Ligand exchange as the first irreversible step in the nickel-catalyzed cross-coupling reaction of Grignard reagents.

Mechanistic studies of the Ni-catalyzed cross-coupling reaction of Grignard reagents through analysis of kinetic isotope effects and theoretical calculations indicated that the product-to-substrate ligand exchange process is the first irreversible step and affects the turnover efficiency and selectivity of the reaction. On the other hand, the oxidative addition step is the first irreversible step in Pd catalysis. This finding has useful implications for the development of efficient Ni catalysis and also illustrates the importance of the catalyst turnover step that has so far received less attention than subsequent catalytic steps.