Mechanochemical Decarbonylative Cross-Coupling of Amides via Cooperative Catalysis and Triple C–N/C–C/C–H Activation

Abstract

Mechanochemical solvent-less cross-couplings have emerged as a powerful frontier in the formation of carbon–carbon and carbon–heteroatom bonds under sustainable conditions. However, despite considerable progress, mechanochemical decarbonylative cross-couplings have been unexplored. Herein, we report the first decarbonylative mechanochemical cross-coupling for the heteroarylation of amides by a triple C–N/C–C/C–H activation. The catalytic system exploits cooperative Ni/Cu catalysis to simultaneously activate the amide N–C(O) and the heterocycle C–H bonds, resulting in a highly chemoselective coupling. The reaction is characterized by a broad scope of the amide and the heterocyclic component to furnish heterobiaryls, which are among the most privileged scaffolds in organic synthesis. We demonstrate that decarbonylative mechanochemical cross-couplings will provide novel access to a range of valuable products that are among the most common structures in organic chemistry.