C‑Glycosidation of Unprotected Di- and Trisaccharide Aldopyranoses with Ketones Using Pyrrolidine-Boric Acid Catalysis

C-Glycoside
derivatives are found in pharmaceuticals, glycoconjugates,
probes, and other functional molecules. Thus, C-glycosidation of unprotected
carbohydrates is of interest. Here the development of C-glycosidation
reactions of unprotected di- and trisaccharide aldopyranoses with
various ketones is reported. The reactions were performed using catalyst
systems composed of pyrrolidine and boric acid under mild conditions.
Carbohydrates used for the C-glycosidation included lactose, maltose,
cellobiose, 3′-sialyllactose, 6′-sialyllactose, and
maltotriose. Using ketones with functional groups, C-glycosides ketones
bearing the functional groups were obtained. The pyrolidine-boric
acid catalysis conditions did not alter the stereochemistry of non-C–C
bond formation positions of the carbohydrates and led to the formation
of the C-glycosidation products with high diastereoselectivity. For
the C-glycosidation of the carbohydrates under the pyrrolidine-boric
acid-catalysis, the hydroxy group at the 6-position of the reacting
aldopyranose was necessary to afford the product. Our analyses suggest
that the carbohydrates form iminium ions with pyrrolidine and that
boric acid forms B–O covalent bonds with the carbohydrates
during the catalysis to forward the C–C bond formation.