Synlett 2010(19): 2899-2904  
DOI: 10.1055/s-0030-1259027
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Syntheses of N-Alkylated Carbazolones via Pd(OAc)2-Mediated Intramolecular Coupling of N-Substituted 3-(Arylamino)cyclohex-2-enones

Wenying Bi, Xiliu Yun, Yanfeng Fan, Xiuxiang Qi, Yunfei Du*, Jianhui Huang*
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R. of China
Fax: +86(22)27404031; e-Mail: duyunfeier@tju.edu.cn; e-Mail: jhuang@tju.edu.cn;
Weitere Informationen

Publikationsverlauf

Received 5 September 2010
Publikationsdatum:
03. November 2010 (online)

Abstract

A variety of functionalized N-alkylated carbazolones were prepared via N-alkylation of 3-(arylamino)cyclohex-2-enones followed by an intramolecular oxidative coupling mediated by Pd(OAc)2 under an oxygen atmosphere. This approach adopts an inverted sequence, consisting of the conventional annulation and subsequent N-alkylation.

    References and Notes

  • 1a Gant TG, and Sarshar S. inventors; US  2010119623. 
  • 1b Barta TE. Barabasz AF. Foley BE. Geng L. Hall SE. Hanson GJ. Jenks M. Ma W. Rice JW. Veal J. Bioorg. Med. Chem. Lett.  2009,  19:  3078 
  • 1c Barta TE. Veal JM. Rice JW. Partridge JM. Fadden RP. Ma W. Jenks M. Geng L. Hanson GJ. Huang KH. Barabasz AF. Foley BE. Otto J. Hall SE. Bioorg. Med. Chem. Lett.  2008,  18:  3517 
  • 1d Yan S. Wu H. Wu N. Jiang Y. Synlett  2007,  2699 
  • 1e Romeo G. Materia L. Pittala V. Modica M. Salerno L. Siracusa M. Russo F. Minneman KP. Bioorg. Med. Chem.  2006,  14:  5211 
  • 1f Li X. Vince R. Bioorg. Med. Chem.  2006,  14:  2942 
  • 1g Kukushkin SY. Ivanov PY. Alekseeva LM. Levina VI. Kobrakov KI. Grigor’ev NB. Granik VG. Russ. Chem. Bull.  2005,  54:  1887 
  • 1h Sorensen US. Pombo-Villar E. Helv. Chim. Acta  2004,  87:  82 
  • 2a Bunce RA. Nammalwar B. J. Heterocycl. Chem.  2009,  46:  172 
  • 2b Scott TL. Burke N. Carrero-Martínez G. Söderberg BCG. Tetrahedron  2007,  63:  1183 
  • 2c Scott TL. Yu X. Gorugantula SP. Carrero-Martinez G. Soederberg BCG. Tetrahedron  2006,  62:  10835 
  • 2d Czeskis BA. Wheeler WJ. J. Labelled Compd. Radiopharm.  2005,  48:  407 
  • 2e Sissouma D. Collet SC. Guingant AY. Synlett  2004,  2612 
  • 2f Scott TL. Söderberg BCG. Tetrahedron  2002,  43:  1621 
  • 2g Tietcheu C. Garcia C. Gardette D. Dugat D. Gramain J. J. Heterocycl. Chem.  2002,  39:  965 
  • 2h Dubois EA. van den Bos JC. Doornbos T. van Doremalen P. Somsen GA. Vekemans J. Janssen A. Batink HD. Boer GJ. Pfaffendorf M. van Royen EA. van Zwieten PA. J. Med. Chem.  1996,  39:  3256 
  • 2i Caubère C. Caubère P. Renard P. Bizot-Espiart J.-G. Jamart-Grégoire B. Tetrahedron Lett.  1993,  34:  6889 
  • 2j Oikawa Y. Yonemitsu O. J. Org. Chem.  1977,  42:  1213 
  • 2k Kawai H. Nagasu T. Takeda T. Fujiwara K. Tsuji T. Ohkita M. Nishida J. Suzuki T. Tetrahedron Lett.  1975,  45:  4533 
  • 3a Weng B. Liu R. Li J.-H. Synthesis  2010,  in press
  • 3b Punniyamurthy T. Velusamy S. Iqbal J. Chem. Rev.  2005,  105:  2329 
  • 3c Knölker H.-J. Reddy KR. Chem. Rev.  2002,  102:  4303 
  • 3d Hagelin H. Oslob JD. Åkermark B. Chem. Eur. J.  1999,  5:  2413 
  • 3e Knölker H.-J. Fröhner W. J. Chem. Soc., Perkin Trans. 1  1998,  173 
  • 4a Kudzma LV. Synlett  2003,  1661 
  • 4b Osuka A. Mori Y. Suzuki H. Chem. Lett.  1982,  2031 
  • 4c Iida H. Yuasa Y. Kibayashi C. J. Org. Chem.  1980,  45:  2938 
  • 4d Iida H. Yuasa Y. Kibayashi C. J. Org. Chem.  1979,  44:  1236 
  • 5a Ge H. Niphakis MJ. Georg GI. J. Am. Chem. Soc.  2008,  130:  3708 
  • 5b Rakshit S. Patureau FW. Glorius F. J. Am. Chem. Soc.  2010,  132:  9585 
  • 5c Neumann JJ. Suri M. Glorius F. Angew. Chem. Int. Ed.  2010,  49: In press
  • 6a Shi Z. Zhang C. Li S. Pan D. Ding S. Cui Y. Jiao N. Angew. Chem. Int. Ed.  2009,  48:  4572 
  • 6b Würtz S. Rakshit S. Neumann JJ. Dröge T. Glorius F. Angew. Chem. Int. Ed.  2008,  47:  7230 
  • 6c Humphrey GR. Kuethe JT. Chem. Rev.  2006,  106:  2875 
  • 6d Cacchi S. Fabrizi G. Chem. Rev.  2005,  105:  2873 
  • 6e Chen C. Lieberman DR. Larsen RD. Verhoeven TR. Reider PJ. J. Org. Chem.  1997,  62:  2676 
  • 6f Koerber-Plé K. Massiot G. Synlett  1994,  759 
  • 6g Sakamoto T. Nagano T. Kondo Y. Yamanaka H. Synthesis  1990,  215 
  • For recent selected examples using oxygen as oxidant, see:
  • 7a Hamada T. Ye X. Stahl SS. J. Am. Chem. Soc.  2008,  130:  833 
  • 7b Jiao N. Zhang C. J. Am. Chem. Soc.  2010,  132:  28 
  • 7c Shi Z. Zhang B. Cui Y. Jiao N. Angew. Chem. Int. Ed.  2010,  49:  4036 
  • 7d Jiao N. Zhang C. Angew. Chem. Int. Ed.  2010,  49:  6174 
  • 8 For the most similar N-methylation of 1 using NaH and methyl iodide in toluene, see: Aragon P.-J. Yapi A.-D. Pinguet F. Chezal J.-M. Teulade J.-C. Chapat J.-P. Blache Y. Chem. Pharm. Bull.  2004,  52:  659 
  • 9a Sissouma D. Collet SC. Guingant AY. Synlett  2004,  2612 
  • 9b Dobbs AP. Jones K. Veal KT. Tetrahedron Lett.  1997,  38:  5379 
  • 11 Rodríguez JG. del Valle C. Esteban-Calderón C. Martinez-Ripoll M. J. Chem. Crystallogr.  1995,  25:  249 
10

