TMSOTf-Promoted Sulfinylation of Electron-Rich Aromatics with Sodium Arylsulfinates

Article abstract of DOI:10.1055/s-0039-1691563

A new transition-metal-free route for the direct sulfinylation of electron-rich aromatics with sodium arylsulfinates in the presence of TMSOTf is reported. Various electron-rich aromatics, including pyrroles, thiophenes, indoles, and electron-rich arenes, with sodium arylsulfinates are converted into the corresponding sulfoxides in moderate to excellent yields. This protocol possesses many advantages such as readily available and stable starting materials, broad substrate scopes, and transition-metal-free reaction conditions.

Full text of DOI:10.1055/s-0039-1691563

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© Georg Thieme Verlag Stuttgart · New York
2020, 31, A–F
letter
A
en
Y.-Z. Ji et al.
Letter
Synlett
TMSOTf-Promoted Sulfinylation of Electron-Rich Aromatics with
Sodium Arylsulfinates
Yuan-Zhao Jia
R1
R2
Hui-Jing Li*a,b
Hao-Ran Yanga
Zheng-Yan Zhanga
Li-Jun Xiea
X
X = NMe, NBn, NPh, NH, S
1 = F, Br, Me, OMe, NO2, CN
R
2 = OMe, OH, Me
O
ArSO2Na, TMSOTf
R
air, room temperature
O
Ar
S
S
Yan-Chao Wu*a,b
0
0
0
0-0
0
0
2-0
1
1
1-7
4
8
4
Ar
R2
R1
12 examples
34 examples
a School of Marine Science and Technology, Harbin Institute of
Technology, 2 Wenhuaxi Road, Weihai 264209, P. R. of China
b Weihai Institute of Marine Biomedical Industrial Technology,
Wendeng District, Weihai 264400, P. R. of China
lihuijing@iccas.ac.cn
X
yield up to 95%
yield up to 90%
ycwu@iccas.ac.cn
Received: 03.10.2019
Accepted after revision: 16.12.2019
Published online: 09.01.2020
quently, we reported a TMSOTf-promoted thiolation of in-
doles with sodium arylsulfinates by in situ overreduction of
the new generated, sulfinylated intermediates (Scheme 1b,
left).15b We envisioned that the sulfoxide reduction process
might be obviated by carefully controlling the reaction con-
ditions, and thus could facilitate a practical sulfoxide syn-
thesis. We report herein the realization of this strategy by
shortening the reaction time (i.e., 12 h vs. 0.5–1 h) and si-
multaneously decreasing the amount of TMSOTf (i.e., 4
equiv vs. 2 equiv), which provide a facile synthetic protocol
to sulfoxides from electron-rich arenes and heteroarenes
with sodium arylsulfinates (Scheme 1b, right).
DOI: 10.1055/s-0039-1691563; Art ID: st-2019-k0654-l
Abstract A new transition-metal-free route for the direct sulfinylation
of electron-rich aromatics with sodium arylsulfinates in the presence of
TMSOTf is reported. Various electron-rich aromatics, including pyrroles,
thiophenes, indoles, and electron-rich arenes, with sodium arylsulfi-
nates are converted into the corresponding sulfoxides in moderate to
excellent yields. This protocol possesses many advantages such as readily
available and stable starting materials, broad substrate scopes, and
transition-metal-free reaction conditions.
Key words sulfinylation, pyrroles, indoles, sulfoxides, sodium arylsulfi-
nates
a) Sulfinate syntheses15a
O
S
O
S
TMSCl
Sulfoxides are prevalent in important and high-value
chemical structures1 such as the natural products,2 phar-
maceutically active compounds,3 ligands,4 organocatalysis,5
and functional materials.6 Traditionally, sulfoxides could be
prepared by oxidation of sulfides7 or nucleophilic substitu-
tion of sulfinyl derivatives with organometallic reagents.8
In addition, other synthetic approaches to sulfoxides, such
as transition-metal-catalyzed arylation of sulfenate an-
ions,9 have also been reported.10 In recent years, direct
sulfinylation of electron-rich arenes and heteroarenes has
been developed by using sulfinic acids,11 sulfinates,12 and
sulfinamides13 as the sulfinylating reagents. Despite these
advances, the direct synthesis of the sulfoxides, using easy-
to-handle reagents under mild reaction conditions, remains
in demand.
