Highly Stereoselective 1,2‐<i>cis</i>‐Xylosylation Enabled by Reagent Modulation, Remote Participation, and Electron‐Withdrawing Synergistic Effects

Abstract Stereoselective constructions of 1,2‐ cis ‐glycosidic bonds are long‐standing challenges in chemical synthesis. In particular, achieving highly stereoselective 1,2‐ cis ‐xylosylation remains a difficult task in carbohydrates chemistry. Here, we report that highly stereoselective 1,2‐ cis ‐xylosylation could be achieved via synergistic combinations of reagent modulation, remote participation, and electron‐withdrawing effects. A variety of α‐xylosides motifs have been effectively prepared by this 1,2‐ cis ‐xylosylation protocol, including hemicellulose xyloglucan, xyloglucosyl trisaccharide motif from mammalian cells, core M3 matriglycan motif, and even α‐(1→3)‐xylosides up to 12‐mer. Furthermore, DFT calculations provided the origins of this stereoselective and synergistic 1,2‐cis‐xylosylation through S N 1 and S N 2 pathways.