An efficient procedure based on a MW-assisted Horner-Wadsworth-Emmons reaction for the synthesis of (Z)-3,3-trisubstituted-α,β-unsaturated esters

Article abstract of DOI:10.3390/molecules15095928

A microwave-assisted HWE olefination process of readily accessible aryl-alkyl ketones has been developed to provide a rapid access to (Z)-3,3-trisubstituted-α,β-unsaturated methyl esters, key building blocks for the synthesis of biologically active compou

Full text of DOI:10.3390/molecules15095928

Molecules 2010, 15, 5928-5942; doi:10.3390/molecules15095928
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
An Efficient Procedure Based on a MW-Assisted Horner–
Wadsworth-Emmons Reaction for the Synthesis of (Z)-3,3-
Trisubstituted--unsaturated Esters
Daniela Rossi, Anna Carnevale Baraglia, Massimo Serra, Ornella Azzolina and Simona Collina *
Dipartimento di Chimica Farmaceutica, viale Taramelli 12, Pavia 27100, Italy
* Author to whom correspondence should be addressed; E-Mail: simona.collina@unipv.it;
Tel.: +39-0382-987379; Fax: +39-0382-422975.
Received: 28 July 2010; in revised form: 18 August 2010 / Accepted: 25 August 2010 /
Published: 27 August 2010
Abstract: A microwave-assisted HWE olefination process of readily accessible aryl-alkyl
ketones has been developed to provide a rapid access to (Z)-3,3-trisubstituted-α,β-
unsaturated methyl esters, key building blocks for the synthesis of biologically active
compounds.
Keywords: (Z)-3,3-trisubstituted α,β-unsaturated methyl esters; aryl-alkyl ketones;
Horner–Wadsworth-Emmons reaction; microwave-assisted reactions
1. Introduction
Recently, as part of our research program on new classes of compounds potentially active in the
treatment of neurodegenerative diseases, we focused on the design and synthesis of novel PKC
ligands. To achieve this goal and to investigate the molecular features involved in PKC binding, a drug
discovery library based on a 3-aryl-4-hydroxybutyrate scaffold (Figure 1) was designed [1].
Figure 1. 3-Aryl-4-hydroxybutyrate scaffold.
OH
O
R
Ar
X
X= O, N

Molecules 2010, 15
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3,3-Trisubstituted α,β-unsaturated methyl esters 1 were identified as valuable synthetic
intermediates to achieve, after simple synthetic elaborations, the desired chemical diversity of the
library (Scheme 1). It has to be outlined that the allylic oxidation step of the proposed synthetic
pathway (Scheme 1, step C) is selective toward α,β-unsaturated esters with (Z)-configuration [2].
Accordingly, our principal aim was to come up with a rapid and economic synthetic plan for the
preparation of (Z)-3,3-trisubstituted-α,β-unsaturated methyl esters in amounts suitable for their
subsequent derivatization and for preparing the whole compound library.
Scheme 1. Proposed synthetic pathway for the preparation of the 3-aryl-4-hydroxybutyrate scaffold.
A
Ar
COXR
H
Ar
COOMe
H
Ar
COOH
H
B
Me
Me
Me
1
2
3
Z-alkene
X= O, N
C
Ar
COXR
D
Ar
COXR
H
H
OH
OH
4
A well known method for the synthesis of disubstituted olefins is the Horner–Wadsworth-Emmons
(HWE) reaction. The (E)- or (Z)- geometrical selectivity of HWE olefination of aldehydes has been
extensively studied under conventional conditions [3] and only recently under microwave irradiation
[4]. Only a few papers on HWE olefination of ketones have been described under conventional
conditions [5] and, to the best of our knowledge, the effect of microwave heating has never
been studied.
Techniques used for the preparation of compounds collections have evolved very rapidly over the
past two decades. Emphasis was initially placed on the development of solid-phase and solution-phase
synthetic methods [6,7]. In recent years, the development of combinatorial synthetic techniques using
microwave irradiation was also emphasized [8]. The use of microwave heating has indeed greatly
affected many aspects of chemical synthesis since it can dramatically reduce the reaction time, increase
the product purity and yield and allow a strict control of the reaction parameters [9]. In this
Communication we report a microwave-assisted HWE olefination process of readily accessible aryl-
alkyl ketones, which quickly provides a small collection of (Z)-3,3-trisubstituted-α,β-unsaturated
methyl esters in high efficiency.
2. Results and Discussion
The first step of our work consisted in comparing conventional and microwave assisted synthesis of
3,3-trisubstituted-α,β-unsaturated methyl esters 1. The procedure of Sano and co-workers was initially
adopted employing bis(2,2,2-trifluoroethyl)(methoxycarbonylmethyl)-phosphonate (5) combined with
stannous trifluoromethanesulfonate [(CF3SO3)2Sn] and N-ethylpiperidine in anhydrous dichloro-
methane (DCM) [5]. The experimental conditions required two reaction steps, low temperatures and
long reaction times. Generally, low yields and especially unsatisfactory reproducibility were

