Tetrabutylammonium Iodide Mediated Synthesis of β-Alkoxy Sulfides and Vinyl Sulfones by Using Benzenesulfonyl Chlorides as the Sulfur Sources under Acidic or Alkaline Conditions

Article abstract of DOI:10.1055/s-0035-1561667

The tetrabutylammonium iodide (TBAI)-promoted generation of sulfur-containing compounds from benzenesulfonyl chlorides and alkenes is described. Under acidic condition, a wide range of β-alkoxy sulfides were obtained in good to excellent yields, whereas under alkaline conditions, various vinyl sulfones were produced in moderate to good yields. A novel preparation of (E)-β-iodovinyl sulfones was achieved through direct difunctionalization of alkynes with benzenesulfonyl chlorides and TBAI.

Full text of DOI:10.1055/s-0035-1561667

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–F
letter
A
D. Wang et al.
Letter
Synlett
Tetrabutylammonium Iodide Mediated Synthesis of β-Alkoxy Sul-
fides and Vinyl Sulfones by Using Benzenesulfonyl Chlorides as the
Sulfur Sources under Acidic or Alkaline Conditions
Dingyi Wang
Rongxing Zhang
Sen Lin*
one-pot process
metal-free
versatile
O
Ar1
Ar2
Ar3
S
Ar
I
or
Ar2
ROH
Ar2
O
Zhaohua Yan
Shengmei Guo*
S
R
O
Ar1 SO2Cl
Ar1
O
S
TBAI-Base
TBAI-Acid
Ar3
O
Ar
College of Chemistry, Nanchang University, Nanchang, Jiangxi
330031, P. R. of China
senlin@ncu.edu.cn
13 examples
up to 90% yield
high regioselectivity
12 examples
high stereoselectivity
smguo@ncu.edu.cn
Received: 22.04.2016
Accepted after revision: 15.05.2016
Published online: 14.06.2016
methods need to be resolved: (1) the use of metallic cata-
lysts is harmful to the environment; (2) the above-men-
tioned sulfur sources are frequently restricted by their high
price, poor stability, and high toxicity; and (3) there are few
reports on the generation of β-alkoxy sulfides or (E)-β-io-
dovinyl sulfones.
DOI: 10.1055/s-0035-1561667; Art ID: st-2016-w0285-l
Abstract The tetrabutylammonium iodide (TBAI)-promoted genera-
tion of sulfur-containing compounds from benzenesulfonyl chlorides
and alkenes is described. Under acidic condition, a wide range of β-
alkoxy sulfides were obtained in good to excellent yields, whereas under
alkaline conditions, various vinyl sulfones were produced in moderate
to good yields. A novel preparation of (E)-β-iodovinyl sulfones was
achieved through direct difunctionalization of alkynes with benzenesul-
fonyl chlorides and TBAI.
To address those issues, Tian and co-workers developed
an I2-catalyzed preparation of β-alkoxy sulfides by opening
the C=C double bonds of styrenes with benzenesulfonylhy-
drazides as sulfur sources.6 Other groups have reported
novel approaches to β-alkoxy sulfides.7 For vinyl sulfones,
synthetic methods have been reported by Wang and co-
workers,8 Shi and co-workers,9 and others.10 The protocols
proved to be convenient and flexible methods for synthe-
sizing vinyl sulfones. Nevertheless, from the point of view
of the raw materials, derivatives of the above-mentioned
sulfur sources needed to be synthesized, because these de-
rivatives are not readily available on the market. It is worth
noting that the relevant substrates are prepared from ben-
zenesulfonyl chlorides. Oddly, the synthesis of various thio-
ethers by direct sulfur-functionalization of alkenes with
benzenesulfonyl chlorides as sulfur sources has rarely been
reported. In 2011, You and co-workers reported a PPh3-me-
diated sulfenylation of indolizines and related hetarenes in
which benzenesulfonyl chlorides were used as sulfur sourc-
es.11 These facts suggest that a simple and efficient ap-
proach to β-alkoxy sulfides and vinyl sulfones from cheap
and easily available sulfur compounds as sulfur sources un-
der metal-free conditions is still required. We therefore de-
veloped a TBAI–acid/base-mediated protocol for the gener-
ation of β-alkoxy sulfides and vinyl sulfones by using ben-
zenesulfonyl chlorides as the sulfur source.
