Unified divergent strategy towards the total synthesis of the three sub-classes of hasubanan alkaloids

Elegant asymmetric synthesis of hasubanan alkaloids have been developed over the past decades. However, a divergent approach leading to all three sub-classes of this family of natural products remains unknown. We report herein the realization of such an endeavor by accomplishing enantioselective total syntheses of four representative members. The synth- esis is characterized by catalytic enantioselective construction of the tricyclic compounds from which three different intramolecular C-N bond forming processes leading to three topologically different hasubanan alkaloids are developed. An aza-Michael addition is used for the construction of the aza-[4.4.3]-propellane structure of (-)-cepharamine, whereas an oxidation/double deprotection/intramolecular hemiaminal forming sequence is developed to forge the bridged 6/6/6/6 tetracycle of (-)-cepharatines A and C and a domino bromina- tion/double deprotection/cyclization sequence allows the build-up of the 6/6/5/5 fused tetracyclic structure of (−)-sinoracutine.