Synthesis of Penta-2,4-dienenitriles by the Horner-Wadsworth-Emmons Olefination of Enones

Article abstract of DOI:10.1055/s-0036-1590871

Three new series of compounds, 5-alkoxy-3-(trifluoromethyl)penta-2,4-dienenitriles, 5-(phenylthio)-3-(trifluoromethyl)penta-2,4-dienenitriles, and ethyl 4-alkoxy-2-(cyanomethylene)but-3-enoates, obtained from the olefination reaction of the respective enones with diethyl cyanomethylphosphonate via the Horner-Wadsworth-Emmons olefination are reported. All products were obtained as single regioisomers; however, the composition of the stereoisomers changed according to the enone substituents. A study based on ¹ H and ¹³ C NMR chemical shifts, ¹ H- ¹⁹ F and ¹³ C- ¹⁹ F NMR coupling constants, ¹ H NMR signal integrals, and HSQC, HMBC, and NOESY experiments was performed in order to assign the structure and percentage of each stereoisomer obtained.

Full text of DOI:10.1055/s-0036-1590871

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–L
paper
A
en
C. E. Bencke et al.
Paper
Synthesis
Synthesis of Penta-2,4-dienenitriles by the Horner–Wadsworth–
Emmons Olefination of Enones
Carlos E. Benckea
O
NC
O
XR2
Mário A. Marangonib
Adriano F. Camargob
Cassio A. Fantinelb
R
(EtO)2PCH2CN
10–93%
XR2
Y
R
Y
R1
R1
Helio G. Bonacorsob
Marcos A. P. Martinsb
22 examples
Y = CF3, CO2Et; X = O, S
R = H, Me, Ar; R1 = H, Me, Alkyl, Br
R
2 = Me, Et, Alkyl, Ph
Nilo Zanatta*b
0
0
0
0
0-
0
0
2
0-
9
5
9
9-
0
4
3
a Laboratory of Chemistry, Instituto Federal Catarinense, 89240-000,
São Francisco do Sul, SC, Brazil
b Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de
Química, Universidade Federal de Santa Maria, 97105-900, Santa
Maria, Brazil
nilo.zanatta@ufsm.br
Received: 14.06.2017
Accepted after revision: 18.07.2017
Published online: 24.08.2017
Penta-2,4-dienenitriles are useful building blocks that
have been used as precursors in organic synthesis, in order
to obtain various heterocyclic compounds such as Diels–
Alder adducts,13 piperidazines,14 pyridines,15 indoles,16 aro-
matic polycycles,17 flavonoid pigments,18 dyes,19 and organ-
ic light-emitting diodes.20
Currently, the main methods for obtaining penta-2,4-
dienenitriles are: (a) the pyrolysis reaction of esters,21
(b) Peterson’s reaction between aldehydes and α-silyl car-
banions,22 (c) oxidative reactions catalyzed by metals,23
(d) the Knoevenagel condensation reaction,24 and (e) the
HWE reaction via double olefination of diethyl (1-cyano-
ethyl)phosphonate.25
Although the HWE reaction has been applied to a vari-
ety of aldehydes and ketones, the use of such a reaction for
the olefination of trifluoromethylated enones has been ex-
plored very little. In fact, a literature search revealed only
one use of this reaction, involving 4-ethoxy-1,1,1-trifluoro-
but-3-en-2-one (I), in a patent reported by Gebhardt and
co-workers (Scheme 1).26 This reaction provided a mixture
of four different products, which are represented by struc-
tures II–V.
DOI: 10.1055/s-0036-1590871; Art ID: ss-2017-m0398-op
Abstract Three new series of compounds, 5-alkoxy-3-(trifluorometh-
yl)penta-2,4-dienenitriles, 5-(phenylthio)-3-(trifluoromethyl)penta-2,4-
dienenitriles, and ethyl 4-alkoxy-2-(cyanomethylene)but-3-enoates,
obtained from the olefination reaction of the respective enones with di-
ethyl cyanomethylphosphonate via the Horner–Wadsworth–Emmons
olefination are reported. All products were obtained as single regioiso-
mers; however, the composition of the stereoisomers changed accord-
ing to the enone substituents. A study based on 1H and 13C NMR chem-
ical shifts, 1H–19F and 13C–19F NMR coupling constants, 1H NMR signal
integrals, and HSQC, HMBC, and NOESY experiments was performed in
order to assign the structure and percentage of each stereoisomer ob-
tained.
Key words pentadienenitriles, olefination, enones, diethyl cy-
anomethylphosphonate, Horner–Wadsworth–Emmons reaction
The Horner–Wadsworth–Emmons (HWE) reaction is
one of the most reliable and widespread synthetic tools for
the olefination of aldehydes and ketones. It has proven a
valuable synthetic tool for preparing simple as well as high-
ly functionalized and complex molecular scaffolds. For ex-
ample, the HWE reaction has been used in the synthesis of
α,β-unsaturated esters and ketones,1 which have been used
as building blocks for the synthesis of fluorinated reti-
noids,2 insect sex pheromones,3 and pyrethoids,4 and of
α,β-unsaturated nitriles,5 which have been used to synthe-
size carbocycles6 and heterocycles.7 The HWE reaction has
also been used for the synthesis of natural products8 and vi-
nylic sulfoximines,9 the olefination of epimerizable alde-
hyde groups adjacent to stereocenters,10 and inter- and in-
tramolecular reactions for preparing trans-bicyclic
enones,11 among other things.12
OEt
Y
Z
Y
Z
+
F3C
OEt
F3C
OEt
O
HWE
II
III
F3C
OEt
O
OEt
Z
I
(RO)2PCHZY
Y
Z
Y
OEt
OEt
Y = CN, CONH2, CO2R
Z = H, SR
+
F3C
OEt
F3C
IV
V
Scheme 1 Mixture of products from the HWE reaction of 4-ethoxy-
1,1,1-trifluorobut-3-en-2-one
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

B
C. E. Bencke et al.
Paper
Synthesis
As outlined in Scheme 1, this reaction gave a complex
mixture of products when enone I was reacted with HWE
reagents. Since only enone I was used in the study,26 we de-
cided to perform the HWE olefination reaction on a range of
substituted enones. Thus, the aim of our study was to per-
form the HWE olefination reaction on a series of enones
with the general structures VI, VII, and VIII (Figure 1) using
diethyl cyanomethylphosphonate, in order to generate new
and valuable building blocks for organic synthesis.
Table 1 Optimized Reaction Conditions for Obtaining Compounds 2
O
OR2
O
SPh
PhSH (2 equiv)
BF3·OEt2 (1.2 equiv)
F3C
R
F3C
R
R1
CH2Cl2, 40 °C, 1.5 h
R1
1
2
Enone
R
R1
R2
Me
Product Yield (%)a
1a
1c
1d
1e
1h
C6H5
H
H
H
H
Br
2a
2c
2d
2e
2h
85b
60
4-BrC6H4
Me
Me
Me
Et
O
OR2
O
OR2
O
SPh
4-MeC6H4
60
F3C
R
EtO2C
R
F3C
R
R1
VI
R1
R1
4-MeOC6H4
H
78
71c
VII
VIII
a Yield of product after purification by crystallization or column chromatogra-
R = H, Alkyl, Ar
1 = H, Alkyl, Br
R2 = Me, Et
phy.
R
b Known compound.30
c Known compound.31
Figure 1 General structures of the enones used in this study
This study began with the preparation of the enones
with the general structure VI, which were obtained in ac-
cordance with our previously developed method,27 and
enones VIII, which were also obtained in accordance with
our previously reported methods.28 The enones of general
structure VII were prepared by the reaction of alkoxy-sub-
stituted enones VI with benzenethiol in dichloromethane
and in the presence of boron trifluoride–diethyl ether com-
plex, following similar procedures reported by Martins and
co-workers29 for the synthesis of 1,1,1-trihalo-4-(phen-
ylseleno)alk-3-en-2-ones. For the compounds of structure
VII, only compounds 2a and 2h were known; however,
compound 2a was synthesized previously by the acylation
of a vinyl sulfide,30 whereas compound 2h was obtained by
the reaction of enone 1h with benzenethiol catalyzed by
hydrated indium trichloride.31 This reaction furnished
product 2h in low yield (27%), together with a mixture of
side products including diphenyl disulfide (18%) and 1,1,1-
trifluoro-3,4-bis(phenylthio)but-3-en-2-one (39%); where-
as, using our method, compound 2h was obtained in 71%
yield, and no side products were observed (Table 1).
The best conditions for the HWE reaction of the enones
with diethyl cyanomethylphosphonate were established
using enone 1a, following the method developed by Thomas
and Boutagy.32 The reaction was performed in a one-pot,
two-step procedure. In the first step, the phosphonate an-
ion 4′ was generated by the reaction of diethyl cyanometh-
ylphosphonate (4) with a base and a solvent, as indicated in
Table 2. For this step, the temperature was maintained at
0 °C for 30 minutes. In the second step, enone 1a was added
to the reaction flask, and various parameters, such as tem-
perature, reaction time, and stoichiometric amounts of the
reagents, were investigated (Table 2).
The amounts of enone 1a and diethyl cyanomethyl-
phosphonate (4) were always kept constant, namely 1.0:1.2
equivalents, respectively. The type and amount of the base
and the reaction conditions were systematically changed.
