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Synlett 2008(15): 2309-2312  
DOI: 10.1055/s-2008-1078276
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Reinvestigation of Highly Diastereoselective Pentacyclic Spirolactone Formation by Direct Anodic Oxidation of 2,4-Dimethylphenol

Joaquin Barjaua, Pia Königsa, Olga Kataevab, Siegfried R. Waldvogel*a
a Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
e-Mail: waldvogel@uni-bonn.de;
b A. E. Arbuzov Institute of the Russian Academy of Sciences, Arbuzov Street 8, Kazan 420088, Russian Federation
Further Information

Publication History

Received 21 May 2008
Publication Date:
21 August 2008 (online)

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Abstract

Direct anodic oxidation of 2,4-dimethylphenol yields an unusual spiropentacyclic scaffold. An intermediate was isolated and structurally elucidated which strongly supports the postulated mechanism for the stereoselective formation of this spirolactone moiety. Additionally, we report an ameliorated protocol for the rearrangement to the spirolactone system.

Key words

phenol - spiro compounds - lactones - diastereoselectivity - rearrangements

    References and Notes

  • 1 Poriel C. Ferrand Y. Le Maux P. Paul-Roth C. Simmoneaux G. Rault-Berthelot J. J. Electroanal. Chem.  2005,  583:  92 
    CrossrefSearch in Google Scholar
  • 2a Ogamino T. Ishikawa Y. Nishiyama S. Heterocycles  2003,  61:  73 
    Search in Google Scholar
  • 2b Yamamura S. In The Chemistry of Phenols   Part 2:  Rappaport Z. Wiley; Chichester: 2003.  Chap. 17. p.1153 
    Search in Google Scholar
  • 2c Quideau S. In Modern Arene Chemistry   Astruc D. Wiley-VCH; Weinheim: 2002.  Chap. 15. p.539 
  • 3a Yamamura S. Nishiyama S. Synlett  2002,  533 
  • 3b Sefkow M. Synthesis  2003,  2595 
  • 3c Quideau S. Pouységu L. Deffieux D. Synlett  2008,  467 
  • 3d Quideau S. Pouységu L. Deffieux D. Curr. Org. Chem.  2008,  8:  113 
    Search in Google Scholar
  • 4 Malkowsky IM. Rommel CE. Wedeking K. Fröhlich R. Bergander K. Nieger M. Quaiser C. Griesbach U. Pütter H. Waldvogel SR. Eur. J. Org. Chem.  2006,  241 
    Crossref
  • 5a Malkowsky IM. Fröhlich R. Griesbach U. Pütter H. Waldvogel SR. Eur. J. Inorg. Chem.  2006,  1690 
  • 5b Malkowsky IM. Rommel CE. Fröhlich R. Griesbach U. Pütter H. Waldvogel SR. Chem. Eur. J.  2006,  7482 
  • 5c Griesbach U, Pütter H, Waldvogel SR, and Malkowsky IM. inventors; WO  2005075709. 
  • 6a Malkowsky IM. Griesbach U. Pütter H. Waldvogel SR. Eur. J. Org. Chem.  2006,  4569 
  • 6b Griesbach U, Pütter H, Waldvogel SR, and Malkowsky IM. inventors; WO  2006077204. 
  • 7a Harrigan GG. Ahmad A. Baj N. Glass TE. Gunatilaka AAL. Kingston DGI. J. Nat. Prod.  1993,  56:  921 
    Search in Google Scholar
  • 7b Nagashima F. Takaoka S. Huneck S. Asakawa Y. Phytochemistry  1999,  51:  563 
    Search in Google Scholar
  • 7c Asakawa Y. Toyota M. Takemoto T. Suire C. Phytochemistry  1979,  18:  1349 
    Search in Google Scholar
  • 7d Toyota M. Nagashima F. Asakawa Y. Phytochemistry  1989,  28:  3383 
    Search in Google Scholar
  • 8 Schäfer HJ. In Radicals in Organic Synthesis   Vol. 1:  Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001.  Chap. 2.6. p.257 
    Search in Google Scholar
  • 9a Hanson JR. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon Press; Oxford: 1991.  Chap. 3.1. p.705 
    Search in Google Scholar
  • 9b Ricknorn B. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon Press; Oxford: 1991.  Chap. 3.2. p.721 
    Search in Google Scholar
  • 9c Ricknorn B. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon Press; Oxford: 1991.  Chap. 3.3. p.733 
    Search in Google Scholar
  • 9d Convency D. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon Press; Oxford: 1991.  Chap. 3.4. p.777 
    Search in Google Scholar
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Anodic Preparation of 5 2,4-Dimethylphenol (1, 24.4 g, 0.2 mol) was mixed with 0.1 M Ba(OH)2˙8H2O in MeOH (100 mL) and transferred into a nondivided standard electrolysis cell equipped with two platinum sheets as anode and cathode, respectively. At 25 ˚C a galvanostatic electrolysis with a current density of 12.5 mA/cm² was performed. During the electrolysis vigorous stirring is necessary and the formation of 5 as a light brown precipitate can be observed. After application of 33200 C (1.7 F/1) the precipitate was filtered off and washed with MeOH (40 mL) to yield analytically pure 5 (12.7 g, 26.34 mmol, 52%) as colorless solid; mp 146-148 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 1.12 (s, 3 H), 1.53 (s, 3 H), 1.94 (d, J = 3 Hz, 3 H), 2.04 (s, 3 H), 2.20 (s, 3 H), 2.24 (s, 3 H), 2.29 (s, 3 H), 2.30 (s, 3 H), 5.05 (d, J = 2.16 Hz, 1 H), 5.17 (s, 1 H), 5.71 (s, 1 H), 6.08 (s, 1 H), 6.73 (d, J = 2.16 Hz, 1 H), 6.78 (s, 1 H), 6.85 (s, 1 H), 6.88 (dd, J = 8.19, 2.16 Hz, 1 H), 7.30 (d, J = 8.19 Hz, 1 H) ppm. ¹³C (100 MHz, CDCl3): δ = 15.03, 15.20, 15.34, 16.69, 20.63, 20.72, 20.85, 23.82, 46.80, 83.12, 84.66, 107.59, 119.63, 120.07, 120.28, 122.99, 123.67, 123.68, 126.89, 128.57, 128.96, 129.06, 130.47, 130.50, 131.28, 133.31, 133.74, 134.02, 134.43, 148.59, 156.74, 154.39 ppm. MS (EI, 70 eV): m/z (%) = 482.3 (34) [M]+ , 361.3 (100), 391.3 (33), 201.2 (76).

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CCDC 686744 (5) and CCDC 686745 (7), respectively, contain the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033, e-mail: deposit@ccdc.cam.ac.uk].