Ag-Catalyzed Cyclization of Arylboronic Acids with Elemental Selenium for the Synthesis of Selenaheterocycles

Article abstract of DOI:10.1002/adsc.202001006

A general method for the synthesis of five-membered and six-membered selenaheterocycles through Ag-catalyzed C?Se bond-forming reaction is reported. This reaction proceeds via intramolecular cyclization of arylboronic acids with selenium powder. Preliminary mechanism studies demonstrate that this transformation involves a selenium-centred radical intermediate. (Figure presented.).

Full text of DOI:10.1002/adsc.202001006

Title: Ag-Catalyzed Cyclization of Arylboronic Acids with Elemental
Selenium for the Synthesis of Selenaheterocycles
Authors: Xue Zhang, Xiaobo Huang, Wenxia Gao, Yun-Bing Zhou,
Miaochang Liu, and Huayue Wu
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202001006
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10.1002/adsc.202001006
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Ag-Catalyzed Cyclization of Arylboronic Acids with Elemental
Selenium for the Synthesis of Selenaheterocycles
Xue Zhang,a Xiao-Bo Huang,a Wen-Xia Gao,a Yun-Bing Zhou,a,* Miao-Chang Liua,*
and Hua-Yue Wua
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, People’s Republic of China.
E-mail: zyb@wzu.edu.cn; mcl@wzu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
selenaheterocycle, and usually suffered from narrow
six-membered selenaheterocycles through Ag-catalyzed C- substrate scope, harsh reaction conditions and the
A general method for the synthesis of five-membered and
Se bond-forming reaction. This reaction proceeds via
intramolecular cyclization of arylboronic acids with
selenium powder. Preliminary mechanism studies
demonstrate that this transformation involves a selenium-
centred radical intermediate.
need for unfavourable selenium sources. In this
regard, the development of a general and facile
method to synthesize various selenaheterocycles
remained to be desirable.
Keywords: Cyclization; Arylboronic Acids; Elemental
Selenium; Selenaheterocycles; Selenium-centred radical
The organoselenium compounds are of significant
interest because they are widely used in numerous
fields such as pharmaceutical, agrochemical, material,
catalysis
and
ligand.[1]
In
particular,
selenaheterocycles, representing an important class of
heterocyclic compounds, attract growing attention.
For example, the benzo[b]selenophene was
considered to be a bioisoster of indole, benzofurane
and benzothiophene though its core was not found in
natural products.[2] Moreover, benzo[b]selenophene
could serve as the key motif for thin film
transistors,[3] as well as AT1 receptor antagonists
which showed better activity than the corresponding
benzo[b]thiophene analogues.[4] Traditional methods
to synthesize benzo[b]selenophenes relied on the use
of Na2Se,[5] SeBr4,[6] (PhCH2)2Se[7] or KSeCN[8] as a
selenium source (Scheme 1.1). Yoshikai’s group[9]
disclosed an alternative synthetic route to
benzoselenophenes
through
copper-catalyzed
Scheme 1. The methods for the construction of
selenaheterocycles.
cyclization reactions between ortho-alkenylaryl
iodines and elemental selenium. On the other hand,
dibenzo[b]selenophenes could be accessed from
Recently, our group[14] disclosed
synthetic route to selenated
a
concise
cyclization
reactions
of
diselenide[10]
or
benzofurans
monoselenide[11] as well as the reaction between 2,2’-
dihalobiphenyls and SeCl2 or selenium powder,[12] but
the substrate scope of these reactions were not
examined (Scheme 1.2). Remarkably, a smart
synthetic route via elemental selenium−iodine
exchange was reported by Jiang.[13] Regardless of
their efficiency, these synthetic approaches were
limited to the synthesis of only one type of
(benzothiophenes) via Ag-catalyzed three-component
radical cyclization, in which a selenium-centred
radical acted as the key intermediate. Herein, we
envisioned that in situ generated selenium-centred
radical would undergo intramolecular radical
cyclization which enables the direct construction of
selenaheterocycles including benzo[b]selenophene,
1
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10.1002/adsc.202001006
Advanced Synthesis & Catalysis
dibenzo[b]selenophenes
and
phenoxaselenine
substantial amount of side product biphenyl could be
observed when the reaction was performed in these
poor solvents. Next, we turned to examine the effect
of Ag catalysts on reaction efficiency. Surprisingly,
the use of other Ag catalysts including Ag2O, Ag2CO3,
AgOAc, AgNO3 and AgOTf did not promote this
transformation at all (entries 12-16). Lowering the
reaction temperature had a significantly negative
impact on the reaction outcome (entries 17-19). The
employment of the O2 atmosphere gave a comparable
yield to that under air atmosphere (entry 20).
However, the reaction under N2 atmosphere gave an
inferior yield, demonstrating that the presence of
oxygen could boost this transformation (entry 21).
