Synthesis of 3-Sulfenylated Coumarins: BF3·Et2O-Mediated Electrophilic Cyclization of Aryl Alkynoates Using N-Sulfanylsuccinimides

Article abstract of DOI:10.1021/acs.joc.6b02271

A simple and efficient metal-free sulfenylation/cyclization of aryl alkynoates has been developed, obtaining various 3-sulfenylated coumarins in moderate to excellent yields. In the presence of BF₃·Et₂O, the stable and readily access

Full text of DOI:10.1021/acs.joc.6b02271

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Article
Synthesis of 3-Sulfenylated Coumarins: BF3.Et2O-Mediated Electrophilic
Cyclization of Aryl alkynoates Using N-Sulfanylsuccinimides
Wen-Chao Gao, Tao Liu, Bing Zhang, Xing Li, Wen-Long Wei, Qiang Liu, Jun Tian, and Hong-Hong Chang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02271 • Publication Date (Web): 05 Oct 2016
Downloaded from http://pubs.acs.org on October 5, 2016
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Synthesis of 3-Sulfenylated Coumarins: BF3·Et2O-Mediated Electrophilic
Cyclization of Aryl alkynoates Using N-Sulfanylsuccinimides
WenꢀChao Gao,a Tao Liu, Bing Zhang,a Xing Li,a WenꢀLong Wei,a Qiang Liu,a Jun Tian,b*
and HongꢀHong Changa*
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aCollege of Chemistry and Chemical Engineering, and bDepartment of Student Affairs,
Taiyuan University of Technology, Taiyuan 030024, P. R. China
Email: tianjun@tyut.edu.cn;
changhonghong@tyut.edu.cn
Graphic Abstract
O
O
O
O
O
S
R3
R1
BF3•Et2O
rt
R1
+
R3
N
S
R2
R2
R1 = H, F, Cl, Br,
O
N-sulfanylsuccinimide
21 examples,
up to 95% yield
Me, t-Bu, Ph, Ac
R2, R3 = aryl, alkyl
Abstract: A simple and efficient metalꢀfree sulfenylation/cyclization of aryl alkynoates
has been developed, obtaining various 3ꢀsulfenylated coumarins in moderate to excellent
yields. In the presence of BF3·Et2O, the stable and readily accessible
Nꢀsulfanylsuccinimides were employed as electrophiles to induce the 6ꢀendoꢀdig
electrophilic cyclization of alkynoates. The reaction using substrates bearing methoxy group
on the phenoxy ring proceeded in an exclusively distinct pathway via either ipso
sulfenylcyclization or sulfenylation of phenoxy ring depending on the different locations of
methoxy substituent. The resulted 3ꢀsulfenylated coumarins can be readily transformed to
3ꢀsulfinylated or 3ꢀsulfonylated coumarins under different oxidation conditions.
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Introduction
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Electrophilic cyclization of alkynes has been considered to be one of the most powerful
methods to form heteroatomꢀ or carbonꢀtethered cycles efficiently in one step.1 Among such
reactions, electrophilic halocyclization of alkynes containing heteroatoms has been
intensively studied because the resulted heterocycles can be transformed to more complex
derivatives by the further conversion of a residual halogen atom. Various haloꢀsubstituted
heterocycles such as iodoꢀsubstituted spiro[4.5]trienones,2a,b 3ꢀiodoꢀ2Hꢀbenzopyrans,2c
3ꢀhaloquinolones,2d,e and 3ꢀhalocoumarins,2f have been synthesized through intramolecular
cyclization using I2, ICl, Br2, NXS or other halo electrophile reagents.2g,h In addition, to
access the desired organoselenium heterocycles, arylselenenylchloride (ArSeCl) or diaryl
diselenides (ArSeSeAr) have been applied to the electrophilic selenoꢀcyclization.3 Despite
these achievement being reported, the electrophilic cyclization of alkynes to directly access
heterocyclic sulfides promoted by sulfurꢀcontaining electrophiles remains rare.4 In the past
few years, electrophilic sulfenylating reagents, such as Nꢀthioanilides and Nꢀthioamides,
have been utilized to perform numerous sulfenylation reactions. For instance, Benati and
coworkers developed a method for the synthesis of βꢀketo sulfides through
BF3·Et2Oꢀpromoted sulfenylation of alkynes using nitrobenzenesulfenanilide as the
sulfenylating reagent.5 Very recently, the direct arylthiolation of (hetero)aromatic C−H
bonds was also achieved with Nꢀsulfanylsuccinimides as stable and readily accessible
sulfenylating reagents.6 The known examples included palladiumꢀcatalyzed C−H
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sulfenylation of unactivated arenes,6a TFAꢀpromoted C−H sulfenylation of electronꢀrich
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arenes and C2 sulfenylation of nonꢀprotected indoles,6b,c and Lewis acid catalyzed C–H
arylthiolation of substituted phenols.6d Inspired by these elegant procedures, we speculate
that the electrophilic cyclization of alkynes could be readily accessed using
Nꢀsulfanylsuccinimides as electrophiles.
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As one of the most important heterocycles, the coumarin skeleton has been extensively
found in a variety of natural products, biologically active molecules, and functional
materials.7 Particularly, the introduction of some functional groups at C3 position of
coumarins would improve the properties of coumarinꢀbased molecules and enrich the
library of coumarinꢀbased compounds. Consequently, various 3ꢀsubstituted coumarins have
been successfully constructed from aryl alkynoates via radical cyclization in recent years.8
For example, it was reported that 3ꢀsulfonylated coumarins could be synthesized via
oxidative radical sulfonylation/cyclization of phenyl propiolates with sulfonic acids or
sulfonylhydrazides as sulfonylating reagents under metalꢀfree conditions (Scheme 1a).8a,b
Similarly, 3ꢀtrifluoromethylthiolated coumarins could also be successfully accessed through
oxidative radical cascade cyclization of aryl alkynoates employing AgSCF as the radical
source (Scheme 1b).8c Sulfenyl group functionalized at the C3 position of coumarins
modifies the molecular reactivity and pharmacological properties, and the resulted
3ꢀsulfenylated coumarins have shown important biological activities like hepatoprotective
effects9a and estrogenic effects.9b In this context, particular emphasis has been put on the
development of strategies to the synthesis of 3ꢀsulfenylated coumarins. Traditionally,
3ꢀsulfenylated coumarins were prepared through esterification/intramolecular cyclization of
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mercaptoacetic acid derivatives with salicylaldehydes or cross coupling reactions of
4ꢀhydroxy coumarin with thiols (Scheme 1c),10 however, these established methods often
suffered from the use of high reaction temperature,10aꢀc excess amount of bases,10a,b or the
preꢀexisting coumarin frameworks.10d,e Therefore, the development of practical and efficient
protocol by direct difunctionalization of readily available aryl alkynoates to access
3ꢀsulfenylated coumarins, is more convenient and highly desirable. As the continuous work
on heterocycle syntheses under metal free conditions,11 we herein report a mild and efficient
approach to 3ꢀsulfenylated coumarins via electrophilic cyclization of aryl alkynoates with
Nꢀsulfanylsuccinimides mediated by BF3·Et2O (Scheme 1d).
