Metal-Free Synthesis of Thiosulfonates via Insertion of Sulfur Dioxide

Article abstract of DOI:10.1002/adsc.201900157

A simple and catalyst-free strategy was developed for the synthesis of unsymmetrical thiosulfonates using readily available DABCO?(SO₂)₂ as a solid and bench-stable sulfur dioxide surrogate. The corresponding thiosulfonates were obtained through a radical pathway with good functional group tolerance. This strategy offers a promising synthesis method for the construction of diverse and useful thiosulfonates in the field of synthetic and pharmaceutical chemistry and extends the number of still limited sulfur dioxide fixation strategies. (Figure presented.).

Full text of DOI:10.1002/adsc.201900157

Title: Metal-Free Synthesis of Thiosulfonates via Insertion of Sulfur
Dioxide
Authors: Guoqing Li, Ziyu Gan, Kexin Kong, Xiaomeng Dou, and
Daoshan Yang
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10.1002/adsc.201900157
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Metal-Free Synthesis of Thiosulfonates via Insertion of Sulfur
Dioxide
Guoqing Li,a,b Ziyu Gan,b Kexin Kong,b Xiaomeng, Dou,c and Daoshan Yanga,b*
a
State Key Laboratory Base of Eco-Chemical Engineering, College of Chemistry and Molecular Engineering, Qingdao
University of Science and Technology, Qingdao, 266042, P. R. China.
E-mail: yangdaoshan@tsinghua.org.cn;
School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, P. R. China.
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan , 411201, P.
b
c
R. China.
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######.((Please
delete if not appropriate))
Abstract. A simple and catalyst-free strategy was developed synthesis method for the construction of diverse and useful
for the synthesis of unsymmetrical thiosulfonates using thiosulfonates in the field of synthetic and pharmaceutical
readily available DABCO·(SO2)2 as a solid and bench-stable chemistry and extends the number of still limited sulfur
sulfur dioxide surrogate. The corresponding thiosulfonates dioxide fixation strategies.
were obtained through a radical pathway with good
functional group tolerance. This strategy offers a promising
Keywords: metal-free; thiosulfonate; sulfur dioxide;
organosulfur compound; thiol
Several other methods including oxidation of
thiosulfinates,[8] reaction of potassium thiosulfonates
with diaryliodonium salts,[9] and reduction of sulfonyl
chlorides[10] have also been developed for the
formation of unsymmetrical thiosulfonates. Despite
the success of these methods, the use of toxic and
unstable sulfenylating agents, unavailability of
starting materials, and low yield of these reactions
have limited their wide applications. Therefore, more
efficient, sustainable, and practical methods should
be developed.
Introduction
Organosulfur compounds are prevalent in natural
products and subunits of diverse bioactive
compounds; they are also widely used in materials
chemistry.[1] Therefore, development of efficient and
practical methods for the synthesis of sulfur-
containing compounds is still an important topic in
green organic chemistry.[2] Recently, C–S bond-
forming reactions have been extensively studied, and
tremendous achievements have been made.[3]
Unfortunately, synthetic methods for the construction
of heteroatom–S bonds have received less attention.[4]
Thiosulfonate derivatives are an important class of
organic compounds containing S-S bond motif.
