Microwave-assisted Cu2O-catalyzed one-pot synthesis of symmetrical diaryl selenides from elemental selenium

Article abstract of DOI:10.1016/j.tetlet.2013.06.117

A novel and simple microwave-assisted one-pot protocol to prepare symmetrical diaryl selenides has been developed. A cross-coupling reaction between aryl iodide and elemental selenium takes place in the presence of KOH and a catalytic amount of Cu₂O/NH₂CH₂CH ₂NH₂, leading to C-Se bond formation. The reactions are highly efficient with a reaction time of 1 h under microwave irradiation and yields from 50% to 90%.

Full text of DOI:10.1016/j.tetlet.2013.06.117

Tetrahedron Letters 54 (2013) 4753–4755
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave-assisted Cu2O-catalyzed one-pot synthesis of symmetrical
diaryl selenides from elemental selenium
⇑
Shaozhong Zhang, Kranthi Karra, Christina Heintz, Erica Kleckler, Jin Jin
Department of Chemistry, Western Illinois University, Macomb, IL 61455, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and simple microwave-assisted one-pot protocol to prepare symmetrical diaryl selenides has
been developed. A cross-coupling reaction between aryl iodide and elemental selenium takes place in
the presence of KOH and a catalytic amount of Cu2O/NH2CH2CH2NH2, leading to C–Se bond formation.
The reactions are highly efficient with a reaction time of 1 h under microwave irradiation and yields from
50% to 90%.
Received 27 May 2013
Revised 15 June 2013
Accepted 22 June 2013
Available online 29 June 2013
Published by Elsevier Ltd.
Keywords:
Diaryl selenides
Symmetrical
Aryl iodides
Microwave-assisted
Copper(I) oxide
Introduction
are economical, less toxic, and take less time. The use of micro-
wave-assisted transition metal-catalyzed coupling reactions has
Selenium is an important trace element involved in different
physiological functions of the human body. Recent research and
clinical studies strongly support the protective role of selenium
against various types of cancer.1 Organoselenium compounds have
attracted much attention in recent decades due to their important
biological effects2 and their application as chiral catalysts.3 In par-
ticular, many diaryl selenides possess anticancer, antitumor, anti-
viral, antimicrobial, and antioxidant properties.4
advanced greatly in recent years.15 Microwave dielectric heating
causes an extremely rapid and uniform energy transfer to the reac-
tants of chemical reactions.16 Here we report a microwave-as-
sisted, copper (I) oxide-catalyzed cross-coupling reaction of aryl
iodide and easily available elemental selenium in the presence of
KOH to yield symmetrical diaryl selenides.
Results and discussion
Traditional methods for the synthesis of diaryl selenides require
the use of strong reducing agents such as Na or NaH, and harsh
reaction conditions, such as high reaction temperatures, UV light,
and the use of toxic solvents like HMPA.5 In order to overcome
these drawbacks, transition metal-catalyzed cross- coupling reac-
tions between aryl halides and aryl selenol,6 diaryl diselenides,7
or potassium selenocyanate8 have emerged as an alternative meth-
od for the synthesis of diaryl selenides. Palladium,9 nickel,10 lan-
thanum,11 iron,12 indium,13 and copper-based14 catalytic systems
have been studied for this cross-coupling reaction. However, most
of these reactions take a long time to complete (12–24 h).6–14
Moreover, one of the two commonly used selenium sources, aryl
selenol, is foul-smelling, and the other, diaryl diselenide, is not al-
ways commercially available and requires extra preparation steps.
Therefore, it is very desirable to explore reaction conditions with
an easily available selenium source and new catalytic systems that
We recently reported a novel method to synthesize diaryl tellu-
rides in a catalyst-free condition using Te0 as the chalcogen source
in the presence of KOH.17 We were trying to apply this approach to
prepare the selenium analogues, diaryl selenides. However, we
found that no reaction occurred for the selenium compounds. We
therefore switched to exploring a catalytic system for the synthesis
of diaryl selenides. In order to optimize the protocol and to under-
stand the influence of different variables in this reaction, p-iodotol-
uene and Se were chosen as the model substrates.
The reaction was screened with various copper catalysts, li-
gands, bases, and solvents (Table 1). First, several copper catalysts
were screened and Cu2O (Table 1, entry 4) was shown to be preem-
inent for this reaction compared to other copper catalysts such as
CuI, CuO, and Cu(OAc)2 (Table 1, entries 1–3). It was then found the
reaction gave a poor yield when no NH2CH2CH2NH2 was added as a
ligand, even if one of two other ligands, L2 and L3, were used (Ta-
ble 1, entries 5, 8, and 9). The amount of elemental Se was screened
and the best yield was given when 0.8 equiv of Se was used
⇑
Corresponding author. Tel.: +1 309 298 2261; fax: +1 309 298 2180.
E-mail addresses: j-jin@wiu.edu, jinegg2@gmail.com (J. Jin).
0040-4039/$ - see front matter Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2013.06.117

