Asymmetric Transfer Hydrogenation of Imines.

亚胺的不对称转移氢化。

• 批准号: EP/F019424/1
• 负责人: Martin Wills
• 金额: $ 38.37万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FF019424%2F1
• 关键词: Asymmetric; Transfer; Hydrogenation; Imines.

Many molecules have the potential to exist in one of two mirror image forms, known as 'enantiomers' (like your hands). Most significantly, a large proportion of the molecules from which biological organisms (cells, animals, plants, us) are made, including carbohydrates, protein and DNA, exist predominantly in a single enantiomeric form, i.e. as a single mirror image.This creates a challenging problem for the pharmaceutical, agrochemical and fine chemicals industries. If a new chemical is made, e.g. a potential drug, pesticide, intermediate etc., then this may also have to potential to exist as a mixture of enantiomers as well, depending on its structure. Although these molecules will be identical in many ways (as your hands are), they are likely to interact very differently with a biological system (i.e. if we swallow them), because they will be seen as two totally different compounds (try shaking hands with a friend's right hand and then with their left hand). The difference in biological effects, however, can be so great that now it is a legal requirement for chemical companies to make all new 'enantiomeric' compounds separately in each 'handedness' and to test each of these for safety and activity (sometimes only one enantiomer works as a drug, sometimes one is dangerous and one is beneficial). Furthermore, it is also often necessary for 'enantiomeric' compounds to be marketed in the single (i.e. most beneficial) handedness.The problem is that this (seemingly easy) task is in fact often quite difficult, because most of the most common and simple routes to new compounds form a 50:50 mixture of both 'enantiomers'. This is analogous to flipping a coin - as each molecule is made (each flip of the coin) then there is a 50:50 chance of making either handedness. To get a product of one 'handedness' it is necessary to make every single molecule the same way round (flip a head every time, or a tail every time). In our research at Warwick, we have developed a series of catalysts which generate 'enantiomeric' molecules through a single step process in which hydrogen is selectively added to a substrate to give a product in which one handedness significantly predominates over the other (i.e. it flips more heads than tails, or vice versa). As well as being active, and selective, the catalyst can be used at low loadings, typically below 0.5 % relative to substrate. This reduces waste, energy use and side products.In previous work, we have applied our catalysts to the synthesis of enantiomerically-pure (i.e. one handedness of) alcohols, which are a pivotal class of molecules represented in many pharmaceutical targets and intermediates. In this project, the catalysts will be adapted to be able to make a further pivotal class of molecules, amines, by adding hydrogen to a simple precursor molecule. If successful, this will provide an effective route to large numbers of valuable synthetic intermediates, target molecules, and complex products which would otherwise be very difficult to prepare.

许多分子有可能以两种镜像形式之一存在，称为“对映体”（就像你的手）。最重要的是，大部分构成生物有机体（细胞、动物、植物、我们）的分子，包括碳水化合物、蛋白质和DNA，主要以单一对映体形式存在，即以单一镜像存在，这对制药、农业化学和精细化学工业造成了挑战性的问题。如果制造了一种新的化学品，例如潜在的药物、杀虫剂、中间体等，那么，根据其结构，这也可能具有作为对映异构体的混合物存在的潜力。虽然这些分子在许多方面都是相同的（就像你的手一样），但它们与生物系统的相互作用可能非常不同（例如，如果我们吞下它们），因为它们将被视为两种完全不同的化合物（尝试与朋友的右手握手，然后与他们的左手握手）。然而，生物效应的差异可能如此之大，以至于现在法律的要求化学公司在每个“手性”中分别制造所有新的“对映体”化合物，并测试每种化合物的安全性和活性（有时只有一种对映体作为药物，有时一种是危险的，一种是有益的）。此外，“对映体”化合物通常也需要以单手性（即最有利的手性）销售。问题是，这一（看似简单的）任务实际上往往相当困难，因为大多数最常见和最简单的新化合物路线形成两种“对映体”的50：50混合物。这类似于抛硬币-当每个分子被制造时（每次抛硬币），那么有50：50的机会制造任何一种手性。为了得到一个“手性”的产物，必须使每个分子都以相同的方式旋转（每次翻转头部，或每次翻转尾部）。在我们在沃里克的研究中，我们开发了一系列催化剂，这些催化剂通过一个单步过程产生“对映体”分子，在该过程中，将氢选择性地加入到底物中，得到一种手性明显优于另一种手性的产物（即，它翻转的头部比尾部多，反之亦然）。除了是活性的和选择性的之外，催化剂可以以低负载使用，通常相对于底物低于0.5%。在之前的工作中，我们已经将我们的催化剂应用于对映体纯（即单手性）醇的合成，这是许多药物靶标和中间体中代表的一类关键分子。在这个项目中，催化剂将被改造成能够通过向简单的前体分子中加入氢来制造另一类关键分子胺。如果成功，这将为大量有价值的合成中间体、目标分子和复杂产品提供一条有效的途径，否则这些产品将非常难以制备。

项目成果

Synthesis of Enantiomerically Pure and Racemic Benzyl-Tethered Ru(II)/TsDPEN Complexes by Direct Arene Substitution: Further Complexes and Applications

• DOI: 10.1021/acs.organomet.7b00731
• 发表时间: 2018-01
• 期刊: Organometallics
• 影响因子: 2.8
• 作者: R. Soni;Katherine E. Jolley;S. Gosiewska;G. Clarkson;Z. Fang;T. H. Hall;Ben N. Treloar;Richard C. Knighton;M. Wills