Nickel-mediated cross-coupling via C-O activation assisted by organoaluminum

We report the alkylation and arylation cross-coupling of aryl ethers based on C-O bond activation using a nickel catalyst and organoaluminum reagents. Ni(cod)(2) in combination with 1,2-bis(dicyclohexylphosphino)ethane ligand in toluene solution at 130 degrees C are the best conditions. The naphthyl ether or methoxy pyridine derivatives are suitable substrates for alkylation and arylation reaction with a wider scope of aluminum reagents in good yields. Computational analysis on the pyridine substrate is provided to help delineate the mechanistic pathway and demonstrate the important aspects of the cooperative interaction bimetallic catalysis. First, the coordination of AlMe3 to the O atom of pyridine is essential for C-O activation. Second, the beta-H transfer from methoxy to pyridine could be discouraged through the use of bidentate phosphine as a ligand. Finally, excess AlMe3 reagent is critical for facilitating a reductive elimination process.