Enantioselective syntheses of coronaridine and 18-methoxycoronaridine

Condensation of indoloazepines bearing the chiral Nb-substituents: 1-(R)-na phthyl-alpha -ethyl, [1-(R)-[(S)-2-(diphenylphospheno)ferrocenyl]-ethyl], o r 2,3-(R)-ferroceno-6,6-dimethyl-1-(S)-cyclohexyl, with 4-(1,3-dioxolan-2-y l)-hexanal, or with 4-(1,3-dioxolan-2-yl)-6-methoxyhexanal, gave diastereos electively, through a secodine-type intramolecular Diels-Alder reaction, te tracyclic intermediates that could be carried to (-)-coronaridine or to the important anti-addictive (-)-18-methoxycoronaridine. The 2,3-(R)-ferroceno -6,6-dimethyl-1-O-cycrohexyl chiral auxiliary was most effective, providing >99% ee of a tetracyclic intermediate after removal of the chiral auxiliar y group. (C) 2001 Elsevier Science Ltd. All rights reserved.