Fluoride, tetrabutylammonium

Solubility sol H2O, THF, MeCN, DMSO, anhydrous TBAF is incompatible with halogenated solvents such as CH2CI2 and CHCI3. 

Form Supplied in trihydrate, 1.0 M solution in THF, and 75 wt % solution in water. 

Preparative Method aqueous Hydrofluoric Acid is passed through an Amberlite IRA 410 OH column, followed by an aqueous solution of Tetrabutylammonium Bromide. After the resin is washed with water, the combined water fractions are repeatedly evaporated until no water is present. Tetrahutylammonium fluoride is collected as an oil in quantitative 3neld. TBAF-a H20 aqueous hydrofluoric acid is passed through an Amberlite IRA 410 OH column, followed by an aqueous solution of tetra- -butylammonium bromide. After the resin is washed with water, the combined water Iractions are repeatedly evaporated until no water is present. Tetrabutylanunonium fluoride is collected as an oil in quantitative yield. The hydrofluoric acid method has been described most recently by Kumar. TBAFanh under nitrogen, hexafluorobenzene is added to a cold (—50 °C) THF solution of tetra-n-butylanunonium cyanide. The highly colored solution is stirred for 4 h at —15 °C, cooled to —60 °C, and filtered. The resulting colorless solid is washed with cold THF and the residual solvent is removed in vacuo to yield anhydrous TBAF (60%).  

Handling, Storage, and Precautions use a fume hood for TBAF-XH2O TBAFanh is hydroscopic it should be handled and stored under dry argon or nitrogen, and stored in a freezer. 

Deprotection of Silyl Groups. Tetrabutylammonium fluoride has been used widely as a reagent for the efficient cleav- 

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In the 1,6-elimination of j -trimethy1si1y1methy1henzy1trimethy1 ammonium iodide with tetrabutylammonium fluoride, yields as high as 56% have been reported (18). The starting materials are not readily accessible, however, and are cosdy. 

The /-butyldimethylsilyl group introduced by TBDMIM has a number of advantages in protecting alcohols (6). The sdylated alcohol hydroly2es more slowly than an alcohol sdylated with TMS by a factor of 10 . The sdyl ether is also stable to powerful oxidi2ing and reducing agents, but it can easily be removed by aqueous acetic acid or tetrabutylammonium fluoride in tetrahydrofuran. 

Tetrabutylammonium fluoride trihydrate (Aldnch) is heated in a round-bottom flask with magnetic stirring at 40-45 C under vacuum (<0.1 mm of Hg) After several hours, the sample liquefies. Heating is continued until the sample loses 20% of its original weight (usually ca 48 h). The resulting anhydrous TBAF (singlet at -99 ppm, F NMR) contains 0 1-03 molar equivalent of water (by NMR) and ca 10% tetrabutylammonium bifluoride (a doublet at -146 ppm, (J = 123 Hz, F NMR) This oil must be used immediately. 

Epoxides are regio- and stereoselectively transformed into fluorohydrins by silicon tetrafluoride m the presence of a Lewis base, such as diisopropyleth-ylamme and, m certain instances, water or tetrabutylammonium fluoride The reactions proceed under very mild conditions (0 to 20 C in 1,2-diohloroethane or diethyl ether) and are highly chemoselective alkenes, ethers, long-chain internal oxiranes, and carbon-silicon bonds remain intact The stereochemical outcome of the epoxide ring opening with silicon tetrafluoride depends on an additive used, without addition of water or a quaternary ammonium fluoride, as fluorohydrins are formed, whereas m the presence of these additives, only anti opening leading to trans isomers is observed [17, 18] (Table 2)... 

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)... 

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... 

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]... 

Prepai ation ot 2-Fluoro-l -indanone, 166 Tetrabutylammonium Fluoride Preparation, 193... 

Examples of dehydrobromination leading to bromoethynylpyrazoles as illustrated by Scheme 36 are described in a patent (99USP5925769). Treatment of 1,1-dibromooleflns with tetrabutylammonium fluoride in THE at room temperature for about 24 h under N2 gives the l-bromo-2-(pyrazol-3-yl)acetylenes where R, R, R, and R" are independently selected from H and alkyl, alkoxy. 

The Henry reactions of A, ALdibenzyl-L-phenylalaninal with nitroalkanes using 1.2 equiv of tetrabutylammonium fluoride (TBAF) as the catalyst proceed in ahighly stereoselective manner, as shown in Eqs. 3.82 and 3.83. This reaction provides rapid and stereoselective access to important molecules containing 1,3-diamino-2-hydroxypropyl segments, which are cenhal structural subunit of the HIV protease inhibitor amprenavir (in Scheme 3.21). 

