Download PDF
Synthesis 2010(13): 2207-2212  
DOI: 10.1055/s-0029-1218788
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Ruthenium Lewis Acid Catalyzed Asymmetric 1,3-Dipolar Cycloadditions between N-Methylnitrones and Enals

Andrei Bãdoiu, Gérald Bernardinelli, E. Peter Kündig*
Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
Fax: +41(22)3793215; e-Mail: Peter.Kundig@unige.ch;
Further Information

Publication History

Received 22 April 2010
Publication Date:
20 May 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

N-Methylisoxazolidines are formed in good yields and high regio-, diastereo- and enantioselectivity via asymmetric 1,3-dipolar cycloaddition of nitrones with enals catalyzed by a chiral ruthenium Lewis acid. Electronic effects in the dipole are the key to activation of these substrates for efficient catalysis.

Key words

asymmetric catalysis - Lewis acid - ruthenium - N-methyl nitrones - 1,3-dipolar cycloaddition

    References

  • 1 Lait SM. Rankic DA. Keay BA. Chem. Rev.  2007,  107:  767 
    CrossrefPubMedGoogle Scholar
  • 2a Huisgen R. In 1,3-Dipolar Cycloaddition Chemistry   Vol. 1:  Padwa A. Wiley; New York: 1984.  p.1 
    Google Scholar
  • 2b Padwa A. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.1069 
    Google Scholar
  • 2c Wade PA. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.1111 
    Google Scholar
  • 2d Gothelf KV. Jørgensen KA. Chem. Rev.  1998,  98:  863 
    Google Scholar
  • 3 Bruin ME. Kündig EP. Chem. Commun.  1998,  2635 
    CrossrefGoogle Scholar
  • 4a Kündig EP. Saudan CM. Bernardinelli G. Angew. Chem. Int. Ed.  1999,  38:  1220 
    Google Scholar
  • 4b Kündig EP. Saudan CM. Alezra V. Viton F. Bernardinelli G. Angew. Chem. Int. Ed.  2001,  40:  4481 
    Google Scholar
  • 4c Kündig EP. Saudan CM. Viton F. Adv. Synth. Catal.  2001,  343:  51 
    Google Scholar
  • 4d Anil Kumar PG. Pregosin PS. Vallet M. Bernardinelli G. Jazzar RF. Viton F. Kündig EP. Organometallics  2004,  23:  5410 
    Google Scholar
  • 4e Alezra V. Bernardinelli G. Corminboeuf C. Frey U. Kündig EP. Merbach AE. Saudan CM. Viton F. Weber J. J. Am. Chem. Soc.  2004,  126:  4843 
    Google Scholar
  • 5 Rickerby J. Vallet M. Bernardinelli G. Viton F. Kündig EP. Chem. Eur. J.  2007,  13:  3354 
    CrossrefGoogle Scholar
  • 6 Viton F. Kündig EP. Bernardinelli G. J. Am. Chem. Soc.  2002,  124:  4968 
    CrossrefGoogle Scholar
  • 7a Mita T. Ohtsuki N. Ikeno T. Yamada T. Org. Lett.  2002,  4:  2457 
    Google Scholar
  • 7b Nagata T. Yorozu Y. Yamada T. Mukaiyama T. Angew. Chem., Int. Ed. Engl.  1995,  34:  2145 
    Google Scholar
  • 7c Kezuka S. Ohtsuki N. Mita T. Kogami Y. Ashizawa T. Ikeno T. Yamada T. Bull. Chem. Soc. Jpn.  2003,  76:  2197 
    Google Scholar
  • 7d Ohtsuki N. Kezuka S. Kogami Y. Mita T. Ashizawa T. Ikeno T. Yamada T. Synthesis  2003,  1462 
    Google Scholar
  • 7e Shirahase M. Kanemasa S. Oderaotoshi Y. Org. Lett.  2004,  6:  675 
    Google Scholar
  • 7f Shirahase M. Kanemasa S. Hasegawa M. Tetrahedron Lett.  2004,  45:  4061 
    Google Scholar
  • 7g Carmona D. Lamata MP. Viguri F. Rodriguez R. Oro LA. Balana AI. Lahoz FJ. Tejero T. Merino P. Franco S. Montesa I. J. Am. Chem. Soc.  2004,  126:  2717 
    Google Scholar
  • 7h Carmona D. Lamata MP. Viguri F. Rodriguez R. Oro LA. Lahoz FJ. Balana AI. Tejero T. Merino P. J. Am. Chem. Soc.  2005,  127:  13386 
    Google Scholar
  • 7i Carmona D. Lamata MP. Viguri F. Rodriguez R. Fischer T. Lahoz FJ. Dobrinovitch IT. Oro LA. Adv. Synth. Catal.  2007,  349:  1751 
