Cobalt’s Dual Role in Promoting C3-Glycosylation of Indoles: Unraveling Mechanistic Insights
Qiu-Qi Mu, Aoxin Guo, Xin Cai, Yang-Yang Qin, Xing-Le Liu, Xing-Le Liu, Fangqi Ye, H.Y. Yang, Xiao Xiong, Xue‐Wei Liu, Xue‐Wei Liu
Abstract
In this study, we present a cobalt-catalyzed C3-glycosylation of indoles using unfunctionalized glycals, yielding 3-indolyl- C -deoxyglycosides. These compounds hold promise as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for treating type 2 diabetes. Control experiments unveiled that cobalt assumes a dual role, facilitating catalytic C -glycosylation while unexpectedly driving the anomerization of α-anomers through endocyclic cleavage of the C1–O5 bond, resulting in the formation of β- C -deoxyglycosides. Furthermore, density functional theory (DFT) calculations shed light on the reaction mechanism, emphasizing the significant role of the pyridine group of indole in stabilizing transition states and intermediates.