heterocyclic chemistry_vol4

Heterocyclic ChemistryVolume 4

A Specialist Periodical Report

Heterocyclic ChemistryVolume 4 A Review of the Literature Abstracted between July 1981 and June 1982

Senior Reporters

H. Suschitzky Department of Chemistry and Applied Chemistry, University of Salford 0 . Meth-Cohn C.S./.R.,Pretoria, South AfricaReporters

G . V. Boyd Chelsea College, London S . D. Carter Queen Elizabeth College, London G . W. H . Cheeseman Queen Elizabeth College, London G . P. Ellis UWIST, Cardiff S. Gronowitz University of Lund, Sweden 0 . Guilloton University of Nantes, France T. V. Lee Brunel University, Middlesex J. R. Malpass University of Leicester T. J. Mason Lanchester Polytechnic, Coventry H. Quiniou University of Nantes, France J. M. E. Quirke Florida International University, USA J. T. Sharp University of Edinburgh

The Royal Society of Chemistry Burlington House, London W I V OBN

ISBN 0-85 186-833-9 ISSN 0144-8773

Copyright 0 1985 The Royal Society of Chemistry

All Rights Reserved No part of this book may be reproduced or transmitted in any form or by any means - graphic, electronic, including photocopying, recording, taping, or information storage and retrieval systems - without written permission from The Royal Society o Chemistry f

Printed in Great Britain at the Alden Press, Oxford, London and Northampton

In tr oduc t ionVolume 4 includes the abstracted literature on heterocyclic chemistry between July 1981 and June 1982 (i.e. Volumes 95 and 96 of Chemical Abstracts). The format of previous volumes in respect of chapter arrangement has been retained, to allow the reader to study readily the progress in an area of heterocyclic chemistry through all of the four volumes, helped also by a detailed list of Contents. Our reviewers have again admirably succeeded in distilling out the salient features of several thousand references and have presented them in a concise and readable report. They have also co-operated with skill and patience in a cost-cutting exercise designed by the RSC editors, and have produced diagrams by a new method. I t is hoped that these efforts will ensure the economic survival of the series and eventually bring down the price to a level which will tempt the individual buyer; the only serious and recurring printing mistake, as one illustrious heterocyclic chemist remarked, is the price! Our thanks to all authors for their forbearance in the handling of gridsheets and supplying excellent manuscripts, and to the editorial staff of the Royal Society of Chemistry for smoothing out difficulties.

H. Suschitzky and 0. Meth-Cohn

Contents

Chapter 1 Three-Membered Ring Systems By T. J. Mason1 Reviews General Rings containing Oxygen Rings containing Nitrogen Rings containing Sulphur2 Oxirans Preparation Oxidation of Alkenes, using Oxygen or Oxygencontaining Gases Oxidation of Alkenes by Peroxy-acids Oxidation of Alkenes, using Peroxides Synthesis by Halohydrin Cyclizations and Related Reactions Synthesis via Attack of a Carbanion on the Carbonyl Group of Aldehydes and Ketones Synthesis of Chiral Oxirans Synthesis and Reactivities of Aromatic Oxides Miscellaneous Syntheses Spectra and Theoretical Chemistry Reactions Ring-opening Reactions with Electrophiles Cyclization Reactions N ucleophilic Ring-opening Reactions With Oxygen Nucleophiles With Nitrogen Nucleophiles With Sulphur Nucleophiles With Carbanions Reduction and Elimination Reactions Thermal and Photochemical Reactions Reactions with Organometallic Compounds Miscellaneous Reactions3 Aziridines Preparation By Direct Insertion

1

1 1

1 3 5 7

9 11 15 19 21 22 22 23 25 25 28 28 30 33 34 38 3940 40 40

viii

Heterocyclic Chemis0By Cyclization Reactions By Ring-contraction Reactions Synthesis of Chiral Aziridines Spectral and Theoretical Studies Reactions Thermal Reactions Ring-opening to Acyclic Compounds Formation of Other Ring Systems 4 Azirines Preparation Reactions

42 43 43 43 44 44 45 46 47 47 48 49 49 50 51 51 52 53 54 54

5 Thiirans Preparation Reactions The Chemistry of Thiiranium Ions6 Thiirens

7 Diaziridines8 Diazirines 9 Dioxirans 10 Oxaziridines

Chapter 2 Four-Membered Ring Systems By T. V. Lee1 Highlights and Reviews

57 57 57 57 58 63 65 65 66 67 68

2 Systems containing One Nitrogen Atom Azetidines and Azetines Azetidinones

3 Systems containing Two Nitrogen Atoms or One Nitrogen Atom and a Second Heteroatom4 Systems containing Oxygen Oxe tans Dioxetans5 Systems containing Sulphur

6 Miscellaneous Four-Membered Rings

ContentsChapter 3 Five-Membered Ring Systems By G. V. Boyd, S. Gronowitz, 0. Guilloton, and H. Quiniou Part I Thiophens and their Selenium and Tellurium AnaloguesBy S. Gronowitz1 General 2 Monocyclic Thiophens Synthesis by Ring-closure Reactions C4 + S Principle C2S + C2 Principle CS 3- C3 Principle Ring-closure of C4S Ring-closure of CzSCz Synthesis from Other Rmgs From Di- and Tetra-hydrothiophens From Other Sulphur Heterocycles From Other Rings Physical Properties of Monocyclic Thiophens Theoretical Calculations Photoelectron and Ultraviolet Spectra Infrared and Raman Spectra Nuclear Magnetic Resonance Mass Spectrometry X-Ray Investigations Miscellaneous Physical Properties Electrophilic Substitution Reactions Electrophilic Ring-closure Reactions Nucleophilic and Radicaloid Substitution Reactions Organometallic Derivatives Lithium Magnesium Mercury, Zinc, and Copper Transition Metals Silicon Photochemistry Cycloaddition Reactions Desulphurization and Hydrogenation of Simple Thiophens Structures and Reactions of Hydroxy-, Mercapto-, and Amino-thiophens Reactivities of Side-Chains Reactions of Thiophen Aldehydes, Ketones, and Carboxylic Acids Reactions of Vinylthiophens and Related Compounds

ix 71

71 71 72 72 72 73 73 74 75 75 75 76 76 77 77 78 78 78 79 79 80 80 83 86 88 88 92 92 92 93 93 95 97 99 101 102 104

X

Heterocyclic ChemistryReactions at Benzylic Positions Various Reactions in the Side-Chains of Thiophens Macrocyclic Thiophens Reaction at Sulphur: Thiophen Dioxides Di- and Tetra-hydrothiophens Arylthiophens and Di- and Poly-heterocycles Naturally Occur ring T hio p hens Thiophen Analogues of Steroids Thiophens of Pharmacological Interest Therapy of the Central Nervous System Pharmacodynamic Agents Therapy of Metabolic Diseases Therapy of Infectious Diseases Veterinary and Agricultural Agents Miscellaneous Activities Thiophens of Technical Interest Polymers from Thiophen 104 105 105 106 108 111 113 114 114 114 115 115 116 118 118 119 119 120 120 120 12 1 12 1 123 123 124 124 125 125 125 127 128 129 129 131 131 131 132 133 135 136 136

3 Eknzo[ blthiophens and their Benzo-fused Systems Benzo [b] thiophens Synthesis Physical Properties Reactions Benzo [ b ] thiophen S-Oxides Benzo [ c ]thiophens Dibenzothiophens Pharmacologically Active Compounds

4 Thiophen Analogues of Polycyclic Aromatic Hydrocarbons Analogues of Anthracene and Phenanthrene Polycyclic Thiophens Thiophen Analogues of Indene Various Carbocycle-fused Systems5 Thiophen Fused to Five-Membered Heteroaromatic

Rings Thieno-, Furo-, and Pyrrolo-thiophens Thiophen Fused to Various Five-Membered Rings6 Thiophen Fused to Six-membered Heteroaromatic Rings Thiophen Analogues of Quinoline Thiophen Analogues of Isoquinoline Pyrimidine-fused Systems Miscellaneous Fused Systems

7 Selenophens and Tellurophens Monocyclic Selenophens

ContentsCondensed Selenophens Tellurophens

xi 137 138

Part I I Systems containing Nitrogen and Sulphur, Selenium, or Tellurium By H. Quiniou and 0. Guilloton

138

1 Introduction and Reviews2 Isothiazoles Synthesis From Dicyanoacetylene and Sulphur Dioxide (Type A: C-C-C-N + S) From 0-Benzoylpropionamides and Th ionyl Chloride (Type A) From 1,3,2-Oxathiazol-5-ones(Type B; S-N-C + C-C) From 3,3-Disulphanedipropionyl Chloride and Amine (Type H; S-C-C-C + N) From Aqueous Ammonia and Thioamide Vinylogues (Type H) From Ring-Cleavage of 3 -Azidot h io ph ens From Substituted Enamines and Benzyl Isothiocyanate (Type C-C-N + S-C) Physical Properties Chemical Properties N-Qu at er niz at ion o f Isothiazole s Reactions of 5-Aminoisothiazoles A3-Is0thiazolines Chemical Properties of Isothiazoline-5-thiones A4-1sothiazolines Chemical Properties of Isothiazolin-3-ones Isothiazolidines Physical Properties of Isothiazolidine 1,l -Dioxides3 1,2-Benzisothiazoles their 1,l-Dioxides and Synthesis From ortho-Halobenzoyl Compounds, Aqueous Ammonia, and Elemental Sulphur Reactions Reduction 3-Chloro-substitution Photochemistry Synthesis of 1,2-Benzisothiazolin-3-ones and their 1,l-Dioxides From 2-(Methylsulphinyl)benzamides and Thionyl Chloride

138139 139 139 139 139 140 140 140 141 141 141 141 142 143 143 143 143 143 143

144 144144 144 144 145 145 145 145

xii

Heterocyclic ChemistryFrom Anilines and 2-Chlorothiobenzoyl Chloride From 2-Aminobenzonitriles and SO2 From 2-(Chlorothio)benzoyl Chloride and Substituted Anilines From Thermal Decomposition of N-Substituted 2-(Me th ylt h io)benzamides Physical Properties of 1,2-Benzisothiazolin-3-ones Chemical Properties of 1,2-Benzisothiazolin-3-ones Hydrolysis, Alcoholysis, and Phenolysis Reactions of 1,2-Benzisothiazolin-3-ones Amines with N-Substitution of 1,2-Benzisothiazolin-3-ones 1,2-Benzisothiazoline-3-thione -Dioxides 1,l 1,2-Benzisothiazolidines their 1,l -Dioxides and 146 146 147 147 148 148 148 148 149 149 149 150 150 150 151 15 1 15 1 15 1 152 152 152 152 152 152 152 153 154 154 154 155 155 157 157 158 160 160 160 16 1 16 1 162 162

4 1,2-Benzisoselenazoles 1,2-Benzisoselenazolin-3-ones

5 2,l -Benzisothiazoles6 Other Condensed Ring Systems incorporating Isothiazole Thieno [2,3c] isothiazoles Isothiazolo [3,4411pyridines Isothiazolo [5,44] pyrimidines 1,2-Dithiolo [4,3c] isothiazoles Naphtho [ 2 , l d ] isothiazole Thieno [3,441isothiazole 1,l-Dioxides7 Thiazoles Synthesis Hantzschs Synthesis (Type A; S-C-N From thioureas From thioamides Type B Syntheses (C-C-N C-S) Type C Syntheses (C-C-N-C + S) Type F Syntheses (C-N-C-S + C) Type H Syntheses (S-C C-N-C) Physical Properties Tautomerism of 2-Aminothiazoles Reactions of Thiazoles Reactions of Thiazolium Salts

+ C-C)

+

+

8 A2-ThiazolinesSynthesis Type B Syntheses (C-C-N + C-S) Type J Syntheses (C-S-C-N-C) Type K Syntheses (C-C-N-C-S) Type E Syntheses (N-C-C-S + C) Reactions

Conten ts9 A3-Thiazolines

xiii 164 165 165 165 167 167 168 169 169 169 169 170 170 17 1 173 173 173 174 174 174 175 175 175 178 178 179 180 180 181 18 1 182 182 182 182 182 182 183 183 184

10 A4-Thiazolines Synthesis Type A Syntheses (S-C-N Type B Syntheses (C-C-N Physical Properties Reactions

+ C-C)+ C-S)

11 ThiazolidinesSynthesis Type B Syntheses (C-C-N + C-S) Type E Syntheses (N-C-C-S C) By Hydrolysis of Fused-Ring Compounds Physical Proper ties Chemical Properties

+

12 Selenazoles Synthesis and Properties Type A Syntheses (Se-C-N

+ C-C)

