Copper-Catalyzed Enantioselective Reductive Aldol Reaction of α,β-Unsaturated Carboxylic Acids to Alkyl Aryl Ketones: Silanes as Activator and Transient Protecting Group

The first enantioselective reductive aldol reaction of unprotected alpha,beta-unsaturated carboxylic acids was developed by employing a copper/bisphosphine catalyst. The reaction features in situ protection and activation of an alpha,beta-unsaturated carboxylic acid by a hydrosilane. The copper enolate formed in situ reacts with an alkyl aryl ketone to afford the beta-hydroxy carboxylic acid with excellent enantioselectivity (up to 99 % ee). The corresponding gram-scale reaction with a low catalyst loading and the derivatization of the beta-hydroxy carboxylic acids highlight the practicality of this transformation.

Automated summary

The first enantioselective reductive aldol reaction of unprotected alpha,beta-unsaturated carboxylic acids has been developed using a copper/bisphosphine catalyst. This reaction involves the in situ protection and activation of the carboxylic acid using a hydrosilane. The copper enolate formed in situ reacts with an alkyl aryl ketone to produce beta-hydroxy carboxylic acid with excellent enantioselectivity (up to 99% ee). The gram-scale reaction with low catalyst loading and the derivatization of the beta-hydroxy carboxylic acids highlight the practicality of this transformation.