Enantioselective Direct Mannich Reactions of Cyclic β-Ketoesters Catalyzed by Chiral Phosphine via a Novel Dual-Reagent Catalysis

A combination of an amino acid derived chiral phosphine catalyst and methyl acrylate efficiently catalyzed the direct Mannich reaction of cyclic beta-ketoesters and N-Boc-aldimines. The dual-reagent catalysis was presumed to function through the formation of a zwitterion, which catalyzed the reaction with excellent stereocontrol via a hydrogen-bonding assisted chiral ion-pair pathway.