Synthesis 2008(22): 3697-3702  
DOI: 10.1055/s-0028-1083208
PSP
© Georg Thieme Verlag Stuttgart ˙ New York

Multiple Regio- and Chemoselective Functionalizations of Pyrimidine Derivatives Using TMPMgCl×LiCl and TMP2Mg×2 LiCl

Marc Mosrin, Marilena Petrera, Paul Knochel*
Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377 München, Germany
Fax: +49(89)218077680; e-Mail: [email protected];
Further Information

Publication History

Received 21 July 2008
Publication Date:
23 October 2008 (online)

Abstract

The multiple successive regio- and chemoselective magnesiation of commercially available 2-bromopyrimidine at the C4, C6, and C5 positions allows the regioselective functionalization of all positions of the pyrimidine ring.

    References

  • 1a Hurst DT. An Introduction to the Chemistry and Biochemistry of Pyrimidines, Purines and Pteridines   Wiley; Chichester: 1980. 
  • 1b Brown DJ. The Pyrimidines   Wiley; New York: 1994. 
  • 1c Comprehensive Heterocyclic Chemistry II   Katrizky AR. Rees CW. Scriven EFV. Pergamon; Oxford: 1996. 
  • 1d Gribble G. Joule J. Progress in Heterocyclic Chemistry   Vol. 18:  Elsevier; Oxford: 2007. 
  • 2a Eicher T. Hauptmann S. Speicher A. The Chemistry of Heterocycles   Wiley; Weinheim: 2003. 
  • 2b Plé N. Turck A. Couture K. Quéguiner G. Synthesis  1996,  838 
  • 2c Plé N. Turck A. Heynderickx A. Quéguiner G. Tetrahedron  1998,  54:  9701 
  • 2d Plé N. Turck A. Heynderickx A. Quéguiner G. J. Heterocycl. Chem.  1997,  34:  551 
  • 3a Turck A. Plé N. Mongin F. Quéguiner G. Tetrahedron Lett.  2001,  42:  4489 
  • 3b Schlosser M. Lefebvre O. Ondi L. Eur. J. Org. Chem.  2006,  6:  1593 
  • 4a Krasovskiy A. Krasovskaya V. Knochel P. Angew. Chem. Int. Ed.  2006,  45:  2958 
  • 4b Lin W. Baron O. Knochel P. Org. Lett.  2006,  8:  5673 
  • 5 Mosrin M. Knochel P. Org. Lett.  2008,  10:  2497 
  • 6 Clososki GC. Rohbogner CJ. Knochel P. Angew. Chem. Int. Ed.  2007,  46:  7681 
  • 8a Negishi E. Valente LF. Kobayashi M. J. Am. Chem. Soc.  1980,  102:  3298 
  • 8b Negishi E. Kobayashi M. J. Org. Chem.  1980,  45:  5223 
  • 8c Negishi E. Acc. Chem. Res.  1982,  15:  340 
  • 8d Milne JE. Buchwald SL. J. Am. Chem. Soc.  2004,  126:  13028 
  • 9a Benderitter P. de Araujo JX. Schmitt M. Bourguignon JJ. Tetrahedron  2007,  63:  12465 
  • 9b Kim JT. Gevorgyan V. Org. Lett.  2002,  4:  4697 
  • 9c Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  16:  4467 
  • 9d Sonogashira K. Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pergamon Press; New York: 1991. 
  • 10 Knochel P. Yeh MCP. Berk SC. Talbert J. J. Org. Chem.  1988,  53:  2390 
  • 11a Lin H.-S. Paquette LA. Synth. Commun.  1994,  24:  2503 
  • 11b Hammett LP. Walden GH. Edmonds SM. J. Am. Chem. Soc.  1934,  56:  1092 
  • 12 Krasovskiy A. Knochel P. Synthesis  2006,  890 
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2-Bromopyrimidine is commercially available from Acros, Aldrich, Fluka (ca $15 for 1 g).