Trifluoromethylation of Salicyl Aldimines†
Trifluoromethyltrimethylsilane, Me3SiCF3, turned out to be
an especially useful reagent as an equivalent of trifluoromethyl
carbanion for the direct introduction of the CF3 group.4a-c,5 The
reactions using Me3SiCF3 are usually performed in the presence
of Lewis base, and processes of this type are very well
establishedforthetrifluoromethylationofcarbonylcompounds.4a-c,6
At the same time, analogous addition of CF3-carbanion to imines
has a number of limitations associated mainly with low reactivity
of C,N double bond.
Thus, while strongly biased substrates such as azirines,7
imines of perfluorinated ketones,8 or N-tosylated or sulfinylated6b,9
imines can be successfully trifluoromethylated using Me3SiCF3,
imines having an aryl group at nitrogen are markedly less
reactive. In the latter case, the reaction requires employment of
fluoride ion for the activation of Me3SiCF3 and proceeds with
moderate yield.10,11 Reactions of imines bearing an N-alkyl
fragment with Me3SiCF3 are expected to be even more difficult
and, to the best of our knowledge, are not described.
Alexander D. Dilman,*,‡ Dmitry E. Arkhipov,‡
Vitalij V. Levin,‡ Pavel A. Belyakov,‡
Alexander A. Korlyukov,§ Marina I. Struchkova,‡ and
Vladimir A. Tartakovsky‡
N. D. Zelinsky Institute of Organic Chemistry,
119991 Moscow, Leninsky prosp. 47, Russian Federation, and
A. N. NesmeyanoV Institute of Organoelement Compounds,
119991 Moscow, VaViloV str. 28, Russian Federation
ReceiVed August 8, 2007
The studies performed by our group have demonstrated that
the iminium cations serve as good electrophiles for the interac-
tion with fluorinated silanes in the presence of weak Lewis
bases, though these investigations mainly focused on the transfer
of C6F5 group.12,13
In this respect, it seemed reasonable to propose that the
electrophilicity of imines can be increased by complexation with
Lewis acids.14 However, the major problem in this case is that
to activate Me3SiCF3 rather strong Lewis bases such as fluoride,
alkoxide, carbonate, or acetate anions are required (Scheme 1,
path a).15 As a result, given that the activation of both imine
and the silane constitute an equilibrium processes, the Lewis
A method for the nucleophilic trifluoromethylation of salicyl
aldimines, which do not contain an activating group at the
nitrogen atom, has been described. The reaction proceeds
through the initial generation of intramolecular boron
complex followed by interaction with Me3SiCF3 activated
by sodium acetate.
(5) For the first synthesis of Me3SiCF3, see: Ruppert, I.; Schlich, K.;
Volbach, W. Tetrahedron Lett. 1984, 24, 2195.
Organofluorine compounds have gained considerable attention
due to their importance for the pharmaceutical and agrochemical
industries.1 In particular, substances with trifluoromethyl group,
as well as methods for their preparation, have become a subject
of intense investigations in recent years.2-4
(6) For recent comprehensive studies, see: (a) Prakash, G. K. S.; Panja,
C.; Vaghoo, H.; Surampudi, V.; Kultyshev, R.; Mandal, M.; Rasul, G.;
Mathew, T.; Olah, G. A. J. Org. Chem. 2006, 71, 6806. (b) Kawano, Y.;
Kaneko, N.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 2006, 79, 1133.
(7) Felix, C. P.; Khatimi, N.; Laurent, A. Tetrahedron Lett. 1994, 35,
3303.
(8) (a) Banks, R. E.; Besheesh, M.; Lawrence, N. J.; Tovell, D. J. J.
Fluorine Chem. 1999, 97, 79. (b) Petrov, V. A. Tetrahedron Lett. 2000,
41, 6959.
(9) (a) Prakash, G. K. S.; Mandal, M.; Olah, G. A. Synlett 2001, 77. (b)
Kawano, Y.; Fujisawa, H.; Mukaiyama, T. Chem. Lett. 2005, 34, 422. (c)
Kawano, Y.; Mukaiyama, T. Chem. Lett. 2005, 34, 894.
(10) (a) Prakash, G. K. S.; Mogi, R.; Olah, G. A. Org. Lett. 2006, 8,
3589. (b) Blazejewski, J.-C.; Anselmi, E.; Wilmshurst, M. Tetrahedron Lett.
1999, 40, 5475.
(11) Nitrones represent another class of substrates with activated C,N
double bond, which can be trifluoromethylated using t-BuOK; see: Nelson,
D. W.; Owens, J.; Hiraldo, D. J. Org. Chem. 2001, 66, 2572.
(12) (a) Dilman, A. D.; Belyakov, P. A.; Korlyukov, A. A.; Struchkova,
M. I.; Tartakovsky, V. A. Org. Lett. 2005, 7, 2913. (b) Dilman, A. D.;
Levin, V. V.; Karni, M.; Apeloig, Y. J. Org. Chem. 2006, 71, 7214. (c)
Dilman, A. D.; Levin, V. V.; Belyakov, P. A.; Struchkova, M. I.;
Tartakovsky, V. A. Synthesis 2006, 447. (d) Levin, V. V.; Dilman, A. D.;
Belyakov, P. A.; Korlyukov, A. A.; Struchkova, M. I.; Antipin, M. Y.;
Tartakovsky, V. A. Synthesis 2006, 489. (e) Dilman, A. D.; Arkhipov, D.
E.; Belyakov, P. A.; Struchkova, M. I.; Tartakovsky, V. A. Russ. Chem.
Bull. 2006, 55, 517. (f) Levin, V. V.; Dilman, A. D.; Belyakov, P. A.;
Korlyukov, A. A.; Struchkova, M. I.; Tartakovsky, V. A. MendeleeV
Commun., 2007, 105. (g) Dilman, A. D.; Gorokhov, V. V.; Belyakov, P.
A.; Struchkova, M. I.; Tartakovsky, V. A. Tetrahedron Lett. 2006, 47, 6217.
(13) In a recent contribution from Makosza and co-workers, pyridinium
salts were shown to be active electrophiles for the interaction with Me3-
SiCF3 activated by KF/Ph3SnF; see: Loska, R.; Majcher, M.; Makosza,
M. J. Org. Chem. 2007, 72, 5574.
† This paper is dedicated to Professor Herbert Mayr on the occasion of his
60th birthday.
‡ N. D. Zelinsky Institute of Organic Chemistry.
§ A. N. Nesmeyanov Institute of Organoelement Compounds.
(1) (a) Dolbier, W. R. J. Fluorine Chem. 2005, 126, 157. (b) Fluorine
in Bioorganic Chemistry; Welch, C. T., Eswarakrishnan, S., Eds.; John
Wiley & Sons: New York 1991. (c) Hiyama, T. Organofluorine Com-
pounds: Chemistry and Applications; Springer, Berlin, 2000. (d) Uneyama,
K. Organofluorine Chemistry; Blackwell Publishing: Oxford, UK, 2006.
(2) Radical trifluoromethylation: (a) Gagosz, F.; Zard, S. Z. Org. Lett.
2003, 5, 2655. (b) Itoh, Y.; Houk, K. N.; Mikami, K. J. Org. Chem. 2006,
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10.1021/jo701734d CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/02/2007
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J. Org. Chem. 2007, 72, 8604-8607