Highly stereoselective construction of polycyclic benzofused tropane scaffolds and their latent bioactivities: bifunctional phosphonium salt-enabled cyclodearomatization process

Structurally fused heterocycles encompassing a centerpiece of benzotropane are significant scaffolds with a plethora of promising biological activities, but such molecular architectures pose a long-standing daunting synthetic challenge. Herein, we reported a highly efficient asymmetric cyclodearomatization of 2-nitrobenzofurans with cyclic azomethine ylides by employing bifunctional phosphonium salts as phase-transfer catalysts. Under optimized reaction conditions, a diverse array of polycyclic benzofused tropane derivatives with four contiguous 4 degrees/3 degrees stereocenters were readily synthesized in both high yields and diastereoselectivities with up to >99% ee. The practicality and utility of this protocol were further demonstrated by the scaled-up reaction and facile elaborations. Moreover, preliminary investigations into their antitumor activities were also presented.