Aerobic copper-catalyzed synthesis of (E)-alkenyl sulfones and (E)-β-halo-alkenyl sulfones via addition of sodium sulfinates to alkynes

Article abstract of DOI:10.1016/j.tet.2014.01.071

Copper-catalyzed sulfonylation of alkynes using sodium sulfinates in air produced regio- and stereoselectively (E)-alkenyl sulfones. When a CuCl catalyst was employed, the hydrosulfonylation proceeded syn-selectively, and (E)-alkenyl sulfones were synthesized in excellent yields. In contrast, the reaction using CuI catalyst produced (E)-β-haloalkenyl sulfones anti-selectively in the presence of potassium halides. Furthermore, the (E)-β-bromoalkenyl sulfones are possible to convert into various alkenyl sulfones by Suzuki-Miyaura coupling.

Full text of DOI:10.1016/j.tet.2014.01.071

Tetrahedron 70 (2014) 1984e1990
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Aerobic copper-catalyzed synthesis of (E)-alkenyl sulfones and
(E)-b-halo-alkenyl sulfones via addition of sodium sulfinates to
alkynes
*
Nobukazu Taniguchi
Department of Chemistry, Fukushima Medical University, Fukushima 960-1295, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Copper-catalyzed sulfonylation of alkynes using sodium sulfinates in air produced regio- and stereo-
selectively (E)-alkenyl sulfones. When a CuCl catalyst was employed, the hydrosulfonylation proceeded
syn-selectively, and (E)-alkenyl sulfones were synthesized in excellent yields. In contrast, the reaction
Received 25 November 2013
Received in revised form 26 January 2014
Accepted 27 January 2014
using CuI catalyst produced (E)-
halides. Furthermore, the (E)- -bromoalkenyl sulfones are possible to convert into various alkenyl sul-
fones by SuzukieMiyaura coupling.
b-haloalkenyl sulfones anti-selectively in the presence of potassium
Available online 4 February 2014
b
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
Sulfonylation
Stereoselective addition
Alkyne
Sodium sulfinate
Copper catalyst
1. Introduction
SO2R
RSO2Cl,
cat.Cu
RSO2Na,
cat.M
R
syn-add.
anti-add.
Organosulfur compounds have been prepared by various pro-
cedures.1 In particular, alkenyl sulfones and their derivatives have
found widespread utilizations as convenient intermediates or re-
agents in organic synthesis.2
Cl
R
SO2R
R
anti-add.
X
Alkenyl sulfones are usually synthesized by traditional methods,3
such as Michael additions,4 HornereEmmons reactions,3b and tran-
sition metal-catalyzed cross-couplings with alkenyl halides.5
Similarly, additions of sulfonyl chlorides by copper catalysts are
SO2R
R
Scheme 1. Previous sulfonylations of alkynes.
able to afford the corresponding b
-chloroalkenyl sulfones.6,7 The
reactions proceed anti-selectively (Scheme 1). Unfortunately, the
utilization of these obtained compounds has been very restricted
owing to the lower reactivity of alkenyl chloride.
To date, there have been few reports of transition metal-
catalyzed sulfonylation of alkynes with sodium sulfinate,8
whereas stoichiometric reactions have been reported by some re-
searchers (Scheme 1).9 As a general rule, previous additions of so-
dium sulfinates are required for excess oxidants to generate
sulfonyl cations or radicals having high reactivities. However, this is
not an efficient procedure. A complete the catalytic reaction has not
been developed. Therefore, a simple synthetic method to produce
these useful compounds is desired.
To carry out sulfonylation of alkynes using sodium sulfinates,
two pathways are estimated (Scheme 2). (Path A) Anti-selective
additions via formation of sulfonyl cations or radicals by oxida-
tion of sodium sulfinates; (Path B) syn-selective hydrosulfonylation
via hydrolysis of alkenyl-metal complexes.
Regrettably, the efficient transition metal-catalyzed stereoselective
preparation of syn- or anti-adducts has not yet been developed.
To solve this problem, a copper-catalyzed system under oxida-
tive conditions was investigated.
From various experiments, it was found that both syn- and anti-
selective sulfonylation of alkynes were possible using copper cat-
alysts, and further improvement of the procedures afforded (E)-
alkenyl sulfones and (E)-b-haloalkenyl sulfones in acceptable
yields.10,11 Here, the details of these reactions, including their scope
and limitations, are described.
* Tel.: þ81 24 547 1369; fax: þ81 24 47 1369; e-mail address: taniguti@fmu.ac.jp.
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.01.071

N. Taniguchi / Tetrahedron 70 (2014) 1984e1990
1985
sulfones 6 in 71e91% yields (entries 1e14). In the alkylacetylenes
reactions, the yields increased slightly by the use of L3 rather
than L2, and a trace amount of b-ketosulfone was often observed
Oxidation
+ X-
MX
RSO2+ or RSO2
RSO2Na
RSO2
M
R
R
as a byproduct (entries 11e14). The utilization of internal alkynes
also afforded excellent results (entries16e20). However, re-
actions of 1-octyne or 4-octyne gave complex mixtures, and the
expected alkenyl sulfone 6 could scarcely be detected (entries 15
and 21).
The stereochemistry of alkenyl sulfones generated from internal
alkynes in entries 16 and 17 was determined by a comparison with
1H NMR of (Z)-alkenyl sulfone 812 or the reported literature3d,13
(Scheme 3).
path A
path B
anti-addition
syn-addition
H+
M
X
R
SO2R
H
R
SO2R
SO2R
R
Scheme 2. A plausible sulfonylation process.
2. Results and discussions
Thus, CuCl-catalyzed sulfonylation of alkynes proceeded syn-
selectively.
