Tetra-n-butylammonium fluoride TBAF

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 %. 

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. 

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. 

Appropriately functionalized resins can sequester excess nucleophiles from solution-phase reactions. Thus the calcium sulfonate resin 4 captures tetra-n-butylammonium fluoride (TBAF) from a variety of desilylation reactions.22,24 Polymer-bound tetra-n-butylammonium sulfonate and insoluble calcium fluoride are formed. The applicability of this strategy was illustrated for deprotection of (3-trimethylsilylethyl esters as well as silyl ethers. 

Silylation of acidic compounds.2 The combination of ethyl trimethylsilylacetate and 2-5 mole % of tetra-n-butylammonium fluoride (TBAF) is a markedly efficient reagent for transfer of trimethylsilyl groups to relatively acidic substrates such as ketones, alcohols, thiols, phenols, and carboxylic acids, and even 1-alkynes. KOCH3/ (18-crown-6) and Triton B are also effective catalysts. 

The fluoride ion is used extensively for cleaving silyl ethers (Equation Si2.5). Reagents used include B114NF (tetra-n-butylammonium fluoride, TBAF) and KF.18-crown-6. 

Several methods have been reported for the preparation of glycosyl fluorides7 but the most common procedure is treatment of a thioglycoside with NBS (iV-bromosuccinimide) and (diethylamino)sulfur trifluoride (DAST)8 or the reaction of a lactol with DAST or 2-fluoro-l-methylpyridinium p-toluenesulfohate.7 9 An alternative and interesting method is the treatment of a 1,2-anhydro-pyranoside with tetra-n-butylammonium fluoride (TBAF). 

Phenyl[2-(trimethylsilyl)phenyl]iodonium triflate (226) has emerged as a superior benzyne precursor i.e., admixture of 226 with tetra-n-butylammonium fluoride (TBAF) enables the generation of benzyne in dichloromethane at room temperature (95JCS(CC)983). When organo azides or -nitrones are available in the reaction medium, high yields of the benzotriazoles 227 or benzisoxazolines 228 are obtained (Scheme 62) (98HC205). 

It is a palladium-catalyzed cross-coupling reaction between organosilanes (vinyl, ethynyl and allylsilanes) and organic halides (aryl, vinyl and allyl halides). Allylpal-ladium chloride dimmer [( ri -C3H5PdCl)2] and either tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF) or tetra-n-butylammonium fluoride (TBAF) are used as catalysts. Fluoride ion acts as an activator for the coupling, forming an intermediate hypervalent anionic silicon species, which can then transmetallate with palladium as a preliminary reaction to coupling. 

The first example of an oxide-anion accelerated retro Diels-Alder reaction was reported by Papies and Grimme [52]. The adduct 19 (Equation 1.23) treated with tetra-n-butylammonium fluoride (TBAF) in THF at room temperature is immediately converted into 20, in contrast to the parent 21 (Equation 1.24) which undergoes cycloreversion into 22 at 100 °C. The dramatic oxide-anion acceleration (> 106) was ascribed to the loss of basicity of about 8pKb units in the transformation of alcoholate ion of precursor 19... 

The reaction of tetra-n-butylammonium fluoride (TBAF) (available as a THF solution although it always contains some water) with benzylsilanes in, the presence of an aldehyde or ketone provided homobenzyl alcohols111 (equation 109). It is presumed that the reaction proceeds through the tetra-n-butylammonium salt of the benzyl anion. This... 

Tebbe olefination, 441 Tebbe olefinations, 368 Tebbe s reagent, 457 Tedania ignis, 246 Tedanolide, 246 tedanolide, 256 TEMPO, 250, 301 temporary silicon tether, 103 Tennant quinoline synthesis, 7 tetra-n-butylammonium fluoride (TBAF), 214 2-(7-aza-1 H-benzotriazole-1 -yl)-1,1,3, 3-tetramethyluronium hexafluorophosphate (HATU), 25... 

The ABC-ring carboxylic acid 17 and the FGH-ring alcohol 18 were connected under Yamaguchi conditions to give ester 19 (Scheme 28.3). Desilylation with tetra-n-butylammonium Fluoride (TBAF), acid-catalyzed acetal formation with y-methoxyallylstannane 20, and acetal cleavage with iodotrimethylsilane/hexamethyldisilazane prodnced (y-alkoxyallyl)stannane 21. The ester 21 was... 

The epoxide-assisted displacement of triflyl groups by fluoride ion is reported to be an efficient approach to deoxyfluoro-sugars. Benzyl 2,3-anhydro-4-0-triflyl-pyranosides undergo inversion at C-4 with tetra-n-butylammonium fluoride (TBAF) at room temperature in good yield thus treatment of the triflate (34-) with TBAF in benzene for 24 h gave the 4-fluoro-sugar (35) in 60% yield. The mild conditions avoid many of the difficulties encountered in fluoride-... 

Homogeneous acylation of cellulose dissolved in dimethyl sulfoxide (DMSO)/tetra-n-butylammonium fluoride (TBAF) with different carboxylic acids, mediated by Af V -carbonyldiimidazole (CDI)... 