Sodium hydride in tetrahydrofuran were the first condi-
tions studied, in accordance with reported HWE olefination
reactions.32 A very low yield was obtained when the reac-
tion was performed at 30 °C for 2 hours (Table 2, entry 1);
however, the yield was improved by refluxing the reaction,
again for 2 hours (Table 2, entries 2–4). When 1.0 or 2.0
equivalents of base was used, the reaction yield was basi-
cally the same (Table 2, entries 4 and 2, respectively); how-
ever, when 1.5 equivalents of base was used, a slightly bet-
ter yield was obtained (Table 2, entry 3). For shorter reac-
tion times, such as 0.5 and 1.0 hour, the reaction furnished
lower yields (Table 2, entries 5 and 6), and the reaction for 4
hours under reflux also gave a very low yield, probably due
to decomposition of product 5a (Table 2, entry 7). Other
bases, such as triethylamine, pyridine, 1,8-diazabicy-
clo[5.4.0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane, N,N-
diisopropylethylamine, sodium hydroxide, and sodium car-
bonate, were tested, but all resulted in low yields (Table 2,
entries 8–15). Other solvents, such as water, diethyl ether,
and dioxane, were tested; however, they either did not im-
prove the yield or no reaction was observed (Table 2, entries
14–17).
The optimized conditions for obtaining compound 5a
(Table 2, entry 3) were applied to the synthesis of all other
products 5 of this series. Enones 1a–k with different sub-
stituents at the α- and the β-position were submitted to the
reaction with diethyl cyanomethylphosphonate (4) in order
to test the regioselectivity and stereoselectivity of the reac-
tion (Table 3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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C. E. Bencke et al.
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Synthesis
Table 2 Optimization of the Reaction Conditions for Obtaining Compound 5a
O
OMe
NC
OMe
F3C
base, solvent
0 °C, 30 min
O
O
(1a)
temp, time
F3C
(EtO)2PCHCN
(EtO)2PCH2CN
4
4'
5a
Entry
Base
Molar ratioa
Solvent
Temp (°C)
Time (h)
Yield (%)b
1
2
NaH
1:1.2:2
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
H2O
H2O
Et2O
dioxane
30
2
2
2
2
0.5
1
4
2
2
2
2
2
2
2
2
2
2
10
53
60
54
5
NaH
1:1.2:2
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
3
NaH
1:1.2:1.5
1:1.2:1
4
NaH
5
NaH
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
1:1.2:1.5
6
NaH
41
7
NaH
5
c
8
Et3N
c
9
Py
10
11
12
13
14
15
16
17
DBU
30
DABCO
DIPEA
NaOH
NaOH
Na2CO3
NaH
17
c
c
18
35
36
46
NaH
a Molar ratio of 1a/4/base.
b Yield of product after purification by column chromatography.
c Enone 1a was recovered.
The same conditions were also applied to the reaction
of enones 2 with diethyl cyanomethylphosphonate (4),
which furnished the expected 5-(phenylthio)-3-(trifluoro-
methyl)penta-2,4-dienenitriles 6 in moderate yields (Table
4).
The reaction of diethyl cyanomethylphosphonate (4)
was also tested with a series of ethyl 4-alkoxy-2-oxobut-3-
enoates 3 as the enone component (Table 5). The reaction
conditions used were the same as those used for the series
of enones 1 and 2. The products obtained from this reaction
were the ethyl 4-alkoxy-2-(cyanomethylene)but-3-enoates
7, which had the corresponding structure and similar yields
as the previous series of compounds 5 and 6.
such as 1g–k, 2h, and 3j,k, furnished the corresponding
products 5g–k, 6h, and 7j,k, respectively, in poor yields, ex-
cept for enones 1j,k, 2h, and 3j, which gave products 5j,k,
6h, and 7j in yields of 70%, 55%, 67%, and 60%, respectively
(Tables 3–5). The low yields obtained with α-substituted
enones are likely due to a steric effect between the α-sub-
stituent and the trifluoromethyl or the ethyl carboxylate
group, which leads to the carbonyl being removed from the
double-bond plane, thus decreasing the reactivity of the
carbonyl group.33 In comparison with the five-membered
ring of the dihydrofuran 1i, the more flexible six-mem-
bered ring of the dihydropyrans 1j,k probably accounts for
the better yields of products 5j,k.
Only a single compound, similar to structure II in
Scheme 1, was formed in all of the reactions studied (Tables
3–5); compounds corresponding to structures III, IV, and V
were not observed. As a general rule, β-substituted enones,
such as 1a–f, 2a,c–e, and 3a–d, furnished products 5a–f or
the corresponding compounds 6a,c–e and 7a–d in moder-
ate to very good yields, except for enone 1f, which gave
compound 5f in low yield. However, α-substituted enones,
As mentioned previously, the products obtained from
the reaction of enones 1, 2, or 3 with diethyl cyanomethyl-
phosphonate (4) were exclusively formed as a single regio-
isomer and, in all cases, the major stereoisomer obtained
was (2E,4E) configured (see Table 6), thus indicating a
greater stability of this isomer compared to the other pos-
sible stereoisomers.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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C. E. Bencke et al.
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Synthesis
Table 3 Optimized Reaction Conditions for Obtaining Compounds 5a–k
Table 5 Optimized Reaction Conditions for Obtaining Compounds 7
NC
O
OR2
R
R
O
enones 1
reflux, 2 h
NC
O
NaH, THF
0 °C, 30 min
R
EtO2C
(EtO)2PCHCN
(EtO)2PCH2CN
F3C
OR2
R1
NaH, THF
0 °C, 30 min
O
O
EtO2C
OR2
R1
3
4
4'
(EtO)2PCH2CN
PCHCN
(EtO)2
R1
5
reflux, 2 h
7
4
4'
Enone
R
R1
R2
Product
Yield (%)a
Enone
R
R1
R2
Me
Product
Yield (%)a
1a
1b
1c
1d
1e
1f
C6H5
H
Me
Me
Me
Me
Me
Me
Et
5a
5b
5c
5d
5e
5f
60
64
84
93
75
28
10
36
20
70
55
3a
3b
3c
3d
3j
C6H5
H
7a
7b
7c
7d
7j
57
66
79
62
60
33
4-FC6H4
H
4-FC6H4
4-BrC6H4
4-MeC6H4
H
H
H
H
Me
Me
Me
4-BrC6H4
H
4-MeC6H4
H
4-MeOC6H4
H
–(CH2)3–
–(CH2)2CH(OEt)–
Me
H
H
3k
H
7k
1g
1h
1i
Me
Br
5g
5h
5i
a Yield of product after purification by column chromatography.
H
Et
H
–(CH2)2–
whereas the stereoisomers with the (2Z,4E), (2E,4Z), and
(2Z,4Z) configurations contributed 12–22%, 10–28%, and 8–
17%, respectively.
1j
H
–(CH2)3–
5j
1k
H
–(CH2)2CH(OEt)–
5k
a Yield of product after purification by column chromatography.
Compounds 7a–d, which are derived from β-substituted
ethyl carboxylate enones, also had a stereoisomeric compo-
sition comparable to that of compounds 5a–e. Compounds
7a and 7d were obtained as a mixture of four stereoiso-
mers, in which the stereoisomer with the (2E,4E) configura-
tion represented 64% and 37% of the product, respectively;
the stereoisomer with the (2Z,4E) configuration represent-
ed 28% and 13%, respectively; the stereoisomer with the
(2E,4Z) configuration represented 4% and 48%, respectively,
while the (2Z,4Z) configuration represented less than 5% of
the product (Table 6). On the other hand, compounds 7b
and 7c were obtained as a mixture of two stereoisomers, in
which the stereoisomer with the (2E,4E) configuration rep-
resented at least 81% of the product, whereas the stereoiso-
mer with the (2Z,4E) configuration contributed 14–19%.
Products 5g–k and 7j,k, which were derived from the α-
substituted enones 1g–k and 3j,k, furnished only two ste-
reoisomers: usually the stereoisomer with the (2E,4E) con-
figuration was predominant over the (2Z,4E) configuration
(see Table 6). An exception was product 5k, which was
composed of one stereoisomer only, the (2E,4E) isomer.
The characterization of products 5, 6, and 7 was unam-
Table 4 Optimized Reaction Conditions for Obtaining Compounds 6
O
SPh
R
NC
F3C
SPh
O
R1
NaH, THF
0 °C, 30 min
O
(EtO)2PCHCN
2
F3C
R
(EtO)2PCH2CN
R1
4
4'
6
reflux, 2 h
Enone
R
R1
Product
Yield (%)a
2a
2c
2d
2e
2h
C6H5
H
H
H
H
Br
6a
6c
6d
6e
6h
67
50
58
44
67
4-BrC6H4
4-MeC6H4
4-MeOC6H4
H
a Yield of product after purification by column chromatography.
Compounds 5a–e, which are derived from β-substituted
trifluoromethylated enones, were obtained as a mixture of
four stereoisomers, in which the stereoisomer with the
(2E,4E) configuration represents 45–61% of the product,
whereas the stereoisomers with the (2Z,4E), (2E,4Z), and
(2Z,4Z) configurations represent 10–38%, 8–23%, and 4–19%
of the product, respectively (see Table 6). Surprisingly,
product 5f was composed of only two stereoisomers:
(2E,4E) and (2Z,4E), in 70% and 30%, respectively. Com-
pounds 6a,c–e had a stereoisomeric composition compara-
ble to compounds 5a,c–e (Table 6). In this series, the stereo-
isomer with the (2E,4E) configuration contributed 43–60%,
1
biguously elucidated by GC-MS, and H and 13C NMR spec-
troscopy, as well as by two-dimensional NMR experiments
such as heteronuclear single quantum coherence (HSQC),
heteronuclear multiple bond correlation (HMBC), and nu-
clear Overhauser effect spectroscopy (NOESY). The struc-
ture and percentage of each stereoisomer obtained was de-
1
termined via a study based on H and 13C NMR chemical
shifts, 1H–19F and 13C–19F NMR coupling constants, 1H NMR
signal integrals, and NOESY experiments on the representa-
tive compounds 5a, 6a, and 7a. Figure 2 shows some of the
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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C. E. Bencke et al.
