Copper(I)-Catalyzed Alkyl- and Arylsulfenylation of 3,4-Dihalo-2(5H)-furanones (X=Br, Cl) with Sulfoxides under Mild Conditions

Article abstract of DOI:10.1002/adsc.201700600

An efficient copper(I)/proline sodium salt-catalyzed alkyl- and arylsulfenylation of C(sp²)–X 3,4-dihalo-2(5H)-furanone compounds with sulfoxides is described. For inexpensive C(sp²)–Cl compounds, there is also a satisfactory reactivity with the moderate yields. This transformation provides a novel approach for the utilization of sulfoxides (not only DMSO) as sulfur source at mild temperatures without the need for an anaerobic atmosphere. More importantly, both sulfoxide and proline sodium salt can play a dual role in this reaction. (Figure presented.).

Full text of DOI:10.1002/adsc.201700600

Title: Copper(I)-catalyzed alkyl- and arylsulfenylation of 3,4-
dihalo-2(5H)-furanones (X=Br, Cl) with sulfoxides under mild
conditions
Authors: Liang Cao, Shi-He Luo, Han-Qing Wu, Liu-Qing Chen, Kai
Jiang, Zhi-Feng Hao, and zhao-yang wang
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700600
Link to VoR: http://dx.doi.org/10.1002/adsc.201700600

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper(I)-catalyzed alkyl- and arylsulfenylation of 3,4-dihalo-
2(5H)-furanones (X=Br, Cl) with sulfoxides under mild
conditions
Liang Cao,a Shi-He Luo,*a Han-Qing Wu,a Liu-Qing Chen,a Kai Jiang,a Zhi-Feng Hao,b
and Zhao-Yang Wang*a
a
School of Chemistry and Environment, South China Normal University; Key Laboratory of Theoretical Chemistry of
Environment, Ministry of Education, Guangzhou 510006, People's Republic of China. E-mail: wangzy@scnu.edu.cn,
pinky_r@163.com; Fax: (+86)-020-3931-0187; Tel: (+86)-020-3931-0258.
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006,
b
People's Republic of China
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. An efficient copper(I)/proline sodium salt without the need for an anaerobic atmosphere. More
catalyzed alkyl- and arylsulfenylation of Csp2-X 3,4-dihalo- importantly, both sulfoxide and proline sodium salt can
2(5H)-furanone compounds with sulfoxides is described. For play a dual role in this reaction.
inexpensive Csp2-Cl compounds, there is also a satisfactory
reactivity with the moderate yields. This transformation
provides a novel approach for the utilization of sulfoxides
(not only DMSO) as sulfur source with mild temperature
Keywords: copper(I)-catalyzed; C-S bond formation; Csp2
X (X=Br, Cl) compounds; sulfoxides; 2(5H)-furanones
-
more important in the viewpoint of atomic economy.
However, the utilization of other sulfoxide
compounds as alkyl- or arylsulfenylation agents in C-
S bond formation has been less reported.[15]
Introduction
The formation of alkyl and aryl C-S bonds is
becoming one of the research hotspots because alkyl
and aryl sulfides are valuable building blocks for the
synthesis of biologically and pharmaceutically active
molecules and organic materials.[1,2] Traditionally,
transition-metal-catalyzed cross-coupling reactions of
thiols (thiophenols) with halides are important
methods for the synthesis of alkyl and aryl sulfides.[1,3]
Even for the direct alkyl- and arylsulfenylation via
the
transition-metal-catalyzed
selective
functionalization of C-H bonds recently developed,
thiols (thiophenols) as sulfur source are necessary for
C-S bond formation.[4] However, these agents have
obvious deficiencies, such as unpleasant odors, high
toxicity and harsh conditions, including high catalyst
loadings, specially designed ligands, high
temperatures due to the fact that they easily bring the
transition-metal catalysts deactivated. Thus, the
development of more practical, environmentally
friendly and atom-economical reagents for the
construction of C-S bonds remains a challenge.
Dimethyl sulfoxide (DMSO), being a cheap and
commercially available solvent, has been widely used
in organic synthesis as an important source of
different units, such as O,[5] CH,[6] CN,[7] CHO,[8]
CH2,[9] CH3,[10] SCH3,[11,12] SOCH3[13] and SO2CH3.[14]
Among them, using DMSO as a sulfenylating agent is
Scheme 1 An overview of previously reported alkyl- and
arylsulfenylation methods vs our approach
On the other hand, in the traditional transition-
metal-catalyzed cross-coupling reactions of Csp2-X
bonds with thiols (thiophenols) for the synthesis of
alkyl and aryl sulfides, the Csp2-X compounds are
usually bromides and iodides; readily available, low-
cost aryl chlorides are often not reactive enough.[1,16]
To our delight, Fu and co-workers[17] recently
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
developed a simple and efficient visible-light
photoredox arylation of thiols with aryl halides at
room temperature (Scheme 1a). More importantly,
aryl chlorides are also effective arylation reagents.
For the reaction of Csp2-X and sulfoxide, Cheng's
group reported Cu(I)-mediated methylthiolation of
aryl iodides and aryl bromides with DMSO using
ZnF2 at 150 oC (Scheme 1b).[18] However,
inexpensive chlorides are not effective and other
sulfoxides are not suitable, both making the
applicability of the substrates seriously affected.
aryl halides to explore their reactions with different
sulfoxides (Scheme 1). To our knowledge, the
method for the reaction of alkyl- and
arylsulfenylation by non-aromatic Csp2-X compounds
with sulfoxides has been not reported yet in the
previous researches. More importantly, molecules
possessing 2(5H)-furanone moiety, frequently found
in natural products, have been considered as potential
bactericides, anti-inflammatory agents, anticancer
agents and anti-HIV agents, which makes the
synthesis of 2(5H)-furanones with polyfunctional
groups more challenging and practical.[19]
Herein, we chose 3,4-dihalo-2(5H)-furanones as
non-aromatic Csp2-X (X=Br, Cl) substrates instead of
Table 1 Optimization of reaction conditions.[a]
Entry
Catalyst
Base (x mol%)
Temp. ( oC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
CuCl
CuBr
CuI
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
Proline sodium salt (20%)
NaOH (20%)
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
95
85
105
95
95
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
10
14
46
48
55
35
34
42
41
42
17
12
0
Cu2O
CuO
Cu(OAc)2
CuSO4·5H2O
Cu(OTf)2
CuCl2
CuBr2
-
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
0
< 5
8
K3PO4 (20%)
Na2CO3 (20%)
NaHCO3 (20%)
K2CO3 (20%)
9
< 5
61
69
77
73
82
25[c]
88[d]
87[e]
80
88
83
87
Proline sodium salt (40%)
Proline sodium salt (60%)
Proline sodium salt (80%)
Proline sodium salt (100%)
Proline sodium salt (80%)[b]
Proline sodium salt (80%)
Proline sodium salt (80%)
Proline sodium salt (80%)
Proline sodium salt (80%)
Proline sodium salt (80%)
Proline sodium salt (80%)
Proline sodium salt (80%)
CuI
CuI
CuI
CuI
CuI
[a] Reaction conditions: all reactions were performed with 1a (0.30 mmol), 2a (1.0 mL) as a substrate and solvent, catalyst
(10 mol%). Yield of isolated product 3a is given.
[b] Proline sodium salt (80 mol%) was added in batches.
[c] DMSO:H2O = 1:1.
[d] Using dried DMSO.