Molecules 2010, 15
5930
evidenced. Consequently, microwave-assisted synthesis was tested on 50 mg of 6a (1 equiv), using 5
(1.5 equiv), (CF3SO3)2Sn (1.7 equiv) and N-ethylpiperidine (1.5 equiv), in 3 mL of anhydrous DCM
under microwave-induced heating at 70 °C for 30 min (Table 1, entry 1).
Table 1. Set up of the experimental conditions for microwave-promoted HWE olefination of 6a.
O
P
COMe
(CF3SO3)2Sn
N-ethylpiperidine
O
O
CF3
CF3
O
O
COOMe
H
CO2Me
+
+
solvent, MW
O
Me
H
Me
(E)-1a
COOMe
5
6a
(Z)-1a
Conversion a (%)
(Z)/(E) ratioa
Entry
Solvent
5 equiv
T (°C)
Time (min)
1
2
DCM
DCM
DCM
DMF
DMF
THF
THF
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
1.5
3
70
70
30
30
30
30
30
30
30
30
30
20
30
20
15
10
30
20
15
10
58
58
63
-
71:29
69:31
70:30
-
3
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
3
70
4
70
5
150
70
-
-
6
-
-
7
150
70
-
-
8
59
69
72
85
98
84
47
77
82
76
61
67:33
64:36
65:35
69:31
81:19
75:25
61:39
61:39
65:35
65:35
50:50
9
120
120
150
150
150
150
150
150
150
150
10
11
12
13
14
15
16
17
18
3
3
3
a Determined on crude products by HPLC-UV/PAD analysis registered at 225 nm.
1H-NMR analysis of the crude 1a evidenced the presence of both the (Z)- and (E)- isomers: two
different signals corresponding to the olefinic hydrogen (5.95 ppm and 6.16 ppm), and two signals
related to the methyl group on the double bond (2.20 ppm and 2.59 ppm) were present; the integration
of the above-mentioned signals allowed us to determine that the ratio between these two species was
about 70/30. The reaction, repeated three times, showed high reproducibility.
Both isomers were isolated from the reaction mixture via flash chromatography and characterized
1
by H-NMR, 13C-NMR, NOESY, IR, and high performance liquid chromatography-ultraviolet
photodiode array (HPLC-UV/PAD) analysis. Concerning NOESY experiments, a significant NOE
effect corresponding to the H-H interaction between the methyl group on the double bond and the
olefinic hydrogen was evidenced for both the isomers; nevertheless these effects resulted of different
intensity, decreasing from the major isomer to the minor one. Accordingly, the (Z)-configuration was
assigned to the major reaction product.

