Polyphosphoric acid (PPA) mediated direct synthesis of γ-pyrones

γ-Pyrones are carbonyl-containing aromatic heterocycles commonly found as scaffolds in bioactive natural products and have been extensively studied for their pharmacological properties including: antibiotic, antibacterial, antiparasitic, analgesic, and antioxidative effects. Unfortunately, existing synthetic routes to γ-pyrones often require the use of transition metal catalysts, multistep procedures, harsh reaction conditions, and prolonged reaction times. Here, a new mild, efficient, one-step, solvent-free method is reported for the synthesis of 26 γ-pyrone derivatives using commercially available ß-ketoesters and polyphosphoric acid (PPA) or Eaton's Reagent. The reactions proceed at 80°C within 2-5 hours to afford the desired products in moderate to excellent yields (44-90%), providing a practical alternative route to these compounds for biological evaluation.