Visible-Light-Mediated Alkylation of Thiophenols via Electron Donor-Acceptor Complexes Formed between Two Reactants

Article abstract of DOI:10.1021/acs.joc.1c01433

A metal-free, photocatalyst-free, photochemical system was developed for the direct alkylation of thiophenols via electron donor-acceptor (EDA) complexes (KEDA = 145 M-1) between two reactants, N-hydroxyphthalimide esters as acceptors and thiophenol anions as donors, in the presence of a tertiary amine. The EDA complexes in the reaction system have a broad range of visible-light absorption (400-650 nm) and can trigger the reaction effectively under sunlight.

Full text of DOI:10.1021/acs.joc.1c01433

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Visible-Light-Mediated Alkylation of Thiophenols via Electron
Donor−Acceptor Complexes Formed between Two Reactants
Yi-Ping Cai, Fang-Yuan Nie, and Qin-Hua Song*
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ABSTRACT: A metal-free, photocatalyst-free, photochemical system was
developed for the direct alkylation of thiophenols via electron donor−
acceptor (EDA) complexes (KEDA = 145 M−1) between two reactants, N-
hydroxyphthalimide esters as acceptors and thiophenol anions as donors,
in the presence of a tertiary amine. The EDA complexes in the reaction
system have a broad range of visible-light absorption (400−650 nm) and
can trigger the reaction effectively under sunlight.
thiolates are prone to inactivate transition metal catalysts, so
the ligands need to be specially designed and are often
sensitive to air. Although these problems have been alleviated
with other alternatives,4 the harsh conditions of a high
temperature and an excessively strong base (i.e., NaOtBu,
LiHMDS, or Grignard reagent) still inevitably restrict the
functional groups of substrates in the reaction.
In recent years, photocatalytic synthesis of sulfides has
attracted more attention by a single or a dual catalytic system
of transition metals or organic photocatalysts (PCs) (Scheme
1b).5,6 The S-alkylation of thiophenols was carried out with N-
hydroxyphthalimide (NHPI) ester as a typical alkylation
precursor.6 In the earliest work, Fu et al. developed
decarboxylative alkylation of thiophenols via a complex
between NHPI esters and inorganic base Cs2CO3.6a
ulfides are widely found in a variety of bioactive natural
Sproducts and commercial drugs, such as Torecan, Femstat,
Viracept, and Brilinta. According to an analysis of FDA-
approved drugs, sulfur is the third most frequently used
heteroatom after oxygen and nitrogen.1 Among them, aryl alkyl
sulfides are some of the common structural units and exhibit
diverse pharmacological activities after further structural
modification such as antiemetic, antifungal, antiviral, and
antiplatelet properties.2 Thus, the development of environ-
mentally friendly and economical methods for constructing
C−S bonds is of great importance in organic synthesis.
The traditional synthesis approach of sulfides is transition
metal-catalyzed cross-coupling between heteroatom-substi-
tuted aromatics and mercaptans (Scheme 1a).3 However,
Scheme 1. Approaches for the Synthesis of Aryl Sulfides
When two colorless or nearly colorless organic molecules are
put together, the appearance of strong color inspired Robert
Mulliken to put forward the charge transfer theory.7 The
association of an electron-rich substrate with an electron-poor
molecule can generate a new molecular aggregate, called an
electron donor−acceptor (EDA) complex8 or charge transfer
complex.9 The photochemical strategy based on the visible-
light-absorbing EDA complex is a cheap and environmentally
friendly organic synthesis method. The photochemistry of the
EDA complex has been attracting the interest of a growing
number of synthetic chemists.10
In this work, we developed a simple photochemical strategy
for the direct alkylation of thiophenols involving visible-light-
Received: June 17, 2021
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© XXXX American Chemical Society
A

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a
Scheme 2. Scope of the Decarboxylative Arylthiation
a
Reaction conditions: NHPI ester (0.3 mmol, 1.5 equiv), aryl thiol (1.0 equiv), DIPEA (0.6 equiv) in DMSO (2 mL), room temperature, N2, 8 h,
b
c
d
blue LEDs (420−450 nm), isolated yields. DMA as the solvent. On a 1 mmol scale. Sunlight irradiation for 2 h.
absorbing EDA complexes between two reactants, NHPI esters
and thiophenols (Scheme 1c).
with electron-donating groups (EDGs; OMe). This result
could be due to thiophenols with EWGs having lower pKa
values being deprotonated more easily in the presence of a
base. In addition, heteroaromatic and extended aromatic
thiophenols (9−12) were effectively adapted for this protocol
in >60% yields.
To optimize the reaction condition, tert-butyl NHPI ester
(1a) and 4-chlorothiophenol (2) were selected as the
substrates of the template reaction shown in Table S1. First,
among a series of organic bases being screened, including n-
butylamine (BuNH2), diethylamine [NH(Et)2], piperidine,
benzylamine (BnNH2), morpholine, diisopropyl ethylamine
(DIPEA), piperazine, and triethylamine (NEt3), DIPEA is the
most efficient (80%, entry 8), and the second most efficient is
NEt3 (74%, entry 7). We found that the effective bases are
tertiary (entries 7 and 8) amines, while primary or secondary
amines are ineffective (entries 1−3); only aminolysis products
were observed due to a direct aminolysis between the active
esters and primary or secondary amines. Furthermore, the dose
of the bases, DIPEA and NEt3, was optimized, 0.6 equiv as the
largest doses for both bases (96% for DIPEA, entry 17, and
78% for NEt3, entry 11). Next, we performed this reaction in
four other solvents, 1,4-dioxane, dimethylacetamide (DMA),
dimethylformamide (DMF), and acetonitrile. Among them,
DMA and DMF gave excellent (94%, entry 25 in Table S1)
and good (79%, entry 26 in Table S1) yields, respectively.
Finally, control experiments show that both a base (entry 28)
and blue light (entry 29) are necessary for the arylthiation
reaction. In addition, the reaction can still work effectively
(80% yield) in an air atmosphere (entry 30). This implies that
the reaction is insensitive to oxygen and water.
