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.