Trimethylsilylethyl ester

Coned. HF, CH3CN, >76% yield. Note that a trimethylsilylethyl ester was not cleaved under these conditions. 

The parent alcohol can be obtained in a straightforward manner from chloromethyltrimethylsilane (Chapter 16). The protection afforded is naturally related to the functionality involved, and liberation is achieved using either fluoride ion or a Lewis acid. For example, 2-trimethylsilylethyl esters (Chapter 16) are stable to a wide variety of conditions such as those used in peptide synthesis, but are readily cleaved by fluoride ion (14,15). 

ETHYL 3-[3-(TRIfETHYLSILYL0XY)CYCL0HEX-2-ENYL)]PR0PI0NATE (2-Cyc1ohexene-l-propanoic acid, 3-[(trimethylsilylethyl ester)... 

Appropriately functionalized resins can sequester excess nucleophiles from solution-phase reactions. Thus the calcium sulfonate resin 4 captures tetra-n-butylammonium fluoride (TBAF) from a variety of desilylation reactions.22,24 Polymer-bound tetra-n-butylammonium sulfonate and insoluble calcium fluoride are formed. The applicability of this strategy was illustrated for deprotection of (3-trimethylsilylethyl esters as well as silyl ethers. 

A series of rapid microwave-mediated ester syntheses using Mo(CO)6 as the carbon monoxide source were published in 200374. In this paper, a range of valuable ester-protected acids (butyl-, benzyl- and trimethylsilylethyl esters) were smoothly produced both in solution (Scheme 2.32) and on solid phase (TentaGel S RAM-resin, Scheme 2.33) after 15-20 min of single-mode microwave irradiation. The use of DMAP as a nucleophilic additive increased the product yields slightly. Unfortunately, the sterically hindered ferf-butanol furnished little or no product formation at all. 

If neither acidic nor basic conditions are compatible with other groups present in the ester to be hydrolyzed, then yS-trimethylsilylethyl esters are often prepared. Trimethylsilylethyl esters are cleaved easily by fluoride under mild, neutral conditions. Typical sources of fluoride are cesium fluoride (CsF) or the more soluble tetrabutylammonium fluoride (TBAF). 

Macrolactonization. The usually difficult lactonization to ll-membcred pyrroli-zidine dilactones can be achieved by use of a trimethylsilylethyl ester (8, 510-511) and activation of the lo-hydroxyl group by mesylation. Thus treatment of 1 with (C4H,)4N F in acetonitrile at 30° liberates the carboxyl group with spontaneous cyclization to the diastereomer 2, the methoxymethyl ether of dZ-crispatine. ... 

Cleavage of 2-bromoethyl esters. These esters can be cleaved by treatment with Still s reagent in THF and then with tetra-n-butylammonium fluoride (cf. cleavage of 2-trimethylsilylethyl esters, 8, 510). 

Acyl chlorides may be replaced with imidazolides, which react with sodium azide to give acyl azides. In the reaction shown in equation (34), 2-trimethylsilylethanol is used for trapping the isocyanate. The resulting 2-trimethylsilylethyl ester is easily cleaved with tetra-n-butylammonium fluoride. 

A mechanistically related and mild fragmentation is that of 2-trimethylsilylethyl esters (Tmse esters). The Tmse residue is a selectively cleavable carboxy-protecting group (see Volume 6, Chapter 3.2) Examples are known for the synthesis, via these esters, of peptides, macrolides such as curvularin and macrocyclic trichothecenes like verrucinol (Scheme 54). °... 

The first synthesis of a member of this class, verrucarin A (116) is a result of the efforts of Still and is outlined in Scheme 4.20. 2" Construction of the muconic acid fragment began with pseudoacid 107, available from the electrochemical oxidation of furfural. A one-carbon homologation with a stabilized ylide afforded solely the ( ,Z)-isomer of (3-trimethylsilylethyl ester 108 in 72% yield. 

Coned. HF, CH3CN, >76% yield. Note that a trimethylsilylethyl ester was not cleaved under these conditions. A dithiane can also be cleaved because of internal participation of the released alcohol during a SEM deprotection. ... 

The allylsilane 212 and the common intermediate 215 were made from this monoester (Scheme 28). The lithium dianion of the acid-ester 209 was treated with the aldehyde 210 and the mixture of four diastereoisomeric aldols 211 esterified with diazomethane. The four possible diastereoisomers, present in a ratio of 76 9 9 6 were separated and the 2-trimethylsilylethyl ester group removed by treatment with tetrabutylammonium fluoride. The individual diastereoisomeric... 

Protection of carboxyl groups. Trimethylsilylethyl esters, —COOCH2-CHaSiCCHala, can be prepared from N-benzyloxycarbonylamino acids and this reagent with DCC in the presence of pyridine (65 95% yield). The esters are stable under usual conditions of peptide synthesis, but are readily cleaved by fluoride ion, preferably by fetra-n-butylammonium fluoride in DMF. ... 

Trimethylsilyl-l-cyclopentene, 509-510 Trimethylsilyldehalogenation, 514 a-Trimethylsilyl esters, 515 2-Tiimethylsilylethanol, 510-511 /3-Trimethylsilylethyl chloroformate, 471 Trimethylsilylethyl esters, 510 a-Trimethylsilyl ketones, 246 Trimethylsilyllithium, 197,514 a-Trimethylsilyl-2-methylbenzothiazole,... 

Amino acid coupling of 1257 with 1252 (R = CH2CH2Si(CH3)3) was accomplished using DCC/DMAP to afford 1258 (Scheme 1.321). Sequential deprotection of the phthalimide and (3-trimethylsilylethyl ester was straightforward. Macrolac-tamization of the resulting amino acid and hydrolysis of the dioxane moiety completed the synthesis of 1183. The authors observed a small amount (8-10%) of double bond isomer, but showed that this resulted from hydrolysis of the mesitylene acetal. 

Membered pyrrolizidine dUactones have been synthesized by treating a trimethylsilylethyl ester with TBAF in MeCN to form an anion, which then undergoes cyclization by displacement of the mesylate. 

Another elegant reaction is the use of the 2-trimethylsilylethyl residue for protection of the carboxyl group by Sieber and colleagues in 1977 (for Ref. see e.g. in [44]). In some cases, saponification of methylesters requires alkaline conditions too strong to leave intact a sensitive peptide. Trimethylsilylethyl esters, however, in a type of jS-elimination, are decomposed at neutral pH by fluoride ions to yield trimethylfluorosilane, ethylene, and the carboxylic acid. 

Phenol and Acid Protection. The synthesis of trimethylsi-lylethyl ethers and esters is readily achieved under a number of conditions. Their ease of preparation and stability under a wide variety of reaction conditions, combined with the fact that deprotection can be achieved under almost neutral conditions, have enlarged the scope of this protecting group. Protection of phenols and acids is easily achieved under Mitsunobu conditions as shown in eqs 19 and 20. Upon conpletion of the synthesis the phenol (eq 19) was deprotected using cesium fluoride in DMF at 160 °C in 89% yield. As well, en route to the synthesis of Daurichromeric acid, the trimethylsilylethyl ester (eq 20) was cleaved with TBAF in THF with a yield of 94%. 

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