Source of fluoride ion

A general process that involves direct and efficient reaction of fluorspar with organic halides would be very desirable but, so far, this has not been realised, except through generation in situ of hydrogen fluoride [60]. 

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Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

The effectiveness of various sources of fluoride ion in the displacement of the trifluoromethanesulfonic group has been demonstrated while introducing a fluorine atom into the five-membered carbocyclic ring of a prostaglandin precursor Treat tnent of the corresponding triflyl derivative with potassium fluoride in acetonitrile or with cesium fluonde in refluxing diinethylformamide or hexamethylphosphoric... 

Fluorodenitration of nitroaliphatics has been primarily restricted to polyni tromethanes (Table 9) Side reactions involving potassium nitnte by-product reduce yields of fluoromtromethane The novel use of the adduct of potassium fluoride with hexafluoroacetone in diglyme as a source of fluoride ion for the fluorodenitration of tetranitromethane significantly increases the yield of fluorotn nitromethane [102] (equation 29)... 

TBAF has been used as a source of fluoride ions in a number of substitution reactions studied by Cox et al. [23]. Allcyl and acyl halides react with TBAF to give the corresponding allcyl or acyl fluoride in good yield. In the reaction between (R)-2-tosyloctane and TBAF, the product was (S)-2-fluorooctane, confirming an Sn2 mechanism for the reaction (Scheme 5.1-5) [18, 23]. 

Fluoride ion is effective in promoting the reduction of aldehydes by organosil-icon hydrides (Eq. 161). The source of fluoride ion is important to the efficiency of reduction. Triethylsilane reduces benzaldehyde to triethylbenzyloxysilane in 36% yield within 10-12 hours in anhydrous acetonitrile solvent at room temperature when tetraethylammonium fluoride (TEAF) is used as the fluoride ion source and in 96% yield when cesium fluoride is used.83 The carbonyl functions of both p-anisaldehyde and cinnamaldehyde are reduced under similar conditions. Potassium bromide or chloride, or tetramethylammonium bromide or chloride are not effective at promoting similar behavior under these reaction conditions.83 Moderate yields of alcohols are obtained by the KF-catalyzed PMHS, (EtO SiH, or Me(EtO)2SiH reduction of aldehydes.80,83,79... 

Tetra-n-butylammonium triphenyldifluorosilicate has been found to be a more reliable source of fluoride ions compared with the simple fluoride or hydrogen fluoride salts. The salt is available as an anhydrous non-hygroscopic material [36] and, although it is less nucleophilic and a weaker base than the ammonium fluo-... 

Table 4. Sources of fluoride ion and their use in drinking water in the United States [125]...

The carbonyl of aldehydes and ketones can be transformed into a gem-difluoro group. This transformation can be performed either directly with DAST or in an indirect manner by treating the corresponding thioacetal or hydrazone with an oxidant (NBS, dibromohydantoin, etc.) in the presence of a source of fluoride ions (e.g., HF-pyridin complex or TBABF prepared from TBAF and KHF2). ... 

Fluoroanions such as [BF4] , [PF6]-, and [AsF6] can be considered as potential sources of fluoride ions. The silver salts tend to be wet and abstraction reactions lead to hydrolysis3 (see the procedure in Section C) or yield either the aqua or fluoroanion complexes ([BF4] or [AsF6] , 4 Using dry reagents such as NO[PF6] can lead to the oxidative addition of fluoride (see the procedure in Section D).5... 

Furthermore, triethylamine trisfhydrogen fluoride) is a highly versatile and easy-to-handle source of fluoride ions. Therefore, its use can be highly recommended for the ring-opening hydrofluorination of aziridines156 (or aziridinium ions166) see also refs 97 and 167. 

The stoichiometric equivalents of halogen fluorides, i.e. chlorine monofluoride, bromine monofluoride and iodine monofluoride, have found a wide application in addition reactions to double bonds. The equivalents are obtained by reacting A -haloamides or free halogens in combination with hydrogen fluoride or its salts as the source of fluoride ions. The reactions proceed under mild conditions at — 80 to 20 "C in anhydrous hydrofluoric acid or diethyl ether, tetrahydro-furan, dichloromethane or chloroform mainly by electrophilic addition with Markovnikov-type regioselectivity (anti addition).26-28... 

Boron trifluoride and boron trifluoride-diethyl ether complex can be used as a source of fluoride ions in the presence of hypobromites and hypochlorites, e.g. methyl hypobromitc, tert-butyl hypobromite, methyl hypochlorite in carbon tetrachloride at 25 C. The addition of bromine monofluoride" and chlorine monofluoride" to various alkenes is accompanied by the formation of the corresponding alkoxybromides and alkoxychlorides which hinder the isolation of the halofluorinated products.57 jV-Bromo- and A -chloro-substiluted alkyl- and arylamines. -amides, and -imides, A -chloro-A,-methylamine, A -bromo-A -methylamine, A -chloro-A, /V-dimethylamine, A-bromo-A.A-dimethylamine, ACV-dichloro-A -methylamine, V,fV-dibromo-,V-mcthylaminc, A -bromosuccinimide, -V-chlorosuccinimide, Af-bromoacct-amide, A.A -dichlorourethane, can be used in the reaction instead of the hypohalites. The reactions with various alkenes conducted in dichloromethane at room temperature in the presence of boron trifluoride-diethyl ether complex produce bromofluoro and chlorofluoro addition products in 40-80 % yield. However, the reactions are complicated by the addition of A -halo-succinimides and Af.A-dichlorourcthane to the C = C bonds.58... 

