Molecular modeling of saccharides, 8. Selective 2‐O‐benzylation of sucrose: A facile entry to its 2‐deoxy‐ and 2‐keto‐derivatives and to sucrosamine

Generation of the molecular electrostatic potential (MEP) profiles, in color‐coded form, on the solvent‐accessible contact surfaces of the two main conformations that sucrose adopts in vacuo as well as in aprotic solvents (e.g. DMF), clearly shows the secondary glucosyl‐2‐OH to be the most electropositive of the altogether eight hydroxyl groups–conceivably due to the persistence of an intramolecular hydrogen bond of the 2g‐O…︁HO‐1f type. The notion that the 2g‐OH is accordingly the hydroxyl group most readily deprotonated in aprotic solvents, and that the resulting sucrose 2g‐O‐alkoxide is the one best stabilized by intramolecular hydrogen bonding, received ample substantiation by smoothly achieving a highly regioselective (>80%) 2g‐O‐benzylation in DMF with NaH/benzyl bromide. The resulting 2g‐O‐benzyl‐sucrose (2)– minor products being the 1f‐O‐ (3) and 3f‐O‐isomers (4)– was converted, by acetylation and hydrogenolysis into the 2g‐OH‐free sucrose heptaacetate 6, isolable in crystalline form in 42% yield based on sucrose, thus opening up a ready entry to 2g‐O‐modified derivatives: 2‐deoxy‐sucrose (12) via radical deoxygenation of a 2g‐O‐thiocarbamate, 2‐keto‐sucrose perbenzoate 7 via PDC oxidation, or N‐acetyl‐sucrosamine 14 and its manno‐analog 16 through oximation of 7 and subsequent borane reduction.