Copper-catalyzed one-pot tandem synthesis of unsymmetrical diaryl chalcogenides from two different aryl iodides

Article abstract of DOI:10.1016/j.tetlet.2015.11.062

Unsymmetrical diaryl chalcogenides were synthesized by a novel one-pot tandem process from two different aryl iodides. A symmetrical diaryl dichalcogenide (ArEEAr, E = Se or Te) was initially obtained by a Cu₂O-cataylzed coupling reaction of Ar

Full text of DOI:10.1016/j.tetlet.2015.11.062

Accepted Manuscript
Copper-catalyzed one-pot tandem synthesis of unsymmetrical diaryl chalcoge-
nides from two different aryl iodides
Shaozhong Zhang, Adam Koe, Christina Heintz, Aunajay Senior, Jin Jin
PII:
S0040-4039(15)30369-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.11.062
TETL 47002
Reference:
Tetrahedron Letters
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Received Date:
Revised Date:
Accepted Date:
11 October 2015
20 November 2015
21 November 2015
Please cite this article as: Zhang, S., Koe, A., Heintz, C., Senior, A., Jin, J., Copper-catalyzed one-pot tandem
synthesis of unsymmetrical diaryl chalcogenides from two different aryl iodides, Tetrahedron Letters (2015), doi:
http://dx.doi.org/10.1016/j.tetlet.2015.11.062
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Graphical Abstract
Copper-catalyzed one-pot tandem synthesis of
unsymmetrical diaryl chalcogenides from two different
aryl iodides
Leave this area blank for abstract info.
Shaozhong Zhang, Adam Koe, Christina Heintz, Aunajay Senior, Jin Jin*
Department of Chemistry, Western Illinois University, Macomb, IL 61455
E0, Cu2O, NH2CH2CH2NH2
Ar'I, Cu2O, NH2CH2CH2NH2
KOH, DMSO
ArI
ArEEAr
ArEAr'
KOH, DMSO
90 oC, 18 h
E = Se or Te 110 oC, 12 h

1
Tetrahedron Letters
Copper-catalyzed one-pot tandem synthesis of unsymmetrical diaryl
chalcogenides from two different aryl iodides
Shaozhong Zhang, Adam Koe, Christina Heintz, Aunajay Senior and Jin Jin*
Department of Chemistry, Western Illinois University, Macomb, IL 61455
ARTICLE INFO
ABSTRACT
Unsymmetrical diaryl chalcogenides were synthesized by a novel one-pot tandem process from
two different aryl iodides. A symmetrical diaryl dichalcogenide (ArEEAr, E = Se or Te) was
initially obtained by a Cu2O-cataylzed coupling reaction of ArI with elemental selenium or
tellurium in the presence of KOH. Without purification, it was subsequently coupled with a
different aryl iodide (Ar’I) to give the unsymmetrical diaryl chalcogenides (ArEAr’) in good
yield.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
unsymmetrical
2009 Elsevier Ltd. All rights reserved.
Diaryl chalcogenides
One-pot tandem synthesis
Aryl iodides
Copper (I) oxide
and PhTeTePh. Otherwise the dichalcogenide precursors need to
be prepared in advance.
Introduction
There has been a growing interest in organochalcogen
compounds in the past few decades. A major breakthrough for
the development of organoselenium chemistry was the
recognition of selenoxide syn-elimination as a powerful olefin
forming method in 1970s.1 It prompted a renewed interest to
discover other chalcogen-based reagents and reactions. A number
of organochalcogenides are known to be biologically active.2 In
particular, diaryl chalcogenides are known to have anticancer,
antitumor, antiviral, antimicrobial and antioxidant properties.3
Today chalcogen chemistry find application in many areas such
In order to avoid the foul-smelling, expensive and less
available arene chalcogens, the use of easily available chalcogen
sources as coupling partners is of great interest. Li and coworkers
developed
a Cu-catalyzed approach for the synthesis of
symmetrical diaryl sulfides or selenides with Na2S or Se as
chalcogen sources.12 We recently reported a microwave-assisted
one-pot protocol to prepare symmetrical diaryl selenides using Se
as the chalcogen source in the catalyst of Cu2O.13 A one-pot
synthesis is much desired by chemists since avoiding a lengthy
separation process and purification of the intermediate
compounds would save time and resources while increase
chemical yields.
