Nickel‐Mediated Trifluoromethylation of Phenol Derivatives via Aryl C−O Bond Activation

The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reaction. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes. We report herein a practical nickel-mediated trifluoromethylation of phenol derivatives with readily available trimethyl(trifluoromethyl)silane (TMSCF3 ). The strategy relies on PMe3 -promoted oxidative addition and transmetalation, and CCl 3 CN-induced reductive elimination. The broad utility of this transformation has been demonstrated through the direct incorporation of trifluoromethyl to aromatic and heteroaromatic systems including bio-relevant compounds.