Alkynylation and Cyanation of Alkenes Using Diverse Properties of a Nitro Group

Article abstract of DOI:10.1021/acs.joc.8b01865

In the work being reported here, β-nitrostyrenes bearing an ethoxycarbonyl group at the β-position serve as scaffolds for the synthesis of α,β-difunctionalized alkenes. Nitrocinnamates undergo Michael addition reactions with versatile sp³- and sp²-nucleophiles such as alcohols, Grignard reagents, alkylcopper, and dialkylzinc to afford β-substituted nitroethane derivatives. However, various attempts to obtain a double bond via nitrous acid elimination failed because steric repulsion between the newly introduced sp³/sp² substituent and the nitro group hampered the required anti-coplanar conformation. This problem was successfully overcome using a smaller sp-nucleophile such as lithium acetylide, potassium cyanide, or trimethylsilyl cyanide. While treatment of the adduct with a strong base did not lead to the elimination of nitrous acid, the weaker triethylamine efficiently afforded functionalized enynes and acrylonitriles in high yields.

Full text of DOI:10.1021/acs.joc.8b01865

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Article
Alkynylation and Cyanation of Alkenes
Using Diverse Properties of a Nitro Group
Haruyasu Asahara, Ayano Sofue, Yasuyuki Kuroda, and Nagatoshi Nishiwaki
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01865 • Publication Date (Web): 25 Oct 2018
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Alkynylation and Cyanation of Alkenes Using Diverse Properties of a Nitro Group
Haruyasu Asahara,*†‡§Ayano Sofue,† Yasuyuki Kuroda,† and Nagatoshi Nishiwaki*†‡
†School of Environmental Science and Engineering, Kochi University of Technology,
‡Research Center for Material Science and Engineering, Kochi University of Technology,
Tosayamada, Kami, Kochi 782-8502, Japan
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§Division of Applied Chemistry, Graduate School of Engineering, Osaka University,
Yamadaoka 2-1, Suita, Osaka 565-0871, Japan
*E-mail: nishiwaki.nagatoshi@kochi-tech.ac.jp.
Tel: +81-887-57-2517, Fax: +81-887-57-2520 (N.N.).
O2N
Ar
COOEt
R
COOEt
R
O2N
Ar
COOEt
H
NEt3
R
Li
Ar
H
HNO2
Abstract: In the work being reported here, β-nitrostyrenes bearing an ethoxycarbonyl group
at the β-position serve as scaffolds for the synthesis of α,β-difunctionalized alkenes.
Nitrocinnamates undergo Michael addition reactions with versatile sp3- and sp2-nucleophiles
such as alcohols, Grignard reagents, alkylcopper, and dialkylzinc to afford β-substituted
nitroethane derivatives. However, various attempts to obtain a double bond via nitrous acid
elimination failed because steric repulsion between the newly introduced sp3/sp2-substituent
and the nitro group hampered the required anti-coplanar conformation. This problem was
successfully overcome using a smaller sp-nucleophile such as lithium acetylide, potassium
cyanide, or trimethylsilyl cyanide. While treatment of the adduct with a strong base did not
lead to the elimination of nitrous acid, the weaker triethylamine efficiently afforded
functionalized enynes and acrylonitriles in high yields.
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Introduction
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Nitro compounds are an important family of organic compounds, widely used as functional
materials or their synthetic intermediates.1 The versatile reactivity of the members of this
family originates from the diverse properties of the nitro group, which 1) is a strong electron-
withdrawing group that reduces the electron density of the adjacent atom or double bond
through both inductive and resonance effects, 2) stabilizes anionic intermediates, 3) is easily
eliminated as nitrous acid with concomitant double bond formation.2 These properties can be
exploited to functionalize the heterocyclic framework. Indeed, the synthesis of unnatural 1-
methyl-2-quinolone derivatives via an addition–elimination protocol has been demonstrated.
When 1-methyl-3,6,8-trinitro-2-quinolone (1) was allowed to react with nucleophiles such as
1,3-dicarbonyl compounds,3 phenols,3 cyanides,4 amines,5 and alcohols,6 regioselective
nucleophilic substitution proceeded at the 4-position, accompanied by elimination of the 3-
nitro group in what is called cine-substitution. In this process, the 3- and 4-positions of
quinolone 1 act as an activated nitroalkene.4 Inspired by these results, it was assumed that α-
nitrocinnamate 2, which is structurally related to 1, should exhibit a reactivity similar to that
of 1, leading to functionalized alkenes via said addition−elimination mechanism (Scheme 1).
Facile syntheses of functionalized enynes and acrylonitriles using α-functionalized
nitroalkenes have been demonstrated.
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Base
Nu
H
H
Nu
NO2
H
O2N
O2N
O2N
NO2
O
Nucleophile
Base
HNO2
N
O
N
O
N
9
O2N
Me
O2N
Me
O2N
Me
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1
Nucleophiles:
_
O
O
_
O
_
_
C N RNH2 RO etc.
R1
R2
This Work
H
Nu
H
Nu
NO2
NO2
O
Nucleophile
Base
HNO2
H
EtO
O
EtO
EtO
O
2
Scheme 1. cine-Substitution of trinitroquinolone 1 and synthetic strategy for functionalized
alkenes via an addition–elimination mechanism.
Results and Discussion
When a methanol solution of α-nitrocinnamate 2A7 (E/Z mixture, ca. 3/2 ratio) was heated at
solvent reflux for 2 days, adduct 3a was obtained in 87% yield as a mixture of diastereomers
in 73:27 ratio (Scheme 2). Ethanol was also a suitable solvent for this addition reaction.
