Transition-metal-free synthesis of vinyl sulfones via tandem cross-decarboxylative/coupling reactions of sodium sulfinates and cinnamic acids

Article abstract of DOI:10.1039/c4gc00542b

A transition-metal-free synthesis of vinyl sulfones, utilizing sodium sulfinates and cinnamic acids through tandem cross-decarboxylative/coupling reactions, has been developed. This transformation is simple, efficient and environmentally benign, with a wide range of substrate scope and exceptional functional group tolerance. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4gc00542b

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Transition-metal-free synthesis of vinyl sulfones
via tandem cross-decarboxylative/coupling
reactions of sodium sulfinates and cinnamic acids†
Cite this: DOI: 10.1039/c4gc00542b
Received 27th March 2014,
Accepted 23rd April 2014
Yanli Xu, Xiaodong Tang, Weigao Hu, Wanqing Wu and Huanfeng Jiang*
DOI: 10.1039/c4gc00542b
www.rsc.org/greenchem
A transition-metal-free synthesis of vinyl sulfones, utilizing sodium et al. have reported a simple and green method for the syn-
sulfinates and cinnamic acids through tandem cross-decarboxyl- thesis of vinyl sulfones from terminal epoxides and sodium
ative/coupling reactions, has been developed. This transformation sulfinates, and two regioisomers (linear and branched vinyl
is simple, efficient and environmentally benign, with a wide range sulfones) were obtained in most cases, which made the separ-
of substrate scope and exceptional functional group tolerance.
ation difficult.14 Therefore, the development of efficient,
environment-friendly, and practical synthetic methods for
synthesising vinyl sulfones with high regioselectivity is still
needed.
The development of environmentally benign, operationally
simple, and efficient tandem cross-coupling strategies for the
construction of privileged molecular skeletons continues to
attract broad interest, due to their economical and environ-
mental impact.1 Recently, such protocols which avoid or mini-
mize the use of transition metals in tandem cross-coupling
reactions, have been intensively pursued by the synthetic com-
munity, as the alternatives are sometimes toxic, expensive,
hard to handle, difficult to dispose of properly in large
quantities, and may possibly leave toxic traces of metals in the
products.2
Cinnamic acids are relatively stable, simple to handle, and
readily prepared by the Perkin reaction from aromatic alde-
hydes. As our interest in sodium sulfinates as substrates con-
tinues,15 we wish to describe a concise and efficient tandem
cross-decarboxylative/coupling reaction for the synthesis of
vinyl sulfones from sodium sulfinates and cinnamic acids,
using DMSO as the oxidant. This reaction, performed under
transition-metal-free conditions, gives coupling products in
good yields, and tolerates a variety of functional groups.
We commenced our study by using benzenesulfinic acid
sodium salt (1a) and trans-cinnamic acid (2a) as model sub-
strates under various conditions and the results are summar-
ized in Table 1. In the absence of a base, the reaction between
1a and 2a gave a low yield of (E)-(2-(phenylsulfonyl)vinyl)-
benzene (3a) (Table 1, entry 1). When this reaction was
performed in the presence of bases, such as CH3COONa,
CH3COOK, NaHCO3, Li2CO3, Na2CO3, K2CO3, and Cs2CO3, the
yield of 3a increased (Table 1, entries 2–7 and 9). The reaction
performed with 50 mol% Cs2CO3 gave the best result (95% GC
yield) (Table 1, entry 9). Considering the costs of Cs2CO3 and
K2CO3, we used K2CO3 to further optimize this transformation.
Notably, not much influence on the yield of 3a was observed
by GC-MS when the reaction was performed in the presence of
50 mol% K2CO3 in DMSO under a N2 atmosphere (Table 1,
entry 8). Screening of different solvents revealed that DMSO
was the best solvent for this process (Table 1, entry 7 vs. 10–12
and 14). No 3a was detected by GC-MS when using toluene or
1,4-dioxane as solvents (Table 1, entries 12 and 14), while 37%
and 46% yields of 3a were obtained when it was performed in
a mixture of toluene–DMSO (v/v = 10 : 1) or 1,4-dioxane–DMSO
(v/v = 10 : 1), respectively (Table 1, entries 13 and 15). In
Vinyl sulfones are valuable synthetic targets3 and constitute
a significant component in naturally occurring products and
in drug discovery,4 and therefore have attracted considerable
interest from organic chemists in pursuing synthetic
efficiency. Conventional methods for the synthesis of vinyl
sulfones involve the oxidation of the corresponding sulfides,5
the manipulation of acetylenic sulfones,6 the condensation of
aromatic aldehydes with sulfonylacetic acids,7 or the β-elimin-
ation of selenosulfones or halo-sulfones.8 In recent years,
these have been replaced by new and more efficient Pd- or
Cu-catalyzed cross-coupling reactions of sulfinate salts with
vinyl halides,9 vinyl tosylates,10 vinyl triflates,11 alkenyl
boronic acids,12 or alkenes.13 In spite of the efficiency and gen-
erality of these reactions, it is still not enough for green chemi-
stry because of the use of toxic metals. Very recently, Yadav
School of Chemistry and Chemical Engineering, South China University of
Technology, Guangzhou 510640, China. E-mail: jianghf@scut.edu.cn;
Fax: +86 20-87112906; Tel: +86 20-87112906
†Electronic supplementary information (ESI) available: Experimental section,
characterization of all compounds, and copies of 1H and 13C NMR spectra for
selected compounds. See DOI: 10.1039/c4gc00542b