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Scheme 1. Different Methods for the Synthesis of 3-Sulfur-containing Coumarins
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(a) Radical Sulf onylation/cyclization of Alkynotes (Ref . 8a,b)
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8
O
O
O
O
R2SO2H
or
Eosin Y/visible light
or TBAI
+
R2
R2SO2NHNH2
S
O2
TBHP
9
R1
R1
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(b) Radical Trif luoromethylthiolation/ cyclization of Alkynotes (Ref. 8c)
O
O
O
O
K2S2O8
AgSCF3
+
SCF3
R1
R1
(c) T raditional Approach to 3-Sulfenylated Coumarins (Ref. 10)
O
O
O
OH
bases
heat
S
+
R2
R2
R2
OH
O
S
R3
O
O
O
O
I2, oxidant
heat
+
HS R2
S
OH
OH
(d) This work: Electrophilic Sulf enylation/cyclization of Alkynoates
O
O
O
O
O
S
R2
BF3•Et2O
rt
+
N S
R2
O
R1
R1
Results and Discussion
Initially, the electrophilic cyclization of alkynoate 1a was chosen as a model reaction by
employing Nꢀ(pꢀtolylthio)succinimide (3a) in CH2Cl2 as the solvent (Table 1). In the
absence of Lewis acid, there is no desired cyclization product detected (entry 1). In contrast,
when the Lewis acid BF3·Et2O was added to this reaction, the electrophilic cyclization
occurred and the yield of desired product 2a could be improved with the increase of the
amount of BF3·Et2O (entries 2ꢀ4). The best yield of 2a (87%) was obtained when 1a was
treated with Nꢀ(pꢀtolylthio)succinimide in the presence of 1.5 equiv of BF3·Et2O in CH2Cl2
(entry 4). Other Lewis acid such as FeCl3 or AlCl3 led to a decrease in the yield of 2a
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(entries 5 and 6). Furthermore, two Brønsted acids, trifluoroacetic acid (TFA) and
trifluoromethanesulfonic acid (TfOH) were also investigated for this transformation. While
no desired product was detected using TFA (entry 7), and the reaction promoted or
catalyzed by the stronger one TfOH gave 2a in lower yield (entries 8 and 9). The influence
of different solvents was also evaluated, and the results revealed that CH2Cl2 was superior
to the other solvents (entry 4 vs. entries 10ꢀ14). In addition, various other electrophilic
sulfenylating reagents were also investigated for this intramolecular cyclization (entries
15ꢀ17): only 14% yield of 2a was produced by using disulfide 4, while the use of
thiosulfonate 5 gave no products at all; as for the sulfenyl chloride 6, although the reaction
proceeded smoothly, the yield of 2a was inferior to that with the utilization of 3a.
Table 1. Evaluation of Reaction Conditionsa
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Entry
RꢀSꢀTol
3a
Acid (equiv)
0
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Yield (%)b
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6
0
BF3·Et2O (0.5)
BF3·Et2O (1.0)
BF3·Et2O (1.5)
FeCl3 (1.5)
AlCl3 (1.5)
10
61
87
82
58
3a
3a
3a
3a
3a
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TFA (1.5)
CH2Cl2
CH2Cl2
CH2Cl2
DCE
0
3a
3a
3a
3a
3a
3a
3a
3a
4
8
TfOH (1.5)
76
52
76
62
67
trace
0
9
TfOH (0.2)
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BF3·Et2O (1.5)
BF3·Et2O (1.5)
BF3·Et2O (1.5)
BF3·Et2O (1.5)
BF3·Et2O (1.5)
BF3·Et2O (1.5)
BF3·Et2O (1.5)
BF3·Et2O (1.5)
CHCl3
Toluene
CH3CN
EtOAc
CH2Cl2
CH2Cl2
CH2Cl2
14
0
5
74
6
a
The reaction was performed with 1a (0.15 mmol) and sulfenyl reagent (0.225 mmol) in 1.5 mL of
solvent. b Isolated yields.
To test the general scope and limitations of the cyclization reaction, various aryl
alkynoates and Nꢀ(arylthio)succinimides were subjected to the optimized conditions (Table
2). Firstly, we examined the reaction scope of aryl 3ꢀphenylpropiolates bearing different
substituents reacting on the phenoxy ring with Nꢀ(pꢀtolylthio)succinimide (3a). Either
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moderate electronꢀdonating groups (methyl and tertꢀbutyl) or electronꢀwithdrawing groups
(fluoro, chloro, bromo, and acetyl groups) located at the paraꢀposition of aryl
3ꢀphenylpropiolates did not significantly affect the reaction efficiency, resulting in the
desired products in good to high yields (Table 2, 2b-g). Substrates bearing bulky groups at
the ortho position of phenoxy ring did not hamper the cyclization reaction, giving the
corresponding product in good to excellent yields (2h-j). Moreover, the structure of 2i was
unambiguously confirmed by Xꢀray crystal analysis (Figure 1). Another aromatic system,
naphthyl group was also well tolerated in this reaction, and delivered the product 2k in 81%
yield. Next, we investigated the compatibility of substituents on the alkynyl moiety. Phenyl
arylpropiolates with either electronꢀdonating or ꢀwithdrawing groups were suitable for this
transformation, and converted to the desired products in moderate to good yields (2lꢀn).
Alkylpropiolates such as methylpropiolate was also tested for this cyclization, and its
product 2o was obtained in 42% yield only. Additionally, the scope of sulfenylating reagent
3 with different arylthiol partners was also investigated. Similarly, Nꢀ(arylthio)succinimides
with substituents on the arylthiol ring, regardless of the electronꢀwithdrawing or ꢀdonating
properties, were all suitable for this cyclization, and the desired products were produced in
moderate to excellent yields (2p-t). Furthermore, by employing Nꢀ(ethylthio)succinimide as
the sulfenylating reagent, the corresponding 3ꢀsulfenylated coumarin 2u was isolated in 35%
yield.
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Table 2. Electrophilic Cyclization of Alkynoates with N-Sulfanylsuccinimides: Scope
and Limitations
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O
O
O
O
O
S
R1
BF3•Et2O (1.5 equiv)
N S
R1
+
R3
R3
CH2Cl2, rt
7
O
R2
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9
R2
1
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a
Reaction conditions: 1 (0.15 mmol), 3 (0.225 mmol), BF3·Et2O (0.225 mmol), in CH2Cl2
(1.5 mL), at room temperature.
b 3a (0.375 mmol) and BF3·Et2O (0.3 mmol) was used.
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c BF3·Et2O (0.3 mmol) was used.
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d The reaction was performed in DCE (1.5 mL) at reflux.
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Figure 1. ORTEP Drawing of 2i; Thermal Ellipsoids at A 30% Probability Level.
Interestingly, when the methoxy group (OMe) was introduced at para position of phenoxy
ring, the desired 3ꢀsulfenylated coumarin 2v was not detected at all, and unexpected
spiro[4.5]trieneꢀ2,8ꢀdione 7, generated via ipso sulfenylcyclization,2a was isolated as the
sole product (Scheme 2, eq.1). Furthermore, alkynoate 1w bearing two methoxy groups at
both meta positions of phenoxy moiety also failed to give the 6ꢀendoꢀdig cyclization
product, and the direct bisulfenylation of phenoxy ring proceeded instead to afford 8 as the
major product due to the strong electronꢀdonating effect (Scheme 2, eq.2).6b
Scheme 2. Unexpected Transformations by Using Substrates with Methoxy Groups on
Phenoxy Ring
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To elucidate the underlying reaction mechanism, two control experiments were
performed as shown in Scheme 3. No reaction occurred when 1a was performed under the
standard conditions in the absence of 3a. Moreover, 4ꢀphenyl coumarin 9 was also prepared
and treated with 3a under standard conditions, while the desired product 3a was not
detected. These results indicated that coumarin 9 might not be the key intermediate in the
present transformation.
Scheme 3. Control Experiments
As shown in Scheme 4, a working mechanism for the synthesis of 3ꢀsulfenylated
coumarins using Nꢀsulfanylsuccinimides was proposed based on the experimental results
and earlier reports.4ꢀ6 Initially, the treatment of 3a with Lewis acid BF3·Et2O gave a thio
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cation A, which can react with carbonꢀcarbon triple bond of 1a to form sulfonium
intermediate B. Subsequent intramolecular nucleophilic attack of the phenoxy ring of
alkynoates to the activated triple bond produced intermediate C, which underwent
deprotonation to form the target product 2a.
