Trimethylsilyl ethers cleaved

The most stable protected alcohol derivatives are the methyl ethers. These are often employed in carbohydrate chemistry and can be made with dimethyl sulfate in the presence of aqueous sodium or barium hydroxides in DMF or DMSO. Simple ethers may be cleaved by treatment with BCI3 or BBr, but generally methyl ethers are too stable to be used for routine protection of alcohols. They are more useful as volatile derivatives in gas-chromatographic and mass-spectrometric analyses. So the most labile (trimethylsilyl ether) and the most stable (methyl ether) alcohol derivatives are useful in analysis, but in synthesis they can be used only in exceptional cases. In synthesis, easily accessible intermediates of medium stability are most helpful. 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable... 

Trimethylsilyl ethers are readily cleaved by fluoride ion, mild acids, and bases. If the TMS derivative is somewhat hindered, it also becomes less susceptible to cleavage. A phenolic TMS ether can be cleaved in the presence of an alkyl TMS ether [Dowex lX8(IfO ), EtOH, rt, 6 h, 78% yield]. ... 

Trimethylsilyl ethers are quite susceptible to acid hydrolysis, but acid stability is quite dependent on the local steric environment. For example, the 17o -TMS ether of a steroid is quite difficult to hydrolyze. TMS ethers are readily cleaved with the numerous HF-based reagents. A polymer-bound ammonium fluoride is advantageous for isolation of small polar molecules. ... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

Protection of Alcohols. Trimethylsilyl ethers, readily prepared from alcohols by treatment with a variety of silylating agents have found considerable use for the protection of alcohols. They are thermally stable and reasonably stable to many organometallic reagents and they are easily cleaved by hydrolysis in acid or base or by treatment with fluoride ion. t, Butyl dimethylsilyl ethers have considerably greater hydrolytic stability and are easier to work with than trimethylsilyl ethers. They are prepared from alcohols by treatment with t. butyl dimethylsilyl chloride. 

Good yields are generally observed, especially for methyl ethers. The combination of boron tribromide with dimethyl sulfide has been found to be particularly effective for cleaving aryl methyl ethers.87 Trimethylsilyl iodide cleaves methyl ethers in a period of a few hours at room temperature.85 Benzyl and /-butyl systems are cleaved very rapidly, whereas secondary systems require longer times. The reaction presumably proceeds via an initially formed silyl oxonium ion ... 

Nitrosonium ion can also act as a mild and selective oxidizing agent. It has been used to cleave oxidatively oximes, hydrazones,498 and thioketals to their corresponding carbonyl compounds,499 to cleave benzylic esters515 [Eq. (5.195)], and to oxidize O-tributylstannyl and (9-trimethylsilyl ethers and benzylic alcohols516 [Eq. (5.196)]. 

Selective deprotection of trialkylsilyl ethers can also be accomplished by Nafion-H. Trimethylsilyl ethers are cleaved to the corresponding alcohols under mild conditions680 [Eq. (5.241)]. Nafion-H with Nal (1 equiv.) in methanol was shown to readily cleave ferf-butyldimethylsilyl ethers (room temperature, 4—25 h,... 

Trimethylsilyl ethers are sensitive to certain reagents used in organic synthesis. For example, they are attacked by nucleophiles, readily cleaved under acidic or basic conditions, and they do not survive hydrogenolysis. To overcome these problems a number of reagents which form more bulky silyl ethers have been developed some of these are shown in Figure Si2.2. 

MeO /MeOH cleavage of trimethylsilyl ethers occurs much more rapidly (by a factor of approximately 104) than the corresponding cleavage of tert-butyldimethylsilyl ethers. Both types of ether, however, are very rapidly cleaved by F. ... 

The silicon-silicon bond is oxidatively cleaved in phenylpenta-methyldisilane, which is converted by peroxybenzoic acid into phenyldi-methylsilyl trimethylsilyl ether in 86% yield (equation 608) [1203]. 

