Metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene: Ortho -quinone methide (VQM)

Article abstract of DOI:10.1039/c8ob02967a

A metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene ortho-quinone methide (VQM) was described herein. The reaction was conducted under mild conditions without any catalysts or additives. Preliminary mechanism studies revealed that the formation of VQM was the key for this alkyne di-functionalization reaction. The reaction could be applied in the enantioselective asymmetric synthesis of axially chiral styrene. Furthermore, the selenosulfonylation adducts can be transformed into useful naphtho[2,1-b]furan and benzofuran scaffolds.

Full text of DOI:10.1039/c8ob02967a

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Metal-free difunctionalization of alkynes to access
tetrasubstituted olefins through spontaneous
selenosulfonylation of vinylidene ortho-quinone
methide (VQM)†
Cite this: DOI: 10.1039/c8ob02967a
Shengli Huang,a,b Zhili Chen,a Hui Mao,c Fangli Hu,a Dongmei Li,a Yu Tan,a
a
Fengqing Yang b and Wenling Qin
*
A metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous seleno-
sulfonylation of vinylidene ortho-quinone methide (VQM) was described herein. The reaction was con-
ducted under mild conditions without any catalysts or additives. Preliminary mechanism studies revealed
that the formation of VQM was the key for this alkyne di-functionalization reaction. The reaction could be
applied in the enantioselective asymmetric synthesis of axially chiral styrene. Furthermore, the seleno-
sulfonylation adducts can be transformed into useful naphtho[2,1-b]furan and benzofuran scaffolds.
Received 28th November 2018,
Accepted 7th January 2019
DOI: 10.1039/c8ob02967a
rsc.li/obc
β-(Seleno)vinyl sulfones can be readily converted into several
useful products such as acetylenic, allenic and β-keto sulfones,
Introduction
Tetrasubstituted olefins have been found as key structural thus proving the significance of synthetic approaches towards
units in a number of biologically active natural products such β-(Seleno)vinyl sulfones.8
as Nileprost analogues and pharmaceutically important mole-
The first method for the construction of β-(Seleno)vinyl sul-
cules such as Tamoxifen and Rofecoxib.1 Tetrasubstituted fones has been established featuring a radical-type reaction as
olefins are also key substrates for various organic transform- the favorite approach (Scheme 1a).9 In this particular case, a
ations such as hydrogenation and epoxidation.2 As a result, radical initiator was required to promote the homolytic clea-
synthetic approaches toward the construction of tetrasubsti- vage of the selenosulfonylation reagent. Recently, many
tuted olefins have attracted considerable attention in organic elegant procedures have been developed for the selenosulfonyl-
chemistry research.3 Nevertheless, a facile synthetic method ation of alkyne through the vinyl radical intermediate.9a For
for introducing two heteroatoms into tetrasubstituted olefins example, Liu and co-workers reported a copper-catalyzed regio-
remains a challenge.4 Among the heteroatom-substituted and stereo-specific selenosulfoylation of alkynes with
olefins, vinyl selenides are valuable synthetic intermediates arylsulfonohydrazides and diphenyl diselenide under mild
and therapeutic entities that have been reported to exhibit a
broad range of biological activities.5 Moreover, selenium can
be readily introduced, manipulated and removed from organic
compounds in a variety of different ways.6 Furthermore, vinyl
sulfones are unique motifs in some biologically active mole-
cules and useful precursors in organic synthesis.7 As a remark-
able combination of selenides and sulfone functionalities,
aChongqing Key Laboratory of Natural Product Synthesis and Drug Research, School
of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, P. R. China.
E-mail: wenling.qin@cqu.edu.cn
bSchool of Chemistry and Chemical Engineering, Chongqing University,
Chongqing 400030, P. R. China
cPharmaceutical and Material Engineering School, Jinhua Polytechnic, Jinhua,
321000 Zhejiang Province, P. R. China
†Electronic supplementary information (ESI) available. CCDC 1877497. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c8ob02967a
Scheme 1 Alkyne difunctionalization through selenosulfonylation.
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Table 1 Optimization of reaction conditionsa
conditions.9b More recently, Sun and co-workers described an
efficient multicomponent regio- and stereo-specific seleno-
sulfonylation of alkynes with the insertion of sulfur dioxi-
de.9c Despite this remarkable progress, vinyl radical species
are commonly considered to be highly reactive and readily
undergo hydrofunctionalization by proton abstraction.9d To
develop a mechanistically new approach for the selenosulfo-
nylation of alkynes, a metal-free method for the 1,2-seleno-
sulfonylation of alkynes through a cationic-species-induced
selenosulfonylation process was achieved by Sun and co-
workers (Scheme 1b).10 Taking all these precedents into con-
sideration, the development of a novel reaction model with a
facile procedure under mild reaction conditions is highly
desirable.
Entry
Solvent
Additive
Yieldb (%)
E/Zc
1
2
DCE
DCE
Et3N
K2CO3
67
69
73
70
72
54
57
49
<5
48
85
69
73
54
63
64
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
3
4
DCE
DCE
KF
DABCO
5
6
DCE
DCE
Malonic acid
Benzoic acid
7
DCE
Citric acid
As a precedent reaction intermediate, vinylidene ortho-
quinone methide (VQM) has attracted much attention in a
variety of synthetic transformations.11 To further explore the
application scope of this versatile intermediate in organic syn-
thesis, herein we described the selenosulfonylation of the
VQM intermediate to realize the difunctionalization of alkynes
under mild conditions. Furthermore, the generated substi-
tuted alkene with an aromatic ring may restrict the rotation of
the single bond between them and the enantiomers of axially
styrene may exist.12 Therefore, this method can be potentially
used to prepare axially chiral styrene bearing selenium and
sulfone moieties.
8
9
DCE
DCE
DCE
DCE
CH3OH
CH2Cl2
CH3CN
Toluene
Toluene
Cinnamic acid
Boric acid
AIBN
—
—
—
—
—
—
10
11
12
13
14
15
16d
a Unless otherwise noted, all reactions were carried out with 1a
(0.1 mmol), 2a (0.1 mmol) and additive (0.1 mmol) in solvent (1.0 mL)
at room temperature for 10 h. b Isolated yield. c Determined by 1H
NMR analysis. d The reaction was carried out at 80 °C.
increasing the temperature to 80 °C, with toluene as the
solvent, the reaction rate and yield were not changed.
