(458e) C-C Coupling through Direct Aldol Condensation Using Lewis Acid Zeolites

The development of biomass conversion schemes has led to considerable interest in aldol condensation, a key carbon-carbon (C-C) coupling reaction in organic synthesis. Aldol reactions are particularly important for transforming short-chain oxygenated molecules into fuels and value-added chemicals. Here, we show that Lewis acid zeolites Hf-, Sn-, and Zr-Beta catalyze the cross-aldol condensation of aromatic aldehydes with acetone. NMR studies with isotopically labelled molecules support a soft enolization pathway wherein the α-proton of acetone is transferred to the zeolite lattice, generating a metal enolate intermediate that can readily attack a carbonyl group to form a C-C bond. These C-C coupling reactions were conducted under mild conditions with near quantitative yields of the single cross-aldol condensation product for several substrates including the biomass-derived platform molecule 5-(hydroxymethyl)furan. Sn-Beta was also used to catalyze coupling of 1,3-dihydroxyacetone and formaldehyde through aldol addition followed by isomerization, dehydration, and keto-enol tautomerization to form α-hydroxy-γ-butyrolactone. Importantly, these Lewis acid zeolites maintain C-C coupling activity in the presence of water. Unlike traditional base catalysts, these materials are also active in acidic solutions.