Total Synthesis of (±)-Aspidospermidine, (±)-Aspidofractinine, (±)-Limaspermidine, and (±)-Vincadifformine via a Cascade and Common Intermediate Strategy

A concise strategy for the total synthesis of several Aspidosperma alkaloids is reported. A Suzuki-Miyaura cross-coupling provides access to a 2-vinyl indole that undergoes a Diels-Alder cascade reaction with butyn-2-one to deliver a pyrroloindoline intermediate. This undergoes cascade amidation, reduction, skeletal rearrangement, and intramolecular Michael addition to provide a common intermediate containing the full framework of the Aspidosperma alkaloids. The utility of this intermediate is shown in the synthesis of four different natural products.