Protection of hydroxyl groups

Other important examples of stable enol-type compounds are the aromatic alcohols, or phenols. The K s of these compounds are about 10 10, some 10s times larger than the Ka s for alcohols. 

The chemistry of these compounds, including their stability as enols, is discussed in Chapter 26. 

Exercise 15-36 Write equations for the dissociation of ascorbic acid to give progressively a monoanion and a dianion. Assign a p/Ca to each dissociation and make your structures clear as to which are the acidic protons. Why is ascorbic acid a stronger diacid than cyclopentane-1,2-diol  

A good protecting group is one that does everything you want it to do when you want it to. It must be easily put into place, stable to the reagents from which protection is required, and easily removed when desired. For this reason simple ethers such as methyl or ethyl ethers usually are not suitable protecting groups because they cannot be removed except under rather drastic conditions (Section 15-10). 

More suitable ethers are phenylmethyl and trimethylsilyl ethers  

An important alternative for the benzyl group is the tert.butyl group. The tert.butyl ethers of serine, threonine and tyrosine 

3-Beta- and 3a-equatorial hydroxyl groups of the 5a- and 5j5-series respectively, as well as the quasi-equatorial 3/ -hydroxyl in A -enes, are highly reactive. Most of the protective groups considered in this review can be readily prepared with these alcohols. 

Tetrahydropyranyl ethers are prepared by reaction with 2,3-dihydropyran, and a catalyst such as hydrochloric acid, phosphorous oxychloride or p-toluenesulfonic acid at room temperature. 3iS-Hydroxy-5-enes also form pyranyl ethers by distillation of a solution of the steroid and dihy-dropyran in ether without a catalyst. 

Crude tetrahydropyranyl ethers are usually a mixture of epimers due to formation of an additional asymmetric center. Consequently these derivatives are sometimes difficult to characterize. 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

As previously discussed, ethyl chlorocarbonate reacts rapidly and selectively with an equatorial 3-hydroxyl group to give the corresponding cathylate. Trityl ethers, usually employed as a selective protecting group for primary hydroxyls, can be prepared from A -3j3-ols by heating with triphenylmethyl chloride in pyridine, and from 5a-3 -alcohols by more prolonged heat- 

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Protection of 22-aldehyde, 401 Protection of 16,17-dihydroxy groups, 404 Protection of 17a,21-dihydroxy groups, 405 Protection of 20,21-dihydroxy group, 405 Protection of 3-hydroxyl groups, 402 Protection of hydroxyl groups, 380, 384,... 

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See also in sourсe #XX -- [ ]

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