Download PDF
Synthesis 2011(2): 199-206  
DOI: 10.1055/s-0030-1258373
PSP
© Georg Thieme Verlag Stuttgart ˙ New York

2,4-Disubstituted Thiazoles by Regioselective Cross-Coupling or Bromine-Magnesium Exchange Reactions of 2,4-Dibromothiazole

Stefan Gross, Stefan Heuser, Carolin Ammer, Golo Heckmann, Thorsten Bach*
Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913315; e-Mail: thorsten.bach@ch.tum.de;
Further Information

Publication History

Received 25 November 2010
Publication Date:
20 December 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

Cross-coupling reactions occur on 2,4-dibromothiazole preferentially at the more electron-deficient 2-position. This fact can be favorably used to prepare 2-substituted 4-bromothiazoles, which serve as precursors for 2,4-disubstituted thiazoles. Protocols for regioselective Negishi and Stille cross-coupling reactions are provided. Alternatively, the title compound can be metalated in 2-position by a halogen-metal exchange reaction. As a supplement to the well-established bromine-lithium exchange, the regioselective bromine-magnesium exchange reaction is presented.

Key words

catalysis - cross-coupling - heterocycles - palladium - regioselectivity - thiazoles

    References

  • Reviews:
  • 4a Kikelj D. Urleb D. In Science of Synthesis   Vol. 11:  Schaumann E. Thieme; Stuttgart: 2002.  p.627 ; and references cited therein
    Google Scholar
  • 4b De Souza MVN.
    J. Sulfur Chem.  2005,  26:  429 
    Google Scholar
  • 4c Bagley MC. Dale JW. Merritt EA. Xiong X. Chem. Rev.  2005,  105:  685 ; and references cited therein
    Google Scholar
  • 5 Hoefle G. Bedorf N. Steinmetz H. Schomburg D. Gerth K. Reichenbach H. Angew. Chem., Int. Ed. Engl.  1996,  35:  1567 ; Angew. Chem. 1996, 108, 1671
    CrossrefGoogle Scholar
  • 6a Donovick R. Pagano JF. Stout HA. Weinstein MJ. Antibiot. Annu.  1955-1956,  3:  554 
    Google Scholar
  • 6b Anderson B. Hodgkin DC. Viswamitra MA. Nature  1970,  225:  223 
    Google Scholar
  • 7a Shimanaka K. Kinoshita N. Iinuma H. Hamada M. Takeuchi T. J. Antibiot.  1994,  47:  668 
    Google Scholar
  • 7b Shimanaka K. Takahashi Y. Iinuma H. Naganawa H. Takeuchi T.
    J. Antibiot.  1994,  47:  1145 
    Google Scholar
  • 7c Shimanaka K. Takahashi Y. Iinuma H. Naganawa H. Takeuchi T. J. Antibiot.  1994,  47:  1153 
    Google Scholar
  • 8 Walsh CT. Acker MG. Bowers AA. J. Biol. Chem.  2010,  285:  27525 ; and references cited therein
    CrossrefGoogle Scholar
  • 9a Hantzsch A. Justus Liebigs Ann. Chem.  1888,  249:  1 
    Google Scholar
  • 9b Bredenkamp MW. Holzapfel CW. Van Zyl WJ. Synth. Commun.  1990,  20:  2235 
    Google Scholar
  • 9c Aguilar E. Meyers AI. Tetrahedron Lett.  1994,  35:  2473 
    Google Scholar
  • 9d Schmidt U. Gleich P. Griesser H. Utz R. Synthesis  1986,  992 
    Google Scholar
  • 10a Gabriel S. Ber. Dtsch. Chem. Ges.  1910,  43:  1283 
    Google Scholar
  • 10b Singh J. Gordon TD. Earley WG. Morgan BA. Tetrahedron Lett.  1993,  34:  211 
    Google Scholar
  • 11 Dondoni A. Fantin G. Fogagnolo M. Medici A. Pedrini P. J. Org. Chem.  1988,  53:  1748 
    CrossrefGoogle Scholar
  • 12 Reynaud P. Robba M. Moreau RC. Bull. Soc. Chim. Fr.  1962,  1735 
    Google Scholar
  • 13a Kelly TR. Jagoe CT. Gu Z. Tetrahedron Lett.  1991,  32:  4263 
    Google Scholar
  • 13b Nickson TE. J. Fluorine Chem.  1991,  55:  173 
    Google Scholar
  • 13c Nicolaou KC. He Y. Roschangar F. King NP. Vourloumis D. Li T. Angew. Chem. Int. Ed.  1998,  37:  84 ; Angew. Chem. 1998, 110, 89
    Google Scholar
  • 13d Ung AT. Pyne SG. Tetrahedron: Asymmetry  1998,  9:  1395 
    Google Scholar
  • 13e Karama U. Höfle G. Eur. J. Org. Chem.  2003,  1042 
    Google Scholar
  • 13f Ganesh T. Schilling JK. Palakodety RK. Ravindra R. Shanker N. Bane S. Kingston DGI. Tetrahedron  2003,  59:  9979 
    Google Scholar