Results and discussion
We initiated our study with 1-(phenylethynyl)naphthalen-2-ol
With the optimized reaction conditions in our hand, we
(1a) and selenosulfonate (2a) as model substrates to optimize then investigated the substrate scope of this alkyne seleno-
the reaction conditions. First, we screened a series of bases sulfonylation reaction. Various tetrasubstituted olefins could
(1.0 equiv.) as additives. Pleasingly, the selenosulfonylation be constructed by this straightforward methodology (Table 2).
product 3a was obtained with high levels of regio- and stereo- R1 groups with both electron-donating and -withdrawing sub-
selectivity at room temperature by using 1,2-dichloroethane stitution groups at the para-position of phenyl were well toler-
(DCE) as the solvent (Table 1, entries 1–4).
ated, thus leading to expected products 3a–3g in good yields
Nevertheless, the reaction output was not satisfactory from with excellent E-selectivity (>99 : 1).
the reaction with bases as additives. We envisioned that an
Next, the substrates with a series of substitution groups at
acid might contribute to the activation of selenosulfonate to the ortho-position of phenyl were examined under standard
increase the reaction yield. Thus, we tried malonic acid conditions. Notably, compared to para-substituted R1 groups,
(Table 1, entry 5) as the additive. As expected, the reaction the ortho-substituted counterparts decreased the reaction
went smoothly, albeit the reaction yield was not improved com- yields (Table 2, 3h–3j). The substrate with meta-substituted R1
pared to that with basic conditions. Other acids as additives groups was also tolerant to our reaction system and gave the
caused the decrease in reaction yields (Table 1, entries 6–9). desired product in moderate yield (Table 2, 3k).
Inspirited by Kobayashi’s work,9a we then evaluated azodiiso-
Moreover, the substrates with 2,4 or 3,5-disubstituted
butyronitrile (AIBN) as the radical initiator in this transform- groups proceeded smoothly under standard reaction con-
ation. Unfortunately, the reaction yield was not improved ditions (Table 2, 3l–3n). The substrate with the pentafluoro-
(Table 1, entry 10).
phenyl group also gave desired product 3o in good yield. In
Next, we performed a reaction in the absence of any addi- particular, heterocyclic rings, such as thiophenes, were also
tives or catalysts. Intriguingly, the reaction went smoothly to tolerated and afforded the desired products in good yields and
give 3a with an improved yield after simply mixing two excellent stereoselectivities (Table 2, 3p–3q). Electron-donating
reagents at room temperature. Then, several solvents were or -withdrawing groups on the different positions of the
screened, including methanol, dichloromethane, acetonitrile naphthalene ring did not influence the reaction output and
and toluene. These solvents did not increase the reaction yield the products 3r and 3s were obtained with good yields and
compared to DCE (Table 1, entries 12–15). Notably, after stereoselectivities. It is noteworthy that 2-(phenylethynyl)
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Table 2 Substrate scopea,c
Table 3 Substrate scopea,b
a Unless otherwise noted, all reactions were carried out with 1a
(0.2 mmol) and 2 (0.2 mmol) in 2.0 mL DCE loading at room tempera-
ture for 10 h. b Isolated yield.
a Unless otherwise noted, all reactions were carried out with
1
(0.2 mmol) and 2a (0.2 mmol) in 2.0 mL DCE loading at room tem-
perature for 10 h. b The reactions were carried out with 1 (1.0 mmol),
2a (1.0 mmol) and Et3N (1.0 mmol) in 10.0 mL toluene reflux for 16 h.
c Isolated yield.
ortho- and meta-positions proceeded smoothly to give desired
products (Table 3, 4h–4m) with good yields and E/Z selectiv-
ities. Furthermore, the adduct with 2,5-difluoro substitution at
the phenyl selenide moiety (Table 3, 4n) could also be success-
fully formed under standard reaction conditions.
In order to gain insight into the reaction mechanism, we
conducted some control experiments (Scheme 2). First, we per-
phenol cannot be tolerant to our reaction system under stan-
dard conditions, probably due to the fact that the formation of
the Vinylidene ortho-Quinone Methide (VQM) analogue from
phenol derivatives is much more difficult than from naphthol
derivatives. Nevertheless, after condition screening (for details,
please see ESI Table 3†), products 3t and 3u could be formed
in the presence of triethyl amine by refluxing in toluene for
16 hours.
Encouraged by these results, we further investigated the
substrate scope of selenosulfonates in this transformation.
First, different substitution groups at R4 were evaluated. The
substrate without substitution groups on the phenyl ring
slightly decreased the reaction yield (Table 3, 4a). Compared to
the para-methyl phenyl group on the sulfone moiety, fluoro,
chloro or bromo at the para-position did not influence the
reaction yields and E/Z selectivities (Table 3, 4b–4d).
Next, we investigated the substitution groups on the
benzene ring of phenyl selenide. With para-methyl-, -fluoro-
and -chloro-substituted phenyl selenide, the desired products
were obtained in good yields (Table 3, 4e–4g). Meanwhile, sub-
strates bearing methyl, bromo, chloro substitution groups at Scheme 2 Mechanistic studies.
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formed the reaction by using acetyl protected substrate 5 to
prevent the formation of the VQM intermediate. The reaction
did not proceed under standard conditions, indicating that
the formation of the VQM intermediate was the key for this
spontaneous selenosulfonylation protocol. Next, (2,2,6,6-tetra-
methyl-1-piperidinyl)oxyl (TEMPO) was added to the reaction
mixture of 1a and 2a under standard conditions. After 72 h,
product 3a was isolated with 55% yield (Scheme 2b). This
result therefore dismisses the possibility of a radical pathway.
Furthermore, the reaction by substituting selenosulfonate
with diphenyl diselenide and sodium p-tolylsulfinate
(Scheme 2c) delivered the mono-functionalized sulfonylation
product 6 in 20% yield within 12 h, indicating that the spon-
taneous cleavage of selenosulfonate was required for the reac-
tion and played a key role in activating 1-(phenylethynyl)
naphthalen-2-ol to form the VQM as the key intermediate.
Based on the mechanism experiments and previous
reports,11a we proposed a plausible mechanism (Scheme 3).
First, selenosulfonate was cleaved by 1-(phenylethynyl)
naphthalen-2-ol; thus, the VQM intermediate A was formed
along with the release of one molecule of p-toluenesulfinic
acid (TsH). According to the theoretical calculation and pre-
vious reports, the terminal carbon of VQM was nucleophilic
and enabled the addition of the selenium cation to form inter-
mediate A.11e Finally, intermediate A was attacked by the pre-
viously formed TsH to afford the desired adduct 3a.
Since the addition of selenosulfonate to 1-(phenylethynyl)
naphthalen-2-ol had been developed as a preparation method
for β-(Seleno)vinyl sulfones, we envisaged that this process
might be carried out in an enantioselective fashion for the
construction of axially chiral styrene. Inspirited by the method-
ology recently developed by Liu,11d we used easily accessible
cat.-A as the catalyst and CH2Cl2 as the solvent. Gratifyingly,
the reaction gave axially chiral 3a′ in moderate yield and
84% enantiomeric excess (Scheme 4). The further exploration
of a new catalyst and substrate scope is ongoing in our
laboratory.
Scheme 4 Enantioselective synthesis of β-(Seleno)vinyl sulfones.
