C?H Bond Arylation of Pyrazoles at the ??Position: General Conditions and Computational Elucidation for a High Regioselectivity

Direct arylation of most five-membered ring heterocycles are generally easily accessible and strongly favored at the ?-position using classical palladium-catalysis. Conversely, regioselective functionalization such concurrent ?-position remains currently very challenging. Herein, we report general conditions for direct pyrazoles, while C?H is free. By aryl bromides as source a judicious choice solvent, reaction variously N-substituted pyrazoles simply proceeds via ?-C?H bond functionalization. The ?-regioselectivity promoted by ligand-free palladium catalyst simple base without oxidant or further additive, tolerates variety substituents on bromoarene. DFT calculations revealed that protic solvent 2-ethoxyethan-1-ol significantly enhances acidity proton thus favors this arylation. This selective was successfully applied straightforward building ?-extended poly(hetero)aromatic structures Pd-catalyzed combined ?-C?H intermolecular intramolecular in an overall highly atom-economical process.