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S. Zhang et al. / Tetrahedron Letters 54 (2013) 4753–4755
Table 1
Screening of reaction conditions for the synthesis of bis(p-tolyl)selenidea
L1: NH2CH2CH2NH2
NH2
I
Se
Se, catalyst/ligand
L2:
NH2
base solvent
120 oC
L3:
N
N
Entry
Se0 (equiv)
Catalyst
Ligand
Base
Solvent
Time (h)
Yieldb (%)
1c
0.6
0.6
0.6
0.6
0.6
0.8
1.0
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
Cul
CuO
L1
L1
L1
L1
–
L1
L1
L1
L1
L1
L1
L1
L1
L1
–
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
NaOH
K2CO3
CS2CO3
KOH
KOH
KOH
–
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
1
67
60
43
74
34
92
77
55
35
70
33
90
44
0
2c
3c
Cu(OAc)2
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
–
4c
5c
6c
7c
8c
9c
10c
11c
12c
13c
14c
15c
16c
17d
CH3CN
DMSO
DMSO
DMSO
0
0
93
Cu2O
Cu2O
L1
L1
KOH
a
b
c
Reaction conditions: p-iodotoluene (1.0 mmol), selenium (0.6–1.0 mmol), catalyst (0.2 mmol), ligand (0.2 mmol), base (2.0 mmol), solvent (2 mL), 120 °C.
Isolated yield.
Using oil bath.
Using microwave synthesizer.
d
Table 2
Synthesis of symmetrical diaryl selenides via the one-pot procedurea
Table 2 (continued)
Se, Cu2O, NH2CH2CH2NH2
Ar
I
Ar Se Ar
Yieldb (%)
1k, 75
KOH, DMSO
Entry Aryl iodide
Product
MW, 120 oC, 1 h
O2N
O2N
NO2
I
Entry Aryl iodide
Product
Yieldb (%)
1a, 93
11
Se
NC
Se
CN
I
I
Se
1
12
1l, 71
CN
I
Se
Se
2
1b, 95
1c, 96
13
1m, 68
1n, 85
I
Se
Se
S
S
3
S
I
I
I
14
HO
Se
OH
N
N
N
4
1d, 58
1e, 82
1f, 95
HO
Reaction conditions: aryl iodide (1 equiv), Se0 (0.8 equiv), Cu2O (20 mol %),
NH2CH2CH2NH2 (20 mol %), KOH (2 equiv), DMSO (2 mL), MW, 120 °C, 1 h.
a
I
H2N
H3CO
Se
NH2
OCH3
5
b
Isolated yield.
H2N
I
I
Se
6
H3CO
(Table 1, entry 6). With 0.6 equiv of Se, some unreacted p-iodotol-
uene remained, while with 1.0 equiv of Se used, a certain amount
of bis(p-tolyl)diselenide was detected as a byproduct. The effect of
bases was also investigated (Table 1, entries 10–12), and KOH was
found to be most effective compared to NaOH and K2CO3. Cs2CO3
was also an effective base for this reaction. DMSO was found to
be the best solvent compared to DMF and CH3CN (Table 1, entries
13 and 14). The control experiments confirmed the reaction did not
occur in the absence of catalyst, or the base (Table 1, entries 15 and
16). Finally the reaction was carried out in a microwave synthe-
sizer (BiotageÒ Initiator) using the optimized conditions obtained
from the oil bath, and the reaction was greatly accelerated with a
reaction time of 1 h to complete (Table 1, entry 17) compared to
H3CO
Se
7
1g, 94
H3CO
OCH3
I
Se
NH2 H2N
Se
8
1h, 77
1i, 93
1j, 78
NH2
I
Cl
Cl
9
Cl
I
O2N
Se
NO2
10
O2N

