Auxiliary-controlled regiodivergent NiH-catalyzed gem-difluoroallylation of alkenyl amines via defluorinative olefin cross-coupling

Abstract

A NiH-catalyzed migratory and non-migratory gem-difluoroallylation reaction of alkenyl amines with trifluoromethyl alkenes has been developed by judicious choice of directing groups. The reaction incorporates gem-difluoroalkene motifs into aliphatic amine derivatives at multiple positions with high levels of chemo- and regioselectivity. This practical protocol features wide substrate scope, great functional group tolerance, and easy removal of the directing groups. Notably, products from these reactions possess versatile chemical reactivity because of the secondary amide and difluoroalkene functionalities, thus building a platform for synthesizing new linear and cyclic fluoro-containing amines, which would benefit drug discovery.