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

Although aminosugars are important components 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 the 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
employs 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.