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Synlett 2009(17): 2821-2824  
DOI: 10.1055/s-0029-1217984
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Bicyclic Pyridones via Cyclocondensation of Heterocyclic Ketene Aminals with β-Ketoester Enol Tosylates

Sheng-Jiao Yan, Yan-Fei Niu, Rong Huang, Jun Lin*
Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. of China
Fax: +86(871)5033215; e-Mail: linjun@ynu.edu.cn;
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Publikationsverlauf

Received 8 July 2009
Publikationsdatum:
24. September 2009 (online)

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Abstract

A series of novel bicyclic pyridones were easily prepared by cyclic condensation of heterocyclic ketene aminals with β-keto ester enol tosylates in the presence of a base to give products in excellent yields (80-95%).

Key words

pyridones - cyclocondensation - heterocyclic ketene aminals - β-keto ester enol tosylates

    References and Notes

  • For reviews, see:
  • 1a Huang Z.-T. Wang M.-X. Heterocycles  1994,  37:  1233 
    Suche in Google Scholar
  • 1b Huang Z.-T. Wang M.-X. Prog. Nat. Sci.  1999,  11:  971 
    Suche in Google Scholar
  • 2a Gupta AK. Ila H. Junjappa H. Synthesis  1988,  284 
  • 2b Huang Z.-T. Liu Z.-R. Chem. Ber.  1989,  122:  95 
    Suche in Google Scholar
  • 2c Zhang J.-H. Wang M.-X. Huang Z.-T. J. Chem. Soc., Perkin Trans. 1  1999,  321 
  • 2d Nie X.-P. Wang M.-X. Huang Z.-T. Synthesis  2000,  1439 
  • 2e Yu C.-Y. Wang L.-B. Li W.-Y. Huang Z.-T. Synthesis  1996,  959 
  • 3 Jones RCF. Patel P. Hirst SC. Turner I. Tetrahedron  1997,  53:  11781 
    CrossrefSuche in Google Scholar
  • 4a Huang Z.-T. Liu Z.-R. Heterocycles  1986,  24:  2247 
    Suche in Google Scholar
  • 4b Jones RCF. Patel P. Hirst SC. Smallridge MJ. Tetrahedron  1998,  54:  6191 
    Suche in Google Scholar
  • 4c Jones RCF. Smallridge MJ. Tetrahedron Lett.  1988,  29:  5005 
    Suche in Google Scholar
  • 4d Yaqub M. Yu C.-Y. Jia Y.-M. Huang Z.-T. Synlett  2008,  1357 
  • 4e Yu C.-Y. Yang P.-H. Zhao M.-X. Huang Z.-T. Synlett  2006,  1835 
  • 4f Yu C.-Y. Yan S.-J. Huang Z.-T. Acta Crystallogr., Sect. E: Struct. Rep. Online  2006,  62:  o2731 
    Suche in Google Scholar
  • 5 Zhang J.-H. Wang M.-X. Huang Z.-T. J. Chem. Soc., Perkin Trans. 1  1999,  2087 
    Crossref
  • 6a Huang Z.-T. Tzai LH. Chem. Ber.  1986,  119:  2208 
    Suche in Google Scholar
  • 6b Huang Z.-T. Liu Z.-R. Synth. Commun.  1989,  19:  1801 
    Suche in Google Scholar
  • 6c Huang Z.-T. Wang M.-X. J. Chem. Soc., Perkin Trans. 1  1993,  1085 
  • 6d Zhao M.-X. Wang M.-X. Huang Z.-T. Tetrahedron  2002,  58:  1309 
    Suche in Google Scholar
  • 6e Wang L.-B. Huang Z.-T. Synth. Commun.  1997,  27:  409 
    Suche in Google Scholar
  • 6f Huang Z.-T. Wang X.-J. Chem. Ber.  1987,  120:  1803 
    Suche in Google Scholar
  • 6g Takao T. Satomi N. Bull. Chem. Soc. Jpn.  1993,  66:  2118 
    Suche in Google Scholar
  • 7 Liao J.-P. Zhang T. Yu C.-Y. Huang Z.-T. Synlett  2007,  761 
    Thieme Connect
  • 8 Yu C.-Y, Yan S.-J, Zhang T, and Huang Z.-T. inventors;  CN101041660. 
  • 9 Xu Z.-H. Jie Y.-F. Wang M.-X. Huang Z.-T. Synthesis  2002,  523 
    Thieme Connect
  • 10a Tieman CH, Kollmeyer WD, and Roman SA. inventors; DE  2,445,421. 
  • 10b Tieman CH, and Kollmeyer WD. inventors; US  3,948,934. 
  • 10c Porter PE, and Kollmeyer WD. inventors; US  4,053,623. 
  • 11a Jordan AD. Vaidya AH. Rosenthal DI. Dubinsky B. Kordik CP. Sanfilippo PJ. Wub WN. Reitza AB. Biomed. Chem. Lett.  2002,  12:  2381 
    Suche in Google Scholar
