Tetraalkylammonium fluoride

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... 

Trimethylsilyl enol ethers can also be cleaved by tetraalkylammonium fluoride (Entry 2) The driving force for this reaction is the formation of the very strong Si-F bond, which has a bond energy of 142 kcal/mol.31 These conditions, too, lead to enolate equilibration. 

Tetraalkylammonium fluorides or metal fluorides are also effective as catalysts for the Michael addition of nitroalkanes (see, Table 4.2).143-145... 

The use of /i-ketocstcrs and malonic ester enolates has largely been supplanted by the development of the newer procedures based on selective enolate formation that permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of ketoesters intermediates. Most enolate alkylations are carried out by deprotonating the ketone under conditions that are appropriate for kinetic or thermodynamic control. Enolates can also be prepared from silyl enol ethers and by reduction of enones (see Section 1.3). Alkylation also can be carried out using silyl enol ethers by reaction with fluoride ion.31 Tetraalkylammonium fluoride salts in anhydrous solvents are normally the... 

The fluoride ion is an effective catalyst for Michael additions involving relatively acidic carbon compounds.85 The reactions can be done in the presence of excess fluoride, where the formation of the [F—H—F ] ion occurs, or by use of a tetraalkylammonium fluoride in an aprotic solvent. 

Introduction of Fluorine with Alkali Metal Fluorides, Including Ammonium Fluoride and Tetraalkylammonium Fluorides (Including Special Methods of Fluorinations, e. g., Phase Transfer Catalysis, Activation by Crown Ethers, Reagents... 

Tetraalkylammonium fluoride (R4N 1 F ) is well known as being highly receptive to protic compounds such as hydrogen halides and water, affording non-stoichiometric hydrogen-bonded adducts, R N F (HY) , in non-polar solvents. This property reasonably accounts for the hygroscopic nature of ammonium fluorides. However, under strictly anhydrous conditions, intramolecular interactions are predominant and result in self-destruction of the tetraalkylammonium cation via Hoffman elimination to furnish tetraalkylammonium bifluoride, trialkylamine, and olefin (Scheme 9.12) [22]. Consequently, the resulting tetraalkylammonium bifluoride,... 

Ooi, T. Sugimoto, H. Doda, K. Maruoka, K. Esterification of carboxylic acids catalyzed by in situ generated tetraalkylammonium fluorides. Tetrahedron Lett. 2001, 42, 9245-9248. 

Hoechst113-114) took a different approach to the synthesis of / -benzoquinone. By oxidation of benzene in methanol solution in the presence of tetraalkylammonium fluorides as conductive salts p-benzoquinone tetramethyl ketal is formed. This can be converted to p-benzoquinone in a simple procedure while methanol can be recycled. 

Selective Organic Electrofluorination. The electrogeneration of fluorine from the electrolysis of a mixture of KF and HF has been well known for many decades. Organic perfluorination using HF and HF/KF is used widely. Now the use of HF complexes with tetraalkylammonium fluoride has led to the anodic difluorination of dithioacetals. 

The effect of the fluoride ion is dramatic and to the extent of posing more questions than it answers. Clark24) showed that dissolved tetraalkylammonium fluorides converted AA entirely to the enol form in solvents such as CHC13 and even in DMF. Crystalline complexes, R4NF AA, can be isolated and this is a useful method for dehydrating these fluoride salts which are notoriously hygroscopic. In the presence of F", AA can be easily alkylated at the a position with alkyl iodides24). 

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). 

Anhydrous reagent. Tetraalkylammonium fluorides are useful catalysts in various synthetic reactions, but their use is hampered by their extreme ability to retain water, which reduces the effectiveness. Clark has found that silica gel (60-120 mesh) can give completely anhydrous salts. Thus a 20% aqueous solution of tetra-n-butylammonium fluoride is shaken with silica gel water is then partially removed under reduced pressure. Methanol is added and evaporation is continued to... 

When activated by anionic catalysts [potassium fluoride, cesium fluoride, tetraalkylammonium fluorides, tris(dimethylamino)sulfonium difluorotrimethylsilicate, phosphazenium, hexa-methylpiperidinium and cobaltoccnium fluorides, tetrabutylammonium difluoroftriphenyl-silyl)silicatc. the complex tetrakis(dimethylamino)ethene/perfluoropropene, ammonium (and phosphonium) perfluorocyclobutane ylides], trimethyl(perfluoroalkyl)silanes will generate C-Rf bonds from carbon-halogen bonds. 