Next, various NHPI active esters (1a−m, shown in Chart
S1) were prepared, including primary (1b and 1e−g) and
secondary (1d and 1h−j) aliphatic carboxylic acids, α-amino
acids (1k and 1l), and tertiary (1a and 1c) aliphatic carboxylic
acids. These reaction partners are all compatible in the reaction
with thiophenols to afford the desired arylthiation products. In
addition, a wide range of functional groups, including carbonyl
(12−14), terminal alkene (15), aryl bromide (16 and 17), and
amide (19−26) groups, were tolerated under our reaction
conditions, exhibiting the excellent compatibility. Only a few
benzylic carboxylic acid esters have previously been reported to
generate benzylation products in the absence of metal
catalysts.11,12 Ibuprofen, an anti-inflammatory agent, also
resulted in the formation of the desired product 18 in 37%
yield. Because of its poor solubility in DMSO, product 15 was
obtained in a low yield of 41% from the NHPI ester bearing a
terminal alkene in DMA, presumably due to a certain degree of
solubility. To our delight, piperidine-derived esters showed
good reactivity and provided a series of α-, β-, and γ-amino
arylthiation products (19−24) in excellent yields. Further-
more, the NHPI esters derived from N-Boc-protected natural
amino acids, alanine and methionine, afforded the correspond-
ing α-amino arylthiation products 25 and 26 in 93% and 66%
yields, respectively. In addition, a series of heteroaromatic
sulfides (29−33) with N-heterocycles, which were generally
bioactive building blocks in pharmaceutical intermediates,13
were obtained by this method. For a 1 mmol scale, the strategy
can give the desired product 22 in 82% yield. The results
demonstrated the scalability of this strategy.
Under the optimized reaction conditions described above,
we evaluated a range of substrates for decarboxylative
arylthiation of NHPI esters with thiophenols (Scheme 2).
First, for the thiophenol partner, we explored the scope of
readily available thiophenols with various substituents,
including fluoride, chloride, bromide, methyl, and methoxyl,
which react with cyclohexyl NHPI esters to give the
corresponding aryl alkyl sulfides in moderate to excellent
yields. Generally, thiophenols with electron-withdrawing
groups (EWGs; F, Cl, and Br) afford higher yields than that
To explore the mechanism, we measured UV/vis absorption
spectra of reaction components at the same ratio as in the
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Figure 1. (a) UV/vis absorption spectra of 1a (1.5 equiv), 4-chlorothiophenol 2 (20 mM, 1.0 equiv), and DIPEA (0.6 equiv) in DMSO. (b) Partial
1H NMR spectra (500 MHz, DMSO-d6) of 2 (50 mM, 1.0 equiv) and 1a (1.5 equiv) with or without DIPEA (0.6 equiv).
reaction (Figure 1a for a low concentration of 2 and Figure S2
for high concentrations of 2). At all three concentrations, there
is almost no absorption beyond 400 nm for either individual or
two components of the reaction. An obvious red-shift was
observed in the solution of 2 with DIPEA, possibly resulting
from the formation of the deprotonated thiophenol anion
(Figure 1a).
Scheme 3. Control Experiments for the Mechanistic Study
Upon addition of 1a to a solution of 2 with DIPEA, we
observed a remarkable red-shift of the absorption onset tailed
into the visible-light region (Figure 1a). The red-shift could be
due to the formation of an electron donor−acceptor (EDA)
complex between the electron-rich thiophenol anion and the
electron-poor NHPI ester. A larger red-shift (400−650 nm) in
the absorption spectrum of the reaction system was observed
(Figure S2ab), accompanied by a change from colorless to
reddish brown (insets of Figure 1a and Figure S2c).
1H NMR spectra provide further support for the formation
of the EDA complex. Consistent with the results presented
1
above, the intensity of the partial H NMR proton signal of
-SH significantly decreased and the aromatic hydrogen peaks
of 2 shift to high field after the addition of 0.6 equiv of DIPEA
(Figure 1b). When 1a, 2, and the base DIPEA are present, the
aromatic proton signal for 1a shifts to the high field and that of
2 to the low field in the 1H NMR spectrum (Figure 1b), which
is consistent with the NHPI ester being the electron acceptor
and thiophenol anion being the electron donor. The
association constant (KEDA) of the EDA complex was
estimated to be 145 M−1 (details provided in the Supporting
Information). The value is much higher than the reported
values (0.9 0.1,14a 22,14b and 8.4 M−114c), implying there is a
strong charge transfer interaction between the NHPI ester and
the thiophenol anion. A thiophenol anion can also associate
with a benzene halide to form an EDA complex.15
To confirm a radical pathway in this reaction, a radical clock
experiment and a radical-trapping experiment were performed
and the results are shown in Scheme 3. The radical clock
experiment with cyclopropyl methyl NHPI ester showed that a
ring-opened product 15 was obtained in 54% yield but no
expected cyclopropyl sulfide was detected (Scheme 3a). This
indicates the formation of alkyl radical in the reaction process.
For the radical-trapping experiment with TEMPO, a radical-
trapping agent, the expected reaction was inhibited completely,
and the captured compound tert-butyl radical was obtained in
58% yield (Scheme 3b). Meanwhile, radical-trapping adducts
of both 4-chlorothiophenol radical and tert-butyl radical by
TEMPO were observed by HPLC-FTMS of the reaction
solution (Figure S3). These results further confirm the
involvement of sulfur radical and alkyl radical in the
arylthiation process.
To further explore the role of DIPEA, sodium 4-
chlorobenzenethiolate was employed to replace 4-chlorothio-
phenol and DIPEA (Scheme 3c). Interestingly, the reaction
can also work, and product 27 was obtained in 22% yield.
Compared with the optimization condition (96% in Table S1,
entry 17), the low yield could be due to the low solubility of 4-
chlorobenzenethiolate salt in DMA. Thus, the role of DIPEA
in the alkylation is to promote the deprotonation of
thiophenols as a base. The quantum yield of the decarbox-
ylative arylthiation was measured to be 0.053 (details in the
Supporting Information), suggesting a closed catalytic cycle
rather than a radical chain process.
On the basis of the mechanistic studies mentioned above, we
propose a visible-light-mediated S-alkylation reaction via an
EDA complex, which forms between two reactants (Scheme
4). First, thiophenol (ArSH) deprotonates in the presence of a
tertiary amine (NR′3), generating a thiophenol anion (ArS−)
and an amine cation (HN+R′3). The electron-rich ArS− can
interact with the electron-poor NHPI ester to form the EDA
complex, which can absorb visible light (400−650 nm). Under
visible-light irradiation, a single-electron transfer (SET)
process occurs from ArS− to the NHPI ester in the EDA
complex, generating thiophenol radical (ArS•) and the ester
radical anion. The latter cleaves to give alkyl radical (R•), CO2,
and phthalimide anion, which is protonated by the amine
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until the acid was consumed (monitored by TLC). After the reaction
had reached completion, the mixture was filtered over Celite and
rinsed with additional CH2Cl2. Then the precipitate was filtered off,
and the solution was concentrated under vacuum. The corresponding
NHPI esters were further purified by column chromatography on
silica gel.
