Tetrabutylammonium fluoride, fluorinating

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)... 

A variety of media have been used for the Wallach fluorination reaction anhydrous hydrogen fluoride alone or with cosolvents such as methylene chloride, benzene, or tetrahydrofuran and hydrogen fluoride-pyridine alone or with co solvents such as benzene, glyme, or acetic acid [42,43, 46 50] Solutions of cesium fluoride, tetraethylammonium fluoride, or tetrabutylammonium fluoride in strong acids such as methanesulfonic acid or trifiuoroacetic acid with numerous cosolvents have also been studied [48, 49]... 

Another example of the fact that primary displacement of sulfonic esters is not always facile101,103-105 is the discovery that vigorous conditions were required for fluorination of l,2 3,5-di-0-isopropylidene-6-0-(methylsulfony])-a-D-galactofuranose with potassium fluoride dihydrate in methanol,85,88 and a comparatively long reaction-time was necessary for the fluorination of the 6-O-p-tolylsulfonyl derivative with tetrabutylammonium fluoride in acetonitrile.106... 

In a comparative study of fluorination of l,2 3,4-di-0-isopropyli-dene-6-O-p-tolylsulfonyl-a-D-galactopyranose with tetrabutylammonium fluoride in a variety of dipolar, aprotic solvents (as well as 1,2-eth-anediol, in which no reaction was observed), acetonitrile was found to give the highest proportion of substitution of the sulfonic esters relative to their elimination.106 Elimination is the major, competing reaction in these nucleophilic-substitution reactions, because of the high basicity and low nucleophilicity of the fluoride ion or, in terms of the... 

Further examples are found in references 196 and 197. Tetrabutylammonium fluoride (TBAF) has found many applications in synthesizing several fluoro derivatives via nucleophilic substitution on the appropriate substrates. Organo-fluorine compounds are not only interesting as medicinal drugs, but they are also useful as technical products. 

Tetrabutylammonium fluoride can also be employed under pressure to substitute tosylate with fluorine. l-(2,5-Dimethoxyphenyl)-2-tosyloxyethane (30) gives the corresponding fluoride 31 in 69 % yield without elimination product at 11.25 Torr.220 The reaction at 760 Torr furnishes only 38 % yield with 26 % of the elimination product. 

Both experimental and theoretical studies have been reported of fluoro-denitration and fluoro-dechlorination reactions using anhydrous tetrabutylammonium fluoride in DMSO. The absences of ion pairing and strong solvation are critical in contributing to the reactivity of the fluorinating agent24 Quaternary ammonium salts derived from cinchona alkaloids have been shown to be effective catalysts in an improved asymmetric substitution reaction of /1-dicarbonyl compounds with activated fluoroarenes. The products may be functionalized to yield spiro-oxindoles.25... 

The best results have been obtained in the non-polar solvents heptane or 0-xylene. Polar aprotic solvents such as Me2CO, MeCN, DMSO or dioxane gave poor yields and byproduct formations. Water-free conditions to avoid hydrolysis of BC14- have been necessary. The best fluorination yields have been achieved in the 373-393 K temperature interval (in 0-xylene with TBAF, tetrabutylammonium fluoride). An increase in the yield was observed if an excess of the diazonium salt was used. The total labelling procedure took 50 min. The tetrachloroborate incorporates fluoride by a halide exchange reaction (equation 3)9 10. 

Table 11. Fluorination of Inorganic Esters of Aliphatic Alcohols with Tetrabutylammonium Fluorides...

Tetrabutylammonium fluoride was first used as a fluorination reagent in the steroid field. The difificult replacement at C17 of the tosylate of testosterone gives the 17a-fluoride in 52% yield. ... 

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.). ... 

Fluoride sources other than hydrogen fluoride, such as tetrabutylammonium fluoride (TBAF) or cesium fluoride in the presence of acids (methanesulfonic acid, trifluoroacctic acid or cation-exchange resins), have been used for the aromatic fluorination of aryltriazenes (see Table Thus, no-carrier-added l F]fluorine-labeled pharmaceuticals, such as spiroperidol. spiperone-" (Table 4, entries 7 and 9). and haloperidol- (entry 8). are available in high radiochemical yield. 

An important ring opening of bicyclic aziridines involves aziridines derived from carbohydrates (in their pyranoside or furanosidc form) which yields interesting fluorinated carbohydrate de-rivates.104-105 An example is the ring opening of aziridine 21 with tetrabutylammonium fluoride to give (benzoylamino)fluoropyranoside 22, an intermediate in the synthesis of protected C 2 analogs of daunosamine.104... 

Albanese, D., Landini, D., Penso, M. Hydrated Tetrabutylammonium Fluoride as a Powerful Nucleophilic Fluorinating Agent. J. Org. Chem. 

Alkoxy-3-chloro-3//-diazirines are obtained by the chlorination (aqueous sodium hypo-chlorite/dimethyl sulfoxide) of the corresponding amidines. They serve as precursors for the synthesis of 3-fluoro derivatives via the reaction with anhydrous tetrabutylammonium fluoride (for an improved procedure for the dehydration of commercial tetrabutylammonium fluoride trihydrate, see ref 26). This is a much simpler method than the earlier described preparation of 3-fluoro-3-methoxy-37/-diazirine involving the elemental fluorination reaction and a shatteringly explosive fluoronitrogen intermediate. 

F]-330, suggested as a potential in vivo marker of hypoxic tissue by PET, has been prepared in the reaction of epoxide 331 with [ F]-tetrabutylammonium fluoride ([ F]TBAF) (equation 142a) in 1-2% radiochemical yield and in the reaction of epifluorohydrin 332 with 2-nitroimidazole 333 (equation 142b) in 30-40% yield in an overall synthesis time of 2 h starting with 200 mCi of fluorine-18 in... 

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