Trimethylsilyl chloride ethers

Merck s thienamycin synthesis commences with mono (V-silylation of dibenzyl aspartate (13, Scheme 2), the bis(benzyl) ester of aspartic acid (12). Thus, treatment of a cooled (0°C) solution of 13 in ether with trimethylsilyl chloride and triethylamine, followed by filtration to remove the triethylamine hydrochloride by-product, provides 11. When 11 is exposed to the action of one equivalent of tm-butylmagnesium chloride, the active hydrogen attached to nitrogen is removed, and the resultant anion spontaneously condenses with the electrophilic ester carbonyl four atoms away. After hydrolysis of the reaction mixture with 2 n HC1 saturated with ammonium chloride, enantiomerically pure azetidinone ester 10 is formed in 65-70% yield from 13. Although it is conceivable that... 

The few exceptions to this general rule arise when the a-carbon carries a substituent that can stabilize carbonium-ion development well, such as oxygen or sulphur. For example, 1-trimethylsilyl trimethylsilyl enol ethers give products (72) derived from electrophilic attack at the /J-carbon, and the vinylsilane (1) reacts with a/3-unsaturated acid chlorides in a Nazarov cyclization (13) to give cyclopentenones such as (2) the isomeric vinylsilane (3), in which the directing effects are additive, gives the cyclopentenone (4) ... 

The addition of sulphinyl chlorides to trimethylsilyl enol ether 138 affording a-ketosulphoxides 139 (equation 76) represents an extension of the reaction of sulphinyl chlorides with ketones. This reaction has attracted attention only recently. Sergeev and coworkers192 reported that treatment of sulphinyl chlorides with acyclic enol ethers afforded a-ketosulphoxides 139 in good to excellent yields. Meanwell and Johnson193 observed that in the case of cyclic enol ethers the corresponding sulphoxides were formed only in very low yields. They found, however, that the introduction of an equivalent amount of a Lewis acid into the reaction mixture markedly promotes the desired reaction, whereas the use of catalytic amounts of a Lewis acid led to a substantial reduction in the yield. This is most probably due to the formation of a complex, between the a-ketosulphoxide and the Lewis acid. 

This procedure illustrates a new three-step reaction sequence for the one-carbon ring expansion of cyclic ketones to the homologous tt,/3-unsaturated ketones. The key step in the sequence is the iron(III) chloride-induced cleavage of the central bond of trimethyl-silyloxycyclopropanes which me obtained by cyclopropanation of trimethylsilyl enol ethers. The procedure for the preparation of 1-trimethylsilyloxycyclohexene from cyclohexanone described in Part A is that of House, Czuba, Gall, and Olmstead. ... 

The /V-acy10xaz01 idi n0nes give anti products when addition is effected by a catalytic amount of MgCl2 in the presence of a tertiary amine and trimethylsilyl chloride. Under these conditions the adduct is formed as the trimethylsilyl ether.129... 

When this type of reaction is quenched with trimethylsilyl chloride, rather than by neutralization, a trimethylsilyl ether of the adduct is isolated. This result shows that the tetrahedral adduct is stable until the reaction mixture is hydrolyzed. 

This must reflect activation of the carbonyl group by magnesium ion, since ketones are less reactive to pure dialkylzinc reagents and tend to react by reduction rather than addition.141 The addition of alkylzinc reagents is also promoted by trimethylsilyl chloride, which leads to isolation of silyl ethers of the alcohol products.142... 

Di-w -pentyl Ether [TMSI-Catalyzed Reduction of an Aldehyde to a Symmetrical Ether].314 A mixture of sodium iodide (0.15 g, 1 mmol), 1-pentanal (1.06 mL, 10 mmol), and trimethylsilyl chloride (2.0 mL, 15.4 mmol) was stirred in MeCN (5.0 mL) at room temperature for 10 minutes, after which 1,1,3,3-tetramethyldisiloxane (TMDO, 1.79 mL, 10 mmol) was added. When the exothermic reaction had ended (30 minutes), a solution of 2.5 N HF in MeOH (30 mL) was added to the reaction mixture, which was then refluxed for 5 minutes. Work-up was carried out by diluting the solution with CH2CI2 (40 mL), washing with water (30 mL) and saturated aqueous NaHC03 solution (20 mL), drying, and evaporating the solvents. Crude di-n-pentyl ether was purified by distillation 0.65 g (84%) bp 185-1897760 Torr. 

