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;
Weitere Informationen

Publikationsverlauf

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

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.

    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 
  • 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 
  • 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 
  • 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 
  • 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 
  • 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 
  • 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 
  • 3 Gribble GW. The Alkaloids  1990,  39:  239 
  • 4 Zhao Z. Jaworski A. Piel I. Snieckus V. Org. Lett.  2008,  10:  2617 
  • 5a Campo MA. Larock RC. J. Org. Chem.  2002,  67:  5616 
  • 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 
  • 7 Janreddy D. Kavala V. Bosco JJW. Kuo C.-W. Yao C.-F. Eur. J. Org. Chem.  2011,  2360 
  • 8a Guchhait SK. Kashyap M. Kamble H. J. Org. Chem.  2011,  76:  4753 
  • 8b Okauchi T. Itonaga M. Minami T. Owa T. Kitoh K. Yoshino H. Org. Lett.  2000,  2:  1485 
  • 8c Ottoni O. Neder ADF. Dias AKB. Cruz RPA. Aquino LB. Org. Lett.  2001,  3:  1005 
  • 9a Alberico D. Scott ME. Lautens M. Chem. Rev.  2007,  107:  174 
  • 9b Ackermann L. Vicente R. Kapdi AR. Angew. Chem. Int. Ed.  2009,  48:  9792 
  • 9c Bellina F. Rossi R. Tetrahedron  2009,  65:  10269 
  • 9d Guchhait SK. Kashyap M. Saraf S. Synthesis  2010,  1166 
  • 9e Satoh T. Miura M. Synthesis  2010,  3395 
  • 9f Williams DR. Fu L. Synlett  2010,  1641 
  • 9g Laidaoui N. Miloudi A. Abed DE. Doucet H. Synthesis  2010,  2553 
  • 10 Chernyak N. Tilly D. Li Z. Gevorgyan V. Chem. Commun.  2010,  46:  150 
  • For our development on use of ZrCl4-catalysis in other reactions, see:
  • 11a Guchhait SK. Madaan C. Tetrahedron Lett.  2011,  52:  56 
  • 11b Guchhait SK. Madaan C. Org. Biomol. Chem.  2010,  8:  3631 
  • 11c Guchhait SK. Madaan C. Synlett  2009,  628 
  • 11d Guchhait SK. Madaan C. Thakkar BS. Synthesis  2009,  3293 
  • 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 
  • 13a Potavathri S. Dumas AS. Dwight TA. Naumiec GR. Hammann JM. DeBoef B. Tetrahedron Lett.  2008,  49:  4050 
  • 13b Zhao J. Zhang Y. Cheng K. J. Org. Chem.  2008,  73:  7428 
  • 14a Ithara T. Sakakibara T. Synthesis  1978,  607 
  • 14b Eisch JJ. Abraham T. Tetrahedron Lett.  1976,  20:  1647