Download PDF
Synthesis 2011(6): 895-900  
DOI: 10.1055/s-0030-1258419
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Synthesis of Hexahydroisobenzofuran and Hexahydro­isoindole Derivatives with Quaternary Stereocenters

Jens Christoffers*, Jonas Sluiter, Jan Schmidt
Institut für Reine und Angewandte Chemie, Carl von Ossietzky-Universität Oldenburg, 26111 Oldenburg, Germany
Fax: +49(441)7983873; e-Mail: jens.christoffers@uni-oldenburg.de;
Further Information

Publication History

Received 3 November 2010
Publication Date:
01 March 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

Oxo esters with pyrrolidine and tetrahydrofuran rings were converted into optically active isobenzofuran and isoindole derivatives. The key step of the sequence was a copper-catalyzed asymmetric Michael reaction with methyl vinyl ketone and en­amines prepared from the oxo esters and l-valine diethylamide. The chiral auxiliary was cleaved from the products during workup and 1,5-diketones with a quaternary stereocenter are obtained with 97-99% ee. Subsequent annulation reactions were achieved in two steps via the intermediate aldol products.

Key words

tetrahydrofurans - pyrrolidines - isoindoles - isobenzofurans - chirality - Michael addition - quaternary stereocenters

    References

  • 1 Review: Pokholenko AA. Voitenka ZV. Kovtunenko VA. Russ. Chem. Rev.  2004,  73:  771 
    CrossrefGoogle Scholar
  • 2 Review: Spreitzer H. Mustafa S. Pharm. Unserer Zeit  1991,  20:  83 
    CrossrefGoogle Scholar
  • 3 Review: Rodrigo R. Tetrahedron  1988,  44:  2093 
    CrossrefGoogle Scholar
  • 4 Ishizumi K. Kojima A. Antoku F. Chem. Pharm. Bull.  1991,  39:  2288 
    CrossrefGoogle Scholar
  • 5a Yamaguchi T. Yanagi T. Hokari H. Mukaiyama Y. Kamijo T. Yamamoto I. Chem. Pharm. Bull.  1997,  45:  1518 
    Google Scholar
  • 5b Yamaguchi T. Yanagi T. Hokari H. Mukaiyama Y. Kamijo T. Yamamoto I. Chem. Pharm. Bull.  1998,  46:  337 
    Google Scholar
  • 5c Liu J. Yang Y. Ji R. Helv. Chim. Acta  2004,  87:  1935 
    Google Scholar
  • 6a Yang G. Pevear DC. Davies MH. Collett MS. Bailey T. Rippen S. Barone L. Burns C. Rhodes G. Tohan S. Huggins JW. Baker RO. Buller RLM. Touchette E. Waller K. Schriewer J. Neyts J. DeClercq E. Jones K. Hruby D. Jordan R. J. Virol.  2005,  79:  13139 
    Google Scholar
  • 6b Bailey TR. Rippin SR. Opsitnick E. Burns CJ. Pevear DC. Collett MS. Rhodes G. Tohan S. Huggins JW. Baker RO. Kern ER. Keith KA. Dai D. Yang G. Hruby D. Jordan R. J. Med. Chem.  2007,  50:  1442 
    Google Scholar
  • 7 Review: Sellars JD. Steel PG. Eur. J. Org. Chem.  2007,  3815 
    Google Scholar
  • 8a Chackalamannil S. Wang Y. Greenlee WJ. Hu Z. Xia Y. Ahn H.-S. Boykow G. Hsieh Y. Palamanda J. Agans-Fantuzzi J. Kurowski S. Graziano M. Chintala M. J. Med. Chem.  2008,  51:  3061 
    Google Scholar
  • 8b Review: Chackalamannil S. J. Med. Chem.  2006,  49:  5389 
    Google Scholar
  • 9 Chackalamannil S. Davies RJ. Wang Y. Asberom T. Doller D. Wong J. Leone D. McPhail AT. J. Org. Chem.  1999,  64:  1932 
    CrossrefGoogle Scholar
  • 10 Christoffers J. Scharl H. Eur. J. Org. Chem.  2002,  1505 
    Google Scholar
  • 11 Review: Christoffers J. Chem. Eur. J.  2003,  9:  4862 
    CrossrefGoogle Scholar
  • 12 Review: Christoffers J. Baro A. Adv. Synth. Catal.  2005,  347:  1473 
    CrossrefGoogle Scholar
  • 13a Christoffers J. Scharl H. Frey W. Baro A. Eur. J. Org. Chem.  2004,  2701 
    Google Scholar
  • 13b Christoffers J. Scharl H. Frey W. Baro A. Org. Lett.  2004,  6:  1171 
    Google Scholar
  • 13c Diedrich CL. Haase D. Christoffers J. Synthesis  2008,  2199 
    Google Scholar
  • 13d Wache N. Christoffers J. Synlett  2009,  3016 
    Google Scholar
  • 14a Clark RD. Ray NC. Williams K. Blaney P. Ward S. Crackett PH. Hurley C. Dyke HJ. Clark DE. Lockey P. Devos R. Wong M. Porres SS. Bright CP. Jenkins RE. Belanoff J. Bioorg. Med. Chem. Lett.  2008,  18:  1312 
    Google Scholar
  • 14b Clark RD, Ray NC, Blaney PM, Hurley CA, and Williams K. inventors; Patent WO 2005/087769  A1.  ; Chem. Abstr. 2005, 143, 306309
  • 14c Clark RD, Ray NC, Blaney P, Hurley C, Williams K, Hunt H, and Clark D. inventors; Patent WO  2005/070893.  ; Chem. Abstr. 2005, 143, 193917
  • 14d Hubschwerlen C, Rueedi G, Surivet J.-P, and Zumbrunn Acklin C. inventors; Patent WO  2009/034546.  ; Chem. Abstr. 2009, 150, 352177
  • 15 Knight DW. Sibley AW. J. Chem. Soc., Perkin Trans. 1  1997,  2179 
    Google Scholar
  • 16 Morandeau L. Remaud-Le Saec P. Ouadi A. Bultel-Riviere K. Mougin-Degraef M. de France-Robert A. Faivre-Chauvet A. Gestin J.-F. J. Labelled Compd. Radiopharm.  2006,  49:  109 
    CrossrefGoogle Scholar
  • 17a Tran JA. Chen CW. Tucci FC. Jiang W. Fleck BA. Chen C. Bioorg. Med. Chem. Lett.  2008,  18:  1124 
    Google Scholar
  • 17b See also: Pflantz R. Sluiter J. Krička M. Saak W. Hoenke C. Christoffers J. Eur. J. Org. Chem.  2009,  5431 
    Google Scholar
  • 18 Review: Christoffers J. Frey H. Chimica Oggi/Chem. Today Suppl.  2008,  26:  26 
    Google Scholar
  • 19 Christoffers J. Mann A. Chem. Eur. J.  2001,  7:  1014 
    CrossrefGoogle Scholar
  • 20 Christoffers J. Frey W. Scharl H. Baro A. Z. Naturforsch., B  2004,  59:  375 
    Google Scholar
  • 21 Diedrich CL. Frey W. Christoffers J. Eur. J. Org. Chem.  2007,  4731 
    Google Scholar
22

CCDC 785562 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.