Scheme 4. Mechanism for the Photochemical Alkylation of
Thiophenols
General Procedure for the Photomediated Arylthiation Reac-
tion. NHPI esters (1.5 equiv) and aryl thiol (1.0 equiv) (if solid) were
added to a 10 mL transparent Schlenk tube equipped with a stirring
bar. The tube was evacuated and refilled with nitrogen (N2) three
times. Then, DMSO (0.1 M), DIPEA (0.6 equiv), and aryl thiol (1.0
equiv) (if liquid) were added via a gastight syringe under a nitrogen
atmosphere. Afterward, the tube was sealed, and the reaction mixture
was stirred under irradiation with a blue LED (420−450 nm,
approximately 3.0 cm from the bulb) at room temperature for 8 h.
The reaction mixture was washed with water and extracted with ethyl
acetate (3 × 10 mL) to remove DMSO. The organic layers were
combined and concentrated under vacuum. The desired product was
purified by flash column chromatography on silica gel.
cation (HN+R′3) to regenerate NR′3 because the pKa of the
phthalimide anion is higher (13.4 in DMSO) than that of a
tertiary amine such as 9 for NEt3.16 Finally, the coupling of two
radicals, ArS• and R•, produces the desired sulfide, ArSR.
In addition, the reaction was carried out under solar light.
Sulfide 27 can be obtained in a high yield of 87% under
sunlight irradiation for 2 h (Table S2; the irradiation time was
not optimized). This result shows the feasibility of utilizing
solar energy to produce aryl alkyl sulfides.
In summary, we have developed a metal-free, photocatalyst-
free, visible-light-mediated decarboxylative alkylation of
thiophenols with NHPI esters in the presence of an organic
base. The approach not only can avoid the use of transition
metals and excessive base but also can utilize green energy,
solar light. Therefore, the alkylation of thiophenols is an
economical and green method for the synthesis of aryl sulfides.
Sunlight-Driven Reaction. The reaction mixture was set up on the
roof of the laboratory according to the general procedure described
above. Four parallel samples were prepared for the irradiation of
sunlight. 4-Chlorothiophenol 2 (0.1 mmol), NHPI esters 1a (0.15
mmol), DIPEA (0.06 mmol), and anhydrous DMSO (1 mL) were
added to the Schlenk tube and exposed to natural-light irradiation on
the roof of the laboratory at the University of Science and Technology
of China from 10:00 a.m. to 14:00 p.m. on May 1, 2021, on a partially
cloudy day with outdoor temperatures of 22−26 °C. The reaction of
one sample was terminated every 1 h for the yield analysis.
Cyclohexyl (4-Fluorophenyl) Sulfide (3).18 NHPI ester 1d (82.0
mg, 0.3 mmol) and 4-fluorothiophenol (25.6 mg, 0.2 mmol) in
DMSO (2 mL) were irradiated in the presence of DIPEA (15.5 mg,
0.12 mmol) to afford compound 3 (41.6 mg, 99%) as a colorless oil.
1
The eluent was petroleum ether. H NMR (500 MHz, CDCl3): δ
7.41−7.38 (m, 2H), 7.00−6.97 (m, 2H), 2.98 (m, 1H), 1.95−1.93
(m, 2H), 1.77−1.65 (m, 2H), 1.62−1.60 (m, 1H), 1.36−1.19 (m,
5H). 13C{1H} NMR (100 MHz, CDCl3): δ 163.5, 161.0, 135.0, 129.8,
115.9, 115.7, 47.6, 33.3, 26.0, 25.7. 19F NMR (375 MHz, CDCl3): δ
−114.9.
EXPERIMENTAL SECTION
■
Materials and General Methods. All aryl thiols and solvents
were obtained from commercial suppliers and used without further
purification unless otherwise stated. Anhydrous DMSO was
purchased from Energy Chemical and added to molecular sieves
(4-Chlorophenyl)(cyclohexyl) Sulfide (4).18 NHPI ester 1d (82.0
mg, 0.3 mmol) and 4-chlorothiophenol (28.9 mg, 0.2 mmol) in
DMSO (2 mL) were irradiated with DIPEA (15.5 mg, 0.12 mmol) to
obtain compound 4 as a colorless oil in 97% (44.0 mg) yield. The
during use and stored at room temperature. The H and 13C{1H}
1
NMR spectra were recorded on a Bruker Ascend 400 MHz
1
1
eluent was petroleum ether. H NMR (500 MHz, CDCl3): δ 7.33−
spectrometer (400 MHz for H NMR and 100 MHz for 13C NMR)
1
7.31 (m, 2H), 7.26−7.24 (m, 2H), 3.08−3.03 (m, 1H), 1.97−1.95
(m, 2H), 1.78−1.76 (m, 2H), 1.63−1.61 (m, 1H), 1.38−1.22 (m,
5H). 13C{1H} NMR (125 MHz, CDCl3): δ 133.6, 133.2, 132.6, 128.9,
46.8, 33.2, 26.0, 25.7.
or on a Bruker Ascend 500 MHz spectrometer (500 MHz for H
1
NMR and 125 MHz for 13C NMR). The chemical shifts (δ) for H
and 13C are reported in parts per million and are referenced to Me4Si
(TMS) and the residual undeuterated solvent resonances (TMS at
(4-Bromophenyl)(cyclohexyl) Sulfide (5).19 This compound was
prepared by NHPI ester 1d (82.0 mg, 0.3 mmol) and 4-
bromothiophenol (37.8 mg, 0.2 mmol) with DIPEA (15.5 mg, 0.12
mmol) in DMSO (2 mL) under irradiation to afford a 85% (45.9 mg)
1
0.00 ppm; CHCl3 at 7.26 ppm for H NMR and 77.16 ppm for 13C
1
NMR; DMSO at 2.50 ppm for H NMR and 39.52 ppm for 13C
NMR). All UV/vis absorption spectra were recorded in 1 cm path
length quartz cuvettes on a Shimadzu UV-2450 UV/vis spectropho-
tometer. High-resolution mass spectra (HRMS) were recorded using
a Q-Exactive plus hybrid quadrupole-orbitrap mass spectrometer (Q-
Orbitrap MS) (Thermo Scientific, San Jose, CA) with an electrospray
ionization (ESI) source or atmospheric-pressure chemical ionization
(APCI) source. A blue LED (an inner diameter of 9.5 cm, 420−450
nm, 45 W), purchased from Xuzhou Aijia Electronic Technology
Company Ltd., was employed as a visible-light source without the use
of filters. The emission spectrum of the lamp is shown in Figure S1.