Initially, a reaction of phenylacetylene 1 with 4-MeC6H4SO2Na was
examined in the presence of the copper catalyst (Table 1). When the
reaction using CuIebpy in acetic acid was performed at 100 ꢀC, the
corresponding product 2 was not observed (entry 1). Employment of
2,20-bis(2-oxazoline) L2 produced 2 in 10% yield, while the reaction in
DMF did not proceed (entries 2 and 3). The use of a mixed solvent
(AcOH and DMF) resulted in a 34% yield (entry 4). The addition of water
Copper-catalyzed synthesis of
b-haloalkenyl sulfones was
attempted. To date, to prepare these compounds, the addition of
sulfonyl cations has been performed by copper or iron catalysts.6,7
In particular, the procedure using sulfonyl chlorides can construct
b-chloroalkenyl sulfones; however, the introduction of other ha-
lides is complicated. The useful transition metal-catalyzed hal-
increased the yield to 51% with a 10% yield of
b-ketosulfone 3 (entry 5).
osulfonylation using sodium sulfinates has not yet been achieved.
Table 1
Investigation of suitable conditionsa
4-MeC6H4SO2Na,
O
cat. [M]-L
SO2C6H4Me-4
NHTs
SO2C6H4Me-4
Ph
+
Ph
Ph
Add. / Solv., air
3
2
1
O
N
O
N
N
N
NHTs
L3
L1
L2
Entry
CuXeL (1:1, 5 mol %)
Condition (mL)
Temp (ꢀC)
Ratio of 2/3b
2 (%)c
1
2
3
4
5
6
7
8
CuIeL1
CuIeL2
CuIeL2
CuIeL2
CuIeL2
CuIeL2
CuIeL3
CuCleL3
CuCleL3
CuCleL2
CuCl2eL2
CuBr2eL2
Cu(OAc)2eL2
None
AcOH (0.3)
AcOH (0.3)
DMF (0.3)
100
100
100
100
100
60
60
60
60
60
d
0
10
0
83/17
d
AcOH, DMF (0.15/0.15)
83/17
83/17
83/17
83/17
95/5
95/5
95/5
95/5
91/9
83/17
0/100
34
51
50
55
80
83
83
80
50
50
0d
AcOH, DMF, H2O (0.1/0.1/0.1)
AcOH, DMF, H2O (0.1/0.1/0.1)
AcOH, DMF, H2O (0.1/0.1/0.1)
AcOH, DMF, H2O (0.1/0.1/0.1)
AcOH, DMI, H2O (0.1/0.1/0.1)
AcOH, DMI, H2O (0.1/0.1/0.1)
AcOH, DMI, H2O (0.1/0.1/0.1)
AcOH, DMI, H2O (0.1/0.1/0.1)
AcOH, DMI, H2O (0.1/0.1/0.1)
AcOH, DMI, H2O (0.1/0.1/0.1)
9
10
11
12
13
14
60
60
60
60
a
Reaction condition: a mixture of 1 (0.3 mmol), 4-MeC6H4SO2Na (0.33 mmol), and CueL catalyst (1:1, 5 mol %) was treated in AcOH or/and DMF, DMI, H2O.
b
c
This ratio was determined by 1H NMR.
Isolated yield after silica gel chromatography.
d
b
-Ketosulfone 3 was obtained in 17% yield.
Surprisingly, it was proved that the reaction proceeded at 60 ꢀC
Therefore, development of a one-step synthetic method for
bromo or iodoalkenyl sulfones is an important research.
To accomplish stereoselective copper-catalyzed
osulfonylation of alkynes, a combination of phenylacetylene 10
with 4-MeC6H4SO2Na was examined (Table 3). At first, the reaction
at 100 ꢀC gave the corresponding product 11 in 40% yield (entry 1).
Fortunately, the addition of KBr (3 equiv) at 80 ꢀC increased the
b-
(entries 6 and 7). Furthermore, when a combination of CuCl with
trans-N,N0-di-(40-toluenesulfonyl)-1,2-cyclohexanediamine L3 in
mixed solvents (AcOH, DMF, H2O or AcOH, DMI, H2O) was used, the
expected alkenyl sulfone 2 was synthesized in 80e83% yields as
a single isomer with a trace amount of 3 (entries 8 and 9). The
reaction using L2 or CuCl2 afforded the same results (entries 10 and
11). The stereochemistry of alkenyl sulfone 2 was evident in the (E)-
configuration determined by NMR analysis.
The reactions using CuBr2 and Cu(OAc)2 catalysts resulted in
lower yields (entries 12 and 13). In the absence of the copper cat-
alyst, b-ketosulfone 3 was obtained in 17% yield (entry 14).
Thus, the combination of copper chlorides (CuCl or CuCl2) with
ligands (L2 or L3) achieved the syn-selective hydrosulfonylation.
According to the developed procedure, hydrosulfonylation of
numerous alkynes was surveyed (Table 2). The employment of
terminal aryl or alkylacetylenes afforded expected (E)-alkenyl
hal-
yield to 74% with trace amounts of b-alkenyl sulfone and b-keto-
sulfone (entry 2). The use of other salts (LiBr, NaBr, and n-Bu4NBr)
did not promote the reaction satisfactorily (entries 3e5). In the
survey of copper catalysts, various results were observed. For ex-
amples, catalysts, such as CuCN, CuOAc, and CuBr2 accelerated the
reaction, whereas other catalysts could not promote it (entries
6e12). Thus, it became apparent that the reaction of terminal al-
kynes gave the best result at 80 ꢀC. However, an internal alkyne
was necessary for reactions performed at 100 ꢀC (entries 13 and
14).

1986
N. Taniguchi / Tetrahedron 70 (2014) 1984e1990
b
Table 2
Isolated yield after silica gel chromatography.
L3 was used.
36 h.
66 h.
c
d
e
f
Hydrosulfonylation of alkynesa
R3SO2Na,
SO2R3
R2
CuCl-L2 or L3 (1:1, 5 mol%)
Complex mixtures were obtained.
