Palladium and copper co-catalyzed Markovnikov hydrothiolation of terminal olefins and alkynes

Article abstract of DOI:10.1016/j.tetlet.2015.09.047

A simple and efficient method for palladium and copper co-catalyzed Markovnikov hydrothiolation of thiols to olefins or alkynes has been developed. The reaction allows olefins or alkynes bearing various functional groups to react with different thiols, pr

Full text of DOI:10.1016/j.tetlet.2015.09.047

Tetrahedron Letters 56 (2015) 6022–6029
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Palladium and copper co-catalyzed Markovnikov hydrothiolation
of terminal olefins and alkynes
⇑
Haojie Ma, Xiaoyu Ren, Xiaoqiang Zhou, Chaowei Ma, Yongqin He, GuoSheng Huang
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry,
Lanzhou University, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient method for palladium and copper co-catalyzed Markovnikov hydrothiolation of
thiols to olefins or alkynes has been developed. The reaction allows olefins or alkynes bearing various
functional groups to react with different thiols, providing good to excellent yields of alkyl sulfides or vinyl
sulfides. A proposed mechanistic study indicated that Cu(II) plays a key role in obtaining Markovnikov
products.
Received 7 August 2015
Revised 11 September 2015
Accepted 15 September 2015
Available online 15 September 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Markovnikov hydrothiolation
Thiols
Olefins or alkynes
Alkyl sulfides or vinyl sulfides
Introduction
(1-bromoethyl)benzene as reaction agents.16 Recently, Warren
and co-workers obtained alkyl sulfides from 1,2-di(pyridin-2-yl)
Heterothiol-involving organic compounds have found impor-
tant applications in pharmaceuticals, agrochemicals, and func-
tional materials.1 The different properties of heterothiol
compared to arylthiol, such as bio-availability,2 and serving as syn-
thetic intermediates,3 have attracted considerable interest in the
development of practical methods to synthesize such compounds.
Among them, alkyl or alkenyl hetero-sulfides, which with Markov-
nikov configuration have been used as building blocks for many
pharmaceutical products including 6-mercaptopurine, ranitidine,
cimetidine,4 suffer from more challenges in synthesis, because
the tendency of addition reaction of thiol to alkenes and alkynes
is in favor of anti-Markovnikov products under the traditional cat-
alysts of H-rho-zeolite and benzene-reflux,5,6 InI,7 CeCl3,8 silica
nano particles,9 and acidic ionic liquids.10 Fortunately, the syner-
gistic transition metal co-catalyst with Markovnikov configuration
for the construction of heterosulfide bonds conducted a high effec-
tive and simple strategy.
disulfane and ethylbenzene with only 25% yield. In 2012, Rupam
Sarma et al. disclosed the synthesis of vinyl sulfides catalyzed by
In(OTf)3 from thiols to alkynes.13 However, the indium catalyst is
very expensive, and the products usually lack controllability of
anti-Markovnikov and Markovnikov. Compared to the early work
done by Ogawa, we only added Cu co-catalyst and expanded the
scope with limited substrates.
Herein, inspired by the pioneering work, we have developed the
full Markovnikov hydrothiolation of thiols to olefins/alkynes co-
catalyzed by Pd(OAc)2 and Cu(OTf)2. To our knowledge, there are
rare reports on catalytic process that can catalyze both olefins
and alkynes under identical reaction conditions to form Markovni-
kov addition products. In our work, it has been come true for ole-
fins and alkynes under identical catalyzed conditions. It is worth
noting that this method, compared with others, represents a more
high efficient way to synthesize alkyl and alkenyl hetero-sulfides.
Some methods for the construction of carbon–sulfur bonds have
been reported.11 Especially some late transition metal to catalyze
alkyne hydrothiolation, including Rh,12 Ir,13 Ni,14 Pd,14a,b Pt14b
and Au15 complexes. Diaryl sulfides and arylalkyl sulfides were
obtained from thiols and ArX derivatives by palladium catalysts.
In 1984, Furukawa and co-workers synthesized alkyl sulfides by
dint of catalyst using 1-phenylethyl 2-pyridyl sulfide and
Results and discussion
Initially, pyridine-2-thiol and phenylacetylene were used as the
representative substrates to screen the optimized conditions. The
reaction of pyridine-2-thiol (1a, 0.2 mmol) with phenylacetylene
(2a, 0.24 mmol) was conducted in the presence of Pd(OAc)2
(10 mol %) in xylene at 120 °C for 4 h, and was able to isolate the
desired 2-((1-phenylvinyl)thio)pyridine (3a) in 26% yield (Table 1,
entry 1). Then, the effect of various additives on the yield of the
target product was investigated to find that Cs2CO3 failed to come
⇑
Corresponding author.
E-mail address: hgs@lzu.edu.cn (G. Huang).
http://dx.doi.org/10.1016/j.tetlet.2015.09.047
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

H. Ma et al. / Tetrahedron Letters 56 (2015) 6022–6029
6023
Table 1
Optimization of reaction conditionsa
catalyst
Additive
+
N
S
solvent
N
SH
1a
3a
2a
Entry
Catalyst (mol %)
Additive (mol %)
Solvent/atmosphere
Temp (°C)
Yields (%)
1
2
3
4
5
6
7
8
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
—
Pd(OAc)2 (5)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
—
Xylene/air
Xylene/air
Xylene/air
Xylene/air
Xylene/air
Xylene/air
Xylene/air
Xylene/air
Xylene/air
DMF/N2
Toluene/N2
Xylene/N2
Xylene/N2
Xylene/N2
Xylene/N2
Xylene/N2
120
120
120
120
120
120
120
120
120
120
120
120
100
140
120
120
26
10
Trace
44
55
45
14
56
59
52
69
76
33
67
60
69
K2CO3 (200)
Cs2CO3 (200)
Cu(OAc)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (10)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
Cu(OTf)2 (5)
9
10
11
12
13
14
15b
16c
a
b
c
Reaction conditions: thiol (0.2 mmol), terminal alkyne (0.24 mmol) and Pd(OAc)2 (2 mol %), Cu(OTf)2 (5 mol %) in 1 mL of xylene under N2 for 4 h at 120 °C.
Reaction time was 2 h.