Synthesis and Characterization of Related Compounds.
General Procedure for the Synthesis of N-Hydroxyphthalimide
(NHPI) Esters. N-Hydroxyphthalimide (NHPI) esters were prepared
according to previously reported procedures.17 In short, carboxylic
acid (10 mmol, 1.0 equiv), N-hydroxyphthalimide (11 mmol, 1.1
equiv), dimethylaminopyridine (DMAP) (1.0 mmol, 0.1 equiv), and
dichloromethane (100 mL, 0.1 M) were placed in a 250 mL round-
bottom flask equipped with a stirring bar. After that, N,N′-
diisopropylcarbodiimide (DIC) (11 mmol, 1.1 equiv) was added
dropwise via syringe and the mixture was stirred at room temperature
1
yield as a colorless oil. The eluent was petroleum ether. H NMR
(500 MHz, CDCl3): δ 7.41−7.38 (m, 2H), 7.26−7.23 (m, 2H),
3.10−3.04 (m, 1H), 1.97−1.95 (m, 2H), 1.77−1.76 (m, 2H), 1.63−
1.60 (m, 1H), 1.39−1.23 (m, 5H). 13C{1H} NMR (125 MHz,
CDCl3): δ 134.4, 133.4, 131.8, 120.6, 46.7, 33.2, 26.0, 25.7.
Cyclohexyl (Phenyl) Sulfide (6).18 This compound was prepared by
NHPI ester 1d (82.0 mg, 0.3 mmol) and thiophenol (22.0 mg, 0.2
mmol) in the presence of DIPEA (15.5 mg, 0.12 mmol) in DMSO (2
mL) under irradiation in 83% (31.9 mg) yield as a colorless oil. The
1
eluent was petroleum ether. H NMR (500 MHz, CDCl3): δ 7.40−
7.38 (m, 2H), 7.29−7.25 (m, 2H), 7.22−7.19 (m, 1H), 3.12−3.07
(m, 1H), 1.99−1.97 (m, 2H), 1.79−1.76 (m, 2H), 1.63−1.60 (m,
1H), 1.41−1.23 (m, 5H). 13C{1H} NMR (125 MHz, CDCl3): δ
135.2, 131.9, 128.7, 126.6, 46.6, 33.3, 26.1, 25.8.
Cyclohexyl (p-Tolyl) Sulfide (7).18 NHPI ester 1d (82.0 mg, 0.3
mmol) and 4-methylthiophenol (24.8 mg, 0.2 mmol) were irradiated
in the presence of DIPEA (15.5 mg, 0.12 mmol) in DMSO (2 mL) to
provide compound 7 (36.7 mg, 89%) as a colorless oil. The eluent
D
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was petroleum ether. 1H NMR (500 MHz, CDCl3): δ 7.31 (d, J = 7.8
Hz, 2H), 7.09 (d, J = 7.8 Hz, 2H), 3.03−2.99 (m, 1H), 2.32 (s, 3H),
1.97−1.94 (m, 2H), 1.75−1.59 (m, 2H), 1.59 (m, 1H), 1.37−1.21
(m, 5H). 13C{1H} NMR (125 MHz, CDCl3): δ 136.9, 132.8, 131.2,
129.5, 47.1, 33.4, 26.1, 25.8, 21.1.
13C{1H} NMR (125 MHz, DMSO-d6): δ 206.9, 135.6, 130.8, 130.1,
129.5, 42.5, 30.2, 26.7.
But-3-en-1-yl (4-Chlorophenyl) Sulfide (15).24 Compound 15 was
obtained by NHPI ester 1f (73.6 mg, 0.3 mmol) and 4-
chlorothiophenol (28.9 mg, 0.2 mmol) in the presence of DIPEA
(15.5 mg, 0.12 mmol) in DMA (2 mL) under irradiation to afford
41% (16.3 mg) yield as a colorless liquid. The eluent was petroleum
ether. 1H NMR (500 MHz, CDCl3): δ 7.27−7.24 (m, 4H), 5.86−5.79
(ddt, J = 17.0, 10.3, 6.7 Hz, 1H), 5.05−5.10 (m, 2H), 2.59 (t, J = 7.5
Hz, 2H), 2.59 (q, J = 7.5 Hz, 2H). 13C{1H} NMR (125 MHz,
CDCl3): δ 136.1, 135.0, 131.9, 130.6, 129.0, 116.4, 33.3, 33.2.
(4-Bromophenethyl)(4-chlorophenyl) Sulfide (16). Compound 16
was obtained by NHPI ester 1g (112.3 mg, 0.3 mmol) and 4-
chlorothiophenol (28.9 mg, 0.2 mmol) with DIPEA (15.5 mg, 0.12
mmol) in DMSO (2 mL) in 82% (53.7 mg) yield as a yellow oil. The
Cyclohexyl (4-Methoxyphenyl) Sulfide (8).19 NHPI ester 1d (82.0
mg, 0.3 mmol), 4-methoxythiophenol (28.0 mg, 0.2 mmol), and
DIPEA (15.5 mg, 0.12 mmol) were irradiated in DMSO (2 mL) to
provide compound 8 (28.9 mg, 65%) as a yellow oil. The eluent was
petroleum ether. 1H NMR (500 MHz, CDCl3): δ 7.40−7.37 (m, 2H),
6.86−6.83 (m, 2H), 3.80 (s, 3H), 2.92−2.88 (m, 1H), 1.94−1.92 (m,
2H), 1.76−1.74 (m, 2H), 1.61−1.59 (m, 1H), 1.34−1.19 (m, 5H).
13C{1H} NMR (125 MHz, CDCl3): δ 159.3, 135.7, 124.9, 114.3, 55.3,
47.9, 33.4, 26.2, 25.8.
2-(Cyclohexylthio) Benzo[d]thiazole (9).20 This compound was
prepared by NHPI ester 1d (82.0 mg, 0.3 mmol) and 2-
mercaptobenzothiazole (33.4 mg, 0.2 mmol) with DIPEA (15.5 mg,
0.12 mmol) in DMSO (2 mL) under irradiation in 45.4 mg (91%)
yield as a yellow solid. The eluent was a 30/1 petroleum ether/ethyl
acetate mixture. 1H NMR (500 MHz, CDCl3): δ 7.88 (d, J = 7.8 Hz,
1H), 7.74 (d, J = 7.8 Hz, 1H), 7.40 (td, J = 7.8, 1.1 Hz, 1H), 7.28 (td,
J = 7.8, 1.1 Hz, 1H), 3.92−3.88 (m, 1H), 2.21−2.18 (m, 2H), 1.82−
1.78 (m, 2H), 1.66−1.55 (m, 3H), 1.51−1.43 (m, 2H), 1.37−1.25
(m, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ 166.5, 153.4, 135.3,
125.9, 124.2, 121.6, 120.9, 47.3, 33.3, 25.8, 25.6.
