Exploring transition metal-catalysed fluorine transfer reactions

Lead Research Organisation: University of Nottingham
Department Name: Sch of Chemistry


Project background (identification of the problem and its importance and relevance to sustainability)

Organofluorine molecules are an important class of compounds which find several diverse applications due to the incredible strength and high polarity of the C-F bond. C-F bonds are found within are found in pharmaceuticals, PET-imaging agents, agrochemicals, polymers, optoelectronics and many other high-performance molecules.

Fluorination is the process of adding fluorine atoms to organic molecules, which throughout the 20th century was an extremely unsafe and challenging feat due to the toxic and hazardous HF and elemental fluorine reagents used. These methods often have poor selectivity and lead to over-fluorination. Therefore, over the past two decades, a portfolio of safe and easy-to-handle reagents have been developed, capable of late-stage fluorination of pharmaceutical targets. However, these developments have prioritised selectivity and control over energy and sustainability concerns. These reagents often react with incredibly low atom-efficiencies, are often required in excess quantities and require tremendous amounts of energy to produce. Furthermore, despite the impact this important class of compounds has had on society, our dependence on this raw material is unsustainable. Fluorine is a finite resource derived almost entirely from inorganic fluoride, in which current estimates suggest will sustain the industry for less than 100 years.

Proposed solution and methodology

The industry requires a shift towards using greener and more sustainable methods for fluorination, whilst utilising fluorinated feedstocks that are cheaper, accessible and have lower environmental impact. Over recent years, poly- and perfluorinated compounds have become a useful feedstock because they are easily accessed via established industrial processes. C-F functionalisation of these compounds gives access to partially fluorinated building blocks, that are otherwise challenging to produce. Several transition metal-catalysed, metal-free catalysed, photocatalytic and electrocatalytic routes have been developed. Transition metal-catalysed routes are dominated by fluorophilic reducing agents, such as silanes and boranes, due to the strong Si-F and B-F bonds formed, which result in the loss of the fluorine from the system.

This project aims to develop insight into transition-metal catalysed transfer fluorination reactions, to strive towards a more circular economy for fluorine. In this reaction, fluorine is removed from an over-fluorinated substrate where it is not required and introduced to where it is desired via a transition-metal catalyst, yielding two valuable products simultaneously. Transfer functionalisation reactions are an emerging and powerful class of transformations as they proceed with high atom economies and produce minimal waste. The design of an efficient and atom-economic fluorine transfer reaction, using available sources of fluorine would mitigate the issues associated with current fluorination and defluorination methods in a single process.

Planned Impact

This CDT will deliver impact aligned to the following agendas:

A2P will provide over 60 PhD graduates with the skill sets required to deliver innovative sustainable products and processes into the UK chemicals manufacturing industry. A2P will inspire and develop leaders who will:
- understand the needs of industrial end-users;
- embed sustainability across a range of sectors; and
- catalyse the transition to a more productive and resilient UK economy.

A2P will promote a step change towards a circular economy that embraces resilience and efficiency in terms of atoms and energy. The benefits of adopting more sustainable design principles and smarter production are clear. For example, the global production of active pharmaceutical ingredients (APIs) has been estimated at 65,000-100,000 tonnes per annum. The scale of associated waste is > 10 million tonnes per annum with a disposal cost of more than £15 billion. Consequently, even a modest efficiency increase by applying new, more sustainable chemical processes would deliver substantial economic savings and environmental wins. A2P will seek and deliver systematic gains across all sectors of the chemicals manufacturing industry. Our goals of providing cross-scale training in chemical sciences with economic and life- cycle awareness will drive uptake of sustainable best practice in UK industry, leading to improved economic competitiveness.

This CDT will deliver significant new knowledge in the development of more sustainable processes and products. It will integrate the philosophy of sustainability with catalysis, synthetic methodology, process engineering, and scale-up. Critical concepts such as energy/resource efficiency, life cycle analysis, recycling, and sustainability metrics will become seamlessly joined to what is considered a 'normal' approach to new molecular products. This knowledge and experience will be shared through publications, conferences and other engagement activities. A2P partners will provide efficient routes to market ensuring the efficient translation and transferal of new technologies is realised, ensuring impact is achieved.

The chemistry-using industries manufacture a rich portfolio of products that are critical in maintaining a high quality of life in the UK. A2P will provide highly trained people and new knowledge to develop smarter, better products, whilst increasing the efficiency and sustainability of chemicals manufacture.
To amplify the impacts of our CDT, effective public engagement and technology transfer will become crucially important. As a general comment, 'sustainability' styled research is often regarded in a positive light by society, however, the science that underpins its effective implementation is often poorly appreciated. The University of Nottingham has developed an effective communication portfolio (with dedicated outreach staff) to tackle this issue. In addition to more traditional routes of scientific communication and dissemination, A2P will develop a portfolio of engagement and outreach activities including blogs, webpages, public outreach events, and contribution of material to our award-winning YouTube channel, www.periodicvideos.com.

A2P will build on our successful Sustainable Chemicals and Processes Industry Forum (SCIF), which will provide entry to networks with a wide range of chemical science end-users (spanning multinationals through to speciality SMEs), policy makers and regulators. We will share new scientific developments and best practice with leaders in these areas, to help realise the full impact of our CDT. Annual showcase events will provide a forum where knowledge may be disseminated to partners, we will broaden these events to include participants from thematically linked CDTs from across the UK, we will build on our track record of delivering hi-impact inter-CDT events with complementary centres hosted by the Universities of Bath and Bristol.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S022236/1 01/10/2019 31/03/2028
2606306 Studentship EP/S022236/1 01/10/2021 30/09/2025 George Cadman