Compound 3b was obtained in 79% yield upon heating 2A in this alcohol. It was also
possible to use a stoichiometric amount of the lithium alkoxide in THF to afford 3c in high
yield even at 0 °C (Scheme 2). Then, adducts 3a and 3b were treated with triethylamine to
promote nitrous acid elimination and lead to the formation of a double bond. However,
bis(ethoxycarbonyl)isoxazole 4 was quantitatively obtained in the absence of any detectable
β-alkoxycinnamates 5a and 5b in both cases (Scheme 3). Adduct 3a is presumably converted
into 3d via 2A in the presence of water contained in the solvent. Furthermore, 3d is then
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hydrolyzed to afford ethyl nitroacetate, which reacts with 3a leading to 4 via cyclization
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followed by aromatization (Scheme 3).8
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O2N
Tol
O2N
Tol
COOEt
COOEt
OR
ROH
65 °C, 2 d
2A
R = Me 3a 87%
Et 3b 79%
Tol = p-MeC6H4
O2N
COOEt
O
OLi
2A
+
THF
p-MeC6H4
0 °C, 3 h
3c 92%
Scheme 2. Addition of an alcohol to nitrocinnamate 2A.
EtOOC
Tol
O2N
Tol
COOEt
OR
NEt3
N
COOEt
OR
O
MeCN
rt, 3 h
quant.
Tol
COOEt
3a or 3b
4
5 (not formed)
_
O
MeOH
EtOOC
+
O2N
Tol
COOEt
OMe
N
_
O
NEt3
Tol
COOEt
O2N
3a
O2N
COOEt
Tol-CHO
OH
+
OH
EtOOC
EtOOC
Tol
N
MeOH
MeOH
N
O
4
H
Tol
O
O2N
Tol
COOEt
OH
O2N
Tol
H2O
H2O
COOEt
COOEt
H
COOEt
3d
2A
Scheme 3. Formation of bis(ethoxycarbonyl)isoxazole 4.
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Although adducts 3 were efficiently obtained, the subsequent elimination of a nitrous acid
from 3 was not observed rather the predominant reaction sequence to form isoxazole 4
occurred. Hence, carbon nucleophiles were used for the reaction with cinnamate 2A as C–C
bonds are not cleaved as easily as C–O bonds. Upon addition of a dialkylcopperlithium, or
dialkylzinc to cinnamate 2A, the corresponding adducts 6 were efficiently obtained in high
yield, however, in cases of adducts 6a and 6c, the yields were moderate because of further
reaction with another molecule of Grignard reagent (Table 1). This reaction facilitates the
introduction of an alkyl or aryl group at the β-position of α-nitrocinnamate 2A. However,
subsequent elimination of nitrous acid from the obtained adducts 6 did not occur even after
treatment with an acid such as p-toluenesulfonic acid or trifluoroborane etherate, or upon
treatment with a base such as triethylamine, pyridine, diazabicycloundecene (DBU), sodium
ethoxide, lithium diisopropylamide, or sodium hydride. The low reactivity toward the desired
elimination is believed to arise from steric repulsion between the substituents, preventing the
β-hydrogen (Hβ) and nitro group from taking the necessary anti-coplanar conformation
(Figure 1, upper left). In order to overcome this problem, less bulky acetylides and cyanides
were employed as nucleophiles to avoid steric repulsion between the nitro group and the
introduced substituent (Figure 1, upper right). There is another possibility that a syn-
elimination proceeds in parallel to a sulfoxide elimination, in which the nitro group assists the
deprotonation at the adjacent position. Even if the elimination proceeds in such mode,
eclipsed conformation of an adduct derived from sp2-nucleophile is less stable than that
derived from sp-nucleophile (Figure 1, lower). Moreover, it was envisioned that the
electronegative sp-carbon would increase the acidity of the adjacent Hβ to accelerate the
elimination of nitrous acid, thus affording functionalized enynes and acrylonitriles (Figure 1,
right).
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Table 1. Reactions of 2A with several organometallic reagents.
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8
H
RM
αCOOEt
COOEt
R
O2N
Tol
O2N
Tol
COOEt
Additive
THF
Tol
R
9
Hβ
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2A
6
7
Entry
Reagent
(equiv.)
Additive
(equiv.)
None
Temp.
Time
Product
R
Et
Yield/%
49
1
2
3
4
5
6
EtMgBr (1.5)
i-PrMgBr (1.5)
PhMgBr (1.7)
Et2Zn (1.5)
BuLi (4)
0 °C, 1 d
rt, 3 h
6a
6b
6c
6a
6d
6d
LiCl (1.5)
None
i-Pr
Ph
Et
90
rt, 1 h
20
89a
None
rt, 1 h
CuI (4), BF3•OEt2 (3) -78 °C~rt, 1 d
CuI (6) BF3•OEt2 (6) -78 °C~rt, 1 d
Bu
Bu
62
BuLi (6)
quant
a Ethyl β-ethylcinnamate 7a9 was also obtained in 3% yield.
_
_
O
O
O
O
N+
N+
Y
R
C
anti-elimination
COOEt
COOEt
Hα
Hα
Hβ
Hβ
less acidic
more acidic
Y = CR, N
R = alkyl (sp3), aryl (sp2)
_
_
O
O
O
O
N+
N+
Hβ
Hβ
syn-elimination
Y
R
C
Hα
Hα
COOEt
COOEt
Figure 1. Required conformation of 6 for the elimination of nitrous acid leading to 7.
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Table 2. Reactions of nitroalkene 2 with several lithium acetylides 8.