R1
R2
R1
AcOH, DMI, H2O, air
60 oC, 18 h
5
6
1. MeONa, Pd(PPh3)4,
MeOH, 100 ºC
Ha
Br
R
Entry
5
6
6 (%)b
R
SO2C6H4Me-4
2. mCPBA / CH2Cl2,
0 ºC, 3 h
SC6H4Me-4
(E)-7
(Z)-8
SO2Ph
1
85
83
80
72
75
71
84
82
91
73
91c
Ph
Ph
R = Me: 79%; Ha = 7.02 ppm
R = Et: 55%; Ha = 6.99 ppm
SO2C6H4Me-4
SO2C6H4OMe-4
SO2C6H4NHAc-4
SO2C6H4Cl-4
SO2C6H4F-4
SO2Me
2
Ph
Ph
Ph
Ph
Ph
Ph
4-MeC H4
Hb
3
SO2C6H4Me-4
R
(E)-9
4
R = Me: Hb = 7.79 ppm
R = Et: Hb = 7.79 ppm
5
Scheme 3. Investigation of stereochemistry.
6
7
Table 3
Investigation of suitable conditionsa
SO2C6H4Me-4
SO2C6H4Me-4
4-MeC6H4
4-MeOC6H4
4-FC6H4
8
6
4-MeC6H4SO2Na, MX,
[Cu]-bpy(8 mol%)
X
R
9
4-MeOC H4
6
Ph
Ph
R
AcOH, air
SO2C6H4Me-4
SO2C6H4Me-4
SO2C6H4Me-4
10
11
10
11
4-Fc6H4
Entry
R
[Cu]
MX (equiv)
Temp (ꢀC)
11 (%)b
1
2
3
4
5
6
7
8
H
CuI
KBr (1.1)
KBr (3.0)
LiBr (3.0)
NaBr (3.0)
n-Bu4NBr (3.0)
KBr (3.0)
KBr (3.0)
KBr (3.0)
KBr (3.0)
KBr (3.0)
KBr (3.0)
KBr (3.0)
KBr (3.0)
KBr (1.5)
100
80
80
80
80
80
80
80
80
80
80
80
80
100
40
74
50
25
10
27
17
70
66
72
26
50
62
75
N
N
OH
OH
SO2C6H4Me-4
SO2C6H4Me-4
12
13
62c
CuBr
CuCl
55c,d
CuOAc
CuCN
CuBr2
CuCl2
Cu(OAc)2
CuI
9
10
11
12
13
14
SO2C6H4Me-4
SO2C6H4Me-4
14
15
40c,e
Me
Me
CuI
Tracef
a
Reaction condition: a mixture of 10 (0.3 mmol), 4-MeC6H4SO2Na (0.33 mmol),
MX and CuIebpy (1:1, 0.024 mmol) was treated in AcOH (0.3 mL).
SO2C6H4Me-4
b
Isolated yields after silica gel chromatography.
Ph
Ph
16
17
18
80
70
64
Ph
Ph
Me
Me
As shown in Table 4, on the basis of the described procedure,
various copper-catalyzed halosulfonylations in acetic acid were
screened. The procedure using terminal alkynes at 80 ꢀC produced
SO2C6H4Me-4
Et
Et
corresponding
b-haloalkenyl sulfones in 35e74% yields (entries
SO2C6H4Me-4
OH
Ph
Ph
1e19). These reactions could effectively introduce iodide and bro-
mine. With the introduction of chlorine, the employment of LiCl
gave better results than KCl (entries 9, 10, and 16). From a com-
parison of the NMR analysis with results reported in the liter-
tures,6,12 it was evident that the stereochemistry had (E)-
configuration. Not only terminal alkynes but also internal alkynes
were available (entries 15e19). The reactions of diphenyl acetylene
and 4-octyne hardly produced b-bromoalkenyl sulfones (entries 20
and 21). Strangely, the use of 4-octyne afforded (E)-4-bromo-5-(4-
tolylthio)-4-octene 13 in 32% yield.
Although reactions with KSCN or KCN were examined, the ex-
pected products were not detected (entries 21 and 22).
To clarify the reaction mechanism, some additional experiments
were performed. When CuCl-catalyzed sulfonylation of 1-phenyl-
1-propyne under hydrosulfonylation conditions was investigated in
OH
Ph
SO2C6H4Me-4
Ph
Ph
19
20
48
76
Ph
Ph
SO2C6H4Me-4
SO2C6H4Me-4
Ph
TMS
21
0f
a
Reaction condition: a mixture of 5 (0.3 mmol), RSO2Na (0.33 mmol), and CueL2
catalyst (1:1, 5 mol %) was treated in AcOH (0.1 mL), DMI (0.1 mL), and H2O (0.1 mL).

N. Taniguchi / Tetrahedron 70 (2014) 1984e1990
Table 4 (continued )
1987
Table 4
Synthesis of b
-haloalkenylsulfonesa
Entry
5
MX
12
12 (%)b
R3SO2Na, MX,
X
CuI-bpy(8 mol%)
R2
R1
R1
R2
Br
Et
SO2R3
63c,e
70c,f
Tracec
5c,d
AcOH, air,
80 or 100 ºC, 18 h
18
19
20
21
22
KBr
Ph
Et
5
Ph
SO2C6H4Me-4
12
Entry
1
5
MX
12
12 (%)b
Br
OAc
Ph
KBr
OH
Ph
Ph
SO2C6H4Me-4
Br
KBr
74
Ph
Br
Ph
Ph
SO2Ph
KBr
Ph
Ph
SO2C6H4Me-4
Br
2
KBr
74
70
42
61f
70
62
71
69
38
64
62
66
Ph
Br
SO2C6H4Me-4
SO2C6H4OMe-4
SO2C6H4NHAc-4
SO2C6H4Cl-4
SO2C6H4F-4
KBr
SO2C6H4Me-4
SO2C6H4Me-4
Br
3
KBr
NCS
Ph
Ph
KSCN
0
Ph
Br
4
KBr
Ph
NC
Ph
23
KCN
0
Ph
Br
SO2C6H4Me-4
5
KBr
Ph
a
Reaction condition: a mixture of 5 (0.3 mmol), RSO2Na (0.33 mmol), MX
(0.9 mmol), and CuIebpy (1:1, 0.024 mmol) in AcOH (0.3 mL) was stirred at 80 or
100 ꢀC.
