Download PDF
Synthesis 2008(16): 2645-2649  
DOI: 10.1055/s-2008-1067182
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart ˙ New York

Ortho-Selective Cross-Coupling of Fluorobenzenes with Grignard Reagents: Acceleration by Electron-Donating Ortho-Directing Groups

Kei Manabe*, Shunpei Ishikawa
RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan
Fax: +81(48)4624662; e-Mail: keimanabe@riken.jp;
Further Information

Publication History

Received 31 March 2008
Publication Date:
17 July 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

Fluorobenzenes with directing groups such as hydroxy, hydroxymethyl, and amino underwent ortho-selective cross-coupling with Grignard reagents in the presence of palladium-based catalysts, with dichlorobis(tricyclohexylphosphine)palladium [PdCl2(PCy3)2] found to be the optimum catalyst. Fluoro and chloro groups at positions other than ortho to the directing groups survived under the reaction conditions.

Key words

fluorine - cross-coupling - palladium - site selective - Grignard reagents

    References

  • 1 Metal-Catalyzed Cross-Coupling Reactions   2nd ed.:  de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004. 
  • Examples of site-selective cross-coupling of dibromo- and dichlorobenzene derivatives:
  • 2a Singh R. Just G. J. Org. Chem.  1989,  54:  4453 
    Search in Google Scholar
  • 2b Dirk SM. Price DW. Chanteau S. Kosynkin DV. Tour JM. Tetrahedron  2001,  57:  5109 
    Search in Google Scholar
  • 2c Ackermann L. Althammer A. Angew. Chem. Int. Ed.  2007,  46:  1627 
    Search in Google Scholar
  • 2d Houpis IN. Hoeck J.-PV. Tilstam U. Synlett  2007,  2179 
  • MeO as a leaving group:
  • 2e Kakiuchi F. Usui M. Ueno S. Chatani N. Murai S. J. Am. Chem. Soc.  2004,  126:  2706 
    Search in Google Scholar
  • Examples of site-selective cross-coupling of polyhalogenated heteroarenes have been reviewed:
  • 3a Schröter S. Stock C. Bach T. Tetrahedron  2005,  61:  2245 
    Search in Google Scholar
  • 3b Fairlamb IJS. Chem. Soc. Rev.  2007,  36:  1036 
    Search in Google Scholar
  • See also:
  • 3c Legault CY. Garcia Y. Merlic CA. Houk KN. J. Am. Chem. Soc.  2007,  129:  12664 
    Search in Google Scholar
  • 4a Ishikawa S. Manabe K. Chem. Lett.  2007,  36:  1304 
    Search in Google Scholar
  • 4b Ishikawa S. Manabe K. Org. Lett.  2007,  9:  5593 
    Search in Google Scholar
  • Examples of cross-coupling of fluorobenzenes with Grignard reagents:
  • 5a Tamao K. Sumitani K. Kiso Y. Zembayashi M. Fujioka A. Kodama S.-i. Nakajima I. Minato A. Kumada M. Bull. Chem. Soc. Jpn.  1976,  49:  1958 
    Search in Google Scholar
  • 5b Böhm VPW. Gstöttmayr CWK. Weskamp T. Herrmann WA. Angew. Chem. Int. Ed.  2001,  40:  3387 
    Search in Google Scholar
  • 5c Mongin F. Mojovic L. Guillamet B. Trécourt F. Quéguiner G. J. Org. Chem.  2002,  67:  8991 
    Search in Google Scholar
  • 5d Dankwardt JW. J. Organomet. Chem.  2005,  690:  932 
    Search in Google Scholar
  • 5e Yoshikai N. Mashima H. Nakamura E. J. Am. Chem. Soc.  2005,  127:  17978 
    Search in Google Scholar
  • 5f Ackermann L. Born R. Spatz JH. Meyer D. Angew. Chem. Int. Ed.  2005,  44:  7216 
    Search in Google Scholar
  • 5g Guan B.-T. Xiang S.-K. Wu T. Sun Z.-P. Wang B.-Q. Zhao K.-Q. Shi Z.-J. Chem. Commun.  2008,  1437 
  • 6a Widdowson DA. Wilhelm R. Chem. Commun.  1999,  2211 
  • 6b Baleizão C. Corma A. García H. Leyva A. J. Org. Chem.  2004,  69:  439 
    Search in Google Scholar
  • 6c Schaub T. Backes M. Radius U. J. Am. Chem. Soc.  2006,  128:  15964 
    Search in Google Scholar
  • 7a Ishii Y. Chatani N. Yorimitsu S. Murai S. Chem. Lett.  1998,  157 
  • 7b Cahiez G. Lepifre F. Ramiandrasoa P. Synthesis  1999,  2138 
  • 7c Kim YM. Yu S. J. Am. Chem. Soc.  2003,  125:  1696 
    Search in Google Scholar
  • 7d Widdowson DA. Wilhelm R. Chem. Commun.  2003,  578 
  • 7e Mikami K. Miyamoto T. Hatano M. Chem. Commun.  2004,  2082 
  • 7f Bahmanyar S. Borer BC. Kim YM. Kurtz DM. Yu S. Org. Lett.  2005,  7:  1011 
    Search in Google Scholar
  • 7g Saeki T. Takashima Y. Tamao K. Synlett  2005,  1771 
  • 7h Wang T. Alfonso BJ. Love JA. Org. Lett.  2007,  9:  5629 
    Search in Google Scholar
  • Site-selective cross-coupling of polyfluoropyridines:
  • 7i Braun T. Perutz RN. Sladek MI. Chem. Commun.  2001,  2254 
  • Preferential reactions of an alkyl fluoride over an alkyl chloride were observed in nickel- or copper-catalyzed cross-coupling with Grignard reagents:
  • 8a Terao J. Ikumi A. Kuniyasu H. Kambe N. J. Am. Chem. Soc.  2003,  125:  5646 
    Search in Google Scholar
  • 8b

