New methodologies in enantioselective catalysis

In a world with increasing population and limited resources, the development of new synthetic chemical methods will be judged not only by their overall yield and product selectivity, but also by their ecological and economic footprint. Catalysis provides a means of achieving more efficient and environmentally friendly processes: the reaction is accelerated, the amount of energy required for the process is diminished and fewer wasteful by-products are obtained. Overall, catalysis plays an important role in saving energy, time and costs in chemical processes. Moreover, in the particular case of enantioselective catalysis, the catalyst also provides the source of asymmetry needed to selectively synthetise one of the two possible non-superimposable mirror images of the product - the so-called enantiomers. The selective synthesis of enantiopure compounds is of vital importance in the preparation of a myriad of products in daily life, from pharmaceutical and agricultural products to polymers and smart materials.

This proposal focuses on the development of a robust catalytic methodology for the preparation of enantiopure building blocks from cheap and readily available starting materials. The chemical reaction that is the main subject of this proposal is the addition of an organometallic reagents to a C=O bond. This reaction is one of the most powerful tools in organic chemistry to create a new C-C bond and has been extensively studied with organozinc and organoboron reagents. However, the higher reactivity of organomagnesium and organolithium reagents has hampered their application in this field. The fact that both organomagnesium and organolithium reagents are more accessible and economically viable nucleophiles, drives the development of novel suitable catalytic systems to fulfil the scientific, economic and environmental demands.

Recent discoveries in our laboratories have brought forward a readily available catalyst as part of an outstanding methodology for the addition of organomagnesium and organolithium reagents to C=O bonds. The mechanism of this recently established methodology is still unknown and, by means of the research proposed here, we intend to get a better understanding of the process - which will allow further improvements of the methodology (e.g. by resolving the current limitations regarding substrate scope). In addition, we will also investigate the use of this novel catalytic system in the production of fluorinated molecules, whose unique properties make them especially attractive as pharmaceutical agents and advanced materials.

Enzymes are Nature's catalysts. They are extremely efficient and selective and they make possible essentially all biological reactions. By comparison with today's technology, enzymes show us how much opportunity there is for improvement in the area of catalysis. The development of new catalytic systems with level of control and efficiency comparable to the ones that Nature demonstrates is a timely and relevant topic of research with important economic and social implications.

Catalysis plays an essential role in the solutions to major problems that our society faces: energy production, environmental damage, and more generally, the quality of life. Investigations in catalysis are timely and relevant in a society that needs to develop more efficient reactions that can be applied in both industry and academia to produce relevant materials, from pharmaceuticals to polymers.

This proposal will create impact by exploiting both fundamental and advanced scientific knowledge in order to generate original science in currently unexplored areas. The proposed projectwill provide economic and social benefits by advancing technological development through the improvement of existing techniques and the possible invention of new ones. This will help further the promotion and development of scientific excellence in the UK and will provide long-term potential benefits, including international recognition and making the UK more attractive to first class researchers.

The research proposed here will be disseminated in several different ways to ensure the widest possible impact:
(1) Publication of articles in international scientific journals will ensure that the work reaches relevant scientific audiences and will prove the quality of the research.
(2) Participation in conferences, seminars and symposiums will bring our work closer to the scientific community and help in the development of possible collaborations.
(3) The implementation of this project will provide international scientific benefits in terms of developing a possible long lasting collaboration with researchers in Spain, which could be funded by European programmes in the future.
(4) The establishment of collaborations with pharmaceutical and chemical companies (e.g. with Syntor Fine Chemicals, Cheshire) will promote dissemination and potential economic impact. It will also allow discussions about opportunities to investigate further routes towards more efficient and sustainable processes and/or commercially exploit the project findings with businesses.
(5) This research will also have impact on teaching activities. In particular, the results of this project would be incorporated and disseminated through Unit 6ACH4117: Research Frontiers in Materials Chemistry, taught in the fourth year of Chemistry Studies at MMU.
(6) A project website will be maintained and regularly updated with the latest information about the project and the research results, allowing a very wide potential audience to see how the research is progressing.
(7) Several outreach activities have also been planned to raise the profile of this research area in society at large: (i) presentations at the Manchester Science festival; (ii) poster presentations during 'Open Days' at MMU; (iii) visits to primary and secondary schools; (iii) Publication of short videos in YouTube; (iv) publication of articles on Wikipedia.

In summary, catalysis is a solution to the sustainability problems that we face nowadays and the promotion of the research proposed here will offer real profit and impact, not only for academia or industry, but also for society in general.