Br
6
KBr
Ph
b
Isolated yields after silica gel chromatography.
c
The reaction was performed at 100 ꢀC using MX (0.33 mmol).
d
Br
(E)-4-Bromo-5-(40-methylphenylthio)-4-octene 13 was obtained in 32%.
36 h.
42 h.
7
KBr
e
Ph
SO2Me
f
I
the presence of KBr, the reaction gave only trace amounts of alkenyl
8
KI
sulfone 14 without the formation of
(Scheme 4). This indicates that the producing mechanisms of
alkenyl sulfone and -haloalkenyl sulfone are different.
b-bromoalkenyl sulfone 15
Ph
SO2C6H4Me-4
SO2C6H4Me-4
SO2C6H4Me-4
Cl
b
9
LiCl
Ph
4-MeC6H4SO2Na,
CuI-L2 (5 mol%)
Cl
SO2C6H4Me -4
Br
10
11
12
13
KCl
Ph
Ph
Ph
AcOH, DMF, H2O,
air, 60 ºC, 18 h
14
trace
Br
4-MeC6H4
KBr
Ph
+
4-MeC6H4
Br
SO2C6H4Me-4
SO2C6H4Me -4
15
Not detected
4-MeOC6H4
KBr
KBr
4-MeOC H4
SO2C6H4Me-4
SO2C6H4Me-4
6
Scheme 4. CuCl-catalyzed sulfonylation in the presence of KBr.
Br
Reaction in the absence of oxygen was also investigated. When
a mixture of phenylacetylene or 1-phenyl-1-propyne with 4-
MeC6H4SO2Na was treated under nitrogen atmosphere, the corre-
sponding alkenyl sulfones were obtained in 76% and 12% yields,
respectively (Scheme 5). When an internal alkyne was used the
yield decreased significantly. Notably, when Cu(II)Cl2 was used, the
expected alkenyl sulfone 14 was produced at 65% yield (Scheme 6).
N
N
Br
14
KBr
35
SO2C6H4Me-4
Br
Me
15
16
17
KBr
LiCl
KI
75c
Ph
Me
Ph
4-MeC6H4SO2Na,
CuCl-L2 (5 mol%)
SO2C6H4Me-4
SO2C6H4Me-4
Ph
R
Cl
Me
Ph
72c,e
AcOH, DMI, H2O,
60 oC, 18 h,
Under N2
10
R
Ph
SO2C6H4Me-4
16
R = H: 76%
R = Me: 12%
I
Me
73c,e
Ph
SO2C6H4Me-4
Scheme 5. Hydrosulfonylation of alkynes in the absence of oxygen.

1988
N. Taniguchi / Tetrahedron 70 (2014) 1984e1990
In cycle B, the halosulfonylation was promoted in the presence
4-MeC6H4SO2Na,
CuCl2-L2 (5 mol%)
of a halide ion with a proton. After oxidation of R2SO2eCu(I)Ln 23,
SO2C6H4Me-4
the sulfonyl radical 28 and cation 29 were formed.9 The reaction of
29 with alkyne gave sulfonium ion intermediate 30. Ultimately, b-
haloalkenyl sulfone 31 is produced by reaction with the halide ion.
In addition, the production of 31 is also presumed to occur in the
pathway via halonium ion 32.18
Thus, it was found that a CuCl2-catalyzed reaction gives syn-
adducts and a CuI-catalyst promotes anti-additions.
Ph
Ph
AcOH, DMI, H2O,
60 oC, 18 h,
Under N2
14
65%
Scheme 6. CuCl2-hydrosulfonylation in the absence of oxygen.
The synthesized b-haloalkenyl sulfones reported here have two
convertible substituents. Unfortunately, the transformation is often
problematic and the results are unsatisfactory.
From these facts, it appears that the copper-catalyzed hydro-
sulfonylation of internal alkynes is necessary for the oxidation of
copper complex intermediates.
These results are summarized in Scheme 7. The hydrolysis of
alkenylecopper (I) complex 17 formed from a terminal alkyne is
promoted easily, whereas the reactivity of 18 formed from an in-
ternal alkyne is very low owing to its stability. Therefore, to pro-
mote the hydrolysis of intermediate 18, formation of
alkenylecopper (II) complex 21 with oxygen is required.14,15
Consequently, conversion of
b-haloalkenyl sulfones to various
alkenyl sulfones was investigated.
To achieve the purpose, reaction of
with arylboronic acids was explored.
b-bromoalkenyl sulfones
As shown in Table 5, when 33 was treated with arylboronic acid
in dioxane and water by cat. Pd(PPh3)4,19 the desired diarylalkenyl
sulfones 34 were produced in excellent yields. Thus, the reaction
enables to introduce various aryl-substituents having functional
groups. However, a reaction with methylboronic acid did not
progress (entry 6).
CuI
H
H
H+
H+
SO2Ar
SO2Ar
SO2Ar
Ph
Ph
Ph
17 (R' = H)
High reactivity
18 (R' = Me)
Low reactivity
Me
H
R'
20
3. Conclusion
18,17
19
CuII
O2
H+
Stereoselective copper-catalyzed sulfonylations of alkynes were
achieved using sodium sulfinates in air. (E)-Alkenyl sulfones could
be synthesized using a CuCl catalyst. In contrast, the reaction using
SO2Ar
Ph
Me
21
a CuI catalyst afforded (E)-b-haloalkenyl sulfones in the presence of
potassium halide. In addition, (E)-bromoalkenyl sulfones could
transform into various alkenyl sulfones.
Scheme 7. Hydrolysis of alkenylecopper complexes.
Bromosulfonylations of terminal and internal alkynes under
nitrogen atmosphere resulted in 10% and 13% yields, respectively
(Scheme 8). In the reaction, it seems that the formation of sulfonyl
cation proceeds at the first step (Scheme 9).
4. Experimental section
4.1. General procedure
All reactions were carried out in air. NMR spectra were recorded
on a JEOL EX-270 spectrometer (270 MHz for 1H, 67.5 MHz for 13C).
