Download PDF
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)

    Permissions and Reprints All articles of this category

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

  • 1 Kita M. Kondo M. Koyama T. Yamada K. Matsumoto T. Lee KH. Woo JT. Uemura D. J. Am. Chem. Soc.  2004,  126:  4794 
    CrossrefPubMedGoogle Scholar
  • 2 Rowan R. Powers DA. Science  1991,  251:  1348 
    CrossrefGoogle Scholar
  • RANKL induces osteoclast-like multinucleated cell formation in cultures of bone marrow cells. See:
  • 3a Yasuda H. Shima N. Nakagawa N. Yamaguchi K. Kiosaki M. Mochizuki S.-i. Tomoyasu A. Yano K. Goto M. Murakami A. Tsuda E. Morinaga T. Higashio K. Udagawa N. Takahashi N. Suda T. Proc. Natl. Acad. Sci. U. S. A.  1998,  95:  3597 
    Google Scholar
  • 3b Lancey DL. Timms E. Tan HL. Kelley MJ. Dunstan CR. Burgess T. Elliott R. Colombero A. Elliott G. Scully S. Hsu H. Sullivan J. Hawkins N. Davy E. Capparelli C. Eli A. Qian YX. Kaufman S. Sarosi I. Shalhoub V. Senaldi G. Guo J. Delaney J. Boyle WJ. Cell  1998,  93:  165 
    Google Scholar
  • 3c Hsu H. Lacey DL. Dunstan CR. Solovyev I. Colombero A. Timms E. Tan H.-L. Elliott G. Kelley MJ. Sarosi I. Wang L. Xia X.-Z. Elliott R. Chiu L. Black T. Scully S. Capparelli C. Morony S. Shimamoto G. Bass MB. Boyle WJ. Proc. Natl. Acad. Sci. U. S. A.  1999,  96:  3540 
    Google Scholar
  • 4a Kita M. Uemura D. Chem. Lett.  2005,  34:  454 
    Google Scholar
  • 4b Kita M. Ohishi N. Washida K. Kondo M. Koyama T. Yamada K. Uemura D. Bioorg. Med. Chem.  2005,  13:  5253 
    Google Scholar
  • Reported total syntheses of symbioimine, see:
  • 5a Varseev GN. Maier ME. Angew. Chem. Int. Ed.  2006,  45:  4767 
    Google Scholar
  • 5b Zou Y. Che Q. Snider BB. Org. Lett.  2006,  24:  5605 
    Google Scholar
  • 5c Kim J. Thomson RJ. Angew. Chem. Int. Ed.  2007,  46:  3104 
    Google Scholar
  • For other synthetic studies, see:
  • 5d Snider BB. Che Q. Angew. Chem. Int. Ed.  2006,  45:  932 
    Google Scholar
  • 5e Sakai E. Araki K. Takamura H. Uemura D. Tetrahedron Lett.  2006,  47:  6343 
    Google Scholar
  • For our own efforts along with 2,3-dihydropyridine strategy, see:
  • 5f Born S. Kobayashi Y. Synlett  2008,  2479 
    Google Scholar
  • 6a Gras J.-L. Bertrand M. Tetrahedron Lett.  1979,  4549 
    Google Scholar
  • 6b Gras J.-L. J. Org. Chem.  1981,  46:  3738 
    Google Scholar
  • 6c Taber DF. Kong S. Malcolm SC. J. Org. Chem.  1998,  63:  7953 
    Google Scholar
  • 6d Coe JW. Roush WR. J. Org. Chem.  1989,  54:  915 
    Google Scholar
  • 6e Frankowski KJ. Golden JE. Zeng Y. Lei Y. Aubé J. J. Am. Chem. Soc.  2008,  130:  6018 
    Google Scholar
  • 7 Sammakia showed an interesting method to prepare an octalone core structure of dihydrocompactin, see: Sammakia T. Johns DM. Kim G. Berliner MA. J. Am. Chem. Soc.  2005,  127:  6504 
    CrossrefGoogle Scholar
  • Preparation of (E)-6-iodohex-5-en-1-ol:
  • 8a Lipshutz BH. Kell R. Ellsworth EL. Tetrahedron Lett.  1990,  31:  7257 
    Google Scholar
  • 8b Nishida A. Shirato F. Nakagawa M. Tetrahedron: Asymmetry  2000,  11:  3789 
    Google Scholar
  • 9 Synthesis of pinacolboronate: Shirakawa K. Arase A. Hoshi M. Synthesis  2004,  1814 
    Article in Thieme ConnectGoogle Scholar
  • 10a More JD. Finney NS. Org. Lett.  2002,  4:  3001 
    Google Scholar
  • 10b Frigerio M. Santagostino M. Sputore S. J. Org. Chem.  1999,  64:  4537 
    Google Scholar
  • 11 Preparation of β-ketophosphonate: Hosokawa S. Seki M. Fukuda H. Tatsuta K. Tetrahedron Lett.  2006,  47:  2439 
    CrossrefGoogle Scholar
  • Attempted Diels-Alder reaction of 11 under conventional conditions:
  • 12a

    xylene, reflux, 2 d, and

    Google Scholar
  • 12b

    MeAlCl2, CH2Cl2, -78 ˚C.

    Google Scholar
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.