[e] Using dried DMSO under N2 atmosphere.
reactions simultaneously using solvent as a substrate
have been developed recently.[21,22] Being interested
Results and Discussion
in 2(5H)-furanone chemistry,[19,23] we surprisingly
discovered that sodium arylsulfinates can react with
solvent DMSO and 3,4-dibromo-5-methoxy-2(5H)-
For organic chemists, killing two birds with one stone
in organic synthesis is usually welcome,[20] and many
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
furanone (1a) to give arylsulfonyl dibromomethane
(Scheme 2b)[24] when investigating the effect of
solvents on the Pd-catalyzed desulfitative arylation of
1a with sodium arylsulfinates (Scheme 2a).[25] And
excitingly, the substitution of inexpensive Cu
catalysts for Pd salts in optimizing catalyst
fortunately gave an unexpected methylthiolation
(Scheme 2c). Namely, sodium arylsulfinates did not
work, and DMSO played a dual role also, but acting
as a solvent and alkylsulfenylating reagent in this
reaction.
furanone 1a as a lactone is easily hydrolyzed in the
environment of an alkaline aqueous solution,
resulting in a decrease of 3a yield. Thus, an improved
reaction was carried out with dry DMSO (entry 23).
It can be found that the yield is further increased to
88%. However, using dried DMSO under N2
atmosphere, the effect is not significant (entry 24).
Therefore, in the following experiments, the reaction
was still carried out in an air atmosphere, only
making the anhydrous treatment of DMSO. In
addition, we did not notice any significant changes
when altering the reaction temperature or time
(entries 25-28 vs. entry 23). In a word, we can
achieve the methylthiolation of 1a in DMSO under
the mild conditions, such as relatively lower
temperature, simple solvent treatment and air
atmosphere.
Under the optimized reaction conditions, we
further studied the scope of the reaction with respect
to 5-substituted 3,4-dibromo-2(5H)-furanones. The
results are summarized in Table 2. As expected, all
reactions proceeded smoothly with yields ranging
from good to excellent. Especially, they tolerated
various steric hindrance groups for 5-alkoxy. For
example, 88% of 3a (methoxy) was isolated while 3d
(tert-butoxy) was obtained in 74% yield (3a vs. 3d).
It is noteworthy that even for the larger menthoxy,
the product 3f was also successfully obtained and the
yield is as high as 71%. In short, the substituted
2(5H)-furanones with 5-alkoxy as an electron-
donating group can give the products in higher yields.
On the contrary, those 3,4-dibromo-2(5H)-furanones
possessing electron-withdrawing analogues, e.g.
aryloxy (3h and 3i), are slightly disadvantageous to
the reaction, and their yields are obviously lower than
that of the substituted 2(5H)-furanone with 5-
benzyloxy (3g).
Scheme 2 Reactions of 1a with sodium arylsulfinates in
different conditions
Once the product 3a was confirmed by single-
crystal X-ray diffraction analysis (Scheme 2c),[26] the
reaction parameters, such as catalyst, base,
temperature and time, were first examined using 3,4-
dibromo-5-methoxy-2(5H)-furanone (1a) and DMSO
(2a) as substrates. The obtained results are listed in
Table 1.
Under the same conditions, the catalytic activity of
Cu(I) compounds is much higher than that of Cu(II)
compounds (Table 1, entries 1-10). Among the
examined catalysts, CuI is the best and the isolated
yield of target compound 3a is 55% (entry 3). With
CuI as the catalyst, some bases were further screened.
Obviously, proline sodium salt as the base is greatly
better than others (entry 3 vs. entries 12-16).
However, even using proline sodium salt as the base,
the reaction in the absence of the catalyst CuI did not
give any target product 3a (entry 11). These results
clearly indicate that both CuI and proline sodium salt
are necessary for this transformation, and proline
sodium salt may not only simply act as a base but
also a ligand for CuI. Then we also examined the
effect of the amount of proline sodium salt on the
reaction (entries 17-20). When proline sodium salt is
80 mol%, the yield is as high as 77%. In addition, it
has been found that the addition of proline sodium
salt in batches is better (entry 21).
Table 2 Substrate scope of various 5-substituted 3,4-
dibromo-2(5H)-furanones[a]
[a] Reaction conditions: all reactions were performed with 1
(0.30 mmol), 2a (1.0 mL) as a substrate and solvent, CuI
(10 mol%), proline sodium salt (80 mol%), under air
atmosphere at 95 oC for 12 h. Yields of isolated products
are given.
Hoping to make the reaction more suitable and
green, we tried to react it in the DMSO/H2O system
(v/v = 1/1), but the yield dropped significantly to
25% (Table 1, entry 22), indicating that the content
of water in solvent DMSO largely impacts the
reaction. This may be due to the fact that 2(5H)-
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
Even when 3,4-dibromo-2(5H)-furanone 1j was
of the corresponding 5-substituted 3,4-dihalo-2(5H)-
furanone substrates. Even so, the arylsulfenylation
reaction still has moderate yields. These phenomena
may be related to the reaction mechanism, which will
be discussed in the following.
used as the substrate, the effects of 5-substituted
groups are similar with the above mentioned.
However, the structure of compound 3j characterized
by single-crystal X-ray diffraction analysis is not
wholly the same as anticipated (Scheme 3).[26]
Perhaps there is an oxidation caused by the solvent
DMSO22 or oxygen in the air, a compound 3j with a
5-hydroxy structure is obtained with the yield of 63%.
Even so, the result further indicates that the
methylthiolation reaction of DMSO 2a occurs to the
C-4 position halogen of 2(5H)-furanone indeed,
which is confirmed by the X-ray diffraction of
compound 3a firstly.[26]
Table 3 Substrate scope of various 5-substituted 3,4-
dichloro-2(5H)-furanones[a]
Scheme 3 Reaction of 1j with DMSO in standard
conditions
[a] Reaction conditions: all reactions were performed with 1
(0.30 mmol), 2a (1.0 mL) as a substrate and solvent, CuI
(10 mol%), proline sodium salt (80 mol%), under air
atmosphere at 105 oC for 12 h. Yields of isolated
products are given.
To further improve the practicability of this
protocol, we also evaluated 3,4-dichloro-2(5H)-
furanones using our procedure. Satisfyingly, 5-
substituted 3,4-dichloro-2(5H)-furanones were also
able to react with 2a at 105 oC, affording the
corresponding methyl sulfide in moderate to good
yields (Table 3). Of course, for the alkylsulfenylation
of 5-substituted 3,4-dihalo-2(5H)-furanones with
DMSO, the yields of compounds 4 (X = Cl) is lower
than those of compounds 3 (X = Br). Not only the
structures of compounds 4a-4h are well characterized
by 1H and 13C NMR, MS (their spectra can be seen in
SI), and elementary analysis, but also the structure of
compound 4f is confirmed using single-crystal X-ray
diffraction analysis.[26] Thus, unlike other copper-
catalyzed methodologies for the synthesis of
methylthiolation from Csp2-X (X = I, Br) compounds
and DMSO,[1,16,18] the present method can well
achieve the conversion of Csp2-Cl compounds.
Table 4 Substrate scope of various sulfoxides[a]
Sulfoxide
Product
The utilization of sulfoxide compounds in organic
synthesis is attracting the attention of chemists.[27] It
can be delightedly found that, not only DMSO, the
methodology developed herein also can be extended
to other sulfoxides (Table 4). For the substrates
dibutyl sulfoxide 2b and dibenzyl sulfoxide 2c, there
is an alkylsulfenylation reaction resulting in the
formation of compounds 5a-5j in 36-83% yields. In
general, other sulfoxides give the lower yields than
DMSO, which may be in touch with the reaction
mechanism. It is a pity that the substrate diphenyl
sulfoxide cannot go through the arylsulfenylation to
generate the corresponding product via this similar
transformation. However, using unsymmetrical
methyl phenyl sulfoxide 2d as the substrate, the
arylsulfenylation products 5k and 5l can be
successfully obtained. It may be due to the greater
steric hindrance of the phenylthio group, and their
yields are lower than those of the alkylsulfenylation
[a] Reaction conditions: all reactions were performed with 1
(0.30 mmol), 2 (1.0 mL, for 2b: 5.1 mmol; 2c: 5.2 mmol;
2d: 8.5 mmol) as a substrate and solvent, CuI (10 mol%),
proline sodium salt (80 mol%), under air atmosphere at
120 oC for 12 h. Yields of isolated products are given.
