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Synthesis 2012(4): 619-627  
DOI: 10.1055/s-0031-1289663
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Friedel-Crafts 3-(2-Bromobenzoylation) of Indoles and Intramolecular Direct Arylation: An Efficient Route to Indenoindolones

Sankar K. Guchhait*, Maneesh Kashyap
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Punjab 160 062, India
Fax: +91(172)22146; e-Mail: skguchhait@niper.ac.in;
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Publikationsverlauf

Received 2 November 2011
Publikationsdatum:
02. Januar 2012 (online)

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Abstract

An efficient two-step approach, comprising the Friedel-Crafts reaction of 2-bromobenzoyl chlorides with indoles to give 3-(2-bromobenzoyl)indoles and their palladium-catalyzed intramolecular direct arylation to give indenoindolones, has been developed. 3-(2-Bromobenzoyl)indoles were crucial intermediates; the method was successful with N-unprotected or N-protected indoles. This approach affords a convenient preparation of diverse substituted and functionalized indenoindolones in good to high yields from easily accessible starting materials. Several moieties, which are commonly integrated into bioactive compounds, can be incorporated with ease by this synthesis.

Key words

acylation - arylation - catalysis - coupling - heterocycles - indoles - Lewis acids - palladium

    References

  • 1a Bal C. Baldeyrou B. Moz F. Lansiaux A. Colson P. Kraus-Berthier L. Leonce S. Pierre A. Boussard MF. Rousseau A. Wierzbicki M. Bailly C. Biochem. Pharmacol.  2004,  68:  1911 
    Google Scholar
  • 1b Wierzbicki M, Boussard MF, Rousseau A, Boutin JA, and Delagrange P. inventors; US  6,844,445. 
  • 1c Shao D. Zou C. Luo C. Tang X. Li Y. Bioorg. Med. Chem. Lett.  2004,  14:  4639 
    Google Scholar
  • 1d Hemmerling H.-J, Götz C, and Jose J. inventors; WO  2008,040,547. 
  • 1e Boussard MF. Truche S. Rousseau-Rojas A. Briss S. Descamps S. Droual M. Wierzbicki M. Ferry G. Audinot V. Delagrange P. Boutin JA. Eur. J. Med. Chem.  2006,  41:  306 
    Google Scholar
  • 1f Sainsbury M, and Sherter HG. inventors; EP  0,409,410. 
  • 2a Ahn G. Lansiaux A. Goossens J.-F. Bailly C. Baldeyrou B. Schifano-Faux N. Grandclaudon P. Couture A. Ryckebusch A. Bioorg. Med. Chem.  2010,  18:  8119 
    Google Scholar
  • 2b Shook BC. Rassnick S. Chakravarty D. Wallace N. Ault M. Crooke J. Barbay JK. Wang A. Leonard K. Powell MT. Alford V. Hall D. Rupert KC. Heintzelman GR. Hansen K. Bullington JL. Scannevin RH. Carroll K. Lampron L. Westover L. Russell R. Branum S. Wells K. Damon S. Youells S. Beauchamp D. Li X. Rhodes K. Jackson PF. Bioorg. Med. Chem. Lett.  2010,  20:  2868 
    Google Scholar
  • 2c Egert-Schmidt A. Dreher J. Dunkel U. Kohfeld S. Preu L. Weber H. Ehlert JE. Mutschler B. Totzke F. Schachtele C. Kubbutat MHG. Baumann K. Kunick C. J. Med. Chem.  2010,  53:  2433 
    Google Scholar
  • 2d Stukenbrock H. Mussmann R. Geese M. Ferandin Y. Lozach O. Lemcke T. Kegel S. Lomow A. Burk U. Dohrmann C. Meijer L. Austen M. Kunick C. J. Med. Chem.  2008,  51:  2196 
    Google Scholar
  • 3 Gribble GW. The Alkaloids  1990,  39:  239 
    Google Scholar
  • 4 Zhao Z. Jaworski A. Piel I. Snieckus V. Org. Lett.  2008,  10:  2617 
    Google Scholar
  • 5a Campo MA. Larock RC. J. Org. Chem.  2002,  67:  5616 
    Google Scholar
  • 5b Nifant’ev I, Kashulin I, Ivchenko P, Klusener P, Korndorffer F, Kloe KD, and Rijsemus J. inventors; US  7,635,781. 
  • 6 Wang JB. Ji QG. Xu J. Wu XH. Xie YY. Synth. Commun.  2005,  35:  581 
    Google Scholar
  • 7 Janreddy D. Kavala V. Bosco JJW. Kuo C.-W. Yao C.-F. Eur. J. Org. Chem.  2011,  2360 
    Google Scholar
  • 8a Guchhait SK. Kashyap M. Kamble H. J. Org. Chem.  2011,  76:  4753 
    Google Scholar
  • 8b Okauchi T. Itonaga M. Minami T. Owa T. Kitoh K. Yoshino H. Org. Lett.  2000,  2:  1485 
    Google Scholar
  • 8c Ottoni O. Neder ADF. Dias AKB. Cruz RPA. Aquino LB. Org. Lett.  2001,  3:  1005 
    Google Scholar
  • 9a Alberico D. Scott ME. Lautens M. Chem. Rev.  2007,  107:  174 
    Google Scholar
  • 9b Ackermann L. Vicente R. Kapdi AR. Angew. Chem. Int. Ed.  2009,  48:  9792 
    Google Scholar
  • 9c Bellina F. Rossi R. Tetrahedron  2009,  65:  10269 
    Google Scholar
  • 9d Guchhait SK. Kashyap M. Saraf S. Synthesis  2010,  1166 
    Google Scholar
  • 9e Satoh T. Miura M. Synthesis  2010,  3395 
    Google Scholar
  • 9f Williams DR. Fu L. Synlett  2010,  1641 
    Google Scholar
  • 9g Laidaoui N. Miloudi A. Abed DE. Doucet H. Synthesis  2010,  2553 
    Google Scholar
  • 10 Chernyak N. Tilly D. Li Z. Gevorgyan V. Chem. Commun.  2010,  46:  150 
    Google Scholar
  • For our development on use of ZrCl4-catalysis in other reactions, see:
  • 11a Guchhait SK. Madaan C. Tetrahedron Lett.  2011,  52:  56 
    Google Scholar
  • 11b Guchhait SK. Madaan C. Org. Biomol. Chem.  2010,  8:  3631 
    Google Scholar
  • 11c Guchhait SK. Madaan C. Synlett  2009,  628 
    Google Scholar
  • 11d Guchhait SK. Madaan C. Thakkar BS. Synthesis  2009,  3293 
    Google Scholar
  • 12 Regina GL. Sarkar T. Bai R. Edler MC. Saletti R. Coluccia A. Piscitelli F. Minelli L. Gatti V. Mazzoccoli C. Palermo V. Mazzoni C. Falcone C. Scovassi AI. Giansanti V. Campiglia P. Porta A. Maresca B. Hamel E. Brancale A. Novellino E. Silvestri R. J. Med. Chem.  2009,  52:  7512 
    Google Scholar
  • 13a Potavathri S. Dumas AS. Dwight TA. Naumiec GR. Hammann JM. DeBoef B. Tetrahedron Lett.  2008,  49:  4050 
    Google Scholar
  • 13b Zhao J. Zhang Y. Cheng K. J. Org. Chem.  2008,  73:  7428 
    Google Scholar
  • 14a Ithara T. Sakakibara T. Synthesis  1978,  607 
    Google Scholar
  • 14b Eisch JJ. Abraham T. Tetrahedron Lett.  1976,  20:  1647 
    Google Scholar