Affiliation:
1. School of Chemistry University of Bristol Cantock's Close Bristol BS8 1TS UK
2. Discovery High-Throughput Chemistry Medicinal Chemistry GSK Medicines Research Centre Stevenage SG1 2NY UK
Abstract
AbstractThe 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.
Funder
Royal Society
Engineering and Physical Sciences Research Council
GlaxoSmithKline foundation