  • 11b Maryanoff BE. Nortey SO. McNally JJ. Sanfilippo PJ. McComsey DF. Dubinsky B. Shank RP. Reitz AB. Biomed. Chem. Lett.  1999,  9:  1547 
    Suche in Google Scholar
  • 11c Kondo H. Taguchi M. Inoue Y. Sakamoto F. Tsukamoto G. J. Med. Chem.  1990,  33:  2012 
    Suche in Google Scholar
  • 11d Maryanoff BE. Ho W. McComsey DF. Reitz AB. Grow PP. Nortey SO. Shank RP. Dubinsky B. Taylor RJ. Gardocki JF. J. Med. Chem.  1995,  38:  16 
    Suche in Google Scholar
  • 12 Suryawanshi SN. Pandey S. . Bhatt BA. Gupta S. Eur. J. Med. Chem.  2007,  511 
    Crossref
  • 13 Abdelhalima MM. El-Saidib MMT. Rabieb ST. ElmegeedaG A. Steroids  2007,  72:  459 
    CrossrefSuche in Google Scholar
  • 14a Kubo K. Ito N. Isomura Y. Sozu I. Homma H. Murakami M. Chem. Pharm. Bull.  1979,  27:  1207 
    Suche in Google Scholar
  • 14b Frohn MJ, Hong F.-T, Liu L, Lopez P, Siegmund AC, Tadesse S, and Tamayo N. inventors; WO  2005070932. 
  • 14c Alonso-Alija C, Michels M, Schirok H, Schlemmer K.-H, Dodd S, Fitzgerald M, Bell J, and Gill A. inventors; WO  2003053967. 
  • 15 Hehemann DG. Winnik W. J. Heterocycl. Chem.  1994,  31:  393 
    CrossrefSuche in Google Scholar
  • 16a Cheng D.-C. Croft L. Abdi M. Lightfoot A. Gallagher T. Org. Lett.  2007,  9:  5175 
    Suche in Google Scholar
  • 16b Cheng D.-C. Gallagher T. Org. Lett.  2009,  11:  2639 
    Suche in Google Scholar
  • 16c Qacemi ME. Ricard L. Zard SZ. Chem. Commun.  2006,  4422 
  • 16d Podhorez DE. J. Heterocycl. Chem.  1991,  28:  971 
    Suche in Google Scholar
  • 16e Sylvia S. Daniel S. Simon S. Zhang X. Volkhard A. Synthesis  2005,  3107 
  • 17a Tilak BD. Ayyangar NR. Rao US. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1984,  23:  24 
    Suche in Google Scholar
  • 17b Jones RCF. Dimopoulos P. Coles SC. Light ME. Hursthouse MB. J. Chem. Soc., Perkin Trans. 1  2000,  2331 
  • 17c Masahiko T. Chiyoshi N. Yoshio S. Chem. Lett.  1987,  1229 
  • 17d Al-Afaleq E. Synth. Commun.  2001,  31:  3557 
    Suche in Google Scholar
  • 18a Hansen LA. Skrydstrup T. J. Org. Chem.  2005,  70:  5997 
    Suche in Google Scholar
  • 18b Jalander L. Mattinen J. Oksanen L. Rosling A. Synth. Commun.  1990,  20:  881 
    Suche in Google Scholar
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General Procedure for the Cyclocondensation Reaction
A 50 mL round-bottom flask was charged with β-keto ester enol tosylates 2 (1 mmol), 1,4-dioxane (10 mL), and Et3N (3 mL), then the solution was added to HKA 1 (1 mmol), and the solution was refluxed. The resulting solution was stirred for 3-14 h until the β-keto ester enol toslates 2 were completely consumed. The mixture was quenched by the addition of H2O (50 mL). The reaction mixture was filtered off, and the residue was washed with H2O to give a crude product that was recrystallized by EtOH or acetone to form the final products 4-6.
Compound 4d: yellow solid; mp 184-187.5 ˚C. IR (KBr): 3366 (NH), 3079 (C=CH), 1679 (C=O), 1602 (C=O), 1558 (C=C), 1324 (CN), 1165 (CF) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 3.68 (t, J = 9.2 Hz, 2 H, CH2), 4.11 (t, J = 9.1 Hz, 2 H, CH2), 6.00 (s, 1 H, CH=), 7.56-7.79 (m, 5 H, ArH, NH). ¹³C NMR (125 MHz, DMSO-d 6): δ = 42.6 (NCH2), 43.7 (NCH2), 91.8 (CCOAr), 104.3 (CHCO), 122.5 (q, J = 211.3 Hz, CF3), 128.5 (2 × CHar), 131.1 (2 × CHar), 137.0 (Car), 137.8 (Car), 140.0 (q, J = 30 Hz, CCF3), 154.4 (C=CCOAr), 159.0 (C=O), 190.2 (COAr). HRMS (TOF
ES-): m/z calcd for C15H9ClF3N2O2 [M - H+]: 341.0310; found: 341.0308.

20

CCDC 738457 contains the supplementary crystallographic data for compound 4d. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.