Regioselective hydrothiolation of alkenes bearing heteroatoms with thiols catalyzed by palladium diacetate

Article abstract of DOI:10.1021/jo500586a

In sharp contrast to many examples of transition-metal-catalyzed hydrothiolation of alkynes, the corresponding catalytic addition of thiols to alkenes has remained undeveloped. However, a novel Pd-catalyzed addition of thiols to alkenes bearing a heteroatom, such as oxygen and nitrogen, is found to proceed under mild conditions to give the corresponding Markovnikov adducts, regioselectively, in good yields.

Full text of DOI:10.1021/jo500586a

Article
pubs.acs.org/joc
Regioselective Hydrothiolation of Alkenes Bearing Heteroatoms with
Thiols Catalyzed by Palladium Diacetate
Taichi Tamai and Akiya Ogawa*
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai,
Osaka 599-8531, Japan
S
* Supporting Information
ABSTRACT: In sharp contrast to many examples of
transition-metal-catalyzed hydrothiolation of alkynes, the
corresponding catalytic addition of thiols to alkenes has
remained undeveloped. However, a novel Pd-catalyzed
addition of thiols to alkenes bearing a heteroatom, such as
oxygen and nitrogen, is found to proceed under mild
conditions to give the corresponding Markovnikov adducts,
regioselectively, in good yields.
Scheme 1. Palladium-Catalyzed Hydrothiolation
INTRODUCTION
■
Transition-metal-catalyzed addition reactions of heteroatom
compounds have attracted much attention, as a variety of
heteroatom functions can be introduced to organic molecules
by this method with good atom economy, high efficiency, and
high selectivity.1 In parallel with these explorations, highly
selective addition reactions of organosulfur compounds to
unsaturated bonds have been developed using transition-metal
catalysts.2 Compounds containing sulfur functions are known
as valuable feedstock chemicals, finding utility in applications
such as synthetic intermediates, bioactive compounds, and
functional materials.3 However, examples of the transition-
metal-catalyzed addition reaction of organosulfur compounds
have been mostly limited to alkynes; thus, the development of a
transition-metal-catalyzed addition to alkenes is strongly
desired.4−7 The difficulties associated with the catalytic addition
of organosulfur compounds to alkenes can be attributed to the
lower coordination ability of alkenes compared with that of
alkynes, which in turn may contribute to catalyst poisoning.8
However, functionalized alkenes bearing a heteroatom are
expected to show stronger coordination to the catalyst through
assistance of the heteroatom.
Thus, we have focused attention on alkenes bearing
heteroatom as functional alkenes and have developed a novel
Pd-catalyzed addition reaction of thiols with heteroatom-
substituted alkenes, which proceeds with excellent regioselec-
tivity to afford the corresponding Markovnikov adducts in good
yield (Scheme 1). In general, radical addition reactions of thiols
with alkenes are well-known to proceed in the anti-
Markovnikov manner.9 In sharp contrast, the present Pd-
catalyzed hydrothiolation of alkenes affords Markovnikov-type
adducts, regioselectively. Both methods are regio-complemen-
tary to each other.
RESULTS AND DISCUSSION
■
We first examined the optimization of the addition reaction of
benzenethiol (2a) to n-butyl vinyl ether (1a) in the presence of
Pd(OAc)2 as the catalyst (Table 1). When the reaction of n-
butyl vinyl ether (1a) and benzenethiol (2a) was conducted at
45 °C for 20 h using 5 mol % Pd(OAc)2, the Markovnikov-type
hydrothiolation product (3aa) was obtained in 95% yield in a
regioselective fashion without formation of an anti-Markovni-
kov-type adduct (entry 1). When the amount of Pd(OAc)2 was
decreased to 1 mol %, the desired hydrothiolation proceeded
inefficiently (entry 2). In the absence of the Pd catalyst, a
complex reaction mixture resulted, yielding 7% of Markovni-
kov-type adduct 3aa and 18% of the corresponding anti-
Markovnikov-type adduct (entry 3). Next, the optimization of
reaction times and temperatures was examined. Results
indicated that hydrothiolation proceeded well in shorter times
under mild conditions (entries 4−7).
Received: March 12, 2014
Published: April 30, 2014
© 2014 American Chemical Society
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a
the transition-metal-catalyzed reaction of internal alkenes
(entry 6). Furthermore, cyclic vinyl ethers 1g and 1h were
also tolerant to the hydrothiolation (entries 7 and 8).
Table 1. Optimization of Hydrothiolation of Vinyl Ether
We next examined the scope and limitations of this Pd-
catalyzed hydrothiolation of vinyl ethers by using several thiols.
The results of the reaction of n-butyl vinyl ether 1a with several
thiols (2) are summarized in Table 3. In the cases of
b
entry
catalyst
time, h
temp, °C
yield, %
1
2
3
4
5
6
7
Pd(OAc)2 (5 mol %)
Pd(OAc)2 (1 mol %)
none
20
20
20
14
5
45
95
11
7
45
c
Table 3. Pd-Catalyzed Hydrothiolation Using Several
45
a
Thiols
Pd(OAc)2 (5 mol %)
Pd(OAc)2 (5 mol %)
Pd(OAc)2 (5 mol %)
Pd(OAc)2 (5 mol %)
45
80
85
77
83
45
20
20
reflux
30
a
Reaction conditions: n-butyl vinyl ether (1a, 0.5 mmol), benzenethiol
b
1
(2a, 0.5 mmol), THF (0.3 mL). Determined by H NMR analysis.
c
Accompanied by 18% of the anti-Markovnikov hydrothiolation
adduct in the reaction mixture. In other entries, no formation of
anti-adducts was observed.
a
Table 2. Hydrothiolation of Several Vinyl Ethers
a
Reaction conditions: n-butyl vinyl ether (1a, 0.5 mmol), thiol (2, 0.5
b
mmol), Pd(OAc)2 (5 mol %), THF (0.3 mL), 45 °C, 20 h. Isolated
yield.
benzenethiols bearing either electron-donating or -withdrawing
groups, such as methyl, methoxy, fluoro, and chloro
substituents on the aryl groups, the Pd-catalyzed Markovnikov
hydrothiolation took place, affording the corresponding
products 3ab, 3ac, 3ad, and 3ae, respectively, in good yields
(entries 2−5). However, aliphatic thiols, such as phenyl-
methylthiol 2f and cyclohexanethiol 2g, gave low yields of the
corresponding hydrothiolation products 3af and 3ag (entries 6
and 7).10
Highly selective hydrothiolation of alkenes bearing nitrogen
functional groups is also of great interest as an application of
the vinyl ether hydrothiolation to other functionalized alkenes.
