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Synlett 2009(8): 1341-1345  
DOI: 10.1055/s-0029-1216729
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Studies towards a Novel Synthesis of Tubulysins: Highly Asymmetric Aza-Michael Reactions of 2-Enoylthiazoles with Metalated Chiral Oxazolidinones

Sreejith Shankar P.a, Monica Sanib,c, Giancarlo Terraneod, Matteo Zanda*c,e
a Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘G. Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy
b KemoTech s.r.l., Parco Scientifico e Tecnologico della Sardegna, Loc.Piscinamanna, 09010 Pula (CA), Italy
c CNR - Istituto di Chimica del Riconoscimento Molecolare, Sezione ‘A. Quilico’, Via Mancinelli 7, 20131 Milano, Italy
Fax: +39(02)23993080; e-Mail: matteo.zanda@polimi.it;
d NFMLab-Dipartimento di Chimica, Materiali e Ingegneria Chimica "G. Natta", Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy
e Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
Further Information

Publication History

Received 11 February 2009
Publication Date:
17 April 2009 (online)

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Abstract

Herein we report the highly asymmetric aza-Michael ­reactions of α,β-enones (2-enoylthiazoles) with metalated chiral ­oxazolidinones under different reaction conditions and for different substituents at the β-position of the Michael acceptor. The reaction proceeds with complete diastereoselectivity to give exclusively one of the two diastereomers. The significance of the reaction is that no catalyst has been used; the steric requirements of the chiral Michael nucleophile drive the stereospecificity of the reaction and the reaction time is much less compared to the reported procedures. This methodology might be useful for an improved total synthesis of the highly cytotoxic peptides known as the tubulysins.

Key words

asymmetric - aza-Michael Reaction - diastereoselectivity - noncatalytic - oxazolidinone