[b]
For dibenzyl sulfoxide 2c (m.p. 130-132 ºC), the
reaction temperature is 135 °C.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
To gain insight into the reaction mechanism,
DMSO 2a as an example is proposed in Scheme 5.
First, CuI and proline sodium salt may form a
complex A.[29] Then, the oxidative addition of A with
5-substituted 3,4-dihalo-2(5H)-furanones 1 gives
intermediate B. Subsequently, in the presence of
proline sodium salt as a base, intermediate C is
formed by the exchange of intermediate B with
methanethiol from the decomposition of DMSO
under the heat.[12,28] In the end, the desired product 3
several mechanistic experiments were carried out.
Firstly, the radical scavenger 2,2,6,6-tetramethyl-
piperidinooxy (TEMPO) was employed for this
transformation. The yield of 3a is not obviously
changed (eq. 1). This result suggests that this reaction
does not follow the radical pathway. Subsequently, a
deuterium labelling experiment with d6-DMSO was
operated to explore the potential role of DMSO in the
methylthiolation process (eq. 2). The deuterated
is produced by
a
reductive elimination of
1
product 3a (its spectra of H NMR and MS can be
intermediate C, and the CuI complex A is regenerated.
seen in SI, Figs. S4 and S5) is generated from d6-
DMSO as desired, indicating that DMSO acts as a
methylthiolation source indeed.
In order to further explain the mechanism, some
control experiments were implemented (Scheme 4).
According to the previous reports,[12,28] DMSO may
go through thermal decomposition to generate
dimethyl disulfide, methanethiol and formaldehyde.
Perhaps one of these sulfur-containing organic
compounds is an intermediate in this newly-
developed transformation. Thus, investigating the
reaction with dimethyl disulfide or diphenyl disulfide
instead of DMSO, but no related products can be
detected (Scheme 4a and 4b). Fortunately, when
using benzyl mercaptan as a substitute for DMSO, the
product 5d can be isolated in the yield of 65%
(Scheme 4c). Only using dibenzyl sulfoxide 2c as the
reactant under the standard conditions (Scheme 4d),
the existence of benzyl mercaptan and benzaldehyde
can be detected by GC-MS (see their MS spectra in
SI, Figs. S6 and S7). These results indicate that thiol
compounds (e.g. benzyl mercaptan) should be the
reaction of intermediates.
Scheme 5 Plausible reaction mechanism
For other symmetrical sulfoxide substrates (e.g. 2b
and 2c), the corresponding thiol compounds (e.g.
butanethiol and benzyl mercaptan) are involved in
this mechanism. However, diphenyl sulfoxide cannot
yield thiophenol as the heat decomposition way of
DMSO,[12,28] thus its arylsulfenylation failed. When
the unsymmetrical methyl phenyl sulfoxide 2d is
used as the substrate, thiophenol can be formed
according to the literature.[12,28] Therefore, there is a
arylsulfenylation but not methylthiolation reaction
(Scheme 6). If the mixture of two different sulfoxides
(DMSO 2a: dibenzyl sulfoxide 2c = 1:1, molar ratio)
reacted with 1a under standard conditions, only the
product 3a was obtained in 82% yield. This indicates
that methanethiol is more readily available under the
same condition, which is consistent with the above-
mentioned experimental results. In other words, these
results also demonstrate the above reaction
mechanism from another side.
Scheme 4 Control experiments
Scheme 6 Arylsulfenylation of methyl phenyl sulfoxide
2d under standard conditions
Based on the above experimental results and
previous reports,[12,28,29] a plausible mechanism using
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
Conclusion
3-Bromo-5-(tert-butoxy)-4-(methylthio)furan-2(5H)-
one (3d): Yellow liquid (62 mg, 74%); H NMR (400
1
In summary, we have developed a general and
MHz, CDCl3), δ: 1.39 (s, 9H, 3CH3), 2.61 (s, 3H, SCH3),
6.06 (s, 1H, CH); 13C NMR (100 MHz, CDCl3), δ: 13.6,
28.6, 79.2, 97.7, 105.8, 160.5, 165.5; MS (EI, 70 eV), m/z:
282, 280 (M+), 224, 207, 179, 153, 99, 84; Anal. Calcd for
C9H13BrO3S: C 38.45, H 4.66, Found: C 38.53, H 4.59.
3-Bromo-5-(cyclohexyloxy)-4-(methylthio)furan-
efficient
copper(I)-catalyzed
alkyl-
and
arylsulfenylation of Csp2-X (X=Br, Cl) compounds
(not only 3,4-dihalo-2(5H)-furanones[30]) with various
sulfoxides without the need for an anaerobic
atmosphere for the first time. The protocol shows
excellent reaction site selectivity, which can realize
sulfenylation of 3,4-dihalo-2(5H)-furanones at the C-
4 position, as well as good functional group tolerance
especially for ester and ether (acetal). Thus, the low
cost of the reagents and wide range of substrates
make this method a powerful route for the synthesis
of 2(5H)-furanone derivatives. Importantly, the
method uses readily available Csp2-X compounds,
including low-reactive Csp2-Cl compounds often
believed before. The present discovery will be helpful
for the development of novel reactions of Csp2-X
compounds (especially chlorides) with various
sulfoxides (not only DMSO) under mild conditions
by the synthetic strategy of killing two birds with one
stone.
1
2(5H)-one (3e): Yellow liquid (72 mg, 78%); H NMR
(400 MHz, CDCl3), δ: 1.21-1.51 (m, 6H, 3CH2), 1.73-2.01
(m, 4H, 2CH2), 2.58 (s, 3H, SCH3), 3.76-3.86 (m, 1H,
OCH), 5.99 (s, 1H, CH); 13C NMR (100 MHz, CDCl3), δ:
13.2, 23.9, 24.0, 25.2, 32.1, 33.2, 79.3, 100.4, 105.4, 160.6,
165.3; MS (EI, 70 eV), m/z: 308, 306 (M+), 207, 178, 163,
151, 99, 83; Anal. Calcd for C11H15BrO3S: C 43.01, H 4.92,
Found: C 43.09, H 4.87.
3-Bromo-5-(L-menthoxy)-4-(methylthio)furan-
2(5H)-one (3f): Yellow solid (78 mg, 71%); m.p. 107.3-
º
1
109.0 C; H NMR (400 MHz, CDCl3), δ: 0.80 (d, J = 8.0
Hz, 3H, CH3), 0.90-0.95 (m, 7H, CH, 2CH3), 1.05-1.15 (m,
2H, CH2), 1.33-1.40 (m, 2H, 2CH), 1.65-1.70 (m, 2H,
CH2), 2.21-2.28 (m, 2H, CH2), 2.66 (s, 3H, SCH3), 3.54-
3.62 (ddd, J1 = 4.0 Hz, J2 = 4.0 Hz, J3 = 4.0 Hz, 1H, OCH),
5.86 (s, 1H, CH); 13C NMR (100 MHz, CDCl3), δ: 13.7,
15.9, 21.1, 22.1, 22.8, 25.1, 31.7, 33.9, 42.2, 48.1, 71.5,
102.4, 106.4, 159.9, 165.5; MS (EI, 70 eV), m/z: 364, 362
(M+), 315, 207, 179, 138, 99, 81; Anal. Calcd for
C15H23BrO3S: C 49.59, H 6.38, Found: C 49.52, H 6.45.
5-(Benzyloxy)-3-bromo-4-(methylthio)furan-2(5H)-
one (3g): Yellow liquid (71 mg, 75%); 1H NMR (400 MHz,
CDCl3), δ: 2.49 (s, 3H, SCH3), 4.70-4.87 (dd, J1 = 12.0 Hz,
J2 = 12.0 Hz, 2H, OCH2), 5.97 (s, 1H, CH); 7.34-7.42 (m,
5H, ArH); 13C NMR (100 MHz, CDCl3), δ: 13.2, 70.5,
99.9, 105.5, 128.8, 128.9, 134.9, 160.4, 165.0; MS (EI, 70
eV), m/z: 316, 314 (M+), 208, 178, 151, 129, 107, 91; Anal.