We chose N-vinyl lactams as alkenes bearing a nitrogen
functional group for the Pd-catalyzed hydrothiolation. The
lactam skeleton is a prominent structural feature found in a
number of biologically active natural products.11 Some of
bioactive lactam compounds containing a N,S-acetal unit, such
as penicillin, exhibit remarkable antibiosis. Therefore, the
a
Reaction conditions: vinyl ether (1, 0.5 mmol), benzenethiol (2a, 0.5
b
mmol), Pd(OAc)2 (5 mol %), THF (0.3 mL), 45 °C, 20 h. Isolated
yield.
Next, the Pd-catalyzed hydrothiolation of several vinyl ethers
was performed, the results of which are summarized in Table 2.
In the cases of branched vinyl ethers 1b and 1c, the desired
Markovnikov hydrothiolation products were obtained in 85%
and 87% yields, respectively (entries 2 and 3). The reaction of
vinyl ethers 1d and 1e bearing chloro and hydroxyl groups,
respectively, afforded corresponding hydrothiolation products
3da and 3ea in good to moderate yields (entries 4 and 5).
Interestingly, the reaction of internal vinyl ether 1f also
proceeded efficiently to yield the corresponding hydro-
thiolation product despite the generally known difficulty of
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a
development of highly selective methods for the introduction of
a sulfur group to lactam units is strongly desired.
Table 5. Hydrothiolation of Several N-Vinyl Lactams
We examined the optimization of the hydrothiolation
reaction conditions by using N-vinyl pyrrolidinone as a
manageable N-vinyl lactam (Table 4). When the reaction of
Table 4. Optimization of Hydrothiolation of N-Vinyl
a
Lactam
b
entry
catalyst
Pd(OAc)2
time, h
temp, °C
yield, %
1
2
3
4
5
6
7
8
9
20
20
20
20
20
20
20
14
5
45
45
45
45
45
45
30
45
45
94
80
14
16
85
77
93
81
87
Pd(OAc)2 (1 mol %)
none
Pd(PPh3)4
PdCl2(PhCN)2
PdCl2(cod)
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
a
Reaction conditions: N-vinyl lactam (4a, 0.5 mmol), benzenethiol
(2a, 0.5 mmol), Pd(OAc)2 (5 mol %), THF (0.3 mL), 45 °C, 20 h.
b
Isolated yield.
N-vinyl pyrrolidinone (4a) and benzenethiol (2a) was
conducted at 45 °C for 20 h using 5 and 1 mol % Pd(OAc)2,
the Markovnikov-type hydrothiolation product (5aa) was
obtained in 94% and 80% yields, respectively (entries 1 and
2). In the absence of Pd(OAc)2, the desired hydrothiolation of
N-vinyl lactam proceeded inefficiently (entry 3). The reaction
using other palladium catalysts, such as Pd(PPh3)4,
PdCl2(PhCN)2, and PdCl2(cod) was examined (entries 4−6).
PdCl2(PhCN)2- and PdCl2(cod)-catalyzed hydrothiolation
yielded the desired Markovnikov-type adduct in moderate
yield, whereas Pd(PPh3)4 did not catalyze the hydrothiolation
of the N-vinyl lactam. Next, the hydrothiolation was conducted
with varying temperature and time (entries 7−9). These results
clearly indicate that the hydrothiolation of the N-vinyl lactam
proceeded under mild conditions.
a
Reaction conditions: N-vinyl lactams (4, 0.5 mmol), benzenethiol
(2a, 0.5 mmol), Pd(OAc)2 (5 mol %), THF (0.3 mL), 45 °C, 20 h.
b
Isolated yield.
fluoro, and chloro group, afforded the corresponding hydro-
thiolation products 5ab, 5ac, 5ad, and 5ae, respectively (entries
2−5). In the case of aliphatic thiols, such as phenylmethylthiol
2f and cyclohexanethiol 2g, the desired hydrothiolation
products were obtained in moderate to good yields (entries 6
and 7).12
Next, under the optimized reaction conditions, the scope and
limitation of the hydrothiolation of N-vinyl lactams was
examined (Table 5). When internal N-vinyl lactams 4b and
4c were used for hydrothiolation, the corresponding hydro-
thiolation products were obtained in 73% and 69% yields,
respectively (entries 2 and 3). In the case of branched and
aromatic internal N-vinyl lactams 4d and 4e, the desired
hydrothiolation proceeded in good to moderate yields (entries
4 and 5). The reaction of N-vinyl caprolactam 4f took place
efficiently to obtain a Markovnikov adduct regioselectively
(entry 6). In the case of 1-(2-methylpropenyl)-2-pyrrolidinone
4g and 1-cyclohexylidene-2-pyrrolidinone 4h, however the
desired reaction did not proceed at all. This is probably because
the bulkiness of the alkene interrupted the approach of the Pd-
sulfide complex to the alkenes. Moreover, the hydrothiolation
using N-vinyl phthalimide 4i as the substrate did not take place
owing to the lower coordination ability of the nitrogen atom.
Furthermore, Pd-catalyzed hydrothiolations of the N-vinyl
lactam using several thiols were performed, and the results are
summarized in Table 6. Benzenethiols bearing either electron-
donating or -withdrawing groups, such as the methyl, methoxy,
To obtain insight into the present Pd-catalyzed hydro-
thiolation reaction, we examined the catalytic hydrothiolation
of a vinyl ether using a preformed Pd-sulfide complex (Scheme
2). Initially, the Pd-sulfide complex was prepared by the
reaction of Pd(OAc)2 and benzenethiol (2a) according to the
literature.6 The reaction of n-butyl vinyl ether (1a) with
benzenethiol (2a) in the presence of 5 mol % of Pd-sulfide
complex A as a catalyst afforded the corresponding
Markovnikov hydrothiolation product (3aa) in 85% yield.
Furthermore, when the equimolar reaction of Pd-sulfide
complex A with a vinyl ether was conducted, no hydro-
thiolation product was obtained at all. These results strongly
suggest that Pd-sulfide complex A is a highly effective catalyst
for the hydrothiolation of vinyl ethers and also thiol is essential
for catalytic reaction.
