Download PDF
Synthesis 2010(14): 2468-2474  
DOI: 10.1055/s-0029-1218768
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Hydroamination of 2-Ethynyl-4,5,6,7-tetrahydroindoles: Toward 2-Substituted Amino Derivatives of Indole

Lyubov’ N. Sobenina, Denis N. Tomilin, Ol’ga V. Petrova, Igor’ A. Ushakov, Al’bina I. Mikhaleva, Boris A. Trofimov*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St., Irkutsk 664033, Russian Federation
Fax: +7(3952)419346; e-Mail: boris_trofimov@irioch.irk.ru;
Further Information

Publication History

Received 19 March 2010
Publication Date:
05 May 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

Hydroamination of 1-phenyl-3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-yn-1-ones with secondary dialkylamines proceeds under mild conditions (room temperature, aqueous ethanol, 1 h) to afford the corresponding (2E)-3-dialkylamino-3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-en-1-ones in 72-92% stereoselectivity and 64-88% yield. Under the same conditions, ethyl 3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-ynoates react with dimethylamine and diethylamine in different ways; dimethylamine converts the ester function into an amide, giving the corresponding N,N-dimethyl-3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-ynamides in 70-86% yield, whereas diethylamine adds to the triple bond to give the corresponding ethyl 3-(diethylamino)-3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-enoates with ∼100% stereoselectivity and up to 85% yield. The difference in the reactivity of the two amines can be rationalized in terms of steric hindrance.