13 BenzothiazolesSynthesis From ortho-Aminobenzenethiols (Type A; S46H4-N + C ) Type B (C6H5-N-C-S) Type E (CGH5-N + C-S) Physical Properties Chemical Properties Substitution Reactions on the Thiazole Ring Reactions of 2 -Aminobenzothiazoles Reactions of 2-Mercaptobenzothiazoles Other Reactions of Benzothiazoles Benzo t h iazolines and Benzot h iazolin -2-ones (and -thiones) Benzothiazolium Salts

14 Condensed Ring Systems incorporating Thiazole Structure comprising Two Five-Membered Rings ( 5 3 ) Thiazolo [3,241 te t razoles [CN4-C3NS] Thiazolo[2,3-c][ 1,2,4] thiadiazole [C2N2S-C3NS] Thiazolo [2,3-b][ 1,3,4]thiadiazoles [C2N2S-C3NS] Thiazolo-[2,3-c]-, -[3,2-b]-, and -[3,4-b]-[1,2,4]triazoles [C2N3-C3NS] Thiazolo[4,5-d]-oxazole, -thiazole, and -selenazole [C3NX-C3NS] Imidazo-[2,1-b]-and -[5,1-b]-thiazoles [C3N2-C3NS] Pyrrolo [2,1-b]thiazoles [C4N-C3NS]

xiv

Heterocyclic ChemistryStructures comprising One Five-Membered and One Six-Membered Ring (5,6) Thiazolo [3,241- 1,3,5-triazines [C3NS-C3N3 ] Thiazolo [3,2471pyridazines [C3NS-C4N2] Thiazolo [3,2-a] pyrimidines [C3NS-C4N2] Thiazolo [5,4-b]pyridines [C3NS-CSN] Structures comprising Two Five-Membered Rings and One Six-Membered Ring (5,5,6) Benzo [ 1,2d;4,5dfIbis-thiazoles [C3NS-C3NS-C6] Benzo[d]imidazo[2 ,l-blthiazoles [C3NS-C3N2-C6] Thiazolo [3,44]benzimidazole [C3NS-C3N2-C6] Th iazolo[3',2' :1,2]imidazo [4,5-b]pyrazine [C3NS-C3N2-C4N2] Pyrrolo [2,1-b]benzothiazole [CSNS-C~N-C~] Structures comprising One Five-Membered Ring and Two Six-Membered Rings (5,6,6) 1,2,4-Triazino[3,4-b]benzothiazole [C3NS-C3N 3 -C61 1,3,5-Triazino [2,1-b] benzothiazole [C3NS-C3N3-C6] Thiazolo [2,3-b]quinazolines [C3NS-C4N,-C6] Thiazolo [3,2-a]thiapyrano [4,3-d]pyrimidines [C~NS-C~NZ-C 51 x 1,2-0xathiino[5,6-g]benzothiazoles [C3NS-C4OS-C6] Thiazolo-[2,3-a]- and -[3,4-b]-isoquinolines [C3NS-CSN-CG] Naphtho [2,3d]thiazole [C3NS-C&6] Other Condensed Systems incorporating Thiazole 185 185 185 185 186 186 186 186 187 187 187187

187 188 188 189 189 189 190 190 190 190 190 19 1 191 19 1 192 192 193 193 194 194 195 195 196 196

15 Thiadiazoles and Selenadiazoles 1,2,3-Thiadiazoles Synthesis Physical Properties Chemical Properties 1,2,3-Selenadiazoles 1,2,4-Thiadiazoles Synthesis Physical Properties Chemical Properties 1,3,4-Thiadiazoles Synthesis Physical Properties Chemical Properties Condensed 1,3,4-Thiadiazoles 1,2,5-Thiadiazoles

ContentsSynthesis Physical Properties Chemical Properties 2,1,3-Benzothiadiazoles and 2,1,3-Benzoselenadiazoles

xv 196 197 197 197 198 198 199 200 200 200 200 201 201 20 1 201 202 203 203 203 205 209 212 214 214 2 17 22 1 22 1 223 227 228 229 229 230 234 236 236 238 240

16 Dithiazoles and Diselenazoles 1,2,3-Dithiazoles 1,2,4-Dithiazoles 1,4,2-Dithiazoles17 Oxathiazoles and Selenathiazoles 1,3,2-0xathiazoles 1,3,4-Oxathiazoles

18 Miscellaneous Ring Systems 1,3,2,4-Dithiadiazoles

Part I I I Other Five-Membered Ring Systems By G. V. Boyd 1 Introduction2 Reviews

3 Systems with One Heteroatom and their Benzo-analogues etc. Furans Formation Reactions Benzo furans Isobenzofurans and 0ther Annelated Furans Pyrrole s Form ation Reactions Indoles and Carbazoles Formation Reactions Isoindoles Other Systems containing One Heteroatom4 Systems containing Two Identical Heteroatoms Dioxoles Dithioles and Related Systems Tetra t hiafulvalenes and Related Compounds Py razoles Formation Reactions Indazoles

xvi

Heterocyclic ChemistryImidazoles Formation Reactions Benzimidazoles and an Imidazoquinoline 24 1 24 1 242 244

5 Systems containing Two Different Heteroatoms Oxathiole s and SelenathiolesIsoxazoles Formation Reactions Benzisoxazoles and Other Annelated Isoxazoles Oxazole s Formation Reactions Benz ox az oles Benzoxaiodoles

245 245 248 248 249 250 25 1 25 1 253 258 260260 260 26 1 264 264 264 264 265 266 267 268 269 270 270 271 272 272 273 273 274 275 276 276 27 6 277 278

6 Systems containing Three Identical Heteroatoms 1,2,3-Triazoles and Benzotriazoles 1,2,4-Triazoles Other Systems

7 Other Systems containing Three Heteroatoms Oxadiazoles 1,2,3-0xadiazoles 1,2,4-Oxadiazoles 1,2,5-Oxadiazoles 1,3,4-0xadiazoles Phosphorus Compounds Miscellaneous 0ther Systems8 Systems containing Four Heteroatoms Tet razoles Other Systems 9 Compounds containing Two Fused Five-Membered Rings (5,5) Hypervalent Sulphur and Selenium Compounds Nitrogen Systems M onoaza-Comp ounds Diaza- and Triaza-Compounds Other Systems

10 Compounds containing Fused Five- and Six-Membered Rings (5,6) Nitrogen Systems Monoaza- and Diaza-Compounds Triaza-Compounds Tetra-aza-Compounds and a Penta-aza-Compound

ContentsMixed Oxygen-Nitrogen Systems and a Diselenoloquinoxaline11 Compounds containing Fused Five- and Seven-Membered and Fused Five- and Eight-Membered Rings [ (5,7), (5,5,7), (5,7,7), and (5,5,8)1

xvii 279

282 285

Chapter 4 Six-Membered Ring Systems B y S. D. Carter, G. W. H. Cheeseman, and G. P. Ellis Part I Systems containing Nitrogen By S. D. Carter and G. W. H. Cheeseman1 Introduction

285 285 285

2 Reviews3 Azines and their Hydro-and Benzoderivatives Pyridines Synthesis Properties Reduced Pyridines Quinoline, Isoquinoline, and their Benzo- and Hydroderivatives4 Diazines and their Reduced and Fused Derivatives 1,2-Diazines 1,3-Diazines 1,4-Diazines

2 86 286 286 29 1 299302

3 12 3 12 3 14 322326 329 333 336 336 339 34 1 344 345 345

5 Triazines and Tetrazines6 Fused Systems containing One Five- and One Six-Membered Ring (5,6)

7 Fused Systems containing Two Six-Membered Rings (6,6)8 Oxazines, Thiazines, and their Fused Derivatives 0x azines Thiazines 9 Other Oxygen- and Sulphur-containing Systems Classified Reference List

Part I I Six-Membered Rings containing Oxygen or Sulphur By G. P. Ellis1 Reviews

xviii

He twocyclic Chemistry2 Heterocycles containing One Oxygen Atom Reduced Pyrans Pyrans Pyrylium Salts Pyran-2 -ones Pyran-3- and -4-ones Chromans Isochromans Chromenes Benzopyrylium Salts Chromanones Chromones F lav ans Flavanones Flavones I sofl av one s Dlhydrocoumarins and Dihydroisocoumarins Coumarins Isocoumarins Xanthenes and Xanthones3 Heterocycles containing One Sulphur Atom T hiopyrans Thiochromans and Thiochromenes Thiochromanones Thiochromones and Thiocoumarins Thioxanthenes and Thioxanthones4 Heterocycles containing One Oxygen and One Sulphur Atom Oxa thiins

346 346 348 349 350 355 357 361 363 365 366 367 370 37 1 372 373 373 375 378 378 380 380 38 1 382 382 383 383 383 384 384 385 385 385 386 389 389 389

5 Heterocycles containing Two Oxygen Atoms Dioxans6 Heterocycles containing Two Sulphur Atoms 1,3-Dithians 1,4-Dithians

7 Heterocycles containing an Oxygen Atom in each of Two or More Rings

Chapter 5 Seven-Membered Ring Systems By J. T. Sharp 1 Introduction2 Reviews

Contents3 Azepines and Diazepines Azepines Formation Reactions 1,2-Diazepines Formation Reactions 1,3-Diazepines Formation Reactions 1,4-Diazepines Formation Reactions4 Oxepins and Dioxepins Oxepins Formation Reactions D i ox epins

XiX

389 389 389 394 395 395 397 399 399 40 1 40 1 40 1 403405 405 405 408 408 409 41 1 41 1 413 415 4 19 419 419 42 1 422 423 423 427 427 427 428 429 429 429 432 434

5 Thiepins6 Systems containing Two Different Heteroatoms Oxazepines T hiazepines

7 Systems containing Three Heteroatoms

Chapter 6 Eight-Membered and Larger Ring Systems By J. M. E. Quirke1 Eight-Membered Rings One Heteroatom Two Heteroatoms

2 Nine- and Ten-Membered Heterocycles

3 Macrocycles Other than Crown Ethers Systems containing Nitrogen as the only Heteroatom Systems containing Sulphur as the only Heteroatom Systems containing Oxygen as the only Heteroatom Syntheses of Macrocyclic Lactones Other Oxygen-containing Derivatives Other Macrocyclic Systems4 Crown Ethers and Related Compounds Synthesis of Crown Ethers Reactions of Crown Ethers Applications of Crown Ethers in Organic Synthesis

xx

Heterocyclic ChemistrySynthesis of Cryptands and Other Polycyclic Systems Host-Guest Complexes of Crown Ethers and Cryptands 43 7 439 44 1 44 1 44 1 44 1 443 444 445 445 445 449 450 453 45 5 45 5 45 5 457 458 460 46 1 463 464 465

Chapter 7 Bridged Systems By J. R. Malpass1 General 2 Physical Methods X-Ray and Electron Diffraction Nuclear Magnetic Resonance Spectroscopy Miscellaneous Methods3 Nitrogen-containingCompounds Synthesis Cycloadditions 0ther Cyclizations Reactions Bridged Azolkanes

4 Oxygencontaining Compounds Synthesis Cycloadditions Miscellaneous Other Methods Re actions Bridged Peroxides5 Sulphur-containingCompounds

6 Silicon- and Germanium-containing Compounds7 Phosphorus-containing Compounds8 Boron-containingCompounds

1Three-Membered Ring SystemsBY T. J. MASON

1 Reviews General. - Thermally induced ring-enlargement of vinyl three-membered heterocycles has been reviewed. Rings containing Oxygen. - The catalytic epoxidations of alkenes with hydroperoxides have been surveyed,2y3as have transition-metal-catalysed stereocontrolled epoxidations! A major review of oxiran chemistry (956 references) has been published as a chapter in Saul Patais series on the Chemistry of Functional Groups (1980). Theoretical aspects of the thermal and general chemical reactions of oxirans have been treated by the application of quantum-mechanical methods to the study of the reactions of the triplet states of isomers.6 Rings containing Nitrogen. - The reactions of aziridines with alkylidenephosphoranes and with phosphorus(II1) nucleophiles and the reactions of 3 -amino-2H-azirines with NH-acidic compounds have been reviewed. Rings containing Sulphur. - The subject of a lecture given in 1980 and published in 1981 was some aspects of the chemistry of episulpho~ides.~2 Oxirans Preparation. - Oxidation of Alkenes to Oxirans, using Oxygen or Oxygencontaining Gases. Research into the improvement of the silver catalysts that are used in the commercial oxidation of ethene has resulted in continued interest in the doping of the catalyst with alkali-metal salts, particularly

* J . Sobczak and J . J .

