Direct C(sp3)−H Trifluoromethylation of Unactivated Alkanes Enabled by Multifunctional Trifluoromethyl Copper Complexes

Abstract A mild and operationally simple C(sp 3 )−H trifluoromethylation method was developed for unactivated alkanes by utilizing a bench‐stable Cu III complex, bpyCu(CF 3 ) 3 , as the initiator of the visible‐light photoinduced reaction, the source of a trifluoromethyl radical as a hydrogen atom transfer reagent, and the source of a trifluoromethyl anion for functionalization. The reaction was initiated by the generation of reactive electrophilic carbon‐centered CF 3 radical through photoinduced homolytic cleavage of bpyCu(CF 3 ) 3 , followed by hydrogen abstraction from an unactivated C(sp 3 )−H bond. Comprehensive mechanistic investigations based on a combination of experimental and computational methods suggested that C−CF 3 bond formation was enabled by radical–polar crossover and ionic coupling between the resulting carbocation intermediate and the anionic CF 3 source. The methylene‐selective reaction can be applied to the direct, late‐stage trifluoromethylation of natural products and bioactive molecules.