How and Why Does Ni0 Promote Smooth Etheric C-O Bond Cleavage and C-C Bond Formation? A Theoretical Study

Ni-catalyzed cross-coupling between aryl alkyl ethers (ArOR) and Grignard reagents (RMgBr), known since 1979, proceeds under mild conditions in many cases. Although the reaction routes of various synthetic protocols involving transition-metal-catalyzed C-O bond activation have been elucidated, the mechanism of this etheric Kumada-Tamao-Curriu reaction remains enigmatic. This is because oxidative addition of inert etheric C-O to Ni-0 is thermodynamically and kinetically unfavorable, making it hard to explain the observed high reactivity of ether toward Ni catalysts. In this work, we used DFT calculations to identify a plausible reaction pathway by the Ni-0-ate complex, which enables smooth C-O bond cleavage and R-group transfer with reasonable activation barriers; this mechanism also accounts for the ineffectiveness of Pd catalysts. These results throw new light on both C-O activation and cross-coupling, and should be valuable for further rational development of the methodologies.