Molecules 2010, 15
5931
With the efficiency of the MW-assisted procedure proven, the second part of our work consisted in
optimizing the reaction conditions in order to maximize both reaction geometrical selectivity and
conversion of 6a into the corresponding 3,3-trisubstituted-α,β-unsaturated methyl ester (Table 1). To
easily determine the conversion percentage and the geometrical selectivity of the reaction during the
set up of the experimental conditions, an opportune HPLC-UV/PAD method was developed. Pure (Z)-
1a and (E)-1a were successfully analyzed employing a Intersil ACE-3 C8 column and water and
acetonitrile as mobile phase. The retention times of (Z)-1a and (E)-1a were 5.5 min and 7.1 min
(Rs = 3.02), respectively. It has to be noted that like other olefinic compounds [10, 11], the (Z)- and
(E)-isomers of 1a showed different UV profiles (Figure 1). Therefore, various attempts were
performed in order to identify the right wavelength for their quantification. The HPLC-UV/PAD
analysis of crude 1a, recorded at 225 nm, evidenced a reaction geometrical selectivity closed to 70%
(Table 1, entry 1), according to the 1H-NMR analysis (Figure 2).
Figure 1. UV absorption spectra of compounds (Z)-1a and (E)-1a.
Figure 2. (a) NMR spectrum of crude 1a ranging from = 5.80 ppm to = 6.25 ppm;
(b) Chromatographic profile of crude 1a.
(a)
(b)
Concerning the set up of the reaction conditions, the effect of reagent amounts was firstly
investigated, keeping constant the reaction temperature at 70 °C and the reaction time at 30 min

Molecules 2010, 15
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(Table 1, entries 1-3). The best results were achieved employing 4.2 equiv of 5 combined with 1.7
equiv of (CF3SO3)2Sn and 1.5 equiv of N-ethylpiperidine. Indeed, (Z)-1a was synthesized with
conversion higher than 60% and selectivity closed to 70% (Table 1, entry 3). The HWE olefination of
6a was also experimented in DCM at room temperature as well as under conventional heating (reflux).
Compound 1a was detected only in traces and the formation of several by-products was evidenced
(TLC analysis).
Encouraged by results obtained for the MW assisted HWE olefination of 6a, further experiments
were conducted using anhydrous dimethylformamide (DMF), dichloroethane (DCE) and tetrahydro-
furan (THF), solvents commonly used in the HWE reaction, keeping constant the number of
equivalents of 5 at 4.2 and varying both reaction time and temperature (Table 1, entries 4-14).
Concerning MW absorber properties, THF is a low absorber (tan  < 0.1) like DCM, while DMF and
DCE are considered medium absorbers (tan  between 0.1 and 0.5). Notably, employing DCE at
150 °C the reaction was driven to completion in 20 min (98% conversion) with a (Z)/(E) selectivity
higher than 80% (Table 1, entry 12), whereas in THF and in DMF 1a was detected only in traces.
Therefore, chlorinated solvents seem to be necessary for the MW assisted HWE reaction.
Concerning the reaction time, the extension from 20 to 30 min significantly decreased both
conversion and selectivity; similarly, reducing the run time from 20 to 15 and to 10 min a progressive
decrease in conversion and reaction selectivity was evidenced. An analogous trend was observed when
3 equivalents of 5 were used (Table 1, entries 15-18), confirming that the optimal reaction time is
20 min. As regards to reaction temperature, a progressive decrease in the conversion was noticed when
the temperature was decreased from 150 to 120 and to 70 °C. In summary, the optimized protocol
involves microwave-induced heating of 6a in anhydrous DCE for 20 min at 150 °C in the presence of
5 (4.2 equiv) combined with (CF3SO3)2Sn (1.7 equiv) and N-ethylpiperidine (1.5 equiv). Olefin 1a was
obtained with a conversion of 98% as a mixture of isomers (Z) / (E) 81:19 (Table 1, entry 12).
Finally, the optimized experimental conditions were extended to all substrates to prepare
compounds 1b-h (Table 2). Crude 1b-h were analyzed using the above-described HPLC-UV/PAD
method. A good resolution between the (Z)- and (E)-isomers was obtained for all compounds.
Nevertheless, (Z)/(E) ratio could not be determined by HPLC analysis, due to the remarkable
differences in the UV spectra of (Z) and (E) isomers (Appendix I). Briefly, various attempts were
performed in order to identify the wavelength suitable to furnish a (Z)/(E) ratio in accordance with 1H-
NMR analysis, but unsatisfactory results were obtained. Therefore the conversion percentage and the
isomeric ratio were determined by 1H-NMR analysis of the crude products.
As stated in Table 2, all compounds were obtained with a conversion higher than 55%. As regards
to the geometrical selectivity of the reaction, a satisfactory (Z)- selectivity (closed to 70%) was
evidenced for all prepared compounds, with the only exception of compound 1g (Table 2, entry 6),
suggesting the good effect of microwave heating on the stereoselective coupling of various aryl-methyl
ketones with bis(2,2,2-trifluoroethyl)-phosphonoester via HWE reaction.

