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.