    Google Scholar
  • 7j Carmona D. Lamata MP. Viguri F. Ferrer J. Garcia N. Lahoz FJ. Martin ML. Oro LA. Eur. J. Inorg. Chem.  2006,  3155 
    Google Scholar
  • 7k Carmona D. Lamata MP. Viguri F. Rodriguez R. Lahoz FJ. Oro LA. Chem. Eur. J.  2007,  13:  9746 
    Google Scholar
  • 7l Carmona D. Lamata MP. Viguri F. Rodriguez R. Lahoz FJ. Fabra MJ. Oro LA. Tetrahedron: Asymmetry  2009,  20:  1197 
    Google Scholar
  • 7m Kano T. Hashimoto T. Maruoka K. J. Am. Chem. Soc.  2005,  127:  11927 
    Google Scholar
  • 7n Hashimoto T. Omote M. Kano T. Maruoka K. Org. Lett.  2007,  9:  4805 
    Google Scholar
  • 7o Hashimoto T. Omote M. Hato Y. Kano T. Maruoka K. Chem. Asian J.  2008,  3:  407 
    Google Scholar
  • 7p Wang YW. Wolf J. Zavalij P. Doyle MP. Angew. Chem. Int. Ed.  2008,  47:  1439 
    Google Scholar
  • 8a Jen WS. Wiener JJM. MacMillan DWC. J. Am. Chem. Soc.  2000,  122:  9874 
    Google Scholar
  • 8b Karlsson S. Hogberg H.-E. Tetrahedron  2002,  13:  923 
    Google Scholar
  • 8c Karlsson S. Hogberg H.-E. Eur. J. Org. Chem.  2003,  2782 
    Google Scholar
  • 8d Puglisi A. Benaglia M. Cinquini M. Cozzi F. Celentano G. Eur. J. Org. Chem.  2004,  567 
    Google Scholar
  • 8e Lemay M. Trant J. Ogilvie WW. Tetrahedron  2007,  63:  11644 
    Google Scholar
  • 8f Chow SS. Nevalainen M. Evans CA. Johannes CW. Tetrahedron Lett.  2007,  48:  277 
    Google Scholar
  • 9a Bãdoiu A. Brinkmann Y. Viton F. Kündig EP. Pure Appl. Chem.  2008,  5:  1013 
    Google Scholar
  • 9b Bãdoiu A. Bernardinelli G. Mareda J. Kündig EP. Viton F. Chem. Asian J.  2008,  3:  1298 ; Erratum: Chem. Asian J. 2009, 4, 1021
    Google Scholar
  • 10 Brinkmann Y. Reniguntala JM. Jazzar R. Bernardinelli G. Kündig EP. Tetrahedron  2007,  63:  8413 
    CrossrefGoogle Scholar
  • 11a Dicken CM. DeShong P. J. Org. Chem.  1982,  47:  2047 
    Google Scholar
  • 11b Chan KS. Yeung ML. Chan W. Wang R.-J. Mak TCW. J. Org. Chem.  1995,  60:  1741 
    Google Scholar
  • 13 Kanemasa S. Uemura T. Wada E. Tetrahedron Lett.  1992,  33:  7889 
    CrossrefGoogle Scholar
  • 16 Altomare A. Burla MC. Camalli M. Cascarano GL. Giacovazzo C. Guagliardi A. Moliterni AGG. Polidori G. Spagna R. J. Appl. Crystallogr.  1999,  32:  115 
    CrossrefGoogle Scholar
  • 17 Hall SR. Flack HD. Stewart JM. Xtal 3.2 User’s Manual   Universities of Western Australia and Maryland; Australia: 1992. 
    Google Scholar
12

Optimization of the reaction conditions was performed with 3e and 2 in the presence of 5 mol% of (R,R)-1. Screening showed -5 ˚C to be the optimal temperature for this combination of substrates and catalyst. Parallel runs in anhyd and commercial grade CH2Cl2, respectively, led to the same result (85% yield, 94:6 endo/exo, 92% ee); consequently, solvent screening was done with nondried, undistilled, commercial grade solvents. The same results as above were obtained with THF and EtOAc. Lower yields (60%) and selectivities were obtained when using CHCl3 (>95:5 endo/exo, 81% ee) or toluene (84:16 endo/exo, 90% ee). Alcohols, DMF, DMSO, or acetone led to extensive decomposition of the nitrone. Surprisingly, good selectivities (95:5 endo/exo, 88% ee) were obtained when running the reaction in H2O (at 0 ˚C), albeit in low yield (30%).

14

For the X-ray structure of (S,S)-1˙methacrolein, see ref. 4a. The approach of the nitrone is modeled.

15

Crystallographic data for compound 4d have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC-773807. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.