Alkylation tetrabutylammonium fluoride

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... 

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. 

Cyclizations of o-(a -haloalk oxy)phenols have been widely studied and were used to afford an expedient synthesis of 5-alkyl-2,3-dihydro-l,4-benzodioxins <2004SC2487>. This approach via a nucleophilic substitution was used for the synthesis of 8-substituted-2-hydroxymethyl-l,4-benzodioxane derivatives 164 in an enantiopure form. Use of CsF instead of more basic conditions allowed higher yields and enantiomeric excess (Equation 28) <2001ASC95>. Dry tetrabutylammonium fluoride (TBAF) in THF was required and was basic enough to initiate an intramolecular Sn substitution from the protected phenol 165 to the fluoro-l,4-benzodioxane 166 <1996T6187>. 

Ogilvie et al.ls0 have described facile alkylation of purines and pyrimidines in THF, using tetrabutylammonium fluoride (TBAF) at room temperature. Uracil, cytosine, and adenine give mainly 1,3-dialkylation. 

Scheme 12.10. Synthesis of a-onocerin using butyldimethylsilyl, THF = tetrahydrofuran, a three-component nucleophilic addition/Brook Tf = trifluoromethanesulfonyl, DME = 1,2-rearrangement/alkylation on acylsilanes, by dimethoxyethane, TMS = trimethylsilyl, Corey and co-workers [33]. TBS = t- TBAF = n-tetrabutylammonium fluoride.

Equation 76) <1993OM3019>, which react as ester and ketone enolate equivalents, respectively. The latter reaction requires the use of fluoride ion activation (tetrabutylammonium fluoride, TBAF) to actuate the addition. Central carbon alkylation is less common for allylpalladium reactions despite this, nucleophilic alkylation of TMEDA-stabilized 1,3-diphenylallyl palladium complexes proceeds selectively to the central carbon (Equation 77) <1995AGE100>. 

Alkyl halides, including bcnzylic and allylic halides, do not react with trimethyl(trifluoro-methyl)silane. even with molar amounts of tetrabutylammonium fluoride. A convenient method has been developed for the perfluoroalkylation of organic (aryl, vinyl, benzyl and allyl) halides, e.g. formation of 1. using a mixture of trialky (perfluoroalkyl)silane/potas-sium fluoride/copper in dimethylformamide. Under these conditions perfluoroalkylcopper RpCu reagents are produced in situ. 

These reactions are convenient methods for incorporating a sulfur-containing group onto an aromatic ring. With Ar S, diazosulfides Ar—N=N—S—Ar are intermediates/° which can in some cases be isolated. ° Thiophenols can be made as shown above, but more often the diazonium ion is treated with EtO-CSS or 82, which give the expected products, and these are easily convertible to thiophenols. Aryldiazonium salts are prepared by the reaction of an aniline derivative with an alkyl nitrite (RONO), and when formed in the presence of dimethyl disulfide (MeS-SMe), the product is the thioether, Ar-S-Me. ° Aryl triflates have been converted to the aryl thiol using NaST(P5) and a palladium catalyst, followed by treatment with tetrabutylammonium fluoride ° (see also, 14-22). 

Transesterification has been carried out with phase-transfer catalysts, without an added solvent. Nonionic superbases (see p. 365) of the type P(RNCH2CH2)3N catalyze the transesterification of carboxylic acid esters at 25°C. ° Silyl esters (R C02SiR3) have been converted to alkyl esters (R C02R) via reaction with alkyl halides and tetrabutylammonium fluoride. Thioesters are converted to phenolic esters by treatment with triphosgene-pyridine and then phenol. 

The same group reported an approach to trisubstituted pyrazolones beginning with a solution-phase acylation of Meldrum s acid 21 and resin-capturing of the intermediates 22 with the add-stable resin 27. The products 23 were a-alky-lated using tetrabutylammonium fluoride (TBAF) and primary alkyl halides under strict exclusion of moisture, as otherwise the yields dropped dramatically. Treatment of the products 24 with phenyUiydrazines produced the corresponding hydrazones 25, which were cleaved from the solid phase by cyclization using 2% TFA in acetonitrile at room temperature to form pyrazolones 26 [15[ (Scheme 7). 

Monoalkylation on polystyrene resin using tetrabutylammonium fluoride (TBAF) (Table 8, entry 12) [454] Resin bearing a 1,3-diketone (20 mg, 8.6 mmol) was treated with a 1 M solution of BU4NF in THF (86 mb) for 2 h at r. t. After the addition of 150 mb of a 2.5 m solution of the appropriate alkylating agent, the reaction was allowed to proceed for a further 2 h. The resin was then filtered off and washed as follows ... 

A -Silylated enaminesv43 can undergo similar acid-catalyzed hydrolysis under the conditions outlined in Scheme 3 to A -alkyl enamines 44, while 45 fail to hydrolyze, presumably due to their sensitivity to the conditions employed. However, by using tetrabutylammonium fluoride as a catalyst enamines 46 are formed". ... 

Naked enolates without any complexation can be made from silyl enol ethers using fluoride ion, a very selective nucleophile for silicon 49, and a non-metallic cation, usually a tetra-alkylammonium ion. The commonest reagent is TBAF (TetraButylAmmonium Fluoride Bu4N+ F ). In this way the naked enolate 50 was made. It proved to be acylated with acetic anhydride exclusively at oxygen to give the enol acetate 53 and alkylated with Mel at carbon to give the ketone 51 in 84% isolated yield.18... 

The TTF(X—SEM) derivatives (X = S, Se SEM = trimethyl-silylethoxymethyl n = 1-4) are extremely useful, since their deprotection with tetrabutylammonium fluoride (TBAF) in the presence of alkylating agents leads to a wealth of new alkylthio derivatives (91EUP408495 91TL2741). This methodology has been applied to TTF—Se—SEM (92), thus rendering it a shelf-stable equivalent of TTF—Se" [93JCS(P1)1403]... 

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