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Synthesis 2010(11): 1865-1882  
DOI: 10.1055/s-0029-1218745
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart ˙ New York

Trifluoromethylation of Organic Compounds and Related Reactions

Kazuyuki Sato, Atsushi Tarui, Masaaki Omote, Akira Ando*, Itsumaro Kumadaki*
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
Fax: +81(72)8507020; e-Mail: aando@pharm.setsunan.ac.jp; e-Mail: kumadaki@ba2.so-net.ne.jp;
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Publication History

Received 1 March 2010
Publication Date:
23 April 2010 (online)

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Abstract

This review concentrates on trifluoromethylation and related reactions from the authors’ group. Mainly, our new rhodium complex catalyzed synthesis of trifluoromethyl and other fluorine compounds will be discussed. However, initially we would like to discuss the origins and development of this reaction. Thus, trifluoromethylation of aromatic and aliphatic halides with trifluoromethyl iodide in the presence copper powder will be discussed first, and then the application of this copper-mediated reaction to ethyl bromodifluoroacetate for the synthesis of difluoromethylene compounds will be presented. The investigation of the mechanism of this reaction led us to the Michael addition of the (ethoxycarbonyl)difluoromethyl group to α,β-unsaturated carbonyl compounds. To improve this reaction, we examined the rhodium-catalyzed Michael reaction, and found that the fluorine substituent was introduced surprisingly not to the β-position but to the α-position. This reaction could be used to introduce other fluoroalkyl groups, including­ the trifluoromethyl group, to the α-position of almost all Michael acceptors. Furthermore, this reaction was developed for the introduction of the trifluoromethyl or other fluoroalkyl groups into the α-position of ketones or carboxylic acid derivatives through silyl­ enol ethers or ketene silyl acetals.

1 Introduction

2 Trifluoromethylation Using Trifluoromethyl Iodide and Copper Powder

3 Copper-Mediated Reactions of Ethyl Bromodifluoroacetate

3.1 Coupling Reactions with Alkenyl and Aryl Iodides

3.2 Michael Reaction

4 Rhodium-Catalyzed Reactions

4.1 Attempted Michael-Type Reaction, and a New Type of Reaction­: Introduction of a Fluorine Substituent to the
α-Position of a Carbonyl Group

4.2 Extension of the α-Substitution Reaction to Trifluoro­methylation

4.3 Other α-Perfluoroalkylations of α,β-Unsaturated Ketones

5 Perfluoroalkylation of Ketones via Silyl Enol Ethers

5.1 Reaction of Long-Chain Perfluoroalkyl Iodides

5.2 Improvement of the Reaction for Trifluoromethylation with Diethylzinc

5.3 α-Trifluoromethylation of Other Carbonyl Compounds

5.4 α-Perfluoroalkylation of Other Carbonyl Compounds

6 Conclusion

Key words

trifluoromethylation - perfluoroalkylation - trifluoromethyl iodide - perfluoroalkyl iodide - α,β-unsaturated ketones - silyl enol ethers - rhodium complexes - diethylzinc

