Pharm Bull

100%

26, 2198

(1978)

Boc and Z(0Me) protecting groups are removed by ethanesulfonic acid i n acetic acid or methylene chloride. Z, benzyl ester, G methoxybenzenesul fonyl groups are , and n-P_ S-p-methoxybenzyl unaffected. Chem Pharm Bull 25, 740 (1977)

1 , 4-cyclohexadiene/Pd-C removes N-benzyloxycarbonyl protecting groups. JOC 43, 4194 (1978)

168


SECTION 1 0 5 A

&p-N02 0

II

CH20C-NHR

R-NH2

8 8 or CF3COOH JOC

R-y

-O ! CH2{ H

42,

399 (1977)

*

R-NH2

CH2C1


SECTION 105A

169


8

NH - C - 0 C H

R-NH2

2

0

H2/cat.

JOC 42, 3286 (1977)


Peoc group:

0 II R3PCH2CH2-O-C-

Q

Enhances t h e w a t e r - s o l u b i l i t y o f p r o t e c t e d amino a c i d s and peptides; extremely r e s i s t a n t t o a c i d s , i n c l u d i n g TFA. Removed by weak bases. 17, 67 (1978) Angew I n t Ed Use o f t h e l-methylcyclobutyloxycarbonyl p r o t e c t i n g group i n p e p t i d e synthesis. More s t a b l e than t-Boc toward HOAc.

H

JOC

42,

143 (1977)

170


SECTION 105A

Adpoc = -C-0-C(Me2)-1 -adamantyl

Ad POC- N H - R

R-NH?

Stab1 e toward h y d r o g e n o l y s i s

.

Angew I n t Ed 17, 944 (1978) I

Me-cYo-y-

t-Boc group. i s more s t a b l e t o TFA t h a n i s t h e 0 Me

I

Rl

C1 eaved by HBr/HOAc

JCS P e r k i n I, 1459 (1979)

0 R-NH-IE-0-

o r 1 ) B r p , 2 ) MeOH

T e t r L e t t , 1563 (1977)

SECTION 105A


KF, 1 8 - c r o w n - 6

or HF o r H2NNH2 JCS P e r k i n I , 627 ( 1 9 7 7 )

R-NH2


171

172

COMPENDIUM

OF ORGANIC SYNTHETIC METHODS VOL 4 SECTION 105A

hv

R2NS02Bz

R2NH

-i-PrOH

T e t r L e t t , 1029 (1978)

10% Pd/C cyclohexene or NaH2P02

*

R2NH

0 T e t r L e t t , 555 (1979)

R-NH2

Chem Pharm B u l l 26, 296 (1978)

SECTION 105A

peptide-NH2


IHC1-dioxane

173

/

Chern L e t t , 7 (1978)

100% 02N'

HOAc

R = peptide AZOC, BPOC, BOC, t - b u t y l e s t e r , MSOC, and Tos are u n a f f e c t e d by the reaction conditions, Helv Chim Acta 61, 1086 (1978)

4

1 ) EtOCSCH2COOH 2 ) ClSCOCl R-NH2

*

Et3N JACS

99, 7363

(1977)

174


R2NH

5

I0I

SECTION 105A

,, 5

R2NCCH2NHCSBz T FA

T e t r L e t t , 325 (1979)

1)

Me0

0

,

Me4NOH

R-NH2

26, 660 (1978) Chem P h a r m B u l l -

SECTION 105A


Ph ph$o 0

Yellow, fluorescent derivatives.

42, 2819 (1977) JOC Review : "Protecting Groups in Peptide Synthesi s " Chem & Ind, 617 (1979)

175


CHAPTER 8

PREPARATION OF ESTERS Section 106

Esters from Acetylenes


Section 107

Esters from Carboxylic Acids and Acid

Halides

The f o l l o w i n g types o f r e a c t i o n s are found i n t h i s s e c t i o n : 1. Est ers from c a r b o x y l i c a c i d s (and a c i d h a l i d e s ) and a l c o h o l s .

2. Lactones from hydroxy acids.

3 . Esters from c a r b o x y l i c acids and h a l i d e s , s u l f o n a t e s , and m i s c e l l aneous compounds. 0

It C-OEt

CH3CH21

anion-exchange r e s i n JOC 44, 2425 (1979)

176

94%

ESTERS FROM CARBOXYLIC A C I D S AND A C I D HALIDES

SECTION 107

177

CH3GN=?HMe NH

*

F&CH20COMe

{

-N

’

CH20COMe 72%

COOH

T e t r L e t t , 5219 (1978)

-

Me3C-COOH

DBU

t

benzene

0 II Me3C-C-0Bu

Bu-Br

81 %

BCS Japan 51 , 2401 (1978)

COOH

Ph

Q

MeOH, DCC

*

Ph-

COOMe

98%

Angew I n t Ed 17, 522 (1978)

CH2COOH EtOH, DCC

96%

Br

T e t r L e t t , 4475 (1978)

178


Ph-CH2CH2COOH

-

SECTION 107

8

DCC, TsOH

Ph-CH2CH2C-O-i--Pr

c

99%

p y r id i ne

i-PrOH

Acts Chem Scand B, 33, 410 (1979)

DCC

*

lauric acid t

cholesteryl laurate 67%

cholesterol Synth Comm 9 , 539 (1979)

M

e

O

e

COOH

H

G

8

PC-0

PPE, DMF

85%


P ( OMe

Ph-COOH

8

Ph-C-OMe

JOC 43, 4672 (1978)

9 0%

SECTION 107

ESTERS

FROM

CARBOXYLIC ACIDS AND A C I D HALIDES

179

8 PhOPOCl 81 %

Ph ( CH2 I30H , p y r i d i ne

T e t r L e t t , 4461 (1978)

( Ph2CH0)3P=0 Q HC O O H

*

TFA, CH2C12

83%

(&I C-OCHPh2 H

T e t r L e t t , 4697 (1978)

EtOH, p y r i d i n e Z-G1 y-Tyr-OH

*

Z - G 1y -Tyr - 0Et

95%

(PhO) PBu 31 Br Synthesis, 355 (1979)

0

Me30BF4 R-COOH

R = a1 k y l , a r y l

II

+

R-C-OMe

, vinyl JOC 44, 1149 (1979)

..go%

180

COMPENDIUM OF ORGANIC SYNTHETIC METHODS VOL

4

SECTION 107

Me3SOH

R-COOH

R-COOMe

100%

JOC 44, 638 (1979)

8

1. Ph3P,

*

R-C-OH

a

R-C-OE t

%70-80%

2. E t O H R = cephalosporinic acid,

Chem L e t t , 979 (1978)

f (

‘

y OH

c=o Ph

BF4

BzEt 3 N C1

Ph Chem L e t t , 441 and 763 (1977) Chem L e t t , 885 (1978)

SECTION 107

ESTERS FROM CARBOXYLIC ACIDS AND A C I D HALIDES 181

2 ) EtOH, Bu3N

BCS Japan 50, 1863 (1977)

1)

*

Me2CHCOOH

0 II Me2CH-C-O-t-Bu -

91 %

2) t-BUOH

-

Chem L e t t , 145 (1979)

@O

H3N-CH-COB

TsOH, EtOH

R

80 TsONH3-&H-COOEt

r e f 1ux

B u l l Chem SOC Japan 52, 1879 (1979)

1 ) cs2c03

Boc-Pro-Pro-OH

Boc-Pro-Pro-OBz

2 ) BzBr

JOC 42, 1286 (1977)

96%

182

COMPENDIUM OF ORGANIC SYNTHETIC METHODS VOL 4 0 II Br-CH2-C-Ph

*

Me3C- COOH

SECTION 108

0 8 II Me3C-C-OCH2CPh

95%

KF, DMF T e t r L e t t , 599 (1977) BOP, E t 3 N w

Boc-Trp-OH

96%

Boc-Trp-OPh

CH2C12, PhOH

Synthesis, 413 (1977) Further examples of t h e r e a c t i o n RCOOH t ROH

-+

RCOOR are included

i n Section 108 (Esters from Alcohols and Phenols) and Section 10A ( P r o t e c t i o n o f Carboxylic Acids).

Section 108

Esters from Alcohols and Phenols

OH

Ph

-CI -CH3 I

Ph

OAc

I

Et3N, Ac20

Ph -C-CH3

&

I

Ph

0 Tetrahedron

34,

2069 (1978)

92%

ESTERS FROM ALCOHOLS AND PHENOLS

SECTION 108

183

Synth Comm 7, 383 (1977)

JOC (USSR) 13, 608 (1977)

e

PhCOCl

*

H3N(CH2)40H MeCN/benzene

c10

0 II H3N(CH2)40-C-Ph

@

58%

ClQ

Synth Comm 8, 327 (1978) 0

II

Ph-C-0-(sal i c y l i c a c i d polymer) BuOH

a

* Ph-C-OBU Synth Comm 7, 57 (1977)

77%

184

COMPENDIUM OF ORGANIC SYNTHETIC METHODS VOL 4 0 ll

PPh3, benzene

OH

( MeOOC)$=o, PhCOOH

SECTION 108

b&

( i nversion )

72%

T e t r L e t t , 3179 (1977)

6

8

0 II O-C-H

fiH2

HC-O-C-CH20Me

>go%

Et3N Rec Trav Chim

98, 324

(1979)

e;' 8

4 OH

ci M e 2 N a N

, benzene

b

>95%

Bull Chem SOC Japan 52, 1989 (1979)

ESTERS FROM ALCOHOLS AND PHENOLS

SECTION 108

185

t- [P t C1 ( C7H4)AcIm] Me

100%

CH2CH2CH20H

CH2CH2CH20Ac AcIm = N - a c e t y l i m i d a z o l e JACS

99, 3531

(1977)

0

II

Ph-C-CN a c y l a t e s s t e r o i d a l c o h o l s s e l e c t i v e l y i n t h e o r d e r 21 > 17 8> 38> 6a, 3a>> 20a>208> 7 8>> 7a> 68>22 8>22a C o l l Czech Chem Commun 44, 2443 (1979) Review: " 4 - D i a l k y l ami n o p y r i d i n e s as H i g h l y A c t i v e Acyl a t i o n C a t a l y s t s II Angew I n t Ed 17, 569 (1978) K I , electrolysis C5H1 CH20H

*

0 II C5H11 C-O-L-Bu

83%

H20, t-BuOH T e t r L e t t , 165 (1979)

F u r t h e r examples o f t h e r e a c t i o n ROH -+ R ' C O O R a r e i n c l u d e d i n S e c t i o n 107 ( E s t e r s f r o m C a r b o x y l i c Acids and A c i d H a l i d e s ) and S e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols).


186

Section 109

Esters from Aldehydes

OCH0

SECTION 109

n

C-OMe

03, MeLi

Me OH/ TH F

63%

Tetr Lett, 1627 (1978)

CH3( CH2)8CH0

8

NBS, hv

CH3(CH2)8C-OEt

t

E tO-TMS JOC 43, 371 (1978)

i

0 SCH

Me0

1 3 1 ) CH2SCH3, base 2) EtOH, HC1

CH2C-OEt

*

~85% OMe

Bull Chem SOC Japan

52,

2013 (1979)

187

ESTERS FROM ALDEHYDES

SECTION 109

Me2C=C( OMe ) 1 ) ZnC12-

t

2 ) H30@

Ph-CH-CMe2

t

I HO

I COOMe

80%

Ph-CHO Synthesis, 400 (1978)

0

Cr03, pyrOHC1 90%

T e t r L e t t , 3483 (1977)

anodic o x i d a t i o n 0‘

*

MeOH, KOH

n

0\c/o

Pr’

72%

O ‘ Me

Synthesis , 283 (1978)

0 It CH3-C-Br

-i-Bu-CHO

ZnCl

i-Bu-CH-OAc I Br


99%


188

6

1 ) Et3SiOP(NMe2)2

0

2) BuLi 3)

JCHo Ph

SECTION 111

p

h

6

65%

JACS 101 , 371 (1979)

Related methods:

Section 110

E s te rs from Ketones (Section 117)

Esters from Alk.vls, Methylenes and A r y l s

No examples o f t h e r e a c t i o n RR

-f

RCOOR' o r R'COOR (R,R'=al k y l ,

a r y l , e t c . ) occur i n t h e l i t e r a t u r e .

For t h e r e a c t i o n RH

o r R'COOR see Section 116 (Esters from Hydrides).

Section 111

-+

RCOOR'

E s te rs from Amides S

1 ) Me1 , MeOH

M

e

90 -OMe

3

*

Me3cv-NMe2

100%

2 ) aq.K2C03

Me

Me JACS

101,1316

(1979)

ESTERS FROM ESTERS

SECTION 113

Section 112

189

Esters from m i n e s

Ph-CH2CH2NH2

+

-i-AmONO

14

CH3-C-OCH2CH2Ph

CH3COOH

Synth Corn

&,

84%

33 (1978)

Ph

8

Bu-O-C-Ph

BuCH2NH2

85%

2) PhCOONa


Section 113

Esters from Esters

Conjugate redudtions and conjugate a l k y l a t i o n s o f unsaturated

-

e s t e r s are found i n Section 74 ( A l k y l s from O l e f i n s ) .