TsNa, KBr,
Br
CuI-bpy(8 mol%),
R
Chemical shifts are reported in
internal tetramethylsilane standard for 1H NMR and chloroform-
d (
77.0) for 13C NMR. IR spectra were measured by PerkineElmer
d parts per million referenced to an
Ph
R
Ph
AcOH, 100 ºC
Under N2
10
d
SO2C6H4Me-4
Spectrum One FT-IR spectrometer. Melting points were measured
12
€
on a BUCHI Melting Point B-540 apparatus. Elemental analysis was
R = H : 10%
R = Me: 13%
performed at the Instrumental Analysis Center for Chemistry,
Tohoku University (Japan) or the Elemental Analysis Center Faculty
of Pharmaceutical Sciences, Kyoto University (Japan).
Scheme 8. Hydrosulfonylations of alkynes in the absence of oxygen.
4.2. Typical procedure hydrosulfonylation of alkynes (Table 2)
O2, CuI-bpy
H+
O2, CuI-bpy
H+
ArSO2
ArSO2
ArSO2
To a mixture of CuCl (1.5 mg, 0.015 mmol), 2,20-bis(2-oxazoline)
(2.1 mg, 0.015 mmol), and PhSO2Na (54.2 mg, 0.33 mmol), in DMI
(0.1 mL), H2O (0.1 mL), and AcOH (0.1 mL) were added phenyl-
acetylene (30.6 mg, 0.3 mmol), and the mixture was stirred at 60 ꢀC
for 18 h in air. After the residuewasdissolved in Et2O, the solutionwas
washed with H2O and saturated sodium chloride and dried over an-
hydrous magnesium sulfate. Chromatography on silica gel (40%
diethyl ether/hexane) gave (E)-1-phenylsulfonyl-2-phenylethene
(61.8 mg, 85%):1 colorless solid; mp 66e67 ꢀC; [C, 68.56; H, 5.02.
Scheme 9. Oxidation of sodium sulfinate.
Isomerization of (Z)-alkenyl sulfone 216 was also investigated
(Fig.1). After treatment of (Z)-22 at 60 ꢀC for 36 h, the ratio of Z and E
became 91/9. Isomerization progressed very slowly. Consequently,
the mechanism is able to ignore isomerization (Scheme 10).
A plausible mechanism is illustrated in Fig. 1. In process A, the
hydrosulfonylation proceeds. Initially R2SO2eCu(I)Ln 23 is pro-
duced from copper chloride with sodium sulfinate. Sequentially,
alkyne insertion into 23 gives alkenylecopper (I) complex 24.17
After the hydrolysis of 24, alkenyl sulfone 26 is produced and
copper catalyst is reproduced again. However, the hydrolysis of 24
generated from an internal alkyne is required for formation of
alkenylecopper (II) complex 25 by oxidation.14
C
14H12O2S: C, 68.83; H, 4.95]; IR (CHCl3) 1613,1447, 1306, 1146 cmꢁ1
;
1H NMR (270 MHz, CDCl3)
d
7.96 (d, J¼8.2 Hz, 2H), 7.68 (d, J¼15.5 Hz,
1H), 7.58e7.30 (m, 8H), 6.87 (d, J¼15.5 Hz, 1H); 13C NMR (67.5 MHz,
CDCl3)d142.4,140.6,133.3,132.2,131.1,129.3,128.9,128.5,127.6,127.2.
4 . 2 .1. ( E ) - 1 - ( 4 0- N - A c e t y l a m i n o p h e n y l s u l f o n y l ) - 2 -
phenylethene. Colorless solid; mp 164e166 ꢀC; [found: C, 63.79; H,
5.11. C16H15NO3S: C, 63.77; H, 5.02]; IR (CHCl3) 3346, 1693, 1591,

N. Taniguchi / Tetrahedron 70 (2014) 1984e1990
1989
SO2R3
R2
R1
ArSO2Na
R1
X
SO2Ar
R2
SO2Ar
CuClnLn
CuIILn
27
26
H+
R1
R2
KX
30
31
NaCl
R3SO2 CuILn
NaI
R1
ArSO2
29
R2
ArSO2Na
+
B
A
CuIILn
SO2R3
X
23
H+, O2
H2O
R1
CuIIL
R1
R2
R2
32
X2
R1
27
CuX
25
CuILn
SO2R3
ArSO2
28
R1
R1
R2
H2O
R2
24
R2
H+, O2
Fig. 1. A plausible mechanism.
cat. CuCl-L2 (5 mol%)
the residue was dissolved in Et2O, the solution was washed with
saturated sodium hydrogencarbonate, H2O, and saturated sodium
chloride and dried over anhydrous magnesium sulfate. Chroma-
tography on silica gel (40% diethyl ether/hexane) gave (E)-2-bromo-
1-phenylsulfonyl-2-phenylethene (71.5 mg, 74%): colorless solid;
mp 78e79 ꢀC; [found: C, 51.42; H, 3.17. C14H11O2SBr: C, 52.03; H,
(E)-22
(Z)-22
+
Ph
SO2C6H4Me-4
(Z)-22
AcOH, DMI, H2O,
air, 60 ºC, 36 h
98%
Z / E = 91 / 9
Scheme 10. Examination of isomerization.
3.43]; IR (CHCl3) 3056, 1611, 1590, 1446, 1324 cmꢁ1
;
1H NMR
Table 5
Transformation of
b
-bromoalkenyl sulfones via SuzukieMiyaura couplinga
(270 MHz, CDCl3)
d 7.61e7.51 (m, 3H), 7.42e7.30 (m, 7H), 7.17 (s,
1H); 13C NMR (67.5 MHz, CDCl3)
130.4, 128.9, 128.5, 127.9, 127.7.
d 140.2, 138.7, 135.9, 134.1, 133.5,
Ar2B(OH)2,
Pd(PPh3)4(5 mol%),
Ar2
Br
K2CO3
4.3.1. (E)-2-Bromo-1-(40-N-acetylaminophenylsulfonyl)-2-
phenylethene. Colorless liquid; [found: C, 49.87; H, 3.57.