Reaction time was 6 h.
up with any useful conversions, and Cu(OTf)2 was more favorable
than Cu(OAc)2 (Table 1, entries 2–5). In addition, 5 mol % Cu
(OTf)2 showed the superior yield than 10 mol % one (Table 1,
entries 5 and 6). Unexpectedly, the bare Cu(OTf)2 can also give
the desired product with a yield of 14% (Table 1, entry 7). Further-
more, when the dosage of Pd(OAc)2 decreased to 2 mol %, the dra-
matic promotion in yield was observed (Table 1, entries 5, 8 and 9),
which indicated that the appropriate assignation of catalysts could
better exert the synergistic effect. The investigations in solvents
and atmospheres presented that the cooperation of nitrogen and
xylene was more outstanding under the catalyzed condition,
affording the product in 76% yield (Table 1, entries 9–12). Addi-
tionally, compared with the effect of reaction time, the suitable
temperature exhibited more efficiency to adjust the product yield.
In the end, the optimized reaction conditions for Markovnikov
hydrothiolation of thiols to both olefins and alkynes are as follows:
Pd(OAc)2 (2 mol %), Cu(OTf)2 (5 mol %) in 1 mL of xylene at 120 °C
for 4 h under N2.
With the optimized conditions in hand, we evaluated the com-
patibility of phenylacetylene bearing diverse substituents to pyri-
dine-2-thiol (Scheme 1). First, the reaction of pyridine-2-thiol
(1a) with phenylacetylene was smoothly performed to give the
desired Markovnikov product (3a) in 76% yield. Next, the effects
of substituents on phenylacetylene were investigated (3a–g), it
can be seen clearly that the electron-donating groups exhibited
more outstanding results in terms of providing the desired prod-
ucts than electron-withdrawing groups (3b–g). It is noteworthy
that the same substituent in different sites on aryl-ring afforded
discrepant yields (3d, 3g, 3b, 3f), indicating that steric effect also
plays an important role for yields. Subsequently, pyridine-4-thiol
was employed to react with phenylacetylene possessing various
groups, the desired products were isolated in moderate yields
(3h–l). The similar effects of substituents were also observed. Fur-
thermore, the scopes of heterothiol were further exploited to dis-
cuss the effects of hetero-aryl ring on the reaction (3m–u),
encouragingly, the multi-hetero-atom aryl thiols can afford the
desired products in good to excellent yields, implying that the high
electron density in hetero-ring is in favor of transformation, which
makes great contributions to shorten routes of some drug
molecules designed and synthesized. Unfortunately, the ben-
zenethiol did not get desired product (3v).
To further explore the applicability and compatibility of this
synthetic route, the reaction of thiols and styrene with various
functional groups was attempted under the same optimized condi-
tions as shown in Scheme 2. First, pyridine-2-thiol reacted with
styrene to give the desired product (4a) in 82% yield, which was
higher than that of phenylacetylene, indicating the more reactivity
of styrene. Concerning the electronic effects of substituents on
phenyl rings, the substrates bearing electron-withdrawing or elec-
tron-donating groups were investigated, affording the desired
products (4a–4h) in good to excellent yields. The results showed
the electron-donating groups were more effective for the product
transformation. Meanwhile, based on the reaction results of styre-
nes with mono or multi methyl groups and 4-tert-butyl (4b, 4d–f),
it was represented distinctly that the steric effect also has
significant influence on the efficiency. Subsequently, thiols with
different hetero-aromatic rings were supplied to explore the effect
of hetero-aromatic rings with multi hetero-atoms on the
transformation (4i–t). Compared to pyridinethiols (4a–4c, 4g–h),
pyrimidinethiols (4i–m) gave the desired product, respectively in
61%, 68%, 85%, 60% and 63% yields, exhibiting low reactivity.
However, 1-methyl-1H-tetrazole-5-thiol gave the desired products
in excellent yields, even styrenes with electron-withdrawing
groups were furnished (4n–q), 5-methyl-1,3,4-thiadiazole-2-thiol
and 1H-benzo[d]imidazole-2-thiol also offered the product (4s)
and (4t) in 80% and 87% yields, respectively. This result suggested
that bearing an electron deficient heterocycle has significant
influence on the efficiency.
Based on the experimental results and literatures, a plausible
mechanism is proposed for the formation of the vinyl and alkyl sul-
fides as shown in Scheme 3. As we have already confirmed that the
reaction can progress under the condition of Pd(OAc)2, it is appar-
ent that the Cu(OTf)2 might facilitate the reaction by connecting
with phenylacetylene/ phenylethylene. The reaction may be
initiated by Pd(OAc)2 with 2 equiv of RSH to generate Pd(SR)2
complex.11e Then Cu(OTf)2 ligates to the phenylacetylene or
phenylethylene to form A.17 Next, a transmetalation between
Pd(SR)2 and A generates intermediate B, which translates into

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H. Ma et al. / Tetrahedron Letters 56 (2015) 6022–6029
2mol % Pd(OAc)2
5mol % Cu(OTf)2
R1
S
R1
R SH
1
+
Xylene, N2,120o
R
C
2
3
N
S
N
N
N
S
S
S
OMe
3c, 87%
F
3d,55%
3a, 76%
3b, 79%
N
N
N
S
N
S
S
F
S
Cl
3e, 52%
3g, 50%
3f,65%
3h, 53%
F
S
N
S
N
S
S
N
OMe
N
3l,50%
3i, 55%
3j, 64%
3k, 48%
N
OMe
N
N
S
N
S
N
S
S
S
S
S
S
3o, 90%
3p,79%
3n, 88%
3m,76%
N
N
N
N
N
N
N
N
N
S
N
S
N
S
OMe
OMe
3t, 85%
3r,93%
3s, 73%
3q,79%
N
N
S
S
S
N
S
OMe
Br
3u, 76%
3v, 0%
3w, 60%
Scheme 1. Markovnikov hydrothiolation of terminal alkynes.
cis-vinylpalladium C. Finally, vinyl or alkyl group was trapped by
RSH to give the product with retention of the stereochemistry.
as an internal standard. 13C NMR spectra were obtained at
100 MHz and were calibrated with CDCl3 (d = 77.00 ppm). The high
resolution mass spectra (HRMS) were recorded on an FT-ICR mass
spectrometer using electrospray ionization (ESI). Products were
purified by flash chromatography on 200–300 mesh silica gels.