Subsequently, Smith and coworkers [63] demonstrated the possibility of a four-component union employing the consecutive addition of two different linchpins such as 176 and 185 (Scheme 4.36). Thus the dithiane (+)-180, an advanced intermediate in the spirastrellolide venture, was treated with the Schlosser base (n-BuLi/KOt-Bu) and the resulting anion was reacted in sequence with linchpins (+)-176 and 185 at —78°C and a final electrophile, allyl bromide, affording the four-component adduct 186 as diastereomeric mixture, in 44% yields. Treatment of the 186 with tetra-n-butylammonium fluoride (TBAF), yielded the diol 187 as a separable mixture (1.3 1) of diastereomers in 37% overall yield (Scheme 4.36) [63]. 

Li et al. developed the solvent-free C-N coupling between A-heterocycles and aryl/ heteroaryl halides promoted by the nano-Cu2O/l,10-phen/tetra-n-butylammonium fluoride (TBAF) catalytic system. Different types of CU2O were evaluated, and the studies showed that CU2O nanoparticles (especially the cubic form) were the most efficient for the C-N coupling reactions (Scheme 4.28) (Tang et al., 2008). 

When a solution of Et2Zn was treated with enantioenriched 225 (er, 76 24) in THF at 40°C for 24h, foUowed by acidic hydrolysis and silyl ether deprotection with tetra-n-butylammonium fluoride (TBAF), the corresponding cyclic alcohol... 

As a Carbon Nncleophile in Fluoride Ion-Catalyzed Reactions. The reactions with aldehydes, ketones (eq 23), and o , -unsaturated esters (eq 24) can also be catalyzed by fluoride ion, usually introduced as tetra-n-butylammonium fluoride (TBAF), or other silicophihc ions such as alkoxide. These reactions produce silyl ether intermediates, which are usually hydrolyzed before workup. The stereochemistry of attack on chiral ketones can sometimes be different for the Lewis acid- and fluoride ion-catalyzed reactions. In addition some electrophiles only react in the fluoride-catalyzed reactions, as with the addition to trinitrobenzene giving an allyl Meisenheimer complex . ... 

Similarly, the reaction of PhSCF2SiMe3 with aldehydes and ketones using 10 mol % of anhydrous tetra-n-butylammonium fluoride (TBAF) reported by Pohmakotr et al. also provided the corresponding adducts, both carbinols and silyl ethers, in moderate to excellent yields (39-92%). The silyl ethers could be converted into the corresponding carbinols in quantitative yields by using KF in acetonitrile/THF (eq 4). Subsequent oxidation of the carbinol sulfides to sulfoxides followed by flash vacuum pyrolysis (FVP) gave the corresponding e/n-difluoroalkenes in 41-82% yields (eq 5). ... 

Trimethysilyl ethers can be easily removed under a variety of conditions, including the use of tetra-n-butylammonium fluoride (TBAF) (eq 7), citric acid (eq 8), or potassium carbonate in methanol (eq 9). Recently, resins (OH and H" form) have been used to remove phenolic or alcoholic TMS ethers selectively (eq 10). 

Silylation Reactions. In the presence of a catalytic amount of tetra-n-butylammonium fluoride (TBAF), ester (1) is a very efficient silylating agent for a wide variety of substrates including carbonyl compounds, alcohols, phenols, carboxylic acids, and alkynes. With unsymmetrical ketones the kinetic enol ether is the preferred product. Indeed, the use of (1) can provide superior selectivity to the use of hindered bases forenolate formation. This is illustrated with a 8,y-epoxy ester which provides an entry to /-keto-a, 8-unsaturated esters (eq 2). These silylation reactions of (1) can also be catalyzed by TBAF supported on silica. ... 

A variety of methods are available for the protection of carboxylic acids as 2-(trimethylsilyl)ethyl esters. 2-(Trimethylsilyl) ethyl esters are stable to conditions used in peptide synthesis. Deprotection of the ester is readily accomplished by treatment with tetra-n-butylammonium fluoride (TBAF). Hemisuccinates have been prepared indirectly under nonacidic conditions by monoprotection of succinic anhydride as 2-(trimethylsilyl)ethyl esters followed by esterification (eq 4) and then selective deprotection of the resultant diester (eq 5). ... 

The thiol-epoxy reaction has proved to be an important synthetic tool in the preparation of a variety of pharmaceutical and natural products [55-64]. As mentioned above, this reaction can be performed using an acid or a base as a catalyst. The acid catalysts include boron trifluoride etherate [57], lanthanide chlorides [65], lithium perchlorate [60], cobalt chloride [66], and neutral alumina [67]. The basic catalysts can be organic or inorganic and include, among others, triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), tetra-n-butylammonium fluoride (TBAF), and LiOH [61-64, 68, 69]. In the literature on small molecules, it is important to note that this reaction is complete in a few minutes to a few hours of reaction time, with quantitative yields and with high regioselectivity. In the case of LiOH and TBAF, quantitative conversion of the epoxide to a desired thio-ether compound is observed within minutes and with 100% regioselectivity (isomer I) [68, 69]. 

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