Metal free synthesis of diaryl selenides using SeO2as a selenium source

Article abstract of DOI:10.1016/j.tetlet.2016.07.075

A simple, efficient, and eco-friendly synthetic protocol has been developed for the preparation of diaryl selenium compounds. To the best of our knowledge, this is the first Letter on the use of selenium dioxide as selenium source for the synthesis of diaryl selenides. Compared with other selenium sources the new source SeO₂gives an environment-friendly and low-cost synthetic route, which may be useful for large-scale synthesis.

Full text of DOI:10.1016/j.tetlet.2016.07.075

Tetrahedron Letters xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Metal free synthesis of diaryl selenides using SeO2 as a selenium
source
⇑
⇑
R. Uday Kumar, K. Harsha Vardhan Reddy , G. Satish, K. Swapna, Y. V. D. Nageswar
MCP Division, Indian Institute of Chemical Technology, Hyderabad 500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple, efficient, and eco-friendly synthetic protocol has been developed for the preparation of diaryl
selenium compounds. To the best of our knowledge, this is the first Letter on the use of selenium dioxide
as selenium source for the synthesis of diaryl selenides. Compared with other selenium sources the new
source SeO2 gives an environment-friendly and low-cost synthetic route, which may be useful for
large-scale synthesis.
Received 7 June 2016
Revised 2 July 2016
Accepted 24 July 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Selenium dioxide
Metal free synthesis
PEG 400
Diaryl selenides
Several improved synthetic protocols that avoid the use of toxic
solvents and reagents have been reported in recent years. The real-
ization of simple and sustainable green synthetic procedures has
become an important development in organic synthesis.1
Organoselenium chemistry has been the subject of constant
research interest over the past 2–3 decades.2 Organoselenium
compounds are not only important reagents in organic synthesis3,4
but also serve as potential drug candidates.5 The versatility and
applicability of organoselenium compounds in organic chemistry
is widely described in reviews6 and books.7 Diaryl selenides are
most studied and a large number of methodologies have been
reported to prepare these compounds.8 Organoselenium com-
pounds are reported to be anti oxidant, anti tumor, anti microbial,
anti cancer, and anti viral.9 Development of an efficient synthetic
method for these compounds is of current interest.
To develop C–Se bond, in particular for diaryl selenium com-
pounds, traditional methods require harsh reaction conditions
such as the use of polar and toxic solvents like HMPA or NMP,
higher reaction temperatures, and longer reaction times, which
mostly result in lower yields.10 Cross-coupling of aryl halides with
aryl selenol in the presence of transition metal catalysts emerged
as an alternate method for the traditional route to diaryl
selenides.11 Further improvement was achieved by replacing
unstable, expensive, and foul-smelling aryl selenol with diphenyl
diselenide. C–Se cross coupling was also achieved using metals
such as palladium,12 nickel,13 copper,12 iron,14 indium,15 and
lanthanum-based16 catalytic systems.
However, these metal-catalyzed reactions involved the addition
of well-designed ligands and well-defined catalysts, which may
increase the cost and limit the scope of applications. Hence it is
desirable to develop an efficient procedure especially in the
absence of any ligand/catalyst for an easy access to such useful
organic compounds.
Selenium dioxide is recently emerging as stable, useful, and
readily available selenium reagent. Thomas Quell et al. reported a
facile synthesis of diaryl selenides and biphenols using SeO2 and
phenols.17
PEG-400 is a high boiling water soluble polyether, which has
the ability to solubilize organic components in water, thus acceler-
ating the rate of the reaction. The use of PEG-400 increases the sol-
ubility of reactants, which leads to a larger interfacial area and
lower mass transfer resistance.18 Earlier our group reported certain
methodologies related to the organoselenium compounds.19 As an
extension of our interest in developing novel and efficient proto-
cols for diaryl selenium compounds, to the best of our knowledge,
we hereby report for the first time, the preparation of diaryl sele-
nium compounds, under transition metal free conditions using
selenium dioxide and PEG-400 (Scheme 1).
OH
OH
K2CO3
Se
SeO2
+
B
R
R
PEG-400
110oC,3hr.
R
Scheme 1. Preparation of diaryl selenium compounds.
⇑
Corresponding authors.
http://dx.doi.org/10.1016/j.tetlet.2016.07.075
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kumar, R. U.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.07.075