1
eluent was a 30/1 petroleum ether/ethyl acetate mixture. H NMR
(400 MHz, CDCl3): δ 7.40 (d, J = 8.3 Hz, 2H), 7.25−7.24 (m, 4H),
7.04 (d, J = 8.3 Hz, 2H), 3.10 (t, J = 7.6 Hz, 2H), 2.84 (t, J = 7.6 Hz,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ 138.8, 134.6, 132.2, 131.6,
130.8, 130.3, 129.1, 120.4, 35.3, 34.9. HRMS (APCI) m/z: [M]+
calcd for C14H12ClBrS+ 325.9532, found 325.9533.
(4-Bromophenethyl)(4-bromophenyl) Sulfide (17). NHPI ester 1g
(112.3 mg, 0.3 mmol) and 4-bromothiophenol (37.8 mg, 0.2 mmol)
were irradiated with DIPEA (15.5 mg, 0.12 mmol) in DMSO (2 mL)
to provide compound 17 (61.0 mg, 82%) as a yellow oil. The eluent
2-(Cyclohexylthio) Pyridine (10).19 NHPI ester 1d (82.0 mg, 0.3
mmol) and 4-mercaptopyridine (22.2 mg, 0.2 mmol) were irradiated
in the presence of DIPEA (15.5 mg, 0.12 mmol) in DMSO (2 mL) to
obtain compound 10 (32.9 mg, 85%) as a yellow solid. The eluent
1
was a 30/1 petroleum ether/ethyl acetate mixture. H NMR (400
MHz, CDCl3): δ 7.41−7.38 (m, 4H), 7.19−7.17 (m, 2H), 7.04 (d, J =
8.3 Hz, 2H), 3.10 (t, J = 7.6 Hz, 2H), 2.85 (t, J = 7.6 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 138.8, 135.3, 132.0, 131.6,
130.9, 130.3, 120.4, 120.0, 35.1, 34.9. HRMS (APCI) m/z: [M]+
calcd for C14H12Br2S+ 369.9026, found 369.9027.
1
was a 30/1 petroleum ether/ethyl acetate mixture. H NMR (500
MHz, CDCl3): δ 8.39 (d, J = 5.8 Hz, 2H), 7.13 (d, J = 5.8 Hz, 2H),
3.38−3.33 (m, 1H), 2.08−2.05 (m, 2H), 1.81 (m, 2H), 1.66 (m, 1H),
1.48−1.31 (m, 5H). 13C{1H} NMR (125 MHz, CDCl3): δ 149.2,
148.7, 121.8, 43.4, 32.9, 25.9, 25.6.
(4-Chlorophenyl)[1-(4-isobutylphenyl)ethyl] Sulfide (18). NHPI
ester 1m (105.4 mg, 0.3 mmol), 4-chlorothiophenol (28.9 mg, 0.2
mmol), and DIPEA (15.5 mg, 0.12 mmol) in DMSO (2 mL) were
irradiated to afford compound 18 (22.6 mg, 37%) as a yellow oil. The
Cyclohexyl (Naphthalen-2-yl) Sulfide (11).3f Compound 11 was
prepared by NHPI ester 1d (82.0 mg, 0.3 mmol) and 2-
naphthalenethiol (32.0 mg, 0.2 mmol) in the presence of DIPEA
(15.5 mg, 0.12 mmol) to obtain 82% (39.7 mg) yield as a colorless oil.
The eluent was petroleum ether. 1H NMR (500 MHz, CDCl3): δ 7.85
(m, 1H), 7.79−7.73 (m, 3H), 7.48−7.41 (m, 3H), 3.22 (m, 1H),
2.04−2.00 (m, 2H), 1.80−1.76 (m, 2H), 1.64−1.60 (m, 1H), 1.45−
1.22 (m, 5H). 13C{1H} NMR (125 MHz, CDCl3): δ 133.7, 132.6,
132.1, 130.2, 129.6, 128.2, 127.7, 127.2, 126.4, 125.8, 46.5, 33.4, 26.0,
25.8.
1
eluent was a 50/1 petroleum ether/ethyl acetate mixture. H NMR
(500 MHz, CDCl3): δ 7.16−7.14 (m, 6H), 7.05−7.03 (m, 2H), 4.28
(q, J = 6.9 Hz, 1H), 2.43 (d, J = 7.1 Hz, 2H), 1.83−1.80 (m, 1H),
1.61 (d, J = 6.9 Hz, 3H), 0.88 (d, J = 6.5 Hz, 1H). 13C{1H} NMR
(125 MHz, CDCl3): δ 140.8, 140.0, 134.1, 133.7, 133.4, 129.2, 128.8,
127.1, 48.1, 45.1, 30.2, 22.4, 22.1. HRMS (ESI) m/z: [M − H]− calcd
for C18H20ClS− 303.0980, found 303.0982.
tert-Butyl 2-[(4-Chlorophenyl)thio] Piperidine-1-carboxylate
(19). Compound 19 was prepared from NHPI ester 1h (112.3 mg,
0.3 mmol) and 4-chlorothiophenol (28.9 mg, 0.2 mmol) in the
presence of DIPEA (15.5 mg, 0.12 mmol) in DMSO (2 mL) under
irradiation in 80% (52.4 mg) yield as a yellow oil. The eluent was a
30/1 petroleum ether/ethyl acetate mixture. The product gives two
sets of NMR signals at an approximate ratio of 4/5, due to there being
conformational isomers of tertiary amines. 1H NMR (500 MHz,
CDCl3): δ 7.41 (m, 2H), 7.27−7.20 (m, 2H), 6.03−5.74 (m, 1H),
4.05−3.84 (m, 1H), 3.29−3.23 (td, J = 13.0, 2.6 Hz, 1H), 1.95 (m,
1H), 1.90−1.81 (m, 2H), 1.72−1.67 (m, 2H), 1.46−1.44 (m, 1H),
1.30 (s, 4H), 1.19 (s, 5H). 13C{1H} NMR (125 MHz, CDCl3): δ
154.0, 153.7, 136.3, 135.4, 134.4, 133.9, 132.3, 132.1, 129.2, 129.0,
80.1, 64.3, 62.0, 39.4, 38.0, 31.1, 30.3, 28.3, 28.0, 25.4, 19.8. HRMS
(ESI) m/z: [M + Na]+ calcd for C16H22ClNO2NaS+ 350.0952, found
350.0948.
