Pd-Catalyzed Stereospecific Glycosyl Cross-Coupling of Reversed Anomeric Stannanes for Modular Synthesis of Nonclassical C‑Glycosides

Nonclassical C-glycosides,distinguished by their unique glycosidic bond connection mode,represent a promising avenue for the development of carbohydrate-based drugs.However,the accessibility of nonclassical C-glycosides hinders broader investigations into their structural features and modes of action.Herein,we present the first example of Pd-catalyzed stereospecific glycosylation of nonclassical anomeric stannanes with aryl or vinyl halides.This method furnishes desired nonclassical aryl and vinyl C-glycosides in good to excellent yields,while allowing for exclusive control of nonclassical anomeric configuration.Of significant note is the demonstration of the generality and practicality of this nonclassical C-glycosylation approach across more than 50 examples,encompassing various protected and unprotected saccharides,deoxy sugars,oligopeptides,and complex molecules.Furthermore,biological evaluation indicates that nonclassical C-glycosylation modifications of drug molecules can positively impact their biological activity.Additionally,extensive computational studies are conducted to elucidate the rationale behind differences in reaction reactivity,unveiling a transmetalation transition state containing silver(Ag)within a six-membered ring.Given its remarkable controllability,predictability,and consistently high chemical selectivity and stereospecificity regarding nonclassical anomeric carbon and Z/E configuration,the method outlined in this study offers a unique solution to the longstanding challenge of accessing nonclassical C-glycosides with exclusive stereocontrol.

Stereoselective Synthesis of C-Vinyl Glycosides via Nickel-Catalyzed Cross-Electrophile Couplings of 1,2-Glycosyl Orthoesters and Vinyl Halides

A highly stereoselective nickel-catalyzed cross-electrophile coupling of readily accessible,novel,stable oxygen-based glycosyl radical precursors,specifically 1,2-glycosyl orthoesters,is developed.This approach offers an effective pathway to synthesize diverse C-vinyl glycosides,characterized by good yields,excellent stereoselectivity,mild reaction conditions,a broad substrate scope,and versatile transformations of the resulting products.