PROTECTIVE GROUPS IN ORGANIC CHEMISTRY

Transcription

1 PROTECTIVE GROUPS IN ORGANIC CHEMISTRY

2 PROTECTIVE GROUPS IN ORGANIC CHEMISTRY Edited by J. F. W. McOmie School of Chemistry University of Bristol Bristol BS81 TS PLENUM PRESS-LONDON AND NEW YORK-1973

3 First Printing - May 1973 Second Printing - April 1976 Library of Congress Catalog Card Number: ISBN-13: e-isbn-13: DOl: / Copyright 1973 by Plenum Publishing Company Ltd Softcover reprint of the hardcover 18t edition 1973 Plenum Publishing Company Ltd Davis House 8 Scrubs Lane Harlesden London NWI0 6SE Telephone u.s. Edition published by Plenum Publishing Corporation 227 West 17th Street New York, New York All Rights Reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from the Publisher

4 Preface During the past decade there has been a great increase in the use of protective groups, especially in the synthesis of large and complex organic molecules. Perhaps the greatest activity has been in the peptide field where such triumphs as the total synthesis of insulin and of bovine ribonuclease (molecular weight 13,700) have been achieved. Correspondingly, more protective groups have been devised for the protection of amino and imino groups than for any other functional group. There are many reviews and books on the synthesis of pep tides but there has been no general survey of protective groups since my own review in At that time the five main methods for the removal of protective groups involved acid or base hydrolysis, reduction, oxidation, or thermal elimination reactions. Recent advances include the use of photo-sensitive and metalion sensitive protective groups, and the attachment of functional groups to reactive polymers as a method of protection during the solid-phase synthesis of peptides and polynucleotides. Another interesting development is the design and use of protective groups with a built-in 'safety-catch', which can be 'released' by a specific chemical reaction, so that an otherwise stable bond is made labile at the appropriate moment thereby allowing the protective group to be removed under very mild conditions. 2 My own interest in protective groups dates from 1944 when, as a student, I gave two lectures on the subject and produced an 11 page review including 70 references. My second review (1963) occupied 104 pages and included about 600 references. The present book contains about 1600 references (after allowing for some duplication in different chapters). Unfortunately there is no systematic way of searching the 1 Advances in Organic Chemistry, 3, 191 (1963). 2 J. RUDINGER, Pure Appl. Chem., 7,335 (1963). v

5 vi PREFACE literature for references to protective groups but, with the object of writing a book one day, I have steadily collected references by regularly scanning current periodicals. However, the task of collating the references and writing a book single-handed became more and more daunting. I therefore gladly accepted the invitation of the Plenum Press to edit a book with chapters written by a group of experts who have made frequent use of protective groups in their research work. The chapters are based partly on my own collection of references and partly on the numerous other references collected separately by the contributors. The aims of the book are twofold: firstly to inform readers about the various methods of protection of all functional groups for which protective groups have been devised and secondly, to help them to choose the most suitable protective group(s) for any particular series of reactions. The treatment of each topic is not intended to be exhaustive, thus many protective groups which have been suggested, but which have found little use, have been omitted. Furthermore the chapter on the protection of amino groups has been restricted mainly to applications other than in the synthesis of pep tides since this topic has been adequately treated in other books and reviews. The contributors were given a free hand with regard to the selection of material and the method of treatment. The presentation therefore varies somewhat from chapter to chapter. In general the length of each chapter reflects the relative importance and current interest in the synthesis of molecules containing the functional group under discussion. One of the most important current problems is the synthesis of cysteine- and cystine-containing peptides. Despite the very great progress which has been made recently, the topic has not been reviewed since For this reason the protection of thiol groups has been given a much fuller treatment than that of the other functional groups. John F. W. McOmie

6 Contributors J. W. Barton School of Chemistry, University of Bristol, Bristol BS8 1 TS, England. F. Eckstein Max-Planck-Institut fur Experimentelle Medizin, Abteilung Chemie, Hermann Rein-Strasse 3, 3400 Gottingen, Germany. E. Haslam Department of Chemistry, University of Sheffield, Sheffield, England. R. G. Hiskey Department of Chemistry, The University of North Carolina, Chapel Hill, North Carolina 27514, U.S.A. H. J. E. Loewenthal Department of Chemistry, Israel Institute of Technology, Haifa, Israel. J. F. W. McOmie School of Chemistry, University of Bristol, Bristol BS8 1 TS, England. V. R. Rao Department of Chemistry, The University of North Carolina, Chapel Hill, North Carolina 27514, U.S.A. C. B. Reese University Chemical Laboratory, Lensfield Road, Cambridge CB2 lew, England. W. G. Rhodes Department of Chemistry, The University of North Carolina, Chapel Hill, North Carolina 27514, U.S.A. D. R. M. Walton The School of Molecular Sciences, University of Sussex, Falmer, Brighton BN 1 9QJ, Sussex, England. D. Y. Young The School of Molecular Sciences, University of Sussex, Falmer, Brighton BN 1 9QJ, Sussex, England. vii

7 Abbreviations Ac acetyl Acm = acetamidomethyl AOe t-amyloxycarbonyl ibm isobutyloxymethyl BhOe = benzhydryloxycarbonyl BMD = bismethylenedioxy BOe = t-butyloxycarbonyl Btm = benzylthiomethyl Bz = benzoyl (Bz = benzene in Tables ) Bzh benzhydryl (diphenylmethyl) BzI = benzyl DEA diethylamine Dec = N,N' -dicyclohexylcarbodi-imide Dce = diethoxycarbonylethyl DMF = N,N-dimethylformamide DMSO = dimethylsulphoxide DNP = 2,4-dinitrophenylhydrazine Ec = ethylcarbamoyl For = formyl HMPT = hexamethylphosphoric triamide MBzI = p-methoxybenzyl NMP = N-methylpyrrolidone NPS = o-nitrophenylsulphenyl Phth = phthaloyl Py pyridine RT = room temperature sez = semicarbazide TF A = trifluoroacetic acid THF = tetrahydrofuran Thp = 2-tetrahydropyranyl TMEDA = N,N,N',N'-tetramethylethylenediamine Tr trityl (triphenylmethyl) Ts = p-toluenesulphonyl (tosyl) ix

8 ABBREVIATIONS TsOH p-toluenesulphonic acid WSC = l-ethyl-3( 3-N,N-dimethylaminopropyl)carbodi-imide hydrochloride Z benzyloxycarbonyl Z(N0 2 ) = p-nitrobenzyloxycarbonyl

9 Contents Preface Contributors Abbreviations IX 1 Protection of C-H Bonds D. R. M. Walton 1 2 Protection of N-H Bonds and NR3 ]. W. Barton 43 3 Protection of Alcholic Hydroxyl Groups and Glycols Systems C. B. Reese 95 4 Protection of Phenols and Catechols E. Haslam Protection of Carboxyl Groups E. Haslam Protection of Phosphoric and Related Acids F. Eckstein Protection of Thiols R. G. Hiskey, V. R. Rao, and W. G. Rhodes Protection of Carbon-Carbon Multiple Bonds D. W. Young Protection of Aldehydes and Ketones H. ]. E. Loewenthal Protection of Miscellaneous Groups ]. F. W. McOmie 403 Index 415 v Vll xi