Copper-Catalyzed Diastereoselective and Enantioselective α-C–H Allenylation of Alkylamines

Abstract

Herein, we report a diastereoselective and enantioselective α-allenylation of N-α-cyanoarylidene alkylamines with propargylic carbonates via a sequential copper-catalyzed imine propargylation and aza-Cope rearrangement process. This method features broad substrate scope with respect to both reaction partners, thereby establishing an unprecedented protocol for the efficient asymmetric synthesis of chiral amines containing both central and axial chirality from readily accessible alkylamines and propargylic carbonates. Additionally, we demonstrated that these chiral α-allenyl amines could be readily transformed into a diverse range of chiral amine derivatives. Mechanistic studies revealed that the simultaneous coordination and π–π interaction between the cyano group and dicopper-allenylidene complex played decisive roles for the induction of the chemoselectivity, diastereoselectivity, and enantioselectivity during imine propargylation. The subsequent aza-Cope rearrangement proceeded with an efficient central-to-axial chirality transfer to generate the chiral allene motif.