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Synlett 2007(2): 0298-0302  
DOI: 10.1055/s-2007-968014
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Diels-Alder Reactions: Effect of the Achiral Template on Reactivity and Selectivity

Mukund P. Sibi*, Jianxie Chen, Levi Stanley
Department of Chemistry, North Dakota State University, Fargo, North Dakota 58105, USA
Fax: +1(701)2311057; e-Mail: Mukund.Sibi@ndsu.edu;
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Publikationsverlauf

Received 2 October 2006
Publikationsdatum:
24. Januar 2007 (online)

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Abstract

Several achiral templates have been evaluated in chiral Lewis acid mediated enantioselective Diels-Alder reactions. Templates such as pyrrolidinones and pyrazolidinones that are capable of forming six-membered chelates with the Lewis acid exhibited the best reactivity and highest selectivity.

Key words

Diels-Alder - achiral template - chiral Lewis acid - chelation

    References and Notes

  • For comprehensive reviews on enantioselective Diels-Alder reactions, see:
  • 1a Corey EJ. Angew. Chem. Int. Ed.  2002,  41:  1650 
    CrossrefGoogle Scholar
  • 1b Dias LC. J. Brazilian Chem. Soc.  1997,  8:  289 
    CrossrefGoogle Scholar
  • 2 For a recent review on chiral bis(oxazolines), see: Desimoni G. Faita G. Jørgensen KA. Chem. Rev.  2006,  106:  3561 
    CrossrefPubMedGoogle Scholar
  • 3a Evans DA. Miller SJ. Lectka T. von Matt P. J. Am. Chem. Soc.  1999,  121:  7559 
    CrossrefGoogle Scholar
  • 3b Evans DA. Barnes DM. Johnson JS. Lectka T. von Matt P. Miller SJ. Murry JA. Norcross RD. Shaughnessy EA. Campos KR. J. Am. Chem. Soc.  1999,  121:  7582 
    CrossrefGoogle Scholar
  • 3c Evans DA. Murry JA. von Matt P. Norcross RD. Miller SJ. Angew. Chem., Int. Ed. Engl.  1995,  34:  798 
    CrossrefGoogle Scholar
  • 3d Evans DA. Miller SJ. Lectka T. J. Am. Chem. Soc.  1993,  115:  6460 
    CrossrefGoogle Scholar
  • 4 Kanemasa S. Oderaotoshi Y. Sakaguchi S.-i. Yamamoto H. Tanaka J. Wada E. Curran DP. J. Am. Chem. Soc.  1998,  120:  3074 
    CrossrefGoogle Scholar
  • 5a Carbone P. Desimoni G. Faita G. Filippone S. Righetti P. Tetrahedron  1998,  54:  6099 
    CrossrefGoogle Scholar
  • 5b Desimoni G. Faita G. Righetti P. Sardone N. Tetrahedron  1996,  52:  12019 
    CrossrefGoogle Scholar
  • 5c Corey EJ. Ishihara K. Tetrahedron Lett.  1992,  33:  6807 
    CrossrefGoogle Scholar
  • 6a

    See ref. 3a.
    Crossref
  • 6b Takacs JM. Lawson EC. Reno MJ. Youngman MA. Quincy DA. Tetrahedron: Asymmetry  1997,  8:  3073 
    CrossrefGoogle Scholar
  • 6c Evans DA. Kozlowski MC. Tedrow JS. Tetrahedron Lett.  1996,  37:  7481 
    CrossrefGoogle Scholar
  • 7 Evans DA. Johnson JS. Burgey CS. Campos KR. Tetrahedron Lett.  1999,  40:  2879 
    CrossrefGoogle Scholar
  • 8a Davies IW. Gerena L. Cai D. Larson RD. Verhoeven TR. Reider PJ. Tetrahedron Lett.  1997,  38:  1145 
    CrossrefGoogle Scholar
  • 8b Davies IW. Gerena L. Castonguay L. Senanayake CH. Larson RD. Verhoeven TR. Reider PJ. Chem. Commun.  1996,  1753 
    CrossrefGoogle Scholar
  • 9a Evans DA. Olhava EJ. Johnson JS. Janey JM. Angew. Chem. Int. Ed.  1998,  37:  3372 
    CrossrefGoogle Scholar
  • 9b Ghosh AK. Cho H. Cappiello J. Tetrahedron: Asymmetry  1998,  9:  3687 
    CrossrefGoogle Scholar
  • 10 Evans DA. Miller SJ. Lectka T. Tetrahedron Lett.  1993,  34:  7027 
    CrossrefGoogle Scholar
  • 11a

