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.
The Ar-CF2 H 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 ArCF2 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 CF3 feedstock to construct fluoromethyl (CF2 H, CFH2 ) moieties will aid the rapid diversification of lead-compounds and compound libraries.
Keywords: Defluorination; Electrochemistry; Fluorine; Nickel; Reduction.
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