    For transition-metal-catalyzed cross-coupling at a fluoro group in the presence of a bromo group, see ref. 7h.

  • 9 Ishikawa S. Manabe K. Chem. Lett.  2007,  36:  1302 
    CrossrefSearch in Google Scholar
  • 10 Netherton MR. Fu GC. Org. Lett.  2001,  3:  4295 
    CrossrefPubMedSearch in Google Scholar
  • 11 Goerlich JR. Fischer A. Jonas PG. Schmutzler R. Z. Naturforsch., B: Phys. Sci.  1994,  49:  801 
    Search in Google Scholar
  • 12 Arduengo AJ. Krafczyk R. Schmutzler R. Craig HA. Goerlich JR. Marshall WJ. Unverzagt M. Tetrahedron  1999,  55:  14523 
    Search in Google Scholar
  • 14 Haga N. Takayanagi H. J. Org. Chem.  1996,  61:  735 
    CrossrefSearch in Google Scholar
  • 15 Shimizu H. Manabe K. Tetrahedron Lett.  2006,  47:  5927 
    CrossrefSearch in Google Scholar
  • 16 Lourak M. Vanderesse R. Fort Y. Caubère P. J. Org. Chem.  1989,  54:  4844 
    CrossrefSearch in Google Scholar
  • 17 Ksander GM, Meredith E, Monovich LG, Papillon J, Firooznia F, and Hu Q.-Y. inventors; WO  2007024945.  ; Chem. Abstr. 2007, 146, 295923
  • 18 Jendralla H. Chen L.-J. Synthesis  1990,  827 
    Thieme Connect
13

Saeki and Tamao et al. assumed a chelating effect of
o-difluorobenzene in their cross-coupling with a Grignard reagent.7g The ortho selectivity in our system may be attributable to a similar chelating effect.