Reactivity, hydroxyl groups, selective protection

With the C-1 and C-2 positions protected, the most reactive hydroxyl group of those remaining is the primary hydroxyl group at C-9. Silylation studies with NeuSAc have shown that the most reactive of the secondary hydroxyl groups is that at C-4 [112] (Scheme 9). For KDN, selective functionalisation may be... 

The reactivity of various steroid alcohols decreases in the order primary > secondary (equatorial) > secondary (axial) > tertiary. The only systematic investigation relating to the selective protection of steroidal hydroxyl functions has been carried out with the cathylate (ethyl carbonate) group. Since only equatorial hydroxyl groups form cathylates this ester has been used as a diagnostic tool to elucidate the configuration of secondary alcohols. 

NaH, /7-MeOQH4CH2Br, DMF, —5°, 1 h, 65%. Other bases, such as BuLi, ° dimsyl potassium," and NaOH under phase-transfer conditions," have been used to introduce the MPM group. The use of (n-Bu)4N I for the in situ preparation of the very reactive p-methoxybenzyl iodide often improves the protection of hindered alcohols." In the following example, selectivity is probably achieved because of the increased acidity of the 2 -hydroxyl group ... 

The presence in carbohydrates of multiple hydroxyl groups of similar reactivity makes the chemo- and regio-selective manipulation frequently required quite difficult. For this reason, multistep protection-deprotection approaches are regularly employed in carbohydrate chemistry, and versatile techniques for these transformations are particularly helpful. The following section addresses this aspect, concentrating on the catalytic procedures that have been developed employing zeolites and related siliceous materials. 

Product distributions obtained on esterification of nucleosides and nucleotides under basic conditions throw further light on factors affecting selective reactivity. p-Toluenesulfonylation of adenosine 5 -monophosphate in aqueous alkali yielded exclusively (in 54-61% yield) the 2 -p-toluenesulfonate.107 Lack of reaction at HO-3 was attributed either to formation of a phosphoric p-toluenesulfonic anhydride, which sterically protected this hydroxyl group, or to the higher acidity of HO-2. It has been shown that the acidic site (with pKa 12.5) in adenosine is associated with the presence of both HO-2 and HO-3, as replacement of either of these by hydrogen, or of HO-2 by methoxyl, results in loss of this acidity.108 Inductive effects, or the sta-... 

Another effective a-selective sialylation involves the use of a 5-N,4-0-carbonyl-protected sialyl donor, which could efficiently be used for the preparation of an a(2,8)-tetrasialoside. It was found that the 5-N,4-0-carbonyl protecting group improves the reactivity of the C-8 hydroxyl group of the sialyl acceptor [168]. 

The subject of relative reactivities of hydroxyl groups in carbohydrates has been discussed previously in this Series.1,2 In these articles, emphasis was placed on the selective introduction of substituents into carbohydrates. A much less exploited approach for the preparation of partially substituted carbohydrates involves the selective removal of hydroxyl-protecting groups from carbohydrate derivatives. The purpose of the present article is to draw attention to this relatively neglected aspect of synthesis in the belief that the greater use of de-... 

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