Key words arenesulfonyl chlorides, oxysulfenylation, aralkenes,
aralkynes, sulfides, sulfones
Because they exhibit good or excellent biological activi-
ties, sulfur-containing compounds play an integral role in
industry and society.1 They are also among the most signifi-
cant chemicals in organic synthesis.2 Over the years, many
different ways have been developed to synthesize sulfur
compounds, such as thiolation, sulfonylation, or thioetheri-
fication.3 In all these synthetic methods, sulfur functional-
ization of unsaturated C–C bonds is regarded as a potential
approach to the construction of C–S bonds, and it has found
widespread use in synthetic transformations such as oxy-
sulfenylation, disulfidation, iodosulfonylation, and oxysul-
fonylation.4 In conventional synthesis and production, the
sulfur functionalization of C–C unsaturated bonds cata-
lyzed by transition metals (Fe, Ni, Cu, etc.) provides a highly
efficient and convenient method for simultaneously pro-
ducing two new vicinal carbon–heteroatom bonds.5 Thio-
phenols and disulfides are often used as sulfur source of
choice in organic syntheses. However, metallic catalysts and
some sulfur sources are of great concern due to their wide-
spread use and their adverse effects on the environment
and human beings. From the ecological perspective, several
problems associated with the above-mentioned synthetic
First, we examined the reaction of 4-methylbenzenesul-
fonyl chloride (1a; tosyl chloride), styrene (2a), ethanol
(3a), and NaI in the presence of HBr at 80 °C in toluene for
15 hours, and we obtained the desired production 4a in 28%
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

B
D. Wang et al.
Letter
Synlett
yield (Table 1, entry 2). To make further improvement, we
tested various iodides and we found that TBAI was the best
choice, giving the corresponding compound 4a in 55% yield
(entries 1–5). We then tested several acids (such as HCl,
HCO2H, and TsOH) for this transformation, and we found
that HBr gave the best results (entries 5–11). We also
screened a number of solvents in an attempt to improve the
reaction conditions, and we found that EtOAc was the opti-
mal reaction medium for this transformation (entries 5 and
12–18). We also examined the effect of the molar ratio of
TBAI and HBr, and we found that the best results were ob-
tained with four equivalents each of TBAI and HBr (entries
19–21). Finally, when the reaction was performed at a low-
er temperature of 50 °C, a 62% yield of 4a was obtained (en-
try 22).
The scope and limitations of the TBAI/HBr-promoted re-
actions of various alkenes with substituted benzenesulfonyl
chlorides in the presence of various alcohols was tested un-
der the optimized reaction conditions. Generally, the target
compounds 4 were obtained in good to excellent yields (Ta-
ble 2). Benzenesulfonyl chlorides 1 with electron-rich aro-
matic groups showed higher reactivities than did those
bearing electron-accepting groups (entries 1–5). For vari-
ous substituted alkenes, the difference between electron-
donating groups and electron-withdrawing groups was not
great (entries 6–8). Unfortunately, when the reaction was
carried out with alcohols other than ethanol, we did not
obtain the corresponding product. By analyzing 1H NMR
spectra, we deduced that in the presence of the acid, an es-
ter-exchange reaction occurred between EtOAc and other
alcohols to form ethanol. We therefore examined the reac-
tions of several other alcohols in DCE, and we obtained the
desired products 4i–k in 62–71% yield (entries 9–11). We
found that the steric hindrance of the alcohols had some ef-
fects on the yield of this reaction. In addition, other kinds of
alkene were also subjected to the addition reaction under
the standard reaction conditions. Note that 1,1′-ethene-1,1-
diyldibenzene reacted with tosyl chloride (1a) in the pres-
ence of EtOH to give a different product 4l (entry 12). Based
on previously reported results12 we reasoned that TsCl was
reduced to TolSCl, which reacts with 1,1′-ethene-1,1-di-
yldibenzene to give an unstable three-membered cyclic sul-
fonium compound B (see Scheme S1 in the Supporting In-
formation). This intermediate B can be easily transformed
into carbocation C. Finally, deprotonation of intermediate C
generates the corresponding product 4l. To our delight,
nonaromatic alkenes could also be used in this reaction sys-
tem; for example, product 4m was obtained by using cyclo-
hexene as the substrate (entry 13).