J . Chuche, Bull. SOC.Chim. Belg., 1981, 9 0 , 535. Ziolkowski, J. Mol. Catal., 1981, 13, 11. R. A. Sheldon, Aspects Homogeneous Catal., 1981, 4, 3. D. Hoppe, Nachr. Chem. Tech. Lab., 1982, 30, 281. M. Bartok and K. L. Lang, in Chemistry of Ethers, Crown Ethers, Hydroxyl Groups, and their Sulphur Analogues, ed. S. Patai, Wiley, Chichester, U.K., 1980, Vol. 2, p. 6 0 9 . G. R . DeMare, NATO A d v. Study Inst. Ser., Ser. C , 1981, 67 (Comput. Theor. Org. Chem.), 335. M. Vaultier and R. Carrie, ACS Symp. Ser., 1981, 1 7 1 (Phosphorus Chem.), 51. H. Heimgartner, Isr. J. Chem., 1981, 21, 151. G. Maccagnani, Org. Sulfur Chem. Invited Lect. I n t . Syinp., 9 t h, 1980 (publ. 1981), 123.

2

Heterocyclic Chemistly

caesium.1-12 Spent catalyst may be rejuvenated by treatment with NH3, MeOH, and CsN03.13 Silver powder with a high surface area has been used to determine the reactivity of adsorbed oxygen for the epoxidation of perde~terioethene.'~ The results suggest that the alkene oxide is formed only if both surface and subsurface adsorbed oxygen are present. Two types of adsorbed oxygen were invoked to explain the results obtained when studying the solid-electrolyteaided oxidation of ethene on polycrystalline silver." Solid electrolyte potentiometry (SEP) was used to monitor the chemical potential of the adsorbed oxygen, the activity of which was not affected by the presence of C02. This latter appeared to inhibit only the epoxidation reaction. The same group have also reported that both the selectivity for and the yield of ethylene oxide on polycrystalline silver may be increased by electrochemical pumping of oxygen (023.16 reaction was studied in the solid electrolyte cell C2H4, C2H40, The C 0 2 ,02, AglZr02(Y203)IAg,air, at temperatures around 400 "C and at atmospheric pressure. The cell behaved as a normal epoxidation catalyst under open-circuit conditions. A study has been made of the bond energies between adsorbed oxygen and various supported silver catalysts and of their relationship to the activity of such catalysts for epoxidation of ethene." A linear freeenergy relationship between the mean heat of formation of a monolayer of surface Ago and the catalytic activity was found. Kinetic performance parameters have been calculated for a number of supported-silver epoxidation cata1ysts.l8 Direct oxygenation of alkenes other than ethene and propene is normally achieved in the liquid phase and in the presence of a catalyst or under U.V. irradiation. Thus aryl-oxirans (1; n = 1 or 4) were obtained in 37-71% yields by autoxidation of the corresponding 1-phenyl-cycloalkenes in the presence of cobalt naphthenate at 50C." Unbranched terminal alkenes yield epoxides during autoxidation in the presence of the soluble catalysts C O Q ~ PrQ3, TiOQ2, and VOQ2 (Q = , pentane-2,4-dionat0).~' The autoxidation of aromatic vinyl ethers proceeds at room temperature even in the dark, but irradiation with U.V. light and the use of a radical generator facilitates the reactions which yield epoxides and carbonyl compounds in significant quantities?llo

I2

Mitsubishi Petrochemical Co. Ltd., Jpn. Kokai Tokkyo Koho 81 05 471. Nippon Shokubai Kagaku Kogyo Co. Ltd., Jpn. Kokai Tokkyo Koho 81 105 750. Nippon Shokubai Kagaku Kogyo Co. Ltd., Jpn. Kokai Tokkyo Koho 81 108 533. J. Alfranseder, S . Mayer, S. Rebsdat, J . Riedl, and 1. Schaffelhofer, Ger. Offen.

2 938 245. C. Backx, J. Moolhuysen, P. Geenen, and R. A. Van Santen, J. Caral., 1981, 72, 364. I s M. Stoukides and C. G. Vayenas, J. Catal., 1981, 69, 18. l6 M. Stoukides and C. G. Vayenas, J. Caral., 1981, 7 0 , 137. A. Auroux and P. C. Gravelle. J. Calorim. Anal. Therm., 1981, 12, 1NT2,-INT2,. P. Kripylo, L. Moegling, D. Klose, and H. Sueptitz, Chem. Tech. (Leipzig), 1982, 34, 85. I 9 S . C. Sethi, A. D. Natu, and M. S. Wadia, Heterocycles, 1982, 18 (Spec. Issue), p. 221.l42o

21

U. Barth, H. Friedler, G. Gross, G. Lauterbach, and D. Schnurpfeil, J. Prakr. Chem., 1981, 323, 887. T. Kanno, M. Hisaoka, H. Sakuragi, and K. Tokumari, Bull. Chem. SOC.Jpn., 1981, 5 4 , 2330.

Three-Membered Ring Systems

3

Photo-epoxidation of alkenes in the presence of benzoins and oxygen has been shown to proceed via the benzoylperoxy radical (2), which is effectively trapped by alkene and subsequently yields predominantly trans-epoxides.22 The same intermediate radical (and, as a result, similar reactivities) has been observed during photo-epoxidation using benzoylformic acid (PhCOCOOH), but the reactivities of the alkenes were different from those obtained using p e r o ~ y - a c i d s A correction has been published to some previous studies on .~~ the efficiency of benzil-sensitized photo-epoxidation of t r i n ~ r b o r n e n eThe .~~ new results indicate a lower yield of < 2 moles of epoxide per mole of diketone that is consumed and thus suggest that a chain mechanism is not involved for such reactions. A new reaction system has been reported in which molecular oxygen oxidizes alkenes to epoxides both thermally and photochemically, in the presence of SO2, under ambient condition^.^' Irradiation of a mixture of propene and SO2 in acetonitrile at 0 "C caused absorption of 02, yield propene to oxide as the sole volatile product. A similar reaction occurred at 25 "C in the dark, in the presence of potassium nitrite. Direct ozonolysis of the parent vinyl sulphide gives (3) (40%), suggesting that oxiran intermediates might be involved more generally in the ozonolysis of vinyl derivatives.26 Ozonolysis of cis- and of trans- 1,2-difluoroethene also yields epoxides with predominantly retained stere~chemistry.~~ Oxidation of Alkenes to Oxirans by Peroxy-acids. An improved procedure for epoxidation using aromatic peroxy-acids has been reported .28 After a normal epoxidation with 3-chloroperoxybenzoic acid (mCPBA) in CH2C12, activated KF is added to the crude mixture, and this results in the precipitation of both mCPBA and the aromatic acid by-product, leaving an acid-free reaction mixture for normal work-up. As an alternative, the insoluble mCPBA-KF complex itself may be used for the epoxidation of alkenes overnight at room temperature. After filtration and treatment of the CH2C12 solution with more KF (to ensure removal of any residual peroxy-acid), normal work-up leads to yields in excess of 95% for cyclohexene and styrene oxides.22

2324

2526

Y. Sawaki and Y . Ogata, J . A m . Chem. SOC., 1981, 103, 2049. Y. Sawaki and Y. Ogata, J. A m . Chem. SOC., 1981, 103,6455. P. D. Bartlett, A. A. M. Roof, and N. Shimizu, J. A m . Chem. SOC., 1982, 104, 3130. T. Sasaki, J. A m . Chem. SOC.,1981, 103, 3882. L. Morin, D. Barillier, M. P. Strobel, and D. Paquer, Tetrahedron L e t t . , 1981, 2 2 ,2267.

2728

J . W. Agopovich and C. W. Gillies, J . A m . Chem. SOC., 1982, 104, 813. F. Camps, J . Coll, A. Messeguer, and A. M. Pericas, Tetrahedron L e t t . , 1981, 22.3895.

4

Heterocyclic Chemi s t y

Ph \ 0 P h

-

1

P Ph o\ h ; ]

@CH2

J$,CH2(7)

Ph(4)

Fh(5)

(6)

The site-selectivity of oxidations by mCPBA is demonstrated in the conversion of (4; R = Me or Ph) into the corresponding ene epoxide (5).2g The product is sensitive to acid, so that the conversion is accomplished in a basic two-phase medium. Normal epoxidation of (6) with mCPBA leads to (7).30 The stereochemistries for such reactions are shown in the predominant formation of the P-epoxide (8) (81%) from the parent alkene, with 12% of the a - p r ~ d u c t Similar epoxidation of the cannabinol (9) leads to a less stereo.~~ specific isomer distribution of 27.3% and 18.2%.32Remarkable stereoselectivity has been shown in the epoxidation of the 14,15-unsaturated oestratrienes ( Whereas oxidation of 170-esters and 170-ethers gave 14a ,15a-epoxides (< 59%),the 170-urethane derivatives displayed a syn-directive effect to yield 140,15P-epoxides (< 87%).

H

29

3031

32

R. Y . S. Tan, R . A. Russell, and R. N. Warrender, Aust. J. Chem., 1981, 34,421. H. M. R. Hoffmann and H. Vathke-Ernst, Chem. Ber., 1981, 114, 1182. Meiji Seika Kaisha, Ltd.. Jpn. Kokai Tokkyo Koho 82 0 2 232. I. Yamamoto, S . Narimatsu, K. Watanabe, and H. Yoshimura, Chem. Pharm. Bull.,1981, 2 9 , 3 3 7 8 .

33

K. Ponsold, G. Schubert, M. Wunderwald, and D. Tresselt, J . Prakt. Chem., 1981,323, 819.


5

The rates of epoxidation of cyclododecene with a series of aliphatic peroxy-acids have been correlated, using the Taft equation.34 The reaction constant ( p * ) was + 2.0 and the steric constant (6) was found to be essentially zero. A two-parameter correlation has been found for the effect of basicity and polarity of the solvent on the rate of epoxidation of propene with peracetic acid.35 Rate constants and activation parameters for the epoxidation of a number of cycloalkenes, including (1 1 ; R = H or COOMe), (12; R = H, Ph, or 2-furyl), (13), (14), and cyclo-octa-1,5-diene, have been measured.36 An isokinetic relationship was demonstrated, with the isokinetic temperature of 3C. There was only a weak dependence of the rate on the structure of the alkene.

Alkenes have been epoxidized in high yield, using peroxyformic acid (prethus pared in situ from formic acid and 85% H202); a 90% yield of monoepoxide has been prepared from trimethylcy~lodecatriene.~~

Oxidation of Alkenes to Oxirans, using Peroxides. The peroxide (1 5; R = OOH) is a useful oxidant for a number of alkenes, giving epoxides in good to moderate yields and generating (15; R = OH).38 The reactivity of this peroxide is two orders of magnitude lower than that of peroxyacetic acid but at least one order of magnitude greater than that of a-peroxy-esters and -nitriles. Its selectivity relative to the structure of the alkene is similar to that for peroxyacetic acid.

34

3s

3637

38

H. J . Schneider, N. Becker, and K. Philippi, Chem. Ber., 1981, 114,1562. V. N. Sarancha, I. A. Opeida, and R. V. Kucher, Dopov. Akad. Nauk Ukr. RSR, Ser. B , 1981, No. 6,p. 74. A. E. Batog, T. V. Savenko, T. A. Batrak, and R. V. Kucher, Zh. Org. Khim., 1981, 17,2085. G . Kaebisch, R. Truebe, H. Wittmann, S. Raupach, and H. Malitius, Ger. Offen. 3 002 785. A. L. Baumstark and R. S. Pilcher, J. Org. Chem., 1982,47, 1141.

6

Heterocyclic Chemistry

A few years ago, hexafluoroacetone was shown to be an effective catalyst for the epoxidation of alkenes by H202.39 reagent is highly toxic, howThe ever, and not commercially available, and so an alternative has been sought. An efficient alternative catalyst has been found to be hexafluoropropan2 - 0 1 , ~ more recently it has been reported that tetrachloroacetone is a usebut ful commercially available alternati~e.~' reactive species is thought to be The (16; R = OOH), the by-product of epoxidation being the hydrate (16; R = OH), which is thermally unstable and from which tetrachloroacetone may be regenerated. The yields are generally good and the selectivity is high, as illustrated by the formation of (17) (60%) from the epoxidation of 4-vinylcyclohexene with only 4% total yield of other possible mono- and di-epoxide products. Two groups have studied the epoxidation of ap-unsaturated ketones with alkaline H202 methanol; a second-order process. Electron-releasing groups in attached to the &carbon atom in the alkene reduced the rate whereas electron-attracting groups had the reverse effect !2 In the case of (1 8; R = H or alkyl), the rate constants in 80%aqueous methanol decreased in the order H > Me > Pr > ~ e n t y l Spectral studies suggested that the origin of this .~~ order of reactivity concerned hindrance to delocalization of charge in the intermediate.

