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Synthesis 2011(1): 142-146  
DOI: 10.1055/s-0030-1258333
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of (±)-Crispine A via a Nitrosoalkene Hetero-Diels-Alder Addition to Ethyl Vinyl Ether

Efthymia G. Yioti, Ioulia K. Mati, Athanassios G. Arvanitidis, Zoe S. Massen, Elli S. Alexandraki, John K. Gallos*
Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Fax: +30(2310)997679; e-Mail: igallos@chem.auth.gr;
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Publication History

Received 16 September 2010
Publication Date:
15 November 2010 (online)

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Abstract

The synthesis of (±)-crispine A in 9 steps and 24% overall­ yield was achieved using a nitrosoalkene hetero-Diels-Alder­ addition to ethyl vinyl ether as the key step. The synthesis starts from commercial 3,4-dimethoxyphenylacetic acid and uses simple methods, easily accessible materials and inexpensive reagents. An isochroman derivative was unexpectedly formed in an attempted reduction of a dihydro-4H-1,2-oxazine intermediate.

Key words

alkaloids - natural products - total synthesis - hetero-Diels­-Alder reaction - hydrogenation

    References

  • 1 Zhang Q. Tu G. Zhao Y. Cheng T. Tetrahedron  2002,  58:  6795 
    CrossrefGoogle Scholar
  • 2a Knölker H.-J. Agarwal S. Tetrahedron Lett.  2005,  46:  1173 
    Google Scholar
  • 2b Meyer N. Opatz T. Eur. J. Org. Chem.  2006,  3997 
    Google Scholar
  • 2c King FD. Tetrahedron  2007,  63:  2053 
    Google Scholar
  • 2d Bailey KR. Ellis AJ. Reiss R. Snape TJ. Turner NJ. Chem. Commun.  2007,  3640 
    Google Scholar
  • 2e Axford LC. Holden KE. Hasse K. Banwell MG. Steglich W. Wagler J. Willis AC. Aust. J. Chem.  2008,  61:  80 
    Google Scholar
  • 2f Coldham I. Jana S. Watson L. Martin NG. Org. Biomol. Chem.  2009,  7:  1674 
    Google Scholar
  • 2g Chiou W.-H. Lin G.-H. Hsu C.-C. Chaterpaul SJ. Ojima I. Org. Lett.  2009,  11:  2659 
    Google Scholar
  • 3a Szawkao J. Zawadzka A. Wojtasiewicz K. Leniewski A. Drabowicz J. Czarnocki Z. Tetrahedron: Asymmetry  2005,  16:  3619 
    Google Scholar
  • 3b Wu TR. Chong JM. J. Am. Chem. Soc.  2006,  128:  9646 
    Google Scholar
  • 3c Szawkao J. Czarnocki SJ. Zawadzka A. Wojtasiewicz K. Leniewski A. Maurin JK. Czarnocki Z. Drabowicz J. Tetrahedron: Asymmetry  2007,  18:  406 
    Google Scholar
  • 3d Allin SM. Gaskell SN. Towler JMR. Page PCB. Saha B. McKenzie WP. Martin MJ. J. Org. Chem.  2007,  72:  8972 
    Google Scholar
  • 3e Kanemitsu T. Yamashita Y. Nagata K. Itoh T. Heterocycles  2007,  74:  199 
    Google Scholar
  • 3f Hou G.-H. Xie J.-H. Yan P.-C. Zhou Q.-L. J. Am. Chem. Soc.  2009,  131:  1366 
    Google Scholar
  • 4a Kapat A. Kumar PS. Baskaran S. Beilstein J. Org. Chem.  2007,  3:  No. 49 ; DOI: 10.1186/1860-5397-3-49
