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: [email protected];
Weitere Informationen

Publikationsverlauf

Received 3 November 2010
Publikationsdatum:
01. März 2011 (online)

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.

    References

  • 1 Review: Pokholenko AA. Voitenka ZV. Kovtunenko VA. Russ. Chem. Rev.  2004,  73:  771 
  • 2 Review: Spreitzer H. Mustafa S. Pharm. Unserer Zeit  1991,  20:  83 
  • 3 Review: Rodrigo R. Tetrahedron  1988,  44:  2093 
  • 4 Ishizumi K. Kojima A. Antoku F. Chem. Pharm. Bull.  1991,  39:  2288 
  • 5a Yamaguchi T. Yanagi T. Hokari H. Mukaiyama Y. Kamijo T. Yamamoto I. Chem. Pharm. Bull.  1997,  45:  1518 
  • 5b Yamaguchi T. Yanagi T. Hokari H. Mukaiyama Y. Kamijo T. Yamamoto I. Chem. Pharm. Bull.  1998,  46:  337 
  • 5c Liu J. Yang Y. Ji R. Helv. Chim. Acta  2004,  87:  1935 
  • 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 
  • 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 
  • 7 Review: Sellars JD. Steel PG. Eur. J. Org. Chem.  2007,  3815 
  • 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 
  • 8b Review: Chackalamannil S. J. Med. Chem.  2006,  49:  5389 
  • 9 Chackalamannil S. Davies RJ. Wang Y. Asberom T. Doller D. Wong J. Leone D. McPhail AT. J. Org. Chem.  1999,  64:  1932 
  • 10 Christoffers J. Scharl H. Eur. J. Org. Chem.  2002,  1505 
  • 11 Review: Christoffers J. Chem. Eur. J.  2003,  9:  4862 
  • 12 Review: Christoffers J. Baro A. Adv. Synth. Catal.  2005,  347:  1473 
  • 13a Christoffers J. Scharl H. Frey W. Baro A. Eur. J. Org. Chem.  2004,  2701 
  • 13b Christoffers J. Scharl H. Frey W. Baro A. Org. Lett.  2004,  6:  1171 
  • 13c Diedrich CL. Haase D. Christoffers J. Synthesis  2008,  2199 
  • 13d Wache N. Christoffers J. Synlett  2009,  3016 
  • 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 
  • 14b Clark RD, Ray NC, Blaney PM, Hurley CA, and Williams K. inventors; Patent WO 2005/087769  A1.  2005; 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.  2005; Chem. Abstr. 2005, 143, 193917
  • 14d Hubschwerlen C, Rueedi G, Surivet J.-P, and Zumbrunn Acklin C. inventors; Patent WO  2009/034546.  2009; Chem. Abstr. 2009, 150, 352177
  • 15 Knight DW. Sibley AW. J. Chem. Soc., Perkin Trans. 1  1997,  2179 
  • 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 
  • 17a Tran JA. Chen CW. Tucci FC. Jiang W. Fleck BA. Chen C. Bioorg. Med. Chem. Lett.  2008,  18:  1124 
  • 17b See also: Pflantz R. Sluiter J. Krička M. Saak W. Hoenke C. Christoffers J. Eur. J. Org. Chem.  2009,  5431 
  • 18 Review: Christoffers J. Frey H. Chimica Oggi/Chem. Today Suppl.  2008,  26:  26 
  • 19 Christoffers J. Mann A. Chem. Eur. J.  2001,  7:  1014 
  • 20 Christoffers J. Frey W. Scharl H. Baro A. Z. Naturforsch., B  2004,  59:  375 
  • 21 Diedrich CL. Frey W. Christoffers J. Eur. J. Org. Chem.  2007,  4731 
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 [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.