Ligand-Controlled Pd(II)-Catalyzed α,β-Unsaturation and β-Arylation of Long-Chain Acids

Direct synthesis of β-aryl α,β-unsaturated carboxylic acids from simple aliphatic acids is challenging because β-C(sp³)-H activation, β-hydride elimination, and C-C bond formation must occur within a single catalytic system. Here, we describe a ligand-enabled Pd-catalyzed method that converts free aliphatic carboxylic acids to trans-cinnamic acid derivatives. A CF₃-substituted pyrazole-pyridone ligand promotes β-methylene C-H activation while accelerating β-hydride elimination and disfavoring premature oxidative addition, generating α,β-unsaturated carboxylic acids in situ that undergo subsequent Heck-type β-arylation. The reaction displays broad functional-group tolerance across heteroaryl and sterically encumbered aryl iodides, and complex substrates, enabling late-stage diversification. Mechanistic experiments are consistent with a sequential unsaturation-arylation pathway rather than initial β-arylation, highlighting the ability of ligand design to influence reaction order and selectivity. This strategy provides a general entry to cinnamic acid derivatives from native carboxylic acid feedstocks.