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Synthesis 2010(13): 2129-2138  
DOI: 10.1055/s-0029-1218787
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Route to Alkenyl-Substituted 4-Hydroxypyridine and Pyrimidine Derivatives via Three-Component Access to β-Alkoxy-β-ketoenamides

Mrinal K. Bera, Hans-Ulrich Reissig*
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: hans.reissig@chemie.fu-berlin.de;
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Publikationsverlauf

Received 29 March 2010
Publikationsdatum:
20. Mai 2010 (online)

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Abstract

β-Alkoxy-β-ketoenamides with an alkenylated side arm were prepared by three-component reaction of lithiated methoxy­allene, nitriles, and α,β-unsaturated carboxylic acids. Their subsequent treatment with trimethylsilyl triflate and base provided 6-alkenyl-4-hydroxypyridine derivatives that were converted into the corresponding nonaflates. Alternatively, condensation of β-alkoxy-β-ketoenamides with an ammonium salt led to the smooth formation of alkenyl-substituted pyrimidine derivatives. The alkenyl group in pyridine or pyrimidine derivatives allows a wide scope of functional group modification. Moreover, the pyridin-4-yl nona­flates are excellent candidates for palladium-catalyzed coupling reactions­ and the 6-methyl group of the pyrimidine derivatives could also be employed for the introduction of functional groups and subsequent reactions. A variety of highly substituted pyridine and pyrimidine derivatives are available by this modular route to heterocycles.

Key words

alkoxyallenes - enamides - pyridines - nonaflates - pyrimidines - Suzuki couplings

