Merging Photoredox and Ruthenium Catalysis for new C-H Activation Chemistry

The proposed research looks to create new ways of manipulating C-H bonds using metal catalysts. Catalysis is central to modern chemistry, with the synthesis of 90% of industrially-produced molecules making use of catalytic chemistry (e.g. biological lipases in washing powder, transition metals used in the Haber process to produce ammonia). We propose to manipulate C-H bonds commonly found in organic molecules, as their selective activation offers a direct way of making new bonds in the creation of valuable chemicals. Selectivity is critical to success - how do we activate the one desired C-H 'tree' in the forest of C-H bonds that typically decorate organic molecules? Ruthenium catalysis offers an exciting solution to this difficult problem, with early work showing that precise C-H activations are possible on benzene rings for a small selection of transformations. In order to grow these exciting preliminary results into a general tool for making molecules, we need to substantially improve our control of the catalyst reactivity.

We propose a light-driven solution to this challenge - using photochemistry to effectively tune the catalyst to react in the right way. Organic molecules are typically colourless, meaning they do not absorb visible light. As a result, the discipline of photochemistry is founded upon the use of UV light, which is absorbed by organic molecules and can initiate chemical reactions. Recent developments, however, have enabled visible light from simple domestic lightbulbs to be harnessed in chemical reactions. The process depends on a second catalyst to absorb the light, which can then interact with the organic substrates to enable new types of chemical reaction. By merging these two catalytic cycles together, C-H activation and photochemistry, we propose a new system that will dramatically accelerate the synthesis of new molecules for diverse applications in medicine, engineering and agriculture.

Catalysis drives innovation in synthesis and has been integral to advances such as organocatalysis, C-H activation, gold-catalysis, and photoredox catalysis - major breakthroughs in recent years that have impacted our approach to the medicine, food, materials, and energy requirements of society. The impact of the proposed research is thus very broad, as it aims to change the way a fundamental class of molecules are made, creating new structures and functions for applications in the chemical and life sciences.

Who will benefit and how?
Academic researchers from other disciplines: Our proposed chemistry aims to simplify and strengthen synthetic chemistry by offering new ways of achieving meta-functionalisations in a single step - enabling simple, labour-saving chemistry that can produce high value molecules with a minimum of operational difficulty. In the short term, this will accelerate multi-disciplinary collaborations as chemists can deliver new structures in a reliable way. In the longer term, we want to develop meta-chemistry that is predictable enough to be used as a general 'tool' reaction, similar to how palladium cross-couplings are viewed today - reactions of such reliability that scientists from other fields can use them to routinely access molecules of interest.

Industry: Photoredox catalysis and C-H activation will have a profound effect on the business of making molecules, directly impacting the economic performance of companies and, in turn, the UK economy. In expanding the scope, expediency and diversity of arene functionalisation, our proposed chemistry will impact all sectors of the fine chemicals industry. Our work will influence process chemists looking to design cleaner, and more efficient routes to key chemicals that save money and ameliorate the environmental impact of chemistry; as well as discovery chemists working in materials, medicinal and agro-chemistry, who will employ our proposed methods to make new motifs that were previously only prepared by difficult and circuitous routes. This will generate new structures in new chemical space, having new functions, ultimately improving the UK's competitiveness.

Society: Chemical synthesis has a vast sphere of influence, in terms of the molecules that structure our society, with a multitude of fine chemical products being integral to the way we live our lives: New medicines, agrochemicals and food technologies, flavours and fragrances, personal care products, and organic materials which represent the next generation of electronic devices. Bulk chemical synthesis produces fuels, paints, coatings, adhesives and polymers as building blocks for devices and manufacturing. The invention of new catalytic routes to these products, using C-H activation and photoredox catalysis, will produce molecules that impact the way people live their lives.

Teachers of young scientists: C-H activation and photoredox catalysis introduce new ways of looking at reactivity that can inspire students to think about synthesis in unconventional ways. Ideas such as the C-H bond as functional group, or the controlled use of single electron transfer as a routine tool in synthesis, expand thinking and can capture the imaginations of students studying chemistry and looking to understand its impact on society.

People: The project will train two postdoctoral scientists in catalysis chemistry, enabling them to solve complex problems, an essential skill-set for all areas of the UK knowledge economy. They will develop project and people-management skills through interactions with other junior members of the Greaney group, and be encouraged to take creative risks in how they tackle the aims of the proposal. Highly skilled and well-trained people are essential to the long term health of UK industry, and both PDRAs will receive the training and inspiration to take up future leadership positions in science and technology.