Further investigations were conducted to acquire information
on the hydrothiolation reaction. When a Lewis acid catalyst
such as Sc(OTf)3 was introduced to the reaction instead of the
Pd catalyst, the desired hydrothiolation product was not
obtained at all. This result indicates that the Pd catalyst did not
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Table 6. Pd-Catalyzed Hydrothiolation Using Several
Thiols
Scheme 3. A Possible Reaction Pathway of Pd-Catalyzed
Hydrothiolation of Heteroatom-Substituted Alkenes
a
Pd-sulfide complex A, providing Pd-sulfide-alkene complex B,
where heteroatoms might coordinate to palladium, stabilizing
complex B. Subsequent insertion generates palladium inter-
mediate C. The following protonation of palladium inter-
mediate C with thiol provides the Markovnikov hydrothiolation
product regioselectively, with regeneration of Pd-sulfide
complex A.13
CONCLUSION
■
In summary, we have developed a novel and highly selective
Pd-catalyzed Markovnikov hydrothiolation of alkenes bearing
heteroatom functional groups, which proceeds under mild
conditions and affords the addition products in good yields; the
nature of the thiol substrate is general and includes thiols
previously reported as problematic in transition-metal-catalyzed
reactions of alkenes. Internal and cyclic alkenes bearing a
heteroatom are also shown to be compatible. In addition, the
present hydrothiolation could produce O,S-acetals or N,S-
acetals with a new stereogenic center in their structure.
Therefore, application of this methodology toward the
enantioselective hydrothiolation will be explored next, because
these heteroacetals units are known as synthetic intermediates
and bioactive products.11,14 We believe that this reaction will
open up a new field of transition-metal-catalyzed reactions of
alkenes.
a
Reaction conditions: N-vinyl lactam (4a, 0.5 mmol), thiol (2, 0.5
b
mmol), Pd(OAc)2 (5 mol %), THF (0.3 mL), 45 °C, 20 h. Isolated
yield.
Scheme 2. Examination of the Effects of Pd Catalyst
EXPERIMENTAL SECTION
■
General Information. Unless otherwise stated, all starting
materials and catalysts were purchased from a commercial source
and used without further purification. The following substrates were
prepared by using dehydration condensation of pyrrolidinone and the
corresponding aldehyde with p-TsOH: (E)-1-(1-pentenyl)-2-pyrroli-
dinone,15 (E)-1-(3-phenyl-1-propenyl)-2-pyrrolidinone,16 (E)-1-(3,3-
dimethyl-1-butenyl)-2-pyrrolidinone,16 (E)-1-styryl-2-pyrrolidinone,15
1-(2-methylpropenyl)-2-pyrrolidinone,16 and 1-cyclohexylidene-2-pyr-
rolidinone.16 THF as solvent and benzenethiol were used after
serve in a Lewis acid capacity to catalyze the hydrothiolation. As
another possibility, it was considered that AcOH generated
from the reaction of Pd(OAc)2 and benzenethiol might catalyze
this hydrothiolation as a Brønsted acid. Thus, the reaction using
AcOH as a protic acid was examined. However, the
hydrothiolation reaction did not proceed.
Although the details of the reaction mechanism are not clear
at present, a possible reaction pathway for the Pd-catalyzed
hydrothiolation of heteroatom-substituted alkene with thiol 2 is
shown in Scheme 3. We think heteroatoms on the alkene are of
great importance for promotion of the hydrothiolation, because
Pd-catalyzed hydrothiolation of normal alkenes did not proceed
at all. Therefore, the Pd(OAc)2 catalyst reacts with thiols to
form Pd-sulfide complex A. Then, vinyl ether 1 coordinates to
1
distillation. H NMR spectra (400 MHz) and 13C NMR spectra (100
MHz) were taken in CDCl3 with Me4Si as an internal standard.
Chemical shifts in H NMR were measured relative to CDCl3 and
converted to δ (Me4Si) values by using δ (CDCl3) 7.26 ppm.
Chemical shifts in 13C NMR were measured relative to CDCl3 and
converted to δ (Me4Si) values by using δ (CDCl3) 77.00 ppm. IR
spectra are reported in wave numbers (cm−1). FAB mass spectra were
obtained by employing double focusing mass spectrometers. Elemental
1
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analyses and EI mass spectra were performed in the analytical section
of Osaka University.
1319, 1115, 1080, 937, 887, 829, 748, 694 cm−1; HRMS (EI) Calcd for
C10H14O2S: 198.0715. Found: 198.0713.
1-(Phenylthio)butyl Ethyl Ether (3fa). This compound was
prepared from ethyl 1-butenyl ether (64.4 μL, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following the general procedure for
hydrothiolation of vinyl ethers. Isolated as a colorless oil (91.3 mg,
General Procedure for Hydrothiolation of Heteroatom-
Substituted Alkenes. In a two-necked 10 mL flask with a magnetic
stirring bar under a N2 atmosphere were placed Pd(OAc)2 (0.025
mmol), freshly distilled THF (0.3 mL), heteroatom-substituted alkene
(0.5 mmol), and thiol (0.5 mmol), in that order. The reaction was
conducted at 45 °C for 20 h, and then the resulting solution was
filtered through Celite with ethyl acetate as an eluent. Concentration
in vacuo and purification by preparative TLC (silica gel, eluent:
hexane) provided the hydrothiolated product.
1
87%); H NMR (400 MHz, CDCl3, ppm) δ 0.89 (t, J = 7.3 Hz, 3H),
1.22 (t, J = 7.3 Hz, 3H), 1.48 (sext, J = 7.3 Hz, 2H), 1.66−1.81 (m,
2H), 3.48 (qd, J = 6.9 Hz, 9.1 Hz, 1H), 3.95 (qd, J = 6.9 Hz, 9.1 Hz,
1H), 4.70 (dd, J = 6.0 Hz, 7.3 Hz, 1H), 7.23−7.30 (m, 3H), 7.46−7.49
(m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 13.6, 14.8, 19.5, 38.0,
63.4, 88.9, 127.3, 128.6, 133.4, 133.6; IR (NaCl) 3059, 2963, 2932,
2870, 1582, 1477, 1439, 1381, 1288, 1261, 1245, 1115, 1080, 1026,
972, 883, 829, 744, 690 cm−1; Anal. Calcd for C12H18OS: C, 68.52; H,
8.63. Found: C, 68.27; H, 8.63.
Tetrahydro-2-(phenylthio)pyran (3ga). This compound was
prepared from 2,3-dihydropyran (45.6 μL, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following the general procedure
for hydrothiolation of vinyl ethers. Isolated as a colorless oil (85.5 mg,
88%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.57−1.69 (m, 3H),
1.78−1.89 (m, 2H), 1.99−2.06 (m, 1H), 3.55−3.60 (m, 1H), 4.14−
4.19 (m, 1H), 5.20 (dd, J = 3.6 Hz, 5.9 Hz, 1H), 7.18−7.29 (m, 3H),
7.45−7.48 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 21.6, 25.4,
31.5, 64.4, 85.2, 126.6, 128.7, 130.7, 135.3; IR (NaCl) 3063, 2940,
2858, 1582, 1477, 1439, 1339, 1323, 1261, 1188, 1103, 1076, 1038,
1007, 868, 810, 741, 691 cm−1.
