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Synlett 2009(12): 1985-1989  
DOI: 10.1055/s-0029-1217543
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 3-Allenylindoles and 3-Dienylindoles by Brønsted Acid Catalyzed Allenylation of 2-Arylindoles with Tertiary Propargylic Alcohols

Roberto Sanz*a, Mukut Gohaina, Delia Miguela, Alberto Martíneza, Félix Rodríguezb
a Departamento de Química, Área de Química Orgánica, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001-Burgos, Spain
Fax: +34(947)258831; e-Mail: rsd@ubu.es;
b Instituto Universitario de Química Organometálica ‘Enrique Moles’, Universidad de Oviedo, C/ Julián Clavería 8, 33006-Oviedo, Spain
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Publication History

Received 5 March 2009
Publication Date:
03 July 2009 (online)

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Abstract

The Brønsted acid catalyzed direct nucleophilic substitution of tertiary propargylic alcohols with 2-aryl-substituted indoles has been studied. A competitive allenylation process takes place with appropriate substituents on the alkynol moiety. Starting from 2-arylindoles, new 3-allenyl and 3-dienylindole derivatives have been easily synthesized.

Key words

catalysis - indoles - allenes - dienes - nucleophilic substitution

    References and Notes

  • 1 Sundberg RJ. Indoles   Academic Press; San Diego: 1996. 
  • For recent reviews, see:
  • 2a Cacchi S. Fabrizi G. Chem. Rev.  2005,  105:  2873 
    Search in Google Scholar
  • 2b Humphrey GR. Kuethe JT. Chem. Rev.  2006,  106:  2875 
    Search in Google Scholar
  • 3 Lakhdar S. Westermaier M. Terrier F. Goumont R. Boubaker T. Ofial AR. Mayr H. J. Org. Chem.  2006,  71:  9088 
    CrossrefSearch in Google Scholar
  • See, for instance:
  • 4a Palmieri A. Petrini M. J. Org. Chem.  2007,  72:  1863 
    Search in Google Scholar
  • 4b Bhuvaneswari S. Jeganmohan M. Cheng C.-H. Chem. Eur. J.  2007,  13:  8285 
    Search in Google Scholar
  • 4c Wang S.-Y. Ji S.-J. Synlett  2007,  2222 
  • 4d Rozenman MM. Kanan MW. Liu DR. J. Am. Chem. Soc.  2007,  129:  14933 
    Search in Google Scholar
  • 4e Kong W. Cui J. Yu Y. Chen G. Fu C. Ma S. Org. Lett.  2009,  11:  1213 
    Search in Google Scholar
  • 1-(3-Indolyl)-buta-1,3-dienes are usually prepared in several steps and poor overall yields. See, for instance:
  • 5a Sheu J.-H. Chen Y.-K. Chung H.-F. Lin S.-F. Sung P.-J. J. Chem. Soc., Perkin Trans. 1  1998,  1959 
  • 5b Wada A. Babu G. Shimomoto S. Ito M. Synlett  2001,  1759 
  • 6 For a review, see: Bandini M. Melloni A. Tommasi S. Umani-Ronchi A. Synlett  2005,  1199 
    Thieme Connect
  • 7a Ru: Nishibayashi Y. Yoshikawa M. Inada Y. Hidai M. Uemura S. J. Am. Chem. Soc.  2002,  124:  11846 
    Search in Google Scholar
  • 7b Re: Kennedy-Smith JJ. Young LA. Toste FD. Org. Lett.  2004,  6:  1325 
    Search in Google Scholar
  • 7c Ru: Zaitsev AB. Gruber S. Pregosin PS. Chem. Commun.  2007,  4692 
  • 7d Ir: Whithney S. Grigg R. Derrick A. Keep A. Org. Lett.  2007,  9:  3299 
    Search in Google Scholar
  • 8a InCl3: Yasuda M. Somyo T. Baba A. Angew. Chem. Int. Ed.  2006,  45:  793 
    Search in Google Scholar
  • 8b Sc(OTf)3: Yadav JS. Subba Reddy BV. Raghavendra Rao KV. Narayana Kumar GGKS. Tetrahedron Lett.  2007,  48:  5573 
    Search in Google Scholar
  • 8c FeCl3: Jana U. Maiti S. Biswas S. Tetrahedron Lett.  2007,  48:  7160 
    Search in Google Scholar
  • 8d I2: Srihari P. Bhunia DC. Sreedhar P. Mandal SS. Shyam Sunder Reddy J. Yadav JS. Tetrahedron Lett.  2007,  48:  8120 
    Search in Google Scholar
  • 9a Shirakawa S. Kobayashi S. Org. Lett.  2007,  9:  311 
    Search in Google Scholar
  • 9b Motokura K. Nakagiri N. Mizugaki T. Ebitani K. Kaneda K. J. Org. Chem.  2007,  72:  6006 
    Search in Google Scholar
  • 9c Le Bras J. Muzart J. Tetrahedron  2007,  63:  7942 
    Search in Google Scholar
  • 10a Sanz R. Martínez A. Álvarez-Gutiérrez JM. Rodríguez F. Eur. J. Org. Chem.  2006,  1383 
  • 10b Sanz R. Martínez A. Miguel D. Álvarez-Gutiérrez JM. Rodríguez F. Adv. Synth. Catal.  2006,  348:  1841 
    Search in Google Scholar
  • 10c Sanz R. Miguel D. Martínez A. Álvarez-Gutiérrez JM. Rodríguez F. Org. Lett.  2007,  9:  727 
    Search in Google Scholar
  • 10d Sanz R. Miguel D. Martínez A. Álvarez-Gutiérrez JM. Rodríguez F. Org. Lett.  2007,  9:  2027 
    Search in Google Scholar
  • 10e Sanz R. Martínez A. Álvarez-Gutiérrez JM. Rodríguez F. Synthesis  2007,  3252 
  • 10f Sanz R. Martínez A. Guilarte V. Álvarez-Gutiérrez JM. Rodríguez F. Eur. J. Org. Chem.  2007,  4642 
  • 11 Sanz R. Miguel D. Álvarez-Gutiérrez JM. Rodríguez F. Synlett  2008,  975 
    Thieme Connect
  • 12 Sanz R. Miguel D. Rodríguez F. Angew. Chem. Int. Ed.  2008,  47:  7354 
    CrossrefSearch in Google Scholar
  • 15a Indoles 1b,d-g were prepared by standard Fisher indole synthesis, see: Fusco R. Sannicolo F. J. Org. Chem.  1981,  46:  83 
    Search in Google Scholar
  • 15b On the other hand, indole 1c was obtained by a modified Madelung synthesis, see: Houlihan WJ. Parrino VA. Uike Y. J. Org. Chem.  1981,  46:  4511 
    Search in Google Scholar
13

We have observed that the presence of an alkyl substituent at the C-2 of the indole nucleus does not give rise to significant competitive allenylation processes.

14

The 1Z,3E-isomer was mainly formed. Variable amounts of the 1Z,3Z-isomer were detected in the crude product. After column chromatography we usually isolated the major isomer slightly contaminated with the minor one, probably due to further isomerization under the purification conditions. The stereochemistry was assessed by NOESY experiments on 4cb, and the rest of the compounds were assigned by inference. Moreover, the structure of 4af was confirmed by single-crystal X-ray diffraction analysis (CCDC 729740 contains the supplementary crystallographic data for this compound. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/ data_request/cif).

16

We have checked that the presence of alkyl or aryl groups at the nitrogen atom of the starting 2-phenylindole derivative mainly gives rise to propargylated products regardless the substituents of the alkynol.