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8
R2
Li
R1
O2N
Ar
R1
O2N
Ar
H+
8
THF
Temp., Time
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R2
2
9
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Entry
1
Nitroalkene 2
Acetylide 8
R2
Temp. Time
Product
Yield/%
Ar
R1
/°C
0
/h
1
p-MeC6H4 COOEt 2A
(Tol)
Ph
8a
9Aa
90
2
3
p-MeC6H4 COOEt 2A
p-MeC6H4 COOEt 2A
p-MeC6H4 COOEt 2A
p-MeC6H4 COOEt 2A
p-MeOC6H4 COOEt 2B
p-CF3C6H4 8b
0
0
3
3
3
3
2
2
1
1
1
9Ab
9Ac
9Ad
9Ae
9Ba
9Ca
9Da
9Ea
9Fa
31
92
92
79
83
94
92
18
Bu
tert-Bu
SiMe3
Ph
8c
8d
8e
8a
8a
8a
8a
8a
4
0
5
0
6
0
7
Ph
COOEt 2C
COOEt 2D
COOEt 2E
Ph
-40
-40
-40
0
8
p-ClC6H4
2-Furyl
Ph
9
Ph
a
10
p-MeC6H4
Me
2F
Ph
—
a A complex mixture was obtained.
Based on these considerations, the addition of acetylide 8 to cinnamate 2 was studied. When
nitrocinnamate 2A was allowed to react with lithium phenylacetylide 8a in THF at 0 °C for 3
h, adduct 9Aa was efficiently obtained (Table 2, Entry 1). Even the acetylide 8b possessing
an electron-withdrawing group underwent the addition reaction to afford 9Ab although the
yield became lower, which was presumably due to low nucleophilicity of 8b and instability
of 9Ab (Entry 2). Aliphatic acetylides 8c and 8d revealed similar reactivity leading to 9Ac
and 9Ad in high yields, respectively (Entries 3 and 4, respectively). Functionalized acetylide
8d also underwent this reaction furnishing 9Ae (Entry 5). This reaction was considerably
influenced by the electronic properties of the aryl group of cinnamate 2 (Entries 1 and 6–8),
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while electron-rich cinnamates 2A and 2B underwent the addition reaction at 0 °C, the
reaction mixture was complex in the cases of more reactive electron-poor cinnamates 2C and
2D under the same conditions. In such cases, conducting the reaction at -40 °C was effective
in obtaining 9Ca and 9Da in high yield. Furthermore, nitroalkene 2E was also successfully
transformed into furan-substituted adduct 9Ea (Entry 9). In contrast, a complex mixture was
obtained when using alkyl substituted nitroalkene 2F, presumably because the anionic
intermediate was not sufficiently stabilized by the nitro group (Entry 10). When the aryl
group of 2A was displaced to an alkyl group, the subsequent reaction with acetylides 8 could
not be conducted because of the instability of the nitroalkene.
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Hα
COOEt
Ph
Li
O2N
Tol
COOEt
8a
NEt3
10Aa
Tol
MeCN
rt, 2 h
MeCN
rt, 18 h
Hβ
9Aa
Ph
10Aa 93%
Ph
_
O
Hα
Hβ
+
_
O
N
COOEt
O2N
COOEt
Ph
10Aa
Tol
Tol
Hβ
9Aa'
Ph
9Aa
NEt3
Scheme 4. Different behavior of 9Aa depending on the base.
Nu
H
Nu
NO2
H
O2N
O2N
NEt3
NaOEt
No Reaction
EtOH
EtOH
0 °C, 3 h
86%
N
O
N
O
0 °C, 3 h
O2N
Me
O2N
Me
O
O
11
EtO
OEt
Nu:
Scheme 5. Different behavior of adduct 11 depending on the base.
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Next, elimination of nitrous acid from 9Aa was studied to obtain enyne 10Aa. When 9Aa (a
mixture of diasteromers with 1:1 ratio) was treated with equimolar lithium acetylide 8a at
room temperature, no reaction occurred. In contrast, functionalized enyne 10Aa was
efficiently formed with high Z:E ratio upon treatment of 9Aa with triethylamine (Scheme 4).
Similar reactivity was observed in the reaction of trinitroquinolone 1 with diethyl malonate;
while no reaction occured upon treatment of the adduct 11 with sodium ethoxide, elimination
of nitrous acid efficiently proceeded upon treatment with triethylamine (Scheme 5).10 Adduct
9Aa has two protons, Hα and Hβ, of which Hα is more acidic. Thus, nitronate 9Aa’ is
exclusively formed upon reaction with a strong base (acetylide) without elimination of
nitrous acid. Conversely, when a weak base (triethylamine) is used, 9Aa exists in equilibrium
with 9Aa’ in the reaction mixture, facilitating the elimination of nitrous acid to afford 10Aa.
To confirm this hypothesis, several other stronger bases were tested, such as sodium hydride,
potassium tert-butoxide, sodium ethoxide and guanidine. However, only complex reaction
mixture was obtained in each case, while excess amounts of lithium acetylide caused no
change, which might be due to the stabilization effect of nitronate 9Aa’ by lithium ion.
Hence, it has not been clarified why weaker triethylamine was effective for the elimination of
nitrous acid. In addition, the influence of the acidity of Hβ for this elimination was also
studied. When 9Aa was treated with triethylamine at 0 °C, only 13% of 10Aa was formed
even after 2 d. To the contrary, 9Ab possessing an electron-withdrawing trifuloromethyl
group exhibited higher reactivity to undergo the elimination reaction under the same
conditions to furnish 10Ab in 50% yield, which supported the acidity of Hβ was important for
the elimination of nitrous acid. Thus, the sp-nucleophile is considered to be advantageous for
this reaction from viewpoints of the less bulkiness and the electronegativity compared with
sp2/sp3-nucleophiles as shown in Figure 1.
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Table 3. Synthesis of functionalized enynes 10.
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8
9
O2N
Ar
COOEt
R
COOEt
NEt3
10
11
12
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Ar
MeCN
H
R
rt, 18 h
9
10
Entry
Substrate
Ar
9
Product 10
R
Yield/%
93
Z:E
1
2
3
4
5
6
7
8
9
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeOC6H4
Ph
Ph
Aa
Ab
Ac
Ad
Ae
Ba
Ca
Da
Ea
97:3
99:1
98:2
98:2
97:3
98:2
99:1
98:2
92:8
p-CF3C6H4
98
Bu
99
tert-Bu
SiMe3
Ph
quant.
