Shedding Light on the Hidden Roles of Lithium in the Nickel-Catalyzed Cross-Coupling of Aryl Ethers

The Ni-catalyzed cross-coupling of aryl ethers is a powerful
synthetic
tool to transform widely available phenol derivatives into functionalized
aromatic molecules. Recent theoretical and experimental mechanistic
studies have identified the involvement of heterobimetallic nickelates
as key intermediates that facilitate the challenging transformation
under mild conditions and often without the need for external ligands
or additives. In this work, based on calculations performed at the
density functional theory (DFT) level and by comparison with spectroscopic
and kinetic data, we investigate the mechanism of the Ni(COD)2-catalyzed cross-coupling of 2-methoxynaphthalene with PhLi
and assess the speciation of lithium nickelate intermediates. The
crucial role of solvent on the reaction is explained, and the multiple
roles played by lithium are unveiled. Experimental studies have identified
key lithium nickelate species which support and help to evolve the
calculated reaction mechanism and ultimately complete the catalytic
cycle. Based on this new mechanistic knowledge, a well-known experimental
challenge of these transformations, the so-called “naphthalene
problem” which restricts the use of electrophilic coupling
partners to π-extended systems, can be addressed to enable the
cross-coupling of unbiased aryl ethers under mild conditions.