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A. Gogoi et al. / Tetrahedron Letters xxx (2013) xxx–xxx
Table 6
Reaction scope with different arylboronic acid and aryl imidazolea
N
Cu-Complex C-1 (5 mol%)
R1
N
(HO)2B
N
K2CO3 (2 equiv), i-PrOH (1.5 mL)
R2
R2
N
H
rt, air
R1
N
N
N
Cl
N
OCH3
N
F
N
N
N
6a, 94%, 10 hr
6d, 81%, 13 hr
6c, 87%, 12 hr
6b, 88%, 18 hr
N
OCH3
N
N
N
N
N
N
N
6h, 84%, 19 hr
6g, 81%, 24 hr
6f, 79%, 21 hr
6e, 75%, 24 hr
N
N
OCH3
N
N
N
N
OCH3
6i, 86%, 18 hr
6k, 85%, 17 hr
6j, 88%, 24 hr
N
N
Cl
N
N
N
N
F
6l, 76%, 24 hr
6n,b 63%, 24 hr
6m, 74%, 24 hr
a Reaction conditions: aryl imidazole (0.5 mmol), arylboronic acid (1 mmol), K2CO3 (1 mmol), C-1 (5 mol %), i-PrOH (1.5 mL), ca. 28 °C unless otherwise noted. All the yields
are of isolated product.
b
Reaction did not complete after 24 h.
low yields of N-phenyl imidazole (Table 4, entries 10–17). We also
examined the effectiveness of other two copper complexes C-2 and
C-3 for the N-arylation of imidazoles. However poor yields of the
product were detected compared to C-1 (Table 4, entries 4 vs 18
&19).
scope make this protocol an attractive alternative for the existing
Chan–Lam cross coupling reaction.
Acknowledgments
During the process of optimization we also tested the amount of
arylboronic acid. Maximum yield was obtained with two equiva-
lents of phenyl boronic acid (Table 4 entries 19 & 20). No signifi-
cant yield of isolated N-aryl imidazole was observed in the
in situ application of Cu(OAc)2ꢀH2O and salen ligand L-1 (Table 4,
entry 21).
We gratefully thank UGC, New Delhi for financial support (No.
41-254/2012 (SR). A.G. thanks the Department of Science and
Technology, New Delhi for an INSPIRE research fellowship. G.S.
thanks UGC for UGC-RFSMS fellowship. A.D. acknowledges DST,
New Delhi for financial support.
In order to study the effect of different bases for this cross cou-
pling reaction we have examined the reaction between imidazole
(0.5 mmol) and phenyl boronic acid (1 mmol) in iso-propanol
(1.5 mL) at room temperature. A wide range of inorganic and or-
ganic bases were tested. The maximum reaction efficiency was ob-
served with two equivalents of K2CO3 (Table 5, entries 2 vs 1 and
3–10).
References and notes
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Pergamon Press: New York, 1991; Vol. 8, (b)Pigment Handbook; Lewis, P. A., Ed.;
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Next, the scope of this protocol with respect to substituted aryl-
boronic acids and imidazoles was examined with 5 mol % of Cu–
complex C-1, K2CO3 as base in iso-propanol at room temperature.29
The results obtained are summarized in Table 6. Arylboronic acids
having electron donating and electron withdrawing groups at the
para-position furnished excellent yields of the isolated N-arylated
product (Table 6, entries 6a–6e). The substitution in the imidazole
ring has a slight effect in the efficiencies. For example, 2-methyl
and 4-methyl imidazoles take longer reaction times (Table 6, en-
tries 6f–6i). In addition, the protocol was also suitable for the N-
arylation of benzimidazole (Table 6, entries 6j–6n).
In conclusion, we have developed a mild and efficient protocol
for the Chan–Lam cross coupling reaction of anilines with arylbo-
ronic acid in water under aerobic conditions. In addition, the pro-
tocol can be utilized for the N-arylation of imidazoles in iso-
propanol. Both the methods have versatile synthetic utility. Mild
reaction conditions, use of non toxic solvent, and broad substrate
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