98
86
Ph
98
p-ClC6H4
2-Furyl
Ph
97
Ph
99
This protocol using triethylamine was applied to other adducts 9 (Table 3). Elimination of
nitrous acid efficiently proceeded to afford the corresponding enynes 10 as a mixture of Z-
and E-isomers in almost quantitative yield.
The enyne framework is often found in natural products and biologically active compounds,
in addition to being present in useful precursors for functional materials.11 Although
numerous enynes have been synthesized,12 a practical battery of preparative methods for
functionalized enynes is not available. Coupling reactions are the most common approach to
desired enynes; however, it is necessary to use expensive noble transition metals.13
Functionalized enynes can also be synthesized by sequential reaction of propargylic
dithioacetal with butyl lithium and α–bromo esters, followed by treatment with alumina.14
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The [2+2] cycloaddition of an alkynyl ketone with a ynolate and subsequent electro-cyclic
reaction leads to enyne compounds bearing a carbonyl group.15 In addition, functionalized
enynes are also formed by oxidation of β-functionalized semicarbazones with selenium
dioxide.16 Although these methods are useful approaches to functionalized enynes, they
present several limitations, such as low availability of starting materials, low reaction
efficiency, and narrow substrate scope. In contrast, the reaction described have represented a
supplementary preparative method for functionalized enynes that does not require a transition
metal and/or special reagent.
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The abovementioned successful results prompted us to investigate the synthesis of
functionalized acrylonitriles by Michael addition of cyanide to cinnamate 1 and subsequent
elimination of nitrous acid. A similar synthetic method for the preparation of dicyanoalkanes
via double conjugate addition of cyanide to nitroalkenes has been demonstrated, in which a
small amount of an acrylonitrile derivative was also obtained, however, this method has not
been applied to the synthesis of functionalized acrylonitriles.17
Table 4. Synthesis of functionalized nitriles.
N
O2N
Tol
C
COOEt
COOEt
COOEt
O2N
Tol
COOEt
H
KCN
+
+
MeOH/MeCN
Tol = p-MeC6H4
Tol
Tol
C
N
12a
C
C
N
14a
H
N
2A
13a
Entry
KCN/
equiv.
Temp.
/°C
60
rt
Time
Additive
(equiv.)
—
Yield/%a
13a
11
/h
4
12a
14a
56
12
44
22
8
1
2
3
4
5
1
1
2
1
1
0
60
55
0
1
—
21
rt
1
—
11
rt
24
2
—
75
rt
NEt3 (2)
0
90
a Based on KCN
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When cinnamate 1a was treated with potassium cyanide at 60 °C, the desired acrylonitrile
13a was obtained albeit in low yield (Table 4, Entry 1). In this reaction, α,β-dicyano-β-
tolylpropionate 14a was the main product, which was resulted from the excess addition of
cyanide to 13a. The same reaction at lower temperature suppressed the double addition, and
adduct 12a was predominantly formed (Entry 2). When two equivalents of cyanide were
employed, the yield of double adduct 14a increased, indicating that the cyanide serves only
as a nucleophile and not as a base (Entry 3). Although the yield of 13a could be increased by
extending the reaction period to 24 h, the addition of triethylamine was more effective
providing a yield of 90% of product in 2 h (Entries 4 and 5).
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This protocol can also be conducted in one pot. After a solution of nitroalkene 2A was stirred
with potassium cyanide at room temperature for 1 h, triethylamine was added to the reaction
mixture and stirred for further 1 h, which afforded acrylonitrile 13a in similar yield but with
simpler experimental operation (Table 4, Entry 5 and Table 5, Entry 1).
Table 5. One-pot synthesis of functionalized acrylonitriles 13.
O2N
Ar
R
C
R
H
KCN
NEt3
rt, 1 h
MeOH/MeCN
rt, 1 h
Ar
N
2
13
Entry
Substrate
R
Product
Ar
Yield/%
86
1
2
p-MeC6H4
p-MeOC6H4
Ph
COOEt
2A
13a
13b
13c
13d
13e
13g
COOEt
COOEt
COOEt
COOEt
COPh
2B
2C
2D
2E
2G
90
3
92
4
5a
p-ClC6H4
2-Furyl
85
66
6
p-MeC6H4
80
a The reaction was conducted at -30 °C for 3 h.
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Cinnamates 2B−D exhibited similar reactivity to afford the corresponding acrylonitriles
13b−d in high yield (Table 5, Entries 2-4). It was possible to replace the phenyl group by a
furyl group leading to 13e, although a lower reaction temperature was needed (Entry 5).
Furthermore, nitroalkene 2G bearing a benzoyl group could be used as the substrate to afford
benzoylacrylonitrile 13g in 80% yield (Entry 6).
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Next, a cyanation procedure was applied to nitroalkene 2F, which is not activated by an
electron-withdrawing group. In the reaction of 2F under the same conditions, only a small
amount of acrylonitrile 13f18 was detected, and the main product was double adduct 14f,17
which was formed by Michael addition of cyanide to 13f (Scheme 5). This problem was
overcome using a combination of trimethylsilyl cyanide and cesium fluoride instead of
potassium cyanide, successfully affording 13f in 84% yield. In this case, the silyl nitronate
intermediate 15f is believed to prevent any side reactions.
N
_
O2N
Tol
Me
H
C
Me
C
Me
C
NEt3
Nucleophile
O
+
+
Me
Tol
N
SiMe3
rt, 2 h
MeCN/MeOH
rt
Tol
Tol
O
N
N
2F
C
13f
14f
N
15f
Nucleophile KCN
Me3SiCN/CsF
11%
84%
31%
14%
Scheme 6. Reaction of nitroalkene 2F with two kinds of cyanides.