Unless otherwise noted, commercially available reagents and
solvents were used without further purification.
Conclusions
In summary, we have developed a Pd(OAc)2 and Cu(OTf)2 co-
catalyzed Markovnikov additive reaction to construct C–S bond
based on heterothiols and alkenes or alkynes. This protocol pro-
vides a simple and efficient method to prepare hetero-sulfides,
which will promote the development of bioactive molecules con-
taining hetero-sulfide moieties.
Typical procedure for the preparation of 2-((1-phenylvinyl)thio)
pyridine (3a)
A test tube was charged with pyridine-2-thiol (0.2 mmol), Pd
(OAc)2 (0.004 mmol), Cu(OTf)2 (0.01 mmol), phenylacetylene
(0.24 mmol), in xylene (1 mL). The reaction tube was evacuated
and back-filled with N2 (3 times, balloon). Then the reaction mix-
ture was stirred at 120 °C (oil bath temperature) under N2 balloon
for 4 h. After cooling to room temperature, the solvent was
extracted with ethyl acetate and washed with brine. After the
Experimental section
General experimental details
1H NMR spectra were recorded at 400 MHz. Chemical shifts (in
ppm) were referenced to tetramethylsilane (d = 0.00 ppm) in CDCl3

H. Ma et al. / Tetrahedron Letters 56 (2015) 6022–6029
6025
2 mol% Pd(OAc)2
5 mol% Cu(OTf)2
R1
S
R1
R SH
1
+
Xylene, N2,120oC
R
4
2
N
N
S
N
N
S
S
S
OMe
4a, 82%
S
4c , 94%
4d,80%
S
4b, 89%
N
S
N
N
S
N
Cl
F
4f, 81%
4e ,73%
4g, 69%
4h,77%
N
S
N
S
N
N
S
N
N
N
S
N
OMe
Cl
Cl
4k, 85%
4i,61%
4l, 60%
4j,68%
N
N
N
N
N
N
N
N
N
N
S
S
S
N
N
N
N
S
F
4n, 95%
4p,86%
4t, 87%
4o, 97%
4m, 63%
S
N N
OMe
OMe
N
N
S
N
N
S
S
S
F
N
N
H
N
4s, 80%
4q, 92%
4r,76%
N
N
S
Br
4u, 58%
Scheme 2. Markovnikov hydrothiolation of terminal olefins.
solvent was evaporated in vacuo, the residues were purified by col-
umn chromatography, eluting with petroleum ether/ EtOAc to
afford pure 2-((1-phenylvinyl)thio)pyridine.
2H), 7.04 (d, J = 8.1 Hz, 1H), 6.93 (m, 1H), 5.98 (s, 1H), 5.86 (s,
1H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3) d 159.4, 149.6,
140.4, 138.5, 136.4, 135.5, 129.1, 127.0, 122.8, 122.3, 120.0, 21.1.
HRMS calcd for C14H14NS [M+H]+ 228.0842, found 228.0843.
Experimental characterization data for products
2-((1-(4-Methoxyphenyl)vinyl)thio)pyridine (3c)
2-((1-Phenylvinyl)thio)pyridine (3a)
Brown oil (42.3 mg, 87%). 1H NMR (400 MHz, CDCl3) d 8.38 (m,
1H), 7.62 (d, J = 8.9 Hz, 2H), 7.41–7.35 (m, 1H), 7.03 (d, J = 8.1 Hz,
1H), 6.94 (m, 1H), 6.83–6.77 (m, 2H), 5.92 (s, 1H), 5.82 (s, 1H),
3.78 (s, 3H). 13C NMR (100 MHz, CDCl3) d 159.9, 159.4, 149.6,
140.0, 136.4, 130.8, 128.5, 122.8, 121.3, 120.0, 113.7, 55.2. HRMS
calcd for C14H14NOS [M+H]+ 244.0791, found 244.0788.
Brown oil (32.4 mg, 76%). 1H NMR (400 MHz, CDCl3) d 8.42–8.31
(m, 1H), 7.71–7.63 (m, 2H), 7.41–7.36 (m, 1H), 7.30–7.25 (m, 3H),
7.05 (d, J = 8.1 Hz, 1H), 6.93 (m, 1H), 6.01 (s, 1H), 5.91 (s, 1H). 13C
NMR (100 MHz, CDCl3) d 159.1, 149.6, 140.7, 138.5, 136.4, 128.5,
128.4, 127.2, 123.0, 122.9, 120.1. HRMS calcd for C13H12NS [M
+H]+ 214.0685, found 214.0688.
2-((1-(4-Fluorophenyl)vinyl)thio)pyridine (3d)
2-((1-(p-Tolyl)vinyl)thio)pyridine (3b)
Yellow oil (25.4 mg, 55%). 1H NMR (400 MHz, CDCl3) d 8.41–
8.33 (m, 1H), 7.69–7.60 (m, 2H), 7.41 (m, 1H), 7.05 (d, J = 8.0 Hz,
1H), 6.99–6.93 (m, 3H), 5.94 (s, 1H), 5.88 (s, 1H). 13C NMR
Brown oil (35.9 mg, 79%). 1H NMR (400 MHz, CDCl3) d 8.38 (m,
1H), 7.57 (d, J = 8.2 Hz, 2H), 7.41–7.35 (m, 1H), 7.09 (d, J = 7.9 Hz,

6026
H. Ma et al. / Tetrahedron Letters 56 (2015) 6022–6029
Ph
4-((1-(p-Tolyl)vinyl)thio)pyridine (3i)
Brown oil (25.0 mg, 55%). 1H NMR (400 MHz, CDCl3) d 8.29 (dd,
J = 4.7, 1.6 Hz, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H),
7.03 (dd, J = 4.7, 1.6 Hz, 2H), 6.04 (s, 1H), 5.86 (s, 1H), 2.31 (s,
3H). 13C NMR (100 MHz, CDCl3) d 149.2, 147.8, 139.1, 139.0,
134.6, 129.3, 126.9, 123.4, 121.9, 21.1. HRMS calcd for C14H14NS
[M+H]+ 228.0842, found 228.0844.