On the other hand, sodium arylsulfinates are stable,
odorless, and easy-to-handle sulfur compounds, and thus
have been widely used as desirable starting materials
for the synthesis of organosulfur compounds.14,15 We have
reported the advantages of using sodium arylsulfinates/
TMSCl system with oxygenated nucleophiles for obtaining
sulfinates under mild conditions (Scheme 1a).15a Subse-
R–OH
+
Ar
ONa
Ar
OR
b) Thioether15b and sulfoxide syntheses
TMSOTf
TMSOTf
(2 equiv)
O
S
O
S
(4 equiv)
S
Ar2–H
Ar1
Ar2
+
Ar1
ONa
Ar1
Ar2
12 h
0.5–1.0 h
this work
Ar2 = indoles
Ar2 = indoles, pyrroles, thiophenes,
electron-rich arenes
Scheme 1 Synthetic application of sodium arylsulfinates
Reaction of sodium p-toluenesulfinate (1a) with N-Me-
pyrrole (2a) was used as a probe for evaluating the reaction
conditions (Table 1). Following our previous procedure (2
equiv of TMSCl, CH2Cl2, rt),15a reaction of sodium p-toluene-
sulfinate (1a) with N-Me-pyrrole (2a, 1.5 equiv) afforded 2-
sulfinylpyrrole 3a and 3-sulfinylpyrrole 4a in 6% and 55%
yields, respectively (Table 1, entry 1). Subsequently, DMSCl,
TIPSCl, TBDMSCl, TMSOTf, BF3·Et2O, CF3SO3H, p-TsOH·H2O,
and AcOH were further investigated for this reaction, and
TMSOTf is found to be the most efficient promoter for this
reaction (Table 1, entries 1–9). The reaction did not work
when it was performed in DMF, DMSO, H2O (Table 1, entries
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y.-Z. Ji et al.
Letter
Synlett
10–12). With the use of MeNO2, MeCN, THF, 1,4-dioxane,
and toluene in comparison to (ClCH2)2, lower yields were
found (Table 1, entries 13–18). No reaction took place in the
absence of TMSOTf (Table 1, entry 19). Further parameters
optimization identified the most effective TMSOTf loading
as 2.0 equiv (Table 1, entries 13 and 20–24). The reaction
was also performed under argon atmosphere, and the same
yield was observed (Table 1, entries 13 and 25), which indi-
cated that noble gas atmosphere is not necessary for this re-
action.
The optimized sulfinylation reaction conditions proved
to be effective for various sodium arylsulfinates 1 and
pyrroles/thiophenes 2 (Scheme 2). With the aromatic ring
bearing hydrogen atoms, electron-withdrawing and elec-
tron-donating groups, sodium arylsulfinates 1 reacted
smoothly with N-Me-pyrrole (2a) in the presence of
TMSOTf (2 equiv) in (ClCH2)2 at 25 °C to afford sulfoxides
4a–l in 31–84% yields within 0.5 h. 1-Naphthyl-, 2-naphth-
yl-, 2-thienyl-, and cyclopropyl-substituted sodium sulfi-
nates reacted with pyrrole 2a to generate the sulfoxides
4m–p in 45–77% yields. N-Substituted pyrroles with benzyl
and phenyl reacted with sodium p-toluenesulfinate (1a) to
afford the sulfoxides 4q and 4r in 90% and 89% yields, re-
spectively. Treatment of 1-tosyl-1H-pyrrole with sodium
arylsulfinate 2a failed to give the desired sulfoxide 4s. The
reaction of 1H-pyrrole and 2,5-dimethyl-1H-pyrrole with
sodium arylsulfinate 2a went smoothly to generate the de-
sired sulfoxides 4t and 4u in 41% and 36% yields, respective-
ly.
