Regio- and Stereoselective Hydrosulfonation of Alkynylcarbonyl Compounds with Sulfinic Acid in Water

Article abstract of DOI:10.1021/acs.joc.6b01549

We report the atom-economic and environmentally friendly synthesis of Z-β-sulfonyl-a,β-unsaturated carbonyl compounds in water. The mechanism study reveals that the hydrosulfonylation of alkynylcarbonyl compounds with sulfinic acids proceeds via a mechanism that features a sulfinic acid molecule protonating an alkynyl motif to form the ethenium intermediate, which subsequently reacted with a sulfonyl anion to afford the desired products. The ethenium intermediate differentiated electronic and steric demands between the two substituents on the C≡C triple bond of the alkyne substrates to exhibit high regio- and stereoselectivity from a wide range of Z-β-sulfonyl-a,β-unsaturated carbonyl compounds.

Full text of DOI:10.1021/acs.joc.6b01549

Article
pubs.acs.org/joc
Regio- and Stereoselective Hydrosulfonation of Alkynylcarbonyl
Compounds with Sulfinic Acid in Water
Chao Wu, Panpan Yang, Zhimin Fu, Yong Peng, Xin Wang, Zuozhi Zhang, Fang Liu, Wenyi Li,
Zhizhang Li, and Weimin He*
Key Laboratory of Comprehensive Utilization of Advantage Plants Resources in Hunan South, College of Chemistry and
Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China
S
* Supporting Information
ABSTRACT: We report the atom-economic and environmentally friendly synthesis of Z-β-sulfonyl-a,β-unsaturated carbonyl
compounds in water. The mechanism study reveals that the hydrosulfonylation of alkynylcarbonyl compounds with sulfinic acids
proceeds via a mechanism that features a sulfinic acid molecule protonating an alkynyl motif to form the ethenium intermediate,
which subsequently reacted with a sulfonyl anion to afford the desired products. The ethenium intermediate differentiated
electronic and steric demands between the two substituents on the CC triple bond of the alkyne substrates to exhibit high
regio- and stereoselectivity from a wide range of Z-β-sulfonyl-a,β-unsaturated carbonyl compounds.
involving a sequential intermolecular C−S bond forming step
via nucleophilic addition at low temperature, followed by an
oxidation reaction (Scheme 1, eq 2).6 However, sulfide sources
are frequently reported to have unstable, toxic, and odorous
properties; the use of hazardous additives (N,N-diisopropyl-
ethylamine, potassium tert-butylate, and lithium perchlorate)
have greatly hindered its application in synthetic chemistry.
Most importantly, these methods are not atom economical, as
only a part of the reagent used for the introduction of sulfonyl
group is retained.
INTRODUCTION
■
Complex organic molecules play a crucial role in the study and
treatment of disease. The extent to which they can be utilized in
these endeavors depends on the efficient and selective chemical
methods for their construction from simple and readily
accessible starting materials. β-Sulfonyl-α,β-unsaturated carbon-
yl compounds are widely represented in biologically active
molecules1 and serve as versatile building blocks in organic
synthesis.2 Consequently, the selective assembly of β-sulfonyl-
α,β-unsaturated carbonyl compounds from commercially
available raw materials is a prominent objective in chemical
research. There are a number of powerful methods for the
preparation of the (E) isomer of β-sulfonyl-α,β-unsaturated
carbonyl compounds.3 However, the synthesis of the
corresponding (Z) isomers are more challenging and typically
require multistep routes that are potentially complicated by
competing isomerization to the more thermodynamically
favored (E) isomer. Examples of direct production of Z-β-
sulfonyl-α,β-unsaturated carbonyl compounds from alkynylcar-
bonyl compounds are rare. Dai and co-workers reported a
single example of NHC catalyzed sulfonylation of ethyl
propiolate with N-tosylbenzaldimine in the presence of DBU
as a base to give Z-ethyl 3-tosyl acrylate only in low yield
(Scheme 1, eq 1).4 In addition, the reaction is intrinsically
limited to costly catalysts and requires an additional
prefunctionalization process of benzenesulfonamide.5 Downey
et al. developed a different method to Z-β-sulfonyl enoates
Reactions in aqueous media are of paramount importance in
organic syntheses.7 The use of many toxic and volatile organic
solvents, particularly chlorinated hydrocarbons, as reaction
media contributes to the environment pollution, and it is highly
desirable to develop environmentally benign processes that can
be conducted in aqueous media. Furthermore, using water as a
solvent offers many advantages such as simple operation,
nonflammability, and high efficiency in many organic reactions
that involve insoluble reagents.8
Continuing with our interest in alkyne chemistry,9 we herein
disclose our investigation on the synthesis of Z-β-sulfonyl-α,β-
unsaturated carbonyl compounds through hydrosulfonation of
alkynylcarbonyl compounds with sulfinic acid10 under environ-
mentally friendly conditions. In addition to the impressive
Received: June 28, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b01549
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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Scheme 1. Synthesis of Z-β-Sulfonyl Enoates
scope, important novel aspects are the organic solvent-, external
catalyst-, additive-free reaction conditions and excellent
chemo-, regio-, and stereoselectivity. Moreover, large-scale
synthesis of (Z)-ethyl 3-tosyl acrylate is described (Scheme 1,
eq 3).
tional simplicity, excellent yields, and high stereoselectivity
make this transformation an alternative method for the facile
construction of numerous Z-β-sulfonyl enoates.
With the optimum conditions in hand, the reaction scope
with regard to the sulfinic acids was first examined (Table 2).
No matter what substitute group (electron-neutral, electron-
rich, electron-deficient, or steric hindrance group) the benzene
ring of benzenesulphinic acid carries, in all cases the sulfonated
products (3aa−ao) were obtained in good to excellent yields
and a satisfactory range of Z/E ratios from 14:1 to 30:1 (based
on the analysis of 1H NMR spectra). Various functional groups
were readily well tolerated, including alkoxyl (3ac and 3ad),
amide (3ae), halide (3af − ai), trifluoromethyl (3aj), acyl
(3ak), cyano (3al), and nitro (3am) groups. Furthermore,
benzenesulphinic acids bearing two- or three-substituents on
the arene rings could also be converted to corresponding
products (3ap and 3aq) in good yields. We were pleased that
the sulfonating of the polycyclic and heterocyclic aromatic
motif was possible and proceeded in good yields as well as high
Z/E ratios (3ar and 3as), thus further enhancing the scope of
our reaction. In addition, aliphatic sulfinic acids were good
coupling partners (3at and 3au). The reaction proceeded
efficiently to afford their corresponding hydrosulfonation
products in moderate to good yields even for the substrates
bearing functional groups such as free chloro.
