Alkenes, fluorination, reagents

Systems usually fluonnated by electropositive fluorine reagents include acti-vated alkenes (enol ethers, enol acetates, silyl enol ethers, and enamines), activated aromatic systems, certain slightly activated carbon-hydrogen bonds, and selected organometallics. 

Electrophilic fluorination is the process by which fluorine is delivered to an electron-donating reactant, such as an alkene, aromatic ring or carbanion, by a formal positive-fluorine reagent to form a carbon-fluorine covalent bond. These reactions are fast and have proven extremely valuable for some important fluorine-18-labelled radiopharmaceuticals. Over the years several reviews on electrophilic fluorination were written. The reader is encouraged to seek out these works for greater detail on the subject [7,68-70]. 

The need for a variety of organofluorine molecules has encountered difficulties with oxygenated substitutes such as carboxylic esters due to their poor nucleophilicity towards electrophilic fluorinating reagents. This has led several groups to explore the conversion of the thiocarbonyl group into the CF2 moiety. It was successful with thioamides [174], dithioesters [175-177] and thionoesters [178, 179], providing new routes to difluoro-sulfides, amines, ethers and alkenes. 

Fluorination of alkenes. The reagent adds in the Markownikofl fashion to alkenes to yield alkyl fluorides (35-90% yield). It converts secondary and tertiary alcohols into the corresponding alkyl fluorides. In situ diazotization followed by dediazotization converts a-amino acids into a-fluorocarboxylic acids (38-98% yield). The reagent converts acid chlorides and anhydrides into acid fluorides. ... 

Several oxaziridines related to (14) (eq 8) have been used, most notably in the enantioselective oxidation of sulfides to sulfoxides, of selenides to selenoxides, and of alkenes to oxiranes, It is also the reagent of choice for the hydroxylation of lithium and Grignard reagents and for the asymmetric oxidation of enolates to give a-hydroxy carbonyl compounds, - A similar chiral fluorinating reagent has also been developed, ... 

Polymer-bound phenyliodine difluoride, which also has been used as a reagent to add fluorine to alkenes, can be prepared by the addition of xenon difluoride to the polymer [134, 135 136] Methyl iodide is converted to trifluoro methyliodine difluoride by treatment with fluorine at -110 C [137] Perfluoro-alkyliodine tetrafluorides could be synthesized from the perfluoroalkyliodine difluorides and fluorine [138] or chlorine trifluoride [139] Perfluoroalkyl [140] and perfluoroaryl [141] iodides are oxidized to the corresponding iodine difluorides by chlorine trifluoride. 

Xenon difluoride [4, 5, 7, 8,10] is a white crystalline material obtained through the combination of fluorine and xenon m the presence of light The reagent is commercially available and possesses a relatively long shelf-life when stored cold (freezer) Xenon difluoride is very effective for small-scale fluormation of alkenes and activated nucleophilic substrates. The reactions are usually conducted between 0 °C and room temperature in chloroform or methylene chloride solutions Hydrogen fluoride catalysis is sometimes helpful Xenon difluoride reacts in a manner that usually involves some complexation between the substrate and reagent followed by the formation of radical and radical cation intermediates... 

Fluorinated a-aminophosphonates containing two pendent alkene chains with catalyst la led to six- or seven-membered cyclic phosphonates as potential antibacterial reagents [36] (Sciieme 8.4). 

The synthetic protocol for many of these reagents is detailed elsewhere9. Note that stereochemistry in EIZ alkenes is preserved in the formation of both the fluorinated vinyl-lithium and the fluorinated vinylzinc reagents, and that hindered bases permit selective metallation vs. metal/halogen exchange. 

Acetyl hypofluorite appears to be a milder reagent than trifluoroacetyl hypofluorite in the fluorination of alkenes and acetylenes. Acetyl hypofluorite undergoes addition to the C = C bond in the fluorination of cyclohexene the ij f7-adduct 4 is obtained in 60% yield, while the reaction with dodec-l-ene gives 2-acctoxy-l-fluorododccanc (5) in 30% yield.10... 

The effect of the reagent structure on the fluorination of phenyl-substituted alkenes 6 has been studied in great detail and the higher svn addition observed with trifluoroacetyl hypofluorite in comparison with acetyl hypofluorite explained on the basis of an intermediately formed... 

The reaction of fluorine with water, producing hypofluorous acid (HOF) and subsequently oxygen difluoride (OF2), has been the subject of intensive study over the last fifty years.1 Additionally, hypofluorous acid in acetonitrile has been characterized.5 The reagents are potentially explosive and present a toxicity hazard similar to fluorine therefore, work should be carried out in an efficient hood and proper safety equipment is required. It was established in the earliest investigations that the reaction of hypofluorous acid with alkenes in nonpolar solvents gives fluoro hydrins, e.g. 1, in high yield.6 However, it is now clear that epoxides are initially formed in acetonitrile7 and 1,2-epoxycyclohexane (2) is formed in reactions with cyclohexene in various solvents.5... 

The fluorination of alkenes with XeF2 has been reviewed.582 Furthermore, PhTeF5 and PhSeF5 have been shown to be powerful difluorinating reagents.583... 

In 1975, it was reported that while lanthanide shift reagents could not be used directly to simplify the NMR spectra of alkenes, when coupled with silver salts substantial shifts could be induced.232 Since then, a number of studies have reported the use of both chiral and achiral lanthanide(III)-silver(I) binuclear shift reagents,233-237 where the ligands were generally fluorinated /3-diketones. 

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