Since the C13-C14 olefin does not alter the reactivity of the C1-C9 portion of the myriaporone intermediates, subsequent efforts were explored on the C13-PMB ether (Scheme 12). Substrate 26 was successfully reduced with Raney nickel, and the trimethylsilyl ether was selectively cleaved with TBAF at -35 C. The C5 alcohol was selectively protected as the corresponding TBS ether, and C7 allylic alcohol was then oxidized under Dess-Martin conditions to provide bis-silyl ether 31. 

Cleavage of TBS ethers. Trimethylsilyl ethers are cleaved on exposure to Zn(Bp4)2 in water. ... 

Transetherification and transesterification. Tin(II) bromide is a catalyst for converting p-methoxybenzyl ethers into methoxymethyl ethers by CH2(OMe)2 and MeOCH2Br. Benzyl ethers and trimethylsilyl ethers are cleaved and acetylated in one operation by the action of SnBr2-AcBr in CH2CI2 at room temperature. 

The 1,2-photocycloaddition of acrylonitrile to naphthols or their methyl or trimethylsilyl ethers produces cyclobutane adducts e,g., 45), and these can be cleaved with base. This provides a synthetic route to (1- or 2-cyanoethyl)-substituted derivatives of the original naphthol. 1-Cyanonaphthalene (46) gives both 1,2-cycloadducts to the ring and a C N cycloadduct on irradiation with 1,2-dimethylcyclopentene, and the two reactions proceed by way of different singlet excited states of the aromatic nitrile. The photophysics of this system has been studied previously, but this is the first report in which the photoproducts are characterized. An intramolecular version of the reaction starting with the substituted 1-cyanonaphthalene (47) gives two 1,2-cycloadducts, the major one... 

The mildest reagent for cleaving TBS ethers is pyridinium p-toluenesulfonate (PPTS) in a protic solvent — usually methanol. Under these conditions a primary TBS ether can be cleaved in the presence of a 2-(trimethylsilyl)ethoxy-methyl (SEM) ether and 2-(trimethylsilyl)ethyl ester [Scheme 4.26]. Primary TBS ethers cleave at room temperature but secondary TBS ethers may require elevated temperature. In the transformation shown in Scheme 4.27 two TBS ethers were cleaved in the presence of a TIPS ether." rerf-Butyldiphenylsilyl (TBDPS) ethers are impervious to attack under these conditions as evinced by the selective removal of a primary TBS ether in the presence of an equally exposed primary TBDPS ether in a synthesis of NodRm-IV factors, glycolipids produced by symbiotic fungi that elicit formation of nitrogen-fixing root nodules in legumes [Scheme 4.28]. ... 

Although oxazoles follow the pattern and lithiate at C-2, 4-substituted products are produced with some electrophiles this is interpreted by a ring opening of the anion, to produce an enolate, which after C-electrophilic attack, recloses. An estimate by NMR spectroscopy showed the ring cleaved tautomer to dominate the equilibrium. The open enolates can be trapped by reaction with chlorotrimethylsi-lane the open, enol trimethylsilyl ether will undergo a thermal rearrangement to form a 2-trimethylsilyloxazole. ... 

Ether cleavage. The reagent is also useful for cleavage of aryl alkyl ethers to phenols (80-907o yield). It also cleaves dialkyl ethers to alkyl trimethylsilyl ethers which are then hydrolyzed to alcohols. This reaction is particularly useful for hydrolysis of methyl ethers (equation III). 

Trimethylsilyl ethers of alcohols and phenols cleave in 15 min in a cleaning bath. The more stable t-butyldimethylsilyl ethers of primary alcohols undergo cleavage even at - 40°C. Ethers of secondary and tertiary alcohols and phenols remain intact. The discrimination between f-butyldimethylsilyl and f-butyldiphenylsilyl groups is also possible, only the former being cleaved after 3 h at room temperature. These reactions require longer irradiation times than for TMS groups due to steric hindrance. 

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