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Synthesis
Table 6 Proportion of the Stereoisomers Obtained for Compounds 5,
6, and 7a
C2, C3, C5, and the ipso-carbon of the phenyl ring. The con-
figuration of each stereoisomer was subsequently identified
through a combination of the NOESY data and interpreta-
R1
XR2
R
R1
Z
R
1
tion of the H–19F and 13C–19F NMR coupling constants. For
NC
H
Y
NC
H
Y
Z
Z
E
R
XR2
R
NC
H
NC
H
Z
E
E
E
example, the NOESY spectrum of the two major stereoiso-
mers of compound 5a (5a and 5a′) showed cross-peaks be-
tween the methyl of the methoxy group and H4, which al-
lows assignment of the (4E) configuration for the double
bond at the 4-position for these two stereoisomers (Figure
2). However, the same NOESY spectrum did not indicate
any cross-peak between the hydrogens of the phenyl group
and H2; this lack of cross-peaks does not allow assignment
of the stereochemistry of the double bond at the 2-position
from this spectrum. Thus, the configuration of the double
bond at the 2-position was provided by an interpretation of
the 1H–19F and 13C–19F NMR coupling constants, as shown in
Figure 2. It was observed that the ‘through-space’ coupling
constant between H2 and the fluorine atoms of the CF3
group is a little larger than the ‘through-bond’ coupling
constant. Additionally, the coupling constant between C2
and the fluorine atoms of the CF3 group is much larger for
the (2E) configuration (6.1 and 7.2 Hz for 5a and 5a′′, re-
spectively) than for the (2Z) configuration (3.3 and 3.5 Hz
for 5a′ and 5a′′′, respectively), while the coupling constant
between C4 and the fluorine atoms of the CF3 group is
smaller for the (2E) configuration (1.4 and 0.0 Hz for 5a and
5a′′, respectively) than the (2Z) configuration (3.0 Hz for
both 5a′ and 5a′′′). Furthermore, it was observed that the
chemical shift of H2 is more shielded on the (2Z) configura-
tion than it is on the (2E) configuration. Thus, the major ste-
reoisomer of compound 5a was assigned the (2E,4E) config-
uration, while the second (5a′), third (5a′′), and minor ste-
reoisomer (5a′′′) were assigned the (2Z,4E), (2E,4Z), and
(2Z,4Z) configuration, respectively (Figure 2).
A very reliable trend with respect to the NMR assign-
ments of the four stereoisomers of compound 5a was also
observed for all other compounds 5 of this series. A similar
study was also done for compounds 6a and 7a, in order to
provide the correct assignment of all other compounds 6
and 7 of these two series. The regions of the 1H NMR spec-
tra in which H2 and H4 appear were expanded for a better
observation of the discussed trends (see the Supporting In-
formation). The 1H and 13C NMR chemical shifts of only the
two major stereoisomers of each compound are reported in
the experimental section. The GC-MS spectra are the same
for both stereoisomers reported in the experimental sec-
tion; the data are given for only one of the stereoisomers.
Compounds 5, 6, and 7 can be considered to be attrac-
tive intermediates for organic synthesis due to the various
electrophilic and nucleophilic centers, as shown in Figure 3.
The carbon atoms shown in red (i.e., A, B, and C) are electro-
philic centers. Carbon A can undergo Michael-type reac-
tions by either nucleophilic addition, or nucleophilic addi-
tion followed by elimination of an alcohol or a benzenethiol
molecule. Carbon atoms B and C are electrophilic centers
XR2
R1
(2Z,4E)
XR2
R1
(2Z,4Z)
Y
Y
(2E,4E)
(2E,4Z)
Compd 5, X = O; Y = CF3; R, R1, and R2 are defined in Table 3
Compd 6, X = S; Y = CF3; R, R1, and R2 are defined in Table 4
Compd 7, X = O; Y = CO2Et; R, R1, and R2 are defined in Table 5
Nitrile
(2E,4E)
(2Z,4E)
(2E,4Z)
(2Z,4Z)
5a
5b
5c
5d
5e
5f
48
57
61
46
45
70
87
50
65
75
100
50
60
47
43
69
64
86
81
37
84
85
38
18
10
22
25
30
13
50
35
25
–
8
21
10
15
23
–
6
4
19
17
7
–
5g
5h
5i
–
–
–
–
–
–
5j
–
–
5k
6a
6c
6d
6e
6h
7a
7b
7c
7d
7j
–
–
12
22
16
16
31
28
14
19
13
16
15
28
10
23
24
–
10
8
14
17
–
4
4
–
–
–
–
48
–
2
–
7k
–
–
a Percentage of the stereoisomers, as determined from 1H NMR signal inte-
grals. A dash indicates <1% of that stereoisomer.
important data that enables the elucidation of the four ste-
reoisomers of compound 5a, referred to as 5a, 5a′, 5a′′, and
5a′′′. H2 and H4 are strategic nuclei for the entire assign-
1
ment of the structure of each stereoisomer. The H NMR
signal integrals enable the assignment of every H2 and H4
that belongs to the same stereoisomer. After each stereoiso-
mer was recognized by its respective signal intensities, a se-
quence of HSQC and HMBC experiments enabled the abso-
lute assignment of all carbon atoms of each stereoisomer.
For example, the HSQC spectrum allows the assignment of
H2/C2 and H4/C4, based on the respective cross-peaks be-
tween them (1JC–H). In the HMBC spectrum, H2 shows cross-
peaks with C1, C3, and C4, while H4 has cross-peaks with
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

F
C. E. Bencke et al.
Paper
Synthesis
1
(4.98)
H
NC
114.1
(5.54)
H
CN
114.4
Ph
2
99.1
Ph
101.4
146.8
1.2 Hz
3.3 Hz
1.1 Hz
92.2
6.1Hz
166.6
145.7
3
166.9
4
5
F3C
F3C
OMe
56.4
OMe
56.6
89.4
3.0 Hz
1.4 Hz
X
X
(5.25)
H
(5.17)
H
isomer (2Z,4E)-5a' (38%)
isomer (2E,4E)-5a (48%)
115.4
NC
H
(5.42)
(5.83)
H
CN 115.4
OMe
100.2
OMe
58.7
58.2
99.3
3.5 Hz
1.4 Hz
7.2 Hz
143.2
167.1
165.4
144.2
F3C
Ph
F3C
97.8
Ph
99.8
3.0 Hz
X
X
(6.78)
H
X
(5.58)
H
isomer (2Z,4Z)-5a''' (6%)
isomer (2E,4Z)-5a" (8%)
Figure 2 1H and 13C NMR chemical shifts (blue and pink, respectively), and 1H–19F and 13C–19F NMR coupling constants (red) of H2/C2 and H4/C4 with
the fluorine atoms of the CF3 group
and are suitable for nucleophilic addition, while carbons D
and E, and the nitrogen F of the nitrile group are nucleo-
philic centers. Additionally, products 7 have an ethoxycar-
bonyl group, which is an electrophilic center suitable for
nucleophilic addition/elimination reactions.
mers changed according to the enone substituents. A study
1
1
based on H and 13C NMR chemical shifts, H–19F and 13C–
1
19F NMR coupling constants, H NMR signal integrals, and
HSQC, HMBC, and NOESY experiments enabled the deter-
mination of the structure and percentage of each stereoiso-
mer obtained. We believe that the penta-2,4-dienenitriles
obtained in this study may be suitable as starting materials
for the synthesis of important heterocyclic compounds,
such as pyran-2-ones, pyridin-2-imines, and pyridin-2-
ones; studies in this direction are under development in
our laboratory, and the results will be disclosed in the near
future.
C
D
R1
OR2
R
N
C
F
C
C
A
C
C
B
Y
E
Figure 3 Reaction sites of the penta-2,4-dienenitriles
Despite the products being obtained as a mixture of ste-
reoisomers, which could impose difficulties in controlling
the stereochemistry for some types of reactions, the penta-
2,4-dienenitriles 5, 6, and 7 obtained in this study could be
efficiently used for preparing important heterocyclic com-
pounds, such as pyran-2-ones, pyridin-2-imines, and pyri-
din-2-ones.
In summary, an efficient synthesis of three new series
of compounds, 5-alkoxy-3-(trifluoromethyl)penta-2,4-di-
enenitriles, 5-(phenylthio)-3-(trifluoromethyl)penta-2,4-
dienenitriles, and ethyl 4-alkoxy-2-(cyanomethylene)but-
3-enoates, obtained from the olefination reaction of the re-
spective enones via the Horner–Wadsworth–Emmons reac-
tion has been outlined. All products were obtained as single
regioisomers; however, the composition of the stereoiso-
Low-resolution mass spectra were recorded in EI mode on an Agilent
5975B GC/MSD spectrometer. The GC was equipped with a split/split-
less injector, autosampler, and cross-linked HP-5 capillary column (30
m, 0.32 mm internal diameter), and helium was used as the carrier
gas. High-resolution mass spectra were recorded on a Bruker LC/MS-
QTOF spectrometer in ESI mode. CHN microanalyses were performed
on an elemental analyzer. 1H and 13C NMR spectra were acquired on a
Bruker DPX 200 spectrometer operating at 200 MHz for 1H NMR and
at 50 MHz for 13C NMR, or on a Bruker Avance III spectrometer operat-
ing at 400 MHz for 1H NMR and at 100 MHz for 13C NMR, on solutions
in CDCl3 and using TMS as the internal reference. All two-dimensional
NMR experiments (HSQC, HMBC, and NOESY) were registered at 400
MHz. 19F NMR spectra of selected compounds were acquired on a
Bruker Avance III 600 spectrometer (operating at 565 MHz), on solu-
tions in CDCl3 and using fluorobenzene as the external reference with
the chemical shifts reported relative to the CFCl3 standard.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

G
C. E. Bencke et al.
Paper
Synthesis
1,1,1-Trifluoro-4-(phenylthio)alk-3-en-2-ones 2; General Proce-
dure
13C NMR (50 MHz, CDCl3): δ = 177.2 (q, 2JC–F = 34.7 Hz, C2), 171.8 (C4),
160.6 (Ar), 134.9–113.3 (Ar), 116.8 (q, 1JC–F = 285.3 Hz, C1), 108.4 (C3),
55.2 (OMe).
