Glycosylation reactions reactivity order

Anomeric halides follow the typical reactivity order F < Cl < Br < I for nucleophilic substitutions. They have been used in stereoselective O-glycosylation, nucleophilic displacement, and carbanion as well as in radical reactions. 

Generally, the reactions are carried out in refluxing benzene solution, since the yield in benzene is better than that in other solvents. Probably, the radicals formed may be somewhat stabilized by the weak orbital-orbital interaction between the radicals and benzene. However, from the environmental point of view, toluene or dioxane is recently used. As substrates, alkyl bromides or alkyl iodides are used, and the reactivity increases in the order prim-alkyl < seoalkyl < te/t-alkyl. Sugar anomeric bromide (3) is generally not so stable, so the reaction is carried out under irradiation conditions with a mercury lamp at room temperature (eqs. 4.2 and 4.3). There are two types of anomeric glycosyl radicals as shown in Figure 4.1. One is the axial radical [I], and the other is the equatorial radical [I ]. The axial radical is more nucleophilic than the equatorial radical due to the stereoelectronic effect, where this effect comes... 

In order to confirm this assumption the authors performed the experiments inO Table 9 [113]. Equimolar amounts of armed and disarmed donors 64, and 200 or 202b were allowed to compete for one equivalent of acceptor 215 under the agency of NIS. When one equivalent of NIS was used the major product obtained was that of glycosylation of armed NPG 216, thus in agreement with a process of intermolecular halonium transfer and preferred reaction of the more reactive donor (O Table 9, entries i, iii). When the amount of NIS was increased to three equivalents, the observed ratio of compounds 216 and 217 indicated enhanced coupling of the disarmed donor (O Table 9, entries ii, iv), thus in agreement with the proposed rationalization for the regiopreferences observed in the three-component reactions. 

In order to evaluate quantitatively the reactivity difference between thioglycosyl donors with variable aglycons, Lahman and Oscarson published a detailed account of their results [73]. Competitive glycosylations were performed using mainly ethyl thioglycosides (Glc-78 or Gal-36) as reference donors and dimethyl(methylthio) sulfonium trifluoromethylsulfonate (DMTST) as promoter (Scheme 24) and the reaction mixtures were analyzed by HPLC. The results are summarized in Table 3. 

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