Palladium-catalyzed picolinamide-directed acetoxylation of unactivated γ-C(sp³)-H bonds of alkylamines

We report a new protocol for palladium-catalyzed acetoxylation of the γ-C(sp³)-H bonds of N-alkylpicolinamide substrates using PhI(OAc)₂ oxidant. These reactions involve the use of substoichiometric amounts of Li₂CO₃ additive, which effectively suppresses the competing intramolecular C-H amination process. Under these conditions, N-propylpicolinamides bearing α substituents can be cleanly converted to γ-acetoxylated amine products in excellent yield. This C-H acetoxylation can also be used in concert with other Pd-catalyzed picolinamide-directed C-H functionalization reactions for rapid scaffold diversification.