Download PDF
Synlett 2009(5): 727-730  
DOI: 10.1055/s-0028-1087957
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

First Example of C-3 Alkylation of Indoles with Activated Azetidines Catalyzed by Indium(III) Bromide

J. S. Yadav*, B. V. Subba Reddy, G. Narasimhulu, G. Satheesh
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax: +91(40)27160512; e-Mail: yadavpub@iict.res.in;
Further Information

Publication History

Received 22 September 2009
Publication Date:
26 February 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

Indoles undergo smooth alkylation with N-tosylazetidines in the presence of indium(III) bromide in dichloroethane under mild conditions to produce the corresponding C-3 substituted indole derivatives in good to high yields and with high selectivity. This is the first report on the alkylation of indoles with activated azetidines.

Key words

indoles - indium(III) bromide - activated azetidine - C-3 alkylation

    References and Notes

  • 1a Sundberg RJ. Indoles   Academic Press; San Diego: 1996. 
  • 1b Faulkner DJ. Nat. Prod. Rep.  2001,  18:  1-49  
    Search in Google Scholar
  • 1c Ninomiya I. J. Nat. Prod.  1992,  55:  541 
    Search in Google Scholar
  • 2a Sundberg RJ. In Comprehensive Heterocyclic Chemistry II   Vol. 2:  Katritzky AR. Rees CW. Scriven EFV. Bird CW. Pergamon Press; Oxford: 1996.  p.207 
    Search in Google Scholar
  • 2b Gilchrist TL. J. Chem. Soc., Perkin Trans. 1  2001,  2491 
  • 2c Horton DA. Bourne GT. Smythe ML. Chem. Rev.  2003,  103:  893 
    Search in Google Scholar
  • 2d Tois J. Franzen R. Koskinen A. Tetrahedron  2003,  59:  5395 
    Search in Google Scholar
  • 3a Bandini M. Melloni A. Umani-Ronchi A. Angew. Chem. Int. Ed.  2004,  43:  550 
    Search in Google Scholar
  • 3b Austin JF. MacMillan DWC. J. Am. Chem. Soc.  2002,  124:  1172 
    Search in Google Scholar
  • 3c Jensen KB. Thorhange J. Hazel RG. Jorgensen KA. Angew. Chem. Int. Ed.  2001,  40:  160 
    Search in Google Scholar
  • 4a Yoshiaki N. Masato Y. Youichi I. Masnobu H. Sakae U. J. Am. Chem. Soc.  2002,  124:  11846 
    Search in Google Scholar
  • 4b Wenkert E. Angell EC. Ferreira VF. Michelotti EL. Piettre SR. Sheu JH. Swindell CS. J. Org. Chem.  1986,  51:  2343 
    Search in Google Scholar
  • 4c Bandini M. Melloni A. Tommasi S. Umani-Ronchi A. Synlett  2005,  1199 
  • 5a Srivastava N. Banik BK. J. Org. Chem.  2003,  68:  2109 
    Search in Google Scholar
  • 5b Bartoli G. Bartolacci M. Bosco M. Foglia G. Giuliani A. Marcantoni E. Sambri L. Torregiani E.
    J. Org. Chem.  2003,  68:  4594 
    Search in Google Scholar
  • 5c Yadav JS. Abraham S. Reddy BVS. Sabitha G. Synthesis  2001,  2165 
  • 5d Yadav JS. Reddy BVS. Singh AP. Basak AK. Tetrahedron Lett.  2007,  48:  4169 
    Search in Google Scholar
  • 6a Campos KR. Woo JCS. Lee S. Tillyer RD. Org. Lett.  2004,  6:  79 
    Search in Google Scholar
  • 6b Hong KB. Lee CW. Yum EK. Tetrahedron Lett.  2004,  45:  693 
    Search in Google Scholar
  • 6c Kohling P. Schmidt AM. Eilbracht P. Org. Lett.  2003,  5:  3213 
    Search in Google Scholar
  • 6d Arcadi A. Bianchi G. Chiarini M. Anniballe G. Marinelli F. Synlett  2004,  6:  944 
    Search in Google Scholar
  • 6e Yadav JS. Reddy BVS. Aravind S. Narayana Kumar GGKS. Srinivas Reddy A. Tetrahedron Lett.  2007,  48:  6117 
    Search in Google Scholar
  • 7a Nenajdenko VG. Karpov AS. Balenkova ES. Tetrahedron: Asymmetry  2001,  12:  2517 
    Search in Google Scholar
  • 7b Yadav JS. Reddy BVS. Satheesh G. Prabhakar A. Kunwar AC. Tetrahedron Lett.  2003,  44:  2221 
    Search in Google Scholar
  • 7c Yadav JS. Reddy BVS. Abraham S. Sabitha G. Tetrahedron Lett.  2002,  43:  1565 
    Search in Google Scholar
  • 7d Yadav JS. Reddy BVS. Satheesh G. Tetrahedron Lett.  2004,  45:  3673 
    Search in Google Scholar
  • 8a Zang ZH. Synlett  2005,  711 
  • 8b Sakai N. Hirasawa M. Konakahara T. Tetrahedron Lett.  2005,  46:  6407 
    Search in Google Scholar
  • 9a Agnusdei M. Bandini M. Melloni A. Umani-Ronchi A. J. Org. Chem.  2003,  68:  7126 
    Search in Google Scholar
  • 9b Huang J.-M. Wong C.-M. Xu F.-X. Loh T.-P. Tetrahedron Lett.  2007,  48:  3375 
    Search in Google Scholar
  • 9c Harada S. Takita R. Ohshima T. Matsunaga S. Shibasaki M. Chem. Commun.  2007,  948 
  • 10a Yadav JS. Reddy BVS. Rao KV. Raj KS. Prasad AR. Kumar SK. Kunwar AC. Jayaprakash PJ. Jagannath B. Angew. Chem. Int. Ed.  2003,  42:  5198 
    Search in Google Scholar
  • 10b Yadav JS. Reddy BVS. Kumar GM. Synlett  2001,  1781 
  • 10c Yadav JS. Reddy BVS. Baishya G. Synlett  2003,  396 
  • 10d Yadav JS. Reddy BVS. Swamy T. Synthesis  2004,  106 
  • 11a Yadav JS. Reddy BVS. Krishna AD. Swamy T. Tetrahedron Lett.  2003,  44:  6055 
    Search in Google Scholar
  • 11b Yadav JS. Reddy BVS. Gakul B. Green Chem.  2003,  5:  264 
    Search in Google Scholar
  • 11c Yadav JS. Reddy BVS. Reddy MS. Parimala G. Synthesis  2003,  2390 
12