4-(Naphthalen-2-ylthio)butan-2-one (12).21 This compound was
prepared by NHPI ester 1e (78.4 mg, 0.3 mmol) and 2-
naphthalenethiol (32.0 mg, 0.2 mmol) with DIPEA (15.5 mg, 0.12
mmol) in DMSO (2 mL) under irradiation in 67% (30.9 mg) yield as
an orange solid. The eluent was petroleum ether. 1H NMR (500
MHz, CDCl3): δ 7.80−7.74 (m, 4H), 7.49−7.40 (m, 3H), 3.23 (t, J =
7.3 Hz, 2H), 2.80 (t, J = 7.3 Hz, 2H), 2.14 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ 206.6, 133.7, 133.1, 131.9, 128.6, 127.7, 127.5,
127.3, 127.1, 126.6, 125.8, 43.0, 30.1, 27.3.
4-[(4-Fluorophenyl)thio]butan-2-one (13).22 NHPI ester 1e (78.4
mg, 0.3 mmol) and 4-fluorothiophenol (25.6 mg, 0.2 mmol) were
irradiated in the presence of DIPEA (15.5 mg, 0.12 mmol) in DMSO
(2 mL) to afford compound 13 (34.1 mg, 86%) as a yellow oil. The
1
eluent was a 20/1 petroleum ether/ethyl acetate mixture. H NMR
(500 MHz, CDCl3): δ 7.37−7.34 (m, 2H), 7.02−6.99 (m, 2H), 3.08
(t, J = 7.3 Hz, 2H), 2.72 (t, J = 7.3 Hz, 2H), 2.14 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3): δ 206.5, 163.0, 161.0, 132.8, 132.7, 130.5,
116.2, 116.1, 43.1, 30.1, 28.9. 19F NMR (375 MHz, CDCl3): δ
−115.1.
tert-Butyl 3-[(4-Fluorophenyl)thio] Piperidine-1-carboxylate
(20). NHPI active ester 1i (112.3 mg, 0.3 mmol), 4-fluorothiophenol
(25.6 mg, 0.2 mmol), and DIPEA (15.5 mg, 0.12 mmol) in DMSO (2
mL) were irradiated to afford 20 (61.7 mg, 99%) as a yellow oil. The
1
eluent was a 20/1 petroleum ether/ethyl acetate mixture. H NMR
4-[(4-Chlorophenyl)thio]butan-2-one (14).23 NHPI ester 1e (78.4
mg, 0.3 mmol) and 4-chlorothiophenol (28.9 mg, 0.2 mmol) were
irradiated with DIPEA (15.5 mg, 0.12 mmol) in DMSO (2 mL) to
obtain compound 14 (32.6 mg, 76%) as a yellow solid. The eluent
(500 MHz, CDCl3): δ 7.44−7.41 (m, 2H), 7.02−6.99 (m, 2H), 4.04
(br, 1H), 3.87−3.85 (m, 1H), 3.10−2.98 (m, 1H), 2.86−2.79 (m,
2H), 2.08−2.05 (m, 1H), 1.77−1.73 (m, 1H), 1.53−1.44 (m, 2H),
1.41 (s, 9H). 13C{1H} NMR (125 MHz, CDCl3): δ 163.4, 161.4,
154.4, 134.9, 128.7, 116.1, 116.0, 79.6, 49.6, 44.8, 43.9, 30.9, 28.4,
25.1. 19F NMR (375 MHz, CDCl3): δ −114.2. HRMS (ESI) m/z: [M
+ Na]+ calcd for C16H22FNO2NaS+ 334.1247, found 334.1243.
1
was a 30/1 petroleum ether/ethyl acetate mixture. H NMR (500
MHz, DMSO-d6): δ 7.37 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.3 Hz,
2H), 3.10 (t, J = 7.0 Hz, 2H), 2.77 (t, J = 7.0 Hz, 2H), 2.10 (s, 3H).
E
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Note
tert-Butyl 3-[(4-Chlorophenyl)thio] Piperidine-1-carboxylate
(21). NHPI ester 1i (112.3 mg, 0.3 mmol) and 4-chlorothiophenol
(28.9 mg, 0.2 mmol) in the presence of DIPEA (15.5 mg, 0.12 mmol)
were irradiated and isolated to give 21 (61.0 mg, 93%) as a yellow oil.
tert-Butyl (4-Chlorophenyl) Sulfide (27).26 Active ester 1a (74.2
mg, 0.3 mmol) and 4-chlorothiophenol (28.9 mg, 0.2 mmol) in
DMSO (2 mL) were irradiated in the presence of DIPEA (15.5 mg,
0.12 mmol), and compound 27 (38.1 mg, 95%) was obtained as a
1
1
The eluent was a 10/1 petroleum ether/ethyl acetate mixture. H
yellow oil. The eluent was petroleum ether. H NMR (500 MHz,
NMR (400 MHz, CDCl3): δ 7.36−7.34 (m, 2H), 7.28−7.26 (m, 2H),
4.06 (br, 1H), 3.88−3.85 (m, 1H), 3.10−3.06 (m, 1H), 2.86−2.83
(m, 2H), 2.09−2.07 (m, 1H), 1.74 (m, 1H), 1.57−1.49 (m, 2H), 1.42
(s, 9H). 13C{1H} NMR (100 MHz, CDCl3): δ 154.4, 133.2, 132.7,
131.0, 129.1, 79.7, 49.8, 49.4, 44.1, 30.8, 28.4, 25.1. HRMS (ESI) m/
z: [M + Na]+ calcd for C16H22ClNO2NaS+ 350.0952, found 350.0949.
tert-Butyl 3-[(4-Bromophenyl)thio] Piperidine-1-carboxylate
(22). NHPI ester 1i (112.3 mg, 0.3 mmol), 4-bromothiophenol
(37.8 mg, 0.2 mmol), and DIPEA (15.5 mg, 0.12 mmol) in DMSO
were irradiated and isolated to afford 22 (66.3 mg, 89%) as a yellow
oil. The eluent was a 20/1 petroleum ether/ethyl acetate mixture. 1H
NMR (500 MHz, CDCl3): δ 7.43−7.41 (m, 2H), 7.29−7.27 (m, 2H),
4.07 (m, 1H), 3.88−3.84 (m, 1H), 3.12−3.07 (m, 1H), 2.90−2.81
(m, 2H), 2.09−2.06 (m, 1H), 1.78−1.74 (m, 1H), 1.57−1.45 (m,
2H), 1.42 (s, 9H). 13C{1H} NMR (125 MHz, CDCl3): δ 154.4,
133.3, 133.1, 132.0, 121.1, 79.7, 49.6, 43.9, 30.8, 28.4, 25.1. HRMS
(ESI) m/z: [M + Na]+ calcd for C16H22BrNO2NaS+ 394.0447, found
394.0442.
