Exploring transition metal-catalysed fluorine transfer reactions

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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.