title: The First Modular Route to Core-Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)-Catalyzed Henry Reactions.
abstract: The first modular and flexible synthesis of core-chiral bispidines was achieved by using an "inside-out" strategy. The key intermediate, a NBoc-activated bispidine lactam, was constructed in enantiomerically pure form from a chirally modified β-amino acid and 2-(acetoxymethyl)acrylonitrile in just five steps and good 48% yield. A simple addition-reduction protocol permitted a highly endo-selective introduction of substituents and, thus, a fast and variable access to 2-endo-substituted and 2-endo,N-fused bi- and tricyclic bispidines. The new diamines were evaluated as the chiral ligands in asymmetric Henry reactions. Excellent enantioselectivities of up to 99% ee and good diastereomeric ratios of up to 86:14 were reached with a copper(II) complex modified by a 2-endo,N-(3,3-dimethylpyrrolidine)-annelated bispidine. Its performance is superior to that of the well-known bispidines (-)-sparteine and the (+)-sparteine surrogate.
authors.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95447 Bayreuth (Germany).
authors.forename: Dagmar
authors.initials: D
authors.lastname: Scharnagel
authors.affiliation: Institute of Organic Chemistry, University of Regensburg, Universitätsstrasse 31, 93040 Regensburg (Germany).
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller
authors.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95447 Bayreuth (Germany).
authors.forename: Felix
authors.initials: F
authors.lastname: Prause
authors.affiliation: Institute of Inorganic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg (Germany).
authors.forename: Martin
authors.initials: M
authors.lastname: Eck
authors.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95447 Bayreuth (Germany).
authors.forename: Jessica
authors.initials: J
authors.lastname: Goller
authors.affiliation: Inorganic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95447 Bayreuth (Germany).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Milius
authors.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95447 Bayreuth (Germany). matthias.breuning@uni-bayreuth.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Breuning
keywords: Henry reaction; asymmetric synthesis; bispidine; polycyclic compounds; stereoselective catalysis