Five-Step Total Synthesis of (±)-Aspidospermidine by a Lactam Strategy via an Azomethine Ylide

A five-step total synthesis of (+/-)-aspidospermidine (1) based on a lactam strategy is reported. Our synthesis features an iridium-catalyzed reductive Michael addition/[3+2] cycloaddition cascade to give a tricyclic ketone intermediate from a simple lactam via an azomethine ylide. The developed strategy enables easily available lactams to be used as stable surrogates of multisubstituted amines and would be applicable to a unified total synthesis of complex Aspidosperma alkaloids.

Automated summary

A five-step total synthesis of (+/-)-aspidospermidine based on a lactam strategy is reported, featuring an iridium-catalyzed reductive Michael addition/[3+2] cycloaddition cascade for the generation of a tricyclic ketone intermediate from a simple lactam. This strategy allows for easily available lactams to be used as stable surrogates of multisubstituted amines and could be applicable to a unified total synthesis of complex Aspidosperma alkaloids.