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Direct Arene Trifluoromethylation Enabled by a High‐Valent Cu<sup>III</sup>−CF<sub>3</sub>Compound

Haoran Zhang, Cong‐Cong Feng, Ning Chen, Songlin Zhang

2022Angewandte Chemie International Edition29 citationsDOI

Abstract

Abstract Direct C−H trifluoromethylation of arenes and heteroarenes poses an important synthetic challenge that is highly desirable. High‐valent Cu III −CF 3 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 −CF 3 compound is disclosed for the first time. The Cu III −CF 3 compound serves CF 3 radical and a Cu II oxidant by homolytic cleavage of a Cu III −CF 3 bond, which engage synergistically in a S E Ar type reaction with arenes. The presence of K 2 S 2 O 8 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 −CF 3 compounds disclosed in this study represents an important progress in organofluorine and Cu III chemistry.

Topics & Concepts

TrifluoromethylationChemistryHomolysisReactivity (psychology)Bond cleavageMedicinal chemistryPhotochemistryCombinatorial chemistryOrganic chemistryRadicalCatalysisTrifluoromethylAlkylPathologyAlternative medicineMedicineFluorine in Organic ChemistryInorganic Fluorides and Related CompoundsCatalytic C–H Functionalization Methods
Direct Arene Trifluoromethylation Enabled by a High‐Valent Cu<sup>III</sup>−CF<sub>3</sub>Compound | Litcius