Efficient Synthesis of Vinyl Sulfones by Manganese-Catalyzed Decarboxylative Coupling of Cinnamic Acids with Aromatic Sulfinic Acid Sodium Salts

Article abstract of DOI:10.1055/s-0035-1562476

An efficient synthesis of vinyl sulfones is described. Reactions of cinnamic acids with aromatic sulfinic acid sodium salts in the presence of a catalytic amount of manganese(II) acetate tetrahydrate (5 mol%) in dimethyl sulfoxide (DMSO) afforded the desired vinyl sulfones in good to excellent yields. Notably, the reaction does not need any base or iodide as additive. The use of DMSO as the solvent and running the reaction under air are critical in achieving good yields.

Full text of DOI:10.1055/s-0035-1562476

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–D
letter
A
N. Xue et al.
Letter
Synlett
Efficient Synthesis of Vinyl Sulfones by Manganese-Catalyzed
Decarboxylative Coupling of Cinnamic Acids with Aromatic
Sulfinic Acid Sodium Salts
Na Xuea
Ruqing Guoa
Xinman Tub
Weiping Luoa
Wei Deng*a
Jiannan Xiang*a
O
Mn(OAc)2
(5% mol)
COOH
R2
S
SO2Na
R1
R1
O
R2
+
DMSO, 110 °C, air
22 examples, 57–86% yield
a College of Chemistry and Chemical Engineering, State Key Laboratory
of Chemo/Biosensing and Chemometrics, Hunan University, Changsha
410082, P. R. of China
b Key Laboratory of Jiangxi Province for Persistent Pollutants Control and
Resources Recycle, School of Environment and Chemical Engineering,
Nanchang Hangkong University, Nanchang 330063, P. R. of China
weideng@hnu.edu.cn
jnxiang@hnu.edu.cn
Received: 08.05.2016
Accepted after revision: 23.06.2016
Published online: 04.08.2016
size vinyl sulfones by decarboxylative coupling of cinnamic
acids with sulfinates,10 because a variety of cinnamic acids
are commercially available. Along this line, metal-catalyzed
or metal-free decarboxylative coupling reactions of cin-
namic acids with sulfinates have been developed by several
groups. For example, Guo and co-workers demonstrated
that vinyl sulfones can be efficiently synthesized from cin-
namic acids and benzenesulfinates through catalysis by CuI
in the presence of KI as an additive.11 Tan and co-workers
have shown that by using Pd as a catalyst and Ag2CO3 as an
oxidant, vinyl sulfones can be efficiently constructed from
various cinnamic acids and arenesulfinates.12 The same
transformation can also be effected with a stoichiometric
DOI: 10.1055/s-0035-1562476; Art ID: st-2016-w0325-l
Abstract An efficient synthesis of vinyl sulfones is described. Reac-
tions of cinnamic acids with aromatic sulfinic acid sodium salts in the
presence of a catalytic amount of manganese(II) acetate tetrahydrate
(5 mol%) in dimethyl sulfoxide (DMSO) afforded the desired vinyl sul-
