Electronically Ambivalent Hydrodefluorination of Aryl‐CF<sub>3</sub> groups enabled by Electrochemical Deep‐Reduction on a Ni Cathode
John R. Box, Mickaël Avanthay, Darren L. Poole, Alastair J. J. Lennox
Abstract
Abstract The Ar‐CF 2 H moiety is featured in an increasing number of bioactive compounds due to its unique combination of properties. The hydrodefluorination of Ar‐CF 3 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‐CF 3 compounds. Exploiting the inherent tunability of electrochemistry and the selectivity enabled by a Ni cathode, the deep reduction garners high selectivity for ArCF 2 H 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 CF 3 feedstock to construct fluoromethyl (CF 2 H, CFH 2 ) moieties will aid the rapid diversification of lead‐compounds and compound libraries.