Subsequently, we further investigated the scope of
alkynylcarbonyl compounds (Table 3). To our satisfaction,
propargylic carboxylates with various chain lengths and
isomeric structures undergo hydrosulfonation to furnish the
β-sulfonyl enoates in good yields with high stereoselectivity in
favor of the (Z)-isomer. Excellent functional group compati-
bility was exhibited, tolerating alkyl (3ba−3ca), Ph (3da),
cyclopropylmethyl (3ea), cyclopentyl (3fa), free OH (3ga), Br
(3ha), and thiophenemethyl (3ia) moieties. Notably, the
reaction could be extended to thermodynamically more stable
internal propargylic carboxylates possessing substituents with
various electronic and steric properties (3ja−na). Subjecting
the substrate ethyl 3-(trimethylsilyl)propiolate 1j to the
standard reaction conditions could successfully afford the
(Z)-ethyl 3-tosyl acrylate in 84% yield, allowing access to ethyl
propiolate via deprotection of the TMS group. Compared with
alkyl-substituted substrates (3ka), phenyl-substituted ethyl
propiolate (3la) exhibit relatively poor reactivity and the
examples indicate steric hindrance play a key role in these
transformations. The electron-rich groups attached to ethyl
propiolate led usually to higher yields than did the electron-
deficient groups (3ka vs 3ma and 3na). Gratifyingly, the
present catalytic reaction was also successfully applied to other
electron-withdrawing group substituted acetylenes, including
carboxyl (3oa), amide (3pa and 3qa), sulfonic ester (3ra), and
RESULTS AND DISCUSSION
■
Initially, we performed the hydrosulfonation of the readily
available ethyl propiolate (1a) with 4-methylbenzenesulfinic
acid (2a) in water at room temperature. To our delight, an 18%
NMR yield of ethyl 3-tosyl acrylate (3aa) based on 21%
conversion of the starting material 1a was obtained after 24 h
(Table 1, entry 1). To check the effect of temperature on the
a
Table 1. Optimization of the Reaction Conditions
b
b
entry
ratio
temp (°C)
time
concn (M) yield
E/Z
1
2
3
4
5
6
7
1:1
rt
24 h
8 h
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0.2
18
24
55
55
72
92
92
90
92
14:1
14:1
16:1
15:1
16:1
16:1
16:1
16:1
16:1
1:1
40
60
80
60
60
60
60
60
1:1
4 h
1:1
4 h
1.1.1
1:1.2
1:1.3
1:1.2
1:1.2
2 h
1.5 h
1.5 h
1.5 h
1 h
c
8
d
9
a
Unless otherwise specified, the reactions were carried out in sealed
tubes in the presence of 1a (0.1 mmol), 2a, and water (1 mL).
b
1
Estimated by H NMR spectroscopy using diethyl phthalate as an
c
d
internal reference. 2 mL of water were used as the solvent. 0.5 mL
water was used as the solvent. rt = room temperature.
reaction, the test reaction was carried out at different
temperatures (entries 2−4). It was found that the maximum
conversion occurred at 60 °C, providing the desired product
3aa in 55% yield after 4 h (entry 3). A higher temperature (80
°C) did not improve the yield (entry 4). Significantly,
employment of a slight excess of 2a (1.1−1.3 equiv) was
found to provide the desirable product 3aa in good to excellent
yields with high stereoselectivity for E/Z = 16:1 isomers
(entries 5−7). These results indicated that the proton has a
significant role in the reactions. Conducting the reaction at a
concentration of 0.05 M did not affect the reaction yield (entry
8 vs 7); however, a higher concentration of 0.2 M was selected
to provide conditions that minimize solvent waste and reduce
the reaction time from 1.5 to 1 h (entry 9 vs 7). Mild reaction
conditions, shorter reaction times, cost-effectiveness, opera-
B
DOI: 10.1021/acs.joc.6b01549
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The Journal of Organic Chemistry
Article
Table 2. Reaction Scope of Sulfinic Acidsa
Table 3. Reaction Scope of Substituted Alkynesa
Table 4. Reaction Scope of Late-Stage Modificationa
acetyl (3sa) groups, which gave the corresponding hydro-
sulfonation products in moderate to good yields.
β-Sulfonylenoates are important multifunctional motifs
present in a wide range of bioactive compounds, synthetic
intermediates, and pharmaceuticals. In addition, late-stage
modification is a valuable strategy for medicinal chemistry
research. Therefore, the hydrosulfonylation method was applied
for the synthesis of vinyl sulfones containing bioactive moieties
(Table 4). Derivatives bearing natural groups such as perillyl,
borneol, indanol, and benzoin could well react with 4-
C
DOI: 10.1021/acs.joc.6b01549
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The Journal of Organic Chemistry
Article
methylbenzenesulfinic acid 2a to give the desired products
(4aa−da) in 50−79% yields and with Z/E ratios ranging from
9:1 to 14:1. These results demonstrate that the present
protocol could be applied in late-stage bioactive compound
modification.
Based on the above results, we propose a potential
mechanistic pathway for this hydrosulfonation of alkynylcar-
bonyl compound (Scheme 4). Initially, sulfinic acid 2 was
Scheme 4. Plausible Reaction Mechanism
For the small-scale reaction, 1.2 equiv of sulfinic acid 2a was
required, and the decrease in 2a loading would dramatically
decrease the yield (Table 1, entry 6 vs 5). Delightedly, the use
of 1.1 equiv of 2a could afford the desired product in 84% yield
(1.06 g) with an increase in the scale of the reaction by 25-fold
(Scheme 2), demonstrating the synthetic utility of this protocol
Scheme 2. Gram Scale Synthesis of (Z)-Ethyl 3-Tosylacrylate
converted into an oxygen-centered anion I resonating with the
sulfonyl anion II via the single electron transfer (SET) and
deprotonation process in water. Simultaneously, propargylic
carboxylates 1 were protonated by sulfinic acid to give the
activated ethenium intermediate III.12 Subsequently, the regio-
and antiselective nucleophilic addition of the sulfonyl anion II
to intermediate III generated the corresponding Z-β-sulfonyl
enoates 3. We speculate that a relatively weak acidity (pH
around 6) of the reaction mixture is crucial. Most of the sulfinic
acid is quickly consumed via reaction with intermediate III;
therefore, the overall acidity of the reaction is dominated by the
acidity of excess sulfinic acid.
from a practical point of view. Importantly, the products were
easily recrystallized to afford the pure Z-isomer of β-sulfonyl
enoates. No column chromatography was used at all during the
purification process.
In order to gain information on the reaction mechanism,
several control experiments were conducted. First, the
hydrosulfonylation reaction of 1k in D2O gave 3ka and D-
3ka in 74% and 8% NMR yields, respectively (Scheme 3A).
