Total Synthesis of (-)-Aspidospermidine via an Enantioselective Palladium-Catalyzed Allylic Substitution Strategy.

A total synthesis of (-)-aspidospermidine via an enantioselective Pd-catalyzed allylic substitution strategy is reported. This represents the first application of a Pd-catalyzed allylic substitution with a 3-substituted indole derivative in the synthesis of alkaloids. In our synthetic route, the allylic substitution reaction was the stereo defining step. The pentacyclic framework was then constructed in a fully diastereoselective sequence. This culminated in the shortest enantioselective synthesis of aspidospermidine reported to date, in seven linear steps.