Conclusion
β-Nitrostyrenes 2 bearing an ethoxycarbonyl group at the α-position have been demonstrated
to serve as excellent precursors for α,β-difunctionalized alkenes. Nitrocinnamate 2 easily
reacts with versatile sp3- and sp2-nucleophiles such as alcohols, Grignard reagents,
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alkylcopper, and dialkylzinc to afford Michael adducts. Although this reaction is useful for
alkoxylation, alkylation, and arylation transformations, the subsequent elimination of nitrous
acid does not proceed due to the favored elimination of an alcohol, steric repulsion, and lower
electronegativity of the newly introduced carbon nucleophile. This problem was addressed
using smaller sp-carbon nucleophiles such as lithium acetylide, potassium cyanide, and
trimethylsilyl cyanide. Treatment of the adducts with triethylamine efficiently afforded
functionalized enynes 10 and acrylonitriles 13 in high yields. This protocol can be carried out
by a simple procedure under mild conditions and is transition-metal free. These features are
advantageous in practical synthesis methods; the present protocol is thus a useful tool for
researchers working on the synthesis of functional materials.
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Experimental Section
One-pot synthesis of isoxazoledicarboxylate 4
A solution of α-nitrocinnamate 2A (76 mg, 0.32 mmol) in methanol (2 mL) was heated at
65 °C for 2 d. Concentration of the reaction mixture afforded a mixture of 3a and unreacted
2A, which is difficult to separate, thus the yield and diastereomeric ratio of 3a was
1
determined by H NMR by comparing the integral values with that of the internal standard,
1,1,2,2-tetrachloroethane. When ethanol was used as a solvent, similar result was obtained.
Further reaction was conducted using the mixture without separation. To a solution of the
mixture in acetonitrile (3.5 mL), triethylamine (97 µL, 0.7 mmol) was added, and the
resultant mixture was stirred at room temperature for 3 h. After removal of the solvent, 1 M
hydrochloric acid (0.7 mL, 0.7 mmol) was added, and the mixture was extracted with
dichloromethane (30 mL ´ 3). The combined organic layer was dried over magnesium sulfate,
concentrated, and chromatographed on silica gel to afford isoxazole 4 (eluted with
hexane/ethyl acetate = 90/10, 85 mg, 0.28 mmol, quant.) as a colorless oil.
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Ethyl 3-methoxy-3-(4-methyphenyl)-2-nitropropanoate (3a) (dr = 1 : 2.7)
5
6
7
8
Pale yellow oil (NMR yield 87%, 23 mg (0.086 mmol, 27%) was isolated in a pure form).
Major isomer: 1H NMR (400 MHz, CDCl3) δ 1.00 (dd, J = 7.2, 7.2 Hz, 3H), 2.36 (s, 3H),
3.22 (s, 3H), 3.95–4.04 (m, 2H), 4.97 (d, J = 9.6 Hz, 1H), 5.28 (d, J = 9.6 Hz, 1H), 7.18 (d, J
9
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= 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H); C NMR (100 MHz, CDCl3) δ 13.5 (CH3), 21.2
(CH3), 56.9 (CH3), 62.8 (CH2), 81.3 (CH), 92.2 (CH), 127.9 (CH), 129.5 (CH), 131.2 (C),
139.5 (C), 161.8 (C). Minor isomer: 1H NMR (400 MHz, CDCl3) δ 1.33 (t, J = 7.2, 7.2 Hz,
3H), 2.44 (s, 3H), 3.25 (s, 3H), 4.32 (q, J = 7.2 Hz, 2H), 4.94 (d, J = 8.0 Hz, 1H), 5.23 (d, J =
8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.24-7.27 (br, 2H); 13C NMR (100 MHz, CDCl3) δ 13.9
(CH3), 21.2 (CH3), 57.2 (CH3), 63.1 (CH2), 81.0 (CH), 91.3 (CH), 127.7 (CH), 129.5 (CH),
132.0 (C), 136.9 (C), 163.2 (C). IR (NaCl) 1320, 1515, 1740 cm-1; HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd. for C13H17NO5Na 290.0999; Found 290.0993.
Ethyl 3-ethoxy-3-(4-methyphenyl)-2-nitropropanoate (3b) (dr = 1 : 3)
Pale yellow oil (NMR yield 79%, 18 mg (0.064 mmol, 20%) was isolated in a pure form).
Major isomer: 1H NMR (400 MHz, CDCl3) δ 0.99 (dd, J = 7.2, 7.2 Hz, 3H),1.11 (dd, J = 7.2,
7.2 Hz, 3H), 2.36 (s, 3H), 3.35–3.44 (m, 2H), 3.94–4.03 (m, 2H), 5.08 (d, J = 9.6 Hz, 1H),
13
5.28 (d, J = 9.6 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H); C NMR (100
MHz, CDCl3) δ 13.5 (CH3), 14.8 (CH3), 21.2 (CH3), 62.8 (CH2), 64.8 (CH2), 79.5 (CH) 92.3
(CH), 127.8 (CH), 129.4 (CH), 132.0 (C), 139.3 (C), 161.9 (C). Minor isomer: 1H NMR (400
MHz, CDCl3) δ 1.13 (t, J = 7.2, Hz, 3H), 1.36 (dd, J = 7.2 Hz, 3H), 2.34 (s, 3H), 3.35–3.44
(m, 2H), 4.33 (q, J =7.2 Hz, 2H), 5.06 (d, J = 8.4 Hz, 1H), 5.22 (d, J = 8.4 Hz, 1H), 7.17 (d, J
13
= 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H); C NMR (100 MHz, CDCl3) δ 13.9 (CH3), 14.9
(CH3), 21.6 (CH3), 63.0 (CH2), 65.1 (CH2), 79.2 (CH), 91.5 (CH), 127.6 (CH), 129.5 (CH),
132.8 (C), 139.3 (C), 162.7 (C). IR (KBr) 1310, 1565, 1749 cm-1; HRMS (ESI-TOF) m/z: [M
+ Na]+ Calcd. for C14H19NO5Na 304.1155; Found 304.1149.
