title: Synthetic and Organocatalytic Studies of Quinidine Analogues with Ring-Size Modifications in the Quinuclidine Moiety.
abstract: Six highly enantiopure analogues of [2.2.2] were synthesized with five- or seven-membered rings in the (original) quinuclidine skeleton. Five of these compounds were prepared through epoxide opening by a secondary cyclic amine, providing the nor- and homoquinuclidine moieties through five- and six-membered ring formation. This method failed in the case of seven-membered ring formation, so for that particular ring size a different synthetic route starting from 3-quinuclidone was applied. The six novel analogues were examined as organocatalysts in four asymmetric conjugate addition reactions and the results compared with those of known cinchona alkaloid catalysts. This study shows that modification of the quinuclidine ring can have a substantial influence on catalyst activity and enantioselectivity. To acquire more insight into the characteristics of the new catalysts, the pKaH values were determined by means of fluorescence spectroscopy. Furthermore, relative reaction rates of conjugate thiol additions reactions catalyzed by these quinidine analogues were measured through polarimetry.
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Arjen C
authors.initials: AC
authors.lastname: Breman
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Gydo
authors.initials: G
authors.lastname: van der Heijden
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: van Maarseveen
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Steen
authors.initials: S
authors.lastname: Ingemann
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands. h.hiemstra@uva.nl.
authors.forename: Henk
authors.initials: H
authors.lastname: Hiemstra
keywords: Michael addition; amino alcohols; asymmetric synthesis; basicity; organocatalysis