Base-catalysed epoxidation of norandrostenone ( 19), using H202 in methanol, produced exclusively the P-epoxide in the A ring.44It was suggested that the conformations of the A ring were such that the hydroperoxide group attached at the 5a- or 50-positions could attain an axial confirmation. cisCyclo-octene oxide (20) has been prepared in 60% yield by epoxidation of3940414243

44

L. Kim, Br. P. 1 399 639. B. Ganem a n d R. P. Heggs, J. A m . Chem. SOC., 1979, 101, 2484. C. J . Stark, Tetrahedron Lett., 1981, 2 2 , 2089. D. S. R. Rao, Indian J. Chem., Sect. B , 1981, 2 0 , 786. I. G. Tishchenko a n d I. F. Revinski, Vestsi Akad. Navuk B S S R , Ser. Khim. Navuk, 1981, No. 1, p. 90. J. R. Hanson, P. B. Hitchcock, a n d H. J . Wadsworth, J. Chem. Soc., Perkin Trans. I ,1981, 3025.


7

cis-cyclo-octene by 30% H 2 0 2 in MeCN at 25-35C.45 A high yield of epoxide may be obtained by two-phase epoxidation of alkenes, using dichloroethane-water with Na2W04 catalyst and a tetra-alkylammonium salt as the phase-transfer agent.& One of the most commonly used types of catalyst for epoxidations using alkyl hydroperoxides is complexes of molybdenum. The yields can be almost quantitative, as observed when using the n-cyclopentadienyl complex Cp2MoX2 (X = C1 or Br) with t-butyl hydroperoxide, which gives 98.4% of diepoxide from the dimer of cyclopentadiene.'" For the epoxidation of propene by t-butyl hydroperoxide and molybdenum salts of organic acids, the catalytic activity was little affected by the ligand on the A similar insensitivity to ligand (and also to valency) was noted in the epoxidation of cholesteryl acetate with M ~ O ~ ( a c a c MO(CO)~, )~, and MoC15.49 When cyclohexene was treated wtith t-butyl hydroperoxide and molybdenum porphyrins, cyclohexene oxide was obtained with up to 85% selectivity at total peroxide conversion (17-24 hr)." A similar catalyst gave 97% of cis- and 99% of transhex-2-ene oxides from the cis- and trans-alkenes respectively. A number of different catalysts have been used in the epoxidation of monoterpenes with t-butyl hydroperoxide and the conditions ~ptimized.'~ While oxidation of a-pinene in the presence of V(acac)3 gave cis-epoxide (4.4%), campholenic aldehyde was also obtained in the presence of Mo(CO)~. The n.m.r. line-broadening method was applied to the determination of the kinetic parameters of the exchange reactions of cumene hydroperoxide, cumyl alcohol, and cyclohexene in the co-ordination sphere of the complex H2 [ M o ~ O ~ ( C ~ O ~ ) ~ (4H20 * (CH3)2C0.52The results revealed that the H~O)~] first stage of both the decomposition of the hydroperoxide and the epoxidation reaction is the formation of an intermediate compound between a molybdenum(V) complex and the hydroperoxide.*

Synthesis of Oxirans by Halohydrin Cyclizations and Related Reactions. One of the oldest commercial methods for the production of ethene oxide is the chlorohydrin route, involving chlorohydration of ethene followed by dehydrochlorination. An improved procedure for the second stage of this process has been reported in which a basic ion-exchange resin is used to

45

47

48 49 51

52

R. D. Bach and J . W. Knight, Org. Synrh., 1981, 6 0 , 6 3 . E. Alneri and G. Lana, Ger. Offen. 3 027 349. A. 0. Kolmakov, V. M. Fomin, T. N. Aizenshtadt, and Yu. A. Aleksandrov, Zh. Obshch. Khim., 1981, 5 1 , 2805. H. R. Hernandez, P. S. Chow, and A. E. Rico, Rev. Ins?. Mex. Pet., 1981, 13, 6 6 . M. Kimura and T. Muto, Chem. Pharm. Bull., 1981, 29, 35. H. J . Ledon, P. Durbut, and F. Varescon, J. A m . Chem. SOC.,1981, 103, 3601. D. V. Banthrope and S. E. Barrow, Chem. Ind. (London), 1981, 502. A. M. Trzeciak, J . Sobczak, and J . J . Ziolkowski, J. Mol. Catal., 1981, 1 2 , 321.

8PCH2CH( OAc)CH2Br


H

4- M e C6H

WCWMeOCOMe

H

c1

(25)

remove the HCl that is generated during c y c l i ~ a t i o n The generation of .~~ styrene oxide (2 1; R = Ph) (85%) from PhCH2ClCH2Cl with 99% purity has been achieved by simple hydrolysis followed by elimination of HCl from the intermediate chlorohydrin, using aqueous NaOH.54Other methods for cyclization include the use of sodium methoxide in methanol to generate (21 ;R = CloH70CH2) from (22),55 reduction of (23) with sodium borohydride to yield the cis-epoxide (24),56 or the heating of 0-halogeno-esters with ammonium or phosphonium salts; e.g. , (25) and Bu4P' Br-, when heated at 180 "C for 2 hours, gave (21 ; R = Me) (95%).57

(27)

Reagents: i, LDA, CH,CII; ii, Bu,N+ F-

Scheme 1The phosphonate epoxide (28) has been prepared in 58% yield from the trimethylsilyl ether (26) via fluoride-ion-induced cyclization of the intermediate (27) (Scheme l).58 The stereochemistry of bromohydrin (31), which yields the oxiran (33) after sequential reduction and treatment with a base, has been proved by the use of a novel oxidative bromocarbonation (Scheme 2).59 Enol (29) of known stereochemistry is converted into the cyclic bromo-carbonate (32) (79%)upon treatment of the lithium alkoxide of (29) with dry C02 followed by Brz. Since (32), on treatment with base, gives54

''s65759

T. B. S. Giddey, S. Afr. P. 7 8 0 5 961. Hogyoku C o . Ltd., Jpn. Kokai Tokkyo Koho 81 92 282. Sagami Chemical Research Center, Jpn. Kokai Tokkyo Koho 82 26 6 7 7 . K. S. Bhat and A. S. Rao, Indian J. Chem., Sect. B , 1981, 20, 355. J . M. Renga and A. H. Emmons, U.S. P. 4 261 906. M. Sekine, M. Nakajima, and T. Hata, J. Org. Chem., 1981, 46, 4030. M. F. Haslanger and S. Ahmed, J. Org. Chem., 1981, 46,4808.


9

mH

OH

A

I

Scheme 2(33), and the stereochemistry of (32) follows from that of (29), the structure of (3 1) is established.Synthesis of Oxirans via Attack of a Carbanion on the Carbonyl Group of Aldehydes and Ketones. The dibromo-ketones [34; R = 4-MeC6H4, 4-MeOCsH4, 4-ClCsH4, or 3,4-(MeO)zC6H3] cyclized on dissolving in MeONa-MeOH, refluxing, and standing for 10 hours at room temperature to give the compounds (35) (86-95%) by the Darzens mechanism!' A rather useful, mild, and stereoselective synthesis of a,@-epoxyphenylketones (36; R = Me, R2 = PhCH2CH2, Ph, octyl, or 4-CIC6H4; R' = Et, R2 = Ph or ' PhCH2CH2)(52-8 1%) involves the reaction of aldehydes R2CH0 with a,adibromo-ketones PhCOCBr2R' in the presence of SnF2.61

Gorc"Br R Br(34)

j;r'Ph CO (36)

R(35)

COR

6o61

T-Y. Kao and S. Shang, Nan-ching Ta Hsueh Hsueh Pao, Tzu Jan K ' o Hsueh, 1980, 39. S . Shoda and T. Mukaiyama, Chem. L e t t . , 1 9 8 1 , 7 2 3 .

10

Heterocyclic ChemistryPh

PhCOCH( B r ) P h(37)

"\T/CN0

(38)

The use of KCN in the synthesis of oxirans from a-bromo-ketones under phase-transfer conditions has been investigated.62 Treatment of (37) in CH2C12with 40% aqueous KCN and aqueous Et3(PhCH2)N' C1- at 20 "C for 4 hours gave (38) (85%) as a 50 : 50 mixture of the cis- and the trans-isomers. Under homogeneous conditions, using DMF as a solvent, the same mixture was obtained in 61% yield, but the reaction can be made stereoselective for the cis-isomer in the presence of solid adsorb ant^.^^ Owing to the insolubility of KCN, no reaction occurs between (37) and KCN in CH2C12,but when the same substrate is treated with aqueous KCN that is adsorbed on silica gel (CH2C12, at 20 OC, for 4 hours), the oxiran (38) (95%) is produced, comprising 88% of the cis-isomer. A similar result is obtained by using benzene as solvent and alumina as adsorbant. Both silica gel and alumina are thought to facilitate the reaction by virtue of adsorbing the reacting species onto a surface upon which OH groups are plentiful. The combination of adsorption and hydrogen-bonding with OH groups on the surface is thought to explain the stereospecificity. Significantly, both activated carbon and Celite do not promote the epoxidation, neither material being able to participate via surface hy drogen-bonding. The reaction of 1,4-(BrCH2)2C6H4with Me2S gave the sulphonium salt, which, in aqueous NaOH-C6H6 (containing Bu4N+ Br- as a phase-transfer catalyst), gave the ylide (39). The ylide reacted in situ with a number of phenyl-substituted benzaldehydes to give the separable diastereoisomers (40).64Similar reactions were reported for 1,2- and 1,3-~lides.~'

Q62

CH=SMe2

CH=SMe2

Ar

6364

K. Takahashi, T. Nishizuka, and H. Iida, Synth. Commun., 1981, 11, 757. K. Takahashi, T. Nishizuka, and H. Iida, Tetrahedron L e t t . , 1981, 22, 2389. L. V. Shubina, I. G. Tishchenko, and S. V. Smatser, Dokl. Akad. Nauk B.SSR,1982, 26, 148.

65

L. V. Shubina, I. G. Tishchenko, and I. I . Medved, Vestsi Akad. Navuk B S S R , Ser. Khim. Navuk, 1982, No. 1, p. 66.

Three-Membered R ing Systems

11

The sulphonium ylides (42; R4 = R1R2C=CHCH2or R3CH2), derived from tetrahydrothiophen, have been used for the synthesis of the halogenated vinyl epoxides [41; R' R2 = Br, C1, or H (however, either R' or R2 must be halogen); R3 = H, Me, Me2CH, MeCH=CH, H2C=CMe, Me2C=CH, Ph, or PhCH=CH] (23-87%) by reaction with the appropriate aldehydes.66 The more complex salt (43), on reaction with HCO(CH2)3COOMe, gave the ( R ,S)-(all-E)-epoxide (44) as a mixture of cis- and trans-is~mers.~'

COOMe

+(45)

-

Ph S e Me CH

The first examples of reactions of non-stabilized selenium ylides with enolisable carbonyl compounds have been reported.68 Ylide (45) was generated in situ from Me,$ePh MeS04 and NaH in the presence of R'COR2 [R' = Ph, 4-O2NC6H4,Bu, or hexyl; R2 = H, Me, or Et; or R1R2 = (CH2)s] to give the corresponding oxirans (76-94%).68 Synthesis of Chiral Oxirans. The recently introduced Katsuki-Sharpless reagent (titanium alkoxide with tartrate) has proved highly effective for the maiden introduction of chirality into prochiral allylic alcohols. An interesting development of this procedure has afforded the possibility of kinetic resolution of racemic allylic alcohols.69 The basis of the method involves the6667

68

J . P. Beny, J . C. Pommelet, and J . Chuche, Bull. SOC.Chim. Fr., Part 2 , 1981, 369. M. Rosenberger, Eur. Pat. Appl. 36 663. K. Takaki, M. Yasumura, and K. Negoro, Angew Chem., Znt. Ed. Engl., 1981, 20,671. V. S. Martin, S. S. Woodard, T. Katsuki, Y. Yamada, M. Ikeda, and K. B. Sharpless, J. A m . Chem. SOC.,1981, 1 0 3 , 6 2 3 7 .

69

12


difference in rates of epoxidation of the enantiomeric alcohols; in the case of (46)) this difference in rate is 138. Starting with racemic (46), the optical purity of the remaining unreacted alcohol at 60% conversion is greater than 99.999999%. The method promises to be of great synthetic value. The epoxy-alcohol products from such reactions are also of synthetic value. It has been reported that the erythro-threo selectivity is profoundly influenced by the catalyst used; thus, in the case of racemic (47), the Katsuki-Sharpless reagent gives 81:19 erythro selectivity whereas in the absence of diethyl tartrate the ratio swings to 5 :95 in favour of the threo-isomer. In both cases, the erythro- or threo-epoxy-alcohols possess high enantiomeric purity (2 92%e.e.).