Key words

indoles - alkynes - aminations - nucleophilic additions - amides

    References

  • 1a Odom AL. Dalton Trans.  2005,  225 
    Google Scholar
  • 1b Hultzsch KC. Adv. Synth. Catal.  2005,  347:  367 
    Google Scholar
  • 1c Hong S. Marks TJ. Acc. Chem. Res.  2004,  37:  673 
    Google Scholar
  • 1d Doye S. Synlett  2004,  1653 
    Google Scholar
  • 1e Roesky PW. Muller TE. Angew. Chem. Int. Ed.  2003,  42:  2708 
    Google Scholar
  • 1f Bytschkov I. Doye S. Eur. J. Org. Chem.  2003,  935 
    Google Scholar
  • 1g Pohlki F. Doye S. Chem. Soc. Rev.  2003,  32:  104 
    Google Scholar
  • 1h Fukumoto Y. Asai H. Shimizu M. Chatani N. J. Am. Chem. Soc.  2007,  129:  13792 
    Google Scholar
  • 1i Facoetti D. Abbiati G. d’Avolia L. Ackermann L. Rossi E. Synlett  2009,  2273 
    Google Scholar
  • 1j Lee AV. Sajitz M. Schafer LL. Synthesis  2009,  97 
    Google Scholar
  • 2a Sammakia T. Abramite JA. Sammons MF. In Science of Synthesis   Vol. 33:  Molander M. Thieme; Stuttgart: 2007.  p.405 
    Google Scholar
  • 2b Adams JP. J. Chem. Soc., Perkin Trans. 1  2000,  125 
    Google Scholar
  • 2c Kucklander U. In The Chemistry of Enamines   Rappoport Z. Wiley; Chichester: 1994.  p.523 
    Google Scholar
  • 3 Freimanis YaF. The Chemistry of Enaminoketones, Enaminoimines, and Enaminothiones (In Russian)   Zinatne; Riga: 1974. 
    Google Scholar
  • 4a Aliev ZG. Krasnykh OP. Konyukhova NA. Maslivets AN. Atovmyan LO. J. Struct. Chem.  2001,  42:  848 
    Google Scholar
  • 4b Bagley MC. Dale JW. Bower J. Chem. Commun.  2002,  1682 
    Google Scholar
  • 4c Elasser AA. El-Khair AA. Tetrahedron  2003,  59:  8463 
    Google Scholar
  • 4d Kascheres C. J. Braz. Chem. Soc.  2003,  14:  945 
    Google Scholar
  • 4e Stanovnik B. Svete J. Chem. Rev.  2004,  104:  2433 
    Google Scholar
  • 4f Tu S.-J. Jiang B. Jia R.-H. Zhang J.-Y. Zhang Y. Yao C.-S. Shi F. Org. Biomol. Chem.  2006,  4:  3664 
    Google Scholar
  • 4g Cunha S. Damasceno F. Ferrari J. Tetrahedron Lett.  2007,  48:  5795 
    Google Scholar
  • 5a Baraldi PG. Barco A. Benetti S. Pollini GP. Simoni D. Synthesis  1987,  857 
    Google Scholar
  • 5b Lue P. Greenhill JV. Adv. Heterocycl. Chem.  1997,  67:  207 
    Google Scholar
  • 6a Trofimov BA. Stepanova ZV. Sobenina LN. Mikhaleva AI. Ushakov IA. Tetrahedron Lett.  2004,  45:  6513 
    Google Scholar
  • 6b Stepanova ZV. Sobenina LN. Mikhaleva AI. Ushakov IA. Elokhina VN. Voronov VK. Trofimov BA. Synthesis  2004,  2736 
    Google Scholar
  • 6c Sobenina LN. Demenev AP. Mikhaleva AI. Ushakov IA. Vasil’tsov AM. Ivanov AV. Trofimov BA. Tetrahedron Lett.  2006,  47:  7139 
    Google Scholar
  • 6d Trofimov BA. Sobenina LN. Stepanova ZV. Demenev AP. Mikhaleva AI. Ushakov IA. Vakul’skaya TI. Petrova OV. Russ. J. Org. Chem.  2006,  42:  1348 
    Google Scholar
  • 6e Trofimov BA. Sobenina LN. Stepanova ZV. Ushakov IA. Petrova OV. Tarasova OA. Volkova KA. Mikhaleva AI. Synthesis  2007,  447 
    Google Scholar
  • 6f Trofimov BA. Sobenina LN. Demenev AP. Stepanova ZV. Petrova OV. Ushakov IA. Mikhaleva AI. Tetrahedron Lett.  2007,  48:  4661 
    Google Scholar
  • 7a Trofimov BA. Sobenina LN. Stepanova ZV. Vakul’skaya TI. Kazheva ON. Aleksandrov GG. Dyachenko OA. Mikhaleva AI. Tetrahedron  2008,  64:  5541 
    Google Scholar
  • 7b Trofimov BA. Sobenina LN. Stepanova ZV. Petrova OV. Ushakov IA. Mikhaleva AI. Tetrahedron Lett.  2008,  49:  3946 
    Google Scholar
  • 8a Trofimov BA. Mikhaleva AI. N-Vinylpyrroles   Nauka; Novosibirsk: 1984. 
    Google Scholar
  • 8b Trofimov BA. Adv. Heterocyclic Chem.  1990,  51:  177 
    Google Scholar
  • 8c Trofimov BA, Mikhaleva AI, Schmidt EYu, Ryapolov OA, and Platonov VB. inventors; RU  2297410.  ; Chem. Abstr. 2007, 146, 462130
  • 9 Yakimovich SI. Golodova KG. In Reactivity and Organic Reaction Mechanisms   Vol. 2:  Temnikova TI. Leningrad State University Publishing House; Leningrad: 1974.  p.186-213  
    Google Scholar
  • 10a Patra R. Maiti SB. Chatterjee A. Chakravarty AK. Tetrahedron Let.  1991,  32:  1363 
    Google Scholar
  • 10b Jacobi PA. Guo J. Rajeswari S. Zheng W. J. Org. Chem.  1997,  62:  2907 
    Google Scholar
  • 10c Katritzky AR. Zhang Y. Singh SK. J. Org. Chem.  2002,  67:  9077 
    Google Scholar
  • 10d Usifoh CO. Okunrobo LO. Monatsh. Chem.  2002,  133:  1067 
    Google Scholar
  • 10e Reisch J. Usifoh CO. Oluwadiya JO. J. Heterocycl. Chem.  2009,  27:  1953 
    Google Scholar
  • 10f Burling S. Field LD. Li HL. Messerle BA. Shasha A. Aust. J. Chem.  2004,  57:  677 
    Google Scholar
  • 12 Kanavarioti A. Stronach MW. Ketner RJ. Hurley TB. J. Org. Chem.  1995,  60:  632 
    CrossrefGoogle Scholar
11

Anon.; Dissociation Constants of Organic Acids and Bases; available at http://www.zirchrom.com/organic.htm.