Synthesis of selenated isochromenones by AgNO3-catalyzed three-component reaction of alkynylaryl esters, selenium powder and ArB(OH)2

Article abstract of DOI:10.1039/d0ra06016j

Reported is the AgNO3-catalyzed three-component reaction of alkynylaryl esters, selenium powder and ArB(OH)2, providing a facile entry to selenated isochromenones. This work highlights the use of selenium powder as a selenium reagent in the synthesis of selenated isochromenones for the first time.

Full text of DOI:10.1039/d0ra06016j

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Synthesis of selenated isochromenones by AgNO3-
catalyzed three-component reaction of alkynylaryl
esters, selenium powder and ArB(OH)2†
Cite this: RSC Adv., 2020, 10, 30439
*
Yun-Bing Zhou, Miao-Chang Liu
*
Guo-Qing Jin, Wen-Xia Gao,
and Hua-Yue Wu
Received 10th July 2020
Accepted 10th August 2020
Reported is the AgNO3-catalyzed three-component reaction of alkynylaryl esters, selenium powder and
ArB(OH)2, providing a facile entry to selenated isochromenones. This work highlights the use of selenium
powder as a selenium reagent in the synthesis of selenated isochromenones for the first time.
DOI: 10.1039/d0ra06016j
rsc.li/rsc-advances
Organoselenium compounds are of increasing importance as ongoing interests in the construction of C–Se bond,9 we report
synthetic targets, largely owing to their applications in drugs,1 the preparation of selenated isochromenones via radical
agriculture chemistry,2 catalysis,3 synthetic intermediates4 and cascade cyclization of 2-alkynylaryl esters, selenium powder and
materials.5 In light of their importance, the incorporation of an arylboronic acids (Scheme 1d). Our synthetic strategy provides
organoselenium group into organic heterocyclic skeletons has an efficient method for the installation of selenium moiety onto
drawn growing attention in organic synthesis. In this context, the isochromenones scaffold. In addition, this methodology
the installation of a selenium moiety onto isochromenones can construct a pyrone ring, two C–Se bonds and a C–O bond in
which exhibit a range of biological activities would be mean- a single step from cheap and accessible raw materials.
ingful, because the resultant selenated isochromenones can
Our investigation began by selecting methyl 2-(phenyl-
serve as potential lead candidates that may bring about a vast ethynyl)benzoate (1a), selenium powder, and PhB(OH)2 as
improvement in enhanced physical and biological properties. model substrates for optimization of reaction conditions (Table
Despite the attractive properties provided by the introduction of 1). Accordingly, when the three-component reaction was
a selenium moiety, the development of the methods for the
synthesis of selenated isochromenones have been less reported.
One of the most commonly used strategies for the preparation
of selenated isochromenones relied on the intramolecular
electrophilic addition of PhSeCl/RFCl to alkynylaryl esters.6
Nevertheless, selenenyl chlorides used as selenium reagents are
usually unstable, costly and not easily available, eroding their
overall appeal (Scheme 1a). Another access to selenated iso-
chromenones via FeCl3-promoted electrophilic cyclization of
alkynylaryl esters with ArSeSeAr was reported by Zeni's group
(Scheme 1b).7 Recently, Du's group disclosed an efficient
approach to in situ generate selenenyl chlorides from the reac-
tion between diselenides and PhICl2, which enabled electro-
philic intramolecular of alkynes to deliver selenated
isochromenones (Scheme 1c).8 As far as we know, there have
been no reports on the use of selenium powder as selenium
reagent in the synthesis of selenated isochromenones.
The utilization of element selenium as selenium source in
the synthesis of organoselenium compounds is undoubtedly
attractive due to its easy availability and stability. As part of our
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
Scheme
1 The synthetic approaches to access selenated
† Electronic supplementary information (ESI) available. See DOI:
isochromenones.
10.1039/d0ra06016j
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Table 1 Optimization of reaction conditionsa
Table 2 Substrate scopea
Entry
Catalyst
Solvent
Temp (ꢀC)
Yield (%)
1
2
3
4
5
6
7
8
AgNO2
AgNO3
AgSbF6
Ag2SO4
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
—
Dioxane
Dioxane
Dioxane
Dioxane
CH3CN
Toluene
THF
120
120
120
120
120
120
120
120
120
130
110
100
120
120
120
120
89
92
46
22
23
49
65
0
30
90
85
77
71
91
46
0
CH3OH
DMF
9
10
11
12
13b
14c
15d
16
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
a
Reaction conditions: 1a (0.3 mmol), selenium powder (0.6 mmol), 2a
(0.6 mmol), catalyst (0.06 mmol), K2S2O8 (0.45 mmol), solvent (2.0
b
mL), under air atmosphere, isolated yield. AgNO3 (15 mol%).
c
Under the O2 atmosphere. d Under the N2 atmosphere.
performed in dioxane at 120 ꢀC under the air atmosphere in the