Table 1 Optimization of the Reaction Conditionsa
EtO
iodide, acid
S
+
EtOH
+
TsCl
Ph
Tol
Ph
solvent
4a
2a
3a
1a
Entry Iodide (equiv) Acid (equiv)
Solvent
Yieldb,c (%)
1
I
2 (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HCl (4.0)
HF (4.0)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
trace
28
2
NaI (4.0)
3
NH4I (4.0)
KI (4.0)
17
4
32
5
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (4.0)
TBAI (3.0)
TBAI (5.0)
TBAI (4.0)
TBAI (4.0)
55
6
11
7
16
8
HCOOH (4.0)
AcOH (4.0)
TsOH (4.0)
PvOH (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (4.0)
HBr (3.0)
HBr (4.0)
trace
21
9
10
11
12
13
14
15
16
17
18
19
20
21
22d
35
Table 2 Scope of the Reaction with Alkenesa
trace
75
RO
DME
47
TBAI, HBr
Ar1SO2Cl
+ Ar2
S
Ar1
ROH
+
Ar2
toluene, 80 °C
1,4-dioxane 15
2
3
1
4
DMSO
DMF
trace
Entry
Productb
Yieldc
(%)
trace
85
EtOAc
H2O
1
2
3
4
5
R1 = 4-Me
R1 = H
4a
4b
4c
4d
4e
85
27
OEt
76
90
80
81
EtOAc
EtOAc
EtOAc
EtOAc
65
S
R1 = 4-MeO
R1 = 4-F
84
R1
60
R1 = 4-Br
62
a Reaction conditions: 1a (0.20 mmol), 2a (0.24 mmol), 3a (0.8 mmol),
acid (0.8 mmol), solvent (1.0 mL), 80 °C, 15 h.
b In all cases, compound 4a was obtained as a single regioisomer.
c Yield of isolated product.
OEt
6
7
8
R1 = 4-Me
R1 = 4-Cl
4f
4g
4h
78
80
72
S
R1 = 4-O2N
R1
d Reaction performed at 50 °C.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

C
D. Wang et al.
Letter
Synlett
Table 2 (continued)
of vinyl sulfones by screening various iodides, bases, and
solvents (entries 2–16). When the amount of TBAI or Et3N
was reduced to 1.5 equivalents, the yield fell to 55% and 63%
yield, respectively (Table 3, entries 14 and 16). When we
tried to increase the amount of TBAI to 2.5 equivalents, the
yield of 5a showed no improvement (entry 15).
Entry
Productb
Yieldc
(%)
O
O
9d
4i
4j
69
71
S
S
Table 3 Optimization of Reaction Conditionsa
O
Tol
TBAI, Et3N
solvent
10d
S
TsCl
+
Ph
Ph
O
2a
1a
5a
Entry Iodide (equiv)
Base (equiv)
Solvent
Yieldb (%)
O
11d
12
4k
4l
62
89
1
TBAI (2.0)
NaI (2.0)
KI (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
py (2.0)
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
DCE
42
25
27
18
11
39
23
25
43
57
67
trace
75
55
72
63
S
2
3
4
NH4I (2.0)
I2 (2.0)
S
5
6
TBAI (2.0)
TBAI (2.0)
TBAI (2.0)
TBAI (2.0)
TBAI (2.0)
TBAI (2.0)
TBAI (2.0)
TBAI (2.0)
TBAI (1.5)
TBAI (2.5)
TBAI (2.0)
7
K2CO3 (2.0)
Na2CO3 (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (2.0)
Et3N (1.5)
8
13
4m 65
OEt
9
MeCN
S
10
11
12
13
14
15
16
toluene
1,4-dioxane
DMSO
DME
a Reaction conditions: 1 (0.20 mmol), 2 (0.24 mmol), 3 (0.80 mmol), TBAI
(0.80 mmol), HBr (0.80 mmol), EtOAc (1.0 mL), 80 °C, 15 h.
b No regioisomer was detected by 1H NMR spectroscopic analysis of the
crude product.
c Yield of isolated product.
