Tetra-A-butylammonium fluorid

This reaction was first reported by Rubottom and Brook et al. concurrently in 1974. It is the transformation of a ketone into the corresponding a-hydroxyketone by means of the epoxidation or dihydroxylation of a silyl enolate of the ketone with wi-chloroperbenzoic acid (m-CPBA) or dimethyldioxirane (DMDO). Therefore, this reaction is generally known as the Rubottom reaction or Rubottom oxidation. Under certain conditions, the Rubottom oxidation can establish a hydroxyl group enantioselectively, such as in the introduction of cw-hydroxyl group with respect to the isopropyl group in 8Q ,llj0-dimethyl-13)3-hydroxy-12/3-isopropyl-5/3,15-isopropylidenedioxy-14-keto-(A , A " )-tricycle. The silyl group can be cleaved by means of tetra-A-butylammonium fluoride (TBAF). ... 

Returning to intermediate 52a, we quickly learned that the C9 alcohol was well shielded by the proximal arene at CIO and that the bulky silyl ethers (TBDPS, TIPS) or esters (PIV) needed to withstand the Lewis acid cmiditions could not be produced in acceptable yield. However, silylatirMi with TBSOTf provided a disUyl product in excellent yield and to our delight the C4 allylic silyl ether could be selectively deprotected in the presence of tetra-A/-butylammonium fluoride (TBAF). Oxidation of 68 utilizing DMP ccniditions provided intermediate 43 (Scheme 16). 

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. 

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 %. 

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. 

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 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. 

The preparation of warfarin derivatives via the catalysed Michael-type reaction of 4-hydroxycoumarins with 4-arylbut-3-en-2-ones is achieved with a ca. 20-fold increase in reaction rate and a twofold increase in yields, compared with traditional methods [60]. Similarly, tetra-H-butylammonium fluoride catalyses the reaction of nitrotoluenes with a,p-unsaturated esters under mild soliddiquid two-phase conditions [14] with increased yields, compared with those observed in the absence of the catalyst. 

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],... 

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]. 

The method by which lactone 17 was obtained was not without its own implications for the synthesis. Treatment of 16 with dry tetra n-butylammonium fluoride in acetonitrile achieved desilylation. Not unexpectedly, this process triggered migration of the C5 benzoyl group to the newly unveiled C4 alcohol. The C5 alcohol thereby liberated underwent lactonization to the desired 17 (61% yield from 16). Indeed, reaction of 17 with stoichiometric osmium tetroxide in pyridine-THF afforded a single diol formulated as 18 in 97% yield (see Figure 4). 

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