Trimethylsilyl chloride, protecting alcohols

Potassium hydroxide, 258 Trimethylsilyl chlorochromate, 327 of carbon-carbon double bonds substituted by heteroatoms m-Chloroperbenzoic acid, 76 of oximes to carbonyl compounds Lithium aluminum hydride-Hexa-methylphosphoric triamide, 159 Titanium(III) chloride-Diisobutylalu-minum hydride, 303 Trimethylsilyl chlorochromate, 327 of protected alcohols Chlorodimethylthexylsilane, 74 Formic acid, 137 p-Methoxyphenol, 181 of thioacetals and -ketals Methoxy(phenylthio)trimethyl-silylmethane, 182... 

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. 

Finally, alcohols can also be protected as silyl ethers. For example, the reaction of the alcohol with trimethylsilyl chloride in the presence of triethylamine (to react with the HC1 that is produced) produces the trimethylsilyl ether of the alcohol as shown in the following equation. (This reaction is a nucleophilic substitution by the oxygen on the silicon.) The silyl group can be removed in high yield by reaction with fluoride anion. 

Optically active P-hydroxysulfoximines which catalyze the asymmetric borane reduction of ketones [110], also catalyze the same reaction with sodium borohydride/trimethylsilyl chloride system as reducing agent [126]. Reduction of a protected a-hydroxyacetophenone afforded the alcohol with 90% ee. 

Tiimethylsilyl)ethanesulphonyl chloride, Me3SiCH2CH2S02Cl, is useful for the protection of primary and secondary amines as sulphonamides, which are smoothly cleaved by fluoride ion. Use of the triazene moiety as a protecting group for aromatic amines is illustrated in eqnation 110. The protected compounds react with s-butyllithium, followed by an electrophile E (carbon dioxide, acetophenone or trimethylsilyl chloride), to give, respectively, the corresponding carboxyhc acid, alcohol or trimethylsilyl daivative, which are converted into the free amines by the action of nickel -aluminium alloy in aqueous-methanolic potassium hydroxide-... 

Silyl ethers have an important role as hydroxyl-protecting groups/ Alcohols can be easily converted to trimethylsilyl ethers by reaction with trimethylsilyl chloride in the presence of an amine or by heating with hexamethyldisilazane. Although these are useful compounds when the objective is preparation of a less polar derivative of... 

The chemistry of rran5-4-r-butyl(diphenyl)silyloxythiane oxide has been investigated by Simpkins in the synthesis of protected, substituted secondary alcohols. Simpkins has found that the anion of fra s-4-r-butyl(diphenyl) silyloxythiane oxide, when treated with trimethylsilyl chloride, can form a 2,4-disubstituted thiane in turn, this product may be easily desulfurized with Raney nickel to liberate (S)-3-r-butyl(diphenyl)silyloxy-l-trimethylsilylpentane in good yield (Scheme 4.49) [101]. 

This protecting group is abbreviated as OTMS. The trimethylsilyl ether is formed via the reaction between an alcohol and trimethylsilyl chloride, abbreviated TMSCl. 

Reactions.—Some examples of new methods for ether cleavage have been dealt with in an earlier section (Protection of Alcohols). Aliphatic and aromatic methyl ethers can be cleaved efficiently by an aluminium halide-ethanethiol combination the process has been rationalized according to the hard and soft acid-base principle. Several methods for the (presumed) in situ preparation of trimethylsilyl iodide, a known reagent for the cleavage of ethers (2,131), have been disclosed recently in an effort to circumvent the expense and moisture sensitivity of MeaSil. (Some of these methods have been mentioned earlier in this Report in connection with the conversion of alcohols into alkyl iodides.) Reports include two on trimethylsilyl chloride-sodium iodide, one on phenylseleno-trimethylsilane-iodine [equation (18)], and three on hexamethyldisilane-iodine [equation (jq)] 102,142,143 method has the advantage of... 

TMSCl, EtsN Trimethylsilyl chloride, in the presence of a base (such as triethylarrrine), will protect an alcohol. 

Protection of Alcohols. Trimethylsilyl ethers, readily prepared from alcohols by treatment with a variety of silylating agents have found considerable use for the protection of alcohols. They are thermally stable and reasonably stable to many organometallic reagents and they are easily cleaved by hydrolysis in acid or base or by treatment with fluoride ion. t, Butyl dimethylsilyl ethers have considerably greater hydrolytic stability and are easier to work with than trimethylsilyl ethers. They are prepared from alcohols by treatment with t. butyl dimethylsilyl chloride. 

Olefination of the Aldehyde 178 using a stabilized Wittig reagent followed by protecting group chemistry at the lower branch and reduction of the a,p-unsaturated ester afforded the allylic alcohol 179 (Scheme 29). The allylic alcohol 179 was then converted into an allylic chloride and the hydroxyl function at the lower branch was deprotected and subsequently oxidized to provide the corresponding aldehyde 161 [42]. The aldehyde 161 was treated with trimethylsilyl cyanide to afford the cyanohydrin that was transformed into the cyano acetal 180. The decisive intramolecular alkylation was realized by treatment of the cyano acetal 180 with sodium bis(trimethylsi-lyl)amide. Subsequent treatment of the alkylated cyano acetal 182 with acid (to 183) and base afforded the bicyclo[9.3.0]tetradecane 184. 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

The 1,4,5-oxadiazepine 63 was transformed into 65 by a four-step reaction sequence (1) cleavage of both /-butoxycarbonyl (BOC) and the lactone, (2) acylation of the remote amino group with 2-(trimethylsilyl)ethyloxy-carbonyl chloride (TeocCl), (3) protection of the alcohol functionality with a silyl group, and (4) ester hydrolysis (Scheme 10) C1998AGE2995, 2001CEJ41>. 

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