Alcohols chlorotrimethylsilane

In several separate small scale experiments, It was noted that the coupling reaction was not impeded by adding pyridine, triethylamine, t-butyl alcohol, chlorotrimethylsilane, or diisopropylamine to the reaction mixture before adding the nickel catalyst. These results suggest that a variety of functional groups can be present in the enone partner of the coupling reaction. In addition toluene can be used instead of tetrahydrofuran as the solvent. 

ALCOHOLS Chlorotrimethylsilane-Sodium iodide. Iron carbonyl. Phenyl chlorothionocarbonate. Potassiurr>-18-Crown-6. Tri-n-bulyhin hydride. CARBONYL COMPOUNDS Bis(ben-zoyloxy)borane. Bis(triphenyIplios-pliine looppert I) te trahydrobora te. Cutecholborane. 

One of the more common methods of alcohol protection is by reaction with a chlorotrialkylsilane, CI-S1R3, to yield a trialkylsilyl ether, R -O-SilTj. Chlorotrimethylsilane is often used, and the reaction is carried out in the presence of a base, such as tciethylamine, to help form the alkoxide anion from the alcohol and to remove the HC1 by-product from the reaction. 

In addition to the boron trifluoride-diethyl ether complex, chlorotrimcthylsilanc also shows a rate accelerating effect on cuprate addition reactions this effect emerges only if tetrahydrofuran is used as the reaction solvent. No significant difference in rate and diastereoselectivity is observed in diethyl ether as reaction solvent when addition of the cuprate, prepared from butyllithium and copper(I) bromide-dimethylsulfide complex, is performed in the presence or absence of chlorotrimethylsilane17. If, however, the reaction is performed in tetrahydrofuran, the reaction rate is accelerated in the presence of chlorotrimethylsilane and the diastereofacial selectivity increases to a ratio of 88 12 17. In contrast to the reaction in diethyl ether, the O-silylated product is predominantly formed in tetrahydrofuran. The alcohol product is only formed to a low extent and showed a diastereomeric ratio of 55 45, which is similar to the result obtained in the absence of chlorotrimethylsilane. This discrepancy indicates that the selective pathway leading to the O-silylated product is totally different and several times faster than the unselective pathway" which leads to the unsilylated alcohol adduct. A slight further increase in the Cram selectivity was achieved when 18-crown-6 was used in order to increase the steric bulk of the reagent. 

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... 

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... 

Selective silylation. Hexamethyldisilazane alone can effect silylation, but only at elevated temperatures. Rapid silylation of amines, alcohols, and acids can be achieved at 0° in CH2C12 if chlorotrimethylsilane is also present. Selective silylation is also possible by adjustment of the proportions of HMDS and TMSCl. Thus only... 

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). 

Cyclic enol ethers are reductively cleaved to produce a,to-diols using a stoichiometric amount of benzyltriethylammonium borohydride and chlorotrimethylsilane [30] acyclic enol ethers give saturated alcohols. 

The most convenient substrates for fluorination with tetrafluoro(phenyl)-25-phosphane are silyl ethers of alcohols 7.13 17 The trimethylsilylation of alcohols with chlorotrimethylsilane in the presence of pyridine is generally quantitative. 

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... 

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. 

An attractive alternative is conversion of 1 into the 1 -chloro derivative (2) followed by alkylation and elimination of chlorotrimethylsilane. The anion of 2 also adds to various aldehydes to give adducts that are convertible into 2-(benzenesulfonyl)allyl alcohols (equation II). 

Esterification.6 Chlorotrimethylsilane is an efficient reagent for esterification of carboxylic acids by primary and secondary alcohols. It is converted into hexamethyl-disiloxane, (CH3)3SiOSi(CH3)3. Yields are typically 70-95%. 

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. 

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,),. 

We can also easily convert hydroxyl groups to silyl ethers. Section 14-10B covered the use of the triisopropylsilyl (TIPS) protecting group for alcohols. Similarly, sugars can be converted to their silyl ethers by treatment with a silyl chloride, such as chlorotrimethylsilane (TMSC1), and a tertiary amine, such as triethylamine. 

In 1993, Bolm reported that these reactions could be performed using catalytic quantities (10 mol%) of the chiral P-hydroxy sulfoximine.132 The enantiomeric purities of the product alcohols ranged from 52% (1-indanone) to 93% (PhCOCHjOSiRj). In many cases the enantiomeric purities were enhanced using sodium borohydride as reductant in the presence of chlorotrimethylsilane.133 These methods have been extended to the asymmetric reductions of imines.134 /V-SPh-substituted imines gave the highest enantioselectivities and these reductions proceeded in the same stereochemical sense as the reductions of ketones. 

A mixture of chlorotrimethylsilane (0.205 mmol) was added to a suspension of n. v-3-aminocyclohexanecarboxylic acid (0.205 mmol) suspended in 500 ml CH2Cl2/acetonitrile, 5 1, and refluxed for 2 hours. Once cooled, triethylamine (0.410 mmol) was added dropwise to the mixture followed immediately by the portionwise addition of triphenylmethyl chloride (0.205 mmol). The mixture was stirred 18 hours and sufficient methyl alcohol was added to dissolve the vessel contents. The solution was concentrated and the residue was partitioned between 800 ml diethyl ether/10% citric acid, 1 1. The ether layer was collected and combined with a 150 ml diethyl ether extraction from the citric acid layer. Combined fractions were extracted three times with 250 ml 2 M NaOH and once with 100 ml water. These layers were washed twice with 150 ml diethyl ether, cooled to 0°C, acidified to pH 7 with 12 M HC1, and re-extracted three times with 200 ml EtOAc. The extract was dried over MgS04, then concentrated, and the product isolated in 85% yield as a white foam. 

Chlorotrimethylsilane, (CH3)3SiCl Reacts with alcohols to add the trimethylsilyl protecting group (Section 17.8). 

The product from Step 5 (Immol) and cytosine (Immol) were dissolved in acetonitrile (25mmol), hexamethyldisilazane (Immol) and chlorotrimethylsilane (4mmol) added, and the mixture stirred at ambient temperature 30 minutes. The solution was cooled to -78 °C, trimethylsilyltrifluoromethane sulfonate (1.2 mmol) added, and the solution stirred 2.5 hours. Thereafter, the mixture was warmed to ambient temperature, concentrated to 5 ml, diluted with 50 ml CH2CI2, washed with 20 ml water, dried, and concentrated. The residue was purified by chromatography over silica gel using chloroform/methyl alcohol, 98 2, and the product isolated in 77.5% yield. H-NMR, elemental analysis, and MS data supplied. 

The trimethylsilyl group was the first to be developed and is widely used for the protection of serine and threonine (Table 6). Chlorotrimethylsilane, l,14 3,3,3-hexamethyldisilazane, and A(0-bis(trimethylsilyl)acetamide are commercially available reagents used for the conversion of alcohols into the corresponding trimethylsilyl derivatives.Furthermore, trimethylsilyl cyanide has been used to protect the side chains of serine, threonine, and ty-rosine.f This silyl protection allows the formation of A -carboxyanhydrides from H-Ser(TMS)-OH and H-Thr(TMS)-OH, and their application in peptide synthesis in the aqueous phase.f l The TMS group can be removed under various conditions, depending on the kind of functional group to which it is bound the TMS ethers are more stable than related amino or carboxy derivatives.These differences in stability allow the direct application of completely silylated hydroxy amino acids in peptide synthesis.b ... 

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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