Enantioselective Hydrogenation of Ketones

由于现有的均相催化剂缺乏反应性和/或立体选择性，因此迫切需要开发立体选择性加氢的实用方法。一种新的Ru （II）配合物，即反式rucl_2 [(S)-木基膦][(S)-daipen]或R， R对映体，作为简单酮（XylBINAP= 2,2 '-双（二- 3,5 -基基膦）- 1,1 '-二萘基）不对称加氢的优良预催化剂。DAIPEN= 1,1 -二乙基-2-异丙基- 1,2 -乙二胺)。在含碱性的2-丙醇中，在1- 80atm（大部分< 10atm）的H_2条件下，以底物/催化剂摩尔比达100000的条件下进行反应。多种前手性酮的氢化具有高度的对映体选择。开链α， β-不饱和酮在C=O键上选择性加氢生成高ee的手性烯丙醇，解决了长期存在的合成难题。环丙基酮的加氢反应在没有骨架变化的情况下，在高ee下产生了更多的碳醇。具有各种取代基的烷基芳基酮氢化具有一致的高对映选择性。2,2,2 -三氟苯乙酮及其环取代衍生物也可用作底物。该反应对芳香族卤化物和CF_3、OCH_2、COOCH(CH_3)_2、NO_2、NH_2基团均具有耐受性。各种邻位取代的二苯甲酮氢化成具有一贯高ee的手性苯甲醇。没有观察到过度还原形成二乙基甲烷。该催化剂体系对杂芳香酮的对映选择性加氢反应非常有效。具有呋喃、噻吩、吡咯、噻唑或吡啶环的底物以相同的不对称意义氢化，得到持续高ee的手性仲醇。杂环的电子性质、路易斯基本倾向和空间尺寸对对映体选择性的影响不大。由于催化剂成本低，操作简单，并且具有环保意识，该方法对大规模反应特别有用。少

The development of practical methods effecting stereoselective hydrogenation of simple ketones is highly desirable, since the existing homogeneous catalysts lack reactivity and/or stereoselectivity. A new Ru (II) complex, trans-RuCl_2 [(S)-xylbinap][(S)-daipen] or the R, R enantiomer acts as an excellent precatalyst for asymmetric hydrogenation of simple ketones (XylBINAP=2, 2'-bis (di-3, 5-xylylphosphino)-1, 1'-binaphthyl. DAIPEN=1, 1-dianisyl-2-isopropyl-1, 2-ethylenediamine). The reaction is conducted with a substrate/catalyst molar ratio of up to 100000 in 2-propanol containing alkaline base under 1-80 atm (mostly <10 atm) of H_2 at room temperature. A wide variety of prochiral ketones are hydrogenated with a high degree of enantioselection. Hydrogenation of open-chain α, β-unsaturated ketones proceeds selectively at the C=O linkage to afford chiral allylic alcohols with a high ee, solving a long-standing synthetic problem. Hydrogenation of cyclopropyl ketones gives the correspondi … More ng carbinols in high ee without skeletal change. Alkyl aryl ketones with various substituents are hydrogenated with a consistently high enantioselectivity. 2, 2, 2-Trifluoroacetophenone and the ring-substituted derivatives are also usable as substrates. The reaction is tolerant of aromatic halides and CF_3, OCH_2, COOCH(CH_3)_2, NO_2, and NH_2 groups. Various ortho-substituted benzophenones are hydrogenated to chiral benzhydrols with consistently high ee. No over-reduction forming to diarylmethanes are observed. The catalyst system is extremely effective for enantioselective hydrogenation of hetero-aromatic ketones. The substrates with furan, thiophene, pyrrole, thiazole, or pyridine rings are hydrogenated with the same asymmetric sense to give chiral secondary alcohols in consistently high ee. The electronic properties, Lewis basic tendency, and steric size of the heterocycles appear to have little effect on the extent of enantioselectivity. This procedure is particularly useful for a large-scale reaction because of the low cost of the catalyst, operational simplicity, and environmental consciousness. Less