Exploiting the interface between aromaticity and non-aromaticity

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry

Abstract

Chemistry is a dynamic subject that is at the centre of many different scientific advances. Organic chemistry is concerned with the reactivity of carbon in all of its different forms and can be viewed as the chemistry taking place within living things. Chemists are constantly looking for new ways of designing and building molecules (synthetic chemistry is essentially molecular architecture) and this proposal describes a short and powerful new way of making valuable molecules using a new catalytic system that works in combination with methanol as a (renewable resource) solvent. The molecules at the heart of the proposal are aromatic ring derivatives which are found in many different compounds of value in both the academic and commercial world.

The idea of catalysis also lies at the heart of this work; and catalysis uses small amounts of key promoters (catalysts) to make reactions run in ways that are not possible without them. Catalysts are also added to a reaction in small quantities which has beneficial consequences for the efficiency of the chemical processes involved.

The novel chemistry proposed herein will provide a new, efficient and powerful way of making cyclic and aromatic compounds using catalysis to control all aspects of the structures of the products formed: this will be of great benefit to both academia and industry who will be able to make interesting molecules in new ways. We have engaged a project partner from the pharmaceutical industry so that the project will develop rapidly into areas that are of direct interest and value to industry.

Given all of the above, it is imperative that we have novel, efficient and powerful methods for making new compounds so that we can study and use them. In addition, the development and application of new catalytic systems is also important because catalysis makes chemical reactions run faster and cleaner with less waste: this is clearly a good thing for industry and also for the environment. The real advantage of this proposal is the development of cutting edge science and its application to solve problems that are relevant to chemical scientists around the world.

Planned Impact

In this section we will answer the following two questions: Who might benefit from this research? and How might they benefit from this research?

The first beneficiary to discuss is academia, and it is my aim that the new chemistry described will find use in science labs around the world (primarily in chemistry and bioscience departments, indeed anywhere that new molecules are made). The beneficiaries outside of academia include: chemical industry including the pharmaceutical industry, the agrochemical industry and the fine chemicals industry. These beneficiaries will be able to exploit the chemistry described in this proposal to achieve the synthesis of biologically active compounds in a more efficient manner, and it will also allow chemical industry to make new molecules that were hitherto difficult to access. Organic molecule therapeutics are important and valuable with many uses, especially in healthcare, and this new science will allow industry to make the commercially valuable compounds of the future in a new and efficient way, which reduces waste and gives them a competitive advantage. Each of the beneficiaries above improves the quality of life and the wealth of the nation, through the application of novel organic chemistry. Chemical industry plays a big role in the U.K. economy and the U.K. has a very strong pharmaceutical industry, who all stand to benefit from this methodology.

Clearly, it is important that the team engages with potential end-users of this chemistry so that I can ensure the project makes the maximum impact in the most relevant areas of research. I have several plans for publicising our work and for getting industry feedback on our routes to new molecules and other potential applications of these new catalytic reactions.

The easiest way to publicise our work and collaboration is to deliver lectures in industrial laboratories, followed by a discussion of the potential applications (I have given many lectures at pharmaceutical companies and I will be speaking to industrial audiences in 2019). Since appointment in 1994, I have had many CASE type collaborations (over 40) with industry and sent many researchers to full-time employment in various industrial chemistry laboratories; so I have many (ongoing) relevant contacts within the industrial organic chemistry community. I am also a consultant for both small and large pharmaceutical companies which gives me another way to discuss this science. I have been, and will continue to be, very active in publicising our methodology and gaining feedback on useful applications of it. I was recently awarded the Society of Chemistry and Industry Prize for Process Research (for catalytic reaction development) which is sponsored by four major chemical companies and which gives an indication of the high level of interaction that I have with the industrial end-users of my work.

The timescales involved in giving a benefit to the end-users of the research is short (months rather than years): as soon as new chemistry is developed and publicised then it can be used in industrial laboratories. In the medium and long term, we expect that the new catalysed reactions that we develop will have such attendant improvements in efficiency and scalability that this will lead industry to use them.
Details of our plans for future exploitation and collaboration are given in the full PIA plan

Publications

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Description New catalytic routes to key three dimensional molecules were discovered- using rhodium catalysts. This project is still ongoing and significant work will be published in the near future.
Exploitation Route This chemistry has the potential to allow the expedient synthesis of complex 3D heterocycles from flat aromatic precursors. Scientists in both industry and academia will be able to use this method to make key compounds for their research programmes.
Sectors Pharmaceuticals and Medical Biotechnology