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

Abstract

AbstractA type of C2‐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.