Alkyl fluorides, synthesis

Landini, D., F. Montanari, andF. Rolla, Reaction of Alkyl Halides and Methanesulfonates with Aqueous Potassium Fluoride in the Presence of Phase Transfer Catalysts A Facile Synthesis of Primary and Secondary Alkyl Fluorides, Synthesis, 428 (1974). 

The synthesis of alkyl fluorides Is best accomplished by heating an allyl chlorlde/bromlde In the presence of a metallic fluoride such as AgF, HggFg, CoFg or SbFg. The reaction is termed as Swarts reaction. 

Moissan and his colleague Meslans then tried other methods for C —F bond synthesis.121 Alkyl fluorides could not be made via reactions of alcohols with hydrogen fluoride or phosphorus fluorides. However, silvcr(l) fluoride was found to function as a halogen-exchange reagent and several alkyl fluorides were made and characterized, all being fairly resistant to alkaline hydrolysis. 

Aliphatic carbamates (readily available from alcohols and sodium cyanate)313 have also been submitted to fluorodediazoniation16,90 314 to give alkyl fluoroformates 890 which are useful tools in peptide synthesis and also valuable precursors of alkyl fluorides.315... 

Summarizing, it can be stated that hydrogen fluoride/pyridine and hydrogen fluoride/amine mixtures are useful for the synthesis of simple secondary and tertiary alkyl fluorides, but probably arc not suitable for fluorination reactions in complex multifunctional structures due to the highly acidic properties of these reagents. 

Not within the scope of this section are the synthesis of a-fluoro sulfides from dithioace-tals, their reduction to alkyl fluorides, and the synthesis of glycosyl fluorides from (phenyl-sulfanyl)glycosides. ... 

Though broadly useful for the synthesis of alkylbenzenes, the Friedel-Crafts alkylation nevertheless has strict limitations. One limitation is that only alkyl halides can be used. Alkyl fluorides, chlorides, bromides, and iodides all react well, but aryl halides and vinylic halides do not react. Aryl and vinylic carbocations are too high in energy to form under Friedel-Crafts conditions. 

The fact that fluoride is a poor leaving group in aliphatic nucleophilic substitutions and the high volatility of fluoroaliphatic compounds are the keys to the Finkelstein synthesis of alkyl fluorides. An alkyl iodide, bromide, or tosylate is heated in a polar solvent vith an alkali fluoride and the volatile alkyl fluoride is removed by distillation during the reaction [30] (Scheme 2.11). For safe handling of primary alkyl fluorides it must be kept in mind that the even-membered compounds of this series are toxic, because they can be oxidatively metabolized to the poisonous fluoroacetate [31]. 

Gandelman and co-workers have reported the synthesis of secondary alkyl fluorides using a Suzuki-Miyaura cross-coupling of 1-halo-l-fluoroal-kanes (Scheme 13.19). Geminal dihaloalkanes were used as starting materials and the report demonstrated that these simple 1-fluoro-l-haloalkanes... 

Scheme 13.19 Gandelman and co-workers synthesis of secondary alkyl fluorides.

Scheme 13.20 The direct asymmetric catal3dic stereoconvergent synthesis of enantioenriched secondary alkyl fluorides.

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