Copper‐Mediated Trifluoromethylation of Benzylic Csp³−H Bonds.

Paeth, Matthew; Carson, William; Luo, Jheng‐Hua; Tierney, David; Cao, Zhi; Cheng, Mu‐Jeng; Liu, Wei

Abstract: 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 CuIII−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 CuIII−CF3 species as the CF3 transfer reagent.

COPPER compounds; METHYLATION; BENZYLIC group; HYDROGEN bonding; PHARMACEUTICAL chemistry; PERSULFATES

Chemistry - A European Journal, 2018, Vol 24, Issue 45, p11559

0947-6539

Academic Journal

10.1002/chem.201802766