P-Glycosyl halides

If controlled conditions and an aptotic polar solvent are used, a SN2-type displacement reaction can be performed to give the inverted anomeric configuration in the product, e.g. a-glycosides from P-glycosyl halide precursors, in spite of the presence of participating 2-0-protecting groups (Scheme 3) [26, 27). 

The glycosyl halide (1.5 mmol), p-dicarbonyl compound (2 mmol), anhydrous K3P04 (0.S5 g) and TBA-Br (24 mg, 0.075 mmol) in McCN (10 ml) are stirred at room temperature. When the reaction is complete, as indicated by TLC analysis, the mixture is filtered and evaporated to yield the C-glycosyl derivative. 

Most of the methods available for the synthesis of this class of compoimd have been referred to in the preceeding pages. These include the modified Koenigs-Knorr reaction (p. 406), the use of glycosyl halides with non-... 

The application of diazo coupling is somewhat limited by the availability of the p-aminophenyl glycosides, particularly of those of the oligosaccharides. Their precursors, the p-nitrophenyl glycosides, are usually obtained by the condensation of a per-O-acetylated glycosyl halide with p-nitrophenol in ethanol (Michael reaction)19,20 or by the reaction of a per-O-acetylated sugar with p-nitrophenol in the presence of a Lewis acid catalyst (Helferich reaction).21 p-Nitrobenzyl 1-thioglycosides have also been prepared by the condensation of the... 

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... 

As briefly indicated in the Introduction (see p. 64), alkyl and acyl halides have been converted into cobalt derivatives by replacing the halide ion with cobalt tetracarbonyl anion. The cobalt derivatives were also cleaved by methanol, resulting in compounds in which carbon monoxide had been inserted. Although application of Heck s procedure to the glycosyl halides failed, use of the modification described next enabled the reactions to be carried out successfully. 

Kartha, K P R, Aloui, M, Field, R A, Iodine a versatile reagent in carbohydrate chemistry. III. Efficient activation of glycosyl halides in combination with DDQ, Tetrahedron Lett., 37, 8807-8810, 1996. 

---