Iodine mediated synthesis of diaryl diselenides using SeO2 as a selenium source

Article abstract of DOI:10.1080/00397911.2020.1728775

A simple, eco-friendly and convenient procedure has been developed for the synthesis of diphenyl diselinides from readily available aryl boronic acids by reaction with SeO₂ in the presence of iodine under simple conditions. The methodology is reported about 19 examples and applicable to a broad scope of aryl boronic acids containing electron-rich and electron-poor substituents. Apart from being milder and environmentally benign conditions, this synthetic protocol comprises a novel, reliable methodology to give good to high yields of the desired diaryl diselenides.

Full text of DOI:10.1080/00397911.2020.1728775

Synthetic Communications
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Iodine mediated synthesis of diaryl diselenides
using SeO2 as a selenium source
Dileep Kommula, Qing Li, Siyang Ning, Wujun Liu, Qian Wang & Zongbao K.
Zhao
To cite this article: Dileep Kommula, Qing Li, Siyang Ning, Wujun Liu, Qian Wang & Zongbao K.
Zhao (2020): Iodine mediated synthesis of diaryl diselenides using SeO2 as a selenium source,
Synthetic Communications, DOI: 10.1080/00397911.2020.1728775
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SYNTHETIC COMMUNICATIONSV
https://doi.org/10.1080/00397911.2020.1728775
Iodine mediated synthesis of diaryl diselenides using SeO2
as a selenium source
Dileep Kommulaa , Qing Lia, Siyang Ninga, Wujun Liub, Qian Wanga, and
Zongbao K. Zhaoa
b
aDalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China; Institute of Cancer
Stem Cell, Dalian Medical University, Dalian, China
ABSTRACT
ARTICLE HISTORY
Received 13 December 2019
A simple, eco-friendly and convenient procedure has been devel-
oped for the synthesis of diphenyl diselinides from readily available
aryl boronic acids by reaction with SeO2 in the presence of iodine
under simple conditions. The methodology is reported about 19
examples and applicable to a broad scope of aryl boronic acids con-
taining electron-rich and electron-poor substituents. Apart from
being milder and environmentally benign conditions, this synthetic
protocol comprises a novel, reliable methodology to give good to
high yields of the desired diaryl diselenides.
KEYWORDS
Aryl boronic acids; selenium
dioxide; iodine; diaryl
diselenides. 2-Me-THF
GRAPHICAL ABSTRACT
Introduction
Organoselenium compoounds, those containing selenium is considered an important
class of chemical entity, and their chemistry, toxicology, and pharmacology are well
documented in numerous reports.[1,2] The main chemistry of symmetric and unsym-
metric organoselenium compounds is a field of great interest owing to their special
structural motifs and unique reactivity.[3] For instance, organoselenium compounds of
diselenides are important synthetic intermediates[1] and have been reported as essential
moieties of pharmaceutically and biologically active compounds such as antioxidant,[4]
anti-ulcer[5] and anti-infammatory agents.[6]
Generally, the preparation of organoselenium (to construct C-Se bond) compounds
involves traditional methods such as cross coupling of aryl halides with selenium metal
employing metal salts[7], oxidation of selenoles,[8] reaction of alkali metal diselenides
CONTACT Kommula Dileep
dilip.kommula@gmail.com, dileepkommula@dicp.ac.cn
Dalian Institute of Chemical
Physics, Chinese Academy of Sciences, Dalian, China.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2020 Taylor & Francis Group, LLC

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K. DILEEP ET AL.
Scheme 1. Some of the methods for organoselenium synthesis using SeO2 as the selenium source.
with different electrophiles[9] and reduction of selenocyanates.[10] Since numerous meth-
ods have been reported for synthesize organoseleniums, there is still much scope and
research gap in exploring new C–Se construction methods due to the most of the
approaches reported so far using harsh reaction conditions such as the use of polar and
toxic solvents, some reactions must be performed at relatively high temperatures, and
longer reaction times, which mostly result in lower yields. Usually, synthetic chemists
are commonly focused on using RSeSeR, Se or KSeCN as a selenium sources for synthe-
sis of organoselenium compounds.[11] Recently, Leng et al.[11e] reported the synthesis of
diaryl diselenides by taking aryl boronic acids and Se metal in the presence of silver
nitrate catalyst. Later, Zhu et al.[12] described Nickel-catalyzed synthesis of diaryl disele-
nides using aryl boronic acids and Se metal as a selenium source.
In recent years, utilization of SeO2 as a selenium source has been gaining a remark-
able approach for the synthesis of organoselenium compounds. For instance, Kumar
et al.[13a] reported using SeO2 and phenylboronic acid to make diarylselenides
(Scheme 1(a)). Quell et al.[13b] described the synthesis of diarylselenides and biphenols
by using SeO2 and phenols (Scheme 1(b)). Later, Shangplianger et al.[13c] reported to

