Base-Mediated (4+3) Strain-Release Cycloaddition of Indoles with Bicyclo[1.1.0]butanes

Strain-release reactivity of bicyclo[1.1.0]butanes (BCBs) has predominantly enabled formal [2+2] annulations, while higher-order cycloadditions remain unexplored. We report a highly diastereoselective, base-mediated (4+3) strain-release cycloaddition of indoles bearing tethered Michael acceptors with BCBs, providing direct access to azabicyclo[4.1.1]octane-fused indoles. The reaction proceeds under mild, transition-metal-free conditions, preserves indole aromaticity, and furnishes products as single diastereomers in good to excellent yields. Control experiments and DFT studies support an ionic pathway initiated by indole deprotonation and strain-release nucleophilic attack on the BCB, with diastereoselectivity arising from a favored annulation transition state. This work expands the synthetic utility of BCBs to unprecedented (4+3) annulations and provides efficient access to three-dimensional azepino-indole scaffolds.