Metal-free synthesis of diverse 2-deoxy-β-N-glycosides through regio- and stereospecific aminoselenenylation of glycals

Abstract

2-Deoxy-β-N-glycosides and their analogues are key components of natural products and pharmaceuticals. However, their stereoselective synthesis remains a significant challenge due to lack of neighboring group assistance. Herein, we present an efficient and metal-free method for synthesizing structurally diverse 2-phenylseleno-β-N-glycosides via phenyliodine bistrifluoroacetate (PIFA)-promoted regio- and stereospecific aminoselenenylation of glycals utilizing readily accessible donors and N-heterocycles. This approach features mild reaction conditions, high atom economy, easy scalability and broad substrate scope (76 examples), enabling stereospecific synthesis of 2-deoxy-β-N-glycosides via a facile deselenization. The synthetic utility is demonstrated by late-stage functionalization of pharmaceutically relevant molecules and various downstream synthetic transformations. Experimental and computational studies suggest a radical-polar crossover pathway and reveal the underlying reasons for β-stereoselectivity. Overall, the present work provides an efficient approach for rapid access to valuable 2-deoxy-β-N-glycosides, and will facilitate their in-depth biological evaluations.