When cyclohexene (5) is treated with bis(pyridine)iodonium tetrafluoroborate (Ipy2BF4, 6) in the presence of tetrafluoroboric acid in dichloromethane, irans- -fluoro-2-iodocyclohexane (7) is obtained in 89% yield, with the tetrafluoroborate counter anion acting as the source of fluoride ion.59 60... 

The nucleophile for which increased reactivity is most critical is the fluoride ion [3,4], Water molecules bind tightly to this ion, and their presence dramatically reduces its effective nucleophilicity. A variety of fluoride ion sources have been used in an effort to improve product yields in deoxyfluoro sugar synthesis [26,34]. The yields of substitution and elimination products generated from reactions with fluoride ion from several sources are listed in Table 2 [26]. Currently, the most attractive source of fluoride ion is tris(dimethylanuno)-5ulfur (trimetbylsilyl)difluoride (TASF), which is soluble in a variety of oiganic solvents and produces an anhydrous fluoride ion [33]. 

The TPS group is a sil> 1 protecting group that can be removed using TBAF as a source of fluoride ion. After removing the protecting group the alcohol function is converted into a mesylate, which is transformed in the third step via a Finkelstein reaction into an iodide. 

The reagent is an anhydrous source of fluoride ion with high anionic activity and solubility in organic solvents.1... 

Electrochemical fluorination of pyridine in the presence of a source of fluoride ion gave 2-fluoropyridine in 22% yield (85M11). With xenon difluoride, pyridine formed 2-fluoropyridine (35%), 3-fluoropyridine (20%), and 2,6-difluoropyridine (11%) in a reaction unlikely to be a conventional electrophilic substitution. Xenon hexafluoride has also been used (76JFC179). With cesium fluoroxysulfate at room temperature in ether or chloroform, the major product was 2-fluoropyridine (61 and 47%, respectively). Some 2-chloropyridine was also formed in chloroform solution. In methanol the entire product was 2-methoxypyridine (90TL775). Fluorine, diluted with argon in acetic acid, gave a 42% yield of the 5-fluoro derivative of l-methyl-2-pyridone [82H( 17)429],... 

Halogen exchange reactions, too, are valuable sources of fluorinated pyrimidines, especially 2-, 4-, and 6-fluoro derivatives. Sources of fluoride ion have included hydrogen, sodium, potassium, cesium, antimony, silver fluorides, and sulfur tetrafluoride. All of the reactions required heating. Prepared from nucleophilic fluorination processes have been... 

A particularly useful reaction of this type involves the direct formation of hexakis(trifluoromethyl)cyclopentadiene (71) (Scheme 31), or the corresponding cyclopentadienide (72), from the diene (38) by a fluoride ion induced reaction with pentafluoropropene [67-69]. Recent work [54] has shown that very active sources of fluoride ion can be generated by direct reaction of amines, especially TDAE (43), with perfluorinated alkenes or perfluorinated aromatic compounds and these essentially solventless systems promote both oligomerisations (see above) and polyfluoroalkylations. The absence of solvent makes recovery of product very easy, e.g. in high-yielding formation of (73), (74) or (75) (Scheme 32). 

Substantial quantities of commercial and captive HF are used in the production of aluminum trifluoride and sodium cryolite, both used by the aluminum industry. The electrolytic process for the production of aluminum involves fused A1203, A1F3, and Na3AlF6. About 8-10% of the world production of HF is consumed by aluminum industry which serves the World s two largest industries automotive and building construction. Due to the recent economic upturn, there is a large demand for aluminum metal in the market. As a result, the aluminum industry has opted for the least expensive source of fluoride ions such as hexafluorosilicic acid. 

Oxidative fluorodesulfuriztuion can also be achieved by the action of nitrosonium tetrafluo-roborate, as oxidant, and hydrogen fluoridc/pyridine, as a source of fluoride ions, on aryl sulfides. The starting compounds are easily prepared from ketones or aldehydes and ben-zenethiol using boron trifluoride monohydratc as catalyst, and subsequent reduction with triethylsihine. - ... 

Table 3.1 Halogen exchange by various sources of fluoride ion...

However, displacement of sulphur ester groups such as tosylate [183], mesylate [184] and triflate [185] groups are of much greater synthetic importance. These excellent leaving groups are readily displaced by an active source of fluoride ion this process represents an efficient method for the overall transformation of hydroxyl groups to fluorinated derivatives (Figure 3.33). 

Oligomerisation of fluoroalkenes can also be initiated by tertiary amines, such as pyridine [147], trimethylamine [148] and tetrakis(dimethylamino)ethylene [149], via processes that involve either initial ylid formation or the generation in situ of an active source of fluoride ion. 

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