Electrochemical Trifluoromethoxylation of (Hetero)aromatics with a Trifluoromethyl Source and Oxygen

Trifluoromethoxylated aromatics (ArOCF3) are valuable structural motifs in the area of drug discovery due to the enhancement of their desired physicochemical properties upon the introduction of the trifluoromethoxy group (CF3O). Although significant progress has been made recently in the introduction of CF3O group into aromatics, current methods either require the use of expensive trifluoromethoxylation reagents or require harsh reaction conditions. We present a conceptually new and operationally simple protocol for the direct C−H trifluoromethoxylation of (hetero)aromatics by the combination of the readily available trifluoromethylating reagent and oxygen under electrochemical reaction conditions. This reaction proceeds through the initial generation of CF3 radical followed by conversion to CF3O radical, addition to (hetero)aromatics and rearomatization. The utility of this electrochemical trifluoromethoxylation is illustrated by the direct incorporation of CF3O group into a variety of (hetero)aromatics as well as bio‐relevant molecules. A conceptually new trifluoromethoxylation reaction through the combination of readily available trifluoromethylating reagent and oxygen under electrochemical conditions was developed. The synthetic utility of this new protocol is illustrated by the C−H trifluoromethoxylation of (hetero)arenes and biorelevant molecules.