Ph-CH2 -COOEt

1 ) CgK

2) Me1

P h -CH-COOEt 1

Me

T e t r L e t t , 653 (1977)

70%

190


6

1 ) PhSCH2CZ,

ZnBr2 o r TiC14

H'

+

2 ) NaI04

3)

SECTION 113

90%

T e t r L e t t , 993 and 995 (1979)

+,PhI

L iCH2 C -0

PhCH2C-0

N i B r 2 , BuLi

JACS

99, 4833

+,

73%

(1977)

boric acid

- F 180"

C02Me 92%

Synth Corn 9, 609 (1979)

ESTERS FROM HALIDES AND SULFONATES

SECTION 115

191

18, 793 (1979) Angew Chem I n t Ed Section 114

Esters from Ethers

Ph- I(OCOCF 3 )

*

R-OBZ

0 II R-O-C-CF3

42-100%

R = n - a l k y l , Ph, Bz

JCS Chem Corn, 615 (1979) BzEt3NMn04 ' Q

-n-Bu-O-CH2Ph

*

8

BU-O-C-Ph

90%

CH2C1 Angew I n t Ed 18, 68 and 69 (1979) Section 115

Esters from Halides and Sulfonates

I - (CH2) 15-COOH

cs2c03

DMF


85%

192

COMPENDIUM


1) W 0 ) 5

*

Bu-MgBr

SECTION 116

0

I

Bu-d-OBz

73%

2 ) BzOH, I 2

T e t r L e t t , 1477 (1978)

Br

T e t r L e t t , 1455 (1978)

R e l a t e d methods: C a r b o x y l i c Acids f r o m Hal i d e s ( S e c t i o n 25)

S e c t i o n 116

E s t e r s f r o m Hydrides

T h i s s e c t i o n c o n t a i n s examples o f t h e r e a c t i o n RH

+

RCOOR' o r

R'COOR ( R = a l k y l , a r y l , e t c . ) .

Ag 0 59% TFA, TFAA Synth Comm

5,

543 (1976)

ESTERS FROM HYDRIDES

SECTION 116

193

4 Q 0

II

oNC\ph

PhCOOH, TSP TFA

OCH3

97%

OCH3

(TSP = 2 - t r i fluoromethanesul f o n y l o x y p y r i d i ne)

Chem L e t t , 1099 (1977)

Se02, L i B r

004c OAc T e t r L e t t , 3279 (1978)

Also v i a :

C a r b o x y l i c a c i d s , S e c t i o n 26; A l c o h o l s , S e c t i o n 41

194


Section 117

SECTION 117

Esters from Ketones 0 II TMS-0-S-0-0-TMS

96%

I1

0

JOC 44, 4969 (1979)

83% \ JCS Chem Corn, 870 (1977)

BF3* E t 2 0

0

AcOOH

0

Acta Chem Scand ( B ) 32, 467 (1978)

SECTION 118

6

195

ESTERS FROM NITRILES

8C-OMe

0

II

1 ) NaH, (EtO)2PCH(CN)O-t-Bu

85%

2) ZnC12, Ac20

3) %Me

JACS

99, 182

bH

(1977)

i Me3

Me3Si

*

*

JCS Chem Comm, 772 (1977) Also via Carboxylic acids, Section 27 Section 118

Esters from Nitriles

No additional examples

73%

196


S e c t i o n 119

SECTION 119

Esters from Olefins

1 ) LiA1H4, TiC14

*

/ -

-0Ac

58%

2) P ~ ( O A C ) ~

*c

T e t r L e t t , 1405 (1979)

0

g

03, HC1

COOMe

COOMe

CH30H

85%

Angew I n t Ed 17, 939 (1978)

1 ) Pb(OCOPh)4

OCOP h

66% 2) Et4NF

OCOPh

JOC 42, 1051 (1977)

80% JACS 101, 3884 (1979) A l s o v i a A l c o h o l s , S e c t i o n 44

OF ESTERS

SECTION 120A

PROTECTION

Section 120

F s t e r s from Miscellaneous Compounds

BzBr

+

-

08

iL2O N,? OLi

MeOOC

&

T e t r L e t t , 1161 (1977)

Section 120A

P r o t e c t i o n o f Esters

HgO, BF3* THF

*

197

8

R-C-OR'

Synthesis , 223 (1 979)

NO2

80%


CHAPTER 9

PREPARATION OF ESTERS AND EPOXIDES S e c t i o n 121

E t h e r s and Euoxides from Acetylenes


E t h e r s and Epoxides from C a r b o x y l i c Acids

No a d d i t i o n a l examples S e c t i o n 123

R-OH

E t h e r s and Epoxides f r o m A l c o h o l s and Phenols

CH2N2

R-OCH3

s i l i c a gel

T e t r L e t t , 4405 (1979)

7 98

25-98%

SECTION 123

ETHERS AND EPOXIDES FROM ALCOHOLS AND PHENOLS

199

1 ) KOH, DMSO Ph2CHOH

Ph2CHOMe

b

97 %

2 ) Me1 Tetrahedron 35, 2169 (1979) CH3C1, benzene

*

H- ( OCH2CH2)4-OH

H3C-(OCH2CH2)4-OCH3

NaOH, H20

95%


n-C6H1 3-OH

+

N i (acac)2

81 %

n-C6H13-0-Bz

Bz-Cl Synthesis, 803 (1977)

- -f Et2S04

-OH

W

KOH/ DMSO

O

E

t

70%


(33

Et30BF4

CH20H

CH20Et

JOC 42, 1801 (1977)

89 %

200

COMPENDIUk OF ORGANIC SYNTHETIC METHODS VOL 4

SECTION 123

0

I1

P ( OCHPh2)3

Bu-OH

*

74%

Bu-OCHPh2

TFA, CH2C12

a\,

T e t r L e t t , 3943 (1978)

Me2N R-OH

Ph3CC1 b

R-0-CPh3

Et3N, DMF

T e t r L e t t , 95 and 99 (1979)

90%

JOC 43, 4672 (1978) I

00

Me3SOH 100%

Ar-OMe

Ar-OH

-

JOC

44,

638 (1979)

80

Me3SeOH

Ph-OH

Ph-OMe T e t r L e t t , 1787 (1979)

100%

SECTION 123

ETHERS AND EPOXIDES FROM ALCOHOLS AND PHENOLS 201

Bu-I

Ph-OH

83%

Ph-0-Bu

KF/Cel i t e

Chem L e t t , 45 (1979)

pyridine

PhOH + t-BuBr

90%

Ph-0-t-Bu -

30"

Chem L e t t , 57 (1978) Ph-OH

Et4NF

t

EtI

75%

P h-0-E t DM F

Can J Chem

57,

1887 (1979)

Related methods: P r o t e c t i o n o f Alcohols (Section 45A). NCOOEt

II

NCOOEt

95%

NCOOEt NCOOEt

0

Ph3P T e t r L e t t , 5153 (1978)

100%


202

H

SECTION 123

H

DMSO

99% 175"

JOC 42, 2012 (1977)

1. EtMgBr

( CH3)3C-OH

2*

Q

w'

Chem L e t t 817 (1977)

\ HU'

H2, MeOH P t ( 11)-Sn(I1)

complex c a t a l y s t

%loo%

OMe

Chem L e t t , 835 (1978)

ETHERS AND EPOXIDES FROM ALDEHYDES

SECTION 124

203

Synthesis, 706 (1977) Related methods:

Section 124

MeO,

Ethers and Epoxides from Aldehydes

Me3SiH

O ,Me C

! PI

P r o t e c t i o n of Alcohols and Phenols ( S e c t i o n 45A)

H‘

+ -

Pr-CH20Me

100%

Me3Si OTf T e t r L e t t , 4679 (1979)

NaCNBH3

CH3( CH2)8CH20Me

HC1 ( 9 ) , MeOH

83%

T e t r L e t t , 1357 (1978) 2LiA1 H4-TiC14 PhCH2CH2CH20Me 87%

BCS Japan 51, 2059 (1978)

204


py-BH3/CF3COOH PhCHO

*

PhCH2-O-CH2Ph

-Q

SECTION 124

87%

CH20(CH2)6CH3

py -BH3/ CF3COOH c1

CH3( CH2)60H

c1

82%

Chem Pharm B u l l 27, 2405 (1979)

*

2PhCHO

PhCH20CH2Ph

87%

2 ) H30Q Chem L e t t , 415 (1979)

(@-?Me2 Ph-CHO

*

Ph

97%

T e t r L e t t , 203 (1979) Re1 a t e d methods : E t h e r s and Epoxides f r o m Ketones ( S e c t i o n 132)

SECTION 128

S e c t i o n 125

ETHERS AND EPOXIDES FROM ESTERS

205

E t h e r s and Epoxides f r o m A l k y l s , Methylenes and A r y l s

No examples o f t h e p r e p a r a t i o n o f e t h e r s and epoxides b y r e p l a c e ment o f a1 k y l methylene and a r y l groups o c c u r i n t h e l i t e r a t u r e . F o r t h e c o n v e r s i o n of RH -+ ROR' ( R , R ' = a l k y l ) see S e c t i o n 131 (Ethers from Hydrides)

S e c t i o n 126

E t h e r s and Epoxides, f r o m Amides


S e c t i o n 127

E t h e r s and Epoxides f r o m Amines


S e c t i o n 128

E t h e r s and Epoxides f r o m E s t e r s

0-77%

Chem and I n d

230 (1977)

206


Section 129

SECTION 130

Ethers and Epoxides from Ethers and Epoxides

'"Yote

A1 C1

76%

JCS Chem Comm, 382 (1979) Section 130

Ethers from Halides and Sulfonates

0

Resin (Ph-0 )

benzene

t

*

Bu-0-Ph

100%

Bu-Br Synthesis, 113 (1977) Ph-OH

Et4NF

t

EtI

*

Ph-0-Et

75%

DMF

Can J Chem

57,

1887 (1979)

ETHERS FROM HYDRIDES

SECTION 131

*

PhCH2Br

207

PhCH20CH2CH2Br

90%

Et4NI T e t r L e t t , 2639 (1979)

0

0

PhONa

80% 6

Synthesis

0

PhO

, 298

0

P

h

(1977)

, DMF

_____)

F

PhO

0

JOC 42, 3425 (1977)

Related methods: Ethers from Alcohols (Section 123)

Section 131

Ethers from H-ydrides


0

85-95%

208


S e c t i o n 132

E t h e r s and Epoxides f r o m Ketones

a

Me-S-CH2Na I1

NTs ( 3 eq.)

es t r o n e

SECTION 132

8

96%

DMSO

JACS 101 , 6135 (1979)

Me3Si H

76%

Me3Si OTf

T e t r L e t t , 4679 (1979)

NaCNBH3 78% HCl(g), MeOH

T e t r L e t t , 1357 (1978)

II 0

P h- C-CH3

*

Ph-!

4 Me

T e t r L e t t , 203 (1979)

94%

SECTION 134

ETHERS AND EPOXIDES FROM OLEFINS

0

1 ) NaBH4

Ph-C-C(Me2)SMe II

__T

2 ) Me1

Ph

209

AMe Me

68%


Related methods:

S e c t i o n 133

Ethers and Epoxides from Aldehydes ( S e c t i o n 124)

Ethers and Epoxides from N i t r i l e s


S e c t i o n 134

Ethers and Epoxides from O l e f i n s

H2°2

H./f

P,


210


SECTION 134

0 011

EtOCCl

85%

JOC 44, 2569 (1979)

CH3C( O E t ) b

H2°2

(yo

99%

T e t r L e t t , 1001 (1979)

0 II PhSeOH, H202 75% buffer

+

JOC 42, 2034 (1977)

"z02

Ph

ArSeOOH

Ph


91%

SECTION 134

21 1


H202, HOAc, EtOAc

28%

T e t r L e t t , 1369 (1977)

\

*6

T e t r L e t t , 623 (1977)

6

t-BuOOH, t r i f l uoroacetyl camphor

78%

PhCH3, Mo02(acac)2

82%ee

Z Chem 18, 218 (1978)

212


SECTION 134

OOH

CF~-~-CF~ AH

90%

JACS 101, 2484 (1979)

MCPBA, CH2C1 95% pH 8 phosphate b u f f e r

d

JOC 44, 1351 (1979)

MCPBA , NaHC03

H20, Ct12C12

59%

T e t r L e t t , 427 (1977)

t-BUOH

75%

B u l l Akad USSR Chem 27, 387 (1978)


SECTION 134

21 3

N-benzoyl peroxy-carbami c a c i d 0

89%

THF

&

JOC 44, 1485 (1979)

p h a sNaoC1 e-transfer *

&go%

JACS 99, 8121 (1977)

1 ) 12, MeCN

OP03Et2

64%

2 ) NaOEt, THF

JACS 99, 4829 (1977)

CH3CH0, O2 hu, PhCl

*

S y n t h e s i s , 711 (1977)

214

COMPENDIUM


SECTION 135

1 ) N-iodosuccinimide 2) KOH T e t r L e t t , 2545 (1979)

8

PhSeCl

8

I

SePh

83%

89%

T e t r L e t t , 1257 (1977)

-

JACS 102, 3784 (1978) Section 135

Ethers and Epoxides from Miscellaneous Compounds

Ph-S-CH2CH2Ph II

N-TS

1 ) NaH, THF

2 ) PhCHO

H--{ l l - C H 2

Ph

H


Ph

80%


CHAPTER 10

PREPARATION OF HALIDES AND SULFONATES Section 136

Halides from Acetylenes CuCl 2-Li C1

Ph-C-C-Et

Ph \ c=,c

*

MeCN

/cl

c1

94% Et

100%

JCS Perkin I , 676 (1977)

