Copper-catalyzed highly selective direct hydrosulfonylation of alkynes with arylsulfinic acids leading to vinyl sulfones

Article abstract of DOI:10.1039/c3ob42522c

A novel Cu-catalyzed direct hydrosulfonylation of alkynes with arylsulfinic acids for the synthesis of (E)-vinyl sulfones has been realized under mild conditions with 100% atom efficiency. The present protocol provides an attractive approach to various vinyl sulfones in good to excellent yields, with the advantages of operation simplicity, atom economy, and high stereo- and regioselectivities.

Full text of DOI:10.1039/c3ob42522c

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Copper-catalyzed highly selective direct
hydrosulfonylation of alkynes with arylsulfinic
Cite this: DOI: 10.1039/c3ob42522c
acids leading to vinyl sulfones
Received 17th December 2013,
Accepted 21st January 2014
Wei Wei,a,b Jinli Li,a,b Daoshan Yang,a,b Jiangwei Wen,a,b Yueting Jiao,a,b
DOI: 10.1039/c3ob42522c
Jinmao Youa,b,c and Hua Wang*a,b
www.rsc.org/obc
A novel Cu-catalyzed direct hydrosulfonylation of alkynes with aryl- biologically active compounds8 and versatile building blocks
sulfinic acids for the synthesis of (E)-vinyl sulfones has been realized for various organic transformations.9 Generally, vinyl sulfones
under mild conditions with 100% atom efficiency. The present pro- are prepared by Knoevenagel condensation of aromatic alde-
tocol provides an attractive approach to various vinyl sulfones in hydes with sulfonylacetic acids,10 Wittig reaction,11 Horner–
good to excellent yields, with the advantages of operation simpli- Emmons reaction of carbonyl compounds with sulfonyl phos-
city, atom economy, and high stereo- and regioselectivities.
phoranes,12 and β-elimination of selenosulfones or halo-
sulfones,13 in which the desired products were usually formed
in a mixture of isomers. A number of alternative methods
towards vinyl sulfones synthesis have also been developed
such as the oxidation of vinyl sulfides with stoichiometric oxi-
dants,14 the cross-coupling of sulfinate salts with vinyl tri-
flates, vinyl bromides, or alkenyl boronic acids with Cu or Pd
catalysts,15 the addition of ArSO2X (X = I, Cl, SePh, HgCl,
ONO2, etc.) to alkenes followed by β-elimination,16 and the
addition of ArSO2X (X = I, Cl, etc.), sodium sulfinates or 1,2-bis-
(phenylsulfonyl)ethane to alkynes.17 However, most of these
methods suffer from some limitations such as inaccessible
starting materials, tedious procedures, relatively harsh reaction
conditions, lack of atom economy, or the generation of large
amounts of unwanted byproducts. Therefore, the development
of mild, convenient, highly-selective and especially atom-
economic, environmentally friendly, and resource efficient
methods to afford vinyl sulfones is still highly desirable.
The present method of direct addition of arylsulfinic acids
to alkynes is realized under mild conditions by employing
simple and cheap copper salts as the catalyst, which provides a
variety of vinyl sulfones in good to excellent yields and high
regio- and stereoselectivity. To the best of our knowledge, this
method is the first example of transition-metal-catalyzed direct
synthesis of vinyl sulfones from simple and readily available
materials with complete atom economy, and does not require
the use of any ligand or additive.
Transition-metal-catalyzed direct addition of H-heteroatom
compounds to carbon–carbon unsaturated triple bonds is one
of the most straightforward and powerful tools for the con-
struction of alkenyl heteroatom compounds because of its
advantages in terms of synthetic efficiency and atom
economy.1 Over the past several decades, considerable efforts
have been made in this area and some important alkenyl
heteroatom compounds, such as phosphonates,2 boronates,3
selenides,4 sulfides,5 and nitrogen-6 and oxygen-containing7
products, have been obtained via the catalytic addition reac-
tion of alkynes. Nevertheless, there is still a great demand for
the development of a new and selective catalytic system to
offer other important alkenyl heteroatom compounds such as
vinyl sulfones. Herein, we report a novel and efficient copper-
catalyzed direct hydrosulfonylation of alkynes with arylsulfinic
acids for the construction of vinyl sulfones in a one-pot pro-
cedure with 100% atom efficiency (eqn (1)).
ð1Þ
As extremely valuable alkenyl heteroatom compounds, vinyl
sulfones have increasingly attracted synthetic pursuit of che-
mists, since they can serve as key structural motifs of many
Initially, the reaction of phenylacetylene 1a with benzene-
sulfinic acid 2a was performed to examine the catalytic activity
of various transition metal complexes including Ru, Pd, Ag,
Cu, Fe, Co, Ni, In and Zn salts in DME at 60 °C under N2. As
shown in Table 1, among the above metal catalysts screened
(entries 1–13), copper salts especially Cu(OAc)2 were found to
aThe Key Laboratory of Life-Organic Analysis, Qufu Normal University, Qufu 273165,
China. E-mail: huawang_qfnu@126.com
bKey Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine,
Qufu Normal University, Qufu 273165, China
cNorthwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810001,
PR China
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Table 1 Optimization of the reaction conditionsa
Table 2 Scope of the reaction of various alkynes with arylsulfinic
acidsa,b
Entry
Catalyst
Solvent
Yieldb (%)
1
2
3
4
RuCl3
DME
DME
DME
DME
0
0
0
0
Pd(OAc)2
In(OAc)3
AgNO3
5
6
7
8
NiCl2
ZnBr2