(Scheme 1.3).
Table 1 Reaction optimization.a
entry catalyst
solve
oxidant
yield(%)
aRea
ction
cond
ition
s: 1a
(0.2
mmo
l), Se
pow
der
(0.4
mmo
l),
Ag
catal
yst
nt
1b
AgNO2
AgNO2
DMSO
DMSO
-
0
0
2
-
3
AgNO2 dioxane
AgNO2 dioxane
AgNO2 dioxane
AgNO2 dioxane
-
39
86
0
4
K2S2O8
Na2S2O8
(NH4)2S2O8
5
6
0
7
AgNO2 dioxane benzoquinone
29
0
8
AgNO2
AgNO2
AgNO2
AgNO2
Ag2O
DMSO
DMF
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
9
0
10
11
12
13
14
15
16
17c
18d
19b
20e
21f
PhCH3
CH3CN
dioxane
0
0
0
Ag2CO3 dioxane
AgOAc dioxane
AgNO3 dioxane
0
(0.02
mmo
l),
oxid
ant
0
0
AgOTf
dioxane
0
AgNO2 dioxane
AgNO2 dioxane
AgNO2 dioxane
AgNO2 dioxane
AgNO2 dioxane
83
52
0
(0.3
mmo
l),
solve
nt
85
51
(2.0
mL),
o
b
o
24 h, air atmosphere, 130 C, isolated yields. At 100 C.
cAt 120 C. dAt 110 C. eUnder O2 atmosphere. Under N2
o
o
f
atmosphere.
Along with the above idea, we commenced our
study by submitting [1,1'-biphenyl]-2-ylboronic acid
(1a) to our previous catalytic system which was used
in the synthesis of selenated benzofurans
(benzothiophenes) (Table 1). It was found that this
catalytic system failed to enable the intramolecular
radical cyclization of 1a to provide the desired
product 1b (entry 1), even with the reaction
Scheme 2. The substrate scope for the synthesis of
dibenzo[b]selenophene. Reaction conditions: 1 (0.2 mmol),
Se powder (0.4 mmol), AgNO2 (0.02 mmol), K2S2O8 (0.3
mmol), 1,4-dioxane (2.0 mL), 24 h, air, isolated yields.
o
temperature being increased to 130 C (entry 2). We
were pleased to find that the use of dioxane as a
solvent successfully led to the desired product 1b in
39% yield (entry 3). The addition of Na2S2O8 as an
oxidant resulted in a significant boost in the yield of
1b (entry 4), but other oxidants including K2S2O8 and
(NH4)2S2O8 didn’t give the desired product but
generated large amount of 2-phenylphenol as the
main byproduct (entries 5 and 6). The reaction with
benzoquinone as an oxidant led to 29% yield of 2b
along with 58% yield of phenylphenol (entry 7).
Systematical screening for solvents revealed that the
intramolecular cyclization process did not occur in
the solvents such as DMSO, DMF, PhCH3, and
CH3CN (entries 8-11). It should be noted that a
To test the substrate scope for the construction of
dibenzo[b]selenophene, a range of arylboronic acids
tethered an aromatic ring were examined (Scheme 2).
These arylboronic acids were typically prepared by
two synthetic steps involving Suzuki coupling
reaction and the reaction of an aryllithium
intermediate with a trialkylborate. The phenyl ring B
of arylboronic acids could tolerate a range of
substituents with diverse electronic properties, such
as halogens (1b and 1c), weakly electron-donating
alkyl groups (1d and 1e), and electron-donating
groups (1f and 1g). Unfortunately, the substrates
2
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10.1002/adsc.202001006
Advanced Synthesis & Catalysis
bearing amino, cyano and ester groups on ring B
failed to the desired products (2h- 2j). In addition,
ring B could be an
conducted (Scheme 4). The addition of TEMPO to
the model reaction led to no formation of the desired
product 2a (Scheme 4a). The control reaction in the
absence of Se powder afforded product 5 in 28%
yield and product 6 in 45% yield (Scheme 4b). The
o
reaction at a lower temperature (100 C) gave a
mixture that consists of starting material 1a (41%),
product 2a (18%), diselenide 7 (30%), selenide 8
(5%) (Scheme 4c). The reaction of diselenide 7 under
standard reaction conditions successfully offered
product 2a in 87% yield, but was inhibited in the
presence of TEMPO (Scheme 4d). No corresponding
product 2a was detected when selenide 8 was
exposed to standard reaction conditions (Scheme 4e).
Scheme 3. The substrate scope for the synthesis of
phenoxaselenines. Reaction conditions: 3 (0.2 mmol), Se
powder (0.4 mmol), AgNO2 (0.02 mmol), K2S2O8 (0.3
mmol), 1,4-dioxane (2.0 mL), 24 h, air atmosphere,
isolated yields. b50 mol% of AgNO2 was used.
aromatic heterocycle (1k) or a fused ring (1l and 1m).
