Efficient iron/copper-cocatalyzed o-arylation of phenols with bromoarenes

Article abstract of DOI:10.1055/s-0030-1259291

Low catalytic amount CuI and Fe(acac)₃ were found to effectively promote the C-O cross-coupling reaction in the presence of K₂CO ₃ as the base. A serious of diaryl ethers with different substitutents can be synthesized in good to excellent yields. This efficient and economic method is attractive for applications on an industrial scale. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1259291

268
LETTER
Efficient Iron/Copper-Cocatalyzed O-Arylation of Phenols with Bromoarenes
O
-Arylation of Phe
i
nols
w
a
ith Bromoa
o
renes yan Liu, Songlin Zhang*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Suzhou
University, Dushu Lake Campus, Suzhou, 215123, P. R. of China
Fax +86(512)65880352; E-mail: zhangsl@suda.edu.cn
Received 2 October 2010
Table 1 Optimization of Reaction Conditionsa
Abstract: Low catalytic amount CuI and Fe(acac)3 were found to
effectively promote the C–O cross-coupling reaction in the pres-
ence of K2CO3 as the base. A serious of diaryl ethers with different
substitutents can be synthesized in good to excellent yields. This ef-
ficient and economic method is attractive for applications on an in-
dustrial scale.
Entry Fe source
Cu source
CuI
Base
Yield (%)b
1
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
FeCl3
K3PO4 70
K2CO3 90
Cs2CO3 95
2
CuI
Key words: catalysis, iron, copper, diaryl ether
3
CuI
4
CuI
Et3N
0
A number of diaryl ethers have been reported to have sig-
nificant biological activity and are valuable intermediates
in the polymer industry.1 Therefore considerable effort
has been made in the development of efficient strategies
for their constructions. Traditionally, the Ullmann cou-
pling reaction promoted by copper salts is a powerful tool
for the formation of diaryl ethers,2,3 but the reaction usu-
ally needs electron-rich ligands and stoichiometric
amount of copper salts. So it is a major goal for organic
synthesis to develop a less expensive and environmentally
more benign catalyst system. Iron salts are inexpensive,
less toxic, and more environmentally benign in compari-
son to other transition metals. Following the pioneering
work by Tamura and Kochi,4 iron-catalyzed carbon–
heteroatom bond-forming reaction is an alternative and
promising strategy.5,6 Bolm and co-workers first reported
the iron-catalyzed C–O cross-coupling reaction.5j Howev-
er, they found lately that such cross-coupling catalytic re-
actions using iron salt may be affected by trace quantities
of other metals, particularly copper.7 Recently, iron/cop-
per-catalyzed C–O cross-coupling reaction has been re-
ported.8 Fu and co-workers developed an iron/copper
cooperative catalysis for O-arylation process using FeCl3,
CuO, and rac-BINOL as the catalyst system.8a Taillefer
and co-workers also disclosed a novel arylation protocol
involving the use of FeCl3, Cu(acac)2, and 2,2,6,6-tetram-
ethyl-3,5-heptane-dione.8b As part of our continuing inter-
est in the use of iron/copper cooperative catalysts, we
report a new facile and efficient iron/copper-catalyzed C–
O cross-coupling reaction by using Fe(acac)3 and CuI as
the catalyst system (Scheme 1).
5
CuSO4·5H2O K2CO3 70
6
–
K2CO3
0
7
CuI
CuI
CuI
CuI
CuI
K2CO3 20
K2CO3 10
K2CO3 25
K2CO3 trace
8
Fe(NO3)3·9H2O
Fe2O3
9
10
11
–
acac
K2CO3 45c
62d
a The reaction was performed with phenol (0.5 mmol), bromobenzene
(0.75 mmol), Fe source (2 mol%), Cu source (1 mol%), and base (1.0
mmol) in DMF (0.8 mL) at 135 °C for 12 h.
b Isolated yield based on 2a.
c Conditions: 1 mol% acac (acac = acetylacetonate).
d Conditions: 6 mol% acac.
