One-Pot Assembly of 2-Pyrones through Copper-Catalyzed Cyclization of Propargylamines with Malonates

Synthesis and application of polysubstituted 2-pyrones have attracted a great deal of attention over the past several decades. Recently, transition metal-catalyzed transformations of propargylamines have emerged as a powerful strategy for accessing diverse heterocyclic frameworks. Here, we report an efficient protocol for the synthesis of structurally diverse 4,6-disubstituted 2-pyrones from readily available propargylamines and malonates. Mechanistic investigations reveal that this formal [1 + 2 + 3] annulation reaction proceeds via a sequential copper-catalyzed oxidative cross-dehydrogenative coupling, 1,3-amino migration, and acid-promoted deaminative cyclization in a one-pot operation. The method exhibits broad functional group tolerance, providing a versatile and robust platform for the rapid assembly of heterocyclic libraries. Furthermore, the synthetic utility of this methodology is demonstrated through further transformations of the obtained products, highlighting its practical value in organic synthesis.