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Scheme 4. Proposed Mechanism for the Synthesis of 3-Sulfenylated Coumarins
O
-F3BO
+ BF3
BF3
O
N
N
O
O
O
N
Me
S
N
O
S
Me
O
S
Me
A
3a
Ph
Me
Me
O
O
O
1a
N
Ph
Ph
O
Ph
H
S
S
Me
S
O
O
O
O
2a
O
O
B
C
Both sulfinyl and sulfonyl groups are versatile functionalities, which have found various
applications in organic synthesis and medicinal chemistry.12 To access the 3ꢀsulfinylated and
3ꢀsulfonated coumarins, we extended our study on the further conversion of 2a. As shown
in Scheme 5, sulfoxide 10 was exclusively obtained in 75% yield by employing the
oxidation combination of KBr and (diacetoxyiodo)benzene (PIDA) (Scheme 5, eq. 1),
whereas sulfone 11 was produced as the sole product in almost quantitative yield by using
metaꢀchloroperbenzoic acid (mꢀCPBA) as the oxidant (Scheme 5, eq. 2). Therefore, the
developed method for the synthesis of 3ꢀsulfenylated coumarins would also provide a
readily and reliably alternative access to the corresponding 3ꢀsulfinylated and
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3ꢀsulfonylated derivatives.
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Scheme 5. Further Oxidation of 2a
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Conclusion
In summary, we have developed a simple and practical approach to 3ꢀsulfenylated
coumarins via electrophilic cyclization of aryl alkynoates. In the presence of BF3·Et2O,
Nꢀsulfanylsuccinimides were utilized as electrophiles to induce the cyclization and
introduce the sulfenyl group at C3 position of coumarins. A series of 3ꢀsulfenylated
coumarins was efficiently prepared in one step from the corresponding aryl alkynoates
under mild and metalꢀfree conditions. Besides, methoxy substituent on the phenoxy ring of
aryl 3ꢀphenylpropiolate favored the formation of either 3ꢀsulfenylspirotrienone product or
sulfenylated arene product depending on different locations of methoxy group. Furthermore,
the selectively oxidative conversions of 3ꢀpꢀtolylthio coumarin were achieved under
different oxidations. Environmentally friendly conditions, broad substrate scope, high
reaction efficiency as well as successfully selective oxidation made this strategy highly
valuable for the synthesis of sulfurꢀcontaining coumarins.
Experimental Section
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General. H NMR spectra were recorded at 600 MHz or 400 MHz and C NMR spectra
were measured at 150 MHz or 100 MHz using NMR spectrometers with CDCl3 as the
solvent. Chemical shifts (δ) were measured in ppm and referenced to the deuterated
chloroform (1H: δ = 7.26 ppm, 13C: δ = 77.00 ppm). Highꢀresolution mass spectrometry
(HRMS) was performed on a TOFꢀQ spectrometer instrument with an ESI source. IR
spectra were recorded on a FTꢀIR spectrometer in KBr pellets. Melting points were
measured with a RDꢀII type melting point apparatus. Xꢀray structural analysis was obtained
with an Xꢀray singleꢀcrystal diffractometer. Aryl alkynoates (1a-w) are all known
compounds and identified by the comparison of their NMR spectra with reported data in
literature. Unless otherwise noted, reagents obtained from commercial sources were directly
used without further purification; all solvents were obtained from commercial sources and
were purified according to standard procedures. Petroleum ether (PE), where used, has the
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boiling point range 60ꢀ90 C. Column chromatography was performed on silica gel
(200ꢀ300 mesh) by using ester acetate and petroleum ether as eluent.
Preparation of Aryl alkynoates.13 To a solution of the respective phenol (5.0 mmol, 1.0
equiv) in CH2Cl2 (20 mL) was added 3ꢀphenylpropiolic acid (5.0 mmol, 1.0 equiv) at 0 oC,
then a mixture of EDC (5.0 mmol, 1.0 equiv) and DMAP (2.0 mmol, 0.4 equiv) in CH2Cl2
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(10 mL) was added dropwise. The mixture was stirred at 0 C for 1 h, and then at room
temperature for 12 h. The resulting reaction mixture was extracted by EtOAc (3 x 10 mL),
and dried over anhydrous Na2SO4. After the organic layer was removed under vacuo, crude
products were purified by column chromatography (Eluent: PE/EtOAc = 95/5).
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Preparation of N-Sulfanylsuccinimides.6c To a solution of thiol (5.0 mmol, 1.0 equiv) and
Et3N (0.5 mmol, 0.1 equiv) in CH2Cl2 (10 mL) was added sulfuryl chloride (5.0 mmol, 1.0
equiv) dropwise at 0 °C. After stirring for 30 min, the reaction mixture was stirred for
another 2 h at room temperature and then cooled to 0 °C. The resulting solution was
transferred dropwise via cannula to a solution of succinimide (5.0 mmol, 1.0 equiv) and
Et3N (6.5 mmol, 1.3 equiv) in CH2Cl2 (8 mL) at 0 °C, and the reaction mixture was allowed
to warm to room temperature and stirred for 2 h. The solution was diluted with H2O (20
mL), extracted with CH2Cl2 (3 × 20 mL), dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The crude product was purified by flash chromatography (Eluent:
PE/EtOAc = 80/10) on silica gel.
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1-(p-Tolylthio)pyrrolidine-2,5-dione (3a).6c Yield: 45%; white solid; m.p. 114ꢀ116 C;
TLC, Rf = 0.32 (PE:EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.58 (d, 2H, J = 8.0 Hz),
7.14 (d, 2H, J = 8.0 Hz), 2.78 (s, 4H), 2.33 (s, 3H).
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1-(Phenylthio)pyrrolidine-2,5-dione (3b).6c Yield: 43%; white solid; m.p. 116ꢀ118 C;
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TLC, Rf = 0.30 (PE:EtOAc = 7:3); H NMR (CDCl3, 600 MHz): δ 7.64ꢀ7.61 (m, 2H),
7.37ꢀ7.31 (m, 3H), 2.82 (s, 4H).
1-((4-Methoxyphenyl)thio)pyrrolidine-2,5-dione (3c).6c Yield: 50%; white solid; m.p.
103ꢀ105 oC; TLC, Rf = 0.43 (PE:EtOAc = 8:2); 1H NMR (CDCl3, 400 MHz): δ 7.75 (d, 2H,
J = 8.8 Hz), 6.85 (d, 2H, J = 8.8 Hz), 3.80 (s, 3H), 2.76 (s, 4H).
1-((4-Chlorophenyl)thio)pyrrolidine-2,5-dione (3d).6a Yield: 46%; white solid; m.p.
142ꢀ144 oC; TLC, Rf = 0.32 (PE:EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.60 (d, 2H,
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J = 8.4 Hz), 7.31(d, 2H, J = 8.4 Hz), 2.82 (s, 4H).
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1-((2-Bromophenyl)thio)pyrrolidine-2,5-dione (3e).6a Yield: 47%; white solid; m.p.
128ꢀ130 oC; TLC, Rf = 0.39 (PE:EtOAc = 8:2); 1H NMR (CDCl3, 600 MHz): δ 7.52 (dd, 1H,
J = 8.4, 1.2 Hz), 7.24 (t, 1H, J = 7.8 Hz),7.09 (td, 1H, J = 7.8, 1.2 Hz), 6.80 (dd,1H, J = 7.8,
1.2 Hz), 2.98 (s, 4H).
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1-((4-Nitrophenyl)thio)pyrrolidine-2,5-dione (3f).6c Yield: 42%; white solid; m.p.
148ꢀ150 oC; TLC, Rf = 0.38 (PE:EtOAc = 8:2); 1H NMR (CDCl3, 600 MHz): δ 8.18 (d, 2H,
J = 9.0 Hz), 7.44 (d, 2H, J = 9.0 Hz), 2.97 (s, 4H).
1-(Ethylthio)pyrrolidine-2,5-dione (3g).6c Yield: 38%; brown oil; TLC, Rf = 0.36
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(PE:EtOAc = 8:2); H NMR (CDCl3, 600 MHz): δ 2.88 (q, 2H, J = 7.2 Hz), 2.84 (s, 4H),
1.22 (t, 3H, J = 7.2 Hz).
Typical Procedure for the Synthesis of 3-Sulfenylated Coumarins. To a solution of aryl
alkynoates (0.15 mmol, 1.0 equiv) and Nꢀsulfanylsuccinimides (0.225 mmol, 1.5 equiv) in
CH2Cl2 (1.5 mL) was added BF3·Et2O (0.225 mmol, 1.5 equiv) dropwise at room
temperature. The reaction mixture was continuously stirred until the starting material was
consumed. The resulting mixture was then diluted with H2O, extracted with EtOAc (3 × 10
mL), and dried over anhydrous Na2SO4. After the organic solvent was removed under
reduced pressure, the crude product was purified by flash chromatography (Eluent:
PE/EtOAc = 95:5).