Table 1 Optimization of the Reaction Conditionsa
O
O
O
S
S
promoter
(X equiv)
S
N
+
+
ONa
N
solvent
rt, 0.5 h
N
1a
2a
3a
4a
Entry
Promoter
(X equiv)
Solvent
Yield of 3a Yield of
(%)b
4a (%)b
1
2
TMSCl (2.0)
DMSCl (2.0)
TIPSCl (2.0)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DMF
6
4
2
3
0
0
0
0
55
22
3
20
4
TBDMSCl (2.0)
TMSOTf (2.0)
BF3·Et2O (2.0)
CF3SO3H (2.0)
62
5
76
6
60
7
66
8
p-TsOH·H2O (2.0)
AcOH (2.0)
23
9
N.D.
N.D.
N.D.
N.D.
N.D.
88 (83c)
60
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25d
TMSOTf (2.0)
TMSOTf (2.0)
TMSOTf (2.0)
TMSOTf (2.0)
TMSOTf (2.0)
TMSOTf (2.0)
TMSOTf (2.0)
TMSOTf (2.0)
TMSOTf (2.0)
–
N.D.
N.D.
N.D.
0
DMSO
H2O
(ClCH2)2
MeNO2
MeCN
THF
0
0
81
0
74
1,4-dioxane
toluene
0
50
Reaction of 3-ethyl-2,5-dimethyl-1H-pyrrole with sodi-
um arylsulfinate 2a is complex under the standard condi-
tions and the expected sulfoxides 4v was not observed. In-
terestingly, treatment of 1-(1-benzyl-1H-pyrrol-2-yl)ethan-
1-one, an electron-deficient pyrrole, with sodium arylsulfi-
nate 2a under the standard conditions did not afford the
corresponding thermodynamic product 3-sulfinylpyrrole.
Instead, kinetic product 2-sulfinylpyrrole 3w was obtained
in 13% yield, whose structure has been determined from
the observed different chemical shifts and coupling con-
0
77
(ClCH2)2
(ClCH2)2
(ClCH2)2
(ClCH2)2
(ClCH2)2
(ClCH2)2
(ClCH2)2
N.R.
6
N.R.
10
TMSOTf (0.5)
TMSOTf (1.0)
TMSOTf (1.5)
TMSOTf (3.0)
TMSOTf (4.0)
TMSOTf (2.0)
4
38
0
73
0
74
0
64
0
88
a General conditions: 1a (0.2 mmol), 2a (0.3 mmol), and promoter (0–0.8
mmol) in solvent (1.0 mL) at rt for 0.5 h. DMS = dimethylsilyl; TIPS = triiso-
stant between Ha/Hb (a = 5.54 ppm, b = 5.50 ppm, Jab = Jba
=
15.0 Hz, Scheme 2). Ethyl 1-benzyl-2,4-dimethyl-1H-pyr-
role-3-carboxylate, an electron-deficient pyrrole with its 3-
positions possessing substituents, was also investigated,
which reacted with sodium arylsulfinate 2a to generate the
overreduction product 5x in 47% yield. The reaction of thio-
phene, 3-hexylthiophene with sodium arylsulfinate 2a
went smoothly to afford sulfoxides 4y and 4z in 23% and
63% yields, respectively.
To prove the synthetic utility of this synthetic method,
gram-scale reaction was carried out under the standard
sulfinylation conditions (Scheme 3). The reaction of sodium
sulfinate 1a (30 mmol, 5.34 g) reacted smoothly with pyr-
role 2a (45 mmol) in the presence of TMSOTf (60 mmol) in
propylsilyl; TBDMS = tert-butyldimethylsilyl; N.D. = no detection; N.R. = no
reaction.
b The yield was determined by 1H NMR spectroscopy using 0.2 mmol of
CH2Br2 as a standard.
c Isolated yield.
d Under argon.