GC-MS (EI, 70 eV): m/z (%) = 338 (10) [M+], 269 (83), 229 (64), 179
(100), 151 (46), 132 (52), 109 (30).
To a solution of benzenethiol (1.03 mL, 10.0 mmol) and an enone 1
(5.0 mmol) in anhydrous dichloromethane (5.0 mL), under stirring
and argon atmosphere, was added dropwise a solution of BF3·OEt2
(0.74 mL, 6.0 mmol) in anhydrous dichloromethane (5.0 mL). After
the addition, the reaction mixture was gradually warmed to 40 °C and
stirred at this temperature for 1.5 h. For the workup, the mixture was
washed with a 5% solution of sodium carbonate (2 × 50 mL) and dis-
tilled water (2 × 50 mL). The organic layer was dried over anhydrous
sodium sulfate and filtered, and the solvent was evaporated. (Phen-
ylthio)alkenones 2a and 2h were purified by crystallization from hex-
ane, whereas 2c–e were purified by column chromatography using
silica gel (230–400 mesh) and hexane as the eluent.
HRMS (ESI): m/z [M + H] calcd for C17H14F3O2S: 339.0661; found:
339.0666.
3-Bromo-1,1,1-trifluoro-4-(phenylthio)but-3-en-2-one (2h)
Yellow solid; yield: 110 mg (71%).
1H NMR (200 MHz, CDCl3): δ = 8.54 (d, J = 0.7 Hz, 1 H, H4), 7.56–7.44
(m, 5 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 171.2 (q, 2JC–F = 35.2 Hz, C2), 157.5 (q,
1
3JC–F = 4.0 Hz, C3), 131.9–129.8 (Ar), 115.7 (q, JC–F = 290.8 Hz, C1),
1,1,1-Trifluoro-4-phenyl-4-(phenylthio)but-3-en-2-one (2a)
112.4 (C4).
Yellow solid; yield: 131 mg (85%); mp 71–74 °C.
1H NMR (200 MHz, CDCl3): δ = 7.20–7.08 (m, 10 H, Ar), 6.69 (d, J = 0.7
GC-MS (EI, 70 eV): m/z (%) = 312 (100) [M + 2], 310 (100) [M+], 243
(83), 241 (81), 134 (67.5), 109 (38).
Hz, 1 H, H3).
Anal. Calcd for C10H6BrF3OS (311.12): C, 38.60; H, 1.94. Found: C,
38.62; H, 1.96.
13C NMR (50 MHz, CDCl3): δ = 177.4 (q, 2JC–F = 35.2 Hz, C2), 172.5 (C4),
137.5–127.9 (Ar), 116.3 (q, 1JC–F = 290.8 Hz, C1), 113.7 (C3).
GC-MS (EI, 70 eV): m/z (%) = 308 (49) [M+], 239 (100), 211 (44), 178
Penta-2,4-dienenitriles 5, 6, and 7; General Procedure
(24), 149 (47), 121 (21), 109 (34).
To a solution of diethyl cyanomethylphosphonate (4; 0.19 mL, 1.2
mmol) in THF (10 mL), under stirring at 0 °C, sodium hydride (0.36 g,
1.5 mmol) was added and the reaction mixture was stirred at 0 °C for
0.5 h. Then, the enone 1, 2, or 3 (1.0 mmol) was added to the reaction
mixture, which was gradually warmed to reflux and stirred at this
temperature for 2.0 h. For the workup, the mixture was washed with
ammonium chloride solution (4 × 50 mL). The organic layer was dried
over anhydrous sodium sulfate and filtered, and the solvent was
evaporated. All penta-2,4-dienenitriles 5, 6, and 7 were purified by
column chromatography using silica gel (230–400 mesh) and chloro-
form as the eluent.
Anal. Calcd for C16H11F3OS (308.32): C, 62.33; H, 3.60. Found: C, 62.44;
H, 3.61.
4-(4-Bromophenyl)-1,1,1-trifluoro-4-(phenylthio)but-3-en-2-one
(2c)
Brown oil; yield: 116 mg (60%).
1H NMR (200 MHz, CDCl3): δ = 7.56–6.96 (m, 9 H, Ar), 6.66 (d, J = 0.6
Hz, 1 H, H3).
13C NMR (50 MHz, CDCl3): δ = 177.8 (q, 2JC–F = 35.2 Hz, C2), 171.3 (C4),
1
3
136.8–112.6 (Ar), 116.7 (q, JC–F = 290.8 Hz, C1), 108.1 (q, JC–F = 11.5
Hz, C3).
5-Methoxy-5-phenyl-3-(trifluoromethyl)penta-2,4-dienenitrile
(5a)
GC-MS (EI, 70 eV): m/z (%) = 388 (9) [M + 2], 386 (9) [M+], 319 (100),
Brown oil; yield: 152 mg (60%).
317 (100), 291 (12), 289 (12), 229 (32), 227 (32), 210 (40), 109 (48).
For the (2E,4E) isomer:
HRMS (ESI): m/z [M + Na] calcd for C16H10BrF3OSNa: 408.9486; found:
1H NMR (400 MHz, CDCl3): δ = 7.44–7.24 (m, 5 H, Ar), 5.54 (q, J = 1.2
408.9482.
Hz, 1 H, H2), 5.17 (s, 1 H, H4), 3.86 (s, 3 H, OMe).
1,1,1-Trifluoro-4-(phenylthio)-4-p-tolylbut-3-en-2-one (2d)
2
13C NMR (100 MHz, CDCl3): δ = 166.9 (C5), 146.8 (q, JC–F = 31.2 Hz,
C3), 134.3–127.8 (Ar), 122.2 (q, 1JC–F = 275.7 Hz, CF3), 114.4 (C1), 101.4
(q, 3JC–F = 6.1 Hz, C2), 89.4 (q, 3JC–F = 1.4 Hz, C4), 56.6 (OMe).
Brown oil; yield: 104 mg (60%).
1H NMR (200 MHz, CDCl3): δ = 7.59–6.92 (m, 9 H, Ar), 6.69 (s, 1 H, H3),
2.23 (s, 3 H, Me).
19F NMR (565 MHz, CDCl3): δ = –68.8 (CF3).
13C NMR (50 MHz, CDCl3): δ = 177.7 (q, 2JC–F = 35.2 Hz, C2), 173.0 (C4),
141.2–128.6 (Ar), 116.8 (q, 1JC–F = 296.8 Hz, C1), 114.0 (C3), 21.6 (Me).
GC-MS (EI, 70 eV): m/z (%) = 322 (9) [M+], 253 (100), 225 (17), 163
For the (2Z,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.44–7.24 (m, 5 H, Ar), 5.25 (s, 1 H, H4),
4.98 (q, J = 1.1 Hz, 1 H, H2), 3.82 (s, 3 H, OMe).
(57), 135 (24), 109 (25).
13C NMR (100 MHz, CDCl3): δ = 166.6 (C5), 145.7 (q, 2JC–F = 31 Hz, C3),
133.7–127.8 (Ar), 121.8 (q, 1JC–F = 276 Hz, CF3), 114.1 (C1), 99.1 (q, 3JC–F
3.3 Hz, C2), 92.2 (q, 3JC–F = 3.0 Hz, C4), 56.4 (OMe).
=
HRMS (ESI): m/z [M + H] calcd for C17H14F3OS: 323.0712; found:
323.0715.
19F NMR (565 MHz, CDCl3): δ = –65.7 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 253 (98) [M+], 202 (33), 184 (100), 169
1,1,1-Trifluoro-4-(4-methoxyphenyl)-4-(phenylthio)but-3-en-2-
one (2e)
(45), 140 (24), 77 (34).
Brown oil; yield: 132 mg (78%).
1H NMR (200 MHz, CDCl3): δ = 7.58–6.67 (m, 9 H, Ar), 6.63 (s, 1 H, H3),
3.71 (s, 3 H, OMe).
HRMS (ESI): m/z [M + Na] calcd for C13H10F3NONa: 276.0612; found:
276.0605.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

H
C. E. Bencke et al.
Paper
Synthesis
5-(4-Fluorophenyl)-5-methoxy-3-(trifluoromethyl)penta-2,4-di-
enenitrile (5b)
1H NMR (400 MHz, CDCl3): δ = 7.38–7.16 (m, 4 H, Ar), 5.22 (s, 1 H, H4),
5.01 (s, 1 H, H2), 3.68 (s, 3 H, OMe), 2.40 (s, 3 H, Me).
2
13C NMR (100 MHz, CDCl3): δ = 167.2 (C5), 143.1 (q, JC–F = 29.1 Hz,
Red oil; yield: 153 mg (64%).
C3), 140.8–127.9 (Ar), 121.7 (q, 1JC–F = 276.9 Hz, CF3), 115.4 (C1), 98.6
(q, 3JC–F = 3.2 Hz, C2), 92.0 (q, 3JC–F = 3.0 Hz, C4), 58.5 (OMe), 21.3 (Me).
GC-MS (EI, 70 eV): m/z (%) = 267 (49) [M+], 252 (100), 237 (25), 232
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 8.02–7.02 (m, 4 H, Ar), 5.57 (q, J = 1.2
Hz, 1 H, H2), 5.17 (s, 1 H, H4), 3.87 (s, 3 H, OMe).
(37), 198 (31), 183 (37), 140 (14), 91 (18).
