title: Total Syntheses of (-)-Mesembrane and (-)-Mesembrine via Palladium-Catalyzed Enantioselective Allylic Substitution and Zirconium-Promoted Cyclization.
abstract: 4-Arylhexahydroindole derivatives 5 were synthesized from 2-arylcyclohexenyl allylamine derivatives 4, which have a large protecting group on nitrogen, using zirconium-promoted cyclization. Reaction of 4e with Cp(2)ZrBu(2), followed by treatment with MeMgBr and then O(2), gave 2a in 63% yield by a one-pot reaction, since the approach of O(2) to zirconium was prevented by the aryl group. The total syntheses of (+/-)-mesembrane and (+/-)-mesembrine were achieved starting from 2a. To synthesize these natural products in a chiral form, the starting allylamine derivative 24 (80% yield, 86% ee, recrystallized from MeOH, 99% ee with 79% recovery) was prepared from allyl carbonate 22a and N-tosylallylamine 23 using palladium-catalyzed asymmetric amination in the presence of (S)-BINAPO as a chiral ligand. (-)-Mesembrane and (-)-mesembrine were synthesized from this allylamine 24.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Mori
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuroda
authors.forename: Chang-Shan
authors.initials: CS
authors.lastname: Zhang
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sato