On the Effect of Iodide and Acids in the Metolachlor Process

Iridium-catalyzed asymmetric imine hydrogenation is the key step in the industrial syntheses of dextromethorphan and metolachlor. Nevertheless, the mechanism of this reaction relying on ferrocenyldiphosphine ligands remains unclear. Through computational studies, we propose a mechanism that is in line with all experimental observations including the enantioselectivity. The calculated mechanism reveals the interplay of potentially three rate-determining transition states, namely, the migratory insertion, amido-ligand protonation, and heterolytic H2-activation. Most salient, the mechanism rationalizes the “magic iodide effect” in combination with proton co-catalysis, which improve the reaction rate as well as enantioselectivity. Acid additives accelerate both the protonation- and H2-splitting steps. Iodide further facilitates the protonation and potentially the H2-activation. Thus, these additives prevent that other elementary steps within the catalytic cycle compromise the enantioselectivity control exerted by the migratory insertion step.