Electrochemical fluorination of proline derivatives

Pascali, Giancarlo, Ryan, Patrick, Bhattacherjee, Dhananjay, Wirth, Thomas ORCID: https://orcid.org/0000-0002-8990-0667 and Hunter, Luke 2025. Electrochemical fluorination of proline derivatives. European Journal of Organic Chemistry , e202500264. 10.1002/ejoc.202500264 Item availability restricted.

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Abstract

The introduction of a fluorine into aliphatic substituents of lead candidates can impart unique structural characteristics that allow fine tuning of drug interactions; therefore, mild, specific or late-stage fluorination procedures are of growing interest in medicinal chemistry, with the potential to be applied in F-18 radiochemistry. In this work, we demonstrate the feasibility of “reagent-less” electrochemical fluorination leading to mono- and gem-difluorinated proline cores featured in important fibroblast-activating protein inhibitors. Our study highlights the importance of using the appropriate activator substituents for allowing the process, the impact of different reaction parameters, and characterizes the various byproducts that are generated in the reaction. We have tested the reaction using a commercially available batch system and flow apparatus, achieving maximum yields of >90% (batch) for mono- and of 6% (batch) and 9% (flow) for the gem-difluorinated proline model. These proof-of-concept results indicate that the flow approach is more efficient, but that different activating substituents will be needed to achieve higher yields

Item Type:	Article
Date Type:	Publication
Status:	In Press
Schools:	Schools > Chemistry
Publisher:	Wiley
ISSN:	1434-193X
Date of First Compliant Deposit:	4 June 2025
Date of Acceptance:	20 May 2025
Last Modified:	09 Jun 2025 13:15
URI:	https://orca.cardiff.ac.uk/id/eprint/178742

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