Scheme 5 Synthetic transformations.
adduct to the desired heterocyclic compound. Product 3a
could be oxidized into selenoxide with 3-chloroperoxybenzoic
acid (m-CPBA) and then gave a naphtho[2,1-b]furan derivative
in high yield under basic conditions. With a similar procedure,
product 3t could be successfully transformed to benzofuran
derivative 9 with good yield (Scheme 5).
Conclusion
In summary, we have developed a metal-free difunctionaliza-
tion of alkynes to access tetrasubstituted olefins through spon-
taneous selenosulfonylation of the vinylidene ortho-quinone
methide (VQM) intermediate. The reaction was conducted
under mild conditions without any catalysts or additives. The
preliminary mechanism investigation indicated that the for-
mation of VQM was the key for this selenosulfonylation
process. The application prospect of this reaction was demon-
strated by the enantioselective asymmetric synthesis of axially
chiral styrene and further transformation of the adducts to
naphtho[2,1-b]furan and benzofuran derivatives.
As mentioned above, apart from the asymmetric synthetic
attempts of the reaction, we evaluated the application of the
selenosulfonylation product by further transformation of the
Experimental section
General information
1H and 13C NMR spectra were recorded on an Agilent 400MR
DD2 (400 MHz) spectrometer and an Agilent 600MR DD2
(600 MHz) spectrometer. Chemical shifts were reported in
parts per million (ppm), and tetramethylsilane or the residual
Scheme 3 Plausible mechanism.
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solvent peak was used as an internal reference: CDCl3 (1H 21.37; HRMS (ESI) m/z calcd for [C32H26NaO4SSe, M + Na]+:
NMR δ 0.00, 13C NMR δ 77.00). Data are reported as follows: 609.0609, found: 609.0613.
chemical shift, multiplicity (s = singlet, d = doublet, t = triplet,
3d: Yield 53% (61.4 mg); white solid; mp 212–213 °C; 1H
q = quartet, m = multiplet, br = broad), coupling constants NMR (400 MHz, CDCl3): δ 7.83 (d, J = 8.9 Hz, 1H), 7.75 (d, J =
(Hz) and integration. High resolution mass spectra (HRMS) 7.8 Hz, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.40–7.23 (m, 6H), 7.02 (t,
were recorded on a Bruker Solarix 7.0T. X-ray crystallography 3H), 6.98–6.89 (m, 4H), 6.85 (q, 4H), 2.20 (s, 3H), 1.21 (s, 9H);
analysis of single crystal was performed on an Agilent 13C NMR (100 MHz, CDCl3): δ 160.70, 153.11, 150.88, 143.75,
SuperNova-CCD X-ray diffractometer. Melting points were 137.15, 136.19, 132.27, 132.07, 131.93, 130.17, 129.02, 128.81,
measured using a SGWX-4A Microscopic melting point meter 128.47, 128.31, 128.29, 128.12, 127.34, 127.06, 123.98, 123.59,
and are uncorrected. Enantiomeric excesses (ee) were deter- 123.14, 119.20, 114.25, 34.39, 31.20, 21.39; HRMS (ESI) m/z
mined by HPLC analysis on a Hitachi Chromaster using calcd for [C35H32NaO3SSe,
M +
Na]+: 635.1130, found:
DAICEL CHIRALCEL AD-H, 4.6 mm Φ × 250 mmL. Unless 635.1126.
otherwise stated, all reagents were purchased from commercial
suppliers and used without further purification.
3e: Yield 81% (92.9 mg); white solid; mp 182–184 °C; 1H
NMR (400 MHz, CDCl3): 7.81 (d, J = 8.9 Hz, 1H), 7.73 (d, J =
7.4 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.36–7.26 (m, 6H),
7.12–7.05 (m, 3H), 7.02 (d, J = 7.1 Hz, 2H), 6.98–6.86 (m, 4H),
6.78 (t, J = 8.3 Hz, 2H), 2.20 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 162.20 (d, J = 258.0 Hz), 158.78, 153.13, 144.17,
137.09, 135.74, 132.20, 132.10, 131.21, 131.18, 128.95, 128.90,
128.82, 128.51, 128.43, 128.34, 127.07, 126.90, 123.61, 122.86,
119.28, 114.40, 114.18, 21.39; HRMS (ESI) m/z calcd for
[C31H23FNaO3SSe, M + Na]+: 597.0409, found: 597.0412.
General procedure for the synthesis of compounds 3 or 4
The substrate 1 (0.2 mmol) and selenosulfonate 2 (0.2 mmol)
were added to a 10 mL flame-dried Schlenk tube with a mag-
netic stirring bar. DCE (2.0 mL) was injected into the tube.
After stirring at room temperature for 10 h, the mixture was
evaporated and purified by column chromatography on silica
gel (PE : EA = 4 : 1) to afford the products 3 or 4.
3f: Yield 47% (55.5 mg); white solid; mp 171–172 °C; 1H
NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.9 Hz, 1H), 7.73 (q, J =
9.2 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.41–7.20 (m, 7H),
General procedure for the synthesis of compounds 3t and 3u
Et3N (1.0 mmol) was added to a solution of substrate 1t or 1u 7.16–7.00 (m, 6H), 6.99–6.84 (m, 4H), 2.20 (s, 3H); 13C NMR
(1.0 mmol) and selenosulfonate 2a (1.0 mmol) in toluene (100 MHz, CDCl3): δ 158.40, 158.40, 153.13, 144.75, 144.29,
(10 mL). After refluxing for 16 h, the mixture was evaporated 137.11, 135.52, 133.93, 133.75, 132.26, 132.06, 131.15, 128.94,
and purified by column chromatography on silica gel 128.58, 128.49, 128.35, 128.26, 127.41, 127.08, 126.69, 123.63,
(PE : EA = 4 : 1) to afford the products 3t or 3u.
3a: Yield 85% (94.4 mg); white solid; mp 171–173 °C; [C31H23ClNaO3SSe, M + Na]+: 613.0114, found: 613.0118.
1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.9 Hz, 1H), 7.73 (d, 3g: Yield 61% (73.3 mg); yellow solid; mp 120–123 °C; 1H
122.78, 119.34, 118.98, 114.09, 21.42; HRMS (ESI) m/z calcd for
J = 7.2 Hz, 1H), 7.49 (t, J = 8.3 Hz, 1H), 7.38–7.24 (m, 6H), NMR (400 MHz, CDCl3): δ 7.99 (s, 2H), 7.85 (d, J = 8.5 Hz, 1H),
7.14–6.96 (m, 8H), 6.93–6.84 (m, 4H), 2.19 (s, 3H); 13C NMR 7.78–7.70 (m, 1H), 7.40 (s, 1H), 7.36–7.22 (m, 8H), 7.14–7.00
(100 MHz, CDCl3): 160.15, 153.19, 144.00, 137.11, 135.87, (m, 3H), 6.99–6.84 (m, 4H), 2.21 (s, 3H); 13C NMR (100 MHz,
135.77, 135.11, 132.19, 132.12, 130.41, 130.27, 128.96, 128.87, CDCl3): δ 156.40, 153.25, 146.83, 144.79, 142.40, 137.25,
128.58, 128.49, 128.30, 127.86, 127.14, 127.01, 123.55, 122.95, 134.74, 132.54, 131.83, 131.57, 129.42, 129.11, 128.95, 128.84,
119.32, 114.29, 21.38; HRMS (ESI) m/z calcd for 128.56, 128.44, 127.18, 125.95, 123.74, 122.43, 119.53, 113.54,
[C31H24NaO3SSe, M + Na]+: 579.0504, found: 579.0508.
