Potassium fluoride-18-Crown

Fluorotris(trimethylsilyl)methane reacted with 2 M equiv. of an aromatic aldehyde in the presence of potassium fluoride/18-crown-6 to give 1,3-disubstituted 2-fluoro-2-propen-1-ols (27) in 65-78% yields [51] (Scheme 7). 

A potassium fluoride/18-crown-6 combination has been used for the conversion of halogenated quinones to fluorinated quinones. Quinone 20 is converted to 21 in 83% yield.113... 

The reactivity of tetraphenylphosphonium hydrogen difluoride is comparable with more conventional chlonne-fluonne exchange reagents It can be used and regenerated as illustrated in equation 18 and its preparation is outlined in Procedure 3, p 193 The rate of reaction of tetraphenylphosphonium hydrogen difluonde with benzyl bromide using a fluoride concentration of 0 12 M in acetomtnle (f1/2=25 min at 52 °C) can be compared with that achieved by replacing it with potassium fluoride- 18-crown-6 (tm = 11 5 h at 82 °C) [28] The... 

Destlylation. Anhydrous cesium fluoride desilylates trimethylsilylmethyl-sulfonium, trimethylsilylmethylammonium, and trimethylsilylmethylphosphonium salts at room temperature to produce ylides, which undergo various useful transformations. Use of potassium fluoride-18-crown-6 or a tetraalkylammonium fluoride gives products in low yield in these reactions. The trimethylsilylmethyl-onium salts are prepared by alkylation of sulfides, amines, imines, and phosphines with (trifluoromethanesulfonylmethyl)trimethylsilane (1). 

Perfluorocyclopentene is exceptional in being obtained from non-fluorinated materials by a simple one-step procedure, i.e. displacement of chlorine in perchlorocyclopentene by fluoride ion [51], although some polyfluorochloro- and polyfluorohydro-alkenes can be made by analogous processes [51, 52]. If a perfluorocarbon is used as the reaction medium with potassium fluoride/18-crown-6 complex, then a variety of products may be obtained, including hexafluoro-2-butyne [53]. 

On heating the 2-yS-azidomethyl penam sulphone (85) with suitable acetylenes, a series of 2-/S-(l,2,3-triazolyl)methyl penam sulphone esters was obtained, which upon deprotection gave the free acids (86) [48, 49]. In particular, reaction of (85) with either vinyl acetate or (trimethylsi-lyl)acetylene provided the parent triazole, tazobactam (30), after hydrogenation (and prior potassium fluoride-18-crown-6 treatment in the case of the TMS acetylene) [50]. 

Reaction of the nitromethyl derivative 77 obtained in four steps from cellobiose peracetate, with the glucose-derived aldehyde 78 and potassium fluoride/18-crown-6 leads to the expected condensation product 79. The acetylation-elimination-reduction sequence (— 80) followed by reductive denitration and total deprotection affords the 0,C-trimer mimic 81. 

Potassium fluoride 18-Crown-6/potassium fluoride complex... 

For the removal of this protecting group, tetrabutylammonium fluoride in oxolane is the most frequently used [388, 389, 409-411]. A much simpler reagent to prepare, potassium fluoride — crown ether, has been introduced for the same purpose [427]. Silyl group at 0-2 of nucleosides is cleaved more rapidly [411] than at 0-5. Acyl migrations occurred under the tetrabutylammonium fluoride-catalyzed desilyla-tion [432, 434, 443], Differencies between the primary and secondary position were also observed for acid- or base-catalyzed solvolysis [391, 409-412], 5 -0-(7ert-butyl-dimethylsilyl)nucleosides are much more labile towards acid than either 2 - or 3 -silyl ethers [391, 410-412], whereas the situation is reversed for base hydrolysis [411], /V-Bromosuccinimide in aqueous DMSO is another alternative for the removal of this type of silyl group [444]. 

The main problem here is removing the phenyl ester groups from the phosphonic moiety.We have found that convenient routes for deblocking are hydrogenation on Adams catalyst and transesterification methods followed by hydrogen bromide in glacial acetic acid treatment. The best results ewre obtained if transesterification was carried out using potassium fluoride-crown ether-methanol system. 

Treatment of thioethers with xenon difluoride, or a-chloro thioethers with potassium fluoride/crown ether, had been reported to give a-fluoro thioethers. McCarthy and... 

The metal-ion complexmg properties of crown ethers are clearly evident m their effects on the solubility and reactivity of ionic compounds m nonpolar media Potassium fluoride (KF) is ionic and practically insoluble m benzene alone but dissolves m it when 18 crown 6 is present This happens because of the electron distribution of 18 crown 6 as shown m Figure 16 2a The electrostatic potential surface consists of essentially two regions an electron rich interior associated with the oxygens and a hydrocarbon like exterior associated with the CH2 groups When KF is added to a solution of 18 crown 6 m benzene potassium ion (K ) interacts with the oxygens of the crown ether to form a Lewis acid Lewis base complex As can be seen m the space filling model of this... 

