Hydroxy-Protecting Groups

Green and P. G. Wuts, Protective Groups in Organic Synthesis, 3rd Edition, Wiley, New York, 1999 P. J. Kocienski, Protective Groups, Thieme, New York, 2000. 

The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 7.1). 

A disadvantage of the THP group is the fact that a new stereogenic center is produced at C(2) of the tetrahydropyran ring. This presents no difficulties if the alcohol is achiral, since a racemic mixture results. However, if the alcohol is chiral, the reaction gives a mixture of diastereomers, which may complicate purification and/or characterization. One way of avoiding this problem is to use methyl 2-propenyl ether in place of dihydropyran (abbreviated MOP, for methoxypropyl). No new chiral center 

Ethyl vinyl ether is also useful for hydroxy group protection. The resulting derivative (1-ethoxyethyl ether) is abbreviated as the EE group.156 As with the THP group, the EE group introduces an additional stereogenic center. 

The methoxymethyl (MOM) and (3-methoxyethoxymethyl (MEM) groups are used to protect alcohols and phenols as formaldehyde acetals. These groups are normally introduced by reaction of an alkali metal salt of the alcohol with methoxymethyl chloride or (3-methoxyethoxymethyl chloride.157 

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The benzyl group can serve as a hydroxy-protecting group if acidic conditions for ether cleavage cannot be tolerated. The benzyl C—O bond is cleaved by catalytic hydrogenolysis,176 or by electron-transfer reduction using sodium in liquid ammonia or... 

These reaction conditions do not affect most of the other common hydroxy-protecting groups and the methoxybenzyl group is therefore useful in synthetic sequences that require selective deprotection of different hydroxy groups. 4-Methoxybenzyl ethers can also be selectively cleaved by dimethylboron bromide.182... 

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. 

Allyl carbonate esters are also useful hydroxy-protecting groups and are introduced using allyl chloroformate. A number of Pd-based catalysts for allylic deprotection have been developed.209 They are based on a catalytic cycle in which Pd° reacts by oxidative addition and activates the allylic bond to nucleophilic substitution. Various nucleophiles are effective, including dimedone,210 pentane-2,4-dione,211 and amines.212... 

Table 3.1 gives the structure and common abbreviation of some of the most frequently used hydroxy-protecting groups. 

INFLUENCE OF HYDROXY PROTECTING GROUPS ON SIALYL DONOR REACTIVITY 147... 

Table 1 lists the commonly used hydroxy protecting groups, together with their stability, selectivity to amino and carboxy protecting groups, and cleavage conditions. 

Table 1 Cleavage Conditions and Stability of Commonly Used Hydroxy Protecting Groups ...

Ichikawa, Y, Kubota, H, Fujita, K, Okauchi, T, Narasaka, K, Stereoselective P-C- and P-5-glycosylation of 2-deoxyribofuranose derivatives controlled by the 3-hydroxy protective group, Bull. Chem. Soc. Jpn., 62, 845-852, 1989. 

F. Roussel, L. Knerr, M. Grathwohl, and R. R. Schmidt, O-Glycosyl trichloroacetimidates bearing Fmoc as temporary hydroxy protecting group A new access to solid-phase oligosaccharide synthesis, Org. Lett., 2 (2000) 3043-3046. 

The diastereofacial preferences of keto ethers (192) are summarized in equation (116) and Table 21. The (Z)-lithium enolate of (192), prepared by reaction of the keto ether with lithium hexamethyldisila-zane, reacts with isobutyraldehyde to give syn aldols (193) and (194), along with small amounts of an anti aldol of undefined stereochemistry (195). - The results of this investigation demonstrate that the facial preference of a chiral 3-hydroxy ketone can be affected to some extent by the hydroxy-protecting group,... 

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