Download PDF
Synthesis 2005(15): 2507-2520  
DOI: 10.1055/s-2005-872080
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Enantioenriched and Diastereomerically Pure cis-Fused Bicyclic α-Oxy-Substituted γ-Lactones via Epoxidation of Optically Active Homoaldol Products

Seda Ünaldi, Roland Fröhlich, Dieter Hoppe*
Institut für Organische Chemie, Westfälischen Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany
Fax: +49(251)8336531; e-Mail: dhoppe@uni-muenster.de;
Further Information

Publication History

Received 9 March 2005
Publication Date:
20 July 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

By applying the (-)-sparteine-mediated asymmetric deprotonation to 1-O-(2-alkylcycloalk-1-enyl)methyl N,N-diisopropylcarbamates, combined with a lithium-titanium exchange followed by addition to achiral aldehydes, enantioenriched homoaldol products 6 were prepared. Hydroxyl-directed epoxidation resulted in the cleavage of the oxirane ring by the migration of the N,N-diisopropylcarbamoyloxy group to form bicyclic γ-lactols 10 via the corresponding γ-hydroxy aldehydes. After oxidation, diastereomerically pure, penta-substituted γ-lactones 11 were obtained.

Key words

carbamates - aldol reactions - sparteine - diastereoselectivity - epoxides - bicyclic compounds - lactones

    References

  • 2 Review: Hoppe D. Hense T. Angew. Chem., Int. Ed. Engl.  1997,  36:  2282 ; Angew. Chem. 1997, 109, 2376
    CrossrefGoogle Scholar
  • Reviews:
  • 3a Hoppe D. Marr F. Brüggemann M. Organolithiums in Enantioselective Synthesis, Topics in Organometallic Chemistry   Vol 5:  Hodgson DM. Springer-Verlag; Berlin: 2003.  p.61-138  
    Google Scholar
  • 3b Hoppe D. Christoph G. The Chemistry of Organolithium Compounds   Vol 2:  Rappoport Z. Marek I. Wiley; Chichester: 2004.  p.1055-1164  
    Google Scholar
  • 4a Hoppe D. Zschage O. Angew. Chem., Int. Ed. Engl.  1989,  28:  69 ; Angew. Chem. 1989, 101, 67
    CrossrefGoogle Scholar
  • 4b Paulsen H. Graeve C. Hoppe D. Synthesis  1996,  141 
    CrossrefGoogle Scholar
  • 4c Deiters A. Hoppe D. J. Org. Chem.  2001,  66:  2842 
    CrossrefGoogle Scholar
  • 4d Beckmann E. Hoppe D. Synthesis  2005,  217 
    CrossrefGoogle Scholar
  • 4e Zeng W. Fröhlich R. Hoppe D. Tetrahedron  2005,  61:  3281 
    CrossrefGoogle Scholar
  • 5a Özlügedik M. Kristensen J. Wibbeling B. Fröhlich R. Hoppe D. Eur. J. Org. Chem.  2002,  414 
    Article in Thieme ConnectGoogle Scholar
  • 5b Özlügedik M. Kristensen J. Reuber J. Fröhlich R. Hoppe D. Synthesis  2004,  2303 
    Article in Thieme ConnectGoogle Scholar
  • 6 Zhu Y. Manske KJ. Shi Y. J. Am. Chem. Soc.  1999,  121:  4080 
    CrossrefGoogle Scholar
  • 7a Hoppe D. Lüßmann J. Jones PG. Schmidt D. Sheldrick GM. Tetrahedron Lett.  1986,  27:  3591 
    Google Scholar
  • 7b Lüßmann J. Hoppe D. Jones PG. Fittschen C. Sheldrick GM. Tetrahedron Lett.  1986,  31:  3595 
    Google Scholar
  • 8 Reuber J. Fröhlich R. Hoppe D. Org. Lett.  2004,  6:  783 
    CrossrefPubMedGoogle Scholar
  • 9 Reuber J. Dissertation   University of Münster; Germany: 2005. see also ref. 5a and 8
    Google Scholar
  • 10 Sharpless KB. Verhoeven TR. Aldrichimica Acta  1979,  12:  63 
    Google Scholar
  • 11 Mihelich ED. Daniels D. Eickhoff DJ. J. Am. Chem. Soc.  1981,  103:  7690 
    CrossrefGoogle Scholar
  • Data sets were collected with Nonius Kappa CCD diffractometers, in case of Mo-radiation equipped with a rotating anode generator. Programs used:
  • 12a Data collection: Nonius BV. COLLECT  1998, 
    Google Scholar
  • 12b Data reduction Denzo-SMN: Otwinowski Z. Minor W. Methods in Enzymology  1997,  276:  307 
    Google Scholar
  • Absorption correction SORTAV:
  • 12c Blessing RH. Acta Cryst.  1995,  A51:  33 
    Google Scholar
  • 12d Blessing RH. J. Appl. Cryst.  1997,  30:  421 ; Denzo: Otwinowski Z., Borek D., Majewski W., Minor W.; Acta Cryst.; 2003, A59: 228;
    Google Scholar
  • 12e Structure solution SHELXS-97: Sheldrick GM. Acta Cryst.  1990,  A46:  467 
    Google Scholar
  • 12f Structure refinement SHELXL-97: Sheldrick GM. Universität Göttingen  1997, 
    Google Scholar
  • 12g Graphics Diamond: Brandenburg K. Universität Bonn  1997, 
    Google Scholar
  • 12h

    CCDC-264379, 264380, and 264831 contain the supplementary crystallographic data for this paper. This data can be obtained free of charge at www.cam.ac.uk/conts/retrieving.html [or from Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (internat.) +44 (1223)336-033; E-mail: deposit@ccdc.cam.ac.uk].
    Google Scholar
1

Responsible for X-ray structure data.