Calcd for C12H11BrO3S: C 45.73, H 3.52, Found: C 45.82,
H 3.47.
Experimental Section
General Procedure for Compounds 3a-5l
The mixture of 1 (0.30 mmol), CuI (10 mol %), and
proline sodium salt (80%, adding in batches) in sulfoxide
(1 mL) was stirred at T °C (oil bath temperature, designed
as request, usually 95 °C) under air for 12 h. At ambient
temperature, the reaction mixture was diluted with H2O (15
mL) and extracted with EtOAc (3 × 15 mL). The organic
extracts were dried over anhydrous Na2SO4. After filtration
and evaporation of the solvents under reduced pressure, the
crude product was purified by column chromatography on
silica gel to afford desired product.
3-Bromo-4-(methylthio)-5-phenoxyfuran-2(5H)-one
1
3-Bromo-5-methoxy-4-(methylthio)furan-2(5H)-one
(3h): Yellow liquid (54 mg, 59%); H NMR (400 MHz,
º
1
(3a): Yellow solid (63 mg, 88%); m.p. 86.7-87.8 C; H
NMR (400 MHz, CDCl3), δ: 2.58 (s, 3H, SCH3), 3.52 (s,
3H, OCH3), 5.89 (s, 1H, CH); 13C NMR (100 MHz,
CDCl3), δ: 13.2, 54.8, 101.8, 105.5, 160.0, 164.9; MS (EI,
70 eV), m/z: 240, 238 (M+), 207, 178, 163, 151, 99, 84;
Anal. Calcd for C6H7BrO3S: C 30.14, H 2.95, Found: C
30.19, H 2.86.
CDCl3), δ: 2.60 (s, 3H, SCH3), 6.36 (s, 1H, CH), 7.13-7.19
(m, 3H, ArH), 7.34-7.40 (m, 2H, ArH); 13C NMR (100
MHz, CDCl3), δ: 13.5, 99.4, 116.8, 117.2, 124.3, 130.0,
155.4, 160.0, 164.7; MS (EI, 70 eV), m/z: 302, 300 (M+),
209, 179, 163, 151, 136, 99; Anal. Calcd for C11H9BrO3S:
C 43.87, H 3.01, Found: C 43.97, H 3.07.
5-([1,1'-Biphenyl]-4-yloxy)-3-bromo-4-(methylthio)
1
3-Bromo-5-ethoxy-4-(methylthio)furan-2(5H)-one
furan-2(5H)-one (3i): Yellow liquid (44 mg, 39%); H
1
(3b): Yellow liquid (63 mg, 83%); H NMR (400 MHz,
NMR (400 MHz, CDCl3), δ: 2.63 (s, 3H, SCH3), 6.39 (s,
1H, CH), 7.23 (d, J = 8.0 Hz, 2H, ArH), 7.35 (t, J = 8.0 Hz,
1H, ArH), 7.42-7.48 (m, 2H, ArH), 7.55 (d, J = 8.0 Hz, 2H,
ArH), 7.59 (d, J = 8.0 Hz, 2H, ArH); 13C NMR (100 MHz,
CDCl3), δ: 13.6, 99.4, 105.8, 117.2, 126.9, 127.3, 128.7,
CDCl3), δ: 1.30 (t, J = 8.0 Hz, 3H, CH3), 2.59 (s, 3H,
SCH3), 3.70-3.91 (m, 2H, OCH2), 5.93 (s, 1H, CH); 13C
NMR (100 MHz, CDCl3), δ: 13.2, 15.0, 64.6, 101.3, 105.3,
160.3, 165.0; MS (EI, 70 eV), m/z: 254, 252 (M+), 207,
178, 163, 151, 99, 84; Anal. Calcd for C7H9BrO3S: C 33.22, 128.9, 137.5, 140.0, 154.9, 159.9, 164.6; MS (EI, 70 eV),
H 3.58, Found: C 33.15, H 3.52.
m/z: 378, 376 (M+), 207, 179, 169, 151, 141, 115; Anal.
3-Bromo-5-isopropoxy-4-(methylthio)furan-2(5H)-
Calcd for C17H13BrO3S: C 54.12, H 3.47, Found: C 54.19,
one (3c): Yellow liquid (63 mg, 79%); 1H NMR (400 MHz, H 3.38.
CDCl3), δ: 1.28-1.33 (m, 6H, 2CH3), 2.58 (s, 3H, SCH3),
3-Bromo-5-hydroxy-4-(methylthio)furan-2(5H)-one
4.08-4.20 (m, 1H, OCH), 5.95 (s, 1H, CH); 13C NMR (100
(3j): Yellow liquid (42 mg, 63%); m.p. 137.6-138.0 ºC; 1H
MHz, CDCl3), δ: 13.2, 22.0, 23.2, 73.7, 100.5, 105.5, 160.4, NMR (400 MHz, d6-DMSO), δ: 2.60 (s, 3H, SCH3), 6.38 (s,
165.2; MS (EI, 70 eV), m/z: 268, 266 (M+), 207, 178, 163,
151, 99, 84; Anal. Calcd for C8H11BrO3S: C 35.97, H 4.15,
Found: C 35.88, H 4.19.
1H, CH), 8.39 (s, 1H, OH); 13C NMR (100 MHz, d6-
DMSO), δ: 13.2, 98.3, 103.0, 164.8, 165.5; MS (EI, 70 eV),
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
m/z: 182, 180 ([M-CO2]+), 151, 136, 101, 84; Anal. Calcd
for C5H5BrO3S: C 26.68, H 2.24, Found: C 26.61, H 2.32.
3-Chloro-5-methoxy-4-(methylthio)furan-2(5H)-one
Calcd for C12H11ClO3S: C 53.24, H 4.10, Found: C 53.18,
H 4.20.
3-Chloro-4-(methylthio)-5-phenoxyfuran-2(5H)-one
1
1
(4a): Yellow liquid (35 mg, 60%); H NMR (400 MHz,
(4h): Yellow liquid (35 mg, 46%); H NMR (400 MHz,
CDCl3), δ: 2.61 (s, 3H, SCH3), 3.54 (s, 3H, OCH3), 5.88 (s,
1H, CH); 13C NMR (100 MHz, CDCl3), δ: 13.1, 55.0,
100.8, 117.1, 155.4, 164.4; MS (EI, 70 eV), m/z: 196, 194
(M+), 163, 134, 119, 106, 91, 84; Anal. Calcd for
C6H7ClO3S: C 37.03, H 3.63, Found: C 37.10, H 3.59.
3-Chloro-5-ethoxy-4-(methylthio)furan-2(5H)-one
CDCl3), δ: 2.62 (s, 3H, SCH3), 6.35 (s, 1H, CH), 7.13-7.20
(m, 3H, ArH), 7.34-7.40 (m, 2H, ArH); 13C NMR (100
MHz, CDCl3), δ: 13.4, 98.4, 116.9, 124.4, 130.0, 155.4,
155.5, 164.1; MS (EI, 70 eV), m/z: 258, 256 (M+), 163,
135, 119, 107, 92; Anal. Calcd for C11H9ClO3S: C 51.47, H
3.53, Found: C 51.52, H 3.48.
1
(4b): Yellow liquid (36 mg, 58%); H NMR (400 MHz,
3-Bromo-4-(butylthio)-5-methoxyfuran-2(5H)-one
1
CDCl3), δ: 1.30 (t, J = 8.0 Hz, 3H, CH3), 2.61 (s, 3H,
SCH3), 3.71-3.93 (m, 2H, OCH2), 5.92 (s, 1H, CH); 13C
NMR (100 MHz, CDCl3), δ: 13.1, 14.9, 64.8, 100.2, 116.9,
155.7, 164.6; MS (EI, 70 eV), m/z: 210, 208 (M+), 163,
134, 119, 106, 91; Anal. Calcd for C7H9ClO3S: C 40.29, H
4.35, Found: C 40.35, H 4.29.