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Ethyl 3-(4-methyphenyl)-2-nitro-3-(prop-2-yn-1-yloxy)propanoate (3c) (dr = 1 : 2.4)
Colorless oil (85 mg, 0.29 mmol, 92%). Major isomer: 1H NMR (400 MHz, CDCl3) δ 1.00
(dd, J = 7.2, 7.2 Hz, 3H), 2.36 (s, 3H), 2.44 (dd, J = 2.4, 2.4 Hz, 1H), 3.89 (dd, J = 2.4, 15.6
Hz, 1H), 3.93–4.06 (m, 2H), 4.12 (dd, J = 2.4, 15.6 Hz, 1H), 5.35 (d, J = 9.8 Hz, 1H), 5.38 (d,
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J = 9.8 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H); C NMR (100 MHz,
CDCl3) δ 13.5 (CH3), 21.1 (CH3), 55.8 (CH2), 62.9 (CH2), 75.5 (CH), 78.2 (C), 78.2 (CH),
91.8 (CH), 128.3 (CH), 129.6 (CH), 130.2 (C), 139.8 (C), 161.6 (C). Minor isomer: 1H NMR
(400 MHz, CDCl3) δ 1.34 (t, J = 7.2 Hz, 3H), 2.34 (s, 3H), 2.45 (dd, J = 2.4, 2.4 Hz, 1H),
3.91 (dd, J = 2.4, 15.6 Hz, 1H), 4.13 (dd, J = 2.4, 15.6 Hz, 1H), 4.34 (q, J = 7.2 Hz, 2H),5.30
(d, J = 9.1 Hz, 1H), 5.35 (d, J = 9.1 Hz, 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz,
13
2H); C NMR (100 MHz, CDCl3) δ 13.9 (CH3), 21.1 (CH3), 56.0 (CH2), 63.2 (CH2), 75.5
(CH), 77.7(CH), 78.0 (C), 91.1 (CH), 128.0 (CH), 129.6 (CH), 131.1 (C), 139.8 (C), 162.3
(C). IR (NaCl) 1310, 1567, 1749, 2120 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for
C15H17NO5Na 314.0999; Found 314.1007.
Reaction of organometallic reagent with cinnamate 2A
To a solution of α-nitrocinnamate 2A (50 mg, 0.21 mmol) in THF (2.5 mL), 0.97 M THF
solution of ethylmagnesium bromide (330 µL, 0.31 mmol) was added at 0 °C for over 10
minutes, and the resultant mixture was stirred for 1 day. After quenching the reaction with 1
M hydrochloric acid (0.5 mL, 0.5 mmol), the mixture was extracted with diethyl ether (20 m
L ´ 3). The organic layer was dried over magnesium sulfate and concentrated. The
1
diastereomeric ratio was determined by H NMR of the residue. The reaction mixture was
treated with column chromatography on silica gel to afford adduct 6a (eluted with
hexane/diethyl ether = 9/1, 27.1 mg, 0.1 mmol, 49%) as a colorless oil. When other
organometallic reagents were used, the experiments were conducted in a similar way.
Ethyl 3-(4-methyphenyl)-2-nitropentanoate (6a) (dr = 1 : 1.1)
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Colorless oil (50 mg, 0.19 mmol, 89%). Major isomer: 1H NMR (400 MHz, CDCl3) δ 0.76 (t,
J = 7.2, 7.2 Hz, 3H), 0.99 (dd, J = 7.2 Hz, 3H), 1.58–1.80 (m, 2H), 2.31 (s, 3H), 3.47–3.54
(m, 1H), 3.92–4.03 (m, 2H), 5.25 (d, J = 10.8 Hz, 1H), 7.07 (d, J = 9.2 Hz, 2H), 7.12 (d, J =
9.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 11.4 (CH3), 13.5 (CH3), 21.1 (CH3), 25.3 (CH2),
48.2 (CH), 62.6 (CH2), 93.0 (CH), 128.5 (CH), 129.5 (CH), 113.6 (C), 137.6 (C), 163.3 (C).
Minor isomer: 1H NMR (400 MHz, CDCl3) δ 0.77 (t, J = 7.2 Hz, 3H), 1.33 (t, J = 7.2 Hz, 3H),
1.58–1.80 (m, 2H), 2.32 (s, 3H), 3.47 (td, J = 10.8, 3.6 Hz, 1H), 4.31 (q, J = 7.2 Hz, 2H),
5.29 (d, J = 10.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ = 11.5 (CH3), 13.9 (CH3), 21.1 (CH3), 24.9 (CH2), 48.0 (CH), 63.0 (CH2),
93.0 (CH), 128.0 (CH), 129.5 (CH), 134.5 (C), 137.5 (C), 163.8 (C). IR (KBr) 1308, 1559,
1749 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for C14H19NO4Na 288.1206; Found
288.1212.
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Ethyl 3-(4-methyphenyl)-2-pentenoate (7a)
1
Colorless oil (1.3 mg, 0.006 mmol, 3%). H NMR (400 MHz, CDCl3) δ 1.17 (t, J = 7.2 Hz,
3H), 1.35 (t, J = 7.2 Hz, 3H), 2.37 (s, 3H), 2.55 (q, J = 7.2 Hz, 2H), 4.27 (q, J = 7.2 Hz, 2H),
7.19 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.61 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 13.8 (CH3), 14.3 (CH3), 20.8 (CH2), 21.3 (CH3), 60.6 (CH2), 129.2 (CH), 129.3 (CH), 133.0
(C), 134.3 (C), 138.3 (CH), 138.4 (C), 168.5 (C); HRMS (ESI-TOF) m/z: [M + H]+ Calcd.
for C14H19O2 219.1380; Found 219.1384.
