A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky -Aryl Imine in the ()-Metolachlor Process.

The hydrogenation of -(2-ethyl-6-methylphenyl)-1-methoxypropan-2-imine is the largest-scale asymmetric catalytic process for the industrial production of agrochemical ()-metolachlor. The challenging hydrogenation across the sterically crowded carbon-nitrogen double bond was achieved using a mixture of [IrCl(COD)], (,)-Xyliphos, NBuI and acetic acid. Acetic acid was critical in achieving excellent productivity and activity. Despite its industrial significance, a mechanism that explains how the sterically hindered bond in the imine is reduced has yet to be proposed. We propose a plausible proton-first, outer-sphere mechanism based on density functional theory calculations that is consistent with the experimentally observed activity and the enantioselectivity of the industrial process. Key findings include transition states involving acetate-assisted dihydrogen splitting, and a hydride transfer from a five-coordinate iridium trihydride directed by a C-H∙∙∙Ir interaction. This article was submitted to a Special Issue in honor of Professor Henri Kagan.