General Procedure for the Synthesis of N-Substituted Carbazolones 3
To a solution of N-substituted 3-(arylamino)cyclohex-
2-enones 2a-n (1 mmol) in AcOH (15 mL) was added Pd(OAc)2 (0.1 mmol), and the resulting solution was heated at 100 ˚C and passed through oxygen flow (1.0 L/min).
TLC was used to monitor the reaction progress. After the consumption of starting material, the reaction mixture was extracted by EtOAc (3 × 15 mL). The organic phase was combined, dried (anhyd Na2SO4). After filtration, the solvent was removed under reduced pressure to give the crude product. The residue was purified by flash column chromatography (EtOAc-PE, 1:3) on silica gel to give the desired products 3a-n. Compound 3a:¹¹ white solid; mp 195-196 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.27-8.23 (m, 1 H, ArH), 7.33-7.27 (m, 3 H, ArH), 3.72 (s, 3 H, NCH3), 2.95 (t, J = 6.0 Hz, 2 H, COCH2), 2.62 (t, J = 6.0 Hz, 2 H, CH2), 2.30-2.23 (m, 2 H, CH2). ESI-LRMS: m/z calcd for C13H13NO+: 200.1 [M + H+]; found: 200.1 [M + H+], 222 [M + Na+].
Compound 3b: brown solid; mp 230-231 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.38 (d, J = 2.0 Hz, 1 H, ArH), 7.34 (dd, J = 9.0, 2.0 Hz, 1 H, ArH), 7.18 (d, J = 9.0 Hz, 1 H, ArH), 3.68 (s, 3 H, NCH3), 2.92 (t, J = 6.0 Hz, 2 H, COCH2), 2.56 (t, J = 6.0 Hz, 2 H, CH2), 2.28-2.22 (m, 2 H, CH2). ¹³C NMR (100 MHz, CDCl3): δ = 193.8, 153.0, 137.6, 134.9, 127.2, 125.8, 124.4, 111.8, 110.8, 37.7, 35.6, 23.1, 21.9. ESI-LRMS: m/z calcd for C13H12 79BrNO+: 280.0 [M + H+]; found: 280.0. The spectroscopic data for all the new compounds can be found in the Supporting Information.