Palladium-Catalyzed Multicomponent Synthesis of Pyrazoles and Isoxazoles

Significance

The palladium-catalyzed four-component coupling of terminal alkynes, hydrazines or hydroxylamine, carbon monoxide, and aryl iodides to furnish pyrazole or isoxazole derivatives is reported. The reaction is regioselective and proceeds at room temperature and at ambient pressure of carbon monoxide in aqueous THF. The reaction involves sequential carbonylative Sonogashira coupling followed by a cyclization reaction of hydrazine or hydroxylamine with the formed α,β-alkynyl ketones. Hydroxylamine may also be used in place of hydrazine to give isoxazole derivatives.