Enantioselective Total Synthesis of Cepharatines via Bioinspired Ring Reconstruction.

We describe enantioselective total syntheses of cepharatines A-D, members of the hasubanan alkaloid family, which feature an unusual tetracyclic skeleton including an azabicyclo[3.3.1]nonane motif. A key reaction is a regio-divergent oxidative phenolic coupling reaction that affords the tricyclic core structure of hasubanan with different substitution patterns on the A-ring, including the all-carbon quaternary stereogenic center at C13, in a single step. The characteristic tetracyclic azabicyclo[3.3.1]nonane motif was constructed by means of a bioinspired cascade reaction involving the retro-aza-Michael reaction/hemiaminal formation.