Ethers, thexyldimethylsilyl

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

Thexyldimethylsilyl chloride (bp 55-56 01.3 kPa) and the corresponding tri-flate have been recommended152 as cheaper substitutes for rm-buty[dimethylsilyl chloride and /er/-butyldimethylsilyl triflate. Thexyldimethylsilyl ethers are formed at comparable rates and they are at least 2-3 times more stable than TBS ethers to acid and base hydrolysis but they introduce unwelcome clutter to NMR spectra, Thexyldimethylsilyl ethers are usually prepared by reaction of the substrate with thexyldimethylsilyl chloride in pyridine151 or in DMF in the presence of imidazole.153... 

Due to the increased steric bulk, thexyldimethylsilyl ethers undergo deprotection approximately two to three times more slowly than f-butyldimethylsUyl ethers under acidic and basic conditions. Similarly, TDS ethers derived from 1° alcohols undergo deprotection more rapidly than 2° TDS ethers. ... 

To a solution of thexyldimethylsilyl chloride (11 mmol) and ImH (15 mmol) in DMF (5 ml) was added the alcohol (11 mmol) at ambient temperature. After being stirred at ambient temperature for 16 h, the mixture was diluted with hexane. The hexane phase was washed with water (2x), and then dried. Concentration followed by distillation (Kugelrohr) gave the silyl ether (86-93%). 

The key intermediate 14, a stable tetrasubstituted tetrahydropyran derivative, was obtained from commercially available methyl o-glucopyranoside 12 via a three-step reaction sequence (Scheme 4). First the primary hydroxyl group was protected as thexyldimethylsilyl (TDS) ether, then the other OH groups were methylated under standard conditions to give 13. The latter glycoside was deoxy-genated at the anomeric position by treatment at room temperature with a Lewis acid (trimethylsilyl triflate) and a hydride donor (triethylsilane). This treatment also... 

Thexyldimethylsilyl chloride is a liquid and is less expensive then TBSCL Furthermore, ROTDS ethers react more slowly under hydrolytic conditions than do RO-TBS ethers. 

Silylating Agent for Protection of Alcohols. Thexyldimethylsilyl chloride (TDS-Cl) was first introduced as a more easily prepared alternative to the more commonly used f-butyl-dimethylsilyl chloride for the protection of alcohols.Direct silylation of 1° and 2° alcohols occurs upon treatment with TDS-Cl and imidazole in DMF as illustrated by the protection of 1-butanol (1) and cyclohexanol (3) to form the corresponding silyl ethers (eqs 1 and I) Phenols can also be protected using TDS-Cl and imidazole. Typical solvents for the formation of silyl ethers using TDS-Cl include DMF, THF, or CH2CI2. ... 

The steric bulk of the thexyldimethylsilyl group allows selective protection of less sterically hindered alcohols in the presence of other alcohols. For example, partially protected sugar 8 was selectively protected at the 1° alcohol to yield 1° silyl ether 9 (eq 5). In this instance, selectivity is obviously due to differing steric constraints on the alcohols. 

In an example of a 2° alcohol being protected in the presence of another 2° alcohol, diol 10 was selectively protected with thexyldimethylsilyl chloride to produce the monosilyl ether 11 (eq 6). Other exan5>les similarly employed thexyldimethylsilyl chloride as the reagent of choice for selective protection... 

Thexyldimethylsilyl chloride has also been used to produce a new protecting group, thexyldimethylsiloxymethyl chloride, via a two-step synthetic process. Ethylthiomethanol 12 was converted to the IDS ether followed by treatment with sulfuryl chloride to produce thexyldimethylsiloxymethyl chloride 13 (eq 7). Siloxymethyl chloride 13 was used to protect 1°, 2°, and 3° alcohols and phenols, and the protecting group was easily removed by treatment with TBAF in THF or EtaNF in CHsCN. ... 

Carboxylic acids can also be converted to silyl esters using thexyldimethylsilyl chloride and triethylamine in DMF, diethyl ether, or CH2Cl2. The resultant silyl ester can be hydrolyzed using triethylamine in aqueous acetone. ... 

Neither ketones nor thiols are reactive with thexyldimethylsilyl chloride as the silylating agent. Ketones require the more reactive thexyldimethylsilyl triflate and triethylamine to form silyl enol ethers. But thiols can be converted into the corresponding thiolates, which then undergo silylation with thexyldimethylsilyl chloride to form alkyl silyl thioethers. ... 

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