Exploiting π and Hydrogen Bonding Interactions of Strain-free Pyridinium Tetrafluoroborate Salt for Stereoselective Synthesis of O-Aryl Glycosides

Abstract

The strategic design and development of organo-catalysts for the efficient and stereoselective synthesis of O-aryl glycosides, an otherwise challenging task in carbohydrate chemistry, remains crucial. Non-covalent interactions (NCIs) based catalysts are emerging as essential synthetic tools for achieving defined anomeric selectivity in glycosylation reactions. However, their use has been predominantly explored for the synthesis of O- and C-glycosides. In this work, we present a highly efficient, robust and practical catalytic strategy for the diastereoselective (α:β > 30:1) synthesis of intriguing O-aryl glycosides using simple, easily accessible, cost-effective and strain-free unsubstituted pyridinium tetrafluoroborate salt as a catalyst at ambient conditions via activation of glycosylimidate donors through non-covalent hydrogen bonding interactions (NCIs). Detailed mechanistic investigations have uncovered a pivotal role of the designed catalyst in diastereoselective O-aryl glycosylations. The catalyst not only activates glycosylimidate donors but also enhances the nucleophilicity of phenols through dual hydrogen bonding and facial selectivity in the reaction is controlled by π-π interactions of the aromatic system. The effectiveness of the present method is further demonstrated through its broad substrate scope with respect to donors and acceptors and its applicability in gram-scale synthesis, allowing for diversification of the phenol moiety.