Tetra-n-butylammonium fluoride

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 Tetra-n-butylammonium Bromide. After the resin is washed with water, the combined water fractions are repeatedly evaporated until no water is present. Tetrabuty-lammonium fluoride is collected as an oil in quantitative yield. 

Cyclobutanone alkyl silyl acetals, obtained from [2 + 2] cycloadditions, can be deprotected with 1 equiv of TBAF in THF to give the open-chain cyano esters in excellent yields (eq 5). When 4-chloro-2-cyanocyclobutane alkyl silyl acetals 

11-Membered pyrrolizidine dilactones have been synthesized by treating a trimethylsilylethyl ester with TBAF in MeCN to form an anion, which then undergoes cyclization by displacement of the mesylate. 

The anions, generated in situ by desilylation of silylacetylenes, allylsilanes, propargylsilanes, a-silyloxetanones, bis(trimethylsilylmethyl) sulfides, and other silane derivatives,can undergo nucleophilic addition to ketones and aldehydes (eq 11). Al-(C,C-bis(trimethylsilyl)methyl) amido derivatives can add to aldehydes followed by Peterson alkenation to form acyl enamines. Treatment of 2-trimethylsilyl-l,3-dithianes can generate dithianyl anions, which are capable of carbocyclization via direct addition to carbonyl or Michael addition (eq 12). The fluoride-catalyzed Michael additions are more general than Lewis acid-catalyzed reactions and proceed well even for those compounds with enolizable protons and/or severe steric hindrance (eq 13).  

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A/ HE, 0.1 M NaF, pH 5. THE, 25°, 2 days, 77% yield. In this substrate, a mixture of products resulted from the attempted cleavage of the t-butyl-dimethylsilyl ether with tetra-n-butylammonium fluoride, the reagent generally used. ... 

The use of tetra-n-butylammonium fluoride (54) in an aprotic solvent such as acetonitrile may be more advantageous. Foster and colleagues (19, 37) have effected an SN2 type of reaction using this reagent in the conversion of l,2 5,6-di-0-isopropylidene-3-0-p-tolylsulfonyl-D-allofura-nose into the C-3 epimeric fluorodeoxy derivative. Note that whereas potassium fluoride is ineffective in displacing secondary sulfonate esters in sugars, tetra-n-butylammonium fluoride is capable of effecting a displacement with Walden inversion even in a furanose drivative. 

Tetra n-butylammonium fluoride. .. 162 2-Thiobarbituric acid-malonaldehyde... 

The next major obstacle is the successful deprotection of the fully protected palytoxin carboxylic acid. With 42 protected functional groups and eight different protecting devices, this task is by no means trivial. After much experimentation, the following sequence and conditions proved successful in liberating palytoxin carboxylic acid 32 from its progenitor 31 (see Scheme 10) (a) treatment with excess 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in ie/t-butanol/methylene chloride/phosphate buffer pH 7.0 (1 8 1) under sonication conditions, followed by peracetylation (for convenience of isolation) (b) exposure to perchloric acid in aqueous tetrahydrofuran for eight days (c) reaction with dilute lithium hydroxide in H20-MeOH-THF (1 2 8) (d) treatment with tetra-n-butylammonium fluoride (TBAF) in tetrahydrofuran first, and then in THF-DMF and (e) exposure to dilute acetic acid in water (1 350) at 22 °C. The overall yield for the deprotection sequence (31 —>32) is ca. 35 %. 

It would appear that when fluoride ion is to be used in stoichiometric amounts, benzyltrimethylammonium fluoride is the preferred source on the other hand, tetra-n-butylammonium fluoride, commercially available as its trihydrate, is more convenient in catalytic situations. However, there are difficulties. (19) in successfully dehydrating the latter source without inducing Hofmann elimination. 

Sulfones with a trimethylsilyl or trialkylstannyl group at the -position or at the -position are readily converted to olefins upon treatment with tetra-n-butylammonium fluoride in THF (equations 39-41). The method is compatible with the presence of a variety of functionalities. 

A palladium catalyst is used in the transformation of a siloxyfuran to a phenyl substituted furanone <00JCS(P1)3350>. Similar products, furan-2(5//)-one derivatives, are afforded through the reaction of tetra-n-butylammonium fluoride with the corresponding substituted 2-siloxyfuran <00S1878>, as well as the oxidation of 3,4-disubstituted furans by singlet oxygen . 

The first promising asymmetric aldol reactions through phase transfer mode will be the coupling of silyl enol ethers with aldehydes utilizing chiral non-racemic quaternary ammonium fluorides,1371 a chiral version of tetra-n-butylammonium fluoride (TBAF). Various ammonium and phosphonium catalysts were tried138391 in the reaction of the silyl enol ether 41 of 2-methyl-l-tetralone with benzaldehyde, and the best result was obtained by use of the ammonium fluoride 7 (R=H, X=F) derived from cinchonine,1371 as shown in Scheme 14. 

