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Synlett 2008(18): 2877-2881  
DOI: 10.1055/s-0028-1083501
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Microwave-Assisted Intramolecular Diels-Alder Reaction towards the Total Synthesis of Symbioimine

Stephen Born, Genesis Bacani, Erin E. Olson, Yoshihisa Kobayashi*
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Mail Code 0343, La Jolla, CA 92093-0343, USA
e-Mail: ykoba@ucsd.edu;
Further Information

Publication History

Received 10 July 2008
Publication Date:
15 October 2008 (online)

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Abstract

Uemura’s proposed biosynthetic pathway of symbioimine was demonstrated by microwave-assisted intramolecular ­Diels-Alder reaction of a trans-enone precursor.

Key words

biomimetic reaction - marine natural product - intramolecular Diels-Alder reaction - microwave-assisted reaction - symbioimine

    References and Notes

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  • 12a

    xylene, reflux, 2 d, and

  • 12b

    MeAlCl2, CH2Cl2, -78 ˚C.

13

Microwave instrument: CEM Discovery Labmate microwave system.

14

Microwave-assisted heating of 11 in ethanol provided the Diels-Alder adducts 12a and 12b in 69% with exo/endo = 1:2.

15

The minor diastereomer was assumed to be the exo-adduct. We do not exclude the possibility of epimerization of the major kinetic endo-adduct 14 to the minor exo-adduct under the reaction conditions.

16

As expected, the bulky dienophile below did not afford any Diels-Alder adduct even under the microwave-assisted heating conditions. The starting material was recovered quantitatively (Scheme  [8] ).

Scheme 8

17

¹ H NMR and ¹³ C NMR Data for Compounds 11, 12a,b, and 14
Compound 11: ¹H NMR (400 MHz, CDCl3): δ = 6.78 (q, J = 11.2, 6.4 Hz, 1 H), 6.70 (dd, J = 11.2, 16.0 Hz, 1 H), 6.51 (d, J = 2.4 Hz, 2 H), 6.35 (d, J = 15.6 Hz, 1 H), 6.32 (t, J = 2.4 Hz, 1 H), 6.18 (dd, J = 15.6, 10.4 Hz, 1 H), 6.02 (dd, J = 16.0, 1.6 Hz, 1 H), 5.78 (dt, J = 14.4, 7.2 Hz, 1 H), 3.77 (s, 6 H), 2.54 (t, J = 7.2 Hz, 2 H), 2.48-2.38 (m, 1 H), 2.16 (dt, J = 13.6, 6.4 Hz, 2 H), 1.74 (app q, J = 8.0 Hz, 2 H), 1.04 (d, J = 6.8 Hz, 6 H). ¹³C NMR (100 MHz, CDCl3): δ = 200.8, 160.8 (2 C), 153.4, 139.5, 135.1, 131.1, 130.3, 129.7, 127.5, 104.1 (2 C), 99.6, 55.3 (2 C), 32.2, 31.1, 23.6, 21.3 (2 C).
Compound 12a (exo): ¹H NMR (400 MHz, CDCl3): δ = 6.44 (d, J = 2.0 Hz, 2 H), 6.35 (t, J = 2.4 Hz 1 H), 5.83 (ddd, J = 6.8, 4.8, 1.6 Hz, 1 H), 5.64 (dt, J = 9.6, 1.6 Hz, 1 H), 3.77 (s, 6 H), 3.45-3.38 (m, 1 H), 2.62 (app t, J = 10.8 Hz, 1 H), 2.56-2.34 (m, 3 H), 2.25-2.02 (m, 4 H), 1.84-1.58 (m, 2 H), 0.69 (d, J = 7.2 Hz, 3 H), 0.43 (d, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 212.6, 160.3 (2 C), 144.6, 131.0, 129.5, 108.6 (2 C), 97.8, 55.3 (2 C), 51.8, 45.6, 43.9, 43.2, 42.1, 33.0, 28.2, 27.0, 19.5, 19.0.
Compound 12b (endo): ¹H NMR (400 MHz, CDCl3): δ = 6.34 (d, J = 2.0 Hz, 2 H), 6.30 (t, J = 1.6 Hz, 1 H), 5.70 (ddd, J = 10.0, 5.2, 2.8 Hz, 1 H), 5.47 (d, J = 9.6 Hz, 1 H), 3.77 (s, 6 H), 3.15 (dd, J = 10.0, 2.4 Hz 1 H), 2.62 (dd, J = 11.2, 4.8 Hz, 1 H), 2.52 (dt, J = 12.8, 6.0 Hz, 1 H), 2.45-2.41 (m, 1 H), 2.31-2.26 (m, 2 H), 2.05 (ddd, J = 12.4, 5.2, 3.2 Hz, 1 H), 1.89 (dd, J = 13.2, 3.6 Hz, 1 H), 1.80-1.60 (m, 3 H), 0.79 (d, J = 7.2 Hz, 3 H), 0.75 (d, J = 7.6 Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 215.6, 160.7 (2 C), 147.8, 131.5, 128.6, 106.8 (2 C), 97.6, 55.2 (2 C), 52.9, 46.0, 43.1, 40.3, 40.0, 29.4, 29.0, 26.6, 19.9.
Compound 14: ¹H NMR (400 MHz, CDCl3): δ = 6.32 (d, J = 2.4 Hz, 2 H), 6.30 (t, J = 2.4 Hz, 1 H), 5.87 (ddd, J = 10.0, 4.8, 2.4 Hz, 1 H), 5.70 (dd, J = 10.4, 1.6 Hz, 1 H), 3.75 (s, 6 H), 3.38 (ddd, J = 11.2, 6.0, 2.4 Hz, 1 H), 2.70 (ddd, J = 13.2, 5.2, 3.2 Hz, 1 H), 2.48-2.40 (m, 1 H), 2.31-2.27 (m, 2 H), 2.04-1.96 (m, 1 H), 1.92-1.83 (m, 2 H), 1.76 (dd, J = 13.2, 11.2 Hz 1 H), 1.66-1.55 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 214.4, 160.8 (2 C), 147.6, 130.9, 129.8, 105.3 (2 C), 98.0, 55.2 (2 C), 50.2, 43.1, 38.5, 37.2, 32.1, 28.3, 24.8.