    References

  • 1a Smart BE. Chem. Rev.  1996,  96:  1555 
    Google Scholar
  • 1b Resnati G. Soloshonok VA. Tetrahedron  1996,  52:  1 
    Google Scholar
  • 1c Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications   Filler R. Kobayashi Y. Yagupolskii LM. Elsevier; Amsterdam: 1993. 
    Google Scholar
  • 1d Welch JT. Tetrahedron  1987,  43:  3123 
    Google Scholar
  • 2a Kobayashi Y. Kumadaki I. Tetrahedron Lett.  1969,  10:  4095 
    Google Scholar
  • 2b Kobayashi Y. Kumadaki I. Sato S. Hara N. Chikami E. Chem. Pharm. Bull.  1970,  18:  2334 
    Google Scholar
  • 3 Kobayashi Y. Yamamoto K. Kumadaki I. Tetrahedron Lett.  1979,  20:  4071 
    CrossrefGoogle Scholar
  • 4 Kobayashi Y. Yamamoto K. Asai T. Nakano M. Kumadaki I. J. Chem. Soc., Perkin Trans. 1  1980,  2755 
    CrossrefGoogle Scholar
  • 5 Sato K. Kawata R. Ama F. Omote M. Ando A. Kumadaki I. Chem. Pharm. Bull.  1999,  47:  1013 
    CrossrefGoogle Scholar
  • 6 Sato K. Tamura M. Tamoto K. Omote M. Ando A. Kumadaki I. Chem. Pharm. Bull.  2000,  48:  1023 
    CrossrefPubMedGoogle Scholar
  • 7 Sato K. Tarui A. Kita T. Ishida Y. Tamura H. Omote M. Ando A. Kumadaki I. Tetrahedron Lett.  2004,  45:  5735 
    CrossrefGoogle Scholar
  • 8a Sato K. Omote M. Ando A. Kumadaki I. Org. Synth.  2006,  83:  177 
    Google Scholar
  • 8b Sato K. Omote M. Ando A. Kumadaki I. Org. Lett.  2004,  6:  4359 
    Google Scholar
  • 9 Sato K. Ishida Y. Murata E. Oida Y. Mori Y. Okawa M. Iwase K. Tarui A. Omote M. Kumadaki I. Ando A. Tetrahedron  2007,  63:  12735 
    CrossrefGoogle Scholar
  • 10 Sato K. Higashinagata M. Yuki T. Tarui A. Omote M. Kumadaki I. Ando A. J. Fluorine Chem.  2008,  129:  51 
    CrossrefGoogle Scholar
  • 11a Sato K. Yuki T. Yamaguchi R. Hamano T. Tarui A. Omote M. Kumadaki I. Ando A. J. Org. Chem.  2009,  74:  3815 
    Google Scholar
  • 11b Sato K. Yamazoe S. Akashi Y. Hamano T. Miyamoto A. Sugiyama S. Tarui A. Omote M. Kumadaki I. Ando A. J. Fluorine Chem.  2010,  131:  86 
    Google Scholar
  • 12 Kobayashi Y. Kumadaki I. Ohsawa A. Yamada T. Chem. Pharm. Bull.  1972,  20:  1839 
    Google Scholar
  • 13 Kobayashi Y. Kumadaki I. Yamamoto K. J. Chem. Soc., Chem. Commun.  1977,  536 
    CrossrefGoogle Scholar
  • 14 Burton DJ. Wiemers DM. J. Am. Chem. Soc.  1985,  107:  5014 
    CrossrefGoogle Scholar
  • 15 Kitagawa O. Miura A. Kobayashi Y. Taguchi T. Chem. Lett.  1990,  1011 
    CrossrefGoogle Scholar
  • 16 Sato K. Nakazato S. Enko H. Tsujita H. Fujita K. Yamamoto T. Omote M. Ando A. Kumadaki I. J. Fluorine Chem.  2003,  121:  105 
    CrossrefGoogle Scholar
  • For example, Honda reported the rhodium-catalyzed Michael reaction of unfluorinated ethyl bromoacetate:
  • 17a Honda T. Wakabayashi H. Kanai K. Chem. Pharm. Bull.  2002,  50:  307 
    Google Scholar
  • 17b Kanai K. Wakabayashi H. Honda T. Org. Lett.  2000,  2:  2549 
    Google Scholar
  • Metal-catalyzed 1,4-addition of carbonyl compound was reported:
  • 18a Fagnou K. Lautens M. Chem. Rev.  2003,  103:  169 
    Google Scholar
  • 18b Hayashi T. Synlett  2001,  879 
    Google Scholar
  • 19 Prakash GSK. Krishnamurti R. Olah GA. J. Am. Chem. Soc.  1989,  111:  393 
    CrossrefGoogle Scholar
  • 20 Wang Z. Lu X. Tetrahedron  1995,  51:  2639 
    CrossrefGoogle Scholar
  • 21a Tsuji J. Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis   John Wiley & Sons; Chichester: 2002. 
    Google Scholar
  • 21b Transition Metals for Organic Synthesis   Beller M. Bolm C. VCH; Weinheim: 1998. 
    Google Scholar
  • 22a Ma J.-A. Cahard D. J. Org. Chem.  2003,  68:  8726 
    Google Scholar
  • 22b Umemoto T. Adachi K. J. Org. Chem.  1994,  59:  5692 
    Google Scholar
  • 23a Crusiani G. Margaretha P. J. Fluorine Chem.  1987,  37:  95 
    Google Scholar
  • 23b Kitazume T. Ishikawa N. J. Am. Chem. Soc.  1985,  107:  5186 
    Google Scholar
  • 24 Sato K. Yuki T. Tarui A. Omote M. Kumadaki I. Ando A. Tetrahedron Lett.  2008,  49:  3558 
    CrossrefGoogle Scholar
  • 25a Itoh Y. Mikami K. Org. Lett.  2005,  7:  649 
    Google Scholar
  • 25b Itoh Y. Mikami K. Org. Lett.  2005,  7:  4883 
    Google Scholar
  • 25c Itoh Y. Mikami K. Tetrahedron  2006,  62:  7199 
    Google Scholar
  • 25d Mikami K. Tomita Y. Ichikawa Y. Amikura K. Itoh Y. Org. Lett.  2006,  8:  4671 
    Google Scholar
  • 25e Itoh Y. Houk KN. Mikami K. J. Org. Chem.  2006,  71:  8918 
    Google Scholar
  • 26 Chen Q.-Y. Yang Z.-Y. Zhao C.-X. Qiu Z.-M. J. Chem. Soc., Perkin Trans. 1  1988,  563 
    CrossrefGoogle Scholar
  • 27 Tarui A. Ozaki D. Nakajima N. Yokota Y. Sokeirik YS. Sato K. Omote M. Kumadaki I. Ando A. Tetrahedron Lett.  2008,  49:  3839 ; and references therein
    CrossrefGoogle Scholar
  • 28 Sato K. Yamazoe S. Yamamoto R. Ohata S. Tarui A. Omote M. Kumadaki I. Ando A. Org. Lett.  2008,  10:  2405 
    CrossrefGoogle Scholar