Domino Michael/Mannich/N-Alkylation Route to the Tetrahydrocarbazole Framework of Aspidosperma Alkaloids: Concise Total Syntheses of (−)-Aspidospermidine, (−)-Tabersonine, and (−)-Vincadifformine

Abstract

We report a novel, asymmetric domino Michael/Mannich/N-alkylation sequence for the rapid assembly of the tetrahydrocarbazole framework of Aspidosperma alkaloids. This method was utilized in the concise total syntheses of classical targets (-)-aspidospermidine, (-)-tabersonine, and (-)-vincadifformine in 10 or 11 steps. Additional key steps include ring-closing metathesis to prepare the D-ring and Bosch-Rubiralta spirocyclization to prepare the C-ring.