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

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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.