Download PDF
Synthesis 2010(23): 4033-4042  
DOI: 10.1055/s-0030-1258284
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Nonsymmetrical 5-Aryl-2-indolopyrrole Derivatives via Controlled Mono Suzuki-Miyaura Cross-Coupling on N-Boc-2,5-dibromopyrrole

Floriane Beaumard, Philippe Dauban, Robert H. Dodd*
Institut de Chimie des Substances Naturelles, UPR 2301, Campus de Recherche de Gif, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
Fax: +33(1)69077247; e-Mail: robert.dodd@icsn.cnrs-gif.fr;
Further Information

Publication History

Received 3 August 2010
Publication Date:
05 October 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

The first example of mono Suzuki-Miyaura cross-coupling of N-Boc-2,5-dibromopyrrole with a boronic acid (indol-2-ylboronic acid) is reported. The resulting 2-indolyl-5-bromopyrrole derivative was in turn coupled with a variety of aryl- or heteroarylboronic acids thereby providing the corresponding non-symmetrical 2,5-disubstituted pyrroles in good to excellent yields. The tert-butoxycarbonyl (Boc) groups could be easily removed to give the completely deprotected products.

Key words

cross-coupling - Suzuki-Miyaura - indole - pyrrole - palladium-catalyzed

    References

  • For generalities on this receptor, see:
  • 1a Galvez T. Pin J.-P. M/S: Médecine/Sciences  2003,  19:  559 
    Google Scholar
  • 1b Pin J.-P. Galvez T. Prézeau L. Pharmacol. Therapeut.  2003,  98:  325 
    Google Scholar
  • 1c Gurevich VV. Gurevich EV. Trends Pharmacol. Sci.  2008,  29:  234 
    Google Scholar
  • 1d Brown EM. Gamba G. Riccardi D. Lombardi M. Butters R. Kifor O. Sun A. Hediger MA. Lytton J. Hebert SC. Nature  1993,  366:  575 
    Google Scholar
  • 1e Chattopadhyay N. Brown EM. Cell. Signalling  2000,  12:  361 
    Google Scholar
  • 1f Chattopadhyay N. Int. J. Biochem. Cell Biol.  2000,  32:  789 
    Google Scholar
  • 1g Chattopadhyay N. Brown EM. Mol. Genet. Metab.  2006,  89:  189 
    Google Scholar
  • 1h Chang W. Shoback D. Cell Calcium  2004,  35:  183 
    Google Scholar
  • 2a Kessler A. Faure H. Petrel C. Ruat M. Dauban P. Dodd RH. Bioorg. Med. Chem. Lett.  2004,  14:  3345 
    Google Scholar
  • 2b Petrel C. Kessler A. Dauban P. Dodd RH. Rognan D. Ruat M. J. Biol. Chem.  2004,  279:  18990 
    Google Scholar
  • 2c Dauban PM, Dodd RH, Faure HV, Ruat M, Potier PJ.-P, and Kessler A. inventors;  WO0212181.  ; Chem. Abstr. 2002, 136, 183621
  • For recent examples on Suzuki-Miyaura cross-couplings on pyrroles, see:
  • 3a Lotter ANC. Pathak R. Sello TS. Fernandes MA. van Otterlo WAL. de Koning CB. Tetrahedron  2007,  63:  2263 
    Google Scholar
  • 3b Kern JC. Terefenko EA. Fensome A. Unwalla R. Wrobel J. Cohen J. Zhu Y. Berrodin TJ. Yudt MR. Winneker RC. Zhang ZM. Zhang PW. Bioorg. Med. Chem. Lett.  2008,  18:  5015 
    Google Scholar
  • 3c Hughes TV. Emanuel SL. O’Grady HR. Connolly PJ. Rugg C. Fuentes-Pesquera AR. Karnachi P. Alexander R. Middleton SA. Bioorg. Med. Chem. Lett.  2008,  18:  5130 
    Google Scholar