S. Zhang et al. / Tetrahedron Letters 54 (2013) 4753–4755
4755
2 Se2- + SeO3 + 3 H2O
2-
3 Se + 6 OH-
Acknowledgments
a
We are grateful to the financial support of the Western Illinois
University Research Council Grant and College of Arts and Sciences.
We also would like to thank Dr. Jeff E. Engel for proofreading our
manuscript.
I-
exchange
I
Ar
b
-Se
Ar
Supplementary data
c
addition
= Cu2O
elimination
Supplementary data (full experimental details and spectro-
scopic data of all compounds, 1H, 13C NMR, and HRMS data) asso-
ciated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2013.06.117.
Ar-Se-
Ar-I
d
elimination
exchange
I
Ar-Se-Ar
Ar
ArSe
References and notes
f
b
Ar
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Figure 1. Proposed mechanism for the Cu2O-catalyzed synthesis of ArSeAr.
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strates also provided high yields of diaryl selenides (Table 2, en-
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On the basis of a previous report19 for the synthesis of diaryl
diselenides, a plausible mechanism for the Cu2O-catalyzed cross-
coupling of aryl iodides with elemental selenium to obtain diaryl
selenides is proposed, as depicted in Figure 1.
Under a superbasic DMSO–KOH system, elemental selenium
undergoes a disproportionation reaction to give selenolate anion
a. We assume that this ion might serve as the active species in
the catalytic cycle. The oxidative addition of ArI to Cu2O catalyst
forms complex b, which is converted to complex c by the ligand
exchange with the selenolate anion a. Complex c could undergo
reductive elimination to give the initial coupling product ArSeÀ
d
and regenerate the Cu2O catalytst. The intermediate d ArSeÀ would
react with another complex b furnishing complex e. Finally, a
reductive elimination could afford the desired diaryl selenide prod-
uct f and release Cu2O for use in the next catalytic cycle.
17. Zhang, S.; Karra, K.; Koe, A.; Jin, J. Tetrahedron Lett. 2013, 54, 2452–2454.
18. General procedure for the synthesis of diaryl selenides:
A microwave tube
containing a magnetic stirring bar was charged with aryl iodide (1.0 mmol), Se0
(1.0 mmol), Cu2O (0.2 mmol), ethylene diamine (0.2 mmol), KOH (2.0 mmol),
and DMSO (2 mL) under nitrogen. The reaction mixture was heated and stirred
in a microwave synthesizer (BiotageÒ Initiator) at 120 °C for 1 h. After the
reaction was complete, the reaction mixture was allowed to cool, and treated
with CH2Cl2 and H2O. The organic layer was washed with brine solution, dried
with Na2SO4, and concentrated under vacuum. The residue was purified by
column chromatography on silica gel with an eluent consisting of hexanes and
ethyl acetate affording the corresponding diaryl selenides in good yields. Di(p-
tolyl)selane (1a). Light yellow solid, mp 65–66 °C; Yield: 93%; 1H NMR
(300 MHz, CDCl3), d (ppm): 7.35 (d, J = 9 Hz, 4H), 7.07 (d, J = 9 Hz, 4H), 2.32 (s,
6H). 13C NMR (75 MHz, CDCl3), d (ppm): 137.3, 133.1, 130.2, 127.9, 21.2. HRMS
(EI): Calcd for [C14H14Se]+ 262.0261; Found 262.0257.
Conclusion
In conclusion, a simple and highly efficient microwave-assisted
one-pot approach is described for the synthesis of symmetrical dia-
ryl selenides. This methodology, using elemental Se powder and
aryl iodide as starting materials, KOH as a base, and Cu2O/NH2CH2-
CH2NH2 as a catalyst, allows the preparation of a wide range of
substituted symmetrical diaryl selenides with good yields.
19. Singh, D.; Deobald, A. M.; Camargo, L. R. S.; Tabarelli, G.; Rodrigues, O. E. D.;
Braga, A. L. Org. Lett. 2010, 12, 3288–3291.