Cesium fluoride-18-Crown

The bis(triflates) can be employed as crude materials immediately after their preparation from aldehydes. The advantages of this method are the easy handling of the fluorinating agent and the mild reaction conditions. Other fluorinating agents, such as tetrabutylammonium fluoride or cesium fluoride/18-crown-6. cleave the S —O bonds of the bis(triflates) and thus produce the starting aldehyde. A variation of this method allows the synthesis of 1-fluoro-l-haloalkanes (see Section 1.1.5.4.). ... 

Dichloroquinoxaline (101) is aminated by morpholine in the presence of excess cesium fluoride/18-crown-6 with simultaneous exchange of chlorine by fluorine to give 102 in 78% yield, whereas glycine ethylester-hydrochloride affords 103 in 61% yield (87HI215). 

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... 

A one-pot conversion of benzyl alcohols to benzyl fluorides by treatment of the alcohols with a combination of methanesulfonyl fluoride, cesium fluoride and 18-crown 6 ether in tetrahydrofuran has been repotted The reaction involves mesylation of the alcohols followed by cleavage of the resultant mesyl esters with a fluoride ion The reaction has been extended also to certain heterocycles bearing the N hydroxymethyl group [43] (equation 31)... 

Isomerization of fluoroolefins by a shift of a double bond is catalyzed by halide 10ns [7] The presence of crown ether makes this reaction more efficient [74] Prolonged reaction time favors the rearranged product with an internal double bond (equations 3-5) Isomerization of perfluoro-l-pentene with cesium fluoride yields perfluoro-2-pentenes in a Z ratio of 1 6 [75] Antimony pentafluoride also causes isomenzation of olefins leading to more substituted products [76]... 

Nucleophilic halogen exchange, using cesium fluoride and 18-crown-6 in tetrahydrofuran, gave high yields of 2-, 3-, and 2,3,-di-fluoroquinoxalines from the chloro analogues [87H)26)1215]. The Balz-Schiemann process has been used successfully to make 2-fluoro-quinoxaline (84MI8). 

Especially for large-scale work, esters may be more safely and efficiently prepared by reaction of carboxylate salts with alkyl halides or tosylates. Carboxylate anions are not very reactive nucleophiles so the best results are obtained in polar aprotic solvents45 or with crown ether catalysts.46 The reactivity order for carboxylate salts is Na+ < K+ < Rb+ < Cs+. Cesium carboxylates are especially useful in polar aprotic solvents. The enhanced reactivity of the cesium salts is due to both high solubility and minimal ion pairing with the anion 47 Acetone is a good solvent for reaction of carboxylate anions with alkyl iodides48 Cesium fluoride in DMF is another useful... 

Cesium fluoride, 21 234, 235, 237, 247 Cesium hexahalogenopolonite, 4 218 Cesium hydrogen phosphate, 4 14 Cesium ion, in crown ether synthesis, 21 24 Cesium isotope, halWife determination, 2 325-326... 

A variety of benzyl fluorides 9 were directly prepared in one-step from the corresponding benzyl alcohols 8 by using a combination of methanesulfonyl fluoride and cesium fluoride in the presence of dibenzo-18-crown-6.167 The mesylates formed in situ are thus easily converted to the fluoro derivatives 9. 

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. 

Treating a-triethylsilylallylimine A with cesium fluoride in the presence 18-crown-6 ether provides excellent access to the corresponding 2-azadiene that is further cyclized into 3-methyl-octahydrobenzo-[h]quinoline.225... 

The application of cesium fluoride as base in the synthesis of crown compounds from phenols and the ditosylates of polyethylene glycols was first described by Reinhoudt [44]. This method uses the high basicity of weakly solvated ( naked ) fluoride anions under aprotic conditions and is based on the formation of very stable H—F bonds (approx. 569 kJ/mol, H—Cl approx. 432 kJ/mol for comparison) [8],... 

The applicability of cesium fluoride for the synthesis of smaller crown ether rings such as benzo[12]crown-4 (35) was investigated by Bartsch et al. [45]. The result of this study was that the 12-membered crown ether 35 and its naphthalene analogue 36 can be obtained from the aromatic diols 33 and the tosylate 34 with the base cesium fluoride in yields of 29 and 25 %, respectively. This means a significant increase in the 4% yield of benzo[12]crown-4 (35) reported by Pedersen, who started with sodium phenolate [38]. 

Potassium fluoride is the most frequently used metal fluoride for the substitution of inorganic ester groups by fluorine. Cesium fluoride in combination with crown ethers is preferable in difficult cases, while silvcr(l) fluoride is seldom used. 

Allylic and benzylic alcohols have been converted into the corresponding fluorides in a one-pot reaction via in situ tosylation with tosyl fluoride and fluorination with lithium fluoride or in situ mesylation with mesyl fluoride and fluorination with cesium fluoride in the presence of crown ethers, respectively. 

More complicated synthons, containing double and triple bonds, can also react with aldehydes in the presence of cesium fluoride and 18-crown-6. Thus, 3-(trifluoromethyl)-l-(trimethyl-silyl)but-3-en-l-yne gives 2-(trinuoromethyl)alk-l-en-3-yn-5-ols 21 with aldehydes. 

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). 

In a limited number of cases, arylsilanes react with aldehydes as if they were aryl Grignard or aryllithium reagents. Both trimethyl(perchlorophenyl)silane and trimethyl(perfluoro-phenyl)silane react with benzaldehyde to give the corresponding 7.-(pcrhalophenyl)bcnzyl tri-methylsilyl ethers.163 Benzaldehyde reacts completely with trimethyl(perfluorophenyl)silane in diethyl ether in the presence of either a catalytic amount of the potassium cyanide/18-crown-6 complex in less than 5 hours at room temperature or potassium fluoride in dimethylform-umide.164 In the case of aryltrimcthylsilanes containing electron-withdrawing substituents in the ortho position, the reaction is observed only under the conditions of nucleophilic catalysis by potassium fluoride or cesium fluoride. 

A convenient method for preparing 2-fluoro- and 2,3-difluoroquinoxalines under mild reaction conditions is fluorination by nucleophilic substitution of one or more chlorine atoms on the heterocyclic ring using cesium fluoride activated by 18-crown-6. This procedure can be modified into a one-pot synthesis of 2-substituted 3-fluoroquinoxalines from 2,3-dichloroquinoxalines by subsequent nucleophilic substitution with various synthons containing a primary or secondary amino group, e.g. synthesis of compound 11 (R = morpholino X = H). 

In fluoride ion catalyzed reactions of allylsilanes, aldehydes are the only carbon electrophiles that work well protodesilylation is unavoidable with most other electrophiles, even in the most rigorously dried media. The most commonly used fluoride ion source, which only needs to be present in catalytic amounts, is TBAF in THF at room temperature or under reflux, benzyltrimethylammonium fluoride may be better, and cesium fluoride in DMF, potassium fluoride with 18-crown-6 in THF, and TASF in polar... 

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