Tetrahydro-2-(phenylthio)furan (3ha). This compound was
prepared from 2,3-dihydrofuran (37.7 μL, 0.5 mmol) and benzenethiol
(51.1 μL, 0.5 mmol) following the general procedure for hydro-
thiolation of vinyl ethers. Isolated as a colorless oil (75.7 mg, 84%); 1H
NMR (400 MHz, CDCl3, ppm) δ 1.79−2.06 (m, 3H), 2.31−2.42 (m,
1H), 3.93−4.05 (m, 2H), 5.63−5.66 (m, 1H), 7.19−7.24 (m, 1H),
7.26−7.31 (m, 2H), 7.49−7.52 (m, 2H); 13C NMR (100 MHz,
CDCl3, ppm) δ 24.8, 32.6, 67.2, 87.0, 126.7, 128.7, 131.0, 135.6; IR
(NaCl) 3063, 2974, 2951, 2870, 1582, 1481, 1296, 1223, 1180, 1049,
907, 741, 691 cm−1.
1-(Phenylthio)ethyl Butyl Ether (3aa). This compound was
prepared from n-butyl vinyl ether (64.7 μL, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following the general procedure
for hydrothiolation of vinyl ethers. Isolated as a colorless oil (105.1
1
mg, 95%); H NMR (400 MHz, CDCl3, ppm) δ 0.92 (t, J = 7.3 Hz,
3H), 1.38 (sext, J = 7.3 Hz, 2H), 1.50 (d, J = 6.3 Hz, 3H), 1.54−1.61
(m, 2H), 3.43 (td, J = 6.3 Hz, 9.0 Hz, 1H), 3.88 (td, J = 6.3 Hz, 9.0 Hz,
1H), 4.88 (q, J = 6.3 Hz, 1H), 7.24−7.31 (m, 3H), 7.46−7.48 (m,
2H); 13C NMR (100 MHz, CDCl3, ppm) δ 14.0, 19.5, 22.7, 31.6, 67.9,
84.8, 127.5, 128.8, 133.3, 133.8; IR (NaCl) 3071, 2959, 2932, 2870,
1582, 1481, 1439, 1369, 1315, 1261, 1111, 1026, 972, 910, 744 cm−1;
HRMS (EI) Calcd for C12H18OS: 210.1078. Found: 210.1080; Anal.
Calcd for C12H18OS: C, 68.52; H, 8.63. Found: C, 68.41; H, 8.67.
1-(Phenylthio)ethyl 2-methylpropyl Ether (3ba). This compound
was prepared from 2-methylpropyl vinyl ether (65.0 μL, 0.5 mmol)
and benzenethiol (51.1 μL, 0.5 mmol) following the general procedure
for hydrothiolation of vinyl ethers. Isolated as a colorless oil (89.6 mg,
1
85%); H NMR (400 MHz, CDCl3, ppm) δ 0.92 (dd, J = 6.9 Hz, 8.2
Hz, 6H), 1.50 (d, J = 6.4 Hz, 3H), 1.86 (sept, J = 6.9 Hz, 1H), 3.21
(dd, J = 6.9 Hz, 9.2 Hz, 1H), 3.63 (dd, J = 6.9 Hz, 9.2 Hz, 1H), 4.89
(q, J = 6.4 Hz, 1H), 7.23−7.31 (m, 3H), 7.46−7.49 (m, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 19.5 (overlap), 22.4, 28.3, 74.7, 84.7,
127.3, 128.6, 133.2, 133.6; IR (NaCl) 3074, 2959, 2932, 2870, 1582,
1474, 1435, 1362, 1323, 1265, 1111, 1053, 1026, 891, 745, 691 cm−1;
HRMS (EI) Calcd for C12H18OS: 210.1078. Found: 210.1076.
1-(Phenylthio)ethyl Cyclohexyl Ether (3ca). This compound was
prepared from cyclohexyl vinyl ether (70.9 μL, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following a general procedure for
hydrothiolation of vinyl ethers. Isolated as a colorless oil (102.6 mg,
87%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.16−1.41 (m, 5H), 1.48
(d, J = 6.0 Hz, 3H), 1.49−1.57 (m, 1H), 1.67−1.75 (m, 2H), 1.84−
1.90 (m, 2H), 3.73−3.80 (m, 1H), 5.01 (q, J = 6.0 Hz, 1H), 7.23−7.31
(m, 3H), 7.48−7.51 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ
23.2, 24.0, 24.2, 25.6, 31.1, 33.1, 74.8, 81.5, 127.4, 128.5, 132.9, 134.0;
IR (NaCl) 3063, 2932, 2855, 1582, 1477, 1450, 1369, 1312, 1265,
1153, 1099, 1057, 1026, 972, 883, 745, 694, 621 cm−1; Anal. Calcd for
C14H20OS: C, 71.14; H, 8.53. Found: C, 70.92; H, 8.52.
1-(Phenylthio)ethyl 2-Chloroethyl Ether (3da). This compound
was prepared from 2-chloroethyl vinyl ether (50.7 μL, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following the general procedure for
hydrothiolation of vinyl ethers. Isolated as a colorless oil (97.3 mg,
90%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.52 (d, J = 6.4 Hz, 3H),
3.64 (t, J = 5.5 Hz, 2H), 3.73 (td, J = 5.5 Hz, 10.5 Hz, 1H), 4.11 (td, J
= 5.5 Hz, 10.5 Hz, 1H), 4.97 (q, J = 6.4 Hz, 1H), 7.24−7.32 (m, 3H),
7.47−7.50 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 22.2, 42.7,
67.6, 84.8, 127.7, 128.7, 132.4, 133.6; IR (NaCl) 3059, 2978, 2928,
2862, 1582, 1477, 1439, 1373, 1296, 1265, 1200, 1111, 1042, 1003,
968, 926, 814, 748, 694 cm−1; Anal. Calcd for C10H13ClOS: C, 55.42;
H, 6.05. Found: C, 55.29; H, 5.95.
1-[(p-Methylphenyl)thio]ethyl Butyl Ether (3ab). This compound
was prepared from n-butyl vinyl ether (64.7 μL, 0.5 mmol) and 4-
methylbenzenethiol (62.1 μL, 0.5 mmol) following the general
procedure for hydrothiolation of vinyl ethers. Isolated as a colorless
1
oil (90.3 mg, 81%); H NMR (400 MHz, CDCl3, ppm) δ 0.92 (t, J =
7.3 Hz, 3H), 1.38 (sext, J = 7.3 Hz, 2H), 1.47 (d, J = 6.4 Hz, 3H),
1.52−1.61 (m, 2H), 2.33 (s, 3 H), 3.42 (td, J = 6.4 Hz, 9.2 Hz, 1H),
3.89 (td, J = 6.4 Hz, 9.2 Hz, 1H), 4.82 (q, J = 6.4 Hz, 1H), 7.10 (d, J =
8.1 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H); 13C NMR (100 MHz, CDCl3,
ppm) δ 13.9, 19.4, 21.1, 22.6, 31.5, 67.8, 84.8, 129.1, 129.4, 134.2,
137.6; IR (NaCl) 3017, 2959, 2932, 2870, 1738, 1493, 1458, 1396,
1315, 1265, 1241, 1107, 1088, 1049, 968, 907, 810, 756, 648 cm−1;
Anal. Calcd for C13H20OS: C, 69.59; H, 8.98. Found: C, 69.36; H,
8.80.
