Bimetallic Cooperative Catalysis for Decarbonylative Heteroarylation of Carboxylic Acids via C‐O/C‐H Coupling

Cooperative bimetallic catalysis is a fundamental approach in modern synthetic chemistry. We report bimetallic cooperative catalysis for the direct decarbonylative heteroarylation of ubiquitous carboxylic acids via acyl C‐O/C‐H coupling. This novel catalytic system exploits the cooperative action of a copper catalyst and a palladium catalyst in decarbonylation, which enables highly chemoselective synthesis of important heterobiaryl motifs through the coupling of carboxylic acids with heteroarenes in the absence of prefunctionalization or directing groups. This cooperative decarbonylative method uses common carboxylic acids and shows a remarkably broad substrate scope (>70 examples), including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents. Extensive mechanistic and computational studies were conducted to gain insight into the mechanism of the reaction. The key step involves intersection of the two catalytic cycles via transmetallation of the copper–aryl species with the palladium(II) intermediate generated by oxidative addition/decarbonylation. Bimetallic cooperative catalysis is reported for the direct decarbonylative heteroarylation of carboxylic acids via acyl C‐O/C‐H coupling. The cooperative action of copper and palladium catalysts is exploited for chemoselective synthesis of heterobiaryl motifs. A broad substrate scope (>70 examples) is accessible, including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents.