Mechanistic Insights into Lewis Acid Metal Salt-Catalyzed Glucose Chemistry in Aqueous Solution

While the mechanisms of glucose transformation via heterogeneous metal-substituted BEA zeolites have recently been elucidated, understanding of the same chemistry in homogeneous metal salt catalysts in water is still limited. Here, we investigate the mechanisms of various Lewis acid metal(III) chlorides in glucose isomerization, epimerization, and other interconversions using nuclear magnetic resonance spectroscopy (C-13 NMR and H-1 NMR). We show that the metal chlorides isomerize glucose to fructose via a C2-C1 intramolecular hydride transfer, despite their wide range of catalytic activity. Glucose epimerization to mannose proceeds via two parallel mechanisms, a reverse C2-C1 hydride transfer, and a C1-C2 intramolecular carbon shift (the Bilik reaction), with the hydride transfer being predominant. We hypothesize that the relative activity for the Bilik reaction correlates with the ionic radius of the catalyzing metal aqua cation, with an optimum at similar to 1 angstrom for lanthanide cations. In addition, we show that the metal chlorides, especially chromium(III), facilitate glucose isomerization to sorbose via a C5-C1 hydride transfer, similar to Ti-BEA. These findings bring new insights into Lewis-acid-mediated sugar rearrangements in aqueous solution.