ASYMMETRIC TRANSFER HYDROGENATION USING TETHERED LIGANDS

许多分子可以存在于一对镜像或“对映体”中，就像一双手一样。组成生物有机体的许多分子(微生物、植物、动物、我们……)只以单一的对映体形式存在。这些包括氨基酸(用来在体内制造多肽和酶)、碳水化合物和DNA链(单手也有螺旋)。我们摄入的任何东西都会与构成我们身体的分子相互作用。因为我们体内的分子是‘单手’的，所以一对对映体中的每一个都会有不同的作用。因此，有许多对映体分子的情况，其中一个对映体具有有益的性质，而另一个可能根本没有，甚至是有害的。因此，任何新的药物化合物，或者实际上任何可能作为对映体存在的新的分子实体，都必须以单一对映体的形式制备。这对合成化学家来说是具有挑战性的，但代表了当代合成化学最重要的目标之一。在以前的工作中，我们已经开发出催化剂，用于将容易获得的起始原料(酮)转化为主要是单手性的对映体产品(醇)。在某些情况下，选择性非常高。然而，在其他情况下，情况并非如此。在这项提案中，我们对我们的催化剂提出了几点修改，预计这些修改将使它们更适合于还原更广泛的底物，从而增加它们的整体实用性。从长远来看，我们的目标是开发对催化剂进行修饰的方法，以便它们可以用于选择性地合成任何所需目标的纯对映体。该项目是朝着这一目标迈出的重要一步。

Many molecules can exist in one of a pair of mirror-images, or 'enantiomers', rather like a pair of hands. Many of the molecules which make up biological organisms (microbes, plants, animals, us...) exist only in a single enantiomer form. These include amino acids (which are used to make peptides and enzymes in the body), carbohydrates, and the chain of DNA (which also has a spiral with a single handedness). Anything we consume interacts with the molecules which make up our bodies. Because the molecules in our bodies are 'one handedness' then each of a pair of enantiomers will interact differently. As a result, there are many cases of enantiomeric molecules where one enantiomer has beneficial properties whilst the other may have none at all, or even be harmful. As a result, any new pharmaceutical compounds, or indeed any new molecular entities with the potential to exist as enantiomers, must be preparable in single-enantiomer form. This is challenging for the synthetic chemist, but represents one of the most important objectives of contemporary synthetic chemistry.In previous work, we have developed catalysts for the conversion of readily-available starting materials (ketones) into predominantly one handedness of an enantiomeric product (alcohols). In some cases the selectivity is very high. However in other cases it is not. In this proposal, we propose several modifications to our catalysts which are predicted to make them more appropriate for the reduction of a much wider series of substrates, thus increasing their overall usefulness. In the long term our objective is to develop ways of modifying our catalysts so that they can be employed for the selective synthesis of pure enantiomers of any desired target. This project represents an important step towards this objective.