Direct Arene Trifluoromethylation Enabled by a High-Valent CuIII -CF3 Compound

Abstract

Direct C-H trifluoromethylation of arenes and heteroarenes poses an important synthetic challenge that is highly desirable. High-valent Cu^III -CF₃ compounds have often been invoked in copper-mediated trifluoromethylation reactions, but the fundamental reactivity toward arenes is elusive. Herein, direct C-H trifluoromethylation of arenes/heteroarenes by a high-valent Cu^III -CF₃ compound is disclosed for the first time. The Cu^III -CF₃ compound serves CF₃ radical and a Cu^II oxidant by homolytic cleavage of a Cu^III -CF₃ bond, which engage synergistically in a S_E Ar type reaction with arenes. The presence of K₂ S₂ O₈ co-oxidant can significantly improve the reaction yields. This reaction shows good efficiency, broad functional group tolerance, and the potential in late-stage functionalization. The reactivity of high-valent Cu^III -CF₃ compounds disclosed in this study represents an important progress in organofluorine and Cu^III chemistry.

Keywords: Arenes; C−H Functionalization; High-Valent Copper Species; Radical Reaction; Trifluoromethylation.