(ClCH2)2 at 25 °C to afford sulfoxides 4a (5.32 g) in 81% yield
within 0.5 h. This result showed the great potential of this
sulfinylation reaction in practical synthesis.
To glean insight into the sulfinylation reaction mecha-
nism, a control experiment was carried out in Scheme 4. By
treating of 2-substituted sulfoxide product 3a in the pres-
ence of TMSOTf (2 equiv) in (ClCH2)2 at 25 °C, 3-substituted
sulfoxide product 4a was generated in 90% yield. This result
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

C
Y.-Z. Ji et al.
Letter
Synlett
O
O
O
S
O
S
TMSOTf (2 equiv)
(ClCH2)2, rt, 0.5 h
S
S
Ar
TMSOTf (2 equiv)
(ClCH2)2, rt, 0.5 h
+
+
ONa
X
N
ONa
Ar
X
N
1
2
4
1a
(30 mmol)
2a
4a
(81%, 5.32 g)
O
O
S
O
(1.5 equiv)
S
S
OMe
Scheme 3 Gram-scale synthesis
N
N
N
N
N
N
N
4a, 83%
4b, 59%
4c, 68%
O
O
O
S
O
O
S
N
S
TMSOTf (2 equiv)
(ClCH2)2, rt, 5 min
S
S
CF3
F
Cl
N
N
3a
4a, 90%
4d, 69%
4e, 32%
4f, 82%
Scheme 4 The control experiment
O
S
O
O
S
S
Br
NO2
Br
N
tion of pyrroles is depicted in Scheme 5. Reaction of sodium
arylsulfinates 1 with TMSOTf generated trimethylsilyl sulfi-
nates 6, which underwent electrophilic substitution reac-
tion with pyrroles 2 at the C3 position to form thermody-
namic intermediates 7. Finally, intermediates 7 were con-
verted into thermodynamic products 4 with the release of
TMSOH (Scheme 5, a). On the other hand, electrophilic sub-
stitution reaction of trimethylsilyl sulfinates 6 with pyr-
roles 2 at the C2 position generated kinetic intermediates 8,
which were converted into kinetic products 3 with the re-
lease of TMSOH (Scheme 5, b). When electron-rich pyrroles
were used as the substrates, thermodynamic products 4
were obtained as the major products under our standard
reaction conditions. When electron-deficient pyrroles were
used as the substrates, kinetic products, such as 2-sulfin-
ylpyrrole 3w, or the related overreduction products, such as
thioether 5x, might be obtained.
Sulfinylation of indoles 9 with sodium arylsulfinates 1
were subsequently investigated (Scheme 6). With the aro-
matic ring bearing electron-withdrawing or electron-
donating groups (Cl, Me, MeO), sodium sulfinates 1 reacted
smoothly with N-methylindole (9a) in the presence of
TMSOTf (2 equiv) in (ClCH2)2 at 25 °C to afford sulfoxides
10a–c in 54–78% yields within 0.5 h. Sodium naphthalene-
1-sulfinate reacted well with indole 9a to afford sulfoxide
10d in 73% yield. A wide variety of indoles with substituent
groups such as halogen, nitro, cyano, and methoxyl reacted
smoothly with sodium p-toluenesulfinate (1a) to afford
sulfoxides 10e–i in 54–79% yields. Unfortunately, treatment
of 1,3-dimethyl-1H-indole with sodium arylsulfinate 2a
failed to provide the desired sulfoxide 10j. N-Substituted in-
dole with benzyl and N-unsubstituted indole reacted with
sodium p-toluenesulfinate (1a) to generate sulfoxides 10k
and 10l in 78% and 15% yields, respectively.