Importantly, these compounds show various
biological activities such as antiviral, antimicrobial,
antibacterial, and antifungicidal activities.[5] In
addition, thiosulfonates are also widely used as
versatile sulfenylating reagents in many organic
transformations.[6] For these reasons, considerable
efforts have been devoted to the development of new
and efficient methods for the construction of
thiosulfonates. However, a literature survey indicates
that synthetic methods for the construction of
thiosulfonate skeletons are rather limited. Classical
methods for the synthesis of thiosulfonate compounds
mainly focus on the oxidation of disulfides to the
corresponding thiosulfonates, affording a mixture of
isomeric products when R1 ≠ R2 (Scheme 1a).[7]
In 1972, Bentley and co-workers attempted the
direct conversion of sodium sulfinates and alkyl
disulfides to thiosulfonates. Unfortunately,
a
stoichiometric amount of AgNO3 is required, and the
substrates are limited to sodium methanesulfinates. [11]
In 2012, Chen’s group reported an elegant Sc(OTf)3-
catalyzed sulfonylation of sodium sulfinates with N-
(organothio)succinimides to afford unsymmetrical
thiosulfonates in ionic liquids (ILs) and water
(Scheme 1b).[12] In 2015, Taniguchi developed an
elegant copper-catalyzed sulfonylation of disulfides
with sodium sulfinates to access unsymmetrical
thiosulfonates under mild conditions (Scheme 1c).[13]
In 2017, Zou and co-workers developed an efficient
method for the synthesis of thiosulfonates via copper-
catalyzed TBHP-mediated radical cross-coupling of
sulfonylhydrazides and thiols (Scheme 1d).[14] Very
recently, Dong and An described a green and eco-
friendly method for the synthesis of unsymmetrical
1
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10.1002/adsc.201900157
Advanced Synthesis & Catalysis
thiosulfonates from sulfonyl hydrazides and
group found that the combination of aryldiazonium
disulfides using PEG-400 as a solvent (Scheme 1e).[15] salts and DABSO produces an arylsulfonyl radical
Notably, during the submission process of our
manuscript, Chen and co-workers reported an elegant
that can be further transformed to N-
aminosulfonamides by reacting with hydazines under
[20]
electrochemical
transformation
of
sulfonyl
metal-free conditions
Afterwards, sulfur dioxide
hydrazides and thiols into thiosulfonates (Scheme
insertion reactions based on aryldiazonium salts have
been extensively studied, and many elegant studies
have been reported.[21] Inspired by these excellent
results, we envisioned that unsymmetrical
thiosulfonates could be constructed starting from
readily available aryldiazonium salts, DABSO, and
thiols via a radical pathway with the insertion of
sulfur dioxide (Scheme 1h). In continuation of our
research in the synthesis of sulfur-containing
compounds, herein, we report a simple and efficient
method for the formation of unsymmetrical
thiosulfonates using DABSO as a sulfur dioxide
surrogate under metal-free conditions.
1f).[16a] Hao and Wang's group also developed an
efficient
symmetrical/unsymmetrical
BF3·OEt2-mediated
method
for
the
synthesis
of
via
coupling
thiosulfonates
disproportionate
reaction of sodium sulfinates (Scheme 1g).[16b]
Although great achievements have been made in this
field, it is still essential to develop new strategies to
prepare unsymmetrical thiosulfonates with high
efficiency and generality.
Results and Discussion
Table 1. Optimization of the reaction conditionsa
Entry
1
Solvent
Additive
Yield b (%)
DMSO
DMF
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
DABCO
TFA
19
11
2
3
DCE
40
4
Toluene
1,4-Dioxane
CH3CN
DCE
38
5
20
6
35
Tracec
36d
40e
41f
41g
0
7
8
DCE
9
DCE
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
DCE
DCE
DCE/DMSO (1:1)
DCE/MeCN (1:1)
0
Scheme 1. Strategies for the synthesis of thiosulfonates.
