Quantum Chemical Calculations with the Inclusion of Nonspecific and Specific Solvation: Asymmetric Transfer Hydrogenation with Bifunctional Ruthenium Catalysts

Details of the mechanism of asymmetric transfer hydrogenation of ketones catalyzed by two chiral bifunctional ruthenium complexes, (S)-RuH­[(R,R)-OCH(Ph)­CH(Ph)­NH2]­(η6-benzene) (Ru-1) or (S)-RuH­[(R,R)-p-TsNCH(Ph)­CH(Ph)­NH2]­(η6-mesityl­ene) (Ru-2), were studied computationally by density functional theory, accounting for the solvation effects by using continuum, discrete, and mixed continuum/discrete solvation models via “solvated supermolecules” approach. In contrast to gas phase quantum chemical calculations, where the reactions were found to proceed via a concerted three-bond asynchronous process through a six-membered pericyclic transition state, incorporation of the implicit and/or explicit solvation into the calculations suggests that the same reactions proceed via two steps in solution: (i) enantio-determining hydride transfer and (ii) proton transfer through the contact ion-pair intermediate, stabilized primarily by ionic hydrogen bonding between the cation and the anion. The calculations suggest that the proton source for neutralizing the chiral RO– anion may be either the amine group of the cationic Ru complex or, more likely, a protic solvent molecule. In the latter case, the reaction may not necessarily proceed via the 16e amido complex Ru[(R,R)-XCH(Ph)­CH(Ph)­NH]­(η6-arene). The origin of enantioselectivity is discussed in terms of the newly formulated mechanism.