Download PDF
Synlett 2002(12): 2086-2088
DOI: 10.1055/s-2002-35601
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Preparation of Polysubstituted Naphthyl Phenyl and Dinaphthyl Ketones from Naphthalenic Esters by Anionic Homo-Fries Rearrangement

Arnaud Piettre, Christine Massardier, Emmanuel Chevenier, Yves Gimbert*, Andrew E. Greene*
Chimie Recherche (LEDSS), Université Joseph Fourier, BP 53X, 38041 Grenoble, France
Fax: +(33)476514494; e-Mail: Yves.Gimbert@ujf-grenoble.fr; e-Mail: Andrew.Greene@ujf-grenoble.fr;
Further Information

Publication History

Received 20 August 2002
Publication Date:
20 November 2002 (online)

    Permissions and Reprints All articles of this category

Abstract

The anionic homo-Fries rearrangement of naphthalenic esters can be effected in good yield to provide regiocontrolled access to complex diaryl ketones.

Key words

Homo-Fries rearrangement - naphthyl phenyl ketone - dinaphthyl ketone - xanthone

    References

  • For reviews on topoisomerase, see:
  • 1a Wang JC. Annu. Rev. Biochem.  1996,  65:  635 
    Google Scholar
  • 1b Bailly C. Curr. Med. Chem.  2000,  7:  39 
    Google Scholar
  • 1c Long BH. Balasubramanian BN. Expert Opin. Ther. Pat.  2000,  10:  635 
    Google Scholar
  • 2 Edwards RL. Fawcett V. Maitland DJ. Nettleton R. Shields L. Whalley AJS. J. Chem. Soc., Chem. Commun.  1991,  1009 
    CrossrefGoogle Scholar
  • 3a Gimbert Y, Chevenier E, Greene AE, Massardier C, and Piettre A. inventors; EP  014025514. 
    Crossref
  • 3b Piettre A. Chevenier E. Massardier C. Gimbert Y. Greene AE. Org. Lett.  2002,  4:  3139 
    CrossrefGoogle Scholar
  • 4 Miller JA. J. Org. Chem.  1987,  52:  322 ; and references cited therein
    CrossrefGoogle Scholar
  • 5a Horne S. Rodrigo R. J. Org. Chem.  1990,  55:  4520 
    CrossrefGoogle Scholar
  • 5b See also: Beak P. Meyers AI. Acc. Chem. Res.  1986,  19:  356 
    CrossrefGoogle Scholar
  • 6a Nicolaou KC. Bunnage ME. Koide K. J. Am. Chem. Soc.  1994,  116:  8402 
    Google Scholar
  • 6b Lampe JW. Hugues PF. Biggers CK. Smith SH. Hu H. J. Org.Chem.  1996,  61:  4572 
    Google Scholar
  • 6c Lampe JW. J. Med. Chem.  2002,  45:  2624 
    Google Scholar
  • 6d See also: Couture A. Deniau E. Lebrun S. Grandclaudon P. J. Chem. Soc., Perkin Trans. 1  1999,  789 
    Google Scholar
  • 6e Focken T. Hopf H. Snieckus V. Dix I. Jones PG. Eur. J Org. Chem.  2001,  12:  2221 
    Google Scholar
  • 7a Esters 1a,b, 3a,b, 5a,b were prepared by coupling under Mitsunobu conditions. See: Mitsunobu O. Synthesis  1981,  1 
    Google Scholar
  • 7b See also: Hughes DL. Org. React.  1992,  42:  335 
    Google Scholar
  • 7c

    For the preparation of the naphthalenic precursors, see ref. [3]

  • For recent references to biologically active xanthones, see:
  • 9a Lin C.-N. Liou S.-J. Lee T.-H. Chuang Y.-C. Won S.-J. J. Pharm. Pharmacol.  1996,  48:  532 
    CrossrefGoogle Scholar
  • 9b Wang L.-W. Kang J.-J. Chen I.-J. Teng C.-M. Lin C.-N. Bioorg. Med. Chem.  2002,  10:  567 ; and references cited therein
    CrossrefGoogle Scholar
8

Anionic Homo-Fries Reaction of Ester 5a: A solution of ester 5a (269 mg, 0.397 mmol) in THF (1.59 mL, from which residual water had been eliminated with n-BuLi and o-phenanthroline) under argon was cooled to -55 to -45 °C and treated dropwise with n-BuLi (0.203 mL, 0.437 mmol). After being stirred for 2 h at this temperature, the reaction mixture was treated with sat. aq NH4Cl solution, allowed to warm to 20 °C, and diluted with EtOAc. The crude product was isolated with EtOAc in the usual manner and purified by radial thin-layer chromatography (hexane in EtOAc, 9:1 to 1:1) to give 43 mg (16%) of recovered starting material, 32 mg (13%) of debrominated starting material, and 130 mg (55%, 65% brsm) of dinaphthyl ketone 6a as a white solid. Ketone 6a: Mp 220-224 °C (cyclohexane-dichloromethane); IR(neat): 3454, 1619, 1573 cm-1; 1H NMR (200 MHz, CDCl3): δ = 3.41 (s, 3 H), 3.57 (s, 3 H), 3.83 (s, 3 H), 3.87 (s, 3 H), 3.90 (s, 6 H), 4.55 (d, J = 6.8 Hz, 2 H), 5.03 (s, 2 H), 6.37 (d, J = 2.4 Hz, 1 H), 6.45 (d, J = 2.4 Hz, 1 H), 6.60 (d, J = 2.1 Hz, 1 H), 6.70 (d, J = 2.1 Hz, 1 H), 6.87 (s, 1 H), 7.05-7.35 (m, 5 H), 7.41 (s, 1 H); 13C NMR (75.4 MHz, CDCl3): δ = 55.3 (CH3), 55.4 (CH3), 56.0 (CH3), 63.9 (CH3), 64.0 (CH3), 64.1 (CH3), 64.7 (CH2), 70.2 (CH2), 97.4 (CH), 98.7 (CH), 99.3 (CH), 103.2 (CH), 111.1 (C), 114.7 (C), 124.4 (CH), 125.4 (C), 127.4 (2 CH), 127.8 (CH), 128.3 (2 CH), 131.3 (C), 136.3 (C), 139.3 (C), 139.5 (C), 155.1 (C), 156.0 (C), 157.6 (C), 157.8 (C), 159.4 (C), 159.6 (C), 198.6 (C); MS (DCI): m/z (%) = 599 (50) [MH+], 279 (100); Anal. Calcd for C35H34O9: Mr, 598.2203. Found: Mr (mass spectrum, EI), 598.2211.