Trimethylsilyl fluoride elimination

Heating perfluorbutylsulfonyl fluoride 1316 with HMDS 2 and CsF in DMF affords the N-nonaflylamidine 1317 in 62% yield, trimethylsilyl fluoride 71, and HMDSO 7 [90]. Di(fluorosulfonyl)phenoxysulfonylmethane 1318 reacts with excess lithium trimethylsilanolate 98 to give, via 1319, vvdth elimination of HMDSO 7, the lithium salt 1320 in 95% yield [91] (Scheme 8.35). 

It was assumed that an a-fluorosilyl potassium species was formed initially, and that this subsequently underwent a self-condensation reaction. The eventual product (1) displayed both nucleophilic as well as electrophilic character, which was demonstrated in various derivatization reactions. Although it contains fluorine and potassium atoms in close proximity, the compound displayed a remarkable thermal stability. Even at 80 °C, potassium fluoride elimination occurred only sluggishly. Attempted transmetalation reactions with various metal halides, though, caused an immediate elimination of metal fluoride and the formation of tetrakis(trimethylsilyl)disilene. The latter can be trapped in cycloaddition reactions [5] or, in the absence of trapping reagents, it dimerizes to a cyclotetrasilane (Scheme 2) [6]. 

A similar elimination in which the tin is attacked by fluoride anions (cf. the reaction of silanes with F ) has been used179 to synthesize terminal methylene compounds as in equation (75). An analogous reaction sequence using a trimethylsilyl group in place of the trialkyltin group has been published by Hsiao and Shechter180 as part of a synthesis of substituted 1,3-butadienes. 

The 2-(trimethylsilyl)ethoxymethyl group (SEM) can be removed by various fluoride sources, including TBAF, pyridinium fluoride, and HF.165 This deprotection involves nucleophilic attack at silicon, which triggers (3-elimination. 

A simple procedure for the synthesis of 4,5-disubstituted 1,2,3-triazoles 1247 involves stirring a mixture of nitroethene 1245 with trimethylsilyl azide and tetrabutylammonium fluoride at 30 °C for 3h. No solvent is needed. Triazoline 1246, which forms in the first step of the reaction, eliminates nitrous acid, and the trimethylsilyl group is cleaved off by the fluoride anion to afford triazole 1247. Various aryl and heteroaryl substituents R are used providing triazoles 1247 in 70-90% yield (Scheme 207) <2005JOC6526>. 

A carbon labelling study has elucidated the rearrangement mechanism for formation of chalcone (97) which accompanies formation of (91) by the expected vicinyl elimination of trimethylsilyl and benzotriazolyl groups from 2-benzotriazolyl-2-aryl-3-ketopropylsilanes, on reaction with fluoride ion in DMF. ° Thus, it has been possible to distinguish between the two alternative mechanisms depicted in Scheme 11 (via intermediates (93) or (95), respectively, by determining the fate of the labelled quaternary carbon of substrate (89). The results are consistent with the formation of a cyclopropane intermediate (95) which subsequently ring opens, with relief of strain, to form delocalized carbanion (96), from which the chalcone (97) is obtained (labelled... 

Numerous synthetic routes to the dinitramide anion have been reported. Cesium dinitramide (149) has been synthesized via the fluoride-catalyzed /1-elimination of 1-(V,A1-dinitramino)-2-trimethylsilylethane (148) with cesium fluoride the latter prepared by treating 2-(trimethylsilyl)ethyl isocyanate with a solution of nitronium tetrafluoroborate and pure nitric acid in acetonitrile. ... 

The o-quinodimethane (40) may also be generated by fluoride-induced 1/4/elimination of trimethyl(2-[(trimethylsilyl)methyl]-benzyl) ammonium iodide (43). When this elimination is carried out at low temperature, the reaction conditions are ecjually compatible with the presence of 27, and this provides an additional route to 42. ... 

Dimethylene-2,3-dihydrofuran derivatives, which are produced by fluoride-induced 1,4-conjugative elimination of trimethylsilyl acetate from the [(trimethylsilyl)methyl]-3-furan precursor 207, undergo subsequent [4-1-4] dimerization reactions to produce cycloocta[l,2-3 6,5-. ]difuran derivatives as a mixture of isomers (Equation 137) <1995JA841 >. A methyl substituent at the 3-methylene position was found to retard the rate of dimerization, an observation which is consistent with the proposed two-step mechanism involving the initial formation of a diradical intermediate in the rate-determining step (Table 16). 

Elimination of p-[(trimethylsilyl)methyl]benzyltrimethylammonium iodide with fluoride leads via the intermediate p-quinodimethene to [2.2]paracyclophane (7). This very versatile method can also be applied for the syntheses of [2.2](2,5)furano-and thiophenophane 48a). 