In our initial study, the reaction between aryl bromoarene
1a and phenol 2a was chosen as a model for the coupling
reaction. As shown in Table 1, a series of experiments was
carried out to evaluate the ability of various iron sources,
Cu sources and bases for the O-arylation process. By in-
vestigating into the base system, we obtained a moderate
yield when K3PO4 was used as the base (Table 1, entry 1)
and no product was obtained when Et3N was used as the
base (Table 1, entry 4). Both K2CO3 and Cs2CO3 were ef-
fective bases in this reaction (Table 1, entries 2 and 3).
Hence the less expensive K2CO3 was used in experiments
to investigate the effect of iron sources and Cu sources on
the coupling reaction. Fe(acac)3 and CuI were found to be
the best combination to catalyze this reaction (Table 1, en-
tries 2, 5–10). Other iron sourses Fe2O3, Fe(NO3)3·9H2O,
and FeCl3 all gave lower yields of target products and Cu
source CuSO4·5H2O gave a moderate yield. Subsequent-
ly, a blank test was performed with only iron source (no
copper source), and it was shown that the arylation reac-
tion did not proceed at all (Table 1, entry 6). There was
also no diaryl ether formed when using CuI as the copper
Br
OH
[Fe], [Cu]
base
O
+
DMF, 12 h
135 °C
1a
2a
3
Scheme 1
SYNLETT 2011, No. 2, pp 0268–0272
x
x.
x
x.
2
0
1
1
Advanced online publication: 23.12.2010
DOI: 10.1055/s-0030-1259291; Art ID: W15810ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
O-Arylation of Phenols with Bromoarenes
269
salt in the absence of iron salt (Table 1, entry 10). When ed that the optimal conditions for the diaryl ethers in-
the ligand acac (acetylacetonate) was added instead of volved the use of Fe(acac)3, CuI, and K2CO3 in DMF at
Fe(acac)3, the product was obtained in moderate yield 135 °C.
(Table 1, entry 11). Based on these results, it was conclud-
Table 2 Fe(acac)3/CuI-Catalyzed C–O Cross-Coupling of Various Phenols and Aryl Bromoarenesa
CuI (1 mol%)
Fe(acac)3 (2 mol%)
Br
OH
O
+
K2CO3, DMF
135 °C, 12 h
R1
R2
R2
R1
Entry
Aryl halide
Phenol
Product9
Yield (%)b
93
O
OH
Br
1
2
OMe
Cl
MeO
Cl
O
OH
Br
Br
Br
95
92
90
O
O
OH
OH
3
4
O
OH
Br
5
94
O
OH
Br
Br
O
O
6
7
80
85
N
N
H
H
OMe
OMe
OH
O
Br
8
9
81
93
OH
OH
O
O
Br
O
O
Br
O
OH
10
95
Br
Br
O
O
OH
OH
11
12
90
96
Synlett 2011, No. 2, 268–272 © Thieme Stuttgart · New York

270
LETTER
Table 2 Fe(acac)3/CuI-Catalyzed C–O Cross-Coupling of Various Phenols and Aryl Bromoarenesa (continued)
CuI (1 mol%)
Fe(acac)3 (2 mol%)
Br
OH
O
+
K2CO3, DMF
135 °C, 12 h
R1
R2
R2
R1
Entry
Aryl halide
Phenol
Product9
Yield (%)b
Br
Br
O
OH
O
O
O
O
13
14
92
93
O
OH
Cl
Cl
Br
O
O
OH
15
16
52
93
H2N
MeO
MeO
NH2
MeO
MeO
Br
Br
OH
O
O
O
OH
17
93
Cl
Cl
O
O
O
O
O
OH
OH
OH
Br
O
O
18
19
94
92
O
MeO
MeO
MeO
MeO
Br
Cl
Cl
O
Br
20
21
95
91
Cl
Cl
OMe
OMe
Br
Br
O
OH
Cl
Cl
Cl
O
OH
22
23
24
94
93
Cl
Cl
Cl
OH
OMe
N
Br
X
MeO
N
O
O
OH
95 (X = I)
5 (X = Cl)
a The reaction was performed with phenol (0.5 mmol), aryl bromoarene (0.75 mmol), K2CO3 (1.0 mmol), Fe(acac)3 (2 mol%), CuI (1 mol%)
in DMF (0.8 mL) at 135 °C for 12 h.
b Isolated yield based on phenol.