Co(OAc)2
FeBr3
CuBr2
CuCl2
CuI
Cu(OTf)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
—
DME
DME
DME
DME
DME
DME
DME
DME
Trace
Trace
Trace
<10
82
90
50
75
94
92
65
51
26
44
0
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
DME
THF
1,4-Dioxane
Toluene
DMSO
CH3OH
CH3CN
H2O
DME
DME
DME
0
42c
0d
0
a Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol), catalyst
(5 mol%), solvent (3 mL), 60 °C, N2, 8 h. b Isolated yields based on 1a.
c Under air. d At room temperature.
a Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), Cu(OAc)2 (5 mol
%), DME (3 mL), 8 h, N2 (balloon). b Isolated yields based on 1.
be the best catalysts for the formation of product 3aa, and
other catalysts such as Pd(OAc)2, RuCl3, In(OAc)3, AgNO3,
NiCl2, ZnBr2, Co(OAc)2, or FeBr3 did not or only sluggishly pro-
moted this reaction. The screening of a range of solvents
showed that the reaction performed in 1,2-dimethoxyethane
(DME) or THF was significantly better than those in 1,4-
dioxane, toluene, DMSO, CH3OH, CH3CN and H2O (entries
13–20). The desired product was obtained in only 42% yield
under an air atmosphere (entry 21). No conversion was
observed when the reaction was performed at room tempera-
ture or in the absence of a copper catalyst (entries 22–23).
Under the optimized conditions, the scope of the reaction
of various alkynes with arylsulfinic acids was investigated and
the results are shown in Table 2. In general, aromatic alkynes
which have electron-donating or withdrawing groups on the
aryl rings were suitable for this protocol, and the products
were obtained in good to excellent yields. Various functional-
ities such as halogen, cyano, and alkynyl groups were tolerated
in this process to afford the corresponding products 3ea–3ja,
which could be employed for further transformations. More-
over, heteroaromatic alkynes such as 3-ethynylpyridine and
3-ethynylthiophene were also compatible with this reaction,
providing the corresponding products (3ka and 3la) in 75%
and 91% yields, respectively. Notably, internal alkynes such as
prop-1-ynylbenzene could also be used in the reaction to give
the expected vinyl sulfone 3ma in moderate yield. Meantime,
1-ethynylnaphthalene and 1-ethynylcyclohex-1-ene could be
used in the reactions to give the expected products (3na and
3oa) in 64% and 91% yields, respectively. Furthermore, the
scope of a variety of arylsulfinic acids was examined. In
addition to benzenesulfinic acid 2a, a series of substituted
arylsulfinic acids containing either electron-rich or electron-
deficient groups were all suitable substrates, and generated
the corresponding products in good yields (3ab–3ae). In
addition, the sterically hindered substituted arylsulfinic acids
such as 2-bromobenzenesulfinic acid and 2-(trifluoromethyl)-
benzenesulfinic acid were also tolerated in this reaction to
afford the products in good yields (3af and 3ag).
The feasibility of the gram-scale reaction was investigated
by using the model reaction between 1a and 2a. It was found
that this reaction could afford 2.1 g of 3aa in 86% yield
without any significant loss of its efficiency (eqn (2)). There-
fore, this procedure could serve as a practical and efficient
protocol to synthesize vinyl sulfones.
ð2Þ
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It is established that the oxidative addition of sulfinic acids acids has been developed under mild conditions. It may
to alkynes leading to β-keto sulfones proceeded via a radical possess some advantages of cheap catalysts, readily-available
process.18a When the reaction of 1a and 2a was performed in starting materials, operation simplicity, high atom economy
the copper catalytic system under air (dioxygen), in addition to and reaction selectivity, opening a new door to the construc-
the desired product 3aa, the β-keto sulfone 10aa was also tion of vinyl sulfones. Studies of the detailed mechanism of
obtained in 20% yield (eqn (3)). Therefore, a radical pathway this process and its application are ongoing.
was also supposed to be involved in this hydrosulfonylation
reaction.
This work was supported by the National Natural Science
Foundation of China (no. 21302109, 21302110, and 21375075),
the Taishan Scholar Foundation of Shandong Province, the
Excellent Middle-Aged and Young Scientist Award Foundation
of Shandong Province (BS2013YY019), and the Scientific
Research Foundation of Qufu Normal University (BSQD
2012020).
ð3Þ
Furthermore, when TEMPO (2,2,6,6-tetramethyl-1-piperidi-
nyloxy, a well known radical-capturing species) was added into
the present reaction system, this hydrosulfonylation process
was significantly inhibited (eqn (4)), indicating that this reac-
tion might involve a radical process.
Notes and references
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ð4Þ
Based on the above information and previous studies,17–19
we propose a postulated reaction pathway shown in Scheme 1.
Firstly, the reaction of sulfinic acid 2 with Cu(OAc)2 gave the
sulfinyl anion 4, which could be further oxidized by CuII via
the single electron transfer (SET) process to afford an oxygen-
centered radical 5 resonating with sulfonyl radical 6.18 Sub-
sequently, the selective addition of sulfonyl radical 6 to alkyne
1 would lead to the formation of reactive vinyl radical 7, which
interacted with CuI species to yield vinyl copper(II) complexes
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Scheme 1 Postulated reaction pathway.
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