DCE/Toluene (1:1)
DCE/Toluene (3:1)
DCE/Toluene (4:1)
DCE/Toluene (5:1)
DCE/Toluene (1:2)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
DCE/Toluene (4:1)
47
48
Sulfur dioxide (SO2), an abundant industrial
emission product, is one of the main sources of air
pollution. There is no doubt that directly fixation of
sulfur dioxide into small molecules leading to
sulfone-containing compounds is promising and
attractive in organic chemistry. DABSO (1,4-
diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct)
as an air-stability solid sulfur dioxide surrogate has
been successfully introduced by Willis and co-
workers. As a pioneer work, Willis’s group initially
52
40
31
16h
64i
52j
21
BF3.Et2O
FeCl3
ZnCl2
TFA
30
53k
57l
59m
56n
TFA
developed
an
elegant
palladium-catalyzed
TFA
aminosulfonylation method for the synthesis of aryl
N-aminosulfonamides using DABSO as a sulfur
dioxide surrogate.[17] In recent years, many
sulfonylation reactions have been developed for the
synthesis of sulfones, N-aminosulfonamides,
sulfamides, and sulfonamides by using DABSO as
the sulfur dioxide (SO2) source.[18] Aryldiazonium
salts are well-known arylation reagents widely used
in various organic transformations [19] In 2014, Wu’s
TFA
[a]
Reaction conditions: phenyldiazoniumtetrafluoroborate
1a (0.6 mmol), DABSO (0.4 mmol), 4-methylbenzenethiol
o
2a (0.4 mmol), solvent (3 mL), at 60 C, reaction time (30
min). [b]Isolated yield. [c]At room temperature. [d]At 50 oC.
[e]At 70 oC. [f]At 80 oC. [g]At 90 oC. [h]DABCO (0.4mmol).
[i]TFA (0.4mmol). [j]BF3 Et2O (0.4 mmol). [k]TFA
.
(0.08mmol). [l]TFA (0.2mmol). [m]TFA (0.6mmol). [n]TFA
(0. 8mmol).
2
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10.1002/adsc.201900157
Advanced Synthesis & Catalysis
As
shown
in
Table
1,
[a] Reaction conditions: phenyldiazonium tetrafluoroborates
1 (0.6 mmol), DABSO (0.4 mmol), thiophenol 2 (0.4
mmol), TFA (0.4 mmol), DCE (2.4 mL), toluene (0.6 mL),
reaction time (30 min). [b] Isolated yield.
phenyldiazoniumtetrafluoroborate (1a), DABSO, and
4-methylbenzenethiol (2a) were selected as model
substrates to explore the optimal reaction conditions,
including solvents, additives, and reaction
temperature under nitrogen atmosphere. Six solvents
such as DMSO, DMF, DCE, toluene, 1,4-dioxane,
and CH3CN were evaluated at at 60 C, DCE
provided S-(p-tolyl) benzenesulfonothioate (3a) in
40% yield. Furthermore, various temperatures were
evaluated (Table 1, entries 3, 7–11) using DCE as the
solvent, 60 C was found to be the best choice.
Notably, a higher reaction temperature did not
increase the conversion efficiency. In addition, mixed
solvents were evaluated; to our delight, the yield of
product reached 52% when the volume ratio of
DCE/Toluene was 4:1 (Table 1, entry 16). Finally,
With the optimized conditions in hand, we next
began to explore the scope and generality of the
sulfur dioxide insertion process, and the results are
summarized in Table 2. To our delight, diverse
phenyldiazonium tetrafluoroborates bearing either
electron-donating groups (-Me, -OMe), or electron-
withdrawing groups (-Cl, -Br, and -NO2), smoothly
reacted with thiols, affording the corresponding
thiosulfonates in moderate yields. Additionally, the
steric effect was evaluated and found that this
transformation is not sensitive to steric hindrance,
Phenyldiazonium tetrafluoroborates bearing -Me, -Cl,
or -Br at different positions efficiently reacted with
thiols (3m, 3n, 3k, and 3s). Furthermore, the effects
of substituent on thiols were also investigated.
Interestingly, the thiols bearing an electron-donating
group showed a slightly higher reactivity than those
bearing an electron-withdrawing group (3a, 3d, 3f,
and 3k). Naphthyl group was compatible in this
reaction with a moderate reactivity (3i, 3l, and 3q).
