Single-Coordination-Site Catalysts for Asymmetric Reduction

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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.