21.43; HRMS (ESI) m/z calcd for [C31H23NNaO5SSe, M + Na]+:
3b: Yield 44% (50.1 mg); white solid; mp 188–190 °C; 624.0354, found: 624.0355.
1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.9 Hz, 1H), 7.71 (d,
3h: Yield 47% (59.6 mg); white solid; mp 175–177 °C; 1H
J = 7.5 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.36–7.23 (m, 6H), NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.9 Hz, 1H), 7.73–7.61
7.09–6.97 (m, 5H), 6.94–6.83 (m, 6H), 2.23 (s, 3H), 2.18 (s, 3H); (m, 3H), 7.43–7.28 (m, 4H), 7.26–7.15 (m, 5H), 7.15–7.07 (m,
13C NMR (100 MHz, CDCl3): δ 160.55, 153.12, 143.95, 137.82, 2H), 6.94 (t, J = 7.5 Hz, 3H), 6.87 (d, J = 8.0 Hz, 2H), 2.16 (s,
136.99, 135.79, 132.22, 132.06, 130.11, 128.92, 128.78, 128.50, 3H); 13C NMR (100 MHz, CDCl3): δ 158.79, 153.18, 144.45,
128.45, 128.26, 127.81, 127.18, 126.95, 123.52, 123.00, 119.28, 137.58, 136.00, 134.24, 132.40, 132.33, 131.90, 131.10, 129.62,
114.43, 21.37, 21.28; HRMS (ESI) m/z calcd for 129.28, 129.07, 128.97, 128.80, 128.24, 127.97, 126.72, 126.45,
[C32H26NaO3SSe, M + Na]+: 593.0660, found: 593.0658.
125.86, 123.62, 123.58, 121.32, 119.71, 113.73, 21.38; HRMS
3c: Yield 76% (89.0 mg); white solid; mp 189–190 °C; 1H (ESI) m/z calcd for [C31H23BrNaO3SSe, M + Na]+: 656.9609,
NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.9 Hz, 1H), 7.72 (d, J = found: 656.9614.
7.6 Hz, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.35–7.24 (m, 6H),
3i: Yield 30% (37.4 mg); white solid; mp 201–204 °C; 1H
7.12–6.97 (m, 5H), 6.97–6.85 (m, 4H), 6.62 (d, J = 8.5 Hz, 2H), NMR (400 MHz, CDCl3): δ 7.85 (d, J = 9.4 Hz, 2H), 7.67 (d, J =
3.73 (s, 3H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.23, 7.6 Hz, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.36 (t, J = 8.9 Hz, 2H),
159.35, 153.04, 143.89, 136.91, 136.01, 132.29, 132.04, 130.53, 7.34–7.26 (m, 4H), 7.26–7.15 (m, 3H), 7.09 (t, J = 8.3 Hz, 3H),
130.22, 128.94, 128.79, 128.47, 128.44, 128.34, 128.27, 127.48, 6.93 (t, J = 7.5 Hz, 2H), 6.84 (d, J = 8.0 Hz, 2H), 2.13 (s, 3H); 13
C
127.38, 126.99, 123.55, 123.08, 119.20, 114.61, 112.66, 55.18, NMR (100 MHz, CDCl3): δ 156.55, 153.12, 144.52, 137.77,
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133.98, 133.25, 132.53, 132.47, 131.27, 130.84, 129.95, 129.11, (t, J = 4.0 Hz), 118.75, 113.32, 21.39; HRMS (ESI) m/z calcd for
129.01, 128.83, 128.76, 128.34, 128.22, 127.93, 126.93, 126.18 [C33H22F6NaO3SSe, M + Na]+: 715.0251, found: 715.0249.
(q, J = 30.0 Hz), 126.15 (q, J = 5.0 Hz), 125.90, 124.06 (q, J =
3o: Yield 61% (78.8 mg); white solid; mp 211–213 °C; 1H
272.0 Hz), 123.64, 122.78, 122.77, 119.80, 113.90, 21.34; HRMS NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.9 Hz, 1H), 7.70 (d, J =
(ESI) m/z calcd for [C32H23F3NaO3SSe, M + Na]+: 647.0377, 7.9 Hz, 1H), 7.43–7.14 (m, 10H), 7.11 (t, J = 7.4 Hz, 2H), 6.93
found: 647.0374.
(d, J = 7.9 Hz, 2H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3):
3j: Yield 55% (70.4 mg); white solid; mp 161–163 °C; 1H δ 153.23, 145.19, 143.37, 137.00, 134.15, 133.54, 132.88,
NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.9 Hz, 1H), 7.68 (d, J = 131.26, 130.16, 129.20, 128.99, 128.83, 128.21, 127.23, 125.57,
10.0 Hz, 2H), 7.43 (d, J = 8.3 Hz, 1H), 7.34 (d, J = 8.9 Hz, 1H), 123.74, 122.53, 119.49, 112.45, 21.43; HRMS (ESI) m/z calcd for
7.29 (d, J = 8.0 Hz, 2H), 7.24–7.19 (m, 1H), 7.19–7.06 (m, 6H), [C31H19F5NaO3SSe, M + Na]+: 669.0032, found: 669.0030.
7.05–6.98 (m, 2H), 6.94 (t, J = 7.5 Hz, 2H), 6.86 (d, J = 7.9 Hz,
3p: Yield 46% (51.7 mg); white solid; mp 97–99 °C; 1H NMR
2H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.24, 153.36, (400 MHz, CDCl3): δ 7.77 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 7.8 Hz,
144.79, 144.53, 137.35, 134.12, 132.41, 132.04, 131.26, 130.69, 1H), 7.56 (d, J = 8.2 Hz, 1H), 7.45–7.34 (m, 3H), 7.33–7.26 (m,
129.51, 129.09, 128.85, 128.82, 128.75, 128.41, 127.94, 126.75, 2H), 7.25–7.20 (m, 1H), 7.16 (d, J = 4.5 Hz, 1H), 7.15–7.06 (m,
126.39, 126.08, 124.56, 123.60, 123.16, 120.56 (q, J = 258.0 Hz), 3H), 7.03–6.93 (m, 3H), 6.90 (d, J = 7.5 Hz, 2H), 6.77–6.70 (m,
119.62, 115.77, 113.71, 21.35; HRMS (ESI) m/z calcd for 1H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 152.99, 150.76,
[C32H23F3NaO4SSe, M + Na]+: 663.0327, found: 663.0330.
