α-Stereoselective 3-Deoxy-<scp>d</scp>-<i>manno</i>-oct-2-ulosonoic Acid (Kdo) <i>O</i>-Glycosylation with a <i>p</i>-Toluenethioglycoside Donor by the (<i>p</i>-Tol)₂SO/Tf₂O Preactivation Strategy

Abstract

A convenient and efficient approach was developed to synthesize α-Kdo <i>O</i>-glycosides based on the Tf₂O/(<i>p</i>-Tol)₂SO preactivation strategy using peracetylated Kdo thioglycoside as a donor. Under the optimized reaction conditions, several <i>O</i>-glycoside products, including α-(2 → 1)-, α-(2 → 2)-, α-(2 → 3)-, and α-(2 → 6)-Kdo products, were stereoselectively synthesized in high yields. Remarkably, a series of aromatic α-Kdo <i>O</i>-glycosides were first and successfully constructed in high yields. An S_N2-like mechanism was revealed by DFT calculations and experimental results.