Unified Synthesis of Cycloheptatriene-Fused Hetero-Bicyclo[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 hetero-bicyclo[3.1.1]heptanes (X-BCHeps) 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 reaction conditions, and high efficiency. Control experiments and DFT calculatioins suggest that the cycloaddition proceeds via a concerted SN2 nucleophilic addition of troponoids to the Lewis acid-activated BCB species I. Scale-up experiments and synthetic transformations further highlight the synthetic utility. We anticipate that our findings will inspire the scientific community and motivate further exciting advances in BCB chemistry.