Download PDF
Synthesis 2009(4): 665-673  
DOI: 10.1055/s-0028-1083342
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Bi- and Tricyclic α,β-Unsaturated Lactams as Potential Michael Acceptors Starting from Heterocyclic Imines

Knut Schulz, Martin Watzke, Katharina Johannes, Pasqual Ullrich, Jürgen Martens*
Institute of Pure and Applied Chemistry, University of Oldenburg, Carl-von-Ossietzky-Straße 9-11, 26129 Oldenburg, Germany
Fax: +49(441)7983757; e-Mail: juergen.martens@uni-oldenburg.de;
Further Information

Publication History

Received 25 August 2008
Publication Date:
27 January 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

New α,β-unsaturated valerolactams showing potential as Michael acceptors were synthesized from heterocyclic imines as starting materials. The synthetic procedure is based on an acid chloride addition in the first step, followed by a modified Hosomi-Sakurai­ reaction, and a final ring-closing metathesis using a ruthenium catalyst.

Key words

heterocycles - imines - unsaturated lactams - Michael acceptor - ring-closing metathesis

    References

  • 1a Navickiene HMD. Alecio AC. Kato MJ. Bolzani VD. Young MCM. Cavalheiro AJ. Furlan M. Phytochemistry  2000,  55:  621 
    Google Scholar
  • 1b Chen JJ. Chang YL. Teng CM. Su CC. Chen IS. Planta Med.  2002,  68:  790 
    Google Scholar
  • 1c Chen JJ. Duh CY. Huang HY. Chen IS. Helv. Chim. Acta  2003,  86:  2058 
    Google Scholar
  • 1d Tsai IL. Lee FP. Wu CC. Duh CY. Ishikawa T. Chen JJ. Chen YC. Seki H. Chen IS. Planta Med.  2005,  71:  535 
    Google Scholar
  • 1e Cardona W. Quinones W. Robledo S. Velez ID. Murga J. Garcia-Fortanet J. Carda M. Cardona D. Echeverri F. Tetrahedron  2006,  62:  4086 
    Google Scholar
  • 1f Ding PL. Liao ZX. Huang H. Zhou P. Chen DF. Bioorg. Med. Chem. Lett.  2006,  16:  1231 
    Google Scholar
  • 2a Sundberg RJ. Bukowick PA. Holcombe FO. J. Org. Chem.  1967,  32:  2938 
    Google Scholar
  • 2b Hua DH. Zhang F. Chen J. J. Org. Chem.  1994,  59:  5084 
    Google Scholar
  • 2c Amat M. Pérez M. Llor N. Bosch J. Org. Lett.  2002,  4:  2787 
    Google Scholar
  • 2d Chandra KL. Chandrasekhar M. Singh VK. J. Org. Chem.  2002,  67:  4630 
    Google Scholar
  • 2e Fuwa H. Kaneko A. Sugimoto Y. Tomita T. Iwatsubo T. Saski M. Heterocycles  2006,  70:  101 
    Google Scholar
  • 2f Maio DG. Tardella PA. Gazz. Chim. Ital.  1964,  94:  590 
    Google Scholar
  • 3a Flemming A. Br. J. Exp. Pathol.  1929,  10:  226 
    Google Scholar
  • 3b Penicilline (C), In Römpp Online V. 3.1   Thieme; Stuttgart: 2008. RD-16-00773
    Google Scholar
  • 3c Dalhoff A. Infection  1979,  7:  294 
    Google Scholar
  • 3d Holzgrabe U. Pharm. Unserer Zeit  2006,  35:  410 
    Google Scholar
  • 4a Gillies PS. Dunn CJ. Drugs  2000,  60:  333 
    Google Scholar
  • 4b Lohray BB. Bhusan V. Rao BP. Medhavan GR. Murali N. Rao KN. Reddy AK. Rajesh BM. Reddy PG. Chakrabarti R. Vikramadithyan RK. Rajagopalan R. Mamidi RNVS. Jajoo HK. Subramanian S. J. Med. Chem.  1998,  41:  1619 
    Google Scholar
  • 5 Elander RP. Appl. Microbiol. Biotech.  2003,  61:  385 
    CrossrefPubMedGoogle Scholar