2
R. U. Kumar et al. / Tetrahedron Letters xxx (2016) xxx–xxx
(Table 1 entry 12). Addition of copper ferrite as a catalyst did not
Results and discussion
improve the yield (Table 1 entry 13). An increase in the reaction
time did not impact the yield (Table 1 entry 14). While further
studying the effect of the quantity of selenium dioxide and base,
experiments were conducted with reduced amounts of selenium
dioxide as well as base (0.25 mmol and 1.0 mmol). However, the
results were not satisfactory (Table 1 entries 15 and 16).
Even though DMF as well as DMSO provide yields of the C–Se
cross coupled product in slightly more quantity due to some limita-
tions PEG-400 can be a preferred solvent. However, from exhaus-
tive study it can be concluded that 4-methoxy phenyl boronic
acid (1.0 mmol), selenium dioxide (0.5 mmol), K2CO3 (2 mmol),
PEG-400 at 110 °C for 3 h are the suitable starting materials and
conditions for the preparation of diaryl selenium compounds
(Table 1 entry 3).
The study was further extended to other aryl and hetero aryl
boronic acids based on the optimization conditions (see Table 2).
It was observed that C–Se cross coupling is effective in the case of
all aromatic boronic acid substrates bearing electron donating groups
such as alkyl, alkoxy groups with good yields, whereas substrates
bearing electron-withdrawing groups provided moderate yields.
While standardizing the reaction conditions, a series of experi-
ments were conducted with several solvents, bases, temperatures,
and reaction times for the representative reaction of 4-methoxy
phenyl boronic acid with selenium dioxide. The results are summa-
rized in Table 1. A variety of solvents including toluene, DMSO,
DMF, H2O, and PEG-400, were studied. In this optimization process,
4-methoxy phenyl boronic acid (1.0 mmol) was treated with sele-
nium dioxide (0.5 mmol) in PEG-400 (2 ml) as a solvent with dif-
ferent bases. Among the different bases examined, Cs2CO3 and
Na2CO3 afforded the expected products in moderate yields (Table 1
entries 1 and 2). While base K3PO4 has only produced trace amount
of the product (Table 1 entry 4), good yield was obtained with KOH
(Table 1 entry 5). Moderate yields were obtained using LiOtBu and
KOtBu (Table 1 entries 6 and 7). Among all bases examined K2CO3
gave an excellent yield (Table 1 entry 3). Among solvents examined
DMSO and DMF provided good yields (Table 1 entries 10 and 11),
where as toluene and water gave trace amounts of yields (Table 1
entries 8 and 9) and PEG-400 resulted in better yield (Table 1 entry
3). At room temperature the reaction was not proceeding well
H
O
OH
O OZ
H
O
Se
O
B
Ph
Ph-B(OH)2
K2CO3
SeO2
Ph
B(OH)2
OZ
Ph
Se
O
K
-(RO)(HO)BOK
Z=COOK
Ph-B(OH)2
Ph
B(OH)2
OZ
K
OH
B
K2CO3
Ph
HO
Ph
Ph
OH
B
OH
OH
O
Ph
Se
H
O
OZ
-H2O OH
O
O
Ph
B
Ph
Se
-PhOB(OH)2 Se
Ph
Se
-(RO)(HO)BOK
Ph
Se
HO
Ph
Ph
Ph
HO
Ph
Plausible mechanism for the formation of diaryl selenides
Table 1
Optimization study of C–Se cross-coupling reaction of 4-methoxy phenyl boronic acid
Conclusions
using seleniumdioxidea
In summary, to the best of our knowledge, an environmentally
benign and transition metal free protocol was developed for the
first time for the preparation of diaryl selenium compounds from
