CuS/Fe: A novel and highly efficient catalyst system for coupling reaction of aryl halides with diaryl diselenides

Article abstract of DOI:10.1016/j.tet.2010.09.061

The CuS catalyzed coupling reactions of aryl halides and diaryl diselenides were accelerated by the addition of Fe powder in only 3-12 h with good to excellent yields. SEM-EDX indicated that the in situ iron oxides as support against catalyst agglomeration accelerated the reaction. This catalyst system was also demonstrated recyclable without significant loss of catalytic activity.

Full text of DOI:10.1016/j.tet.2010.09.061

Tetrahedron 66 (2010) 8583e8586
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
CuS/Fe: a novel and highly efficient catalyst system for coupling reaction of aryl
halides with diaryl diselenides
*
Yaming Li , Huifeng Wang, Xiaoying Li, Tao Chen, Defeng Zhao
State Key Laboratory of Fine Chemicals, College of Chemical Engineering, Dalian University of Technology, Dalian 116012, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 July 2010
Received in revised form 11 September 2010
Accepted 17 September 2010
Available online 22 September 2010
The CuS catalyzed coupling reactions of aryl halides and diaryl diselenides were accelerated by the
addition of Fe powder in only 3e12 h with good to excellent yields. SEMeEDX indicated that the in situ
iron oxides as support against catalyst agglomeration accelerated the reaction. This catalyst system was
also demonstrated recyclable without significant loss of catalytic activity.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
like HMPA and high reaction temperature.8 The direct syntheses by
transition metal-catalyzed (Pd,9 Ni,10 Cu,11 and La12) coupling re-
During the past decade, a lot of efforts have been directed to-
ward the development of organoselenium compounds for their
potential as drug candidates.1 The examples include human breast
cancer cell growth inhibitor 1;2 Urdpase (uridine phosphorylase)
inhibitor 2 for treatment of various human solid tumors;3 a possible
lead compound for antitumor agent 3;4 potent inhibitor of 5-LOX
(lipoxygenases) 4;5 and RAR (retinoic acid receptors, 10 times more
potent than its sulfur analogue) agonist 5.6 In addition, many chiral
and achiral organoselenium compounds also exert catalytic role in
organic synthesis.7
actions of aryl donors with diaryl diselenides have become versatile
tools. However, these metal-catalyzed reactions involve the addi-
tion of ligands, well-defined catalysts, and long reaction times,
which may increase the cost and limit the scope of applications.
Thus, it is desirable to explore novel catalytic procedures for an
efficient route to such highly useful organic products. Nano CuO
was employed on the basis of this strategy.13 These processes were
demonstrated as efficient protocols for the synthesis of organo-
selenium. For the practical purpose, it is worthwhile to develop
a general, simple, and economical catalyst system for the coupling
of aryl halides with diaryl diselenides.
Br
O
MeO
MeO
Se
Br
N
H
Metal-Catalyzed
OMe
Se
ArX
+
(Ar'Se)2
ArSeAr'
OMe
NO2
3
OH
X=I, Br, Cl
9-12
Se
Pd, Ni, Cu, La /Ligand
Nano CuO 13
NO2
1
O
N
4
CuS / Fe, Ligand-f ree, 3-12 h, Recyclable This work
Se
HN
Se
O
CO OH
In the previous studies, our and other groups have reported that
copper-catalyzed S-arylation of diaryl disulfides with aryl ha-
lides.11,14 Based on the bond energy that the CeSe bond (243 kJ/
mol) is weaker than the CeS bond (272 kJ/mol), we considered our
catalyst systems for CeS coupling should be more efficient for
preparing the organic selenides. Herein, we would like to release it.