    References

  • 1a Coutts RT. Casy FA. Chem. Heterocycl. Compd. (Engl. Transl.)  1975,  14:  445 
    Google Scholar
  • 1b McInnes AG. Smith DG. Wright JLC. Vining LC. Can. J. Chem.  1977,  55:  4159 
    Google Scholar
  • 1c Berthel SJ. Marks IM. Yin X. Mischke SG. Orzechowski L. Pezzoni G. Sala F. Vassilev LT. Anti-Cancer Drugs  2002,  13:  359 
    Google Scholar
  • 1d Bringmann G. Reichert Y. Kane V. Tetrahedron  2004,  60:  3539 
    Google Scholar
  • 1e Chinchilla R. Nájera C. Yus M. Chem. Rev.  2004,  104:  2667 
    Google Scholar
  • 1f Schnermann MJ. Boger DL. J. Am. Chem. Soc.  2005,  127:  15704 
    Google Scholar
  • 1g Whitson EL. Mala SMVD. Veltri CA. Bugni TS. de Silva ED. Ireland CM. J. Nat. Prod.  2006,  69:  1833 
    Google Scholar
  • 1h Horiuch M. Murakami C. Fukamiya N. Yu D. Chen T.-S. Bastow KF. Zhang D.-C. Taishi Y. Imakura Y. Lee K.-H. J. Nat. Prod.  2006,  69:  1271 
    Google Scholar
  • 1i Kariya Y. Kubota T. Fromont J. Kobayashi J. Tetrahedron Lett.  2006,  47:  997 
    Google Scholar
  • 1j Nishi T. Kubota T. Fromont J. Sasaki T. Kobayashi J. Tetrahedron  2008,  64:  3127 
    Google Scholar
  • 1k Aida W. Ohtsuki T. Li X. Ishibashi M. Tetrahedron  2009,  65:  369 
    Google Scholar
  • 1l Hayashi A. Arai M. Fujita M. Kobayashi M. Biol. Pharm. Bull.  2009,  32:  1261 
    Google Scholar
  • 2 Functional Organic Materials   Müller TJJ. Bunz UHF. Wiley-VCH; Weinheim: 2007. 
    Google Scholar
  • 3a Hofmeier H. Schubert US. Chem. Commun.  2005,  2423 
    Google Scholar
  • 3b Schubert US. Eschbaumer C. Angew. Chem. Int. Ed.  2002,  41:  2892 ; Angew. Chem. 2002, 114, 3016
    Google Scholar
  • 3c Lehn J.-M. Supramolecular Chemistry-Concepts and Perspective   Wiley-VCH; Weinheim: 1995. 
    Google Scholar
  • 4a Karpov AS. Müller TJJ. Synthesis  2003,  2815 
    Google Scholar
  • 4b Bevk D. Groselj U. Meden A. Svete J. Stanovnik B. Helv. Chim. Acta  2007,  90:  1737 
    Google Scholar
  • 4c Sagar R. Kim M.-J. Park SB. Tetrahedron Lett.  2008,  49:  5080 
    Google Scholar
  • 4d Xie F. Zhao H. Zhao L. Lou L. Hu L. Bioorg. Med. Chem. Lett.  2009,  19:  275 
    Google Scholar
  • For reviews, see:
  • 5a Varela JA. Saá C. Chem. Rev.  2003,  103:  3787 
    Google Scholar
  • 5b Henry GD. Tetrahedron  2004,  60:  6043 
    Google Scholar
  • 5c Bagley MC. Glover C. Merritt EA. Synlett  2007,  2459 
    Google Scholar
  • For selected recent examples, see:
  • 5d Movassaghi M. Hill MD. J. Am. Chem. Soc.  2006,  128:  4592 
    Google Scholar
  • 5e Movassaghi M. Hill MD. Ahmad OK. J. Am. Chem. Soc.  2007,  129:  10096 
    Google Scholar
  • 5f Lu J.-Y. Arndt H.-D. J. Org. Chem.  2007,  72:  4205 
    Google Scholar
  • 5g Craig D. Paina F. Smith SC. Chem. Commun.  2008,  3408 
    Google Scholar
  • 5h Manning JR. Davies HML. J. Am. Chem. Soc.  2008,  130:  8602 
    Google Scholar
  • 5i Liu S. Liebeskind LS. J. Am. Chem. Soc.  2008,  130:  6918 
    Google Scholar
  • 5j Barluenga J. Ángel M. Rodríguez F. García-García P. Aguilar E. J. Am. Chem. Soc.  2008,  130:  2764 
    Google Scholar
  • 5k Donohoe TJ. Fishlock LP. Procopiou PA. Org. Lett.  2008,  10:  285 
    Google Scholar
  • For examples with alkenyl-substituted pyridine derivatives, see:
  • 5l Beveridge RE. Arndtsen BA. Synthesis  2010,  1000 
    Google Scholar
  • 6a Brown DJ. In Comprehensive Heterocyclic Chemistry   Vol. 3:  Katritzky AR. Rees CW. Pergamon; Oxford: 1984.  Chap. 2.13.
    Google Scholar
  • 6b Eicher T. Hauptmann S. Chemie der Heterocyclen   Thieme; Stuttgart: 1994.  p.398 
    Google Scholar
  • 6c Gilchrist TL. Heterocyclenchemie   Neunhoeffer H. Wiley-VCH; Weinheim: 1995.  p.270 
    Google Scholar
  • 6d Hoffmann MG. In Houben-Weyl   Vol. E9:  Schaumann E. Thieme; Stuttgart: 1996. 
    Google Scholar
  • 6e Von Angerer S. Science of Synthesis   Vol. 16:  Yamamoto Y. Thieme; Stuttgart: 2004.  p.379 