4-Phenyl-3-(p-tolylthio)-2H-chromen-2-one (2a). Yield: 45 mg (87%); time: 3 h; yellow
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solid; m.p. 117ꢀ119 C; TLC, Rf = 0.40 (PE:EtOAc = 9:1); H NMR (CDCl3, 400 MHz): δ
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7.54ꢀ7.46 (m, 4H), 7.37 (d, 1H, J = 8.4 Hz), 7.27ꢀ7.23 (m, 2H), 7.16 (t, 1H, J = 7.2 Hz),
7.16 (d, 2H, J = 8.0 Hz), 7.08 (dd, 1H, J = 8.0, 1.2 Hz), 7.01 (d, 2H, J = 8.0 Hz), 2.27 (s,
3H); 13C NMR (CDCl3, 100 MHz): δ 159.1, 158.2, 153.2, 136.8, 134.9, 132.0, 131.0, 129.9,
129.7, 128.9, 128.5, 128.3, 128.0, 124.2, 122.3, 120.5, 116.7, 21.0; IR (neat) 3071, 3021,
2924, 1726, 1589, 1489, 1339, 1173, 1119, 993, 804, 754, 704 cmꢀ1; HRMS (ESI) m/z calcd.
for C22H17O2S [M+H]+: 345.0944, found: 345.0950.
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6-Methyl-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2b). Yield: 47 mg (88%); time: 10
h; yellow solid; m.p. 134ꢀ136 oC; TLC, Rf = 0.40 (PE:EtOAc = 9:1); 1H NMR (CDCl3, 600
MHz): δ 7.52ꢀ7.48 (m, 3H), 7.33 (dd, 1H, J = 8.4 , 1.8 Hz), 7.28 (d, 1H, J = 8.4 Hz),
7.26ꢀ7.23 (m, 2H), 7.11 (d, 2H, J = 7.8 Hz), 7.01 (d, 2H, J = 7.8 Hz), 6.84 (d, 1H, J = 1.8
Hz), 2.27 (d, 6H); 13C NMR (CDCl3, 150 MHz): δ 159.4, 158.3, 151.5, 136.8, 135.2, 134.0,
133.0, 131.3, 130.0, 129.7, 128.9, 128.5, 128.4, 127.7, 122.4, 120.3, 116.6, 21.0, 20.9; IR
(neat) 3023, 2920, 1726, 1537, 1491, 1252, 1180, 1132, 1003, 816, 700 cmꢀ1; HRMS (ESI)
m/z calcd. for C23H19O2S [M+H]+: 359.1100, found: 359.1107.
6-(tert-Butyl)-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2c). Yield: 55 mg (88%); time:
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9 h; yellow solid; m.p. 158ꢀ160 C; TLC, Rf = 0.43 (PE:EtOAc = 8:1); H NMR (CDCl3,
400 MHz): δ 7.58 (dd, 1H, J = 8.8, 2.0 Hz), 7.52ꢀ7.48 (m, 3H), 7.32 (d, 1H, J = 8.4 Hz),
7.29ꢀ7.24 (m, 2H), 7.10 (d, 2H, J = 8.0 Hz), 7.05 (d, 1H, J = 2.4 Hz), 7.00 (d, 2H, J = 8.0
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Hz), 2.27 (s, 3H), 1.19 (s, 9H); C NMR (CDCl3, 100 MHz): δ 159.5, 158.9, 151.4, 147.3,
136.7, 135.0, 131.4, 129.72, 129.69, 129.6, 129.0, 128.4, 124.3, 121.9, 119.8, 116.3, 34.5,
31.2, 21.0; IR (neat) 3023, 2957, 2868, 1732, 1537, 1493, 1385, 1134, 1003, 804 cmꢀ1;
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HRMS (ESI) m/z calcd. for C26H25O2S [M+H]+: 401.1570, found: 401.1578.
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6-Fluoro-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2d). Yield: 37.5 mg (69%); time:
10.5 h; yellow solid; m.p. 122ꢀ124 oC; TLC, Rf = 0.40 (PE:EtOAc = 9:1); 1H NMR (CDCl3,
400 MHz): δ 7.54ꢀ7.49 (m, 3H), 7.35 (dd, 1H, J = 9.2, 4.4 Hz), 7.26ꢀ7.20 (m, 3H), 7.12 (d,
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2H, J = 8.0 Hz), 7.02 (d, 2H, J = 8.0 Hz), 6.77 (dd, 1H, J = 8.8, 3.2 Hz), 2.28 (s, 3H); C
NMR (CDCl3, 100 MHz): δ 158.8, 158.6 (d, J = 242.5 Hz), 156.7 (d, J = 2.8 Hz), 149.3 (d,
J = 1.9 Hz), 137.2, 134.4, 130.5, 130.3, 129.8, 129.2, 128.7, 128.3, 124.1, 121.4 (d, J = 8.5
Hz), 119.3 (d, J = 24.5 Hz), 118.3 (d, J = 8.4 Hz), 113.4 (d, J = 25.1 Hz), 21.1; IR (neat)
3063, 2922, 2855, 1719, 1541, 1493, 1422, 1256, 1132, 997, 810, 700 cmꢀ1; HRMS (ESI)
m/z calcd. for C22H16FO2S [M+H]+: 363.0850, found: 363.0849.
6-Chloro-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2e). Yield: 50 mg (88%); time: 8.5
h; yellow solid; m.p. 148ꢀ150 oC; TLC, Rf = 0.42 (PE:EtOAc = 8:1); 1H NMR (CDCl3, 400
MHz): δ 7.55ꢀ7.50 (m, 3H), 7.45 (dd, 1H, J = 8.8, 2.4 Hz), 7.32 (d, 1H, J = 8.8 Hz),
7.26ꢀ7.22 (m, 2H), 7.12 (d, 2H, J = 8.0 Hz), 7.05ꢀ7.00 (m, 3H), 2.28 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 158.5, 156.4, 151.5, 137.2, 134.2, 131.8, 130.5, 130.3, 129.8, 129.7,
129.3, 128.7, 128.3, 127.1, 124.2, 121.6, 118.2, 21.0; IR (neat) 3057, 2916, 2855, 1726,
1532, 1179, 1125, 1001, 708 cmꢀ1; HRMS (ESI) m/z calcd. for C22H15ClNaO2S [M+Na]+:
401.0373, found: 401.0367.
6-Bromo-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2f). Yield: 42 mg (65%); time: 7 h;
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yellow solid; m.p. 156ꢀ158 C; TLC, Rf = 0.48 (PE:EtOAc = 9:1); H NMR (CDCl3, 400
MHz): δ 7.60 (dd, 1H, J = 8.8, 2.4 Hz), 7.54ꢀ7.50 (m, 3H), 7.26 (d, 1H, J = 4.0 Hz),
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7.25ꢀ7.22 (m, 2H), 7.18 (d, 1H, J = 2.4 Hz), 7.11 (d, 2H, J = 8.4 Hz), 7.02 (d, 2H, J = 8.0
Hz), 2.28 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.4, 156.4, 152.0, 137.3, 134.6, 134.2,
130.5, 130.4, 129.8, 129.3, 128.8, 128.3, 124.2, 122.1, 118.5, 117.1, 21.1; IR (neat) 3057,
2918, 2855, 1722, 1530, 1489, 1400, 1265, 1179, 1128, 1003, 810, 706 cmꢀ1; HRMS (ESI)
m/z calcd. for C22H16BrO2S [M+H]+: 423.0049, found: 423.0054.