0 C r CH

1) LiA1H4 2 ) Acetone ~

9

/c=c\cl/ I

H

3) IC1

JAG 101, 5101 (1979)

21 5

89%

216


SECTION 136

0 0

Et3NH HC12 Ph-CECH

*

Ph

73%

\

\

/C=CH2

JCS P e r k i n I,1797 (1977)

Ph

1 ) TeC14

Ph - C X - Me

\

+

/c=c\I

2 ) 12, MeCN

/

Me 85%

c1 Chem L e t t , 1357 (1979)

1 ) Cp2ZrC12, Me3A1

Bu-CZC-H

*

2 ) 12, THF

Bu

\

/H

/c=c\, Me

85%

S y n t h e s i s , 501 (1 979)

1 ) [EtCuBrlMgBr

Ph

2 ) NBS

Q Et-CEC-Et

TH F

\

/H /C=C\Br Et

w

Ph-CGCH

>go%

96, 168 (1977) Rec Trav Chim -

(HF)n

* 7 75%

F

F

HALIDES AND SULFONATES FROM ALCOHOLS

SECTION 138 Section 137

21 7

Halides from Carboxylic Acids

HgO, Br2

0

2

b

B

r

97%

CC14, hv

02N

(0% y i e l d w i t h o u t l i g h t )

JOC

9, 3405

(1979)

Hal i d e s and Sulfonates from Alcohols

Section 138

- 6

Me3Si Br

90%

T e t r L e t t , 4483 (1978)

H\ /OH

Me3Si I ._____)

CH3 "\C6H,

I

A\ CH3

95%

'sHl

3

>90% i n v e r s i o n T e t r L e t t , 2659 (1977) OH I

Me3SiC1, NaI MeCN

-6


85%

218


SECTION 138

Me3Si C1

98 %

Na I

JOC

44,

OH

4

1247 (1979)

-4 i

1 ) Me3SiSiMe3/12 2) H20

86%

Angew I n t Ed 18, 612 (1979) 1 ) Me3SiCI, p y r i d i n e Ph-CH-CH2COOEt AH

*

2 ) PhPF4

Ph-CH-CH2COOEt

;

92%

T e t r L e t t , 4507 (1978)

PPh3

CH2'CH-CH-CH3 I

OH

CH2=CH-CH-CH3

c1 3cccc1

!

I

c1

T e t r L e t t , 2999 (1977)

94%

SECTION 138

HALIDES AND SULFONATES FROM ALCOHOLS

-

21 9

DMPADC*

PhCH20CH2CH20H

,!*

PhCH20CH2CH2C1

92 X

l-Dimethylphosphoramidic d i c h l o r i d e Chem L e t t , 923 (1978) HC1, ZnC12 R-OH

+

R-C1

tri nonyl b o r a t e

R = 1" a l k y l

JOC (USSR)

13,604

(1977)

>90% i n v e r s i o n

Chem L e t t , 383 (1977)

%80% HO

F T e t r L e t t , 1823 (1979)

220


s

SECTION 138

T e t r L e t t , 4575 (1978)

c1 3c-c-cc1

+

100%

Ph3P

CH2C1

JOC 44, 359 (1979)

T f OTf

R-OH

R-OTf

213-89%

pyr id in e

JOC 42, 3109 (1977) PhS02C1 , benzene Bu-CH20H

Bu-CH20S02Ph

S y n t h e s i s , 822 (1979)

85%

SECTION 139

HALIDES FROM ALDEHYDES

221

-

Aust J Chem 30, 2479 and 2487 (1977)

Section 139

Hal i d e s from A1 dehydes

72%

Synth Corn

9,

341 (1979)

90% ’H

DMF JOC

43,

4367 (1978)

222


Section 140

Halides from Alkyls

b

O N

HC1

CH3CN

ASection 141

+

h

Synthesis, 227 (1978) HBr Helv Chim Acta

$-

Br 94%

62,

2338 (1979)

RHal see Section 146 (Halides from Hydrides)

Halides and Sulfonates from Amides

No additional examples

76%

CH2C7

HOAc

For the conversion RH

SECTION 141

SECTION 142

HALIDES FROM AMINES

223

H a l i d e s from Amines

S e c t i o n 142

Ph

Bu-NH2

4;;

4

69%

S y n t h e s i s , 634 (1977)

*

t-BUSNO MeCN, CuC12

N02

98%

N02

T e t r L e t t , 4519 (1978)

t-BUONO,

CUCl

MeCN

N02 JOC

42,

6 N02

2426 (1977)

12, benzene Chem L e t t , 939 (1979)

92%

224


SECTION 1 4 2

Me1 or I2

>go%

CHCl 3 , 1 8 - c r o w n - 6

Br

Br T e t r L e t t , 3519 (1977)

0

II

Me-C-O-CH2 Ph’

c= c’

C1 COOEt

\

‘CH2NEt2

0 II Me-C-O-CH \ 2 H, Ph°C=CLCH2C1

91%

S y n t h e s i s , 786 ( 1 9 7 7 )

30% Angew I n t E d 16, 8 5 4 (1977) KHF2, H20 Ph2CN2

*

Ph2CHF

Bu4NC104, CH2C12 T e t r L e t t , 1447 ( 1 9 7 7 )

60%

SECTION 144

S e c t i o n 143

HALIDES FROM ETHERS

22 5

H a l i d e s and S u l f o n a t e s f r o m E s t e r s and Epoxides


S e c t i o n 144

H a l i d e s from E t h e r s

0-

1 ) Me3SiSiMe3/12

OEt

98% 2) H20 18, 612 (1979) Angew I n t Ed -

HBr

-n-C16H33-OCH3

R4PBr

n-C

H

- 16 33

Br

88%

S y n t h e s i s , 771 (1978)

do-&, C1

Br

Br

Chem L e t t , 891 (1977)

87%

226


Q

Et

I

SECTION 145

I

P-n

v-

I

Et4NC1 , E t 3 N

Chem L e t t , 1013 (1977) S e c t i o n 145

H a l i d e s from H a l i d e s and S u l f o n a t e s K I , Bu4PI

BuBr

Bu I

w

96%

s i l i c a g e l column

-

S y n t h e s i s , 952 (1979)

PhSbF4

Ph-CC1

91%

PhCF3

,,,

JOC (USSR) 13, 561 (1977)

N i B r 2 , Zn powder M

e

0

*

0Br KI

Chem L e t t , 191 (1978)

7 8%

227

HALIDES FROM HYDRIDES

SECTION 146

8

1) Ph2AsCH2Li

BuBr

*

79%

BuCH2Br

2 ) Br2

-

Angew I n t Ed

BuLi

76, 53

(1977)

1) Et20

+

BuS02CF3

74%

2 ) H*0

PhN ( S02CF3)2 JOC 42, 3875 (1977)

S e c t i o n 146

H a l i d e s f r o m Hydrides

a-Halogenations o f ketones, e s t e r s , and a c i d s a r e found i n S e c t i o n s 369 (Haloketones), 359 ( H a l o e s t e r s ) , and 319 ( H a l o a c i d s ) .

Me

I

Et2C-H

PhIC12

*

Me

I

Et2C-C1

Chetn L e t t , 961 (1979)

82%

228


‘gH1 3CH2CH3

* Fe ( I I ) , CF3COOH

JOC

44,

SECTION 146

76% ‘gH1 3fHCH3 c1

3728 (1979)

1 ) T1 (OCOCF3)3 71 %

JOC 42, 362 (1977)

Chem Ber

E, 1677 (1979)

NBS-DMF

JOC 44, 4733 (1979)

Br

SECTION 146

HALIDES FROM HYDRIDES

229

Chem L e t t , 223 (1978) DBU-BrCC1

Br

Br

99%

same c o n d i t i o n s PhCXH

+

PhC-CBr

99%

Chem L e t t , 73 (1978)

C12, hu ~50% cc14 Chem and I n d , 127 (1977)

1 ) KOH, H20

C7H15-CH2N02

*

F’

C7H15-CHN02

2) C12, CH2C12

JOC 42, 3764 (1977)

92%

230


4

H=CH- CMe3

SECTION 147

F

0I 1) CHJNHBr,

C=CH-CMe3 I

HF

2 ) KOH

OMe

'Q

74%

OMe


*

Ph-H A1 C1

Ph-SO,CF, L

J

61 %

JOC 42, 3875 (1977)

" S e l e c t i v e Halogenation of S t e r o i d s Using Attached Aryl I o d i d e Temp1 a t e s " 99, 905 (1977) JACS S e c t i o n 147

H a l i d e s from Ketones

poEt2NSF3

JCS P e r k i n I , 1354 (1 979)

up t o %go%

HALIDES FROM OLEFINS

SECTION 149

2 31

JOC 43, 4367 (1978)

S e c t i o n 148

Hal i d e s and Sul f o n a t e s f r o m N i t r i l e s

No examples

S e c t i o n 149

Halides from Olefins

For h a l o c y c l o p r o p a n a t i o n s see S e c t i o n 74 ( A l k y l s f r o m O l e f i n s )

0

1 . LiA1H4, TiC14 73%

2.

*

CUCl*

Chem L e t t , 833 (1978) CH=CH2 I

1 ) HSiC13

2) KF

P

3 ) NBS JACS

2, 290

(1978)

232


Bu-CHZCH~ *

1. LiA1H4, Cp2Ti (A1H3I2

*

2. Br2

SECTION 149

Bu-CH2CH2Br

79%

Chem Lett, 1117 (1977)

-

44, 3872 (1979) JOC 1 ) LiA1H4, TiC14

*

rB-

J Organometal Chem

142,71

HC1 , H202 phase-transfer cat. Synthesis, 676 (1977)

(1977)

76%

HALIDES FROM MISCELLANEOUS COMPOUNDS

SECTION 150

233

60%

JOC 42, 1559 (1977)

+

cc1

c

1

~

c

c

1

3

83%

R u ( I 1 ) complex Chem L e t t , 115 (1978)

Use o f a heterogeneous s o l v e n t suspension method f o r benchtop f l u o r i n a t i o n o f a1 kenes u s i n g XeF2. T e t r L e t t , 363 (1977)

S e ct ion 150

Hal i d e s from M i s c e l l aneous Compounds

HF, p y r i d i n e Ph-N=N-NMe2

+

Ph-F

97%

JCS Chem Comm, 914 (1979) Review:

“ I n t r o d u c t i o n of F l u o r i n e i n t o Organic Molecules:

and How” Tetrahedron

34, 3

(1978)

Why

234


SECTION 150

Review: "The Invention of Reactions Useful for the Synthesis of Specifically Fluorinated Natural Products" Pure and Appl Chem

49,

1241 (1977)


CHAPTER 11

PREPARATION OF HYDRIDES T h i s chapter l i s t s hydrogenolysis and r e l a t e d r e a c t i o n s by which f u n c t i o n a l groups are replaced by hydrogen, e.g.

RCH2X

+

RCH2-H

o r R-H

Section 151

Hydrides from Acetylenes

No examples of t h e r e a c t i o n R G C R

Section 152

+

RH occur i n t h e l i t e r a t u r e .

Hydrides from Acid Halides

4

0

COCl

Pr3Si H

JCS P e r k i n I , 1137 (1979)

235

68%

236


S e c t i o n 153

SECTION 153

Hydrides f r o m A l c o h o l s and Phenols

T h i s s e c t i o n l i s t s examples o f t h e h y d r o g e n o l y s i s o f a l c o h o l s and phenols, ROH + RH

1 ) CH3S02C1 63% 2) e l e c t r o l y s i s , DMF, Et4NOTs

T e t r L e t t , 2157 (1979)

K, 18-crown- 6

86%

TH F

S

[I

0-C-NEt2

-


Ph3SnH

n-C H O H 4 c-C,2H25SePh 12 25

fl-C,2H26


73%

HYDRIDES FROM ALCOHOLS AND PHENOLS

SECTION 153

H

1 -naphthyl-

I

C-OH I

Ph

NaBH4/CF3COOH

-

1-naphthyl-

237

YC - H i

97%

Ph

S y n t h e s i s , 172 (1977)

0 II C5H1 -C-NHCH20H

0

NaCNBH3

II

C5H1 -C-NHMe

86 %

T FA

Synth Comm 7, 549 (1977) Me2Si I2

P h2CHOH

Ph2CH2

7 1 )

96%

CH2C12

8 Ph-C-CHPh I

OH

1s

Me2Si I2

Ph-CCH-Ph

_7

45%

L

CH2C12

T e t r L e t t , 4941 (1979)

0 OH

II

I

Ph-C-CH-Ph

1 ) Me3SiI, CH C1 2

2

0

II Ph-C-CH2Ph

2 ) sodium t h i o s u l f a t e Synth Comm 9, 665 (1979)

95%

238


00

-9 00

SECTION 154

96%

JOC 44, 4813 (1979)

1 ) NaH, THF 2) C1PO(OEt)2

*

C

g

H

,

g

~

H 92%

3 ) T i " , THF

4) MeOH JOC 43, 4797 (1978)

Zn, HC1

ether

Me'o 97%

Tetrahedron 33, 511 (1977)

Also v i a Halides and Sulfonates , S e c t i o n 160 S e c t i o n 154

Hydrides from Aldehydes

No a d d i t i o n a l examples For t h e conversion RCHO Aldehydes)

-+

RMe e t c . see Section 64 ( A l k y l s from

SECTION 157

Section 155

239

HYDRIDES FROM AMINES

Hydrides from A l k y l s

bBr 90%

$fBr

JCS Perkin I , 176 (1979)

Section 156

Hydrides from Amides

N o a d d i t i o n a l examples

Section 157

Hydrides from Amines

This s e c t i o n l i s t s examples o f t h e conversion RNH2 -+ RH

NaBH3CN 91 % HMPA COOEt

COOEt


240


6

SECTION 157

Me3C-ON0 82%

*

DMF

N02

N02

JOC 42, 3494 (1977)

NH20S03H

&cooH

72%

@OH

-

JACS 100, 341 (1978)

Ph-NHNH2

+-,

TosN3, NaOH

Ph-H

benzene/H20

40%

Et4NBr

T e t r L e t t , 3059 (1978)

84-1 00% A r = s u b s t . Ph Chem L e t t , 1051 (1979)

SECTION 158

S e ct ion 158

HYDRIDES FROM ESTERS

Hydrides from Esters

This s e c t i o n l i s t s examples of t h e r e a c t i o n s RCOOR' RCOOR'

EtOOC

-+

241

-+

RH and

R'H

COOEt

COOE t

1 ) KOH, 18-crown-6 benzene

70%

2) HC1 , 100" Synthesis, 37 (1977) OAc

I

T e t r L e t t , 613 (1979) O ,Ac

85%


242

Ac


XI

SECTION 159

Na &

40%

HMPA/ t-BuOH


Li H2NCH2CH2NH2

AcO

I n d i a n J Chem 188, 179 (1979)

A8 C=CH

CZC-BU

3 ) H20 JOC 42, 2650 (1977)

S e c t i o n 159

Hydrides from E t h e r s

T h i s s e c t i o n l i s t s examples o f t h e r e a c t i o n K - X - R ' X=O or S.

