Copper quinolate: A simple and efficient catalytic complex for coupling reactions

Article abstract of DOI:10.1002/aoc.5303

We describe an effective and novel method to prepare N-aryl imidazoles via the copper quinolate-catalyzed N-arylation of aryl halides and imidazoles. A wide range of products were obtained in moderate to excellent yields under the optimal reaction conditions. Applying standard conditions, the model reaction could be performed on a gram scale. This method also presents a new avenue to the “click” reaction of terminal alkynes, benzyl bromide, and sodium azide and to the construction of C–C bonds by homocoupling of phenylboronic acid or phenylacetylene derivatives with the aid of copper quinolate.

Full text of DOI:10.1002/aoc.5303

Received: 10 August 2019
DOI: 10.1002/aoc.5303
Revised: 17 September 2019
Accepted: 18 September 2019
F U L L P A P E R
Copper quinolate: A simple and efficient catalytic complex
for coupling reactions
1
2
3
Fengtian Wu
| Huiqin Li | Jianwei Xie
1
Jiangxi Province Key Laboratory of
Polymer Micro/Nano Manufacturing and
Devices, East China University of
We describe an effective and novel method to prepare N‐aryl imidazoles via the
copper quinolate‐catalyzed N‐arylation of aryl halides and imidazoles. A wide
range of products were obtained in moderate to excellent yields under the
optimal reaction conditions. Applying standard conditions, the model reaction
could be performed on a gram scale. This method also presents a new avenue to
the “click” reaction of terminal alkynes, benzyl bromide, and sodium azide and
to the construction of C–C bonds by homocoupling of phenylboronic acid or
phenylacetylene derivatives with the aid of copper quinolate.
Technology, Nanchang 330013, China
2
Department of Chemistry and Chemical
Engineering, Baoji University of Arts and
Sciences, Baoji 721013, China
3
College of Chemistry and
Bioengineering, Hunan University of
Science and Engineering, Yongzhou
425199, China
Correspondence
KEYWORDS
Huiqin Li, Department of Chemistry and
Chemical Engineering, Baoji University of
Arts and Sciences, Baoji 721013, China.
Email: huiqinli@yeah.net Jianwei Xie,
College of Chemistry and Bioengineering,
Hunan University of Science and
Engineering, Yongzhou 425199, China.
Email: cesxjw@foxmail.com
complex, copper, coupling reactions, imidazoles, N‐arylation
Funding information
The National Natural Science Foundation
of China, Grant/Award Number:
51702006; National Natural Science
Foundation of China, Grant/Award
Number: 51702006
[
6]
1
| INTRODUCTION
catalyzed by copper–diamine complex.
Using
sulfonato–Cu (salen) and bifunctional salen–Cu(II) com-
plex as the catalyst, Zhou and Yi groups achieved the
cross‐coupling reaction of aryl halides and imidazoles in
Copper complex represents a remarkable class of coordi-
nated metal compounds which is widely used in
[1]
[2]
[7]
membrane perturbation, DNA oxidation, anticancer
2009 and 2015, respectively. In 2013, Xie et al. demon-
[3]
and anti‐inflammatory processes, and various chemical
reactions, such as asymmetric transformation, trifluoro-
methylation, electrophilic amination, and radical addition
strated that pyrrolecarbaldiminato–Cu complexes could
[8]
promote the reaction of aryl halides and imidazoles. In
2015, Liu et al. found that 2N O–Cu complexes also medi-
2
[9]
[4]
and polymerization. The Ullmann‐type reaction is usu-
ally utilized for efficient construction of C–N bonds using
ated the aforesaid reaction. In 2017, Hashem et al. real-
ized the coupling reaction of aryl halides and imidazoles
[5]
the copper complex as a catalyst.
under the catalytic system of N‐salicylidene‐N‐phenyl
[
10]
Several synthetic strategies have been developed to con-
struct C–N bonds with the aid of a copper complex
amine–Cu complex. In 2017, Sepehri et al. documented
the N‐arylation between aryl halides and imidazoles using
the Cu(II) complex of pyridine‐based polydentate as the
(
Figure 1). In 2000, Collman and Zhong reported the
[
11]
coupling reaction of arylboronic acids and imidazoles
catalyst.
In 2018, Gou et al. described successful cross‐
Appl Organometal Chem. 2019;e5303.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5303

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WU ET AL.
FIGURE 1 Some typical copper complexes.
coupling reactions of aryl halides and imidazoles in the
presence of 1,8‐naphthyridine copper(I) complex.
Although these methods have been developed to transform
TABLE 1 Screening reaction conditions for N‐arylation of imid-
azole and 4‐iodotoluene
[
12]
a
f
Entry
Base
Solvent
Yield (%)
b
1
NaOH
NaOH
DMF
0
65
67
63
55
78
71
61
92
72
69
45
2
3
4
5
6
7
8
DMF
Na
2
CO
CO
PO
3
DMF
K
2
3
3
DMF
K
4
DMF
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
CO
CO
CO
CO
CO
CO
CO
3
DMF
3
3
3
3
3
3
Toluene
1,4‐Dioxane
DMSO
DMSO
DMSO
DMSO
9
c
1
1
1
0
1
2
d
e
a
Reaction conditions: 1a (0.5 mmol), 2a (0.55 mmol), copper quinolate
10 mol%), solvent (1 ml), base (1.0 mmol), 100 °C, 12 hr.
(
b
Without copper quinolate.
0 °C.
c
9
d
8
hr.
e
Copper quinolate (5 mol%).
Isolated yields.
f
SCHEME 1 N‐arylation of imidazoles and aryl halide. DMF,
dimethylformamide; DMSO, dimethyl sulfoxide
DMF, dimethylformamide; DMSO, dimethyl sulfoxide.