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6-Acetyl-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2g). Yield: 46 mg (79%); time: 10
h; yellow solid; m.p. 190ꢀ192 oC; TLC, Rf = 0.20 (PE:EtOAc = 9:1); 1H NMR (CDCl3, 400
MHz): δ 8.11 (dd, 1H, J = 8.4, 2.0 Hz), 7.70 (d, 1H, J = 2.4 Hz), 7.56ꢀ7.52 (m, 3H), 7.43 (d,
1H, J = 8.8Hz), 7.30ꢀ7.26 (m, 2H), 7.13 (d, 2H, J = 8.0 Hz), 7.02 (d, 2H, J = 8.0 Hz), 2.47(s,
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3H), 2.28(s, 3H); C NMR (CDCl3, 100 MHz): δ 196.0, 158.3, 157.3, 155.9, 137.3, 134.2,
133.4, 131.5, 130.41, 130.38, 129.8, 129.4, 128.75, 128.72, 128.4, 123.9, 120.4, 117.3, 26.4,
21.1; IR (neat) 3073, 3044, 2916, 1736, 1678, 1493, 1364, 1250, 1119, 1001, 959, 810, 718
cmꢀ1; HRMS (ESI) m/z calcd. for C24H19O3S [M+H]+: 387.1049, found: 387.1046.
4,8-Diphenyl-3-(p-tolylthio)-2H-chromen-2-one (2h). Yield: 55 mg (87%); time: 5 h;
yellow oil; TLC, Rf = 0.48 (PE:EtOAc = 9:1); 1H NMR (CDCl3, 600 MHz): δ 7.62 (d, 2H, J
= 7.8 Hz), 7.57 (dd, 1H, J = 7.2, 1.2 Hz), 7.53ꢀ7.50 (m, 3H), 7.47 (t, 2H, J = 7.2 Hz), 7.40 (t,
1H, J = 7.8 Hz), 7.29 (dd, 2H, J = 7.8, 2.4 Hz), 7.22 (t, 1H, J = 7.8 Hz), 7.14 (d, 2H, J = 7.8
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Hz), 7.07 (dd, 1H, J = 8.4, 1.2 Hz), 7.00 (d, 2H J = 8.4 Hz) 2.27 (s, 3H); C NMR (CDCl3,
100 MHz): δ 158.7, 158.1, 150.1, 137.0, 136.5, 135.6, 135.3, 133.2, 130.9, 130.4, 134.24,
130.18, 129.7, 129.6, 129.3, 128.9, 128.8, 128.54, 128.45, 128.4, 128.0, 127.6, 127.4,124.1,
122.8, 121.0, 21.0; IR (neat) 2961, 2870, 1641, 1385, 1121, 636, 615 cmꢀ1; HRMS (ESI)
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m/z calcd. for C28H21O2S [M+H]+: 421.1257, found: 421.1258.
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8-Methyl-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2i). Yield: 51 mg (95%); time: 5 h;
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yellow solid; m.p. 110ꢀ112 C; TLC, Rf = 0.44 (PE:EtOAc = 9:1); H NMR (CDCl3, 400
MHz): δ 7.50ꢀ7.45 (m, 3H), 7.37 (d, 1H, J = 7.2 Hz), 7.26ꢀ7.23 (m, 2H), 7.12 (d, 2H, J =
8.4 Hz), 7.06 (t, 1H, J = 7.6 Hz), 7.01 (d, 2H, J = 8.0 Hz), 6.91 (dd, 1H, J = 8.4, 1.2 Hz),
2.49 (s, 3H), 2.27 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 159.3, 158.7, 151.6, 136.8, 135.3,
133.3, 131.2, 129.9, 129.6, 128.8, 128.4, 128.3, 126.2, 125.9, 123.7, 122.0, 120.3, 21.0, 15.6;
IR (neat) 3067, 3032, 2920, 2861, 1730, 1543, 1491, 1341, 1080, 957, 800, 770, 704 cmꢀ1;
HRMS (ESI) m/z calcd. for C23H19O2S [M+H]+: 359.1100, found: 359.1104.
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6,8-Di-tert-butyl-4-phenyl-3-(p-tolylthio)-2H-chromen-2-one (2j). Yield: 48 mg (70%);
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time: 5 h; yellow oil; TLC, Rf = 0.48 (PE:EtOAc = 10:1); H NMR (CDCl3, 600 MHz): δ
7.57 (dd, 1H, J = 2.4 Hz), 7.50ꢀ7.47 (m, 3H), 7.26ꢀ7.23 (m, 2H), 7.15 (d, 2H, J = 8.4 Hz),
7.01 (d, 2H, J = 7.8 Hz), 6.89 (d, 1H, J = 2.4 Hz), 2.27 (s, 3H), 1.54 (s, 9H), 1.19 (s, 9H);
13C NMR (CDCl3, 100 MHz): δ 159.3, 158.9, 150.1, 146.2, 137.2, 136.8, 135.7, 131.3,
130.2, 129.6, 128.7, 128.34, 128.31, 127.3, 122.7, 121.3, 120.4, 35.2, 34.7, 31.2, 30.0, 21.0;
IR (neat) 2961, 2870, 1641, 1572, 1385, 1121, 810, 615 cmꢀ1; HRMS (ESI) m/z calcd. for
C30H33O2S [M+H]+: 457.2196, found: 457.2191.
4-Phenyl-3-(p-tolylthio)-2H-benzo[g]chromen-2-one (2k). Yield: 48 mg (81%); time: 6 h;
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yellow solid; m.p. 202ꢀ204 C; TLC, Rf = 0.40 (PE:EtOAc = 9:1); H NMR (CDCl3, 600
MHz): δ 8.00 (d, 1H, J = 9.0 Hz), 7.83 (d, 1H, J = 7.8 Hz), 7.57ꢀ7.50 (m, 4H), 7.38 (t, 1H, J
= 7.8 Hz), 7.28 (dd, 2H, J = 7.8, 1.8 Hz), 7.13 (d, 2H, J = 7.8 Hz), 7.10 (t, 1H, J = 7.8 Hz),
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7.03 (d, 2H, J = 7.8 Hz), 7.00 (d, 1H, J = 9.0 Hz), 2.28 (s, 3H); 13C NMR (CDCl3, 150
MHz): δ 158.7, 158.4, 154.1, 139.1, 136.8, 134.4, 131.5, 131.48, 129.8, 129.7, 129.20,
129.15, 129.0, 128.1, 127.2, 125.6, 125.4, 123.0, 117.3, 114.0, 21.0; IR (neat) 3057, 2922,
2853, 1732, 1518, 1489, 1269, 1011, 990, 812, 696 cmꢀ1; HRMS (ESI) m/z calcd. for
C26H19O2S [M+H]+: 395.1100, found: 395.1104.
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4-(4-Methoxyphenyl)-3-(p-tolylthio)-2H-chromen-2-one (2l). Yield: 46.6 mg (83%); time:
8 h; yellow oil; TLC, Rf = 0.36 (PE:EtOAc = 9:1); 1H NMR (CDCl3, 400 MHz): δ 7.54ꢀ7.49
(m, 1H), 7.37 (d, 2H, J = 8.4 Hz), 7.22ꢀ7.17 (m, 4H), 7.12 (d, 2H, J = 8.0 Hz), 7.04ꢀ7.00 (m,
13
4H), 3.89 (s, 3H), 2.27 (s, 3H); C NMR (CDCl3, 100 MHz): δ 160.1, 159.3, 158.2, 153.3,
136.8, 131.9, 131.3, 130.0, 129.7, 128.2, 127.1, 124.2, 122.3, 120.7, 116.8, 113.9, 55.3, 21.0;
IR (neat) 2922, 1726, 1605, 1385, 1252, 1119, 754, 615 cmꢀ1; HRMS (ESI) m/z calcd. for
C23H19O3S [M+H]+: 375.1049, found: 375.1037.