selenium dioxide in the presence of eco-friendly solvent PEG-400
to obtain products in moderate to good yields. The attractive and
notable features of this green approach are high functional group
compatibility, high yields, avoiding harmful organic solvents, and
toxic catalysts. This protocol may be useful for basic as well as
industrial research.
B(OH)2
SeO2
Se
Solvent
3 h, 110 0
C
O
O
O
3a
1a
2a
Entry
Base
Solvent
Temp (°C)
Yield (%)b
1
2
3
4
5
6
7
8
Cs2CO3
Na2CO3
K2CO3
K3PO4
KOH
PEG 400
PEG 400
PEG 400
PEG 400
PEG 400
PEG 400
PEG 400
Toluene
H2O
110
110
110
110
110
110
110
110
100
110
110
rt
43
51
81
Trace
77
60
57
Trace
Trace
83
LiOtBu
KOtBuO
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Experimental section
9
General experimental procedure
10
11
12
13
14
15
16
DMSO
DMF
82
0
PEG 400
PEG 400
PEG 400
PEG 400
PEG 400
The reaction was carried out in a 25 mL round bottom flask
equipped with magnetic stirbar charged with phenyl boronic acid
(1.0 equiv), selenium dioxide (0.5 equiv), K2CO3 (2.0 equiv), and
PEG-400 (2 mL). The resulting reaction mixture was stirred at
110 °C temperature for 3 h. The reaction progress was monitored
by TLC. After completion of the reaction, it was worked up with
ethyl acetate (3 Â 10 ml) and saturated brine solution. Crude
product was purified by column chromatography. The identity
and purity of the product was confirmed by 1H NMR, 13C NMR,
and ESI-MS.
110
110
110
110
81c
81d
44e
50f
a
Reaction conditions: 4-methoxy phenylboronic acid (1.0 mmol), selenium
dioxide (0.5 mmol), base (2.0 mmol), solvent (2.0 mL), 3 h, 110 °C.
b
Isolated yield.
c
Presence of catalyst copper ferrite (5 mol %).
Higher reaction time (3–5 h).
Selenium dioxide in less quantity (0.25 mmol).
K2CO3 in less quantity (1.0 mmol).
d
e
f
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R. U. Kumar et al. / Tetrahedron Letters xxx (2016) xxx–xxx
3
Table 2
Cross coupling reaction of SeO2 with various boronic acidsa
B(OH)2
Se
K2CO3, PEG-400
3 h, 110 0C
SeO2
Entry
Ar-B(OH)2
Product
Se
Yield (%)b
1
2
3
4
Phenylboronic acid
p-Tolylboronic acid
78
80
80
81
Se
Se
(4-Ethylphenyl)boronic acid
Se
OMe
OMe
(4-Methoxyphenyl)boronic acid
MeO
MeO
OMeMeO
5
6
(2,4-Dimethoxyphenyl)boronic acid
82
71
Se
F
F
(3-Fluorophenyl)boronic acid
Se
Se
Se
SMe
N
7
8
(4-(Methylthio)phenyl)boronic acid
77
77
MeS
N
(4-(Dimethylamino)phenyl)boronic acid
(3-Nitrophenyl)boronic acid
O2N
NO2
9
70
76
Se
Se
10
Naphthalen-1-ylboronic acid
11
12
13
14
Thiophen-2-ylboronic acid
Thiophen-3-ylboronic acid
(5-Methylthiophen-2-yl)boronic acid
Pyridin-3-ylboronic acid
74
78
79
68
Se
Se
S
S
S
S
S
S
Se
Se
N
N
N
N
Se
15
Pyrazin-2-ylboronic acid
67
N
N
a
Reaction conditions: aryl/heteroaryl boronic acid (1.0 mmol), selenium dioxide (0.5 mmol), base (2.0 mmol), solvent (2.0 mL), 3 h, 110 °C.
b
Yields of pure isolated products, characterized by 1H NMR and 13C NMR.
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Acknowledgments
We thank the University Grants Commission (UGC) and the
Council of Scientific and Industrial Research (CSIR), New Delhi for
financial assistance for the research scholars.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.07.
075.
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