DME
d The reaction was carried out in DCE.
DME
DME
a Reaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), solvent (1.0 mL),
100 °C, 12 h, sealed Schlenk tube.
On the basis of the above satisfactory results, we wished
to apply this reaction system in organic synthesis. We se-
lected 2-allylphenol (2f) as substrate to synthesize the 2-
substituted 2,3-dihydrobenzofuran 4n in a preliminary ex-
periment (Scheme 1). As expected, 4n was successfully pre-
pared in good yield. We believe that this method provides
an alternative way to prepare 2-substituted 2,3-dihydro-
benzofurans.
b Yield of isolated product.
By using the standard conditions, a range of benzene-
sulfonyl chlorides and terminal alkenes were employed in
the procedure to test the scope and universality of this
method (Table 4). A variety of substituents on the aromatic
ring of the benzenesulfonyl chloride were well tolerated, in-
cluding electron-accepting groups (chloro or bromo; en-
tries 6 and 8) and electron-donating groups (methyl or me-
thoxy; entries 1 and 3). It must be pointed out that sensitive
functional groups (F, Cl, and Br) on the phenyl group of ben-
zenesulfonyl chlorides did not affect the reaction, and the
corresponding products were obtained in moderate yields
(entries 4–6). Furthermore, a series of styrenes were sub-
jected to the reaction, and some gave the corresponding
products in moderate to good yields (entries 7 and 8). How-
ever, with a styrene bearing a strongly electron-attracting
group (4-O2N), the yield of the target product was low (en-
try 9).
S
Tol
TBAI, HBr
+
TsCl
EtOAc, 80 °C
O
OH
2f
4n, 78%
1a
Scheme 1 Reaction of 2-allylphenol (2f) with tosyl chloride (1a)
To go a step further and to confirm that different prod-
ucts can be obtained under different conditions, we carried
out the reaction in the presence of Et3N instead of HBr. We
were pleased to see that (E)-2-phenylvinyl 4-tolyl sulfone
(5a) was obtained in 42% yield (Table 3, entry 1). We there-
fore reexamined the optimal conditions for the formation
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

D
D. Wang et al.
Letter
Synlett
Table 4 Scope of the Reaction with Alkynesa
to the corresponding sulfenyl chloride A by HI formed by
the reaction of TBAI with HBr. Sulfenyl chloride A then re-
acts with styrene 2 to form thiiranium ion B. Finally, ring
opening of intermediate B with alcohol 3 generates the cor-
responding thio ether 4 and acid (HCl).
O
Ar1
TBAI, Et3N
Ar1SO2Cl
S
Ar2
+
Ar2
O
DME
1
2
5
Entry
Product
Yieldb
(%)
TBAI + HBr
Ar1SO2Cl
I2
Ar1SCl
A
Ar2
1
1
2
3
4
5
6
R = 4-Me
R = H
R = 4-MeO
R = 4-F
R = 4-Cl
R = 4-Br
5a
5b
5c
5d
5e
5f
75
69
72
55
64
67
R
2
O
HCl
S
RO
Ar2
Ar1
S
O
S
Ar1
Cl–
4
Ar2
B
ROH
O
3
7
8
9
R = 4-Me
R = 4-Cl
R = 4-O2N
5g
5h
5i
76
61
52
S
Scheme 4 A plausible mechanism for oxysulfenylation of alkenes
O
R
a Reaction conditions: 1 (0.4 mmol), 2 (0.2 mmol), Et3N (0.4 mmol), TBAI
(0.4 mmol), DME (1.0 mL), 100 °C, 12 h, sealed Schlenk tube.
b Yield of isolated product.
We also performed relevant control experiment for vi-
nyl sulfones (Scheme 5). When the reaction was carried out
in the presence of butylated hydroxytoluene (BHT) under
the standard conditions, the progress of the reaction was
severely suppressed and only a trace amount of target prod-
uct 5a was obtained.
In addition, when the reaction was carried out in ab-
sence of Et3N by using ethynylbenzene (6a) as substrate in
DME, the corresponding (E)-β-iodovinyl sulfones were ob-
tained in moderate yields (Scheme 2).
