Exploiting π and hydrogen bonding interactions of a 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 interaction (NCI)-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 (β : α > 30 : 1) synthesis of intriguing O-aryl glycosides using a simple, easily accessible, cost-effective and strain-free unsubstituted pyridinium tetrafluoroborate salt as a catalyst under 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 of 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.