Download PDF
Synlett 2011(8): 1171-1173  
DOI: 10.1055/s-0030-1260532
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Enantioselective Total Synthesis of (+)-Helianane

Kana Soga, Makoto Kanematsu, Masahiro Yoshida, Kozo Shishido*
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
Fax: +81(88)6337287; e-Mail: shishido@ph.tokushima-u.ac.jp;
Further Information

Publication History

Received 1 February 2011
Publication Date:
20 April 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

The enantiocontrolled total synthesis of (+)-helianane, a marine-derived heterocyclic sesquiterpene, has been accomplished with an efficient chirality transfer during the Me3Al-mediated aromatic Claisen rearrangement and a ring-closing metathesis as the key steps. The absolute structure of the natural product has been firmly established by total synthesis.

Key words

metathesis - total synthesis - terpenoids - Claisen rearrangement - helianane

    References and Notes

  • 1 Harrison B. Crews P. J. Org. Chem.  1997,  62:  2646 
    CrossrefGoogle Scholar
  • 2a McEnroe FJ. Fenical W. Tetrahedron  1978,  34:  1661 
    Google Scholar
  • 2b Wright AE. Pomponi SA. McConnell OJ. Kohmoto S. McCarthy PJ. J. Nat. Prod.  1987,  50:  976 
    Google Scholar
  • 2c Butler MS. Capon RJ. Nadeson R. Beveridge AA. J. Nat. Prod.  1991,  54:  619 
    Google Scholar
  • 3 Martin MJ. Berrué F. Amade F. Fernández R. Francesch A. Reyes F. Cuevas C. J. Nat. Prod.  2005,  68:  1554 
    CrossrefGoogle Scholar
  • 4a Stefinovic M. Snieckus V. J. Org. Chem.  1998,  63:  2808 
    Google Scholar
  • 4b Sabui SK. Venkateswaran RV. Tetrahedron Lett.  2004,  45:  9653 
    Google Scholar
  • 4c Sen PK. Biswas B. Venkateswaran RV. Tetrahedron Lett.  2005,  46:  8741 
    Google Scholar
  • 4d Ghosh S. Tuhina K. Bhowmik DR. Venkateswaran RV. Tetrahedron  2007,  63:  644 
    Google Scholar
  • 4e Sabui S. Ghosh S. Sarkar D. Venkateswaran RV. Tetrahedron Lett.  2009,  50:  4683 
    Google Scholar
  • 5 For a review, see: Kamei T. Morimoto S. Shishido K. J. Synth. Org. Chem. Jpn.  2006,  64:  1021 
    CrossrefGoogle Scholar
  • 6 Kishuku H. Shindo M. Shishido K. Chem. Commun.  2003,  350 
    Google Scholar
  • 7a Kaiho T. Yokoyama T. Mori H. Fujiwara J. Nobori T. Okada H. Kamiya J. Maruyama M. Sugawara T. JP 06128238, 1994  Chem. Abstr. 1995,  123, 55900 
    Google Scholar
  • 7b Kaiho T. Miyamoto M. Nobori T. Katakami T. J. Synth. Org. Chem. Jpn.  2004,  62:  27 
    Google Scholar
  • 7c Kamei T. Shindo M. Shishido K. Tetrahedron Lett.  2003,  44:  8505 
    Google Scholar
  • 7d Morimoto S. Shindo M. Shishido K. Heterocycles  2005,  66:  69 
    Google Scholar
  • For examples of the construction of a tertiary stereogenic center at the benzilic position by chirality transfer during the aromatic Claisen rearrangement, see:
  • 8a Goerring HL. Kimoto WI. J. Am. Chem. Soc.  1965,  87:  1748 
    Google Scholar
