Copper-catalyzed enantioselective three-component radical 1,4-perfluoroalkylamination of 1,3-dienes

Abstract

Catalytic enantioselective three-component aminative difunctionalization of readily available 1,3-dienes offers a straightforward methodology to fast access significant and complex chiral allylic amines. Nevertheless, compared to the widely studied two-component reactions, the three-component reactions, especially using anilines—very common bulk feedstock chemicals as aminating reagents are underdeveloped. More importantly, the limited examples of enantioselective three-component aminative difunctionalization of 1,3-dienes with anilines only showed 1,2-selectivity; and the corresponding 1,4-regioselectivity remains unknown. Here, we report a copper-catalyzed enantioselective radical three-component 1,4-perfluoroalkylamination of 1,3-dienes with anilines and perfluoroalkyl reagents, efficiently providing an array of valuable perfluoroalkylated chiral allylic amines in good to excellent yields with excellent enantioselectivity. Mechanistic investigations, including controlled experiments and DFT studies, elucidate the origination of the regioselectivity and enantioselectivity, and suggest a radical reaction pathway involving an asymmetric cross-coupling between allylic radical and copper-stabilized nitrogen radical species to construct C–N bond enantioselectively.