4g, 65%
4h, 35%
4i, 65%
F
O
S
O
O
S
S
Cl
F
N
N
N
N
N
N
4j, 78%
4k, 31%
4l, 84%
O
S
O
S
O
S
S
4m, 77%
4n, 66%
4o, 45%
4r, 89%
4u, 36%
O
S
O
S
O
S
N
N
N
Bn
Ph
4p, 50%
4q, 90%
O
S
O
S
O
S
N
N
H
N
H
Ts
4s, 0%
4t, 41%
O
S
EtO2C
Et
O
Tol
S
N
S
Ha
O
N
N
Ph
Hb
H
Bn
4v, 0%
3w, 13%
5x, 47%
O
O
S
S
S
S
4y, 23%
4z, 63%
Scheme 2 TMSOTf-promoted sulfinylation of pyrroles/thiophenes 2
with sodium sulfinates 1. Reagents and conditions: 1 (0.2 mmol), 2 (0.3
mmol), and TMSOTf (0.4 mmol) in (ClCH2)2 (1.0 mL) at rt for 0.5 h. Iso-
lated yields are given.
The feasibility of this sulfoxide synthesis was also explored
by using various arenes 11 as the substrates (Scheme 7).
Arenes 11 bearing electron-donating groups (EDG) such as
OMe, OH, and Me reacted with sodium arylsulfinates
1 in the presence of TMSOTf (2 equiv) in (ClCH2)2 at 25 °C
to afford sulfoxides 12a–i in 39–95% yields within 1 h.
indicated that the sulfinylation reaction probably under-
went a rearrangement from C2-sulfinylpyrroles 3 to C3-
sulfinylpyrroles 4.
Based on the experimental results and literature re-
ports,15,16 the possible reaction pathway for the sulfinyla-
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

D
Y.-Z. Ji et al.
Letter
Synlett
a) Thermodynamic products
O
S
O
S
O
S
O
S
– TMSOH
TMSOTf
– TfONa
Ar
Ar
Ar
OTMS
Ar
ONa
TMSO–
H
N
N
1
6
7
4
R
R
N
R
2
b) Kinetic products
O
S
O
S
R
N+
O
R
N
TMSO–
S
Ar
N
OTMS
Ar
Ar
TMSOH
H
R
2
6
8
3
Scheme 5 Proposed mechanism for the sulfinylation of pyrroles 2 with sodium arylsulfinates 1
O
O
S
Ar
S
O
TMSOTf (2 equiv)
(ClCH2)2, rt, 1 h
Ar
TMSOTf (2 equiv)
EDG
O
S
S
EDG
+
R1
R1
Ar
ONa
+
N
R2
(ClCH2)2, rt, 0.5 h
N
Ar
ONa
1a
11
12
R2
1
9
10
O
O
S
O
S
S
Cl
OMe
O
O
O
S
S
S
S
MeO
MeO
Cl
HO
HO
12a, 55%
12b, 48%
12c, 52%
N
N
N
O
S
O
S
O
S
10a, 78%
10b, 62%
10c, 54%
O
O
O
S
S
HO
HO
HO
Br
12d, 55%
12e, 39%
12f, 55%
N
N
O
S
O
S
OMe
O
S
N
F
10d, 73%
10e, 78%
10f, 79%
O
O
S
O
S
HO
MeO
OMe
S
MeO
NC
O2N
12g, 95%
12h, 80%
12i, 70%
N
N
N
OMe
O
S
OH
O
S
O
S
10g, 64%
10h, 66%
10i, 54%
O
O
S
HO
MeO
OH
S
12j, 50%
12ka, 44%
12kb, 32%
S
N
N
O
N
O
S
O
S
H
Bn
O2N
NC
10j, 0%
10k, 78%
10l, 15%
Scheme 6 TMSOTf-promoted sulfinylation of indoles 9 with sodium ar-
ylsulfinates 1. Reagents and conditions: 1 (0.2 mmol), 9 (0.4 mmol), and
TMSOTf (0.4 mmol) in (ClCH2)2 (1.0 mL) at rt for 0.5 h. Isolated yields
are given.
12l, 0%
12m, 0%
Scheme 7 TMSOTf-promoted sulfinylation of arenes 11 with sodium
arylsulfinates 1. Reagents and conditions: 1 (0.2 mmol), 11 (0.4 mmol),
and TMSOTf (0.4 mmol) in (ClCH2)2 (1.0 mL) at rt for 1 h. Isolated yields
are given.
