REDUCTIONS IN ORGANIC CHEMISTRY MILOS HUDLICKY Professor of Chemistry Virginia Polytechnic Institute and State University USA ELLIS HORWOOD LIMITED Publishers • Chichester Halsted Press: a division of JOHN WILEY & SONS New York • Chichester • Brisbane • Toronto First published in 1984 by ELLIS HORWOOD LIMITED Market Cross House, Cooper Street, Chichester, West Sussex, P019 lEB, England The publisher's colophon is reproduced from James Gillison's drawing of the ancient Market Cross, Chichester. Distributors: Australia, New Zealand, South-east Asia: Jacaranda-Wiley Ltd., Jacaranda Press, JOHN WILEY & SONS INC., G.P.O. Box 859, Brisbane, Queensland 40001 , Australia Canada: JOHN WILEY & SONS CANADA LIMITED 22 Worcester Road, Rexdale, Ontario, Canada. Europe, Africa: JOHN WILEY & SONS LIMITED Baffins Lane, Chichester, West Sussex, England, North and South America and the rest of the world: Halsted Press: a division of JOHN WILEY & SONS 605 Third Avenue, New York, N.Y. 10016, U.S.A. ©1984 M. Hudlicky /Ellis Horwood Umited British Library Cataloguing in Publication Data Hudlicky, Milog Reductions in organic chemistry. - (Ellis Horwood series in chemical science) 1. Reduction, Chemical 2. Chemistry, Organic I. Title 547’.23 QD281.R4 Library of Congress Card No. 84-3768 ISBN 0-85312-345-4 (Ellis Horwood Limited) ISBN 0-470-20018-9 (Halsted Press) Printed in Great Britain by Butler <Sc Tanner, Frome, Somerset. COPYRIGHT NOTICE - All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the permission of Ellis Horwood Limited, Market Cross House, Cooper Street, Chichester, West Sussex, England. To whom it may concern Sic ait, et dicto citius tumida aequora placat collectasque fugat nubes solemque REDUCIT. Publius Vergilius Maro, Aeneis, I, 142-3 All springs REDUCE their currents to mine eyes. William Shakespeare, The Tragedy ofKing Richard the Third, II, 2, 68-70. 2311 TABLE OF CONTENTS PREFACE xiii INTRODUCTION xv CATEGORIES OF REDUCTION 1 Catalytic Hydrogenation 1 Mechanism and Stereochemistry of Catalytic Hydrogenation 4 Catalysts 5 Platinum 5 Palladium 7 Rhodium, Ruthenium and Rhenium 7 Nickel 8 Other Catalysts 9 Activators and Deactivators of Catalysts 10 Effects of the Amount of Catalyst, Solvent, Temperature and Pres- 1 sure Carrying out Catalytic Hydrogenation 1 Catalytic Transfer of Hydrogen 13 Reduction with Hydrides and Complex Hydrides 1 Mechanism, Stoichiometry and Stereochemistry of Reductions with 17 Hydrides Handling of Hydrides and Complex Hydrides 20 Electroreduction and Reductions with Metals 22 Mechanism and Stereochemistry 23 Electrolytic Reduction 24 Reductions with Alkali Metals 25 Reductions with Magnesium 27 Reductions with Aluminum 27 Reductions with Zinc 28 Reductions with Iron 29 Reductions with Tin 29 Reductions with Metal Compounds 30 Reductions with non-Metal Compounds 31 Reductions with Hydrogen Iodide 3 Reductions with Sulfur Compounds 32 31 viii Table of Contents Reductions with Diimide and Hydrazine 33 Reductions with Phosphorus Compounds 34 Reductions with Organic Compounds 35 THE REDUCTION OF SPECIFIC TYPES OF ORGANIC COMPOUNDS Reduction of Alkanes and Cycloalkanes 39 Reduction of Alkenes and Cycloalkenes 39 Reduction of Dienes and Polyenes 42 Reduction of Alkynes and Cycloalkynes 43 Reduction of Carbocyclic Aromatics 46 Reduction of Heterocyclic Aromatics 53 Reduction of Halogen Derivatives of Hydrocarbons and Basic Het- 62 erocycles Reduction of Haloalkanes and Halocycloalkanes 63 Reduction of Haloalkenes, Halocycloakenes and Haloalkynes 66 Reduction of Haloaromatics 67 Reduction of Nitro, Nitroso, Diazo and Azido Derivatives of Hydro- 69 carbons and Basic Heterocycles Reduction of Alcohols and Phenols and their Substitution Derivatives 76 Reduction of Ethers and their Derivatives 8 Reduction of Epoxides, Peroxides and Ozonides 83 Reduction of Sulfur Compounds (Except Sulfur Derivatives of Al- 86 dehydes. Ketones and Acids) Reduction of Amines and their Derivatives 92 Reduction of Aldehydes 96 Reduction of Aliphatic Aldehydes 96 Reduction of Aromatic Aldehydes 99 Reduction of Derivatives of Aldehydes 103 Reduction of Ketones 107 Reduction of Aliphatic Ketones 107 Reduction of Aromatic Ketones 109 Reduction of Cyclic Ketones 1 1 Reduction of Unsaturated Ketones 1 19 Reduction of Derivatives of Ketones 1 22 Reduction of Substitution Derivatives of Ketones 122 Reduction of Hydroxy and Amino Ketones 125 Reduction of Diketones and Quinones 126 Reduction of Ketals and Thioketals 1 30 Reduction of Ketimines, Ketoximes and Hydrazones 1 32 Reductive Alkylation (Reductive Amination) 134 Reduction of Carboxylic Acids 136 Reduction of Aliphatic Carboxylic Acids 137 Reduction of Aromatic Carboxylic Acids 139 Reduction of