    References and Notes

  • 1a Perlmutter P. Conjugate Addition Reactions in Organic Synthesis   Pergamon Press; Oxford: 1992. 
    Google Scholar
  • 1b Rossiter BE. Swingle NM. Chem. Rev.  1992,  92:  771 
    Google Scholar
  • 1c Tomioka K. Nagaoka Y. In Comprehensive Asymmetric Catalysis   Vol. 3:  Springer; Berlin: 1999.  Chap 31.1.
    Google Scholar
  • 1d Modern Carbonyl Chemistry   Otera J. Wiley-VCH; Weinheim: 2000.  Chap. 12.
    Google Scholar
  • 1e Sibi MP. Manyem S. Tetrahedron  2000,  56:  8033 
    Google Scholar
  • 1f Krause N. Hoffmann-Röder A. Synthesis  2001,  171 
    Google Scholar
  • 2a Cardillo G. Tomasini C. Chem. Soc. Rev.  1996,  25:  117 
    Google Scholar
  • 2b Fustero S. Pina B. Salavert E. Navarro A. Ramirez de Arellano MC. Fuentes AS. J. Org. Chem.  2002,  67:  4667 
    Google Scholar
  • 2c George GI. The Organic Chemistry of β-Lactams   Wiley-VCH; New York: 1993. 
    Google Scholar
  • 2d Juaristi E. Lopez-Ruiz H. Curr. Med. Chem.  1999,  6:  983 
    Google Scholar
  • 2e Seebach D. Matthews JL. Chem. Commun.  1997,  2015 
    Google Scholar
  • 3a Kakumoto K. Kobayashi S. Sugiura M. Org. Lett.  2002,  4:  1319 
    Google Scholar
  • 3b Xu L.-W. Li J.-W. Xia C.-G. Zhou S.-L. Hu X.-X. Synlett  2003,  2425 
    Google Scholar
  • 3c Xu L.-W. Xia C.-G. Tetrahedron Lett.  2004,  45:  4507 
    Google Scholar
  • 3d Nakama K. Seki S. Kanemasa S. Tetrahedron Lett.  2001,  42:  6719 
    Google Scholar
  • 3e Nakama K. Seki S. Kanemasa S. Tetrahedron Lett.  2002,  43:  3891 
    Google Scholar
  • 3f Volonterio A. Zanda M. Tetrahedron Lett.  2003,  44:  8549 
    Google Scholar
  • 4a Matsunaga H. Sakamaki T. Nagaoka H. Yamada Y. Tetrahedron Lett.  1983,  24:  3009 
    Google Scholar
  • 4b D’Angelo J. Maddaluno J. J. Am. Chem. Soc.  1986,  108:  8112 
    Google Scholar
  • 4c Hawkins JM. Lewis TA. J. Org. Chem.  1992,  57:  2114 
    Google Scholar
  • 4d Loh T.-P. Wei L.-L. Synlett  1998,  975 
    Google Scholar
  • 4e Bull SD. Davies SG. Delgado-Ballester S. Fenton G. Kelly PM. Smith AD. Synlett  2000,  1257 
    Google Scholar
  • 4f Sani M. Bruché L. Chiva G. Fustero S. Piera J. Volonterio A. Zanda M. Angew. Chem. Int. Ed.  2003,  42:  2060 
    Google Scholar
  • 4g Fleck TJ. McWhorter WW. DeKam RN. Pearlman BA. J. Org. Chem.  2003,  68:  9612 
    Google Scholar
  • 4h Lurain AE. Walsh PJ. J. Am. Chem. Soc.  2003,  125:  10677 
    Google Scholar
  • 5a Enders D. Müller SF. Raabe G. Angew Chem. Int. Ed.  1999,  38:  195 ; Angew. Chem. 1999, 111, 2112
    Google Scholar
  • 5b Enders D. Wallert S. Synlett  2002,  304 
    Google Scholar
  • 5c Job A. Janeck CF. Bettray W. Peters R. Enders D. Tetrahedron  2002,  58:  2253 
    Google Scholar
  • 5d Enders D. Wallert S. Runsink J. Synthesis  2003,  1856 
    Google Scholar
  • 6 Doi H. Sakai T. Iguchi M. Yamada K. Tomioka K.
    J. Am. Chem. Soc.  2003,  125:  2886 
    CrossrefPubMedGoogle Scholar
  • 7 Luo-Ting Y. Huang J. Chang CY. Yang TK. Molecules  2006,  11:  641 ; and references cited therein
    CrossrefGoogle Scholar
  • 8a Urbach H. Henning R. Tetrahedron Lett.  1984,  25:  1143 
    Google Scholar
  • 8b Yamada M. Nagashima N. Hasegawa J. Takahashi S. Tetrahedron Lett.  1998,  39:  9019 
    Google Scholar
  • 8c Ferencic M. Gärtner P. Girreser U. Klinge M. Gaischin L. Mereiter K. Noe CR. Monatsh. Chem.  1999,  130:  769 
    Google Scholar
  • 9 Kakumoto K. Kobayashi S. Sugiura M. Org. Lett.  2002,  4:  1319 
    CrossrefPubMedGoogle Scholar
  • 10 Bigotti S. Volenterio A. Zanda M. Synlett  2008,  958 
    Article in Thieme ConnectGoogle Scholar
  • 11 Sani M. Fossati G. Huguenot F. Zanda M. Angew. Chem. Int. Ed.  2007,  46:  3526 
    CrossrefGoogle Scholar
  • 12 For other aza-Michael reactions on 2-enoyl-thiazoles, see: Dondoni A. Marra A. Boscarato A. Chem. Eur. J.  1999,  5:  3562 
    Google Scholar
  • 13 Hughes RA. Thompson SP. Alcaraz L. Moody CJ. J. Am. Chem. Soc.  2005,  127:  15644 
    CrossrefPubMedGoogle Scholar
  • 14 Turconi J. Lebeau L. Paris JM. Mioskowski C. Tetrahedron  2006,  62:  8109 
    CrossrefGoogle Scholar
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Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no CCDC 718419. Copies of the data can be obtained, free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax:+44 (1223)336033; or e-mail: deposit@ccdc.cam.ac.uk].