WU ET AL.
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molecules using the copper complex as a catalyst, explora-
tion of the use of widely available copper complexes for
N‐arylation under relative conditions remains desirable.
2 | RESULTS AND DISCUSSION
We began this study by investigating the reaction of
4‐iodotoluene (Table 1, 1a) and imidazole (Table 1, 2a)
in dimethyl sulfoxide (DMSO) at 100 °C. As shown in
Table 1, the reaction did not proceed without copper
quinolate (entry 1). Among the various bases examined,
8
‐Hydroxyquinoline, which is not known to be a carci-
[13]
nogenic compound,
has been used as a ligand to
combine with copper for N‐arylation. In 2005, the reaction
between imidazoles and aryl bromides was achieved using
[14]
CuI/8‐hydroxyquinoline (Scheme 1, a). In 2008, Li et al.
reported that 1,2,3,4‐tetrahydro‐8‐hydroxyquinoline pro-
moted the N‐arylation of imidazoles with aryl bromides
Cs CO was found to be the best for promoting the reac-
2 3
tion (entries 2–6). Some solvents were screened, with
DMSO identified as the best (entries 7–9). When the reac-
tion temperature was decreased to 90 °C, the yield of 3a
was 72% (entry 10). The reaction time and catalytic
amount were also examined, and results showed that
12 hr and 10 mol% copper quinolate were the optimal
values (entries 11 and 12).
[15]
catalyzed by CuBr (Scheme 1, b).
In 2012, Han et al.
developed a method to achieve C–N coupling of imidazoles
with aryl bromides using Cu O/8‐hydroxyquinoline as the
2
[16]
catalyst (Scheme 1, c).
Despite these achievements,
however, the methods used are limited by high reaction
temperature, long reaction time, and the need for a large
amount of active Cu(I) catalyst. In this regard, we have
found that copper quinolate could be used as a powerful
catalyst for the N‐arylation of imidazoles and aryl halides
(
Scheme 1, d).
SCHEME 3 Gram scale of the reaction. DMSO, dimethyl
sulfoxide
SCHEME 2 Substrate scope of the
reaction. DMSO, dimethyl sulfoxide

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WU ET AL.
SCHEME 4 Proposed reaction
mechanism
With the optimized reaction conditions in hand, the
substrate scope of the reaction was investigated
Scheme 2). Aryl bromide and chloride did not undergo
the reaction as actively as aryl iodide (3a, 3b, 3c, 3e, 3f,
l, 3m, 3n, and 3o). Electron‐rich‐substituted aryl halo-
intermediate II by reacting with I generated from imidaz-
ole with the aid of a base. Finally, the product was
obtained by the reductive elimination of II.
(
1,2,3‐Triazoles are prevalent motifs that are utilized in
[
18]
3
pharmaceuticals and agrochemicals.
With the aid of
gen yielded more of the desired products than did
electron‐deficient ones (3a and 3c vs. 3 h‐3 k), and
copper quinolate, 1,4‐diphenyl‐1H‐1,2,3‐triazole 7a could
be obtained from 4a, 5a, and 6a in 91% yield (Scheme 5).
The C–C bond could be formed in the presence of cop-
4
‐iodoaniline produced lower yield of the products, which
may be attributed to the coordination between the amino
group in 4‐iodoaniline and copper (3d). The steric hin-
drance effect of the substituents on aryl halogen and
imidazole clearly influenced the reaction (3a vs. 3b and
per quinolate and O . As presented in Schemes 6 and 7,
2
the homocoupling reaction of arylboronic acid was effi-
ciently performed to obtain the desired products in good
yields. Moreover, 10a was obtained with the aid of copper
quinolate in 8–6% yield.
3
m). Heterocyclic iodides such as 3‐iodothiophene
were survivable in the reaction (3l). Pyrazole and benz-
imidazole could react with 4‐iodotoluene to produce the
corresponding products (3n and 3o) in good yields.
The scalability of the reaction was determined under
standard conditions, and the results indicated that the tar-
get product could be afforded in 87% yield (Scheme 3).
3
| CONCLUSION
We have developed a simple approach to synthesize N‐
aryl imidazoles in the presence of simple and commer-
cially available copper quinolate. Various products were
obtained under the standard reaction conditions, and
the reaction could be scaled up to the gram level, which
is significant for academic research and industrial
[17]
Based on the literature,
we propose a plausible
mechanism for the model reaction in Scheme 4. Initially,
aryl halide was oxidized by [CuL ] to form Ar–[CuL ]–X.
2
2
Then, Ar–[CuL ]–X was rapidly converted into
2
SCHEME 5 Reactions of 4a, 5a, and 6a. DMSO, dimethyl
SCHEME 7 Homocoupling reaction of 10a. DMSO, dimethyl
sulfoxide
sulfoxide
SCHEME 6 Homocoupling reaction of
arylboronic acid

WU ET AL.
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applications. In addition, the proposed protocol showed
positive effects on the three‐component reaction of benzyl
halides, sodium azide, and terminal alkynes as well as on
the construction of C–C bonds.
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[
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The National Natural Science Foundation of China
(
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CONFLICTS OF INTEREST
STATEMENT
[
14] L. Liu, M. Frohn, N. Xi, C. Dominguez, R. Hungate, P. J.
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Fengtian Wu https://orcid.org/0000-0002-0760-809X
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Copper quinolate: A simple and efficient catalytic
complex for coupling reactions. Appl Organometal
Chem. 2019;e5303. https://doi.org/10.1002/aoc.5303
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