Aromatic trifluoromethylation catalytic in copper

Article abstract of DOI:10.1039/b823249k

Cu(i)-diamine complexes were found to catalyse the trifluoromethylation of aryl iodides. In the presence of a small amount of CuX (X = Cl, Br, I) and 1,10-phenanthroline (phen), the cross-coupling reactions of iodoarenes with trifluoromethylsilanes proceeded smoothly to afford trifluoromethylated aromatics in good yields.

Full text of DOI:10.1039/b823249k

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Aromatic trifluoromethylation catalytic in copperw
Masahiro Oishi, Hideaki Kondo and Hideki Amii*
Received (in Cambridge, UK) 24th December 2008, Accepted 30th January 2009
First published as an Advance Article on the web 23rd February 2009
DOI: 10.1039/b823249k
Cu(I)-diamine complexes were found to catalyse the trifluoro-
methylation of aryl iodides. In the presence of a small amount of
CuX (X = Cl, Br, I) and 1,10-phenanthroline (phen), the cross-
coupling reactions of iodoarenes with trifluoromethylsilanes
proceeded smoothly to afford trifluoromethylated aromatics in
good yields.
The propitious candidate for aromatic trifluoromethylation
promoted by a small amount of copper is cross-coupling of
7
–9
aryl iodides with fluoroalkyl silanes. Originally, Urata and
Fuchikami reported the CuI-mediated cross-coupling proto-
cols using CF SiEt , C F SiMe , and C F SiMe as conveni-
3
3
2
5
3
3
7
3
7
ent fluoroalkyl sources under mild reaction conditions.
In spite of their operational simplicity, the singular, but
significant drawback of the protocols is the loading of CuI
(1–1.5 equiv.) to complete the desired reactions. The cross-
coupling of aryl iodides 1 with trifluoromethyl silane 2 can be
explained by assuming the pathway pictured in Scheme 3.
The cross-coupling reaction of organometallic reagents with
aromatic halides in the presence of group 8–11 metal catalysts,
notably nickel and palladium complexes, is the method of
choice for wide range of aromatic C–C, C–N, C–O, C–S, C–P,
1
or C–M bond-forming process. Selective introduction of
trifluoromethyl groups into aromatic compounds is of great
importance in the medicinal, agricultural, and material
3 3
First, a fluoride ion reacts with CF SiEt (2) to give a
1
0
trifluoromethyl anion species (4), which readily undergoes
generation of trifluoromethylcopper (5) (eqn (1a)) in
2
,3
sciences.
versatile methods to construct trifluoromethylated aromatics.
Fluoroalkyl cross-coupling is one of the most
4
3
Scheme 3). Next, s-bond metathesis between CF Cu (5) and
Ar–I (1) yields trifluoromethyl arenes 3 and CuI (eqn (2a)).
The regenerated CuI in the second step would be reused to
,5
However, the progress of fluoroalkyl cross-coupling reactions
has been much slower than that of general (non-fluorinated)
cross-coupling reactions. Among aromatic trifluoromethyl-
ation reactions, the most promise has been demonstrated by
form CF Cu (5) in the first step again. However, the reaction
3
rate of the first step leading to 4 seems to be much higher than
that of second step affording 3 and CuI. Due to the sluggish
regeneration of CuI in the second step, the net transformation
cannot supply sufficient amount of CuI which reacts with
trifluoromethyl anion 4 before its decomposition. This is the
reason why a stoichiometric amount of CuI is needed for the
cross-coupling process. Actually, Urata and Fuchikami
reported that the use of a decreased amount (0.5 equiv.) of
CuI resulted in the formation of the desired products 3 in less
6
–9
the use of copper (Scheme 1).
7a
Scheme 1
than 50% yields.
Despite such synthetic utility, stoichiometric (sometimes,
excess) amounts of copper reagents are required to complete
these cross-coupling reactions. For the development of new
practical and environmentally benign processes, it is desirable
to reduce the quantity of heavy metal reagents employed in these
transformations. Herein, we disclose an efficient procedure of
aromatic trifluoromethylation using a diamine ligand, which
makes possible a reaction using catalytic copper (Scheme 2).
Scheme 2
Department of Chemistry, Graduate School of Science,
Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
E-mail: amii@kobe-u.ac.jp; Fax: +81-78-803-5799;
Tel: +81-78-803-5799
w Electronic supplementary information (ESI) available: Experimental
and NMR data. See DOI: 10.1039/b823249k
Scheme 3
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To overcome this shortcoming, we conceived a strategy to
