Synthesis of unsymmetrical urea derivatives via domino ring-opening/Pd-catalyzed decarboxylative cross-coupling reaction of isatin-3-oxime and isocyanide

Abstract

This study presents a novel palladium-catalyzed method to efficiently synthesize unsymmetrical urea derivatives by domino ring-opening and decarboxylative cross-coupling involving isatin-3-oxime with isocyanides. The optimized protocol demonstrates excellent substrate compatibility, yielding a broad array of urea derivatives in moderate to good yields. A plausible reaction mechanism is proposed which was investigated using various control experiments that revealed key roles of palladium catalysis, offering insights into the ring-opening and decarboxylative coupling steps along with the necessity of free N–H functionality on isatin-3-oxime. Moreover, the synthesized derivatives were further transformed into quinazolinone heterocycles, underscoring their synthetic versatility.