title: Synthetic and DFT studies towards a unified approach to phlegmarine alkaloids: aza-Michael intramolecular processes leading to 5-oxodecahydroquinolines.
abstract: A diastereoselective synthesis of cis-5-oxodecahydroquinolines is described in which three stereocenters are generated in a one-pot reaction. The reaction involves a lithium hydroxide-promoted Robinson annulation/intramolecular aza-Michael domino process from an achiral acyclic tosylamine-tethered β-keto ester. The development and scope of this reaction was facilitated through the use of DFT-based mechanistic studies, which enabled the observed diastereodivergent course of the azacyclization to be rationalized. The varying stereochemistry and stability of the resulting decahydroquinolines was found to depend on whether a β-keto ester or ketone were embedded in the substrates undergoing aminocyclization. This synthetic approach gave access not only to both diastereomeric cis-decahydroquinolines from the same precursor, but also to the corresponding trans isomers, through an epimerization processes of the corresponding N-unsubstituted cis-5-oxodecahydroquinolines. The described methodology provides advanced building-blocks with the three relative stereochemistries required for the total synthesis of phlegmarine alkaloids.
authors.affiliation: Laboratori de Química Orgànica, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028-Barcelona (Spain), Fax: (+34) 934024539. benbradshaw@ub.edu.
authors.forename: Ben
authors.initials: B
authors.lastname: Bradshaw
authors.forename: Carlos
authors.initials: C
authors.lastname: Luque-Corredera
authors.forename: Gisela
authors.initials: G
authors.lastname: Saborit
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
authors.forename: Ruth
authors.initials: R
authors.lastname: Dorel
authors.forename: Carles
authors.initials: C
authors.lastname: Bo
authors.forename: Josep
authors.initials: J
authors.lastname: Bonjoch
keywords: alkaloids; aza-Michael reaction; density functional calculations; nitrogen heterocycles; stereoselective synthesis