Significant differences in the yields were observed
when the same group is located on a different ring
(1d vs 1d’, 1f vs 1f’). The present of trifluoromethyl
group on ring A resulted in 42% yields (2n).
Substrates with two substituted aromatic rings
delivered the corresponding products in relatively
low yields, which was attributed to the formation of
biphenyl derivatives (2o-2q). Alkenylboronic acid
proved
to
be
a
suited
precursor
to
Scheme 4. The control experiments.
benzo[b]selenophene (2r).
Next, we intended to extend this synthetic
approach to the synthesis of six-membered
selenaheterocycles (Scheme 3). It was found that (2-
phenoxyphenyl)boronic acid reacted well with Se
powder to furnish phenoxaselenine with 81% yield
(4a). The transformation was also operable with
substrates bearing a halogen (3b and 3g), an alkyl
group (3c, 3e and 3f) or a methoxyl group (3d). Low
yields (4c and 4i) were observed under the standard
conditions, which was attributed to the formation of
diaryl ethers from the protonation of substrates.
Dibenzo[b,e][1,4]thiaselenine (4j) was also obtained
in 43% yield albeit with 50 mol% of AgNO2. The
Scheme 5. The possible mechanism.
attempt
to
synthesize
10-methyl-10H-
In line with these results and previous
references,[15] a possible mechanism for the Ag-
catalyzed cyclization of arylboronic acids with
elemental selenium is proposed (Scheme 5). The
reaction is initiated by the oxidation of 1a to afford
phenoselenazine (4k) failed with the complete
recovery of the starting materials.
To investigate how this C-Se forming reaction
takes place, some control experiments were
3
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10.1002/adsc.202001006
Advanced Synthesis & Catalysis
radical A in the presence of AgNO2/K2S2O8/O2. The
radical A was trapped by selenium powder to yield
McCarthy-Ward, J. Shaw, D.-H. Lim, Y.-J. Kim, S.
Mathur, M. Heeney, D.-Y. Kim, Adv. Sci. 2019, 6,
1900245-1900251.
selenium-centred
radical
B,
followed
by
intramolecular radical cyclization/oxidation to
provide the final product 2a. Alternatively, the in-situ
generated B either undergoes homocoupling to give 7
in a reversible way, or reacts with radical A to furnish
8.
[2] R. Lisiak, J. Mochowski, Synth. Commun. 2009, 39,
4271-4281.
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In conclusion, we have developed an Ag-catalyzed
C-Se bond-forming strategy, providing an efficient
method for the synthesis of selenaheterocycles
including
benzo[b]selenophene,
dibenzo[b]selenophenes and phenoxaselenines. The
studies on the substrate scope showed a significant
influence on the nature of the electron-rich group of
arylboronic acids. We also demonstrated key
mechanistic features of this C-Se bond-forming
reaction by control experiments.
[4] M. K. Staples, R. L. Grange, J. A. Angus, J. Ziogas, N.
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2473-2475.
Experimental Section
[6] E. Paegle, S. Belyakov, P. Arsenyan, Eur. J. Org.
Chem. 2014, 3831-3840.
Typical procedure for the synthesis of selenaheterocycles.
A 10 mL Schlenk tube equipped with a stir bar was
charged with arylboronic acid (0.2 mmol), Se (0.4 mmol),
AgNO2 (10 mol %) and K2S2O8 (0.3 mmol). Then dioxane
(2 mL) was added in the Schlenk tube through the rubber
septum using syringes. The reaction mixture was stirred in
a heating mantle preheated to 130 °C for 24 h. After
cooling down, the reaction mixture was diluted with 10 mL
of ethyl ether, filtered through a pad of silica gel and
concentrated under reduced pressure. The residue was then
purified by flash chromatography on silica gel to provide
the corresponding product.
[7] J. E. Lyons, C. H. Schiesser, K. Sutej, J. Org. Chem.
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R. Waldvogel, Chem. Eur. J. 2019, 25, 1936-1940; d)
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Acknowledgements
We are grateful for financial support from the National Natural
Science Foundation of China (21901187, 21372177 and
21672164).
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Chem. Scand, 1993, 47, 208-211; b) M. Tobisu, Y.
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4
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10.1002/adsc.202001006
Advanced Synthesis & Catalysis
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202001006
Advanced Synthesis & Catalysis
COMMUNICATION
Ag-Catalyzed Cyclization of Arylboronic Acids
with Elemental Selenium for the Synthesis of
Selenaheterocycles
Adv. Synth. Catal. Year, Volume, Page – Page
Xue Zhang, Xiao-Bo Huang, Wen-Xia Gao, Yun-
Bing Zhou,* Miao-Chang Liu* and Hua-Yue Wu
6
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