Y.-P. Zhang et al. / Tetrahedron Letters 54 (2013) 6494–6497
6495
Table 1
Optimization of reaction conditionsa
O
OH Br
Cu O/Cu-CNTs catalyst
2
+
Entry Base
Solvent
Temperature
(°C)
Amount of solvent
(mL)
Yieldb
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17c
18d
19e
20f
21g
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
NaOMe DMF
KOH
K3PO4
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
NMP
DMSO
Pyridine 70
CH3CN
CH3OH
DMF
120
150
10
10
10
10
10
10
10
10
10
10
10
15
5
5
5
5
5
5
5
5
5
15
12
14
15
7
47
23
24
20
0
68
76
96
0
0
0
75
45
(c)
50
40
30
20
10
0
140
140
140
140
140
140
140
140
80
100
120
140
140
140
140
140
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
0
5
10 15 20 25 30 35 40
Trace
42
0
13
39
Size (nm)
Figure 1. (a) TEM image of Cu2O/Cu-CNTs; (b) A high-magnification TEM image of
Cu2O/Cu-CNTs; (c) size distribution diagram of Cu2O/Cu-CNTs.
a
Reaction conditions: phenol (1.0 mmol), bromobenzene (1.2 mmol), base
(1.0 mmol), Cu2O/Cu-CNTs catalyst (0.06 g), 24 h, under nitrogen atmosphere.
b
Isolated yields.
Reaction for 12 h.
Reaction for 18 h.
Without catalyst.
10 mol % Cu2O.
20 mol % Cu.
c
d
e
f
g
Cu2O (JCPDS 05-0667)
Cu (JCPDS 04-0836)
20 25 30 35 40 45 50 55 60 65 70 75 80
2θ
the CNTs led to a significant increase in the yield of C–O cross-cou-
pling (Table 1, entries 13, 20, and 21).
Figure 2. XRD pattern of Cu2O/Cu-CNTs.
After having optimized the reaction parameters, the scope of
the reaction was explored with a range of substituted phenols
and aryl halides (Table 2). The presence of a p-methyl group or
p-methoxy group in phenol increased the yield of the coupling
reaction (Table 2, entries 2, 10, 16 and 18, and 20). The yield in this
coupling reaction decreased when the electron-donating group
was present at the ortho or meta position in phenol (Table 2, entries
3, 4, 6, and 12–14). The steric hindrance of chlorobenzene made no
effect on the O-arylation with phenol (Table 2, entries 15 and 19).
When reacting with m-cresol, bromobenzene bearing an o-alde-
hyde group hindered the cross-coupling reaction (Table 2, entries
3 and 7). The electron-rich chlorobenzene could react with phenol
easily and produce a moderate yield (Table 2, entry 17). Iodoben-
zene and bromobenzene showed the same reactivity when react-
ing with phenol (Table 2, entries 1 and 11). However, with the
effect of steric factors increasing, iodobenzene gradually showed
its advantage on the cross-coupling reaction (Table 2, entries 3,
4, 6, and 12–14). p-Cresol was successfully coupled with 4-bromo-
benzaldehyde to give the corresponding diarylether in an excellent
yield (Table 2, entry 10). 4-(4-Methoxyphenoxy)benzaldehyde was
obtained only in moderate yield compared to 4-(p-tolyloxy)benzal-
dehyde (Table 2, entries 9 and 10).
To develop the protocol for C–O cross-coupling, the reaction of
bromobenzene (1.2 mmol) and phenol (1.0 mmol) catalyzed by
Cu2O/Cu-CNTs (0.06 g) under nitrogen atmosphere was selected
as a model reaction to optimize the reaction conditions. In terms
of the effect of solvent on the cross-coupling reaction, DMF was
found to be the best solvent for the reaction (Table 1, entry 6).
Other solvents, including NMP, DMSO, pyridine, and CH3CN, were
less efficient (Table 1, entries 1–4). CH3OH gave the corresponding
product in a 7% yield, which was the worst among these solvents
(Table 1, entry 5). Nevertheless, all of these yields were generally
low before further optimizations. To increase the efficiency of the
coupling reaction, the effects of different bases were investigated
(Table 1, entries 6–11). Cs2CO3 exhibited the best performance
(76%). Et3N, NaOMe, KOH, and K3PO4 gave 47%, 23%, 24%, and
20% yields, respectively. K2CO3 showed no activity for this reaction.
The reaction was carried out in different amounts of DMF over the
range of 5–15 mL (Table 1, entries 11–13). Among different
amounts of the solvent, 5 mL of DMF turned out to be the best
choice with a yield of 96% (Table 1, entry 13). The amount of cata-
lyst was decreased from 0.08 to 0.02 g and 0.06 g of catalyst was
found to be the most effective catalytic system (Fig. 3). At lower
temperatures (80, 100 and 120 °C) and shorter reaction times (12
and 18 h), no significant amount of product was formed (Table 1,
entries 14–18). The presence of Cu2O and Cu nanoparticles on
The reusability of the catalyst in this coupling reaction was also
examined using iodobenzene (1.2 mmol) and phenol (1.0 mmol) as
substrate in DMF (5 mL) at 140 °C. After the completion of the reac-
tion, the catalyst was filtrated, washed with ethyl acetate
(3 Â 10 mL), followed by distilled water and ethanol, and then