CONCLUSIONS
■
Scheme 3. Mechanism Study Experiments
In conclusion, we have developed the atom-economic hydro-
sulfonation of activated alkynes with sulfinic acid to afford
valuable Z-β-sulfonyl-α,β-unsaturated carbonyl compounds in
environmentally friendly conditions. In this reaction, the
sulfinic acid plays three roles, acting as the sulfonation reagent,
hydrogen source, and activating reagent. This transformation
can also tolerate a range of functional groups due to its weak
acidity and redox-neutral conditions. The intermolecular
hydrosulfonation of activated alkynes shows excellent chemo-
and regioselectivity as well as high stereoselectivity. Finally, the
proposed mechanism was carefully explored through competi-
tion experiments, control experiments, and deuterium-labeling
experiments. We expect this detailed study would shed light on
the scope and potential of the activation strategy of activated
alkynes.
EXPERIMENTAL SECTION
■
General Information. Commercially available reagents were of
reagent grade (AR grade) and were used without further purification.
Reactions were monitored by thin layer chromatography (TLC) using
silicycle precoated silica gel plates. Chromatographic purifications were
This result clearly demonstrated that the α-hydrogen atom of
β-sulfonyl-α,β-unsaturated carbonyl compound 3 originated
from sulfinic acid 2. Next, addition of a radical scavenger (for
example, TEMPO and BHT) to the reaction mixture under the
standard reaction conditions did not make this hydro-
sulfonylation reaction completely suppressed, excluding the
possibility of a radical process (Scheme 3B).10e−i,11 Moreover,
the acetylene 1t, 3,3-dimethylbut-1-yne 1u, ethynyl acetate 1v,
and phenylacetylene 1w were subjected to the reaction with 2a,
but no sulfonylated products were observed (Scheme 3C),
confirming the electron-withdraw group is essential for this
transformation. These observations indicating the electron-
donating substitution, which may promote the electrophilic
addition of alkynyl group, has a negative influence on the
reaction. These results exclude the possibility of the electro-
philic mechanism.
carried out on a Biotage Isolera Four instrument. H NMR and 13C
1
NMR spectra were recorded on a 400 and 500 MHz NMR plus
spectrometer using residue solvent peaks as internal standards.
Infrared spectra were recorded with an IR spectrometer and are
reported in reciprocal centimeter (cm−1). High resolution mass spectra
were obtained using a GCT-TOF instrument with an EI or ESI source.
General Procedure for the Synthesis of Z-β-Sulfonyl
Enoates. In a sealed tube were placed alkynylcarbonyl compound
(0.2 mmol), sulfinic acid (0.24 mmol), and H2O (1 mL), and then the
contents were stirred at 60 °C. The progress of the reaction was
monitored by TLC. The reaction typically took 1−2 h. Upon
completion, the reaction was cooled down to room temperature,
mixed with silica gel, and concentrated under vacuum. Gradient
elution with ethyl acetate/hexane was accomplished in both instances.
This residue was purified by flash chromatography on silica gel
(eluent: hexanes/ethyl acetate) to afford 3−4.
D
DOI: 10.1021/acs.joc.6b01549
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The Journal of Organic Chemistry
Article
The Experimental Procedure for Larger-Scale Synthesis of
3aa. In a sealed tube were placed ethyl propiolate (5 mmol, 0.49 g), 4-
methylbenzenesulfinic acid (5.5 mmol, 0.855 g), and H2O (10 mL),
and then the contents were stirred at 60 °C for 1.5 h. The reaction was
cooled down to room temperature and concentrated under vacuum.
This residue was recrystallized by hexane and tetrahydrofuran to give
3aa (1.06 g, yield 84%).
142.9, 135.6 (q, J = 32.7 Hz), 134.5, 133.5, 128.8, 126.4 (q, J = 3.8
Hz), 123.1 (q, J = 271.8 Hz), 62.3, 13.9. IR (neat, cm−1): 3077, 2989,
1726, 1680, 1320, 1086, 755. HRMS calcd (ESI) m/z: for
C12H11NaF3O4S [M + Na]+, 331.0222; found, 331.0217.
(Z)-Ethyl 3-((4-Acetylphenyl)sulfonyl)acrylate (3ak). White solid
(46.8 mg, 83%), mp 53−54 °C. 1H NMR (400 MHz, CDCl3) δ 8.09−
8.05 (m, 4H), 6.56 (d, J = 11.2 Hz, 1H), 6.53 (d, J = 11.6 Hz, 1H),
4.33 (q, J = 7.2 Hz, 2H), 2.63 (s, 3H), 1.35 (t, J = 6.8 Hz, 3H).
13C{1H}NMR (100 MHz, CDCl3) δ 196.6, 163.6, 143.0, 140.8, 134.5,
133.0, 128.8, 128.4, 62.1, 26.8, 13.8. IR (neat, cm−1): 3077, 2956,
1732, 1720, 1659, 1298, 1106, 752. HRMS calcd (ESI) m/z: for
C13H14NaO5S [M + Na]+, 305.0454; found, 305.0448.
(Z)-Ethyl 3-Tosyl Acrylate (3aa).6 White solid (45.2 mg, 89%), mp
1
41−42 °C. H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.0 Hz, 2H),
7.37 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 11.6 Hz, 1H), 6.48 (d, J = 11.6
Hz, 1H), 4.32 (q, J = 6.8 Hz, 2H), 2.45 (s, 3H), 1.38 (t, J = 7.2 Hz,
3H). 13C{1H}NMR (100 MHz, CDCl3) δ 164.0, 145.1, 136.4, 135.3,
131.4, 130.0, 128.2, 62.1, 21.7, 13.9.
(Z)-Ethyl 3-(4-Cyanophenylsulfonyl)acrylate (3al). White solid
(Z)-Ethyl 3-(Phenylsulfonyl)acrylate (3ab).6 Colorless oil (41.7 mg,
87%). 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.0 Hz, 2H), 7.69−
7.65 (m, 1H), 7.61−7.56 (m, 2H), 6.54 (d, J = 11.2 Hz, 1H), 6.50 (d, J
= 11.2 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H).
13C{1H}NMR (100 MHz, CDCl3) δ 164.0, 139.4, 135.1, 134.0, 131.9,
129.4, 128.2, 62.2, 14.0.
1
(43.5 mg, 82%), mp 66−67 °C. H NMR (400 MHz, CDCl3) δ 8.14
(d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.8 Hz, 2H), 6.62 (d, J = 11.2 Hz,
1H), 6.55 (d, J = 11.6 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H), 1.37 (t, J =
7.2 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 163.5, 143.6, 134.5,
134.0, 133.0, 128.9, 117.7, 117.0, 62.4, 13.9. IR (neat, cm−1): 3074,
2982, 2224, 1730, 1680, 1086, 793. HRMS calcd (ESI) m/z: for
C12H11NaNO4S [M + Na]+, 288.0301; found, 288.0298.