Ph
Ph
SO2Ar1
dioxane, H2O, 100ºC
SO2Ar1
33
34
C
16H14NO3SBr: C, 50.54; H, 3.71]; IR (CHCl3) 3019, 1699, 1590, 1528,
1323, 1216 cmꢁ1 1H NMR (270 MHz, CDCl3)
7.68 (br, 1H),
7.56e7.47 (m, 4H), 7.37e7.26 (m, 5H), 7.14 (s, 1H), 2.17 (s, 3H); 13C
NMR (67.5 MHz, CDCl3) 168.8, 142.9, 138.7, 136.0, 134.5, 134.0,
;
d
Entry
Ar1
Ar2
Time (h)
34 (%)b
1
2
3
4
5
6
7
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-OHCC6H4
4-MeO2C6H4
Me
18
18
18
20
20
18
18
94
95
85
88
60
Trace
62
d
130.5, 129.0, 128.5, 128.0, 119.1, 24.7.
4.3.2. (E)-2-Bromo-1-(40-methylphenylsulfonyl)-1-octene. Pale yel-
low liquid; [found: C, 53.52; H, 6.10. C16H23O2SBr: C, 53.48; H, 6.45];
IR (CHCl3) 2930, 1609, 1458, 1321 cmꢁ1; 1H NMR (270 MHz, CDCl3)
4-ClC6H4
4-MeC6H4
Reaction condition: a mixture of 33 (0.2 mmol), Ar2B(OH)2 (0.22 mmol), K2CO3
(0.1 mmol), and Pd(PPh3)4 (5 mmol%) in dioxane (0.8 mL) and H2O (0.1 mL) was
stirred at 100 ꢀC.
a
d
7.79 (d, J¼8.0 Hz, 2H), 7.36 (d, J¼8.0 Hz, 2H), 6.75 (s, 1H), 3.04 (t,
J¼7.6 Hz, 2H), 2.45 (s, 3H), 1.58 (br, 2H), 1.29 (br, 6H), 0.89 (br, 3H);
13C NMR (67.5 MHz, CDCl3)
144.8, 138.2, 132.1, 130.1, 130.0, 127.4,
b
d
Isolated yields after silica gel chromatography.
36.7, 31.5, 28.4, 28.3, 22.4, 21.6, 14.0.
1530, 1318, 1142 cmꢁ1 1H NMR (270 MHz, CDCl3)
; d 8.22 (br, 1H),
7.83 (d, J¼8.8 Hz, 2H), 7.71 (d, J¼8.8 Hz, 2H), 7.63 (d, J¼15.2 Hz, 1H),
7.48e7.36 (m, 5H), 6.84 (d, J¼15.2 Hz, 1H), 2.19 (s, 3H); 13C NMR
4.4. Typical procedure for transformation of b-bromoalkenyl
sulfones via SuzukieMiyaura coupling (Table 5)
(67.5 MHz, CDCl3)
d 169.2, 142.9, 142.2, 134.8, 132.2, 131.2, 129.1,
128.8, 128.5, 127.2, 119.6, 24.6.
To a mixture of Pd(PPh3)4 (11.6 mg, 0.01 mmol), 4-tolylboronic
acid (29.9 mg, 0.22 mmol), and K2CO3 (10.6 mg, 0.1 mmol), in DMF
(0.8 mL) and H2O (0.2 mL) were added (E)-2-bromo-1-(40-toluene-
sulfonyl)-2-phenylethene (67.4 mg, 0.2 mmol), and the mixture was
stirred at 100 ꢀC for 18 h under nitrogen atmosphere. After the
residue was dissolved in Et2O, the solution was washed with H2O
and saturated sodium chloride and dried over anhydrous magne-
sium sulfate. Chromatography on silica gel (20% diethyl ether/hex-
ane) gave (Z)-2-(40-methylphenyl)-1-(40-methylphenylsulfonyl)-2-
phenylethene (65.4 mg, 94%): colorless solid; mp 89e91 ꢀC;
[found: C, 75.52; H, 5.74. C22H20O2S: C, 75.83; H, 5.79]; IR (CHCl3)
0
4 . 2 . 2 . ( E ) - 1 - ( 4 - M e t h y l p h e n y l s u l f o n y l ) - 2 -
cyclohexenylethene. Colorless solid; mp 82e85 ꢀC; [found: C, 68.33;
H, 6.86. C15H18O2S: C, 68.67; H, 6.92]; IR (CHCl3) 2930, 1628, 1591,
1312, 1144 cmꢁ1; 1H NMR (270 MHz, CDCl3)
d
7.77 (d, J¼8.2 Hz, 2H),
7.31 (d, J¼8.2 Hz, 2H), 7.23 (d, J¼15.2 Hz, 1H), 6.27 (t, J¼3.9 Hz, 1H),
6.18 (d, J¼15.2 Hz, 1H), 2.43 (s, 3H), 2.21 (br, 2H), 2.04 (br, 2H),
1.68e1.57 (m, 4H); 13C NMR (67.5 MHz, CDCl3)
d 145.4, 143.9, 141.3,
138.4, 133.4, 129.8, 127.5, 124.0, 26.5, 24.2, 21.8, 21.7, 21.6.
4.3. Typical procedure for copper-catalyzed synthesis of
haloalkenyl sulfone (Table 4)
b-
3029,1586,1444 cmꢁ1; 1H NMR (270 MHz, CDCl3)
2H), 7.36e7.25 (m, 3H), 7.14e7.06 (m, 8H), 6.97 (s, 1H), 2.37 (s, 3H),
2.33 (s, 3H); 13C NMR (67.5 MHz, CDCl3)
154.7, 143.6, 140.7, 138.7,
d
7.46 (d, J¼8.2 Hz,
d
To a mixture of CuI (4.6 mg, 0.024 mmol), bpy (3.7 mg,
0.024 mmol), PhSO2Na (54.2 mg, 0.33 mmol), and KBr (107.1 mg,
0.9 mmol) in AcOH (0.3 mL) were added phenylacetylene (30.6 mg,
0.3 mmol), and the mixture was stirred at 80 ꢀC for 18 h in air. After
136.3, 135.6, 129.7, 129.2, 128.7, 128.1, 127.9, 127.7, 127.6, 21.5, 21.2.
