Synlett 2010(10): 1455-1458  
DOI: 10.1055/s-0029-1219923
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Synthesis of New Aza-Substituted Indoles via Michael-Type Addition

Sinan Bayindir, Esra Erdogan, Haydar Kilic, Nurullah Saracoglu*
Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum 25240, Turkey
Fax: +90(442)2360948; e-Mail: nsarac@atauni.edu.tr;
Further Information

Publication History

Received 24 February 2010
Publication Date:
06 May 2010 (online)

Abstract

An efficient method has been developed for the synthesis of new aza-substituted indoles. The methodology involves a two-step synthesis. The first step involves the Michael addition of indoline with various Michael acceptors. The other includes the oxidation of the indoline ring in the Michael adducts to an indole

    References and Notes

  • 1 Noble RL. Beer CT. Cutts JH. Ann. N. Y. Acad Sci.  1958,  76:  882 
  • 2 Svoboda GH. Neuss N. Gorman MJ. Am. Pharm. Assoc. Sci. Ed.  1959,  48:  659 
  • 3 Yokoshima S. Ueda T. Kobayashi S. Sato A. Kuboyama T. Tokuyama H. Fukuyama T. Pure Appl. Chem.  2003,  75:  29 
  • 4 Neus N. Neus MN. The Therapeutic Use of Bisindole Alkaloids from Catharanthus, In The Alkaloids   Vol. 37:  Brossi A. Suffness M. Academic Press; New York: 1990.  p.232 
  • 5 Cordell GA. Saxton JE. Bisindole Alkaloids, In The Alkaloids   Vol. 20:  Rodrigo RGA. Academic Press; San Diego: 1981. 
  • 6 Liu K. Wood HB. Jones AB. Tetrahedron Lett.  1999,  40:  5119 
  • 7 Tasuta K. Mukai H. Mitsumoto K. J. Antibiot.  2001,  54:  105 
  • 8 Physician"s Desk Reference   51st ed.:  Medical Economics; Oradell (NJ / USA): 1997.  p.2395 
  • 9 Merour JY. Coadou JY. Tatibouet F. Synthesis  1982,  1053 
  • 10 Bader T. Fazili J. Madhoun M. Aston C. Hughes D. Rizvi S. Seres K. Hasan M. Am. J. Gastroenterol.  2008,  103:  1383 
  • 11 Gupta RR. Heterocyclic Chemistry   Vol. 2:  Springer; New York / NY: 1999.  p.192 
  • 12 Physician"s Desk Reference   51st ed.:  Medical Economics; Oradell / NJ: 1997.  p.1521 
  • 13 Sundberg RJ. In Comprehensive Heterocyclic Chemistry   Vol. 4:  Katritzky RA. Reese W. Pergamon; Oxford: 1984.  p.314-476  
  • 14 Jones RA. In Comprehensive Heterocyclic Chemistry   Vol. 4:  Katritzky RA. Reese W. Pergamon; Oxford: 1984.  p.201-312  
  • 15 Praveen C. Karthikeyan K. Perumal PT. Tetrahedron  2009,  65:  9244 
  • 16 Zhu J. Wong H. Zhang Z. Yin Z. Meanwell NA. Kadow JF. Wang T. Tetrahedron Lett.  2006,  47:  5653 
  • 17 Miyagi T. Hari Y. Aoyama T. Tetrahedron Lett.  2004,  45:  6303 
  • 18 Zhang D. Liebeskind LS. J. Org. Chem.  1996,  61:  2594 
  • 19 Robert MM. Ku YY. Tuncay MS. Tetrahedron Lett.  1987,  28:  3071 
  • 20 Ernest WE. Charles A. Vitor FF. Enrique LM. Serge RP. Jhy HS. Charles SS. J. Org. Chem.  1986,  51:  2343 
  • 21 Rubottom GM. Chabala JC. Synthesis  1972,  566 
  • 22 Bocchi V. Casnati G. Dossena A. Villani F. Synthesis  1976,  414 
  • 23 Cardillo B. Casnati G. Pochini A. Ricca A. Tetrahedron Lett.  1967,  23:  3771 
  • 24 Physician"s Desk Reference   51st ed.:  Medical Economics; Oradell (NJ / USA): 1997.  p.1723 
  • 25 Antitumor Bisindole Alkaloids from Catharanthus roseus (L.), In The Alkaloids   Vol. 37:  Brossi A. Suffness M. Academic; San Diego: 1990.  p.133-204  
  • 26 Saracoglu N. Top. Heterocycl. Chem.  2007,  11:  1 
  • 27 Moghaddam FM. Bardajee GR. Taimoory MD. Lett. Org. Chem.  2006,  3:  157 
  • 28 Sundberg RJ. The Chemistry of Indoles   Academic Press; New York: 1996. 
  • 29 Xiong X. Pirrung MC. J. Org. Chem.  2007,  72:  5832 
  • 30 Sugiyama H. Yokokawa F. Aoyama T. Shioiri T. Tetrahedron Lett.  2001,  42:  7277 
  • 31 Delest B. Tisserand J.-Y. Robert J.-H. Nourrisson M.-R. Pinson P. Duflos M. Le Baut G. Renard P. Pfeiffer B. Tetrahedron  2004,  60:  6079 
  • 32 Ishiyama K. Yamada Y. Tetrahedron Lett.  2005,  46:  1021 
  • 33 Chandra T. Brown KL. Tetrahedron Lett.  2005,  46:  2071 
  • 34 McNab H. Nelson DJ. Rozgowska EJ. Synthesis  2009,  2171 
  • 35 McNab H. Tyas RG. J. Org. Chem.  2007,  72:  8760 
  • 36 Zewge D. Chen C.-y. Deer C. Dormer PG. Hughes DL. J. Org. Chem.  2007,  72:  4276 
37