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Scheme 2. Synthesis of diaryl diselenides from aryl boronic acids.
construct C¼Se double bonds without any catalyst using SeO2 as a selenium source
(Scheme 1(c)). Recently, Ren et al.[13d] described the synthesis of R-Se Substituted
Aniline and Imidazo[1,2-a]pyridine derivatives using SeO2 as a selenium source
(Scheme 1(d)).
On the other hand, researchers are focusing on replacement of volatile organic com-
pounds (VOCs) by biomass derived solvents. Biomass derived solvents are a type of
green solvent that have attracted intensive investigations due to their advantages over
conventional VOCs, such as low toxicity, biodegradability and renewability.[14] Among
the biomass derived solvents, 2-methyl-tetrahydrofuran (2-Me-THF) has gained atten-
tion as a promising alternative solvent in the search for environmentally benign synthe-
sis strategies because of its physical and chemical properties, such as its low miscibility
with water, boiling point, remarkable stability compared to other cyclic-based solvents
such as THF.[15] Hence, 2-Me-THF have been extensively used for applications in syn-
theses involving organometallics, organocatalysis, and biotransformations or for process-
ing lignocellulosic materials.[14–16]
In our continued search for the development of novel green novel protocols,[17] here
in, we report a novel method for the synthesis of diayrl diselenides from arylboronic
acids and SeO2 using 2-Me-THF solvent in the presence of molecular Iodine at 60ꢀC
for 2–4 h (Scheme 2).
Result and discussion
We began our study by optimizing the reaction conditions for the synthesis of diphenyl
diselenide 2a as a model reaction (Table 1). Initially, the reaction of phenyl boronic
acid 1a (1.0 mmol), SeO2 (1.0 mmol), molecular Iodine (1.0 mmol) was carried out in
DMSO as a solvent (1 mL) at room temperature gave the corresponding compound 2a
in yield 69% (Table 1, entry 2). While checking the reaction parameters, it was observed
that reaction did not proceeded without presence of iodine after prolonged reaction
time 24 h, (Table 1, entry 1). Later, the temperature effect on reaction conditions was
carried out, and it was observed that the increase in reaction temperature from rt to
40 ꢀC, resulted in improved the yield from 69% to 82% (Table 1, entry 6). When
increases the temp from 40 ꢀC to 60 ꢀC, resulted in enhanced to 90% yield (Table 1,
entry 4). Further, increasing the temperature to 80 ꢀC observed that there was no obvi-
ous improvement of product 2a yield (Table 1, entry 8).
In order to optimize the protocol, the impact of the loading molecular Iodine on the
reaction efficiency was investigated. We found that increasing I2 from 1.0 to 1.2, 1.5
and 2.0 equiv. there was no substantial improvement of yield (Table 1, entry 4, 5, 6).
Finally, the effect of solvents was studied and it was observed that the reaction was also

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K. DILEEP ET AL.
Table 1. Optimization table for the synthesis of diphenyl diselenidea.
Entry
Catalyst
Catalyst (m.mol)
Solvent
DMSO
Temperature (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
–
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
–
rt
rt
0
69
90
90
91
92
82
90
91
89
84
85
66
60
55
40
0
1.0
1.0
1.2
1.5
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
2-Me-THF
THF
1,4-Dioxane
DMF
C2H3CN
C2H5OH
Toulene
H2O
60
60
60
60
40
60
80
60
60
60
60
60
60
60
60
9
10
11
12
13
14
15
16
17
aThe reactions were carried out as follows: Phenyl boronic acid (1.0 equiv.), I2 (1.0 equiv.), SeO2 (1.0 equiv.), 2-Me-THF
(1 mL), at 60 oC, 2 h.
bIsolated yields are based on reactant.
effective in 2-Me-THF, 1,4-Dioxane, THF, DMF, CH3CN, CH3OH, EtOH and Toluene,
obtained the product 2a in 89%, 85%, 84%, 69%, 60%, 55% and 40% yield (Table 1,
entry 10–17), respectively. It’s noteworthy to mention that the desired product 2a for-
mation was not observed in aqueous medium (entry 18). However, the reaction was
highly effective with polar aprotic solvents (entries 10–15). Among the different solvents
examined, 2-Me-THF (Table 1, entry 10) was provided the highest product 2a in 89%
yield after the DMSO solvent which was afforded product 2a in 90% yield (Table 1,
entry 8). Therefore, 2-Me-THF was chosen as a preferred solvent over DMSO, because
of its economical and greenery properties (derived from biomass). From exhaustive
study, the optimized reaction conditions were chosen as phenyl boronic acid (1.0 equiv),
SeO2 (1.0 equiv), Iodine (1.0 equiv) was carried out in 2-Me-THF as a solvent (2 mL) at
ꢀ
60 C for the preparation of diaryl diselenide compounds. Under the selected optimum
reaction condition, different electron-withdrawing and electron-donating groups on the
aryl boronic acids were selected and reacted with SeO2 in the presence of Iodine gave
the corresponding diaryl diselenides in good to excellent yields were presented in
Table 2.
From the Table 2 it was indicated that present method was effective in the case
of all aromatic boronic acid substrates bearing either electron-withdrawing or elec-
tron-donating groups provided good yields. Aryl boronic aicds bearing EDGs on the
benzene ring showed higher reactivity’s and afforded a little bit higher yields than