4
as organic synthesis,2c, synthesis of conducting materials and
semiconductors,5 and ligand chemistry.6 Additionally,
organochalcogen compounds have been used extensively in
carbon-carbon bond forming reactions.7 For example, diaryl
tellurides have been used as electrophilic partners in some
palladium-catalyzed cross-coupling reactions including Heck8
and Negishi reactions.9
Here we report a one-pot tandem process to synthesize
unsymmetrical diaryl selenides and tellurides involving two
coupling reactions. The first coupling reaction was accomplished
by aryl iodide (ArI) and elemental selenium or tellurium
catalyzed by Cu2O to give a symmetrical diaryl dichalcogenide
(ArEEAr), which was subsequently coupled with a second aryl
iodide (Ar’I) in a one-pot reaction without any purification. With
this protocol, a various combination of unsymmetrical diaryl
selenides (ArSeAr’) and tellurides (ArTeAr’) were obtained in
good yields.
The preparation of unsymmetrical diaryl chalcogenides was
mainly achieved by two pathways: (a) traditional methods in
which aryllithiums/aryl Grignard reagents were coupled with aryl
dichalcogenide (ArEEAr, E = Se, Te) precursors10 and (b)
transition metal-catalyzed coupling of aryl halides/boronic acids
with aryl dichalcogenide precursors.11 Transition metal-catalyzed
aryl carbon-chalcogen bond formation is an important method for
the preparation of unsymmetrical organo-chalcogenides and have
been explored by many researchers.11 Various metals including
palladium, nickel, iron, indium and copper have been utilized to
catalyze the coupling reactions of aryl halides or boronic acids
with aryl dichalcogenide precursors.11 Many of the syntheses,
however, are limited to phenyl selenides (PhSeAr) or phenyl
tellurides (PhTeAr), since only limited numbers of diaryl
Results and discussion
In the one-pot synthesis, intermediate purification isn’t
necessary, so the risk of unwanted products and side reactions are
more probable. In order to get better yields and selectivity,
selection of the catalyst is critical to the catalytic system. Tandem
catalysis is categorized into three subclasses: orthogonal-, auto-,
and assisted-tandem catalysis. Auto-tandem catalysis is defined
as a process in which one catalyst promotes more than two
dichalcogenides are commercially available such as PhSeSePh
———
* Corresponding author. Tel.: +1-309-298-2261; e-mail: j-jin@wiu.edu

2
Tetrahedron Letters
Under the optimized conditions, various combinations of aryl
fundamentally different reactions in a single reactor. Since
iodides were investigated for the one-pot tandem synthesis of
unsymmetrical diaryl selenides as well as unsymmetrical diaryl
tellurides.15 The outcome is listed in Table 2. It was observed that
the electronic properties of different substituents on the aryl rings
did not affect the two coupling reactions much since both
electron-donating groups (e.g., Me, NH2, and OMe) and electron-
withdrawing groups (e.g., Cl, NO2, and CN) worked well. It was
also noticed that sterically hindered ortho and meta substrates
also provided good yields of unsymmetrical diaryl selenides. A
larger scale (5 mmol) reaction was performed on the one-pot
synthesis of 4-chlorophenyl 4’-methylphenyl selenide, 2. The
yield was found to be 64%, which suggests this methodology
also applies to larger scale reactions.
diaryl dichalcogenide (ArEEAr) is an important intermediate to
prepare unsymmetrical diaryl chalcogenide (ArEAr’) through the
coupling reaction, our main goal in this work is to seek a catalyst
which will work effectively for both symmetrical diaryl
dichalcogenides
(ArEEAr)
and
unsymmetrical
diaryl
chalcogenides (ArEAr’) syntheses. Therefore if the common
catalyst is found, the tandem synthesis of unsymmetrical diaryl
chalcogenide could be accomplished.
There are a variety of methods to prepare organic
diselenides or ditellurides,14 such as the reaction between
Grignard or organolithium reagents and elemental selenium or
tellurium followed by oxidation. However these methods are not
suitable for our tandem synthesis in consideration of the second
coupling leading to the final product ArEAr’. Since we
successfully prepared symmetrical diaryl selenides (ArSeAr)
through the coupling reaction between aryl iodide and elemental
selenium in the presence of a catalytic amount of Cu2O,4 we
attempted to use the same catalytic system to first give diaryl
diselenide (ArSeSeAr) intermediate, which expectantly would
further couple with a second aryl iodide (Ar’I) to form the final
unsymmetrical diaryl selenide (ArSeAr’) under the same catalyst.
Table 1
Optimum of reaction conditions
H3CO
ArSeSeAr
I
[Cu]
Se
Se, [Cu]
i.
,
ii.
OCH3
I
Entry
Yield (%)a
[Cu]
Se (equiv.)
