Conversion\nof Abundant Aldoses with Acetylacetone:\nUnveiling the Mechanism and Improving Control in the Formation of\nFunctionalized Furans Using Lewis Acidic Salts in Water

The exploration and exploitation of reactions extending\nabundant\ncarbohydrates by multiple-bond-forming reactions have recently experienced\na renaissance. Such reactions can form drug-like structural motifs\nfrom renewable substrates in water at mild temperatures. A combined\nreaction tracking and kinetic modeling approach was conducted here\nfor the conversion of glucose and other simple carbohydrates with\nacetylacetone to densely functionalized furans in the Lewis-acid-catalyzed\nGarcia Gonzalezreaction in water. Real-time <sup>13</sup>C NMR data\nwas used to identify major intermediates toward furan products, and\nkinetic modeling supports the deduced pathway and reveals its energetics.\nAlbeit the main dihydrofuran intermediate is bicyclic, with the C4\noxygen of glucose attached to the dihydrofuran ring, the use of C4-functionalized\ncarbohydrate (maltose) shows that this intermediate is not the only\non-pathway intermediate toward functionalized furans. The use of nearly\nsolvent-free eutectic mixtures favors the intermolecular initial steps\nand renders the conversion of glucose and acetylacetone largely complete\nwithin 4 h at 323 K, even in the presence of only 0.01 equiv Zr(IV).\nAs the conversion proceeds in an initial bimolecular and subsequent\nunimolecular reaction, sufficiently high substrate concentrations\nfavor the initial bimolecular reaction to polyhydroxyalkyl furan,\nwhich equilibrates with C-glycosyl furan. The use of various Lewis\nacid salt catalysts indicates that the conversion of glucose and acetylacetone\nis not uniquely favored by Zr(IV) catalysis. For instance, similarly\nefficient enolization of acetylacetone and reaction are achieved using\nHf(IV) catalysis in water. Alternative media were correctly predicted\nto catalyze the reaction at milder temperatures along the same pathway,\nincluding a concentrated solution of ZnCl<sub>2</sub> in water that\nhad previously been described as a nontoxic and recyclable homogeneous\nreaction medium for converting polysaccharides into dehydrated chemicals.