Alcohol reaction with chlorotrimethylsilane

One of the most common methods of alcohol protection is reaction with chlorotrimethylsilane to yield a trimethylsilyl (TMS) ether. The reaction is carried out in the presence of a base (usually triethylamine) to help form the alkoxide anion from the alcohol and to remove the HCl by-product from the reaction. 

The ionic P-P bond polarization renders P-phosphino-NHPs highly active reactants for various metathesis and addition reactions at exceedingly mild conditions. Metathesis is observed in reactions with alcohols, chloroalkanes, and complex transition metal halides (Schemes 11 and 12) [39, 73], Of particular interest are the reactions with chlorotrimethylstannane which yield equilibria that are driven by a subtle balance of P-X bond strengths to yield either diphosphines or P-chloro-NHPs as preferred product (Scheme 11). Chlorotrimethylsilane does not react with... 

A very short and elegant synthesis of the 16-rtiembered dilactone ( )-pyrenophorin (515) has been accomplished by the dipolar cycloaddition reaction of a trialkylsilyl nitronate (81TL735). Nitromethane was added to 3-buten-2-one and the carbonyl group of the product reduced with sodium borohydride. The nitro alcohol (511) was converted to the acrylate (512) which was then subjected to a dimerization-cyclization reaction by treatment with chlorotrimethylsilane and triethylamine in dry benzene. Hydrogenation of the mixture of isoxazoline products (513) over palladium on charcoal followed by double dehydration of the intermediate bis-/3-hydroxyketone (514) led to ( )- and meso-pyrenophorin (Scheme... 

ClSi(CH3)3 is essential use of NH4C1 quench results in large amounts of a tertiary alcohol. This route to ketones is apparently limited to methyl ketones, since reactions with butyl- or phenyllithium promoted with chlorotrimethylsilane give significant amounts of a tertiary alcohol and starting material. 

A number of cyclopropyl silyl ethers have been prepared by treating cyclopropanols with chloro-silanes. Most frequently the alcohol is reacted with chlorotrimethylsilane in the presence of a weak base such as triethylamine, or pyridine, but reactions without base present have also been performed. The yields are often good thus, l-(l-ethylidenehexyl)cyclopropanol reacted with chlorotrimethylsilane in diethyl ether and dimethyl sulfoxide containing triethylamine to give l-(l-ethylidenehexyl)-l-trimethylsiloxycyclopropane (1) in excellent yield. ... 

The possibility of carrying out Mannich reactions with cyclic aminol ethers has been alluded to earlier. It has so been shown that the in situ method using chlorosilanes can be applied to oxazolidines such as 3-methyl-1,3-oxazolidine. The ring-chain tautomerlsm of 1,3-oxazolidines in the presence of protlc acids has been studied by NMR spectroscopy and the hydroxy Schiff base oxazolidine tautomerlsm has been discussed in terms of the apparent violation of Baldwin s rules. The idea that a Mannich reaction could be carried out while at the same time protecting the resulting alcoholic function was explored in a reaction of 2-methylfuran with 3-methyl-1,3-oxazolidine and f-butyldimethylchlorosilane. The yield in this reaction is only modest (33%) but catalysis with 1,2,4-triazole results in an improvement to 61% (equation 30). Go yields are obtained in reactions of 2-methylfuran with 3-methyl-1,3-oxazolidine and chlorotrimethylsilane (73%) or trichloromethylsilane (87%). Even the reaction of furan gives a good yield (75%) with trichloromethylsilane. 

This process is iterative. Ester 824 can be converted to imine 827 by reduction of the ester function to an alcohol, oxidation to an aldehyde, and Schiff-base formation with 4-methoxy-aniline. The [2 + 2] cycloaddition reaction of 827 with benzyloxyketene gives -lactam 828 in 75% yield as a single diastereomer. Subsequent dearylation affords 829 (50% yield), which upon treatment with chlorotrimethylsilane in methanol furnishes 830 in quantitative yield as a single diastereomer. 

The structurally simplest silicon reagent that has been used to reduce sulphoxides is the carbene analog, dimethylsilylene (Me2Si )29. This molecule was used as a mechanistic probe and did not appear to be useful synthetically. Other silanes that have been used to reduce sulphoxides include iodotrimethylsilane, which is selective but unstable, and chlorotrimethylsilane in the presence of sodium iodide, which is easy to use, but is unselective since it cleaves esters, lactones and ethers it also converts alcohols into iodides. To circumvent these complications, Olah30 has developed the use of methyltrichlorosilane, again in the presence of sodium iodide, in dry acetonitrile (equation 8). A standard range of sulphoxides was reduced under mild conditions, with yields between 80 and 95% and with a simple workup process. The mechanism for the reaction is probably very similar to that given in equation (6), if the tricoordinate boron atoms in this reaction scheme are replaced... 

Alkylzinc iodides These reagents are prepared by reaction of alkyl iodides with Zn/Cu in toluene-N,N-dimethylacetamide (DMA). In the presence of 1 equiv. of chlorotrimethylsilane they can add to aldehydes to form alcohols. DMA may be replaced as the cosolvent by N-methylpyrrolidone (NMP), but HMPT retards this reaction. This reaction can be used to obtain y-, 8-, and e-hydroxy esters from P-, y-, and 8-zinc esters (equation I). 

This method offers an alternative to the reaction of allylic alcohols with tetrafluoroethene to form acids 3 via an aliphatic Claisen rearrangement (see Section 5.1.5.2.). The reaction of la is four times as fast as that of allyl trjchloroacetate under similar conditions. In the absence of chlorotrimethylsilane, no rearrangement occurs. 

Chlorotrimethylsilane (2.7 g, 25 mmol) (1) (CAUTION) is added to a solution of lithium bromide (1.74g, 20 mmol) in dry acetonitrile (20 ml) (2) with good stirring under a nitrogen atmosphere. Cinnamyl alcohol (1.34 g, 10 mmol) is then added and the reaction mixture heated under reflux for 12 hours. The progress of the reaction is monitored by t.l.c. on silica gel plates with hexane as the eluant. On completion of the reaction (12 hours), the reaction mixture is taken up in ether (50 ml), washed successively with water (2 x 25 ml), sodium hydrogen carbonate solution (10%, 50 ml) and finally brine, and dried over anhydrous sodium sulphate. Evaporation of the ether affords the pure bromide in 93 per cent yield. The product may be recrystallised from ethanol and has m.p. 31-32 °C CAUTION this compound is lachrymatory. 

ROH -> RCl. Chlorotrimethylsilane itself does not convert alcohols into alkyl chlorides, but this conversion proceeds readily in the presence of Se02. The actual reagent is believed to be selenium(IV) oxychloride, SeOCl2, which can be isolated in 74% yield from the reaction of SeO, with ClSi(CH,),. 

The additions of tellurium tetrahalides to olefins in the presence of alcohols proceed equally well when the tetrahalides are generated in the reaction mixture from tellurium dioxide and chlorotrimethylsilane in methanoP or concentrated hydrochloric acid/methanol. trans-2-Methoxycyclohexyl tellurium trichloride was obtained in this manner in quantitative yield . In the reactions of terminal alkenes, the TeCl3 group (from TeO and concentrated hydrochloric acid) added according to the Markovnikov rule producing 2-alkoxy-1 -alkyl tellurium trichlorides. The trichlorides were not isolated but were reduced with disodium disulfite to the ditellurium compounds, which, in turn, were converted to the tellurium trichlorides by treatment with sulfuryl chlorides. For data on these tellurium trichlorides see p. 316. The overall yields range from 15 to 70%. 

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