The scope of the acid-catalyzed formation of C-glycosyl compounds has been greatly expanded with the finding that enol ethers and ketene acetals can be used as the carbon source in electrophilic substitution reactions at the anomeric center.126 Treatment of 198 with the trimethylsilyl enol ether derived from cyclohexanone, in the presence of stannic chloride, led to 2-(2,3,5-tri-0-benzoyl-/J-D-ribofuranosyl)cyelohexanone (206), presumably by way of the inter-... 

Hydroboration of alkenes in non-ethereal solvent has been reported using diborane generated in situ from a quaternary ammonium borohydride and bromoethane (see Section 11.5). Almost quantitative yields of the alcohols are reported [e.g. 1 ]. As an alternative to the haloalkane, trimethylsilyl chloride has also been used in conjunction with the ammonium borohydride [2]. Reduction of the alkene to the alkane also occurs as a side reaction (<20%) and diphenylethyne is converted into 1,2-diphenylethanol (70%), via the intermediate /ra 5-stilbene. 

The etiolate intermediate, generated by the addition of higher-order cyanocuprates to enones, has been trapped with several electrophiles. Thus the addition of trimethylsilyl chloride, diethyl or diphenyl phosphorochloridate and iV-phenyltrifluoro methane-sulphonamide affords the corresponding vinyl silyl ethers, vinyl phosphates and vinyltri-flates. " ... 

Trimethylsilyl enol ethers can be prepared directly from ketones. One procedure involves reaction with trimethylsilyl chloride and a tertiary amine.20 This procedure gives the regioisomers in a ratio favoring the thermodynamically more stable enol ether. Use of... 

Other papers of interest in this section report transamination of camphor-3-carbothioamides with secondary cyclic amines, reaction of camphorquinone with dimethyl /S-ketoglutarate, the use of fenchone (212 X=0) in alkene formation from Grignard reagents, bromination of 2-e/itfo-6-endo-dibromobornane to yield 2,3,6-endo-tribromoborn-2-ene, and camphor-enol trimethylsilyl ether formation by quenching the reaction mixture of butyl-lithium and camphor tosyl-hydrazone with trimethylsilyl chloride. ... 

TMS and TBS ethers can be cleaved and oxidized to aldehydes or ketones in a one-pot reaction, employing a standard PDC oxidation in which trimethylsilyl chloride is added.138... 

The mixture of chromium trioxide with one equivalent of trimethylsilyl chloride, with no solvent added, results in the formation of an explosive red liquid that is soluble in dichloromethane or tetrachloromethane.428 It is suggested, with no spectroscopic evidence, that it consists of trimethylsilyl chlorochromate [Me3Si-0-Cr(0)2-Cl]. This compound, which can safely be used in organic solvents, is able to oxidize alcohols to aldehydes or ketones, and interacts with r-butyldimethylsilyl ethers producing deprotection, followed by oxidation of the liberated alcohol.138 Compounds analogue to trimethylsilyl chlorochromate are also able to oxidize alcohols, although they possess lesser reactivity. They can be prepared by reaction of chromium trioxide with dimethyldichlorosilane and diphenyldichlorosilane.428b... 

Diketones.1 Trimethylsilyl enol ethers are C-acylated by acid chlorides in the presence of zinc chloride or antimony(III) chloride. No other Lewis acids are useful. The reaction provides a convenient route to 1,3-diketones in good to excellent yield. Addition of diethyl ether before quenching of the reaction catalyzed by ZnCl2 improves the yield but has no effect on the SbCl3-promoted reaction. 

The trimethylsilyl group has been used extensively for the protection of alcohols. One of the many methods which have been used for protecting a hydroxy group as its trimethylsilyl ether involves adding trimethylsilyl chloride (trimethylchlorosiiane, TMCS) to the alcohol in the presence of a weak base as exemplified in Equation Si2.1. 

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