In media such as water and alcohols fluoride ion is strongly solvated by hydro gen bonding and is neither very basic nor very nucleophilic On the other hand the poorly solvated or naked fluoride 10ns that are present when potassium fluoride dis solves m benzene m the presence of a crown ether are better able to express their anionic reactivity Thus alkyl halides react with potassium fluoride m benzene containing 18 crown 6 thereby providing a method for the preparation of otherwise difficultly acces sible alkyl fluorides... 

When added to nonpolar solvents, the crown ethers increase the solubility of ionic materials. For example, in the presence of 18-crown-6, potassium fluoride is soluble in benzene and acts as a reactive nucleophile ... 

In the absence of die polyether, potassium fluoride is insoluble in benzene and unreactive toward alkyl halides. Similar enhancement of solubility and reactivity of other salts is observed in the presence of crown ethers The solubility and reactivity enhancement result because the ionic compound is dissociated to a tightly complexed cation and a naked anion. Figure 4.13 shows the tight coordination that can be achieved with a typical crown ether. The complexed cation, because it is surrounded by the nonpolar crown ether, has high solubility in the nonpolar media. To maintain electroneutrality, the anion is also transported into the solvent. The cation is shielded from interaction with the anion as a... 

Difluoromethoxy-2-chloro-l,l,l-trifluoroethane and potassium fluoride produce 2-difluoromethoxy-1,1,1,2-tetrafluoroethane [50] The yield of the latter reaction is improved by adding a phase transfer catalyst or crown ether, tetra-methylammonium chlonde, tetrabutylammonium chloride, or 18-crown-6 with a solvent like sulfolane can be used for this purpose [5/] (equation 32)... 

The conversion of octachloronaphthalene to octafluoronaphthalene with potassium fluoride and either 18-crown-6, dibenzo-18-crown-6, cis,j>m,cis-dicyclohexano-18-crown-6, cis,anti,cis-dicyclohexano-l 8-crown-6, or irons,syn,trails-dicyclohexano-18-crown-6 demonstrates that 18-crown-6 or dibenzo-18-crown-5 increases the yield and selecuvity and decreases the reaction time [55] Treatment of 3,4-dichloro-],2,5-thiadiazole with potassium fluonde in sulfolane with and without 18-crown-6 present shows that less severe conditions can be used with either 18-crown-6 or dibenzo-18-crown-6 to form 3,4-difluoro-l,2,5-thiadiazole (equation 34)... 

When potassium fluoride is combined with a variety of quaternary ammonium salts its reaction rate is accelerated and the overall yields of a vanety of halogen displacements are improved [57, p 112ff. Variables like catalyst type and moisture content of the alkali metal fluoride need to be optimized. In addition, the maximum yield is a function of two parallel reactions direct fluorination and catalyst decomposition due to its low thermal stability in the presence of fluoride ion [5,8, 59, 60] One example is trimethylsilyl fluoride, which can be prepared from the chloride by using either 18-crown-6 (Procedure 3, p 192) or Aliquot 336 in wet chlorobenzene, as illustrated in equation 35 [61],... 

Tetrasubstituted phosphonium halides are just as effective as their ammonium counterparts. A combination of tetraphenylphosphonium bromide and either 18-crown-6 or polyethylene glycol dimethyl ether with spray-dried potassium fluoride converts 4-chlorobenzaldehyde to 4-fluorobenzaldehyde in 74% yield [67] In addition, the halogen of a primary alkyl chloride or bromide is easily displaced by fluorine in aqueous saturated potassium fluoride and a catalytic amount of hexadecyltributylphosphonium bromide [68] (Table 7 Procedure 4, p 194)... 

The use of cesium fluoride is limited because of its cost and its availability as a truly anhydrous reagent. Its use with 18-crown-6 shows a 5 times higher rate for the formation of benzyl fluoride from benzyl bromide when compared with cesium fluonde or potassium fluoride supported on calcium fluoride [21] Either cesium fluoride or potassium fluoride supported on calcium fluoride (Procedures 5a and 5b, p 194) provides about a twofold improvement over either unsupported alkali metal fluoride [55, 69], Cesium fluoride and Aliquat 336 convert benzyl bromide to the fluoride in 94% yield. Using tetrabuty lammonium fluoride in place of Aliquat... 

MorphoHnosulfur trifluoride and tetrafluoroethylene in the presence of potassium fluoride and 18-crown 6 give morphohnopentalluoroethylsulfur di-fluoride, which is subsequently oxidized sequentially to pentafluoroethanesulfinic acid and pentafluoroethanesulfonic acid [7] (equation 7)... 