In a series of papers, the application of titanium alkoxide catalysts to the synthesis of sugars has been described. Asymmetric epoxidation and kinetic resolution of (48) afforded (+)-(49) (27%; > 95%e.e.) and (-)-(48) (33%; 72%e.e.).70 The ring-opening reactions of the chiral epoxides that are produced, for example, from cis- and from trans-(50) provide new routes to The reagents also find use in the synthesis of pheromones; e.g., (+)-di~parlure~~ (+)-2,6-dimethylhepta-l,S-dien-3-01 and acetate via the epoxide (52), which was obtained from the dienol (51) by using D ( ) --70 71

W. R. Roush and R. J . Brown, J . Org. Chern., 1 9 8 2 , 4 7 , 1371. T. Katsuki, A. W. M. Lee, P. Ma, V. S. Martin, S. Masamune, D. Tuddenham, and F. J . Walker, J. Org. Chem., 1982, 47, 1373.1982,47,1378.

K. B. Sharpless,

72

P. Ma, V. S. Martin, S. Masamune, K. B. Sharpless, and S . M. Viti, J. Org. Chem.,

73

K. Mori and T. Ebata, Tetrahedron Lett., 1981, 2 2 , 4 2 8 1 .


Fewo):qcJMe

pCOOMe

13

tartrate.74 Under the conditions of such epoxidations it is surprising to note that no decomposition of the iron complex occurred in the formation of (54) from (53) as part of a total synthesis of an analogue of trichothecene. Leucotrienes are substances that are implicated in asthmatic conditions, and thus their synthesis, or at least the synthesis of their precursors, is of pharmaceutical interest. Two approaches to the synthesis of (56) have been published. The first involves the treatment of the threo-hydroxy-ester lactone ( 5 5 ) with K2C03 in methanol,76 while the second uses LDA to convert (57) into the epoxide (58), which may then be transformed into (56) (Scheme 3).770

HMe02S0

PhCOO

H CHZOTs

f

ICH2COOEtii 0

H(58)

HO (57)

Reagents i, K,CO,, MeOH; ii, LDA

Scheme 37475 76

K. Mori and H. Ueda, Tetrahedron, 1981, 37, 2581.

77

A. J. Pearson and C. W. Ong, J. Am. Chem. SOC.,1981, 103, 6686. N. Cohen, B. 1. Banner, and R. J . Lopresti, Tetrahedron Lett., 1980, 21, 4163. J. Rokach, C-K. Lau, R. Zamboni, and Y . Guindon, Tetrahedron Lett., 1981, 2 2 ,2763.

14


(59)

Highly stereoselective epoxidations of acyclic homoallylic alcohols have been achieved, using the vanadium(v) t-butyl hydroperoxide method .78 A yield of 90%, with selectivity of > 400 :1, was achieved in the preparation of (60) from (59), and a detailed model of the transition state was proposed. The model involves a cyclic transition state (61), for which the required form is attained by minimizing the steric interactions engendered by the various substituents. The model successfully predicts the stereochemical outcome of a range of such epoxidations.

R~CH=CR~COOH(62)

- Ia , ,COCR =C H R ~(63)

I

Scheme 4An efficient process for the synthesis of a,P-epoxy-aldehydes from a,Punsaturated acids has been rep~rted.~ The acid (62) is converted into the bromo-lactone [64; R = a- or P-Me, R2 = Ph or (CH2)5Me; or RR2 = (CH2)4 or 2-C,H4(CH2),], via asymmetric bromolactonization of the corresponding acylproline (63; R3 = H or Et). Sequential epoxidation and reductive cleavage of (64) gives the (2R,3S)-epoxy-aldehydes (65) in good yield, with e.e. 84-98% (Scheme 4). The possibility of preparing oxirans via microbial oxidation offers the prospect of considerable stereoselectivity, owing to the enzymes involved in such processes. Thus far, however, such conversions have not been a practical proposition, because of the very low concentrations of alkene that may be used with the cultures (generally, no more than 1% by volume). A good yield has been obtained, however, in the microbial transformation of oct-1-ene, using Pseudomoms oZeovorans.sOThe method employs a two-phase system in78

79

E. D. Mihelich, K. Daniels, and D. J . Eickhoff, J. Am. Chem. SOC.,1981, 103, 7690. M . Hayashi, S. Terashima, and K. Koga, Tetrahedron, 1981, 37, 2797. M. J . DeSmet, B. Witholt, and H . Wynberg, J. Org. Chem., 1981, 46, 3128.

Three-Membered Ring SystemsHI

15

Me aCO *OE

t

-

?MeOS03Me(67)

OR(66)

CH20H

-mH.

Me

0

(68)

Scheme 5which octene is present in sufficient quantities to serve as the second phase. By this method, 5.6 g (1.4%) of the oxiran, containing 85% of the (R)-isomer, was obtained from 500 cm3 of octene. A useful preparation of (+)-(R)-methyloxiran (68) is shown in Scheme 5.81 The overall yield, based on the readily available (+)-@)-ethyl lactate (66; R = OH), from which (66; R = MeS03) is formed, is 7 1%. The cyclization of (67) involves distillation of the oxiran as it is produced.COOEt

COOEt

The epoxysuccinate (2R ,3R)-(70) (94%) is prepared from (2S,3S)-(69) by treatment with Et3N in CH2C12overnight.82 A number of enantiomerically pure synthetic building blocks have been prepared from hydroxybutanoic, malic, and tartaric acids.83 Examples of those with at least two functional groups are (21; R = CH2CH2Br), (71), and (72; R = H, CH2Ph, CMe20Me, or Ph).

Synthesis and Reactivities of Aromatic Oxides. The synthesis and absolute configurations of benzene and naphthalene ( 1S,2S,3S,4S)-diepoxides, (+)-(73) and (+)-(74), have been reported,84 as have those of the naphthoquinone derivative (2S,3R)-(+)-( 75) .85L. R. Hillis and R. C. Ronald, J. Org. Chem., 1981, 46, 3348. Taisho Pharmaceutical Co. Ltd., Jpn. Kokai Tokkyo Koho 81 110 683. E. Hungerbuehler, D. Seebach, and D. Wasmuth, Helu. Chim-. A c t a , 1981, 64, 1467. K. Koreeda and M . Yoshihara, J. Chem. SOC.,Chem. Commun., 1981, 974. Y. Harigaya, H. Yamaguchi, and M. Onda, Chem. Pharm. Bull., 1981, 29, 1321.

82

8384

16


H@

--H

H @\

--H

o @/0

/

/

;H

o

:(74IH

o

3-Me00CC6H4 O (75)

(73)

The hexahydrophenanthrene 9,lO-oxide (76) has been synthesized, together with its diastereoisomeric isomer (77).& Both isomers are conformationally rigid and give rise to different diol products under acid hydrolysis; (76) yields the cis-diol (75%) at a faster rate than (77), which leads to transdiol exclusively. This reactivity of (76) has been ascribed to the fact that the benzilic C-0 bond of the epoxide ring is aligned nearly parallel to the n-orbitals of the aromatic ring and the epoxide oxygen iscis to the hydrogen at the adjacent ring junction. For the other isomer the benzilic C-0 is not aligned and it has the epoxide oxygen trans to the hydrogen at the adjacent ring junction. Under neutral conditions, (76) gives the rearranged ketone (78) (85%). n

(76)

A possible explanation for the difference in carcinogenicity of K - and bayregion arene oxides has been s~ggested.~' Phenanthrene 9,lO-oxide (79) reacts with the phosphodiester HOP(O)(OEt), to give 9-phenanthrol (80) whereas cyclohexene oxide, under the same conditions, gives the phosphotriester (8 1). If bay-region arene oxides react in the same manner as cyclohexene oxide (to give potentially carcinogenic diol derivatives) then K-region oxides may well be detoxified by conversion into phenols, on approaching a molecule of DNA (or RNA), by the phosphate groups that are present.

' P 0 ) ( OEt ) 2 O(

86

87

J. M. Sayer, H. Yagi, J . V. Silverton, S. L. Friedman, D. L. Whalen, and D. M. Jerina, J. Am. Chem. SOC.,1982, 1 0 4 , 1 9 7 2 . P. DiRaddo and T. H. Chan, J, Org. Chem., 1 9 8 2 , 4 7 , 1427.

Three-MemberedRing Systems

17

The first examples of syn stereoselective epoxidation of arene dihydrodiols have been reported with the preparation of (82) and (83) from the corresponding diols.88 Thus unexpected synepoxidation has been interpreted as due to the exertion of steric control by the axial benzylic hydroxy-groups, whereas such control is usually exhibited by equatorial hydroxy-groups.OH

(84)

(85)

The enantiomeric bay-region diol epoxides of benz[a]anthracene (84) and of chrysene (85) have been synthesized and a rather interesting relationship between stereochemistry and turnorigenic activity has emerged.89 It appears that for each of the four metabolically possible bay-region diol epoxides of both of the above fused systems and for the diol epoxides (86) of benzo[a]pyrene, those with the (+)-(R ,S)-diol (S,R)-epoxide trans configuration (87) have practically all of the tumorigenic activity. One attractive explanation for this phenomenon is that the cellular covalent binding site of these ultimate carcinogens is highly chiral and that only these isomers effectively bind to the site. The benz[c]acridine analogues of (84), i.e. (88), have been prepared.g0

(87)

H. Lee and R. G. Harvey, Terrahedron Lett., 1981, 2 2 , 1657. H. Yagi, K. P. Vyas, M. Tanada, D. R. Thakker, and D. M. Jerina, J. Org. Chem.,1982,47,1110.

R. E. Lehr and S. Kumar, J. Org. Chem., 1981, 46, 3675.

18


The optically active benz[a]anthracene oxides (89) and (90) have been synthesi~ed.~' Thermal recemization (at 293-322 K, in CDC13) of the chiral chrysene 3,4-oxide (91) has been shown to occur via first-order kinetics, with an activation energy of 25.2 kcal m01-l.'~ The results are consistent with a reaction mechanism involving an oxepine intermediate (92), as predicted by theory.

The novel bay-region diol epoxide isomers (93) have proved to be remarkably biologically active, despite their relative lack of reactivity towards hydrolysis (as expected from simple PMO calculations).93 Both diastereoisomers prefer the conformation in which the OH groups are quasidiequatorial, and these are the most tumorigenic diol epoxides yet tested on mouse skin.D. R. Boyd, G . S. Fadaginamath, N. D. Sharma, A. F. Drake, S. F. Mason, and D. M. Jerina, J. Chem. SOC.,Perkin Trans. 1, 1981, 2233. 92 D. R. Boyd, M . G. Burnett, and R. M. E. Greene, J. Chem. SOC.,Chem. Commun., 1981, 839. 93 J . M. Sayer, H. Yagi, M. Croisy-Delcey, and D. M. Jerina, J . Am. Chem. SOC., 1981, 103,4970.91

Three-membered Ring Systems

19

Two bis-imines (94) and (95) have been prepared from the corresponding diepoxides by reaction with NaN3 and subsequent cyclization of the transazido -alcohols .%

Miscellaneous Syntheses of Oxirans. The vinyl-oxirans (97; R' = Ph or phenethyl, R2 = H or Me) were prepared by refluxing the benzimidazole derivatives [96; R3 = CH2CH2(0CH2CH2)20Me] with NaH in THF.95CR~=CH~CHR'OH0 (97)

R3

I

Diazomethane reacts with (98) in the presence of Et3N to give a mixture of (99) and (loo), but, without Et3N, the reaction yields mainly the two oxirans (101) and (102) (Scheme 6).% Trimethylsilyldiazomethane, Me3SiCHN2, reacts with aromatic aldehydes RCHO in the presence of Et3N to give the oxirans (103) and (104), amongst other product^.^'

94 959697

I. Yona and J . Blum, J. Heterocycl. Chem., 1981, 18, 1473. Mitsubishi Chemical Industries Co. Ltd., Jpn. Kokai Tokkyo Koho 81 125 379. H. Meier and A. Binder, Chem.-Ztg., 1981, 105, 149. N. Hashimoto, T. Aoyama, and T. Shioiri, Heterocycles, 1981, 1 5 , 975.

