Tandem Iminium/Copper Catalysis: Highly Enantioselective Synthesis of α,β‐Disubstituted Aldehydes

Abstract

Abstract With the goal of synthesizing biologically and synthetically valuable products under environmentally benign and economic conditions, an asymmetric organocatalytic reaction was combined with a copper catalytic reaction. This iminium/copper catalysis allowed highly optically active α,β‐disubstituted aldehydes to be synthesized with good yields in one‐pot fashion. The β‐substitution took place through iminium‐catalyzed Michael addition of nitromethane or diethyl malonate to the α,β‐unsaturated aldehydes, followed by copper‐assisted addition of TEMPO (2,2,6,6‐tetramethylpiperidin‐1‐yloxyl) at the aldehyde α‐position. An iminium/copper‐catalyzed tandem addition product was converted into a 3,4,5‐trisubstituted piperidine for X‐ray crystallographic analysis.