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: [email protected];
Further Information

Publication History

Received 2 October 2006
Publication Date:
24 January 2007 (online)

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.

    References and Notes

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

    See ref. 3a.

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

    See ref. 3d and 4. For select additional examples, see:

  • 11b Sibi MP. Venkatraman L. Liu M. Jasperse CP. J. Am. Chem. Soc.  2001,  123:  8444 
  • 11c Jensen KB. Gothelf KV. Hazell RG. Jørgensen KA. J. Org. Chem.  1997,  62:  2471 
  • 11d Corey EJ. Houpis IN. Tetrahedron Lett.  1993,  34:  2421 
  • 12a

    See ref. 8b. For recent examples from our laboratory, see:

  • 12b Sibi MP. Stanley LM. Jasperse CP. J. Am. Chem. Soc.  2005,  127:  8276 
  • 12c Sibi MP. Petrovic G. Zimmerman J. J. Am. Chem. Soc.  2005,  127:  2390 
  • 12d Sibi MP. Prabagaran N. Ghorpade SG. Jasperse CP. J. Am. Chem. Soc.  2003,  125:  11796 
  • 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 
  • 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 
  • 14c Basha A. Tetrahedron Lett.  1988,  29:  2525 
  • 14d

    For compound 9, see ref. 11b.

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

    See ref. 12c.

  • 17 Koukcovsky C. Pouilhes A. Langlois Y. J. Am. Chem. Soc.  1990,  112:  6672 
  • 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.