Notably, a strong electron-withdrawing group such as
nitro was also tolerated under the reaction standard
conditions (3k). Gratifyingly, a heterocycle thiol such
as 2-methylfuran-3-thiol afforded the desired product
in 36% yield (3r). Subsequently, the coupling
reactions of phenyldiazonium tetrafluoroborates with
alkyl thiols were evaluated (Table 3). Luckily, the
more challenging and simple linear alkyl thiols
DABCO
(1,4-Diazabicyclo[2.2.2]octane),
TFA
.
(Trifluoroacetic acid), BF3 Et2O, FeCl3 and ZnCl2
were used as the additives to further optimize the
efficiency of this transformation. Gratifyingly,
DABCO
(1,4-diazabicyclo[2.2.2]octane;
triethylenediamine) was not suitable for this
transformation, but 1 equiv of TFA (trifluoroacetic
acid) produced the desired thiosulfonate in 64% yield
(Table 1, entry 20). Changing the content of
trifluoroacetic acid in the reaction system could not
significantly increase the yield of the reaction (Table
1, entries 24-27).
Table 2. Substrate scope of phenyldiazonium
tetrafluoroborates with aryl thiols[a], [b]
showed
good
reactivity,10–14 affording
the
corresponding thiosulfonates in moderate-to-good
yields, irrespective of the chain length (5a–5i).
Although
thiols
exhibited
high
reactivity,
unfortunately, phenols and aliphatic alcohols were
poor substrates, and no desired products were
obtained under the standard conditions. The domino
multicomponent reactions tolerated some functional
groups such as C–Cl bonds, C–Br bonds, methyl
group, nitro group, and methoxy group, leaving
ample room for further modification.
Table 3. Substrate scope of phenyldiazonium
tetrafluoroborates with alkyl thiols [a], [b]
3
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10.1002/adsc.201900157
Advanced Synthesis & Catalysis
[a]
Reaction
conditions:
phenyldiazonium
In order to explore the possible mechanism of this
sulfur dioxide insertion pathway, several control
experiments were conducted (Scheme 2). When 4-
chlorobenzenethiol (2b) was added independently
under the standard conditions, no 1,2-bis(4-
chlorophenyl)disulfane (6) was observed [eq (1),
Scheme 2]. Furthermore, treatment of 2-
tetrafluoroborates 1 (0.6 mmol), DABSO (0.4 mmol),
thiols 4 (0.4 mmol), TFA (0.4 mmol), DCE (2.4 mL),
toluene (0.6 mL), reaction time (30 min). [b] Isolated yield.
Table 4. One pot synthesis of thiosulfonates from
arylamines [a], [b]
chlorophenyldiazoniumtetrafluoroborate
(1d),
DABSO with 1,2-bis(4-chlorophenyl)disulfane (6)
under the standard conditions, no desired product
was obtained [eq (2), Scheme 2]. These results
indicated that disulfides might not be intermediates
for this reaction. Additionally, When 2.0 equiv of
TEMPO was added into the reaction solution, the
formation of 3m was completely suppressed, and the
TEMPO-phenyl adduct 7 was detected by ESI-MS
(see Fig. 1 in the ESI†), showing that aryl radical
might be generated in this transformation.
[a]
Reaction conditions: aniline 6 (0.6 mmol), DABSO
(0.4 mmol), thiols 2 or 4 (0.4 mmol), t-BuONO (0.9 mmol),
TFA (0.4mmol), DCE (2.4 mL), toluene (0.6 mL), reaction
time (30 min). [b]Isolated yield.