20PhCOCOCH2N2+

Heterocyclic ChemistryCH2C1 @COPh(100)

PhCOCOCl(98)

~ 1 dPh 1 :0 COCH2NH2

/

(99)

(101)

Reagents: i, CH,N,, Et,N; ii, CH,N,

Scheme 6

When the valence tautomer of cyclo-octa-1,5-diene (stable below - 20 "C) is treated with O2 under irradiation from a sodium vapour lamp (a street lamp), in the presence of tetraphenylporphyrin as sensitizer, the endoperoxide (105) can be prepared in 85% yield.98 The endoperoxide serves as the starting material for three triepoxides (106), (107), and (108) (Scheme 7). The structures of all three triepoxides have been confirmed by X-ray analysis.

iiii i

Reagents: i, heat, ii, mCPBA; iii, PPh,

Scheme 798

W. Adam, 0. Cueto, 0. DeLucchi, K. Peters, E. M. Peters, and H. G . Von Schnering, J. Am. Chem. SOC.,1981,103, 5822.

+

2

( 102)

0

QV

0

Three-Membered Ring SystemsCHO

21

'H

P0

Torr gave (1 10) Flash vacuum thermolysis of (109) at 420 "C and 2 x (95%)." The Dewar-furan (1 11; X = 0) has been prepared in six steps from the corresponding Dewar-thiophen (1 1 1; X = S ) because the direct route via photolysis of furan proved

Spectra and Theoretical Chemistry of Oxirans.- The use of conformational analysis, with the aid of torsion-angle notation, permits the interpretation and prediction of regioselective opening of epoxides."' Values for the molar refraction, electron polarization, and permanent electron dipole moments for oxiran and its simple derivatives have been calculated from literature data.lo2 The molar Kerr constants for oxiran and its methyl derivatives in CC14 were also calculated. The pericyclic reactivities of three-membered heterocycles have been rationalized, using the relaxation method.lo3

The 13C n.m.r. spectra for (1 12; X = 0, NH, S , or SO) have been recorded and compared with that for (1 12; X = CH2).lWThe annelation effects of the three-membered rings were determined. Using 350 MHz 'H n.m.r. and dipole moments, ( 1 13; R = H) and (1 13; R = OMe) were shown to adopt a boat conformation, with the 0 of the oxiran ring in a pseudo-axial position.'05 The absolute configuration of alliacolide (1 16) has been established by c.d.

99

100

101102

103 104

105

A. J. H. Klunder, W. Bos, J . M. M. Verlaak, and B. Zwanenberg, Tetrahedron Lett., 1981, 22,4553. D.Wirth and D. M. Lemal, J. Am. Chem. SOC.,1982,104,847. E. Toromanoff, Tetrahedron, 1981, 37, 3141. D. Pitea, R. Todeschini, and F. Gatti, J. Chem. SOC., Faraday Trans. 1 , 1981, 77, 1611. 0 Henri-Rousseau, P. Pujol, and F. Texier, Bull. SOC.Chim. Fr., Part 2 , 1980,496. . M. Christl, H. Leininger, and E. Brunn,J. Org. Chem., 1982,47, 661. J. Huet, Z. Kotkowska-Machnik, and J . Zakrzewski, Org. Magn. Reson., 1981, 16, 236.

22

MeOOCCHZCH2

we weHeterocyclic ChemistryMe Me OH(114)

0(115)

Me

MeH' O

measurements on the degradation products (1 14) and (1 15), both of which exhibit positive Cotton curves.1o6 The molecular structure of the perfluoro-oxiran (1 17) has been determined, using gas-phase electron diffracti~n.''~

Reactions of Oxirans. - Ring-opening Reactions with Electrophiles. A ringcontraction resulted from the treatment of the piperidine (118) with BF3. OEt,, to yield (1 19) rather than the expected piperidone (12O).lo8The C-19 group has been shown to have a significant effect on the BF3-catalysed reactions of SP,6P-~teroids.'~~ androstanone (121 ; R = H) reacted with Thus gaseous BF3 in benzene with loss of the hydroxymethyl group as HCHO and subsequent dehydration to give the diene (122), but, for (121; R = OAc), ring-contraction led to ( 1 23). For steroidal Sar,6c~-epoxides,however, an alternative pathway is possible, involving participation of the C-19 group and leading to ring-closed products; eg., chloestanol (121 ; R = H) gives (124) with BF3 log or with HC1O4."'

8I(118)

( Y C H O

hoCOOCH2CC13( 120)

COOCH2CC13

COOCH2CC13(119)

I

I

A. P. W. Bradshaw, J . R. Hanson, D. N. Kirk, and P. M. Scopes, J. Chem. Soc., Perkin Trans. I , 19 8 1, 17 94. lo' B. Beagley, R. G. Pritchard, and R. E. Banks, J. Fluorine Chem., 1981, 18, 159. F. H. Hershenson and L. Christensen, Synth. Commun., 1981, 11, 61 5. l o g H. Mastalerz and P. Morand, J . Chem. SOC., Perkin Trans. 1 , 1981, 154. ' l o P. Kocovsky and V. Cerny, Collect. Czech, Chem. Commun., 1980, 45, 3190.lo6


23

The mechanism for the gas-phase reaction of trans-2,3-dideuterioethene oxide with HBr and HCl has been shown to involve anti ring-opening, with the formation of erythro-R(CHD)*OH ( R = C1 or Br)."' The reaction of ethene oxide with HF followed a somewhat different course, affording only 5% of fluorohydrin together with (126) (37%) and oligomers and polymers. A possible mechanism for this reaction is shown (see Scheme 8) in which two moles of oxiran react with HF to give intermediate (125), which is open to polymerization with other oxiran molecules or to ring-expansion, with the subsequent formation of dioxane (1 26).

H(125)

Cyclization Reactions of Oxirans. The search for non-enzymatic cyclizations of squalene oxide and its analogues continues with the report of the direct sterol synthesis of (128) (2%) from (127).'12 Although the yield is low, the procedure involving treatment of (127) in CHzC12 that contains BF3 - OEt2 and ethene carbonate at 0C for 20 minutes affords four new rings and seven new asymmetric centres in one laboratory operation. The diepoxide'I1112

G. Bellucci, G. Berti, R . Bianchini, G. Ingrosso, and A. Moroni, J. Chem. SOC., Perkin Trans. 2 . 1981, 1336. E. E. Van Tamelen and T. M. Leiden, J. Am. Chem. SOC.,1982, 104, 2061.

+

T7 F+O I

TJ-

[ y7JHIF--[ci>].-- 50%) from (177) has been r e ~ 0 r t e d . lSequential treatment of (177) in THF at 0 "C with one equiv~~alent each of BuLi, methanesulphonyl chloride, and then BuLi again, to give (17$), may be accomplished in 10 minutes. Terminal yepoxy-sulphones, on treatment with two equivalents of MeMgI , give cis-3-phenylsulphonylcyclobutanols; thus (179) yields (180).13' This reaction contrasts with that of (179) with MeLi or with LiNPr:, which gives derivatives of cyclopropylmethanol.Ph

phso>(179)

phs+h

OH

The reaction of organomagnesium reagents RMgBr with y ,S -epoxy-ketones, e.g. (181), affords functionalized tetrahydrofurans (182; R = Et, Ph, or CH=CH2) (71-75%).138 The ring-opening of the oxiran by the intermediate alkoxide occurs with inversion of configuration, but, with both organomagnesium and organolithium reagents, the cyclization affords a 1 : 1 mixture of both cis- and trans-tetrahydrofurans (1 82).

+ T(181)

M:eAT4:OH(182)

The opening of epoxides, e.g. cyclopentene oxide, with the allylic Grignard reagent (1 83), in the presence of CuI , affords (1 84) in high ~ie1d.l~' The allyl-silane (184) may then be converted into the allylic alcohol (185). The overall process demonstrates the use of (1 83) as a hydroxypropenyl synthon.Me3Siw

/

MgBr

136

137 138

13'

Y. Gaoni, Tetrahedron Lett., 1981, 2 2 , 4339. J. M. Decesare, B. Corbel, T. Durst, and J . F. Blount, Can. J. Chem., 1981, 59, 1415. M. Chastrette and G. P. Axiotis, J. Organomet. Chem., 1981, 206, 139. H. Nishiyama, S. Narimatsu, and K. Itoh, Terrahedron Lert., 1981, 2 2 , 5289.

32


Reactions of alkyl-lithiums with isoprene oxide (1 86) yield p,-ydisubstituted allylic alcohols of Z c~nfiguration.'~'The proportion of Z isomer can be increased by using a base; thus the formation of (187) from (186) and BunLi is improved fron an isomer yield of 88% in hexane at 0C (76% overall yield of allylic alcohols) to an isomer yield of 97% (73% overall) in the presence of Bu"0Li.

I ,Enantioselective SN2' reactions of epoxy vinyl sulphones have been rep~rted.'~' The chiral epoxide (-)-( 188) reacts with MeLi in the presence of LiC104 in a 1:1 mixture of CH2C12and Et,O at - 78 "C to yield a 95 : 5 mixture of (+)-(189; R' = Me, R2 = H) and (+)-(189; R' = H, R2 = Me) (81%). Using a mixture of Et3A1 and MeCu, however, the reaction affords solely (+)-(189; R' = Me, R' = H).

In contrast to their reaction with R'R'CuLi (R' = alkyl, R2 = alkyl or CN), the reactions of epoxides with the higher order mixed organocuprates R2Cu(CN)Li2 (R = various alkyl or aryl) give excellent yields of ring-opened products.'42 The trisubstituted oxiran (190), on reaction with Pr"Cu(CN)Li, affords only 23% of (191), but with Prn2Cu(CN)Li2 the yield is increased to 86%.

140

1' 41 4 '

M. Tamura and G. Suzukamo, Tetrahedron Lett., 1981, 2 2 , 577. J . C. Saddler and P. L. Fuchs, J. Am. Chem. SOC.,1981, 103, 2112. B. H. Lipshutz, J . Kozlowski, and R. S. Wilhelm, J. Am. Chem. Soc., 1982, 104,2305.

Three-Mem bered Ring SystemsOS iMeOSiMe3

33I

I

M e(193)

The enol ethers of substituted 2,3-epoxycyclohexanones, (192), react e.g. with organocuprates, e.g. MeCu(CN)Li, in a regio- and stereo-specific manner to yield (in most cases) the 1,4-trans-adducts (193) (95%).'43

Reduction and Elimination Reactions of Oxirans. - The liquid-phase hydrogenolysis of the spiro-oxirans (194; X = 0, Y = CH2) and (194; X = CH2, Y = 0) on supported metal catalysts (Pd, Pt,Rh, and Ni) in various solvents leads to preferential cleavage of the more substituted C-0 bond.'@ For Pd and Rh catalysts the major products are aldehydes (60 and 80%respectively) whereas with Pt or Ni the liydrogenoiysis leads mainly to primary alcohols. Catalytic hydrogenolysis of 3,4-epoxybut-l-ene with cationic rhodium complexes at 30C under 1 atm of hydrogen gives but-2-enal as the major product .14' The hydrogenolysis of methyloxiran on unsupported Pt/C catalysts leads mainly t o Me2CHOH, and to EtCHO, whereas the aldehyde was produced if a supported catalyst was used.14 The interpretation of these results in terms of the role of acidic centres in the isomerization and hydrogenolysis of oxirans has received some criti~ism.'~'

Epoxides may be reduced t o the less substituted alcohol, using a combination of NaBH3CN, BF3. OEt2, and THF. The reaction is both regio- and stereo-~elective;'~~ 1-methylcyclohexene oxide gives a 97 : 3 ratio of thus (195):(196) (overall 87%), with only a trace of trans-(195) being produced. Stereospecific reduction of epoxybutanoic acid (197) with NaBD4 gave (198) (52%).149 The reduction of (+)-(R)-(l99) with A1D3 gives a nearly equal mixture of (+)-(S)-(200) and (-)-(S)-(201),150 The inversion that is involved in143 144

J. P. Marino and J. C. Jaen, J . A m . Chem. SOC.,1982, 104, 3165. G. Accrombessi, P. Geneste, J. L. Olive, and A. A . Pavia, Bull. SOC. Chim. Fr., Part 2 ,1981, 19.

1' 4146

1 4 ' 1' 4149

H. Fujitsu, E. Matsumura, S. Shirahama, K. Takeshita, and I. Mochida, J . Chem. SOC., Perkin Trans. I , 1982, 855. M. Bartok, F. Notheisz, and J . T. Kiss, J. Catal., 1981, 6 8 , 249. M. Kraus and H. Davidova, J. Catal., 1981, 68, 252. R. 0. Hutchins, I. M. Taffer, and W. Burgoyne, J. Org. Chem., 1981, 46, 5214. J. R. Mohrig, P. J . Vreede, S. C. Schultz, and C. A. Fierke, J . Org. Chem., 1981 46,46 5 5.

R. L. Elsenbaumer, H. S. Mosher, J. D. Morrison, and J . E. Tomaszewski, J. Org. Chem., 1981, 46,4034.

34


OH

PhI

D3C+--Ph H

HC ZH D*

D

the formation of (201) points to a classical s N 2 attack by A1D3 on the benzylic site. Deoxygenation of epoxides to alkenes can be achieved with a number of reagents, including WCls and BuLi,lS1NbCIS and NaA1H4,lS2and Me3SiCl and NaI. The last combination of reagents has been shown to react stereoselectively, affording (E)-2,2-dimethylhex-3-ene (95%) from the corresponding (E)-epoxide.

