Electrochemical Nucleophilic Fluorination

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

Nucleophilic fluorination ([F-]) reagents are more desirable than electrophilic reagents ([F+]), because they are inexpensive, produce less waste and are more sustainable. Conversely, [F+] reagents typically have more controllable and selective reactivity, but are difficult to implement on manufacturing scales. The combination of electrochemical oxidation and nucleophilic fluorination, however, should provide the perfect partnership to achieve selective fluorination with the use of [F-] reagents.
Electrochemistry promises to revolutionise redox reactions in organic synthesis: the
inherent tunability of the applied potential provides high selectivity, as well as milder
and safer conditions. Electrochemistry is the most sustainable way to conduct redox
reactions, as there is complete control over the ultimate destination (or source) of
electrons, undesirable redox reagents and their waste can be avoided. The technique is
practical, as demonstrated by a number of industrial processes that are in operation. For
these reasons the field is currently experiencing a resurgence of interest.
The overall aim of the project is to combine electrochemical oxidation and nucleophilic fluorination into a unified method for the fluorination of common functional groups using convenient and inexpensive nucleophilic F- reagents.
A number of target reactions will be explored:
Benzylic fluorination - expand on limited literature precident for direct oxidation/fluorination of benzylic C-H bonds to develop a milder and more selective process. Demonstrate the fluorination of heterocyclic methyl groups
Carbonyl fluorination - use reagent umpolung or fluoride umpolung approaches to develop the first one-pot procedure for carbonyl fluorination using an [F-] reagent, under electrochemical control.
Alkyne fluorination - develop a general method for the oxidative di-functionalisation of alkynes, with the selective addition of [F-] and another nucleophile, affording alkenyl fluorides which are important as mimetics of amides and enols

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/T51763X/1 01/10/2019 30/09/2024
2286771 Studentship EP/T51763X/1 01/10/2019 30/09/2023 Alexander Atkins