presence of the catalytic system containing AgNO2 and K2S2O8,
we observed the formation of the selenated product 3a in 89%
yields (entry 1). The survey of silver salts revealed that the
employment of AgNO3 as a catalyst afforded the best result
(entry 2), while other silver salts such as AgSbF6 and Ag2SO4 also
catalyzed the transformation albeit in inferior yields (entries 3
and 4). Further investigations of solvents including CH3CN,
toluene, THF, CH3OH and DMF led to no improvements in the
yields of the desired product (entries 5–9). It was found that the
reaction temperature had a signicant impact on the reaction
outcome (entries 10–12). In addition, decreasing the loading of
catalyst to 15 mol% had a negative effect on the yield of the
desired product (entry 13). The reaction under the O2 atmo-
sphere gave a similar yield to that under the air atmosphere
(entry 14). The use of N2 atmosphere resulted in the formation
of 3a in low yield with about 50% of 1a being recovered (entry
15). In the absence of an Ag catalyst, the reaction didn't take
place (entry 16). Therefore, the conditions employed in entry 2
proved to be optimal.
a
Reaction conditions: 1 (0.3 mmol), selenium powder (0.6 mmol), 2 (0.6
mmol), AgNO3 (0.06 mmol), K2S2O8 (0.45 mmol), dioxane (2.0 mL),
120 ꢀC, under the air atmosphere, isolated yields.
at the meta- and ortho-position also yielded the desired products
(3ia–3ma) efficiently. Note that shiing the substituents from
the para position to the ortho position led to a reduced yield
probably due to the increased steric hindrance (3la vs. 3fa; 3ma
vs. 3ca). (2,4,6-trimethylphenyl)boronic acid was a suitable
substrate for this transformation despite its steric repulsion.
Additionally, arylboronic acid bearing a fused ring or a hetero-
cyclic ring was also compatible, affording the corresponding
products in 46% (3oa) and 53% (3pa) yields respectively. Next,
the scope with respect to 2-alkynylaryl esters was assessed by
reacting with 2a and selenium powder. Moderate to good yields
were obtained (3ab–3ad) using substrates containing electron-
withdrawing and electron-rich substituents on ring B (1b–1d).
Ring B was also a fused ring (1e) and resulted in a good yield.
The substituents such as chloro or methoxy group on the ring C
(1f and 1g) were compatible with the reaction conditions. The
With the optimal reaction conditions in hand, we turned our
attention to exploring the generality of our method (Table 2).
We started our investigations with organoboronic acids. The
reaction was efficient for various arylboronic acids carrying
a series of substituents on the phenyl ring. For example, the
groups such as halogens, alkyls and triuoromethyl at the para
position of ring A were well tolerated and gave the expected
products (3ba–3ha) in 36–92% yields. Arylboronic acids bearing
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Based on our experimental observations and previous
studies,9,10 a plausible mechanism for the three-component
reaction is proposed in Scheme 3. At the beginning, phenyl-
boronic acid produces a phenyl radical (I) in the presence of
AgNO3. The trapping of the phenyl radical by selenium powder
provides a selenium-centred radical, followed by radical addi-
tion with 1a to generate intermediate III. The intermediate III
undergoes intramolecular radical cyclization to afford the nal
product 3a as well as methyl radical which goes through H-
abstraction to give methane.
Conclusions
In summary, we have disclosed an AgNO3-catalyzed radical
cyclization of alkynylaryl esters, selenium powder and
ArB(OH)2. The methodology displays good efficiency towards
a variety of arylboronic acids and 2-alkynylaryl esters, and
allows facile access to various selenated isochromenones. The
three-component reactions are exibly scalable and proceed via
a radical way. Such a radical strategy in which selenium powder
serves as the selenium reagent should contribute to construct-
ing other valuable selenium-containing heterocycle skeletons.
Scheme 2 The control experiments.
three-component tandem cyclization reaction could be scaled Conflicts of interest
up to 10 mmol scale as demonstrated with the synthesis of
product 45.
There are no conicts to declare.
To further investigate the substituents on oxygen atom on
the reaction efficiency, the methyl group in 1a was replaced by
other substituents. It was found that the replacement of the
methyl group by other groups such as ethyl, isopropyl, benzyl or
phenyl respectively led to inferior yields (Scheme 2a). When the
substituent on oxygen atom was changed into 4-PhC6H4, the
Acknowledgements
We are grateful for nancial support from the National Natural
Science Foundation of China (21901187 and 21672164).
reaction delivered a byproduct biphenyl in 35% yield aside from Notes and references
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