4-(p-Tolyl)-3-(p-tolylthio)-2H-chromen-2-one (2m). Yield: 46.8 mg (87%); time: 9 h;
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yellow solid; m.p. 147ꢀ149 C; TLC, Rf = 0.40 (PE:EtOAc = 9:1); H NMR (CDCl3, 400
MHz): δ 7.52 (t, 1H, J = 7.6 Hz), 7.37 (d, 1H, J = 7.6 Hz), 7.31 (d, 2H, J = 7.6 Hz),
13
7.20ꢀ7.10 (m, 6H), 7.02 (d, 2H, J = 8.0 Hz), 2.45 (s, 3H), 2.28 (s, 3H); C NMR (CDCl3,
100 MHz): δ 159.2, 158.6, 153.3, 139.0, 136.8, 132.0, 131.9, 131.2, 129.74, 129.69, 129.2,
128.4, 128.2, 124.2, 122.2, 120.6, 116.8, 21.4, 21.0; IR (neat) 3028, 2916, 2864, 1736, 1591,
1491, 1121, 993, 802, 766 cmꢀ1; HRMS (ESI) m/z calcd. for C23H19O2S [M+H]+: 359.1100,
found: 359.1103.
4-(4-Bromophenyl)-3-(p-tolylthio)-2H-chromen-2-one (2n). Yield: 40.6 mg (64%); time:
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9 h; yellow solid; m.p. 145ꢀ147 C; TLC, Rf = 0.47 (PE:EtOAc = 9:1); H NMR (CDCl3,
400 MHz): δ 7.62 (d, 2H, J = 8.4 Hz), 7.54 (t, 1H, J = 7.6 Hz), 7.39 (dd, 1H, J = 8.4, 0.8
Hz ), 7.18 (t, 1H, J = 7.6 Hz), 7.14ꢀ7.08 (m, 4H), 7.06 (dd, 1H, J = 8.0, 1.2 Hz), 7.02 (d, 2H,
J = 8.0 Hz), 2.28 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 159.0, 156.8, 153.2, 137.2, 133.7,
132.2, 131.8, 130.7, 130.10, 130.07, 129.8, 127.7, 124.4, 123.3, 122.9, 120.1, 116.9, 21.1;
IR (neat) 3088, 2916, 2849, 1721, 1595, 1387, 1117, 995, 804, 762, 617 cmꢀ1; HRMS (ESI)
m/z calcd. for C22H16BrO2S [M+H]+: 423.0049, found: 423.0054.
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4-Methyl-3-(p-tolylthio)-2H-chromen-2-one (2o). Yield: 18 mg (42%); time: 13 h; yellow
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solid; m.p. 78ꢀ80 oC; TLC, Rf = 0.47 (PE:EtOAc = 9:1); H NMR (CDCl3, 400 MHz): δ
7.68 (d, 1H, J = 8.0 Hz ), 7.56 (t, 1H, J = 7.6 Hz), 7.36ꢀ7.30 (m, 2H), 7.21 (d, 2H, J = 8.0
13
Hz), 7.07 (d, 2H, J = 8.0 Hz), 2.77 (s, 3H), 2.29 (s, 3H) ; C NMR (CDCl3, 100 MHz): δ
159.2, 156.4, 152.8, 136.7, 132.2, 131.3, 129.9, 129.2, 125.6, 124.4, 121.7, 120.2, 117.1,
21.0, 18.0; IR (neat) 3019, 2920, 2855, 1730, 1597, 1447, 1132, 1071, 978, 806, 748 cmꢀ1;
HRMS (ESI) m/z calcd. for C17H15O2S [M+H]+: 283.0787, found: 283.0783.
4-Phenyl-3-(phenylthio)-2H-chromen-2-one (2p). Yield: 46.6 mg (94%); time: 12 h;
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yellow solid; m.p. 148ꢀ150 C; TLC, Rf = 0.47 (PE:EtOAc = 9:1); H NMR (CDCl3, 600
MHz): δ 7.54 (t, 1H, J =7.2 Hz), 7.50ꢀ7.46 (m, 3H), 7.39 (d, 1H, J = 7.8 Hz), 7.26ꢀ7.24 (m,
2H), 7.22ꢀ7.14(m, 6H), 7.10 (dd, 1H, J = 7.8, 1.2 Hz); 13C NMR (CDCl3, 100 MHz): δ
159.2, 158.9, 153.3, 134.9, 134.8, 132.2, 129.3, 129.0, 128.9, 128.5, 128.3, 128.1, 126.7,
124.3, 121.8, 120.4, 116.8; IR (neat) 3073, 2924, 2853, 1722, 1541, 1441, 1342, 1121, 990,
743 cmꢀ1; HRMS (ESI) m/z calcd. for C21H15O2S [M+H]+: 331.0787, found: 331.0786.
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3-((4-Methoxyphenyl)thio)-4-phenyl-2H-chromen-2-one (2q). Yield: 46 mg (85%); time:
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6 h; yellow solid; m.p. 90ꢀ92 C; TLC, Rf = 0.20 (PE:EtOAc = 9:1); H NMR (CDCl3, 400
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MHz): δ 7.54ꢀ7.48 (m, 4H), 7.37 (dd, 1H, J = 8.4 ,0.8 Hz), 7.26ꢀ7.23 (m, 2H), 7.21 (d, 2H, J
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= 8.8 Hz), 7.16 (td, 1H, J = 7.2, 1.2 Hz), 7.07 (dd, 1H, J = 8.0, 1.2 Hz), 3.75 (s, 3H); C
NMR (CDCl3, 100 MHz): δ 159.4, 159.3, 157.4, 153.2, 135.0, 133.1, 131.9, 128.9, 128.51,
128.48, 128.0, 124.7, 124.2, 123.4, 120.6, 116.7, 114.5, 55.3; IR (neat) 2924, 1719, 1385,
1117, 999, 758, 615 cmꢀ1; HRMS (ESI) m/z calcd. for C22H17O3S [M+H]+: 361.0893, found:
361.0898.
3-((4-Chlorophenyl)thio)-4-phenyl-2H-chromen-2-one (2r). Yield: 52 mg (95%); time: 9
h; yellow solid; m.p. 118ꢀ120 oC; TLC, Rf = 0.44 (PE:EtOAc = 9:1); 1H NMR (CDCl3, 600
MHz): δ 7.55 (t, 1H, J = 7.2 Hz), 7.52ꢀ7.49 (m, 3H), 7.40 (d, 1H, J = 8.4 Hz ), 7.25ꢀ7.22 (m,
2H), 7.21ꢀ7.12 (m, 5H), 7.10 (dd, 1H, J = 8.4, 1.2 Hz); 13C NMR (CDCl3, 150 MHz): δ
159.0, 158.9, 153.4, 134.8, 133.4, 133.0, 132.3, 131.1, 129.2, 129.1, 128.6, 128.3, 128.2,
124.4, 121.7, 120.5, 116.9; IR (neat) 3075, 3048, 1724, 1539, 1474, 1342, 1175, 1092, 995,
814, 758 cmꢀ1; HRMS (ESI) m/z calcd. for C21H14ClO2S [M+H]+: 365.0397, found:
365.0398.
3-((2-Bromophenyl)thio)-4-phenyl-2H-chromen-2-one (2s). Yield: 40 mg (65%); time:
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18 h; pale yellow solid; m.p. 160ꢀ162 C; TLC, Rf = 0.36 (PE:EtOAc = 9:1); H NMR
(CDCl3, 600 MHz): δ 7.56 (t, 1H, J = 8.4 Hz), 7.48ꢀ7.44 (m, 4H), 7.42 (d, 1H, J = 7.8 Hz ),
7.25ꢀ7.22 (m, 2H), 7.20 (t, 1H, J = 7.8 Hz), 7.16ꢀ7.11 (m, 2H), 7.06 (dd, 1H, J = 7.8, 1.8
13
Hz), 7.00 (t, 1H, J = 7.8 Hz); C NMR (CDCl3, 150 MHz): δ 158.9, 158.7, 153.5, 136.3,
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134.6, 133.1, 132.3, 129.6, 129.2, 128.6, 128.10, 128.08, 127.6, 127.5, 124.4, 123.3, 121.1,
120.5, 116.9; IR (neat) 3055, 2924, 2853, 1724, 1603, 1445, 1342, 1121, 1001, 762, 743
cmꢀ1; HRMS (ESI) m/z calcd. for C21H14BrO2S [M+H]+: 410.9872, found: 410.9869.
