Synthetic studies on quinine: quinuclidine construction via a ketone enolate regio- and diastereoselective Pd-mediated allylic alkylation.
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.
Johns
Deidre M
DM
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
Mori
Makoto
M
Williams
Robert M
RM
D000478:Alkylation; D002384:Catalysis; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011803:Quinine / Q000737:chemistry*; D011812:Quinuclidines / Q000138:chemical synthesis*
D007659:Ketones; D011812:Quinuclidines; D010165:Palladium; D011803:Quinine