Unexpected T3P-Mediated Enaminoester Cascade Cyclization to Access 4-Pyridones

The development of novel one-pot cascade protocols for synthesizing biologically significant nitrogen heterocycles plays a vital role in drug discovery and development. We report here a new and unexpected T3P-mediated one-pot transformation of amines and β-ketoesters into 4-pyridones via an enaminoester cascade cyclization process. This method affords structurally diverse and readily multi-tailorable 4-pyridones with up to 99% yields in 1 h at 70 °C, providing rapid access to a pharmaceutically significant heterocyclic motif. Furthermore, this method shows a low E-factor (5.18), a low process mass intensity (PMI, 6.18), and an excellent GreenScore (86). To the best of our knowledge, this study presents the first highly efficient and straightforward multicomponent synthesis of 4-pyridones using readily available substrates.