The C‐4 Configuration as a Probe for the Study of Glycosidation Reactions

Abstract

The difference in the electron-withdrawing powers of axial and equatorial OBn was used as a probe to investigate the glycosidation reaction. The reactivity of perbenzylated glucosyl and galactosyl donors were compared under a range of glycosidation conditions that involved variations in catalyst, solvent, and glycosyl acceptor. Generally, the galactosyl donor had a reactivity four to five times higher than the glu-

Cation Clock Reactions for the Determination of Relative Reaction Kinetics in Glycosylation Reactions: Applications to Gluco- and Mannopyranosyl Sulfoxide and Trichloroacetimidate Type Donors

“…Superposition of Figures 1a and c, as in Figure 1e, reveals the very shallow concentration dependence for the formation of 40 and 41 to approximate that for the formation of the 4,6- O -benzylidene protected α-mannoside 38 and strongly suggests that 40 and 41 are formed by dissociative mechanisms that involve the oxocarbenium ion 34 (Scheme 7, R = Bn) only loosely associated with the counterion. This observation is consistent with the strongly disarming nature of the 4,6- O -benzylidene acetal, 52,134–136 as compared to two benzyl ethers, which in turn is a function of the imposition of the trans - gauche conformation 137 of the C5-C6 bond in which the electron-withdrawing effect of the C5-O5 bond is maximized. 138–140 A caveat to this argument concerns the use of different clock reactions in Figures 1a and c (vide infra), however, we believe that the comparison is justified here in view of the similarity of the two oxocarbenium ions (Scheme 7, 34 , R = Bn and R-R = PhCH).…”

Determination of the Influence of Side‐Chain Conformation on Glycosylation Selectivity using Conformationally Restricted Donors

“…Thus, the spatial relationship between O6 and the ring oxygen in the tg conformation is identical to that between the equatorial O4 and the ring oxygen in glucopyranosides, whereas the O6 and the ring oxygen in the gg conformer share the same spatial relationship as the axial O4 and the ring oxygen in galactopyranosides (Figure 4). The axial O4 in galactose and the gg conformer of the side chain are spatially closer to the ring oxygen and better able to stabilize positive charge on it, than the equatorial O4 in glucose and tg conformer of the side chain, resulting in the generally greater reactivity and α-selectivity of galactosyl over glucosyl systems [27] and in the greater reactivity [3, 4g] and now the α-selectivity of the gg over the tg confomers of the side chain. The ability of the axial O4 in galactose, and by extrapolation O6 in the gg conformer, to stabilize positive charge on the ring oxygen better than the equatorial O4 in glucose and consequently O6 in the tg conformer is usually considered in terms of a simple electrostatic effect with the electron density on axial group being closer to the positive charge than is the case with the equatorial group.…”

Glycosidation Promoted by a Reusable Solid Superacid in Supercritical Carbon Dioxide

“…Glycosidation by using glycosyl donors 2 and 3 protected by O-benzyl groups were also examined under the same conditions, in scCO 2 at 34 8C and 8.0 MPa. The results summarized in Table 2 suggest that both glycosyl donors 2 and 3 were efficiently activated by SO 4 / ZrO 2 in scCO 2 and afforded the expected glycosides 13, [14] 14, [15] 15, [16] and 16 [17] in 51-91 % yields as a mixture of stereoisomers. These results indicate that the combination of SO 4 /ZrO 2 with SFC did not work for the improvement of stereoselectivity in the selected glycosidation.…”