Thermal and Photochemical Reactions of Oxirans. - Isotopic labelling has been used to prove that the thermal rearrangement of phenyloxiran proceeds via a 1,2-shift of hydrogen, and not phenyl migration (Scheme 13).lS4The epoxide (202), labelled with 13C at C-2, gives entirely C(2)-labelled phenylethanol (203) and 3,3-2H2-labelled(202) gives (203) with 2H at both C-1 and C-2. The method does not, however, distinguish between the transfer of H and of H-.

Ph

w z1 (202 1

* PhCH-

-0

CD2 PhCHD

I

-CDO

\

+ PhCH-CD2 I

0-

/

(203)

Scheme 13Cycloaddition reactions of the carbonyl ylides derived from the thermolysis of (204; n = 1 , 3 , 5 , or 10) led to annelated products (205;n = 1 , 3 , or 5), but the bridged compound (206) was produced from (204;n = The stereochemistry of 6n and 8 7 ring-cyclization reactions of 2-oxaheptatrienyl 7IslS3

M. A. Umbreit and K. B. Sharpless, Org. Synth., 1981, 6 0 , 29. M. Sato and K. Oshima, Chem. Lett., 1982, 157. R. Caputo, L. Mangoni, 0. Neri, and G. Palumbo, Tetrahedron L e n . , 1981, 22, 3 5 5 1 . R. M. Roberts and L. W. Elrod, J . Org. Chem., 1981, 46, 3732. J . Brokatzky and W. Eberback, Tetrahedron Lett., 1980, 2 1 , 4 9 0 9 .


35

MeOOC

ph-aM e\ /

M

M e e

O

O

C

b

(208)

( 209 1

dipoles has been ~ t u d i e d . ~ The eight-electron cyclization of the con,15 jugated carbonyl ylide (208), generated by thermolysis of (207), gave the dihydro-oxepin (209). The reaction followed the theoretically expected conrotatory process. The thermal decompositions of the three isomers of (210) all yield mixtures of PhCHO, PhOH, C6H6, and furan.lS8It is suggested that two of the decompositions proceed by similar mechanisms; for trans-(210), via (21 l), and for the isomer of cis-(210) in which epoxide rings are anti to cyclobutene, via (212). The first step in the decomposition of the isomer of cis-(210) in which epoxide rings are syn to cyclobutene is thought to involve the formation of (213). The first topologically non-planar molecule (2 15) has been produced by the thermolysis of (214).15

lS7158

W. Eberback, E. Haedicke, and U . Trostmann, Tetrahedron Lett., 1981, 22,4953. W. Eberback and U. Trostmann, Chem. Ber., 1981, 114, 2979. H. Prinzbach, M. Mass, H. Fritz, and G . McMullen, Tetrahedron L e t t . , 1980, 21,4897. S . A. Benner, J . E. Maggio, and H. E. Simmons, J. A m . Chem. SOC.,1981, 103, 1581.

36


Direct (457.9 nm) or photosensitized (by benzophenone) irradiation of (216) gives rise to the exclusive formation of (217).l6' In contrast to this, irradiation of the isomer of (216) in which the epoxide oxygen is syn to the benzene ring yields a mixture of products, of which the major constituent is (218) (ca 25%). The difference in reactivities of these isomers was explained in terms of the stereoelectronic effect of the epoxide ring.Pr

Photolysis of a-epoxy-ketones that are excited in their triplet states leads to 0-diketones, a-diketones, or fragmentation products.'61 The reaction pathway depends on the localization of energy for the system; thus (219; Ar' = Ph, Ar2 = 1-naphthyl), on irradiation at 366 nm, at room temperature, in MeCN, gave naphthaldehyde (75%)and the a-diketone (220) (8%)whereas (219; Ar' = 2-naphthyl, Ar2 = Ph), under the same conditions, gave (221) (66%). The absorption spectra of the ylide intermediates in these reactions were reported. 0

0

OH

I6O

C. C. Liao, H. S. Lin, T. H. Hseu, C. P. Tang, and J . L. Wang, J. Am. Chem. Soc.,1982,104, 292.

16'

P. Hallet, J . Muzart, and J. P. Pete, J. Org. Chem., 1981, 46,4275.


37

Carbonyl ylides that are derived photochemically from symmetrically substituted diaryl-oxirans (222; R = Me, Ar = Ph or 2-naphthyl; R = H, Ar = 2-naphthyl) retain their configuration during cycloaddition reactions with dipolarophiles.'62 Both isomers of (222; R = Me, Ar = Ph) give the same furan products (223) on irradiation in the presence of maleonitrile. This result implies that the same ylide (224) is generated from both oxirans. Adverse interactions of aryl groups would seem to prevent alternative opening of the oxiran ring. The ylides derived from (222; R = Me, Ar = 2naphthyl) do not undergo addition reactions whereas those from (222; R = H, Ar = 2-naphthyl) do; this result may also be explained in terms of steric effects. Another group has concluded that the regioselectivity in cycloaddition reactions of carbonyl ylides is high with electron-rich alkenes but is low with electron-deficient ones.163

A series of papers on photochemical reactions has reached number 122, with ten publications concerning the reactions of various vinyl~xirans;'~~ for example, triplet sensitization of (E)-(225) gave (226) and (227) via cleavage of the C(6)-0 bond.16'16'163164

J. P. K. Wong, A. A. Fahmi, G. W. Griffin, and N. S. Bhacca, Tetrahedron, 1981, 37, 3345. J. Brokatzky-Geiger and W. Eberbach, Hererocycles, 1981, 16, 1907. N. Bischofberger, G. DeWeck, B. Frei, H. R. Wolf, and 0. Jeger, Helu. Chim. A c t a ,1981,64, 1766.

1' 6

K. Murato, B. Frei, W. B. Schweizer, H. R. Wolf, and 0. Jeger, Helu. Chim. Acta,1 9 8 0 , 6 3 , 1856.

38


PhCH2CO0

clD) y -/(228) PdLm0

Ph CH2 C 1

0

PhCH2!!-ia

Ph CH C-P dC l L m

li

Scheme 14 Reactions of Oxirans with Organometallic Compounds. - A general method for the preparation of halohydrin esters via the reaction of organic halides with CO (20atm) in the presence of PhPd(PPh3)21 has been described.'66 In the particular case of benzyl chloride and cyclohexene oxide, (228) (57.5%) was obtained. A possible mechanism for this reaction is shown in Scheme 14. Isomerization of a$-epoxy-ketones in the presence of palladium complexes leads to 1,3-diones; thus heating (229) in toluene that contains Pd(PPh3)4 and (Ph2PCH2)2,at 140C, for 90 hours gives (230) (94.3%).16'0

Perilla alcohol (232) (98%) has been prepared by treating 0-pinene epoxide (231) with HgS04 that is suspended in a water-THF mixture, extracting into ether, and treating the ethereal extract with dilute H2S04.16'

( 2 3 11166

1 6 ' 16*

(232) M. Tanaka, M. Koyanagi, and T. Kobayashi, Tetrahedron Lett., 1981,22, 3875. Teijin Ltd., Jpn. Kokai Tokkyo Koho 81 1 5 216. M. Fetizon, J. E. Ecoto, and S. Lazare, Eur. Pat. Appl. 21 952.


39

Miscellaneous Reactions of Oxirans. - Ethylene carbonate (233; R' = R2 = H, X = 0) may be prepared by the reaction of ethylene oxide with C02 under pressure, at 140 OC, in the presence of alkali-metal halide^.'^' The reaction is catalysed by free anion, which is generated by the use of the complex between 18-crown-6 and KI.I7O Using complexes of this type, the compounds (233; X = 0; R' = Me, Ph, or ClCH2; R2 = H or Me) have also been prepared.17' The oxazolidone (233; R' = H, R2 = C1CH2, X = NPr') is prepared by the reaction of (chloromethy1)oxiran with isopropyl isocyanate in the presence of ~ i c 1 . I ~ ~

xKo0

OO Ph Y

(233)

(234)

The 1,3-dioxolans (234; R = CH2Cl, Me, or Et) have been prepared under neutral conditions by the reactions of the corresponding epoxides with benza 1 d e h ~ d e . I ~ ~ reactions are catalysed by halide ion and provide a mixture The of cis- and trans-2,4-disubstituted compounds. Using Lewis acid catalysts, the cis-isomer was preferentially formed whereas catalysis by lithium halides favoured the trans-isomer.

Thioamides RCSNH2 react with the chloro-oxiran (235) to yield the thiazoles (236; X = S, R = Me or Ph) (78%).'74 When (235) reacts with selenourea in CH2C12 at O'C, in the dark, and this is followed by treatment with Et3N, the selenazole (236; X = Se, R = NH2) (52%) is produced. Cyclization Of (237; R=4-C1CbH4, 4-NO2C6H4, or 4-MeOC6H4) with the cyclic t h o amides (238; X = HC=CHNMe, HC=CHCH=N, or CH2CH2S) provides a general synthesis of the ring-fused meso-ionic thiazolones (239).17'

Nippon Shokubai Kagaku Kogyo Co., Ltd., Jpn. Kokai Tokkyo Koho 8 2 31 682. Nippon Shokubai Kagaku Kogyo Co., Ltd., Jpn Kokai Tokkyo Koho 81 1 2 8 778. 171 K. Naito, H. Koinuma, and H. Hirai, Nippon Kagaku Kaishi, 1982, 290. 1 7 ' Seitetsu Kagaku C o . , Ltd., Jpn. Kokai Tokkyo Koho 81 7 3 077. 173 T. Takeda, S. Yasuhara, and S. Watanabe, Yukagaku, 1 9 8 1 , 30,486. 174 J. Gasteiger and C. Herzig, Tetrahedron, 1 9 8 1 , 37, 2607. 1' 7 M. Baudy-Floc 1.1 and A. Robert, Synthesis, 1 9 8 1 , 981.170

169

40


Thermal uncatalysed insertion of silicon halides into oxirans normally requires long reaction times and high temperatures. It has been reported, however, that nucleophilic catalysis renders this reaction of greater synthetic importance, providing a regioselective route to @protected vicinal haloh y d r i n ~ . 'The most effective catalysts appear to be Bun4NC1and Ph3P, the ~~ latter allowing the conversion of phenyl glycidyl ether into (241) (99%) in CHC13at 0 OC, using (240; X = Cl), after 5 minutes. This should be contrasted with the uncatalysed reaction, which affords only 23% of product after 24 hours at 25 "C. The conversion of epoxides into protected vicinal halohydrins, using (240; X = Br or I) in the presence of Et3N, has been incorporated into a one-pot synthesis of a-bromo- and a-i~do-ketones.'~'The oxidation step is achieved by adding Jones reagent (Cr03-H2S04) to the first-formed 0-halogenosilyl ether. Overall yields of 58-73% have been achieved (based on starting epoxide) for (242; R = alkyl, X = Br or I) and cyclic a-halogenoketones. Trialkylsilyl triflate (240; X = OS02CF3) promotes the ring-opening of oxirans and affords allylic alcohol silyl ethers from tetra-, tri-, and 2,2di-substituted oxirans; thus cyclohexene oxide gives (243).'78

3 Aziridines Preparation. - Direct Insertion. Ethoxycarbonylnitrene (EtOOCN:), generated by the Et3N-induced a-elimination of 4-N02C6H4S03NHCOOEt, adds to vinyl chlorides to give aziridines without appreciable contamination by insertion prod~cts."~The reaction is stereospecific; thus the addition to (244) gives (245), and the a-chloro-aziridines undergo facile rearrangements to alkenylamines, e.g. (246).

177

1 7 ' 1 7 '

G. C. An d r e w, T. C. Crawford, and L. G. Contillo, Tetrahedron Lett., 1981, 2 2 , 3803. J. N. Denis and A. Krief, Tetrahedron Lett., 1981, 2 2 , 1429. S. Murata, M. Suzuki, and R. Noyori, Bull. Chem. SOC.Jpn., 1982, 5 5 , 247. L. Pellacani, F. Persia, and P. A. Tardella, Tetrahedron Lett., 1980, 21, 4967.