Ethyl 4-methyl-3-(4-methyphenyl)-2-nitropentanoate (6b) (dr = 1 : 1.7)
Colorless oil (53 mg, 0.19 mmol, 90%). Major isomer: 1H NMR (400 MHz, CDCl3) δ 0.85 (d,
J = 7.2 Hz, 6H), 0.98 (dd, J = 7.2, 7.2 Hz, 3H), 1.95–2.08 (m, 1H), 2.31 (s, 3H), 3.60 (dd, J =
10.8, 10.8 Hz, 1H), 3.90–4.12 (m, 2H), 5.57 (d, J = 10.8 Hz, 1H), 7.02 (J = 8.0 Hz, 2H), 7.10
13
(J = 8.0 Hz, 2H); C NMR (100 MHz, CDCl3) δ 13.4 (CH3), 17.7 (CH3), 21.0 (CH3), 21.0
(CH3), 29.2 (CH), 51.9 (CH), 62.6 (CH2), 90.8 (CH), 128.9 (CH), 129.5 (CH), 131.7 (C),
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137.3 (C), 164.1 (C). Minor isomer: 1H NMR (400 MHz, CDCl3) δ 0.87 (d, J = 7.2 Hz, 6H),
1.32 (t, J = 7.2 Hz, 3H), 1.95–2.08 (m, 1H), 2.30 (s, 3H), 3.59 (dd, J = 10.8, 10.8 Hz, 1H),
4.31 (q, J = 7.2 Hz, 2H), 5.61 (d, J = 10.8 Hz, 1H), 7.05 (J = 8.0 Hz, 2H), 7.07 (J = 8.0 Hz,
13
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2H); C NMR (100 MHz, CDCl3) δ 13.9 (CH3), 17.8 (CH3), 21.0 (CH3), 21.6 (CH3), 29.3
(CH), 51.9 (CH), 63.0 (CH2), 91.1 (CH), 128.9 (CH), 129.1 (CH), 132.0 (C), 137.3 (C), 163.3
(C). IR (NaCl) 1307, 1564, 1748 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for
C15H21NO4Na 302.1363; Found 302.1356.
Ethyl 3-(4-methyphenyl)-2-nitro-3-phenylpropanoate (6c) (dr = 1 : 1.2)
1
Colorless oil (13 mg, 0.04 mmol, 20%). Major isomer: H NMR (400 MHz, CDCl3) δ 1.00
(dd, J = 7.2, 7.2 Hz, 3H), 2.27 (s, 3H), 3.97–4.10 (m, 2H), 4.98 (d, J = 12.0 Hz, 1H), 5.92 (d,
J = 12.0 Hz, 1H), 7.08–7.32 (m, 9H); 13C NMR (100 MHz, CDCl3) δ 13.5 (CH3), 21.0 (CH3),
52.0 (CH), 62.9 (CH2), 91.3 (CH), 127.2 (CH), 127.7 (CH), 128.2 (CH), 129.1 (CH), 129.8
(CH), 135.4 (C), 137.5 (C), 137.9 (C), 163.3 (C). Minor isomer: 1H NMR (400 MHz, CDCl3)
δ 1.03 (dd, J = 7.2, 7.2 Hz, 3H), 2.27 (s, 3H), 3.97–4.10 (m, 2H), 4.98 (d, J = 12.0 Hz, 1H),
13
5.92 (d, J = 12.0 Hz, 1H), 7.08–7.32 (m, 9H); C NMR (100 MHz, CDCl3) δ 13.5 (CH3),
21.0 (CH3), 52.0 (CH), 63.0 (CH2), 91.3 (CH), 127.3 (CH), 127.7 (CH), 128.1 (CH), 129.0
(CH), 129.6 (CH), 134.6 (C), 137.6 (C), 138.7 (C), 163.2 (C). IR (NaCl) 1315, 1563, 1749
cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for C18H19NO4Na 336.1206; Found 336.1206.
Ethyl 3-(4-methyphenyl)-2-nitroheptanoate (6d) (dr = 1 : 1)
Colorless oil (62 mg, 0.21 mmol, quant.). Isomer A: 1H NMR (400 MHz, CDCl3) δ 0.80 (dd,
J = 7.2, 7.2 Hz, 3H), 0.99 (t, J = 7.2 Hz, 3H), 2.32 (s, 3H), 3.58 (td, J = 10.8 Hz, 3.6 Hz, 1H),
3.91–4.03 (m, 2H), 5.23 (d, J = 10.8, 1H), 7.08 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 13.7 (CH3), 13.7 (CH3), 21.0 (CH3), 22.2 (CH2), 28.8 (CH2),
31.7 (CH2), 46.5 (CH), 62.5 (CH2), 93.1 (CH), 128.0 (CH), 129.4 (CH), 133.9 (C), 137.5 (C),
163.8 (C). Isomer B: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J = 7.2 Hz, 3H), 1.33 (t, J = 7.2
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Hz, 3H), 2.31 (s, 3H), 3.58 (td, J = 10.8, 3.6 Hz, 1H), 4.32 (q, J = 7.2 Hz, 2H), 5.27 (d, J =
10.8 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 13.5 (CH3), 13.9 (CH3), 21.0 (CH3), 22.2 (CH2), 28.9 (CH2), 31.3 (CH2), 46.3 (CH),
63.0 (CH2), 93.2 (CH), 128.4 (CH), 129.4 (CH), 134.8 (C), 137.4 (C), 163.3 (C). IR (NaCl)
1372, 1558, 1748 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for C16H23NO4Na
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316.1519; Found 316.1507.
