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

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.