Three-Membered Ring SystemsCOOEt

41

I

c1

pr+pr

c1(244)

Bu

H(245)

Bu

On treatment with Pb(OAc)4 in CHC13, the quinazolone derivative (247) gives (248) stereospecifically, and in good yield, via N-nitrene addition.'" The stereochemistry of these reactions may be explained in terms of a nonconcerted electrophilic addition of nitrene to the double-bond through a seven-membered transition state (249). Oxidation, with Pb(OAc), , of R' ONH2 18' and of RSNH2 lB2 afforded nitrenes, which add to alkenes to has produce the corresponding aziridines, e.g. (250; R' = Et, Pr", Pr', Bun, Bu', or Bus; R2 = R3 = R5 = Me, or R2 = R3 = R4 = Me, R5 = H, or R2 = R4 = Me, R3 = R5 = H, or R2 = R5 = Me, R3 = R4 = H) and [251; R = 2,4(N02)2C6H3].Sulphenyl-aziridines, e.g. (252), have been produced by irradiation of N S F in the presence of perfluor~propene.'~~

"- ; \&:RN

SR

1

OR

I

Fw:3FN

SNSF2(252)

I

180

lS3

R. S. Atkinson, J . R. Malpass, K. L. Skinner, and K. L. Woodthorpe, J. Chem. SOC., Chem. Commun., 1981, 549. B. V. Ioffe and Yu. P. Artsybasheva, Zh. Org. Khim.,1981, 1 7 , 91 1. R. S. Atkinson and B. D. Judkins, J. Chem. SOC.,Perkin Trans. I , 1981, 261 5. W. Bludssus and R. Mews, Chem. Ber., 1981, 114, 1539.

42

Heterocyclic Ch emistry

Preparation by Cyclization Reactions. A new route to 2-cyano-aziridineshas been developed, using the reaction of 2-chloro-ketimines with KCN in methanol.lW Initial nucleophilic attack by cyanide ion on (253; R = Pr', But , or cyclohexyl) gives (254), which is followed by cyclization to form (255) (73-88%). A convenient two-step synthesis of 2-cyano-aziridines has also been reported in which (256; R = Ph, halogenophenyl, 4-MeC6H4, or 4-MeOC6H4) is cyclized t o (257), using NaOH and the phase-transfer catalyst PhCH2NEti Cl-.ls5 The compounds (256) were synthesized by the reaction of the appropriate aromatic amine with CH2CC1(CN), using CU(OAC)~ catalyst.0

iii

\N R

\

JR

X

N

Br H

(258)

Reagents: i, LiAIH, ;ii, Ph,P, Br, ;iii, RNH, ;iv, BuLi

Scheme 15An jmproved synthesis of the N-substituted isopropylideneaziridines (258;

R = Pr', But, neopentyl, cyclopropyl, Ph, or 1-adamantyl) is shown inScheme 15.lS6 A method for the preparation of 2-bromo-amines, which are precursors for synthesis of aziridines, has been reported in which DBPA (259) reacts with styrene or with (E)- or (2)-1-phenylpropene to yield (260; R = H or Me), which with HCl in benzene give 2-bromo-amine hydrochlorides (261) in reasonable overall yields.'"R0

184

N. DeKimpe, L. Moens, R. Verhe, L. DeBuyck, and N. Schamp, J. Chern. SOC.,Chem. Commun., 1982, 19. S. A. Rao, A. Kumar, H. Ila, and H. Junjappa, Synrhesis, 1981, 623. J . B. P. A. Wijnberg, P. G . Wiering, and H. Steinberg, Synthesis, 1981, 901. S. Zawadzki and A. Zwierzak, Tetrahedron, 1981, 37, 2 6 7 5 .

Three-MemberedRing Systems

43

F?R1 O Y N R 2

R2

T-7 NR2

hR1

Preparation by Ring-contraction. The phot ofragment ation of oxazolidines, e.g. (262; R' = H or Ph, R2 = aryl), provides a new route to aziridines.'" The reaction proceeds via the elimination of an aldehyde. The vinyl azides [263; R1 = Me, R2 = Ph; R' = H, R2 = Bun; R' = But, R2 = H; or R'R2 = (CH,),], on treatment with dimethylsulphoxonium ylide, give the vinyltriazolines (264) (89-95%).ls9 Flash vacuum pyrolysis of (264) gave the vinylaziridines (265) (91-94%). Preparation of Chiral Aziridines. Asymmetric chlorination of the nitrogen atom of aziridines has been achieved, using Bu'OCl, in the presence of optically active trifluoromethylcarbinols, as chiral solvating agents.'" Thus (266; R' = COOEt or Ph, R2 = H) with Bu*OCl in the presence of (+)-(S)PhCH(OH)CF3 in CH2C12, at - 60C, for 3 hours gave chiral (266; R' = COOEt or Ph, R2 = Cl). Aziridines of opposite chirality were generated by using (-)-(R)-(C H7)CH(0H)C F 3 . The aziridinecarboxylic acid (267) has been prepared and resolved, using PhMeCHNH2.'"

Spectral and Theoretical Studies of Azkidines. Optically active 2-alkylaziridines (268; R' = H or Me, R2 = Me, Prl, or Bu') have been prepared from their corresponding L-amino-acids and their chiroptical properties recorded.'% From their 0.r.d. and c.d. spectra it was concluded that a negative Cotton

"' 0. Tsuge, K. Oe, and N . Kawaguchi, Chem. Lett., 1981, 1585.A. Hassner, B. A. Belinka, M . Haber, and P. Munger, Tetrahedron Lett., 1981, 2 2 ,1863.

A. Forni, I. Moretti, A. V. Rosyanik, and G. Torre, J . Chem. Soc., Chem. Commun., 1981, 588. l p 1 R. G . Kostyanovskii, G. K. Kadorkina, G . V. Shustov, I. I. Chervin, S. S. Nasibov, and S.V . Var\amov, Izv. Akad. Nauk SSSR, Ser. Khim., 1982, 145. 192 L. Maat and R,W. Wulkan, R e d . Trav. Chim. Pays-Bas, 1981, 100, 204.

44


effect at 200nm was connected with a cis orientation of the lone pair on nitrogen with the 2-alkyl substituent. Circular dichroism spectra have also been reported for benzoylaziridines, allowing configurations to be derived.lg3 The I3C chemical shifts of the unsubstituted carbon in the ring of (268; R' = H; R2 = H, Me, Et, CONH2, CONHNH2, CH2NH2,CN, or COOMe) and of 2,2-dimethylaziridine have been correlated with the "N shifts.'% The 15N shifts were also correlated to Taft inductive and steric constants. The proton-accepting abilities of cis(269; R' = H, Me, or PhCH,; R2 = H or NO2) and of trans-(269; R' = H, Me, or PhCH2; R2 = H, Br, or NO2) have been estimated, using the i.r. spectral shifts that are induced by these aziridines is phenol, 4-bromophenol, and trichloroacetic acid.lg5 The cis-isomers reacted with all three proton donors but trans-isomers only with CC13COOH. The absence of complexation for the trans-isomers was attributed to intramolecular hydrogen-bonding (when R' is H) and to steric hindrance when R' is Me or PhCH2. Two theoretical studies on the structure of aziridine have been published, one relating to the effect of hyperconjugation on the barriers to the inversion of nitrogen" and the other to the structures of aziridine-enarnine~."~ The reaction by which (270; R = H, Me, or NH2) are hydrolysed to cis- and to trans-(27 1) has been subjected to ab initio calculations.198Theoretical predictions have been found to agree with experimental results. Reactions of Aziridines. - Thermal. Thermolysis of (272; R', R2, R3 = H or Me) gave (274) and R'CH=CR2R3 (R' and R3 are cis) via the intermediate (27 3).

(272)lg3

(273)

J . M. J. Tronchet, E. Winter-Mihaly, M. A. M. Massoud,and J. Guist, Helv. Chim. Acta,1981, 64, 2350.

lg5'1 9197

199

E. Liepins, I. Kalvins, and P. T. Trapentsier, Khim. Geterotsikl. Soedin., 1981, 1231. v. D. Orlov, F. G. Yaremenko, N. V. Lishtvan, and Yu. N. Surov, Khim. Gererotsikl. Soedin., 1981, 1641. D. Kost and M. Raban,J. Am. Chem. SOC.,1982,104, 2960. K. Mueller and F. Previdoli, Helv. Chim. Acta, 1981, 64, 2508. A. M. Sapse, Int. J. Quantum Chem., Quanrum Biol. Symp., 1980, 7, 155. H. G. Zoch, E. Kinzel, and G. Szeimies,Chem. Ber., 1981, 114, 968.

Three-Mem bered Ring Systems

45

H

The vinylaziridine (27 5) underwent ring-expansion in refluxing toluene to give (276).200The mechanism involves a [3,3]-sigmatropic shift.

Ring-opening to Acyclic Compounds. The aziridines (277; R1,R2 = B u t , 1-adamantyl) undergo selective cleavage with 2-lithio-1,3-dithian to give the respective compounds (278).201 The A1C13-catalysed addition of 14C-labelled (279; R = Br) to benzene gives (280) with the label almost exclusively in the position shown.202 The mechanism proposed for this conversion involves a primary route via the intermediate (279; R = Ph).R1

voR2(277)

I

RcH23Ph 2CHCH2CH2NHS02Ph (280 1

*

S02Ph

The ring-opening of aziridines by fluorinating agents yields a,P-difluoroamines. The stereochemistry of opening can be controlled by the correct choice of reagent, e.g. anhydrous HF, Olah's reagent, or Et,N.nHF (n = 2, 2.5, or 3).203 Thus (281) with anhydrous HF gives (282) (100%) whereas (283) (92%) is formed with Olah's reagent.

zoo'01

202

203

H. P. Figeys and R. Jammar, Tetrahedron Lett., 1981, 2 2 , 637. E. R. Talaty, A. R. Clague, J . M. Behrens, M. 0. Agho, D. H. Burger, T. L. Hendrixson, K. M. Korst, T. T. Khanh, R. A. Kell, and N. Dibaji, Synth. Commun., 1981, 11,455. W. J . Kensler and S. K. Dheer, J. Org. Chem., 1981,46,4051. G. M. Alvernhe, C. M. Ennakoua, S. M. Lacombe, and A. J . Laurent, J. Org. Chem., 1981.46,4938.

46


Electrochemical oxidation of N-acetyl- and N-formyl-aziridine in methanol at a platinum anode afforded MeCONHCH2CH20Meand HCONHCH2CH2CH(OMe)2 respectively; no cyclic products were obtained.2w The polarographic behaviour of aziridinium salts (284; R = Ph, 4-MeC&, or 3- or 4-BrC6H4) in water has been reported.205

4-RC6H4S02(284 1( 285 1

Formation of Other Ring Systems. A new synthesis of the azetidines (285; n = 2; R = H, Me, or C1) has been reported, based on methylene insertion into the aziridine (285; n = 1 ;R = H, Me, or Cl), using Me2S-OcH2.206 Heating the BF3 adducts of the trans-aziridines (286; R' = 4-Br, 4-C1, 4-Me, H, or %No2; R2 = H, 4-Br, or 4-C1) with MeCN gave the BF3 adducts of the imidazolidines (287) (62-78%).207 With MeONa, (287) isomerized to the trans-imidazolidines. The same aziridines (286) were found to condense with acetone in the presence of Et,N to yield the oxazolidines (288) (55-80%).208 The reaction of (289; R' = OEt, 4-C1C6H4NH,Ph, or Ph2N) with R2CH(COOEt), (R2 = Ph or Me) afforded (290) via ring-opening and subsequent cyclization. 209

N y N M e

Me

'04 '05207

2. Blum, M. Malmberg, and K. Nyberg, Acra Chem. Scand., Ser. B , 1981, 3 5 , 739. D. R. Crist, A. P. Borsetti, and M. B. Kass, J. Heterocycl. Chem., 1981, 18, 991. U. K. Nadir and V. K. Koul, J. Chem. SOC.,Chem. Commun., 1 9 8 1 , 4 1 7 . I. G. Tishchenko, 0. N. Bubel, and V. A. Konovalov, Khim. Geterorsikl. Soedin.,1981, 952.

208

I. G . Tishchenko, 0. N. Bubel, and V. A. Konovalov, Khim. Gererotsikl. Soedin.,1981, 38.

209

J. Budny and H. Stamm, Arch. Pharm. (Weinheim, Ger.), 1981, 314,657.


47

H( 2 9 11

II

Ph

02N

4 Azirines Preparation. - The reaction of (292) with HN3 in 95% acetic acid at room temperature gave a mixture of cis- and trans(296) in the ratio 40: 60.211 Heating cis(296) to 45-50C gave the azirine (297). The amidoxime (298; R' = 2,4,6-C13C6H2NHC0,R2 = H), prepared from the corresponding nitrile, has been converted into its 0-tosyl derivative (298; R' = same, R2 =COOMe

3

MeOOC

COOMe R CH

'

NOR^ II CNH

( 296)210

A. Hassner, R. D'Costa, A. T. McPhail, and W. Butler, Tetrahedron L e t t . , 1981, 2 2 ,3691. G. L'abbh, J . P. Dekerk, and P. Van Stappen, Bull. SOC.Chim. Belg., 1981, 90, 1073.

'1 1

48


heterocyclic chemistry_vol4

Documents

membered ring systems

related reactions synthesis

ringclosure reactions

azirines preparation

thiirans preparation

elimination reactions

area of heterocyclic

applied chemistry