PDF icon Download PDF
Synlett 2011(19): 2852-2856  
DOI: 10.1055/s-0031-1289544
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 1,2,3-Trisubstituted Pyrrolidines and 2,3-Disubstituted Tetrahydrofurans via Diastereoselective Reductive Cyclization of γ-Chloroimines and γ-Chloroketones

Mudiganti Naga Venkata Sastry, Sven Mangelinckx, Bart Lucas, Norbert De Kimpe*
Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
Fax: +32(9)2646221; e-Mail: norbert.dekimpe@ugent.be;
Further Information

Publication History

Received 16 August 2011
Publication Date:
19 October 2011 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

A new diastereoselective synthetic approach towards 1,2,3-trisubstituted pyrrolidines and 2,3-disubstituted tetrahydrofurans is described. The synthesis of the pyrrolidines involves reductive cyclization of γ-chloroketimines, which were generated in situ from the reaction of 3-substituted 5-chloro-2-pentanones and a primary amine. Various reduction conditions were explored to induce a diastereoselective reductive cyclization. 2,3-Disubstituted tetrahydrofurans were obtained by the direct reduction of 3-substituted 5-chloro-2-pentanones with sodium borohydride.

Key words

pyrrolidines - tetrahydrofurans - cyclization - halo­imines - haloketones

    References and Notes

  • 2 Wolfe JP. Eur. J. Org. Chem.  2007,  571 ; and references cited therein
  • 3 Mauger AB. J. Nat. Prod.  1996,  59:  1205 
    Search in Google Scholar
  • 4 Norton Matos M. Afonso CAM. Batey RA. Tetrahedron  2005,  61:  1221 
    Search in Google Scholar
  • 5 Kluender HCE, Benz GHHH, Britelli DR, Bullock WH, Combs KJ, Dixon BR, Schneider S, Wood JE, Van Zandt MC, Wolanin DJ, and Wilhelm SM. inventors; US  5789434.  ; Chem. Abstr. 1998, 129, 161412h
  • 6 Huang PQ. Wang SL. Ye JL. Ruan YP. Huang YQ. Zheng H. Gao JX. Tetrahedron  1998,  54:  12547 
    Search in Google Scholar
  • 7 Bermejo A. Figadère B. Zafra-Polo M.-C. Barrachina I. Estornell E. Cortes D. Nat. Prod. Rep.  2005,  22:  269 
    Search in Google Scholar
  • 8 Saleem M. Kim HJ. Ali MS. Lee YS. Nat. Prod. Rep.  2005,  22:  696 
    Search in Google Scholar
  • 9 Faul MM. Huff BE. Chem. Rev.  2000,  100:  2407 
    Search in Google Scholar
  • 10 Kang EJ. Lee E. Chem. Rev.  2005,  105:  4348 
    Search in Google Scholar
  • 11 Jones AD. Knight DW. Hibbs DE. J. Chem. Soc., Perkin Trans. 1  2001,  1182 
  • 12a Minatti A. Muñiz K. Chem. Soc. Rev.  2007,  36:  1142 
    Search in Google Scholar
  • 12b Wolfe JP. Synlett  2008,  2913 
  • 13 Miura K. Hosomi A. Synlett  2003,  143 
  • 14a Husinec S. Savic V. Tetrahedron: Asymmetry  2005,  16:  2047 
    Search in Google Scholar
  • 14b Pandey G. Banerjee P. Gadre SR. Chem. Rev.  2006,  106:  4484 
    Search in Google Scholar
  • 15a Pichon M. Figadère B. Tetrahedron: Asymmetry  1996,  7:  927 
    Search in Google Scholar
  • 15b Mitchinson A. Nadin A. J. Chem. Soc., Perkin Trans. 1  2000,  2862 
  • 16 Wolfe JP. Hay MB. Tetrahedron  2007,  63:  261 
    Search in Google Scholar
  • For isolated examples of reductive cyclizations of aromatic γ-chloroketones to 2-phenyltetrahydrofurans, see:
  • 17a Dahlenburg L. Götz R. Eur. J. Inorg. Chem.  2004,  888 
  • 17b Rang H, Goetz N, Harreus A, and Kast J. inventors; DE  4314656.  ; Chem. Abstr. 1994, 120, 269823