143.93, 136.39, 135.89, 135.38, 134.57, 132.29, 132.04, 130.64,
3k: Yield 51% (56.7 mg); white solid; mp 175–178 °C; 1H 128.83, 128.58, 128.44, 128.42, 128.29, 128.05, 127.73, 127.18,
NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.9 Hz, 1H), 7.74 (d, J = 126.16, 123.61, 123.16, 119.02, 114.63, 21.40; HRMS (ESI) m/z
7.9 Hz, 1H), 7.59–7.50 (m, 1H), 7.39–7.25 (m, 6H), 7.09–6.93 calcd for [C29H22NaO3SSe,
(m, 5H), 6.93–6.79 (m, 5H), 6.67 (s, 1H), 2.20 (s, 3H), 2.11 (s, 585.0070.
M +
Na]+: 585.0068, found:
3H); 13C NMR (100 MHz, CDCl3): δ 160.21, 153.21, 143.80,
3q: Yield 62% (69.6 mg); white solid; mp 188–189 °C; 1H
137.11, 136.55, 136.20, 134.73, 132.04, 130.34, 128.97, 128.82, NMR (400 MHz, CDCl3): δ 7.75 (dd, J = 8.1, 4.6 Hz, 2H), 7.66
128.55, 128.46, 128.29, 128.08, 127.17, 127.04, 123.54, 123.08, (d, J = 8.3 Hz, 1H), 7.39 (d, J = 8.0 Hz, 3H), 7.31 (t, J = 7.4 Hz,
119.20, 114.21, 21.37, 21.02; HRMS (ESI) m/z calcd for 1H), 7.25 (d, J = 6.3 Hz, 1H), 7.20 (d, J = 8.9 Hz, 1H), 7.16–7.00
[C32H26NaO3SSe, M + Na]+: 593.0660, found: 593.0657.
(m, 4H), 7.01–6.84 (m, 5H), 6.67 (d, J = 4.8 Hz, 1H), 2.21 (s,
3l: Yield 31% (40.8 mg); white solid; mp 182–184 °C; 1H 3H); 13C NMR (100 MHz, CDCl3): δ 154.16, 153.04, 143.73,
NMR (400 MHz, CDCl3): δ 7.88–7.79 (m, 2H), 7.67 (d, J = 136.56, 136.51, 134.52, 132.63, 132.27, 131.97, 128.93, 128.84,
7.7 Hz, 1H), 7.43 (s, 1H), 7.38–7.31 (m, 2H), 7.31–7.07 (m, 9H), 128.49, 128.42, 128.38, 128.32, 128.17, 127.45, 127.15, 125.97,
6.97 (t, J = 7.4 Hz, 2H), 6.85 (d, J = 7.8 Hz, 2H), 2.13 (s, 3H); 13
NMR (100 MHz, CDCl3): δ 155.00, 153.04, 144.72, 137.74, calcd for [C29H22NaO3SSe,
C
124.15, 123.59, 123.25, 118.96, 114.31, 21.40; HRMS (ESI) m/z
M +
Na]+: 585.0068, found:
134.31, 133.74, 132.63, 132.55, 132.37, 131.97, 130.94, 130.79, 585.0071.
129.44, 128.99, 128.90, 128.75, 128.60, 127.99, 127.63 (q, J =
3r: Yield 76% (94.4 mg); white solid; mp 172–175 °C; 1H
31.0 Hz), 126.99, 126.48 (q, J = 5.0 Hz), 125.62, 123.70, 123.20 NMR (400 MHz, CDCl3): δ 7.89 (s, 1H), 7.69 (d, J = 8.9 Hz, 1H),
(q, J = 273.0 Hz) 122.59, 119.82, 113.73, 21.35; HRMS (ESI) m/z 7.52 (s, 1H), 7.46–7.38 (m, 2H), 7.32–7.23 (m, 3H), 7.15–7.00
calcd for [C32H22ClF3NaO3SSe, M + Na]+: 680.9988, found: (m, 6H), 6.99 (d, J = 7.5 Hz, 2H), 6.95–6.80 (m, 4H), 2.23 (s,
680.9989.
3H); 13C NMR (100 MHz, CDCl3): δ 160.42, 153.67, 144.17,
1
3m: Yield 43% (50.2 mg); white solid; mp 192–193 °C; H 137.04, 135.91, 134.80, 131.04, 130.84, 130.25, 130.22, 130.11,
NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.9 Hz, 1H), 7.76 (d, J = 130.04, 129.01, 128.66, 128.38, 128.35, 127.91, 127.13, 126.80,
8.0 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.44–7.37 (m, 1H), 124.86, 120.48, 117.22, 114.41, 21.45; HRMS (ESI) m/z calcd for
7.36–7.24 (m, 5H), 7.04 (t, J = 7.3 Hz, 1H), 7.01–6.95 (m, 2H), [C31H23BrNaO3SSe, M + Na]+: 656.9609, found: 656.9607.
6.91 (d, J = 7.8 Hz, 4H), 6.63 (s, 1H), 6.57 (s, 2H), 2.22 (s, 3H),
3s: Yield 72% (84.3 mg); white solid; mp 171–172 °C; 1H
2.12 (s, 3H), 2.08 (s, 3H); 13C NMR (100 MHz, CDCl3): 160.28, NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.3 Hz, 1H), 7.75 (d, J =
153.24, 143.62, 137.11, 136.57, 136.40, 134.46, 132.36, 131.94, 8.0 Hz, 1H), 7.47 (t, 1H), 7.40 (t, J = 7.4 Hz, 1H), 7.32 (d, J =
130.42, 129.17, 128.97, 128.75, 128.50, 128.45, 128.29, 127.87, 7.7 Hz, 2H), 7.25 (s, 2H), 7.07–6.94 (m, 5H), 6.94–6.78 (m, 6H),
127.29, 127.06, 125.90, 123.52, 123.19, 119.12, 114.17, 21.35, 6.56 (s, 1H), 4.06 (s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz,
20.92; HRMS (ESI) m/z calcd for [C33H28NaO3SSe, M + Na]+: CDCl3): δ 157.06, 146.81, 144.91, 142.92, 138.53, 136.94,
607.0817, found: 607.0818.
134.93, 133.52, 129.46, 129.00, 128.54, 128.33, 128.23, 128.21,
3n: Yield 46% (63.6 mg); white solid; mp 179–182 °C; 1H 127.80, 127.52, 127.35, 127.08, 126.81, 125.34, 124.40, 123.94,
NMR (400 MHz, CDCl3): δ 7.81 (t, J = 7.8 Hz, 2H), 7.57–7.50 (m, 114.54, 107.61, 55.99, 21.46; HRMS (ESI) m/z calcd for
2H), 7.44 (t, J = 7.2 Hz, 2H), 7.40–7.30 (m, 5H), 7.22 (d, J = [C32H26NaO4SSe, M + Na]+: 609.0609, found: 609.0605.
