Ethers as alcohol protecting groups

The utility of but-2-enyl ethers as alcohol protecting groups has been described the function is stable to mild acid and base, but is readily cleaved by potassium t-butoxide in DMSO at room temperature. A full description of the use of tritylone ethers as protecting groups has been published. 

A major disadvantage of the tetrahydropyranyl ether as a protecting group is that an asymmetric center is produced at C-2 of the tetrahydropyran ring on reaction with the alcohol. This asymmetry presents no difficulties if the alcohol is achiral, since a racemic mixture results. If the alcohol has an asymmetric center anywhere in the molecule, however, condensation with dihydropyran can afford a mixture of diastereomeric tetrahydropyranyl ethers, which may complicate purification and characterization. One way of surmounting this problem is to use methyl 2-propenyl ether, rather than dihydropyran. No asymmetric center is introduced, and the acetal offers the further advantage of being hydrolyzed under milder conditions than those required for tetrahydropyranyl ethers. Ethyl vinyl ether is also useful as a hydroxyl-... 

The benzyl group can serve as an alcohol-protecting group when acidic conditions for ether cleavage cannot be tolerated. The benzyl C-O bond is cleaved by catalytic hydrogenolysis," or with sodium in liquid ammonia. Allyl ethers are an alternative to benzyl ethers as a protecting group. Allyl ethers may be isomerized quantitatively by potassium r-butoxide in dimethyl sulfoxide to propenyl ethers, which are quite labile to dilute acid. ... 

Protecting Group. Triphenylsilane is used in certain cases for the preparation of triphenylsilyl ethers, which serve as alcohol protecting groups. The triphenylsilyl group is considerably more stable (about 400 times) than the TMS group toward acidic hydrolysis. ... 

Silyl ethers play a very important role as hydroxyl-protecting groups. Alcohols can be easily converted to trimethylsilyl ethers by reaction with trimethylsilyl chloride in the presence of an amine or by heating with hexamethyldisilazane. f-Butyldimethylsilyl ethers are also of considerable use as alcohol-protecting groups. The increased steric bulk of the r-butyldimethylsilyl group improves the... 

Full details are now available of the oxidative cleavage of ethers by uranium hexafluoride. An interesting new mild method of oxidative removal of p-methoxybenzyl ethers (used as alcohol protecting groups) employs as an electron-transfer reagent the stable cation radical (69), used either stoicheiometrically or in catalytic quantities, and regenerated electrochemically during the reaction (Scheme 48). 

Silyl linkers are very common in solid phase chemistry in their function as alcohol-protecting groups [332-338]. Cleavage from those silyl ether resins... 

Methoxyphenyl (PMP) ethers find occasional use as hydroxy protecting groups. Unlike benzylic groups, they cannot be made directly from the alcohol. Instead, the phenoxy group must be introduced by a nucleophilic substitution.185 Mitsunobu conditions are frequently used.186 The PMP group can be cleaved by oxidation with CAN. 

Thermolytic Cleavage of Allvlic and Benzvlic Ethers and Polvethers. The thermal lability of the types of ethers which are of interest in the context of this study was discovered during a thorough study of the application of certain benzylic carbonates as labile protecting groups for alcohols and phenols [IS]. It was observed that, under acid catalysis, the bis-methylcarbonate derivative of l-(4-hydroxyphenyl)ethanol (4, in Equation 1) was transformed into the benzylic ether (5) which then underwent clean acid-catalyzed thermolysis to the corresponding styrene (6) in very high yield [14]. 

Notes This is often used as a protecting group for alcohols, where it is observed that primary alcohols form more readily than secondary hydroxy groups, which in turn are more reactive than tertiary alcohols. As with most benzylic ethers, this protecting group can be removed by hydrogenolysis over Pd or by metal-ammonia reduction.1 Examples ... 

Dihydropyran is of value as a protecting group for alcohols and phenols, and to a lesser extent amines, carboxylic acids and thiols (B-67MI22403, B-81MI22404). The resulting tetrahydropyranyl ethers (736) are stable to base, but are readily cleaved under acidic conditions (Scheme 284). 

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