Asymmetric Direct Aldol Reaction of α-Keto Esters and Acetone Catalyzed by Bifunctional Organocatalysts

✍ Scribed by Fei Wang; Yan Xiong; Xiaohua Liu; Xiaoming Feng

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 312 KB
• Volume: 349
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/adsc.200700285

✦ Synopsis

Abstract

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.