Using the optimized conditions, we set out to study the ef- tron-neutral (Table 2, entries 9, 14 and 19) and electron-
fect of substituent for the coupling reactions of a various rich ones (Table 2, entries 10–13) offered the desired
of aryl bromides and phenols (Table 2). Both the electron- products in good to excellent yields. This represents a sig-
rich (Table 2, entries 1, 3, 7, and 8) and electron-deficient nificant improvement over the classical copper- or palla-
phenols (Table 2, entries 2 and 6) provided the coupling dium-catalyzed ether formation reactions in which
products in excellent yields. As for bromoarenes, elec- electron-donating groups on the halide and electron-
Synlett 2011, No. 2, 268–272 © Thieme Stuttgart · New York

LETTER
O-Arylation of Phenols with Bromoarenes
271
R.; Gómez-Bengoa, E. Chem. Commun. 1998, 2091.
(d) Buck, E.; Song, Z. J.; Tschaen, D.; Dormer, P. G.;
Volante, R. P.; Reider, P. J. Org. Lett. 2002, 4, 1623.
withdrawing groups on the phenol make the reaction be-
come slower or even fail to work.2d,e Furthermore, the
steric hindrance of phenols exerted little effect on this re-
action as both reactions involving 4-methoxyphenol and
2-methoxyphenol gave products in high yield (Table 2,
entries 1 and 7). 2-tert-Butylphenol also gave high yield
with bromoarenes (Table 2, entry 8). It is noteworthy that
the cross-coupling reaction conditions have high toler-
ance to various functional groups. For example, 1-(4-bro-
mophenyl)ethanone offered the desired products in good
to excellent yields with different phenols (Table 2, entries
9, 16, and 17), and so did 4-bromoaniline with 4-methox-
yphenol (Table 2, entry 15). Despite the basic conditions
and the reaction temperature of 135 °C, the acetyl group
of N-(4-hydroxyphenyl) acetamide (Table 2, entry 6) was
not cleaved. Under the current conditions, 1-bromo-4-
chlorobenzene and various phenols reacted to give the
corresponding products in excellent yields (Table 2, en-
tries 14 and 19–22). This indicated that aryl bromides pos-
sessed better reactivity than aryl chlorides in this reaction.
Additionally, aryl iodide was found to be more reactive
than aryl bromide and aryl chloride as a substrate
(Table 2, entry 24). Finally, it was also noted that 2-bro-
mopyridine reacted with 4-methoxyphenol to give prod-
uct in excellent yield (Table 2, entry 23).
(e) Cristau, H.-J.; Cellier, P. P.; Hamada, S.; Spindler, J.-F.;
Taillefer, M. Org. Lett. 2004, 6, 913. (f) Cai, Q.; Zou, B.;
Ma, D. Angew. Chem. 2006, 118, 1298. (g) Chen, Y.-J.;
Chen, H.-H. Org. Lett. 2006, 8, 5609. (h) Rao, H.; Jin, Y.;
Fu, H.; Jiang, Y.; Zhao, Y. Chem. Eur. J. 2006, 12, 3636.
(i) Ouali, A.; Spindler, J.-F.; Cristau, H.-J.; Taillefer, M.
Adv. Synth. Catal. 2006, 348, 499. (j) Ouali, A.; Laurent,
R.; Caminade, A.-M.; Majora, J.-P.; Taillefer, M. J. Am.
Chem. Soc. 2006, 128, 15990. (k) Lipshutz, B. H.; Unger, J.
