Tris ethers protect alcohols

Noyori and coworkers found that tetrafluorosilane or trimethylsilyl tri-flate catalyzes the condensation of appropriately protected glycopyranosyl fluorides with trimethylsilyl ethers or alcohols. The strong affinity of silicon for fluorine was considered to be the driving force for this reaction. In the case of Sip4, attack of a nucleophile on the glycosyl cation-SiFj ion-pair intermediate was anticipated. Thus, condensation of 2,3,4,6-tetra-O-benzyl-a- and - -D-glucopyranosyl fluorides (47a and 47fi) with methyl... 

Treatment of the monochloro diethylene glycol 9 with dihydropyran yields the protected alcohol 10. Reaction of 2,2, 2"-triaminotriethylamine (tren) 11 with toluenesulfonyl chloride gives the tritoluenesulfonyl derivative 12. The pyranyl ether 10 may be condensed with the tris(sodium) salt of 12 leading to 13. Removal of the tetrahydropyranyl group is achieved in high yield under... 

Weak base (neutral to phenolphthalein). forms water-soluble salts with strong acids pK 9.5. Difficultly so] in cold wa. ter, more easily in hot water. Miscible with alcohol, ether, carbon disulfide. Dissolves sulfur, phosphorus, arsenic tri-oxide. Protect from light and moisture. LDW orally in rats 460 mg /kg (Smyth). 

Silyl protecting groups are the gold standard for the protection of alcohols.234 Novel photochemically removable protection groups for alcohols have been developed by Brook et a/.23S and Pirrung et al,236 For instance, cyclo-pentanol can be reacted with tris(trimethylsilyl)chlorosilane 53 in the presence of a mild base to yield the protected silyl ether 54. The protection group can be removed conveniently upon UV irradiation or by the use of Bu4NF (Scheme 12). 

It has been reported that (TMS)3SiCl can be used for the protection of primary and secondary alcohols [55]. Tris(trimethylsilyl)silyl ethers are stable to the usual conditions employed in organic synthesis for the deprotection of other silyl groups and can be deprotected using photolysis at 254 nm, in yields ranging from 62 to 95%. Combining this fact with the hydrosilylation of ketones and aldehydes, a radical pathway can be drawn, which is formally equivalent to the ionic reduction of carbonyl moieties to the corresponding alcohols. 

A one-liter flask fltted with a stirrer, reflux condenser and separatory flask is charged with 7.6 g (0.2 mol) of lithium aluminum hydride and 500 ml of anhydrous ether. A solution of 44.4 g (0.6 mol) of anhydrous terr-butyl alcohol in 250 ml of ether is added slowly from the separatory funnel to the stirred contents of the flask. (The hydrogen evolved is vented to a hood.) During the addition of the last third of the alcohol a white precipitate is formed. The solvent is decanted and the flask is evacuated with heating on the steam bath to remove the residual ether and tert-butyl alcohol. The solid residue - lithium tri-/er/-butoxyaluminohydride - is stored in bottles protected from atmospheric moisture. Solutions 0.2 m in reagent are prepared by dissolving the solid in diglyme. 

Alcohols protected as methyl ethers can be retrieved by reaction with tribromo-borane. Activation of the methyl ether by co-ordination of the Lewis acidic tri-bromoborane followed by nucleophilic cleavage of the O—Me bond (with concomitant formation of bromomethane) is typical behaviour. However, the cleavage took a different course with 39.1 [Scheme L39] instead of the O—Me bond being cleaved, the alternative C—O bond cleaved owing to participation of the remote acetoxy group.72 The formation of bromide 39.4 with retention of configuration is circumstantial evidence implicating dioxonium ion intermediate 393. 

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