  • 14 Wellmar U. Hörnfeldt A.-B. Gronowitz S. J. Heterocycl. Chem.  1995,  32:  1159 
    CrossrefGoogle Scholar
  • 15 Nicolaou KC. King NP. Finlay MRV. He Y. Roschangar F. Vourloumis D. Vallberg H. Sarabia F. Ninkovic S. Hepworth D. Bioorg. Med. Chem.  1999,  7:  665 
    CrossrefGoogle Scholar
  • 16a Abarbri M. Thibonnet J. Berillon L. Dehmel F. Rottländer M. Knochel P. J. Org. Chem.  2000,  65:  4618 
    Google Scholar
  • 16b Review: Knochel P. Dohle W. Gommermann N. Kneisel FF. Kopp F. Korn T. Sapountzis I. Vu VA. Angew. Chem. Int. Ed.  2003,  42:  4302 ; Angew. Chem. 2003, 115, 4438
    Google Scholar
  • Reviews:
  • 17a Schröter S. Stock C. Bach T. Tetrahedron  2005,  61:  2245 
    Google Scholar
  • 17b Fairlamb IJS. Chem. Soc. Rev.  2007,  36:  1036 
    Google Scholar
  • Previous examples from our group:
  • 18a Bach T. Krüger L. Tetrahedron Lett.  1998,  39:  1729 
    Google Scholar
  • 18b Bach T. Krüger L. Synlett  1998,  1185 
    Google Scholar
  • 18c Bach T. Krüger L. Eur. J. Org. Chem.  1999,  2045 
    Google Scholar
  • 18d Bach T. Bartels M. Synlett  2001,  1284 
    Google Scholar
  • 19 Bach T. Heuser S. Tetrahedron Lett.  2000,  41:  1707 
    CrossrefGoogle Scholar
  • 20 Bach T. Heuser S. J. Org. Chem.  2002,  67:  5789 
    CrossrefPubMedGoogle Scholar
  • 21 Bach T. Heuser S. Synlett  2002,  2089 
    Article in Thieme ConnectGoogle Scholar
  • 22a Bach T. Heuser S. Angew. Chem. Int. Ed.  2001,  40:  3184 ; Angew. Chem. 2001, 113, 3283
    Google Scholar
  • 22b Bach T. Heuser S. Chem. Eur. J.  2002,  8:  5585 
    Google Scholar
  • 23a Hayashi T. Konishi M. Kobori Y. Kumada M. Higuchi T. Hirotsu K. J. Am. Chem. Soc.  1984,  106:  158 
    Google Scholar
  • 23b Bishop JJ. Davison A. Katcher ML. Lichtenberg DW. Merrill RE. Smart JC. J. Organomet. Chem.  1971,  27:  241 
    Google Scholar
  • 24 Ammer C. Bach T. Chem. Eur. J.  2010,  16:  14083 
    CrossrefGoogle Scholar
  • 25a Müller HM. Delgado O. Bach T. Angew. Chem. Int. Ed.  2007,  46:  4771 ; Angew. Chem. 2007, 119, 4855
    Google Scholar
  • 25b Delgado O. Müller HM. Chem. Eur. J.  2008,  14:  2322 
    Google Scholar
  • 26a Shao J. Panek JS. Org. Lett.  2004,  6:  3083 
    Google Scholar
  • 26b Le Flohic A. Meyer C. Cossy J. Org. Lett.  2005,  7:  339 
    Google Scholar
  • 26c Le Flohic A. Meyer C. Cossy J. Tetrahedron  2006,  62:  9017 
    Google Scholar
  • 26d Hoffman TJ. Dash J. Rigby JH. Arseniyadis S. Cossy J. Org. Lett.  2009,  11:  2756 
    Google Scholar
  • 27a Bey E. Marchais-Oberwinkler S. Werth R. Negri M. Al-Soud YA. Kruchten P. Oster A. Frotscher M. Birk B. Hartmann RW. J. Med. Chem.  2008,  51:  6725 
    Google Scholar
  • 27b Strotman NA. Chobanian HR. He J. Guo Y. Dormer PG. Jones CM. Steves JE. J. Org. Chem.  2010,  75:  1733 
    Google Scholar
  • 28 Schweizer SA. Bach T. Synlett  2010,  81 
    Article in Thieme ConnectGoogle Scholar
  • 29 Spieß A. Heckmann G. Bach T. Synlett  2004,  131 
    Article in Thieme ConnectGoogle Scholar
  • 30a Heckmann G. Bach T. Angew. Chem. Int. Ed.  2005,  44:  1199 ; Angew. Chem. 2005, 117, 1223
    Google Scholar
  • 30b Delgado O. Heckmann G. Müller HM. Bach T. J. Org. Chem.  2006,  71:  4599 
    Google Scholar
  • 31a Liu G. Cogan DA. Ellman JA. J. Am. Chem. Soc.  1997,  119:  9913 
    Google Scholar
  • 31b Liu G. Cogan DA. Owens TD. Tang TP. Ellman JA. J. Org. Chem.  1999,  64:  1278 
    Google Scholar
  • 31c Cogan DA. Liu G. Ellman JA. Tetrahedron  1999,  55:  8883 
    Google Scholar
  • 31d Ellman JA. Owens TD. Tang TP. Acc. Chem. Res.  2002,  35:  984 
    Google Scholar
1

Current address: Georg-Simon-Ohm Hochschule, Fakultät für Angewandte Chemie, Prinzregentenufer 47, 90489 Nürnberg, Germany.

2

Current address: Pharmazell GmbH, Rosenheimer Straße 43, 83064 Raubling, Germany.

3

Current address: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216 Ingelheim, Germany.