Representative Procedure - Synthesis of 3-(1 H -Indol-1-yl)cyclohexanone (4)
To a solution of indoline (500 mg, 4.19 mmol) and cyclohex-2-enone (429 mg, 4.19 mmol) in MeCN (15 mL) was added DMAP (25 mg, 0.05 mmol). The mixture was stirred at r.t. for 24 h. After evaporation of the solvent, the crude product 3-(indolin-1-yl)cyclohexanone (3) was purified by crystalli-zation from EtOAc-hexane (pale yellow crystals, 850 mg, 94%, mp 235-236 ˚C).
¹H NMR (400 MHz, CDCl3): δ = 7.08-7.03 (m, =CH, 2 H), 6.64 (t, J = 7.6 Hz, =CH, 1 H), 6.42 (d, J = 7.6 Hz, =CH, 1 H), 3.82-3.75 (m, CH, 1 H), 3.49-3.43 (m, CH2, 1 H), 3.38-3.31 (m, CH2, 1 H), 2.98 (t, J = 8.2 Hz, CH2, 2 H), 2.60-2.57 (m, CH2, 1 H), 2.56-2.50 (m, CH2, 1 H), 2.47-2.41 (m, CH2, 1 H), 2.33-2.25 (m, CH2, 1 H), 2.16-2.07 (m, CH2, 2 H), 1.86-1.70 (m, CH2, 1 H), 1.69-1.60 (m, CH2, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 210.0, 150.2, 130.1, 127.6, 124.8, 117.9, 107.3, 55.0, 46.7, 43.9, 41.3, 28.5, 28.4, 22.9.
To a solution of 3-(indolin-1-yl)cyclohexanone (1.00 g, 4.65 mmol) in CH2Cl2 (10 mL) was added activated MnO2 (869 mg, 10 mmol). The mixture was then stirred at r.t. for 24 h. After filtration, the mixture was evaporated in vacuo to give 3-(1H-indol-1-yl)cyclohexanone (4) as yellow oil (890 mg, 90%). ¹H NMR (400 MHz, CDCl3): δ = 7.65 (dd, J = 7.8, 2.0 Hz, =CH, 1 H), 7.35 (d, J = 8.4 Hz, =CH, 1 H), 7.26-7.20 (m, =CH, 2 H), 7.16-7.12 (m, =CH, 1 H), 6.57 (d, J = 2.9 Hz, =CH, 1 H), 4.72-4.66 (m, CH, 1 H), 2.94-2.91 (m, CH2, 1 H), 2.90-2.77 (m, CH2, 1 H), 2.56-2.40 (m, CH2, 2 H), 2.35-2.30 (m, CH2, 1 H), 2.25-2.10 (m, CH2, 2 H), 1.85-1.78 (m, CH2, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 208.2, 135.7, 128.9, 124.0, 122.0, 121.5, 120.1, 109.6, 102.6, 54.4, 48.4, 41.1, 31.6, 22.5.