(5a): Yellow liquid (68 mg, 81%); H NMR (400 MHz,
CDCl3), δ: 0.95 (t, J = 8.0 Hz, 3H, CH3), 1.41-1.51 (m, 2H,
CH2), 1.64-1.72 (m, 2H, CH2), 3.12 (t, J = 8.0 Hz, 2H,
SCH2), 3.51 (s, 3H, OCH3), 5.88 (s, 1H, CH); 13C NMR
(100 MHz, CDCl3), δ: 13.5, 21.7, 30.1, 31.6, 54.8, 102.0,
105.6, 160.0, 165.0; MS (EI, 70 eV), m/z: 282, 280 (M+),
163, 141, 113, 85, 57; Anal. Calcd for C9H13BrO3S: C
3-Chloro-5-isopropoxy-4-(methylthio)furan-2(5H)-
one (4c): Yellow liquid (37 mg, 55%); 1H NMR (400 MHz, 38.45, H 4.66, Found: C 38.52, H 4.58.
CDCl3), δ: 1.28-1.33 (m, 6H, 2CH3), 2.60 (s, 3H, SCH3),
4.09-4.19 (m, 1H, OCH), 5.94 (s, 1H, CH); 13C NMR (100
MHz, CDCl3), δ: 13.1, 22.0, 23.2, 73.8, 99.4, 117.0, 155.8,
164.8; MS (EI, 70 eV), m/z: 224, 222 (M+), 163, 134, 119,
106, 92; Anal. Calcd for C8H11ClO3S: C 43.15, H 4.98,
Found: C 43.20, H 4.87.
3-Bromo-4-(butylthio)-5-isopropoxyfuran-2(5H)-one
(5b): Yellow liquid (77 mg, 83%); H NMR (400 MHz,
1
CDCl3), δ: 0.94 (t, J = 8.0 Hz, 3H, CH3), 1.29 (t, J = 8.0 Hz,
6H, CH3), 1.41-1.50 (m, 2H, CH2), 1.63-1.70 (m, 2H, CH2),
3.05-3.20 (m, 2H, SCH2), 4.08-4.18 (m, 1H, CH), 5.93 (s,
1H, CH); 13C NMR (100 MHz, CDCl3), δ: 13.5, 21.7, 22.0,
23.2, 30.0, 31.6, 73.6, 100.6, 105.7, 160.3, 165.3; MS (EI,
70 eV), m/z: 310, 308 (M+), 250, 163, 141, 113, 85, 57;
Anal. Calcd for C11H17BrO3S: C 42.73, H 5.54, Found: C
42.81, H 5.42.
5-(tert-Butoxy)-3-chloro-4-(methylthio)furan-2(5H)-
1
one (4d): Yellow liquid (35 mg, 49%); H NMR (400
MHz, CDCl3), δ: 1.36 (s, 9H, 3CH3), 2.61 (s, 3H, SCH3),
5.95 (s, 1H, CH); 13C NMR (100 MHz, CDCl3), δ: 13.1,
28.3, 64.8, 100.2, 116.9, 155.6, 164.6; MS (EI, 70 eV), MS
(EI, 70 eV), m/z: 210, 208, 163, 134, 119, 106, 91; Anal.
Calcd for C9H13ClO3S: C 45.67, H 5.54, Found: C 45.72, H
5.49.
3-Bromo-4-(butylthio)-5-phenoxyfuran-2(5H)-one
1
(5c): Yellow liquid (59 mg, 57%); H NMR (400 MHz,
CDCl3), δ: 0.91 (t, J = 8.0 Hz, 3H, CH3), 1.39-1.48 (m, 2H,
CH2), 1.65-1.74 (m, 2H, CH2), 3.05-3.21 (m, 2H, SCH2),
6.34 (s, 1H, CH), 7.13-7.19 (m, 3H, ArH), 7.34-7.40 (m,
2H, ArH); 13C NMR (100 MHz, CDCl3), δ: 13.4, 21.6,
30.4, 31.5, 99.6, 106.0, 116.8, 124.3, 130.0, 155.5, 159.8,
164.7; MS (EI, 70 eV), m/z: 344, 342 (M+), 249, 195, 165,
94, 77; Anal. Calcd for C14H15BrO3S: C 48.99, H 4.41,
Found: C 48.91, H 4.50.
3-Chloro-5-(cyclohexyloxy)-4-(methylthio)furan-
1
2(5H)-one (4e): Yellow liquid (40 mg, 51%); H NMR
(400 MHz, CDCl3), δ: 1.23-1.45 (m, 6H, 3CH2), 1.73-2.01
(m, 4H, 2CH2), 2.60 (s, 3H, SCH3), 3.78-3.85 (m, 1H,
OCH), 5.98 (s, 1H, CH); 13C NMR (100 MHz, CDCl3), δ:
13.1, 23.8, 23.9, 25.2, 32.0, 33.2, 79.3, 99.4, 116.9, 156.0,
164.8; MS (EI, 70 eV), m/z: 264, 262 (M+), 180, 163, 134,
119, 106, 92; Anal. Calcd for C11H15ClO3S: C 50.28, H
5.75, Found: C 50.35, H 5.69.
4-(Benzylthio)-3-bromo-5-methoxyfuran-2(5H)-one
1
(5d): Yellow liquid (66 mg, 70%); H NMR (400 MHz,
CDCl3), δ: 3.52 (s, 3H, OCH3), 4.29-4.42 (m, 2H, SCH2),
5.73 (s, 1H, CH), 7.34-7.42 (m, 5H, ArH); 13C NMR (100
MHz, CDCl3), δ: 34.8, 55.0, 101.8, 105.9, 128.3, 128.7,
129.1, 134.9, 159.3, 164.7; MS (EI, 70 eV), m/z: 316, 314
(M+), 282, 203, 163, 91, 65; Anal. Calcd for C12H11BrO3S:
C 45.73, H 3.52, Found: C 45.80, H 3.43.
4-(Benzylthio)-3-bromo-5-isopropoxyfuran-2(5H)-
one (5e): Yellow liquid (66 mg, 64%); 1H NMR (400 MHz,
CDCl3), δ: 1.30-1.35 (m, 6H, 2CH3), 4.09-4.17 (m, 1H,
OCH), 4.33-4.45 (m, 2H, SCH2), 5.90 (s, 1H, CH), 7.33-
7.42 (m, 5H, ArH); 13C NMR (100 MHz, CDCl3), δ: 22.2,
23.3, 34.7, 73.7, 100.7, 106.2, 128.3, 128.8, 129.1, 134.7,
159.7, 165.1; MS (EI, 70 eV), m/z: 344, 342 (M+), 282,
203, 163, 91, 65; Anal. Calcd for C14H15BrO3S: C 48.99, H
3-Chloro-5-(L-menthoxy)-4-(methylthio)furan-
2(5H)-one (4f): Yellow solid (54 mg, 57%); m.p. 91.6-
º
1
92.9 C; H NMR (400 MHz, CDCl3), δ: 0.81 (d, J = 8.0
Hz, 3H, CH3), 0.88-0.97 (m, 7H, CH, 2CH3), 0.99-1.18 (m,
2H, CH2), 1.31-1.44 (m, 2H, 2CH), 1.63-1.70 (m, 2H,
CH2), 2.19-2.28 (m, 2H, CH2), 2.60 (s, 3H, SCH3), 3.53-
3.61 (ddd, J1 = 4.0 Hz, J2 = 4.0 Hz, J3 = 4.0 Hz, 1H, OCH),
5.80 (s, 1H, CH); 13C NMR (100 MHz, CDCl3), δ: 13.7,
15.9, 20.8, 22.0, 23.0, 25.3, 31.6, 33.9, 42.1, 48.0, 84.5,
102.2, 124.0, 155.6, 164.1; MS (EI, 70 eV) m/z: 320, 318
(M+), 271, 207, 163, 138, 107, 95; Anal. Calcd for
C15H23ClO3S: C 56.50, H 7.27, Found: C 56.45, H 7.32.