fones in good to excellent yields. Notably, the reaction does not need
any base or iodide as additive. The use of DMSO as the solvent and run-
ning the reaction under air are critical in achieving good yields.
Key words manganese catalysis, decarboxylation, coupling, cinnamic
acids, sodium arenesulfinates, vinyl sulfones
13
amount of PhI(OAc)2 or under Cu catalysis by using tert-
Vinyl sulfones (α,β-unsaturated sulfones) are important
organic molecules and they are crucial structural scaffolds
in many bioactive compounds and drugs.1 In addition, they
are also widely used as Michael acceptors2 in organic chem-
istry. Because of their synthetic utility and their potential
biological activities, the synthesis of vinyl sulfones has re-
ceived considerable attention in organic synthesis and me-
dicinal chemistry. Conventionally, vinyl sulfones are syn-
thesized either by the oxidation of thioethers3 or through
condensation of aldehydes with sulfonylacetic acids.4 How-
ever, two of the most straightforward approaches to vinyl
sulfone synthesis involve the addition of sulfinates to
alkenes5 or alkynes.6 Because alkenes and alkynes are basic
building blocks and can be easily prepared, their use as
starting materials for the synthesis of vinyl sulfones can be
highly advantageous. Alternatively, vinyl sulfones can be
synthesized by transition-metal-catalyzed cross-coupling
reactions of sulfinates with vinyl halides,7 triflates,8 or bo-
ronic acids.9 More recently, chemists have begun to synthe-
butyl hydroperoxide (TBHP) as the oxidant.14 Note that the
same reaction can also be accomplished in the presence of
I2 and TBHP.15 More impressively, Jiang and co-workers
were able to carry out the same transformation without
any catalyst.16 All the reaction needed was 0.5 equivalents
of a simple inorganic base, such as K2CO3. It is proposed that
the solvent DMSO is the actual oxidant.16,17 Interestingly, a
similar reaction can also be run in water by using I2 as the
oxidant.18 Even though these methods provide efficient
routes for the synthesis of vinyl sulfones from cinnamic ac-
ids, the need to use iodides is a disadvantage. Here, we dis-
close a novel and efficient synthesis of vinyl sulfones by de-
carboxylative coupling of cinnamic acids with arenesulfi-
nates without the need for any base or iodide additive.
Instead, only a catalytic amount of a simple Mn(II) salt is re-
quired.
We began the study by using cinnamic acid (1a; 1 equiv)
and sodium benzenesulfinate (2a; 3 equiv) as our model re-
actants. Inspired by Guo’s method, we wondered whether
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