To simplify the process of this SO2 fixation method,
we
tried
to
replace
phenyldiazonium
tetrafluoroborates by directly using arylamines as the
substrates (Table 4). Luckily, we found that in the
presence of 1.5 equiv of t-BuONO, the reaction
efficiently occurred at 60C, and the desired products
were obtained in moderate yields. Not only aryl thiols
but also alkyl thiols were well tolerated in this
reaction. To our delight, benzo[d]oxazol-2-amine also
furnished the corresponding thiosulfonate 8c in 34%
yield, indicating that the developed metal-free sulfur
dioxide insertion protocol can be applied to
heterocyclic phenyldiazonium tetrafluoroborates and
anilines. This simplified approach provides
possibility for industrial production.
a
Scheme 3. A proposed mechanism for the direct
transformation
On the basis of the preliminary results above and
20
together with the previous related reports,19,
a
plausible mechanism would be herein presented
(Scheme 3). Initially, arydiazonium cation might
react with DABCO·(SO2)2 to give the complex (I)
which could be further transformed into the
intermediate (III) and aryl radical (II) with releasing
of N2 and SO2 through a single electron transfer
(SET) pathway. Subsequently, the aryl radical would
react with SO2 to afford the sulfonyl radical (V).
Meanwhile, the radical cation (III) abstracted
hydrogen from thiols (2), leading to the thiyl radical
(IV). Finally, sulfonyl radical (V) coupled with thiyl
radical (IV), forming the coupling product (4). On the
other hand, direct cross-coupling of aryl radical (II)
with thiyl radical (IV) leads to thioether 8, and homo-
Scheme 2. Control experiments
4
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10.1002/adsc.201900157
Advanced Synthesis & Catalysis
coupling of thiyl radical (IV) gives sulfide 9 as by-
Xie, Y.-J. Li, J. Qu, Y. Duan, J. Hu, K.-J. Liu, Z. Cao,
W.-M. He. Green Chem. 2017, 19, 5642−5646; f) D.-Q.
Dong, S.-H. Hao, D.-S. Yang, L.-X. Li, Z.-L. Wang.
Eur. J. Org. Chem. 2017, 6576−6592; g) L.-Y. Xie, S.
Peng, F. Liu, G.-R. Chen, W. Xia, X. Yu, W.-F. Li, Z.
Cao, W.-M. He. Org. Chem. Front. 2018, 5,
2604−2609.
products in the present transformation.
Conclusion
In conclusion, a novel and efficient protocol was
developed for the synthesis of unsymmetrical
[2] a) C. Wu, X. Xin, Z.-M. Fu, L.-Y. Xie, K.-J. Liu, Z.
Wang, W. Li, Z.-H. Yuan, W.-M. He. Green Chem.
2017, 19, 1983; b) S.-h. Hao, L.-X. Li, D.-Q. Dong, Z.-L.
Wang, X.-Y. Yu. Tetrahedron Lett. 2018, 59,
4073−4075; c) D. Yang, P. Liu, W. Wei, N. Zhang, M.
Yue, J. You, H. Wang. ChemCatChem. 2014, 6,
3434−3439; d) K.-J. Liu, S. Jiang, L.-H. Lu, L.-L. Tang,
S.-S. Tang, H.-S. Tang, Z. Tang, W.-M. He, X. Xu.
Green Chem. 2018, 20, 3038−3043; e) C. Wu, L.-H. Lu,
A.-Z. Peng, G.-K. Jia, C. Peng, Z. Cao, Z. Tang, W.-M.
He, X. Xu. Green Chem. 2018, 20, 3683−3688; f) Z. Lai,
Z. Li, Y. Liu, P. Yang, X. Fang, W. Zhang, B. Liu, H.
Chang, H. Xu, Y. Xu. J. Org. Chem. 2018, 83, 145−153;
g) L.-Y. Xie, J. Qu, S. Peng, K.-J. Liu, Z. Wang, M.-H.
Ding, Y. Wang, Z. Cao, W.-M. He. Green Chem. 2018,
20, 760−764; h) N. Zhang, D. Yang, W. Wei, L. Yuan,
Y. Cao, H. Wang. RSC Advances. 2015, 5, 37013–37017;
i) L.-Y. Xie, S. Peng, L.-L. Jiang, X. Peng, W. Xia, X.
Yu, X.-X. Wang, Z. Cao, W.-M. He. Org. Chem. Front.
