Highly enantioselective aldol reactions using N-arylprolinamides with enhanced acidity and double H-bonding potential

We have designed and synthesized N-arylprolinamides 7-10 with a potential to involve in the binding of electrophilic aldehydes via two N-H center dot center dot center dot O hydrogen bonds for application in organocatalytic aldol reactions. The catalyst 10 is shown to afford aldol products in excellent isolated yields with very high diastereo- and enantioselectivites. In addition to enhanced acidity and double hydrogen bonding, the stacking interactions of the p-toluenesulfonyl ring in 10 with the electrophilic aldehyde are proposed to stabilize the transition state. (C) 2009 Elsevier Ltd. All rights reserved.