PDF icon PDF herunterladen
Synthesis 2010(4): 567-572  
DOI: 10.1055/s-0029-1217146
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Microwave-Assisted Organocatalytic Quadruple Domino Reactions of Acetaldehyde and Nitroalkenes

Dieter Enders*, Ralf Krüll, Wolfgang Bettray
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Fax: +49(241)8092127; e-Mail: enders@rwth-aachen.de;
Weitere Informationen

Publikationsverlauf

Received 13 October 2009
Publikationsdatum:
27. November 2009 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik
Preview

Abstract

A microwave-assisted, organocatalytic domino Michael/Henry condensation/Michael/aldol condensation reaction has been developed. Employing acetaldehyde and nitroalkenes as substrates, this quadruple cascade allows an efficient asymmetric synthesis of trisubstituted cyclohexene carbaldehydes in moderate to good yields (25-45%) and high enantioselectivities (ee = 89 to >99%). ESI-MS measurements were carried out to support the proposed complex catalytic cycle.

Key words

organocatalysis - cascade reaction - Michael addition - aldol condensation - cyclohexene carbaldehydes

    References

  • For recent reviews on organocatalysis, see:
  • 1a Berkessel A. Gröger H. Asymmetric Organocatalysis   Wiley-VCH; Weinheim: 2005. 
  • 1b Dalko PI. Enantioselective Organocatalysis   Wiley-VCH; Weinheim: 2007. 
  • 1c Special issue on organocatalysis: Chem. Rev.  2007,  107:  issue 12 
  • 1d Pellisier H. Tetrahedron  2007,  63:  9267 
    Suche in Google Scholar
  • 1e de Figueiredo RM. Christmann M. Eur. J. Org. Chem.  2007,  2575 
  • 1f Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 ; Angew. Chem. 2008, 120, 4716
    Suche in Google Scholar
  • 1g Kotsuki H. Ikishima H. Okuyama A. Heterocycles  2008,  75:  493 
    Suche in Google Scholar
  • 1h Kotsuki H. Ikishima H. Okuyama A. Heterocycles  2008,  75:  757 
    Suche in Google Scholar
  • 1i Enders D. Narine AA. J. Org. Chem.  2008,  73:  7857 
    Suche in Google Scholar
  • 1j Melchiorre P. Marigo M. Carlone A. Bartoli G. Angew. Chem. Int. Ed.  2008,  47:  6138 ; Angew. Chem. 2008, 120, 6232
    Suche in Google Scholar
  • 1k Bella M. Gasperi T. Synthesis  2009,  1583 
  • 1l Bertelsen S. Jørgensen KA. Chem. Soc. Rev.  2009,  38:  2178 
    Suche in Google Scholar
  • For recent reviews on domino reactions, see:
  • 2a Tietze LF. Chem. Rev.  1996,  96:  115 
    Suche in Google Scholar
  • 2b Tietze LF. Brasche G. Gericke K. Domino Reactions in Organic Synthesis   Wiley-VCH; Weinheim: 2006. 
  • 2c Pellisier H. Tetrahedron  2006,  62:  1619 
    Suche in Google Scholar
  • 2d Pellisier H. Tetrahedron  2006,  62:  2143 
    Suche in Google Scholar
  • 2e Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed.  2006,  45:  7134 ; Angew. Chem. 2006, 118, 7292
    Suche in Google Scholar
  • 2f Chapman CJ. Frost CG. Synthesis  2007,  1 
  • 2g Walji AM. MacMillan DWC. Synlett  2007,  1477 
  • For reviews on organocatalytic domino reactions, see:
  • 3a Enders D. Grondal C. Hüttl MRM. Angew. Chem. Int. Ed.  2007,  46:  1570 ; Angew. Chem. 2007, 119, 1590
    Suche in Google Scholar
  • 3b Yu X. Wang W. Org. Biomol. Chem.  2008,  6:  2037 
    Suche in Google Scholar
  • For selected examples of organocatalytic domino reactions, see:
  • 4a Yang JW. Fonseca MTH. List B. J. Am. Chem. Soc.  2005,  127:  15036 
