Chemo- and regioselective oxygenation of C(sp3)-H bonds in aliphatic alcohols using a covalently bound directing activator and atmospheric oxygen.

Chemically reactive directing groups (directing activators) represent a promising strategy for mild and regioselective C(sp3)-H functionalization. The use of a radical N-oxyl directing activator promoted the aerobic oxygenation of benzylic, propargylic, tertiary, and unactivated acyclic methylene C(sp3)-H bonds in aliphatic alcohols with γ- (or δ-) selectivity under mild conditions (room temperature to 50 °C). The reaction was unaffected by the presence of various oxidation-sensitive functional groups, which proved to be problematic in previously reported studies on the oxidation of C(sp3)-H bonds. Structural modifications on the directing activator altered the regioselectivity, and thus provided an ultra-remote aerobic C(sp3)-H oxygenation. The observed reactivity and regioselectivity could be rationalized in terms of the intramolecular conformational accessibility of the N-oxyl radical and the electronic characteristics of C(sp3)-H bonds.