Download PDF
Synlett 2003(10): 1494-1496
DOI: 10.1055/s-2003-40832
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel Medium Ring Sized Estradiol Derivatives by Intramolecular Heck Reactions

Lutz F. Tietze*a, Konrad M. Sommera, Gyula Schneider*b, Pál Tapolcsányib, János Wölflingb, Peter Müllerc, Mathias Noltemeyerc, Heinrich Terlaud
a Institut für Organische Chemie, Universität Göttingen, Tammannstr. 2, 37077 Göttingen, Germany
Fax: +49(551)399476; e-Mail: ltietze@gwdg.de;
b Department of Organic Chemistry, University of Szeged, Dóm tér 8, 6720 Szeged, Hungary
Fax: +36(62)544200; e-Mail: schneider@chem.u-szeged.hu;
c Institut für Anorganische Chemie, Universität Göttingen, Tammannstr. 4, 37077 Göttingen, Germany
Fax: +49(551)393373; e-Mail: m.noltemeyer@gmx.de; e-Mail: peterm@shelx.uni-ac.gwdg.de;
d Max-Planck-Institut für Experimentelle Medizin, Hermann-Rein-Straße 3, 37075 Göttingen, Germany
Fax: +49(551)3899475; e-Mail: hterlau@gwdg.de;
Further Information

Publication History

Received 7 April 2003
Publication Date:
24 July 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

New steroids with a seven-, eight- or nine-membered d-ring have been synthesized from a d-seco-estrone derivative by a Grignard and an intramolecular Heck reaction.

Key words

carbocycles - steroids - Grignard reactions - Heck reaction - estradiol derivatives

    References

  • For an overview of the Heck reaction see:
  • 1a Beletskaya IP. Cheprakov AV. Chem. Rev.  2000,  100:  3009 
    Google Scholar
  • 1b Bräse S. de Meijere A. In Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  p.99-166  ; and references cited therein
    Google Scholar
  • 2a Tietze LF. Nöbel T. Spescha M. Angew. Chem., Int. Ed. Engl.  1996,  35:  2259 ; Angew. Chem. 1996, 108, 2385
    Google Scholar
  • 2b Tietze LF. Nöbel T. Spescha M. J. Am. Chem. Soc.  1998,  120:  8971 
    Google Scholar
  • 2c Tietze LF. Petersen S. Eur. J. Org. Chem.  2000,  1827 
    Google Scholar
  • 2d Tietze LF. Ferraccioli R. Synlett  1998,  145 
    Google Scholar
  • 2e Tietze LF. Petersen S. Eur. J. Org. Chem.  2001,  1619 
    Google Scholar
  • 3 Schneider G. Bottka S. Hackler L. Wölfling J. Sohár P. Liebigs Ann. Chem.  1989,  263 
    Google Scholar
  • 4 Yokoyama Y. Matsushima H. Takashima M. Suzuki T. Murakami Y. Heterocycles  1997,  46:  133 
    CrossrefGoogle Scholar
  • 5 Piers E. Oballa RM. Tetrahedron Lett.  1995,  36:  5857 
    Google Scholar
  • 6 Masters JJ. Jung DK. Bornmann WG. Danishefsky SJ. de Gala S. Tetrahedron Lett.  1993,  34:  7253 
    CrossrefGoogle Scholar
  • 7 Kwon O. Su D. Meng O. Deng W. D’Amico DC. Danishefsky SJ. Angew. Chem. Int. Ed.  1998,  37:  1880 ; Angew. Chem. 1998, 110, 1981
    CrossrefGoogle Scholar
  • 8 Ma S. Negishi E. J. Am. Chem. Soc.  1995,  117:  6345 
    CrossrefGoogle Scholar
  • 9 Joung WB. Masters JJ. Danishefsky SJ. J. Am. Chem. Soc.  1995,  117:  5228 
    CrossrefGoogle Scholar
  • 10 Gibson SE. Middleton RJ. J. Chem. Soc., Chem. Commun.  1995,  1743 
    Google Scholar
  • 11 Beeby MH. Mann FG. J. Chem. Soc.  1951,  411 
    Google Scholar
  • 12 Joyeau R. Yadav LDS. Wakselman M. J. Chem. Soc., Perkin Trans. 1  1987,  1899 
    CrossrefGoogle Scholar
  • 13 Ang HG. Chang B. Kwik WL. Sim ESH. J. Organomet. Chem.  1994,  474:  153 
    Google Scholar
  • 14 Barkov A. Grützmacher HF. Int. J. Mass Spectrom. Ion Processes  1995,  142:  195 
    Google Scholar
  • 15 Iambushev FD. Kokorev GI. Khalimov FG. Zh. Obshch. Khim.  1984,  54:  2005 
    Google Scholar
  • 16 Herrmann WA. Broßmer C. Öfele K. Reisinger CP. Priermeier T. Beller M. Fischer H. Angew. Chem., Int. Ed. Engl.  1995,  34:  1844 ; Angew. Chem. 1995, 107, 1989
    CrossrefGoogle Scholar
  • 17 Horwell DC. Nichols PD. Ratcliffe GS. Roberts E. J. Org. Chem.  1994,  59:  4418 
    CrossrefGoogle Scholar
18