When treated with a tetraalkylammonium fluoride, various 1-substituted trimethylsilylcyclo-propanes are converted to tetraalkylammonium salts of the corresponding cyclopropyl anions. Such anions are trapped by performing the reaction in the presence of an aldehyde, a ketone or carbon dioxide. The reaction is carried out successfully with electron-donating and electron-withdrawing substituents a to the silyl moiety. The best yield was obtained when methyl 1-trimethylsilylcyclopropanecarboxylate was treated with tetrabutylammonium fluoride in tetra-hydrofuran and acetaldehyde, methyl l-(l-hydroxyethyl)cyclopropanecarboxylate (la) was obtained in 90% yield.Under similar conditions (Z)-2,6-dimethyl-l-[(l-trimethylsilylcy-clopropyl)methylene]cyclohex-2-ene was transformed to (Z)-l- [l-(l-hydroxy-l-methyl-ethyl)cyclopropyl]methylene -2,6-dimethylcyclohex-2-ene (2) in 90% yield in the presence of acetone.Similarly, when carbon dioxide was used as electrophile in the presence of cesium fluoride, typically 1-trimethylsilylcyclopropane-l-carbonitrile was converted quantitatively to 1-cyanocyclopropanecarboxylic acid (3a). ... 

Desilylation with cesium fluoride has been the most common use of cesium compounds in organic synfhesis. HI and tetraalkylammonium fluoride are also commonly used for desilylation but these reagents are difficult to use under anhydrous conditions. The cesium fluoride-induced reaction can be performed easily under anhydrous conditions, so desilylation produces carbanion-equivalent species which can be used for further C-C bond-forming reactions. The reaction seems to... 

Tetraalkylammonium fluorides, commonly available, are soluble in a wide range of solvents. However, they are very hygroscopic (ref. 16) and several hydrates are known for Me4NF.nH20 (n = 1,2,3,4), Et4NF.nH20... 

Hydrated tetraalkylammonium fluorides can be, nevertheless, used in "Halex reactions but water, the nucleophilicity of which is enhanced by hydrogen-bonding with F, competes with the fluoride and delivers phenols and diaryl ethers as byproducts. A typical situation is shown below for 3,4-dichloronitrobenzene (ref. 17). 

Table 4. Reaction of 3,4-dichloronitrobenzene with soluble hydrated tetraalkylammonium fluorides according to (ref. 17).

A number of oi ganoaluminum reagents, especially Me2AlCl, have been found to be effective catalysts for reactions of enol silyl ethers with aldehydes.It is possible that in these reactions, aluminum enol-ates may be involved as the intermediates. Similarly, bismuth trichloride has been reported to be an efficient catalyst.Since BiCh is considered to be a weak Lewis acid, the involvement of a bismuth enolate is perhaps implicated. Enolate intermediates are definitely generated when tetraalkylammonium fluorides or tris(dialkylamino)sulfonium (TAS) difluorotrimethylsiliconates (104) are used as reagents to promote the reactions of enol silyl ethers. Their chemistry will therefore not be discussed in this chapter. 

The oligomerisation process consists in anionic polymerisation of tetrafluoroethylcne in suitable aprotic solvents, e.g., diglyme or dimethylformamide, using KF, CsF or tetraalkylammonium fluoride as catalyst. The oligomerisation products are branched perfluoroolefins able to by further modified. Trimers, tetramers and pentamers of tetrafluoroethylene as well as dimers and trimers of hexafluoropropylene are useful essentially as a lyophobic backbone of fluorinated surfactants. This approach was initiated by ICI and Neos (Jap.), respectively. 

Since a wide range of F-18 reactive intermediates is now available, any published synthesis of a fluorocarbohydrate can in principle be adapted to use the radioisotope. The synthesis must be completed within at most an hour or two, which necessitates considerable attention to the rate of each step which occurs after incorporation of the isotope. This incorporation step should be as late in the synthetic scheme as possible. Christman et al. ( ) investigated the influence of several reaction parameters on the synthesis of 6-deoxy 6-fluoro-D-galactose. They used a labeled tetraalkylammonium fluoride solution in acetonitrile to displace a variety of leaving groups in the 6-position of... 

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