title: Synthetic studies on quinine: quinuclidine construction via a ketone enolate regio- and diastereoselective Pd-mediated allylic alkylation.
abstract: 7-Hydroxy-quinine was synthesized by an asymmetric aldol reaction that establishes the C8 and C9 stereochemistry, followed by construction of the 3-vinyl-quinuclidine azabicyclo[2.2.2]octane by C3-C4 ring closure using an intramolecular palladium-mediated allylic alkylation with excellent regio- and diastereoselectivity. This is the first report of a ketone-enolate-stereocontrolled allylic alkylation mediated by palladium. The title compound and a dehydro-quinine analogue were evaluated for antimalarial activity.
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
authors.forename: Deidre M
authors.initials: DM
authors.lastname: Johns
authors.forename: Makoto
authors.initials: M
authors.lastname: Mori
authors.forename: Robert M
authors.initials: RM
authors.lastname: Williams
mesh_terms: D000478:Alkylation; D002384:Catalysis; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011803:Quinine / Q000737:chemistry*; D011812:Quinuclidines / Q000138:chemical synthesis*
chemical_list: D007659:Ketones; D011812:Quinuclidines; D010165:Palladium; D011803:Quinine