Total synthesis of (-)-2-oxo epimesembranol and (+)-dihydromaritidine a key Johnson-Claisen rearrangement.

A general approach to alkaloids of the family following a key Johnson (orthoester)-Claisen rearrangement of an enantioenriched allylic alcohol has been disclosed. The tricyclic core (1c) of -3-octahydroindoline skeleton was achieved an ester-aminolysis followed by an intramolecular aza-Michael reaction with amine under elevated temperature. Utilizing aforementioned strategy, a collective total syntheses of alkaloids, such as (-)-2-oxo-epimesembranol (1d) [the first total synthesis], (-)-6-epimesembranol (1b), and (-)-mesembrine (1a) were shown. Further this strategy was applied for total synthesis of (+)-dihydromaritidine (2c) sharing [5,11]-ethanophenanthridine skeleton.