Chiral 2-endo-substituted 9-oxabispidines: novel ligands for enantioselective copper(II)-catalyzed Henry reactions.
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.
Breuning
Matthias
M
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. breuning@chemie.uni-wuerzburg.de
Hein
David
D
Steiner
Melanie
M
Gessner
Viktoria H
VH
Strohmann
Carsten
C
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
D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D003300:Copper