  • 18 For a related example on the stereospecific cyclization of diastereomeric quaternized amino alcohols, prepared by reduction of the corresponding ketones, to 2,3-disubstituted tetrahydrofurans, see: Grasshoff L. Haller R. Arch. Pharm.  1986,  319:  493 
    Search in Google Scholar
  • For selected examples, see:
  • 19a Sulmon P. De Kimpe N. Schamp N. Tinant B. Declercq JP. Tetrahedron  1988,  44:  3653 
    Search in Google Scholar
  • 19b Verniest G. Claessens S. Bombeke F. Van Thienen T. De Kimpe N. Tetrahedron  2005,  61:  2879 
    Search in Google Scholar
  • 19c Verniest G. Surmont R. Van Hende E. Deweweire A. Deroose F. Thuring JW. De Kimpe N. J. Org. Chem.  2008,  73:  5458 
    Search in Google Scholar
  • 19d D’hooghe M. De Meulenaer B. De Kimpe N. Synlett  2008,  2437 
  • 19e Denolf B. Leemans E. De Kimpe N. J. Org. Chem.  2007,  72:  3211 
    Search in Google Scholar
  • 19f Denolf B. Mangelinckx S. Törnroos KW. De Kimpe N. Org. Lett.  2006,  8:  3129 
    Search in Google Scholar
  • 19g De Kimpe N. Stevens C. Synthesis  1993,  89 
  • 19h Leemans E. Mangelinckx S. De Kimpe N. Chem. Commun.  2010,  46:  3122 
    Search in Google Scholar
  • 19i De Kimpe N. Verhé R. De Buyck L. Schamp N. J. Org. Chem.  1980,  45:  5319 
    Search in Google Scholar
  • 19j De Kimpe N. Sulmon P. Verhé R. De Buyck L. Schamp N. J. Org. Chem.  1983,  48:  4320 
    Search in Google Scholar
  • 19k Sulmon P. De Kimpe N. Schamp N. J. Chem. Soc., Chem. Commun.  1985,  715 
  • 20a Mangelinckx S. Giubellina N. De Kimpe N. Chem. Rev.  2004,  104:  2353 ; and references cited therein
    Search in Google Scholar
  • 20b Giubellina N. Aelterman W. De Kimpe N. Pure Appl. Chem.  2003,  75:  1433 ; and references cited therein
    Search in Google Scholar
  • 20c Aelterman W. De Kimpe N. Tyvorskii V. Kulinkovich O. J. Org. Chem.  2001,  66:  53 
    Search in Google Scholar
  • 21a Brimble MA. Prabaharan H. Tetrahedron  1998,  54:  2113 
    Search in Google Scholar
  • 21b Allen PR. Brimble MA. Prabaharan H. J. Chem. Soc., Perkin Trans. 1  2001,  379 
  • 21c Johnson WS. inventors; DT 1948369  .  ; Chem. Abstr. 1970, 73, 14222
  • 21d Roman BI. De Kimpe N. Stevens CV. Chem. Rev.  2010,  110:  5914 
    Search in Google Scholar
  • 22a De Kimpe N. Verhé R. De Buyck L. Moens L. Schamp N. Synthesis  1982,  43 
  • 22b De Kimpe N. Verhé R. In The Chemistry of α-Haloketones, α-Haloaldehydes and α-Haloimines   Patai S. Rappoport Z. Wiley; New York: 1988. 
  • 22c De Kimpe N. Schamp N. Org. Prep. Proced. Int.  1979,  11:  115 
    Search in Google Scholar
  • 23 Meyers AI. Snyder L. J. Org. Chem.  1992,  57:  3814 
    Search in Google Scholar
  • 24 Katritzky AR. Feng D. Qi M. Aurrecoechea JM. Suero R. Aurrekoetxea N. J. Org. Chem.  1999,  64:  3335 ; and references cited therein
    Search in Google Scholar
  • 25a Øezanka T. Prell A. Sigler K. Folia Microbiol.  2008,  53:  315 
    Search in Google Scholar
  • 25b Jáchymová J. Votruba J. Viden I. Øezanka T. Folia Microbiol.  2002,  47:  37 
    Search in Google Scholar
  • 26 Frauenrath H. Philipps T. Liebigs Ann. Chem.  1985,  1951 
  • 27 Eliel EL. Rao VS. Pietrusiewicz KM. Org. Magn. Reson.  1979,  12:  461 
    Search in Google Scholar
1

Postdoctoral Fellow of the Research Foundation-Flanders (FWO).