Cu2O
Cu2O
Cu2O
Cu2O
CuO
1
3
50
72
64
In order to find proper reaction conditions and to explore the
influence of different variables in the one-pot synthesis, several
components were studied. To this end, our initial investigation
aimed at the preparation of 4-methylphenyl 4’-methoxyphenyl
selenide as a model target molecule. We undertook a detailed
study on the two consecutive coupling reactions and the results
are summarized in Table 1.
2
2
3
4
1.5
1
2
50
60
5
6
CuI
2
54
Cu(OAc)2
CuI/Cu2Sb
The first coupling reaction to generate the intermediate 1,2-
di(p-tolyl)diselenide employed 4-iodotoluene and elemental Se as
substrates. Without purification, the diselenide intermediate
would subsequently couple with 4-iodoanisole to give the final
unsymmetrical product 4-methylphenyl 4’-methoxyphenyl
selenide, 1. Herein several variables for the reactions were
studied: copper catalyst, amount of Se powder, and reaction
temperatures for the two coupling reactions. It should be noted
that the two possible by-products in the one-pot synthesis are the
symmetrical diaryl selenides (ArSeAr and Ar’SeAr’) formed
from the first and second aryl iodide respectively.
7
8
2
2
39
trace
a. Isolated yield
b. CuI in step i; Cu2S in step ii.
Reaction conditions: i. 4-iodotoluene (1 mmol), Se, [Cu] (0.2 equiv.), H2NCH2CH2NH2
(0.2 equiv.), KOH (2 equiv.), and DMSO (2 mL) stirred at 90 oC for 18 h under N2. ii.
4-iodoanisole (1 mmol), [Cu] (0.2 equiv.), H2NCH2CH2NH2 (0.2 equiv.), KOH (2
equiv.), and DMSO (2 mL) stirred at 110 oC for 12 h under N2.
Finally a plausible reaction pathway based on the Cu2O-
catalyzed one-pot tandem synthesis of unsymmetrical diaryl
selenides was proposed as shown in Figure 1.
Using Cu2O as the catalyst, different equivalents of Se
powder were attempted. We found the best yield was obtained
when 2 equiv. of Se powder was used (Table 1, entry 2). With 3
equiv. of Se (Table 1, entry 1), an increased ratio of the
symmetrical selenide from the second aryl iodide (p-OMePh)2Se
was detected due to the residue of excess selenium source.
However, when the amount of Se was reduced to 1.5 equiv. or 1
Under
a superbasic DMSO-KOH system, elemental
selenium undergoes a disproportionation reaction to give
selenolate anion a, which may further react with Se0 to give
diselenolate anion b. The oxidative addition of ArI to Cu2O
catalyst forms complex c, which is converted to complex d by the
ligand exchange with the diselenolate anion b. Complex d could
undergo reductive elimination to give the initial coupling product
ArSeSe- e and regenerate the Cu2O catalytst. The intermediate e
ArSeSe- would react with another complex c furnishing the
complex f. A reductive elimination could afford the diselenide
intermediate g and release Cu2O for use in the next catalytic
cycle.
equiv. (Table 1, entry 3 and 4),
an increased ratio of the
symmetrical selenide from the first aryl iodide (p-MePh)2Se
suggested that the diselenide intermediate was not efficiently
prepared. With 2 equiv. of Se powder, we also tried other copper
catalysts such as CuO (Table 1, entry 5), CuI (Table 1, entry 6),
Cu(OAc)2 (Table 1, entry 7) or the combination of two catalysts
(CuI and Cu2S, Table 1, entry 8) for the two coupling reactions
respectively, but none obtained better yields compared to Cu2O.
The reaction temperature was also studied and we found the first
coupling reaction to give the diselenide intermediate required a
Similarly, the second coupling reaction started once
complex h was formed after addition of the second aryl iodide
Ar’I. Ligand exchange might give complex i, which would
undergo reductive elimination to give the final unsymmetrical
diaryl selenide.
o
relatively lower temperature 90 C to prevent the decomposition,
while the second coupling reaction between diselenide and a
second aryl iodide would benefit from a higher temperature 110
oC.

3
Conclusion
Table 2.
In conclusion, we have developed a one-pot tandem process to
prepare unsymmetrical diaryl chalcogenides from two different
aryl iodides. The synthesis involves two consecutive coupling
reactions catalyzed by Cu2O. The first coupling reaction between
the first aryl iodide and elemental chalcogen (Se/Te) afforded the
intermediate diaryl dichalcogenide. Without purification, it was
subsequently coupled with a second aryl iodide (Ar’I) to give the
final product unsymmetrical diaryl selenide (ArEAr’) in good
yield.
