Bismuth(III) Triflate-Catalyzed Cascade Annulation of Hydroxy-α-Pyrones and δ-Unsaturated-γ-Ketoesters for the Assembly of 2-Pyrone-Fused Oxaspirolactones.

Pyrones and oxaspirolactones constitute prominent structural motifs found in a wide range of bioactive natural products and synthetic analogues. Owing to their intriguing structural features and diverse biological activities, these scaffolds represent valuable targets in natural product synthesis and medicinal chemistry. Herein, we report a cascade annulation reaction between hydroxy-α-pyrones and δ-unsaturated-γ-ketoesters, affording tricyclic 2-pyrone-fused [6,5]-oxaspirolactones via a reaction sequence of Michael addition, hemiketalization, and lactonization. Comprehensive optimization studies identified Bi(OTf)3 as an efficient catalytic system, enabling broad substrate scope and delivering the desired products in good to excellent yields.