(58f) Stereospecific Sugar Rearrangements Mediated By Lewis Acidic Molecular Sieves

Lewis acidic tetravalent heteroatoms (Sn⁴⁺, Ti⁴⁺, Zr⁴⁺) isolated within silica-based molecular sieves catalyze sugar isomerization and epimerization reactions, with selectivity and stereochemical specificity that is inaccessible to homogeneous or heterogeneous bases that mediate sugar rearrangements via enediol intermediates. The selectivity and stereospecificity characteristic of sugar catalysis by Lewis acids reflect the ability of a single electrophilic metal center to: (i) coordinate with two oxygenated functional groups (a carbonyl and an alcohol) within a single monosaccharide, and (ii) subsequently mediate intramolecular Meerwein-Ponndorf-Verley reduction and Oppenauer oxidation (MPVO) cycles between the bound oxygenated moieties. Intramolecular MPVO cycles involve the nucleophilic addition of electron-rich H and C atoms, which are located on the carbon center adjacent to the bound alkoxide oxygen, to electron-deficient carbon atoms in bound carbonyl groups. Such intramolecular MPVO cycles, the mechanistic details of which are confirmed via isotopic tracer studies and via kinetic studies of ²H and ¹³C-labeled reactants with Lewis acidic heterogeneous solids, describe: (i) glucose-fructose isomerization via intramolecular H-shift from C2 to C1 centers, (ii) glucose-mannose epimerization via intramolecular C-shift of C3 atoms from C2 to C1 centers, and (iii) glucose-sorbose isomerization via intramolecular H-shift from C5 to C1 centers. Analogous mechanisms for glucose-fructose isomerization and glucose-mannose epimerization are found in enzymatic (Mg²⁺- and Mn²⁺-based D-xylose isomerase) and homogeneous (Ni²⁺ diamine complexes) Lewis acids, respectively, while no enzymatic or homogeneous analog appears to have been reported for glucose-sorbose isomerization. The catalytic effects of the environments that confine and surround Lewis acid centers are also probed in kinetic studies of sugar isomerization in liquid media (water, methanol) on hydrophobic (defect-free) and hydrophilic (defective) titanosilicates. The presence of one or more Lewis acid centers, and of hydrophobic pockets that confine them, reflect archetypal structural features of catalytic ensembles found in homogeneous, heterogeneous and biological systems that mediate stereospecific intramolecular sugar rearrangements.