Iodide-Catalyzed Intermolecular Formal (3 + 3) Cycloaddition of Bicyclo[1.1.0]butanes and Amides: Modular Access to Heteroatom-Enriched Bicyclo[3.1.1]heptane Scaffolds

Heterobicyclo[3.1.1]heptanes (HBCHeps) are highly valuable bioisosteres of heteroaromatics. Herein, we report an iodide-catalyzed formal (3 + 3) cycloaddition of bicyclo[1.1.0]butanes with amides, providing modular access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes.This practical, metal-free method exhibits broad functional group tolerance and enables late-stage diversification of bioactive molecules, offering a versatile platform for constructing sp3-rich pyridine bioisosteres in drug discovery.