4.4.1. (Z)-2-(40-Methoxyphenyl)-1-(40-methylphenylsulfonyl)-2-
phenylethene. Pale yellow liquid; [found: C, 72.56; H, 5.16.

1990
N. Taniguchi / Tetrahedron 70 (2014) 1984e1990
C22H20O3S: C, 72.50; H, 5.53]; IR (CHCl3) 3019, 1602, 1510,
1300 cmꢁ1 1H NMR (270 MHz, CDCl3)
References and notes
;
d
7.44 (d, J¼8.2 Hz, 2H),
1. (a) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon
Ltd.: New York, NY, 1991; Vol. 4; (b) Krief, A. In Comprehensive Organometallic
Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Ltd.: New
York, NY, 1995; Vol. 11, Chapter 13; (c) Metal-Catalyzed Cross-Coupling Reactions;
Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; (d)
Metzner, P.; Thuillier, A. In Sulfur Reagents in Organic Synthesis; Katritzky, A. R.,
Meth-Cohn, O., Rees, C. W., Eds.; Academic: San Diego, USA, 1994; (e) Ley, S. V.;
Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400e5449; (f) Kondo, T.; Mit-
sudo, T. Chem. Rev. 2000, 100, 3205e3220; (g) Beletskaya, I. P.; Ananikov, V. P.
Chem. Rev. 2011, 111, 1596e1636; (h) Partyka, D. V. Chem. Rev. 2011, 111,
1529e1595.
7.34e7.28 (m, 3H), 7.15e7.11 (m, 4H), 7.06 (d, J¼8.6 Hz, 2H), 6.93 (s,
1H), 6.80 (d, J¼8.2 Hz, 2H), 3.78 (s, 3H), 2.37 (s, 3H); 13C NMR
(67.5 MHz, CDCl3)
d 161.3, 154.3, 143.5, 138.8, 135.6, 131.3, 129.7,
129.6, 129.2, 128.7, 127.7, 127.5, 126.6, 113.9, 55.3, 21.5.
4.4.2. (Z)-2-(40-Chlorophenyl)-1-(40-methylphenylsulfonyl)-2-
phenylethene. Colorless liquid; [found: C, 68.32; H, 4.54.
C
21H17ClO2S: C, 68.38; H, 4.65]; IR (CHCl3) 3020, 1587, 1489,
1313 cmꢁ1; mp 98e99 ꢀC; 1H NMR (270 MHz, CDCl3)
7.47 (d,
J¼8.2 Hz, 2H), 7.36e7.25 (m, 5H), 7.17e7.06 (m, 6H), 6.97 (s, 1H),
2.38 (s, 3H); 13C NMR (67.5 MHz, CDCl3)
153.3, 143.9, 138.3, 137.6,
d
€
2. (a) Enders, D.; Muller, S. F.; Raabe, G.; Runsink, J. Eur. J. Org. Chem. 2000,
879e892; (b) Lebrun, M.-E.; Marquand, P. L.; Berthelette, C. J. Org. Chem. 2006,
71, 2009e2013; (c) Mauleon, P.; Alonso, I.; Rivero, M. R.; Carretero, J. C. J. Org.
Chem. 2007, 72, 9924e9935.
ꢀ
d
136.4, 135.1, 129.7, 129.4, 129.3, 129.2, 129.0, 128.8, 127.9, 127.7, 21.5.
3. (a) Truce, W. E.; Goralski, C. T. J. Org. Chem. 1971, 36, 2536e2538; (b) Posner, G.
H.; Brunelle, D. J. J. Org. Chem. 1972, 37, 3547e3549; (c) Hoogenboom, B. E.; El-
Faghi, M. S.; Fink, S. C.; Ihrig, P. I.; Langsjoen, A. N.; Linn, C. J.; Maehling, K. L. J.
Org. Chem. 1975, 40, 880e883; (d) Back, T. G.; Collins, S.; Krishna, M. V.; Law, K.-
W. J. Org. Chem. 1987, 52, 4258e4264; (e) Kamigata, N.; Sawada, H.; Kobayashi,
M. J. Org. Chem. 1983, 48, 3793e3796; (f) Kamigata, N.; Narushima, T.; Sawada,
H.; Kobayashi, M. Bull. Chem. Soc. Jpn. 1984, 57, 1421e1422; (g) Huang, X.; Duan,
D.; Zheng, W. J. Org. Chem. 2003, 69, 1958e1963; (h) Guan, Z.-H.; Zuo, W.; Zhoo,
L.-B.; Ren, Z.-H.; Liang, Y.-M. Synthesis 2007, 1465e1470; (i) da Silva Correa, C.
M. M.; Fleming, C. M.; Oliveira, M. A. B. C. S.; Garrido, E. M. J. J. Chem. Soc., Perkin
Trans. 2 1994, 1993e1996.
4. (a) Perrlmutter, P. In Conjugate Addition Reactions in Organic Synthesis; Baldwin,
J. L., Magnus, F. P. D., Eds.; Pergamon: Oxford, UK, 1992; (b) Ochiai, M.; Kita-
gawa, Y.; Toyonari, M.; Uemura, K.; Oshima, K.; Shiro, M. J. Org. Chem. 1997, 62,
8001e8008.
5. (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M.; Bernini, R. J. Org. Chem.
2004, 69, 5608e5614; (b) Battace, A.; Zair, T.; Doucet, H.; Santelli, M. Synthesis
2006, 3495e3505; (c) Bian, M.; Xu, F.; Ma, C. Synthesis 2007, 2951e2956.
6. (a) Truce, W.; Wolf, G. C. J. Org. Chem. 1971, 36, 1727e1732; (b) Amiel, Y. J. Org.
Chem. 1970, 36, 3691e3696; (c) Amiel, Y. J. Org. Chem. 1971, 36, 3697e3701.
