Enantioselective syntheses of coronaridine and 18-methoxycoronaridine

Condensation of indoloazepines bearing the chiral Nb-substituents: 1-(R)-naphthyl-α-ethyl, [1-(R)-[(S)-2-(diphenylphospheno)ferrocenyl]-ethyl], or 2,3-(R)-ferroceno-6,6-dimethyl-1-(S)-cyclohexyl, with 4-(1,3-dioxolan-2-yl)-hexanal, or with 4-(1,3-dioxolan-2-yl)-6-methoxyhexanal, gave diastereoselectively, through a secodine-type intramolecular Diels–Alder reaction, tetracyclic intermediates that could be carried to (−)-coronaridine or to the important anti-addictive (−)-18-methoxycoronaridine. The 2,3-(R)-ferroceno-6,6-dimethyl-1-(S)-cyclohexyl chiral auxiliary was most effective, providing >99% ee of a tetracyclic intermediate after removal of the chiral auxiliary group.