Transition-metal free chemoselective C–H hydroxylation of bisarylmethanes enabled by a phosphite as a sacrificial reductant

A transition-metal free (hetero)benzylic C-H hydroxylation approach for the synthesis of di(hetero)arylmethanols has been developed. The reaction is promoted by a KO<i>t</i>Bu/DMSO/P(OEt)₃ system, with atmospheric air as the sole oxidant at room temperature. This methodology has been employed to synthesize useful active pharmaceutical ingredients (APIs), modafinil and adrafinil. By using DMSO-<i>d</i>₆ as the deuterium reagent, the hydroxylation-deuteration of 3-benzylpyridines and diphenylmethanes proceeded well, with excellent deuterium ratios. Preliminary kinetic experiments and ¹H NMR studies provided significant insight into the reaction mechanism.