Enantioselective Organocatalytic Electrochemical α-Chlorination of Aldehydes

Abstract

The enantioselective organocatalytic α-chlorination of aldehydes using electrochemistry to activate the enamine intermediate through SOMO strategy was investigated. Based on mechanistic insights, an improved procedure was developed, that directly employs CuCl2 in the electrochemical reaction. Under the optimized setup (potentiostatic condition of 1 V, glassy-carbon electrodes, in a 0.2 M solution of LiClO4), in the presence of catalytic amounts of a chiral imidazolidinone as organocatalyst, the aldehyde reacts with copper chloride (II) and leads to the formation of the corresponding α-chlorinated aldehydes in high yields and high enantioselectivities (up to 97% ee). Thanks to the electrochemistry approach, stoichiometric amounts of chemical oxidants were successfully replaced by electrons, enabling a more sustainable and efficient, catalytic stereoselective reaction. In addition, the transformation was successfully translated to a continuous flow process, which significantly enhanced productivity and reduced the reaction time to 1.73 minutes only, and that was performed also on gram scale