+

RH, where

SECTION 160

HYDRIDES FROM HALIDES AND SULFONATES

24 3

T e t r L e t t , 4679 (1979)

Zn, TMSCl

fic5Hll

Synth Corn

Section 160

7,

84%

427 (1977)

H.ydrides from Halides and Sulfonates

This s e c t i o n l i s t s t h e r e d u c t i o n o f halides and sulfonates RX+RH NaBH4, Me2S04

I

*

82 %

/\/\/\/ H

F u l l paper, many examples.

JOC 43, 2259 (1978)

244


SECTION 160

NaBH3CN, g-BBNCN, o r p o l y m e r i c cyanoborane R-X

*

R-H

HMPA R = alkyl

x

= halide, tosylate

JOC 42, 82 (1977)

TH F

96%

JOC

Br

I C3H7-CH-C6H1

42,

L i A1 H4-CoC1

L i A1 H4-NiC1

2166 (1977)

*

0

decane

*

T e t r L e t t , 4481 (1977)

98 %

100%

SECTION 160


0 II NaOMe o r NaOCH cat. PdL4

-8

245

89%

JOC 43, 1619 (1978) T e t r L e t t , 1913 (1978)

&

NaH, t-AmONa 100%

*

DME

T e t r L e t t , 3951 (1977) Et3N*HCOOH

Ph-Br

*

Ph-H

92%

Pt/C

"& - && JOC 42, 3491 (1977)

83%

,HIOH

Br

JOC

42, 835

(1977)


246

SECTION 160

CFh? -I

H2

BzCl

BzH

PPh3, NaOH

86%

J Organometal Chem 148, 311 (1978) 100%

JOC 43, 1557 (1978) Fe( CO)5

COOE t

73%

JOC 44, 641 (1979)

V

Ph

B

r

3

N i (CO)4

TH F

CHBr2

Ph

Chem Pharm 25, 1749 (1977)

60%

--


SECTION 160

247

COCl2

98%

LiA1H4

Br

JOC 43, 1263 (1978)

Li CuH2

-n-C 10H21 I

+ -,

100%

c-cl OH22

8 1

JOC 43, 183 (1978) I

&I

0

/

Bu3SnH

~

c1

0

/

63%

c1

JOC 44, 151 (1979)

1 ) Bu3SnH, AIBN 80%

JACS 101 , 5414 (1979)


248

($‘1

SECTION 160

NaI, Zn

TsO

DME

H

C o l l Czech Chem Comm 44, 246 (1979)

Me

Yr

Zn, KOH Me

JOC

Br

Br

c1

43,

NaTeH EtOH

95%

3500 (1978)

axCH 74%


m!Cli213r

Mo(C0)6/A1203 THF JOC 44, 2568 (1979)

80%

SECTION 160


0

electrogenerated T i (111)

!! Ph/L\

p

*

CH2Br

249

58%

Ph+H3 Can J Chem 56, 2269 (1978)

polymer-bound FeH( CO)?

92%

JOC 43, 1598 (1978)

C e ( I I I ) , NaI TH F

-0””

90%

Synth Corn 9, 241 (1979)

Na I p y r i d ine SO3

.

-4


86%

250

COMPENDIUM

Section 161


SECTION 164

Hydrides from Hydrides


S e c t i o n 162

Hydrides from Ketones


For t h e conversion R2C0

+

R2CH2 o r R2CHR' see Section 72 ( A l k y l s

and Methylenes from Ketones)

S e c t i o n 163

Hydrides from N i t r i l e s

L i , NH3(1 )

JOC 42, 3309 (1977)

S e c t i o n 164

Hydrides from O l e f i n s


80%

SECTION 165

Section 165

HYDRIDES FROM MISCELLANEOUS COMPOUNDS

251

Hydrides from Miscellaneous Compounds

Many examples (must be t e r t i a r y ) . JACS 101, 647 (1979) Na, NH3(1) R-N=C

8

0

*

+JOX

R-H

o r Na Napth

JOC

43,

2396 (1978)


CHAPTER 12

PREPARATION OF KETONES Section 166

Ketones from Acetylenes

Bu-CZC-H

Hg/Nafion-H

*

E t O H , H20

0 BU - II C- CH3

90%

Synthesis, 671 (1978) Ph-Cr C-Pr

KMn04, H20

88

+ Ph-C-C-Pr CH2C1 2, Adogen Synthesis, 462 (1978)

CH3

JOC 44, 1574 (1979)

252

81 %

KETONES FROM CARBOXYLIC ACIDS AND A C ID HALIDES 253

SECTION 167

1) Et3N

Ph t

HC- C-COPh

Section 167

Chem Ber 112, 322 (1979)

Ketones from Carboxylic Acids and Acid Halides

1 ) 2 LDA 2 ) MeSSMe

COOH

3) NCS, E t O H

JACS

OH

99, 3101

(1977)

oo Chem L e t t , 49 (1978)

66%


254

HOOC

e le c t r o ly s i s

COOH

C 6 H l 3-C\ J ( CH2)2COCH3

'gH1 3

\

*

e t h e r / w a t e r , NaOH

SECTION 167

/c=o

63%

CH3CO ( CH2 12

T e t r L e t t , 1047 (1979)

LCOO NaCl A1 C1

96%

170"

JOC

cl-(y-cl

+

44,

3724 (1979)

- p:: Nafion-H

c1

Ph-CH3 S y n t h e s i s , 672 (1978)

4

'c-c1

I

0

L

S y n t h e s i s , 54 (1977)

SECTION 167

KETONES FROM CARBOXYLIC A C I D S AND A C I D HALIDES

J Chem Research ( S )

-

0 II

THF

+ Ph-C-C1

PrMgBr

, 46

0 II Pr-C-Ph

255

(1978)

86%

T e t r L e t t , 4303 (1979)

n-C4HgMn I

+ 0

-

AL\

‘qH9

C7H15

91 %

II

n-C7H15C-C1 S y n t h e s i s , 130 (1977)

Et4Si

+ 0 II -i-Pr-C-C1

A1 C1

0

II

/c\

Et

i-Pr -

CH2C12

Synthes is , 677 ( 1377)

82%

256


A

0

11

1 ) Me3Si CH2A1C1

C11 H23-C-Cl

/\

*

2 ) H20

SECTION 167

'llH23

CH3

70%

J P r a k t Chem 320, 341 (1978)

0 It

0 It PhCH2CHZCCH3

Me4Sn

PhCH2CH2C-C1

99%

BzPdL2C1 JOC 44, 1613 (1979)

Bu3B, MeLi ,

8

CuCl * COD

Ph-C-C1

*

0

II

Ph-C-Bu

T e t r L e t t , 173 (1977)

A

2 C7HI5-C-C1

T e t r L e t t , 3861 (1977)

85%

--

KETONES FROM ALCOHOLS AND PHENOLS

SECTION 168

TMS

T i C1

t

CH2C1

0

257

Bu

65%

II

BU-C-C1 T e t r L e t t , 4045 (1977)

Section 168

Ketones from Alcohols and Phenols

6

Cr03 100%

poly ( v i n y l p y r i d i n e ) r e s i n JOC 43, 2618 (1978)

OH Il

f

i

Cr03/Cel it e E t 2 0 / CH2C1

+

6


71 %

258


HO

x)

SECTION 168

H2Cr04/Si02

88%

steroid


Bu4NHCr04 CHCl

70% 0


Tetr L e t t , 1601 (1978) chromic acid 76% s i l i c a gel Tetrahedron

35, 1789

(1979)

--

SECTION 168


259

KMn04

OH

96%

CuS04

JOC

44,

3446 (1979)

O0

*

BaMn04

0

90%

T e t r L e t t , 839 (1978)

Synthesis, 297 (1978) Tetrahedron 34, 1651 (1978) JOC

0 OH

43,

2480 (1978)

1 ) Me2S0, (COC1 l2 98% 2) E t 3 N

0 JOC 44, 4148 (1979)

260


DMSO, TFAA

SECTION 168

*

94%

R3N, CH2C12

c; OH I

/CHCH3 Ph


O2

, PdCl 2-NaOAc 88%


PdL4, K2C03 w

0 II Ph-C-CH3

95%

PhBr, DMF T e t r L e t t , 1401 (1979)

Ce+4/

Ph-fHCH3

OH

0

Br03

*

Ph-C-CH3 II

0


86%

SECTION 168


ooH KI, e l e c t r o l y s i s

261

59%

H20, L-BuOH

T e t r L e t t , 165 (1979)

CuCl , 02, K2C03

P h -CH- CH3

d"

phenanthroli n e

*

Ph-C-CH3 II

'd

T e t r L e t t , 1215 (1977)

doH

93%

JOC 44, 2955 (1979)

L

FeCl L

hv JOC 42, 171 (1977)

75%

262


SECTION 168


HO

1 1

(Ph3BiC1)20

*

~80%

0



CC13CH0

2'3

*

d"


99%

S E C TION 168


6 xi

6

5-deazaflavin

* KOH

263

82%


1 ) PrMgBr

chol es tanol

2) azodicarbonyl

HO

dipiperidine

0

BCS Japan 50, 2773 (1977)

OH I

DDQ, HI04

Ph-CH=CH-CH-Me

0 It Ph-CH=CH-C-Me

80%

HCl/benzene


Ph3CBF4 59%

I

CH2C1 T e t r L e t t , 2771 (1978)

264


SECTION 169

1 ) MCPBA

86%

JOC 42, 2077 (1977)

88% HO OH

Ph Chem L e t t , 179 (1977)

Aldehydes f r o m A l c o h o l s and Phenols ( S e c t i o n 48)

R e l a t e d Methods:

S e c t i o n 169

Ar-CHO

- -

Ketones f r o m Aldehydes Me3Si CN

OTMS I

1) LDA, THF

Ar-CH I

CN

P /c\R Ar

2 ) RBr

3 ) H3@ A r = subst. Ph, p y r i d y l , f u r y 1 R = Me, i-Pr,

Bz Chem Ber 112, 2045 (1979)

~80%

SECTION 169

KETONES FROM ALDEHYDES

1 ) Et-CBr2Li 2 ) BuLi

265

0

*

3 ) H3@

53% S y n t h e s i s , 968 (1979)

8 ii

1) Ph-S-CHCl

BU-CHO

0

II

81 %

Bu-C-CH2C1

T e t r L e t t , 1225 (1977) Chem L e t t , 209 (1979)

1 ) (PhS)2CHLi TMEDA n-C6H1 3-CH0

0

II

*

79%

n-C6H1HC\ 3 CH2SPh

2 ) TsOH, benzene

JCS P e r k i n I , 1074 (1979)

266


SECTION 170

-fJQzm

S e c t i o n 170

Ketones f r o m A1 k y l s

Methylenes , and Ar,yl s

0

70%

S y n t h e s i s , 144 (1979)

0

Bz Et 3NMn04

+

Ph- CH2CH2CH2CH

II

Ph-C-CH2CH2CH

Angew I n t Ed

8 8 PhSe-O-SePh

18,68

44%

and 69 (1979)

0

II

*

PhCH2Ph

90%

Ph"\Ph

T e t r L e t t , 3331 (1979) Se02 C7H1 5-CH2-CH=CH 2 -

x

C7H1 5-C-CH=CH2 t-BUOOH -

JACS 99, 5526 (1977)

61 %

SECTION 170

KETONES FROM ALKYLS, METHYLENES, AND ARYLS

267

Cr03-C5H5N AcO

AcO 87%

-

J Chem Res (S), 42 (1979)

Cr03

-n-C5H1 -CH2-CH=CH-COOMe

Ac20, HOAc

A

n-C5H1 -C-CH=CH-COOMe 86%

B u l l Chem SOC Japan

52,

T e t r L e t t , 5021 (1978)

184 (1979)