(Z)-Ethyl 3-(4-Methoxyphenylsulfonyl)acrylate (3ac).6 White solid
1
(Z)-ethyl 3-(4-Nitrophenylsulfonyl)acrylate (3am).14 White solid
(49.1 mg, 91%), mp 47−48 °C. H NMR (400 MHz, CDCl3) δ 7.92
1
(d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 6.49 (d, J = 11.2 Hz,
1H), 6.45 (d, J = 11.2 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H), 3.88 (s, 3H),
1.39 (t, J = 7.2 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 164.2,
164.1, 135.6, 130.9, 130.6, 114.6, 62.1, 55.7, 14.0.
(43.9 mg, 77%), mp 59−60 °C. H NMR (400 MHz, CDCl3) δ 8.41
(d, J = 8.8 Hz, 2H), 8.23 (d, J = 8.8 Hz, 2H), 6.64 (d, J = 11.6 Hz,
1H), 6.58 (d, J = 11.2 Hz, 1H), 4.38 (q, J = 7.2 Hz, 2H), 1.39 (t, J =
7.2 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 163.4, 151.0, 145.2,
134.5, 134.3, 129.8, 124.4, 62.5, 13.8.
(Z)-Ethyl 3-(4-(Trifluoromethoxy)phenylsulfonyl)acrylate (3ad).
1
Light yellow solid (51.8 mg, 80%), mp 46−48 °C. H NMR (400
(Z)-Ethyl 3-(m-Tolylsulfonyl)acrylate (3an). Colorless oil (41.1 mg,
1
MHz, CDCl3) δ 8.15 (d, J = 8.4 Hz, 2H), 7.83(d, J = 8.4 Hz, 2H), 6.60
(d, J = 11.2 Hz, 1H), 6.55 (d, J = 11.2 Hz, 1H), 4.37 (q, J = 7.2 Hz,
2H), 1.37 (t, J = 7.2 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ
163.7, 142.9, 135.6 (d, J = 32.6 Hz), 134.5, 133.5, 128.9, 126.4 (q, J =
3.8 Hz), 123.0 (d, J = 271.8 Hz), 62.3, 13.9. IR (neat, cm−1): 3076,
2981, 1732, 1669, 1313, 1150, 735, 701. HRMS calcd (ESI) m/z: for
C12H11NaF3O5S [M + Na]+, 347.0171; found, 347.0177.
81%). H NMR (400 MHz, CDCl3) δ 7.83−7.77 (m, 2H), 7.46−7.2
(m, 2H), 6.52 (d, J = 11.2 Hz, 1H), 6.48 (d, J = 11.6 Hz, 1H), 4.35 (q,
J = 7.2 Hz, 2H), 2.44 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H). 13C{1H}NMR
(100 MHz, CDCl3) δ 163.0, 138.6, 138.3, 134.1, 133.8, 130.7, 128.2,
127.4, 124.3, 61.1, 20.3, 13.0. IR (neat, cm−1): 3081, 2979, 1723, 1339,
1141, 789. HRMS calcd (ESI) m/z: for C12H14NaO4S [M + Na]+,
277.0505; found, 277.0501.
(Z)-Ethyl 3-(4-Acetamidophenylsulfonyl)acrylate (3ae).13 White
solid (52.8 mg, 89%), mp 52−54 °C. 1H NMR (400 MHz, CDCl3) δ
7.92 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.8 Hz, 2H), 7.64 (s, 1H), 6.53
(d, J = 11.2 Hz, 1H), 6.49 (d, J = 11.2 Hz, 1H), 4.36 (q, J = 6.8 Hz,
2H), 2.22 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H). 13C{1H}NMR (100 MHz,
CDCl3) δ 168.6, 164.0, 143.2, 135.4, 133.9, 131.5, 129.7, 119.3, 62.1,
24.6, 13.8.
(Z)-Ethyl 3-(Phenylsulfonyl)acrylate (3ao). Colorless oil (40.1 mg,
1
77%). H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.6 Hz, 1H), 7.52
(t, J = 7.2 Hz, 1H), 7.38(t, J = 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H),
6.61 (d, J = 12 Hz, 1H), 6.51 (d, J = 11.6 Hz, 1H), 4.28 (q, J = 6.8 Hz,
2H), 2.65 (s, 3H), 1.33 (t, J = 7.2 Hz, 3H). 13C{1H}NMR (100 MHz,
CDCl3) δ 163.6, 138.4, 137.8, 135.6, 134.0, 132.6, 131.6, 129.7, 126.5,
62.1, 20.3, 13.9. IR (neat, cm−1): 3070, 2972, 1729, 1669, 1327, 1081,
722. HRMS calcd (ESI) m/z: for C12H14NaO4S [M + Na]+, 277.0505;
found, 277.0501.
(Z)-Ethyl 3-(4-Fluorophenylsulfonyl)acrylate (3af).6 Light yellow
solid (41.8 mg, 81%), mp 46−48 °C. 1H NMR (400 MHz, CDCl3) δ
8.09−8.06 (m, 2H), 7.29 (d, J = 8.0 Hz 2H), 6.57 (s, 2H), 4.40 (q, J =
7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H). 13C{1H}NMR (100 MHz,
CDCl3) δ 165.8 (d, J = 255.5 Hz), 163.8, 135.3 (d, J = 3.0 Hz), 134.9,
132.2, 131.1 (d, J = 9.7 Hz), 116.5 (d, J = 22.7 Hz), 62.3, 14.0.
(Z)-Ethyl 3-(4-Chlorophenylsulfonyl)acrylate (3ag).13 Colorless oil
(Z)-Ethyl 3-(4-Chloro-3-fluorophenylsulfonyl)acrylate (3ap).
1
White solid (47.3 mg, 81%), mp 77−78 °C. H NMR (400 MHz,
CDCl3) δ 8.10−8.08 (m, 1H), 7.94−7.90 (m, 1H), 7.33 (t, J = 8.4 Hz,
1H), 6.58 (d, J = 11.6 Hz, 1H), 6.53 (d, J = 11.6 Hz, 1H), 4.35 (q, J =
7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H).13C{1H}NMR (100 MHz,
CDCl3) δ 166.1 (d, J = 271.2 Hz), 163.9, 135.5 (d, J = 3.7 Hz), 135.2,
132.2, 131.3 (d, J = 9.4 Hz), 116.7 (d, J = 22.6 Hz), 62.3, 13.9. IR
(neat, cm−1): 3077, 2985, 1732, 1324, 1153, 822. HRMS calcd (ESI)
m/z: for C11H10NaClFO4S [M + Na]+, 314.9865; found, 314.9860.
