Ethers, thexyldimethylsilyl alcohol protection

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. 

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. ... 

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