utilize copper (I)-diamine complexes 6 for the catalytic version
of aromatic trifluoromethylation (eqn (1b) and (2b) in
Scheme 3). Diamine ligands in trifluoromethylated complexes
Table 2
7
would increase electron density at the metal centers by
coordination and improve the nucleophilicity of the CF3
moieties in 7 in the second step (eqn (2b)). Moreover, biden-
tate ligands are able to stabilize the soluble Cu(I) complexes by
chelation. Thus, the use of diamine ligands is expected to
accelerate the second step to regenerate sufficient amount of
reusable complexes 6. By this means, aromatic trifluoromethyl-
ation catalytic in copper would be accomplished.
ab
Entry Iodoarene 1
Product 3
%Yield of 3a
1
90 (70)
c
2
3
54
16
d
Table 1
4
90(63)
80
5
a
Entry
CuX
Ligand
%Yield of 3a
b
e
1
2
3
4
5
Cul
Cul
Cul
CuBr
CuCl
TMEDA
bipy
phen
phen
phen
40
50
90
68
71
6
89
63
c
d
7
8
a
19
NMR yield, which was calculated by F NMR integration of product
b
a relative to the 2,2,2-trifluoroethanol internal standard. N,N,N ,N -
0 0
3
Tetramethylethylenediamine. 2,2 -Bipyridine. 1,10-Phenanthroline.
c
0
d
44
In order to test our proposed methodology, catalytic
0
9
69
0
amounts (10 mol%) of CuI and N,N,N ,N -tetramethylethylene-
diamine (TMEDA) were added to a mixture containing
4
-iodonitrobenzene, triethyl(trifluoromethyl)silane and KF in
DMF/ NMP (entry 1 in Table 1). After 24 h at 60 1C, we were
pleased to obtain 4-(trifluoromethyl)nitrobenzene (3a) in 40%
10
99 (95)
0
NMR yield. The use of 2,2 -bipyridine (bipy) as a diamine
ligand was found to be also effective for the cross-coupling
reaction (entry 2). In particular, when 1,10-phenanthroline
1
1
63
1
phen) was employed as a catalyst ligand, a significant
1
(
a
19
NMR yield, which were calculated by F NMR integration of
increase of the product yield (90% NMR yield, 70% isolated
yield) was observed (entry 3). Utilizing the phenanthroline
ligand, CuBr and CuCl were applicable to the present trifluoro-
methylation to give 3a in 68% and 71% yield, respectively
products 3 relative to the 2,2,2-trifluoroethanol internal standard.
b
c
The values in parentheses indicate the isolated yields of 3. The
reaction was carried out in the presence of CuI (5 mol%) and phen
d
(5 mol%). The reaction was carried out in the presence of CuI
e
(1 mol%) and phen (1 mol%). CF
(
entries 4, 5).
3
SiEt
3
(1.2 eq) and KF
(
1.2 eq) were used.
Representative examples of the formation of trifluoro-
methyl arenes 2 are summarized in Table 2. Using 10 mol%
of the copper(I) complex prepared in situ from CuI and phen in
1
a molar ratio of 1 : 1 worked well for the cross-coupling of
2
butyl group (an electron-donating group) with trifluoro-
methylsilane delivered p-butyl(trifluoromethyl)benzene
aryl iodides 1 with CF SiEt (2) to afford the corresponding
3
2
3
trifluoromethylated arenes 3 (entries 1, 4–11). In each case,
selective aromatic trifluoromethylation was achieved; less than
(3f) in 44% yield (entry 8). Furthermore, heteroaromatic
iodides 1g–i participated in cross-coupling reactions smoothly
to yield the corresponding trifluoromethylated hetero-
aromatics 3g–i. (entries 9–11).
6
h,7
3
% yield of pentafluoroethylated by-product
was observed.
Even at 5 mol% and 1 mol% catalyst loading, 54% and 16%
yields of 3a were observed, respectively (entries 2, 3). Iodo-
benzenes 1a–e endowed with electron-withdrawing groups
on the aryl rings underwent catalytic trifluoromethylation
smoothly to provide the desired cross-coupling products in
high yields (entries 1, 4–7). The reaction of 1f possessing a
In conclusion, we have demonstrated that a small amount of
the CuI–phenanthroline complex engenders the cross-coupling
3 3
reactions of aryl/heteroaryl iodides with CF SiEt to give
trifluoromethylated arenes in moderate to high yield. The
substrate scope of the present methodology is broad and a
1
910 | Chem. Commun., 2009, 1909–1911
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3
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(
j) M. A. Willert-Porada, D. J. Burton and N. C. Baenziger,
Funding from the Ministry of Education, Culture, Sports,
Science and Technology of Japan (Grant-in-Aid for Scientific
Research (B), No. 18350054 and Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Chemistry of Concerto
Catalysis’’, No. 20037050) is gratefully acknowledged.
We would like to thank Prof. Masahiko Hayashi (Kobe
University) for his useful suggestions.
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