5-(Benzyloxy)-3-chloro-4-(methylthio)furan-2(5H)-
one (4g): Yellow liquid (42 mg, 52%); 1H NMR (400 MHz, 4.41, Found: C 48.92, H 4.48.
CDCl3), δ: 2.51 (s, 3H, SCH3), 4.69-4.90 (dd, J1 = 12.0 Hz,
J2 = 12.0 Hz, 2H, OCH2), 5.95 (s, 1H, CH), 7.35-7.40 (m,
5H, ArH); 13C NMR (100 MHz, CDCl3), δ: 13.2, 70.6,
98.9, 117.0, 128.8, 128.9, 134.9, 155.9, 164.5; MS (EI, 70
eV), m/z: 272, 270 (M+), 207, 164, 134, 106, 91; Anal.
4-(Butylthio)-3-chloro-5-methoxyfuran-2(5H)-one
(5f): Yellow liquid (36 mg, 51%); H NMR (400 MHz,
CDCl3), δ: 0.95 (t, J = 4.0 Hz, 3H, CH3), 1.45-1.51 (m, 2H,
CH2), 1.65-1.72 (m, 2H, CH2), 3.14 (t, J = 8.0 Hz, 2H,
SCH2), 3.53 (s, 3H, OCH3), 5.85 (s, 1H, CH); 13C NMR
(100 MHz, CDCl3), δ: 13.5, 21.6, 30.0, 31.8, 55.0, 101.0,
1
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
117.1, 155.3, 164.5; MS (EI, 70 eV), m/z: 238, 236 (M+),
204, 148, 133, 119, 103, 91, 57; Anal. Calcd for
C9H13ClO3S: C 45.67, H 5.54, Found: C 45.73, H 4.45.
4-(Butylthio)-3-chloro-5-isopropoxyfuran-2(5H)-one
Science and Technology Project (No. 2017A010103016), the
Guangzhou Science and Technology Project Scientific Special
(General Items, No. 201607010251) and Applied Science and
Technology Research and Development Special Foundation of
Guangdong Province (No. 2016B090930004) is greatly
appreciated.
1
(5g): Yellow liquid (36 mg, 46%); H NMR (400 MHz,
CDCl3), δ: 0.95 (t, J = 8.0 Hz, 3H, CH3), 1.30 (t, J = 8.0 Hz,
6H, 2CH3), 1.42-1.51 (m, 2H, CH2), 1.64-1.72 (m, 2H,
CH2), 3.07-3.23 (m, 2H, SCH2), 4.08-4.18 (m, 1H, OCH),
5.92 (s, 1H, CH); 13C NMR (100 MHz, CDCl3), δ: 13.5,
21.7, 22.0, 23.2, 29.9, 31.8, 73.7, 99.7, 117.2, 155.6, 164.9;
MS (EI, 70 eV), m/z: 266, 264 (M+), 204, 148, 133, 113, 92,
57; Anal. Calcd for C11H17ClO3S: C 49.90, H 6.47, Found:
C 49.98, H 6.41.
References
[1] A. N. Desnoyer, J. A. Love, Chem. Soc. Rev., 2017, 46,
197-238.
[2] a) F.-G. Sun, M. Li, C.-F. He, B. Wang, B. Li, X.-W.
Sui, Z.-H. Gu, J. Am. Chem. Soc., 2016, 138, 7456-
7459; b) L. Yao, Q. Zhu, L. Wei, Z.-F. Wang, C.-J.
Wang, Angew. Chem. Int. Ed., 2016, 55, 5829-5833; c)
T. Tamai, K. Fujiwara, S. Higashimae, A. Nomoto, A.
Ogawa, Org. Lett., 2016, 18, 2114-2117; d) R. M. P.
Dias, A. C. B. Burtoloso, Org. Lett., 2016, 18, 3034-
3037; e) S.-F. Li, Z.-W. Lu, L. Meng, J. Wang, Org.
Lett., 2016, 18, 5276-5279; f) F.-H. Xiao, S.-Q. Chen,
C. Li, H.-W. Huang, G.-J. Deng, Adv. Synth. Catal.,
2016, 358, 3881-3886; g) J.-X. Li, C.-S. Li, S.-R. Yang,
Y.-N. An, W.-Q. Wu, H.-F. Jiang, J. Org. Chem., 2016,
81, 2875-2887; h) J.-X. Li, C.-S. Li, S.-R. Yang, Y.-N.
An, W.-Q. Wu, H.-F. Jiang, J. Org. Chem., 2016, 81,
7771-7783; i) S. Song, Y.-Q. Zhang, A. Yeerlan, B.-C.
Zhu, J.-Z. Liu, N. Jiao, Angew. Chem. Int. Ed., 2017,
56, 2487-2491; j) P. Wang, S. Tang, P.-F. Huang, A.-W.
Lei, Angew. Chem. Int. Ed., 2017, 56, 3009-3013.
4-(Butylthio)-3-chloro-5-phenoxyfuran-2(5H)-one
1
(5h): Yellow liquid (33 mg, 36%); H NMR (400 MHz,
CDCl3), δ: 0.92 (t, J = 8.0 Hz, 3H, CH3), 1.40-1.48 (m, 2H,
CH2), 1.65-1.74 (m, 2H, CH2), 3.08-3.24 (m, 2H, SCH2),
6.33 (s, 1H, CH), 7.12-7.19 (m, 3H, ArH), 7.34-7.40 (m,
2H, ArH); 13C NMR (100 MHz, CDCl3), δ: 13.4, 21.6,
30.3, 31.7, 98.7, 116.9, 124.3, 130.0, 155.2, 155.6, 164.2;
MS (EI, 70 eV), m/z: 300, 298 (M+), 205, 149, 121, 57;
Anal. Calcd for C14H15ClO3S: C 56.28, H 5.06, Found: C
56.17, H 5.14.
4-(Benzylthio)-3-chloro-5-methoxyfuran-2(5H)-one
1
(5i): Yellow liquid (42 mg, 52%); H NMR (400 MHz,
CDCl3), δ: 3.52 (s, 3H, OCH3), 4.30-4.43 (m, 2H, SCH2),
5.72 (s, 1H, CH), 7.34-7.42 (m, 5H, ArH); 13C NMR (100
MHz, CDCl3), δ: 34.7, 55.1, 100.8, 117.5, 128.3, 128.7,
129.1, 135.0, 154.7, 164.2; MS (EI, 70 eV), m/z: 272, 270
(M+), 238, 119, 103, 91, 65; Anal. Calcd for C12H11ClO3S:
C 53.24, H 4.10, Found: C 53.18, H 4.16.
4-(Benzylthio)-3-chloro-5-isopropoxyfuran-2(5H)-
one (5j): Yellow liquid (42 mg, 47%); 1H NMR (400 MHz,
CDCl3), δ: 1.29-1.35 (m, 6H, 2CH3), 4.08-4.16 (m, 1H,
OCH), 4.34-4.46 (m, 2H, SCH2), 5.87 (s, 1H, CH), 7.30-
7.41 (m, 5H, ArH); 13C NMR (100 MHz, CDCl3), δ: 22.2,
23.2, 34.6, 73.9, 99.7, 117.8, 128.3, 128.8, 129.1, 134.8,
155.0, 164.7; MS (EI, 70 eV), m/z: 300, 298 (M+), 238,
203, 119, 91, 65; Anal. Calcd for C14H15ClO3S: C 56.28, H
5.06, Found: C 56.34, H 4.98.