Experimental Procedure for the Synthesis of 19 and 20: To a degassed solution of 10 (300 mg, 0.64 mmol) and n-Bu4NOAc (484 mg, 1.60 mmol) in DMF/CH3CN/H2O (5:5:1) (10 mL) was added under a nitrogen atmosphere trans-di(µ-acetato)-bis[o-(di-o-tolylphosphino)-benzyl]dipalladium(II) (12 mg, 2 mol%) and the mixture was stirred at 120 °C under reflux for 4 h. After cooling, H2O (40 mL) was added; the resulting mixture was extracted with Et2O (3 × 25 mL), washed with brine, dried over MgSO4 and concentrated in vacuo. Purification by column chromatography (silica gel, CH2Cl2/petrol ether = 6/4) and repeated chromatography using AgNO3-coated silica gel (CH2Cl2) afforded 149 mg (60%) of 19 as a colorless oil and 35 mg (14%) of 20 as white crystals.
Selected data for 19: [α]D 20 +22.7 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3, TMS): δ = 1.23 (s, 3 H, 18-H), 1.10-2.40 (m, 10 H), 2.76 (d, 1 H), 2.80 (m, 2 H, 6-H), 3.58 (d, 1 H, J = 15.2 Hz, 17b-H), 3.76 (s, 3 H, 3-OMe), 4.57 (d, 1 H, J = 15.2 Hz, 17b-H), 4.92 (s, 1 H, 16a-H), 5.28 (s, 1 H, 16a-H), 6.62 (d, 1 H, J = 2.6 Hz, 4-H), 6.73 (dd, 1 H, J = 8.6 Hz, 2.6 Hz, 2-H), 7.02-7.24 (m, 5 H, 1-H, 3′-H, 4′-H, 5′-H and 6′-H). 13C NMR (125 MHz, CDCl3, TMS): δ = 14.2 (C-18), 26.2 and 26.4 (2 C, C-11 and C-12), 29.9 (C-6), 37.3, 40.3, 41.2, 41.9, 42.9, 44.1 (C-17b), 53.0 (C-13), 55.2 (3-OCH3), 111.7 (C-2), 113.4 (C-4), 120.7 (C-16a), 126.2, 126.5, 127.1, 129.0, 130.2, 132.0 (C-10), 134.0, 137.7 (C-5), 141.1, 147.4 (C-16), 157.7 (C-3), 215.3 (C-17c).

19

Crystallographic data for 4 and 20 can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Centre CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. Deposition numbers: CCDC 168413 for 4 and CCDC 168412 for 20.

20

Selected data for 12: [α]D 20 -28 (c 1.0, CHCl3). Mp 173-175 °C. 1H NMR (500 MHz, CDCl3, TMS): δ = 1.01 (s, 3 H, 18-H), 1.10-2.50 (m, 13 H), 2.88 (m, 2 H, 6-H), 3.12 (d, 1 H, J = 11.9 Hz, 17c-H), 3.79 (s, 3 H, CH3O), 4.00 (d, 1 H, J = 10.0 Hz, 17d-H), 5.99 (dt, 1 H, J = 15.5, J = 6.2 Hz, 16-H), 6.62 (d, 1 H, J = 15.5 Hz, 17-H), 6.65 (d, 1 H, J = 2.7 Hz, 4-H), 6.74 (dd, 1 H, J = 8.6 Hz, 2.7 Hz, 2-H), 7.08-7.37 (m, 5 H, 1-H, 3′-H, 4′-H, 5′-H, 6′-H). 13C NMR (125 MHz, CDCl3): δ = 17.8 (C-18), 25.7 (C-11), 28.1 (C-7), 30.4, 30.5, 32.4, 35.8, 41.1, 42.2 (C-8), 43.1 (C-9), 44.8 (C-14), 55.2 (CH3O), 73.6 (C-17d), 111.6 (C-2), 113.5 (C-4), 126.3, 126.6, 126.9 (2C), 127.1, 131.4, 133.0 (C-10), 135.7, 136.2, 137.3, 138.1 (C-5), 157.5 (C-3).