A convenient approach to the mechanosynthesis of benzophenones from amines and amides using oxo acids and acid esters

Herein, we report a mechanochemical, Cu − Ni-catalyzed decarboxylative cross-coupling between aromatic amines and amides with α-keto acids (pyruvate derivatives) towards the efficient synthesis of benzophenones. The reaction proceeds under solvent-minimized ball mill conditions, enabled by cooperative Ni/Cu catalysis and a small volume of HFIP as a liquid additive (LAG). In an alternative approach, it has also been demonstrated that the same reaction can occur via mechanochemical ball milling of in situ-generated pyridinium salts with aryl (acid) esters, using ZrO 2 , NaCl, and hexamethyldisilane (Si 2 Me 6 ) in place of Ni/Cu catalysts. A wide range of amines and amides reacted smoothly with α-keto acids/aryl esters, including electron-rich and electron-deficient heteroarylamides, to deliver the respective benzophenone products in excellent yields (up to 85%). The developed protocols were found to be simple and efficient under solvent-less conditions, providing a robust route to diaryl ketones via mechanochemical cross-coupling of aryl amines/amides with α-keto acids/aryl esters without the need for harsh conditions or stoichiometric organometallic reagents.