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 Csp(2)-H bonds, direct conversion of Csp(3)-H bonds to Csp(3)-CF3 remains challenging. We report herein an efficient protocol for the selective tri-fluoromethylation 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 tri-fluoromethylated 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.