Cu(OTf)2
Ph
Cu(OTf)2
A
4-((1-(4-Methoxyphenyl)vinyl)thio)pyridine (3j)
Pd(SR)2
Ph
Yellow oil (31.1 mg, 64%). 1H NMR (400 MHz, CDCl3) d 8.30 (dd,
J = 4.6, 1.6 Hz, 2H), 7.58–7.53 (m, 2H), 7.03 (dd, J = 4.6, 1.6 Hz, 2H),
6.85–6.79 (m, 2H), 5.99 (s, 1H), 5.82 (s, 1H), 3.79 (s, 3H). 13C NMR
(100 MHz, CDCl3) d 160.1, 149.3, 147.9, 138.6, 129.9, 128.3, 122.5,
121.9, 113.9, 55.3. HRMS calcd for C14H14NOS [M+H]+ 244.0791,
found 244.0794.
SR
2RSH
Cu(OTf)2
2AcOH
Ph
RSH
Pd(SR)2
B
Pd(OAc)2
4-((1-(2-Fluorophenyl)vinyl)thio)pyridine (3k)
Yellow oil (22.2 mg, 48%). 1H NMR (400 MHz, CDCl3) d 8.33 (dd,
J = 4.6, 1.6 Hz, 2H), 7.55 (td, J = 7.8, 1.7 Hz, 1H), 7.26–7.20 (m, 1H),
7.10 (dd, J = 4.6, 1.6 Hz, 2H), 7.08–6.98 (m, 2H), 6.16 (d, J = 0.9 Hz,
1H), 6.14 (d, J = 1.9 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 160.3
(d, J = 248 Hz), 149.4, 147.0, 132.8, 130.3 (d, J = 2 Hz), 130.1 (d,
J = 9 Hz), 129.4 (d, J = 6 Hz), 125.8 (d, J = 12 Hz), 124.1 (d,
J = 4 Hz), 122.1, 116.1 (d, J = 23 Hz). HRMS calcd for C13H11FNS
[M+H]+ 232.0591, found 232.0590.
Ph
PdSR
C
SR
Scheme 3. Plausible mechanistic pathway.
4-((1-(m-Tolyl)vinyl)thio)pyridine (3l)
Brown oil (22.7 mg, 50%). 1H NMR (400 MHz, CDCl3) d 8.30 (dd,
J = 4.7, 1.5 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.19 (t, J = 7.7 Hz, 1H),
7.11 (d, J = 7.4 Hz, 1H), 7.05 (dd, J = 4.6, 1.6 Hz, 2H), 6.07 (s, 1H),
5.89 (s, 1H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3) d 149.3,
147.8, 139.5, 138.3, 137.6, 129.8, 128.5, 127.6, 124.2, 123.1,
122.0, 21.4. HRMS calcd for C14H14NS [M+H]+ 228.0842, found
228.0840.
(100 MHz, CDCl3) d 162.8 (d, J = 247 Hz), 158.6, 149.7, 139.7, 136.5,
134.6 (d, J = 3 Hz), 128.9 (d, J = 8 Hz), 123.0, 122.7, 120.2, 115.2 (d,
J = 22 Hz). HRMS calcd for C13H11FNS [M+H]+ 232.0591, found
232.0590.
2-((1-(4-Chlorophenyl)vinyl)thio)pyridine (3e)
Yellow oil (25.7 mg, 52%). 1H NMR (400 MHz, CDCl3) d 8.39–
8.34 (m, 1H), 7.60 (d, J = 8.5 Hz, 2H), 7.41 (m, 1H), 7.26–7.23 (m,
2H), 7.05 (d, J = 8.0 Hz, 1H), 6.96 (dd, J = 7.4, 4.9 Hz, 1H), 5.98 (s,
1H), 5.92 (s, 1H). 13C NMR (100 MHz, CDCl3) d 158.5, 149.8,
139.7, 137.1, 136.6, 134.4, 128.5, 128.5, 123.4, 123.0, 120.3. HRMS
calcd for C13H11ClNS [M+H]+ 248.0295, found 248.0298.
2-((1-Phenylvinyl)thio)benzo[d]thiazole (3m)
Brown oil (40.9 mg, 76%). 1H NMR (400 MHz, CDCl3) d 7.87 (d,
J = 8.0 Hz, 1H), 7.76–7.69 (m, 2H), 7.65 (d, J = 8.0 Hz, 1H), 7.41–
7.37 (m, 1H), 7.37–7.28 (m, 4H), 6.12 (s, 1H), 6.09 (s, 1H). 13C
NMR (100 MHz, CDCl3) d 166.4, 153.5, 139.7, 137.7, 136.1, 129.1,
128.6, 127.4, 126.1, 125.3, 124.4, 122.1, 120.9. HRMS calcd for
2-((1-(m-Tolyl)vinyl)thio)pyridine (3f)
Brown oil (29.5 mg, 65%). 1H NMR (400 MHz, CDCl3) d 8.38 (m,
1H), 7.53–7.44 (m, 2H), 7.39 (m, 1H), 7.17 (t, J = 7.6 Hz, 1H), 7.06
(m, 2H), 6.94 (m, 1H), 6.00 (s, 1H), 5.89 (s, 1H), 2.31 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 159.3, 149.6, 140.7, 138.4, 138.0, 136.5,
129.4, 128.2, 127.8, 124.4, 122.9, 122.8, 120.0, 21.4. HRMS calcd
for C14H14NS [M+H]+ 228.0842, found 228.0844.
C
15H12NS2 [M+H]+ 270.0406, found 270.0409.
2-((1-(p-Tolyl)vinyl)thio)benzo[d]thiazole (3n)
Yellow oil (49.8 mg, 88%). 1H NMR (400 MHz, CDCl3) d 7.87 (d,
J = 8.2 Hz, 1H), 7.63 (m, 3H), 7.37 (m, 1H), 7.26–7.23 (m, 1H),
7.13 (d, J = 7.9 Hz, 2H), 6.08 (s, 1H), 6.03 (s, 1H), 2.32 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 166.7, 153.5, 139.5, 139.2, 136.1, 134.8,
129.3, 127.3, 126.0, 124.4, 124.3, 122.1, 120.8, 21.2. HRMS calcd
for C16H14NS2 [M+H]+ 284.0562, found 284.0563.