(Z)-Ethyl 3-(Mesitylsulfonyl)acrylate (3aq). Light yellow solid
(44.0 mg, 78%), mp 82−83 °C. 1H NMR (400 MHz, CDCl3) δ
6.96 (s, 2H), 6.66 (d, J = 12 Hz, 1H), 6.42 (d, J = 12 Hz, 1H), 4.21 (q,
J = 7.2 Hz, 2H), 2.65 (s, 6H), 2.31 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H).
13C{1H}NMR (100 MHz, CDCl3) δ 163.5, 143.7, 140.2, 138.2, 133.6,
132.1, 129.5, 61.9, 22.6, 21.0, 13.9. IR (neat, cm−1): 3072, 2928, 1726,
1677, 1310, 1143, 782. HRMS calcd (ESI) m/z: for C14H18NaO4S [M
+ Na]+, 305.0818; found, 305.0815.
1
(47.1 mg, 86%). H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.4 Hz,
2H), 7.54 (d, J = 8.8 Hz 2H), 6.52 (s, 2H), 4.36 (q, J = 7.2 Hz, 2H),
1.38 (t, J = 2.8 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 163.9,
140.9, 138.0, 135.0, 132.5, 129.8, 129.7, 62.3, 14.0.
(Z)-Ethyl 3-(4-Bromophenylsulfonyl)acrylate (3ah).6 White solid
1
(53.3 mg, 84%), mp 65−66 °C. H NMR (400 MHz, CDCl3) δ 7.87
(d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 6.53 (s, 2H), 4.36 (q, J =
7.2 Hz, 2H), 1.37 (t, J = 7.3 Hz, 3H). 13C{1H}NMR (100 MHz,
CDCl3) δ 163.9, 138.6, 135.1, 132.7, 132.5, 129.9, 129.5, 62.4, 14.0.
(Z)-Ethyl 3-(4-Iodophenylsulfonyl)acrylate (3ai). White solid (59.3
mg, 81%), mp 72−73 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J =
8.8 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 6.54 (d, J = 11.2 Hz, 1H), 6.50
(d, J = 11.6 Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H).
13C{1H}NMR (100 MHz, CDCl3) δ 163.8, 139.0, 138.7, 134.8, 132.5,
129.6, 102.2, 62.3, 13.9. IR (neat, cm−1): 3081, 2978, 1723, 1670,
1323, 1172, 735. HRMS calcd (ESI) m/z: for C11H11NaIO4S [M +
Na]+, 388.9315; found, 388.9311.
(Z)-Ethyl 3-(Naphthalen-2-ylsulfonyl)acrylate (3ar).6 White solid
1
(41.8 mg, 72%), mp 83−84 °C. H NMR (400 MHz, CDCl3) δ 8.58
(s, 1H), 8.03−7.93 (m, 4H), 7.70−7.63 (m, 2H), 6.60 (d, J = 11.6 Hz,
1H), 6.53 (d, J = 11.6 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 1.42 (t, J =
7.2 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 164.0, 136.3, 135.5,
135.2, 132.2, 131.9, 130.2, 129.7, 129.6, 129.5, 128.0, 127.7, 122.7,
62.2, 14.0.
(Z)-ethyl 3-(4-(trifluoromethyl)phenylsulfonyl)acrylate (3aj).
1
White solid (49.2 mg, 80%), mp 61−62 °C. H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 6.62 (d, J
= 11.6 Hz, 1H), 6.57 (d, J = 11.6 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H),
1.38 (t, J = 6.8 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 163.9,
(Z)-Ethyl 3-(Thiophen-2-ylsulfonyl)acrylate (3as). White solid
(45.8 mg, 93%), mp 73−74 °C. 1H NMR (400 MHz, CDCl3) δ
7.82 (d, J = 3.6 Hz, 1H), 7.74 (d, J = 5.6 Hz, 1H), 7.17 (t, J = 4.4 Hz,
E
DOI: 10.1021/acs.joc.6b01549
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1H), 6.64 (d, J = 11.6 Hz, 1H), 6.48 (d, J = 11.2 Hz, 1H), 4.37 (q, J =
7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H).13C{1H}NMR (100 MHz,
CDCl3) δ163.8, 140.7, 135.9, 135.2, 135.2, 131.6, 128.3, 62.4, 14.1. IR
(neat, cm−1): 3068, 2954, 1738, 1666, 1298, 1073, 811. HRMS calcd
(ESI) m/z: for C9H10NaO4S2 [M + Na]+, 268.9913; found, 268.9906.
(Z)-Ethyl 3-(Butylsulfonyl)acrylate (3at). Colorless oil (26.8 mg,
61%). 1H NMR (400 MHz, CDCl3) δ 6.61 (d, J = 11.2 Hz, 1H), 6.57
(d, J = 11.6 Hz, 1H), 4.28 (q, J = 7.6 Hz, 2H), 3.20 (t, J = 8.0 Hz, 2H),
1.81−1.75 (m, 2H), 1.47−1.40 (m, 2H), 1.32 (t, J = 7.2 Hz, 3H), 0.94
(t, J = 7.2 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 163.4, 135.8,
134.1, 62.1, 55.1, 23.8, 21.6, 13.8, 13.4. IR (neat, cm−1): 3076, 2974,
1732, 1651, 1314, 1147, 742. HRMS calcd (ESI) m/z: for
C9H16NaO4S [M + Na]+, 243.0662; found, 243.0658.
(Z)-2-Bromoethyl 3-Tosyl Acrylate (3ha). White solid (59.1 mg,
89%), mp 63−64 °C. 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4
Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 6.55 (d, J = 11.6 Hz, 1H), 6.50 (d, J
= 11.6 Hz, 1H), 4.61 (t, J = 6.4 Hz, 2H), 3.63 (t, J = 6.4 Hz, 2H), 2.45
(s, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 163.7, 145.4, 136.2,
135.9, 130.4, 130.1, 128.3, 65.1, 27.9, 21.7. IR (neat, cm−1): 3063,
2968, 1738, 1673, 1327, 1148, 923, 748. HRMS calcd (ESI) m/z: for
C12H13NaBrO4S [M + Na]+, 354.9610; found, 354.9603.
(Z)-Thiophen-2-ylmethyl 3-Tosyl Acrylate (3ia). White solid (48.9
mg, 76%), mp 133−134 °C. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J
= 8.4 Hz, 2H), 7.39 (d, J = 4.8 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.19
(d, J = 3.2 Hz, 1H), 7.02 (m, 1H), 6.52 (d, J = 11.2 Hz, 1H), 6.46 (d, J
= 11.2 Hz, 1H), 5.47 (s, 2H), 2.43 (s, 3H). 13C{1H}NMR (100 MHz,
CDCl3) δ 163.6, 145.1, 136.3, 136.1, 135.8, 130.6, 129.8, 129.1, 128.2,
127.3, 126.9, 61.8, 21.6. IR (neat, cm−1): 3078, 2973, 1744, 1670,
1146, 965, 781. HRMS calcd (ESI) m/z: for C15H14NaO4S2 [M +
Na]+, 345.0226; found, 345.0223.