  • 4 Jana GH. Jain S. Arora SK. Sinha N. Bioorg. Med. Chem. Lett.  2005,  15:  3592 
    CrossrefGoogle Scholar
  • 5 Kurotobi K. Tabata H. Miyauchi M. Murafuji T. Sugihara Y. Synthesis  2002,  1013 
    Article in Thieme ConnectGoogle Scholar
  • 6 Itahara T. J. Org. Chem.  1985,  50:  5272 
    CrossrefGoogle Scholar
  • 7 Gryko DT. Vakuliuk O. Gryko D. Koszarna B. J. Org. Chem.  2009,  74:  9517 
    CrossrefGoogle Scholar
  • 8 Rieth RD. Mankad NP. Calimano E. Sadighi JP. Org. Lett.  2004,  6:  3981 
    Google Scholar
  • 9 Wang X. Gribkov DV. Sames D. J. Org. Chem.  2007,  72:  1476 
    CrossrefGoogle Scholar
  • 10 Vachal P. Toth LM. Tetrahedron Lett.  2004,  45:  7157 
    CrossrefGoogle Scholar
  • 11 Pinkerton DM. Banwell MG. Willis AC. Org. Lett.  2007,  9:  5127 
    CrossrefGoogle Scholar
  • 12a Miyaura N. Metal-Catalyzed Cross-Coupling Reactions   De Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004.  p.41-123  
    Google Scholar
  • 12b Miyaura N. Top. Curr. Chem.  2002,  219:  11 
    Google Scholar
  • 12c Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
    Google Scholar
  • 13a Uozumi Y. Kikuchi M. Synlett  2005,  1775 
    Google Scholar
  • 13b Sinclair DJ. Sherburn MS. J. Org. Chem.  2005,  70:  3730 
    Google Scholar
  • 13c Dong CG. Hu QS. J. Am. Chem. Soc.  2005,  127:  10006 
    Google Scholar
  • 14a Bennacef I. Haile CN. Schmidt A. Koren AO. Seibyl JP. Staley JK. Bois F. Baldwin RM. Tamagnan G. Bioorg. Med. Chem.  2006,  14:  7582 
    Google Scholar
  • 14b Jacquemard U. Dias N. Lansiaux A. Bailly C. Loge C. Robert JM. Lozach O. Meijer L. Merour JY. Routier S. Bioorg. Med. Chem.  2008,  16:  4932 
    Google Scholar
  • 15a Dang TT. Rasool N. Dang TT. Reinke H. Langer P. Tetrahedron Lett.  2007,  48:  845 
    Google Scholar
  • 15b Tùng DT. Tuân DT. Rasool N. Villinger A. Reinke H. Fischer C. Langer P. Adv. Synth. Catal.  2009,  351:  1595 
    Google Scholar
  • 16 Dang TT. Ahmad R. Reinke H. Langer P. Tetrahedron Lett.  2008,  49:  1698 
    CrossrefGoogle Scholar
  • 17 Johnson CN. Stemp G. Anand N. Stephen SC. Gallagher T. Synlett  1998,  1025 
    Article in Thieme ConnectGoogle Scholar
  • 18 Martina S. Enkelmann V. Wegner G. Schlueter A.-D. Synthesis  1991,  613 
    Article in Thieme ConnectGoogle Scholar
  • 19 Donohoe TJ. Harji RR. Cousins RPC. Tetrahedron Lett.  2000,  41:  1327 
    CrossrefGoogle Scholar
  • 20 Fürstner A. Radkowski K. Peters H. Seidel G. Wirtz C. Mynott R. Lehmann CW. Chem. Eur. J.  2007,  13:  1929 
    CrossrefGoogle Scholar
  • 22 Lee IYC. Jung MH. Lim HJ. Lee HW. Heterocycles  2005,  65:  2505 
    CrossrefGoogle Scholar
  • 23 Beaumard F. Dauban P. Dodd RH. Org. Lett.  2009,  11:  1801 
    CrossrefGoogle Scholar
21

Langer demonstrated that use of palladium(II) diacetate together with the phosphine ligand, SPhos increased the yield of mono-coupled product with dibromothiophene by 20% (see reference 15b). Application of these same reaction conditions to substrate 3 led mainly to degradation products.