Download PDF
Synlett 2011(4): 503-507  
DOI: 10.1055/s-0030-1259527
CLUSTER
© Georg Thieme Verlag Stuttgart ˙ New York

l-Proline-Catalyzed Asymmetric Michael Addition of 2-Oxindoles to Enones: A Convenient Access to Oxindoles with a Quaternary Stereocenter

Matthias H. Freund, Svetlana B. Tsogoeva*
Department of Chemistry and Pharmacy, Chair of Organic Chemistry I, University of Erlangen-Nuremberg, Henkestr. 42, 91054 Erlangen, Germany
Fax: +49(9131)8526865; e-Mail: tsogoeva@chemie.uni-erlangen.de;
Further Information

Publication History

Received 30 November 2010
Publication Date:
02 February 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A new organocatalytic approach for 1,4-conjugate addition of 2-oxindoles to α,β-unsaturated ketones using the combination of readily available and nonexpensive l-proline and achiral trans-2,5-dimethylpiperazine as catalytic system is provided. The reaction results in oxindole derivatives with vicinal quaternary and tertiary carbon centers in up to 99% yield and 91% ee.

Key words

l-proline - organocatalysis - 2-oxindoles - quaternary stereocenters - Michael addition

    References and Notes

  • For reviews and literature concerning the construction of quaternary stereocenters, see:
  • 1a Martin SF. Tetrahedron  1980,  36:  419 
    Google Scholar
  • 1b Fuji K. Chem. Rev.  1993,  93:  2037 
    Google Scholar
  • 1c Corey EJ. Guzman-Perez A. Angew. Chem. Int. Ed.  1998,  37:  388 
    Google Scholar
  • 1d Christoffers J. Mann A. Angew. Chem. Int. Ed.  2001,  40:  4591 
    Google Scholar
  • 1e Christoffers J. Baro A. Angew. Chem. Int. Ed.  2003,  42:  1688 
    Google Scholar
  • 1f Denissova I. Barriault L. Tetrahedron  2003,  59:  10105 
    Google Scholar
  • 1g Ramon DJ. Yus M. Curr. Org. Chem.  2004,  8:  149 
    Google Scholar
  • 1h Douglas CJ. Overman LE. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5363 
    Google Scholar
  • 1i Peterson EA. Overman LE. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  11943 
    Google Scholar
  • 1j Quaternary Stereocenters - Challenges and Solutions for Organic Synthesis   Christoffers J. Baro A. Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 1k Christoffers J. Baro A. Adv. Synth. Catal.  2005,  347:  1473 
    Google Scholar
  • 1l Trost BM. Jiang C. Synthesis  2006,  369 
    Google Scholar
  • 1m Cozzi PG. Hilgraf R. Zimmermann N. Eur. J. Org. Chem.  2007,  5969 
    Google Scholar
  • 1n Bella M. Gasperi T. Synthesis  2009,  1583 
    Google Scholar
  • For reviews on the syntheses of alkaloids bearing a quaternary stereocenter, see:
  • 2a Marti C. Carreira EM. Eur. J. Org. Chem.  2003,  2209 
    Google Scholar
  • 2b Lin H. Danishefsky SJ. Angew. Chem. Int. Ed.  2003,  42:  36 
    Google Scholar
  • 2c Galliford CV. Scheidt KA. Angew. Chem. Int. Ed.  2007,  46:  8748 
    Google Scholar
  • 2d Trost BM. Brennan MK. Synthesis  2009,  3003 
    Google Scholar
  • 3a Tian X. Jiang K. Peng J. Du W. Chen Y.-C. Org. Lett.  2008,  10:  3583 
    Google Scholar
  • 3b Sano D. Nagata K. Itoh T. Org. Lett.  2008,  10:  1593 
    Google Scholar
  • 3c Cheng L. Liu L. Jia H. Wang D. Chen Y.-J. J. Org. Chem.  2009,  74:  4650 
    Google Scholar
  • 3d Cheng L. Liu L. Wang D. Chen Y.-J. Org. Lett.  2009,  11:  3874 
    Google Scholar
  • 3e Bencivenni G. Wu L.-Y. Mazzanti A. Giannichi B. Pesciaioli F. Song M.-P. Bartoli G. Melchiorre P. Angew. Chem. Int. Ed.  2009,  48:  7200 
    Google Scholar
  • 3f Jiang K. Peng J. Cui H.-L. Chen Y.-C. Chem. Commun.  2009,  3955 
    Google Scholar
