Electronically Ambivalent Hydrodefluorination of Aryl‐CF3 groups enabled by Electrochemical Deep‐Reduction on a Ni Cathode

The Ar‐CF2H moiety is featured in an increasing number of bioactive compounds due to its unique combination of properties. The hydrodefluorination of Ar‐CF3 compounds is a direct and efficient route toward this motif. As reported methods for this transformation have focused on specific substrate families, herein we describe a general—electronically ambivalent—procedure for the single‐step direct mono‐hydrodefluorination of a variety of feedstock and functionalized Ar‐CF3 compounds. Exploiting the inherent tunability of electrochemistry and the selectivity enabled by a Ni cathode, the deep reduction garners high selectivity for ArCF2H products, with good to excellent yields up to gram scale. The protocol has been extended to a single‐step di‐hydrodefluorination yielding benzyl fluorides. The late‐stage peripheral editing of a single CF3 feedstock to construct fluoromethyl (CF2H, CFH2) moieties will aid the rapid diversification of lead‐compounds and compound libraries. We report a general procedure for the direct mono‐ and di‐hydrodefluorination of ArCF3 compounds. Exploiting the tunability of electrochemistry and the selectivity enabled by a Ni cathode, the deep reduction garners high selectivity with good to excellent yields up to gram scale. The late‐stage peripheral editing of CF3 feedstocks to construct fluoromethyl moieties will aid the rapid diversification of lead‐compounds and compound libraries.