Unified Synthesis of Cycloheptatriene-Fused Heterobicyclo[3.1.1]heptanes by Lewis Acid-Catalyzed Higher-Order (8 + 3) Cycloaddition of Bicyclo[1.1.0]butanes with Troponoids

Herein, we developed a unified strategy to synthesize three libraries of medicinally attractive cycloheptatriene-fused heterobicyclo[3.1.1]heptanes (X-BCHeps, X = N, O, S) through a Lewis acid-catalyzed higher-order (8 + 3) cycloaddition of bicyclo[1.1.0]butanes (BCBs) with troponoids including azaheptafulvenes, tropones, and tropothiones. This method features excellent periselectivity, simple operation, mild conditions, and high efficiency. DFT calculations suggest that the cycloaddition proceeds via a concerted SN2 nucleophilic addition of troponoids to the Lewis acid-activated BCB species I. We anticipate that our findings will inspire the scientific community and motivate further exciting advances in BCB chemistry.