Dual ActiveForms of Milstein’s Catalyst forEster Hydrogenation

In this article, we report that Milstein’s ruthenium-pincer catalyst for ester hydrogenation, previously shown to convert to a highly active form through release of ethane, is also moderately active in its original form prior to ethane release, provided an alcohol cocatalyst is present. We describe a detailed experimental and computational study of ester hydrogenation catalyzed by the catalyst’s original form. The reaction rate is first-order in ester and ruthenium catalyst, zero-order in hydrogen, and exhibits a saturation dependence on the concentration of the product alcohol. We establish that an equilibrium between two potential resting states, a dihydride complex and a hydridoalkoxide complex, is shifted nearly completely toward the dihydride under catalytically relevant conditions. We report a thorough computational analysis of the mechanism, which is consistent with the observed kinetics and catalyst resting speciation. In the minimum-energy pathway, ester reduction proceeds through dechelation of the pincer’s diethylamino group, and the CH2 linkers of the pincer ligand are not involved in catalytic turnover. Two alternative pathways involving H/OR metathesis or pincer ligand dearomatization proceed with free-energy barriers that are 1.1 and 1.5 kcal/mol higher, respectively; these computationally identified pathways are not fully consistent with the kinetic data.