(Z)-Ethyl 3-(3-Chloropropylsulfonyl)acrylate (3au). White solid
1
(31.2 mg, 65%), mp 55−56 °C. H NMR (400 MHz, CDCl3) δ 6.65
(d, J = 12.0 Hz, 1H), 6.59 (d, J = 11.6 Hz, 1H), 4.32 (q, J = 7.2 Hz,
2H), 3.69 (t, J = 6.4 Hz, 2H), 3.43 (t, J = 7.6 Hz, 2H), 1.35 (t, J = 7.2
Hz, 3H), 1.31−1.24 (m, 2H). 13C{1H}NMR (100 MHz, CDCl3) δ
163.3, 135.7, 134.8, 62.4, 52.7, 42.7, 25.2, 13.9. IR (neat, cm−1): 3070,
2970, 1737, 1340, 1089, 904. HRMS calcd (ESI) m/z: for
C8H13NaClO4S [M + Na]+, 263.0115; found, 263.0111.
(Z)-Ethyl 3-tosyl acrylate (3ja).6 White solid (42.7 mg, 84%), mp
41−42 °C.1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.0 Hz, 2H),
7.36 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 11.6 Hz, 1H), 6.27 (d, J = 11.6
Hz, 1H), 4.32 (q, J = 7.2 Hz, 2H), 2.45 (s, 3H), 1.35 (t, J = 7.2 Hz,
3H). 13C{1H}NMR (100 MHz, CDCl3) δ 164.1, 145.2, 136.5, 135.4,
131.4, 123.0, 128.3, 62.2, 21.7, 14.0.
(Z)-Isopropyl 3-Tosyl Acrylate (3ba). White solid (38.6 mg, 72%),
mp 102−103 °C. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.4 Hz,
2H), 7.36 (d, J = 8.0 Hz, 2H), 6.48 (d, J = 11.6 Hz, 1H), 6.44 (d, J =
11.6 Hz, 1H), 5.28−5.19 (m, 1H), 2.45 (s, 3H), 1.38 (s, 3H), 1.37 (s,
3H). 13C{1H}NMR (100 MHz, CDCl3) δ 163.6, 145.1, 136.6, 134.9,
131.8, 129.9, 128.3, 70.3, 21.7, 21.6. IR (neat, cm−1): 3082, 2956,
1741, 1662, 1086, 977, 755. HRMS calcd (ESI) m/z: for
C13H16NaO4S [M + Na]+, 291.0662; found, 291.0657.
(Z)-tert-Butyl 3-Tosyl Acrylate (3ca). White solid (44.6 mg, 79%),
mp 114−115 °C. 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.0 Hz,
2H), 7.34 (d, J = 8.4 Hz, 2H), 6.40 (s, 2H), 2.44 (s, 3H), 1.58 (s, 9H).
13C{1H}NMR (100 MHz, CDCl3) δ 163.0, 145.0, 136.7, 133.6, 132.5,
129.9, 128.1, 83.9, 28.0, 21.83. IR (neat, cm−1): 3076, 2956, 1743,
1697, 1311, 1128, 820. HRMS calcd (ESI) m/z: for C14H18NaO4S [M
+ Na]+, 305.0818; found, 305.0815.
(Z)-Phenyl 3-Tosyl Acrylate (3da). White solid (43.5 mg, 72%), mp
113−114 °C. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.4 Hz, 2H),
7.46−7.42 (m, 2H), 7.37−7.29 (m, 5H), 6.69 (d, J = 11.6 Hz, 1H),
6.65 (d, J = 11.6 Hz, 1H), 2.45 (s, 3H). 13C{1H}NMR (100 MHz,
CDCl3) δ 163.0, 150.2, 145.6, 136.4, 130.7, 130.2, 129.8, 129.6, 128.6,
126.6, 121.7, 21.9. IR (neat, cm−1): 3068, 2932, 1733, 1675, 1135, 976,
747. HRMS calcd (ESI) m/z: for C16H14NaO4S [M + Na]+ 325.0505;
found, 325.0501.
(Z)-Ethyl 3-Tosylbut-2-enoate (3ka). White solid (43.4 mg, 81%),
1
mp 47−48 °C. H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.4 Hz,
2H), 7.35 (d, J = 8.0 Hz, 2H), 6.26 (s, 1H), 4.35 (q, J = 7.2 Hz, 2H),
2.44 (s, 3H), 1.96 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H). 13C{1H}NMR
(100 MHz, CDCl3) δ 165.1, 145.1, 142.4, 135.3, 129.9, 128.8, 128.6,
61.9, 21.7, 17.9, 14.0. IR (neat, cm−1): 3081, 2977, 1724, 1327, 1139,
861, 784. HRMS calcd (ESI) m/z: for C13H16NaO4S [M + Na]+,
291.0662; found, 291.0658.
(Z)-Ethyl 3-Phenyl-3-tosyl Acrylate (3la).15 White solid (36.3 mg,
55%), mp 86−87 °C. 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 8.4
Hz, 2H), 7.36−7.31 (m, 1H), 7.27−7.25 (m, 4H), 7.19 (d, J = 8.0 Hz,
2H), 6.39 (s, 1H), 4.41 (q, J = 7.2 Hz, 2H), 2.36 (s, 3H), 1.44 (t, J =
7.2 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 165.1, 146.2, 144.8,
135.5, 132.3, 130.4, 129.6, 129.6, 129.5, 128.7, 128.2, 62.1, 21.6, 14.0.
(E)-Ethyl 3-Bromo-3-tosyl acrylate (3ma). White solid (37.2 mg,
56%), mp 94−95 °C. 1H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 8.0
Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 6.79 (s, 1H), 4.42 (q, J = 7.2 Hz,
2H), 2.45 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H). 13C{1H}NMR (125 MHz,
CDCl3) δ 161.6, 144.6, 135.1, 132.5, 129.2, 127.2, 124.7, 62.5, 20.7,
12.8. IR (neat, cm−1): 3064, 2968, 1730, 1344, 1142, 927, 762. HRMS
calcd (ESI) m/z: for C12H13NaBrO4S [M + Na]+ 354.9610; found,
354.9606.
