Cationic Carbon Lewis Acids in Frustrated Lewis Pairs as New Reduction Catalysts

The reduction of carbon-carbon and carbon-heteroatom (C=E) double bonds is an extremely important catalysed reaction in industry used for example during the production of herbicides, multiple drug molecules and cosmetics. This reaction is currently dominated by catalysts based on precious transition metals (e.g., Rh, Ir, Ru etc.). The replacement of precious metal-based catalysts with equally efficient metal-free catalysts is highly attractive in terms of cost and toxicity, whilst also eliminating any potential supply risk (associated with utilising scarce metals sourced from an extremely limited number of countries).

In recent years two metal-free methods have been developed to reduce C=E moieties: (i) using organic reductants (carbon based sources of hydride (H-)) in combination with organocatalysts (e.g., phosphoric acids), (ii) using Frustrated Lewis pairs (a Lewis acid and Lewis base that do not quench each other by formation of a dative bond) generally consisting of boron based Lewis acids as catalysts with either H2 or R3Si-H as the terminal reductant. Whilst these approaches represented significant scientific advances there are still considerable drawbacks to both (particularly on a preparative scale). The former requires stoichiometric quantities of organic reductant (with the obvious cost and waste implications) whilst the latter utilises boron Lewis acids that are not water tolerant and have functional group tolerance limitations.

The research proposed herein will utilise cationic carbon based Lewis acids in FLPs to activate H2 / R3SiH. Importantly, these Lewis acids are water tolerant and have good functional group tolerance. Post H2 activation the cationic carbon Lewis acid is transformed into the organic reductant (or a close analogue of) previously used in many stoichiometric reductions of C=E bonds. C=E reduction regenerates the cationic carbon based FLP enabling it to be used for further H2 activation, thus making the overall process catalytic in Lewis acid. This novel catalytic cycle targets the key drawbacks associated with the two former metal-free approaches (i) making reductions catalytic in organic hydride, and (ii) generating a H2O / functional group tolerant FLP catalyst. This potentially transformative approach is based on our exciting preliminary results where we demonstrated that a cationic carbon Lewis acid based FLP can activate H2 and R3Si-H in wet solvent and reduce C=E bonds (albeit slowly and under forcing conditions). This proposal seeks to develop this initial breakthrough into a truly useful catalytic methodology that in the medium to long term may replace existing transition metal systems in a range of societally important catalytic reductions.

The ultimate aim of this proposal is to develop cationic carbon based Lewis acids as new catalysts for the reduction of polar unsaturated bonds. This proposal initially focuses on achiral catalysts to determine the key parameters for effective reduction processes using carbon Lewis acid catalysts before subsequently targeting asymmetric catalysts. These are adventurous goals, whose feasibility are supported by our recent breakthrough in this area. Catalysis is crucial to the chemical and wider manufacturing sector whilst it is essential to achieve the green and sustainable processes that society demands. The importance of catalysis to the UK was recognised by a designation for growth by the EPSRC and the realisation that it underpins key challenges in the EPSRC priority areas of Energy and Manufacturing for the Future. This proposal clearly fits within the EPSRC's own definition of catalysis "Structural and kinetic studies to understand the molecular mechanisms involved in catalytic reactions, preparation of novel or improved catalysts and the development of new catalytic processes."

More specifically, the catalytic reduction of C=E (E = NR, CR2 and O) moieties is a crucial reaction in industry and academia, particularly asymmetric versions e.g., used to generate chiral amines. Amines are used throughout the chemicals industry including fine chemicals, in agrochemicals, polymers and cosmetics etc. Furthermore, 40% of the optically active drugs sold on the market contain chiral amines, thus they are vital in APIs.The catalysts most widely used for forming amines by reduction (e.g., of imines or enamides) are based on precious metals, particularly Ru, Ir and Rh. The use of these elements is highly undesirable due to cost, toxicity and supply chain risk (as indicated in recent reports from the British Geological society, the EU and the CS3, a body which includes the RSC), the later factor is likely to become an increasing issue due to increased demand (from wider industrialization) coupled with finite supplies. Developing a system that replaces these precious metal catalysts with abundant and non-toxic catalysts is highly desirable and would significantly benefit the chemicals industry and the wider synthetic community in general (in academia and industry).

Beyond the considerable scientific impact of this innovative research, this proposal will supply a highly trained researcher for UK industry. They will be equipped with essential advanced skills in synthesis and catalysis of particular relevance to many areas of chemical manufacturing sector where the UK has a significant presence.