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Synlett 2009(19): 3175-3178  
DOI: 10.1055/s-0029-1218282
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Organocatalytic Asymmetric Triple Domino Reactions of Nitromethane with α,β-Unsaturated Aldehydes

Dieter Enders*a, Matthieu Jeantya, Jan W. Batsb
a Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Fax: +49(241)8092127; e-Mail: enders@rwth-aachen.de;
b Institute of Organic Chemistry and Chemical Biology, University Frankfurt, Marie-Curie-Str. 11, 60439 Frankfurt am Main, Germany
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Publication History

Received 11 September 2009
Publication Date:
08 October 2009 (online)

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Organocatalytic Asymmetric Triple Domino Reactions of Nitromethane with α,β-Unsaturated AldehydesSynlett 2009; 2009(19): e5-e5
DOI: 10.1055/s-0029-1218349

Abstract

An organocatalytic asymmetric multicomponent domino reaction employing the bulk chemical nitromethane and α,β-unsaturated aldehydes as substrates is described. The new triple cascade reaction based on two subsequent Michael additions and an intramolecular aldol condensation provides an atom-economic entry to diastereo- and enantiomerically pure 5-nitrocyclohexene carbaldehydes after flash chromatography.

Key words

domino reaction - organocatalysis - Michael addition - nitroalkane - aldol condensation

    References and Notes

  • 1 For a recent review on nitroalkane additions to α,β-unsaturated carbonyl compounds, see: Ballini B. Bosica G. Fiorini G. Palmieri A. Petrini M. Chem. Rev.  2005,  105:  933 
    CrossrefPubMedSearch in Google Scholar
  • For selected examples, see:
  • 2a Hanessian S. Pham V. Org. Lett.  2000,  2:  2975 
    Search in Google Scholar
  • 2b Corey EJ. Zhang F.-Y. Org. Lett.  2000,  2:  4257 
    Search in Google Scholar
  • 2c Halland N. Hazell RG. Jørgensen KA. J. Org. Chem.  2002,  67:  8331 
    Search in Google Scholar
  • 2d Tsogoeva SB. Jagtap SB. Synlett  2004,  2624 
  • 2e Mitchell CET. Brenner SE. Ley SV. Chem. Commun.  2005,  5346 
  • 2f Prieto A. Halland N. Jørgensen KA. Org. Lett.  2005,  7:  3897 
    Search in Google Scholar
  • 2g Vakulya B. Varga S. Csámpai A. Soós T. Org. Lett.  2005,  7:  1967 
    Search in Google Scholar
  • 2h Ooi T. Takada S. Fujioka S. Maruoka K. Org. Lett.  2005,  7:  5143 
    Search in Google Scholar
  • 2i Hanessian S. Shao Z. Warrier JS. Org. Lett.  2006,  8:  4787 
    Search in Google Scholar
  • 2j Enders D. Narine AA. Benninghaus TR. Raabe G. Synlett  2007,  1667 
  • 2k Zu L. Xie H. Li H. Wang J. Wang W. Adv. Synth. Catal.  2007,  349:  2660 
    Search in Google Scholar
  • 2l Gotoh H. Ishikawa H. Hayashi Y. Org. Lett.  2007,  9:  5307 
    Search in Google Scholar
  • 2m Hojabri L. Hartikka A. Moghaddam FM. Arvidsson PI. Adv. Synth. Catal.  2007,  349:  740 
    Search in Google Scholar
  • 2n Wang Y. Li P. Liang X. Zhang TY. Ye J. Chem. Commun.  2008,  1232 
  • 2o Li P. Wang Y. Liang X. Ye J. Chem. Commun.  2008,  3302 
  • 2p Enders D. Wang C. Bats JW. Synlett  2009,  1777 
  • 2q Zhong S. Chen Y. Petersen JL. Akhmedov NG. Shi X. Angew. Chem. Int. Ed.  2009,  48:  1279 
    Search in Google Scholar
  • 2r Mei K. Jin M. Zhang S. Li P. Liu W. Chen X. Xue F. Duan W. Wang W. Org. Lett.  2009,  11:  2864 
    Search in Google Scholar
  • 2s Gotoh H. Okamura D. Ishikawa H. Hayashi Y. Org. Lett.  2009,  11:  4056 
    Search in Google Scholar
  • 2t Chen Y. Zhong C. Sun X. Akhmedov NG. Petersen JL. Shi X. Chem. Commun.  2009,  5150 
  • For recent reviews on organocatalysis, see:
  • 3a Berkessel A. Gröger H. Asymmetric Organacatalysis   Wiley-VCH; Weinheim: 2005. 
  • 3b Seayad J. List B. Org. Biomol. Chem.  2005,  3:  719 
    Search in Google Scholar
  • 3c Marigo M. Jørgensen KA. Chem. Commun.  2006,  2001 
  • 3d List B. Chem. Commun.  2006,  819 
  • 3e Lelais G. MacMillan DWC. Aldrichimica Acta  2006,  39:  79 
    Search in Google Scholar
  • 3f Special issue on organocatalysis: Chem. Rev.  2007,  107: 5413
  • 3g Dalko PI. Enantioselective Organocatalysis, Reactions and Experimental Procedures   Wiley-VCH; Weinheim: 2007. 
  • 3h de Figueiredo RM. Christmann M. Eur. J. Org. Chem.  2007,  2575 
  • 3i Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 
    Search in Google Scholar
  • 3j Melchiorre P. Marigo M. Carlone A. Bartoli G. Angew. Chem. Int. Ed.  2008,  47:  6138 
    Search in Google Scholar
  • 3k Yu X. Wang W. Org. Biomol. Chem.  2008,  6:  2037 
    Search in Google Scholar
  • 3l Bella M. Gasperi T. Synthesis  2009,  1583 
  • 3m Bertelsen S. Jørgensen KA. Chem. Soc. Rev.  2009,  38:  2178 
    Search in Google Scholar
  • For reviews on domino reactions, see:
  • 4a Tietze LF. Chem. Rev.  1996,  96:  115 
    Search in Google Scholar
  • 4b Tietze LF. Brasche G. Gericke K. Domino Reactions in Organic Synthesis   Wiley-VCH; Weinheim: 2006. 
  • 4c Pellissier H. Tetrahedron  2006,  62:  1619 
    Search in Google Scholar
  • 4d Pellissier H. Tetrahedron  2006,  62:  2143 
    Search in Google Scholar
  • 4e Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed.  2006,  45:  7134 
    Search in Google Scholar
  • 4f Chapman CJ. Frost CG. Synthesis  2007,  1 
  • 4g Poulin J. Grisé-Bard CM. Barriault L. Chem. Soc. Rev.  2009,  in press; DOI: 10.1039/b819798a
  • 5a Enders D. Hüttl MRM. Grondal C. Raabe G. Nature (London)  2006,  441:  861 
    Search in Google Scholar
  • 5b Enders D. Hüttl MRM. Runsink J. Raabe G. Wendt B. Angew. Chem. Int. Ed.  2007,  46:  467 
    Search in Google Scholar
  • 5c Enders D. Hüttl MRM. Raabe G. Bats JW. Adv. Synth. Catal.  2008,  350:  267 
    Search in Google Scholar
  • For reviews on organocatalytic domino reactions, see:
  • 6a Enders D. Grondal C. Hüttl MRM. Angew. Chem. Int. Ed.  2007,  46:  1570 
    Search in Google Scholar
  • 6b Yu X. Wang W. Org. Biomol. Chem.  2008,  6:  2037 
    Search in Google Scholar
  • 7 Carlone A. Cabrera S. Marigo M. Jørgensen KA. Angew. Chem. Int. Ed.  2007,  46:  1101 
    CrossrefSearch in Google Scholar
  • 8 Battistuzzi G. Cacchi S. Fabrizi G. Org. Lett.  2003,  5:  777 
    CrossrefSearch in Google Scholar
  • 11 Trost BM. Acc. Chem. Res.  2002,  35:  695 
    CrossrefPubMedSearch in Google Scholar
9