    See ref. 3d and 4. For select additional examples, see:
    Crossref
  • 11b Sibi MP. Venkatraman L. Liu M. Jasperse CP. J. Am. Chem. Soc.  2001,  123:  8444 
    CrossrefGoogle Scholar
  • 11c Jensen KB. Gothelf KV. Hazell RG. Jørgensen KA. J. Org. Chem.  1997,  62:  2471 
    CrossrefGoogle Scholar
  • 11d Corey EJ. Houpis IN. Tetrahedron Lett.  1993,  34:  2421 
    CrossrefGoogle Scholar
  • 12a

    See ref. 8b. For recent examples from our laboratory, see:
    Crossref
  • 12b Sibi MP. Stanley LM. Jasperse CP. J. Am. Chem. Soc.  2005,  127:  8276 
    CrossrefGoogle Scholar
  • 12c Sibi MP. Petrovic G. Zimmerman J. J. Am. Chem. Soc.  2005,  127:  2390 
    CrossrefGoogle Scholar
  • 12d Sibi MP. Prabagaran N. Ghorpade SG. Jasperse CP. J. Am. Chem. Soc.  2003,  125:  11796 
    CrossrefGoogle Scholar
  • Templates 3, 4, 8 and 11-14 are commercially available. Templates 5-7, 9, and 10 were prepared using literature procedures. For compound 5, see:
  • 14a Reddy PA. Hsiang BCH. Latifi TN. Hill W. Woodward KE. Rothman SM. Ferrendelli JA. Covey DA. J. Med. Chem.  1996,  39:  1898 
    CrossrefGoogle Scholar
  • For compounds 6 and 7, see:
  • 14b Bhatia PA. Brooks CDW. Basha A. Ratajczyk JD. Gunn BP. Bouska JB. Lanni C. Young PR. Bell RL. Carter GW. J. Med. Chem.  1996,  39:  3938 
    CrossrefGoogle Scholar
  • 14c Basha A. Tetrahedron Lett.  1988,  29:  2525 
    CrossrefGoogle Scholar
  • 14d

    For compound 9, see ref. 11b.
    CrossrefGoogle Scholar
  • 15 Akiyama T. Horiguchi N. Ida T. Ozaki S. Chem. Lett.  1995,  975 
    CrossrefGoogle Scholar
  • 16a Sibi MP. Guerrero MA. Synthesis  2005,  1528 
    CrossrefGoogle Scholar
  • 16b Sibi MP. Shay JJ. Liu M. Jasperse CP. J. Am. Chem. Soc.  1998,  120:  6815 
    CrossrefGoogle Scholar
  • 16c Sibi MP. Shay JJ. Ji J. Tetrahedron Lett.  1997,  38:  5955 
    CrossrefGoogle Scholar
  • 16d

    See ref. 12c.
    Crossref
  • 17 Koukcovsky C. Pouilhes A. Langlois Y. J. Am. Chem. Soc.  1990,  112:  6672 
    CrossrefGoogle Scholar
  • 18a

    See ref. 3c.