General Procedure To a stirred solution of indole (1 mmol) in DCE (3 mL) were added the N-tosylazetidine (1 mmol) and InBr3 (0.1 mmol). The resulting mixture was stirred at reflux temperature for the appropriate time (Table  [¹] ).
After complete conversion as indicated by TLC, the solvent was removed by evaporation, and the residue was diluted with H2O and extracted with EtOAc (2 × 10 mL). The combined organic layers were dried over anhyd Na2SO4 and concentrated in vacuo. The resulting product was purified by column chromatography on SiO2 (Merck, 100-200 mesh) using EtOAc-hexane (3:7) as eluent to afford pure 3-alkenyl indole derivative.
Spectroscopic Data for Selected Products
N -1-[3-(1 H -3-indolyl)propyl]-4-methyl-1-benzenesulfon-amide (3a) Semisolid. IR (KBr): νmax = 3405, 3054, 2923, 2853, 1598, 1455, 1322, 1156, 1091, 813, 771, 745 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 1.71-1.85 (m, 2 H), 2.38 (s, 3 H), 2.72 (t, J = 6.6 Hz, 2 H), 2.94 (q, J = 6.6 Hz, 2 H), 4.74 (br s, 1 H, NH), 6.85-7.30 (m, 6 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.65 (d, J = 8.0 Hz, 2 H), 7.88 (br s, 1 H, ArNH). LC-MS: m/z = 351 [M + Na], 169, 139. HRMS: m/z calcd for C18H20N2O2NaS: 351.1143; found: 351.1131. N -1-[3-(2-Methyl-1 H -3-indolyl)propyl]-4-methyl-1-benzenesulfonamide (3c) Solid; mp 107-109 ˚C. IR (KBr): νmax = 3397, 3290, 3054, 2923, 2856, 1596, 1462, 1322, 1156, 1091, 814, 745 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 1.65-1.72 (m, 2 H), 2.25 (s, 3 H), 2.40 (s, 3 H), 2.65 (t, J = 6.6 Hz, 2 H), 2.87 (q, J = 6.6 Hz, 2 H), 4.65 (t, J = 6.6 Hz, 1 H), 6.89-7.07 (m, 2 H), 7.10-7.30 (m, 4 H), 7.60 (d, J = 8.0 Hz, 2 H), 7.73 (br s, 1 H, ArNH): LC-MS: m/z = 381 [M + K], 365 [M + Na], 242, 197, 169, 139. HRMS: m/z calcd for C19H22N2O2KS: 381.1039; found: 381.1043. N-1-[3-(2-Methyl-1 H -3-indolyl)-3-phenylpropyl]-4-methyl-1-benzenesulfonamide (3i)
Solid: mp 76-78 ˚C. IR (KBr): νmax = 3380, 3026, 2924, 2855, 1601, 1457, 1323, 1156, 1092, 813, 753 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 2.30 (s, 3 H), 2.30-2.35 (m, 2 H), 2.38 (s, 3 H), 2.84 (t, J = 5.2 Hz, 2 H), 4.23 (dd, J = 6.4, 9.4 Hz, 1 H), 4.57 (t, J = 6.0 Hz, 1 H), 6.85-7.24 (m, 10 H), 7.28 (d, J = 7.5 Hz, 1 H), 7.54 (d, J = 8.3 Hz, 2 H), 7.84 (br s, 1 H, ArNH). LC-MS: m/z = 441 [M + Na], 139, 111. HRMS: m/z calcd for C25H26N2O2NaS: 441.1612; found: 441.1619.