CCDC-743470 (3a) contains the supplementary crystallographic data for this paper. More data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www. ccdc.cam.ac.uk/data_request/cif.

10

General Procedure
In an ordinary vial equipped with a magnetic stirring bar, the α,β-unsaturated aldehyde 1 (2.2 mmol, 2.2 equiv) was dissolved in CHCl3 (1 mL). The catalyst (S)-2 (0.2 mmol, 0.2 equiv) and nitromethane (1 mmol, 1 equiv) were added to the solution. The vial was sealed, and the mixture was stirred for 20 h at r.t. The crude reaction mixture was diluted in CH2Cl2, washed with H2O, and dried over MgSO4. After concentration, the crude product was purified by flash chromatography (silica gel, pentane-EtOAc). All new compounds gave satisfactory spectroscopic and analytical data. As a typical example, the data of the compound 3a are given.
(4 S ,5 R ,6 R )-5-Nitro-4,6-diphenylcyclohex-1-ene carbaldehyde (3a, Figure 2)
Isolated as a yellow solid (202 mg, 65%). The ee (>99%) was determined by HPLC on a chiral stationary phase [Chiralcel OD; n-heptane-i-PrOH (8:2); 1.0 mL/min, t R = 9.93 min(major), 18.25 min (minor, based on the racemic mixture)]; mp 108 ˚C; [α]D ²0 -123 (c 1.1, CHCl3). IR (ATR): 3060, 2807, 2718, 2323, 2115, 1684, 1653, 1547, 1494, 1450, 1410, 1366, 1247, 1162, 1078, 946 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 2.89 (ddd, J = 5.2, 5.2, 20.0 Hz, 1 H, H3); 3.25 (dddd, J = 2.4, 11.2, 11.2, 20.0 Hz, 1 H, H3 ′), 3.35-3.40 (m, 1 H, H4), 4.32-4.38 (m, 1 H, H6); 4.96 (dd, J = 1.9, 3.0 Hz, 1 H, H5), 7.03-7.07 (m, 2 H, HPh- para ), 7.22-7.38 (m, 9 H, HPh and H2), 9.57 (s, 1 H, HCHO). ¹³C NMR (100 MHz, CDCl3): δ = 28.0 (C3), 37.3 (C4), 43.2 (C6), 91.3 (C5), 127.3 (CH), 128.0 (CH), 128.9 (CH), 129.2 (CH), 137.9, 138.0, 138.8 (CPh, C1), 150.4 (C2), 191.65 (CHO). HRMS (EI): m/z calcd for C19H1703N1: 307.1203; found: 307.1208.

Figure 2