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.将Goodwin–Lions型手性N4配体(R)-Ph-BINAN-H-Py（(R)-3,3′-二苯基-N²,N²′-双((吡啶-2-基)甲基)-1,1′-联萘-2,2′-二胺；配体L）与Ru(π-CH₂C(CH₃)CH₂)₂(cod)（A，cod为1,5-环辛二烯（1,5-cyclooctadiene)）结合，可催化苯乙酮（AP）氢化生成(R)-1-苯乙醇（PE），且具有极高的对映体比例（er）。反应体系中几乎无钌配合物生成，A与L在全程保持完整，且PE的生成量遵循[PE] = k_obs t²的动力学规律，实现定量转化。极微量具有C₂-Λ-cis-α立体构型的活性不稳定物种RuH₂L（B），可在H₂与L的作用下由A缓慢且不可逆地生成；该物种可通过Noyori提出的供体-受体双功能机制快速催化AP的氢化反应。由CH-π相互作用稳定的Si面选择性过渡态CSi，可生成(R)-PE与中间体钌酰胺D，该过程会被苯乙酮的钌烯醇盐的形成显著抑制。中间体D的决速步氢解反应最终完成整个催化循环。反应中的时间平方项同时关联催化循环前的预反应步骤与催化循环本身，且B的生成与周转频率之间存在极不寻常的八阶差异。该催化机制得到了一系列实验的充分验证，包括详细的动力学研究、速率定律分析、初始反应阶段t/[PE]曲线的模拟拟合与实验观测结果匹配、与B相关的八面体金属配合物的X射线晶体衍射分析，以及针对电子性质不同的底物与配体的对映选择性哈米特图分析。