Tetrabutylammonium fluoride (TBAF) is usually used in the form of the trihydrate or as a solution in tetrahydrofuran (THF). The pure form is difficult to isolate, owing to decomposition to FFF, tributylamine, and but-l-ene [18, 19] on dehydration. It has been used for a variety of reactions, including as a catalyst for various reactions with silicon compounds [20, 21]. One of its main uses is in the cleavage of silyl ether protecting groups [22]. 

Moderate yields of the 1- (47%) and 4- (51%) fluoro derivatives of benzo[c]cinnoline were obtained by fluorodenitration of the nitro precursors using tetrabutylammonium fluoride. The 2- and 3-fluoro isomers have been made by Schiemann reactions, though yields were only 25 and 35%, respectively (92SC545). 

Allylsilanes react with carbonyl compounds to transfer the allyl group with 1,3-transposition, in the presence of Lewis acids, typically titanium(IV) chloride47. Recently this reaction has been carried out under super-acid catalysis48. Transfer of the allyl group is also induced by tetrabutylammonium fluoride, but in this case reaction takes place regioselectively at the less substituted end of the allyl fragment49. 

The chemical yield of the classical Henry reaction is not always good and depends on steric factors thus, highest yields are obtained when nitromethane is used. Performing the reaction under high pressure (9 kbar, 30 °C) with tetrabutylammonium fluoride catalysis19 enlarges the scope of the reaction dramatically. Thus, addition of nitropropane to 2-methylcyclohexanone, which is not reactive under the classical conditions, was achieved in 40 % yield. Improved yields... 

In the presence of a catalytic amount of tetrabutylammonium fluoride, either freshly dried over molecular sieves22 or as the trihydrate16, silylnitronates 2 derived from primary nitroalkanes react readily at — 78 C or below, via their in situ generated nitronates. with aromatic and aliphatic aldehydes to give the silyl-protected (/J, S )-nitroaldol adducts 3 in excellent yield4,22-24-26,27. Silylnitronates, derived from secondary nitroalkanes. afford the adducts in 30 40% overall yield24. In contrast to the classical Henry reaction (vide supra), the addition of silylnitronates to aldehydes is irreversible. Ketones are unreaetive under such conditions. 

To achieve reproducible (R. . ) selectivities in these nitroaldol reactions pure, distilled /m-butyldimcthylsilylnitronates and anhydrous tetrabutylammonium fluoride should be used22. The corresponding trimethylsilylnitronates furnish mixtures of (R, S )- and (R, R )-isomers22. 

Reaction of the secondary silylnitronate 4 with acetaldehyde, catalyzed by anhydrous tetra-butylammonium fluoride, furnished only 20% of the desired product 5 as a 56 44 (R, S )j (R, R ) mixture. With tetrabutylammonium fluoride trihydrate as base the yield increased to 89% while the diastereoselectivity remained low16. 

The diethyl acetal of nitroacetaldehyde combines with (f )-2-(benzyloxy)-3-hydroxypropanal (Id) in the presence of tetrabutylammonium fluoride trihydrate to give an 89% yield of an 88 12 mixture of only two diastereomers17. 

It has been reported that an allylic C-Si bond can be cleaved by tetrabutylammonium fluoride to give an anionic allylic species, which chemoselectively adds to carbonyl compounds (nitriles, esters, and epoxides failed) to form homoallylsilyloxy compounds13. 

A solution of tetrabutylammonium fluoride (TBAF) in THF (1.0M) is prepared from colorless, crystalline tetrabutylammonium fluoride trihydrate purchased from Fluka Chemical Corp. 

The palladium-catalyzed cross-coupling of alkenylsilanols has been extensively studied with respect to the structure of both the silicon component and the acceptor halide. The preferred catalyst for coupling of aryl iodides is Pd(dba)2 and for aryl bromides it is [allylPdCl]2. The most effective promoter is tetrabutylammonium fluoride used as a 1.0M solution in THF. In general the coupling reactions occur under mild conditions (room temperature, in 10 min to 12 hr) and some are even exothermic. 

To a solution of (5)-ester 6 (0.566 g, 1.90 mmol) in 20 mL of THF at 0°C is added tetrabutylammonium fluoride (3.0 mL, 3.0 mmol) (Note 19). After 15 min, the reaction mixture is warmed to room temperature. After 3 hr, 20 mL of aqueous saturated NH4C1 is added and the mixture is extracted with three 10-mL portions of Et20. The combined organic extracts are washed with 20 mL of brine, dried over MgS04, filtered, and concentrated under reduced pressure. The residue is purified by chromatography on silica gel (elution with 20% EtOAc/hexanes) to afford 0.271 g (78%) of alcohol 7 (Note 20). 

Tetrabutylammonium fluoride (1.0M in THF) was obtained from Aldrich Chemical Company and used as received. 

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