OH
O
2
5
Practical methods for the synthesis aryl selenides involved
harsh reaction conditions such as the use of polar and toxic solvent
2. Results and discussion
Our initial studies focused on the development of an optimum
set of reaction condition. In this approach, diphenyl diselenide and
* Corresponding author. Tel./fax: þ86 411 39893900; e-mail addresses: ymli@
dlut.edu.cn, yamingli@chem.dlut.edu.cn (Y. Li).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.061

8584
Y. Li et al. / Tetrahedron 66 (2010) 8583e8586
Table 1
4-methyl-iodobenzene were used as model substrates. These
studies showed that the desired aryl selenide formed in 88% yield
with 2 mol % CuI as catalyst, K2CO3 as base, and DMSO as solvent at
110 ꢀC in 15 h (Table 1, entry 1). However, the formation of the aryl
selenide product under the standard conditions also produced
undesired symmetrical diphenyl selenide in a 3% yield. Cu or CuS as
catalyst occurred to higher conversion but also along with the
byproduct observation. To our delight, the reaction was dramati-
cally accelerated by the addition of Fe powder and the aryl selenide
formed in 99% yield without side product. Further careful moni-
toring indicated that the reaction was able to complete only in 6 h
(Table 1, entry 6). Control experiments showed that Mg powder as
reductant formed lower yield product, FeCl3 and FeCl2 as co-cata-
lyst resulted in much low conversion and the sole Fe and FeS as
catalyst demonstrated no catalyst effect (Table 1, entries 7e10). The
Cu2S as catalyst shows similar activity as CuS (Table 1, entry 11), but
without the addition of Fe, the yield was decreased (Table 1, entry
12). It was noted that the polar donor solvent DMF was slightly
inferior to DMSO and weak polar solvent dioxane only gave trace
desired product.
Optimum of reaction conditionsa
Se
I
2.0 mol% [Cu]
+
(PhSe)2
K2CO3, DMSO
additive, 110 oC, A r
Entry
[Cu]
Time (h)
Additive
Yieldb (%)
1
2
3
4
5
6
7
8
CuI
Cu
15
15
15
15
15
6
6
6
6
6
88 (3)
93 (3)
94 (2)
99 (0)
89 (2)
99 (0)
30
CuS
CuS
CuS
CuS
CuS
CuS
Fe
Mg
Fe
FeCl3
FeCl2
Fe
FeS
Fe
45
9
Trace
Trace
99 (0)
73
10
11
12
13
Cu2S
Cu2S
CuS
6
6
6
Fe
30c
a
Reaction conditions: 1-iodo-4-methylbenzene (0.6 mmol), diphenyl diselenide
(0.3 mmol), [Cu] (0.012 mmol), additive (0.36 mmol), K2CO3 (0.6 mmol), and DMSO
(1 mL) stirred at 110 ꢀC under Ar.
To investigate the role of Fe powder, the prepared CuS and re-
covered CuS were characterized by scanning electron microscopic
scanning (SEM) and energy dispersive X-ray spectroscopy, re-
spectively (Fig. 1). The prepared CuS was flake by the SEM and the
b
GC yield (little symmetrical selenide was observed).
Without addition of K2CO3.
c
Fig. 1. SEMeEDX analyzed the catalyst: (a) SEM of CuS before reaction, (b) EDX of CuS before reaction, (c) SEM of surface CuS/Fe after reaction, (d) EDX of region CuS/Fe after
reaction, (e) SEM of point CuS/Fe after reaction and (f) EDX of point CuS/Fe after reaction.

Y. Li et al. / Tetrahedron 66 (2010) 8583e8586
8585
Table 3
elemental composition was regular 1:1 ratio of Cu and S by the EDX.
Recyclability experiments of the CuSa
After the reaction, the region EDX showed that the ratio of Cu and S
is also about 1:1, but the concentration of Fe increased dramatically
(Fig. 1c and d). It is presumable that CuS was reductive to Cu2S
based on the redox potential of Cu2þ/Fe. From the random points of
SEM, we observed that the 2:1 ratio of Cu and S appeared (Fig. 1e
and f), which indicated the formation of Cu2S. Besides, based on the
fact that the Fe powder binded to magneton as its magnet before
the stirring but most divorced after the reaction, we speculated that
the Fe powder not only reduced CuS to form the real catalyst Cu2S
but also in situ generated FexOy by the oxidation of DMSO. In the
course of redox reaction, the in situ formation of FexOy as support
dispersed the in situ Cu2S against agglomeration to accelerate the
reaction.