  • 6a Matsumoto Y. Tsuzuki R. Matsuhisa A. Takayama K. Yoden T. Uchida W. Asano M. Fujita S. Yanagisawa I. Fujikura T. Chem. Pharm. Bull.  1996,  44:  103 
    Google Scholar
  • 6b Kobayashi T. Strobeck M. Schwartz A. Mori Y. Eur. J. Pharmacol.  1997,  332:  313 
    Google Scholar
  • 6c Matsumoto Y. Tsuzuki R. Matsuhisa A. Yoden T. Yamagiwa Y. Yanagisawa I. Shibanuma T. Nohira H. Bioorg. Med. Chem.  2000,  8:  393 
    Google Scholar
  • 6d Okuyama K. Kiuchi S. Okamoto M. Narita H. Kudo Y. Eur. J. Pharmacol.  2000,  398:  209 
    Google Scholar
  • 6e Cecchetti V. Calderone V. Tabarrini O. Sabatini S. Filipponi E. Testai L. Spogli R. Martinotti E. Fravolini A. J. Med. Chem.  2003,  46:  3670 
    Google Scholar
  • 7a Trapani G. Reho A. Morlacchi F. Latrofa A. Marchini P. Venturi F. Cantalamessa F. Farmaco, Ed. Sci.  1985,  40:  369 
    Google Scholar
  • 7b Armenise D. Trapani G. Stasi F. Morlacchi F. Arch. Pharm. (Weinheim, Ger.)  1998,  331:  54 
    Google Scholar
  • 8a Hayakawa I. Atarashi S. Yokohama S. Imamura M. Sakano K. Furukawa M. Antimicrob. Agents Chemother.  1986,  29:  163 
    Google Scholar
  • 8b Atarashi S. Tsurumi H. Fujiwara T. Hayakawa I. J. Heterocycl. Chem.  1991,  28:  329 
    Google Scholar
  • 8c Hirata T. Saito H. Tomioka H. Sato K. Jidoi J. Hosoe K. Hidaka T. Antimicrob. Agents Chemother.  1995,  39:  2295 
    Google Scholar
  • 9 Martens J. Offermanns H. Scherberich P. Angew. Chem., Int. Ed. Engl.  1981,  20:  668 ; Angew. Chem. 1981, 93, 680
    Google Scholar
  • 10 Weber M. Jakob J. Martens J. Liebigs Ann. Chem.  1992,  1 
    CrossrefGoogle Scholar
  • 11 Gröger H. Martens J. Sulf. Lett.  1996,  19:  197 
    Google Scholar
  • 12 Watzke M. Schulz K. Johannes K. Ullrich P. Martens J. Eur. J. Org. Chem.  2008,  3859 
    CrossrefGoogle Scholar
  • 13 Böhme H. Hartke K. Chem. Ber.  1963,  96:  600 
    CrossrefGoogle Scholar
  • 14 Schwarze W. Drauz K. Martens J. Chem.-Ztg.  1987,  111:  149 
    Google Scholar
  • 15 Hosomi A. Sakurai H. Tetrahedron Lett.  1976,  1295 
    CrossrefGoogle Scholar
  • 16a Hart DJ. Tsai Y.-M. Tetrahedron Lett.  1981,  22:  1567 
    Google Scholar
  • 16b Kraus GA. Neuenschwander K. J. Chem. Soc., Chem. Commun.  1982,  134 
    Google Scholar
  • 16c Kano S. Yuasa Y. Shibuya S. Heterocycles  1987,  26:  373 
    Google Scholar
  • 16d Herborn C. Zietlow A. Steckhan E. Angew. Chem., Int. Ed. Engl.  1989,  28:  1399 ; Angew. Chem. 1989, 101, 1392
    Google Scholar
  • 17a Rodriguez S. Castillo E. Carda M. Marco JA. Tetrahedron  2002,  58:  1185 
    Google Scholar
  • 17b Chen Y. Zhang H. Nan F. J. Comb. Chem.  2004,  6:  684 
    Google Scholar
  • 17c Deiters A. Pettersson M. Martin SF. J. Org. Chem.  2006,  71:  6547 
    Google Scholar
  • 17d Liu G. Tai W.-Y. Li Y.-L. Nan F.-J. Tetrahedron Lett.  2006,  47:  3295 
    Google Scholar
  • 17e Fiorelli C. Savoia D. J. Org. Chem.  2007,  72:  6022 
    Google Scholar
18

In former investigations using similar substrates, a first-generation Grubbs catalyst showed less activity.¹²

19

CCDC 706274 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.