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Table 2. Synthesis of various substituted diaryl diselenidesa.
aThe reactions were carried out as follows: Phenyl boronic acid (1.0 equiv.), I2 (1.2 equiv.), SeO2 (1.0 equiv.), 2-Me-THF
(1 mL), at 60 oC, 2 h.
bIsolated yields are based on reactant.

6
K. DILEEP ET AL.
Scheme 3. Radical scavenger experiments of iodine mediated synthesis of diphenyl diselenides.
Scheme 4. Proposed plausible mechanism for the synthesis of diaryl diselenides.
those bearing EWG. Later, we checked this protocol on some alkylboronic acids;
unfortunately, this protocol was not successful for converting to corresponding alkyl
diselenides.
To gain insight into the mechanism of this reaction, free radical trapping
experiments were conducted (Scheme 3). It was found that compound 2a could be
isolated in 85% and 83% yields in the presence of 1,4 Benzoquinone (1.0 equiv.)
and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO, 1.0 equiv.), respectively, under the
optimized conditions, indicating
transformations.
a
non-radical process involved in these
In Scheme 4, a plausible mechanism for iodine mediated facile synthesis of aryl
diphenyl diselenides is outlined. Initially, the molecular iodine and selenium dioxide
interact to form selenium iodide and iodide, then, nucleophilic aryl group from the phe-
nylboronic acid reacts with selenium iodide to give phenylselenium iodide, which was
detected by GC mass (obtained at m/z 281) and 77Se NMR data[18] (peak appeared at
d ¼ 507 ppm (See the supporting information). Later, it was reduced by HI to give the
product diphenyl diselenide.

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Experimental
General experimental procedure for the synthesis of diaryl diselenides
The reaction was carried out in a 25 mL round bottom flask equipped with magnetic
stirbar charged with aryl boronic acid (1.0 equiv), selenium dioxide (1.0 equiv), I2 (1.0
equiv), and 2-Me-THF (2 mL). The resulting reaction mixture was stirred at 60 ꢀC tem-
perature for 2–4 h. The reaction progress was monitored by TLC. After completion of
the reaction, iodine quenched with hypo solution and it was worked up with ethyl acet-
ate (3 ꢁ 10 mL) and saturated brine solution. Crude product was purified by column
chromatography (petroleum ether/ethyl acetate, 100:0–95:5). The identity and purity of
1
the product was confirmed by H NMR, 13C NMR, and EI-MS.
Data of representative example: Diphenyl Diselenide (2a)[19]: Orange solid; mp
1
57–59 ꢀC.; H NMR (400 MHz, CDCl3) d 7.81 (dd, J ¼ 8.0, 1.4 Hz, 4 H), 7.55 ꢂ 7.49 (m,
2 H), 7.48 ꢂ 7.41 (m, 4 H).; 13C NMR (101 MHz, CDCl3) d 134.7, 131.0, 128.9, 127.9.;
MS (EI, m/z): 312 [Mþ].
Conclusion
In summary, we developed metal free, base free procedure, highly efficient and can pro-
ceed under mild and environmentally friendly conditions for the synthesis of diaryl dis-
elenides. The transformation feature is use of SeO2 as a selenium source, is operational
simple with high functional group compatibility, high yields, base free, avoiding harmful
organic solvents, and toxic catalysts. We hope that this novel method may be useful for
basic as well as industrial research.
1
Full experimental details, spectral data of the products, and H NMR, 13C NMR and
HRMS spectra of all the new compounds can be found via the Supplementary content
section of this article’s Web page.
Funding
We thank DICP for providing Analytical instruments data, this study was funded by the
National Natural Science Foundation of China [Nos. 21721004].
ORCID
Dileep Kommula
http://orcid.org/0000-0003-1195-665X
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