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 -C(sp(3))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 CH amination process. Under these conditions, N-propylpicolinamides bearing substituents can be cleanly converted to -acetoxylated amine products in excellent yield. This CH acetoxylation can also be used in concert with other Pd-catalyzed picolinamide-directed CH functionalization reactions for rapid scaffold diversification.