8.9 Hz, 1H), 7.08 (t, J = 7.2 Hz, 1H), 7.00–6.89 (m, 6H), 2.25 (s,
3t: Yield 20% (101.2 mg); white solid; mp 76–78 °C; 1H
3H); 13C NMR (100 MHz, CDCl3): δ 154.88, 153.39, 144.80, NMR (600 MHz, CDCl3): δ 7.48 (s, 4H), 7.40 (s, 1H), 7.26 (d, J =
137.39, 137.27, 135.91, 133.70, 132.44, 131.96, 130.46 (q, J = 8.4 Hz, 2H), 7.13 (d, J = 7.7 Hz, 2H), 7.10–7.05 (m, 3H),
33.0 Hz), 129.36, 129.29, 129.03, 128.88, 128.55, 128.26, 6.95–6.88 (m, 3H), 6.58 (d, J = 8.1 Hz, 1H), 6.54 (d, J = 7.5 Hz,
127.48, 126.18, 123.82, 123.29 (q, J = 270.0 Hz), 122.71, 121.13 1H), 6.50 (t, J = 7.4 Hz, 1H), 5.62 (s, 1H), 2.35 (s, 3H); 13C NMR
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(150 MHz, CDCl3): δ 151.88, 151.78, 143.78, 139.38, 137.47,
4e: Yield 56% (63.8 mg); white solid; mp 179–181 °C; 1H
136.91, 134.33, 129.88, 129.79, 129.59, 129.11, 128.86, 128.77, NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.9 Hz, 1H), 7.72 (d, J =
128.30, 128.12, 127.13, 123.62, 119.96, 116.95, 21.55; HRMS 7.9 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.45 (s, 1H), 7.36–7.23 (m,
(ESI) m/z calcd for [C27H22NaO3SSe, M + Na]+: 529.0347, found: 5H), 7.07 (s, 5H), 6.86 (d, J = 7.6 Hz, 4H), 6.68 (d, J = 7.7 Hz,
529.0351.
2H), 2.18 (s, 3H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3):
1
3u: Yield 26% (139.3 mg); white solid; mp 183–184 °C; H δ 160.30, 153.22, 143.84, 138.68, 136.93, 136.03, 135.15,
NMR (600 MHz, CDCl3): δ 7.42–7.29 (m, 2H), 7.27–7.23 (m, 132.22, 131.98, 130.30, 129.07, 129.07, 128.89, 128.82, 128.40,
2H), 7.13 (d, J = 7.6 Hz, 2H), 7.07 (t, J = 7.2 Hz, 3H), 7.00 (d, J = 128.40, 128.24, 127.74, 127.05, 126.97, 123.48, 123.41, 123.02,
8.3 Hz, 2H), 6.92 (dt, J = 18.7, 7.1 Hz, 3H), 6.59 (d, J = 8.1 Hz, 119.19, 114.21, 21.36, 21.04; HRMS (ESI) m/z calcd for
1H), 6.50 (q, J = 7.7 Hz, 2H), 5.52 (s, 1H), 3.88 (s, 3H), 2.35 (s, [C32H26NaO3SSe, M + Na]+: 593.0660, found: 593.0659.
3H); 13C NMR (150 MHz, CDCl3): δ 160.54, 151.99, 151.75,
4f: Yield 65% (74.6 mg); white solid; mp 159–161 °C; 1H
143.68, 139.20, 137.59, 136.92, 131.83, 129.86, 129.79, 129.10, NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.9 Hz, 1H), 7.73 (d, J =
128.75, 128.30, 128.07, 127.27, 126.30, 123.78, 120.01, 116.99, 7.9 Hz, 1H), 7.55 (d, J = 8.3 Hz, 1H), 7.48 (s, 1H), 7.38–7.26 (m,
114.32, 55.30, 21.56; HRMS (ESI) m/z calcd for 4H), 7.24 (s, 1H), 7.19–6.99 (m, 5H), 6.99–6.92 (m, 2H), 6.88 (d,
[C28H24NaO4SSe, M + Na]+: 559.0453, found: 559.0449.
J = 7.9 Hz, 2H), 6.57 (t, J = 8.5 Hz, 2H), 2.19 (s, 3H); 13C NMR
4a: Yield 59% (63.9 mg); white solid; mp 121–123 °C; 1H (100 MHz, CDCl3): δ 162.91 (d, J = 248.0 Hz), 159.30, 153.29,
NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.9 Hz, 1H), 7.73 (d, J = 143.93, 139.13, 139.05, 136.01, 134.91, 132.16, 132.07, 131.01,
7.9 Hz, 1H), 7.55 (d, J = 8.3 Hz, 1H), 7.50–7.38 (m, 3H), 7.34 (t, 128.87, 128.39, 128.30, 127.94, 127.21, 127.06, 123.53, 122.91,
J = 7.5 Hz, 1H), 7.30–7.22 (m, 3H), 7.18–6.94 (m, 10H), 6.89 (t, 121.95 (d, J = 3.0 Hz), 119.18, 115.49 (d, J = 22.0 Hz), 115.38,
J = 7.5 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 160.49, 113.97, 21.36; HRMS (ESI) m/z calcd for [C31H23FNaO3SSe, M +
153.27, 138.97, 137.06, 134.97, 132.92, 132.16, 130.32, 128.93, Na]+: 597.0409, found: 597.0411.
128.58, 128.38, 128.31, 128.22, 127.89, 127.17, 127.11,
4g: Yield 75% (88.5 mg); white solid; mp 158–160 °C; 1H
126.96, 123.60, 122.89, 119.21, 114.02; HRMS (ESI) m/z NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.9 Hz, 1H), 7.73 (d, J =
calcd for [C30H22NaO3SSe,
565.0349.
M
+
Na]+: 565.0347, found: 7.8 Hz, 1H), 7.56–7.47 (m, 2H), 7.37–7.22 (m, 5H), 7.18–7.00
(m, 5H), 6.99–6.78 (m, 6H), 2.19 (s, 3H); 13C NMR (100 MHz,
4b: Yield 64% (71.6 mg); white solid; mp 158–159 °C; 1H CDCl3): δ 158.98, 153.28, 144.02, 138.22, 135.89, 135.19,
NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.9 Hz, 1H), 7.76 (d, J = 134.94, 132.16, 132.14, 131.17, 128.89, 128.48, 128.45, 128.32,
8.0 Hz, 1H), 7.63–7.57 (m, 1H), 7.48–7.37 (m, 3H), 7.36–7.28 128.12, 127.30, 127.08, 125.22, 123.57, 122.87, 119.24, 114.03,
(m, 2H), 7.25 (d, J = 8.5 Hz, 1H), 7.18–6.95 (m, 8H), 6.90 (t, J = 21.38; HRMS (ESI) m/z calcd for [C31H23ClNaO3SSe, M + Na]+:
