A New Family of Powerful Asymmetric Bifunctional Organocatalysts and their Reactions

某些有机分子具有非平坦的三维结构，这种结构具有不能在其镜像上重叠的固有特性。这样的分子被认为是手性的，这两个镜像被称为对映体。这些对映体在几乎所有情况下的行为都是相同的，除非放在手性环境中，如细胞、受体和酶等生物系统中发现的那些。因此，生物活性手性化合物的一个对映体可能会引起非常不同的生物反应，有时会造成灾难性的后果。因此，化学家们一直在寻找完美的反应，以允许创建(或合成)这样的手性化合物作为单一对映体，而不是它们的混合物。手性化合物可以通过将一种化合物加到另一种“平面”化合物上来合成，例如含有碳-碳双键(或烯烃)、碳-氮双键(或亚胺)、碳氧双键(醛或酮)的化合物。加成反应破坏了平面性并产生了手性产物，但由于烯烃的每一面都有可能加成，所以形成了等量的两种对映体(外消旋混合物)。通过使用额外的外部手性试剂或催化剂，可以影响反应以导致一种对映体的优势(称为不对称合成)。这些催化剂通常与平板底物结合，并在一定程度上阻止或促进试剂与烯烃、亚胺或醛的一个或另一个表面的加成反应。在这个建议中，我们希望建立在一些初步研究的基础上，这些研究表明，一种新型的手性双功能催化剂可以同时激活底物和试剂，并促进它们之间的有效反应。这种类似酶的过程允许选择性地形成主要作为一个对映体的产物。现在，我们希望通过创建一大类相关催化剂来探索这一化学的潜力和范围，以促进具有良好对映体控制的新型和重要类型的反应，并将这些发现应用于生物活性化合物的合成。由于适用于这种类型催化的底物和试剂的数量很大，因此潜在的发现新反应的数量是巨大的。幸运的是，我们系统的设计允许简单的化学修饰，因此可以简单地粗略或精细地调整催化剂的结构和反应特性。这最终将允许一种特定的催化剂与给定的试剂/底物对匹配，并促进具有高对映体控制性的键的形成。与文献中许多其他高效的手性催化剂不同，这一家族的优点是由纯有机材料制成，不含金属离子。这使得它们易于合成，易于操作，价格低廉，毒性比金属离子同类化合物低。因此，这些新型的环境友好型催化剂及其反应将对工业界和学术界的化学家具有重要的价值。

Certain organic molecules have non-flat 3 dimensional structures which have the inherent property of not being superimposable on their own mirror images. Such a molecule is said to be chiral and the two mirror images are known as enantiomers. These enantiomers behave identically in nearly all situations except when placed in a chiral environment like those found inside biological systems, such as cells, receptors and enzymes. Accordingly one enantiomer of a bioactive chiral compound may elicit very different biological responses with sometimes catastrophic consequences. As a result, chemists have been seeking to discover the perfect reaction that will allow the creation (or synthesis) of such chiral compounds as single enantiomers, not mixtures of them. Chiral compounds may be synthesised by adding one compound to another 'flat' compound such as one containing a carbon-carbon double bond (or alkene), a carbon-nitrogen double bond (or imine), a carbon-oxygen double bond (aldehyde or ketone). The addition reaction destroys the planarity and results in the chiral product, but as addition to each face of the alkene is equally likely, an equal amount of both enantiomers is formed (a racemic mixture). Influencing the reaction to lead to a predominance of one enantiomer (known as asymmetric synthesis) is possible by using additional external chiral reagents or catalysts. These catalysts often affiliate with the flat substrate and prevent or promote, to some extent, an addition reaction of a reagent to one or other of the faces of the alkene, imine or aldehyde. In this proposal we wish to build on some preliminary studies, which have shown that a new type of chiral bifunctional catalyst can simultaneously activate the substrate and reagent and facilitate an efficient reaction between them. This enzyme-like process allows the selective formation of the product as predominantly one enantiomer. We now wish to explore the potential and scope of this chemistry by creating a large family of related catalysts to promote new and important types of reaction with excellent enantiocontrol and apply the findings in the synthesis of biologically active compounds. As the numbers of substrates and reagents amenable to this type of catalysis is large, the potential number of new reactions to be discovered is enormous. Fortunately, the design of our system allows for easy chemical modification and hence simple coarse or fine tuning of the catalyst's structure and reactivity profile. This will ultimately allow one particular catalyst to be matched to a given reagent/substrate pair and facilitate bond formation with high enantiocontrol.Unlike many other efficient chiral catalysts in the literature this family benefits from being made of purely organic materials and is free from metal ions. This makes them easy to synthesise, easy to handle, cheap and less toxic than their metal ion counterparts. Accordingly these new environmentally friendly catalysts and their reactions will be of great value to chemists in industry and academia alike.