Naphthalen-2-ol reacted well with sodium p-toluenesulfi-
nate (1a) to afford the desired sulfoxide 12j in 50% yield.
Treatment of 3-methoxyphenol with sodium arylsulfinate
1a afforded the two sulfoxide isomers 12ka and 12kb in
44% and 32% yields, respectively. Treatment of nitrobenzene
and cyanobenzene with sodium sulfinate 2a under the
standard conditions failed to give the desired sulfoxides 12l
and 12m; meanwhile, the starting material nitrobenzene
and cyanobenzene were recovered in 89% and 86% yields,
respectively.
transition-metal-free conditions.17 A wide variety of sulfox-
ides were obtained with moderate to excellent yields. These
reactions could take place under mild conditions without
the need for using transition-metal catalysts, which offers
attractive industrial application prospects.
Funding Information
In summary, we have developed a facile sulfoxides syn-
thesis via the TMSOTf-promoted sulfinylation of electron-
rich aromatics, including pyrroles, thiophenes, indoles, and
electron-rich arenes, with sodium arylsulfinates under
This project was funded by the Key Research and Development Pro-
gram of Shandong (Grant No. 2019GSF108089), the Natural Science
Foundation of Shandong Province (ZR2019MB009), the National Nat-
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

E
Y.-Z. Ji et al.
Letter
Synlett
ural Science Foundation of China (Grant No. 21672046 and
Am. Chem. Soc. 2008, 130, 2172. (j) Mellah, M.; Voituriez, A.;
Schulz, E. Chem. Rev. 2007, 107, 5133. (k) Kobayashi, S.; Ogawa,
C.; Konishi, H.; Sugiura, M. J. Am. Chem. Soc. 2003, 125, 6610.
(5) (a) Zhang, M.; Jia, T.; Sagamanova, I. K.; Pericás, M. A.; Walsh, P.
J. Org. Lett. 2015, 17, 1164. (b) Schwan, A. L. ChemCatChem 2015,
7, 226. (c) Zhang, M.; Jia, T.; Yin, H.; Carroll, P. J.; Schelter, E. J.;
Walsh, P. J. Angew. Chem. Int. Ed. 2014, 53, 10755.
(6) (a) Yanagi, T.; Nogi, K.; Yorimitsu, H. Synlett 2019, in press; doi:
10.1055/s-0037-1611767. (b) Chena, D.; Liu, J. G.; Zhang, X.; Xu,
M. H. Synlett 2019, 30, 1693. (c) Numata, M.; Aoyagi, Y.; Tsuda,
Y.; Yarita, T.; Takatsu, A. Anal. Chem. 2007, 79, 9211. (d) Oyama,
T.; Naka, K.; Chujo, Y. Macromolecules 1999, 32, 5240.
21372054), and the Found from the Huancui District of Weihai City.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691563.
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References and Notes
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© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

F
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MHz, CDCl3):  = 141.9, 140.3, 129.3, 126.8, 124.5, 124.3, 123.9,
107.4, 36.4, 21.2. Data are in accordance to those previously
reported.13a
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General Procedure for the Preparation of Sulfoxides 10
The mixture of sodium arylsulfinate (0.2 mmol, 1.0 equiv),
indole (0.4 mmol, 2.0 equiv), and TMSOTf (0.4 mmol, 2.0 equiv)
in (ClCH2)2 (1.0 mL) was stirred at 25 °C for 0.5 h. After comple-
tion of the reaction, water (5 mL) and dichloromethane (10 mL)
were added. The two layers were separated, and the aqueous
phase was extracted with dichloromethane (3 × 10 mL). The
combined organic extracts were washed by brine, dried over
anhydrous Na2SO4, filtered, and concentrated. The residue was
purified by flash chromatography on silica gel (ethyl acetate–
petroleum ether = 1:1) to afford the desired sulfoxides 10.