To demonstrate the scope of this novel transformation, we
studied the electronic and steric effects of attached groups at the
aryl halides and diphenyl diselenides moiety. In general, this
protocol efficiently coupled diphenyl diselenide with electron-
rich, electron-neutral, and electron-deficient aryl iodides. Sub-
strates with electron-withdrawing groups were more reactive
than those with electron-donating groups. It took only 3 h for
electron-withdrawing substituents (Table 2, 2i, 2j, 2k, and 2l).
Sterically ortho substituents did not hamper the arylation reaction
2 mol% CuS, Fe
I
+
Se Se
Se
DMSO, K2CO3,
110 oC, Ar, 6 h
0.6 mmol
Entry
0.3 mmol
Recycle
GC yield (%)
1
2
3
4
Run 1
Run 2
Run 3
Run 4
99
98
93
87
a
Reaction conditions: After the first run, a drop of resulting mixture was removed
and treated with H2O (1 mL) and ethyl acetate (0.2 mL). The organic layer was
detected by GC. Then to the tube was added fresh Fe powder (20.2 mg, 0.36 mmol),
diselenide (0.3 mmol), aryl halide (0.6 mmol) and reacted at 110 ꢀC for 6 h under
argon. The catalyst was used four times.
(Table 2, 2c, 2f, and 2h). Furthermore, methyl, methoxy, chloro,
bromo, ester, and cyano groups were well tolerated to afford the
corresponding cross-coupled products in excellent yield.
Aryl iodide with a free amino group was well tolerant without
the need of a protecting group (Table 2, 2g). We also observed
that iodobenzene was more reactive. Consequently, cross-
coupling reactions with chloro or bromo substituted aryl iodides
showed an interesting chemoselectivity to proceed exclusively at
the iodo group (Table 2, 2j, 2k, 2l). In fact, by prolonging the re-
action time, electron-deficient bromobenzene could also be effi-
ciently transformed in 12 h under the optimized conditions.
Heterocycle 2-bromopyridine was efficiently transformed to
corresponding aryl selenide in 93% yield (Table 2, 2o). At last,
when 4-chloro diphenyl diselenides were used, the correspond-
ing products were obtained in excellent to good yield (Table 2, 2l0,
2p, and 2q).
Table 2
Couplings of aryl halides with diaryl diselenidesa
X
Se
2.0 mol% CuS, Fe
+
(ArSe)2
K2CO3, DMSO
R1
R2
R1
X = I, Br
3 - 12 h, 110 oC, A r
R2 = H, Cl
Se
Se
Se
The recyclability of catalyst was also checked. After the first run,
a drop of reaction mixture was removed for GC analysis and to the
remaining mixture was added new raw materials for further cata-
lytic reactions. It was found that the catalyst could be reused for the
fresh cross-coupling reaction without significant loss of catalytic
activity (Table 3). This novel and efficient system is valuable in large
scale synthesis of aryl selenides considering the economical cost of
the catalyst.
2a, 6 h, 99%
2b, 6 h, 99%
2c, 6 h, 99%
Me O
Se
OMe
Se
Se
MeO
H2N
OMe
2d, 6 h, 94%
2e, 6 h, 90%
2f, 6 h, 90%
3. Conclusion
Se
Se
Se
In conclusion, we have explored a highly efficient and ligand-
free CuS/Fe catalyzed cross-coupling reaction of aryl halides with
diaryl diselenides. In this catalytic process, the addition of Fe
played an important role not only reduced CuS to form the real
catalyst Cu2S but also in situ generated FexOy as support against
catalyst agglomeration to accelerate the reaction. By this new
protocol, aryl halides reacted with diaryl diselenides at 110 ꢀC for
3e12 h giving corresponding aryl organoselenium with good to
excellent yields. In addition, this novel CuS/Fe system showed
widely functional-group-tolerant and well chemoselective. At last,
this catalyst system was also demonstrated recyclable without
significant loss of catalytic activity. We believe this simple and
effective catalyst system may find application in the synthesis of
the related organoselenium compounds.