Tetrabromopyridine reacts with 1,2-dihydroxybenzcne to yield the dibromoazaphenoxane [34], Tetra-n-butylammonium fluoride catalyses the conversion of 5-chloro-l-phenyltetrazole into tetrazol-5-yl glycosides, which are useful precursors for the formation of glycosyl fluorides [45]. 

Intramolecular cyclization of 5-trimethylsilyloxy mesylates to produce 6-membered cyclic ethers is catalysed by tetra-n-butylammonium fluoride on a stoichiometric scale [52] and has found particular application in a high yielding (>90%) synthesis of 0-2-isocephams. 

The almost instantaneous intramolecular ether formation by reaction of phenoxy anions, generated from the silyl ethers with a stoichiometric amount of tetra-n-butylammonium fluoride, on mesylate esters has been used to synthesize labile benzo-0-2-isocephams (>90%) [20]. 

The reaction of silyl enol ethers with fluoroformates and fluoroformamides, catalysed by the addition of tetra-n-butylammonium fluoride, produces enol carbonates and carbamates in acceptable yields [60],... 

V-(Ethoxycarbonylmethyl)carbodiimides, obtained from the reaction of iminophos-phoranes with aryl isocyanates, undergo cyclization when treated with an excess of tetra-n-butylammonium fluoride at room temperature to yield l,3-oxazlin-5-ones [75] (Scheme 3.9). The ammonium fluoride probably enhances the electrophilic character... 

The preparation of thiols by nucleophilic displacement reactions using aqueous potassium or sodium hydrogen sulphide under catalytic conditions is not particularly effective. A limited number of simple alkane thiols have been obtained under mild and neutral conditions in moderate yield (70-80%) from the reaction of bis(n-butyltin) sulphide with bromoalkanes in the presence of a ca. twofold amount of tetra-n-butylammonium fluoride [1], but there has been no exploitation of this procedure. 

Thione-S-oxides react regiospecifically with allyl and benzylsilanes in the presence of a stoichiometric amount of tetra-n-butylammonium fluoride to produce allyl and benzyl sulphoxides [8], cf. the analogous fluoride initiated reaction of thio-ketones and dithiocarboxylic esters with silanes [9, 10]. The yields of sulphoxides... 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

Aromatic aldehydes undergo a pinacol reaction when treated with hexamethyl-disilane and tetra-n-butylammonium fluoride [55] using procedure 3.1.14.D. 

Cyloheptatrienylidene carbene is generated when trimethylsilyltropylium tetra-fluonoborate is treated with a stoichiometric excess of tetra-n-butylammonium fluoride in dichloromethane [50], Although the carbene dimerizes readily, it will react with electron-deficient alkenes (see Section 7.3). Tetra-n-butylammonium fluoride in a stoichiometric amount promotes the formation of adamantylidenevinylidene from 2-bromo-2-(trimethylsilylethynyl)adamantane [51 ]. 

Concomitant C-Si cleavage by tetra-n-butylammonium fluoride and extrusion of a phenylthiolate anion from ot-trialkylsilyldisulphides provides a route to reactive thioaldehydes [44],... 

Lewis acid-catalysed deprotection of enol ethers to yield carbonyl compounds is aided by the addition of tetra-n-butylammonium fluoride. Optimum yields were obtained with equimolar amounts of the enol ether in dichloromethane with the fluoride and boron trifluoride etherate [20, 21]. 

Epoxidation of ot.fl-unsaturated ketones by hydrogen peroxide or /-butyl peroxide is promoted by the addition of tetra-n-butylammonium fluoride [10], whereas the corresponding reaction with 1,4-disubstituted but-2-en-l,4-diones is catalysed by quaternary ammonium iodides [11], Oxiranes are also produced by the catalysed reaction of /-butyl peroxide with a,f)-unsaturated sulphonates under basic conditions [12]. 

The catalytic effect of tetra-n-butylammonium fluoride in the homogeneous reduction of heterocyclic A-oxides and nitroarenes by hexamethyldisilane in tetra-hydrofuran can occur with EXPLOSIVE violence, but can be controlled by the slow addition of the disilane to the A-oxide (or nitroarene) and tetra-n-butylammonium fluoride to yield the parent heterocycle (>70%) (or azobenzene 84%). In a similar manner, azoxybenzene is converted into azobenzene (95%), and 4-nitropyridine-l-oxide, is reduced to azoxypyridine-l,l -dioxide (78%), with minor amounts of azopyridine-1, l -dioxide and azopyridine-1-oxide [5,6]. 

Related reactions, catalyzed by tetra-n-butylammonium fluoride (TBAF), have been reported (74). Under the influence of 5 to 10 mol % of TBAF (THF, -78°C), enolsilane 75 afforded the erythro and threo adducts 76E and 76T whose ratios were time dependent (5 min, E T =1 2 10.5 hr, E T =1 3) (74). The reaction of enolsilane 77 at various temperatures has also been reported (2). At -78 C (1 hr) complete kinetic erythro diastereoselection was observed under the conditions reported by Noyori (74), but at higher temperatures product equilibration was noted (2). It is significant that the kinetic aldol condensation of this tetraalkylammonium enolate exhibits complete erythro selection as noted for the analogous lithium derivative. 

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