1-[(p-Methoxylphenyl)thio]ethyl Butyl Ether (3ac). This com-
pound was prepared from n-butyl vinyl ether (64.7 μL, 0.5 mmol) and
4-methoxylbenzenethiol (61.5 μL, 0.5 mmol) following the general
procedure for hydrothiolation of vinyl ethers. Isolated as a pale yellow
1
oil (69.8 mg, 58%); H NMR (400 MHz, CDCl3, ppm) δ 0.93 (t, J =
7.3 Hz, 3H), 1.39 (sext, J = 7.3 Hz, 2H), 1.43 (d, J = 6.4 Hz, 3H),
1.54−1.61 (m, 2H), 3.41 (td, J = 6.9 Hz, 9.2 Hz, 1H), 3.80 (s, 3H),
3.90 (td, J = 6.9 Hz, 9.2 Hz, 1H), 4.74 (q, J = 6.4 Hz, 1H), 6.82−6.86
(m, 2H), 7.38−7.42 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ
13.9, 19.4, 22.5, 31.5, 55.2, 68.0, 84.9, 114.2, 122.8, 136.4, 159.7; IR
(NaCl) 2959, 2932, 2870, 1593, 1493, 1462, 1366, 1285, 1246, 1173,
1107, 1034, 907, 829, 648, 610 cm−1; Anal. Calcd for C13H20O2S: C,
64.96; H, 8.39. Found: C, 64.87; H, 8.45.
1-(Phenylthio)ethyl 2-Hydroxyethyl Ether (3ea). This compound
was prepared from 2-hydroxyethyl vinyl ether (45.0 μL, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following the general procedure for
hydrothiolation of vinyl ethers. Isolated as a colorless oil (56.1 mg,
57%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.53 (d, J = 6.4 Hz, 3H),
2.02 (br, 1H), 3.55−3.60 (m, 1H), 3.75 (br, 2H), 3.95−4.00 (m, 1H),
4.97 (q, J = 6.4 Hz, 1H), 7.27−7.33 (m, 3H), 7.46−7.50 (m, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 22.3, 61.6, 68.8, 84.8, 127.7, 128.8,
132.5, 133.7; IR (NaCl) 3402, 3074, 2928, 1585, 1477, 1439, 1377,
1-[(p-Fluorophenyl)thio]ethyl Butyl Ether (3ad). This compound
was prepared from n-butyl vinyl ether (64.7 μL, 0.5 mmol) and 4-
fluorobenzenethiol (53.3 μL, 0.5 mmol) following the general
procedure for hydrothiolation of vinyl ethers. Isolated as a colorless
1
oil (95.7 mg, 83%); H NMR (400 MHz, CDCl3, ppm) δ 0.93 (t, J =
7.3 Hz, 3H), 1.38 (sext, J = 7.3 Hz, 2H), 1.45 (d, J = 6.4 Hz, 3H),
1.54−1.63 (m, 2H), 3.42 (td, J = 6.4 Hz, 9.1 Hz, 1H), 3.88 (td, J = 6.4
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Hz, 9.1 Hz, 1H), 4.80 (q, J = 6.4 Hz, 1H), 6.96−7.02 (m, 3H), 7.42−
7.46 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 13.8, 19.4, 22.4,
31.5, 67.9, 84.6, 115.7 (d, JC−F = 22.0 Hz), 127.6 (d, JC−F = 3.8 Hz),
136.2 (d, JC−F = 8.6 Hz), 162.7 (d, JC−F = 247.3 Hz); 19F NMR (376
MHz, CDCl3, ppm) δ −113.9; IR (NaCl) 2959, 2932, 2870, 1894,
1740, 1589, 1489, 1462, 1396, 1369, 1265, 1227, 1157, 1107, 1088,
1034, 972, 907, 829, 760 cm−1; Anal. Calcd for C12H17FOS: C, 63.12;
H, 7.50. Found: C, 62.98; H, 7.56.
1-[(p-Chlorophenyl)thio]ethyl Butyl Ether (3ae). This compound
was prepared from n-butyl vinyl ether (64.7 μL, 0.5 mmol) and 4-
chlorobenzenethiol (72.3 μL, 0.5 mmol) following the general
procedure for hydrothiolation of vinyl ethers. Isolated as a colorless
oil (118.6 mg, 97%); 1H NMR (400 MHz, CDCl3, ppm) δ 0.92 (t, J =
7.3 Hz, 3H), 1.38 (sext, J = 7.3 Hz, 2H), 1.47 (d, J = 6.4 Hz, 3H),
1.53−1.64 (m, 2H), 3.42 (td, J = 6.9 Hz, 9.0 Hz, 1H), 3.85 (td, J = 6.9
Hz, 9.0 Hz, 1H), 4.85 (q, J = 6.4 Hz, 1H), 7.25 (d, J = 8.2 Hz, 2H),
7.39 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 13.8,
19.4, 22.4, 31.4, 67.7, 84.5, 128.7, 131.5, 133.6, 134.9; IR (NaCl) 2959,
2932, 2870, 1570, 1474, 1389, 1373, 1315, 1269, 1111, 1092, 1015,
972, 907, 822, 741, 625 cm−1; Anal. Calcd for C12H17ClOS: C, 58.88;
H, 7.00. Found: C, 58.65; H, 6.88.
1-(Phenylmethylthio)ethyl Butyl Ether (3af). This compound was
prepared from n-butyl vinyl ether (64.7 μL, 0.5 mmol) and
phenylmethylthiol (58.6 μL, 0.5 mmol) following the general
procedure for hydrothiolation of vinyl ethers. Isolated as a colorless
oil (39.2 mg, 35%); 1H NMR (400 MHz, CDCl3, ppm) δ 0.93 (t, J =
7.3 Hz, 3H), 1.39 (sext, J = 7.3 Hz, 2H), 1.52 (d, J = 6.3 Hz, 3H),
1.51−1.59 (m, 2H), 3.41 (td, J = 6.3 Hz, 9.1 Hz, 1H), 3.61 (td, J = 6.4
Hz, 9.1 Hz, 1H), 3.45 (d, J = 13.1 Hz, 1H), 3.79 (d, J = 13.1 Hz), 4.64
(q, J = 6.3 Hz, 1H), 7.19−7.34 (m, 5H); 13C NMR (100 MHz, CDCl3,
ppm) δ 13.9, 19.5, 22.1, 31.7, 32.6, 66.4, 80.6, 126.8, 128.4, 128.9,
138.8; IR (NaCl) 3028, 2959, 2932, 2866, 1597, 1489, 1454, 1369,
1265, 1231, 1103, 1030, 972, 907, 764, 702, 629 cm−1.
