Alkoxylation reactions of aryl halides catalyzed by magnetic copper ferrite

Article abstract of DOI:10.1016/j.tet.2013.02.077

Copper ferrite (CuFe₂O₄), which is easy-made, air-stable, low cost, easy separable, and regenerable, was applied as catalyst in an efficient method for C-O coupling reactions between various kinds of unactivated alkyl alcohols and aryl halides. This method only adopts 2.5% mol CuFe₂O₄ catalyst and selectively proceeds to C-O bond formation even sensitive substituents exist in the system.

Full text of DOI:10.1016/j.tet.2013.02.077

Tetrahedron 69 (2013) 3415e3418
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Alkoxylation reactions of aryl halides catalyzed by magnetic copper
ferrite
,
,
Shuliang Yang a b, Wenbing Xie a, Hua Zhou a, Cunqi Wu a, Yanqin Yang a b, Jiajia Niu c,
Wei Yang a , Jingwei Xu
,
a,
*
*
a State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, China
b Graduate School of Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049, China
c Zhengzhou Tobacco Research Institute of CNTC, No. 2, Fengyang Street, High-Tech Zone, Zhengzhou 450001, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Copper ferrite (CuFe2O4), which is easy-made, air-stable, low cost, easy separable, and regenerable,
was applied as catalyst in an efficient method for CeO coupling reactions between various kinds of
unactivated alkyl alcohols and aryl halides. This method only adopts 2.5% mol CuFe2O4 catalyst and
selectively proceeds to CeO bond formation even sensitive substituents exist in the system.
Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
Received 20 November 2012
Received in revised form 5 February 2013
Accepted 22 February 2013
Available online 27 February 2013
Keywords:
Alkoxylation
Cross-coupling
Copper ferrite
Magnetic
Recycle
1. Introduction
CuFe2O4 was in good agreement with the standard one (JCPDS34-
0425) (Fig. 1). From the TEM and SEM images, it was found that the
The formation of CeO bond is very useful in organic synthesis
because it occurs in the synthesis of numerous natural products,
biological compounds and pharmaceuticals.1 In recent years,
methods using palladium1a,2,3 have been extensively improved and
high catalytic efficiency has been achieved. However, the draw-
backs, such as high cost, toxicity, and the utilization of environ-
mental unfriendly phosphine ligands often limit their applications
inorganic synthesis. Meanwhile, copper4,5 systems are cheaper but
the recycle of the catalyst is still a challenge. Thus, there is still
requirement for the development of less expensive and recyclable
catalysts with high efficiency. Herein, we report the magnetic
CuFe2O4 as the catalyst, which couples the inactive alcohols with
both aryl and heteroaryl halides successfully and can be easily
recycled.
morphology of the prepared CuFe2O4 was blocky with many mac-
2. Results and discussion
Fig. 1. XRD spectrum of the prepared CuFe2O4.
The magnetic CuFe2O4 powder was prepared according to the
previous report.6 The X-ray diffraction (XRD) pattern of this
ropores on the surface (Figs. S1eS4, ESI). The magnetization-field
plots showed that CuFe2O4 exhibited ferrimagnetic behavior with
a coercivity about 296 Oe and a saturation magnetization about
26 emu/g at 300 K (Fig. S5, ESI).
* Corresponding authors. Tel.: þ86 431 8526 2649; fax: þ86 431 8526 2643;
e-mail addresses: yangwei@ciac.jl.cn (W. Yang), jwxu@ciac.jl.cn (J. Xu).
0040-4020/$ e see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.077