These are good dienophiles. and aryl vinyl sulfones have found use as equivalents of ethylene and ketene through functional modifications of their adducts. However, as the base-induced elimination of a sulfinic acid to yield an olefin occurs only with difficulty, they are not direct precursors of acetylene equivalents, unless suitably modified as in ( )-l-phenyl-sulfonyl-2-trimethylsilyl ethylene (PhS02-CH=CH-TMS). In its cycloadducts the elimination to an alkene is smoothly realized by the fluoride ion. If an alkylation step is previously carried out on the adduct, the overall process realizes an indirect addition of a terminal acetylene, as in the examples given here [533]. 

The latter reaction involves the addition of the pcrfluoro(l-iodohexane) to phenyl trimethylsilyl ketone and a Brook rearrangement with lithium fluoride and fluorotrimethylsilane elimination. In the case of the corresponding magnesium derivative, which is more stable at the reaction temperature, warming up to room temperature before hydrolysis is necessary.214... 

Elimination of iodobenzene alone from 2-phenyliodonio benzoate leads to generation of another transient 1,4-dipole which was trapped by phosphaalkynes [55], A new precursor, 2-trimethylsilyl-diphenyliodonium triflate, obtained from 1,2-bis-trimethylsilylbenzene, (diacetoxyiodo)benzene and triflic acid, permitted the generation of benzyne with tetrabutylammonium fluoride, at room temperature [56] ... 

Cycloaddition of thiazolium azomethine ylides with dialkyl acetylenedicarboxylates 61 provides another approach to pyrrolo[2,1 -bjthiazoles 64 <070L4099>. Quatemization of 2-methylthiothiazole with trimethylsilylmethyl trifluoromethanesulfonate (TMSChkOTf) and subsequent fluoride-induced desilylation of the resulting (trimethylsilyl)methylammonium salt generate the acyclic azomethine ylide 62. This ylide readily participates in 1,3-dipolar cycloadditions with acetylene derivatives 61 to give adducts 63, which undergo spontaneous elimination of methylmercaptan to give the A-fuse cl thiazoles 64. ... 

Fluoride-induced -elimination of p-(trimethylsily )ethyl ethers, which is the cornerstone of the 2-(trtmethylsilyl)ethoxymethyl (SEM) protecting group for hydroxyl functions (see section 4.4.5), has been modified for use in deprotecting cyclic acetals. For example, 4-(trimethylsilyl)methyM,3-dioxolanes46 and 5-tri-methylsilyl-13-dioxanes47 cleave on heating with lithium tetrafluoroborate [Scheme 2.16], The method works well for unhindered aldehydes and ketones. 

The ability of fluoro-2 -phosphanes to transform silyl ethers into fluorides was first observed during a study of the reactions of phosphorus pentafluoride and its derivatives R PF5 (n = 1, 2, 3 R = hydrocarbon group) with trimethylsilyl ethers. Subsequently, this reaction was proposed as a new method for the preparation of C-F compounds from silyl ethers or silicic acid esters with fluoro-A -phosphanes. Pentafluorophenyl-substituted fluoro-A -phos-phanes were found to react similarily, Other workers found that tctrafluoro(phenyl)-A -phos-phane. which was chosen as the most convenient reagent with regard to reactivity and stability, gave considerable amounts of elimination products, especially with primary and cyclic alcohols. Good yields of fluorinated products are obtained when stable carbocations can be formed at the site of substitution, such as in tertiary alcohols, but 2-phcnylethanol. benzyl alcohol and diphcnylmethanol, on the other hand, give only poor yields of fluorinated products ethers and polymers are the main products. ... 

Besides the Fmoc (Section 2.1.1.1.1.3) and the substituted sulfonylethyl groups (Section 2.1.1.1.1.4) that are cleaved by (3-elimination under basic conditions, the A -2-(trimethylsi-lyl)ethoxycarbonyl (Teoc, 43)P 1 and 2-phenyl-2-(trimethylsilyl)ethoxycarbonyl (44)P 1 derivatives (Scheme 21) are readily removed by the action of the fluoride anion, the elimination products of the Grob-type reaction being TMSF, ethene or styrene, and a carbamate which releases carbon dioxide upon aqueous workup. The nature of the cleavage byproducts allows for easy isolation of the free amino compound. 

N-Alkoxymethyl(trimethylsilyImethyl)amines are convenient precursors for C-unsubstituted azomethine ylides 43 since the N-alkoxymethyl(trimeth-ylsilylmethyl)amines are readily available by the reaction of N-alkylated silylmethylamines with formaldehyde in alcohol solvents (84CL1117). Treatment of the amines with trimethylsilyl triflate in acetonitrile or tetrahy-drofuran brings about the elimination of alkoxy group R O to form N-silylmethyliminium trifiates 42. The subsequent desilylation with cesium fluoride generates C-unsubstituted azomethine ylides 43 (84CL1117). Both steps of the alkoxy elimination and subsequent desilylation of 42 are induced by trifluoroacetic acid (85CPB896, 85CPB2762), tetrabutylammonium... 

