Alkyl silyl-fluorides

Benzyl and alkyl tnalkylsilyl ethers undergo clean fluonnation to give good yields of benzyl and alkyl fluorides, respectively, when reacted with a combination of d quaternary ammonium fluoride and methanesulfonyl orp- toluenesulfonyl fluoride. The reactions are applicable strictly to a primary carbon-oxygen bond, secondary and tertiary alkyl silyl ethers remain intact or, under forcing conditions, aie dehydrated to olefins [29] (equation 22)... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

Alkoxysilanes, however, react with COFj (at 0-20%) in a similar way to that described for COClj to give silyl fluoride and alkyl fluoroformate derivatives [1452] in high yields ... 

Lithium enolates 85 and silyl enol ethers 86 are probably widest in application in modern organic synthesis. The basic rules of selectivity were laid down in chapters 2-4 where many examples were given. We shall simply summarise the position and add some extra versatility from chapters 5-9. These two methods must be taken together because easy interconversion means that a way of making one is a way of making another. In addition, the silyl enol ethers 86 are a source of naked enolates 87 when fluoride is used to remove silicon in the absence of a metal cation. Tetra-alkyl ammonium fluorides such as TBAF (Bu4N+ I ) are usually used. 

Transition states for inversion and retention of configuration channels in the reactions of alkyl and silyl fluorides with a water molecule " ... 

Mukaiyama-Michael Reactions. 1,4-Addition of ketene alkyl silyl acetals to a./S-unsaturated carbonyl compounds (eq 10) is promoted by a variety of Lewis acids (for example, TiCU, Ti(OR)4, SnCU, trityl perchlorate, lanthanide salts, Al-montmo-rillonite clay), or Lewis bases such as fluoride ion (eq 11), or quaternary ammonium carboxylates. Lanthanide salts are particularly effective catalysts, and in the case of ytterbium(III) tri-fluoromethanesulfonate, the catalyst can be recovered (eq 10). ... 

Other Reactions. Trityl fluoroborate has been used often to prepare cationic organometallic complexes, as in the conversion of dienyl complexes of iron, ruthenium, and osmium into their cationic derivatives. It alkylates pyridines on the nitrogen atom in a preparation of dihydropyridines and acts as a tritylating agent. It has also been used in attempts to form silyl cations and silyl fluorides from silanes. Finally, it has been reported to be a usefiil desiccant. ... 

Fluoride promoted alkylation of silyl enol ethers Acc. Cfiem. Res. 1985, 18, 181... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

The BOC group can be cleaved with TBDMSOTf and the intermediate silyl carbamate converted to other nitrogen-protective groups by treatment with fluoride followed by a suitable alkylating agent. ... 

The combination of silyl enol ethers and fluoride ion provides more reactive anions to give alkylated nitre compounds in good yields after oxidation v/ith DDQ, as shovm in Eq. 9.22. This process provides a new method for synthesis of indoles and oxyindoles fsee Chapter 10, Symhesis of Hatarocydic Compoioids). 

The first of the few low-temperature methods for the formation of an o-QM was a method developed by Rokita.5 It is principally used for reversible DNA alkylation. However, it has recently begun to find its way into some synthetic applications. It utilizes a silylated phenol, which proves vastly more manageable as an o-QM precursor than the corresponding o-hydroxyl benzyl halide (Fig. 4.6). In this kinetically controlled process, expulsion of a benzylic leaving group is triggered at low temperature by treatment with a fluoride ion, which causes a (3-elimination. 

In 1998, Harmata and co-workers <98T9995> published a new synthesis of 2-alkenyl anilines. The silylated 2,1-benzothiazines 187 could be deprotonated by n-BuLi and alkylated by different electrophiles. The corresponding products could be desilylated by fluoride with concomitant cleavage of the carbon-sulfur bond to give 2-alkenylsulfinanilides that can then be hydrolyzed by base to the anilines 195 in good yields (Scheme 55). 