7.6 Hz, 2H), 6.75 (t, J = 8.4 Hz, 2H); 13C NMR (100 MHz, 613.0114, found: 613.0115.
CDCl3): δ 165.20 (d, J = 254.0 Hz), 160.49, 153.24, 137.04,
4h: Yield 61% (69.5 mg); white solid; mp 188–191 °C; 1H
135.32 (d, J = 2.0 Hz), 134.89, 132.24, 132.11, 131.21, 131.11, NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.9 Hz, 1H), 7.72 (d, J =
130.51, 128.95, 128.63, 128.48, 128.34, 127.98, 127.32, 127.20, 7.7 Hz, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.40 (s, 1H), 7.34–7.22 (m,
126.90, 123.76, 122.84, 119.06, 115.43 (d, J = 22.0 Hz), 113.81; 5H), 7.15–7.01 (m, 6H), 6.96 (t, J = 7.6 Hz, 1H), 6.87 (d, J =
HRMS (ESI) m/z calcd for [C30H21FNaO3SSe, M + Na]+: 8.2 Hz, 3H), 6.71 (t, J = 7.6 Hz, 1H), 2.18 (s, 3H), 2.16 (s, 3H);
583.0253, found: 583.0250.
13C NMR (100 MHz, CDCl3): δ 159.95, 153.16, 143.91, 142.74,
4c: Yield 76% (87.6 mg); white solid; mp 166–169 °C; 1H 138.89, 135.88, 135.28, 132.37, 131.97, 130.95, 129.48, 128.89,
NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.9 Hz, 1H), 7.77 (d, J = 128.83, 128.43, 128.27, 128.03, 127.94, 126.98, 126.93, 125.79,
8.0 Hz, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 123.52, 123.02, 119.27, 114.54, 23.21, 21.37; HRMS (ESI) m/z
7.38–7.30 (m, 3H), 7.27–7.23 (m, 1H), 7.18 (s, 1H), 7.13–7.03 calcd for [C32H26NaO3SSe,
(m, 7H), 7.01 (d, J = 7.7 Hz, 3H), 6.90 (t, J = 7.5 Hz, 2H); 13C 593.0662.
NMR (100 MHz, CDCl3): δ 161.00, 153.20, 139.58, 137.82,
M +
Na]+: 593.0660, found:
4i: Yield 66% (77.9 mg); white solid; mp 197–199 °C; 1H
137.07, 134.85, 132.33, 132.10, 130.27, 129.79, 129.01, 128.68, NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.8 Hz, 1H), 7.72 (d, J =
128.52, 128.46, 128.38, 128.05, 127.38, 127.22, 126.88, 123.82, 7.8 Hz, 1H), 7.59 (d, J = 8.2 Hz, 1H), 7.38 (s, 1H), 7.36–7.17 (m,
122.84, 119.07, 113.75; HRMS (ESI) m/z calcd for 7H), 7.17–7.01 (m, 5H), 6.97 (t, J = 7.7 Hz, 1H), 6.87 (d, J =
[C30H21ClNaO3SSe, M + Na]+: 598.9957, found: 598.9960.
7.9 Hz, 2H), 6.77 (t, J = 7.5 Hz, 1H), 2.18 (s, 3H); 13C NMR
4d: Yield 70% (86.9 mg); white solid; mp 110–111 °C; 1H (100 MHz, CDCl3): δ 159.25, 153.23, 143.97, 140.06, 139.59,
NMR (400 MHz, CDCl3): δ 7.79 (t, J = 7.7 Hz, 2H), 7.66 (d, J = 135.82, 134.96, 132.25, 132.12, 131.43, 130.57, 129.04, 128.84,
8.4 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 128.44, 128.23, 128.15, 127.79, 127.02, 126.48, 123.60, 123.13,
7.32–7.26 (m, 3H), 7.25–7.19 (m, 3H), 7.13–6.92 (m, 8H), 6.88 119.17, 114.11, 21.38; HRMS (ESI) m/z calcd for
(t, J = 7.5 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 160.78, [C31H23ClNaO3SSe, M + Na]+: 613.0114, found: 613.0113
153.31, 138.66, 137.03, 134.78, 132.24, 132.17, 131.43, 130.64,
4j: Yield 54% (68.5 mg); white solid; mp 189–191 °C; 1H
129.79, 128.97, 128.63, 128.51, 128.34, 128.10, 127.99, 127.41, NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.9 Hz, 1H), 7.72 (d, J =
127.17, 126.90, 123.77, 122.91, 118.98, 113.63; HRMS (ESI) m/z 7.7 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.37–7.23 (m, 9H), 7.15 (d,
calcd for [C30H21BrNaO3SSe, M + Na]+: 642.9452, found: J = 7.6 Hz, 1H), 7.12–7.05 (m, 3H), 6.87 (d, J = 7.9 Hz, 3H), 6.82
642.9449.
(t, J = 7.5 Hz, 1H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3):
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δ 159.42, 153.18, 144.03, 139.59, 135.75, 134.97, 132.42, 7.48–7.30 (m, 7H), 7.30–7.20 (m, 5H), 6.94 (d, J = 8.0 Hz, 3H),
132.29, 132.16, 131.72, 131.32, 130.51, 130.28, 128.90, 128.85, 6.80 (d, J = 7.7 Hz, 2H), 2.25 (s, 3H); 13C NMR (100 MHz,
128.49, 128.25, 128.21, 127.12, 127.06, 127.00, 123.61, 123.19, CDCl3): δ 155.60, 154.16, 146.43, 143.96, 137.63, 136.64,
119.23, 114.12, 21.38; HRMS (ESI) m/z calcd for 134.25, 132.34, 131.66, 130.73, 129.34, 129.13, 128.68, 128.47,
[C31H23BrNaO3SSe, M + Na]+: 656.9609, found: 656.9610.
128.32, 127.88, 127.66, 127.14, 126.78, 126.05, 124.35, 123.55,
4k: Yield 79% (90.0 mg); white solid; mp 187–189 °C; 1H 118.61, 111.07, 21.52; HRMS (ESI) m/z calcd for
NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.9 Hz, 1H), 7.72 (d, J = 7.8 [C31H24NaO4SSe, M + Na]+: 595.0453, found: 595.0458.
Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.39 (s, 1H), 7.36–7.22 (m, 5H),
7.07 (s, 5H), 6.92–6.71 (m, 6H), 2.18 (s, 3H), 2.02 (s, 3H); 13C
General procedure for the synthesis of compound 8
NMR (100 MHz, CDCl3): δ 160.27, 153.20, 143.90, 137.99, 137.73,
135.94, 135.04, 133.87, 132.18, 132.04, 130.25, 129.25, 128.92,
128.84, 128.44, 128.25, 128.05, 127.77, 126.97, 126.94, 126.73,
123.51, 123.00, 119.23, 114.18, 21.36, 20.79; HRMS (ESI) m/z
calcd for [C32H26NaO3SSe, M + Na]+: 593.0660, found: 593.0663.