Synthesis of unsymmetrical diaryl selenides via the one-pot
procedure
E0 (2 eq), Cu2O (0.2 eq),
Ar'I (1 eq), Cu2O (0.2 eq),
NH2CH2CH2NH2 (0.2 eq)
NH2CH2CH2NH2 (0.2 eq)
ArI
ArEAr'
ArEEAr
KOH (2 eq), DMSO, 90 oC, 18 h, N2
,
KOH (2 eq), DMSO, 110 oC, 12 h
E = Se or Te
Entry
Yield (%)
E
Ar
Ar'
Product
Se
I
I
I
Se
1
1
72
H3CO
Cl
OCH3
Se
Acknowledgments
I
I
I
Se
69
58
2
3
2
3
,
,
,
Cl
We are grateful to NSF MRI award (Acquisition of a 400-
MHz NMR Spectrometer to Support Faculty-Student Research
and Training at WIU and Partner Institutions), college of arts and
science at WIU for financial support.
S
Se
Se
S
I
Se
I
I
4
5
Se
4
5
68
70
O2N
NO2
Se
I
Se
Se
Se
H3CO
H3CO
Supplementary data
Se
Se
I
I
I
I
6
7
65
81
Full experimental details and spectroscopic data of all
compounds, 1H and 13C NMR, HRMS data can be found.
Supplementary data associated with this article can be found.
6
7
H3CO
H3CO
Cl
H3CO
H3CO
Cl
H2N
NH2
Se
I
I
Se
8
62
8
H3CO
H3CO
H3CO
H3CO
NC
CN
I
References and notes
Se
I
I
Se
Se
9
9
76
57
1. (a) Walter, R.; Roy, J. J. Org. Chem. 1971, 36, 2561-2563. (b) Juguet, L. J.
Adv. Chem. Ser. 1967, 76, 345-351.
Cl
Cl
H3CO
Se
H3CO
I
I
10
10
O2N
NO2
2. (a) Wirth, T., Ed.; Organoselenium Chemistry: Topics in Current
Chemistry, Springer: Berlin, 2000; Vol. 208. (b) Ogawa, A. Selenium and
Tellurium in Organic Synthesis. In Main Group Metals in Organic Synthesis;
Yamamoto, H.; Oshima, K., Ed.; Wiley-VCH: Weinheim, Germany, 2004,
Vol. 2, pp 813-866. (c) Nogueira, C. W.; Rocha, J. B. Arch. Toxicol. 2011,
85, 1313-1359.
I
I
Se
Se
Se
Te
Te
11
12
88
82
11
12
13
Cl
Cl
Se
Te
Te
I
I
I
,
H3CO
H3CO
Cl
OCH3
I
I
3. (a) Sarma, B. K.; Manna, D.; Minoura, M; Mugesh, G. J. Am. Chem. Soc.
2010, 132, 5364-5374. (b) Bernardon, J.-M.; Diaz, P. PCT Int. Appl. 1999,
WO 9965872 A1 19991223. (c) Back, T. g.; Moussa, Z. J. Am. Chem. Soc.
2003, 125, 13455-13460. (d) Anderson, C.-M.; Hallberg, a.; Hogberg, T. Adv.
Drug. Res. 1996, 28, 65-180.
13
56
64
OCH3
Cl
14
14
,
4. (a) Paulmier, C. In Selenium Reagents and Intermediates in Organic
Synthesis; Baldwin , J. E. ed.; Pergamon Press: Oxford, 1986, Organic
Chemistry Series 4. (b) Wirth, T. Tetrahedron 1999, 55, 1-28. (c) Wirth, T.
Angew. Chem. Int. Ed. 2000, 39, 3740-3749. (d) Freudendahl, D. M.; Santoro.
S.; Shahzad, S. A.; Santi, C.; Wirth, T. Angew. Chem. Int. Ed. 2009, 48,
8409-8411.
2-
2 Se2- + SeO3 + 3 H2O
3 Se + 6 OH-
a
Se
2-
Se2
ArSeAr'
b
5. (a) Bryce, M. R. Chem. Soc. Rev. 1991, 20, 355-390. (b) Kanatzidis, M. G.;
Huang, S. Coord. Chem. Rev. 1994, 130, 509-621. (c) Hitchman, M. L.;
Jenson, K. f. Chemical Vapou Deposition: Principles and Applications;
Academic Press: London, 1993.
