Single-Coordination-Site Catalysts for Asymmetric Reduction

Metal complexes that contain two labile coordination sites have been studied extensively in
the field of homogenous catalysis. However, it is also possible to synthesise catalysts that
contain 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 due
to their near coordination saturation, and they are easy to prepare and have the capability to
catalyse reactions with industrially-desired versatility, productivity and selectivity. Building
on previous work conducted within the Xiao group, the aim of the project is to synthesise
novel SCS Ir(III) and Rh(III) complexes and use them for selective asymmetric reduction
reactions. Asymmetric hydrogenation of N-heterocycles and asymmetric reductive amination
will be the focus of the reduction reactions as these transformations are of great importance to
the pharmaceutical, agrochemical and fine chemical industries. The project will consist of
four 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 to
form rigid SCS complexes. These complexes will be characterised using routine
characterisation techniques such as NMR, UV, HRMS, IR and X-diffraction.
Once these complexes have been successfully synthesised, they will be investigated for their
ability to effect asymmetric catalysis. The asymmetric reduction of pyridines to chiral
piperidines will be a focus as this useful reaction remains to be a challenge. There are a few
catalytic methods reported; however these are generally substrate specific. In this project, we
will aim to reduce the more challenging substrates like di- and tri- substituted pyridines using
either hydrogen gas or formic acid as the hydrogen source. Both of these hydrogen sources
have previously been shown to readily form Ir-H hydrides with SCS iridium complexes.
Another reaction that will be investigated is asymmetric reductive amination for chiral
primary amines as it is one of the easiest methods to access chiral amines. This is a challenge
as there are few known catalysts reported for enantioselective reductive amination, especially
in the case of primary amines. However, previous work has shown the high activity and
scope of the SCS iridium complexes synthesised within the group. It is therefore believed
that the target compounds will make reductive amination to afford chiral primary amines
practical with high enantioselectivity, productivity and scope. Two different approaches for
the reduction will be explored, hydrogenative and transfer-hydrogenative methods.
The project will also involve a mechanistic study and computer modelling which will be
supervised by Dr Jon Iggo and Dr Neil Berry, respectively. The mechanistic study will
involve 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.