4l: Yield 61% (72.0 mg); white solid; mp 183–185 °C; 1H
NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.9 Hz, 1H), 7.74 (d, J =
6.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.40 (s, 1H), 7.35–7.25 (m,
5H), 7.18–7.07 (m, 5H), 7.02 (d, 1H), 6.96 (s, 1H), 6.89 (t, J =
8.4 Hz, 3H), 6.83 (t, J = 7.8 Hz, 1H), 2.20 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 159.03, 153.28, 144.11, 136.68, 135.74,
134.97, 134.72, 133.54, 132.24, 132.08, 131.02, 129.29, 128.93,
128.76, 128.49, 128.37, 128.34, 128.17, 127.26, 127.12, 123.62,
122.82, 119.29, 113.95, 21.40; HRMS (ESI) m/z calcd for
[C31H23ClNaO3SSe, M + Na]+: 613.0114, found: 613.0113
A solution of 355.8 mg of KOH (6.34 mmol) in 5.0 mL of water
was added dropwise to 7 (0.2 mmol) in 10.0 mL of THF. After
5 h at room temperature, the mixture was extracted with EA.
The combined organic layers were dried with anhydrous
Na2SO4 and concentrated in vacuo. The crude product was pur-
ified by column chromatography on silica gel (PE : EA = 4 : 1)
to afford 8 as a white solid with a yield of 95% (76.0 mg); mp
1
167–168 °C; H NMR (400 MHz, CDCl3): δ 9.15 (d, J = 8.5 Hz,
1H), 7.92 (d, J = 8.1 Hz, 1H), 7.83 (d, J = 8.9 Hz, 1H), 7.80–7.68
(m, 4H), 7.66 (d, J = 8.9 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H),
7.55–7.44 (m, 4H), 7.14 (d, J = 8.0 Hz, 2H), 2.29 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 160.35, 151.91, 143.89, 139.45,
131.43, 130.82, 130.41, 129.55, 129.15, 129.01, 128.41, 127.74,
127.07, 126.99, 126.61, 126.11, 125.25, 119.95, 118.93, 111.82,
21.47; HRMS (ESI) m/z calcd for [C25H18NaO3S, M + Na]+:
421.0869, found: 421.0862.
1
4m: Yield 76% (96.4 mg); white solid; mp 189–191 °C; H
NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.9 Hz, 1H), 7.74 (d, J =
6.9 Hz, 1H), 7.45 (d, J = 7.5 Hz, 1H), 7.38 (s, 1H), 7.34–7.25 (m, General procedure for the synthesis of compound 9
5H), 7.24–7.05 (m, 7H), 6.96 (d, J = 7.7 Hz, 1H), 6.89 (d, J =
m-CPBA (1.2 mmol, 2.4 equiv.) was dissolved in 5 mL of CHCl3
8.0 Hz, 2H), 6.78 (t, J = 7.8 Hz, 1H), 2.20 (s, 3H); 13C NMR
and added to a solution of 3t (0.5 mmol, 1 equiv.) in 20 mL of
(100 MHz, CDCl3): δ 159.13, 153.26, 144.15, 139.48, 135.65,
135.36, 134.71, 132.27, 132.06, 131.63, 130.87, 129.60, 128.94,
128.66, 128.52, 128.34, 128.22, 127.28, 127.11, 123.63, 122.80,
CHCl3. After allowing to stand for 10 min at room temperature,
the solvent was removed under reduced pressure to afford a
residue. The residue was dissolved in 20 mL of THF, and then
5 mL of 1 M aqueous KOH solution was added dropwise to the
reaction mixture. After 1.5 h at room temperature, the mixture
was extracted with EA. The combined organic layers were dried
121.67, 119.34, 113.97, 21.41; HRMS (ESI) m/z calcd for
[C31H23BrNaO3SSe, M + Na]+: 656.9609, found: 656.9610.
4n: Yield 64% (75.7 mg); white solid; mp 203–204 °C; 1H
NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.9 Hz, 1H), 7.73 (d, J =
with anhydrous Na2SO4 and concentrated in vacuo. The crude
7.8 Hz, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.42–7.24 (m, 6H),
product was purified by column chromatography on silica gel
(PE : EA = 15 : 1) to afford 9 as a white solid with a yield of 76%
7.24–7.07 (m, 5H), 6.89 (d, J = 7.9 Hz, 2H), 6.82–6.69 (m, 2H),
6.69–6.60 (m, 1H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3):
(132 mg); mp 112–114 °C; 1H NMR (600 MHz, CDCl3):
δ 158.58 (d, J = 241.0 Hz), 158.30, 157.28 (d, J = 244.0 Hz),
δ 8.09–8.03 (m, 1H), 7.82 (d, J = 7.1 Hz, 2H), 7.58 (d, J = 8.1 Hz,
153.34, 144.21, 135.52, 134.77, 132.37, 132.01, 131.55, 128.94,
2H), 7.43–7.37 (m, 4H), 7.29–7.25 (m, 2H), 7.05 (d, J = 8.1 Hz,
128.54, 128.39, 128.30, 124.98, 124.74, 123.70, 122.83, 119.31,
118.31 (d, J = 8.0 Hz), 118.08 (d, J = 7.0 Hz), 115.97 (d, J = 8.0
2H), 2.21 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 158.70, 153.16,
144.08, 139.43, 130.78, 130.05, 129.51, 128.14, 128.10, 126.66,
Hz), 115.70 (d, J = 8.0 Hz), 113.86, 21.41; HRMS (ESI) m/z calcd
125.87, 125.47, 124.51, 121.62, 118.72, 111.36, 21.44; HRMS (ESI)
for [C31H22F2NaO3SSe, M + Na]+: 615.0315, found: 615.0313.
m/z calcd for [C21H16NaO3S, M + Na]+: 371.0712, found: 371.0717.
General procedure for the synthesis of compound 7
m-CPBA (0.6 mmol, 1.2 equiv.) was dissolved in 5.0 mL of
Conflicts of interest
CHCl3 and added to a solution of 3a (0.5 mmol, 1.0 equiv.) in
20.0 mL of CHCl3. After allowing to stand for 10 min at room
temperature, the solvent CHCl3 was removed under reduced
pressure and the residue was purified by column chromato-
graphy on silica gel (PE : EA = 1 : 10) to afford compound 7 as a
white solid with a yield of 89% (254.0 mg); mp 123–126 °C; 1H
There are no conflicts to declare.
Acknowledgements
NMR (400 MHz, CDCl3): δ 8.01 (d, J = 8.3 Hz, 1H), 7.80 (d, J = This study was supported by Fundamental Research Funds for
8.1 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), the Central Universities (2018CDYXYX0027), Chongqing
Org. Biomol. Chem.
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(2018-4-105).
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