B.; Taft, B. R. Org. Lett. 2007, 9, 1089. (l) Altman, R. A.;
Buchwald, S. L. Org. Lett. 2007, 9, 643. (m) Lv, X.; Bao,
W. J. Org. Chem. 2007, 72, 3863. (n) Ouali, A.; Spindler,
J.-F.; Jutand, A.; Taillefer, M. Adv. Synth. Catal. 2007, 349,
1906. (o) Ouali, A.; Taillefer, M. Organometallics 2007, 26,
65. (p) Benyahya, S.; Monnier, F.; Taillefer, M.; Man, M.
W. C.; Bied, C.; Ouazzani, F. Adv. Synth. Catal. 2008, 350,
2205. (q) Monnier, F.; Taillefer, M. Angew. Chem. Int. Ed.
2008, 47, 3096. (r) Zhang, Q.; Wang, D.; Wang, X.; Ding,
K. J. Org. Chem. 2009, 74, 7187. (s) Liu, Y.-H.; Li, G.;
Yang, L.-M. Tetrahedron Lett. 2009, 50, 343. (t) Tye, J.
W.; Weng, Z.; Giri, R.; Hartwig, J. F. Angew. Chem. Int. Ed.
2010, 49, 2185.
(3) For general reviews, see: (a) Ley, S. V.; Thomas, A. W.
Angew. Chem. Int. Ed. 2003, 42, 5400. (b) Beletskaya, I. P.;
Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337.
(c) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008,
108, 3054. (d) Monnier, F.; Taillefer, M. Angew. Chem. Int.
Ed. 2009, 48, 6954.
(4) (a) Tamura, M.; Kochi, J. K. J. Am. Chem. Soc. 1971, 93,
1487. (b) Tamura, M.; Kochi, J. K. Synthesis 1971, 303.
(c) Tamura, M.; Kochi, J. K. J. Organomet. Chem. 1971, 31,
289.
In summary, we have demonstrated an efficient iron/cop-
per-catalyzed O-arylation of phenols with aryl bromoare-
nes to produce diaryl ethers in good to excellent yields
under mild conditions. Due to the low catalytic loading
and the use of inexpensive base, the reaction is very con-
venient and can be easily applied on an industrial scale.
(5) For recent contributions on iron catalysis, see: (a) Plietker,
B. Angew. Chem. Int. Ed. 2006, 45, 6053. (b) Komeyama,
K.; Morimoto, T.; Takaki, K. Angew. Chem. Int. Ed. 2006,
45, 2938. (c) Gelalcha, F. G.; Bitterlich, B.; Anilkumar, G.;
Tse, M. K.; Beller, M. Angew. Chem. Int. Ed. 2007, 46,
7293. (d) Taillefer, M.; Xia, N.; Ouali, A. Angew. Chem. Int.
Ed. 2007, 46, 934. (e) Jadhav, V. H.; Dumbre, D. K.;
Phapale, V. B.; Borate, H. B.; Wakharkar, R. D. Catal.
Commun. 2007, 8, 65. (f) Correa, A.; Bolm, C. Angew.
Chem. Int. Ed. 2007, 46, 8862. (g) Guo, D.; Huang, H.; Xu,
J.; Jiang, H.; Liu, H. Org. Lett. 2008, 10, 4513. (h) Du, Y.;
Chang, J.; Reiner, J.; Zhao, K. J. Org. Chem. 2008, 73,
2007. (i) Correa, A.; Bolm, C. Adv. Synth. Catal. 2008, 350,
391. (j) Bistri, O.; Correa, A.; Bolm, C. Angew. Chem. 2008,
120, 596. (k) Bonnamour, J.; Bolm, C. Org. Lett. 2008, 10,
2665. (l) Correa, A.; Carril, M.; Bolm, C. Angew. Chem. Int.
Ed. 2008, 47, 2880. (m) Correa, A.; Carril, M.; Bolm, C.