O
O
BHT (2.0 equiv)
Ph
Tol
S
Cl
S
+
Ph
Ph
optimized conditions
O
O
I
1a
2a
5a, trace
DME
Ar1SO2Cl
O
+ Ph
TBAI
+
Ph
S
reflux, 5 h
Scheme 5 Control experiments for the generation of vinyl sulfones
O
6a
1 equiv
1
Ar1
2 equiv
2 equiv
7a, Ar = Ph (47%)
7b, Ar = 4-BrC6H4 (42%)
7c, Ar = 4-MeOC6H4 (45%)
We therefore reason that a radical process is involved in
this reaction. We propose a plausible mechanism for the
formation of vinyl sulfones (Scheme 6), based on previous
reports.8–10 First, the arenesulfonyl chloride 1 reacts with
TBAI to generate the sulfonyl iodide C. This undergoes ho-
molytic cleavage to produce a sulfonyl radical D, which re-
acts with styrene 2 to form intermediate E. Intermediate E
reacts with an iodine radical to form iodo compound F.
Elimination of HI from F finally gives the product 5 together
with HI, which reacts with Et3N to form the amine salt.
Scheme 2 Scope of the reaction with ethynylbenzene
We also performed a preliminary study to gain further
insight into the reaction mechanism for the generation of
β-alkoxy sulfides (Scheme 3). When the reaction was com-
pleted by using 4.0 equivalents of HI as a reducing agent in a
closed tube, the target product was obtained in 47% yield.
When the reaction was carried out with benzenesulfenyl
chloride (A) instead of benzenesulfonyl chloride as a sub-
strate, the corresponding product 4b was obtained in 51%
yield.
O
S
O
S
homolytic cleavage
NaI
Ar1 SO2Cl
Ar1
I
Ar1
O
C
O
D
1
Ar2
EtO
HI (4.0 equiv)
2
NEt3
IHNEt3
Ph SO2Cl
+
+
+
+
Ph
Ph
EtOH
S
1
2
Ph
Ph
Ar1
O
Ph
Ph
EtOH, 80 °C
Ar1
1b
2a
2a
3a
4b, 47%
HI
O
O
Ar1
I
S
I– , I
S
EtO
O
TBAI, HBr
O
S
S
Ar2
EtOH
Ph
Cl
S
Ar2
H
O
Ar2
EtOH,, 80 °C
I–
F
A
3a
E
5
4b, 51%
I–
Scheme 3 Control experiments for the generation of β-alkoxy sulfides
Scheme 6 Plausible mechanism for the formation of vinyl sulfones
On the basis of these observations and previous re-
ports,7,11,13,14 a plausible reaction pathway is proposed
(Scheme 4). First, the benzenesulfonyl chloride is reduced
In summary, two simple and efficient approaches have
been developed for the synthesis of β-alkoxy sulfides and
vinyl sulfones.15–17 Easily available and cheap benzenesulfo-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

E
D. Wang et al.
Letter
Synlett
nyl chlorides are used as sulfur sources to generate the cor-
responding sulfides. These two synthetic methods might be
useful for the functionalization of aromatic alkenes or
alkynes, and they are complementary to previous strate-
gies.
(10) (a) Xu, Y.; Tang, X.; Hu, W.; Wu, W.; Jiang, H. Green Chem. 2014,
16, 3720. (b) Handa, S.; Fennewald, J. C.; Lipshutz, B. H. Angew.
Chem. Int. Ed. 2014, 53, 3432. (c) Lu, Q.; Zhang, J.; Zhao, G.; Qi,
Y.; Wang, H.; Lei, A. J. Am. Chem. Soc. 2013, 135, 11481. (d) Lu,
G.-p.; Cai, C.; Chen, F.; Ye, R.-l.; Zhou, B.-j. ACS Sustainable Chem.
Eng. 2016, 4, 1804. (e) Jiang, Y.; Loh, T.-P. Chem. Sci. 2014, 5,
4939. (f) Zeng, X.-M.; Ilies, L.; Nakamura, E. Org. Lett. 2012, 14,
954. (g) Huang, X.; Liang, C.-G.; Xu, Q.; He, Q.-W. J. Org. Chem.
2001, 66, 74.
References and Notes
(11) Wu, Q.; Zhao, D.; Qin, X.; Lan, J.; You, J. Chem. Commun. 2011,
47, 9188.