3-((4-Nitrophenyl)thio)-4-phenyl-2H-chromen-2-one (2t). Yield: 43 mg (77%); time: 9 h;
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pale yellow solid; m.p. 190ꢀ192 C; TLC, Rf = 0.21 (PE:EtOAc = 9:1); H NMR (CDCl3,
400 MHz): δ 8.07 (d, 2H, J = 8.8 Hz), 7.62 (t, 1H, J = 8.4 Hz), 7.53ꢀ7.49 (m, 3H), 7.46 (d,
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1H, J = 8.4 Hz), 7.29ꢀ7.22 (m, 5H), 7.16 (dd, 1H, J = 8.0, 1.6 Hz); C NMR (CDCl3, 100
MHz): δ 161.4, 158.7, 153.6, 145.9, 145.0, 134.3, 133.2, 129.5, 128.7, 128.5, 127.9, 127.3,
124.7, 124.1, 120.1, 118.8, 117.1; IR (neat) 3090, 2916, 2849, 1721, 1576, 1508, 1337,
1123, 1094, 997, 853, 756, 702, 617cmꢀ1; HRMS (ESI) m/z calcd. for C21H14NO4S [M+H]+:
376.0638, found: 376.0630.
3-(Ethylthio)-4-phenyl-2H-chromen-2-one (2u). Yield: 15 mg (35%); time: 15 h; yellow
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solid; m.p. 120ꢀ122 C; TLC, Rf = 0.45 (PE:EtOAc = 9:1); H NMR (CDCl3, 400 MHz): δ
7.55ꢀ7.46 (m, 4H), 7.38 (dd, 1H, J = 8.0, 1.2 Hz), 7.26ꢀ7.22 (m, 2H), 7.15 (t, 1H, J = 7.2
13
Hz), 7.02 (dd, 1H, J = 8.0, 1.2 Hz), 2.95 (q, 2H, J = 7.2 Hz), 1.13(t, 3H, J = 7.2 Hz) ; C
NMR (CDCl3, 100 MHz): δ 159.4, 156.7, 152.8, 135.3, 131.4, 128.8, 128.53, 128.48, 127.6,
124.2, 122.4, 120.6, 116.6, 27.4, 15.0; IR (neat) 3059, 2920, 1717, 1638, 1385, 1119, 999,
760, 615 cmꢀ1; HRMS (ESI) m/z calcd. for C17H15O2S [M+H]+: 283.0798, found: 283.0787.
4-Phenyl-3-(p-tolylthio)-1-oxaspiro[4.5]deca-3,6,9-triene-2,8-dione (7). Yield: 47 mg
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(87%); time: 8 h; yellow solid; m.p. 143ꢀ145 C; TLC, Rf = 0.28 (PE:EtOAc = 8:2); H
NMR (CDCl3, 400 MHz): δ 7.40ꢀ7.34 (m, 1H), 7.33ꢀ7.27 (m, 4H), 7.23 (d, 2H, J = 8.0 Hz),
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7.02 (d, 2H, J = 7.6 Hz), 6.65 (d, 2H, J = 10.0 Hz), 6.38 (d, 2H, J = 10.4 Hz), 2.29 (s, 3H);
13C NMR (CDCl3, 100 MHz): δ 183.8, 168.4, 159.5, 142.75, 138.7, 132.2, 131.8, 130.5,
129.9, 129.2, 128.6, 127.9, 126.9, 126.2, 81.8, 21.1; IR (neat) 3041, 2918, 1776, 1672, 1491,
1209, 1117, 1001, 860, 808, 692 cmꢀ1; HRMS (ESI) m/z calcd. for C22H17O3S [M+H]+:
361.0893, found: 361.0892.
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3,5-Dimethoxy-2,6-bis(p-tolylthio)phenyl 3-phenylpropiolate (8). Yield: 51mg (65%);
time: 4h; white solid; m.p. 147ꢀ149 oC; TLC, Rf = 0.30 (PE:EtOAc = 4:1); 1H NMR (CDCl3,
400 MHz): δ 7.58 (d, 2H, J = 8.4 Hz), 7.45 (t, 1H, J = 7.2 Hz), 7.37 (t, 2H, J = 7.2 Hz), 7.10
13
(d, 4H, J = 8.0 Hz), 7.00 (d, 4H , J = 8.0 Hz), 6.49 (s, 1H), 3.86 (s, 6H), 2.27 (s, 6H); C
NMR (CDCl3, 100 MHz): δ 162.8, 155.8, 151.4, 135.5, 133.3, 133.1, 130.8, 129.4, 128.5,
128.2, 119.5, 108.1, 94.4, 88.6, 80.2, 56.5, 21.0; IR (neat) 3078, 3017, 2918, 2851, 2224,
1724, 1586, 1491, 1219, 1153, 1103, 1015, 813, 758 cmꢀ1; HRMS (ESI) m/z calcd. for
C31H27O4S2 [M+H]+: 527.1345, found: 527.1344.
Synthesis of 3-Sulfinylated Coumarin 10. To a stirred suspension of 3a (0.15 mmol, 1
equiv) and KBr (0.03 mmol, 0.2 equiv) in H2O (1.0 mL), PIDA (0.30 mmol, 2 equiv) was
added at room temperature, and the resulting mixture was stirred vigorously for 20 h. Then,
the mixture was extracted with EtOAc (3 × 10 mL), dried, and evaporated. The residue was
purified by column chromatography (Eluent: PE/EtOAc = 70/30). Yield: 40.5 mg (75%);
time: 20 h; pale yellow solid; m.p. 118ꢀ120 oC; TLC, Rf = 0.45 (PE:EtOAc = 3:2); 1H NMR
(CDCl3, 600 MHz): δ 7.62ꢀ7.57 (m, 4H), 7.54 (d, 2H, J = 8.4 Hz), 7.52ꢀ7.49 (m, 1H),
7.36ꢀ7.33 (m, 2H), 7.26ꢀ7.24 (m, 2H), 7.21 (t, 1H, J = 8.4 Hz), 7.15 (dd, 1H, J = 8.4, 1.2
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Hz), 2.37 (s, 3H); 13C NMR (CDCl3, 150 MHz): δ 158.5, 154.6, 154.2, 141.1, 138.8, 133.8,
131.9, 129.8, 129.6, 129.5, 129.1, 128.9, 128.8, 128.49, 128.47, 125.0, 124.6, 119.8, 117.1,
21.3; IR (neat) 3063, 2920, 2859, 1742, 1721, 1593, 1543, 1346, 1248, 1036, 997, 756, 702
cmꢀ1; HRMS (ESI) m/z calcd. for C22H17O3S [M+H]+: 361.0893, found: 361.0899.
Synthesis of 3-Sulfonylated Coumarin 11.8a To a stirred solution of 3a (0.15 mmol, 1
equiv) in CH2Cl2 (1.0 mL), was added mꢀCPBA (0.45 mmol, 3 equiv) at room temperature,
and the resulting mixture was continuously stirred for another 4 h. Then, the mixture was
diluted with H2O (10 mL), extracted with EtOAc (3 × 10 mL), dried, and evaporated. The
residue was purified by column chromatography (Eluent: PE/EtOAc = 90/10). Yield: 55 mg
(98%); time: 5 h; white solid; m.p. 158ꢀ160 oC; TLC, Rf = 0.27 (PE:EtOAc = 8:1); 1H NMR
(CDCl3, 400 MHz): δ 7.89 (d, 2H, J = 8.4 Hz), 7.64ꢀ7.56 (m, 4H), 7.37ꢀ7.32 (m, 3H), 7.29
(d, 2H, J = 8.0 Hz), 7.19 (t, 1H, J = 7.6 Hz), 7.01 (dd, 1H, J = 8.0, 1.2 Hz), 2.41 (s, 3H); 13C
NMR (CDCl3, 100 MHz): δ 159.1, 155.6, 153.8, 144.7, 137.2, 134.5, 132.6, 129.9, 129.3,
129.2, 128.1, 127.4, 126.1, 124.8, 120.2, 116.7, 21.7.