(Z)-Cyclopentyl 3-Tosyl Acrylate (3ea). White solid (41.7 mg,
1
(Z)-Ethyl 4,4,4-Trifluoro-3-tosylbut-2-enoate (3na). Yellow solid
71%), mp 128−129 °C. H NMR (400 MHz, CDCl3) δ 7.87 (d, J =
1
(41.9 mg, 65%), mp 90−91 °C. H NMR (500 MHz, CDCl3) δ 7.92
8.0 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 6.47 (d, J = 11.6 Hz, 1H), 6.44
(d, J = 11.2 Hz, 1H), 5.40−5.35 (m, 1H), 2.45 (s, 2H), 1.95−1.90 (m,
4H), 1.82−1.77 (m, 2H), 1.68−1.61 (m, 2H). 13C{1H}NMR (100
MHz, CDCl3) δ 163.9, 145.1, 136.6, 134.9, 131.8, 129.9, 128.3, 79.6,
32.4, 23.7, 21.7. IR (neat, cm−1): 3066, 2971, 1740, 1162, 947, 702.
HRMS calcd (ESI) m/z: for C15H18NaO4S [M + Na]+, 317.0818;
found, 317.0812.
(d, J = 6.8 Hz, 2H), 7.38 (d, J = 6.4 Hz, 2H), 7.04 (s, 1H), 4.45 (q, J =
5.6 Hz, 2H), 2.46 (s, 3H), 1.43 (t, J = 5.6 Hz, 3H). 13C{1H}NMR
(123 MHz, CDCl3) δ 162.8, 146.1, 136.1, 135.4, 135.3,129.9, 128.9,
119.1, 62.8, 21.7, 13.8. IR: 2973, 1722, 1345, 1143, 734, 705. IR (neat,
cm−1): 3077, 2972, 1728, 1681, 1076, 765. HRMS calcd (ESI) m/z:
for C13H13F3NaO4S [M + Na]+ 345.0379; found, 345.0373.
1
(Z)-3-Tosylacrylic Acid (3oa). Light yellow oil (34.4 mg, 76%). H
(Z)-Cyclopropylmethyl 3-Tosyl Acrylate (3fa). Light yellow solid
1
NMR (400 MHz, CDCl3) δ 9.03 (brs, 1H), 7.86 (d, J = 7.6 Hz, 2H),
7.35 (d, J = 7.6 Hz, 2H), 6.57 (d, J = 11.6 Hz, 1H), 6.53 (d, J = 11.6
Hz, 1H), 2.42 (s, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 166.6,
144.5, 134.8, 134.7, 130.0, 129.1, 127.3, 20.7. IR (neat, cm−1): 3085,
2970, 1725, 1672, 1147, 931, 791. HRMS calcd (ESI) m/z: for
C10H10NaO4S [M + Na]+, 249.0192, found 249.0188.
(Z)-N-Benzyl-3-tosylacrylamide (3pa). Light yellow solid (39.1 mg,
62%), mp 77−78 °C. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.4
Hz, 2H), 7.33−7.24 (m, 7H), 6.80 (s, 1H), 6.46 (d, J = 12.0 Hz, 1H),
6.43 (d, J = 12.0 Hz, 1H), 4.49 (d, J = 5.6 Hz, 2H), 2.37 (s, 3H).
13C{1H}NMR (100 MHz, CDCl3) δ 163.0, 145.4, 137.1, 136.4, 134.8,
130.1, 128.9, 128.8, 128.2, 128.0, 127.8, 44.13, 21.72. IR (neat, cm−1):
3073, 2976, 1724, 1337, 1028, 972, 740. HRMS calcd (ESI) m/z: for
C17H17NaNO3S [M + Na]+, 338.0821; found, 338.0816.
(43.7 mg, 78%), mp 97−98 °C. H NMR (400 MHz, CDCl3) δ 7.91
(d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 11.2 Hz,
1H), 6.48 (d, J = 11.6 Hz, 1H), 4.13 (d, J = 7.6 Hz, 2H), 2.45 (s, 3H),
1.28−1.23 (m, 1H), 0.64 (d, J = 5.6 Hz, 2H), 0.38 (d, J = 4.8 Hz, 2H).
13C{1H}NMR (100 MHz, CDCl3) δ 164.2, 145.2, 136.6, 135.4, 131.4,
139.9, 128.4, 71.1, 21.7, 9.52, 3.53. IR (neat, cm−1): 3078, 2946, 1731,
1643, 1116, 953, 782. HRMS calcd (ESI) m/z: for C14H16NaO4S [M +
Na]+, 303.0662; found, 303.0658.
(Z)-2-Hydroxyethyl 3-Tosyl Acrylate (3ga). White solid (38.3 mg,
71%), mp 59−60 °C. 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4
Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 6.54 (d, J = 11.6 Hz, 1H), 6.51 (d, J
= 11.6 Hz, 1H), 4.48 (t, J = 4.4 Hz, 2H), 3.96 (t, J = 4.0 Hz, 2H), 2.88
(s, 1H), 2.46 (s, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 164.2,
145.6, 136.0, 135.3, 130.8, 130.1, 128.2, 68.1, 60.7, 21.7. IR (neat,
cm−1): 3069, 2970, 1746, 1317, 1143, 872, 763. HRMS calcd (ESI) m/
z: for C12H14NaO5S [M + Na]+, 293.0454; found, 293.0451.
(Z)-N-Phenyl-3-tosylacrylamide (3qa). Light yellow solid (37.9
mg, 63%), mp 69−70 °C. 1H NMR (400 MHz, DMSO-d6) δ 9.51 (s,
F
DOI: 10.1021/acs.joc.6b01549
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The Journal of Organic Chemistry
Article
1H), 6.96 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 6.60 (d, J = 8.0
Hz, 2H), 6.47 (t, J = 8.0 Hz, 2H), 6.23 (t, J = 8.0 Hz, 1H), 6.14 (d, J =
8.0 Hz, 1H), 6.02 (d, J = 8.0 Hz, 1H), 1.59 (s, 3H). 13C{1H}NMR
(100 MHz, DMSO-d6) δ 162.1, 144.7, 138.6, 137.0, 136.3, 133.1, 19.9,
128.8, 127.8, 123.8, 119.6, 21.1. IR (neat, cm−1): 3076, 2969, 1747,
1681, 1210, 1012, 785. HRMS calcd (ESI) m/z: for C16H15NaNO3S
[M + Na]+, 324.0665; found, 324.0661.
AUTHOR INFORMATION
Corresponding Author
*E-mail: weiminhe2016@yeah.net.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(Z)-1,2-Ditosylethene (3ra). White solid (38.9 mg, 58%), mp 75−
76 °C. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.0 Hz, 4H), 7.38
(d, J = 8.0 Hz, 4H), 6.77 (s, 2H), 2.48 (s, 6H).13C{1H}NMR (100
MHz, CDCl3) δ 145.8, 140.4, 136.6, 129.9, 128.9, 21.8. IR (neat,
cm−1): 3072, 2964, 1736, 1675, 1240, 827. HRMS calcd (ESI) m/z:
for C16H16NaO4S2 [M + Na]+, 359.0382; found, 359.0379.
■
We are grateful for financial support from the National Natural
Science Foundation of China (No. 21302048), Hunan
Provincial Natural Science Foundation of China (Nos.
