C–F Bond Functionalization with Organolithium Compounds

Abstract

Cross-coupling of alkyl fluorides and organolithium compounds is achieved by liquid-assisted stirring and mild heating without the need for expensive catalysts or additives. The reaction proceeds with a variety of primary, secondary, and tertiary fluorides; several functional groups, including alkyl halides, ether, amide, and heteroaryl groups, are tolerated; and both aryl and alkyllithium compounds can be used. Mechanistic studies indicate that the reaction involves heterolytic C–F bond activation and proceeds either via generation of short-lived carbocation intermediates or through a concerted pathway, which probably predominates with primary substrates, while the formation of thermodynamically stable lithium fluoride is the driving force.

Keywords

Alkyl fluorides - Cross-coupling - Organolithium reagents - C–F bond functionalization - Liquid-assisted mixing

Publication History

Received: 20 August 2025

Accepted after revision: 01 October 2025

Accepted Manuscript online:
01 October 2025

Article published online:
27 October 2025

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