2019, 6, 167–169; j) L.-H. Lu, S.-J. Zhou, M. Sun, J.-L.
Chen, W. Xia, X. Yu, X. Xu, W.-M. He. ACS
Sustainable Chem. Eng. 2019, 7, 1574−1579.
thiosulfonates
reactions
via
three-component
coupling
of
phenyldiazonium
tetrafluoroborates/arylamines, DABSO, and thiols. A
series of unsymmetrical thiosulfonates were
conveniently obtained through a radical pathway with
excellent functional group tolerance. Notably, more
challenging linear alkyl thiols showed good reactivity,
affording the corresponding thiosulfonates in
moderate-to-good yields. This easy and simple
method provides a highly attractive approach for the
synthesis of various unsymmetrical thiosulfonates,
and it will broaden the strategies of sulfur dioxide
fixation in the field of organic chemistry.
Experimental Section
General procedure for synthesis of compounds 3a-u:
Under
nitrogen
atmosphere,
phenyldiazonium
tetrafluoroborates (0.6 mmol), DABSO (0.4 mmol),
thiols (0.4 mmol), were introduced to a 20 mL oven-
dried Schlenk tube. Then a solution of TFA (0.4 mmol),
DCE (2.4 mL) and toluene (0.6 mL) were introduced by
a injection syringe. The solution was stirred at 60C for
30 min under N2. After completion of the reaction, the
solvent was removed with the aid of a rotary evaporator.
The residue was purified by column chromatography on
silica gel using petroleum ether/ethyl acetate as eluent to
give the corresponding products.
[3] Selective reviews, see: a) J. Zhu, W.-C. Yang, X.-D.
Wang, L. Wu. Adv. Synth. Catal. 2018, 360, 386−400;
b) I. P. Beletskaya, V. P. Ananikov. Chem. Rev. 2011,
111, 1596–1636; c) F. Dénès, M. Pichowicz, G. Povie, P.
Renaud. Chem. Rev. 2014, 114, 2587–2693.
General procedure for synthesis of compounds 5a-i:
Under nitrogen atmosphere, Arylamines (0.6 mmol), t-
BuONO (0.6 mmol), DABSO (0.4 mmol), thiols (0.4
mmol), were introduced to a 20 mL oven-dried Schlenk
tube. Then a solution of TFA (0.4 mmol), DCE (2.4
mL) and toluene (0.6 mL) were introduced by a
injection syringe. The solution was stirred at 60 C for
30 min under N2. After completion of the reaction, the
solvent was removed with the aid of a rotary evaporator.
The residue was purified by column chromatography on
silica gel using petroleum ether/ethyl acetate as eluent to
give the corresponding products.
[4] a) S. E. Allen, R. R. Walvoord, R. Padilla-Salinas, M.
C. Kozlowski. Chem. Rev. 2013, 113, 6234−6458; b) D.
V. Partyka. Chem. Rev. 2011, 111, 1529−1595.
[5] a) J. P. Weidner, S. S. Block. J. Med. Chem. 1964, 7,
671−673; b) P. Natarajan. Tetrahedron Lett., 2015, 56,
4131−4134.
[6] Selected examples, see: a) B. M. Trost. Chem. Rev.
1978, 78, 363–382; b) V. Girijavallabhan, C. Alvarez, F.
G. Njoroge. J. Org. Chem. 2011, 76, 6442–6446; c) S.
Kim, S. Kim, N. Otsuka, I. Ryu. Angew. Chem., Int. Ed.,
2005, 44, 6183–6186.
Acknowledgements
This work was supported by the Natural Science
Foundation of Shandong Province (ZR2016JL012), and
the National Natural Science Foundation of China
(21302110). We thank Kexin Li and Guomeng Zhang in
this group for reproducing the results of 3a, 3n, 3h, 5e,
and 8b.
[7] a) E. Block and J. O' Connor. J. Am. Chem. Soc. 1974,
96, 3921−3929; b) K. Bahrami, M. M. Khodaei, D.
