conditions. As illustrated in Scheme 1, these strategies can
be classified into the following: (1) An aryl halide coupling
of aryl- and alkenylboronic acids in the presence of Togni’s
reagent.
ꢀ
with a nucleophilic “CF ” reagent with a catalytic amount
3
5
of copper or palladium catalyst. For example, Amii re-
ported the first copper-catalyzed trifluoromethylation of
electron-poor aryl iodides with RuppertꢀPrakash’s reagent
Table 1. CuI-Catalyzed Trifluoromethylation of 4-Biphenyl-
boronic Acid with Togni’s Reagent in the Presence of Different
Ligands
4
,6
a
CF SiEt in the presence of CuI/1,10-phenanthroline. In
3
3
a landmark report, Buchwald reported a Pd-catalyzed
trifluoromethylation of aryl chlorides by use of judiciously
7
selected ancillary ligands. (2) An arylboronic acid coupling
ꢀ
with a nucleophilic “CF ” reagent in the presence of a
3
stoichiometric amount of copper catalyst under oxidation
8
9
conditions. Qing and Buchwald independently reported
such a process using an oxidant such as Ag CO or O ,
respectively. (3) An arene coupling with an electrophilic
2
3
2
þ
10
“
CF ” reagent through CꢀH activation. Yu reported
3
a straightforward protocol for direct trifluoromethylation
of arenes using Umemoto’s reagent in the presence of
11
Pd(OAc)2. Inspired by these studies, we envisioned an
alternative strategy for the preparation of trifluoromethyl
arenes by coupling of a nucleophilic [ArCu] species gener-
ated from arylboronic acid with a copper salt and an
þ
12
electrophilic [CF ] reagent (Scheme 1, eq 4). Herein,
3
we disclose the first copper-catalyzed trifluoromethylation
(
3) (a) Kobayashi, Y.; Kumadaki, I. Tetrahedron Lett. 1969, 47, 4095.
(b) McLaughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25, 5921. (c)
Wiemers, D. M.; Burton, D. J. J. Am. Chem. Soc. 1986, 108, 832. (d)
Carr, G. E.; Chambers, R. D.; Holmes, T. F.; Parker, D. G. J. Chem.
Soc., Perkin Trans. I 1988, 921. (e) Suzuki, H.; Yoshida, Y.; Osuka, A.
Chem. Lett. 1982, 135. (f) Urata, H.; Fuchikami, T. Tetrahedron Lett.
a
Reaction conditions: 4-biphenylboronic acid (0.2 mmol), Togni’s
reagent (0.2 mmol), CuI (5 mol %), ligand (10 mol %), and K
1991, 32, 91. (g) Chen, Q.-Y.; Wu, S.-W. Chem. Commun. 1989, 705. (h)
Su, D.-B.; Duan, J.-X.; Chen, Q.-Y. Tetrahedron Lett. 1991, 32, 7689. (i)
Chen, Q.-Y.; Duan, J.-X. Chem. Commun. 1993, 1389. (j) Dubinina,
G. G.; Furutachi, H.; Vicic, D. A. J. Am. Chem. Soc. 2008, 130, 8600. (k)
Zhang, C.-P.; Wang, Z.-L.; Chen, Q.-Y.; Zhang, C.-T.; Gu, Y.-C.; Xiao,
J.-C. Angew. Chem., Int. Ed. 2011, 50, 1896. (l) Morimoto, H.; Tsubogo,
T.; Litvinas, N. D.; Hartwig, J. F. Angew. Chem. Int. Ed. doi: 10.1002/
anie.201100633.
2
3
CO (0.4
b
mmol) in diglyme (1.0 mL) at 35 °C for 14 h. Yields were determined by
F NMR analysis of the crude reaction mixture with an internal
1
9
c
standard. 5 mol % of L1 was used.
The trifluoromethylation of 4-biphenylboronic acid
13,14
with Togni’s reagent
(
4) Oishi, M.; Kondo, H.; Amii, H. Chem. Commun. 2009, 1909.