Molecules 2010, 15
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Table 2. HWE olefination of aryl methyl ketones 6b-h.
O
(CF3SO3)2Sn
Ar
COOMe
Ar
H
CF3
CF3
O
O
N-ethylpiperidine
P
CO2Me
+
ArCOMe
+
Me
H
Me
COOMe
DCE, 150°C (MW)
20 min
6b-h
(Z)-1b-h
(E)-1b-h
5
Entry
1
Ar
Olefin
1b
Conversion (%)a
(Z)/(E) ratioa
55
66:34
O
2
3
1c
99
86
74:26
76:24
1d
S
4
5
6
1e
1f
58
92
56
79:21
66:34
61:39
1g
S
S
Br
7
1h
60
74:26
a.Determined on crude products by 400-MHz 1H-NMR.
3. Experimental
3.1. General
Unless otherwise specified, commercially available reagents were used as received from the
supplier. Solvents were purified according to the guidelines in Purification of Laboratory Chemicals
[12]. All MW reactions were performed in a CEM Corporation Discover® LabMate, equipped with an
IR probe. Melting points were measured on SMP3 Stuart Scientific apparatus and are uncorrected.
Analytical TLC were carried out on silica gel precoated glass-backed plates (Fluka Kieselgel 60 F254,
Merck) and visualized by ultra-violet radiation, acidic ammonium molybdate (IV) or potassium
permanganate. Flash SiO2 column chromatographies were performed with a Biotage High-
1
Performance Flash Chromatography system with 12-mm or 25-mm flash cartridges. H-NMR spectra
were measured with a Bruker AVANCE 400 spectrometer (Germany) at room temperature. Chemical
shifts are given in ppm (), coupling constants (J) are in Hertz (Hz) and signals are designated as
follows: (s) singlet, (d) doublet, (t) triplet, (q) quartet, (br s) broad singlet, and (m) multiplet. TMS was
used as internal standard. Elemental analyses (C, H, N) were performed on a Carlo Erba 1106 analyzer
and the analysis results were found to be in good agreement ( ± 0.2%) with the theoretical values.
HPLC-UV/PAD analyses were performed on a Jasco system (Japan) consisting of a PU-1580 pump
and a MD-1510 UV detector; a Spectra System auto-sampler AS3000 was used for sample injections,
experimental data were acquired and processed by Borwin PDA and Borwin Chromatograph Software.
Chromatographic separations were carried out using a Intersil ACE-3 C8 column (50 × 4.6 mm, 3 μm,
CPS Analitica) and a security guard LiChrosorb® RP-8 column (LiChroCART® 4-4, 5 μm). The