3416
S. Yang et al. / Tetrahedron 69 (2013) 3415e3418
Table 2
Optimation
Various solvents were examined by choosing iodobenzene (1a)
and n-butyl alcohol (1b) as the model substrates and 1,10-
phenanthroline as the ligand. The other commonly used polar
and non-polar solvents did not supply any products under
the experimental conditions. Surprisingly, an 88% yield was
reached by using n-butyl alcohol (1b) as both solvent and sub-
strate (Table 1).
Table 1
Solvent explorationa
Entry Catalyst (mol %) Ligand (mol %) Base
T/[ꢀC] Yield [%]a
Entry
Solvent
GC yield [%]
1
d
d
d
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
n.r.
n.r.
n.r.
2%
n.r.
4%
71%
48%
69%
70%
73%
78%
74%
87%
72%
79%
<1%
25%
23%
n.r.
1
2
3
4
5
6
7
8
NMP
DMSO
DMF
DMAc
Toluene
THF
Dioxane
d
0
0
0
0
0
2
3
4
5
6
7
8
9
CuFe2O4 (10)
d
d
d
L8 (20)
L8 (20)
L8 (20)
d
d
d
Cs2CO3
d
CuFe2O4 (10)
d
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K3PO4
0
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (10)
CuFe2O4 (5)
CuFe2O4 (2.5)
CuFe2O4 (1)
CuFe2O4 (2.5)
CuFe2O4 (2.5)
CuFe2O4 (2.5)
CuFe2O4 (2.5)
CuFe2O4 (2.5)
Fe3O4 (2.5)
L1 (20)
L2 (20)
L3 (20)
L4 (20)
L5 (20)
L6 (20)
L7 (20)
L8 (20)
L9 (20)
L10 (20)
L8 (20)
L8 (20)
L8 (20)
L8 (20)
L8 (20)
L8 (10)
L8 (5)
L8 (2)
L8 (5)
L8 (2.5)
L8 (5)
L8 (5)
L8 (5)
L8 (5)
0
88b
a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Reaction conditions were: iodobenzene (0.5 mmol), n-butyl alcohol (1.0 mmol),
CuFe2O4 (2.5 mol %), 1,10-phenanthroline (5.0 mol %), Cs2CO3 (1.0 mmol, 2.0 equiv),
solvent (1.0 mL), 110 ꢀC, under argon atmosphere, 12 h.
b
1.0 mL n-butyl alcohol was used as both reactant and solvent.
Next, a series of ligands were examined using iodobenzene (1a,
0.5 mmol), 10 mol % CuFe2O4, 20 mol % ligand, 2.0 equiv Cs2CO3,
110 ꢀC, 12 h and n-butyl alcohol (1b) as both solvent and substrate
(Table 2). Among them, 1,10-phenanthroline (L8) gave the highest
yield (Table 2, entry 14). In addition, the molar ratio of metal and
ligand, temperature, base, and reaction time were also tested. Un-
der the optimized conditions (2.5 mol % CuFe2O4, 5.0 mol % 1,10-
phenanthroline, 2.0 equiv of Cs2CO3, 110 ꢀC, 12 h reaction time,
and under argon atmosphere), an 88% GC yield of butyl phenyl
ether (1c) was obtained (Table 2, entry 23).
With the optimized conditions, the substrate scope was
subsequently investigated (Table 3). Aryl iodides with either
electron-donating or electron-neutral groups at the para posi-
tion reacted with n-butyl alcohol smoothly and the corre-
sponding aryl alkyl ethers were obtained with good yields
(Table 3, entries 1e3). Ortho-substituted iodobenzene was
slightly inert and only afforded a yield of 58%(Table 3, entry 4).
Interesting, the existence of free amino group was well toler-
ated, producing the desired product with a 72% yield. No CeN
self-coupling product was detected by GCeMS analysis (Table 3,
entry 5). Additionally, the system was chemoselective toward
iodides, providing a complete replacement of the iodo-group in
the presence of a bromo substituent on the aryl ring (Table 3,
entry 6). The left CeBr bond was very useful for late-stage
modifications.
In order to extend the scope of the proposed catalytic
system, the thioetherification had also been studied. As shown in
Scheme 1, both alkyl- and aryl thiols7 afforded good yields also.
The recycle experiment was also carried out adopting iodo-
benzene and n-butyl alcohol as the model substrates and the re-
sults were shown in Fig. 2. After the third run, when this catalyst
was simply grinded by an agate mortar, the yield raised to 82%
dramatically with 2.5 mol % of the used catalyst. In addition, even
in the seventh run, 86% yield could also be obtained with 2.5 mol %
previous used CuFe2O4, which indicated that the as-prepared
catalyst was highly stable in the reaction system. The XRD
K3PO4$3H2O 110
Net3
110
110
110
110
110
100
110
110
110
110
110
CsOAc
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
n.r.
89%
88%
70%
84%
81%
82%b
88%c
35%d
n.r.
a
AreI (0.5 mmol), CuFe2O4 (10 mol %), ligand (20 mol %), base (2.0 equiv), n-BuOH
(1.0 mL), 110 ꢀC, 12 h. GC yields.
b
Cs2CO3 was 1.5 equiv.
Reaction time was 24 h.
150 mg 4A molecular sieves were added.
c
d
patterns indicated that the crystal structure of the CuFe2O4
remained intact after third run (Fig. S7, ESI). This suggested that
the loss of the activity mainly came from the aggregation of the
CuFe2O4, which could be observed even by naked eyes. The
grinding re-dispersed the catalyst, which resulted in the dramatic
yield increase.
Only 4% GC yield was obtained when CuFe2O4 was absent, which
implied that the ROꢁ nucleophilic attack of AreX was not the main
mechanism. Aryl radical mechanism could also be excluded be-
cause very strong bases, such as t-BuOK or t-BuONa, were often
required to produce the aryl radical in the previous reports about
CeH activation of AreX.8 In addition, during our previous report,9
we found that Cs2CO3 was not strong enough to remove an ortho-
hydrogen from the AreX to produce aryne, which told us that the
aryne mechanism was not included. According to the above discuss
and the reactivity information of Table 3, we thought that the re-
action should proceed through oxidative addition followed by
a reductive elimination process. Firstly, AreX reacted with CuFe2O4,

