Palladium-catalyzed double strain-release (3 + 3) cycloaddition for the synthesis of vinylbicyclo[3.1.1]heptanes

Abstract

All-carbon bicyclo[3.1.1]heptanes are important structural motifs in bioactive compounds and serve as bioisosteres for substituted benzenes. However, their synthesis, especially through polar (3 + 3) cycloaddition strategies, remains underexplored. Herein, we present a palladium-catalyzed double strain-release (3 + 3) cycloaddition involving Bicyclo[1.1.0]butanes (BCBs) and vinylcyclopropanes. The reaction tolerates a variety of BCBs and vinylcyclopropane derivatives, including spirovinylcyclopropane oxindoles, providing access to structurally diverse BCHeps with potential applications in drug discovery. The practicality of this method is demonstrated through scale-up reactions and downstream transformations of the cycloadducts.