Molecules 2010, 15
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mobile phase consisted of water (solvent A) and acetonitrile (solvent B). The starting mixture (50% A
and 50% B) persisted for 5 minutes and then in 20 minutes the mobile phase composition became
0% A, 100% B; in the following 3 min the mixture composition came back to the initial eluting
system. The flow rate was set at 1 mL/min.
3.2. General Procedure for the Synthesis of 3,3-Trisubstituted-α,β-Unsaturated Methyl Esters
Compound 5 (1.5, 3 or 4.2 equiv), (CF3SO3)2Sn (1.7 equiv) and N-ethylpiperidine (1.5 equiv) were
added to a stirred solution of appropriate ketones (1 equiv) in anhydrous solvent (DCM, DCE, THF,
DMF, 3 mL) under nitrogen atmosphere and then the reaction mixture was exposed to microwave
irradiation, applying conditions stated in Tables 1 and 2. After cooling, the mixture was filtered on a
pad of Silica and crude products were purified by flash chromatography. Products of Table 2 were
1
characterized by H-NMR, IR, and HPLC-UV/PAD analysis (Appendix I); experimental data were in
agreement with the literature ones.
(Z)-Methyl 3-(3-(benzyloxy)phenyl)but-2-enoate [(Z)-1a, Table 1, entry 12]: 45 mg (74% yield).
1
Yellow oil. Rf 0.37 (n-hexane/ethyl acetate 95:5); IR: 1932, 1717, 1678, 1275, 712 cm-1; H-NMR
(CDCl3)  (ppm): 2.20 (d, 3H, J = 1.3 Hz), 3.60 (s, 3H), 5.09 (s, 2H), 5.95 (q, 1H, J = 1.3 Hz), 6.85 (d,
1H, J = 7.6 Hz), 6.88 (t, 1H, J = 2.2 Hz), 6.97 (dd, 1H, J = 1.9, 7.8 Hz), 7.31 (t, 1H, J = 7.9 Hz),
7.35-7.52 (m, 5H); 13C-NMR (CDCl3)  (ppm): 27.6, 51.5, 70.4 (t), 114.0, 114.4, 117.7, 120.0, 128.0,
128.4, 129.0, 129.2, 137.4 (s), 142.6 (s), 155.9 (s), 158.9 (s), 166.6 (s); UV: λmax = 223 nm; HPLC-
UV/PAD analysis: RT = 5.2 min.
(E)-Methyl 3-(3-(benzyloxy)phenyl)but-2-enoate [(E)-1a, Table 1, entry 12]: 10 mg (16% yield).
Yellow oil. Rf 0.48 (n-hexane/ethyl acetate 95: 5); IR: 2946, 1712, 1574, 1289, 1204, 1159, 1024, 734,
693 cm-1; 1H-NMR (CDCl3)  (ppm): 2.59 (d, 3H, J = 1.2 Hz), 3.78 (s, 3H), 5.11 (s, 2H), 6.16 (q, 1H,
J = 1.2 Hz), 6.98-7.04 (m, 1H), 7.07-7.14 (m, 2H), 7.27-7.33 (m, 1H), 7.33-7.40 (m, 1H), 7.40-7.50
(m, 4H); 13C-NMR (CDCl3)  (ppm): 18.5, 51.6, 70.5 (t), 113.7, 115.6, 117.3, 119.5, 128.0, 128.5,
129.1, 130.0, 137.2 (s), 144.1 (s), 156.1 (s), 159.3 (s), 167.6 (s); UV: λmax =217 and 267; HPLC-
UV/PAD analysis: RT = 6.7 min.
4. Conclusions
In this study we have developed an efficient (Z) selective HWE reaction of bis(2,2,2-trifluoroethyl)
(methoxy-carbonylmethyl)-phosphonate with various aryl alkyl ketones combined with (CF3SO3)2Sn
and N-ethylpiperidine using anhydrous DCE as solvent. These one-pot reactions can efficiently be
performed under microwave conditions. The main favorable characteristics of our method are: (1) a
short synthetic route; (2) a good selectivity for the (Z)- olefination of various ketones using the HWE
reaction; (3) suitability for library synthesis. Further studies and applications of this new methodology
will be reported in due course.

Molecules 2010, 15
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Appendix I
Physical data for compounds 1b-h
(Z)-Methyl 3-(4-(benzyloxy)phenyl)but-2-enoate [(Z)-1b)] Yellow oil. Rf 0.18
(n-hexane/ethyl acetate 95:5); 1H-NMR (CDCl3)ppm): 2.20 (d, 3H, J = 1.4 Hz), 3.61 (s,
3H), 5.10 (s, 2H), 5.91 (q, 1H, J = 1.4 Hz), 6.99 (d, 2H, J = 8.8 Hz), 7.22 (d, 2H,
J = 8.8 Hz), 7.33-7.39 (m, 1H), 7.39-7.50 (m, 4H); HPLC-UV/PAD analysis: RT 5.2 min.
UV spectrum
1 . 2
1
A b s
0 . 5
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]
(E)-Methyl 3-(4-(benzyloxy)phenyl)but-2-enoate [(E)-1b] White solid (Mp = 79.4-81.0 °C).
Rf 0.28 (n-hexane/ethyl acetate 95:5); 1H-NMR (CDCl3)ppm): 2.59 (d, 3H, J = 1.1 Hz),
3.77 (s, 3H), 5.12 (s, 2H), 6.14 (q, 1H, J = 1.1 Hz), 7.00 (d, 2H, J = 8.8 Hz), 7.34-7.39 (m, 1H),
7.40-7.50 (m, 6H); HPLC-UV/PAD analysis: RT 6.5 min.
UV spectrum
1 . 5
1
A b s
0 . 5
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]

