Diverse Synthesis of C-Glycosides by Stereoselective Ni-Catalyzed Carboboration of Glycals

Abstract

C-Glycosides are important structures that are common to natural products and pharmaceutical agents. Established methods for their synthesis involve the reaction of an activated anomeric carbon. In this study, we report a conceptually new approach that involves the stereoselective Ni-catalyzed carboboration of glycals. In these reactions, not only is a C−C bond formed at the anomeric carbon, but a synthetically useful C−B bond is also installed. Upon C−B oxidation, differentially protected Cglycosides to be formed. In addition, stereospecific manipulation of the C−B bond leads to diverse C-glycosides. Finally, we report the application of this method in the synthesis of established C-glycosides, such as C-glycosyl amino acids, as well as a strategy to make all possible diastereomers at C1 and C2.

Stereoselective Construction of Multifunctional C-Glycosides Enabled by Nickel-Catalyzed Tandem Borylation/Glycosylation

“…In summary, a simple nickel-catalyzed stereoselective borylation/glycosylation cascade of readily available glycals with commercially available carbon halides and a diboron reagent under mild conditions has been developed . Leveraging the in situ generated glycosyl-Ni intermediate, a diversity of multifunctional C-glycosides that bear an alkyl, aryl, or alkenyl anomeric group and associated boron functionality can be produced in a stereoselective C–C cross-coupling manner.…”