Palladium-Catalyzed Direct β-C(sp3)–H Hydroxylation of Aliphatic Amides with Aqueous H2O2

Carbonyl-directed Pd(II)-catalyzed β-C(sp3)–H hydroxylation of aliphatic amides has been accomplished using H2O2 (30% aq.) as the oxidant. Promoted by 3-pyridinesulfonic acid, the transformation proceeds under mild conditions to furnish β-hydroxy amides that are important structural motifs in bioactive molecules. The oxidation accommodates diverse native amides, including secondary, tertiary, cyclic, and α-hydrogen-containing substrates. The use of environmentally benign H2O2 (30% aq.) as the oxidant improves the sustainability and practicality of the procedure. The substrate scope, functional group tolerance, monoselectivity, and postsynthetic modifications are important practical features.