title: Chiral 2-endo-substituted 9-oxabispidines: novel ligands for enantioselective copper(II)-catalyzed Henry reactions.
abstract: A flexible approach, applicable on a gram scale, to chiral 2-endo-substituted 9-oxabispidines was developed. The key intermediate, a cis-configured 6-aminomethylmorpholine-2-carbonitrile, was prepared from (R)-3-aminopropane-1,2-diol and 2-chloroacrylonitrile. The 2-endo substituent was introduced by Grignard addition, cyclization, and exo-selective reduction, thus furnishing the enantiomerically pure bi- and tricyclic 9-oxabispidines in 19-59 % yield. The CuCl(2) complex of the tricyclic 9-oxabispidine, which carries an 2-endo,N-anellated piperidine ring, is an excellent catalyst for enantioselective Henry reactions giving the S-configured beta-nitro alcohols in 91-98 % ee (13 examples). Surprisingly, the analogous copper complexes of the bicyclic 9-oxabispidines delivered the enantiocomplementary R-configured products in 33-57 % ee. The respective transition states were discussed.
authors.affiliation: Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. breuning@chemie.uni-wuerzburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Breuning
authors.forename: David
authors.initials: D
authors.lastname: Hein
authors.forename: Melanie
authors.initials: M
authors.lastname: Steiner
authors.forename: Viktoria H
authors.initials: VH
authors.lastname: Gessner
authors.forename: Carsten
authors.initials: C
authors.lastname: Strohmann
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D003300:Copper