B
N. Xue et al.
Letter
Synlett
other transition metals might catalyze the decarboxylative
coupling of cinnamic acids with arenesulfinates, so we test-
ed the coupling of acid 1a with sulfinate 2a in the presence
of various transition-metal catalysts (5 mol%) under air
with KI (20 mol%) as an additive in DMSO at 110 °C for 12
hours (Table 1, entries 1–3). With Co(OAc)2, or FeCl3 as cata-
lyst, the desired vinyl sulfone 3a was isolated in 26% and 8%
yield, respectively (entries 1 and 2). The stereochemistry of
the product 3a was determined to be trans, because the
coupling constant between the two olefinic hydrogens was
15.5 Hz. Much to our delight, when the catalyst was
switched to Mn(OAc)2, the yield improved to 76% (entry 3).
As a result, we chose Mn(OAc)2 as the catalyst to screen
other reaction parameters. Interestingly, we found that the
coupling reaction occurred even in the absence of KI, and
this gave an even better yield of 3a (86%; entry 4).
tion in the temperature range 80–125 °C was also investi-
gated, and the reaction performed at 110 °C gave the best
result (entry 4); lowering or raising the reaction tempera-
ture gave much lower yields (entries 8 and 9). When the
amount of the catalyst was reduced to 3 mol%, the yield
reached 72% (entry 10). Surprisingly, the vinyl sulfone 3a
could be isolated in 28% yield in the absence of a manga-
nese catalyst (entry 11). In addition, the manganese cata-
lysts
MnCl2
and
chloro[tris(4-chlorophenyl)phos-
phine]manganese [(TCPP)MnCl] gave sulfone 3a in 27% and
19% yield, respectively (entries 14 and 15). On the basis of
these results, we decided to set the optimal conditions as
follows: 1a (0.5 mmol), 2a (1.5 mmol), and Mn(OAc)2·4H2O
(5 mol%) in DMSO at 110 °C under air for 12 hours.
With the optimized protocol in hand, we explored the
substrate scope of the decarboxylation reaction. As shown
in Table 2, the reaction worked well for a wide variety of
Table 1 Optimization of Reaction Conditionsa
O
Table 2 Substrate Scope for the Synthesis of Vinyl Sulfonesa,19
COOH
+
SO2Na
S
catalyst, additive
solvent
O
O
Mn(OAc)2
(5 mol%)
COOH
R2SO2
S
1a
2a
3a
R2
R1
R1
O
+
DMSO, air, 110 °C
Yieldb (%)
3a
1a
Entry
Catalyst (mol%)
Solvent
Additive
2a
1
2
Co(OAc)2
DMSO
DMSO
DMSO
DMSO
DMAc
KI
KI
KI
−
26
8
Entry
R1
4-Me
R2
Ph
Product
Yieldb (%)
FeCl3
1
2
3ab
3ac
3ad
3ae
3af
74
69
64
65
63
72
67
62
80
61
73
63
57
53
62
65
66
70
57
63
3
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
−
76
86
47
25
13
66
47
72
28
12
32
27
19
4-Cl
4-F
Ph
4
3
Ph
5
−
4
4-Br
2-Cl
Ph
6
toluene
DCE
−
5
Ph
7
−
6
4-OMe
2-OMe
3-OMe
4-NO2
2-NO2
3-NO2
H
Ph
3ag
3ah
3ai
8d
9e
10f
11
12g
13h
14
15
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
−
7
Ph
−
8
Ph
−
9
Ph
3aj
−
10
11
12
13
14
15
16
17
18
19
20
21
Ph
3ak
3al
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
MnCl2·4H2O
(TCPP)MnCli
−
Ph
−
4-MeC6H4
4-BrC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
Me
3am
3an
3ao
3ap
3aq
3ar
3as
3at
3au
3av
−
H
−
4-NO2
3-NO2
4-Me
4-F
a Reaction conditions: 1a (0.5 mmol), 2a (1.5 mmol), catalyst (5 mol %), sol-
vent (2 mL), 110 °C, 12 h, under air.
b Isolated yield.
c DMA = N,N-dimethylacetamide
d 125 °C.
e 80 °C.
f Mn(OAc)2 (3 mol%).
g Under N2.
4-Cl
2-Cl
h Solvent 1 mL.
i TCPP = T(p-Cl)PP.
4-Br
c
H
–
A screening of solvents revealed that DMSO was better
than other solvents such as N,N-dimethylacetamide (DMA),
DCE, or toluene (Table 1, entries 4–7). The effects of the re-
action temperature on the decarboxylative coupling reac-
a Reaction conditions: 1 (0.5 mmol), 2 (1.5 mmol), catalyst (5 mol %), sol-
vent (2 mL), 110 °C, 12 h, under air.
b Isolated yield.
c Messy reaction.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