2-((1-(2-Fluorophenyl)vinyl)thio)pyridine (3g)
Yellow oil (23.1 mg, 50%). 1H NMR (400 MHz, CDCl3) d 8.38 (dd,
J = 4.8, 0.9 Hz, 1H), 7.64 (m, 1H), 7.43 (m, 1H), 7.23–7.18 (m, 1H),
7.16 (dd, J = 7.2, 5.0 Hz, 1H), 7.07–6.99 (m, 2H), 6.96 (m, 1H),
6.16 (s, 1H), 6.07 (d, J = 1.9 Hz, 1H). 13C NMR (100 MHz, CDCl3) d
160.4 (d, J = 248 Hz), 158.7, 149.7, 136.6, 134.0, 130.7 (d,
J = 2 Hz), 129.7 (d, J = 9 Hz), 128.1 (d, J = 6 Hz), 126.7 (d,
J = 12 Hz), 123.9 (d, J = 4 Hz), 122.7, 120.3, 115.8 (d, J = 22 Hz),
HRMS calcd for C13H11FNS [M+H]+ 232.0591, found 232.0590.
2-((1-(4-Methoxyphenyl)vinyl)thio)benzo[d]thiazole (3o)
White oil (53.8 mg, 90%). 1H NMR (400 MHz, CDCl3) d 7.86 (t,
J = 8.3 Hz, 1H), 7.65 (m, 3H), 7.41–7.34 (m, 1H), 7.27–7.22 (m,
1H), 6.87–6.81 (m, 2H), 6.01 (s, 1H), 5.98 (s, 1H), 3.78 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 166.8, 160.3, 153.4, 139.0, 136.1, 130.0,
128.7, 126.0, 124.3, 123.3, 122.0, 120.8, 113.9, 55.3. HRMS calcd
for C16H14NOS2 [M+H]+ 300.0512, found 300.0515.
4-((1-Phenylvinyl)thio)pyridine (3h)
Brown oil (22.6 mg, 53%). 1H NMR (400 MHz, CDCl3) d 8.30
(dd, J = 4.6, 1.6 Hz, 2H), 7.65–7.60 (m, 2H), 7.34–7.27 (m, 3H),
7.04 (dd, J = 4.6, 1.6 Hz, 2H), 6.08 (s, 1H), 5.91 (s, 1H). 13C NMR
(100 MHz, CDCl3) d 149.3, 147.5, 139.4, 137.5, 128.9, 128.6,
127.0, 124.2, 122.0. HRMS calcd for C13H12NS [M+H]+ 214.0685,
found 214.0682.
4,6-Dimethyl-2-((1-phenylvinyl)thio)pyrimidine (3p)
Brown oil (38.2 mg, 79%). 1H NMR (400 MHz, CDCl3) d 7.69–7.59
(m, 2H), 7.29–7.21 (m, 3H), 6.58 (s, 1H), 5.93 (s, 1H), 5.91 (s, 1H),
2.24 (s, 6H). 13C NMR (100 MHz, CDCl3) d 170.1, 167.0, 140.6,
140.2, 127.8, 127.8, 127.3, 123.2, 116.0, 23.6. HRMS calcd for
C
14H15N2S [M+H]+ 243.0951, found 243.0947.

H. Ma et al. / Tetrahedron Letters 56 (2015) 6022–6029
6027
4,6-Dimethyl-2-((1-(p-tolyl)vinyl)thio)pyrimidine (3q)
2-((1-(4-Methoxyphenyl)ethyl)thio)pyridine (4c)
Brown oil (40.4 mg, 79%). 1H NMR (400 MHz, CDCl3) d 7.53 (d,
J = 8.2 Hz, 2H), 7.06 (d, J = 7.9 Hz, 2H), 6.58 (s, 1H), 5.88 (d,
J = 2.6 Hz, 2H), 2.30 (s, 3H), 2.25 (s, 6H). 13C NMR (100 MHz, CDCl3)
d 170.2, 167.0, 140.3, 137.6, 137.3, 128.5, 127.2, 122.5, 116.0, 23.7,
21.1. HRMS calcd for C15H17N2S [M+H]+ 257.1107, found 257.1109.
Yellow oil (46.1 mg, 94%). 1H NMR (400 MHz, CDCl3) d 8.45 (d,
J = 4.2 Hz, 1H), 7.42 (m, 1H), 7.37 (d, J = 8.7 Hz, 2H), 7.09 (d,
J = 8.0 Hz, 1H), 6.95 (dd, J = 6.9, 5.3 Hz, 1H), 6.84 (t, J = 5.8 Hz,
2H), 5.07 (q, J = 7.0 Hz, 1H), 3.77 (s, 3H), 1.72 (d, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3) d 159.0, 158.6, 149.4, 135.9, 135.2,
128.4, 122.8, 119.5, 113.8, 55.2, 43.0, 22.6. HRMS calcd for C14H16
-
2-((1-(4-Methoxyphenyl)vinyl)thio)-4,6-dimethylpyrimidine
(3r)
NOS [M+H]+ 246.0947, found 246.0949.
Brown oil (50.6 mg, 93%). 1H NMR (400 MHz, CDCl3) d 7.57 (d,
J = 8.7 Hz, 2H), 6.78 (t, J = 5.9 Hz, 2H), 6.59 (s, 1H), 5.84 (d,
J = 6.4 Hz, 2H), 3.78 (s, 3H), 2.26 (s, 6H). 13C NMR (100 MHz, CDCl3)
d 170.2, 167.0, 159.3, 139.9, 132.6, 128.5, 121.7, 116.0, 113.1, 55.2,
23.7. HRMS calcd for
273.1053.
