Synlett 2011(5): 589-593  
DOI: 10.1055/s-0030-1259553
SYNPACTS
© Georg Thieme Verlag Stuttgart ˙ New York

Cyclization of Aminocyclopropanes in Indole Alkaloids Synthesis

Filippo De Simone, Jérôme Waser*
Laboratory of Catalysis and Organic Synthesis, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO BCH 4306, 1015 Lausanne, Switzerland
Fax: +41(21)6939700; e-Mail: jerome.waser@epfl.ch;
Further Information

Publication History

Received 9 December 2010
Publication Date:
11 February 2011 (online)

Abstract

The regioselective and diastereoselective cyclization of acyliminium intermediates generated from aminocyclopropanes on unprotected indoles is presented. The recent results obtained in our group are compared with previous intermolecular reactions with aminocyclopropanes as well as with other cyclization methods involving iminium ions and unprotected indoles. A first speculative analysis of possible reaction mechanisms allows rationalizing the observed selectivity. The high potential of the method for the synthesis of natural alkaloids is demonstrated in the formal synthesis of aspidospermidine and the total synthesis of goniomitine.

    References and Notes

  • 1 Ma SM. In Handbook of Cyclization Reactions   Wiley-VCH; Weinheim: 2009. 
  • 2a Reissig HU. Zimmer R. Chem. Rev.  2003,  103:  1151 
  • 2b Gnad F. Reiser O. Chem. Rev.  2003,  103:  1603 
  • 2c Yu M. Pagenkopf BL. Tetrahedron  2005,  61:  321 
  • 2d Carson CA. Kerr MA. Chem. Soc. Rev.  2009,  38:  3051 
  • 2e De Simone F. Waser J. Synthesis  2009,  3353 
  • 2f Lebold TP. Kerr MA. Pure Appl. Chem.  2010,  82:  1797 
  • 3a Stork G. Marx M. J. Am. Chem. Soc.  1969,  91:  2371 
  • 3b Stork G. Gregson M. J. Am. Chem. Soc.  1969,  91:  2373 
  • 3c Stork G. Grieco PA. J. Am. Chem. Soc.  1969,  91:  2407 
  • 3d Corey EJ. Balanson RD. Tetrahedron Lett.  1973,  3153 
  • 3e Danishefsky S. Acc. Chem. Res.  1979,  12:  66 
  • 4a Wenkert E. Alonso ME. Buckwalter BL. Chou KJ. J. Am. Chem. Soc.  1977,  99:  4778 
  • 4b Wenkert E. Acc. Chem. Res.  1980,  13:  27 
  • 4c Reissig HU. Hirsch E. Angew. Chem., Int. Ed. Engl.  1980,  19:  813 
  • 4d Brückner C. Reissig HU. Angew. Chem., Int. Ed. Engl.  1985,  24:  588 
  • For a few leading references, see:
  • 5a Yu M. Pagenkopf BL. J. Am. Chem. Soc.  2003,  125:  8122 
  • 5b Yu M. Pagenkopf BL. Org. Lett.  2003,  5:  5099 
  • 5c Young IS. Kerr MA. Org. Lett.  2004,  6:  139 
  • 5d Young IS. Williams JL. Kerr MA. Org. Lett.  2005,  7:  953 
  • 5e Pohlhaus PD. Johnson JS. J. Org. Chem.  2005,  70:  1057 
  • 5f Parsons AT. Johnson JS. J. Am. Chem. Soc.  2009,  131:  14202 
  • 5g Parsons AT. Smith AG. Neel AJ. Johnson JS. J. Am. Chem. Soc.  2010,  132:  9688 
  • 6 Piers E. In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Pergamon; New York: 1991.  p.971 
  • 7a Nazarov IN. Zaretskaya II. Izv. Akad. Nauk. SSSR. Ser. Khim.  1941,  211 
  • 7b Habermas KL. Denmark SE. Jones TK. Org. React. (N. Y.)  1994,  45:  1 
  • 8a Jones TK. Denmark SE. Helv. Chim. Acta  1983,  66:  2377 
  • 8b Liang GX. Trauner D. J. Am. Chem. Soc.  2004,  126:  9544 
  • For reviews, see:
  • 8c Frontier AJ. Collison C. Tetrahedron  2005,  61:  7577 
  • 8d Pellissier H. Tetrahedron  2005,  61:  6479 
  • 8e Tius MA. Eur. J. Org. Chem.  2005,  2193 
  • 8f Nakanishi W. West FG. Curr. Opin. Drug Discovery Dev.  2009,  12:  732 
  • 9a Murphy WS. Wattanasin S. Tetrahedron Lett.  1980,  21:  1887 
  • 9b Murphy WS. Wattanasin S. J. Chem. Soc., Perkin Trans. 1  1981,  2920 
  • 9c Murphy WS. Wattanasin S. J. Chem. Soc., Perkin Trans. 1  1982,  1029 
  • 9d Tsuge O. Kanemasa S. Otsuka T. Suzuki T. Bull. Chem. Soc. Jpn.  1988,  61:  2897 
  • 9e De Simone F. Waser J. Chimia  2009,  63:  162 
  • 10 De Simone F. Andres J. Torosantucci R. Waser J. Org. Lett.  2009,  11:  1023 
  • 11 He W. Herrick IR. Atesin TA. Caruana PA. Kellenberger CA. Frontier AJ. J. Am. Chem. Soc.  2008,  130:  1003 
  • 12 Yadav VK. Kumar NV. Chem. Commun.  2008,  3774 
  • The introduction of an ester group in α position to the ketone also allows a further polarization of the cyclopropane and an extension of the scope:
  • 13a Saget, T.; De Simone, F.; Waser, J. unpublished results
  • 13b Patil DV. Phun LH. France S. Org. Lett.  2010,  12:  5684 
  • 14a Wenkert E. Halls TDJ. Kwart LD. Magnusson G. Showalter HDH. Tetrahedron  1981,  37:  4017 
  • 14b Wenkert E. Hudlicky T. J. Org. Chem.  1988,  53:  1953 
  • 14c Kaufman MD. Grieco PA. J. Org. Chem.  1994,  59:  7197 
  • 14d Grieco PA. Kaufman MD. J. Org. Chem.  1999,  64:  7586 
  • 15 De Simone F. Gertsch J. Waser J. Angew. Chem. Int. Ed.  2010,  49:  5767 
  • 16 Jackson A. Wilson NDV. Gaskell AJ. Joule JA.
    J. Chem. Soc. C  1969,  2738 
  • 17a Diez A. Castells J. Forns P. Rubiralta M. Grierson DS. Husson HP. Solans X. Fontbardia M. Tetrahedron  1994,  50:  6585 
  • 17b Forns P. Diez A. Rubiralta M. Solans X. FontBardia M. Tetrahedron  1996,  52:  3563 
  • 18 Amat M. Perez M. Llor N. Escolano C. Luque FJ. Molins E. Bosch J. J. Org. Chem.  2004,  69:  8681 
  • 19 Forns P. Diez A. Rubiralta M. J. Org. Chem.  1996,  61:  7882 
  • 20 Cutri S. Diez A. Bonin M. Micouin L. Husson HP. Org. Lett.  2005,  7:  1911 
21

The biological assays were done in the laboratory of Prof. Jürg Gertsch at the University of Bern in the framework of a COST CM0804 (Chemical Biology with Natural Products) collaboration.