Rainer Mahrwald. Aldol Reactions

Transcription

1 Aldol Reactions

2 Rainer Mahrwald Aldol Reactions

3 Rainer Mahrwald Institute of Chemistry Humboldt University Brook Taylor Str Berlin Germany rainer.mahrwald@rz.hu-berlin.de ISBN: e-isbn: DI: / Springer Dordrecht Heidelberg London New York Library of Congress Control Number: Springer Science+Business Media B.V No part of this work 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, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Cover illustration: Photographs by the author Cover design: WMXDesign GmbH Heidelberg Printed on acid-free paper Springer is part of Springer Science+Business Media (

4 Preface Without doubt, the aldol reaction belongs to the most important methods of stereoselective C-C bond formation processes. ne of the requirements of modern synthetic methods is receiving chiral products in their enantiomerically pure form or pure diastereoisomers. This requirement is not only important for synthetic chemistry but also an imperative for nature. The aldol reaction fits in easily with nature's chemistry. A great number of enzymatic transformations are based on the aldol addition. This fact has been known for a long time and was best expressed with the following statement: Nature, it seems, is an organic chemist having some predilection for aldol condensation. J. W. Cornforth in Perspectives in rganic Chemistry, Todd, A. Ed.; Wiley-Interscience, New York, 1956, page 371. The stormy and meteoric development in the field of aldol additions over the last 20 years has led to a plethora of options in the total syntheses of complicated natural products. This book illustrates the basic principals and the new variants of the classical aldol addition. This includes aldol additions with various metal enolates as well as metal complex-catalyzed, organocatalytic methods and biocatalytic transformations. Moreover, advances made in the development of new aldol methodologies to provide pure stereoisomers are preferentially discussed in this work. The exciting progress being made in organocatalytic aldol additions is of particular interest. This highly active topic of research will continue to develop an increasing number of new concepts of configuration-control. This idea is perfectly illustrated by the following scheme something unimaginable 10 years ago. This scheme brings together organocatalyzed aldol additions and enzymatic transformations, which flow perfectly into the idea of Cornforth mentioned above. v

5 vi Preface fructose + C psicose sorbose tagatose Using four different organocatalysts, an approach to four differently configured ketohexoses is possible today. In nature, on the other hand, a selective and asymmetric access to the described ketohexoses is accomplished by a family of four aldolases. These enzymes selectively target one of the four isomers of the 1,2-diol junction that link dihydroxyacetone with (R)-glyceraldehyde. Thus, an approach is given selectively to one of the four enantiomers by biochemical as well as organocatalytic methods. It is now my pleasure to express my gratitude to my co-workers and my son for countless hours of assistance. Special thanks are also due to Springer UK, especially to Miss Claudia Thieroff and Dr. Sonia jo. Humboldt-University, Berlin Rainer Mahrwald March 2009

6 Contents 1 Introduction Aldol Reactions with Preformed Enolates Lithium Enolates Magnesium Enolates Boron Enolates Titanium Enolates Tin Enolates Catalytic Aldol Additions Lewis Acid-Catalysed Aldol Reactions Titanium Lewis Acids Tin Lewis Acids Boron Lewis Acids Copper Lewis Acids Silver, Palladium and Platinum Lewis Acids Zirconium Lewis Acids Miscellaneous Lewis Acids Lewis Base-Catalysed Aldol Additions Direct Aldol Addition Gold- and Rhodium-Catalysed Aldol Additions Antibody-Catalysed Aldol Addition Enzyme-Catalysed Aldol Addition rganocatalysed Aldol Addition Index vii

7 List of Abbreviations 9-BBN ab Ac Ac ALB Ar BDMS BINAP BINAP BINL Bn Boc BM box BPS Bu Bz c CAB Cbz CD Cp CSA Cy DBU DHA DHAP DIPEA DMS Dppe Et 9-Borabicyclo[3.3.1]nonane Antibody Acetyl Acetic acid Aluminium lithium bis[(s)-binaphthoxide] complex Aryl Benzyldimethylsilyl 2,2 bis(diphenylphosphino) 1,1 binaphthyl 2,2 bis(diphenylphosphinoxide) 1,1 binaphthyl 1,1 -bi-2-naphthol Benzyl tert-butoxycarbonyl Benzyloxymethyl xazoline tert-butyldiphylsilyl Butyl Benzoyl Cyclo Chiral acyloxyboranes Benzyloxycarbonyl Cyclooctadien Cyclopentadienyl Camphorsulfonic acid Cyclohexyl 1,8-Diazabicyclo[5.4.0]undec-7-ene Dihydroxyacetone Dihydroxyacetone phosphate Diisopropylethylamine Dimethyl sulfoxide 2-(Diphenylphosphino)ethyl Ethyl ix

8 x List of Abbreviations FBP FruA FucA GABB HMDS HMG-CoA HMPA HYTRA Ipc LDA LLB Me MEM Mes MM MS NAL NeuA Ph PMB PMP Pr p-ts pybox RhuA RibA TagA TBAF TBAI TBDPS TBS TCE TES Tf TFA THF Thr TIPS TMEDA Fructose-l,6-bisphosphate Fructose-l,6-bisphosphate-aldolase L-Fuculose-1-phosphate-aldolase α-amino-β-hydroxybutanoic acid 1,1,1,3,3,3-Hexamethyldisilazane 3-Hydroxy-3-methylglutaryl-coenzyme A Hexamethylphosphoramide Hydroxy-1,1,2-triphenyl ethyl acetate Isopinocampheyl Lithium-diisopropylamine LLB Lanthanium lithium BINL Methyl 2-Methoxyethoxymethyl Methanesulfonyl Methoxymethyl Molsieve N-Acetylneuraminic acid lyase N-Acetylneuraminic acid aldolase Phenyl p-methoxybenzyl p-methoxyphenyl Propyl p-toluenesulfonic acid Pyridyl bis(oxazoline) L-Rhamnulose-1-phosphate-aldolase 2-Deoxy-D-ribose 5-phosphate aldolase Tagatose-1,6-bisphosphate aldolase Tetrabutylammonium fluoride Tetrabutylammonium iodide t-butyldiphenylsilyl t-butyldimethylsilyl 1,1,1-Trichloroethyl Triethylsilyl Trifluoromethanesulfonate Trifluoroacetic acid Tetrahydrofuran Threonine Triisopropylsilyl N,N,N,N -Tetramethylethylenediamine

9 List of Abbreviations xi TMS Tol-BINAP TPS Tr TRAP Troc Ts Trimethylsilyl 2,2 bis(di-p-toluylphosphino) 1,1 binaphthyl Triphenylsilyl Triphenylmethyl (trityl) (R,R)-2,2 -bis[(s)-1-(dialkylphosphanyl)ethyl]1,1 -biferrocene 2,2,2-Trichloroethoxycarbonyl p-toluenesulfonyl