Total Synthesis of (−)-Owerreine and (−)-Anhydrovobtusine

We report the first total synthesis of the heterodimeric aspidosperma-aspidosperma alkaloids (-)-owerreine and (-)-anhydrovobtusine. Our synthesis of these bisindole alkaloids was achieved via a late-stage double C7 methylenation sequence, leading to the union of two hexacyclic aspidosperma components. Our synthetic strategy was based on our hypothesis for the biosynthesis of these alkaloids and required the directed assembly of complex fragments related to natural alkaloids (-)-beninine (the northern half) and (-)-deoxoapodine (the southern half). The (-)-beninine-related intermediate was accessed via an oxidative Pd-catalyzed intramolecular C6'-O bond formation, an Ir-catalyzed C17' boronation as a prelude to introduction of the C17'-ether, and transannular spiro-cyclization to afford the C12'-C19' bond. A readily available and enantiomerically enriched lactam, previously used in our total synthesis of (-)-deoxoapodine, served as the common precursor to both halves of these bisindole alkaloids.