  • 3g Qian Z.-Q. Zhou F. Du T.-P. Wang B.-L. Ding M. Zhao X.-L. Zhou J. Chem. Commun.  2009,  6753 
    Google Scholar
  • 3h Wei Q. Gong L.-Z. Org. Lett.  2010,  12:  1008 
    Google Scholar
  • 3i Jiang K. Jia Z.-J. Chen S. Wu L. Chen Y.-C. Chem. Eur. J.  2010,  16:  2852 
    Google Scholar
  • 3j Deng J. Zhang S. Ding P. Jiang H. Wang W. Li J. Adv. Synth. Catal.  2010,  352:  833 
    Google Scholar
  • 3k Chen W.-B. Wu Z.-J. Pei Q.-L. Cun L.-F. Zhang X.-M. Yuan W.-C. Org. Lett.  2010,  12:  3132 
    Google Scholar
  • 3l Liu Y.-L. Wang B.-L. Cao J.-J. Chen L. Zhang Y.-X. Wang C. Zhou J. J. Am. Chem. Soc.  2010,  132:  15176 
    Google Scholar
  • 3m Liu X.-L. Liao Y.-H. Wu Z.-J. Cun L.-F. Zhang X.-M. Yuan W.-C.
    J. Org. Chem.  2010,  75:  4872 
    Google Scholar
  • For recent reviews on 1,4-conjugate addition reactions catalyzed by chiral organocatalysts, see:
  • 4a Tsogoeva SB. Eur. J. Org. Chem.  2007,  1701 
    Google Scholar
  • 4b Almasi D. Alonso DA. Nájera C. Tetrahedron: Asymmetry  2007,  18:  299 
    Google Scholar
  • 4c Sulzer-Mossé S. Alexakis A. Chem. Commun.  2007,  3123 
    Google Scholar
  • 4d Vicario JL. Badía D. Carrillo L. Synthesis  2007,  2065 
    Google Scholar
  • 5a Li X. Xi Z.-G. Luo S. Cheng J.-P. Org. Biomol. Chem.  2010,  8:  77 
    Google Scholar
  • 5b Li X. Zhang B. Xi Z.-G. Luo S. Cheng J.-P. Adv. Synth. Catal.  2010,  352:  416 
    Google Scholar
  • 5c Liao Y.-H. Liu X.-L. Wu Z.-J. Cun L.-F. Zhang X.-M. Yuan W.-C. Org. Lett.  2010,  12:  2896 
    Google Scholar
  • 5d Ding M. Zhou F. Qian Z.-Q. Zhou J. Org. Biomol. Chem.  2010,  8:  2912 
    Google Scholar
  • 5e Pesciaioli F. Tian X. Bencivenni G. Bartoli G. Melchiorre P. Synlett  2010,  1704 
    Google Scholar
  • 6 Baudequin C. Zamfir A. Tsogoeva SB. Chem. Commun.  2008,  4637 
    Google Scholar
  • 7a Tsogoeva SB. Jagtap SB. Synlett  2004,  2624 
    Google Scholar
  • 7b Tsogoeva SB. Jagtap SB. Ardemasova ZA. Kalikhevich VN. Eur. J. Org. Chem.  2004,  4014 
    Google Scholar
  • 7c Tsogoeva SB. Yalalov DA. Hateley MJ. Weckbecker C. Huthmacher K. Eur. J. Org. Chem.  2005,  4995 
    Google Scholar
  • 7d Tsogoeva SB. Wei S.-W. Chem. Commun.  2006,  1451 
    Google Scholar
  • 7e Tsogoeva SB. Jagtap SB. Ardemasova ZA. Tetrahedron: Asymmetry  2006,  17:  989 
    Google Scholar
  • 7f Yalalov DA. Tsogoeva SB. Schmatz S. Adv. Synth. Catal.  2006,  348:  826 
    Google Scholar
  • 7g Wei S.-W. Yalalov DA. Tsogoeva SB. Schmatz S. Catal. Today  2007,  121:  151 
    Google Scholar
  • 7h Freund M. Schenker S. Tsogoeva SB. Org. Biomol. Chem.  2009,  7:  4279 
    Google Scholar
  • 8 Hanessian S. Pham V. Org. Lett.  2000,  2:  2975 
    CrossrefGoogle Scholar
9

We also introduced defined amounts of H2O into the reaction system while using CHCl3 as solvent, with negative results. An increase in the reaction time was observed with increasing amounts of H2O, accompanied by a decrease in the enantioselectivity.

10

Besides, when both the proline and additive loadings were reduced, a somewhat decreased enantioselectivity was observed, along with increased reaction time.

11

General Procedure To a suspension of l-proline (0.3 equiv) and trans-2,5-dimethylpiperazine (1 equiv) in CHCl3 (c base = 0.2 M) 2-oxindole (1 equiv) was added, followed by the α,β-unsatured ketone (1 equiv). The reaction mixture was stirred at ambient temperature, until the conversion was judged complete by TLC, and transferred directly to purification by column or flash chromatography (over SiO2). For more details, see Supporting Information.