Mechanism of Asymmetric Hydrogenation of Ketones

手性双膦/1，2-二胺钌（II）配合物催化简单酮的快速、高产和对映选择性氢化。在室温下，反应在常压H_2下也能顺利进行，加入碱性碱或有机强碱可进一步加速反应。最重要的是，随着碱摩尔浓度的增加，氢化速率最初在很大程度上增加，但随后降低。无碱时，在1-16个大气压范围内，反应速率与氢压无关;有碱时，反应速率随氢压的增加而加快。对映选择的程度不受氢压、碱的存在或不存在、碱和共存的金属或有机阳离子的种类、溶剂的性质或底物浓度的影响。在无碱条件下，用H_2/（CH_3）_2CHOH的反应比用D_2/（CD_3）_2CDOD的反应快50倍，但速率相差不大 ...更多信息 r = 2。这些结果表明，在反应过程中存在着双重机理，这两种机理都依赖于反应条件，并且都涉及H_2的异裂裂解，形成一个共同的反应中间体。通过ESI-TOFMS和NMR光谱检测了关键的[RuH（diphosphine）（diamine）]^+及其溶剂合物。酮的加氢反应是通过一个非经典的金属-配体双官能机理进行的，该机理涉及手性RuH_2（双膦）（二胺），其中Ru上的氢化物和配体NH_2上的质子通过六元周环过渡态同时转移到C=O官能团上.二胺配体中的NH_2单元在催化反应中起着关键作用。反应发生在18 e RuH_2配合物的外配位层，没有C=O/金属相互作用。前手性芳香酮的对映体在配位饱和的手性RuH_2中间体的分子表面上而不是在配位不饱和的Ru模板中动力学分化。少

Chiral diphosphine/1,2-diamine Ru(II) complexes catalyze the rapid, productive, and enantioselective hydrogenation of simple ketones. The reaction proceeds smoothly even at an atmospheric pressure of H_2 at room temperature and is further accelerated by addition of an alkaline base or a strong organic base. Most importantly, the hydrogenation rate is initially increased to a great extent with an increase in base molarity, but subsequently decreases. Without a base, the rate is independent on H_2 pressure in the range of 1-16 atm, while in the presence of a base, the reaction is accelerated with increasing H_2 pressure. The extent of enantioselection is unaffected by hydrogen pressure, the presence or absence of base, the kind of base and coexisting metallic or organic cations, the nature of the solvent, or the substrate concentrations. The reaction with H_2/(CH_3)_2CHOH proceeds 50-times faster than that with D_2/(CD_3)_2CDOD in the absence of base, but the rate differs only by a facto … More r of 2 in the presence of KO-t-C_4H_9. These findings indicate that dual mechanisms are in operation, both of which are dependent on reaction conditions and involve heterolytic cleavage of H_2 to form a common reactive intermediate. The key [RuH(diphosphine)(diamine)]^+ and its solvate complex have been detected by ESI-TOFMS and NMR spectroscopy. The hydrogenation of ketones is proposed to occur via a nonclassical metal-ligand bifunctional mechanism involving a chiral RuH_2(diphosphine)(diamine), where a hydride on Ru and a proton of the NH_2 ligand are simultaneously transferred to the C=O function via a six-membered pericyclic transition state. The NH_2 unit in the diamine ligand plays a pivotal role in the catalysis. The reaction occurs in the outer coordination sphere of the 18e RuH_2 complex without C=O/metal interaction. The enantiofaces of prochiral aromatic ketones are kinetically differentiated on the molecular surface of the coordinatively saturated chiral RuH_2 intermediate rather than in a coordinatively unsaturated Ru template. Less