Download PDF
Synthesis 2011(5): 708-710  
DOI: 10.1055/s-0030-1259483
SHORTPAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Easy Access to 9-Epimers of Cinchona Alkaloids: One-Pot Inversion by Mitsunobu Esterification-Saponification

Łukasz Sidorowicz, Jacek Skarżewski*
Department of Organic Chemistry, Faculty of Chemistry, Wrocaw University of Technology, 50-370 Wrocaw, Poland
Fax: +48(71)3284064; e-Mail: jacek.skarzewski@pwr,wroc.pl;
Further Information

Publication History

Received 22 November 2010
Publication Date:
31 January 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

Cinchona alkaloids were efficiently converted into their 9-epi diastereomers. The applied one-pot procedure was based on the Mitsunobu esterification with 4-nitrobenzoic acid followed by in situ saponification of the ester. This method requires only one column chromatography, easily separating the epi-isomer from the native alkaloid and the Mitsunobu byproducts. The procedure gives higher yields and is operationally simpler than the previously used stereoselective hydrolysis of the corresponding sulfonic acid esters.

Key words

cinchona alkaloids - Mitsunobu reaction - inversion - alcohols - chiral pool

    References

  • 1a Kacprzak K. Gawroñski J. Synthesis  2001,  961 
  • 1b Hoffmann HMR. Frackenpohl J. Eur. J. Org. Chem.  2004,  4293 
  • 1c Tian S.-K. Chen Y. Hang J. Tang L. Deng L. Acc. Chem. Res.  2004,  37:  621 
    Search in Google Scholar
  • 1d Connon SJ. Chem. Commun.  2008,  2499 
  • 1e Cinchona Alkaloids in Synthesis and Catalysis, Ligands, Immobilization and Organocatalysis   Song CE. Wiley-VCH; Weinheim: 2009. 
  • 1f Marcelli T. Hiemstra H. Synthesis  2010,  1229 
  • 2 Caner H. Biedermann PU. Agranat I. Chirality  2003,  15:  637 ; and refs cited therein
    CrossrefSearch in Google Scholar
  • 3a Suszko J. Szelg F. Bull. Int. Acad. Pol. Sci. Lett. Cl. Sci. Math. Nat., Ser. A  1936,  403 ; Chem. Abstr. 1937, 31, 1816
  • 3b Braje WM. Holzgrefe J. Wartchow R. Hoffmann HMR. Angew. Chem. Int. Ed.  2000,  39:  2085 
    Search in Google Scholar
  • 4a Zieliñska-Bajet M. Kucharska M. Skar¿ewski J. Synthesis  2006,  1176 
  • 4b Zielñska-Bajet M. Siedlecka R. Skar¿ewski J. Tetrahedron: Asymmetry  2007,  18:  131 
    Search in Google Scholar
  • 4c Zieliñska-Bajet M. Skar¿ewski J. Tetrahedron: Asymmetry  2009,  20:  1992 
    Search in Google Scholar
  • 5a Mitsunobu O. Kimura J. Fujisawa Y. Bull. Chem. Soc. Jpn.  1972,  45:  245 
    Search in Google Scholar
  • For general reviews on the Mitsunobu reaction, see:
  • 5b Mitsunobu O. Synthesis  1981,  1 
  • 5c Huges DL. Org. React.  1992,  42:  335 
    Search in Google Scholar
  • 5d Dembinski R. Eur. J. Org. Chem.  2004,  2763 
  • 5e But TYS. Toy PH. Chem. Asian J.  2007,  2:  1340 
    Search in Google Scholar
  • 5f Swamy KCK. Kumar NNB. Balaraman E. Kumar KVPP. Chem. Rev.  2009,  109:  2551 
    Search in Google Scholar
  • 6a Hughes DL. Reamer RA. J. Org. Chem.  1996,  61:  2967 
    Search in Google Scholar
  • 6b Hughes AB. Sleebs MM. J. Org. Chem.  2005,  70:  3079 
    Search in Google Scholar
  • 6c Schenk S. Weston J. Anders E. J. Am. Chem. Soc.  2005,  127:  12566 
    Search in Google Scholar
  • 7a Brunner H. Bügler J. Bull. Soc. Chim. Belg.  1997,  106:  77 
    Search in Google Scholar
  • 7b For a recent example, see: Kacprzak K. Gierczyk B. Tetrahedron: Asymmetry  2010,  21:  2740 
    Search in Google Scholar
  • 8a Röper S. Franz MH. Wartchow R. Hoffmann HMR. J. Org. Chem.  2003,  68:  4944 
    Search in Google Scholar
  • 8b Franz MH. Röper S. Wartchow R. Hoffmann HMR. J. Org. Chem.  2004,  69:  2983 
    Search in Google Scholar
  • 9 Hiratake J. Inagaki M. Yamamoto Y. Oda J. J. Chem. Soc., Perkin Trans. 1  1987,  1053 
    Crossref