Nickel‐mediated cross‐coupling via C–O activation assisted by organoaluminum

Abstract

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°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 β‐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.

Coupling of Heteroarene and Arenol via Nickel‐Catalyzed C−H/C−OH Activation

“…[8] The key success of this reaction is the facile CÀ O cleavage enabled by the coordination of Al onto O atoms of CÀ O. Lee also reported cobalt-catalyzed functionalization of aryl ether assisted by Lewis acidic of Mg reagent. [9] Our group has developed a series of Ni-mediated coupling reactions with aryl methyl ether in recent years using reactive coupling partners like trialkylaluminum, [10] Grignard reagents, [11] and Grignardassisted tandem CÀ H/CÀ O activation reactions. [12] The drawback of this catalytic manifold based on strong Lewis acid is the functional intolerance, reducing the utility of the reaction to wider scope.…”