4.4.3. (Z)-2-(40-Formylphenyl)-1-(40-methylphenylsulfonyl)-2-
phenylethene. Pale yellow liquid; [found: C, 72.51; H, 4.81.
C
22H18O3S: C, 72.90; H, 5.01]; IR (CHCl3) 3019, 1703, 1215 cmꢁ1; 1H
NMR (270 MHz, CDCl3)
d
9.99 (s, 1H), 7.80 (d, J¼7.6 Hz, 2H), 7.49 (d,
J¼7.9 Hz, 2H), 7.41e7.26 (m, 5H), 7.18e7.06 (m, 5H), 2.38 (s, 3H); 13
C
NMR (67.5 MHz, CDCl3)
d 191.4, 153.0, 144.8, 144.1, 137.9, 136.9,
134.8, 131.2, 129.7, 129.6, 129.4, 129.2, 128.8, 128.0, 127.7, 21.5.
4.4.4. (Z)-2-(40-Methoxycarbonylphenyl)-1-(40-methyl-
phenylsulfonyl)-2-phenylethene. Pale yellow liquid; [found: C,
72.12; H, 5.40. C22H20O3S: C, 72.50; H, 5.53]; IR (CHCl3) 3020, 1721,
1286, 1216 cmꢁ1; 1H NMR (270 MHz, CDCl3)
d
7.95 (d, J¼8.6 Hz, 2H),
7.49 (d, J¼8.2 Hz, 2H), 7.40e7.25 (m, 5H), 7.18e7.08 (m, 4H), 7.03 (s,
1H), 3.90 (s, 3H), 2.38 (s, 3H); 13C NMR (67.5 MHz, CDCl3)
166.2,
d
7. Recently, iron-catalyzed synthesis of
b-haloalkenylsulfones are reported: (a)
153.3, 144.0, 143.4, 138.1, 135.0, 131.3, 130.6, 129.7, 129.6, 129.4,
129.1, 128.1, 127.9, 127.7, 52.3, 21.5.
Xiaoming, Z.; Laurean, I.; Nakamura, E. Org. Lett. 2012, 14, 954e956; (b) Li, X.;
Shi, X.; Fang, M.; Xu, X. J. Org. Chem. 2013, 78, 9499e9504.
8. Sulfonylations of ArX using Ar0SO2Na has been reported. (a) Suzuki, H.; Abe, H.
Tetrahedron Lett. 1995, 36, 6239e6242; (b) Baskin, J. M.; Wang, Z. Org. Lett.
2002, 4, 4423e4425; (c) Beaulieu, C.; Guay, D.; Wang, Z.; Evans, D. A. Tetra-
hedron Lett. 2004, 45, 3233e3236.
4.4.5. (Z)-2-(40-Methylphenyl)-1-(40-chlorophenylsulfonyl)-2-phe-
nylethene. Pale yellow solid; mp 134e135 ꢀC; [found: C, 68.62; H,
4.64. C21H17ClO2S: C, 68.38; H, 4.65]; IR (CHCl3) 319, 1585, 1314,
9. (a) Nair, V.; Augustine, A.; Suja, T. D. Synthesis 2002, 2259e2265; (b) Mochizuki,
T.; Hayakawa, S.; Narasaka, K. Bull. Chem. Soc. Jpn. 1996, 69, 2317e2325; (c)
Katrun, P.; Chiampanichayakul, S.; Korworapan, K.; Pohmakotr, M.; Reutrakul,
V.; Jaipetch, T.; Kuhakarn, C. Eur. J. Org. Chem. 2010, 5633e5641.
10. Taniguchi, N. Synlett 2011, 1308e1312.
1215 cmꢁ1
;
1H NMR (270 MHz, CDCl3)
d
7.45 (d, J¼8.6 Hz, 2H),
7.37e7.25 (m, 5H), 7.10 (s, 4H), 7.04 (d, J¼8.6 Hz, 2H), 7.00 (s, 1H),
2.34 (s, 3H); 13C NMR (67.5 MHz, CDCl3)
155.7, 141.1, 134.0, 139.3,
d
11. Taniguchi, N. Synlett 2012, 1245e1249.
12. (a) Taniguchi, N. Tetrahedron 2009, 65, 2782e2790; (b) Taniguchi, N. Synlett
135.9, 135.4, 129.7, 129.4, 129.1, 128.9, 128.8, 128.1, 127.9, 127.5, 21.3.
2008, 849e852; (c) Zask, A.; Helquist, P. J. Org. Chem. 1978, 43, 1619e1620; (d)
€
Backvall, J.-E.; Ericsson, A. J. Org. Chem. 1994, 59, 5850e5851.
13. Amiel, Y. J. Org. Chem. 1974, 39, 3867e3870.
14. (a) Cohen, T.; Cristea, I. J. Org. Chem. 1975, 40, 3649e3651; (b) Cohen, T.; Cristea,
I. J. Am. Chem. Soc. 1976, 98, 748e753; (c) Ebert, G. W.; Rieke, R. D. J. Org. Chem.
1988, 53, 4482e4488.
Acknowledgements
15. (a) Kochi, J. K. Organometallic Mechanisms and Catalysis; Academic: London, UK,
1978; (b) Modern Organocopper Chemistry; Krause, N., Ed.; Wiley-VCH: Wein-
heim, Germany, 2002.
This work was supported by Grant for Basic Science Research
Project from The Sumitomo Foundation.
16. Wang, Z.-L.; Tang, R.-Y.; Luo, P.-S.; Deng, C.-L.; Zhong, P.; Li, J.-H. Tetrahedron
2008, 64, 10670e10675.
17. Hydrofunctionalization; Ananikov, V. P., Tanaka, M., Eds.Topics in Organometallic
Chemistry; Springer: Heidelberg, Germany, 2013; Vol. 43.
18. It is reported that the thermal decomposition of CuX2 (X¼I or Br) to X2: Tanaka,
N.; Kagawa, M. Bull. Chem. Soc. Jpn. 1970, 43, 3468e3471.
19. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457e2483.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.01.071.