Axial C-glycopyranosides

C-Glycosides. Axial C-glycopyranosides arc obtained exclusively by photolysis of a mixture of an ot-D-glycopyranosyl bromide, acrylonitrile, and tributyltin hydride. The diastereoselectivity may involve an anomcric effect or rapid trapping of the initial radical before inversion can occur. 

In their study of Bronsted acid induced cleveage of a [with axial C(l)-OMe] and (3 [with equatorial C(l)-OMe] glycopyranosides, Fraser-Reid et al.46 demonstrated that the (3/a rate ratios for hydrolysis of methyl pyranosides (Table 5) can be explained by the different intermediates and transition-state structures through which proceed the heterolysis of a and [3 isomers (Fig. 18). 

Sakurai et al. as well as Sandhoff et al. used this approach for the synthesis of allyl-C-glycopyranosides 21 from readily accessible peracetylated or perbenzylated glycopyranoses 19 [12, 13]. Addition of allylsilane to oxonium 20 proceeds with an axial/equatorial selectivity that is considerably affected by the polarity of the solvent (Scheme 13.9). 

The axial a-D-tribuyltin-glycopyranoside can be obtained by reaction of 3 with lithium naphthalenide and then with Bu3SnCl. Transmetallation (BuLi) and reaction with an electrophile results in a-C-glycosides. 

In Ref. 1 (pp. 1114-1115) the effect of the axial or equatorial orientation of the aglycon in the rate of oxidation of a number of /f-D-glycopyranosides is described. When the aglycon adopts an equatorial orientation [a / anomer in the 4Ci(d) conformation] the oxidation takes place at a higher rate (two to ten times) than for the a anomer. In the case of methyl L-arabinopyranosides, the a-L anomer, which, in the (l) conformation has an equatorially attached group at C-l, is oxidized more rapidly. 

The oxidation of methyl glycopyranosides with periodic acid in DMSO is unusual in that only 1 mole of oxidant is consumed. Most of the stereoselective oxidation observed can be explained on the assumption that nic-cis-diols (axial-equatorial) are more reactive than ei c-tra/w-diols (diequatorial ordiaxial).10h... 

The conformational effect of the aglycon in alkyl glycopyranosides has been examined with the methyl, ethyl, isopropyl, and tert-butyl tri-0-acetyl-/3-D-ribopyranosides, and the corresponding benzoates. In each series, there was a negligible change in conformational population as between the methyl, ethyl, and isopropyl derivatives, but the terf-butyl derivatives contained somewhat less of that con-former [IC(d)] having the aglycon axially attached, presumably because there is loss of some rotational freedom about the C-1-0-1 bond in the tert-butyl derivatives as a result of steric hindrance. 

Step 6 Cyclization of the oxonium ion. An unshared electron pair of the C-5 oxygen is used to form a bond to C-1, forming the six-membered ring of the glycopyranoside. Both the a and (3 stereoisomers are formed in this reaction with the a stereoisomer (axial OCH3) predominating. 

If a true oxycarbenium ion is involved, one can expect that the stereoselectivity will be governed by the kinetic anomeric effect [6-8] leading to a predominant axial stereochemistry at C-1, the a/P ratio being of course modulated by steric effects (a 3-axial substituent can override the stereoelectronic effect). Oxycarbenium ions 2 and 3 lead to a-D-manno 6 and a-u-gluco 9 pyranosides respectively. Altogether, 2-deoxy-a-glycopyranosides can be predicted to be more easily attained after replacement of E by hydrogen. 

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