Changing the nature of chemical synthesis through metal catalyzed C-H bond functionalization

Despite the changing face of science, the importance of synthesis - the ability to make molecules - has not diminished. To solve the increasingly complex synthetic problems posed by Nature, medicine and materials, we must question the dogma that defines what we know about making organic molecules. This proposal seeks to address the 'synthesis grand challenge' to develop a new blueprint for chemical synthesis that will revolutionize the way that molecules are made in response to societies needs. In contrast to conventional synthesis, that often requires numerous chemical operations to link two molecules together, we will activate traditionally inert, but ubiquitous, carbon-hydrogen (C-H) chemical bonds with metal catalysts and transform them directly into a useful chemical architecture thereby streamlining the synthesis of natural products, medicines and materials. This will impact broadly in academia, industry and across modern society, providing (a) better ways of making molecules, (b) cheaper medicines through accelerated drug discovery, (c) advances in materials and chemical biology through chemical modification of polymers and proteins, (d) potential advances in energy related research through understanding the mechanism of hydrocarbon oxidation, and (e) an enhanced chemistry knowledge base.

The impact of this research programme arises from the development of a new blueprint for chemical synthesis that will revolutionize the way that molecules are made. In contrast to conventional synthesis strategies, the paradigm shifting research concepts of this proposal represent a major step-change from the chemist's current approach to molecule assembly. By using a metal catalyst to selectively transform specific C-H bonds in hydrocarbons directly into a useful chemical structure, we will make this traditionally unreactive and ubiquitous motif behave as a highly versatile functional group that will underpin efficient complex molecule synthesis. Chemical synthesis based on this concept will be Innovative, Green, and High value. The broader impact of this research will be felt across modern society because the molecules that make up everyday products such as medicines, plastics, chemical commodities and fuels are almost always derived from arene, alkene, or alkanes hydrocarbons. Therefore, the outputs from this research will provide (a) better ways of making molecules, that lead to (b) new & cheaper medicines through accelerated drug discovery, (c) advances in materials and chemical biology through chemical modification of macromolecules, (d) potential advances in energy related research through understanding the mechanism of hydrocarbon oxidation, and (e) an enhanced knowledge base that will underpin the future of the Britain's 'Chemical Economy'. The following will benefit from this research, and how will they benefit 1. Academic community Acquiring knowledge and skills through the development of new methods and theoretical advances related to the research. In particular students and PDRA's will see the biggest benefit 2. Industry Acquiring knowledge and skills through the development of new methods and theoretical advances related to the research. This will lead to faster ways to make medicines, more cost effective drug synthesis, new fine chemicals, new fuels and better energy efficiency 3. General Public The public will benefit from improved health, energy and quality of life as a result of this research, from cheaper medicines, new materials and fuels. 4. Those in Education Those in education will benefit from learning about paradigm shifting new research, inspire them to become tomorrow's scientists. 5. The UK's Economy Will see impact in the knowledge base through our research. Spin out companies will increase prosperity by creating jobs and new technology business. Leveraging funding from other agencies will be provide high value for money to the grant. What will be be done to ensure they benefit. Broad dissemination though high profile publication, conferences, meetings, workshops, scientific and popular media and public engagement. Consultancy with industry, collaboration with academia and industry will all be mechanism to implement the impact. Setting up a enterprise though spin-out companies and job creation will stimulate the economy. The training of the researchers will be the biggest driver to impact this research. This research will be paradigm shifting and its impact will affect many aspects of modern society. The PI is dedicated to ensuring that the research results in the maximum impact.