Silyl chloride method

The 0-silylation reaction of alcohols is important as a protection method of hydroxyl groups. 0-Silylations of liquid or crystalline alcohols with liquid or crystalline silyl chlorides were found to be possible in the solid state. For example, when a mixture of powdered L-menthol (26), ferf-butyldimethylsilyl chloride (27), and imidazole (28) was kept at 60 °C for 5 h, 0-tert-butyldi-methylsilyl L-menthol (29) was obtained in 97% yield [8] (Scheme 4). Similar treatments of 26 with the liquid silyl chlorides, trimethyl- (30a) and triethylsilyl chloride (30b), gave the corresponding 0-silylation products 31a (89%) and 31b (89%), respectively, in the yields indicated [8] (Scheme 4). However, 0-silylation of triisopropyl- (30c) and triphenylsilyl chloride (30d) proceeded with difficultly even at 120 °C and gave 31c (57%) and 31d (70%), respectively, in relatively low yields. Nevertheless, when the solvent-free silylation reactions at 120 °C were carried out using two equivalents of 30c and 30d, 31c (77%) and 31d (99%) were obtained, respectively, in relatively high yields. 

The classical Henry reaction conditions (base catalyzed addition) have some drawbacks sometimes the nitro alcohols are obtained in low yields and diastereoselectivities are not always high. To improve these results, a number of modifications were introduced. One of them is the Seebach s silyl nitronate method,25 that involves a reaction between an aldehyde with a silyl nitronate prepared by metalation of the corresponding nitro alkane with LDA, followed by reaction of the resulting nitronate with tert-butyldimethylsilyl chloride.26... 

The reaction of toluene solutions of indium trichloride and tris(trimethylsilyl)arsine resulted in the formation of a very fine dark-brown powder subsequently annealed up to 400°C to drive to completion the elimination of trimethyl-silyl-chloride. Nanocrystalline InAs was obtained. Similar reactions with InBr3 and Inl3 and P compounds have been discussed. Previously a similar reaction was described by Uchida et al. (1993) (reaction of indium acetylacetonate with tris(trimethylsilyl)arsine in refluxing triglyme). Subsequently the reaction with InCl3 was used by Guzelian et al. (1996) in the preparation of nano-crystal quantum dots. They compared different preparation methods and techniques useful to isolate specific size distributions. 

The silanolysis of alcohols to form silyl ethers is an attractive method since the only by-product, H2, is easily removed making workup procedures trivial. Many transition metal catalysts for this exothermic process have been introduced, but most suffer from low activities and inconvenient preparations. The silane activation mechanism has parallels to the mechanisms by which transition metal compounds bring about this transformation and the B(C6F5)3/silane catalytic system turns out to be highly active for this transformation.255 In contrast to the normal procedures involving silyl chlorides... 

Since sUyl ynol ethers have an electron-rich triple bond, they are useful for Lewis acid catalyzed synthetic reactions. Lithium ynolates 175 are silylated by TIPSCl or TIPSOTf and TBSCl to afford the corresponding silyl ynol ethers 176 and 177, which are thermally stable and isolable, but sensitive toward acids (equation 71) . See also equations 9 and 10 in Section ll.C. An experimentally improved procedure for the purification of 176 derived from Kowalski s method is described. Lithium ynolate derived from Julia s method is also used for the preparation of 176. TMSCl and TESCl provide silyl ketenes 179, however, by C-silylation. These small silyl chlorides primarily gave the silyl ynol ethers 178, but, upon warming the reaction mixture, isomerization to the more stable silyl ketenes takes place. The soft electrophilic silyl chlorides like PhsSiCl afford silyl ketenes. Disi-lyl ynol ethers, prepared from ynolate dianions, are rearranged to disilylketenes mediated by salts . 

The most predictable results are obtained with conformation-ally rigid systems, such as those represented in eqs 5 and 6, which possess axially oriented a-protons. This minimizes complications resulting from the presence of diastereotopic a-protons, although unexpected modes of deprotonation have been described with related chiral amides, which may involve boat conformations. To prevent enolate equilibration (with the resulting loss of stereoselectivity), Corey s internal quench method for enolate trapping with silyl chlorides is frequently used. The stereospecificity of this deprotonation is highly dependent on solvent and temperature conditions. Best results are obtained at —100 °C or lower temperatures, with THF as the solvent. 