268

COMPENDIUM OF ORGANIC SYNTHETIC METHODS VOL

4 SECTION 172

L i , NH3(1)

THF, t-pentanol OMe

OMe 31, 1625 (1978) Aust J Chem -

S e c t i o n 171

Ketones f r o m Amides


S e c t i o n 172

Ketones f r o m Amines

1 ) L-BuLi

, THF

phyx 75%

2 ) Me1

JOC 44, 3585 (1979)

SECTION 173

S e c t i o n 173

KETONES FROM ESTERS

269

Ketones f r o m E s t e r s

COOPh

6x3

K CH2N02, DMSO

*

82 %

S y n t h e s i s , 295 (1979)

Me3AI, TFA

95%

OTMS

JACS 9 9 , 4192 (1977)

270


S e c t i o n 174

SECTION 174

Ketones f r o m E t h e r s and Epoxides

F6

1

86%

JACS 100, 5396 (1978)

57%

JOC

$

42,

1 ) PhSeNa, E t O H 2) MCPBA, p y r

'8

3097 (1977)

JACS 99, 7601 (1977)

~80%

SECTION 175

S e c t i o n 175

271

KETONES FROM HALIDES

Ketones from H a l i d e s

72% Chem & I n d , 213 (1979)

Ph

H

ONa

Ph

Me

2)

--

0 II Ph

Me

60%

A

JCS P e r k i n I, 2493 (1979)

-

Ph-I

N i ( CO)4

t

P h - b O C l

benzene

C1-

HgCl S y n t h e s i s , 776 (1977)

90%

272


-

R

1 ) Fe(C0)5

Bu-MgBr

2 ) Me1

SECTION 175

70%

BuAC\Me

T e t r L e t t , 761 (1978)

CO, HMPA

PhI +

Me4Sn

fl

Ph-C-Me

123%

PhPd (PPh3) 21

T e t r L e t t , 2601 (1979)

2 PhCH2Br

Fe (CO) 5, NaOH

*

0

II

PhCHZ-C-CH2Ph

94%

Bu4NBr Chem L e t t , 321 (1979) 1 ) 2BuMgx

*

MeOCH2 COOMe

P Bu /‘\BU

2 ) anodic o x i d a t i o n

T e t r L e t t , 3625 (1977)

64%

SECTION 175

KETONES FROM HALIDES

273

1 ) Et2NCH2CN, LDA 2 ) LDA, R ' X

*

R- X

0

II R-C-R'

~80%

3 ) (COOH)2, H20/THF

R , R ' = 1" a l k y l T e t r L e t t , 5175 (1978)

1 ) NaOH, B u 4 N I 2) B z B r

*

TosCH2N=C

3) i-PrI

0 II

/"\ i- P r BZ

65%

-

T e t r L e t t , 4229 (1977)

@ J ,,

Hg ( O A C ) ~ , BF3-

HOAc T e t r L e t t , 1943 (1978)

Cl T e t r L e t t , 3489 (1979)

60%

274


SECTION 176

Related methods: Ketones f r o m Ketones ( S e c t i o n 177), Aldehydes from H a l i d e s ( S e c t i o n 55)

S e c t i o n 176

Ketones f r o m Hydrides

T h i s s e c t i o n l i s t s examples o f t h e k e t o n i c groups, RH

R2CH2

-+

-t

replacement o f hydrogen by

For t h e o x i d a t i o n o f methylenes

RCOR'.

R2C0 see S e c t i o n 170 (Ketones f r o m A l k y l s and Methylenes)

8

C F3 COS02 C F3

81 %

JOC 44, 313 (1979)

C L

NaCl A1 C l ___L

170"

COOH

JOC 44, 3724 (1979)

96%

KETONES FROM KETONES

SECTION 177

275

PhCH3 t

P h2C= C=O Chem L e t t , 535 (1978)

S e ct ion 177

Ketones from Ketones

Th i s s e c t i o n contains a l k y l a t i o n s o f ketones and p r o t e c t e d ketones, ketone t r a n s p o s i t i o n s and annelations, r i n g expansions and r i n g openings, and d i m e r i z a t i o n s .

Conjugate r e d u c t i o n s and Michael

a l k y l a t i o n s of enones are l i s t e d i n Section 74 ( A l k y l s f r o m O l e f i n s ) .

For t h e p r e p a r a t i o n o f enamines from ketones see S e c t i o n 356

(hine-01 e f in)

.

TH F T e t r L e t t , 845 (1979)

276


Me

SECTION 177

1 ) LDA 2) B(OCH2CH2)3N, DMSO Me 3) Me1 Synth Corn

1 ) Ph3CQ, DME Ph/‘\CHMe2

2) Me1

8,

9 (1978) 0 II

*

PhYC\ CMe

76%

Synth Comm 7, 137 (1977)

JOC 43, 1834 (1978) 1 ) K-0-t-Am, DMF/DME

2) BzBr 3) NH4Cl , H20

b

Synth Corn 8, 563 (1978)

77%

SECTION 177


Me I

277

Pe “Me,

Chem Ber

111, 1337

95%

(1978)

1 ) CH2=CHCH2Br

Me

82%ee

JOC 42, 1663 (1977)

O-t-Bu

I-

t-Bu-CH

-

*

\ 1) LDA 70%

2) PrBr 97%ee(S) T e t r L e t t , 573 (1978)

278


SECTION 177

1 ) R-NH2

w 0

2 ) LDA, Me1

3) HOAc, %Ac

0

*

R = -CHBzCH,OMe

98%ee

L

8

JOC 43, 3245 (1978)

HCHO, CO

%40%

RhCl

6

Chem L e t t , 215 (1978)

I

65%

T i C1

T e t r L e t t , 1427 (1979)

0

/OCH3 h-CH=c\

COP h

[~eH(co)~l

a

PhCH2CH2CPh

EtOH

BCS Japan

51, 835

(1978)

69%

SECTION 177


279

b OTMS

-t-BuC1

41 %

TiC14

T e t r L e t t , 4183 (1977)

t-BUC1 T i C1

Angew I n t Ed

6 OTMS

85%

17,48

(1978)

PhCH2Br, AgCl O4

CH2Ph

CH2C12, BF3* Et20

*

82%


Br I P h-CH-CH

3

ZnBr2

T e t r L e t t , 1519 (1979)

71%


280

SECTION 177

98 %

CH2=CHCH2Br

T e t r L e t t , 3121 (1 977)

0 II 2

CH3

R

TMS-N H

w COO-TMS

30-70%

*

Angew I n t Ed 16, 251 (1977)

n

BF3 E t p O

o r Na/NH3

66%

8 413 (1978) Synth Comm -

Chem L e t t , 231 (1978)

L

SECTION 177


281

d"

Also works w i t h s ty re n e e t c , JACS 100, 1791 and 1799 (1978)

1 ) LDA, THF Ph-CH-CN I NMe2

*

fi

Ph-C-CH2-BU

63%

2 ) BuBr


Review:

"Synthesis o f Aldehydes, Ketones, and Carboxyl i c Acids

from Lower Carbonyl Compounds by C-C Coupling Reactions" Synthesis, 633 (1979)

Ketones may a l s o be a l k y l a t e d and homologated v i a o l e f i n i c ketones (Section 374) Related methods:

Aldehydes from Aldehydes (Section 49)

282


S e c t i o n 178

SECTION 179

Ketones f r o m N i t r i l e s

No a d d i t i o n a l exampl es S e c t i o n 179

Ketones f r o m O l e f i n s

1 ) LiA1H4, TiC14

2)

.pyCH3

*

C8H1

18

54%

7-C-CH3

0

Chem L e t t , 167 (1979)

1 ) LiA1H4, TiC14

*

B U- CH=CH2

0 \I BuCH2CH2C-Ph

71%

2 ) PhCOCl Chem L e t t , 623 (1979)

I n d i a n J Chem

E, 704

(1976)

SECTION 179

KETONES FRON OLEFINS

283

b

PdCl 2-CUC1

*

75%


T e t r L e t t , 1827 (1977)

JOC

hv,

42,

4268 (1977)

o2 40%

p y r i d i n e , FeC13 Chem L e t t , 161 (1978) See a l s o Section 134 (Ethers and Epoxides from O l e f i n s ) and Section 174 (Ketones from Ethers and Epoxides).

284


Section 180

SECTION 180

Ketones f r o m Miscellaneous Compounds

Conjugate r e d u c t i o n s and r e d u c t i v e a1 k y l a t i o n s o f enones are l i s t e d i n Section 74 ( A l k y l s from O l e f i n s ) .

6

NO,

basic s i l i c a gel 99% ether JACS 99, 3861 (1977)

1 ) L-BuOK

82 %

*+

2) t-BUOOH VO( acac)2, benzene

Ll

T e t r L e t t , 331 (1977)

1 ) NaOH, MeOH

+

JOC 43, 1271 (1978)

66%

SECTION 180

KETONES

FROM MISCELLANEOUS COMPOUNDS

(yN3

285

Na2S, E t 3 N

85%

JOC 44, 4712 (1979)

-)q 'yo i -Bu

Ph

a

1)

)-c

~50%

2)

H20

3)

Pb(OAc)4, HMPT/TH 17, 450 (1978) Angew I n t Ed -

Me I II I

Me 0

N-c-cH\ 2 H 2 ) 8

97%

p H 2 0 T e t r L e t t , 4487 (1979)

286


1)

NaH, DMF

3)

AcOH

SECTION 180

88%

*

JOC 44, 4 5 9 7 ( 1 9 7 9 )

Ra -N i

Chem L e t t , 4 2 3 (1977)

T e t r L e t t , 1 8 9 3 (1979)

SECTION 180A

S e ct ion 180A

PROTECTION OF KETONES

287

P r o t e c t i o n o f Ketones

See Section 367 (Eth e r-Ol e fi n ) f o r t h e formation o f enol e t h e r s . Many o f t h e methods i n Section 60A ( P r o t e c t i o n o f Aldehydes) are a1 so appl i c a b l e t o ketones.

HC(OMe)3 w

montmori 11o n i t e

Meo6 97%


- togoE HC( O E t )

65%

graphite bisulfate

8

BSC France, 499 (1977)

* CHCl

T e t r L e t t , 4175 (1977)

90%

288

COMPENDIUM OF ORGANIC SYNTHETIC METHODS VOL 4 SECTION 180A

0

A

HOCH2CH20H/THF

II

R

*

Amberlyst 15

R'

n

0 \C/O

I\ R '

R

JCS Perkin I , 158 (1979) HOCH2CH20H , benzene

92%


n

8

wet s i l i c a gel

*

8

65%


MeSSMe

0

R

? / \

__L

R'

Bu3P

MeS

\ /SMe

R YC\R'

Chem Lett, 767 (1979)

SECTION 180A


289

EtSH, Me3SiC1

100%

CHCl Synth Corn 7, 283 (1977)

Tetr Lett, 675 (1978)

8

6

Chem Pharm Bull 27, 538 (1979)

hu, Ph2C0 ,02

hexane


65%

290


Synthesis, 720 (1979) e 1ec troc hemi c a1 ox i d a t i on

h

L i C1 O4

THF/H20,

xi

0



1)

s\c/

S

I\

R'

R

NPor N&

L

* R

i)l A R'


%5D%

SECTION 180A


291

Chem Pharm 26, 3743 (1978)

Synth Comm 9, 301 (1979)


02’ hv

59% methyl ene blue


292

COMPENDIUM

OF ORGANIC SYNTHETIC METHODS VOL 4 SECTION 180A

76%

t

S y n t h e s i s , 212 (1978)

x

HON

1 ) NOCl

, pyridine

2) H20, r e f l u x

-x

81%

0

Chem and I n d , 454 (1977)

NOCl

0

*

II R

~80% R'

I n d i a n J Chem 158, 578 (1977)

e l e c t r o g e n e r a t e d T i (111)

NOH

II Ph

CH3

*

0 II

/\

80%

Ph

CH3

Can J Chem 56, 2269 (1978)

SECTION 180A


293

T i tanous c h l o r i d e dioxane

HON

6

NNHts

Chem and Ind, 742 (1977) B r 2 , CH2C12

NaHC03, H20

-8

81 %

B r 2 , CH2C12

69% NaHC03, H20/HMPT

Synthesis, 113 (1979) ,,,/NHTs

Synthesis, 308 (1979) NNHTs NaN02, CF3COOH R

R'

0

*

II

R


R'

294


6

d

NNHTs

95%

100, 5396 (1978) JACS -

R

>c= N -NH T ~

R'

Synthesis, 919 (1978) NNHTs

II

R

/"\

R'

CuS04, H20

*

MeOH, THF

v

0

/\ R

%go% R'

Gazz Chim Ital 108, 137 (1978) NNTs

II R

T1 (OAc)3

0

II

_ L

R'

HOAc

R

Tetr Lett, 4583 (1979)

R'


SECTION 180A

Hydrazones

( PhSeO) 2O

Oximes Semicarbazones

6

t

295

Ketones


CO (CO

PhMe2SiH

l8

OSi Me2P h 85%

PYr

T e t r L e t t , 2671 (1977)

0

g S i Me3 Me3SiI , HN(SiMe3)2

81% CH2C1

6-

S y n t h e s i s , 730 (1979)

6,,,

PhS-TMS

JACS

99, 5009

(1977)

296

COMPENDIUM

OF ORGANIC S Y N T H E T I C METHODS VOL 4 SECTION 180A

S e l e c t i v e formation o f enolate i o n s t o p r o t e c t carbonyl groups from r e d u c t i o n by LiA1H4.

