Expanding the Chemical Space of Sugar Frameworks by Quaternization of the Anomeric Carbon Atom

The anomeric position of carbohydrates is a privileged site for structural diversification in the development of glycomimetics. Quaternization of the anomeric carbon represents a promising strategy to enable dual and orthogonal functionalization at C‐1, while preserving critical binding features. Herein, the synthesis of novel bifunctional C‐ fucoside scaffolds, bearing a quaternary anomeric center, is reported. The strategy employs radical bromination of β‐cyano and β‐carbomethoxy fucosides to access key anomeric α (axial) bromide intermediates, which enable downstream derivatization via azide substitution or CC bond formation through radical allylation. The latter reaction occurs with high α (axial) selectivity from the β‐carbomethoxy‐α‐fucosyl bromide, while mixtures are obtained from the corresponding β‐cyano derivative. Azide substitution occurs with full inversion of configuration starting from both bromides. While attempts at amide coupling are hampered by anomeric epimerization, copper‐catalyzed azide–alkyne cycloaddition proceeds efficiently, yielding α‐C,β‐ N ‐fucosides with high yields and selectivity. The developed methodology expands the chemical space at the anomeric position and supports future applications in ligand design, multivalent systems, and carbohydrate‐based therapeutics.