    Google Scholar
  • 6f Müller TJJ. Braun R. Ansorge M. Org. Lett.  2000,  2:  1967 
    Google Scholar
  • 6g Sakai N. Aoki Y. Sasada T. Kanakahara T. Org. Lett.  2005,  7:  4705 
    Google Scholar
  • 6h Movassaghi M. Hill HD. J. Am. Chem. Soc.  2006,  128:  14254 
    Google Scholar
  • 7a Pinner A. Ber. Dtsch. Chem. Ges.  1890,  23:  2919 
    Google Scholar
  • 7b Pinner A. Ber. Dtsch. Chem. Ges.  1892,  25:  1414 
    Google Scholar
  • 7c Pinner A. Ber. Dtsch. Chem. Ges.  1895,  28:  483 
    Google Scholar
  • 8a Biginelli P. Ber. Dtsch. Chem. Ges.  1891,  24:  1317 
    Google Scholar
  • 8b Biginelli P. Ber. Dtsch. Chem. Ges.  1891,  24:  2962 
    Google Scholar
  • 8c Biginelli P. Ber. Dtsch. Chem. Ges.  1893,  26:  447 
    Google Scholar
  • 8d Kappe CO. J. Org. Chem.  1997,  62:  7203 
    Google Scholar
  • 8e Kappe CO. Bioorg. Med. Chem. Lett.  2000,  10:  49 
    Google Scholar
  • Recent pyrimidine derivative syntheses starting from enamides:
  • 9a Barthakur MG. Borthakur M. Devi P. Saikia CJ. Saikia A. Bora U. Chetia A. Boruah RC. Synlett  2007,  223 
    Google Scholar
  • 9b Hill MD. Movassaghi M. Chem. Eur. J.  2008,  14:  6836 
    Google Scholar
  • For reviews on alkoxyallenes, see:
  • 10a Zimmer R. Synthesis  1993,  165 
    Google Scholar
  • 10b Zimmer R. Khan FA. J. Prakt. Chem.  1996,  338:  92 
    Google Scholar
  • 10c Reissig H.-U. Hormuth S. Schade W. Okala Amombo MG. Watanabe T. Pulz R. Hausherr A. Zimmer R. J. Heterocycl. Chem.  2000,  37:  597 
    Google Scholar
  • 10d Zimmer R. Reissig H.-U. In Modern Allene Chemistry   Vol. 2:  Krause N. Hashmi ASK. Wiley-VCH; Weinheim: 2004.  p.425-492  
    Google Scholar
  • 10e Reissig H.-U. Zimmer R. Science of Synthesis   Vol. 44:  Krause N. Thieme; Stuttgart: 2007.  p.301-352  
    Google Scholar
  • 10f Brasholz M. Reissig H.-U. Zimmer R. Acc. Chem. Res.  2009,  42:  45 
    Google Scholar
  • For selected recent applications developed by our group, see:
  • 10g Al-Harrasi A. Reissig H.-U. Angew. Chem. Int. Ed.  2005,  44:  6227 ; Angew Chem. 2005, 117, 6383
    Google Scholar
  • 10h Kaden S. Reissig H.-U. Org. Lett.  2006,  8:  4763 
    Google Scholar
  • 10i Sörgel S. Azap C. Reissig H.-U. Org. Lett.  2006,  8:  4875 
    Google Scholar
  • 10j Brasholz M. Reissig H.-U. Angew. Chem. Int. Ed.  2007,  46:  1634 ; Angew. Chem. 2007, 119, 1659
    Google Scholar
  • 10k Gwiazda M. Reissig H.-U. Synthesis  2008,  990 
    Google Scholar
  • 11a Flögel O. Dash J. Brüdgam I. Hartl H. Reissig H.-U. Chem. Eur. J.  2004,  10:  4283 
    Google Scholar
  • 11b Flögel O, and Reissig H.-U. inventors; DE  10,336,497. 
  • 11c Dash J. Lechel T. Reissig H.-U. Org. Lett.  2007,  9:  5541 
    Google Scholar
  • 11d Eidamshaus C. Reissig H.-U. Adv. Synth. Catal.  2009,  351:  1162 
    Google Scholar
  • 11e Dash J. Reissig H.-U. Chem. Eur. J.  2009,  15:  6811 
    Google Scholar
  • 11f Lechel T. Dash J. Hommes P. Lentz D. Reissig H.-U. J. Org. Chem.  2010,  75:  726 
    Google Scholar
  • 11g Lechel T. Dash J. Eidamshaus C. Brüdgam I. Reissig H.-U. Org. Biomol. Chem.  2010,  7:  DOI: 10.1039/B925468D 
    Google Scholar
  • 12a Lechel T. Möhl S. Reissig H.-U. Synlett  2009,  1059 
    Google Scholar
  • 12b Lechel T. Reissig H.-U. Eur. J. Org. Chem.  2010,  2555 
    Google Scholar
  • 13 Lechel T. Dash J. Brüdgam I. Reissig H.-U. Eur. J. Org. Chem.  2008,  3647 
    CrossrefGoogle Scholar
  • 14a Miyaura N. Yamada K. Suzuki A. Tetrahedron Lett.  1979,  20:  3437 
    Google Scholar
  • 14b Miyaura N. Suzuki A. J. Chem. Soc., Chem. Commun.  1979,  866 
    Google Scholar
  • 14c Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
    Google Scholar
  • 15 Lindsay KB. Pyne SG. Aust. J. Chem.  2004,  57:  669 
    CrossrefGoogle Scholar
  • 16 Riley HL. Morley JF. Friend NAC. J. Chem. Soc.  1932,  1875 
    CrossrefGoogle Scholar