Carboxylic Acids Containing Substituents or Other 141 Functional Groups Table of Contents IX Reduction of Acyl Chlorides 144 Reduction of Acid Anhydrides 146 Reduction of Esters and Lactones of Carboxylic Acids 147 Reduction of Unsaturated Esters 1 56 Reduction of Substitution Derivatives of Esters 1 59 Reduction of Hydroxy Esters, Amino Esters, Keto Esters, Oximino 160 Esters and Ester Acids Reduction of Ortho Esters, Thio Esters and Dithio Esters 163 Reduction of Amides, Lactams and Imides 164 Reduction of Amides and Lactams Containing Double Bonds and 169 Reducible Functional Groups Reductive Amination with Carboxylic Acids 171 Reduction of Amidines, Thioamides, Imidoyl Chlorides and Hydra- 171 zides Reduction of Nitriles 1 73 Reduction of Nitriles Containing Double Bonds and Other Redu- 175 cible Functions Reduction of Organometallic Compounds 176 CORRELATION TABLES 1 77 PROCEDURES 1. Catalytic Hydrogenation under Atmospheric Pressure 201 2. Catalytic Hydrogenation with Hydrogen Generated from Sodium 202 Borohydride Hydrogenation ex situ Hydrogenation in situ 3. Catalytic Hydrogenation under Elevated Pressure 203 4. Preparationof Palladium Catalyst 205 5. Reduction with Raney Nickel 205 Hydrogenolysis of Halogens 6. Desulfurization with Raney Nickel 205 Preparation of Aldehydes from Thiol Esters Deactivation of Raney Nickel 7. Preparation of Nickel Catalyst 205 8. Homogeneous Hydrogenation 206 Preparation of the Catalyst Tris(triphenylphosphine)rhodium Chloride Reduction of Unsaturated Aldehydes to Saturated Aldehydes 9. Preparation of Lindlar Catalyst 206 10. Reduction by Catalytic Transfer of Hydrogen 206 1 1 . Preparation of Alane (Aluminum Hydride) 206 12. Preparation of Lithium Tri-rerr-butoxyaluminohydride 207 13. Analysis of Hydrides and Complex Hydrides 207 14. Reduction with Lithium Aluminum Hydride 207 Acidic Quenching. Reduction of Aldehydes and Ketones 31 X Table of Contents 15. Reduction with Lithium Aluminum Hydride 207 Alkaline Quenching. Reduction of Nitriles 16. Reduction with Lithium Tris-/er/-butoxyaluminohydride 208 Reduction of Acyl Chlorides to Aldehydes 17. Reduction with Alane (Aluminum Hydride) /n 5//W 208 Reduction of Nitriles to Amines 18. Reduction with Diisobutylalane 208 Reduction of a,P-Unsaturated Esters to Unsaturated Alcohols 19. Reduction with Borane 209 Reduction of Carboxylic Acids to Alcohols 20. Reduction with Borane in situ 209 Reduction of Esters to Alcohols 21. Reduction with Sodium Borohydride 209 Reduction of Ketones to Alcohols 22. Reduction with Sodium Cyanoborohydride 210 Reduction of Enamines to Amines 23. Reduction with Triethylsilane 210 Ionic Reduction of Alkenes Capable of Forming Carbonium Ions 24. Reduction with Stannanes 210 Hydrogenolysis of Alkyl Halides 25. Electrolytic Reduction 210 Partial Reduction of Aromatic Rings 26. Reduction with Sodium (Birch Reduction) 21 Partial Reduction of Aromatic Rings 27. Reduction with Sodium 211 Acyloin Condensation of Esters 28. Reduction with Sodium Naphthalene 212 Cleavage of Sulfonamides to Amines 29. Reduction with Sodium Amalgam 212 Preparation of Sodium Amalgam Reduction of a,P-Unsaturated Acids 30. Reduction with Aluminum Amalgam 212 Reduction of Aliphatic-Aromatic Ketones to Pinacols 3 1 . Reduction with Zinc (Clemmensen Reduction) 2 1 Reduction of Ketones to Hydrocarbons 32. Reduction with Zinc in Alkaline Solution 213 Reduction of Nitro Compounds to Hydrazo Compounds 33. Reduction with Zinc and Sodium Iodide 213 Reductive Cleavage of Sulfonates to Hydrocarbons 34. Reduction with Iron 213 Partial Reduction of Dinitro Compounds 35. Reduction with Tin 214 Preparation of Tin Amalgam Reduction of Quinones to Hydroquinones Table of Contents XI 36. Reduction with Stannous Chloride 214 Deoxygenation of Sulfoxides 37. Reduction with Chromous Chloride 214 Preparation of Chromous Chloride Reduction of lodo Ketones to Ketones 38. Reduction with Titanium Trichloride 214 Reduction of 2,4-Dinitrobenzaldehyde to 2-Amino-4-nitro- benzaldehyde 39. Reduction with Low-Valence Titanium 215 Intermolecular Reductive Coupling of Carbonyl Compounds 40. Reduction with Vanadous Chloride 215 Preparation of Vanadous Chloride Reduction of Azides to Amines 4 1 . Reduction with Hydriodic Acid 215 Reduction of Acyloins to Ketones 42. Reduction with Hydrogen Sulfide 216 Reduction of a-Diketones to Acyloins and Ketones 43. Reduction with Sodium Sulfite 216 Partial Reduction of Geminal Polyhalides 44. Reduction with Sodium Hydrosulfite (Dithionate) 216 Reduction of Nitro Compounds to Amino Compounds 45. Reduction with Hydrazine 216 WolfT-Kizhner Reductions of Ketones to Hydrocarbons 46. Reduction with Hypophosphorous Acid 217 Replacement of Aromatic Primary Amino