Novel zinc (II)-mediated epimerization of 2′-carbonylalkyl-α-C-glycopyranosides to their β-anomers

2-Aldehydes and 2-ketones of α-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their β-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate. The β-stereoselectivity is independent of the neighboring group at 2-O-substitution of sugar substrates. Therefore, this provides a particularly useful method for the preparation of manno-β-C-glycosides. The epimerization is likely initiated by the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chair-boat structure. Due to the activation generated by the Zn-O coordination, fission of the C1-O bond occurs, leading to opening of the pyranose ring, which is spontaneously followed by a change in conformation. The more stable anti chair-boat transition state is favored, and the subsequent hetero-intramolecular Michael addition results in the formation of β-C-glycoside in a ring-closure step. Copyright © 2002 American Chemical Society.