  • 18b

    General Procedure for the Enantioselective Diels-Alder Reactions.
    A mixture of 1 (20 mg, 0.055 mmol) and Cu(OTf)2 (18 mg, 0.05 mmol) in CH2Cl2 (2 mL) was stirred at r.t. for 1 h to give a clear green solution. A solution of dienophile (0.5 mmol) in CH2Cl2 (2 mL) was added at the temperature given in the tables, followed by freshly distilled cyclopentadiene (165 mg, 2.5 mmol). The reaction was monitored by TLC. After completion of the reaction, H2O (2 mL) was added and the mixture was extracted with CH2Cl2, washed with brine and dried. The solvent was evaporated and the residue was purified by chromatography to give pure product. The endo/exo ratio was evaluated on the basis of 1H NMR spectrum and the enantiomeric purity was determined by HPLC.
    DA Adduct from Compound 4. [α]D 25 -176.3 (c 2.2, CHCl3); 97% ee estimated on the basis of HPLC using a chiral column [Daicel Chiralcel AD with hexane-2-PrOH, 97:3 v/v, 0.5 mL/min, t R (S-isomer) = 34.5 min, t R (R-isomer) = 30.4 min].
    1H NMR (400 MHz, CDCl3): δ = 1.30-1.50 (m, 3 H), 1.82-1.90 (m, 1 H), 1.93-2.02 (m, 2 H), 2.57 (t, J = 8.0 Hz, 2 H), 2.86 (s, 1 H), 3.20 (s, 1 H), 3.64-3.76 (m, 2 H), 3.90-3.97 (m, 1 H), 5.80 (dd, J = 5.6, 2.7 Hz, 1 H), 6.17 (dd, J = 5.6, 3.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 17.3, 29.4, 34.1, 42.9, 44.7, 46.0, 46.2, 50.2, 131.8, 137.9, 175.1, 175.6.
    DA Adduct from Compound 5. [α]D 25 -164.76 (c 2.1, CHCl3); 99% ee estimated on the basis of HPLC using a chiral column [Daicel Chiralcel OD with hexane-2-PrOH, 99:1 v/v, 0.6 mL/min, t R (S-isomer) = 18.8 min, t R (R-isomer) = 22.9 min].
    1H NMR (400 MHz, CDCl3): δ = 1.16 (s, 3 H), 1.20 (s, 3 H), 1.32-1.47 (m, 3 H), 1.78-1.91 (m, 3 H), 2.87 (s, 1 H), 3.20 (s, 1 H), 3.56-3.66 (m, 2 H), 3.92-3.98 (m, 1 H), 5.81 (dd, J = 5.6, 3.0 Hz, 1 H), 6.18 (dd, J = 5.6, 3.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 24.4, 24.5, 29.4, 32.4, 42.1, 42.9, 43.2, 44.7, 46.2, 50.1, 131.8, 138.0, 176.0, 180.1.
    DA Adduct from Compound 9. [α]D 25 -129.3 (c 1.0, CHCl3); 98% ee estimated on the basis of HPLC using a chiral column [Daicel Chiralcel OD-H with hexane-2-PrOH, 98:2 v/v, 1.0 mL/min, t R (S-isomer) = 22.6 min, t R (R-isomer) = 24.3 min].
    1H NMR (400 MHz, CDCl3): δ = 1.18 (s, 6 H), 1.31-1.46 (m, 3 H), 1.83 (ddd, J = 11.6, 9.2, 3.6 Hz, 1 H), 2.52 (d, J = 17.2 Hz, 1 H), 2.58 (d, J = 17.2 Hz, 1 H), 2.87 (s, 1 H), 3.19 (s, 1 H), 3.79 (dt, J = 7.6, 4.0 Hz, 1 H), 3.98 (d, J = 14.0 Hz, 1 H), 4.04 (d, J = 14.0 Hz, 1 H), 5.76 (dd, J = 5.6, 3.2 Hz, 1 H), 6.17 (dd, J = 5.6, 3.2 Hz, 1 H), 7.18-7.22 (m, 1 H), 7.24-7.28 (m, 2 H), 7.42-7.45 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 26.3, 26.5, 29.5, 43.0, 44.1, 44.5, 46.3, 50.2, 57.0, 60.7, 127.4, 128.4, 129.0, 131.7, 138.1, 138.3, 171.7, 174.3.
    DA Adduct from Compound 17. [α]D 25 -155.9 (c 1.2, CHCl3); 98% ee estimated on the basis of HPLC using a chiral column after conversion to the known benzyl ester [Daicel Chiralcel OJ with hexane-EtOH-i-PrOH, 100:0.5:0.4, 0.25 mL/min, t R (S-isomer) = 47.4 min, t R (R-isomer) = 50.6 min].
    1H NMR (500 MHz, CDCl3): δ = 1.12 (d, J = 7.3 Hz, 3 H), 1.23 (s, 3 H), 1.25 (s, 3 H), 1.44-1.46 (m, 1 H), 1.69 (d, J = 8.3 Hz, 1 H), 2.11-2.13 (m, 1 H), 2.52 (s, 1 H), 2.62 (s, 2 H), 3.20 (s, 1 H), 3.40 (dd, J = 3.9, 3.4 Hz, 1 H), 4.03 (AB q, J = 17.6, 14.2 Hz, 2 H), 5.73 (dd, J = 5.9, 2.9 Hz, 1 H), 6.36 (dd, J = 5.9, 2.9 Hz, 1 H), 7.25-7.34 (m, 3 H), 7.48-7.50 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 20.7, 26.4, 26.6, 36.5, 44.3, 47.2, 47.3, 49.7, 52.8, 57.1, 60.8, 127.6, 128.6, 129.1, 131.1, 138.4, 140.0, 171.6, 174.6.

13

All new compounds showed analytical and spectral characteristics consistent with their structure. An experimental procedure and spectral data for select cycloadducts are provided.