Used t o e f f e c t s e l e c t i v e reductions o f

s t e r o i d diones and t r i o n e s .

JCS Perkin I , 1075 (1977)


CHAPTER 13

PREPARATION OF NITRILES S e c t i o n 181

N i t r i l e s from Acetylenes

[ N i ( CN),I2PhCH2CH2CzCH

0

CN, NaBH4

PhCH CH CHCH3 2 21 CN

92%


Section 182

N i t r i l e s from Carboxylic Acids and Acid Halides

No addi t i onal examples

S e c t i o n 183

N i t r i l e s from Alcohols


297

298


Section 184

SECTION 184

Nitriles from Aldehydes 1 ) (i-Pr)3PhS02NHNH2

*

CgH1 3-CH0

2) v

C H -CZN 6 13

92%


63% Synthesis,703 (1978)

1 ) NH20H*HC1 Pyrid ine/CHC1

R-CHO

2) Se02

R = a1 kyl ,

P

R-CN

%80%

a w l , heterocycl ic Synthesis, 722 (1979)

Ph -CH=N -OH

+ -'

TFAA py r id i ne

Ph - CZN


90%

SECTION 184

NITRI LES FROM ALDEHYDES

n-C6H13-CH=NOH -

Et3N

299

C H -CzN 6 13

83%


C1S02NC0

C5H1 1-CH=NOH

C5H1 -CN

75%

Et3N


Q

CH=NOH Me-C:C-NEt2

*

CH3CN

No2

Ph -CH=NOH

80% N02


@-PPh2*CC14

*

Ph-C-N


76%

COMPENEIUM OF ORGANIC SYNTHETIC METHODS VOL 4

300

SECTION 184

P2IqY pyridine

*

n-C7H, 5-CH=NOH

C7H1 5-C=N

64%

Synthesis, 905 (1978) Ph

*

NH2

Ph-CHO

2)

Ph-CN

99%

A

JCS P e r k i n

y

1957 ( 379)

n i c k e l peroxide

+

Ph-CHO

Ph-CN

73%

NH3, benzene, Na2S04 Synth Corn

I

HN-NMe2CH2CHCH3 C

H

Et

O

(1979)

OH

08

T

zy529

_ L

ycN

Me2CHOH Synthesis, 301 (1978)

76%

Et

NITRILES FROM AMIDES

SECTION 186

1 ) (i--Pr)3PhS02NHNH2 C6Hl 3-CH0

301

*

C6HI3CH2CN

72%

2) KCN, MeOH JCS Chem Corn, 280 (1977)

Section 185

N i t r i l e s from Alkyls. Methylenes and Ar-yls

No a d d i t i o n a l examples Section 186

N i t r i l e s from Amides

A n-C1 7H35-C-NH2

-

@-PPh2

eCC1

n-C, 7H35-CzN


T e t r L e t t , 1813 (1977)

100%

302


S Ph-C-NH2 I1

N-COOEt N-COOE t

SECTION 186

I1

T

Ph3P

Ph-C-N

59%

JCS Chem Corn, 220 (1977) JOC 44, 3436 (1979)

R

BZ - C- NH2

C1S02NC0 Et3N

Bz-CN

84%


CH3CH2-NH-CH0

bismuth phosphomol y b d a t e 02, 400-500"

*

CH3CH2CN

90%

Chem & Ind, 852 (1979)

ISI

Ph-C-NH2

BrCH2CN %Et

Ph-CgN

Synth Corn 9 , 569 (1979)

85%

SECTION 190

Section 187

NITRILES FROM HALIDES

303

N i t r i l e s from Amines -___-_CUCl

Ph-CH2NH2

y

o2

p y r id ine

*

Ph-CGN

35%


Section 188

Y i_L r i l e s from E s t e r s

0 II

Me2A1NH2

R-C-OR'

R = alkyl

xylene , A

*

R-CN

, aryl T e t r L e t t , 4907 (1979)

Section 189

N i t r i l e s from E t h e r s a n d Epoxides


Section 190

N i t r i l e s from Halides

HMPA

JOC 43, 1017 (1978)

%70%

304


SECTION 190

NaCN (on alumina) M

B

b

r

m

C

N

93%

JOC 44, 2029 (1979)

JOC 44, 3436 (1979) Et4NCN

wBr v

mcN 80%

CH2C1


Bux KCN, PdL4

Br

*

Bu

%CN

crown e t h e r , benzene

T e t r L e t t , 4429 (1977)

NaCN , a1 umi na Pd(I1) c a t a l y s t

JOC -_ 44, 4443 (1979)

96%

SECTION 191

305

NITRILES FROM HYDRIDES

1 ) 1-pentyl-ONO, HC1 2) NaN3, DMF 560% overall Synthesis, 102 (1979) Section 191

Nitriles from Hydrides-

_ i _

1 ) DMF acetal 2) H2N-OS03H

Q

CH2CN

*

N02

N02

Tetr L e t t , 1361 (1979)

$N

BrCN

A1C13, CS2 35, 2927 (1979) Tetrahedron -

64%

306


S e c t i o n 192

SECTION 193

N i t r i l e s from Ketones

___.___

1 ) (I-Pr)3PhS02NHNH2 71 % 2) KCN, MeOH JCS Chem Comm, 280 (1977)

C= N- C H 2 T ~ 80% t-BuOK

JOC

S e c t i o n 193

42,

3114 (1977)

N e - r i l e s from N i t r i l e s -____-_____-

Conjugate r e d u c t i o n s and Michael a l k y l a t i o n s o f o l e f i n i c n i t r i l e s a r e found i n S e c t i o n 74 ( A l k y l s from O l e f i n s ) .

1 ) Bu [ CuBrIMgC1

Ph-CZC-CN

v 2 ) H30

Ph

\

/C=CHCN Bu (cis)


96%

SECTION 195

NITRILES FROM MISCELLANEOUS COMPOUNDS

307


Section 194

N i t r i l e s from O l e f i ns

J4

OH I Me2CCN, KCN

0

18-crown-6 benzene

0

CN

I

86*

T e t r L e t t , 1117 (1977)

Section 195

N i tri 1es from _- M i scel 1aneous Compounds

Et3N/S02

C6Hi3-CH2-NO2

C 6H13-C=N

CH2C1


78%

308


'2'4

SECTION 195

78%

Tetr Lett, 3995 (1979)


CHAPTER 14

PREPARATION OF OLEFINS Section 196

O l ef i ns from Acetylenes -

- 4 Yb, N H 3 ( 1 )

C H C-C-C3H7 3 7-

C3H7

85%

C3H7

JOC 43, 4555 (1978)

1 ) LiA1H4

Bu-C:C-(CH

2 ) 6 -OH

2 ) H20

Bu

\ c=c /H

H

S y n t h e s i s , 561 (1977)

309

93%

310


P h- CECH

1 ) (Sia)2BH

SECTION 196

*

2) Pd(OAcI2, Et3N, THF JCS Chem Corn, 852 (1977)

C6H1 3-C-C-Et

1 ) Sia2BH

2) Et3N, THF Pd(OAc)*

‘gH1 3

Et

\=/

70%


HC-C-C 6H 13

Li A1 H4-Ni C1

*

H2C=CH-C6H1

Tetr Lett, 4481 (1977)

96%

SECTION 196

Me

Me

1 ) DIBAH

\ / 02

31 1

OLEFINS FROM ACETYLENES

96%

\ N-CH~-CH;CHQ

/

BZ

(IT stereochem)

T e t r L e t t , 3145 (1979)

C H CZC-C H 3 73 7

Et I

il C

EI t

HZ

90%

b

C3H7

polymer-bound PdC12

HE, NaH, Ni(OAc)z

98% /7 Et Et

+

THF/E t O H

T e t r L e t t , 3955 (1977)

L i A1 H4

CH3-C-C-Pr

NiClz

H

\

/H

CH3 /c=c\

JOC 43, 2567 (1978)

92%

Pr

312


c+

MgH2 CH3-C:C-C

SECTION 196

/3H7

z

H 3 7

81 %

/"="\ H

CU -0- t -Bu

H

JOC 43, 757 (1978) I

-

H

\

1 . BuCECH

(C6H11)2BH

2. PhI(OAc)2

Iu

'sHl /c=c\1

60%

H

Chem L e t t , 665 (1978)

BU

''=c'qoxl

\

PhI

/H

H

NaOEt, Pd$ benzene

0

H

Bu)=( H

Ph

100%

JCS Chem Comm, 866 (1979) Me 1) C7H1 5-CrCH

CH2ZnBr

*

BSC France, 1173 (1976)

72%

31 3

OLEFINS FROM ACETYLENES

SECTION 196

T e t r L e t t , 1363 (1978)

1) Me3A1 -C1 2ZrCp2 PhC-CD 2)

Ph

*

Hp

\

/D

Me/"="\

98% H

JACS 100, 2252 (1978)

OH

CzCH

H2C=0, CuBr

&CH=C=CH2

OH

97%

i-Pr2NH, dioxane JCS Chem Comm, 859 (1979)

Review: "The S e l e c t i v e Hydrogenation o f T r i p l e Bonds w i t h Organometall i c T r a n s i t i o n Metal Compounds" Pure and Appl Chem 50, 941 (1978)

314


S e c t i o n 197

SECTION 198

Olefins. f r o m C a r b o x y l i c Acids and A c i d H a l i d e s


S e c t i o n 198

O l e f i n s f r o m A l c o h o-ls

FeCl 90%

s i l i c a gel JOC 43, 1020 (1978)

%40-80%

JOC 44, 1221 (1979)

DMPADC*

*

-N, -N -

*d m

72%

Dimethylphosphoramidic d i c h l o r i d e

Chem L e t t , 923 (1978)

SECTION 198

OLEFINS FROM ALCOHOLS

315

Acta Chem Scand (6) 31, 721 (1977)

0 Ph

OeN Et3N

74%

JACS 100, 5981 (1978) TiC13/K

0-0

85%

JOC 43, 3255 (1978) Me

OH JOC 42, 1317 (1977)

316


SECTION 198

1 ) Me2NCH(OMe)2 2) Me1

0:::; 3 ) toluene, r f x .

T e t r L e t t , 737 (1978)

Examples u s i n g carbohydrates JCS Chem Cow, 866 (1977) JCS Perkin I,2378 (1979)

Chem L e t t , 413 (1978)

90%

SECTION 199

OLEFINS FROM ALDEHYDES

CH2SPh

H o w c t r o l y s i s

DMF, TsOH

w

T e t r L e t t , 2807 (1978)

Section 199

31 7

O l e f i n s from Aldehydes

JOC 43, 790 (1978)

I n d i a n J Chem 15B, 290 (1977)

92%

318


-

SECTION 199

0

II ( Et0)2PCH2X

Ph-CHO

PhCH=CHX

90-98%

KOH, THF

X = CN, COOEt Synthesis, 884 (1979)

Ph3P=CHC1 81%

Ph-CHO

JCS Chem Comn, 446 (1978)

( Me2N)3P=CC12 C5H1, CHO

*

C5H1 1CH=CC12

T e t r L e t t , 1239 (1977)

T e t r L e t t , 2417 (1978)

94%

SECTION 199

31 9

OLEFINS FROM ALDEHYDES

-

PhCH2CH2CH=NNHTs t

PhCH2CH2CH=CHEt

70%

E t CH ( L i ) CN JACS 101 , 249 (1979)

PhCHO

t

oq SCOOEt

-*,

0

84% Chem L e t t , 197 (1978)

T i C1 3/K

M

C

H

O

C4HgCH=CHC4Hg

77%

-

JOC 43, 3255 (1978:

2 Ph-CHO

WC16, LiA1H4

JOC

b

43,

/dPh 73% Ph 2477 (1978)


320

SECTION 200

0 NMe I\ JJ 1 ) Ph-S-Me

THF, Ph3CH, B u L i CH3( CH2) 8CH0

56%

CH3( CH2)&H=CH2

b

2 ) A1/Hg THF/H20/HOAc JACS 101, 3602 (1979)

S e c t i o n 200

O l e f i n s f r o m A l k y l s , Methylenes and A r y l s

T h i s s e c t i o n c o n t a i n s dehydrogenations t o f o r m o l e f i n s and u n s a t u r a t e d ketones, e s t e r s , and amides.

It also includes t h e

reduction o f aromatic r i n g s t o o l e f i n s .

Hydrogenation o f a r y l s t o alkanes and dehydrogenations t o f r o m a r y l s a r e i n c l u d e d i n S e c t i o n 74 (A1 k y l s , Methylenes, and A r y l s f r o m O l e f i n s ) .

t-BuOH , PdCl HC1 , 80"

*

I

80%

S y n t h e s i s , 773 (1977)

0

\I

( PhSe) 2O

0


39-92%

OLEFINS FROM ALKYLS, METHYLENES, AND ARYLS

SECTION 200

C-NMe2

1 ) C0Cl2

32 1

C-NMe2

‘’Q

70%

Meow , Et3N

J.