Molecules 2010, 15
(Z)-Methyl 3-([1,1'-biphenyl]-4-yl)but-2-enoate [(Z)-1c] Yellow oil. Rf 0.11
5937
(n-hexane/ethylacetate 99:1);1H-NMR (CDCl3) ppm): 2.25 (d, 3H, J = 1.4 Hz), 3.61 (s, 3H),
5.98 (q, 1H, J = 1.4 Hz), 7.30-7.39 (m, 3H), 7.43-7.49 (m, 2H), 7.59-7.66 (m, 4H); HPLC-
UV/PAD analysis: RT 5.1 min.
UV spectrum
1 . 3
1
A b s
0 . 5
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]
(E)-Methyl 3-([1,1'-biphenyl]-4-yl)but-2-enoate [(E)-1c] White solid (Mp = 135.3-137.0 °C).
Rf 0.19 (n-hexane/ethylacetate 99:1); 1H-NMR (CDCl3)ppm): 2.65 (d, 3H, J = 1.2 Hz),
3.80 (s, 3H), 6.24 (q, 1H, J = 1.3 Hz), 7.37-7.42 (m, 1H), 7.45-7.51 (m, 2H), 7.57-7.67 (m,
6H); HPLC-UV/PAD analysis: RT 6.7 min.
UV spectrum
1 . 4
1
A b s
0 . 5
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]

Molecules 2010, 15
(Z)-Methyl 3-(4-(phenylthio)phenyl)but-2-enoate [(Z)-1d] Yellow oil. Rf 0.21
5938
(n-hexane/ethyl-acetate 94:6);1H-NMR (CDCl3)ppm): 2.19 (d, 3H, J = 1.4 Hz), 3.60 (s, 3H),
5.94 (q, 1H, J = 1.4 Hz), 7.17 (d, 2H, J = 8.4 Hz ), 7.26-7.38 (m, 5H), 7.40-7.44 (m, 2H);
HPLC-UV/PAD analysis: RT 7.0 min.
UV spectrum
1 . 4
1
A b s
0 . 5
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]
(E)-Methyl 3-(4-(phenylthio)phenyl)but-2-enoate [(E)-1d] Yellow oil. Rf 0.28
(n-hexane/ethylacetate 94:6);1H-NMR (CDCl3) ppm): 2.58 (d, 3H, J = 1.2 Hz), 3.77 (s, 3H),
6.15 (q, 1H, J = 1.2 Hz), 7.25-7.46 (m, 9H); HPLC-UV/PAD analysis: RT 9.2 min.
UV spectrum
1 . 2
1
A b s
0 . 5
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]

Molecules 2010, 15
(Z)-Methyl 3-(naphthalen-1-yl)but-2-enoate [(Z)-1e] Yellow oil. Rf 0.10
5939
(n-hexane/ethylacetate 98:2);1H-NMR (CDCl3)  ppm): 2.31 (d, 3H, J = 1.2 Hz), 3.43 (s, 3H),
6.24 (q, 1H, J = 1.4 Hz), 7.21 (d, 1H, J =7.0Hz ), 7.60-7.67 (m, 1H), 7.72-7.83 (m, 3H),
7.95-8.05 (m, 2H); HPLC-UV/PAD analysis: RT 3.6 min.
UV spectrum
2 . 3
2
A b s
1
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]
(E)-Methyl 3-(naphthalen-1-yl)but-2-enoate [(E)-1e] Yellow oil. Rf 0.16
(n-hexane/ethylacetate 98:2);1H-NMR (CDCl3) ppm): 2.66 (d, 3H, J = 1.1 Hz), 3.82 (s, 3H),
6.02 (q, 1H, J = 1.1 Hz), 7.31 (dd, 1H, J =7.0, 1.1 Hz ), 7.45-7.50 (m, 1H), 7.50-7.55 (m,
2H), 7.84 (d, 1H, J = 8.3 Hz ), 7.87-7.94 (m, 2H); HPLC-UV/PAD analysis: RT 4.7 min.
UV spectrum
3
2
1
A b s
0
-1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]

