Stereoselective Synthesis of 2‐Deoxy Glycosides via a Novel 2‐O‐Resided (o‐Alkynyl)benzoate‐Initiated 1,2‐Sulfur Migration/Glycosylation and Desulfurization Protocol as well as Mechanism Elucidation

Comprehensive Summary Stereoselective construction of 2‐deoxy‐glycosidic linkages has been achieved by the 1,2‐sulfur migration/glycosylation and desulfurization strategy; however, current protocols suffer from harsh reaction conditions and unsatisfactory stereoselectivity, particularly during the 1,2‐ S ‐migration/glycosylation step. With 2‐ O ‐resided ( o ‐alkynyl)benzoate and anomeric p ‐methoxyphenylsulfenyl groups as the initiating and migrating groups, respectively, a novel protocol for the efficient synthesis of 2‐deoxy‐glycosides via the 1,2‐sulfur migration/glycosylation‐desulfurization strategy has been established, which is featured by the mild and catalytic reaction conditions, expanded substrate scope, as well as good to excellent diastereoselectivity. Mechanism studies determined hyperconjugation‐stabilized oxocarbenium ion as the key intermediate, achieving high 1,2‐ trans stereocontrol through thermodynamic, steric, as well as electrostatic effects. This provides the fresh insight for the operative mechanism of the 1,2‐sulfur migration/glycosylation and desulfurization strategy, further corroborated by the elaborately designed testing reactions and DFT calculations. Moreover, the synthetic potential of the newly established protocol was examined by the practical synthesis of natural product, culminating in the acquisition of digoxin from acetylated digoxigenin in 25% overall yield through an 8‐step longest linear sequence.