Reversible-Hydrogen-Transfer-Mediated Anomerization of Azaheterocyclyl 2-Deoxy-C-glycosides and Mechanistic Studies

Abstract

Mutarotation of O-glycans and O-glycosides has long been well-established and exploited in the stereocontrolled chemical synthesis of O-glycosides, while few examples of C-glycoside anomerization are known to date. During the development of a simple iridium catalyst-promoted α-stereoselective C-glycosylation of 2-indoly-pyridine with glycal donors, we serendipitously discovered the occurrence of 2-deoxy-C-glycoside anomerization, enabling α-to-β configuration conversion. Control experiments and density functional theory calculations were performed to explore the mechanistic details of the anomerization of the C-glycosylation products, which could tolerate C-aryl and C-alkyl-glycosides. The anomerization reaction plausibly proceeds through the pathway involving the activation of the C(sp3)–H bond mediated by the iridium catalyst and reversible hydrogen transfer, rather than the classical anomerization mechanisms involving the endocyclic cleavage of the C1–O5 bond or exocyclic cleavage of the glycosidic bond.