Tandem Iminium/Copper Catalysis: Highly Enantioselective Synthesis of ,-Disubstituted Aldehydes

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 ,-disubstituted aldehydes to be synthesized with good yields in one-pot fashion. The -substitution took place through iminium-catalyzed Michael addition of nitromethane or diethyl malonate to the ,-unsaturated aldehydes, followed by copper-assisted addition of TEMPO (2,2,6,6-tetramethylpiperidin-1-yloxyl) at the aldehyde -position. An iminium/copper-catalyzed tandem addition product was converted into a 3,4,5-trisubstituted piperidine for X-ray crystallographic analysis.