C-F Bond Functionalization with Organolithium Compounds

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.