On the NH effect in ruthenium-catalysed hydrogenation of ketones: rational design of phosphine-amino-alcohol ligands for asymmetric hydrogenation of ketones.
On the NH effect in ruthenium-catalysed hydrogenation of ketones: rational design of phosphine-amino-alcohol ligands for asymmetric hydrogenation of ketones.
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DOI：
10.1002/chem.201000790
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发表时间：
2010-07
期刊：
影响因子：
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通讯作者：
S. Phillips;J. Fuentes;M. Clarke
中科院分区：
文献类型：
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作者：
S. Phillips;J. Fuentes;M. Clarke
由于Noyori和他的同事开发了[RuCl2(双膦)ACHTUNGRENNUNG(二胺)]催化剂，苯乙酮等简单酮的不对称氢化已成为一种重要的合成方法。现在已经制备了大量的这种普通类型的催化剂。它们的反应活性与简单的MACHTUNGTRENNUNG(Diphos)Xn盐形成鲜明对比，后者几乎不能作为酮的催化剂，因为酮不能与金属中心螯合。单酮还原反应活性的提高是由于酮氢键连接到配体的伯胺末端，使其被Ru氢化物攻击并控制立体选择性的“双功能机理”。有报道指出，这些催化剂对某些酮类化合物无效，例如体积大的酮(低活性)、空间相似的芳香酮(低选择性)、一些具有强配位取代基的酮(低活性)、烷基烷基酮(低选择性)以及一系列不容易进行不对称还原的单个底物。因此，发现结构不同的、偏离[RuCl2(双膦)(二伯胺)]蓝图的酮加氢催化剂可能是解决这些问题的最佳机会之一；手性仲醇的重要性要求为每一种可能的底物提供方法学，以便看到这项技术在工业和更广泛的合成中得到广泛应用。结果表明，由P^N、NH_2配体衍生的Ru催化剂可以加氢一些活性较差的酮，具有良好的对映体选择性。该催化剂的最初设计设想了在配位环境中通过配体的伯胺末端促进极性键的氢化，相对于Noyori催化剂，对于体积较大的底物来说，该环境更容易进行。与其合成一个非常大的新型P^N^NH2催化剂文库，我们认为对催化剂-结构活性关系的研究可能会为新催化剂提供一些线索，并揭示一些机理问题，因为在我们之前的研究中，无法分离反应中间产物。在这篇通讯中，我们报告了一些令人惊讶的发现，来自我们的动力学实验和引入膦氨醇配体用于Ru催化的氢化。新的非手性配体1-3可以从商业原料中一步合成，然后在120 8C的四氢呋喃中与[RuCl2ACHTUNGTRENNUNG(DMSO)4]在微波辅助下络合成[RuCl2ACHTUNGTRENNUNG(P^NR1N(R2)2ACHTUNGTRENNUNG(dmso)]类型的配合物(方案1)。络合物4-7可以通过层析或重结晶得到纯的，并且很容易在空气中处理。我们对底物α，a-二甲基苯丙酮的加氢反应进行了动力学研究.
The asymmetric hydrogenation of simple ketones, such as acetophenones, has become an important synthetic method as a result of the development of [RuCl2(diphosphine)ACHTUNGTRENNUNG(diamine)] catalysts by Noyori and co-workers. A large range of catalysts of this general type have now been prepared. Their reactivity is quite in contrast to simple MACHTUNGTRENNUNG(diphos)Xn salts that are barely active as catalysts for ketones that cannot chelate to the metal centre. The enhanced reactivity for reduction of simple ketones is proposed to be due to the “bifunctional mechanism” in which the ketone hydrogen bonds to the primary amine terminus of the ligand, activating it to attack by Ru–hydride and controlling stereoselectivity. There are reports that suggest these catalysts are not effective for certain ketones, such as bulky ketones (low reactivity), sterically similar aryl–aryl ketones (low selectivity), some ketones with strongly co-ordinating substituents (low reactivity), and alkyl–alkyl ketones (low selectivity) as well as a range of individual substrates that do not undergo asymmetric reduction readily. The discovery of structurally distinct, new classes of ketone hydrogenation catalyst that deviate from the [RuCl2(diphosphine)(di-primary-amine)] blueprint therefore might present one of the best opportunities to solve these problems; the importance of chiral secondary alcohols requires that methodology exists for every possible type of substrate in order to see this technology widely exploited in industry and more generally in synthesis. We have shown that Ru catalysts derived from P^N^NH2 ligands can hydrogenate some poorly reactive ketones with good enantioselectivity. The initial design of the catalyst envisaged hydrogenation of polar bonds facilitated by the primary amine terminus of the ligand in a co-ordination environment that is more accessible for bulky substrates relative to the Noyori catalysts. Rather than synthesising a very large library of new P^N^NH2 catalysts, we felt that an investigation of catalyst– structure activity relationships might throw up some leads for new catalysts, along with shedding light on some mechanistic issues, since it had not been possible to isolate the reaction intermediates in our previous studies. In this communication, we report some surprising findings from our kinetic experiments and the introduction of phosphino-amino-alcohol ligands for Ru-catalysed hydrogenation. The new achiral ligands, 1–3 can be prepared in one step from commercial starting materials and then converted into complexes of type [RuCl2ACHTUNGTRENNUNG(P^NR1N(R2)2ACHTUNGTRENNUNG(dmso)] by microwave-assisted complexation with [RuCl2ACHTUNGTRENNUNG(dmso)4] in THF at 120 8C (Scheme 1). Complexes 4–7 can be obtained pure by chromatography or recrystallisation and are easily handled in air. We carried out kinetic studies on the hydrogenation of a,a-dimethylpropiophenone, a substrate that was initially re-