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Table 1 Optimization of reaction conditionsa
Table 2 Synthesis of vinyl sulfonesa,b
Entry
Base
Solvent
Yieldb (%)
1
2
3
4
5
6
—
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
H2O
Toluene
Toluene
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
DMSO
32
55
52
39
62
75
92 (82)
90
95
27
<10
nd
37
nd
46
83
90 (78)
CH3COONa
CH3COOK
NaHCO3
Li2CO3
Na2CO3
K2CO3
K2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
7
8c
9
10
11
12
13d
14
15e
16f
17g
a Reaction conditions: unless otherwise noted, all of the reactions were
performed with 1a (0.45 mmol), 2a (0.3 mmol), 0.5 equiv. base, in
solvent (2.0 mL) at 100 °C (bath temperature) for 10 h. b Determined by
GC using dodecane as the internal standard. The data in parentheses
are the yields of the isolated products. c The reaction was performed
under a N2 atmosphere. d 2.0 mL of toluene–DMSO (v/v = 10 : 1).
e 2.0 mL of 1,4-dioxane–DMSO (v/v = 10 : 1). f 2.0 mL of 1,4-dioxane–
DMSO (v/v = 1 : 1). g Conditions: 1a (7.5 mmol), 2a (5 mmol), K2CO3
(2.5 mmol), DMSO (4.0 mL), 12 h.
a Reaction conditions: unless otherwise noted, all of the reactions were
performed with 1 (0.75 mmol), 2 (0.5 mmol), and K2CO3 (0.25 mmol),
in DMSO (2.0 mL) at 100 °C (bath temperature) for 10 h. b The data in
parentheses are the yields of the isolated products.
addition, the GC-yield of 3a was up to 83% when the reaction
was performed in a mixture of 1,4-dioxane–DMSO (v/v = 1 : 1),
which suggested that DMSO could play some unique role in
this process (Table 1, entry 16). Therefore, the best conditions
for this transformation involved 50 mol% K2CO3, in DMSO at
100 °C for 10 h. Besides, the reaction was scalable and practi-
cal since a satisfactory yield (78%) could be obtained in the
presence of 50 mol% K2CO3 when the reaction was performed
on a 5 mmol scale (Table 1, entry 17).
Using the optimal conditions, various sulfinic acid sodium
salts and cinnamic acids were explored as substrates, and the
results are summarized in Table 2. A series of para-substituted
sulfinic acid sodium salts, including some with electron-donat-
ing groups (R′ = OMe, Me), and some with electron-withdraw-
ing groups (R′ = F, Cl, Br, CF3), proceeded smoothly and
afforded the desired vinyl sulfone products in high yields.
Other substituted sulfinic acid sodium salts such as 2-chloro-
benzene sulfinic acid sodium salt, could also provide the
desired product in a 78% yield. These results showed that this
transformation was tolerant towards the electronic and steric
effects of the aromatic ring. In addition, a 73% yield of 3i was
obtained when 2-thienylsulfinic acid sodium salt reacted with
2a. More sterically hindered substrates, such as 2-naphthylsul-
finic acid sodium salt, reacted with 2a giving the desired
product 3j in an 80% yield. Moreover, methane sulfinic acid
sodium salt, ethane sulfinic acid sodium salt and cyclopropane-
sulfinic acid sodium salt, were also good substrates for this
transformation, affording the corresponding products 3k–3m
in excellent yields.
Substituted cinnamic acids bearing electron-donating
groups such as Me or OMe, or electron-withdrawing groups
such as Cl, Br, CN, or NO2, on the aromatic ring performed
well in this process, and led to the formation of the expected
vinyl sulfones in good to excellent yields. On the whole,
cinnamic acids with an electron-withdrawing group on the
benzene ring gave the corresponding products in higher yields
than those with an electron-donating group on the benzene
ring. In addition, both (E)-3-(pyridin-2-yl)acrylic acid and (E)-3-
(thiophen-2-yl)acrylic acid showed high reactivities, and the
desired products 3u and 3v were obtained in 73% and 85%
yields, respectively.
To investigate the reaction mechanism, several control
experiments were conducted (Scheme 1). The reaction failed to
give the desired product 3a when benzenesulfinic acid sodium
salt (1a) was treated with styrene under the standard con-
ditions (eq (1)). No 3a was detected in the presence of the radical
scavengers TEMPO or BHT (eq (2)), which indicated that a
radical pathway could be involved. According to the above
results, a possible mechanism is proposed in Scheme 2.
An oxygen centered radical generated by the oxidation of
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sulphinate by DMSO, resonates with the sulphonyl radical
intermediate A,16 followed by radical addition to B (formed
from cinnamic acid under basic conditions). This leads to the
formation of intermediate C. The loss of carbon dioxide
results in intermediate D, which gives the vinyl sulfone
products under the DMSO conditions.13,15b,17
In summary, we have developed a simple and efficient
metal-free synthesis of vinyl sulfones through the cross-decarb-
oxylative/coupling reactions of sodium sulfinates and cin-
namic acids. The reaction presents a convenient method with
good functional group tolerance for the preparation of vinyl
sulfones in medicinal chemistry. Due to its simplicity, this pro-
tocol may have potential applications in organic synthesis, and
further studies on the applications of vinyl sulfones in drug
design are currently ongoing in our laboratory.
We thank the National Natural Science Foundation of
China (21172076), the National Basic Research Program of
China (973 Program) (2011CB808600), the Guangdong Natural
Science Foundation (10351064101000000) and the Fundamen-
tal Research Funds for the Central Universities (2014ZP0004
and 2014ZZ0046) for financial support.
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