Abstract
Polysaccharides, particularly glycosaminoglycans (GAGs) such as chondroitin sulfate and heparan sulfate, are essential biological macromolecules with complex stereochemical architectures that pose significant challenges to synthetic chemists. These polysaccharides contain both cis and trans glycosidic linkages, which are difficult to form selectively. This thesis explores novel iron-catalyzed strategies for stereoselective glycosylation to construct key 1,2-cis-α and 1,2-trans-β glycosidic linkages without the need for neighboring group participation or pre-installed directing groups. We first examine the formation of 1,2-cis-α glycosidic bonds through an iron-catalyzed amidoglycosylation strategy utilizing a newly synthesized oxidant containing a trifluoromethyl carbonyl group. This oxidant improves reactivity with electron-deficient donors and minimizes side-product formation such as amidoacyloxylation. Building on this methodology, we further investigate the iron-catalyzed formation of 1,2-trans-β linkages. By leveraging the steric and electronic properties of the catalyst and substrates, this approach facilitates highly stereoselective glycosylation. Additionally, mechanistic studies reveal that counterion effects and epoxide intermediates play pivotal roles in directing stereoselective outcomes. Collectively, this work contributes to the advancement of glycosynthetic methods, providing new tools for the efficient and selective construction of biologically important polysaccharides and paving the way for the synthesis of therapeutically relevant GAG analogs.