Fluoride desilylation

Destlylation. Anhydrous cesium fluoride desilylates trimethylsilylmethyl-sulfonium, trimethylsilylmethylammonium, and trimethylsilylmethylphosphonium salts at room temperature to produce ylides, which undergo various useful transformations. Use of potassium fluoride-18-crown-6 or a tetraalkylammonium fluoride gives products in low yield in these reactions. The trimethylsilylmethyl-onium salts are prepared by alkylation of sulfides, amines, imines, and phosphines with (trifluoromethanesulfonylmethyl)trimethylsilane (1). 

Our synthesis of homochiral acetylenic sulfoxides is outlined in Scheme 1. The Grignard reagent of trimethylsilyl acetylene was reacted with sulfinates 6a-c in toluene. After potassium fluoride desilylation, optically pure acetylenic sulfoxides ( )-(+)- were obtained in good yield (Scheme 1) [7,8]. 

The first synthesis of acetylenic sulfonate 72 was achieved by MCPBA oxidation of sulfinate 68 a to 71, followed by potassium fluoride desilylation, in 90% overall yield. However, to our surprise, the triisopropylsilyl-protected acetylenic sulfinate 68 b resisted oxidation with the oxidants we tried, including MCPBA, oxone, H202/Se02, and Ru04 generated from RuCl3/NaI04 [37],... 

Fluoride desilylation yielded the spiroketal target II. Swem oxidation of the C-5 hydroxyl group gave milbemycin H ansdog III. 

Monosubstitution of acetylene itself is not easy. Therefore, trimethylsilyl-acetylene (297)[ 202-206] is used as a protected acetylene. The coupling reaction of trimethylsilylacetylene (297) proceeds most efficiently in piperidine as a solvent[207]. After the coupling, the silyl group is removed by treatment with fluoride anion. Hexabromobenzene undergoes complete hexasubstitution with trimethylsilylacetylene to form hexaethynylbenzene (298) after desilylation in total yield of 28% for the six reactions[208,209]. The product was converted into tris(benzocyclobutadieno)benzene (299). Similarly, hexabutadiynylben-zene was prepared[210j. 

Lithium silylamides react smoothly with tiifluoronitrosomethane to give diazenes Traces ot water initiate the decomposition of the latter with liberation of a trifluoromethyl carbanion, which is trapped by carbonyl compounds [775] (equation 116) Desilylation of trialkyl(trifluoromethyl)silanes by fluoride ion produces also a trifluoromethyl carbanion, which adds to carbonyl carbon atoms [136, 137] (equations 117 and 118)... 

Intramolecular cyclization of 2-phenysulfonylmethyl lactam 3 took place upon reaction with lithium hexamethyldisilazan via generating its a-sulfonyl carbanion to give a cyclized postulated intermediate that can be quenched with trimethylchlorosilane to afford the stable silyl ketal 4. The later ketal was desulfonylated by Raney-Ni and desilylated through treatment with tetrabutyl ammonium fluoride (BU4NF) to afford the carbacephem 5 (94M71) (Scheme 1). 

Methoxymethoxy)(phenyl)methylcesium has been generated at room temperature in di-methylformamide by fluoride-induced desilylation from optically active benzyltrimethylsilane and trapped in situ by 2-cyclohexenone with 89% racemization41. 

The reactions of a-methyl-branched acylsilanes with 2-propenylmagnesium bromide exhibit surprisingly high diastereoselectivilies, although further improvement is accomplished by application of allyltrimethylsilane/ titanium(IV) chloride (> 100 I)27. The fluoride-induced desilylation proceeds with retention of configuration. 

Intermolecular reaction of the mannose-derived 2,3-0-isopropylideiie-a-D-/y.vc>-pentodialdo-l,4-furanoside 13 affords a diastereomeric mixture of nitroalcohols 14. Upon fluoride-catalyzed desilylation, a stereoisomerically pure nitrocyclitol 15 was obtained from a successive intramolecular nitroaldol reaction as a consequence of the reversibility of the nitroaldol reaction which, in this case, allows the equilibration of isomers through open-chain intermediates33. 

Fluoride-induced desilylation has also been used to effect ring closures.117... 

