Conversion of Abundant Aldoses with Acetylacetone: Unveiling the Mechanism and Improving Control in the Formation of Functionalized Furans Using Lewis Acidic Salts in Water

Abstract

The exploration and exploitation of reactions extending abundant carbohydrates by multiple-bond-forming reactions have recently experienced a renaissance. Such reactions can form drug-like structural motifs from renewable substrates in water at mild temperatures. A combined reaction tracking and kinetic modeling approach was conducted here for the conversion of glucose and other simple carbohydrates with acetylacetone to densely functionalized furans in the Lewis-acidcatalyzed Garcia Gonzalezreaction in water. Real-time 13 C NMR data was used to identify major intermediates toward furan products, and kinetic modeling supports the deduced pathway and reveals its energetics. Albeit the main dihydrofuran intermediate is bicyclic, with the C4 oxygen of glucose attached to the dihydrofuran ring, the use of C4-functionalized carbohydrate (maltose) shows that this intermediate is not the only on-pathway intermediate toward functionalized furans. The use of nearly solvent-free eutectic mixtures favors the intermolecular initial steps and renders the conversion of glucose and acetylacetone largely complete within 4 h at 323 K, even in the presence of only 0.01 equiv Zr(IV). As the conversion proceeds in an initial bimolecular and subsequent unimolecular reaction, sufficiently high substrate concentrations favor the initial bimolecular reaction to polyhydroxyalkyl furan, which equilibrates with C-glycosyl furan. The use of various Lewis acid salt catalysts indicates that the conversion of glucose and acetylacetone is not uniquely favored by Zr(IV) catalysis. For instance, similarly efficient enolization of acetylacetone and reaction are achieved using Hf(IV) catalysis in water. Alternative media were correctly predicted to catalyze the reaction at milder temperatures along the same pathway, including a concentrated solution of ZnCl 2 in water that had previously been described as a nontoxic and recyclable homogeneous reaction medium for converting polysaccharides into dehydrated chemicals.