    Suche in Google Scholar
  • 4b Huang Y. Walji AM. Larsen CH. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  15051 
    Suche in Google Scholar
  • 4c Enders D. Hüttl MRM. Grondal C. Raabe G. Nature  2006,  441:  861 
    Suche in Google Scholar
  • 4d Wang W. Li H. Wang J. Zu L. J. Am. Chem. Soc.  2006,  128:  10354 
    Suche in Google Scholar
  • 4e Enders D. Hüttl MRM. Runsink J. Raabe G. Wendt B. Angew. Chem. Int. Ed.  2007,  46:  467 ; Angew. Chem. 2007, 119, 471
    Suche in Google Scholar
  • 4f Enders D. Narine AA. Benninghaus TR. Raabe G. Synlett  2007,  1667 
  • 4g Carlone A. Cabrera S. Marigo M. Jørgensen KA. Angew. Chem. Int. Ed.  2007,  46:  1101 ; Angew. Chem. 2007, 119, 1119
    Suche in Google Scholar
  • 4h Hayashi Y. Okano T. Aratake S. Hazelard D. Angew. Chem. Int. Ed.  2007,  46:  4922 ; Angew. Chem. 2007, 119, 5010
    Suche in Google Scholar
  • 4i Vicario JL. Reboredo L. Badía D. Carillo L. Angew. Chem. Int. Ed.  2007,  46:  5168 ; Angew. Chem. 2007, 119, 5260
    Suche in Google Scholar
  • 4j Rueping M. Sugiono E. Merino E. Angew. Chem. Int. Ed.  2008,  47:  3046 ; Angew. Chem. 2008, 120, 3089
    Suche in Google Scholar
  • 4k Enders D. Wang C. Bats JW. Angew. Chem. Int. Ed.  2008,  47:  7539 ; Angew, Chem. 2008, 120, 7649
    Suche in Google Scholar
  • 4l Zhao G.-L. Rios R. Vesley J. Eriksson L. Córdova A. Angew. Chem. Int. Ed.  2008,  47:  8468 ; Angew. Chem. 2008, 120, 8596
    Suche in Google Scholar
  • 4m Lu M. Zhu D. Lu Y. Hou Y. Tan B. Zhong G. Angew. Chem. Int. Ed.  2008,  47:  10187 ; Angew. Chem. 2008, 120, 10341
    Suche in Google Scholar
  • 4n Enders D. Hüttl MRM. Raabe G. Bats JW. Adv. Synth. Catal.  2008,  350:  267 
    Suche in Google Scholar
  • 4o Kotame P. Hong B.-C. Liao J.-H. Tetrahedron Lett.  2009,  50:  704 
    Suche in Google Scholar
  • 4p Franzén J. Fisher A. Angew. Chem. Int. Ed.  2009,  48:  787 ; Angew. Chem. 2009, 121, 801
    Suche in Google Scholar
  • For reviews on organocatalytic Michael additions, see:
  • 5a Tsogoeva SB. Eur. J. Org. Chem.  2007,  1701 
  • 5b Sulzer-Mossé S. Alexakis A. Chem. Commun.  2007,  3123 
  • 5c Vicario JL. Badía D. Carillo L. Synthesis  2007,  2065 
  • 5d Almasi D. Alonso DA. Nájera C. Tetrahedron: Asymmetry  2007,  18:  299 
    Suche in Google Scholar
  • 6 For a review on organocatalytic aldol reactions, see: Guillena G. Nájera C. Ramón DJ. Tetrahedron: Asymmetry  2007,  18:  2249 
    CrossrefSuche in Google Scholar
  • For selected examples of organocatalytic intramolecular aldol reactions, see:
  • 7a Pidathala C. Hoang L. Vignola N. List B. Angew. Chem. Int. Ed.  2003,  42:  2785 ; Angew. Chem. 2003, 115, 2891
    Suche in Google Scholar
  • 7b Kriis K. Kanger T. Laars M. Müürisepp A.-M. Pehk T. Lopp M. Synlett  2006,  1699 
  • 7c Enders D. Niemeier O. Straver L. Synlett  2006,  3399 
  • 7d Hayashi Y. Sekiziwa H. Yamaguchi J. Gotoh H. J. Org. Chem.  2007,  72:  6493 
    Suche in Google Scholar
  • 7e Yoshitomi Y. Makino K. Hamada Y. Org. Lett.  2007,  9:  2457 
    Suche in Google Scholar
  • For selected examples of organocatalytic domino reactions involving intramolecular aldol reactions, see refs 4c-g, 4n, 4o and:
  • 8a Halland N. Abruel PS. Jørgensen KA. Angew. Chem. Int. Ed.  2004,  43:  1272 ; Angew. Chem. 2004, 116, 1292
    Suche in Google Scholar
  • 8b Brandau B. Maerten E. Jørgensen KA. J. Am. Chem. Soc.  2006,  128:  14986 