14JJ7028 and 2016JJ4035), Scientific Research Hunan
Provincial Education Department (No. 15B095), the Science
and Technology Innovative Research Team in Higher Educa-
tional Institutions of Hunan Province (2012-318) and the
Construct Program of the Key Discipline in Hunan Province.
(Z)-4-Tosylbut-3-en-2-one (3sa).16 White solid (17.5 mg, 39%),
1
mp 45−46 °C. H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz,
2H), 7.39 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 15.2 Hz, 1H), 6.97 (d, J =
15.6 Hz, 1H), 2.47 (s, 3H), 2.35 (s, 3H).13C{1H}NMR (100 MHz,
CDCl3) δ 196.8, 141.4, 138.0, 135.7, 131.9, 130.4, 128.4, 29.1, 26.9.
(Z)-(4-(Prop-1-en-2-yl)cyclohex-1-enyl)methyl 3-tosyl Acrylate
REFERENCES
■
1
(4aa). White solid (56.9 mg, 79%), mp 94−95 °C. H NMR (400
(1) (a) Ni, L.; Zheng, X. S.; Somers, P. K.; Hoong, L. K.; Hill, R. R.;
Marino, E. M.; Suen, K.-L.; Saxena, U.; Meng, C. Q. Bioorg. Med.
Chem. Lett. 2003, 13, 745−748. (b) Stevens, M.; Pannecouque, C.; De
Clercq, E.; Balzarini, J. Antimicrob. Agents Chemother. 2003, 47, 2951−
MHz, CDCl3) δ 7.89 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H),
6.56 (d, J = 11.2 Hz, 1H), 6.51 (d, J = 11.6 Hz, 1H), 5.89 (s, 1H),
4.76−4.74 (m, 2H), 4.69 (s, 1H), 2.47 (s, 3H), 2.24−2.17 (m, 4H),
2.06−1.98 (m, 1H), 1.92−1.85 (m, 1H), 1.77 (s, 3H), 1.58−1.49 (m,
1H), 1.28 (s, 2H). 13C{1H}NMR (100 MHz, CDCl3) δ 164.3, 149.7,
145.4, 136.6, 135.6, 132.0, 131.5, 130.1, 128.5, 127.6, 109.0, 70.4, 40.8,
30.7, 27.4, 26.5, 21.8, 20.9. IR (neat, cm−1): 3078, 2967, 1739, 1672,
1312, 1042, 783. HRMS calcd (ESI) m/z: for C20H24NaO4S [M +
Na]+, 383.1288; found, 383.1284.
2957. (c) Hof, F.; Schutz, A.; Fah, C.; Meyer, S.; Bur, D.; Liu, J.;
̈
̈
Goldberg, D. E.; Diederich, F. Angew. Chem., Int. Ed. 2006, 45, 2138−
2141. (d) Uttamchandani, M.; Liu, K.; Panicker, R. C.; Yao, S. Q.
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Neamati, N.; North, T. W.; Gervay-Hague, J. Bioorg. Med. Chem. 2007,
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(Z)-(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl 3-tosyl
A.; Pradel, G.; Vicí
̌
k, R.; Schirmeister, T.; Micale, N.; Grasso, S.;
1
Acrylate (4ba). Yellow solid (36.2 mg, 50%), mp 107−108 °C. H
Zappala, M. J. Med. Chem. 2008, 51, 988−996. (g) Dunny, E.;
̀
NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.0
Hz, 2H), 6.51 (d, J = 11.6 Hz, 1H), 6.62 (d, J = 11.2 Hz, 1H), 5.07 (d,
J = 7.6 Hz, 1H), 2.43 (s, 3H), 2.04−1.60 (m, 1H), 1.80−1.73 (m, 2H),
1.40−1.26 (m, 4H), 0.94 (s, 3H), 0.93 (s, 3H), 0.90 (s, 3H).
13C{1H}NMR (100 MHz, CDCl3) δ 164.4, 145.1, 136.5, 134.6, 131.6,
129.9, 128.3, 82.5, 51.4, 48.8, 47.9, 44.7, 35.8, 27.8, 27.1, 19.7, 18.7. IR
(neat, cm−1): 3082, 2947, 1731, 1385, 1160, 1034, 827. HRMS calcd
(ESI) m/z: for C20H26NaO4S [M + Na]+, 385.1444; found, 385.1441.
(Z)-2,3-dihydro-1H-inden-1-yl 3-tosyl acrylate (4ca). Light yellow
solid (39.7 mg, 58%), mp 110−111 °C. 1H NMR (400 MHz, CDCl3)
δ 7.81 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 1H), 7.35−7.33 (m,
2H), 7.30−7.28 (m, 3H), 6.49 (d, J = 11.2 Hz, 1H), 6.46 (d, J = 11.2
Hz, 1H), 6.43−6.41 (m, 1H), 3.23−3.16 (m, 1H), 3.24−3.15 (m, 1H),
2.98−2.91 (m, 1H), 2.62−2.53 (m, 1H), 2.44 (s, 3H), 2.44−2.35 (m,
1H). 13C{1H}NMR (100 MHz, CDCl3) δ 164.1, 145.4, 145.1, 140.3,
136.8, 135.5, 131.7, 130.2, 129.5, 128.6, 127.1, 126.3, 125.0, 80.8, 32.2,
30.6, 21.8. IR (neat, cm−1): 3077, 2964, 1746, 1372, 1041, 860, 782.
HRMS calcd (ESI) m/z: for C19H18NaO4S [M + Na]+, 365.0818;
found, 365.0815.
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1
(47.0 mg, 56%), mp 123−124 °C. H NMR (500 MHz, CDCl3) δ
(5) Chemla, F.; Hebbe, V.; Normant, J.-F. Synthesis 2000, 75−77.
(6) Downey, C. W.; Craciun, S.; Neferu, A. M.; Vivelo, C. A.;
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7.92 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.0 Hz, 2H), 7.53−7.47 (m, 3H),
7.39−7.33 (m, 5H), 7.11 (d, J = 8.0 Hz, 2H), 7.05 (s, 1H), 6.58 (d, J =
11.6 Hz, 1H), 7.63 (d, J = 11.6 Hz, 1H), 2.34 (s, 3H). 13C{1H}NMR
(125 MHz, CDCl3) δ 193.0, 163.4, 145.7, 126.1, 134.4, 133.6, 132.9,
130.5, 129.9, 129.8, 129.2, 129.2, 128.9, 128.8, 128.7, 128.3, 79.0, 21.7.
IR (neat, cm−1): 3073, 2961, 1748, 1286, 1124, 942, 728. HRMS calcd
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ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b01549.
1H and 13C NMR spectra of compounds 3aa−3ja, 4−7
(PDF)
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DOI: 10.1021/acs.joc.6b01549
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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