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 GoodwinLions-type chiral N4 ligand, (R)-Ph-BINAN-H-Py ((R)-3,3'-diphenyl-N-2,N-2'-bis((pyridin-2-yl)methyl)-1,1'-binaphthyl-2,2'-diamine; <bold>L</bold>), with Ru(pi-CH2C(CH3)CH2)(2)(cod) (<bold>A</bold>) (cod = 1,5-cyclooctadiene) catalyzes the hydrogenation of acetophenone (<bold>AP</bold>) to (R)-1-phenylethanol (<bold>PE</bold>) with a high enantiomer ratio (er). Almost no Ru complex forms, with <bold>A</bold> and <bold>L</bold> remaining intact throughout the reaction while generating <bold>PE</bold> quantitatively according to [<bold>PE</bold>] = k(obst)(2). An infinitesimal amount of reactive and unstable RuH2<bold>L</bold> (<bold>B</bold>) with C-2-gamma-cis-a stereochemistry is very slowly and irreversibly generated from <bold>A</bold> by the action of H-2 and <bold>L</bold>, which rapidly catalyzes the hydrogenation of <bold>AP</bold> via Noyoris donoracceptor bifunctional mechanism. A CH-pi-stabilized Si-face selective transition state, <bold>C-Si</bold>, gives (R)-<bold>PE</bold> together with an intermediary Ru amide, <bold>D</bold>, which is inhibited predominantly by formation of the Ru enolate of <bold>AP</bold>. The rate-determining hydrogenolysis of <bold>D</bold> 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 <bold>B</bold>. This mechanism is fully supported by a series of experiments including a detailed kinetic study, rate law analysis, simulation of t/[<bold>PE</bold>] curves with fitting to the experimental observations at the initial reaction stage, X-ray crystallographic analyses of <bold>B</bold>-related octahedral metal complexes, and Hammett plot analyses of electronically different substrates and ligands in their enantioselectivities.