Copper-Mediated Trifluoromethylation of Benzylic Csp³ -H Bonds

Trifluoromethyl-containing compounds play a significant role in medicinal chemistry, materials and fine chemistry. Although direct C-H trifluoromethylation has been achieved on Csp² -H bonds, direct conversion of Csp³ -H bonds to Csp³ -CF₃ remains challenging. We report herein an efficient protocol for the selective trifluoromethylation of benzylic C-H bonds. This process is mediated by a combination Cu^III -CF₃ species and persulfate salts. A wide range of methylarenes can be selectively trifluoromethylated at the benzylic positions. A combination of experimental and theoretical mechanistic studies suggests that the reaction involves a radical intermediate and a Cu^III -CF₃ species as the CF₃ transfer reagent.