(12) Tu, H.-Y.; Hu, B.-L.; Deng, C.-L.; Zhang, X.-G. Chem. Commun.
2015, 51, 15558.
(13) (a) Hiebel, M.-A.; Berteina-Raboin, S. Green Chem. 2015, 17, 937.
(b) Liu, C.-R.; Ding, L.-H. Org. Biomol. Chem. 2015, 13, 2251.
(14) (a) Olah, G. A.; Narang, S. C.; Field, L. D.; Karpeles, R. J. Org. Chem.
1981, 46, 2408. (b) Dubbaka, S. R.; Vogel, P. J. Am. Chem. Soc.
2003, 125, 15292. (c) Olah, G. A.; Narang, S. C.; Field, L. D.;
Salem, G. F. J. Org. Chem. 1980, 45, 4792. (d) Kabalka, G. W.;
Reddy, M. S.; Yao, M.-L. Tetrahedron Lett. 2009, 50, 7340.
(15) β-Alkoxy Sulfides 4; General Procedure
(1) (a) Takimiya, K.; Shinamura, S.; Osaka, I.; Miyazaki, E. Adv.
Mater. (Weinheim, Ger.) 2011, 23, 4347. (b) Nakazawa, T.; Xu, J.;
Nishikawa, T.; Oda, T.; Fujita, A.; Ukai, K.; Mangindaan, R. E. P.;
Rotinsulu, H.; Kobayashi, H.; Namikoshi, M. J. Nat. Prod. 2007,
70, 439. (c) Oda, T.; Fujiwara, T.; Liu, H.; Ukai, K.; Mangindaan, R.
E. P.; Mochizuki, M.; Namikoshi, M. Mar. Drugs 2006, 4, 15.
(d) Gingras, M.; Chabre, Y. M.; Roy, M.; Roy, R. Chem. Soc. Rev.
2013, 42, 4823. (e) Sizov, A. Y.; Kovergin, A. N.; Ermolov, A. F.
Russ. Chem. Rev. 2003, 72, 357. (f) Mori, T.; Nishimura, T.;
Yamamoto, T.; Doi, I.; Miyazaki, E.; Osaka, I.; Takimiya, K. J. Am.
Chem. Soc. 2013, 135, 13900.
(2) (a) Casini, A.; Winum, J.-Y.; Montero, J.-L.; Scozzafava, A.;
Supuran, C. T. Bioorg. Med. Chem. Lett. 2003, 13, 837.
(b) Ramsden, C. A.; Hansch, C. In Comprehensive Medicinal
Chemistry: The Rational Design, Mechanistic Study and Thera-
peutic Application of Chemical Compounds; Vol. 2, Chap. 7.1;
Hansch, C.; Sammes, P. G.; Taylor, J. B., Eds.; Pergamon: Oxford,
1990, 2.
(3) (a) Lin, Y.-m.; Lu, G.-p.; Cai, C.; Yi, W.-b. Org. Lett. 2015, 17,
3310. (b) Gao, Y.; Gao, Y.; Tang, X.; Peng, J.; Hu, M.; Wu, W.;
Jiang, H. Org. Lett. 2016, 18, 1158. (c) Trostyanskaya, I. G.;
Beletskaya, I. P. Synlett 2012, 23, 535. (d) Feng, J.; Lu, G.; Lv, M.;
Cai, C. Synlett 2015, 26, 915. (e) Parumala, S. K. R.; Peddinti, R. K.
Green Chem. 2015, 17, 4068. (f) Reddy, V. P.; Swapna, K.; Kumar,
A. V.; Rao, K. R. Synlett 2009, 2783. (g) Akkilagunta, V. K.; Reddy,
V. P.; Rao, K. R. Synlett 2010, 1260. (h) Prasad, C. D.; Balkrishna,
S. J.; Kumar, A.; Bhakuni, B. S.; Shrimali, K.; Biswas, S.; Kumar, S.
J. Org. Chem. 2013, 78, 1434. (i) Gogoi, P.; Gogoi, S. R.; Kalita, M.;
Barman, P. Synlett 2013, 24, 873. (j) Pan, X.-Q.; Zou, J.-P.; Yi, W.-
B.; Zhang, W. Tetrahedron 2015, 71, 7481.