EtOOC
2i, 3 h, 91%
Se
2g, 6 h, 82%
2h, 6 h, 98%
Se
Se
Br
Cl
Br
2l, X = I, 3 h, 91%
2j, 3 h, 98%
2k, 3 h, 98%
X = Br, 12 h, 28%
Se
Se
Se
N
O
NC
2m, X = I, 3 h, 98%
2n, X = Br, 12 h, 99%
2o, X = Br, 12 h, 99%
X = Br, 12 h, 96%
Se
Se
Se
4. Experimental
Cl
Cl MeO
Cl
2l', 6 h, 90%
2p, 6 h, 92%
2q 6 h, 84%
4.1. General information
a
Reaction conditions: 1-iodo-4-methylbenzene (0.6 mmol), diaryl diselenide
All reagents were obtained from commercial source (>99%)
and used without further purification. The reactions were
(0.3 mmol), CuS (0.012 mmol), Fe powder (0.36 mmol), K2CO3 (0.6 mmol) and
DMSO (1 mL) stirred at 110 ꢀC for 3e12 h under argon. Isolated yields.

8586
Y. Li et al. / Tetrahedron 66 (2010) 8583e8586
carried out under argon atmosphere. Gas chromatography
analyses were performed with an FID detector. All products
were isolated by column chromatography on silica gel (200e300
mesh) using petroleum ether (60e90 ꢀC) and ethyl acetate as
eluate. Compounds described in the literature were character-
ized by comparison of their 1H NMR, 13C NMR spectra and MS to
the reported data. 1H NMR and 13C NMR spectra were measured
in CDCl3 and chemical shifts were reported in parts per million
relative to TMS.
under argon. This process was repeated and the catalyst was used
four times.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (Project No. 20876021) and the Education
Department of Liaoning Province (2009S021).
Supplementary data
4.2. Experimental procedure for all compounds
Experimental procedures and characterization of the products.
Supplementary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2010.09.061.
4.2.1. The preparation of copper sulfide. CuS can be prepared by
slowly adding the solution of CuSO4 to the aqueous solution of
Na2S. The precipitated CuS was produced by filtration and
washing sequentially with H2O, EtOH, EtOAc and drying in vacuo
for 24 h. The block CuS was ground up into fine powder prior
to use.
References and notes
1. Sarma, B. K.; Mugesh, G. Org. Biomol. Chem. 2008, 6, 965e974; Nogueira, C. W.;
Zeni, G.; Rocha, J. B. Chem. Rev. 2004, 104, 6255e6285; Mugesh, G.; du Mont, W.
W.; Sies, H. Chem. Rev. 2001, 101, 2125e2179; Mugesh, G.; Singh, H. B. Chem. Soc.
Rev. 2000, 29, 347e357.
4.2.2. General procedure for the coupling of aryl halides with diaryl
diselenides. A flame-dried test tube with a magnetic stirring bar
was charged with CuS (1.3 mg, 0.012 mmol), Fe powder
(20.2 mg, 0.36 mmol), K2CO3 (82.8 mg, 0.6 mmol), diselenide
(0.3 mmol), aryl halide (0.6 mmol), and DMSO (1 mL) under ar-
gon. The mixture reacted at the indicated temperature for
3e12 h and cooled to room temperature. The resulting mixture
was extracted with ethyl acetate (3ꢁ25 mL). The combined or-
ganic layers were dried over Na2SO4 and then were concentrated
under vacuum. The residue was purified by column chroma-
tography on silica gel with an eluent of petroleum ether and
ethyl acetate. All the physical data of the known compounds
were in agreement with those reported in the literatures (see:
Supplementary data).
2. Engman, L.; Cotgreave, I.; Angulo, M.; Taylor, C. W.; Paine-Murrieta, G. D.;
Powis, G. Anticancer Res. 1997, 17, 4599e4605.
3. Goudgaon, N. M.; Naguib, F. N.; el Kouni, M. H.; Schinazi, R. F. J. Med. Chem. 1993,
36, 4250e4254.
4. Woods, J. A.; Hadfield, J. A.; McGown, A. T.; Fox, B. W. Org. Biomol. Chem. 1993, 1,
333e340.