[3] a) I. P. Beletskaya, V. P. Ananikov, Chem. Rev., 2011,
111, 1596-1636; b) C.-F. Lee, Y.-C. Liu, S. S. Badsara,
Chem. Asian J., 2014, 9, 706-722; c) A. Sujatha, A. M.
Thomas, A. P. Thankachan, G. Anilkumar, ARKIVOC,
2015, 1-28; d) A. Ghaderi, Tetrahedron, 2016, 72,
4758-4782; e) M. Jouffroy, C. B. Kelly, G. A.
Molander, Org. Lett., 2016, 18, 876-879.
[4] a) C. Shen, P.-F. Zhang, Q. Sun, S.-Q. Bai, T. S. A.
Hor, X.-G. Liu, Chem. Soc. Rev., 2015, 44, 291-314; b)
T. Gensch, F. J. R. Klauck, F. Glorius, Angew. Chem.
Int. Ed., 2016, 55, 11287-11291; c) Z.-H. Yang, Y.-L.
An, Y. Chen, Z.-Y. Shao, S.-Y. Zhao, Adv. Synth.
Catal., 2016, 358, 3869-3875.
3-Bromo-5-methoxy-4-(phenylthio)furan-2(5H)-one
1
(5k): Yellow liquid (48 mg, 53%); H NMR (400 MHz,
CDCl3), δ: 3.16 (s, 3H, OCH3), 5.37 (s, 1H, CH), 7.42-7.52
(m, 3H, ArH), 7.59-7.65 (m, 2H, ArH); 13C NMR (100
MHz, CDCl3), δ: 56.1, 102.5, 106.2, 125.4, 129.5, 130.7,
135.8, 159.5, 164.9; MS (EI, 70 eV), m/z: 302, 300 (M+),
161, 133, 109, 89, 77; Anal. Calcd for C11H9BrO3S: C
43.87, H 3.01, Found: C 43.92, H 3.09.
3-Bromo-5-isopropoxy-4-(phenylthio)furan-2(5H)-
one (5l): Yellow liquid (48 mg, 49%); 1H NMR (400 MHz,
CDCl3), δ: 0.70 (d, J = 8.0 Hz, 3H, CH3), 1.11 (d, J = 8.0
Hz, 3H, CH3), 3.47-3.56 (m, 1H, OCH); 5.60 (s, 1H, CH),
7.42-7.50 (m, 3H, ArH), 7.56-7.64 (m, 2H, ArH); 13C
NMR (100 MHz, CDCl3), δ: 20.9, 22.9, 73.9, 100.6, 106.5,
125.9, 129.6, 130.4, 135.5, 159.8, 165.2; MS (EI, 70 eV),
m/z: 330, 328 (M+), 269, 161, 134, 109, 77; Anal. Calcd for
C13H13BrO3S: C 47.43, H 3.98, Found: C 47.51, H 3.92.
[5] a) R. N. Reddi, P. K. Prasad, A. Sudalai, Angew. Chem.
Int. Ed., 2015, 54, 14150-14153; b) T. Jiang, X. Quan,
C. Zhu, P. G. Andersson, J. E. Bäckvall, Angew. Chem.
Int. Ed. 2016, 55, 5824-5828; c) N. García, R. Rubio-
Presa, P. García-García, M. A. Fernández-Rodríguez,
M. R. Pedrosa, F. J. Arnáiz, R. Sanz, Green Chem.,
2016, 18, 2335-2340; d) J.-G. Sun, W.-Z. Weng, P. Li,
B. Zhang, Green Chem., 2017, 19, 1128-1133.
[6] a) Y.-H. Lv, Y. Li, T. Xiong, W.-Y. Pu, H.-W. Zhang,
K. Sun, Q. Liu, Q. Zhang, Chem. Commun., 2013, 49,
6439-6411; b) Z.-G. Zhang, Q. Tian, J.-J. Qian, Q.-F.
Liu, T.-X. Liu, L. Shi, G.-S. Zhang, J. Org. Chem.,
2014, 79, 8182-8188; c) J.-J. Qian, Z.-G. Zhang, Q.-F.
Liu, T.-X. Liu, G.-S. Zhang, Adv. Synth. Catal., 2014,
356, 3119-3124.
Acknowledgements
[7] X.-Y. Ren, J.-B. Chen, F. Chen, J. Cheng, Chem.
Commun., 2011, 47, 6725-6727.
Financial support from the Guangdong Natural Science
Foundation (No. 2014A030313429), Guangdong Provincial
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
[8] H. Cao, S. Lei, N.-Y. Li, L.-B. Chen, J.-Y. Liu, H.-Y.
Cai, S.-X. Qiu, J.-W. Tan, Chem. Commun., 2015, 51,
1823-1825.
2016, 55, 9224-9228; d) T. J. Greshock, K. P. Moore, R.
T. McClain, A. Bellomo, C. K. Chung, S. D. Dreher, P.
S. Kutchukian, Z.-W. Peng, I. W. Davies, P. Vachal, M.
Ellwart, S. M. Manolikakes, P. Knochel, P. G.
Nantermet, Angew. Chem. Int. Ed., 2016, 55, 13714-
13718; e) A. Manchoju, S. V. Pansare, Org. Lett., 2016,
18, 5952-5955; f) M. J. Goldfogel, C. C. Roberts, R. S.
Manan, S. J. Meek, Org. Lett., 2017, 19, 90-93; g) R.
Wehlauch, S. M. Grendelmeier, H. Miyatake-
Ondozabal, A. H. Sandtorv, M. Scherer, K. Gademann,
Org. Lett., 2017, 19, 548-551; h) B. Zhou, Q.-F. Liu, S.
Dalal, M. B. Cassera, J.-M. Yue, Org. Lett., 2017, 19,
734-737; i) X.-Y. Li, C.-H. Han, H.-Q. Yao, A.-J. Lin,
Org. Lett., 2017, 19, 778-781.
[9] a) O. P. S. Patel, D. Anand, R. K. Maurya, P. P. Yadav,
J. Org. Chem., 2016, 81, 7626-7634; b) P. Liu, Z.-Y.
Shen, Y. Yuan, P.-P. Sun, Org. Biomol. Chem., 2016,
14, 6523-6530.
[10] Z.-J. Li, X.-S. Cui, L. Niu, Y.-M. Ren, M.-H. Bian,
X.-B. Yang, B. Yang, Q.-Q. Yan, J.-C. Zhao, Adv.
Synth. Catal., 2017, 359, 246-249.
[11] a) P. J. A. Joseph, S. Priyadarshini, M. L. Kantam, B.
Sreedhar, Tetrahedron, 2013, 69, 8276-8283; b) H.-Y.
Li, L.-J. Xing, M.-M. Lou, H. Wang, R.-H. Liu, B.
Wang, Org. Lett., 2015, 17, 1098-1101; c) Y.-F. Xu,
T.-T. Cong, P. Liu, P.-P. Sun, Org. Biomol. Chem.,
2015, 13, 9742-9745; d) K. Ghosh, S. Ranjit, D. Mal,
Tetrahedron Lett., 2015, 56, 5199-5202; e) Z.-Y. An, Y.
She, X.-D. Yang, X.-B. Pang, R.-L. Yan, Org. Chem.
Front., 2016, 3, 1746-1749; f) A. A. Pereira, A. S.
Pereira, A. C. de Mello, A. G. Carpanez, B. A. C. Horta,
G. W. Amarante, Eur. J. Org. Chem., 2017, 1578-1582.
[20] a) P. G. Janson, I. Ghoneim, N. O. Ilchenko, K. J.
Szabó, Org. Lett., 2012, 14, 2882-2885; b) G.
Fumagalli, S. Boyd, M. F. Greaney, Org. Lett., 2013,
15, 4398-4401; c) A. Yoshimura, V. V. Zhdankin,
Chem. Rev., 2016, 116, 3328-3435; d) P. Ricci, T.
Khotavivattana, L. Pfeifer, M. Médebielle, J. R.