Compound 10a: white solid, mp 138–139 °C; 42.0 mg, 78%
yield. 1H NMR (400 MHz, CDCl3):  = 7.62 (d, J = 8.2 Hz, 2 H),
7.48 (d, J = 8.7 Hz, 2 H),7.34–7.24 (m, 4 H), 7.12–7.08 (m, 1 H),
3.79 (s, 3 H), 2.40 (s, 3 H). 13C NMR (100 MHz, CDCl3):  = 140.9,
140.3, 137.6, 132.5, 129.5, 124.8, 124.3, 123.2, 121.3, 119.8,
116.5, 110.0, 33.2, 21.2. Data are in accordance to those previ-
ously reported.13a
(16) (a) Hostier, T.; Ferey, V.; Ricci, G.; Pardo, D. G.; Cossy, J. Chem.
Commun. 2015, 51, 13898. (b) Carson, J. R.; Davis, N. M. J. Org.
Chem. 1981, 46, 839. (c) Carmona, O.; Greenhouse, R.; Landeros,
R.; Muchowski, J. M. J. Org. Chem. 1980, 45, 5336.
General Procedure for the Preparation of Sulfoxides 12
The mixture of sodium arylsulfinate (0.2 mmol, 1.0 equiv),
arene (0.4 mmol, 2.0 equiv), and TMSOTf (0.4 mmol, 2.0 equiv)
in (ClCH2)2 (1.0 mL) was stirred at 25 °C for 1 h. After comple-
tion of the reaction, water (5 mL) and dichloromethane (10 mL)
were added. The two layers were separated, and the aqueous
phase was extracted with dichloromethane (3 × 10 mL). The
combined organic extracts were washed by brine, dried over
anhydrous Na2SO4, filtered, and concentrated. The residue was
purified by flash chromatography on silica gel (ethyl acetate–
petroleum ether = 1:1) to afford the desired sulfoxides 12.
(17) General Procedure for the Preparation of Sulfoxides 4
The mixture of sodium arylsulfinate (0.2 mmol, 1.0 equiv), pyr-
role/thiophenes (0.3 mmol, 1.5 equiv), and TMSOTf (0.4 mmol,
2.0 equiv) in (ClCH2)2 (1.0 mL) was stirred at 25 °C for 0.5 h.
After completion of the reaction, water (5 mL) and dichloro-
methane (10 mL) were added. The two layers were separated,
and the aqueous phase was extracted with dichloromethane (3
× 10 mL). The combined organic extracts were washed by brine,
dried over anhydrous Na2SO4, filtered, and concentrated. The
residue was purified by flash chromatography on silica gel
(ethyl acetate–petroleum ether = 1:1) to afford the desired sulf-
oxides 4.
1
Compound 12a: colorless oil, 27.0 mg, 55% yield. H NMR (400
MHz, CDCl3):  = 7.55 (d, J = 8.8 Hz, 2 H), 7.49 (d, J = 8.1 Hz, 2 H),
7.25 (d, J = 7.3 Hz, 2 H), 6.95 (d, J = 8.8 Hz, 2 H), 3.81 (s, 3 H), 2.36
(s, 3 H). 13C NMR (100 MHz, CDCl3):  = 161.8, 142.5, 141.2,
136.9, 129.8, 127.0, 124.7, 114.7, 55.4, 21.3. Data are in accor-
dance to those previously reported.11a
Compound 4a: white solid, mp 84–86 °C; 36.3 mg, 83% yield. 1H
NMR (400 MHz, CDCl3):  = 7.53 (d, J = 8.2 Hz, 2 H), 7.27 (d, J =
8.0 Hz, 2 H), 6.95 (t, J = 2.0 Hz, 1 H), 6.58 (t, J = 2.5 Hz, 1 H), 6.16
(dd, J = 3.0, 1.7 Hz, 1 H), 3.64 (s, 3 H), 2.39 (s, 3 H). 13C NMR (100
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F