New Insights, New Catalysts and New Processes using Enantioselective Carbonylations.

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EPSRC
EPSRC
EPSRC
EPSRC
EPSRC

£2,602,675

Aug. 31, 2014

Nov. 30, 2017

This project is in the field of chemo-catalysis. Catalysis is used somewhere in the manufacture of most everyday items (plastics, drugs, food supplements, flavours/fragrances, finishes and coatings). Amongst the most important reactions, generally used in the manufacture of diverse products such as varnishes, plastics, banana flavouring and anti-inflammatories!, are those that use carbon monoxide as a building block. Carbon monoxide is one of the cheapest chemicals and can come from coal, oil, gas and renewables. Due to the low price of carbon monoxide and the fact that it can, in the presence of a catalyst, react in a very clean fashion with other molecules, these catalytic carbonylation reactions generate very little waste and are economical even at very large scale (Millions of tonnes).
These features also potentially make this type of reaction a clean and economical way to make much higher value, more sophisticated molecules such as drugs. However, to make these molecules, exquisite control of several types of selectivity is needed.
For example, many drugs exist as two mirror image forms (optical isomers) and one isomer must be made prefentially. The other optical isomer is often inactive, or in fact can cause an alternative biological effect (The side effects of Thalidomide are a tragic example of one optical isomer causing unwanted biological effects). This has led to a massive research effort by chemists to develop chemical reactions that are capable of selectively producing a single optical isomer ('Asymmetric Synthesis'). Significant developments have been made in this area, with several Nobel prizes in chemistry being awarded to some of the pioneers in asymmetric synthesis.
The investigators group has recently obtained exciting preliminary results developing catalysts that can control several aspects of selectivity in model studies on a few types of carbonylation, including excellent selectivity to one optical isomer. This new project addresses building on these results to develop routes to different target chemicals.
Development of new types of carbonylation or the ability to work on hitherto unreactive substrates is needed for the higher value fine chemicals/pharma intermediates sector. A number of potentially exciting new reactions such as combining several reaction into one stage of a synthesis, and one reactor, one set of solvents, purification etc. are proposed.
This project will also gain mechanistic insights on the new catalyst and use this information to generate refined catalyst design and rational design of catalysts to accomplish new tasks. Overall the project has the potential to impact on fundamental knowledge, generate proof of concept for new industrial targets, and provide better, more benign routes to a range of important chemicals.

Potential Impact:
The project combines mechanism and catalyst optimisation studies with new applications. This project incorporates developing an understanding of how an important catalyst system operates. That information will be used to improve (already state-of-the-art) performance and to develop more sustainable routes to new targets. The potential impact is significant and broad. Potential economic impacts are three-fold. Potentially short-medium-term direct impacts, medium-long term direct impacts, and indirect impacts. The project is built upon two exciting preliminary studies, and recognising the possibilities for shorter term direct impact, patents are filed. Companies who manufacture pharmaceuticals and fragrances may wish to licence this technology if this further research is carried out. The project is also aiming to increase the range of chemicals that can be advantageously made using this technology. This provides further opportunities for a broader range of companies who may have products that could be economically accessed using this technology once it is extended in scope. The fundamental understanding of how these catalysts work can impact in different sectors, such as commodity chemicals where this general class of reaction is widely applied, and understanding is vital to improve catalyst activity, stability, branched selectivity etc.
There may also be new variants of this reaction that could spring from the principles built up here that could be useful for industry and might form new collaborative research with the investigators. There are also sure to be indirect impacts; this project is in the discipline of Catalysis. This field is known to contribute in a huge way to the global economy. It has been estimated that the majority of all products (not just chemicals) use catalysis at some stage in their production. Catalysis relies, to a strong extent, on using previous research results in ways that were not foreseen initially. Thus, many commercially applied reactions have relied on information from a range of academic studies on unrelated challenges in totally different topics. In the same way, a novel project such as this is also likely to indirectly impact other economically important catalysis projects. The fact that this project does address real industrial issues, and is also novel, and not following the crowd in an academic context increases the odds of these indirect impacts on knowledge and possibly the commercial sector. In addition several foreseeable indirect impacts are noted in the case for support and/or the pathway to impact document.
The project has teamed up with a commercial partner that offers technology to end users (and markets its own generic drugs). Another company has been identified with a possible interest. Both manufacture in the north-east of England. It is frequently noted that the UK economy depends on development of high-tech, high value manufacturing. Regardless if this makes it to a significant commercial application, it is envisaged that this new technology will be available in a company's portfolio of technology. It therefore can be envisaged to help underpin the UK and EU's position in high-tech manufacturing. If a full commercial process is commissioned, then this secures manufacturing jobs. It is also likely to be a greener route to a target, producing less waste, lower energy demand etc. This therefore could contribute to european targets to develop more sustainable processes, and the European reputation in this area. Other socio-economic impacts include possible export and transfer of knowledge. When overseas companies support follow-on projects in the investigators laboratories, this is an export of knowledge. If this grant enables this to be sustained, it contributes in cash terms and in sustaining St Andrews reputation as a global recognised centre for research.