0

JACS 101 , 4381 (1979)

r

Me0

I*, D M S O / H ~ S O ~

0

Me0

0

%loo% Chem & I n d , 315 (1979) C3H7

5--

DDQ dioxane

C3H7

N ,

0

&C6H,

89%

‘gH1 3

80

J Chem Res ( S )

, 311 (1979)

, CF3COOH2NMePh 0 8 b

THF T e t r L e t t , 2111 (1978)

90%

322

M


Mefy -

e OTM6S Z n / C u , CH212

H2°C:isOq

C1 CH20CH3

A

JACS

Me I Et-CH-CH2CH ( O E t ) 2

101,984

Me2NH*HC1

*

Me SECTION 200

(1979)

Me I Et-CH-C-CHO

HCHO

II CH2

82%

J Chem Research ( S ) , 262 (1978)

43, 4555 (1978) JOC -

SECTION 203

Ca, CH3NH2

*

JOC

Related methods: 65)

6

OLEFINS FROM ESTERS

44,

323

85%

3737 (1979)

A l k y l s and A r y l s from A l k y l s and A r y l s (Section

A l k y l s and Aryls from O l e f i n s ( S e c t i o n 74)

S e c t i o n 201

O l e f i n s from Amides


S e c t i o n 202

O l e f i n s from Amines

cN+

1 ) CF3S03CH2COOEt 2) DBU

*

EtOOC&

tOOEt

(64:36 E : Z ) T e t r L e t t 1241 (1977) S e c t i o n 203

O l e f i n s from

Esters

N02 Also works w i t h lactones.

Chem L e t t , 189 (1977)

89%


324

SECTION 204

1. TsCH,MgI L

2. NaBH4 63% 3. E l e c t r o c h e m i c a l r e d u c t ion

COOMe

k

'6

Chem L e t t , 69 (1978)

0 80

COOMe

4 Ph3P-CH2

C' H

0

S OCH

CH2

DMSO

JOC

S e c t i o n 204

H\ Bu

/c-c,

78%

44,

3157 (1979)

O l e f i n s f r o m Epoxides

NaI , TFAA

/"\ H, Bu

CH3CN, THF

H

* Bu/c=c\u

JOC 43, 1841 (1978)

95%

OLEFINS FROM EPOXIDES

SECTION 204

P214, pyridine

*

325

/J

95%


A

n-C 8H17 -

p13

A

n-'8"17

1> M

=

Nouveau J Chem

2, 705

MeP(OPh)31 BF3*Et20

*

(1979)

p

JOC 43, 2076 (1978)

No, W , Ti, Zr

83%


%go%


326

SECTION 204

Do 0

II

( EtO)pP-TeNa

88%


Do

T i C13 , L i A1 H4

0

*

0 0:: TiC13, LiA1H4

*

JOC 43, 3249 (1978)

Fe ( CO ) 4TMU

* 0

0

TMU = t e t r a m e t h y l u r e a T e t r L e t t , 4155 (1977)

69%

96%

OLEFINS FROM HALIDES AND SULFONATES

SECTION 205

-

327

1) HBr

‘gH1 *TMs 3

H

2) BF3*Et20

85% Br

‘sHl 3

JACS 99, 1993 (1977)

S e c t i o n 205

___Olefins

6

from H a l i d e s and S u l f o n a t e s

t-BuOK/pet.

ether

+

18-crown-6

0

S y n t h e s i s , 372 (1979)

Angew I n t Ed

16,44

(1977)

83%

328

6


6

8 0

1) CH2=NMe21

*

2 ) H202

3) 150"

SECTION 205

~80%

T e t r L e t t , 1299 (1977)

Me0 92%

CH2 I

R = -CX-CMe20Me JOC 43, 3418 (1978)

CH2=CH2

Me

, Et3N

*

Pd( OAc)2L2

JOC 43 , 2454 (1978)

OTHP

SECTION 205

OLEFINS FROM HALIDES AND SULFONATES

1) MeLi, CuI

*

('sH1 3)3B

C7H14-CH=CH2

329

53%

2) & B r BCS Japan 50, 2199 (1977)

1 ) BuLi CH2= CHSeP h

*

2, !!.-CIOH1lBr

\

H

,ClOH11 80%

Bu/="\

3) 03, ( i - P r ) 2 N H JOC 43, 4252 (1978)

I

3 ) toluene, r f x T e t r L e t t , 4917 (1978)

T e t r L e t t , 323 (1978)

H

330


SECTION 205

NaHTe

76%

EtOH


VCl,/LiA1H4 PhCH=CHPh

97%

THF Synthesis , 170 (1977)

A1203, 25" Et20

-Q

81 %

JOC --42, 3173 (1977)

CH3 ( CH2) 7-iH-CH2TMS S02Ph

-

CH3(CH2)7-CH=CH2

T e t r L e t t , 2649 (1979)

80%

OLEFINS FROM KETONES

SECTION 207

P

‘gH1 7

-

S02Ph

sugar

‘gK

CgH1 7CH=CHMe

JCS P e r k i n I , 123 (1977)

Na

THF

Chem Pharm 25, 2134 (1977)

S e c t i o n 206

O l e f i n s f r o m Hydrides -


S e c t i o n 207

77%

TH F

1 TOMsm, .‘OMS

331

O l e f i n s f r o m Ketones

T e t r L e t t , 2417 (1978)

~65% -

332

COMPENDIUM

6


Cp2Ti CH2A1 C1( CD3)2 b

SECTION 207

65%

JACS 100, 3611 (1978)

C1 CH2Si Me3

Ph2C=0

Ph2 C= CH2

78%

Ph3P

JOC 44, 413 (1979)

16, 862 (1977) Angew I n t Ed -

NMe

II

1 ) Ph-S-Me, THF, II 0 Ph3CH, BuLi

-6

45%

2) THF/H20/AcOH

JACS 101 , 3602 (1979)

SECTION 217

OLEFINS FROM KETONES

333


0 I1 ( Et0)2PCH2CN

Ph

\

1

Ph

Me

/"=

KOH, THF

Me

88% CN


T i C1 3/3Li

79%

JOC 43, 3255 (1978) Ph

TiCl3/LiA1H4

~50% Ph Ph

r i n g s i z e 3-12 JOC 43, 3609 (1978)

334


n

=

2-14

0 II

2 C3H7-C-Me

JOC

42,

TiC12, pyridine

*

THF/dioxane

SECTION 207

2655 (1977) Me

Me

\ I C3 7

H -C=C-C3H7

61%


NNHTs Ph +ph

&-.'

L DA

TMEDA

P

h

T Ph

66%

JOC 43, 1404 (1978) 1 ) EtMgBr ___)

2) Li JCS Chem Comm, 847 (1978)

87%

SECTION 208

OLEFINS FROM NITRILES

OPO( OEt)2

brH3

1 ) Active T i

*

2) EtOH

335

OcH3 83%

JOC 43, 2715 (1978)

~80%

2) base

TMS


Related methods:

Section 208

O l e f i n s from Aldehydes, Section 199.

O l e f i n s from Nitriles

NaClOH8

CN

HMPA

JOC 44, 2994 (1979)

90%

336


PhCH2CH2CH=NNHTs t

-

PhCH2CH2CH=CHEt

SECTION 209

70%

E t C H ( L i ) CN

-

JACS 101 , 249 (1979)

1 ) NaNH2, benzene 79 %

T e t r L e t t , 3187 (1977)

S e c t i o n 209

-fins

from O l e f i n s

Me3A1, CH2C12 C8H1 7-CH=CH2

Cp2Ti C1

*

‘gH1 7

\

/c=CH2 Me

JOC 44, 3603 (1979)

74%

SECTION 210 Section 210

OLEFINS FROM MISCELLANEOUS COMPOUNDS

337

Olefins from Miscellaneous Compounds

a-H - (7) Me2S04

53%

A

JACS 99, 1172 (1977)

P h2C=CHN02

Na2S, PhSH

*

DMF

Ph2C=CH2

94%

Tetr Lett, 1733 (1979) YO2 Me- CH2CH2COOMe

e-I

Me-;-CH2CH2COOMe

Me *-

,I#-

La/ ng T

NO2

CH CH COOMe

\ / 2

'C 84% II C / \ I \ CH,CLI H2COOMe Me

JOC 42, 2944 (1977) BF3 Et20 100"

C ~ -CH=CHCH~ H ~ 88%


338


Co2 ( co l8

Ph C=S 2

SECTION 210A

Ph2C=CPh2

71 %

JOC 42, 3522 (1977)

S e c t i o n 21 OA

L r o t e c t i o n o f 0 1 e f ins -

A1C13, CS2

bBr

*

90%

Use o f t h e t - b u t y l group t o b l o c k p o s i t i o n s on an a r o m a t i c r i n g . I

JCS P e r k i n I , 176 (1979)

Br

1) B r 2

@ B

THF o r CHC13

r

62%

75% Br

Synthesis, 964 and 966 (1979)

SECTION 210A

PROTECTION OF OLEFINS

Review: "Selective Synthesis o f Aromatic Compounds Using Pos it i onal Pro t e c t i ve Groups " Synthesis, 921 (1979)

339


CHAPTER 15

PREPARATION OF DIFUNCTIONAL COMPOUNDS S e c t i o n 300

Acetylene - Acetylene -

HCE C-CH20Ts

Bu-CEC-MgBr

Bu-CzC-CH2-C=CH

75%

CuBr/THF

S y n t h e s i s , 292 (1979)

Sect on 301

Acetylene

-

Carboxylic Acid

. -

No a d i t i onal examples S e c t i o n 302

Acetylene - Alcohol

0 It

Me-CEC-C-i-Bu -

LiA1H4

Darvon

H &-CzC--(---OH i-Bu -

94% 82%ee

JACS 99, 8339 (1977) 340

SECTION 302

ACETYLENE

ALCOHOL

c h i r a l LAH complex

0 II t-Bu-C-CECH

*

-

341

*

*

*

t-Bu-CH-CXH

90%ee

AH [ L i A1 H4, ti--methylephedrine,

3,5-dimethyl phenol]

T e t r L e t t , 2683 (1979)

1 ) 9-BBN C6H, $zCCH2C=CH2

I

CH3

2) H202,

0

*

98 I C6Hl 3C~CCli2CHCH20H

I

OH

CH3

JOC 44, 2328 (1979)

1 ) LiNH2, NH3

H-C:C-CH2CH20H

Bu-CZC-CH~CH~OH

2) BuBr

H e l v Chim Acta

61,2275

(1978)

72%

342


( CH2C-C)Li2

1) BuBr

*

SECTION 302

BuCH2CsCCH2CH20H

66%

JCS Perkin I , 1218 (1979)

-

r \

2 ) NaOH, H202

OH

JACS 100, 5561 (1978)

PhCHO

Me S i - C X L i 3 chiral pyrrolidine catalyst

*

"f C z C-S i Me3 OH

Chem L e t t , 447 (1979)

99% 89%ee

SECTION 304

ACETYLENE

Section 303

Acetylene

-

CXLi

- AMIDE

343

Aldeh.yde

ether

CZC-CHO

63%

t

0

H

AOET


1 ) BuLi, THF 2)

CUI

97%

HCs CCH ( O E t ) 2

JOC 42, 2626 (1977)

Section 304

Acetylene


CrCCH ( O E t )

-

Amide-

344


Section 305

Acetylene -_Amine

Me, 0 II Ph-CH-C-Cl

N-CrC-SnPh

Ph’

3

*

81 %

1

Ph- H-C-CZC-N

F

I

OAc

OAc Angew I n t Ed

S e c t i o n 306

SECTION 307

Acetylene

L i [Bu3B-C=C-COOEt]

-

‘Ph

(1979)

Ester

I2

18,405

/ Me

Bu-CzC-COOEt

79%


Section 307

Acetylene __

OH OH

I I

-

Ether, Epoxide -_____

T s C l , NaOH

Ph-CH-CH-CECH

Ph-CH-CH-CrCH

Synthesis

, 706

(1977)

83%

ACETYLENE - KETONE

SECTION 309

S e c t i o n 308

Acetylene

-

345

Halide

1) BuLi

Ph-C-C-H

Ph-CEC-Cl

69%

2) NCS

S y n t h e s i s , 296 ( 1 979)

S e c t i o n 309

Acetylene

-

Ketone

JACS 99, 954 (1977)

8

t-Bu-C-C1

L2PdC1

t

8

t-BU-C-CSC-Ph -

CuI, E t 3 N

Ph-C-C-H Synthesis, 777 (1977)

79%

346


SECTION 309

Bu-C-C-A1Me2 D i BAH t

71 % sC-BU

JACS 100, 2244( 1978)

CO2

W6

HBF4 Me20 86%

T e t r L e t t , 4349 (1978)

@ @

Ph3C-OCH2CH2C=C L i

+

c

THF O Ph3C-0

O

H 99%

HG+

T e t r L e t t , 937 (1978)

SECTION 310

ACETYLENE

-

NITRILE

34 7

H

T e t r L e t t , 2301 (1978)

JOC 42, 2380 (1977) S e c t i o n 310

Review :

Acetylene

-

Nitrile

"a-Cyanoacetyl enes" Russ Chem Rev

46,

374 (1977)

348

COMPENDIUM

Section 311

OF ORGANIC

SYNTHETIC METHODS VOL 4

SECTION 311

Acetylene - O l e f i n ..__I

1 ) MeLi 0DIBAL-H 92%


Bu-C-C-B

3)

+

Me0

85%

Bu-C-C'

JOC 42, 3106 (1977)

T e t r L e t t , 3873 (1979)

SECTION 312

Bu

\

H/c=c\I

CARBOXYLIC A C I D

C1 ZnC-C-C5H1

/H

-

CARBOXYLIC A C I D

Bu

\

*

/H

H/c=c\

PdL4

349

CzC-C

H

76%

5 11

dCS Chem Comm, 683 (1977)

0

0+ 4

THF

PhMgC1

Ph

%C-CH

76%

JCS Perkin I,2136 (1979)

Section 312

Carboxylic Acid

-

Carboxylic Acid

1) 03 2)

H2, L i n d l a r

*

C O O H 'OH

B u l l Akad USSR Chem JOC (USSR)

14,48

25,

(1978)

98%

1790 (1977)

350


*

K02 phase-transfer c a t .