Pr)2SiH)20, PdCl2, CCI4, 60°C, 2h, then substrate in pyridine. This method produces the silyl chloride in situ."... 

To date the most simple and general procedure for the preparation of silyl ynol ethers is the reaction of lithium alkynolates, generated in situ from ethyl esters, with silyl chlorides, according to equation 25 k However, this method (equation 25) does not work for the preparation of siloxyalkynes in which R is a lower alkyl group or hydrogen. Danheiser... 

Enzymatic 7-ACA splitting procedures [for general review, see 261] have been developed and commercialized by companies like Asahi Chemical, Hoechst, and Novartis. The replacement of the hitherto employed chemical deacylation processes like the imino ether (Figure 1.1-3) or the nitrosyl chloride method [262] resulted in a cost reduction of 80% and a decrease of the waste volume by a factor 100 from 311 to 0.3 tons per 1-ton 7-ACA. Chlorinated hydrocarbons like dimethyl aniline and methylene cloride as well as heavy metal ions can be completely avoided. Instead of zinc salt formation, multiple silylation, formation of the imino chloride, imino ether, and finally an imino ether hydrolysis, the side chain is removed in two enzymatic steps (Figure 1.1-3). 

The termination method using substituted silyl chloride provides a useful, general methodology for the synthesis of a wide variety of functional end groups. However, this methodology requires the use of protection and deprotection protocols for most functional groups of interest. In addition, the long-term stability of these protected, functionalized silyl chlorides has been found to be a problem. 

He reports that the reaction proceeded smoothly even in the absence of the silyl chloride, although reaction times could be reduced to less than 30 min in its presence (Scheme 76). In fact, the highest yields were obtained using sterically hindered tetrasubstituted ketones and the method appears to be indispensible in such cases. In addition, ultrasound was reported to promote the diiron-nonacarbonyl mediated reaction, although reaction times were somewhat longer. 

A new method for the preparation of trimethylsilyl (TMS) and TBDMS ethers under mild phase-transfer conditions" involves treatment of an alcohol with the appropriate silyl chloride and solid K2CO3 (or Na2C03) in the presence of... 

Formation of Trimethylsilyl Enol Ethers from Enolizable Aldehydes and Ketones. The most common methods for preparing silyl enol ethers use silyl chlorides or silyl triflate/base combinations and need careful attention during workup of the reaction and isolation of the enol ether. Silylations with BS A are generally mild and nearly neutral and do not require the addition of a supplementary base. Ionic liquids have been used for the preparation of silyl enol ethers 31 from aldehydes and ketones 30 with BS A in good yields (eq 38). These new reaction conditions open an important alternative to the use of highly toxic HMPA as solvent. ... 

Preparative Methods lithiation of 1,3-dichloropropene followed by treatment with a silyl chloride reaction of 1,3-dichloropropene with Mg° and a silyl chloride electrophile treatment of allylsilanes with BuLi/TMEDA and a silyl electrophile reaction of allyl alcohol with HMPA, Mg°, and a Lewis acid catalyst cross-metathesis of allylsilanes reductive lithiation of allylthioethers. ... 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

Silylation of alcohols, amines and carboxylic acids with hydrosilanes is catalyzed by Pd catalysts[l 19], Based on this reaction, silyl protection of alcohols, amines, and carboxylic acids can be carried out with /-butyldimethylsilane using Pd on carbon as a catalyst. This method is simpler and more convenient than the silylation with /-butyldimethylsilyl chloride, which is used commonly for the protection. Protection of P-hydroxymethyl-(3-lactam (125) is an example 120]. 

Method G Highruiri-selecdvity is also observed in the fluoride-catalyzed reacdonof silyl nitronates v/ith aldehydes. Trialkyl silyl nitronates are prepared in good yield from primary nitroalkanes by consecndve treatment v/ith iithiiim dusopropylamide and trialkylsilyl chloride at -78 C in THF. 

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