Naidu et al.
SCHEME 1
FIGURE 1. Oxygen-based ligands for copper-catalyzed C-O bond
formation.
3,5-dione,10 tripod ligands,11 tetraethyl orthosilicate (as sol-
vent),12 silica supported Cu(II) complex,13 aryl boronic acid,14
N,N-dimethylglycine,15 diimine ligands,16 ꢀ-keto ester,17 and
bipyridyl complex.18 Very recently diketone along with iron19,20
has also been used as efficient catalyst for the formation of
C(aryl)-O bond.
TABLE 1. Effect of the Ratio of Ligand and CuI
Recently we have shown that 1,1′-binaphthyl-2,2′-diamine
(BINAM)-Cu(OTf)2 complex can be used as an efficient catalyst
for diaryl ether and alkyl aryl ether synthesis through C-O bond
formation in dioxane from aryl iodides and phenols/alcohols at
110 °C.21 As a part of our ongoing research toward finding more
efficient copper catalyst for diaryl ether and alkyl aryl ethers
synthesis from aryl halides and phenols/alcohols, herein for the
first time we report an easily available racemic anthracene-based
diol, trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dimetha-
nol22 L3-CuI complex, as an efficient catalyst for Ullmann
coupling for the formation of diaryl and alkyl aryl ethers through
C-O bond formation in acetonitrile under very mild conditions
(82 °C). This procedure is very simple, mild, clean and works
efficiently (Scheme 1).
entry
ligand
Cul
time (h)
yield (%)
1
2
3
4
5
6
7
8
L1 (20 mol %)
L2 (20 mol %)
L3 (20 mol %)
L4 (20 mol %)
L5 (20 mol %)
L3 (10 mol %)
L3 (20 mol %)
L6 (20 mol %)
L6 (20 mol %)
L6 (7.5 mol %)
L6 (7.5 mol %)
-
20 mol %
20 mol %
20 mol %
20 mol %
20 mol %
10 mol %
10 mol %
20 mol %
20 mol %
2 mol %
2 mol %
-
28
28
17
30
30
24
24
16
17
18
18
32
32
55
49
97
00
45
76
33
55
80a
75a
42
00
39
9
10
11
12
13
-
20 mol %
a Dioxane was used as solvent.
2. Results and Discussion
yield to 80% (entry 9). Then the reaction was carried out with
different ratios of L3 and CuI, and it was found that a 20 mol
% ligand L3-copper combination was the most effective catalytic
system. The coupling reaction did not provide even a trace
amount of diaryl ether when the reaction was carried out without
L3-CuI (entry 12). When the reaction was carried out only with
CuI without L3, the reaction provided only 39% yield for the
coupling product (entry 13), which shows that ligand is
mandatory for quantitative yield of the product.
The reaction was screened with several copper salts, solvents,
and bases to increase the efficiency of the coupling reactions,
and the results are summarized in Table 2. Although several
copper salts catalyzed the reaction, CuI turned out to be the
copper salt of choice in view of yield (Table 2, entry 1).
Similarly acetonitrile was the best solvent among those exam-
ined. Cs2CO3 as base gave the best yields of product in
comparison with bases such as Na2CO3 and K2CO3.
Using the above-mentioned optimized conditions, we initiated
our investigations into the scope of the L3-CuI catalyzed
Ullmann-type coupling reaction, and the results are summarized
in Table 3. Various aryl iodides and phenols reacted to give
the corresponding diaryl ethers under very mild reaction
conditions. We found that iodobenzene containing electron-
releasing groups as well as electron-withdrawing groups reacted
with phenols to give corresponding diaryl ethers.
The yields were different with electron-rich and electron-
deficient phenols. The presence of electron-releasing groups such
as methyl and methoxy groups in phenol at para and meta
positions increased the yield of the diaryl ethers by 5-23%
(entries 2 vs 1, 4, 5, and 8), whereas an electron-withdrawing
group such as a chloro group at the para position of phenol
decreased the yield to 64% yield (entries 1 vs 10). The presence
of an electron-releasing group such as a methoxy or methyl
In preliminary studies, we used 20 mol % 1,1′-binaphthyl-
2,2′-diol L1 (BINOL) (Figure 1) as ligand with 20 mol % CuI
for the coupling of iodobenzene with p-cresol in acetonitrile at
82 °C. After 28 h the coupling reaction provided 55% yield for
the corresponding diaryl ether (Table 1, entry 1). When the
BINOL L1 was replaced by diester ligand L2, the reaction
provided only 49% yield of diaryl ether. Surprisingly, when
diol L3 was used as ligand along with CuI, it provided 97%
yield (entry 3). However, replacing L3 by L4, the reaction failed
to provide any coupling product (entry 4), and using (+)-diethyl
tartarate L5 as ligand gave only 45% yield for corresponding
diaryl ether (entry 5). The C(aryl)-O bond formation between
iodobenzene and p-cresol in the presence of 20 mol % N,N-
dimethylglycine L6-CuI gave only 55% yield in acetonitrile at
82 °C (entry 8). Changing the solvent to dioxane increased the
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(22) Diol ligand L3 was easily synthesized from known literature procedure.
See Supporting Information for experimental details.
3676 J. Org. Chem. Vol. 74, No. 10, 2009