SECTION 312

c:::; 92%

T e t r L e t t , 3689 (1978)

1 ) PhSSPh, LICA*

2) Pb(OAC)4 3) NaOH, H202

$C02H

*

4) H3@

*LICA = l i t h i u m isopropylcyclohexylamide JACS 99, 4405 (1977)

qCH3 1 ) LDA, THF

COOH

OMe

2) (MeO)$O

OMe Synthesis, 245 (1977)

63%

CARBOXYLIC ACID

SECTION 313

- ALCOHOL

6 HOOC

1) CH2(COOEt)2,

NaNH2, dioxane

6Ts

351

*

COOH 65%

2) saponification Synth Corn

Section 313

_Carboxylic Acid

0

II

Me -C-COOH

6 n-C5H1 -CHO

I,

1 (1977)

- Alcohol OH 1 Me-CH-COOH

1) (Et0I3P *

2) NaOH

94 %

JOC 42, 2797 (1977) COOH *COOL1 LiNEtp, THF JCS Perkin I , 1651 (1978)

1 ) TMS-O-CH=C(OTMS)2, SnCl

8

2 ) H30

+

&

E-C5H11 Synthesis, 27 (1979)

COOH

OH

70%


352

SECTION 315

Rr% o&(ie+

COOH

O C O O H

R

R

H

' I CH2R I A

COOH

T e t r L e t t , 1005 (1977)

S e c t i o n 314

Carboxylic Acid

-

Aldehyde


S e c t i o n 315

Carboxylic Acid - Amide ____

HOCHCOOH

I

NHC-OBZ II 0 Tetrahedron

2, 467

(1978)

OH

CARBOXYLIC A C I D

SECTION 315

H2’ ( S ,S)-PPPM-Rh CH2=C-COOH

I

-

ALDEHYDE

353

*

*

CH3-CH-COOH

NHCOOCH2P I h

NHCOOCH2Ph

%go%

(R) 59%ee Chem L e t t , 777 (1977)

dooH H2

Ph

*

NHAc

Ph-CH2-CH

c h i r a l Rh phosphines

90-100%

‘NHAc 78-99%ee

JACS 99, 6262 (1977) I

T e t r L e t t , 3497 (1977)

JACS 700, 5491 (1978)

J Organometal 150, C14 (1978)

PhCH=C

\ NHAc

H2 polymer-bound c h i r a l Rh c a t a l y s t

PhCH2-CH

100%

\ NHAc 78%ee

JACS 100, 264 and 268 (1978)


354

Related Methods:

SECTION 316

Section 316 (Acid-Amine) Section 344 ( h i d e - E s t e r ) Section 351 (Amine-Ester)

6

Section 316

Carboxvlic Acid

-

Amine FOOH

Q

CHNH2

+

CHX3

+

NH3

KOH, LiC1 , R4NC1

*

CH2C12/H20

c1

81%

c1

X = C1, B r

Synthesis, 852 (1977) Synthesis, 26 (1979)

0 II Ph-C-COONa

electrochemical r e d u c t i o n

YH2 Ph-CH-COOH

*

45%

NH40H, NH4C1, H20 Aust J Chem 31, 73 (1978) I

OY:xMe J:gMe Ac

H

I

several steps

I

RCH2

H

HC1

CH2R

I

H2N-CH-COOH

Ac

*

-90%ee T e t r L e t t , 4483 (1979)

SECTION 316

CARBOXYLIC A C I D

I

Bt-

AMINE

355

- 1 ) KOCN

R-CH-COOMe

-

R,/OOMe

HC1

CH I NHCOOMe

2) MeOH

,COOH

R

C‘ H

I

~60%

NH2

Angew I n t Ed 18, 474 (1979)

-

FH2

1 ) BzBr

Bz--- C-COOH

d

2) KOH

Me

86% 100% ee

Angew I n t Ed

-

17,117

(1978)

1 ) (i --Pr)*NET

H0

BZ

,Yo

Cllyl

2) a l l y 1 B r

Bz-C-COOH

3) HC’I/AcOH

Ph

93% 112, 128 (1979) Chem Ber 1 ) NH20H.HC1, NaOAc

~50-80% R-CH-CH2COOH

*

R- CH=CH - COOH

I

2 ) H2’ Pd/C

Synth Corn

NH2

9,

705 (1979)


356

i-Bu

Me

1) BrCN

NBz

II

Me

2) Et3N

SECTION 316

I

@

i-Bu- C- NH3 I

74%

COOH

I n d i a n J Chem 18B, 273 (1979) 1 ) BzCl , TBABr

Me

I

Ph-CH2N=C-COOBZ

H2N-C 2 ) H2, Pd/C

Ye

-COOH

I BZ

86%

JCS P e r k i n I, 1730 (1977)

Ph2C=N-CH2CN

1 ) BzEt3NC1 50% NaOH, t o l u e n e

+

it

H2N-CH-COOH

90%

2 ) HC1 EtBr T e t r L e t t , 4625 (1978) 1 ) KOt-Bu 2) E t I

( MeS ) 2C=NCH2C02Et

Et I H2N-CH-COOH

3 ) HC03H

Liebigs Anna1 en, 2066 (1979)

81 %

-

CARBOXYLIC A C I D

SECTION 316

-i-Pr-CHO

1 ) KOH

+ CN -CH2-CONH2

AMINE

357

OH I -i-Pr-CH-CHCOOH

90%

I

2 ) HC1, H20

NH2

S y n t h e s i s , 216 (1979)

(TMS) 2NCH2COOTMS

1 ) LDA

+

2 ) HC1, MeOH

)-

Me2CH- CH- CHCOOH I bH NH2*HC1

90%

CHO JOC

CH2COOH

CHO

I

CHO

-t

i=O COOH

44,

3967 (1979)

1)

-co2

2 ) NH40H

41 % Hb

3) NaBH4

JOC 42, 3440 (1 977)

H

COOH

358


SECTION 316

1 ) CH2=CHCN

Me

84%

Et3N, P Y ~ 2 ) Dowex (@)

Me P

C

O

O

H

HOOC

Hoocxoo" S y n t h e s i s , 150 (1979)

NNHPh

158, 573 (1977) I n d i a n J Chem -

Several methods f o r s y n t h e s i s o f 6 - s u b s t i t u t e d t r y p t o p h a n s a r e presented. JOC _-44, 3741 and 3748 (1979)

Asymmetric s y n t h e s i s o f amino a c i d s by c a t a l y t i c r e d u c t i o n o f a z a l a c t o n e s by s u b s t i t u t e d a - a c y l a m i n o a c r y l i c a c i d s .

B u l l Acad USSR Chem .27, 957, 1186, and 1190 (1978)

SECTION 317

Review:

CARBOXYLIC A C I D

-

359

ESTER

"Production and U t i l i z a t i o n o f Amino Acids" Angew I n t Ed 17, 176 (1978)

Related methods:

Section 315 ( A c i d - h i d e ) Section 344 ( h i d e - E s t e r ) Section 351 (Amine-Ester)

Section 317

Carboxylic Acid

-

Ester

EtOH/H2S04 HOOC-( CH2)4-COOH

* HOOC-(CH2)4-COOEt

~90%

continuous e x t r a c t i o n Synth Corn

MeOOC,qCOOMe

COOMe

: I$l2

2, 669

(1979)

COOMe

~

H

o

o

c

COOMe

T e t r L e t t , 1403 (1978)

~

80%

360

COMPENDIUM

S e c t i o n 318


Carboxvlic --

Acid

-

SECTION 319

Ether, Epoxide -_

1 ) CHC13, NaOH

54%

TH F M

C

H

O

COOH

2 ) NaOH, MeOH JOC 43, 2702 (1978) Section 319

Carboxylic Acid

-

Halide

c1

C12’ 02 >

CH3 ( CH2) 3CH2COOH

I

CH3( CH2) 3-CH-COOH

chlorosulfuric acid

92%

B u l l Chem SOC Japan 5 2 , 255 (1979)

1 ) CF2=C(SEt)2 BuMgBr

F

F I BU-CH-COOH

2 ) H20 Chem L e t t , 175 (1979)

81 %

SECTION 320

-

CARBOXYLIC A C I D

id10

L i [E t 0) P-C- COO]

96%

*

0

CHo

Ph

361

KETONE

P

h

v

C

2) H30

o

o

H

c1 Synth Corn 8, 19 (1978)

Section 320

0

C a r b o w l i c Acid

II n-C5H1 -C-C1

-

Ketone

1 ) L i CH ( COOTMS )

*

0 n-C5H,, -!-CHpCOOH

91 %

2) H20

Q n

Synthesis , 787 (1 979) Li i 1) CF2=C-OTS 2) H30Q

~68%

3) @OH

T e t r L e t t , 4809 (1978)

-

0

NaOH

0

J Prakt Chem

319, 213

CH2 CH2 CH

(1977)


362

CN I

SECTION 322

0 II R-C-COOH

acetone

R-C= NPh

%80%

HC1 R = Subst. Ph, s t y r y l

I n d i a n J Chem 178, 169 (1979)

A l s o v i a : K e t o e s t e r s ( S e c t i o n 360)

S e c t i o n 321

Carboxylic Acid - N i t r i l e

No a d d i t i o n a l examples See a l s o :

S e c t i o n 322

S e c t i o n 361 (Cyanoesters)

C a r b o w l i c Acid

-

Olefin

Ro

0

H\ C O C O O H

1 ) ( EtO)2P-CHC00

70%

2 ) H30@

Synth Comm 8, 463 (1978)

SECTION 322

CARBOXYLIC A C I D

-

OLEFIN

363

Syn t h e s i s , 133 (1 978)

0 Me-C-( CH2)5-CH0 II

wo -

( Et o ) 2P -CH COOTMS 70%

-(CH2)5-CH=CHCOOH

A1 so works w i t h ketones. Synthesis, 131 (1978)

-COOH

*

Ph W

C

JOC 43, 5018 (1978) Also Via:

Hydroxy acids (Section 313) O l e f i n i c amides (Section 349) O l e f i n i c e s t e r s (Section 362) O l e f i n i c n i t r i l e s (Section 376)

O

O

92% H

364


Alcohol

Section 323

-

SECTION 323

Alcohol

80% 35, 1109 (1 979) Tetrahedron -

0 -

acetone, Et4NOAc 52%

t-BUOOH, OS04

JOC 43, 2063 (1978)

Me8Sn3, hv OH

59%

benzene Tetr Lett, 2847 (1978)

L i [Bu3BCH=CH2] t

Me2CHCHO

2 ) H202, @OH

- 'B

CHMe2 OH

OH

Tetrahedron 33, 1949 (1 977)

74%

ALCOHOL - ALCOHOL

SECTION 323

365

OL i 1 Ph-CH-CH2Li t

PH

G

*

JOC

3, 4798

Ph-CH-CH

2) H30

OH I CH

2- I Et

62%

EtCHO

2 PhCH20TMS

1) t-BUOOH

(1979)

Ph-CH-CH-Ph I

2 ) NaOH, EtOH

I

69%

OH OH

0 44, 295 (1979)

Me

A Tetrahedron 33, 1945 (1977)

1) Arc,

( CH3)2C=0

//o-..

i

0 ,kHCH3

h

OH OH

\ I Me C - CH CH

JOC 43, 4255 (1978)

38%


366

Also v i a :

SECTION 324

Hydroxyesters ( S e c t i o n 327) D i e s t e r s ( S e c t i o n 357)

S e c t i o n 324

Alcohol

( CH2)6COOMe

-

Aldehvde

CeCl

NaBH4

'CHO

JACS 101, 5848 (1979)

pH 1) RMgX

Ph

Ph-{!

R

67-82%

2) NH4C1

NPh

0

>94%ee

3 ) H30

0

(R = Me, E t , i-Pr,

vinyl)

Chem L e t t , 1253 (1978)

II 0

a CH H 2 N H P h

*

Me-C-CHO 2 ) PhMgBr

CHO /t_-Ph Me

76%

OH

3 ) H20, NH4C1 Chem L e t t , 705 (1979)

99%ee

SECTION 326

ALCOHOL

-

AMINE

367

Review: "Aldol Condensations"

F o r t s c h r i t t e der Chem Forsch Related methods:

Section 325

-

Alcohol

Alcohol

-

67,1

(1976)

Ketone (Section 330)

hide

C6F50Ac

HO-CH2CH2CH2NH2

.

-

HO-CH CH CH -NH 2 2 2 1

DMF

91 %

JCH3 0

JOC 44, 654 (1979)

Section 326

Alcohol

-

Amine

O30sN-L-Bu pyridine

0-

TsNCl Na

a::+

1% oso4 JOC 43, 2544 (1978) JOC 43, 2628 (1978)

79%

368


SECTION 326

BuNH2 75% 2'3 JACS

99, 8208

and 8214 (1977)

HZ OMe

OMe c h i r a l Rh - f e r r o c e n y l phosphi ne

86%ee OMe

T e t r L e t t , 425 (1979)

NO I

1) t-BUN-CH2Li

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