Lewis Acid‐Catalyzed Strain‐Enabled (3+3) Annulation of Bicyclo[1.1.0]Butanes With Indolylalcohols: Synthesis of Indole‐Fused Aza‐Bicyclo[3.1.1]Heptanes

ABSTRACT Strain release has long inspired the discovery of unique reactivity, enabling diverse synthetically valuable transformations. Bicyclo[1.1.0]butanes (BCBs), due to their high ring strain, have emerged as versatile building blocks for constructing complex bicyclic architectures. Herein, we report a Lewis acid‐catalyzed formal (3 + 3) annulation of BCBs with indolyl alcohols, providing rapid access to indole‐fused aza‐bicyclo[3.1.1]heptanes. The reaction proceeds under mild conditions, tolerates a broad range of functional groups, and delivers rigid, sp 3 ‐rich scaffolds efficiently. Mechanistic studies, including control experiments and computational analysis, indicate a stepwise pathway in which Lewis acid activation of indolyl alcohols generates reactive intermediates, while strain‐release of BCBs drives C–C bond formation, followed by C–N bond formation via ring expansion to furnish the fused Aza‐bicyclic products.