Organocatalytic Asymmetric α-C-H Functionalization of Alkyl Amines

Catalytic enantioselective α-C–H functionalization of achiral amines could provide an ideal synthetic approach toward chiral amines. The alkyl amines constitute the most diverse and synthetically important class of achiral amines. However, the inert nature of the α-C–H of alkyl amines renders the activation of alkyl amines as carbanionic nucleophiles for catalytic asymmetric reactions an important yet unmet challenge. We describe here that N-arylidene alkyl amines could be activated as carbanions for asymmetric conjugate addition and Mannich reaction. In their own right, these results represent a new and generally useful approach to the synthesis of chiral α, α-dialkyl amines. More importantly, they highlight the enormous potential of N-arylidene amines as readily available and widely applicable synthons for the asymmetric synthesis of chiral amines.