1-(Cyclohexylthio)ethyl Butyl Ether (3ag). This compound was
prepared from n-butyl vinyl ether (64.7 μL, 0.5 mmol) and 4-
methylbenzenethiol (61.2 μL, 0.5 mmol) following the general
procedure for hydrothiolation of vinyl ethers. Isolated as a pale yellow
oil (42.7 mg, 39%); 1H NMR (400 MHz, CDCl3, ppm) δ 0.93 (t, J =
7.3 Hz, 3H), 1.21−1.43 (m, 8H), 1.51−1.63 (m, 5H), 1.72−1.75 (m,
2H), 1.93−2.02 (m, 2H), 2.81−2.89 (m, 1H), 3.44 (td, J = 6.4 Hz, 9.2
Hz, 1H), 3.63 (td, J = 6.4 Hz, 9.2 Hz, 1H), 4.78 (q, J = 6.4 Hz, 1H);
13C NMR (100 MHz, CDCl3, ppm) δ 13.9, 19.4, 22.6, 25.7, 31.7, 34.5,
35.0, 41.4, 66.1, 80.6; IR (NaCl) 2928, 2855, 1447, 1369, 1312, 1265,
1204, 1103, 1034, 999, 973, 907, 887, 772, 741, 637 cm−1; HRMS (EI)
Calcd for C12H24OS: 216.1548. Found: 216.1549.
1186, 1091, 1025, 928, 745, 692 cm−1; HRMS (FAB) Calcd for
C15H22NOS [M + H]+: 264.1422. Found: 264.1425.
1-[3-Phenyl-(1-Phenylthio)propyl]-2-pyrrolidinone (5ca). This
compound was prepared from 1-(3-Phenyl-1-propenyl)-2-pyrrolidi-
none (112 mg, 0.5 mmol) and benzenethiol (51.1 μL, 0.5 mmol)
following the general procedure for hydrothiolation of a N-vinyl
lactam. Isolated as a yellow oil (107.0 mg, 69%); 1H NMR (400 MHz,
CDCl3, ppm) δ 1.66−1.84 (m, 2H), 2.00−2.26 (m, 4H), 2.59−2.66
(m, 1H), 2.74−2.81 (m, 1H), 3.14−3.20 (m, 1H), 3.50−3.56 (m, 1H),
5.80 (dd, J = 6.0 Hz, 9.2 Hz, 1H), 7.17−7.30 (m, 8H), 7.38−7.40 (d, J
= 6.9 Hz, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 17.6, 31.0, 33.0,
34.3, 41.4, 58.9, 126.1, 127.4, 128.2, 128.4, 128.8, 132.2, 132.6, 140.5,
174.9; IR (NaCl) 3500, 3061, 3024, 2942, 1685, 1585, 1501, 1489,
1411, 1359, 1283, 1265, 1082, 1027, 908, 838, 745, 693 cm−1; HRMS
(FAB) Calcd for C19H22NOS [M + H]+: 312.1422. Found: 312.1417.
1-[3,3-Dimethyl-(1-Phenylthio)butyl]-2-pyrrolidinone (5da). This
compound was prepared from 1-(3,3-dimethyl-1-butenyl)-2-pyrrolidi-
none (83.6 mg, 0.5 mmol) and benzenethiol (51.1 μL, 0.5 mmol)
following the general procedure for hydrothiolation of a N-vinyl
1
lactam. Isolated as a yellow oil (98.3 mg, 71%); H NMR (400 MHz,
CDCl3, ppm) δ 0.97 (s, 9H), 1.57 (dd, J = 3.2 Hz, 14.7 Hz, 1H),
1.61−1.70 (m, 1H), 1.74−1.87 (m, 2H), 1.90−1.99 (m, 1H), 2.09−
2.20 (m, 1H), 3.26−3.32 (m, 1H), 3.50−3.56 (m, 1H), 5.94 (dd, J =
3.2 Hz, 9.6 Hz, 1H), 7.20−7.28 (m, 3H), 7.40−7.42 (m, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 17.7, 29.3, 31.3, 31.3, 41.2, 44.7,
56.3, 127.5, 128.6, 132.3, 132.6, 174.4; IR (NaCl) 3492, 3057, 2953,
2878, 1691, 1582, 1476, 1411, 1362, 1283, 1266, 1153, 1020, 933, 895,
843, 744, 692 cm−1; Anal. Calcd for C16H23NOS: C, 69.27; H, 8.36; N,
5.05. Found: C, 69.00; H, 8.38; N, 5.13.
1-[2-Phenyl-(1-phenylthio)ethyl]-2-pyrrolidinone (5ea). This
compound was prepared from 1-styryl-2-pyrrolidinone (93.5 mg, 0.5
mmol) and benzenethiol (51.1 μL, 0.5 mmol) following the general
procedure for hydrothiolation of a N-vinyl lactam. Isolated as a yellow
1
oil (70.9 mg, 48%); H NMR (400 MHz, CDCl3, ppm) δ 1.65−1.81
(m, 2H), 1.95−2.12 (m, 2H), 2.99−3.05 (m, 1H), 3.16−3.29 (m, 2H),
3.53−3.59 (m, 1H), 6.05 (dd, J = 6.9 Hz, J = 9.2 Hz, 1H), 7.21−7.31
(m, 8H), 7.39−7.41 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ
17.7, 30.9, 38.9, 41.7, 59.4, 126.9, 127.5, 128.4, 128.7, 128.8, 132.2,
132.6, 136.4; IR (NaCl) 3491, 3068, 3024, 2969, 1690, 1646, 1583,
1482, 1456, 1438, 1410, 1265, 1157, 1078, 1025, 993, 929, 926, 746,
697 cm−1; HRMS (FAB) Calcd for C18H20NOS [M + H]+: 298.1266.
Found: 298.1261.