Chem. Eur. J. 2008, 14, 10919. (n) Wang, Z.; Zhang, Y.;
Fu, H.; Jiang, Y.; Zhao, Y. Org. Lett. 2008, 10, 1863.
(o) Yao, B.; Liang, Z.; Niu, T.; Zhang, Y. J. Org. Chem.
2009, 74, 4630. (p) Teo, Y.-C. Adv. Synth. Catal. 2009, 351,
720. (q) Mao, J.; Xie, G.; Zhan, J.; Hua, Q.; Shi, D. Adv.
Synth. Catal. 2009, 351, 1268. (r) Qiu, J.-W.; Zhang, X.-G.;
Tang, R.-Y.; Zhong, P.; Li, J.-H. Adv. Synth. Catal. 2009,
351, 2319. (s) Wu, J.-R.; Lin, C.-H.; Lee, C.-F. Chem.
Commun. 2009, 4450. (t) Li, P.; Zhang, Y.; Wang, L. Chem.
Eur. J. 2009, 15, 2045. (u) Ku, X.; Huang, H.; Jiang, H.;
Liu, H. J. Comb. Chem. 2009, 11, 338. (v) Swapna, K.;
Kumar, A. V.; Reddy, V. P.; Rao, K. R. J. Org. Chem. 2009,
74, 7514. (w) Liang, Z.; Hou, W.; Du, Y.; Zhang, Y.; Pan,
Y.; Mao, D.; Zhao, K. Org. Lett. 2009, 11, 4978. (x) Lee,
H. W.; Chan, A. S. C.; Kwong, F. Y. Tetrahedron Lett. 2009,
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Primary Data for this article are available online at http://
www.thieme-connect.com/ejournals/toc/synlett and can be cited
using the following DOI: 10.4125/pd0008th.
Acknowledgment
We gratefully acknowledge the Program for Hi-Tech Research of
Jiangsu Science and Technology Department (BE2008063), Inno-
vation
Fund
for
Small
Technology-based
Firms
(08C26223201851), Innovator Fund of Suzhou Government
(ZXJ0726), Suzhou LAC Co., LTD and Suzhou Chiral Chemistry
Co., LTD (www.suzhoulac.com) for financial support.
References and Notes
(1) (a) Nicolaou, K. C.; Boddy, C. N. C.; Bräse, S.; Winssinger,
N. Angew. Chem. Int. Ed. 1999, 38, 2096. (b) Blankenstein,
J.; Zhu, J. Eur. J. Org. Chem. 2005, 1949. (c) Frlan, R.;
Kikelj, D. Synthesis 2006, 2271. (d) Theil, F. Angew. Chem.
Int. Ed. 1999, 38, 2345. (e) Ley, S. V.; Thomas, A. W.
Angew. Chem. Int. Ed. 2003, 42, 5400.
(2) (a) Paine, A. J. J. Am. Chem. Soc. 1987, 109, 1496.
(b) Marcoux, J.-F.; Doye, S.; Buchwald, S. L. J. Am. Chem.
Soc. 1997, 119, 10539. (c) Palomo, C.; Oiarbide, M.; López,
Synlett 2011, No. 2, 268–272 © Thieme Stuttgart · New York

272
LETTER
50, 5868. (y) Xu, X.; Liu, J.; Liang, L.; Li, H.; Li, Y. Adv.
Synth. Catal. 2009, 351, 2599.
Diphenyl Ether (3a)
1H NMR (400 MHz, CDCl3): d = 7.33 (t, J = 7.6 Hz, 4 H),
7.10 (t, J = 7.2 Hz, 2 H), 7.01 (d, J = 7.8 Hz, 4 H). 13C NMR
(100 MHz, CDCl3): d = 157.70, 130.19, 123.70, 119.34.
