Selective trimethylsilylation

TABLE 3.4 Characteristic Fragment Ions of Selected Trimethylsilylated Steroids Using Electron Ionization"... 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

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. ... 

Good to excellent diastereoselectivities have been reported when 2-(trimethylsilyl)thiazole (3), an effective equivalent of an aldehyde group, is used as nucleophile24,27. Thus, addition to TV-Boc-protected amino aldehydes in dichloromethane at — 30 C afforded mixtures of amino alcohols in comparatively good yields with reasonable syn selectivity. However, the stereoselectivity decreased substantially when the reaction was carried out in tetrahydrofuran at 25 °C. 

Addition of anhydrous magnesium bromide to [l,3-bis(trimethylsilyl)-2-propenyl]lithium improves the antijsyn selectivity of the reaction with benzaldehyde from 80 20 to 94 6 23. 

A potentially useful route to substituted (Z)-allylboron derivatives involves the selective cis hydrogenation of propynylboron derivatives. One recent report applied this approach in the synthesis of a (Z)-3-trimethylsilyl-2-propenylboronate, which cannot be prepared by the allyl-organometallic route discussed in Section 1.3.3.3.3.1.1.1. The selectivity for the Z-isomer was only 9 1 21. The scope of this method remains to be fully documented35. 

The reagent generated by treatment of 3-trimethylsilyl-2-propenyllitliium and ethylaluminum dichloride, however, shows good to excellent selectivity for the aw//-diastereomer (86- >99%)9. 

The enantioselective addition of organometallic reagents to, V-(trimethylsilyl)benzaldehyde imine (1) in the presence of enantiomerically pure modifiers has been investigated. The best result is obtained with butyllithium (the corresponding Grignard reagent affords both lower yield and selectivity, 1 fails to react with diethylzinc) and two equivalents of the enantiomerically pure diol 2 in diethyl ether. It should be noted that the choice of the solvent is crucial for the stereoselectivity of the reaction1 2 3 5 7 8 9. 

Interestingly, the diastereofacial selectivity can be reversed in the Strecker reaction of aldimines derived from galactosylamine 1 by simply changing the solvent. When the reaction of trimethylsilyl cyanide with the Schiff bases 2 catalyzed by zinc chloride, is carried out in chloroform instead of 2-propanol, there is a preferred formation of the (.S)-amino nitrile diastereomers63. 

Considerable efforts have been devoted to the stereoselective introduction of a /(-methyl function in intermediates for the synthesis of 1 jS-methylcarbapenems. While the trimethylsilyl trifluoromethanesulfonate catalyzed reaction of a 4-acetoxyazetidinone derivative with ketene acetals shows no selectivity, ketene thioacetals lead to stereoselective formation of the a-methyl isomer108. The zirconium enolate, however, shows high /(-methyl selectivity. 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

The preparation of cyclopentadienes with up to four trimethylsilyl groups can be performed easily on a large scale starting with monomeric cyclopentadiene by repeated metalation with n-butyllithium and treating the resulting anion with chlorotrimethylsilane [84], Any complication caused by formation of regioisomers does not occur, since all trimethylsilyl-substituted cyclopentadienes are fluxional by virtue of proto- and silatropic shifts [85], Upon deprotonation with n-butyllithium the thermodynamically most favorable anion is formed selectively (Eqs. 20, 21). Thus, metalation of bis(trimethylsilyl)cyclopentadiene 74, which exists preferentially as the 5,5-isomer, selectively affords the 1,3-substituted anion 75. Similarly, tris(trimethylsilyl)cyclopentadiene 76, which is found to be mainly as the 2,5,5-isomer, affords the 1,2,4-substituted anion 77. 

Using sulphonic acid ion-exchange resins in ether solvent, selective removal of the trimethylsilyl group from oxygen in bistrimethylsilylated terminal alkynols can be achieved. This method is particularly suitable for low-molecular-weight compounds, where water solubility would make efficient extraction from an aqueous layer difficult. 

Non-Kolbe electrolysis of carboxylic acids can be directed towards a selective fragmentation, when the initially formed carbocation is better stabilized in the y-position by a hydroxy or trimethylsilyl group. In this way the reaction can be used for a three-carbon (Eq. 36) [335] (Table 14, No. 1) or four-carbon ring extension (Eq. 37) [27] (Table 14, Nos. 2-4). Furthermore it can be employed for the stereo-... 

The synthesis of S-phosphonothiazolin-2-one 133 started with 2-bromothiazole 129. Nucleophilic displacement of the 2-bromide proceeded cleanly with hot anhydrous sodium methoxide to give 2-methoxythiazole 130. Low-temperature metalation of 130 with n-butyl lithium occurred selectively at the 5-position (76), and subsequent electrophilic trapping with diethyl chlorophosphate produced the 5-phosphonate 131. Deprotection of 131 was accomplished either stepwise with mild acid to pn uce the thiazolin-2-one intermediate 132, or directly with trimethylsilyl bromide to give the free phosphonic acid 133, which was isolated as its cyclohexylammonium salt. 

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