Synthetic work commenced with evaluation of an azomethine ylide dipole for the proposed intramolecular dipolar cycloaddition. A number of methods exist for the preparation of azomethine ylides, including, inter alia, transformations based on fluoride-mediated desilylation of a-silyliminium species, electrocyclic ring opening of aziridines, and tautomerization of a-amino acid ester imines [37]. In particular, the fluoride-mediated desilylation of a-silyliminium species, first reported by Vedejs in 1979 [38], is among the most widely used methods for the generation of non-stabilized azomethine ylides (Scheme 1.6). 

A general route to allylanilines, reported by Harmata and co-workers <95TL4769> could be of value in organic synthesis. Deprotonation of 2,1-benzothiazines 193 with n-BuLi followed by alkylation with iodomethyltrimethylsilane, and subsequent desilylation with fluoride followed by hydrolysis led to allyl aniline 194 in good yields (Scheme 54). 

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). 

An efficient method for the generation of oquinodimethanes via desilylation reaction involves treatment of a 2-[(trimethylsilylmethyl)benzyl]trimethylarmnonium iodide with fluoride ion (equation 31)64. This reaction was applied by Saegusa and coworkers for the synthesis of estrone in which an intramolecular Diels-Alder reaction of an o-quinodimethane, generated in situ, served as the key reaction (equation 32)65. 

This reaction was easily performed with malonic ester derivatives using approaches described above for nitro carbanions. It should be noted that the anion of malonic ester can be prepared not only by the reactions of bases with malonates but also by desilylation of silyl ketene acetal (449) with fluoride anion. 

After the formation of tautomeric anions A=A. the anion A a rearranges to give the anion B, which reacts with the second nitroso acetal molecule to form a mixture of stereoisomers of silyl derivative 509a. After desilylation of 509a, oxime 510a is isolated. The reaction with the fluoride anion proceeds at low temperature, whereas the use of triethylamine is efficient only at room temperature. The yield of oxime (510a) is virtually independent of the reaction conditions, whereas the diastereomeric ratio varies substantially. 

Evidently, an increase in steric hindrance around the reduced fragment requires the presence of ammonium fluoride in the reaction mixture. It should be noted that potassium fluoride has no effect. It is highly probable that ammonium fluoride is required for slow elimination of HF, which gradually desilylates the nitroso acetal fragment thus facilitating its reduction. As can be seen from Scheme 3.284, many reduction products are derivatives of unnatural amino acids. Since the initial nitroso acetals can be prepared by silylation of simple acyclic AN, possibilities have been opened for the synthesis of unnatural amino acids from available AN. 

The isopropenyl side chain may derive by elimination of a tertiary alcohol or ether as in 202. Such a masking of the olefin avoids a possible competing vinylcyclopropane rearrangement. The correspondence of the cyclopentene of 202 with the vinylcyclopropane in 203 now becomes obvious. The presence of the dimethylcarbinol side chain now also offers the opportunity for its introduction by addition of a cyclopropyl anion to acetone. The feasibility of creating such an anion by fluoride initiated desilylation... 

The aryl bromide 40, prepared from cross-coupling between 1,2-dibromobenzene and (trimethylsilyl)acetylene, was converted to the corresponding arylzinc halide 41a and arylboronic acid 41b for subsequent coupling with the haloallenes 42 to produce the benzannulated enyne-allene 43 in -40% yield (Scheme 20.10) [38]. Desilylation with tetrabutylammonium fluoride (TBAF) then afforded 44 in 67% yield. 

The aldol condensation of benzaldehyde with the thioacetamide carbanion (RCHCSNRV), derived from the desilylation of the silyl-thioether with tetra-/i-buty-lammonium fluoride, is stereoselective at—80°C producing the erythro isomer of the p-hydroxy thioamide preferentially (Scheme 6.18, R = Me, erythro threo 95 5) via a conformationally mobile intermediate. However, when R is bulky, a greater amount of the threo isomer is formed. Predictably, as the reaction temperature is raised, so the stereoselectively decreases. This procedure contrasts with the corresponding condensation catalysed by titanium salts, where the complexed intermediate produces the threo isomer [47, 48],... 

From the point of view of the synthesis of dissonant systems the most important finding reported by Reissig [19c] is the opening of cyclopropanes by fluoride ion-induced desilylation to give carboxylic ester stabilised "homoenolate" anions, from which a series of 4-oxoalkanoic esters (21a ). with a 1,4-D relationship, were prepared (Table 5.6) ... 

---