Selective Electrochemical Nucleophilic Fluorination

Projektinformationen

SENF

ID Finanzhilfevereinbarung: 949821

DOI

10.3030/949821

EK-Unterschriftsdatum 22 Oktober 2020

Startdatum 1 August 2021

Enddatum 31 Januar 2027

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 553 043,00

EU-Beitrag

€ 1 553 043,00

Koordiniert durch

UNIVERSITY OF BRISTOL
United Kingdom

Periodic Reporting for period 3 - SENF (Selective Electrochemical Nucleophilic Fluorination)

Berichtszeitraum: 2024-08-01 bis 2026-01-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The incorporation of the element fluorine into organic compounds is extremely important for designing molecules with specific function. Fluorine is primed for improving the pharmacokinetic properties of drugs and agrochemicals, and is crucial for the life-changing imaging technique, Positron Emission Tomography (PET). Thus, the selective addition of fluorine into compounds is an area of significant interest in the field of organic synthesis.

Currently, the methods for incorporating fluorine into organic molecules are limited. The types of substrate, the types of bond and the types of functional groups that can be fluorinated are limited. In addition, the types of reagent that are employed are generally unsustainable, as they generate a lot of waste and also require a large energy input to prepare them. In this project we are working to solve these problems through the development of a suite of novel and sustainable fluorination methods.

This research project is developing a concept that is delivering new, selective and sustainable methods for fluorination chemistry. Our strategy relies on the combination of catalysis and electrochemical oxidation with nucleophilic sources of fluoride to design thermodynamically-challenging transformations. The use of electrochemical oxidation is an integral part of our strategy because it is inherently tuneable and sustainable. We are focussing our efforts on several functional groups and substrate classes that have not been previously fluorinated in a selective manner. Medicinal, process and radio chemists will all benefit from the methods developed, thereby facilitating the discovery and manufacture of drugs and chemicals that improve the quality of human life around the globe.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The main objectives in the project are to develop new fluorination reactions. Thus far, we have published two papers:

The first, which is published in in Organic Chemistry Frontiers, is a report on the development of an electrochemical method for the C-H fluorination of primary benzylic compounds using the nucleophilic form of fluoride. This is a reaction that has not been successfully performed well before. Key to the success was the use of an unusual electrochemical pulsed waveform during electrolysis, which led to an enhancement in the yield of product. We studied the effect of pulsing in-depth and elucidated the reasons behind the observed enhancement.

In the second publication, we report the development of an interesting reaction that adds fluoride and chloride onto alkenes in a way that is highly selective, in terms of their relative position, but also in their stereochemical orientation. We discovered reaction conditions that were able to switch the orientations of the fluoride and chlorides, which a strange and remarkable finding. We explored the application of this reaction by testing many different substrates. We then embarked on a very intensive mechanistic study to elucidate the effect and we discovered some novel reactivity. This report has just been accepted into Nature Chemistry.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

In each of the work packages, we are proposing to go beyond the state of the art by delivering novel chemical transformations. In each of our outputs we are reporting such novel transformations in sustainable ways and with a deep mechanistic understanding. Going forwards, we expect to finish up the projects that have been initiated and continue to discover new ways to fluorinate molecules in different ways.