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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;
Further Information

Publication History

Received 2 October 2006
Publication Date:
24 January 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

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    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.