In the presence of dicyclohexyl-18-crown-6 ether, potassium fluoride converts fluonnated vinylic iodides to acetylenes [2] (equation 2)... 

Dehydrochlorination of bis(tnfluoromethylthio)acetyl chloride with calcium oxide gives bis(trifluoromethylthio)ketene [5] (equation 6) Elimination of hydrogen chloride or hydrogen bromide by means of tetrabutylammonium or potassium fluoride from vinylic chlorides or bromides leads to acetylenes or allenes [6 (equation 7) Addition of dicyclohexyl-18-crown-6 ether raises the yields of potassium fluoride-promoted elimination of hydrogen bromide from (Z)-P-bromo-p-ni-trostyrene in acetonitrile from 0 to 53-71 % In dimethyl formamide, yields increase from 28-35% to 58-68%... 

Treatment of (1,1 -difluoro-2,5-diphenylsilacyclopentadiene)tricarbonyliron with a mixture of potassium fluoride and 18-crown-6 gives 279 [88J0M(347)C1]. 

Finally, the reaction of 19b with potassium fluoride in the presence of a crown-ether phase-transfer agent118 to yield the sulfonyl fluoride 67 and diphenylacetylene119 belongs to the same category in which a nucleophile (F in this case) attacks the electrophilic sulfur of the sulfone group (equation 19). 

Nucleophilic substitution reactions of halide anions in aprotic solvents are often accompanied by elimination reactions. For instance, reactions of secondary alkyl halides with potassium fluoride solubilized in acetonitrile with the aid of 18-crown-6 [3] give olefins as the main reaction product (Liotta and Harris, 1974). Similarly, the dicyclohexyl-18-crown-6 complex of potassium iodide acted exclusively as a base in its reaction with 2-bromo-octane in DMF (Sam and Simmons, 1974). The strongly basic character of weakly solvated fluoride has been exploited in peptide synthesis (Klausner and Chorev, 1977 Chorev and Klausner, 1976). It was shown that potassium fluoride solubilized... 

Chloroalkyl carbonates do not undergo direct nucleophilic substitution with fluorine on heating with potassium fluoride either neat or in solution in the presence of 18-crown-6. They easily fragment to aldehydes and fluoroformates. This reaction has been exploited to synthesize valuable tertiary alkyl fluoroformates and benzyl fluoroformate. fert-Butyl fluoroformate (Boc-F) is a superior reagent for the preparation of Boc-amino acids.51... 

The chlorine —fluorine exchange in l-chloro-2,4-dinitrobenzene has been systematically investigated using potassium fluoride among other reagents in the presence of several crown ethers.93... 

To study the ort/m-directing influence of the fluorine atoms, 2,4-difluoropyrimidine (3) and 4-fluoro-2-(methylsulfonyl)pyrimidine (4) have been prepared from the precursor chlorides 1 and 2 by treating with potassium fluoride in tetraglyme in the presence of 18-crown-6. 19... 

This method has been extended to heterocycles bearing a hydroxymethyl-substituted nitrogen. Thus, ethyl l-(hydroxymethyl)pyrazole-4-carboxylate (10) is converted into ethyl 1-(fluoromethyl)pyrazole-4-carboxylate (11) in 76% yield with cesium fluoride/methanesulfonyl fluoride/18-crown-6 system.167 Potassium fluoride did not react at all and tetrabutylammonium fluoride leads to decomposition and formation of coupling products. 

Analogous reactions with perfluoro(isopropyl-l,3,5-triazine) and per-fluoro(diisopropyI-l,3,5-triazine) with CsF yielded adducts 116 and 117, respectively, which were detected by 19F-NMR. Use of potassium fluoride, either alone or associated with 18-crown-6, did not lead to the formation of the adducts. In contrast, from tris(perfluoroisopropyl)-l,3,5-triazine no adduct was detected. This is quite interesting because it would indicate the importance of the gem-difluoro substitution to stabilize the adduct,160 in analogy with the effect of gem-dimethoxy substitution.76... 

Dehydroiodination of 3,3,3-trifluoro-l-iodoprop-l-ene (18) using potassium fluoride in the presence of a crown ether gives 3.3,3-trifluoroprop-l-yne (19).58... 

A patent assigned to Central Glass describes the rearrangement of internal perfluoroalkenes with potassium fluoride and a crown ether in acetonitrile. For example, periluoro(4-methylpent-2-ene) (7) can rearrange to the more stable isomer perfluoro(2-methylpent-2-ene) (8) by heating for 3 hours at 40 C in acetonitrile in the presence of catalytic amounts of potassium fluoride and 18-crown-6.32... 

---