Silylations 4-dimethylaminopyridine

Dimethylaminopyridine [1122-58-3] (DMAP) (24) has emerged as the preferred catalyst for a variety of synthetic transformations under mild conditions, particularly acylations, alkylations, silylations, esterifications, polymeri2ations, and rearrangements (100). POLYDMAP resin [1122-58-3], a polymeric version of DMAP, is available, and is as effective as DMAP as a catalyst for acylation reactions. Furthermore, it can be recycled without regeneration more than 20 times with very Htde loss in activity. POLYDMAP is a trademark of Reilly Industries, Inc. 

Et3SiCl, Pyr. Triethylsilyl chloride is by far the most common reagent for the introduction of the TES group. Silylation also occurs with imidazole and DMF arid with dimethylaminopyridine as a catalyst. Phenols, carboxylic acids, and amines have also been silylated with TESCl. 

Photocycloaddition of cyclopentene (116) to the trimethylsilyl ether (117) gave 2 stereoisomers (118) and (119). When (118) was reduced with LiAlH4 in Et20, followed by treatment will MsCl, pyridine and dimethylaminopyridine (DMAP), the silyl ether (120) was obtained. Finally, (120) was allowed ro react with KF in the presence of [18]-crown-6 in CH2C12, as a result, hexahydroazulenone (121) was isolated41 >. On the other hand, the cyclobutane (119) could also be converted similarly to (121) in an overall yield of 47 % 41K... 

Oxygen at the heterocyclic sulfur atom has been functionalized in two ways (1) by a TMSOTf-catalyzed Pummerer reaction in the presence of a silyl enol ether (Scheme 95) <1998TL9131> or (2) by reductive removal of the oxygen using Ac20/Zn/cat. 4-dimethylaminopyridine (DMAP) <1996SL885>. The formation of 1,3-dithiane from 1,3-dithiane 1-oxide proceeds efficiently in 95% yield (Equation 70). 

Using a chiral 4-dimethylaminopyridine-ferrocenyl catalyst, acyclic silyl ketene acetals react with anhydrides to furnish 1,3-dicarbonyl compounds containing allcarbon quaternary stereocentres in good yield and ee.144 Evidence for dual activation (anhydride -> acylpyridinium, and acetal -> enolate) is presented. 

Such ionic species could also be detected in solution by 29Si NMR spectroscopy. Nucleophiles like TV-methylimidazole, pA M-dimethylaminopyridine and HMPA showed the strongest coordinating effects110. Mixtures of electrophilic trimethylsilyl compounds and nucleophiles(L), such as amines and amides, are common silylation agents111 and salts Me3SiL+X have been discussed as the active silylation species112. 

SILYLATION Chlorotrimethylsilane. 4-Dimethylaminopyridine. Methylketene methyl trimethylsilyl acetal. 

A. (1R,4S)-(-)-4-tert-Butyldimethylsiloxy-2-cyclopentenyl acetate. A dry, 500-mL, three-necked, round-bottomed flask, equipped with a Teflon-coated magnetic stirring bar, rubber septum, and nitrogen inlet, is purged with nitrogen and charged with 7.67 g (54 mmol) of (1R,4S)-(+)-4-hydroxy-2-cyclopentenyl acetate (Note 1). 660 mg (5.4 mmol) of 4-dimethylaminopyridine (Note 2), 17 mL (122 mmol) of triethylamine (Note 3), and 175 mL of dichloromethane (Note 3). The reaction mixture is cooled to 0°C in an ice-water bath, and tert-butyldimethylsilyl chloride (10.24 g, 68 mmol) (Note 2) is introduced in one portion. The ice-water bath is removed and the mixture is allowed to warm to room temperature and stir for 3 hr. At this point, more silyl chloride is added if necessary (Note 4). After 5 hr, 200 mL of water is added, the mixture is transferred to a separatory funnel and the organic phase separated. The aqueous phase is extracted with three 100-mt portions of dichoromethane. The combined... 

A new and efficient combination for silylation is trimethylsilyl chloride-lithium sulphide. Even hindered hydroxy-groups are silylated at room temperature in neutral conditions, although the mechanism of the process is not yet clear. 4-Dimethylaminopyridine (DMAP) has been shown to be an efficient catalyst for the silylation of alcohols by t-butyldimethylsilyl chloride and to be more selective than the imidazole traditionally used. Two new methods for removal of the t-butyldimethylsilyl group are treatment with boron trifluoride etherate and reaction with aqueous HF in acetonitrile. The O-silyl derivatives of normal carboxylic esters, i.e. keten methyl trialkylsilyl acetals (59), have been investigated in silyl transfer to alcohols (Scheme 31) they have the advantage of... 

Lovastatin can be prepared by a fermentation process in the presence of a specific microorganism. Lovastatin can be converted to simvistatin. Hydrolysis of the ester followed by reclosure of the lactone gives the diol. The less-hindered alcohol can be selectively protected using the bulky t-butyldimethylchlorosilane. The free alcohol can be esterified by the acid chloride in the presences of dimethylaminopyridine acylation catalyst. The silyl ether can be selectively removed by treatment with tetrabutyl ammonium fluoride. The fluoride anion reacts at the silicon without hydrolyzing the lactone or ester. 

Another common method for alcohol protection is reaction with RjSiCl to give a silyl ether. Reaction conditions usually involve RjSiCl, with 4-dimethylaminopyridine (DMAP) as the base. Both the ease of preparation of the silyl ether and the stability of the protected species depend on the nature of the R groups. Trimethylsilyl ethers (ROTMS) are very labile and readily removed with water and dilute acid. The triethylsilyl group (ROTES) is a little more robust but may be removed with fluoride ion (the use of fluoride to cleave silyl groups reflects the strength of the Si-F bond). r-BuMejSiCl (TBDMSCl) reacts selectively with... 

The efficiency of HMDS-mediated silylations can be markedly improved by conducting reactions in polar aprotic solvents. For example, treatment of methylene chloride solutions of primary alcohols or carboxylic acids at ambient temperatures with HMDS (0.5-1 equiv) in the presence of catalytic amounts of TMSCl (0.1 equiv) gives the corresponding silyl ether and the trimethylsilyl ester, respectively (eq 4). Al-Silylation of secondary amines occurs in preference to primary alcohols when treated with I equiv of HMDS and 0.1 equiv TMSCl (eq 5). The silylation of secondary amines caimot be effected in the absence of solvent. Secondary and tertiary alcohols can also be silylated at ambient temperatures in dichloromethane with HMDS and TMSCl mixtures however, stoichiometric quantities of the silyl chloride are required. Catalysis by 4-Dimethylaminopyridine (DMAP) is neeessary for the preparation of tertiary silyl ethers. 

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