Carbon-fluorine bond formation

In contrast to phosphorus esters, sulfur esters are usually cleaved at the carbon-oxygen bond with carbon-fluorine bond formation Cleavage of esteri nf methanesulfonic acid, p-toluenesidfonic acid, and especially trifluoromethane-sulfonic acid (tnflic acid) by fluoride ion is the most widely used method for the conversion of hydroxy compounds to fluoro derivatives Potassium fluoride, triethylamine trihydrofluoride, and tetrabutylammonium fluoride are common sources of the fluoride ion For the cleavage of a variety of alkyl mesylates and tosylates with potassium fluoride, polyethylene glycol 400 is a solvent of choice, the yields are limited by solvolysis of the leaving group by the solvent, but this phenomenon is controlled by bulky substituents, either in the sulfonic acid part or in the alcohol part of the ester [42] (equation 29)... 

Recent progress on the use of hypervalent iodine reagents for the construction of carbon-het-eroatom (N, O, P, S, Se, Te, X) bonds is reviewed. Reactions of aryl-A3-iodanes with organic substrates are considered first and are loosely organized by functional group, separate sections being devoted to carbon-azide and carbon-fluorine bond formation. Arylations and alkenyla-tions of nucleophilic species with diaryliodonium and alkenyl(aryl)iodonium salts, and a variety of transformations of alkynyl(aryl)iodonium salts with heteroatom nucleophiles are then detailed. Finally, the use of sulfonyliminoiodanes as aziridination and amidation reagents, and reactions of iodonium enolates formally derived from monoketones are summarized. 

Oxidation involving carbon-oxygen and carbon-fluorine bond formation... 

The importance of fluorinated organic componnds both in medicinal chemistry and biochemistry has resulted in much recent attention towards efficient carbon fluorine bond formation [30]. The reactions developed include a very successful electrophilic asymmetric mono-fluormation of 1,3-dicarbonyl compounds [31]. A nucleophilic variant was also investigated. In this context, the groups of Togni and Mezzetti have established that ruthenium Lewis acids could efficiently catalyze fluorination reactions [32]. In the presence of [Ru(l,2-bis(diphenylphosphino)ethane)2Cl][PF6] (8) (10 mol%), fert-butyl iodide reacted at room temperature with TIF (1.1 equiv.) to yield fert-butyl fluoride (84% yield). This reaction was extended successfully to a range of organic halides (Entries 1-3, Scheme 10.19). The use of the chiral complex [Ru((lS,2S)-N,N bis[2-diphenylphos-phino)benzylidene]diaminocydohexane))Cl][PF6] (9) showed modest chiral induction at the outset of the reaction (Entry 4, Scheme 10.17). The near-racemic mixture obtained at completion points to an SNl-type process in this nucleophilic halide... 

N. Shibata, H. Yasui, S. Nakamura, T. Torn, DNA-mediated enantioselective carbon-fluorine bond formation, Synlett, 2007, 1153-1157. 

O Hagan D, Schaffrath C, Cohh SL, Hamilton JTG, Murphy CD. Biosynthesis of an organofluorine molecule-a fluorinase enzyme has been discovered that catalyses carbon-fluorine bond formation. Nature 2002 416 279-279. 

Furuya T, Kuttmff CA, Ritter T. Carbon-fluorine bond formation. Curr. Opin. Drug Discov. Develop. 2008 11 803-819. 

Enantioselective synthesis of, y-unsaturated a-fiuoroesters catalysed by Af-hetero-cyclic carbenes has been reported. " In the presence of an appropriate combination of a precatalyst, a base, and an additive, the carbon-fluorine bond formation occurs efficiently at the a-position of enals, thus overcoming nontrivial challenges, such as competitive y-fluorination, difluorination, nonfluorination, and interaction between Af-heterocyclic carbenes and Af-fluorobis(phenylsulfonyl)imide (NFSI). The reaction proceeds with very good enantioselectivity (up to 96% ee). 

Pyrolysis of chlorodifluoromethane is a noncatalytic gas-phase reaction carried out in a flow reactor at atmospheric or sub atmospheric pressure yields can be as high as 95% at 590—900°C. The economics of monomer production is highly dependent on the yields of this process. A significant amount of hydrogen chloride waste product is generated during the formation of the carbon—fluorine bonds. 

Recent Advances in the Selective Formation of the Carbon-Fluorine Bond ... 

The search for new selective synthons is an important area in organo-fluorine chemistry.1 4 In recent years organosilicon chemistry has become important in the development of new methodologies in organic synthesis.5-8 Anionic activation of tetracoordinate organosilicon species has been utilized for a variety of C —C and carbon heteroatom bond formation strategies in syntheses of highly fluorinated materials.9 13... 

The first observation of penta- and hexaeoordinate silicon compounds was reported at the beginning of the 19th century by Gay-Lussac [87] and Davy [88], Subsequent investigation of hypercoordination in silicon compounds stimulated widespread use of nucleophilic activation and catalysis in the application of organosilicon compounds as reactive species in organic synthesis. Synthetic application for silicon-fluorine bond formation can be found in several reviews over the last two decades, and this section focuses on recent advances in the use of hypervalent organosilicon compounds in selective organic synthesis, in particular, selective carbon-carbon bond formation [89]. 

Initial formation of an aryne, followed by nucleophilic attack, is not a likely mechanism. The most important factors that detract from such a mechanism are the following (1) the base is not a strong base, and (2) the carbon-fluorine bond is very strong. 

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