An attempt to construct an indole-fused azabicyclo[3.3.1]nonane framework <i>via</i> radical cyclization.

Overview

The structural motif of an indole-fused azabicyclo[3.3.1]nonane is common in many biologically significant indole-based natural products. Because of its structural complexity, this N-bridged scaffold has become an enticing target for organic chemists. Many efficient strategies have been developed to access this ring system synthetically, but a radical approach remains unexplored. Herein, we report a radical-based strategy to construct an indole-fused azabicyclo[3.3.1]nonane structural framework. Although our initial attempt to use a Cp₂TiCl-mediated radical cyclization method was found to be unsuccessful, an alternative approach using a SmI₂-mediated radical cyclization protocol was effective for enabling the desired ring closure, leading to the target indole-fused azabicyclo[3.3.1]nonane ring system. The modular approach developed here can be extended with appropriate functionalities on this indole-fused N-bridged ring system to synthesize many alkaloids.