2-Deoxy-β-glycosides are essential components of natural products and pharmaceuticals; however, the corresponding 2-deoxy-β-glycosidic bonds are challenging to chemically construct. Herein, we describe an efficient catalytic protocol for synthesizing 2-deoxy-β-glycosides via either IPrAuNTf₂-catalyzed activation of a unique 1,2-trans-positioned C2-S-propargyl xanthate (OSPX) leaving group or (PhO)₃PAuNTf₂-catalyzed activation of a 1,2-trans-C2-ortho-alkynylbenzoate (OABz) substituent of the corresponding thioglycosides. These activation processes trigger 1,2-alkyl/arylthio-migration glycosylation, enabling the synthesis of structurally diverse 2-deoxy-β-glycosides under mild reaction conditions. The power of this strategy is demonstrated by the first synthesis of the pentasaccharide chain corresponding to velutinoside A, which features gold(I)-catalyzed construction of four successive β-l-oleandrosidic bonds in both a convergent and a one-pot glycosylation manner. Mechanistic studies, including control experiments and deuterium-labeling experiments, emphasize the crucial role of the OSPX and the involvement of the gold(I)-activated C≡C triple bond during the glycosylation process. The low-temperature NMR experiments unveiled a unique dual-coordination pattern of the gold(I) catalyst to the thiocarbonyl group and the alkynyl group of the OSPX, initiating a 5-exo-dig cyclization process. Furthermore, density functional theory (DFT) simulations reveal the ligand-induced match-mismatch effect between leaving groups OSPX and OABz and gold catalysts IPrAuNTf₂ and (PhO)₃PAuNTf₂. The DFT simulations also suggest that the formation of 2-deoxy-β-glycosidic bonds occurs via the bottom-face attack of the acceptor to the oxocarbenium intermediate, which adopts a ⁴H₃ half-chair conformation, leading to an energetically favored, ⁴C₁-conformed intermediate Dβ that is stabilized by a hydrogen bonding interaction.

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