Mechanism of Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by a Combined System of Ru(π-CH₂C(CH₃)CH₂)₂(cod) and the Chiral sp²N/sp³NH Hybrid Linear N4 Ligand Ph-BINAN-H-Py

The combination of a Goodwin–Lions-type chiral N4 ligand, (R)-Ph-BINAN-H-Py ((R)-3,3′-diphenyl-N2,N2′-bis­((pyridin-2-yl)­methyl)-1,1′-binaphthyl-2,2′-diamine; L), with Ru­(π-CH2C­(CH3)­CH2)2(cod) (A) (cod = 1,5-cyclooctadiene) catalyzes the hydrogenation of acetophenone (AP) to (R)-1-phenylethanol (PE) with a high enantiomer ratio (er). Almost no Ru complex forms, with A and L remaining intact throughout the reaction while generating PE quantitatively according to [PE] = kobst2. An infinitesimal amount of reactive and unstable RuH2L (B) with C2-Λ-cis-α stereochemistry is very slowly and irreversibly generated from A by the action of H2 and L, which rapidly catalyzes the hydrogenation of AP via Noyori’s donor–acceptor bifunctional mechanism. A CH-π-stabilized Si-face selective transition state, CSi, gives (R)-PE together with an intermediary Ru amide, D, which is inhibited predominantly by formation of the Ru enolate of AP. The rate-determining hydrogenolysis of D completes the cycle. The time-squared term relates both to the preliminary step before the cycle and to the cycle itself, with a highly unusual eight-order difference in the generation and turnover frequency of B. This mechanism is fully supported by a series of experiments including a detailed kinetic study, rate law analysis, simulation of t/[PE] curves with fitting to the experimental observations at the initial reaction stage, X-ray crystallographic analyses of B-related octahedral metal complexes, and Hammett plot analyses of electronically different substrates and ligands in their enantioselectivities.