Molecules 2010, 15
5940
(Z)-Methyl 3-phenylbut-2-enoate [(Z)-1f] Yellow oil. Rf 0.14 (n-hexane/ethylacetate
98:2);1H-NMR (CDCl3) ppm): 2.21 (d, 3H, J = 1.4 Hz), 3.58 (s, 3H), 5.96 (q, 1H, J = 1.4 Hz),
7.21-7.26 (m, 2H), 7.31-7.42 (m, 3H); HPLC-UV/PAD analysis: RT 2.1 min.
UV spectrum
1
0 . 5
A b s
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]
(E)-Methyl 3-phenylbut-2-enoate [(E)-1f] Yellow oil. Rf 0.24 (n-hexane/ethylacetate
98:2); 1H-NMR (CDCl3) ppm): 2.61 (d, 3H, J = 1.3 Hz), 3.78 (s, 3H), 6.17 (q, 1H, J =
1.3 Hz), 7.36-7.44 (m, 3H), 7.46-7.54 (m, 2H); HPLC-UV/PAD analysis: RT 2.7 min.
UV spectrum
3
2
1
A b s
0
-1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]

Molecules 2010, 15
(Z)-Methyl 3-(thiophen-2-yl)but-2-enoate (Z-1g) Yellow solid (Mp = 88.7-90.0 °C). Rf
5941
0.21 (n-hexane/ethylacetate 97:3); 1H-NMR (CDCl3) ppm): 2.32 (d, 3H, J =1.2 Hz), 3.71
(s, 3H), 5.88 (q, 1H, J =1.2), 7.40-7.43 (m, 2H), 7.49-7.52 (m, 1H); HPLC-UV/PAD
analysis: RT 1.9 min.
UV spectrum
0 . 1 6
0 . 1 5
0 . 1
A b s
0 . 0 5
0
-0 . 0 1
1 9 5
3 0 0
4 0 0
4 5 0
W
a v e l e n g t h [ n m ]
(E)-Methyl
3-(thiophen-2-yl)but-2-enoate
[(E)-1g]
Yellow
oil
Rf 0.26
(n-hexane/ethylacetate 97:3); 1H-NMR (CDCl3) ppm): 2.64 (d, 3H, J =1.2 Hz), 3.77 (s, 3H),
6.29 (q, 1H, J =1.2), 7.06-7.09 (m, 1H), 7.33-7.37 (m, 2H); HPLC-UV/PAD analysis: RT
2.4 min.
UV spectrum
3
2
1
A b s
0
-1
1 9 5
3 0 0
4 0 0
4 5 0
W
a v e l e n g t h [ n m ]

Molecules 2010, 15
(Z)-Methyl 3-(5-bromothiophen-2-yl)but-2-enoate [(Z)-1h] Yellow oil Rf 0.32
5942
(n-hexane/ethylacetate 95:5);1H-NMR (CDCl3) ppm): 2.30 (q, 3H, J = 1.2 Hz), 3.74 (s, 3H);
5.86 (d, 1H, J = 1.1 Hz), 7.09 (d, 1H, J =4.0), 7.26 (d, 1H, J =4.0); HPLC-UV/PAD
analysis: RT 3.4 min.
UV spectrum
0 . 4
0 . 3
0 . 2
A b s
0 . 1
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]
(E)-Methyl 3-(5-bromothiophen-2-yl)but-2-enoate [(E)-1h] Yellow oil Rf 0.32
(n-hexane/ethylacetate 95:5);1H-NMR (CDCl3) ppm): 2.57 (d, 3H, J = 1.1 Hz), 3.76 (s, 3H);
6.15 (q, 1H, J = 1.0 Hz), 7.00-7.05 (m, 2H); HPLC-UV/PAD analysis: RT 4.1 min.
UV spectrum
0 . 5
0 . 4
0 . 2
A b s
0
-0 . 1
1 9 5
3 0 0
4 0 0
W
a v e l e n g t h [ n m ]
Sample Availability: Samples of the compounds are available from the authors.
© 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).