Ruthenium(II)-Catalyzed Remote Alkylation of 2-Pyridones via Cleavage of C–H or C–Cl Bonds

A ruthenium(II)-catalyzed remote alkylation of 2-pyridones has been developed via selective cleavage of either C–H or C–Cl bonds. Despite significant advances in ortho-C–H functionalization, distal modification of 2-pyridones remains challenging due to inherent regioselectivity issues and electronic bias. By leveraging a nitrogen-directed σ-activation strategy, this protocol enables C5-alkylation as well as C3,C5-dialkylation in the absence of a ligand. Notably, the method accommodates both C–H activation and directed C–Cl bond cleavage pathways, providing complementary reactivity patterns from readily accessible substrates. The transformation exhibits broad substrate scope, good functional group tolerance, and operational simplicity. This study expands the synthetic utility of ruthenium catalysis for remote functionalization of heterocycles and offers a practical approach for the late-stage diversification of biologically relevant 2-pyridone scaffolds.