2-((1-(2,5-Dimethylphenyl)ethyl)thio)pyridine (4d)
Yellow oil (38.9 mg, 80%). 1H NMR (400 MHz, CDCl3) d 8.45 (dd,
J = 4.9, 0.8 Hz, 1H), 7.43 (m, 1H), 7.30 (s, 1H), 7.09 (d, J = 8.1 Hz, 1H),
7.04 (d, J = 7.7 Hz, 1H), 6.97–6.92 (m, 2H), 5.29 (q, J = 6.9 Hz, 1H),
2.40 (s, 3H), 2.31 (s, 3H), 1.73 (d, J = 6.9 Hz, 3H). 13C NMR
(100 MHz, CDCl3) d 159.2, 149.5, 140.5, 135.8, 135.6, 132.5,
130.3, 127.7, 127.3, 122.4, 119.4, 39.5, 22.0, 21.1, 18.9. HRMS calcd
for C15H18NS [M+H]+ 244.1155, found 244.1158.
C
15H17N2OS [M+H]+ 273.1056, found
4,6-Dimethyl-2-((1-(m-tolyl)vinyl)thio)pyrimidine (3s)
Brown oil (37.4 mg, 73%). 1H NMR (400 MHz, CDCl3) d 7.47–
7.41 (m, 2H), 7.14 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 7.5 Hz, 1H),
6.59 (s, 1H), 5.91 (s, 1H), 5.89 (s, 1H), 2.31 (s, 3H), 2.26 (s,
6H). 13C NMR (100 MHz, CDCl3) d 170.2, 167.0, 140.5, 140.2,
137.3, 128.9, 128.6, 128.0, 127.7, 124.6, 123.2, 116.1, 29.7,
23.7, 21.4. HRMS calcd for C15H17N2S [M+H]+ 257.1107, found
257.1108.
2-((1-Mesitylethyl)thio)pyridine (4e)
Yellow oil (37.5 mg, 73%). 1H NMR (400 MHz, CDCl3) d 8.45 (m,
1H), 7.42 (m, 1H), 7.11 (m, 1H), 6.94 (m, 1H), 6.82 (d, J = 7.3 Hz,
2H), 5.82 (q, J = 7.3 Hz, 1H), 2.55 (s, 3H), 2.45 (s, 3H), 2.23 (s, 3H),
1.77 (d, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 159.2, 149.3,
136.7, 136.2, 135.8, 130.8, 129.0, 122.5, 119.3, 38.1, 21.5, 21.1,
20.7. HRMS calcd for C16H20NS [M+H]+ 258.1311, found 258.1314.
5-((1-(4-Methoxyphenyl)vinyl)thio)-1-methyl-1H-tetrazole (3t)
Brown oil (42.2 mg, 85%). 1H NMR (400 MHz, CDCl3) d 7.20 (d,
J = 8.9 Hz, 2H), 6.89 (d, J = 8.9 Hz, 2H), 5.94 (d, J = 1.5 Hz, 1H),
5.71 (d, J = 1.5 Hz, 1H), 3.96 (s, 3H), 3.82 (s, 3H). 13C NMR
(100 MHz, CDCl3) d 160.7, 140.4, 129.8, 127.6, 126.0, 114.4,
114.2, 55.3, 34.9. HRMS calcd for C11H13N4OS [M+H]+ 249.0805,
found 249.0807.
2-((1-(4-(tert-Butyl)phenyl)ethyl)thio)pyridine (4f)
Yellow oil (43.9 mg, 81%). 1H NMR (400 MHz, CDCl3) d 8.46 (dd,
J = 4.9, 0.9 Hz, 1H), 7.46–7.40 (m, 1H), 7.39–7.35 (m, 2H), 7.35–7.31
(m, 2H), 7.11 (d, J = 8.0 Hz, 1H), 6.96 (m, 1H), 5.10 (q, J = 7.0 Hz,
1H), 1.74 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H). 13C NMR (100 MHz, CDCl3)
d 159.1, 150.0, 149.5, 139.9, 135.9, 127.0, 125.4, 122.7, 119.5, 43.1,
34.5, 31.3, 22.6. HRMS calcd for C17H22NS [M+H]+ 272.1468, found
272.1472.
2-((1-(4-Methoxyphenyl)vinyl)thio)-5-methyl-1,3,4-thiadiazole
(3u)
Brown oil (40.1 mg, 76%). 1H NMR (400 MHz, CDCl3) d 7.61–7.53
(m, 2H), 6.89–6.82 (m, 2H), 5.83 (s, 2H), 3.80 (s, 3H), 2.62 (s, 3H).
13C NMR (100 MHz, CDCl3) d 166.7, 165.1, 160.4, 139.9, 129.5,
128.9, 121.1, 114.0, 55.3, 15.7. HRMS calcd for C12H13N2OS2 [M
+H]+ 265.0464, found 265.0462.
2-((1-(4-Chlorophenyl)ethyl)thio)pyridine (4g)
Yellow oil (34.4 mg, 69%). 1H NMR (400 MHz, CDCl3) d 8.51–
8.31 (m, 1H), 7.45–7.40 (m, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.27–
7.23 (m, 2H), 7.08 (m, 1H), 6.96 (m, 1H), 5.09 (q, J = 7.1 Hz, 1H),
1.70 (d, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 158.3, 149.5,
142.1, 136.0, 132.6, 128.7, 128.5, 122.8, 119.7, 42.7, 22.4. HRMS
calcd for C13H13ClNS [M+H]+ 250.0452, found 250.0450.
2-((1-(4-Bromophenyl)vinyl)thio)-4,6-dimethylpyrimidine (3w)
Yellow oil (38.4 mg, 60%). 1H NMR (400 MHz, CDCl3) d 7.47–
7.37 (m, 2H), 7.36–7.25 (m, 2H), 6.53 (s, 1H), 5.85 (s, 1H), 5.81 (s,
1H), 2.18 (s, 6H). 13C NMR (100 MHz, CDCl3) d 169.8, 167.1,
139.6, 139.3, 130.9, 128.9, 123.7, 121.7, 116.2, 23.6. HRMS calcd
for C14H13BrN2S [M+H]+ 321.0056, found 321.0054.