(4) (a) Wang, X.-R.; Chen, F. Tetrahedron 2011, 67, 4547. (b) Sun, K.;
Lv, Y.; Zhu, Z.; Jiang, Y.; Qi, J.; Wu, H.; Zhang, Z.; Zhang, G.;
Wang, X. RSC Adv. 2015, 5, 50701. (c) Wei, W.; Liu, C.; Yang, D.;
Wen, J.; You, J.; Suo, Y.; Wang, H. Chem. Commun. 2013, 49,
10239. (d) Wei, W.; Wen, J.; Yang, D.; Jing, H.; You, J.; Wang, H.
RSC Adv. 2015, 5, 4416. (e) Li, X.; Xu, X.; Shi, X. Tetrahedron Lett.
2013, 54, 3071.
40% aq HBr (117 μL, 0.8 mmol) was added to a solution of the
appropriate benzenesulfonyl chloride 1 (0.20 mmol), styrene 2
(0.24 mmol), alcohol 3 (0.8 mmol), and TBAI (295.5 mg, 0.8
mmol) in EtOAc or DCE (2 mL), and the mixture was stirred at
80 °C for 15 h in a sealed Schlenk tube. When the reaction was
complete, the mixture was diluted with EtOAc, the reaction was
quenched with sat. aq Na2S2O3 (10 mL), and the mixture was
extracted with EtOAc (2 × 15 mL). The organic layer was washed
with H2O, dried (Na2SO4), and concentrated in vacuo. The
residue was purified by column chromatography (silica gel,
EtOAc–PE).
1-[(2-Ethoxy-2-phenylethyl)sulfanyl]-4-methylbenzene (4a)
Colorless oil; yield: 46.3 mg (85%). 1H NMR (400 MHz, CDCl3):
δ = 7.35–7.25 (m, 7 H), 7.08 (d, J = 8.0 Hz, 2 H), 4.39–4.35 (m, 1
H), 3.42–3.26 (m, 3 H), 3.09–3.05 (m, 1 H), 2.31 (m, 3 H), 1.17 (t,
J = 8.0 Hz, 3 H).
1-{1-Ethoxy-2-[(4-tolyl)sulfanyl]ethyl}-4-nitrobenzene (4h)
Colorless oil; yield: 45.6 mg (72%). 1H NMR (400 MHz, CDCl3):
δ = 8.18 (d, J = 8.0 Hz, 2 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.24 (d, J =
8.0 Hz, 2 H), 7.09 (d, J = 8.0 Hz, 2 H), 4.47–4.44 (m, 1 H), 3.41–
3.31 (m, 3 H), 3.27–3.03 (m, 1 H), 2.32 (s, 3 H), 1.19 (t, J = 8.0 Hz,
3 H). 13C NMR (100 MHz, CDCl3): δ = 148.8, 147.6, 136.7, 131.9,
130.5, 129.8, 127.6, 123.7, 80.0, 65.3, 41.9, 21.0, 15.2. HRMS
(ESI): m/z [M + Na]+ calcd for C17H19NNaO3S: 340.0978; found:
340.0972.
1-{[2-(Benzyloxy)-2-phenylethyl]sulfanyl}-4-methylben-
zene (4k)
(5) (a) Taniguchi, T.; Idota, A.; Ishibashi, H. Org. Biomol. Chem. 2011,
9, 3151. (b) Nair, V.; Augustine, A.; Suja, T. D. Synthesis 2002,
2259. (c) Jiang, Q.; Xu, B.; Jia, J.; Zhao, A.; Zhao, Y.-R.; Li, Y.-Y.; He,
N.-N.; Guo, C.-C. J. Org. Chem. 2014, 79, 7372. (d) Zhu, W.; Ma, D.
J. Org. Chem. 2005, 70, 2696. (e) Huang, F.; Batey, R. A. Tetrahe-
dron 2007, 63, 7667.