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Supporting Information
Copies of NMR and IR spectra for all new compounds and Crystallography of 2i; Xꢀray
crystal data for 2i (CIF). This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgements
We gratefully acknowledge the National Natural Science Foundation of Shanxi Province
(Grant No. 2015021037) and Scientific and Technological Innovation Programs of Higher
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Education Institutions in Shanxi (STIP) (Grant No. 2015133).
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References
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(1) Godoi, B.; Schumacher, R. F.; Zeni, G. Chem. Rev. 2011, 111, 2937.
(2) (a) Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2005, 127, 12230. (b) Tang, B.ꢀX.; Tang,
D.ꢀJ.; Tang, S.; Yu, Q.ꢀF.; Zhang, Y.ꢀH.; Liang, Y.; Zhong, P.; Li, J.ꢀH. Org. Lett. 2008, 10,
1063. (c) Worlikar, S. A.; Kesharwani, T.; Yao, T.; Larock, R. C. J. Org. Chem. 2007, 72,
1347. (d) Zhang, X.; Campo, M. A.; Yao, T.; Larock, R. C. Org. Lett. 2005, 7, 763. (e) Ali,
S.; Zhu, H.ꢀT.; Xia, X.ꢀF.; Ji, K.ꢀG.; Yang, Y.ꢀF.; Song, X.ꢀR.; Liang, Y.ꢀM. Org. Lett. 2011,
13, 2598. (f) Reddy, M. S.; Thirupathi, N.; Babu, M. H.; Puri, S. J. Org. Chem. 2013, 78,
5878. (g) Barluenga, J.; VázquezꢀVilla, H.; Ballesteros, A.; González, J. M. Org. Lett. 2003,
5, 4121. (h) Barluenga, J.; VázquezꢀVilla, H.; Ballesteros, A.; González, J. M. J. Am. Chem.
Soc. 2003, 125, 9028.
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(3) (a) Mantovani, A. C.; Goulart, T. A. C.; Back, D. F.; Menezes, P. H.; and Zeni, G. J. Org.
Chem. 2014, 79, 10526. (b) Stein, A. L.; Rosário, A. R.; Zeni, G. Eur. J. Org. Chem. 2015,
5640.
(4) For two examples on the electrophilic cyclization of alkynes with ArSCl, see: (a) Yao, T.;
Larock, R. C. J. Org. Chem. 2003, 68, 5936. (b) Chen, Y.; Cho, C.ꢀH.; Larock, R. C. Org.
Lett. 2009, 11, 173.
(5) Benati, L.; Montevecchi, P. C.; Spagnolob, P. Tetrahedron Lett. 1988, 29, 2381.
(6) (a) Saravanan, P.; Anbarasan, P. Org. Lett. 2014, 16, 848. (b) Hostier, T.; Ferey, V.; Ricci,
G.; Pardo, D. G.; Cossy, J. Org. Lett. 2015, 17, 3898. (c) Hostier, T.; Ferey, V.; Ricci, G.;
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Pardo, D. G.; Cossy, J. Chem. Commun. 2015, 51, 13898. (d) Tian, H.; Zhu, C.; Yang, H.;
Fu, H. Chem. Commun. 2014, 50, 8875.
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(7) (a) R. O. Kennedy and R. D. Thornes, Coumarins: Biology, Applications and Mode of
Action; Wiley: New York, 1997. (b) Silvan, A.M.; Abad, M. J.; Bermejo, P.; Sollhuber, M.;
Villar, A. J. Nat. Prod. 1996, 59, 1183. (c) Kostova, I. Curr. Med. Chem. 2005, 5, 29. (d)
Santana, L.; Uriarte, E.; Roleira, F.; Milhazes, N.; Borges, F. Curr. Med. Chem. 2004, 11,
3239. (e) Borges, F.; Roleira, F.; Milhazes, N.; Santana, L.; Uriarte, E. Curr. Med. Chem.
2005, 12, 887. (f) Swanson, S. A.; Wallraff, G. M.; Chen, J. P.; Zhang, W. J.; Bozano, L. D.;
Carter, K. R.; Salem, J. R.; Villa, R.; Scott, J. C. Chem. Mater. 2003, 15, 2305.
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12
13
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15
16
17
18
19
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21
22
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57
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(8) For C3ꢀsulfonylation, see: (a) Wei, W.; Wen, J.; Yang, D.; Guo, M.; Wang, Y.; You, J.;
Wang, H. Chem. Commun. 2015, 51, 768. (b) Yang, W.; Yang, S.; Li, P.; Wang, L. Chem.
Commun. 2015, 51, 7520. For C3ꢀtrifluoromethylthiolation, see: (c) Zeng, Y.ꢀF.; Tan, D.ꢀH.;
Chen, Y.; Lv, W.ꢀX.; Liu, X.ꢀG.; Li, Q.; Wang, H. Org. Chem. Front. 2015, 2, 1511. For
acylation, see: (d) Liu, T.; Ding, Q.; Zong, Q.; Qiu, G. Org. Chem. Front. 2015, 2, 670, and
references cited therein. For C3ꢀphosphorylation, see: (e) Mi, X.; Wang, C.; Huang, M.;
Zhang, J.; Wu, Y.; Wu, Y. Org. Lett. 2014, 16, 3356. For C3ꢀtrifluoromethylation, see: (f) Li,
Y.; Lu, Y.; Qiu, G.; Ding, Q. Org. Lett. 2014, 16, 4240. For C3ꢀdifluoroacetylation, see: (g)
Fu, W.; Zhu, M. ; Zou, G.; Xu, C.; Wang, Z.; Ji, B. J. Org. Chem. 2015, 80, 4766. For
bromination. see: (h) Qiu, G.; Liu, T.; Ding, Q. Org. Chem. Front. 2016, 3, 510.
(9) (a) Refouvelet, B.; Guyon, C.; Jacquot, Y.; Girard, C.; Fein, H.; Bévalot, F.; Robert, J.ꢀF.;
Heyd, B.; Mantion, G.; Richert, L.; Xicluna, A. Eur. J. Med. Chem. 2004, 39, 931. (b)
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Page 29 of 29
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Jacquot, Y.; Cleeren, A.; Laios, I.; Ma, Y.; Boulahdour, A.; Bermont, L.; Refouvelet, B.;
Adessi, G.; Leclercq, G.; Xicluna, A. Biol. Pharm. Bull. 2002, 25, 335.
8
9
(10) (a) Mikolajczyk, M.; Midura, W. H. Synlett 1991, 245. (b) Mashraqui, S. H.; Vashi, D.;
Mistry, H. D. Synth.Commun. 2004, 34, 3129. (c) Yadav, L. D. S.; Singh, S.; Rai, V. K.
Green Chem. 2009, 11, 878. (d) Parumala, S. K. R.; Peddinti, R. K. Green Chem. 2015, 17,
4068. (e) Saima; Equbal, D.; Lavekara, A. G.; Sinha, A. K. Org. Biomol. Chem. 2016, 14,
6111.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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27
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54
55
56
57
58
59
60
(11) (a) Gao, W.ꢀC.; Hu, F.; Huo, Y.ꢀM.; Chang, H.ꢀH.; Li, X.; Wei, W.ꢀL. Org. Lett. 2015,
17, 3914. (b) Gao, W.ꢀC.; Jiang, S.; Wang, R.ꢀL.; Zhang, C. Chem. Commun. 2013, 49,
4890.
(12) (a) Du, L.; Cao, P.; Xing, J.; Lou, Y.; Jiang, L.; Li, L.; Liao, J. Angew. Chem. Int. Ed.
2013, 52, 4207. (b) Melzig, L.; Rauhut, C. B.; NarediꢀRainer, N.; Knochel, P. Chem. Eur. J.
2011, 17, 5362. (c) Abramovitch, A.; Marek, I. Eur. J. Org. Chem. 2008, 4924. (d) Aziz, J.;
Messaoudi, S.; Alami, M.; Hamze, A. Org. Biomol. Chem. 2014, 12, 9743.
(13) Do, J. H.; Kim, H. N.; Yoon, J.; Kim, J. S.; Kim, H.ꢀJ. Org. Lett. 2010, 12, 932.
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