Glycosyl halides reactivity

Tetramethylguanidinium azide, an azide salt that is readily soluble in halogenated solvents, is a useful source of azide ions in the preparation of azides from reactive halides such as a-haloketones, a-haloamides, and glycosyl halides.74... 

Acetimidate formation with A-methylacetamide and acylated glycosyl halides according to Sinay et al (212,213), using three equivalents of silver oxide as an activator, leads neither to particularly stable nor to reactive donors. Any other developments along these lines have already been summarized in previous reviews (1,3). The same is mainly true for anomeric... 

Specifically, Paulsen recognized that glycosyl halides bearing C2-benzylethers were much more prone to hydrolysis than the corresponding C2 esters. Similarly, Paulsen noted that the glycosyl iodides were more prone to hydrolysis than glycosyl bromides, and these bromides were more reactive than glycosyl chlorides. 

The classical, Fischer7 synthesis of sugar isothiocyanates involves treatment of an acylated glycosyl halide with an inorganic thiocyanate in a polar solvent. Depending on the reactivity of the halide and the reaction conditions, either a thiocyanate or an isothiocyanate is formed directly. 

Activation of thioglucosides. Thioglucosides are useful for glycosidation since they are more reactive than glycosyl halides. They are known to be activated by methyl triflate, but this triflate is a potent carcinogen. Methylsulfenyl trifluoromethanesulfonate (1) is also an activator and has the advantage that it can be prepared in situ. Thus the 1-thio-p-D-glucopyranoside (p—2) couples with a-D-... 

If one can find ways to effect SN2 reactions of glycosyl halides with oxygen nucleophiles (e.g., sugar alcohols), selective access to both sets of anomeric halides could prove invaluable. Other studies which employ SN2 chemistry at glycosidic centers include the halide-assisted glycosylation developed by Lemieux et al.,45 the use of a participating solvent such as acetonitrile,46 and exploitation of torsional control of anomeric reactivity.47 This latter approach has been very successfully exploited by Crich and Sun in the synthesis of P-mannosides (Fig. 19).48... 

Reactive glycosyl halides which cannot form an intermediate acyloxonium ion, such as 2-de-oxysugar halides, usually give mixtures of a- and j8-nucleosides. 

The intrinsic interest in the chemistry of glycosyl halide derivatives will no doubt center on their use in determining the influence of the conformation of the molecule, and of the positions in space of the various substituents, on the reactivity of the halogen atom. Already, there exists a large amount of data, but the task of organizing these data to produce a coherent account of the chemistry of the glycosyl halide derivatives is only begun. 

It has been pointed out that the high reactivity of the poly-O-acyl-glycosyl halides is typical of the a-halogeno ethers. In this class of compound, the inductive polarization of the C—X bond is increased by an electromeric release of electrons from the oxygen atom and this promotes a unimolecular (rather than a bimolecular) reaction. Comparison of the rate of methanolysis of 2,3-dichlorotetrahydropyran (XXII) with those of 3,4,6-tri-0-acetyl-2-chloro-2-deoxy-a-D-glucosyl chloride (XXIII) and... 

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