Khaledian. Tetrahedron Lett. 2012, 53, 354−358; c) N.
Iranpoor, H. Firouzabadi, A.-R. Pourali. Synlett. 2004,
15, 347–349; d) M. Cai, G. Lv, J. Chen, W. Gao, J. Ding,
H. Wu. Chem. Lett. 2010, 39, 368–369.
[8] Y. H. Kim, T. Takata, S. Oae. Tetrahedron Lett. 1978,
19, 2305–2308.
References
[1] Selective reviews, see: a) T. Kondo, T. Mitsudo.
Chem. Rev. 2000, 100, 3205−3220; b) A. Y. Sizov, A.
N. Kovregin, A. F. Ermolov. Russ. Chem. Rev. 2003,
72, 357−374; c) S. S. Mansy, J. A. Cowan. Acc. Chem.
Res., 2004, 37, 719−725; d) I. P. Beletskaya, V. P.
Ananikov. Chem. Rev. 2011, 111, 1596−1636; e) L.-Y.
[9] M. Xia, Z. C. Chen. Synth. Commun. 1997, 27, 1309–
1313.
[10] Y. Liu, Y. Zhang. Tetrahedron Lett. 2003, 44, 4291–
4294.
5
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10.1002/adsc.201900157
Advanced Synthesis & Catalysis
[11] M. D. Bentley, I. B. Douglass, J. A. Lacadie. J. Org.
Chem. 1972, 37, 333–334.
J. Wu, Chem. Asian J. 2017, 12, 465–469; m) Y. Li, R.
Mao, J. Wu, Org. Lett. 2017, 19, 4472−4475.
[12] G. Liang, J. Chen, J. Chen, W. Li, J. Chen, H. Wu.
Tetrahedron Lett. 2012, 53, 6768–6770.
[19] a) N. A. Romero, D. A.Nicewicz. Chem. Rev. 2016,
116, 10075–10166; b) C,-L. Sun, Z,-J. Shi. Chem. Rev.
2014, 114, 9219–9280.
[13] N. Taniguchi. J. Org. Chem. 2015, 80, 1764–1770.
[20] D. Zheng, Y. An, Z. Li, J. Wu, Angew. Chem. Int. Ed.
2014, 53, 2451–2454.
[14] G.-Y. Zhang, S.-S. Lv, A. Shoberu, J.-P. Zou. J. Org.
Chem. 2017, 82, 9801–9807.
[21] a) D. Zheng, M. Chen, L. Yao, J. Wu, Org. Chem.
Front. 2016, 3, 985–988; b) K. Zhou, M. Chen, L. Yao,
J. Wu, Org. Chem. Front. 2018, 5, 366–370; c) T. Liu,
W. Zhou, J.Wu. Org. Lett. 2017, 19, 6638–6641; d) T.
Liu, D. Zheng, Z. Li, J. Wu. Adv. Synth. Catal. 2018,
360, 865–869; e) H. Xia, Y. An, X. Zeng, J. Wu. Chem.
Commun. 2017, 53, 12548–12551; f) Y. An, J. Wu. Org.
Lett. 2017, 19, 6028–6031; g) Z.-J. Shen, Y.-N. Wu, C.-
L. He, L. He, W.-J. Hao, A.-F. Wang, S.-J. Tu, B. Jiang.
Chem. Commun. 2018, 54, 445–448; h) D. Zheng, J. Yu,
J. Wu. Angew. Chem. Int. Ed. 2016, 55, 11925 –11929;
i) F. Liu, J.-Y. Wang, P. Zhou, G. Li, W.-J. Hao, S.-J.
Tu, B. Jiang, Angew. Chem. Int. Ed. 2017, 56, 15570–
15574; j) A.-F. Wang, W.-J. Hao, Y.-L. Zhu, G. Li, P.