1-(1-Phenylthio)ethyl-2-caprolactam (5fa). This compound was
prepared from 1-vinyl-2-caprolactam (69.6 mg, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following the general procedure
for hydrothiolation of a N-vinyl lactam. Isolated as a yellow oil (108.0
1
1-[(1-Phenylthio)ethyl]-2-pyrrolidinone (5aa). This compound
was prepared from 1-vinyl-2-pyrrolidinone (53.2 μL, 0.5 mmol) and
benzenethiol (51.1 μL, 0.5 mmol) following the general procedure for
hydrothiolation of a N-vinyl lactam. Isolated as a pale yellow oil (104.4
mg, 87%); H NMR (400 MHz, CDCl3, ppm) δ 1.38−1.66 (m, 6H),
1.42 (d, J = 6.9 Hz, 3H), 2.32−2.43 (m, 2H), 3.27−3.33 (m, 1H),
3.41−3.47 (m, 1H), 6.05 (q, J = 6.9 Hz, 1H), 7.15−7.19 (m, 1H),
7.23−7.27 (m, 2H), 7.33−7.35 (m, 2H); 13C NMR (100 MHz,
CDCl3, ppm) δ 19.0, 23.1, 28.9, 29.7, 37.3, 42.5, 55.7, 126.4, 128.6,
130.0, 133.9, 175.5; IR (NaCl) 3512, 3050, 2929, 2854, 1640, 1477,
1438, 1412, 1366, 1310, 1183, 1147, 1094, 1059, 923, 888, 846, 743,
691 cm−1; Anal. Calcd for C14H19NOS: C, 67.43; H, 7.68; N, 5.62.
Found: C, 67.17; H, 7.87; N, 5.68.
1
mg, 94%); H NMR (400 MHz, CDCl3, ppm) δ 1.48 (d, J = 6.9 Hz,
3H), 1.76−1.83 (m, 1H), 1.86−1.96 (m, 1H), 2.04−2.12 (m, 1H),
2.22−2.30 (m, 1H), 3.28−3.34 (m, 1H), 3.52−3.58 (m, 1H), 5.89 (q, J
= 6.9 Hz, 1H), 7.20−7.30 (m, 3H), 7.39−7.41 (m, 2H); 13C NMR
(100 MHz, CDCl3, ppm) δ 17.5, 18.7, 31.0, 41.1, 54.2, 127.3, 128.6,
132.0, 132.8, 174.3; IR (NaCl) 3495, 3071, 2986, 2881, 1686, 1585,
1481, 1458, 1416, 1350, 1269, 1200, 1092, 1065, 1018, 953, 926, 837,
748, 694 cm−1; HRMS (EI) Calcd for C12H15NOS: 221.0874. Found:
221.0875.
1-[(1-Phenylthio)pentyl]-2-pyrrolidinone (5ba). This compound
was prepared from 1-(1-pentenyl)-2-pyrrolidinone (76.6 mg, 0.5
mmol) and benzenethiol (51.1 μL, 0.5 mmol) following the general
procedure for hydrothiolation of N-vinyl lactam. Isolated as a yellow
oil (96.3 mg, 73%); 1H NMR (400 MHz, CDCl3, ppm) δ 0.90 (t, J =
6.9 Hz, 3H), 1.25−1.42 (m, 4H), 1.68−1.97 (m, 4H), 2.04−2.12 (m,
1H), 2.24−2.32 (m, 1H), 3.20−3.26 (m, 1H), 3.52−3.58 (m, 1H),
5.73 (dd, J = 5.7 Hz, 9.4 Hz, 1H), 7.19−7.29 (m, 3H), 7.38−7.40 (m,
2H); 13C NMR (100 MHz, CDCl3, ppm) δ 13.8, 17.7, 22.0, 28.5, 31.1,
32.2, 41.3, 58.8, 127.2, 128.7, 132.0, 132.9, 174.8; IR (NaCl) 3441,
3049, 2931, 2861, 1685, 1583, 1486, 1458, 1412, 1348, 1281, 1265,
1-{[1-(p-Methylphenyl)thio]ethyl}-2-pyrrolidinone (5ab). This
compound was prepared from 1-vinyl-2-pyrrolidinone (53.2 μL, 0.5
mmol) and 4-methylbenzenethiol (62.1 μL, 0.5 mmol) following the
general procedure for hydrothiolation of a N-vinyl lactam. Isolated as a
pale yellow oil (100.6 mg, 85%); 1H NMR (400 MHz, CDCl3, ppm) δ
1.47 (d, J = 6.8 Hz, 3H), 1.75−1.98 (m, 2H), 2.05−2.13 (m, 1H),
2.22−2.30 (m, 1H), 2.30 (s, 3H), 3.28−3.34 (m, 1H), 3.56−3.62 (m,
1H), 5.82 (q, J = 6.8 Hz, 1H), 7.08 (d, J = 7.7 Hz, 2H), 7.28−7.31 (m,
2H); 13C NMR (100 MHz, CDCl3, ppm) δ 17.6, 18.7, 21.0, 31.1, 41.1,
54.7, 129.0, 129.5, 132.7, 137.7, 174.3; IR (NaCl) 3499, 2974, 2951,
1928, 2885, 1693, 1493, 1458, 1412, 1350, 1265, 1200, 1099, 1088,
1061, 957, 810, 691 cm−1; HRMS (FAB) Calcd for C13H18NOS [M +
H]+: 236.1109. Found: 236.1123.
1-{[1-(p-Methoxylphenyl)thio]ethyl}-2-pyrrolidinone (5ac). This
compound was prepared from 1-vinyl-2-pyrrolidinone (53.2 μL, 0.5
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mmol) and 4-methoxybenzenethiol (61.5 μL, 0.5 mmol) following the
general procedure for hydrothiolation of a N-vinyl lactam. Isolated as a
pale yellow oil (109.2 mg, 87%); 1H NMR (400 MHz, CDCl3, ppm) δ
1.45 (d, J = 6.9 Hz, 3H), 1.77−1.98 (m, 2H), 2.04−2.12 (m, 1H),
2.21−2.29 (m, 1H), 3.28−3.34 (m, 1H), 3.57−3.63 (m, 1H), 3.77 (s,
3H), 5.74 (q, J = 6.9 Hz, 1H), 6.79−6.83 (m, 2H), 7.33−7.37 (m,
2H); 13C NMR (100 MHz, CDCl3, ppm) δ 17.5, 18.5, 31.0, 41.0, 55.0,
55.3, 114.2, 123.0, 135.3, 159.6, 174.2; IR (NaCl) 3483, 2974, 2889,
2835, 1686, 1593, 1493, 1458, 1416, 1354, 1285, 1246, 1200, 1177,
1103, 1057, 1030, 957, 930, 829, 745, 683 cm−1; Anal. Calcd for
C13H17NO2S: C, 62.12; H, 6.82; N, 5.57. Found: C, 61.83; H, 7.00; N,
5.58.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ogawa@chem.osakafu-u.ac.jp.