Morphy, V. Gouverneur, Chem. Sci., 2017, 8, 1195-
1199; e) C. J. Teskey, S. M. A. Sohel, D. L. Bunting, S.
G. Modha, M. F. Greaney, Angew. Chem. Int. Ed.
2017, 56, 5263-5266.
,
[12] a) X.-F. Gao, X.-J. Pan, J. Gao, H.-F. Jiang, G.-Q.
Yuan, Y.-W. Li, Org. Lett., 2015, 17, 1038-1041; b) G.
Shukla, A. Srivastava, A. Nagaraju, K. Raghuvanshi, M.
S. Singh, Adv. Synth. Catal., 2015, 357, 3969-3976; c)
P. Sharma, S. Rohilla, N. Jain, J. Org. Chem., 2015, 80,
4116-4122.
[21] a) T. Wu, X. Mu, G.-S. Liu, Angew. Chem. Int. Ed.,
2011, 50, 12578-12581; b) K. D. Hesp, R. J. Lundgren,
M. Stradiotto, J. Am. Chem. Soc., 2011, 133, 5194-
5197; c) X.-S. Wu, Y. Zhao, H.-B. Ge, J. Am. Chem.
Soc., 2015, 137, 4924-4927; d) X.-W. Lan, N.-X. Wang,
W. Zhang, J.-L. Wen, C.-B. Bai, Y.-L. Xing and Y.-H.
Li, Org. Lett., 2015, 17, 4460-4463.
[13] M. M. D. Pramanik, N. Rastogi, Chem. Commun.,
2016, 52, 8557-8560.
[14] a) G.-Q. Yuan, J.-H. Zheng, X.-F. Gao, X.-W. Li, L.-
B. Huang, H.-J. Chen, H.-F. Jiang, Chem. Commun.,
2012, 48, 7513-7515; b) X.-F. Gao, X.-J. Pan, J. Gao,
H.-W. Huang, G.-Q. Yuan, Y.-W. Li, Chem. Commun.,
2015, 51, 210-212; c) J.-Y. Chen, X.-L. Chen, X. Li,
L.-B. Qu, Q. Zhang, L.-K. Duan, Y.-Y. Xia, X. Chen,
K. Sun, Z.-D. Liu, Y.-F. Zhao, Eur. J. Org. Chem.,
2015, 314-319; d) A.-L. Shao, M. Gao, S.-T. Chen, T.
Wang, A.-W. Lei, Chem. Sci., 2017, 8, 2175-2178.
[22] a) R.-S. Xu, J.-P. Wan, H. Mao, Y.-J. Pan, J. Am.
Chem. Soc., 2010, 132, 15531-15533; b) Y.-F. Liang,
X.-Y. Li, X.-Y. Wang, M.-C. Zou, C.-H. Tang, Y.-J.
Liang, S. Song, N. Jiao, J. Am. Chem. Soc., 2016, 138,
12271-12277.
[23] a) Y.-H. Tan, J.-X. Li, F.-L. Xue, J. Qi, Z.-Y. Wang,
Tetrahedron, 2012, 68, 2827-2843; b) J.-P. Huo, P.
Peng, G.-H. Deng, W. Wu, J.-F. Xiong, M.-L. Zhong,
Z.-Y. Wang, Macromol. Rapid Commun., 2013, 34,
1779-1784; c) J.-P. Huo, J.-C. Luo, W. Wu, J.-F. Xiong,
G.-Z. Mo, Z.-Y. Wang, Ind. Eng. Chem. Res., 2013, 52,
11850-11857.
[15] a) T.-Z. Jia, M.-N. Zhang, I. K. Sagamanova, C. Y.
Wang, P. J. Walsh, Org. Lett., 2015, 17, 1168-1171; b)
X.-F. Wu, K. Natte, Adv. Synth. Catal., 2016, 358, 336-
352; c) X.-J. Li, Y. Sun, X. Huang, L. Zhang, L. Kong,
B. Peng, Org. Lett., 2017, 19, 838-841; d) D. Kaldre, B
Maryasin, D Kaiser, O. Gajsek, L. Gonzáez, N.
Maulide, Angew. Chem. Int. Ed., 2017, 56, 2212-2215.
[24] J. Shi, X.-D. Tang, Y.-C. Wu, J.-F. Fang, L. Cao, X.-
Y. Chen, Z.-Y. Wang, RSC Adv., 2016, 6, 25651-25655.
[25] J. Shi, X.-D. Tang, Y.-C. Wu, H.-N. Li, L.-J. Song,
Z.-Y. Wang, Eur. J. Org. Chem., 2015, 1193-1197.
[16] C. F. Lee, Y.-C. Liu, S. S. Badsara, Chem. Asian J.,
2014, 9, 706-722.
[26] CCDC-1544747 (for 3a), CCDC-1544748 (for 3j),
and CCDC-1544749 (for 4f) contain the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
[17] M. Jiang, H.-F. Li, H.-J. Yang, H. Fu, Angew. Chem.
Int. Ed., 2017, 56, 874-879.
[18] F. Luo, C.-D. Pan, L.-P. Li, F. Chen, J. Cheng, Chem.
Commun., 2011, 47, 5304-5306.
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
[19] a) J. Luo, H.-F. Wang, X. Han, L.-W. Xu, J.
Kwiatkowski, K.-W. Huang, Y.-X. Lu, Angew. Chem.
Int. Ed., 2011, 50, 1861-1864; b) W. Kaplan, H. R.
Khatri, P. Nagorny, J. Am. Chem. Soc., 2016, 138,
7194-7198; c) J. Zhu, Y.-J. Cheng, X.-K. Kuang, L.-J.
Wang, Z.-B. Zheng, Y. Tang, Angew. Chem. Int. Ed.,
[27] a) F. Gelat, J. F. Lohier, A. C. Gaumont, S. Perrio,
Adv. Synth. Catal., 2015, 357, 2011-2016; b) J. A.
Fernández-Salas, A. P Pulis, D. J. Procter, Chem.
Commun., 2016, 52, 12364-12367; c) A. U. Meyer, A.
Wimmer, B. König, Angew. Chem. Int. Ed., 2017, 56,
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
409-412; d) L. Shang, Y.-H. Chang, F. Luo, J.-N. He,
X. Huang, L. Zhang, L.-C. Kong, K.-X. Li, B. Peng, J.
Am. Chem. Soc., 2017, 139, 4211-4217.
[30] To further investigate the versatility of copper(I)-
catalyzed sulfenylation of Csp2-X compounds, we also
simply applied this method into the synthesis of aryl
methyl sulfides. When using different halogenated
benzene derivatives 6a-6c and DMSO as starting
materials, the expected products 7a-7c can be obtained
(the corresponding discussions on these preliminary
observations, the characterization data and spectra of
the products 7a-7c can be seen in SI).
[28] V. J. Traynelis, W. L. Hergenrother, J. Org. Chem.,
1964, 29, 221-222.
[29] a) G. D. Allred, L. S. Liebeskind, J. Am. Chem. Soc.,
1996, 118, 2748-2749; b) W. Zhu, D.-W. Ma, J. Org.
Chem., 2005, 70, 2696-2700; c) J. Kim, S. Chang,
Chem. Commun., 2008, 26, 3052-3054; d) D.-W. Ma,
Q. Cai, Acc. Chem. Res., 2008, 41, 1450-1460.
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700600
Advanced Synthesis & Catalysis
FULL PAPER
Copper(I)-catalyzed alkyl- and arylsulfenylation of
3,4-dihalo-2(5H)-furanones (X=Br, Cl) with
sulfoxides under mild conditions
Adv. Synth. Catal. 2017, 359, 1 – 11
Liang Cao,a Shi-He Luo,*a Han-Qing Wu,a Liu-
Qing Chen,a Kai Jiang,a Zhi-Feng Hao,b Zhao-Yang
Wang*a
11
This article is protected by copyright. All rights reserved.