ORGANIC
LETTERS
2012
Vol. 14, No. 15
3966–3969
Trifluoromethylation of Propargylic
Halides and Trifluoroacetates Using
(Ph3P)3Cu(CF3) Reagent
,†
ꢀ ꢀ
ꢀ
Tony S. N. Zhao and Kalman J. Szabo*
Department of Organic Chemistry, Stockholm University, SE-106 91 Stockholm,
Sweden
Received June 23, 2012
ABSTRACT
A copper-mediated trifluoromethylation of propargylic halides and trifluoroacetates was performed with high allenyl or propargyl selectivity. The
reaction proceeds smoothly with aliphatic and aromatic substituents bearing either electron-withdrawing or -supplying groups. Preliminary
mechanistic results indicate an ionic mechanism involving nucleophilic transfer of the CF3 group from the Cu complex to the propargylic
substrate.
The development of new methods for the preparation of
trifluoromethylated compounds has become an important
field in organic synthesis, because of the large demand for
structurally diverse species by the pharmaceutical and
agrochemical industries.1 In particular, the late stage
introduction of the CF3 group into aromatic and hetero-
aromatic substrates hasreceiveda lot of recent attention.2,3
Several excellent methods have also been published for the
trifluoromethylation of alkenes, including allylic CꢀH
functionalization based methods.4 However, despite the
importance of functionalized allenes5 and propargylic
compounds, very few methods have been reported for
preparation of CF3-derivatives. Most of the reported
methods are based on the transformation of alkynyl-CF3
compounds.6 To the best of our knowledge, only two
previous reports7 have been published for the late stage
introduction of the CF3 group into propargylic substrates.
One possible reason is that the late stage introduction was
† Home page: http://www.organ.su.se/ks/.
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1943. (d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem.
€
Soc. Rev. 2008, 37, 320. (e) Muller, K.; Faeh, C.; Diederich, F. Science
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49, 9322. (b) Cho, E. J.; Senecal, T. D.; Kinzel, T.; Zhang, Y.; Watson,
D. A.; Buchwald, S. L. Science 2010, 328, 1679. (c) Wang, X.; Truesdale,
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L.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 3648. (d) Hafner, A.; Brase, S.
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H.; Amii, H. Chem. Commun. 2009, 1909.
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(b) Morimoto, H.; Tsubogo, T.; Litvinas, N. D.; Hartwig, J. F. Angew.
Chem., Int. Ed. 2011, 50, 3793. (c) Litvinas, N. D.; Fier, P. S.; Hartwig,
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(4) (a) Janson, P. G.; Ghoneim, I.; Ilchenko, N. O.; Szabo, K. J. Org.
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B.; Liu, Z.-J.; Gong, T.-J.; Liu, L. J. Am. Chem. Soc. 2011, 133, 15300.
(d) Wang, X.; Ye, Y.; Zhang, S.; Feng, J.; Xu, Y.; Zhang, Y.; Wang, J.
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Figure 1. Well-defined, stable nucleophilic CF3 transfer
reagents.
€
Chem., Int. Ed. 2012, 51, 2947. (g) Hafner, A.; Brase, S. Adv. Synth.
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r
10.1021/ol3017287
Published on Web 07/17/2012
2012 American Chemical Society