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Catalytic Appel fluorination of alcohols with potassium fluoride.

Created on 31 Jul 2026

Authors

Anirban Mondal, Job J C Struijs, Caleb J N Doyle, Zijun Chen, Zian Wang, Worawit Tangamornchaipattana, Christophe Allais, Paul F Richardson, Jared Piper, Robert S Paton, Simon Aldridge, Véronique Gouverneur

Published in

Science (New York, N.Y.). Volume 393. Issue 6810. Pages 514-521. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

Appel halogenation reactions are widely used to convert alcohols to alkyl halides but are not suitable to prepare alkyl fluorides because fluoride is sequestered as a difluorophosphorane. In this work, we introduce bench-stable neopentoxyphosphonium salts to solve this enduring challenge. With these reagents, various alcohols undergo fluorination with potassium fluoride under hydrogen bonding phase-transfer catalysis, a manifold offering a pathway to enantioselective fluorination of alcohols. Mechanistically, a neopentoxyfluorophosphorane is formed, which undergoes reversible exchange with the alcohol substrate in preference to difluorophosphorane formation. The catalyst assists with potassium fluoride solubilization and with phosphorus-fluorine bond dissociation, leading to the alkoxyphosphonium fluoride ion pair undergoing stereoinvertive fluorination. Turnover results from stronger binding of the catalyst to fluoride than phosphine oxide, the by-product of the reaction, which is recyclable as starting material for the synthesis of the phosphonium reagents.

PMID:
42531410
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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