Notes
The authors declare no competing financial interest.
1-{[1-(p-Fluorophenyl)thio]ethyl}-2-pyrrolidinone (5ad). This
compound was prepared from 1-vinyl-2-pyrrolidinone (53.2 μL, 0.5
mmol) and 4-fluorobenzenethiol (53.3 μL, 0.5 mmol) following the
general procedure for hydrothiolation of a N-vinyl lactam. Isolated as a
pale yellow oil (97.1 mg, 81%); 1H NMR (400 MHz, CDCl3, ppm) δ
1.48 (d, J = 6.9 Hz, 3H), 1.76−2.00 (m, 2H), 2.05−2.13 (m, 1H),
2.23−2.32 (m, 1H), 3.29−3.35 (m, 1H), 3.54−3.60 (m, 1H), 5.82 (q, J
= 6.9 Hz, 1H), 6.94−7.00 (m, 2H), 7.31−7.41 (m, 2H); 13C NMR
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research for JSPS Fellows (1381002900). T.T. thanks the
Japan Society for the Promotion of Science for the Research
Fellowship for Young Scientists.
(100 MHz, CDCl3, ppm) δ 17.5, 18.6, 30.9, 41.0, 55.0, 115.8 (d, JC−F
=
REFERENCES
■
21.1 Hz), 127.9 (d, JC−F = 2.9 Hz), 134.9 (d, JC−F = 8.6 Hz), 162.4 (d,
JC−F = 248.2 Hz), 174.3; 19F NMR (376 MHz, CDCl3, ppm) δ
−113.2; IR (NaCl) 3483, 2978, 2932, 2885, 1686, 1589, 1489, 1458,
1416, 1354, 1269, 1223, 1157, 1092, 1057, 1015, 957, 930, 833, 745,
683 cm−1; Anal. Calcd for C12H14FNOS: C, 60.23; H, 5.90; N, 5.85.
Found: C, 60.03; H, 5.97; N, 5.84.
1-{[1-(p-Chlorophenyl)thio]ethyl}-2-pyrrolidinone (5ae). This
compound was prepared from 1-vinyl-2-pyrrolidinone (53.2 μL, 0.5
mmol) and 4-chlorobenzenethiol (72.3 μL, 0.5 mmol) following the
general procedure for hydrothiolation of a N-vinyl lactam. Isolated as a
pale yellow oil (109.4 mg, 86%); 1H NMR (400 MHz, CDCl3, ppm) δ
1.49 (d, J = 6.9 Hz, 3H), 1.75−1.86 (m, 1H), 1.89−2.00 (m, 1H),
2.09−2.18 (m, 1H), 2.25−2.33 (m, 1H), 3.29−3.35 (m, 1H), 3.50−
3.56 (m, 1H), 5.88 (q, J = 6.9 Hz, 1H), 7.22−7.25 (m, 2H), 7.31−7.34
(m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 17.5, 18.7, 30.1, 41.0,
54.3, 128.8, 131.4, 133.2, 133.4, 174.3; IR (NaCl) 3479, 3078, 2978,
2882, 1686, 1574, 1477, 1458, 1412, 1354, 1266, 1204, 1096, 1011,
957, 822, 744, 687, 644 cm−1; Anal. Calcd for C12H14ClNOS: C,
56.35; H, 5.52; N, 5.48. Found: C, 56.13; H, 5.43; N, 5.50.
1-{[1-(Phenylmethylthio]ethyl}-2-pyrrolidinone (5af). This com-
pound was prepared from 1-vinyl-2-pyrrolidinone (53.2 μL, 0.5 mmol)
and phenylmethylthiol (58.6 μL, 0.5 mmol) following the general
procedure for hydrothiolation of a N-vinyl lactam. Isolated as a yellow
oil (85.3 mg, 72%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.35 (d, J =
7.3 Hz, 3H), 1.42−1.54 (m, 1H), 1.77−1.88 (m, 1H), 2.06−2.14 (m,
1H), 2.24−2.32 (m, 1H), 3.15−3.21 (m, 1H), 3.34−3.40 (m, 1H),
3.63 (d, J = 14.2 Hz, 1H), 3.73 (d, J = 14.2 Hz, 1H), 5.61 (q, J = 7.3
Hz, 1H), 7.19−7.23 (m, 1H), 7.26−7.34 (m, 4H); 13C NMR (100
MHz, CDCl3, ppm) δ 17.1, 19.1, 31.3, 35.8, 40.8, 52.8, 126.7, 128.2,
128.4, 138.4, 174.5; IR (NaCl) 3503, 3028, 2974, 2928, 2882, 1686,
1597, 1493, 1454, 1416, 1350, 1312, 1269, 1196, 1061, 1026, 957, 918,
849, 768, 710, 640 cm−1; Anal. Calcd for C13H17NOS: C, 66.34; H,
7.28; N, 5.95. Found: C, 65.95; H, 7.35; N, 6.01.
1-(1-Cyclohexylthio)ethyl-2-pyrrolidinone (5ag). This compound
was prepared from 1-vinyl-2-pyrrolidinone (53.2 μL, 0.5 mmol) and
cyclohexylthiol (61.2 μL, 0.5 mmol) following the general procedure
for hydrothiolation of a N-vinyl lactam. Isolated as a pale yellow oil
(67.1 mg, 59%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.22−1.38 (m,
5H), 1.38 (d, J = 6.9 Hz, 3H), 1.55−1.58 (m, 1H), 1.71−1.80 (m,
3H), 1.98−2.06 (m, 2H), 2.10−2.14 (m, 1H), 2.42 (t, J = 8.2 Hz, 2H),
2.50−2.61 (m, 1H), 3.27−3.33 (m, 1H), 3.61−3.66 (m, 1H), 5.61 (q, J
= 6.9 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ 17.7, 19.5, 25.6,
25.7, 26.0, 31.5, 33.3, 34.0, 40.9, 42.9, 50.4, 174.2; IR (NaCl) 3510,
2974, 2928, 2851, 1686, 1497, 1447, 1412, 1265, 1196, 1061, 995, 953,
929, 888, 849, 748, 694 cm−1; HRMS (FAB) Calcd for C12H22NOS
[M + H]+: 228.1422. Found: 228.1420.
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̃
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The Journal of Organic Chemistry
Article
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intermediate from the N-vinyl lactam may proceed easily compared
with the case of vinyl ether.
(13) An alternative reaction mechanism, which proceeds via
palladium intermediate C′, is possible as shown below. Although we
try to obtain some information about the reaction intermediates, clear
evidence could not be obtained. Palladium intermediate C
immediately converts to C′ due to stabilization by intramolecular
coordination of the ether oxygen atom. We think this stabilization
prevents β-elimination of C from taking place. The subsequent
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