13C NMR (100 MHz, CDCl3): δ = 165.8 (C5), 160.0 (d, JC–F = 266.9 Hz,
1
Ar), 146.8 (q, 2JC–F = 31.5 Hz, C3), 130.8 (d, 3JC–F = 8.7 Hz, 2 C, Ar), 122.1
(q, 1JC–F = 275.6 Hz, CF3), 115.3 (d, 2JC–F = 21.9 Hz, 2 C, Ar), 114.1 (C1),
101.6 (q, 3JC–F = 5.9 Hz, C2), 89.5 (q, 3JC–F = 1.2 Hz, C4), 56.6 (OMe).
HRMS (ESI): m/z [M + H] calcd for C14H13F3NO: 268.0944; found:
268.0940.
5-Methoxy-5-(4-methoxyphenyl)-3-(trifluoromethyl)penta-2,4-
dienenitrile (5e)
19F NMR (565 MHz, CDCl3): δ = –68.8 (CF3), –109.7 (ArF).
For the (2E,4Z) isomer:
1H NMR (200 MHz, CDCl3): δ = 8.02–7.02 (m, 4 H, Ar), 5.85 (q, J = 1.4
Hz, 1 H, H2), 5.56 (s, 1 H, H4), 3.66 (s, 3 H, OMe).
Brown oil; yield: 212 mg (75%).
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.94–6.86 (m, 4 H, Ar), 5.53 (s, 1 H, H2),
5.11 (s, 1 H, H4), 3.84 (s, 3 H, OMe), 3.80 (s, 3 H, OMe).
1
13C NMR (100 MHz, CDCl3): δ = 165.2 (C5), 163.7 (d, JC–F = 250.8 Hz,
Ar), 144.1 (q, 2JC–F = 32.1 Hz, C3), 130.7 (d, 3JC–F = 8.5 Hz, 2 C, Ar), 121.6
(q, 1JC–F = 277.2 Hz, CF3), 116.3 (d, 2JC–F = 21.9 Hz, 2 C, Ar), 113.9 (C1),
99.6 (q, 3JC–F = 1.7 Hz, C4), 99.6 (q, 3JC–F = 7.7 Hz, C2), 56.4 (OMe).
13C NMR (100 MHz, CDCl3): δ = 166.8 (C5), 161.0 (Ar), 147.0 (q, 2JC–F
=
30.1 Hz, C3), 130.2–126.3 (Ar), 122.2 (q, 1JC–F = 274.9 Hz, CF3), 114.5 (2
3
3
C, Ar), 114.0 (C1), 100.6 (q, JC–F = 6.6 Hz, C2), 88.7 (q, JC–F = 1.5 Hz,
19F NMR (565 MHz, CDCl3): δ = –67.2 (CF3), –109.4 (ArF).
GC-MS (EI, 70 eV): m/z (%) = 271 (95) [M+], 220 (33), 202 (100), 187
C4), 56.2 (OMe), 55.1 (OMe).
For the (2Z,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.94–6.86 (m, 4 H, Ar), 5.19 (q, J = 1.4
Hz, 1 H, H2), 5.06 (s, 1 H, H4), 3.83 (s, 3 H, OMe), 3.80 (s, 3 H, OMe).
(36), 158 (28), 123 (30), 95 (31).
HRMS (ESI): m/z [M + Na] calcd for C13H9F4NONa: 294.0518; found:
294.0523.
13C NMR (100 MHz, CDCl3): δ = 165.3 (C5), 161.2 (Ar), 144.4 (q, 2JC–F
=
1
32.0 Hz, C3), 130.0–126.2 (Ar), 122.0 (q, JC–F = 275.0 Hz, CF3), 114.4
(C1), 113.9 (Ar), 98.2 (q, 3JC–F = 3.0 Hz, C2), 91.6 (q, 3JC–F = 3.0 Hz, C4),
56.4 (OMe), 55.2 (OMe).
5-(4-Bromophenyl)-5-methoxy-3-(trifluoromethyl)penta-2,4-di-
enenitrile (5c)
Brown oil; yield: 278 mg (84%).
GC-MS (EI, 70 eV): m/z (%) = 283 (100) [M+], 257 (35), 252 (72), 232
(39), 214 (98), 199 (34), 183 (24), 135 (31).
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.61–7.26 (m, 4 H, Ar), 5.58 (s, 1 H, H2),
5.18 (s, 1 H, H4), 3.86 (s, 3 H, OMe).
13C NMR (50 MHz, CDCl3): δ = 165.7 (C5), 146.7 (q, 2JC–F = 31.7 Hz, C3),
133.2–129.4 (Ar), 122.0 (q, 1JC–F = 275.4 Hz, CF3), 114.5 (C1), 101.9 (q,
3JC–F = 5.7 Hz, C2), 89.7 (q, 3JC–F = 1.5 Hz, C4), 56.8 (OMe).
HRMS (ESI): m/z [M + Na] calcd for C14H12F3NO2Na: 306.0718; found:
306.0727.
5-Methoxy-3-(trifluoromethyl)hexa-2,4-dienenitrile (5f)
Brown oil; yield: 54 mg (28%).
For the (2Z,4Z) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.61–7.26 (m, 4 H, Ar), 6.79 (s, 1 H, H4),
5.44 (s, 1 H, H2), 3.68 (s, 3 H, OMe).
13C NMR (50 MHz, CDCl3): δ = 165.6 (C5), 142.8 (q, 2JC–F = 30.0 Hz, C3),
132.5–129.4 (Ar), 121.6 (q, 1JC–F = 277.2 Hz, CF3), 115.2 (C1), 100.0 (q,
3JC–F = 1.4 Hz, C4), 99.8 (q, 3JC–F = 7.0 Hz, C2), 58.8 (OMe).
GC-MS (EI, 70 eV): m/z (%) = 333 (25) [M + 2], 331 (26) [M+], 252
(100), 232 (58), 183 (74), 140 (44).
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 5.43 (s, 1 H, H2), 5.10 (s, 1 H, H4), 3.68
(s, 3 H, OMe), 2.07 (s, 3 H, Me).
2
13C NMR (100 MHz, CDCl3): δ = 165.8 (C5), 147.7 (q, JC–F = 31.6 Hz,
1
3
C3), 121.9 (q, JC–F = 275.6 Hz, CF3), 112.4 (C1), 99.8 (q, JC–F = 5.9 Hz,
C2), 89.4 (q, 3JC–F = 1.7 Hz, C4), 55.4 (OMe), 19.0 (Me).
For the (2Z,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 5.84 (s, 1 H, H4), 5.08 (s, 1 H, H2), 3.69
(s, 3 H, OMe), 2.00 (s, 3 H, Me).
HRMS (ESI): m/z [M + H] calcd for C13H10BrF3NO: 331.9892; found:
331.9891.
2
13C NMR (100 MHz, CDCl3): δ = 165.9 (C5), 146.6 (q, JC–F = 30.7 Hz,
1
3
C3), 121.6 (q, JC–F = 276.8 Hz, CF3), 112.3 (C1), 96.9 (q, JC–F = 3.0 Hz,
5-Methoxy-5-p-tolyl-3-(trifluoromethyl)penta-2,4-dienenitrile
(5d)
C2), 91.8 (q, 3JC–F = 3.0 Hz, C4), 55.4 (OMe), 19.0 (Me).
GC-MS (EI, 70 eV): m/z (%) = 191 (100) [M+], 164 (71), 149 (16), 121
(18), 95 (33), 65 (21).
Brown oil; yield: 248 mg (93%).
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.38–7.16 (m, 4 H, Ar), 5.52 (s, 1 H, H2),
5.14 (s, 1 H, H4), 3.85 (s, 3 H, OMe), 2.35 (s, 3 H, Me).
HRMS (ESI): m/z [M + H] calcd for C8H9F3NO: 192.0631; found: com-
pound did not ionize.
13C NMR (100 MHz, CDCl3): δ = 167.1 (C5), 147.0 (q, JC–F = 31.5 Hz,
2
5-Ethoxy-4-methyl-3-(trifluoromethyl)penta-2,4-dienenitrile
(5g)
C3), 140.3–127.6 (Ar), 122.2 (q, 1JC–F = 275.5 Hz, CF3), 114.6 (C1), 101.1
(q, 3JC–F = 5.9 Hz, C2), 89.1 (q, 3JC–F = 1.6 Hz, C4), 56.5 (OMe), 21.3 (Me).
Brown oil; yield: 21 mg (10%).
For the (2Z,4E) isomer:
For the (2E,4E) isomer:
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

I
C. E. Bencke et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 6.83 (s, 1 H, H5), 5.40 (s, 1 H, H2), 4.05
(q, J = 7.1 Hz, 2 H, H6), 1.78 (s, 3 H, Me), 1.33 (t, J = 7.1 Hz, 3 H, H7).
HRMS (ESI): m/z [M + H] calcd for C8H7F3NO: 190.0474; found: com-
pound did not ionize.
13C NMR (100 MHz, CDCl3): δ = 153.2 (C5), 147.6 (q, JC–F = 30.1 Hz,
2
C3), 121.7 (q, 1JC–F = 278.0 Hz, CF3), 114.9 (C1), 108.1 (C2), 93.5 (q, 3JC–F
=
3-(3,4-Dihydro-2H-pyran-5-yl)-4,4,4-trifluorobut-2-enenitrile (5j)
Brown oil; yield: 142 mg (70%).
3.6 Hz, C4), 70.1 (C6), 15.2 (Me), 10.9 (C7).
For the (2Z,4E) isomer:
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 6.77 (s, 1 H, H5), 5.67 (s, 1 H, H2), 4.05
(q, J = 7.1 Hz, 2 H, H6), 1.90 (s, 3 H, Me), 1.33 (t, J = 7.1 Hz, 3 H, H7).
1H NMR (400 MHz, CDCl3): δ = 7.06 (s, 1 H, H5), 5.67 (q, JH–F = 1.32 Hz,
1 H, H2), 4.11–4.06 (m, 2 H, H6), 2.14 (t, J = 6.28 Hz, 2 H, H8), 2.03–
1.96 (m, 2 H, H7).
