Total Synthesis of the Spirocyclic Bis‐Indole Alkaloid (−)‐Owerreine via a [4+2] Annulation

We report the total synthesis of (−)‐owerreine, a bis‐indole alkaloid biosynthetically assembled from two deoxoapodine units. This aspidosperma monomeric template was synthesized via a domino Michael/Mannich/ N ‐allylation sequence from a chiral indolyl‐ N ‐sulfinylimine and a DIAD‐oxidation‐promoted cycloetherification. It was further divergently transformed into an enamine precursor and an α,β−unsaturated indolenine, which were diastereoselectively assembled in the presence of the Eschenmoser salt through a [4+2] annulation. DFT calculations were deployed to gain insight into the mechanism and diastereoselectivity of this key step.