Mechanism of Asymmetric Hydrogenation of Ketones

酮的不对称氢化机理

基本信息

批准号：
15350079
负责人：
OHKUMA Takeshi
金额：
$ 8.77万
依托单位：
HOKKAIDO UNIVERSITY (2004)Nagoya University (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

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

手性双辣/1,2-二胺RU（II）复合物催化简单酮的快速，富有生产力和对映选择性氢化。即使在室温下H_2的大气压力下，该反应也可以顺利进行，并通过添加合金碱或强大的有机碱进一步加速反应。最重要的是，氢化速率最初随着基础摩尔度的增加而大大提高，但随后下降。没有基数，该速率在1-16 atm范围内的H_2压力上是独立的，而在碱的存在下，反应随着H_2压力的增加而加速。对映射的程度不受氢压，碱的存在或不存在的影响，碱的种类和共存的金属或有机阳离子，溶液的性质或底物浓度。与H_2/（CH_3）_2CHOH的反应比在没有碱基的情况下使用D_2/（CD_3）_2CDOD快了50次，但在KO-T-C_4H_9的情况下，速率仅在2个事实上。这些发现表明双重机制正在运行，这两者都取决于反应条件，涉及H_2的杂裂裂解以形成一个常见的反应性中间体。键[RUH（Diphasphine）（二氨酸）]^+及其已解决的复合物已通过ESI-TOFMS和NMR光谱检测到。提出酮的氢化是通过涉及手性RUH_2（二氨氨）（二氨酸）的非经典金属配体双功能机制发生的，其中RU上的Hydrode和NH_2配体的质子简单地通过六启动的周期性的过度过渡状态转移到C = O功能中。直径配体中的NH_2单位在催化剂中起关键作用。反应发生在没有C = O/金属相互作用的18E RUH_2复合物的外部配位球中。术前芳香族酮的对映体在协同饱和的手性RUH_2中间体的分子表面上具有动力学区分，而不是在协调不饱和的RU模板中。较少的