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

Abstract

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.

Bifunctionality of Zn dust in Ullmann C–C cross-coupling by Ni/Pd dual catalysis: theoretical insight

“…The yields of the reactions are difficult to optimize (8-63%) without such additives, but they greatly increase to 79-84% with them. Although theoretical and experimental studies of C-C cross-coupling have been carried out for a number of dual catalytic systems containing Ni/Cu, 7 Ni/Ce, 17 Ir/Ni, [18][19][20][21] Pd/Cu, 22 and Ni/Pd, 23 the role of these additives in the reaction is still unclear.…”