Direct Arene Trifluoromethylation Enabled by a High‐Valent CuIII−CF3 Compound

• Published in: Angewandte Chemie International Edition Vol. 61; no. 40; pp. e202209029 - n/a
• Main Authors: Zhang, Hao‐Ran, Feng, Cong‐Cong, Chen, Ning, Zhang, Song‐Lin
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 04.10.2022
• Edition: International ed. in English
• Subjects: Arenes; Aromatic compounds; Chemical compounds; C−H Functionalization; Functional groups; High-Valent Copper Species; Organic chemistry; Oxidants; Oxidizing agents; Potassium persulfate; Radical Reaction; Trifluoromethylation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202209029

Direct C−H trifluoromethylation of arenes and heteroarenes poses an important synthetic challenge that is highly desirable. High‐valent CuIII−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 CuIII−CF3 compound is disclosed for the first time. The CuIII−CF3 compound serves CF3 radical and a CuII oxidant by homolytic cleavage of a CuIII−CF3 bond, which engage synergistically in a SEAr type reaction with arenes. The presence of K2S2O8 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 CuIII−CF3 compounds disclosed in this study represents an important progress in organofluorine and CuIII chemistry. A high‐valent CuIII−CF3 compound enables direct C−H trifluoromethylation of arenes for the first time. Thermolysis of CuIII−CF3 bond provides concurrently CF3 radical and a CuII oxidant, which synergistically engage in a SEAr type reaction with arenes. This study establishes an unprecedented fundamental reactivity of CuIII−CF3 compounds, and thus represents a significant progress for CuIII chemistry.