2
13C NMR (100 MHz, CDCl3): δ = 152.3 (C5), 146.6 (q, JC–F = 29.9 Hz,
C3), 122.0 (q, 1JC–F = 276.8 Hz, CF3), 115.8 (C1), 106.2 (C2), 96.6 (q, 3JC–F
=
4
13C NMR (100 MHz, CDCl3): δ = 150.9 (q, JC–F = 1.0 Hz, C5), 148.3 (q,
2JC–F = 30.0 Hz, C3), 122.0 (q, JC–F = 276.0 Hz, CF3), 115.8 (C1), 105.9
(C4), 96.2 (q, 3JC–F = 7.0 Hz, C2), 66.3 (C6), 21.8 (8), 21.2 (C7).
7.1 Hz, C4), 69.6 (C6), 15.3 (Me), 11.3 (C7).
GC-MS (EI, 70 eV): m/z (%) = 205 (32) [M+], 150 (100), 149 (22), 122
(12), 101 (7), 69 (7).
19F NMR (565 MHz, CDCl3): δ = –64.3 (CF3).
HRMS (ESI): m/z [M + H] calcd for C9H11F3NO: 206.0787; found: com-
For the (2Z,4E) isomer:
pound did not ionize.
1H NMR (400 MHz, CDCl3): δ = 7.14 (s, 1 H, H5), 5.35 (s, 1 H, H2),
4.11–4.06 (m, 2 H, H6), 2.42 (t, J = 6.32 Hz, 2 H, H8), 2.03–1.96 (m, 2 H,
H7).
4-Bromo-5-ethoxy-3-(trifluoromethyl)penta-2,4-dienenitrile
(5h)
4
13C NMR (100 MHz, CDCl3): δ = 151.7 (q, JC–F = 4.0 Hz, C5), 146.7 (q,
Brown oil; yield: 97 mg (36%).
2JC–F = 30.0 Hz, C3), 121.6 (q, JC–F = 276.0 Hz, CF3), 114.9 (C1), 107.0
(C4), 92.6 (q, 3JC–F = 3.0 Hz, C2), 66.2 (C6), 21.1 (C8), 21.0 (C7).
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.24 (s, 1 H, H5), 5.94 (q, J = 1.3 Hz, 1 H,
H2), 4.23 (q, J = 7.1 Hz, 2 H, H6), 1.40 (t, J = 7.1 Hz, 3 H, H7).
13C NMR (50 MHz, CDCl3): δ = 154.0 (C5), 143.0 (q, 2JC–F = 31.2 Hz, C3),
120.4 (q, 1JC–F = 278.6 Hz, CF3), 114.2 (C1), 103.6 (q, 3JC–F = 6.1 Hz, C2),
86.2 (q, 3JC–F = 1.0 Hz, C4), 71.6 (C6), 15.2 (C7).
19F NMR (565 MHz, CDCl3): δ = –58.8 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 203 (100) [M+], 202 (11), 188 (19), 174
(55), 147 (25), 127 (47), 106 (34), 79 (26).
HRMS (ESI): m/z [M + H] calcd for C9H9F3NO: 204.0631; found:
204.0641.
For the (2Z,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.08 (s, 1 H, H5), 6.16 (s, 1 H, H2), 4.19
(q, J = 7.1 Hz, 2 H, H6), 1.40 (t, J = 7.1 Hz, 3 H, H7).
3-(2-Ethoxy-3,4-dihydro-2H-pyran-5-yl)-4,4,4-trifluorobut-2-
enenitrile (5k)
13C NMR (50 MHz, CDCl3): δ = 152.7 (C5), 145.4 (q, 2JC–F = 32.4 Hz, C3),
121.1 (q, 1JC–F = 276.8 Hz, CF3), 114.2 (C1), 100.5 (q, 3JC–F = 3.0 Hz, C2),
95.2 (q, 3JC–F = 0.8 Hz, C4), 70.9 (C6), 15.3 (C7).
GC-MS (EI, 70 eV): m/z (%) = 271 (37) [M + 2], 269 (38) [M+], 243 (18),
241 (20), 216 (95), 214 (100), 196 (10), 194 (10), 142 (11), 107 (12),
69 (13).
Brown oil; yield: 140 mg (55%).
Only the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.02 (s 1 H, H5), 5.39 (s, 1 H, H2), 5.13
(t, J = 8.6 Hz, 1 H, H6), 3.92–3.53 (m, 2 H, H9), 2.35–1.84 (m, 4 H, H7,
H8), 1.21 (t, J = 7.1 Hz, 3 H, H10).
13C NMR (100 MHz, CDCl3): δ = 148.1 (q, J = 4.0 Hz, C5), 146.5 (q, 2JC–F
=
1
HRMS (ESI): m/z [M + Na] calcd for C8H7BrF3NONa: 291.9561; found:
291.9570.
30.7 Hz, C3), 121.4 (q, JC–F = 278.3 Hz, CF3), 114.6 (C1), 107.8 (C6),
3
96.9 (C4), 93.4 (q, JC–F = 3.5 Hz, C2), 64.4 (C9), 25.6 (C8), 17.5 (C7),
14.9 (C10).
19F NMR (565 MHz, CDCl3): δ = –58.9 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 247 (50) [M+], 202 (31), 192 (18), 163
3-(4,5-Dihydrofuran-3-yl)-4,4,4-trifluorobut-2-enenitrile (5i)
Brown oil; yield: 38 mg (20%).
For the (2E,4E) isomer:
(18), 148 (8), 127 (15), 104 (9), 72 (100).
1H NMR (400 MHz, CDCl3): δ = 7.12 (q, J = 1.76 Hz, 1 H, H5), 5.52 (q, J =
HRMS (ESI): m/z [M + Na] calcd for C11H12F3NO2Na: 270.0718; found:
0.48 Hz, 1 H, H2), 4.64–4.56 (m, 2 H, H6), 3.32 (tq, Jt = 9.44 Hz, Jq
=
270.0714.
0.68 Hz, 2 H, H7).
4
13C NMR (100 MHz, CDCl3): δ = 155.1 (q, JC–F = 3.0 Hz, C5), 141.8 (q,
2JC–F = 31.0 Hz, C3), 122.0 (q, JC–F = 276.0 Hz, CF3), 116.1 (C1), 109.5
(C4), 91.6 (q, 3JC–F = 7.0 Hz, C2), 72.6 (C6), 29.5 (C7).
5-Phenyl-5-(phenylthio)-3-(trifluoromethyl)penta-2,4-diene-
nitrile (6a)
Brown oil; yield: 220 mg (67%).
For the (2Z,4E) isomer:
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.08 (q, J = 1.48 Hz, 1 H, H5), 5.10 (d, J =
1H NMR (400 MHz, CDCl3): δ = 7.58–7.12 (m, 10 H, Ar), 6.42 (s, 1 H,
H4), 6.11 (q, J = 1.1 Hz, 1 H, H2).
0.72 Hz, 1 H, H2), 4.64–4.56 (m, 2 H, H6), 2.81 (tq, Jt = 9.56 Hz, Jq
=
0.68 Hz, 2 H, H7).
2
13C NMR (100 MHz, CDCl3): δ = 151.5 (C5), 145.9 (q, JC–F = 32.2 Hz,
13C NMR (100 MHz, CDCl3): δ = 153.5 (q, JC–F = 4.0 Hz, C5), 142.2 (q,
2JC–F = 32.0 Hz, C3), 121.5 (q, JC–F = 276.0 Hz, CF3), 114.9 (C1), 110.3
(C4), 92.4 (q, 3JC–F = 3.0 Hz, C2), 71.6 (C6), 29.6 (C7).
GC-MS (EI, 70 eV): m/z (%) = 189 (100) [M+], 188 (39), 162 (29), 134
(45), 114 (33), 92 (15), 69 (11).
4
1
3
C3), 134.8–127.5 (Ar), 121.5 (q, JC–F = 275.6 Hz, CF3), 118.3 (q, JC–F
=
1.5 Hz, C4), 114.4 (C1), 104.4 (q, 3JC–F = 6.1 Hz, C2).
19F NMR (565 MHz, CDCl3): δ = –67.9 (CF3).
For the (2E,4Z) isomer:
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

J
C. E. Bencke et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.58–7.12 (m, 10 H, Ar), 6.48 (s, 1 H,
H4), 6.44 (q, J = 0.9 Hz, 1 H, H2).
5-(4-Methoxyphenyl)-5-(phenylthio)-3-(trifluoromethyl)penta-
2,4-dienenitrile (6e)
2
13C NMR (100 MHz, CDCl3): δ = 151.1 (C5), 143.1 (q, JC–F = 30.4 Hz,
Brown oil; yield: 160 mg (44%).
1
3
C3), 135.0–128.1 (Ar), 121.4 (q, JC–F = 277.4 Hz, CF3), 119.3 (q, JC–F
=
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.53–6.74 (m, 9 H, Ar), 6.37 (s, 1 H, H4),
6.06 (q, J = 1.0 Hz, 1 H, H2), 3.75 (s, 3 H, OMe).
3.0 Hz, C4), 113.8 (C1), 102.3 (q, 3JC–F = 3.4 Hz, C2).
19F NMR (565 MHz, CDCl3): δ = –64.6 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 331 (46) [M+], 304 (100), 253 (22), 222
13C NMR (50 MHz, CDCl3): δ = 160.7 (Ar), 150.7 (C5), 145.9 (q, JC–F
=
2
32.0 Hz, C3), 134.8–127.3 (Ar), 121.6 (q, 1JC–F = 275.7 Hz, CF3), 117.1 (q,
3JC–F = 0.9 Hz, C4), 114.9 (C1), 103.9 (q, 3JC–F = 6.1 Hz, C2), 55.2 (OMe).