CDCl3): δ 7.45 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 1.27 (s,
9H). 13C{1H} NMR (125 MHz, CDCl3): δ 138.6, 135.1, 131.2, 128.6,
46.1, 30.8.
1-Adamantyl (4-Chlorine) Phenyl Sulfide (28).27 NHPI ester 1c
(97.6 mg, 0.3 mmol) and 4-chlorothiophenol (28.9 mg, 0.2 mmol) in
DMSO were irradiated in the presence of DIPEA (15.5 mg, 0.12
mmol) to afford 28 (50.2 mg, 90%) as a white solid. The eluent was
1
petroleum ether. H NMR (500 MHz, CDCl3): δ 7.42−7.41 (d, J =
8.3 Hz, 2H), 7.29−7.28 (d, J = 8.3 Hz, 2H), 2.01 (s, 3H), 1.79 (m,
6H), 1.66−1.58 (m, 6H). 13C{1H} NMR (125 MHz, CDCl3): δ
138.82, 135.07, 129.12, 128.52, 48.17, 43.55, 36.11, 29.97.
4-(Benzo[d]thiazol-2-ylthio)butan-2-one (29). Active NHPI ester
1e (78.4 mg, 0.3 mmol) and 2-mercaptobenzothiazole (33.4 mg, 0.2
mmol) in the presence of DIPEA (15.5 mg, 0.12 mmol) were
irradiated to give 29 (24.7 mg, 52%) as a yellow needle solid. The
1
eluent was a 20/1 petroleum ether/ethyl acetate mixture. H NMR
(500 MHz, CDCl3): δ 7.48 (d, J = 7.8 Hz, 1H), 7.43 (td, J = 7.8, 1.2
Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.30 (td, J = 7.8, 1.2 Hz, 1H), 4.67
(t, J = 7.3 Hz, 2H), 3.04 (t, J = 7.3 Hz, 2H), 2.21 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3): δ 205.9, 189.1, 141.2, 127.9, 127.1, 124.9,
121.4, 112.6, 41.0, 39.9, 30.2. HRMS (ESI) m/z: [M + H]+ calcd for
tert-Butyl 4-[(4-Fluorophenyl)thio] Piperidine-1-carboxylate
(23).25 NHPI ester 1j (112.3 mg, 0.3 mmol) and 4-fluorothiophenol
(25.6 mg, 0.2 mmol) in the presence of DIPEA (15.5 mg, 0.12 mmol)
were irradiated to afford 23 (50.4 mg, 81%), or NHPI ester 1j (561.6
mg, 1.5 mmol) and 4-fluorothiophenol (168.2 mg, 1.0 mmol) in the
presence of DIPEA (77.5 mg, 0.6 mmol) were irradiated for a
prolonged time of 24 h to give 23 (255.4 mg, 82%) as a yellow oil.
+
C11H12NOS2 238.0355, found 238.0353.
2-[(4-Bromophenethyl)thio]benzo[d]thiazole (30). NHPI ester 1g
(112.3 mg, 0.3 mmol) and 2-mercaptobenzothiazole (33.4 mg, 0.2
mmol) in the presence of DIPEA (15.5 mg, 0.12 mmol) were
irradiated to afford compound 30 (58.8 mg, 84%) as a yellow oil. The
1
The eluent was a 30/1 petroleum ether/ethyl acetate mixture. H
1
NMR (500 MHz, CDCl3): δ 7.44−7.41 (m, 2H), 7.03−6.99 (m, 2H),
3.97(dt, J = 13.6, 3.8 Hz, 2H), 3.09 (tt, J = 10.3, 3.8 Hz, 1H), 2.90−
2.85 (m, 2H), 1.90−1.85 (m, 2H), 1.53−1.46 (m, 2H), 1.44 (s, 9H).
13C{1H} NMR (125 MHz, CDCl3): δ 163.6, 161.6, 154.7, 135.8,
eluent was a 30/1 petroleum ether/ethyl acetate mixture. H NMR
(400 MHz, CDCl3): δ 7.88 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.0 Hz,
1H), 7.44−7.40 (m, 3H), 7.29 (td, J = 7.6, 1.0 Hz, 1H), 7.14 (d, J =
8.3 Hz, 2H), 3.55 (t, J = 7.6 Hz, 2H), 3.08 (t, J = 7.6 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 166.3, 153.2, 138.6, 135.2,
131.7, 130.5, 126.1, 124.3, 121.5, 121.0, 120.6, 35.0, 34.5. HRMS
135.7, 128.6, 128.5, 116.1, 116.0, 79.6, 45.4, 43.2, 32.1, 28.4. 19F
NMR (375 MHz, CDCl3): δ −113.8.
+
(ESI) m/z: [M + H]+ calcd for C15H13BrNS2 349.9667, found
tert-Butyl 4-[(4-Chlorophenyl)thio] Piperidine-1-carboxylate
(24). NHPI ester 1j (112.3 mg, 0.3 mmol) and 4-chlorothiophenol
(28.9 mg, 0.2 mmol) were irradiated in the presence of DIPEA (15.5
mg, 0.12 mmol) to afford 24 (97%, 63.6 mg) as a yellow oil. The
349.9668.
4-[(4-Bromophenethyl)thio]pyridine (31). Active ester 1g (112.3
mg, 0.3 mmol) and 4-mercaptopyridine (22.2 mg, 0.2 mmol) in
DMSO (2 mL) were irradiated in the presence of DIPEA (15.5 mg,
0.12 mmol) to give 31 (42.9 mg, 73%) as a yellow oil. The eluent was
1
eluent was a 20/1 petroleum ether/ethyl acetate mixture. H NMR
(500 MHz, CDCl3): δ 7.34 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz,
2H), 3.98−3.95 (m, 2H), 3.16 (m, 1H), 2.91 (m, 2H), 1.90 (m, 2H),
1.54−1.47 (m, 2H), 1.45 (s, 9H). 13C{1H} NMR (125 MHz, CDCl3):
δ 154.6, 134.0, 133.5, 132.3, 129.1, 79.6, 44.8, 43.1, 32.0, 28.4. HRMS
(ESI) m/z: [M + Na]+ calcd for C16H22ClNO2NaS+ 350.0952, found
350.0950.