    Suche in Google Scholar
  • 8c Govender T. Hojbri L. Moghaddam FM. Arvidsson PI. Tetrahedron: Asymmetry  2006,  17:  1763 
    Suche in Google Scholar
  • 8d Wang J. Li H. Xie H. Zu L. Shen X. Wang W. Angew. Chem. Int. Ed.  2007,  46:  9050 ; Angew. Chem. 2007, 119, 9208
    Suche in Google Scholar
  • 8e Li H. Wang J. Xie H. Zu L. Liang W. Duesler EN. Wang W. Org. Lett.  2007,  9:  965 
    Suche in Google Scholar
  • 8f Hong B.-C. Nimje RY. Sadani AA. Liao J.-H. Org. Lett.  2008,  10:  2345 
    Suche in Google Scholar
  • 8g Penon O. Carlone A. Mazzanti A. Locatelli M. Sambri L. Bartoli G. Melchiorre P. Chem. Eur. J.  2008,  14:  4788 
    Suche in Google Scholar
  • For reviews on diphenylprolinol TMS-ether, see:
  • 9a Palomo C. Mielgo A. Angew. Chem. Int. Ed.  2006,  45:  7876 ; Angew. Chem. 2006, 118, 8042
    Suche in Google Scholar
  • 9b Mielgo A. Palomo C. Chem. Asian J.  2008,  3:  922 
    Suche in Google Scholar
  • For reactions with acetaldehyde, see:
  • 10a Gijsen HJM. Wong C.-H. J. Am. Chem. Soc.  1994,  116:  8422 
    Suche in Google Scholar
  • 10b Bogevig A. Kumaragurubaran N. Jørgensen KA. Chem. Commun.  2002,  620 
  • 10c Cordova A. Notz W. Barbas CF. J. Org. Chem.  2002,  67:  301 
    Suche in Google Scholar
  • 10d Northrup AB. MacMillan DWC. Science  2004,  305:  1752 
    Suche in Google Scholar
  • 10e Denmark SE. Bui T. J. Org. Chem.  2005,  70:  10190 
    Suche in Google Scholar
  • 10f Boxer MB. Yamamoto H. J. Am. Chem. Soc.  2006,  128:  48 
    Suche in Google Scholar
  • 10g Boxer MB. Yamamoto H. J. Am. Chem. Soc.  2007,  129:  2762 
    Suche in Google Scholar
  • 10h Dean SM. Greenberg WA. Wong C.-H. Adv. Synth. Catal.  2007,  349:  1308 
    Suche in Google Scholar
  • 10i García-García P. Ladépêche A. Halder R. List B. Angew. Chem. Int. Ed.  2008,  47:  4719 ; Angew. Chem. 2008, 120, 4797
    Suche in Google Scholar
  • 10j Hayashi Y. Itoh T. Aratake S. Ishikawa H. Angew. Chem. Int. Ed.  2008,  47:  2082 ; Angew. Chem. 2008, 120, 2112
    Suche in Google Scholar
  • 10k Hayashi Y. Itoh T. Ohkubo M. Ishikawa H. Angew. Chem. Int. Ed.  2008,  47:  4722 ; Angew. Chem. 2008, 120, 4800
    Suche in Google Scholar
  • 10l Hayashi Y. Okano T. Itoh T. Urushima T. Ishikawa H. Uchimaru T. Angew. Chem. Int. Ed.  2008,  47:  9053 ; Angew. Chem. 2008, 120, 9193
    Suche in Google Scholar
  • 10m Hayashi Y. Samanta S. Itoh T. Ishikawa H. Org. Lett.  2008,  10:  5581 
    Suche in Google Scholar
  • 10n Yang JW. Chandler C. Stadler M. Kampen D. List B. Nature  2008,  452:  453 
    Suche in Google Scholar
  • 10o Chandler C. Galzerano P. Michrowska A. List B. Angew. Chem. Int. Ed.  2009,  48:  1978 ; Angew. Chem. 2009, 121, 2012
    Suche in Google Scholar
  • 10p Itoh T. Ishikawa H. Hayashi Y. Org. Lett.  2009,  11:  3854 
    Suche in Google Scholar
  • For organocatalytic quadruple domino reactions, see:
  • 11a Kotame P. Hong B.-C. Liao J.-H. Tetrahedron Lett.  2009,  50:  704 
    Suche in Google Scholar
  • 11b Zhang F.-L. Xu A.-W. Gong Y.-F. Wei M.-H. Yang X.-L. Chem. Eur. J.  2009,  15:  6815 
    Suche in Google Scholar
  • 12 For the elucidation of the mechanism of an organocatalytic reaction, see: Schrader W. Handayani PP. Zhou J. List B. Angew. Chem. Int. Ed.  2009,  48:  1463 ; Angew. Chem. 2009, 121, 1491
    CrossrefPubMedSuche in Google Scholar