2-((1-(4-Fluorophenyl)ethyl)thio)pyridine (4h)
Yellow oil (35.9 mg, 77%) 1H NMR (400 MHz, CDCl3) d 8.44 (d,
J = 4.2 Hz, 1H), 7.46–7.36 (m, 3H), 7.09 (d, J = 8.0 Hz, 1H), 6.98
(dd, J = 5.1, 1.5 Hz, 1H), 6.97 (d, J = 1.9 Hz, 1H), 6.96 (dd, J = 3.0,
1.6 Hz, 1H), 5.11 (q, J = 7.1 Hz, 1H), 1.71 (d, J = 7.1 Hz, 3H). 13C
NMR (100 MHz, CDCl3) d 161.7 (d, J = 244 Hz), 158.5, 149.5, 139.1
(d, J = 3 Hz), 136.0, 128.9 (d, J = 8.0 Hz), 122.8, 119.7, 115.2 (d,
2-((1-Phenylethyl)thio)pyridine (4a)
Yellow oil (35.3 mg, 82%). 1H NMR (400 MHz, CDCl3) d 8.45–
8.40 (m, 1H), 7.44 (d, J = 7.4 Hz, 2H), 7.38 (m, 1H), 7.28 (t,
J = 7.5 Hz, 2H), 7.21 (d, J = 7.4 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H),
6.92 (dd, J = 6.9, 5.3 Hz, 1H), 5.11 (q, J = 7.0 Hz, 1H), 1.73 (d,
J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 158.8, 149.4, 143.2,
135.8, 128.4, 127.3, 127.0, 122.7, 119.5, 43.4, 22.5. HRMS calcd
for C13H14NS [M+H]+ 216.0842, found 216.0840.
J = 21 Hz), 42.7, 22.6. HRMS calcd for
C
13H13FNS [M+H]+
234.0747, found 234.0750.
4,6-Dimethyl-2-((1-phenylethyl)thio)pyrimidine (4i)
Yellow oil (29.8 mg, 61%). 1H NMR (400 MHz, CDCl3) d 7.48 (d,
J = 7.3 Hz, 2H), 7.30 (t, J = 7.5 Hz, 2H), 7.21 (t, J = 7.3 Hz, 1H), 6.65
(s, 1H), 5.08 (q, J = 7.1 Hz, 1H), 2.38 (s, 6H), 1.75 (d, J = 7.1 Hz,
3H). 13C NMR (100 MHz, CDCl3) d 170.8, 166.8, 143.6, 128.2,
127.6, 126.9, 115.6, 43.9, 29.7, 23.8, 22.3. HRMS calcd for
2-((1-(p-Tolyl)ethyl)thio)pyridine (4b)
Yellow oil (40.8 mg, 89%). 1H NMR (400 MHz, CDCl3) d 8.54–
8.36 (m, 1H), 7.45–7.38 (m, 1H), 7.34 (d, J = 8.1 Hz, 2H), 7.10
(t, J = 7.7 Hz, 3H), 6.95 (m, 1H), 5.07 (q, J = 7.0 Hz, 1H), 2.31 (s,
3H), 1.73 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 159.0,
149.4, 140.2, 136.7, 135.9, 129.1, 127.2, 122.7, 119.5, 43.3,
22.6, 21.1. HRMS calcd for C14H16NS [M+H]+ 230.0998, found
230.0997.
C
14H17N2S [M+H]+ 245.1107, found 245.1104.
4,6-Dimethyl-2-((1-(p-tolyl)ethyl)thio)pyrimidine (4j)
Yellow oil (35.1 mg, 68%). 1H NMR (400 MHz, CDCl3) d 7.37 (d,
J = 8.0 Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 6.64 (s, 1H), 5.05 (q,
J = 7.1 Hz, 1H), 2.38 (s, 6H), 2.31 (s, 3H), 1.73 (d, J = 7.1 Hz, 3H).

6028
H. Ma et al. / Tetrahedron Letters 56 (2015) 6022–6029
13C NMR (100 MHz, CDCl3) d 170.9, 166.8, 140.5, 136.5, 128.9,
127.4, 115.5, 43.6, 23.8, 22.3, 21.1. HRMS calcd for C15H19N2S [M
+H]+ 259.1264, found 259.1268.
139.1, 137.4, 129.5, 126.9, 122.0, 44.7, 23.0, 21.1. HRMS calcd for
14H16NS [M+H]+ 230.0998, found 230.0997.
C
2-((1-(4-Methoxyphenyl)ethyl)thio)-5-methyl-1,3,4-thiadiazole
(4s)
2-((1-(4-Methoxyphenyl)ethyl)thio)-4,6-dimethylpyrimidine
(4k)
Yellow oil (42.6 mg). 1H NMR (400 MHz, CDCl3) d 7.42 (d,
J = 8.6 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 6.44 (q, J = 7.0 Hz, 1H),
3.78 (s, 3H), 2.42 (s, 3H), 1.77 (d, J = 7.1 Hz, 3H). 13C NMR
(100 MHz, CDCl3) d 185.5, 159.3, 155.5, 131.5, 128.7, 113.8,
Yellow oil (46.6 mg, 85%). 1H NMR (400 MHz, CDCl3) d 7.40 (d,
J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 6.64 (s, 1H), 5.05 (q,
J = 7.1 Hz, 1H), 3.77 (s, 3H), 2.38 (s, 6H), 1.73 (d, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3) d 170.9, 166.8, 158.5, 135.5, 128.6,
115.5, 113.6, 55.2, 43.4, 23.8, 22.3. HRMS calcd for C15H19N2OS
[M+H]+ 275.1213, found 275.1214.
57.1, 55.2, 19.5, 16.3. HRMS calcd for
267.0621, found 267.0625.
C
12H15N2OS2 [M+H]+
2-((1-(4-Methoxyphenyl)ethyl)thio)-1H-benzo[d]imidazole (4t)
Yellow oil (49.4 mg, 87%). 1H NMR (400 MHz, CDCl3) d 11.10
(s, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.26 (t, J = 3.9 Hz, 1H), 7.17–7.07
(m, 1H), 7.00–6.92 (m, 1H), 6.90–6.83 (m, 2H), 6.79 (d,
J = 8.2 Hz, 1H), 6.69 (q, J = 7.1 Hz, 1H), 3.79 (s, 3H), 1.90 (d,
J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 168.3, 159.0, 130.9,
130.8, 130.7, 128.1, 123.0, 122.5, 114.0, 111.3, 110.0, 55.2, 53.2,
2-((1-(4-Chlorophenyl)ethyl)thio)-4,6-dimethylpyrimidine (4l)
Yellow oil (33.4 mg, 60%). 1H NMR (400 MHz, CDCl3) d 7.42 (d,
J = 8.4 Hz, 2H), 7.25 (d, J = 8.5 Hz, 2H), 6.65 (s, 1H), 5.03 (q,
J = 7.2 Hz, 1H), 2.37 (s, 6H), 1.71 (d, J = 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3) d 170.4, 166.9, 142.4, 132.5, 129.0, 128.3,
115.7, 43.2, 23.8, 22.1. HRMS calcd for C14H16ClN2S [M+H]+
279.0717, found 279.0720.
