Silver-Mediated Oxidative Trifluoromethylation of Phenols: Direct Synthesis of Aryl Trifluoromethyl Ethers

Aryl trifluoromethyl ethers (ArOCF3) are prevalent in pharmaceuticals, agrochemicals, and materials. However, methods for the general and efficient synthesis of these compounds are extremely underdeveloped and limited. Herein, we describe a highly efficient and general procedure for the direct O-trifluoromethylation of unprotected phenols through a silver-mediated cross-coupling reaction using CF3SiMe3 as the CF3 source and exogenous oxidants. This novel oxidative trifluoromethylation provides access to a wide range of aryl trifluoromethyl ethers from simple phenols. The mild process was also applied to the late-stage trifluoromethylation of a medicinally relevant compound.