I-
exchange
I
Ar
c
-SeSe
Cu2O
Ar
Ar'I
ArSe
d
Ar' addition
6. (a) Levason, W.; Reid, G. In Handbook of Chalcogen Chemistry;
Devillanova, F. A., Ed., RSC Publishing: Cambridge, U.K., 2007. (b)
Englich, U.; Ruhlandt-Senge, K. Coord. Chem. Rev. 2000, 210, 135-179. (c)
Panda, A. Coord. Chem. Rev. 2009, 253, 1056-1098.
i
= Cu2O
elimination
ArSeI
Ar-SeSe-
e
Ar-I
I
Ar'
elimination
h
Ar-SeSe-Ar
I
g
7. (a) Patai, S.; Rappoport, Z. In The Chemistry of Organic Selenium and
I-
ArSeSe
Ar
Tellurium Compounds; John Wiley & Sons: New York, 1985; Vol 1. (b)
Petragnani, N.; Comasseto, J. V. Synthesis 1991, 793-817. (c) Petragnani, N.;
Stefani, H.A. Tetrahedron, 2005, 61, 1613-1679. (d) Kawaguchi, S.;
Srivastava, P.; Engman, L. Tetrahedron Lett. 2011, 52, 4120-4122. (e)
Nishibayashi, Y.; Cho, C. S.; Uemura, S. J. Organomet. Chem. 1996, 507,
197-200.
Ar
c
f
Figure 1. Proposed mechanism for the Cu2O-catalyzed synthesis of ArSeAr'

4
Tetrahedron Letters
8. Nishibayashi, Y.; Cho, C. S.; Uemura, S. J. Organomet. Chem. 1996, 507,
197-200.
9. Stefani, H. A.; Pena, J. M.; Manarin, F.; Ando, R. A.; Leal, D. M.;
Petranani, N. Tetrahedron Lett. 2011, 52, 4398-4401.
10. (a) Mugesh, G.; Singh, H. B. Acc. Chem. Res. 2002, 35, 226-236. (b)
Kumar, S.; Singh, H. B.; Wolmershauser, G. Organometallics, 2006, 25, 382-
393.
11 (a) Li, Y.; Wang, H.; Li, X.; Chen, T.; Zhao, D. Tetrahedron, 2010, 66,
8583-8586. (b) Alves, D.; Santos, C. G.; Paixao, M. W.; Soares, L. C.; Souza,
D.; Rodrigues, O. E. D.; Braga, A. L. Tetrahedron Lett. 2009, 50, 6635-6638.
(c) Kumar, S.; Engman, L. J. Org. Chem. 2006, 71, 5400-5403. (d) Gujadhur,
R. K.; Venkataraman, D. Tetrahedron, 2003, 44, 81-84. (e) Beletskaya, I. P.;
Sigeev, A. S.; Peregudov, A. S.; Petrovskii, P. V. J. Organomet. Chem. 2000,
605, 96-101. (f) Bhadra, S.; Saha, A.; Ranu, B. J. Org. Chem. 2010, 75, 4864-
4867. (g) Ren, K.; Wang, M.; Wang, L. Org. Biomol. Chem. 2009, 7, 4858-
4861. (h) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett.
2009, 11, 951-953.
12. Li, Y.; Nie, C.; Wang, H.; Li, X.; Verpoort, F.; Duan, C. Eur. J. Org.
Chem. 2011, 7331-7338.
13. Zhang, S.; Karra, K.; Heintz, C.; Kleckler, E.; Jin, J. Tetrahedron Lett.
2013, 54, 4753-4755.
14 (a) Gladysz, J.; Hornby, J.; Garbe, J. E.; J. Org. Chem. 1978, 43, 1204-
1207. (b) Krief, A.; Derock, M. Tetrahedron Lett. 2003, 43, 3083-3086. (c)
Krief, A.; Dumont, W.; Delmotte, C. Angew. Chem., Int. Ed. 2000, 39, 1669-
1672. (d) Salama, P.; Bernard, C. Tetrahedron Lett. 1998, 39, 745-748. (e)
Lee, S.; Kim, S.; Park, M. J. Korean Chem. Soc. 2011, 55, 546-549. (f)
Singh, D.; Deobald, A. M.; Camargo, L. R. S.; Tabarelli, G.; Rodrigues, O. E.
D.; Braga, A. L. Org. Lett. 2010, 12, 3288-3291.
15 General procedure for the synthesis of diaryl selenides:
A sealed tube containing a magnetic stirring bar was charged with the first
aryl iodide I (ArI) (1.0 mmol), Se0 (or Te0, 2.0 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 in oil bath at 90 oC for 18 h. The
reaction mixture was allowed to cool, and then the second aryl iodide II
(Ar’I) was added, followed by adding Cu2O (0.2 mmol), ethylene diamine
(0.2 mmol). The tube was resealed and the mixture was heated at 110 oC for
12 h. The reaction mixture was 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 unsymmetrical diaryl chalcogenides.