Design and Development of Stereoselective Methods for C-, O-, and S-Glycoside Synthesis Utilizing Sterically Strained Nitrogen Bases and Cyclic Sulfonium Salts

Abstract

The thesis focuses on the design and development of stereoselective methodologies for C-, O-, and S-glycoside synthesis, employing sterically strained nitrogen bases and cyclic sulfonium salts. Glycosylation, a cornerstone of carbohydrate chemistry, demands precise control over regio- and stereoselectivity, and this work introduces innovative catalytic strategies to address these challenges. The thesis introduces organocatalytic methods that exploit sterically strained pyridinium salts to achieve highly selective N-O-linked glycosides and establishes sulfonium-stabilized phenols as hydrogen-bonding catalysts for the strain-release glycosylation of cyclopropanated sugars, enabling access to septanoside frameworks. A palladium-catalyzed approach is also demonstrated, where proton sponge plays a unique triple role as a reductant, ligand, and base, furnishing biologically significant aryl C-glycosides with excellent yields and selectivity. In addition, new sterically hindered pyridine derivatives are synthesized and evaluated to understand the interplay of sterics, inductive, and through-space effects on basicity and reactivity, offering cost-effective alternatives to established non-nucleophilic bases. Collectively, these studies provide novel catalytic concepts, mechanistic insights, and practical synthetic applications, advancing stereoselective glycosylation and expanding the toolkit for carbohydrate chemistry and related fields.