(32), 202 (68), 152 (17), 121 (27), 110 (26), 77 (16).
HRMS (ESI): m/z [M + Na] calcd for C18H12F3NSNa: 354.0540; found:
354.0523.
For the (2E,4Z) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.53–6.74 (m, 9 H, Ar), 6.44 (s, 1 H, H4),
6.41 (q, J = 1.2 Hz, 1 H, H2), 3.83 (s, 3 H, OMe).
5-(4-Bromophenyl)-5-(phenylthio)-3-(trifluoromethyl)penta-2,4-
dienenitrile (6c)
2
13C NMR (50 MHz, CDCl3): δ = 160.8 (Ar), 150.4 (C5), 143.1 (q, JC–F
=
Yellow oil; yield: 210 mg (50%).
30.3 Hz, C3), 134.6–129.2 (Ar), 121.5 (q, 1JC–F = 277.4 Hz, CF3), 118.6 (q,
3JC–F = 2.9 Hz, C4), 114.6 (C1), 101.6 (q, 3JC–F = 3.2 Hz, C2), 55.3 (OMe).
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.56–7.11 (m, 9 H, Ar), 6.41 (s, 1 H, H4),
6.11 (q, J = 1.0 Hz, 1 H, H2).
GC-MS (EI, 70 eV): m/z (%) = 361 (33) [M+], 334 (21), 284 (5), 252
(100), 232 (31), 209 (9), 189 (9), 151 (12).
13C NMR (100 MHz, CDCl3): δ = 155.1 (C5), 150.3, 146.9 (Ar), 145.6 (q,
HRMS (ESI): m/z [M + H] calcd for C19H15F3NOS: 362.0821; found:
362.0817.
1
2JC–F = 32.4 Hz, C3), 137.2–127.8 (Ar), 121.5 (q, JC–F = 275.8 Hz, CF3),
118.8 (q, 3JC–F = 1.5 Hz, C4), 114.2 (C1), 104.9 (q, 3JC–F = 6.1 Hz, C2).
For the (2Z,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.56–7.11 (m, 9 H, Ar), 5.67 (s, 1 H, H4),
5.55 (q, J = 1.0 Hz, 1 H, H2).
4-Bromo-5-(phenylthio)-3-(trifluoromethyl)penta-2,4-diene-
nitrile (6h)
Brown oil; yield: 220 mg (67%).
13C NMR (100 MHz, CDCl3): δ = 153.8 (C5), 149.5 (Ar), 146.4 (q, 2JC–F
=
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.55–7.37 (m, 5 H, Ar), 7.51 (s, 1 H, H5),
6.00 (q, J = 1.2 Hz, 1 H, H2).
32.1 Hz, C3), 137.3–123.8 (Ar), 121.5 (q, 1JC–F = 275.7 Hz, CF3), 111.7 (q,
3JC–F = 1.1 Hz, C4), 111.7 (C1), 103.0 (q, 3JC–F = 6.2 Hz, C2).
GC-MS (EI, 70 eV): m/z (%) = 411 (20) [M + 2], 409 (20) [M+], 384 (12),
382 (11), 342 (7), 340 (7), 302 (1), 300 (12), 252 (13), 221 (100), 201
(21), 171 (15), 152 (14), 110 (23), 109 (35).
2
13C NMR (100 MHz, CDCl3): δ = 146.6 (q, JC–F = 32.6 Hz, C3), 143.9
1
(C4), 143.4 (C5), 138.2–128.9 (Ar), 120.7 (q, JC–F = 279.3 Hz, CF3),
113.8 (C1), 104.3 (q, 3JC–F = 6.0 Hz, C2).
HRMS (ESI): m/z [M + Na] calcd for C18H11BrF3NSNa: 431.9645; found:
431.9639.
For the (2Z,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.55–7.37 (m, 5 H, Ar), 7.51 (s, 1 H, H5),
6.22 (s, 1 H, H2).
5-(Phenylthio)-5-p-tolyl-3-(trifluoromethyl)penta-2,4-diene-
nitrile (6d)
13C NMR (100 MHz, CDCl3): δ = 146.1 (q, JC–F = 30.2 Hz, C3), 145.6
2
1
(C5), 144.7 (C4), 137.2–129.2 (Ar), 120.3 (q, JC–F = 278.8 Hz, CF3),
Brown oil; yield: 200 mg (58%).
113.7 (C1), 102.9 (q, 3JC–F = 2.3 Hz, C2).
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.49–7.06 (m, 9 H, Ar), 6.42 (s, 1 H, H4),
6.08 (q, J = 1.2 Hz, 1 H, H2), 2.30 (s, 3 H, Me).
GC-MS (EI, 70 eV): m/z (%) = 335 (100) [M + 2], 333 (100), 254 (60),
221 (25), 190 (18), 109 (75), 65 (23).
HRMS (ESI): m/z [M + Na+] calcd for C12H8BrF3NS: 355.9332; found:
355.9313.
13C NMR (100 MHz, CDCl3): δ = 151.2 (C5), 145.9 (q, JC–F = 32.1 Hz,
2
1
3
C3), 139.7–127.3 (Ar), 121.6 (q, JC–F = 275.7 Hz, CF3), 117.9 (q, JC–F
=
0.9 Hz, C4), 114.5 (C1), 104.2 (q, 3JC–F = 5.9 Hz, C2), 21.1 (Me).
Ethyl 2-(Cyanomethylene)-4-methoxy-4-phenylbut-3-enoate (7a)
Yellow oil; yield: 150 mg (57%).
19F NMR (565 MHz, CDCl3): δ = –67.9 (CF3).
For the (2E,4Z) isomer:
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.49–7.06 (m, 9 H, Ar), 6.50 (s, 1 H, H4),
6.44 (q, J = 0.7 Hz, 1 H, H2), 2.40 (s, 3 H, Me).
1H NMR (400 MHz, CDCl3): δ = 7.42–7.32 (m, 5 H, Ar), 5.81 (s, 1 H, H2),
5.70 (d, J = 1.2 Hz, 1 H, H4), 3.90 (s, 3 H, OMe), 3.61 (q, J = 7.1 Hz, 2 H,
H7), 0.96 (t, J = 7.2 Hz, 3 H, H8).
13C NMR (100 MHz, CDCl3): δ = 165.4 (C6), 150.6 (C5), 135.5 (C3),
130.0–128.2 (Ar), 116.3 (C4), 100.4 (C1), 94.8 (C2), 61.7 (C7), 56.4
(OMe), 13.4 (C8).
2
13C NMR (100 MHz, CDCl3): δ = 150.8 (C5), 143.2 (q, JC–F = 30.1 Hz,
1
3
C3), 139.9–127.9 (Ar), 121.3 (q, JC–F = 277.4 Hz, CF3), 119.3 (q, JC–F
=
3.0 Hz, C4), 114.4 (C1), 102.1 (q, 3JC–F = 3.3 Hz, C2), 21.3 (Me).
19F NMR (565 MHz, CDCl3): δ = –64.6 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 345 (33) [M+], 318 (100), 267 (13), 236
For the (2Z,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.42–7.32 (m, 5 H, Ar), 5.58 (s, 1 H, H4),
5.30 (d, J = 0.9 Hz, 1 H, H2), 3.84 (q, J = 7.1 Hz, 2 H, H7), 3.82 (s, 3 H,
OMe), 1.16 (t, J = 7.2 Hz, 3 H, H8).
(61), 216 (52), 167 (22), 135 (22), 110 (14), 91 (5).
HRMS (ESI): m/z [M + Na] calcd for C19H14F3NSNa: 368.0697; found:
368.0694.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

K
C. E. Bencke et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3): δ = 165.8 (C6), 149.8 (C5), 134.6 (C3),
130.1 (Ar), 128.8–128.4 (Ar), 116.2 (C4), 98.4 (C1), 96.7 (C2), 61.9 (C7),
56.2 (OMe), 13.5 (C8).
GC-MS (EI, 70 eV): m/z (%) = 257 (30) [M+], 228 (26), 210 (21), 184
(100), 169 (44), 140 (25), 115 (18), 77 (24).
Ethyl 2-(Cyanomethylene)-4-methoxy-4-p-tolylbut-3-enoate (7d)
Brown oil; yield: 170 mg (62%).
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 7.40–7.14 (m, 4 H, Ar), 5.80 (s, 1 H, H2),
5.68 (d, J = 0.9 Hz, 1 H, H4), 3.90 (s, 3 H, OMe), 3.63 (q, J = 7.1 Hz, 2 H,
H7), 2.35 (s, 3 H, Me), 0.98 (t, J = 7.2 Hz, 3 H, H8).
13C NMR (100 MHz, CDCl3): δ = 166.2 (C6), 165.6 (C5), 151.0 (Ar),
140.3 (C3), 128.9–125.4 (Ar), 116.5 (C4), 99.9 (C1), 94.6 (C2), 61.8
(C7), 56.4 (OMe), 21.3 (Me), 13.5 (C8).
HRMS (ESI): m/z [M + Na] calcd for C15H15NO3Na: 280.0950; found:
280.0951.
Ethyl 2-(Cyanomethylene)-4-(4-fluorophenyl)-4-methoxybut-3-
enoate (7b)
For the (2E,4Z) isomer:
Red oil; yield: 182 mg (66%).
1H NMR (400 MHz, CDCl3): δ = 7.40–7.14 (m, 4 H, Ar), 6.01 (s, 1 H, H2),
5.52 (s, 1 H, H4), 4.33 (q, J = 7.0 Hz, 2 H, H7), 3.53 (s, 3 H, OMe), 2.40 (s,
3 H, Me), 1.37 (t, J = 7.2 Hz, 3 H, H8).
13C NMR (100 MHz, CDCl3): δ = 166.7 (C6), 163.9 (C5), 149.1 (Ar),
140.6 (C3), 129.4–124.0 (Ar), 116.1 (C4), 104.7 (C1), 97.8 (C2), 61.9
(C7), 58.4 (OMe), 21.3 (Me), 14.1 (C8).
