Electrochemical aminotrifluoromethylation of unactivated alkenes with Langlois’ reagent as the CF3 source

Abstract

The straightforward synthesis of trifluoromethylated N-heterocycles from readily available amines has attracted significant interest from the academic community. Herein, we established a general and sustainable electrochemical approach for synthesizing various trifluoromethylated pyrrolidines. By utilizing the inexpensive and easily accessible Langlois’ reagent as the source of CF₃, a broad range of unactivated alkenes was transformed into corresponding heterocycles through a trifluoromethylation/cyclization cascade process in 43–80% yields. Mechanistic investigations indicated that this reaction may be initiated with the formation of a CF₃ radical through anodic single-electron transfer oxidation. The great benefit of this protocol is avoiding the use of metal catalysts and oxidants. More importantly, the late-stage modification of celecoxib and large-scale synthesis have revealed exceptionally beneficial and potential applications of the present method.