5. Engman, L.; Stern, D.; Frisell, H.; Vessman, K.; Berglund, M.; Ek, B.; Andersson,
C. M. Org. Biomol. Chem. 1995, 3, 1255e1262.
6. Millois, C.; Diaz, P. Org. Lett. 2000, 2, 1705e1708.
7. Wirth, T. Tetrahedron 1999, 55, 1e28.
8. Liotta, D. Acc. Chem. Res.1984,17, 28e34; Suzuki, H.; Abe, H.; Osuka, A. Chem. Lett.
1981, 151e152; Rossi, R. A.; Penenory, A. B. J. Org. Chem. 1981, 46, 4580e4582.
9. Ranu, B. C.; Chattopadhyay, K.; Banerjee, S. J. Org. Chem. 2006, 71, 423e425;
Fukuzawa, S.; Tanihara, D.; Kikuchi, S. Synlett 2006, 2145e2147; Bonaterra, M.;
Martin, S. E.; Rossi, R. A. Tetrahedron Lett. 2006, 47, 3511e3515; Beletskaya, I. P.;
Sigeev, A. S.; Peregudov, A. S.; Petrovskii, P. V. J. Organomet. Chem. 2000, 605,
96e101; Gomez-Benitez, V.; Baldovino-Pantaleon, O.; Herrera-Alvarez, C.;
Toscano, R. A.; Morales-Morales, D. Tetrahedron Lett. 2006, 47, 5059e5062.
10. Baldovino-Pantaleon, O.; Hernandez-Ortega, S.; Morales-Morales, D. Adv. Synth.
Catal. 2006, 348, 236e242; Taniguchi, N. J. Org. Chem. 2004, 69, 6904e6906;
Cristau, H. J.; Chabaud, B.; Labaudiniere, R.; Christol, H. Organometallics 1985, 4,
657e661.
11. Taniguchi, N. J. Org. Chem. 2007, 72, 1241e1245; Kumar, S.; Engman, L. J. Org.
Chem. 2006, 71, 5400e5403; Chang, D. Z.; Bao, W. L. Synlett 2006, 1786e1788;
Wang, L.; Wang, M.; Huang, F. P. Synlett 2005, 2007e2010; Taniguchi, N.; Onami,
T. J. Org. Chem. 2004, 69, 915e920; Taniguchi, N.; Onami, T. Synlett 2003,
829e832; Gujadhur, R. K.; Venkataraman, D. Tetrahedron Lett. 2003, 44, 81e84.
12. Murthy, S. N.; Madhav, B.; Reddy, V. P.; Nageswar, Y. V. D. Eur. J. Org. Chem. 2009,
5902e5905; Nishino, T.; Okada, M.; Kuroki, T.; Watanabe, T.; Nishiyama, Y.;
Sonoda, N. J. Org. Chem. 2002, 67, 8696e8698.
4.2.3. The SEMeEDX experiments for recovered CuS. Following the
general procedure, the resulting mixture was treated with H2O
(10 mL) and ethyl acetate (3ꢁ5 mL). The catalyst was recovered
from the solution by centrifugation and then was dried under
vaccum. The brown solid was collected and then characterized by
SEMeEDX.
4.2.4. Recyclability experiments of the CuS. Following the general
procedure, after the first run completion, a drop of resulting mix-
ture was removed and treated with H2O (1 mL) and ethyl acetate
(0.2 mL). The organic layer was detected by GC. Then to the tube
was added fresh Fe powder (20.2 mg, 0.36 mmol), diselenide
(0.3 mmol), aryl halide (0.6 mmol) and reacted at 110 ꢀC for 6 h
13. Singh, D.; Alberto, E. E.; Rodrigues, O. E. D.; Braga, A. L. Green Chem. 2009, 11,
1521e1524; Saha, A.; Saha, D.; Ranu, B. C. Org. Biomol. Chem. 2009, 7,
1652e1657; Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11,
951e953; Alves, D.; Santos, C. G.; Paixao, M. W.; Soares, L. C.; de Souza, D.;
Rodrigues, O. E. D.; Braga, A. L. Tetrahedron Lett. 2009, 50, 6635e6638.
14. Wang, H. F.; Jiang, L. L.; Chen, T.; Li, Y. M. Eur. J. Org. Chem. 2010, 2324e2329.