Organocatalytic Fluorinations with Fluoride Salts

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Fluorine is a unique element of the periodic table that impacts hugely on society because many pharmaceuticals, agrochemicals and anaesthetics owe their important properties to the presence of fluorine atoms within their structures. For example, the small and highly electronegative fluorine atom plays a remarkable role in medicinal chemistry. Selective installation of fluorine into a therapeutic or diagnostic small molecule candidate can enhance molecular properties such as improved metabolic stability and enhanced membrane permeation. Fluorine substitution as a strategy to increase binding affinity of drug candidates to target protein has also been documented in a number of cases. One of the challenges associated with the discovery and production of these compounds is the availability of highly efficient and cost effective catalytic methods for carbon-fluorine (C-F) bond formation. To date, many chemists worldwide have actively worked in this area of research, and developed a range of processes for this purpose, but the reactions discovered to date employ expensive fluorine source derived from F2, a gas yellow in colour that is highly reactive and corrosive. Only a minority of these processes make use of cheaper fluoride salts, but these then require expensive transition metal catalysts, and suffer from narrow substrate scope.With this project, we propose to develop and study a novel catalytic reaction for carbon-fluorine bond formation, that benefits from the use of cost effective fluoride salts and cost effective catalysts made of purely organic materials and free from transition metal ions. The design of our system allows for easy chemical modification and hence simple coarse or fine-tuning of the catalysts structure and reactivity profile. The catalytic process that we have designed for fluoride activation is mechanistically unprecedented, and will be applied to the preparation of important fluorinated molecules for immediate application in medicinal chemistry. Accordingly these new catalytic fluorination and the products of these reactions will be of great value to chemists in industry and academia alike, and have the potential to impact widely on society by improving health and quality of life.