5) Lundgren, R. J.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49,
was chosen at the start of our
(
322.
investigation as a model reaction. We first examined CuI
and 1,10-phenanthroline L1 as a potential catalyst for
reaction of 4-biphenyl boronic acid and Togni’s reagent
in the presence of 2.0 equiv of K CO asthe base indiglyme
9
(
6) Knauber, T.; Arikan, F.; G., R.; Goossen, L. J. Chem.;Eur. J.
2011, 17, 2689.
(
7) (a) Cho, E. J.; Senecal, T. D.; Kinzel, T.; Zhang, Y.; Watson,
D. A.; Buchwald, S. L. Science 2010, 328, 1679. (b) Grushin, V. V.;
Marshall, W. J. J. Am. Chem. Soc. 2006, 128, 4632. (c) Grushin, V. V.;
Marshall, W. J. J. Am. Chem. Soc. 2006, 128, 12644.
2
3
(
Table 1). The reaction occurred smoothly to give the
1
9
(
8) (a) Chu, L.; Qing, F.-L. Org. Lett. 2010, 12, 5060. (b) Chu, L.;
Qing, F.-L. J. Am. Chem. Soc. 2010, 132, 7262.
9) Senecal, T. D.; Parsons, A. T.; Buchwald, S. L. J. Org. Chem.
011, 76, 1174.
10) Ball, N. D.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc.
010, 132, 2878.
desired product in 90% yield as determined by F NMR
spectroscopy with an internal standard (Table 1, entry 3).
Various copper precursors were evaluated to understand
the effect of the precursor on the reaction. Copper catalyst
was essential to the reaction efficiency as the reaction
occurred in 36% yield in the presence of 5 mol % of CuI
but no conversion was observed in the absence of CuI
(Table 1, entries 1 and 2). Using other copper precursors
such as CuCl, Cu(OAc) , or Cu(OTf) led to much lower
(
2
2
(
(
11) Wang,X.;Truesdale,L.;Yu,J.-Q.J. Am. Chem. Soc. 2010,132, 3648.
(12) For selected metal-mediated functionalization of arylboronic
acids, see: (a) Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem.,
Int. Ed. 2011, 50, 519. (b) Liskey, C. W.; Liao, X.; Hartwig, J. F. J. Am.
Chem. Soc. 2010, 132, 11389. (c) Murphy, J. M.; Liao, X.; Hartwig, J. F.
J. Am. Chem. Soc. 2007, 129, 15434. (d) Kang, S.; Lee, H.; Jang, S.; Ho,
P. J. Org. Chem. 1996, 61, 4720. (e) Kang, S.; Yamaguchi, T.; Kim, T.;
Ho, P. J. Org. Chem. 1996, 61, 9082. (f) Kang, S.; Lee, H.; King, J.; Choi,
S. Tetrahedron Lett. 1996, 37, 3723.
2
2
yields (Table 1, entries 5, 7, and 8). Using CuBr resulted in
comparableyield. The ratioofmetal/ligand alsoinfluenced
the conversion of the reaction. The best result was ob-
served with a 1/2 ratio of CuI/L1, while a much lower 33%
yield of the product was observed with a 1/1 ratio of CuI/
L1 (Table 1, entry 4). We then further investigated whether
the yield could be improved by adding other chelating
amine ligands. Reactions with hindered 2,9-dimethyl-1,
(13) For recent reviews on applications of hypervalent iodine see: (a)
Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 109, 5299. (b) Brand,
J. P.; Gonz ꢀa lez, D. F.; Nicolai, S.; Waser, J. Chem. Commun. 2011, 47,
102.
(14) (a) Eisenberger, P.; Gischig, S.; Togni, A. Chem.;Eur. J. 2006,
2, 2579. (b) Niedermann, K.; Fr u€ h, N.; Vinogradova, E.; Wiehn, M. S.;
1
Moreno, A.; Togni, A. Angew. Chem., Int. Ed. 2011, 50, 1059. (c) Koller,
R.; Stanek, K.; Stolz, D.; Aardoom, R.; Niedermann, K.; Togni, A.
Angew. Chem. 2009, 121, 4396.
Org. Lett., Vol. 13, No. 9, 2011
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