N-(4-Phenoxyphenyl)acetamide (Table 2, Entry 6)
1H NMR (400 MHz, CDCl3): d = 7.45 (d, J = 8.8 Hz, 2 H),
7.42 (s, 1 H), 7.31 (t, J = 7.8 Hz, 2 H), 7.08 (t, J = 7.4 Hz, 1
H), 6.97 (d, J = 7.8 Hz, 4 H), 2.17 (s, 3 H). 13C NMR (100
MHz, CDCl3): d = 169.25, 157.87, 153.82, 133.90, 130.15,
123.51, 122.29, 119.92, 118.82, 24.71.
(6) For pertinent reviews on Fe-catalyzed coupling reactions,
see: (a) Sherry, B. D.; Fürstner, A. Acc. Chem. Res. 2008, 41,
1500. (b) Correa, A.; Mancheńo, O. G.; Bolm, C. Chem. Soc.
Rev. 2008, 37, 1108. (c) Czaplik, W. M.; Mayer, M.;
Cvengros, J.; von Wangelin, A. J. ChemSusChem 2009, 2,
396.
(7) Buchwald, S. L.; Bolm, C. Angew. Chem. Int. Ed. 2009, 48,
5586.
(8) (a) Wang, Z.; Fu, H.; Jiang, Y.; Zhao, Y. Synlett 2008, 2540.
(b) Taillefer, M.; Xia, N.; Ouali, A. US 60/818,334, 2006
WO 001836, 2007.
1-tert-Butyl-2-phenoxybenzene (Table 2, Entry 8)
1H NMR (400 MHz, CDCl3): d = 7.42 (d, J = 7.7 Hz, 1 H),
7.33 (t, J = 7.8 Hz, 2 H), 7.15 (t, J = 7.0 Hz, 1 H), 7.10–7.05
(m, 2 H), 6.99 (d, J = 8.0 Hz, 2 H), 6.84 (d, J = 7.9 Hz, 1 H),
1.44 (s, 9 H). 13C NMR (100 MHz, CDCl3): d = 158.24,
156.30, 141.40, 130.13, 127.67, 127.57, 123.68, 123.08,
120.65, 119.13, 35.24, 30.62.
4-(4-Methoxyphenoxy)aniline (Table 2, Entry 15)
1H NMR (400 MHz, CDCl3): d = 6.90 (d, J = 8.8 Hz, 2 H),
6.84–6.81 (m, 4 H), 6.65 (d, J = 8.4 Hz, 2 H) 3.78 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 155.43, 152.46, 150.46,
142.47, 120.37, 119.49, 116.66, 115.08, 56.09
3-(4-Methoxyphenoxy)pyridine (Table 2, Entry 23)
1H NMR (400 MHz, CDCl3): 8.19 (d, J = 4.9 Hz, 1 H,) 7.66
(t, J = 7.7 Hz, 1 H), 7.08 (d, J = 9.1 Hz, 2 H), 6.97 (d, J = 6.0
Hz, 1 H), 6.93 (d, J = 9.1 Hz, 2 H), 6.86 (s, 1 H), 3.82 (s, 3
H).13C NMR (100 MHz, CDCl3): 164.64, 156.93, 148.08,
147.73, 139.69, 122.77, 118.47, 115.14, 111.42, 55.95.
(9) General Procedure for the Synthesis of Diaryl Ethers
A Schlenk tube equipped with a magnetic stir bar was
charged with K2CO3 (138 mg, 1 mmol), Fe(acac)3 (3.5 mg,
2% mol), CuI (1.0 mg, 1% mol), and the phenol (0.5 mmol)
in anhyd DMF (0.8 mL). The reaction mixture was heated at
135 °C. After being stirred at this temperature for 12 h, the
mixture was cooled to r.t. and diluted with Et2O. The
resulting suspension was directly filtered through a pad of
Celite, and the filtrate was washed with sat. NaCl and dried
over anhyd Na2SO4. The organic phase was concentrated,
and the crude mixtures were purified by column chroma-
tography on silica gel (300–400 mesh) using PE–EtOAc
solvent mixture as the eluent.
Synlett 2011, No. 2, 268–272 © Thieme Stuttgart · New York

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