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N. Joubert et al. / Tetrahedron Letters 51 (2010) 2994–2997
methodologies involving boronic acids.23 N-Arylation of imidazole
Table 3
Arylation of N-heterocyles
with para-, meta- or ortho-substituted phenylborates 4b–g was
studied (entries 4–8 and 10). With methoxy-substituted aryl
groups (entries 5–7), the reaction was favoured when the substitu-
ent was in para position (4d), leading to the 40-methoxyphenylim-
idazole 2g in an excellent 80% yield (entry 6). For the meta -
substituted borate, with lowered electron donating effect, the de-
sired compounds 2f was isolated in 68% yield (entry 5). For the
ortho-substituted aryl group for which the steric hindrance is lim-
iting, no N-arylated compound was isolated, and only the corre-
sponding boronic acid was recovered.
No clear electronic effects were observed regarding the electron
demand of the aryl substitution and N-arylation occurred smoothly
giving 2e–i in decent to excellent yields (entries 4–8 and 10). The
only limitation was found using trifluoro(4-nitrophenyl)borate 4g,
which gave only the homocoupling product (4,40-dinitrobiphenyl)
in 79% yield39–41 (entry 10). Finally, the reaction of 4-methoxyphe-
nylborate on pyrazole, benzimidazole and indazole afforded the
expected N-arylated products 2m, 2n and 2o in satisfying yields
ranging from 73% to 89% (entries 12–14). N-Arylation of 2-ethyl-
4-methylimidazole 1f with 4d gave the N-arylated compound 2p
in a moderate 45% yield, while reaction with dimethylpyrazole
1c afforded the desired compound 2q in 62% yield. Further studies
into the scope of the reaction, specially using more complex het-
erocycles are currently underway and will be reported in due
course.
Entry
1
ArBF3K
ArN–H
Product
Yield (%)
BF3K
N
N
2b
78
72
H
4a
1b
N
N
2
3
4a
4a
2c
H
1c
N
N
H
2d
59
1d
N
BF3K
N
H
1a
4
5
2e
2f
77
68
4b
BF3K
In summary, we have developed a mild, efficient methodology
for the N-arylation of various nitrogen heterocycles with tri-
fluoro(organo)borates, using inexpensive commercially available
copper as a catalyst, in water under air atmosphere. This simple
method could be adapted for the synthesis of more advanced
intermediates.
1a
MeO
MeO
4c
BF3K
6
7
1a
1a
2g
2h
80
64
4d
4e
4f
F3C
Cl
BF3K
BF3K
Acknowledgement
Both E.B. and N.J. thank gratefully the Region Bretagne for finan-
cial support (ICPOLOC and CATAPROTID grant, respectively).
8
9
1a
1c
2i
2j
66
41
4e
Supplementary data
O2N
BF3K
10
1a
2k
0
Supplementary data associated with this article can be found, in
4g
11
12
13
4b
4d
4d
1b
1b
1d
2l
2m
2n
92
89
89
References and notes
N
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73a (53/47)
N
H
14
4d
2o
1e
N
N
H
15
16
4d
4d
2p
2q
45
62
1f
1c
a
Isolated as mixture of isomers.
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tween imidazole 1a and potassium trifluorophenylborate 4a, we
evaluated the reactivity of various N–H heterocycles and potas-
sium aryltrifluoroborates (Table 3). N-Arylation of pyrazoles (en-
tries 1 and 2) and benzimidazole (entry 3) with potassium
trifluorophenylborate 1a afforded the desired compounds 2b–d
in good yields from 59% to 78%. N-Arylation using aryltrifluorobo-
rates in water appears more effective than the previously reported