    Google Scholar
  • 4b Kumar PS. Kapat A. Baskaran S. Tetrahedron Lett.  2008,  49:  1241 
    Google Scholar
  • 4c Saber M. Comesse S. Dalla V. Daïch A. Sanselme M. Netchitaïlo P. Synlett  2010,  2197 
    Google Scholar
  • 5a Gilchrist TL. Chem. Soc. Rev.  1983,  12:  53 
    Google Scholar
  • 5b Gilchrist TL. Wood JE. In Comprehensive Heterocyclic Chemistry II   Vol. 6:  Boulton AJ. Pergamon Press; Oxford: 1996.  p.279-299  
    Google Scholar
  • 5c Tietze LF. Kettschau G. Top. Curr. Chem.  1997,  189:  1 
    Google Scholar
  • 5d Tsoungas PG. Heterocycles  2002,  57:  1149 
    Google Scholar
  • 5e Reissig H.-U. Zimmer R. In Science of Synthesis, Houben-Weyl Methods of Molecular Transformations   Vol. 33:  Molander GA. Georg Thieme; Stuttgart: 2007.  p.371-379  
    Google Scholar
  • 5f Lemos A. Molecules  2009,  14:  4098 
    Google Scholar
  • 6a Gilchrist TL. Roberts TG. J. Chem. Soc., Perkin Trans. 1  1983,  1283 
    Google Scholar
  • 6b Gilchrist TL. Lemos A. J. Chem. Soc., Perkin Trans. 1  1993,  1391 
    Google Scholar
  • 7a Gallos JK. Sarli VC. Koftis TV. Coutouli-Argyropoulou E. Tetrahedron Lett.  2000,  41:  4819 
    Google Scholar
  • 7b Gallos JK. Sarli VC. Stathakis CI. Koftis TV. Nachmia VR. Coutouli-Argyropoulou E. Tetrahedron  2002,  58:  9351 
    Google Scholar
  • 7c Gallos JK. Sarli VC. Varvogli AC. Papadoyanni CZ. Papaspyrou SD. Argyropoulos NG. Tetrahedron Lett.  2003,  44:  3905 
    Google Scholar
  • 7d Gallos JK. Sarli VC. Massen ZS. Varvogli AC. Papadoyanni CZ. Papaspyrou SD. Argyropoulos NG. Tetrahedron  2005,  61:  565 
    Google Scholar
  • 7e Gallos JK. Alexandraki ES. Stathakis CI. Heterocycles  2007,  71:  1127 
    Google Scholar
  • 7f Zimmer R. Arnold T. Homann K. Reissig H.-U. Synthesis  1994,  1050 
    Google Scholar
  • 8a Beugelmans R. Bois-Choussy M. Tetrahedron  1992,  48:  8285 
    Google Scholar
  • 8b Catsoulacos P. J. Pharm. Sci.  1976,  65:  625 
    Google Scholar
  • 9a Denmark SE. Cramer CJ. Dappen MS. J. Org. Chem.  1987,  52:  87 
    Google Scholar
  • 9b Shatzmiller S. Dolitzky B.-Z. Meirovich R. Neidlein R. Weik C. Liebigs Ann. Chem.  1991,  161 
    Google Scholar
  • 9c Lee I.-YC. Lee JH. Lee HW. Bull. Korean Chem. Soc.  2002,  23:  537 
    Google Scholar
  • 9d Smirnov VO. Sidorenkov AS. Khomutova YA. Ioffe SL. Tartakovsky VA. Eur. J. Org. Chem.  2009,  3066 
    Google Scholar
  • 11a Reissig H.-U. Angew. Chem., Int. Ed. Engl.  1992,  31:  288 
    Google Scholar
  • 11b Arnold T. Orschel B. Reissig H.-U. Angew. Chem., Int. Ed. Engl.  1992,  31:  1033 
    Google Scholar
  • 11c Boa AN. Dawkins DA. Hergueta AR. Jenkins PR. J. Chem. Soc., Perkin Trans. 1  1994,  953 
    Google Scholar
10

H-11b of the major isomer 16 is coupled with both neighboring protons, as well as with the methylene protons of the dihydropyridinone ring with J = 2.2 Hz.