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Synlett 2005(18): 2767-2768  
DOI: 10.1055/s-2005-918954
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Palladium-Assisted Ring Annulation for the Synthesis of the Batrachotoxin Ring System

Pierre Lacrouts, Philip J. Parsons*, Clive S. Penkett, Abdul Rauf Raza
Department of Chemistry, School of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QJ, UK
Fax: +44(1273)678661; e-Mail: P.J.Parsons@sussex.ac.uk;
Further Information

Publication History

Received 1 July 2005
Publication Date:
21 October 2005 (online)

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Abstract

A method for the synthesis of the steroidal nucleus in general and in particular for the cardiotoxin batrachotoxin has been carried out using a ‘one-pot’ palladium-mediated annulation sequence.

Key words

palladium - cyclisation - microwave

    References

  • 1 Daly JW. Science  1967,  156:  1970 
    Google Scholar
  • 2a Grinsteiner TJ. Kishi Y. Tetrahedron Lett.  1994,  35:  8333 
    Google Scholar
  • 2b Trudeau S. Deslongchamps P. J. Org. Chem.  2004,  69:  932 
    Google Scholar
  • 3 Imhof R. Graf W. Berner-Ferz L. Berner H. Schaufilberfer R. Wehrli H. Biochem. Pharmacol.  1973,  56:  139 
    Google Scholar
  • 4a Larock RC. Gong WH. J. Org. Chem.  1989,  54:  2047 
    Google Scholar
  • 4b

    Typical Experimental Procedure for the Synthesis of Tetracycle 3.
    A flame dried microwave tube was charged with (1R,3R,7R,8S)-4-bromo-3-ethynyl-1-methoxy-8-methyl-2-oxatricyclo[5.3.1.03,8]undec -4-ene (4, 200 mg, 0,67 mmol), cyclopent-2-enone (0.11 mL, 110 mg, 1.34 mmol) and Et3N (0.28 mL, 203 mg, 2.01 mmol) under nitrogen. The tube was sealed and irradiated under microwave conditions until a temperature of 110 °C was reached. The temperature was maintained for a further 5 min and the reaction mixture was rapidly cooled. The reaction mixture was partitioned between brine 10 mL and Et2O (3 × 20 mL). The combined organic layer was dried (MgSO4), filtered and concentrated. Purification of the resulting crude dark oil using flash silica chromatography with 20% Et2O-PE (60:80) gave the title compound 3 (48%) and the ketone 17 (10%).
    Physical Data for 3. R f = 0.56 (Et2O-PE 1:1). IR: νmax = 2974 (C=C-H), 2933 (sat. C-H), 1714 (α,β-unsat.C=O) cm-1. [α]D 24 -81.4 (c 1.02, CHCl3). ESI-MS [M + Na]+ (amu): 323.1616 (found), 323.1618 (calcd; 0.2 mmu difference). LRMS (EI): m/z (%) = 300(100) [M+ ], 285 (9) [M+ - Me], 272 (12) [M+ - CO]. H1 NMR (300 MHz, CDCl3): δ = 0.69 (s, 3 H, C-CH3), 1.40 (m, 1 H, 7-Hα), 1.52 (ddd, 1 H J = 13.6, 12.5, 5.0 Hz, 16-Hα), 1.65-2.00 (m, 6 H, 12-H, 13-H, 11-Hα, 13-H, 15-H), 2.14 (d, 3 H, J = 2.9 Hz, =C-CH3), 2.17-2.31 (m, 3 H, 11-Hβ, 7-Hβ, 16-Hβ), 2.40-2.55 (m, 2 H, 6-H), 3.23 (s, OCH3), 3.85 (m, 1 H, 8-H), 5.39 (m, 1 H, 10-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.0 (q), 19.4 (q), 27.3 (t), 30.1 (s), 30.7, 30.9, 31.2 (t), 37.0 (d), 37.1 (t), 44.0 (t), 48.5 (d), 50.0 (q), 93.5 (s), 98.1 (s), 117.0 (d), 143.9, 145.1, 145.9 (s), 204.4 (s) ppm.

  • 5a Shih C. Fritzen EL. Swenton JS. J. Org. Chem.  1980,  45:  4462 
    CrossrefGoogle Scholar
  • 5b Hudson P. Pairaudeau G. Parsons PJ. Jahans AW. Drew MGB. Tetrahedron Lett.  1993,  34:  7295 
    CrossrefGoogle Scholar
  • 6 Jones CS. Elliott E. Siegal JS. Synlett  2004,  187 
    Article in Thieme ConnectGoogle Scholar
  • 7 Scheffer JR. Wostradowski RA. J. Org. Chem.  1972,  37:  4317 
    CrossrefGoogle Scholar
  • 8 Parsons PJ. Stefinovic M. Willis P. Meyer FE. Synlett  1992,  864 
    Article in Thieme ConnectGoogle Scholar
  • 9 Schweizer S. Song Z.-Z. Meyer FE. Parsons PJ. de Meijere A. Angew. Chem. Int. Ed.  1999,  38:  1452 ; Angew. Chem. 1999, 111, 1550
    CrossrefPubMedGoogle Scholar
  • 10 Nilsson P. Hold H. Larhed M. Halberg A. Synthesis  2002,  1611 
    Article in Thieme ConnectGoogle Scholar