Single-Coordination-Site Catalysts for Asymmetric Reduction

含有两个不稳定配位的金属配合物在均相催化领域得到了广泛的研究。然而，也有可能合成含有一个不稳定配位位点的催化剂。这些化合物被称为单配位位点（SCS）配合物，尚未被详细研究过。由于其接近配位饱和，SCS配合物具有鲁棒性，易于制备，并且具有催化工业所需的多功能性，生产力和选择性的反应能力。在Xiao小组先前工作的基础上，该项目的目标是合成新型SCS Ir（III）和Rh（III）配合物，并将其用于选择性不对称还原反应。n -杂环的不对称加氢和不对称还原胺化将成为还原反应的重点，因为这些转化对制药、农化和精细化工具有重要意义。该项目将包括四个部分，如下所述。该项目的第一步是合成和表征新的SCS Ir（III）和Rh（III）配合物。多种三齿和双齿配体将与IrCl3和RhCl3偶联形成刚性SCS配合物。这些配合物将使用常规表征技术进行表征，如NMR， UV， HRMS， IR和x -衍射。一旦这些配合物被成功合成，它们将被研究其影响不对称催化的能力。吡啶的不对称还原为手性哌啶将是一个重点，因为这个有用的反应仍然是一个挑战。报道了几种催化方法；然而，这些通常是特定于底物的。在这个项目中，我们将致力于减少更具挑战性的底物，如二取代和三取代吡啶，使用氢气或甲酸作为氢源。这两种氢源以前都被证明很容易与SCS铱配合物形成Ir-H氢化物。另一个将研究的反应是手性伯胺的不对称还原胺化反应，因为它是最容易获得手性胺的方法之一。这是一个挑战，因为很少有已知的催化剂报道对映选择性还原胺化，特别是在伯胺的情况下。然而，先前的工作已经表明，在该组内合成的SCS铱配合物具有高活性和范围。因此，我们认为目标化合物可以进行还原性胺化反应，得到具有高对映选择性、高产率和范围的手性伯胺。将探讨两种不同的还原方法，氢化法和转移氢化法。该项目还将包括机械研究和计算机建模，分别由Jon Iggo博士和Neil Berry博士监督。机制研究将包括原位高压核磁共振，试图了解SCS催化剂如何工作，而计算工作将提供有关配体设计，手性空间，对映体选择决定步骤和机制的重要信息。

Metal complexes that contain two labile coordination sites have been studied extensively inthe field of homogenous catalysis. However, it is also possible to synthesise catalysts thatcontain one labile coordination site. These compounds are known as single-coordination- site(SCS) complexes and have not been studied in as much detail. SCS complexes are robust dueto their near coordination saturation, and they are easy to prepare and have the capability tocatalyse reactions with industrially-desired versatility, productivity and selectivity. Buildingon previous work conducted within the Xiao group, the aim of the project is to synthesisenovel SCS Ir(III) and Rh(III) complexes and use them for selective asymmetric reductionreactions. Asymmetric hydrogenation of N-heterocycles and asymmetric reductive aminationwill be the focus of the reduction reactions as these transformations are of great importance tothe pharmaceutical, agrochemical and fine chemical industries. The project will consist offour parts that are described below.The first step of the project is to synthesise and characterise novel SCS Ir(III) and Rh(III)complexes. A variety of tridentate and bidentate ligands will be coupled to IrCl3 and RhCl3 toform rigid SCS complexes. These complexes will be characterised using routinecharacterisation techniques such as NMR, UV, HRMS, IR and X-diffraction.Once these complexes have been successfully synthesised, they will be investigated for theirability to effect asymmetric catalysis. The asymmetric reduction of pyridines to chiralpiperidines will be a focus as this useful reaction remains to be a challenge. There are a fewcatalytic methods reported; however these are generally substrate specific. In this project, wewill aim to reduce the more challenging substrates like di- and tri- substituted pyridines usingeither hydrogen gas or formic acid as the hydrogen source. Both of these hydrogen sourceshave previously been shown to readily form Ir-H hydrides with SCS iridium complexes.Another reaction that will be investigated is asymmetric reductive amination for chiralprimary amines as it is one of the easiest methods to access chiral amines. This is a challengeas there are few known catalysts reported for enantioselective reductive amination, especiallyin the case of primary amines. However, previous work has shown the high activity andscope of the SCS iridium complexes synthesised within the group. It is therefore believedthat the target compounds will make reductive amination to afford chiral primary aminespractical with high enantioselectivity, productivity and scope. Two different approaches forthe reduction will be explored, hydrogenative and transfer-hydrogenative methods.The project will also involve a mechanistic study and computer modelling which will besupervised by Dr Jon Iggo and Dr Neil Berry, respectively. The mechanistic study willinvolve in situ high pressure NMR in an attempt to understand how the SCS catalysts work,whilst the computational work will provide important information regarding ligand design,chiral space, enantioselectivity-determining step and mechanism.