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Asymmetric Direct Aldol Reaction of α‐Keto Esters and Acetone Catalyzed by Bifunctional Organocatalysts
Author(s) -
Wang Fei,
Xiong Yan,
Liu Xiaohua,
Feng Xiaoming
Publication year - 2007
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200700285
Subject(s) - chemistry , bifunctional , aldol reaction , acetone , catalysis , enantioselective synthesis , reagent , organocatalysis , organic chemistry , medicinal chemistry
A type of C 2 ‐symmetrical bisprolinamide has been developed for the asymmetric aldol reaction between acetone and α‐keto esters, which furnishes the chiral tertiary alcohols in high yields (up to 99 %) with high enantioselectivities (up to 94 % ee ). Aliphatic, heteroaromatic and aromatic α‐keto esters including those with electron‐donating or electron‐withdrawing group substituents were found to be suitable substrates in the presence of bisprolinamide 2a (15 mol %) and AcOH (150 mol %) with reaction times of no more than 16 h. This process is easily manipulated with readily available reagents. The geometry of catalyst 2a was fully optimized at the B3LYP/6‐31G(d) level with all electron calculations. Based on the experimental investigations and DFT calculations of catalyst 2a , a possible transition state A has been proposed to explain the origin of the activation and asymmetric inductivity.