Photothermal catalysis versus thermal catalysis: A palladium-catalyzed intermolecular three-component C─H...

Although transition metal-catalyzed C─H activation has notably advanced C─H functionalization, achieving highly selective C─H difunctionalization remains a substantial challenge. Current C─H difunctionalization strategies remain largely constrained to two-component annulation reactions or dicarbofunctionalization, which inherently limit structural diversity and synthetic efficiency. Here, we report a palladium-catalyzed three-component C─H 1,3-N,O-difunctionalization of 3-phenylpropanamide using azodicarboxylate in conjunction with either dioxygen or carboxylic acid. This approach selectively delivers distinct 1,3-N,O-difunctionalized products through either photothermal or thermal pathway, affording moderate to high yields with excellent site selectivity and broad functional group tolerance, which can be readily transformed into various valuable heterocyclic compounds. Extensive experimental and computational studies reveal that the reaction operates via a complex and continuous catalytic cycle rather than by tandem, independent steps. By integrating principles of C─H activation, electrophilic amination, difunctionalization, and photothermal catalysis, this work expands the toolbox for selective multiple bond formation and will attract more interest in various fields.