GC-MS (EI, 70 eV): m/z (%) = 271 (39) [M+], 256 (14), 228 (20), 210
(36), 198 (95), 184 (100), 183 (55), 169 (17), 154 (21), 140 (28), 119
(24), 91 (29).
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.38–7.31 (m, 2 H, Ar), 7.09–7.00 (m, 2
H, Ar), 5.79 (s, 1 H, H2), 5.74 (d, J = 1.2 Hz, 1 H, H4), 3.91 (s, 3 H, OMe),
3.71 (q, J = 7.2 Hz, 2 H, H7), 1.02 (t, J = 7.1 Hz, 3 H, H8).
13C NMR (100 MHz, CDCl3): δ = 165.4 (C6), 164.7 (C5), 163.3 (d, 1JC–F
250.7 Hz, Ar), 150.3 (Ar), 131.8 (C3), 130.7 (d, JC–F = 8.6 Hz, 2 C, Ar),
116.4 (C4), 115.3 (d, 2JC–F = 21.8 Hz, 2 C, Ar), 100.9 (C1), 94.8 (C2), 62.0
(C7), 56.5 (OMe), 13.6 (C8).
=
3
For the (2Z,4E) isomer:
HRMS (ESI): m/z [M + Na] calcd for C16H17NO3Na: 294.1106; found:
294.1103.
1H NMR (200 MHz, CDCl3): δ = 7.38–7.31 (m, 2 H, Ar), 7.09–7.00 (m, 2
H, Ar), 5.57 (s, 1 H, H2), 5.35 (d, J = 1.0 Hz, 1 H, H4), 3.84 (s, 3 H, OMe),
3.71 (q, J = 7.2 Hz, 2 H, H7), 1.19 (t, J = 7.2 Hz, 3 H, H8).
13C NMR (100 MHz, CDCl3): δ = 165.4 (C6), 164.1 (C5), 163.3 (d, 1JC–F
250.7 Hz, Ar), 149.8 (Ar), 131.7 (C3), 131.0 (d, JC–F = 8.6 Hz, 2 C, Ar),
116.2 (C4), 115.5 (d, 2JC–F = 21.8 Hz, 2 C, Ar), 98.7 (C1), 96.9 (C2), 62.1
(C7), 56.4 (OMe), 13.6 (C8).
Ethyl 3-Cyano-2-(3,4-dihydro-2H-pyran-5-yl)acrylate (7j)
Yellow oil; yield: 120 mg (60%).
=
3
For the (2E,4E) isomer:
1H NMR (400 MHz, CDCl3): δ = 6.98 (s, 1 H, H5), 5.09 (s, 1 H, H2), 4.36
(q, J = 7.2 Hz, 2 H, H10), 4.05 (t, J = 5.4 Hz, 2 H, H6), 2.10 (t, J = 6.4 Hz, 2
H, H8), 1.96 (q, J = 6.0 Hz, 2 H, H7), 1.36 (t, J = 7.1 Hz, 3 H, H11).
13C NMR (100 MHz, CDCl3): δ = 165.3 (C9), 152.4 (C5), 150.7 (C3),
116.8 (C4), 109.3 (C1), 89.3 (C2), 66.5 (C6), 62.4 (C10), 21.0 (C8), 19.7
(C7), 13.9 (C11).
GC-MS (EI, 70 eV): m/z (%) = 275 (40) [M2+], 202 (100), 158 (26), 123
(26), 95 (22).
HRMS (ESI): m/z [M + Na] calcd for C15H14FNO3Na: 298.0855; found:
298.0862.
For the (2Z,4E) isomer:
Ethyl 4-(4-Bromophenyl)-2-(cyanomethylene)-4-methoxybut-3-
enoate (7c)
1H NMR (400 MHz, CDCl3): δ = 6.99 (s, 1 H, H5), 5.73 (s, 1 H, H2), 4.24
(q, J = 7.1 Hz, 2 H, H10), 4.07 (t, J = 5.3 Hz, 2 H, H6), 2.45 (t, J = 6.3 Hz, 2
H, H8), 1.96 (q, J = 6.0 Hz, 2 H, H7), 1.30 (t, J = 7.1 Hz, 3 H, H11).
13C NMR (100 MHz, CDCl3): δ = 165.4 (C9), 153.1 (C5), 151.1 (C3),
117.0 (C4), 108.9 (C1), 97.8 (C2), 66.3 (C6), 62.2 (C10), 22.1 (C7), 21.4
(C8), 14.0 (C11).
Yellow oil; yield: 270 mg (79%).
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.49 (d, J = 8.6 Hz, 2 H, Ar), 7.22 (d, J =
8.6 Hz, 2 H, Ar), 5.79 (s, 1 H, H2), 5.76 (d, J = 1.2 Hz, 1 H, H4), 3.90 (s, 3
H, OMe), 3.72 (q, J = 7.1 Hz, 2 H, H7), 1.00 (t, J = 7.2 Hz, 3 H, H8).
13C NMR (100 MHz, CDCl3): δ = 164.4 (C6), 164.0 (C5), 149.5 (Ar),
133.5 (C3), 131.7–124.6 (Ar), 116.1 (C4), 99.2 (C1), 97.0 (C2), 62.2
(C7), 56.4 (OMe), 13.6 (C8).
GC-MS (EI, 70 eV): m/z (%) = 207 (1) [M+], 170 (24), 141 (100), 125 (8),
113 (12), 95 (32), 69 (12).
HRMS (ESI): m/z [M – H] calcd for C11H14NO3: 206.0817; found:
206.0831.
For the (2Z,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 7.51 (d, J = 8.5 Hz, 2 H, Ar), 7.25 (d, J =
8.0 Hz, 2 H, Ar), 5.57 (s, 1 H, H2), 5.36 (d, J = 1.0 Hz, 1 H, H4), 3.83 (s, 3
H, OMe), 3.72 (q, J = 7.1 Hz, 2 H, H7), 1.19 (t, J = 7.2 Hz, 3 H, H8).
13C NMR (100 MHz, CDCl3): δ = 164.4 (C6), 164.0 (C5), 149.5 (Ar),
133.5 (C3), 132.1–124.6 (Ar), 116.1 (C4), 99.1 (C1), 96.7 (C2), 62.2
(C7), 56.4 (OMe), 13.6 (C8).
Ethyl 3-Cyano-2-(2-ethoxy-3,4-dihydro-2H-pyran-5-yl)acrylate
(7k)
Brown oil; yield: 83 mg (33%).
For the (2E,4E) isomer:
1H NMR (200 MHz, CDCl3): δ = 6.80 (s, 1 H, H5), 5.10 (s, 1 H, H2), 5.04
(t, J = 3.0 Hz, 1 H, H6), 4.31 (q, J = 7.1 Hz, 2 H, C(O)OCH2), 3.82–3.46
(m, 2 H, OCH2), 1.98–1.91 (m, 4 H, H7, H8), 1.31 (t, J = 7.1 Hz, 3 H, O–
C–CH3), 1.11 (t, J = 7.1 Hz, 3 H, C(O)O–C–CH3).
13C NMR (50 MHz, CDCl3): δ = 165.6 (C=O), 153.1 (C5), 149.5 (C3),
117.1 (C4), 110.4 (C1), 97.8 (C2), 90.6 (C6), 64.8 (OCH2), 62.9
(C(O)OCH2), 25.9–16.7 (C7, C8), 15.4–14.3 (O–C–CH3, C(O)O–C–CH3).
GC-MS (EI, 70 eV): m/z (%) = 337 (16) [M + 2], 335 (16) [M+], 264 (20),
262 (21), 210 (23), 184 (65), 183 (100), 169 (18), 153 (18), 140 (35).
HRMS (ESI): m/z [M + Na] calcd for C15H14BrNO3Na: 358.0055; found:
358.0070.
For the (2Z,4E) isomer:
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

L
C. E. Bencke et al.
Paper
Synthesis
1H NMR (200 MHz, CDCl3): δ = 6.80 (s, 1 H, H5), 5.75 (s, 1 H, H2), 5.04
(t, J = 3.0 Hz, 1 H, H6), 4.19 (q, J = 7.2 Hz, 2 H, C(O)OCH2), 3.82–3.46
(m, 2 H, OCH2), 2.26–2.03 (m, 4 H, H7, H8), 1.31 (t, J = 7.1 Hz, 3 H, O–
C–CH3), 1.11 (t, J = 7.1 Hz, 3 H, C(O)O–C–CH3).
13C NMR (50 MHz, CDCl3): δ = 165.6 (C=O), 151.1 (C5), 147.8 (C3),
117.2 (C4), 110.1 (C1), 99.3 (C6), 97.6 (C2), 64.6 (OCH2), 62.6
(C(O)OCH2), 26.3–19.1 (C7, C8), 15.5–14.4 (O–C–CH3, C(O)O–C–CH3).
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J. A.; Orelli, L. R. Curr. Org. Chem. 2015, 19, 744.
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GC-MS (EI, 70 eV): m/z (%) = 251 (9) [M+], 205 (12), 178 (14), 159 (16),
134 (21), 93 (8), 72 (100), 65 (17).
HRMS (ESI): m/z [M + H] calcd for C13H18NO4: 252.1230; found:
252.1234.
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Funding Information
The authors are grateful for financial support from the Fundação de
Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS/CNPq –
PRONEX – Grant No. 16/2551-0000477-3) and fellowships from CNPq
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Supporting Information
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Supporting information for this article is available online at
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13C, and 19F NMR spectra, HSQC, HMBC, and NOESY data for selected
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L