Ligand-Enabled Pd-Catalyzed C(sp 3 )–H/C(sp 2 )–H Coupling

Palladium-catalyzed β and γ-C–H arylation of free carboxylic acids with both aryl boron reagents and aryl iodides has been extensively developed in recent years. Replacing these aryl coupling partners with simple arenes remains a significant challenge. By developing pyridone-morpholine ligands, we disclosed the β-methylene C–H (hetero)arylation of acyclic aliphatic acids and the γ-(hetero)arylation of cycloalkane carboxylic acids using benzene, furan, thiophene, and C-2 substituted pyridine as coupling partners. Preliminary mechanistic studies suggest that the reaction proceeds via ligand-promoted dehydrogenation of aliphatic carboxylic acids, C(sp 2 )–H activation of (hetero)arenes, and subsequent hydroarylation. Building on the mechanistic insights, we developed a dual-ligand catalysis system with one ligand promoting dehydrogenation and the other enhancing subsequent steps to enable coupling of C(sp 3 )–H bonds with indoles and pyrroles as reaction partners.