C
N. Xue et al.
Letter
Synlett
nate, sodium methanesulfinate, was used as the reactant
(entry 21).
O
S
O
S
(a)
COOH
+
standard
conditions
ONa
O
To shed some light on the reaction mechanism, several
control reactions were carried out. When the reaction of 1a
with 2a was conducted under the optimal conditions in the
presence of radical inhibitors such as TEMPO or 2,4-di-tert-
butyl-4-methylphenol (BHT), the reaction was completely
inhibited (Scheme 1, a and b). These results suggested that
our reaction might be a free-radical-based process. In addi-
tion, when we ran the reaction without the Mn(OAc)2·4H2O
catalyst, the yield of 3a was only 28% (Scheme 1, c), show-
ing that the catalyst is essential for obtaining 3a in good
yield. On the other hand, when the reaction was performed
with a stoichiometric amount of Mn(OAc)2·4H2O in DMA
under N2, the product 3a was only isolated in a trace
amount (Scheme 1, d). In comparison, replacing the
Mn(OAc)2·4H2O catalyst with one equivalent of
Mn(OAc)3·2H2O afforded 3a in 45% yield (Scheme 1, e). This
suggested that the true catalyst in the reaction might be a
Mn(III) species. Because a much lower yield was obtained in
DMA than in DMSO, we believe that DMSO might play an
important role in the reaction in addition to forming com-
plexes with the Mn catalyst.
TEMPO (1.1 equiv)
1a
2a
3a
not observed
O
S
O
S
(b)
COOH
+
standard
conditions
ONa
ONa
O
BHT (1.1 equiv)
2a
3a
1a
<5%
O
S
O
S
(c)
COOH
+
air, 12 h
O
DMSO, 110 °C
1a
2a
3a
28%
O
S
O
S
(d)
COOH
+
ONa
ONa
Mn(OAc)2 (1 equiv)
DMAc, N2, 110 °C
O
2a
3a
trace
O
1a
O
S
(e)
COOH
+
S
Mn(OAc)3 (1 equiv)
DMAc, N2, 110 °C
O
On the basis of these results and literature prece-
dents,10–18 we propose the tentative mechanism shown in
Scheme 2.
1a
2a
3a
45%
Scheme 1 Control experiments
We believe that the reaction begins with the oxidation
of Mn(OAc)2 by O2 to give a Mn(III) species that forms inter-
mediate A by anion exchange with cinnamic acid. At the
same time, sodium benzenesulfinate is oxidized by DMSO
or a Mn(III) species to the corresponding sulfinate radical B.
Next, B adds to the double bond of intermediate A to form
adduct C. Subsequently, through homolysis of the Mn–car-
boxylate bond, adduct C is transformed into the biradical
intermediate D, which, upon loss of one molecule of CO2,
gives the final product 3a. Because the trans product is
formed exclusively, this reaction is clearly a thermodynami-
cally controlled process.
substituted cinnamic acids 1, and the products were isolat-
ed in yields of 57–80% (Table 2, entries 1–8). Substrates
with electron-donating or electron-withdrawing groups on
the phenyl ring of the cinnamic acids all provided the de-
sired vinyl sulfones in good yields. Cinnamic acids 1 with
ortho-, meta- or para-nitro substituents all gave similar
yields of the corresponding products (Table 2, entries 9–
11); these results are important because the nitro group
can be easily converted into other functional groups. Addi-
tionally, we found that methyl- and bromo-substituted so-
dium benzenesulfinates 2 gave the desired vinyl sulfones 3
satisfactorily in 53–76% yield (entries 12–20). Unfortunate-
ly the reaction was quite messy when a sodium alkanesulfi-
In summary, an efficient method has been developed for
the synthesis of vinyl sulfones through decarboxylation of
various cinnamic acids with sodium benzenesulfinates
with air as the oxidant. Unlike other methods, our reaction
COOMn(III)+
COOH
Mn(OAc)2
O2
A
O
S
O
S
DMSO
Na
or Mn(III)
O
O
B
O
O
OMn(III)+
Mn(II)
O
S
O
S
O
S
O
S
O
A
Ar
CO2
O
O
O
O
Ar
Ar
3a
C
D
Scheme 2 Possible reaction mechanism
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

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N. Xue et al.
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does not use any iodide salt as additive. The success of the
reaction is critically dependent on the use of Mn(OAc)2 as
catalyst. In addition, the use of DMSO as the solvent is also
pivotal. Preliminary mechanistic studies suggest that this
reaction is likely to proceed through a radical pathway.
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Acknowledgment
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We are grateful for grants from the Key Laboratory of Jiangxi Province
for Persistent Pollutants Control and Resources Recycle.
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562476.
S
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p
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(E)-1-Bromo-4-[2-(4-tosyl)vinyl]benzene (3au)5c as a repre-
sentative product: C15H13SO2Br. Yield: 63%; white solid; mp
163–164 °C. 1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8.2 Hz, 2
H), 7.51 (d, J = 15.4 Hz, 1 H), 7.45 (d, J = 8.4 Hz, 2 H), 7.27 (t, J =
7.6 Hz, 4 H), 6.77 (d, J = 15.4 Hz, 1 H), 2.37 (s, 3 H). 13C NMR (101
MHz, CDCl3): δ = 143.5, 139.4, 136.4, 131.3, 130.3, 128.9, 128.7,
127.3, 126.7, 124.4, 20.6. MS: m/z = 337 (M+).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D