  • 8b Borgulya J. Madeja R. Fahrni P. Hansen H.-J. Schmid H. Barner R. Helv. Chim. Acta  1973,  56:  14 
    Google Scholar
  • 8c Takano S. Akiyama M. Ogasawara K. J. Chem. Soc., Perkin Trans. 1  1985,  2447 
    Google Scholar
  • 8d Trost BM. Toste FD. J. Am. Chem. Soc.  1998,  120:  815 
    Google Scholar
  • For reviews, see:
  • 9a Castro AMM. Chem. Rev.  2004,  104:  2939 
    Google Scholar
  • 9b The Claisen Rearrangement   Hiersemann M. Nubbemeyer U. Wiley-VCH; Weinheim: 2007. 
    Google Scholar
  • 9c Majumdar KC. Almam S. Chattopadhyay B. Tetrahedron  2008,  64:  597 
    Google Scholar
  • 10 Takano S. Sekiguchi Y. Sato N. Ogasawara K. Synthesis  1987,  139 
    Article in Thieme ConnectGoogle Scholar
  • For reviews, see:
  • 11a Mitsunobu O. Synthesis  1981,  1 
    Google Scholar
  • 11b Hughes DL. Org. React.  1992,  42:  335 
    Google Scholar
  • 11c Hughes DL. Org. Prep. Proced. Int.  1996,  28:  127 
    Google Scholar
  • 12a Tsunoda T. Ito S. J. Synth. Org. Chem. Jpn.  1997,  55:  631 
    Google Scholar
  • 12b Tsunoda T. Yamamiya Y. Ito S. Tetrahedron Lett.  1993,  34:  1639 
    Google Scholar
  • 14 Chan TH. Osanai K. Milacic V. Dou QP. Heterocycles  2008,  76:  485 
    CrossrefGoogle Scholar
  • 15 Fusetani N. Sugano M. Matsunaga S. Hashimoto K. Experientia  1987,  43:  1234 
    CrossrefGoogle Scholar
  • 16a Blackemore PR. Cole WJ. Kocienski PJ. Morley A. Synlett  1998,  26 
    Google Scholar
  • 16b Blackemore PR. J. Chem. Soc., Perkin Trans. 1  2002,  2563 
    Google Scholar
  • 16c Meyers C. Carreira EM. Angew. Chem. Int. Ed.  2003,  42:  694 
    Google Scholar
  • 16d Osaka M. Kanematsu M. Yoshida M. Shishido K. Heterocycles  2010,  80:  1003 
    Google Scholar
  • 17 For a review, see: Trnka TM. Grubbs RH. Acc. Chem. Res.  2001,  34:  18 
    CrossrefPubMedGoogle Scholar
  • 18a Jiménez-G onzález L. Álvarez-Corral M. Munõz-Dorado M. Rodríguez-García I. Chem. Commun.  2005,  2689 
    Google Scholar
  • 18b Oppolzer W. Pimm A. Sammen B. Hume WE. Helv. Chim. Acta  1997,  80:  623 
    Google Scholar
  • 19 Grieco PA. Gilman S. Nishizawa M. J. Org. Chem.  1976,  41:  1485 
    Google Scholar
13

The regioisomer generated from the SN2′ process was obtained in 14% yield. The stereochemistry and the ee of it have not been determined.

20

Analytical Data for Helianane (1)
[α]D +24.0 (c 2.28, CH2Cl2) {Lit.¹ [α]D +8.0 (c 1.01, CH2Cl2)}. IR (neat): 2973, 2926, 1456, 1382, 1256, 1138 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 7.06 (d, J = 8.0 Hz, 1 H), 6.88 (d, J = 8.0 Hz, 1 H), 6.71 (d, J = 1.5 Hz, 1 H), 3.19 (br s, 1 H), 2.27 (s, 3 H), 1.78-1.70 (m, 1 H), 1.62-1.56 (m, 1 H), 1.52 (m, 2 H), 1.46-1.32 (m, 2 H), 1.41 (s, 3 H), 1.28 (s, 3 H), 1.25 (d, J = 7.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 153.0, 138.8, 135.3, 125.8, 125.8, 124.9, 80.9, 39.7, 38.1, 31.5, 29.2, 26.7, 21.9, 21.2, 20.9. ESI-HRMS:
m/z calcd for C15H22ONa [M+ + Na]+: 241.1568; found: 241.1577.