Equation 54 describes the preparation of dienes by a similar cyclopropane cleavage followed by proton transfer and elimination of sulfinate. The weak donor ability of a (trimethylsilyl)methyl group also assists Lewis acid-promoted ring cleavage according to equation 55, which allows synthesis of y, -unsaturated ketones Interestingly, the related ester opens smoothly only if fluoride reagents are employed (equation 56) ... 

Saegusa s group (81JA5250) found that [o-[(trimethylsilyl)alkylamino]-benzyljtrimethylammonium halide underwent the fluoride-anion induced 1,4-elimination under mild conditions to generate an o-quinone methide N-alkylamine intermediate. They performed the formal synthesis of gephyro-toxin 434 on the basis of an intramolecular cycloaddition of the o-quinone methide A-alkylamine 426 (83TL2881). Treatment of azadiene precursor 425... 

For the liberation of acetal-masked alcohols under nonacidic conditions, p-eliminations, already mentioned in Section 3.1.2.1, were adopted. Following this concept the 2,2,2-trichloroethoxymethyl (35) and the 2-(trimethylsilyl)ethoxymethyl (SEM) ethers (36) were proposed. Both are introduced via Williamson syntheses and their removal is initiated by treatment with Zn or Zn/Cu in methanol or by fluoride-induced P-elimination respectively. Similarly, the trichloroethyl ether had already been applied in carbohydrate chemistry (Scheme 26). ... 

The fluoride-induced elimination of P-trimethylsilyl sulfones to give terminal alkenes was first reported in 1979. The p-silyl sulfone (120 Scheme 42), prepared by the alkylation of the readily available crystalline sulfone (119), undergoes elimination on warming with TBAF in THF to give 1-decene in 80% yield. A second alkylation-elimination sequence can then be performed to give a 1,1-dialkyle-thylene derivative (121). Thus, the sulfone (119) may serve as a synthon for CH2=CH" or in... 

A fluoride-induced 1,4-elimination reaction illustrates the use of l-trimethylsilyl-4-phenylsulfony 1-2-butene (129) as a synthon for a butadiene anion (Scheme 46). The elimination is stereoselective, giving the ( )-diene (130) exclusively. 

Fluoride-induced fragmentation reactions were used in two stages of a synthesis of hexahydrocannabi-nol methyl ether (144 Scheme 52). One of the phenolic hydroxy functions in the resorcinol derivative (140) was selectively liberated from the SEM ether to give the diol (141), which was converted to the bis (trimethylsilyl) ether (142). Subsequent treatment with CsF resulted in a 1,4-elimination to the o-quinone methide (143) intermediate, which underwent an intramolecular [4 -i- 2] cycloaddition to give the product in good yield. 

The recently disclosed facile generation of benzyne 61 from 2-(trimethylsilyl)phenyltriflate 60, by fluoride ion-initiated elimination has generated renewed interest in this reactive species. For example, Cheng et al. have reported a palladinm-catalyzed three-component reaction involving benzyne, allyl chloride, and an allenylstannane to afford l-allyl-2-allenyl benzene 62 (Scheme 5.6.21). 

As the alcohol is not formed, there is no need to use sterically hindered alkoxides. This reaction is usually carried out in pentane or in an excess of alkene at 0 to 10 °C and is recommended for the preparation of thermally unstable 1,1-dichlorocyclopropanes. An interesting modification for the synthesis of 1,1-dichlorocyclopropanes which eliminates strongly alkaline medium, utilizes trimethylsilyl trichloroacetate and potassium fluoride in the presence of a catalyst (a quaternary ammonium salt or a crown ether),... 

When a fluorine atom in ( .I is replaced by another halogen, a fluorine atom rather than a chlorine" or iodine atom is eliminated as alkyl fluoride from the reaction with trialkyl phosphites. Trimethylsilyl phosphites react with perfluoroalkenes to give fcrs(ti iiuclhylsilyl) perfluoroalke-nylphosphonates in very good yields (81-95%), - probably because of the greater nucleophilicity of the trimethylsilyl phosphites and the stability of fluorotrimethylsilane. ... 

Although the nitrogen of the N = S = N group has low nucleophilicity, an intramolecular cyclization can occur in the presence of a catalyst (fluoride ion). Thus, heating of l-pentafluorophenyl-3-trimethylsilyl-l,3-diaza-2-thiaallene 170 in acetonitrile in the presence of cesium fluoride leads to 4,5,6,7-tetrafluoro-2,l,3-thiadiazole 171 (90JFC(50)359) (Scheme 157). It is assumed that 171 is formed via the intermediate pentacoordinated silicon anion, which is further transformed into the N-nucleophile with elimination of trimethylfluorosilane. 

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