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

A mild and operationally simple C(sp3)−H trifluoromethylation method was developed for unactivated alkanes by utilizing a bench‐stable CuIII complex, bpyCu(CF3)3, as the initiator of the visible‐light photoinduced reaction, the source of a trifluoromethyl radical as a hydrogen atom transfer reagent,...

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Bibliographic Details
Published in:Angewandte Chemie 2021-03, Vol.133 (10), p.5527-5534
Main Authors: Choi, Geunho, Lee, Geun Seok, Park, Beomsoon, Kim, Dongwook, Hong, Soon Hyeok
Format: Article
Language:English
Subjects:
Alkanes
Chemistry
Computer applications
Coordination compounds
copper
Copper compounds
Coupling (molecular)
Crossovers
C−H activation
Hydrogen bonds
late-stage functionalization
Natural products
Organic chemistry
radical–polar crossover
Reagents
trifluoromethylation
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Summary:A mild and operationally simple C(sp3)−H trifluoromethylation method was developed for unactivated alkanes by utilizing a bench‐stable CuIII complex, bpyCu(CF3)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 CF3 radical through photoinduced homolytic cleavage of bpyCu(CF3)3, followed by hydrogen ion from an unactivated C(sp3)−H bond. Comprehensive mechanistic investigations based on a combination of experimental and computational methods suggested that C−CF3 bond formation was enabled by radical–polar crossover and ionic coupling between the resulting carbocation intermediate and the anionic CF3 source. The methylene‐selective reaction can be applied to the direct, late‐stage trifluoromethylation of natural products and bioactive molecules. A photoinduced C(sp3)−H trifluoromethylation reaction of alkanes was developed by employing bpyCu(CF3)3 as a multifunctional reagent: photoinduced‐reaction initiator, precursor of the hydrogen‐atom‐transfer reagent, and trifluoromethyl anion source (see scheme). The operatively simple reaction enables the direct, late‐stage trifluoromethylation of complex molecules under mild reaction conditions.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202012263