Glycosylidene carbenes. Part 14. Glycosidation of partially protected galactopyranose-, glucopyranose-, and mannopyranose-derived vicinal diols

Article abstract of DOI:10.1002/hlca.19940770128

The relation between H-bonding in diequatorial trans-1,2 and axial,equatorial cis-1,2-diols and the regioselectivity of glycosidation by the diazirine 1 was examined. H-Bonds were assigned on the basis of FT-IR and ¹H-NMR spectra (Fig. 1). Glycosidation by 1 of the gluco-configurated diequatorial trans-2,3-diols 4-7 yielded the mono-glucosylated products 16/17/20/21 (69-89%); 1,2-/1,3-linked products 37-46:63-54), 24/25/28/29 (60-63%; 1,2-/1,3,-linked products 46-51:54-49), 32-35 (69-94%; 1,2-/1,3-linked products 45-52:55-48), and 36/37/40/41 (59-63%; 1,2-/1,3-linked products 52-59:48-41), respectively (Scheme 1, Table 3). The disaccharides derived from 4, 5, and 7 were characterized as their acetates 18/19/22/23, 26/27/30/31, and 38/39/42/43, respectively. Glycosidation of the galacto-configurated diequatorial 2,3-diols 8 and 9 and the manno-configurated diequatorial 3,4-diol 10 by 1 (Scheme 2, Table 3) also proceeded in fair yields to give the disaccharides 44-47 (69-80%; 1,2-/1,3-linked products ca. 1:1), 48-51 (51-61%; 1,2-/1,3-linked products 54-56:56-54), and 56/57/60/61 (71-80%; 1,3-/1,4-linked products 49-54:51-46), respectively. The 1,3-linked disaccharides 56/57 derived from the diol 10 were characterized as the acetates 58/59. The regio- and stereoselectivities of the glycosidation by 1 were much better for the α-D-manno-configurated axial,equatorial cis-2,3-diol 11 and the galacto-configurated axial, equatorial cis-3,4-diol 13 (1,2-/1,3-linked disaccharides ca. 3:7 for 11 and 1,3,-/1,4-linked disaccharides ca. 4:1 for 13; Scheme 3, Table 4). The regio- and stereoselectivity for the β-D-manno-configurated cis-2,3-diol 12 were, however, rather poor (1,2-/1,3-linked products 48:52). The 1,2-linked disaccharides 66/67 derived from 12 were characterized as the acetates 70/71. Koenigs-Knorr-type glycosidation of the cis-diols 11-13 by 2 or 3 proceeded with a similar regio- and a higher stereoselectivity (α-D > β-D with the donor 2 and α-D < β-D with the donor 3) than with 1, with the exception of 12 which did not react with 2. The regioselectivity of the glycosidations by 1 agrees fully with the H-bonding scheme of the diols and with the hypothesis that the intermediate carbene is preferentially protonated by the most weakly H-bonded OH group. The regioselectivity of the glycosidation by 2 and by 3 is determined by a higher reactivity of the equatorial OH groups and by H-bonding. Several H-bonded and equilibrating isomers of a given diol may intervene in the glycosidation by 1, or 2 and 3, resulting in the same regioselectivity. The low nucleophilicity of 12 and the low degree of regioselectivity in its reaction with 3 show that stereoelectronic effects may also profoundly influence the nucleophilicity of OH groups.