16.4. HRMS calcd for
285.1058.
C
16H17N2OS [M+H]+ 285.1056, found
2-((1-(4-Fluorophenyl)ethyl)thio)-4,6-dimethylpyrimidine (4m)
Yellow oil (33.0 mg, 63%). 1H NMR (400 MHz, CDCl3) d 7.45 (dd,
J = 8.6, 5.4 Hz, 2H), 6.97 (t, J = 8.7 Hz, 2H), 6.65 (s, 1H), 5.06 (q,
J = 7.2 Hz, 1H), 2.37 (s, 6H), 1.72 (d, J = 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3) d 170.5, 166.9, 161.7 (d, J = 244 Hz), 139.5 (d,
J = 3 Hz), 129.1 (d, J = 8 Hz), 115.6, 115.0 (d, J = 21 Hz), 43.1, 23.8,
2-((1-(4-Bromophenyl)ethyl)thio)-4,6-dimethylpyrimidine (4u)
Yellow oil (37.4 mg, 58%). 1H NMR (400 MHz, CDCl3) d 7.38
(q, J = 8.6 Hz, 4H), 6.65 (s, 1H), 5.02 (q, J = 7.2 Hz, 1H), 2.37 (s,
6H), 1.70 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
170.4, 166.9, 143.0, 131.3, 129.4, 120.6, 115.7, 43.3, 29.7, 23.8,
22.3. HRMS calcd for
263.1011.
C
14H16FN2S [M+H]+ 263.1013, found
22.0. HRMS calcd for
323.0214.
C
14H15BrN2S [M+H]+ 323.0212, found
1-Methyl-5-((1-phenylethyl)thio)-1H-tetrazole (4n)
Yellow oil (41.8 mg, 95%). 1H NMR (400 MHz, CDCl3) d 7.52–
7.42 (m, 2H), 7.35 (m, 3H), 6.06 (q, J = 7.2 Hz, 1H), 3.89 (s, 3H),
1.94 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 163.8, 138.3,
128.8, 128.6, 127.2, 57.8, 34.6, 20.1. HRMS calcd for C10H13N4S
[M+H]+ 221.0856, found 221.0860.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.09.
047.
References and notes
1-Methyl-5-((1-(p-tolyl)ethyl)thio)-1H-tetrazole (4o)
Yellow oil (45.4 mg, 97%). 1H NMR (400 MHz, CDCl3) d 7.36 (d,
J = 8.1 Hz, 2H), 7.16 (d, J = 7.9 Hz, 2H), 6.02 (q, J = 7.2 Hz, 1H),
3.87 (s, 3H), 2.32 (s, 3H), 1.92 (d, J = 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3) d 163.6, 138.5, 135.4, 129.4, 127.1, 57.6, 34.6,
21.1, 20.0. HRMS calcd for C11H15N4S [M+H]+ 235.1012, found
235.1010.
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Peters, D. J. Med. Chem. 2000, 43, 2217; (c) Liu, G.; Huth, J. R.; Olejniczak, E. T.;
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Faucher, A.-M.; White, P. W.; Brochu, C.; Maitre, C. G.; Rancourt, J.; Fazal, G. J.
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Commun. 2014, 1039.
5-((1-(4-Chlorophenyl)ethyl)thio)-1-methyl-1H-tetrazole (4p)
Yellow oil (43.7 mg, 86%). 1H NMR (400 MHz, CDCl3) d 7.45–
7.37 (m, 2H), 7.33 (d, J = 8.6 Hz, 2H), 6.02 (q, J = 7.2 Hz, 1H), 3.88
(s, 3H), 1.92 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) d
163.7, 136.7, 134.5, 129.0, 128.6, 57.0, 34.6, 19.9. HRMS calcd for
2. (a) Hulme, C.; Lee, Y.-S. Mol. Div. 2008, 12, 1; (b) Gudmundsson, K. S.; Drach, J.
C.; Townsend, L. B. J. Org. Chem. 1997, 62, 3453; (c) Rupert, K. C.; Henry, J. R.;
Dodd, J. H.; Wadsworth, S. A.; Cavender, D. E.; Olini, G. C.; Fahmy, B.; Siekierka,
J. J. Bioorg. Med. Chem. Lett. 2003, 13, 347; (d) Ranjit, S.; Duan, Zh. Y.; Zhang, P.
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C
10H12ClN4S [M+H]+ 255.0466, found 255.0463.
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5-((1-(4-Fluorophenyl)ethyl)thio)-1-methyl-1H-tetrazole (4q)
Yellow oil (43.8 mg, 92%). 1H NMR (400 MHz, CDCl3) d 7.47 (dd,
J = 8.6, 5.3 Hz, 2H), 7.04 (t, J = 8.6 Hz, 2H), 6.04 (q, J = 7.2 Hz, 1H),
3.88 (s, 3H), 1.92 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) d
163.6, 162.6 (d, J = 246 Hz), 134.1 (d, J = 3 Hz), 129.0 (d, J = 8 Hz),
115.7 (d, J = 22 Hz), 57.0, 34.5, 20.0. HRMS calcd for C10H12FN4S
[M+H]+ 239.0761, found 239.0765.
4-((1-(p-Tolyl)ethyl)thio)pyridine (4r)
Yellow oil (34.8 mg, 76%). 1H NMR (400 MHz, CDCl3) d 8.33 (dd,
J = 4.7, 1.5 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H),
7.07 (dd, J = 4.6, 1.6 Hz, 2H), 4.55 (q, J = 7.0 Hz, 1H), 2.32 (s, 3H),
1.67 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 149.2, 148.5,

H. Ma et al. / Tetrahedron Letters 56 (2015) 6022–6029
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