Enantioselective C-H bond functionalization triggered by radical trifluoromethylation of unactivated alkene

Abstract

An asymmetric unactivated alkene/C-H bond difunctionalization reaction for the concomitant construction of C-CF3 and C-O bonds was realized by using a Cu/Brønsted acid cooperative catalytic system, thus providing facile access to valuable chiral CF3-containing N,O-aminals with excellent regio-, chemo-, and enantioselectivity. Mechanistic studies revealed that this reaction may proceed by an unprecedented 1,5-hydride shift involving activation of unactivated alkenes and a radical trifluoromethylation to initiate subsequent enantioselective functionalization of C-H bonds. Control experiments also suggested that chiral Brønsted acid plays multiple roles and not only controls the stereoselectivity but also increases the reaction rate through activation of Togni's reagent.

Keywords: CH activation; copper; enantioselectivity; radical chemistry; reaction mechanisms.