Zhou, S.-J. Tu, B. Jiang. ACS Omega. 2018, 3, 1482–
1491; k) G. Qiu, L. Lai, J. Cheng, J. Wu. Chem.
Commun. 2018, 54, 10405–10414; l) Y. Li, R. Mao, J.
Wu. Org. Lett. 2017, 19, 4472–4475; m) X. Gong, J.
Chen, L. Lai, J. Cheng, J. Sun, J. Wu. Chem. Commun.
2018, 54, 11172–11175; n) D. Yang, P. Sun, W. Wei, F.
Liu, H. Zhang, H. Wang; Chem. Eur. J. 2018, 24, 4423–
4427; o) S. Liu, K. Chen, W.-J. Hao, X.-C. Tu, S.-J. Tu,
B. Jiang, J. Org. Chem. 2019, 84, 1964−1971; p) M.-H.
Huang, W.-J. Hao, G. Li, S.-J. Tu, B. Jiang, Chem.
Commun. 2018, 54, 10791−10811; q) M.-H. Huang, M,-
H, Huang, W,-J, Hao, B. Jiang, Chem. Asian J. 2018, 13,
2958−2977
[15] Z. Peng, X. Zheng, Y. Zhang, D. An, W. Dong. Green
Chem., 2018, 20, 1760–1764.
[16] a) Z.-Y. Mo, T. R. Swaroop, W. Tong, Y.-Z. Zhang,
H.-T. Tang, Y.-M. Pan, H.-B. Sun, Z.-F. Chen, Green
Chem. 2018, 20, 4428–4432; b) L. Cao, S.-H. Luo, K.
Jiang, Z.-F. Hao, B.-W. Wang, C.-M. Pang, Z.-Y. Wang,
Org. Lett. 2018, 20, 4754–4758.
[17] B. Nguyen, E. J. Emmett, M. C. Willis, J. Am. Chem.
Soc. 2010, 132, 16372–16373.
[18] For selected examples, see: a) A. S. Deeming, C. J.
Russell, M. C. Willis. Angew. Chem. Int. Ed. 2015, 54,
1168–1171; b) A. T. Davies, J. M. Curto, S. W. Bagley,
M. C. Willis. Chem. Sci. 2017, 8, 1233–1237; c) P.
Bisseret, N. Blanchard. Org. Biomol. Chem. 2013, 11,
5393–5398; d) S. Ye, H. Wang, Q. Xiao, Q. Ding, J. Wu,
Adv. Synth. Catal. 2014, 356, 3225–3230; e) Y. An, D.
Zheng, J. Wu, Chem. Commun. 2014, 50, 11746–11748;
f) D. Zheng, Y. Li, Y. An, J. Wu, Chem. Commun. 2014,
50, 8886–8888; g) F. Zhang, D. Zheng, L. Lai, J. Cheng,
J. Sun, J. Wu, Org. Lett. 2018, 20, 1167−1170; h) S. Ye,
J. Wu. Chem. Commun. 2012, 48, 7753–7755; i) W. Li,
M. Beller, X.-F. Wu, Chem. Commun. 2014, 50, 9513–
9516; j) X. Wang, L. Xue, Z. Wang. Org. Lett. 2014, 16,
4056–4058; k) A. S. Tsai, J. M. Curto, B. N. Rocke, A.
R. Dechert-Schmitt, G. K. Ingle, V. Mascitti. Org. Lett.
2016, 18, 508–511; l) T. Liu, D. Zheng, Y. Ding, X. Fan,
6
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10.1002/adsc.201900157
Advanced Synthesis & Catalysis
FULL PAPER
Metal-Free
Synthesis
of
Unsymmetrical
Thiosulfonates via Insertion of Sulfur Dioxide
Adv. Synth. Catal. Year, Volume, Page – Page
Guoqing Li,a,b Ziyu Gan,b Kexin Kong,b Xiaomeng,
Dou,c and Daoshan Yang*a,b
7
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