Synthesis of 2-Amino-2-Deoxy Sugars via Boron-Catalyzed Coupling of Glycosyl Fluorides and Silyl Ether Acceptors

Whereas aminosugars are an important component in a variety of bioactive molecules, their stereoselective formation is made challenging by the Lewis basic nature of amino substituents. Additionally, the use of N-acyl protecting groups is often problematic due to competing formation of oxazolines during the glycosylation of 2-aminosugar derivatives. Herein, we report a boron-catalyzed strategy utilizing silyl ether glycosyl acceptors and 2-aminosugar donors that utilize the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group for the C2 amino functionality in glycosyl fluorides. This modification allows for operationally simple, room-temperature glycosylations and features a rapid reaction profile that addresses some of the limitations in the synthesis of 2-amino-2-deoxy sugar containing glycosides. Tailoring the order of reactivity of the silyl acceptors enables one-pot iterative glycosylations, thus streamlining the synthesis of complex oligosaccharides while allowing fewer intermediates and purification steps.