S. Yang et al. / Tetrahedron 69 (2013) 3415e3418
3417
Table 3
CuFe2O4-catalyzed CeO coupling reactions between alkyl alcohols and aryl halides
Entry
1
AreX
ReOH
Product
Yielda
73
Scheme 1. The CuFe2O4/1,10-phenanthroline catalytic system was used in CeS bond-
forming reactions.
nBuOH
2
3
4
nBuOH
nBuOH
nBuOH
83
80
58
5
nBuOH
72
6
7
nBuOH
nBuOH
EtOH
82
65
71
81
82
Fig. 2. Cycle performance of the magnetic CuFe2O4, GC yields. 2.5 mol % catalyst (dark
gray color) and 5.0 mol % catalyst were used (gray color).
forming an [AreCuFe2O4eX] intermediate (a1). Then the ROH took
part in the reaction and coordinated with a1 using the oxygen atom
to form a2. Then a2 leaded to the product through reductive
elimination step with the help of Cs2CO3 (Scheme 2).
8
9
nPrOH
10
nAmylOH
11
12
13
nHexylOH
BnOH
78
80
75
14
15
iPrOH
n.r.
63
16
17
nBuOH
58
Scheme 2. A plausible mechanism.
3. Conclusions
nBuOH
nBuOH
44
In summary, we have demonstrated an efficient method for the
CeO coupling reactions between various kinds of unactivated alkyl
alcohols and aryl halides by using CuFe2O4 as catalyst, which is easy-
made, air-stable, low cost, easy separable and regenerable. The re-
action selectively proceeds to CeO bond formation when other
sensitive substituents, such as free amino group and double bond
exist in the system. It prefers to CeI bond over the CeBr bond in the
substrate also. In addition, primary aliphatic, cyclic alkyl, benzylic,
and allylic alcohols are all suitable substrates for this method.
18
n.r.
a
Unless otherwise stated, reaction conditions are: aryl halides (1.0 mmol),
CuFe2O4 (2.5 mol %), 1,10-phenanthroline (5.0 mol %), Cs2CO3(1.0 mmol, 2.0 equiv),
alcohol as solvent (1.0 mL), 110 ꢀC, under argon atmosphere, 12 h. Isolated yields.

3418
S. Yang et al. / Tetrahedron 69 (2013) 3415e3418
A. W. Angew. Chem., Int. Ed. 2003, 42, 5400e5449; (d) Monnier, F.; Taillefer, M.
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Chem., Int. Ed. 2009, 48, 6954e6971.
4.1. General
2. For palladium-catalyzed CeO coupling of alcohols, see: (a) Prim, D.; Campagne,
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All reactions were carried out in screw-capped pressure test tube
under argon. All the reagents are commercially available and were
used without further purification. DMSO, DMAc, NMP, DMF and tol-
uene were dried according to the standard processing. All solid ma-
terials were weighed inthe air.1H and 13C NMR spectra were recorded
on a 400 MHz spectrometer using CDCl3 as solvent and TMS as an
internal standard. Flash column chromatography was performed on
silica gel (200e300 mesh) using ethyl acetate and oil ether as eluant.
4.2. Generalprocedure forthecouplingreactionsofarylhalides
with alkyl alcohols
4. For copper-catalyzed CeO coupling of alcohols, see: (a) Manbeck, G. F.; Lipman,
A. J.; Stockland, R. A.; Freidl, A. L.; Hasler, A. F.; Stone, J. J.; Guzei, I. A. J. Org. Chem.
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A 25-mL Synthware pressure tube was flame-dried under vac-
uum and filled with argon after cooling to room temperature. To
this tube were added aryl halide (0.5 mmol), CuFe2O4 (2.5 mol %),
ligand (5.0 mol %), Cs2CO3 (1.0 mmol, 2.0 equiv). The tube was then
evacuated and backfilled with argon (3 cycles). Then, 1.0 mL alkyl
alcohol was loaded into a plastic syringe. After the tube was purged
with argon, the n-butyl alcohol was injected into bottom of the tube
using a long needle syringe. The rubber septum was replaced with
a Teflon screwcap, and the flask was sealed and placed into the
preheated 110 ꢀC oil bath stirring for 12 h. When the reaction was
cooled down to room temperature, the mixture was filtered
through a short plug of silica gel and washed with 40 mL CH2Cl2.
The combined organic phase was concentrated under vacuum. The
product was purified through flash column chromatography on
200e300 mesh silica gel with petroleum ether/ethyl acetate as
eluant with a suitable ratio according to the TLC experiments. The
identity and purity of the product were ascertained by GCeMS, FT-
IR, 1H, and 13C NMR spectroscopy.
Z.; Xu, J.; Hu, S. J. Org. Chem. 2009, 74, 5075e5078;
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(i) Zhang, H.; Ma, D.; Cao, W.
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Supplementary data
6. Zhang, R.; Miao, C.; Shen, Z.; Wang, S.; Xia, C.; Sun, W. ChemCatChem 2012, 4,
824e830.
Supplementary data (experimental procedures and compound
characterization data) associated with this article could be found in
the support information. Supplementary data associated with this
article can be found in the online version, at http://dx.doi.org/
10.1016/j.tet.2013.02.077.
7. GC yield. The product separation was interfered by the surplus benzenethiol.
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