Organocatalytic asymmetric α-C–H functionalization of alkyl amines

Abstract

Catalytic enantioselective α-C–H functionalization of widely available achiral alkyl amines could provide an ideal synthetic approach towards chiral amines. However, the inert nature of the α-C–H of alkyl amines renders their activation as carbanionic nucleophiles for catalytic asymmetric reactions an important yet unmet challenge. Here we describe how N-arylidene-protected alkyl amines could be activated as carbanions for asymmetric conjugate addition and the Mannich reaction. These results represent an intriguing and generally useful approach to the synthesis of chiral α,α-dialkyl amines. More importantly, they highlight the enormous potential of N-arylidene-protected amines as readily available and widely applicable synthons for the asymmetric synthesis of chiral amines. The catalytic activation of alkyl amines as α-nitrogen carbanions is challenging. Now the activation of N-arylidene-protected alkyl amines as carbanions by chiral ammonium organocatalysis for asymmetric conjugate addition and the Mannich reaction is reported, affording chiral α,α-dialkyl amines.