Colorless oil; yield: 41.4 mg (62%). 1H NMR (600 MHz, CDCl3):
δ = 7.36–7.21 (m, 12 H), 7.05 (d, J = 4.0 Hz, 2 H), 4.49–4.47 (m, 2
H), 4.29 (d, J = 4.0 Hz, 1 H), 3.37–3.34 (m, 1 H), 3.12–3.09 (m, 1
H), 2.30 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 140.7, 138.0,
136.1, 132.8, 130.1, 129.7, 128.6, 128.3, 128.2, 127.8, 127.7,
127.6, 80.1, 70.8, 42.4, 21.0. HRMS (ESI): m/z [M + Na]+ calcd for
(6) Yang, F.-L.; Wang, F.-X.; Wang, T.-T.; Wang, Y.-J.; Tian, S.-K. Chem.
Commun. 2014, 50, 2111.
C
22H22NaOS: 357.1284; found: 357.1280.
(7) (a) Gao, X.; Pan, X.; Gao, J.; Jiang, H.; Yuan, G.; Li, Y. Org. Lett.
2015, 17, 1038. (b) Vieira, A. A.; Azeredo, J. B.; Godoi, M.; Santi,
C.; da Silva, E. N. Jr.; Braga, A. L. J. Org. Chem. 2015, 80, 2120.
(8) Zhang, N.; Yang, D.; Wei, W.; Yuan, L.; Cao, Y.; Wang, H. RSC Adv.
2015, 5, 37013.
(16) Vinyl Sulfones 5; General Procedure
Et3N (56 μL, 0.4 mmol) was added to a solution of the appropri-
ate benzenesulfonyl chloride 1 (0.40 mmol), styrene 2 (0.20
mmol), and TBAI (147.8 mg, 0.4 mmol) in DME (1 mL), and the
mixture was stirred at 100 °C for 15 h in a sealed Schlenk tube.
When the reaction was complete, the mixture was diluted with
EtOAc, the reaction was quenched with sat. aq Na2S2O3 (10 mL),
and the mixture was extracted with EtOAc (2 × 15 mL). The
(9) Chen, J.; Mao, J.; Zheng, Y.; Liu, D.; Rong, G.; Yan, H.; Zhang, C.;
Shi, D. Tetrahedron 2015, 71, 5059.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

F
D. Wang et al.
Letter
Synlett
organic layer was washed with H2O, dried (Na2SO4), and con-
centrated in vacuo. The residue was purified by column chro-
matography (silica gel, EtOAc–PE).
1-Methyl-4-{[(E)-2-phenylvinyl]sulfonyl}benzene (5a)
White solid; yield: 38.7 mg (75%); mp 120–122 °C. 1H NMR (400
MHz, CDCl3): δ = 7.83 (d, J = 4.0 Hz, 2 H), 7.66 (d, J = 8.0 Hz, 1 H),
7.46 (s, 2 H), 7.35 (t, J = 8.0 Hz, 5 H), 6.86 (d, J = 8.0 Hz, 1 H), 2.42
(s, 3 H).
complete, the mixture was diluted with EtOAc, the reaction was
quenched with sat. aq Na2S2O3 (10 mL), and the mixture was
extracted with EtOAc (2 × 15 mL). The organic layer was washed
with H2O, dried (Na2SO4), and concentrated in vacuo. The
residue was purified by column chromatography (silica gel,
EtOAc–PE).
(E)-2-Iodo-2-phenylvinyl 4-Methoxyphenyl Sulfone (7c)
Yellow oil; yield: 35.9 mg (45%). 1H NMR (400 MHz, CDCl3):
δ = 7.48 (d, J = 4.0 Hz, 2 H), 7.37 (s, 1 H), 7.30–7.22 (m, 5 H), 6.84
(d, J = 4.0 Hz, 2 H), 3.85 (s, 3 H). 13C NMR (100 MHz, CDCl3):
δ = 163.55, 141.4, 132.5, 132.1, 131.0, 129.9, 129.0, 128.5, 127.9,
114.6, 55.7. HRMS (ESI): m/z [M + NH4]+ calcd for C15H17INO3S:
417.9968; found: 417.9963.
(17) (E)-β-Iodovinyl Sulfones 7; General Procedure
TBAI (147.8 mg, 0.4 mmol) was added to a solution of the
appropriate benzenesulfonyl chloride
1 (0.40 mmol) and
aralkyne 2 (0.20 mmol) in DME (1 mL), and the mixture was
stirred in a sealed tube at reflux for 5 h. When the reaction was
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F