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Direct C(sp 3 )−H Trifluoromethylation of Unactivated Alkanes Enabled by Multifunctional Trifluoromethyl Copper Complexes
Author(s) -
Choi Geunho,
Lee Geun Seok,
Park Beomsoon,
Kim Dongwook,
Hong Soon Hyeok
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202012263
Subject(s) - trifluoromethylation , chemistry , trifluoromethyl , electrophile , carbocation , bond cleavage , hydrogen atom abstraction , photochemistry , reagent , methylene , hydrogen atom , medicinal chemistry , radical , organic chemistry , alkyl , catalysis
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.