Download PDF
Synlett 2011(20): 2939-2942  
DOI: 10.1055/s-0031-1289878
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a Chiral Key Intermediate of Neurokinin Antagonist SSR 240600 by Asymmetric Allylic Alkylation

Jérôme Keldenicha,c, Christophe Michona,b,c, Audrey Nowickia,c, Francine Agbossou-Niedercorn*a,b,c
a Université Lille Nord de France, 59000 Lille, France
Fax: +33(3)20436585; e-Mail: francine.agbossou@ensc-lille.fr;
b CNRS, UCCS UMR 8181, 59655 Villeneuve d’Ascq, France
c ENSCL, CCM-CCCF, Bât C7, BP 90108, 59652 Villeneuve d’Ascq, France
Further Information

Publication History

Received 25 August 2011
Publication Date:
11 November 2011 (online)

   Permissions and Reprints All articles of this category

Abstract

The preparation of optically active morpholine-2-aryl-2-acetaldehyde from morpholine-2-aryl-3-one is reported. The quaternary carbon is introduced during a palladium-promoted asymmetric allylic alkylation. This is a useful intermediate in the synthesis and development of potent NK antagonist.

Key words

alkylation - palladium - asymmetric catalysis - hetero­cycle

    References and Notes

  • 1 Regoli D. Bourdon A. Fauchere JL. Pharmacol. Rev.  1994,  46:  551 
    Search in Google Scholar
  • 2 Pennefather JN. Lecci A. Candenas ML. Patak E. Pinto FM. Maggi CA. Life Sci.  2004,  74:  1445 
    Search in Google Scholar
  • 3a Rupniak NMJ. Kramer MS. Trends Pharmacol. Sci.  1999,  20:  485 
    Search in Google Scholar
  • 3b Severini C. Improta G. Falconieri-Erspamer G. Salvadori S. Erspamer V. Pharmacol. Rev.  2002,  54:  285 
    Search in Google Scholar
  • 3c Lecci A. Capriati A. Maggi CA. Br. J. Pharmacol.  2004,  141:  1249 
    Search in Google Scholar
  • 4a Emonds-Alt X. Proietto V. Steinberg R. Oury-Donat F. Vigé X. Vilain P. Naline E. Daoui S. Advenier C. Le Fur G. Mafrand J.-P. Soubié P. Pascal M.
    J. Pharmacol. Exp. Ther.  2002,  303:  1171 
    Search in Google Scholar
  • 4b Steinberg R. Alonso R. Rouquier L. Desvignes C. Michaud J.-C. Cudennec A. Jung M. Simiand J. Griebel G. Emonds-Alt X. Le Fur G. Soubié P. J. Pharmacol. Exp. Ther.  2002,  303:  1180 
    Search in Google Scholar
  • 5 Wijtmans R. Vink MKS. Schoemaker HE. van Delft FL. Blaauw RH. Rutjes FPJT. Synthesis  2004,  641 
  • 6 Nishi T. Ishibashi K. Nakajima K. Iio Y. Fukazawa T. Tetrahedron: Asymmetry  1998,  9:  3251 
    Search in Google Scholar
  • 7 Takemoto T. Iio Y. Nishi T. Tetrahedron Lett.  2000,  41:  1785 
    Search in Google Scholar
  • 8 Takamura M. Yabu K. Nishi T. Yanagisawa H. Kanai M. Shibasaki M. Synlett  2003,  353 
  • 9 Okachi T. Murai N. Onaka M. Org. Lett.  2003,  5:  85 
    Search in Google Scholar
  • 10a Cochi A. Métro T.-X. Gomez-Pardo D. Cossy J. Org. Lett.  2010,  12:  3693 
    Search in Google Scholar
  • 10b Métro T.-X. Cochi A. Gomez-Pardo D. Cossy J. J. Org. Chem.  2011,  76:  2594 
    Search in Google Scholar
  • 11a Trost BM. Schäffner B. Osipov M. Wilton DAA. Angew. Chem. Int Ed.  2011,  50:  3548 
    Search in Google Scholar
  • 11b Guerrero Rios I. Rosas-Hernandez A. Martin E. Molecules  2011,  16:  970 
    Search in Google Scholar
  • 11c Trost BM. Czabaniuk LC. J. Am. Chem. Soc.  2010,  132:  15534 
    Search in Google Scholar
  • 11d Trost BM. Schroeder GM. Kristensen J. Angew. Chem. Int. Ed.  2002,  41:  3492 
    Search in Google Scholar
  • 11e Nowicki A. Mortreux A. Agbossou-Niedercorn F. Tetrahedron Lett.  2005,  46:  1617 
    Search in Google Scholar
  • 11f Nowicki A. Mortreux A. Agbossou-Niedercorn F. Tetrahedron: Asymmetry  2005,  16:  1295 
    Search in Google Scholar
  • 12 Nowicki A. Keldenich J. Agbossou-Niedercorn F. Eur. J. Org. Chem.  2007,  6124 
  • 14 Drefahl G. Hartmann M. Skurk A. Chem. Ber.  1966,  2716 
  • 15 Imada Y. Mitsue Y. Ike K. Washizuka K. Murahashi S. Bull. Chem. Soc. Jpn.  1996,  69:  2079 
    Search in Google Scholar
  • 16a Snieckus V. Chem. Rev.  1990,  90:  879 
    Search in Google Scholar
  • 16b Whisler MC. MacNeil S. Snieckus V. Beak P. Angew. Chem. Int. Ed.  2004,  43:  2206 
    Search in Google Scholar
  • 16c Gschwend HW. Rodriguez HR. Org. React.  1979,  26:  1 
    Search in Google Scholar
  • 16d Clayden J. In Directed Metallation of Aromatic Compounds in the Chemistry of Organolithium Compounds   Part 1:  Rappoport Z. Marek I. John Wiley and Sons; Chichester: 2004.  p.495 
    Search in Google Scholar
  • 16e Hartung CG. Snieckus V. In Modern Arene Chemistry   Astruc D. Wiley- VCH; Weinheim: 2002.  p.330 
13

Michon, C.; Béthegnies, A.; Roussel, P.; Capet, F.; de Filippis, A.; Cossy, J.; Agbossou-Niedercorn, F. manuscript in preparation.

17

X-ray crystal data of compound II were deposited under reference CCDC 836129. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre: www.ccdc.cam.ac.uk/data_request/cif.