1
a 6/1 petroleum ether/ethyl acetate mixture. H NMR (500 MHz,
CDCl3): δ 8.40 (d, J = 5.3 Hz, 2H), 7.45−7.43 (m, 2H), 7.11−7.09
(m, 4H), 3.20 (t, J = 7.6 Hz, 2H), 2.95 (t, J = 7.6 Hz, 2H). 13C{1H}
NMR (125 MHz, CDCl3): δ 149.2, 148.8, 138.3, 131.8, 130.3, 120.8,
120.7, 34.2, 31.9. HRMS (ESI) m/z: [M + H]+ calcd for
C13H13BrNS+ 293.9947, found 293.9947.
tert-Butyl {1-[(4-Chlorophenyl)thio]ethyl}carbamate (25). NHPI
ester 1k (100.3 mg, 0.3 mmol), 4-chlorothiophenol (28.9 mg, 0.2
mmol), and DIPEA (15.5 mg, 0.12 mmol) in DMSO (2 mL) were
irradiated to give 25 (53.5 mg, 93%) as a white solid. The eluent was a
tert-Butyl 3-(Benzo[d]thiazol-2-ylthio) Piperidine-1-carboxylate
(32). Active ester 1i (112.3 mg, 0.3 mmol) and 2-mercaptobenzo-
thiazole (33.4 mg, 0.2 mmol) in the presence of DIPEA (15.5 mg,
0.12 mmol) were irradiated to afford 32 (55.4 mg, 79%) as a yellow
oil. The eluent was a 20/1 petroleum ether/ethyl acetate mixture. 1H
NMR (500 MHz, CDCl3): δ 7.87 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.0
Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 4.13 (br,
1H), 4.01 (m, 1H), 3.68−3.64 (m, 1H), 3.44−3.35 (m, 1H), 3.23 (br,
1H), 2.20 (br, 1H), 1.80−1.76 (m, 2H), 1.64 (m, 1H), 1.46−1.42 (m,
9H). 13C{1H} NMR (125 MHz, CDCl3): δ 165.2, 154.6, 153.2, 135.2,
126.1, 124.4, 121.6, 121.0, 79.9, 49.5, 44.5, 30.4, 28.4, 25.8, 24.3.
1
30/1 petroleum ether/ethyl acetate mixture. H NMR (500 MHz,
CDCl3): δ 7.42−7.41 (d, J = 8.3 Hz, 2H), 7.28−7.26 (d, J = 8.3 Hz,
2H), 5.25 (s, 1H), 4.71−4.70 (m, 1H), 1.48−1.46 (m, 3H), 1.34 (s,
9H). 13C{1H} NMR (100 MHz, CDCl3): δ 154.2, 135.2, 134.2, 131.3,
129.0, 80.1, 54.9, 28.2, 22.4. HRMS (ESI) m/z: [M + Na]+ calcd for
C13H18ClNO2NaS+ 310.0639, found 310.0637.
tert-Butyl {1-[(4-Chlorophenyl)thio]-3-(methylthio)propyl} Car-
bamate (26). NHPI ester 1l (118.3 mg, 0.3 mmol) and 4-
chlorothiophenol (28.9 mg, 0.2 mmol) in the presence of DIPEA
(15.5 mg, 0.12 mmol) were irradiated to give 26 (45.9 mg, 66%) as a
yellow oil. The eluent was a 20/1 petroleum ether/ethyl acetate
+
HRMS (ESI) m/z: [M + H]+ calcd for C17H23N2O2S2 351.1195,
found 351.1193.
tert-Butyl 4-(Benzo[d]thiazol-2-ylthio)piperidine-1-carboxylate
(33).28 NHPI ester 1j (112.3 mg, 0.3 mmol) and 2-mercaptobenzo-
thiazole (33.4 mg, 0.2 mmol) in the presence of DIPEA (15.5 mg,
0.12 mmol) were irradiated to afford 33 (68.7 mg, 98%) as a yellow
oil. The eluent was a 30/1 petroleum ether/ethyl acetate mixture. 1H
NMR (400 MHz, CDCl3): δ 7.90 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0
Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 4.13 (m,
1H), 3.99−3.96 (m, 2H), 3.16−3.09 (m, 2H), 2.21−2.17 (m, 2H),
1
mixture. H NMR (500 MHz, CDCl3): δ 7.42−7.41 (m, 2H), 7.28−
7.27 (m, 2H), 5.24−5.23 (m, 1H), 4.79−4.77 (d, J = 9.5 Hz, 1H),
2.63 (t, J = 7.2 Hz, 2H), 2.10 (s, 3H), 2.06−2.02 (m, 1H), 1.99−1.93
(m, 1H), 1.48−1.46 (m, 1H), 1.35 (s, 8H). 13C{1H} NMR (125
MHz, CDCl3): δ 154.4, 135.1, 134.3, 130.8, 129.1, 80.2, 58.6, 35.5,
30.7, 28.2, 12.6. HRMS (ESI) m/z: [M + Na]+ calcd for
+
C15H22ClNO2NaS2 370.0673, found 370.0676.
F
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Note
1.76−1.69 (m, 2H), 1.47 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3):
δ 165.4, 154.6, 152.9, 135.1, 126.2, 124.5, 121.6, 121.0, 79.8, 44.7,
43.2, 32.1, 28.4.
Efficient nickel/N-heterocyclic carbene catalyzed C-S cross-coupling.
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Johannes, J. W. Photoredox Mediated Nickel Catalyzed Cross-
Coupling of Thiols with Aryl and Heteroaryl Iodides via Thiyl
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X.; Berritt, X.; Walters, C. R.; Petersson, E. J.; Molander, G. A.
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under Ni/photoredox catalysis. Chem. Sci. 2018, 9, 336−344.
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as a visible-light pro-photosensitizer in photoredox decarboxylative
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01433.
■
sı
Condition optimization, mechanistic investigations,
calculation of association constant KEDA, and copies of
NMR spectra of related compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Qin-Hua Song − Department of Chemistry, University of
Science and Technology of China, Hefei 230026, P. R.
China; orcid.org/0000-0001-6501-1382;
Email: qhsong@ustc.edu.cn
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Authors
Yi-Ping Cai − Department of Chemistry, University of Science
and Technology of China, Hefei 230026, P. R. China
Fang-Yuan Nie − Department of Chemistry, University of
Science and Technology of China, Hefei 230026, P. R. China
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Mechanisms via the Donor/Acceptor Bindings in the Critical
Encounter Complex. Acc. Chem. Res. 2008, 41, 641−653.
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful for financial support from the
National Natural Science Foundation of China (21772188
and 22074135).
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