Fluoride ion catalyzes the hydrosilylation of both alkyl and aryl aldehydes to silyl ethers that can be easily hydrolyzed to the free alcohols by treatment with 1 M hydrogen chloride in methanol.320 The most effective sources of fluoride are TBAF and tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF). Somewhat less effective are CsF and KF. Solvent effects are marked. The reactions are facilitated in polar, aprotic solvents such as hexamethylphosphortriamide (HMPA) or 1,3-dimethyl-3,4,5,6-tetrahydro-2(l //)-pyrirnidinone (DMPU), go moderately well in dimethylformamide, but do not proceed well in either tetrahydrofuran or dichloromethane. The solvent effects are dramatically illustrated in the reaction of undecanal and dimethylphenylsilane to produce undecyloxyphenyldimethylsi-lane. After one hour at room temperature with TBAF as the source of fluoride and a 10 mol% excess of silane, yields of 91% in HMPA, 89% in DMPU, 56% in dimethylformamide, 9% in tetrahydrofuran, and only 1% in dichloromethane are obtained (Eq. 164).320... 

The use of /i-ketocstcrs and malonic ester enolates has largely been supplanted by the development of the newer procedures based on selective enolate formation that permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of ketoesters intermediates. Most enolate alkylations are carried out by deprotonating the ketone under conditions that are appropriate for kinetic or thermodynamic control. Enolates can also be prepared from silyl enol ethers and by reduction of enones (see Section 1.3). Alkylation also can be carried out using silyl enol ethers by reaction with fluoride ion.31 Tetraalkylammonium fluoride salts in anhydrous solvents are normally the... 

Super anions. Unlike quaternary ammonium fluorides, 1 can be obtained anhydrous, li reacts with enol silyl ethers to form an unsolvated tris(diethylamino)-sulfonium (TAS) enolate in which there is negligible interaction hetween the ions.3 The naked enolate undergoes C-alkylation at —78 to — 30°. ... 

Arylation of silyl enol ethers.1 Silyl enol ethers of methyl n- or sec-alkyl ketones undergo arylation when treated with an aryl bromide and tri-n-butyltin fluoride and a... 

Magnesium enamides with a tethered nitrogen coordination site (91) undergo alkylation with alkyl chlorides or fluorides to give the corresponding a-substituted ketone, (g with some diastereoselectivity, and tolerance of silyl groups elsewhere in the substrate.345... 

Under strictly anhydrous conditions which minimize competing protiodesilylation, (Z)-a-silyl vinyl sulfides with an co-carbonyl moiety attached to the S atom undergo a fluoride-promoted intramolecular cyclization which yields 2-alkenyltetrahydropyran-3-ols. The substrates are derived from (Z)-a-silyl enethiols by alkylation with co-halocarbo-nyl compounds (Scheme 157) <2000EJ02391>. 

The Pandey group has developed a silver fluoride-promoted desily lation of tertiary bis(silyl)amines as an interesting alternative method to access azomethine ylides (Scheme 2.10).18 Notably, this method allows the generation of nonstabilized azomethine ylides under essentially neutral conditions. The starting materials are prepared by a three-step process, sometimes coupled into a single operation. For example, Boc-protected pyrrolidine 36 can be sequentially deprotonated and silylated twice in a one-pot reaction (Scheme 2.10). Removal of the Boc group and alkylation of the free amine leads to bis(silyl)amine 37. When this compound is treated with 2 equiv of silver fluoride in the presence of phenyl vinyl sulfone, rapid formation of products 39 as single stereoisomers results. 

The addition of alkoxycarbonylcarbene derived by catalysed decomposition of methyl diazoacetate to several simple, and in particular terminal, alkynes leads to low yields S7), but the reaction with 1 -trimethylsilylalkynes proceeds reasonably efficiently subsequent removal of the silyl-group either by base or fluoride ion provides a route to l-alkyl-3-cyclopropenecarboxylic acids. In the same way 1,2-bis-trimethylsilyl-ethyne can be converted to cyclopropene-3-carboxylic acid itself58 . The use of rhodium carboxylates instead of copper catalysts also generally leads to reasonable yields of cyclopropenes, even from terminal alkynes 59). 

Friedel-Crafts alkylation has been used in an important synthesis of aryl C-glycosides, which are potent anti-tumor agents, from glycosyl fluorides (equation 99)65 661. The reaction takes place rapidly in dichloromethane, at room temperature using a novel zirconium complex and silver perchlorate combination catalyst. A similar alkylation has been performed by replacing the aromatic compound with either a silyl enol ether or an allylic compound using silver triflate as the catalyst662,663. 

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