Ethynylation of cinnamate 2A
To a solution of ethynylbenzene (76 µL, 0.7 mmol) in THF (1 mL), 2.6 M hexane solution of
butyllithium (226 µL, 0.6 mmol) was added at 0 °C with over 5 min. The resultant mixture
was added to a solution of α-nitrocinnamate 2A (115 mg, 0.5 mmol) in THF at 0 °C with over
15 min. period, and the resultant mixture was stirred for further 1 h. After quenching the
reaction with 1 M hydrogen chloride (0.6 mL, 0.6 mmol), the mixture was extracted with
diethyl ether (30 mL ´ 3). The organic layer was dried over magnesium sulfate concentrated.
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The diastereomeric ratio was determined by H NMR of the residue. The reaction mixture
was treated with column chromatography on silica gel to afford ethynylated product 9Aa
(eluted with hexane/ethyl acetate = 90/10, 144.1 mg, 0.43 mmol, 90%) as a colorless oil.
When other acetylides were used, the experiments were conducted in a similar way.
Ethyl 3-(4-methyphenyl)-2-nitro-5-phenyl-4-pentynoate (9Aa) (dr = 1 : 1.1)
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Colorless oil (152 mg, 0.45 mmol, 90%). Major isomer: H NMR (400 MHz, CDCl3) δ 1.10
(dd, J = 7.2, 7.2 Hz, 3H), 2.34 (s, 3H), 4.04–4.16 (m, 2H), 4.87 (d, J = 9.6 Hz, 1H), 5.39 (d, J
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= 9.6 Hz, 1H), 7.15–7.42 (m, 9H); C NMR (100 MHz, CDCl3) δ 13.6 (CH3), 21.1 (CH3),
39.7 (CH), 63.3 (CH2), 84.3 (C), 85.8 (C), 91.9 (CH), 122.3 (C), 128.3 (CH), 128.5 (CH),
128.6 (CH), 130.0 (CH), 131.2 (C), 131.9 (CH), 138.5 (C), 162.3 (C). Minor isomer: 1H
NMR (400 MHz, CDCl3) δ 1.31 (t, J = 7.2 Hz, 3H), 2.33 (s, 3H), 4.34 (q, J = 7.2 Hz, 2H),
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4.87 (d, J = 9.6 Hz, 1H), 5.38 (d, J = 9.6 Hz, 1H), 7.15-7.42 (m, 9H); C NMR (100 MHz,
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CDCl3) δ 13.9 (CH3), 21.1 (CH3), 39.6 (CH), 63.1 (CH2), 84.9 (C), 86.4 (C), 92.0 (CH),
122.3 (C), 128.2 (CH), 128.3 (CH), 128.7 (CH), 130.0 (CH), 131.7 (CH), 132.1 (C), 138.5
(C), 162.5 (C) ppm. IR (ATR) 1563, 1749, 2354 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+
Calcd. for C20H19NO4Na 360.1206; Found 360.1199.
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Ethyl 3-(4-methyphenyl)-2-nitro-5-(4-trifluoromethyl)phenyl-4-pentynoate (9Ab) (dr =
2 : 1)
Pale yellow oil (57 mg, 0.14 mmol, 31%). Major isomer: 1H NMR (400 MHz, CDCl3) δ 1.11
(t, J = 7.2 Hz, 3H), 2.35 (s, 3H), 4.05–4.18 (m, 2H), 4.89 (d, J = 9.6 Hz, 1H), 5.40 (d, J = 9.6
Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.55 (d,
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J = 8.4 Hz, 2H); C NMR (100 MHz, CDCl3) δ 13.6 (CH3), 21.1 (CH3), 39.7 (CH), 63.3
(CH2), 84.3 (C), 87.5 (C), 91.7 (CH), 123.8 (q, JCF = 271 Hz, C), 125.2 (q, JCF = 3.6 Hz,
CH), 126.1 (C), 128.4 (CH), 129.8 (CH), 130.4 (q, JCF = 33 Hz, C), 130.7 (C), 132.1 (CH),
138.8 (C), 162.1 (C). Minor isomer: 1H NMR (400 MHz, CDCl3) δ 1.31 (t, J = 7.2 Hz, 3H),
2.34 (s, 3H), 4.30–4.38 (m, 2H), 4.89 (d, J = 9.6 Hz, 1H), 5.40 (d, J = 9.6 Hz, 1H), 7.18 (d, J
= 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 13.9 (CH3), 21.1 (CH3), 39.5 (CH), 63.4 (CH2), 84.9 (C), 86.9 (C),
91.5 (CH), 125.3 (q, JCF = 3.6 Hz, CH), 126.2 (C), 128.1 (CH), 129.9 (CH), 130.4 (q, JCF
=
39 Hz, C), 131.5 (C), 132.0 (CH), 138.8 (C), 162.3 (C). one peak derived from CF3 was not
identified. IR (ATR) 1323, 1566, 1751, 2206 cm-1; HRMS (EI, [M]+) Calcd. for C21H18F3NO4
405.1188; Found 405.1190.
Ethyl 3-(4-methylphenyl)-2-nitro-4-nonynoate (9Ac) (dr = 1 : 1)
Colorless oil (146 mg, 0.46 mmol, 92%). Isomer A: 1H NMR (400 MHz, CDCl3) δ 0.89 (dd,
J = 7.2, 7.2 Hz, 3H), 1.32 (t, J = 7.2 Hz, 3H), 1.34–1.50 (m, 4H), 2.18 (td, J = 7.2, 2.0 Hz,
2H), 2.31 (s, 3H), 4.00–4.11 (m, 2H), 4.61 (dt, J = 10.0 Hz, 2.0 Hz, 1H), 5.27 (d, J = 10.0 Hz,
1H), 7.13 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H);13C NMR (100 MHz, CDCl3) δ 13.5
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(CH3), 13.6 (CH3), 18.3 (CH2), 21.0 (CH3), 21.8 (CH2), 30.1 (CH2), 39.4 (CH), 62.9 (CH2),
75.7 (C), 86.4 (C), 92.2 (CH), 128.4 (CH), 130.1 (CH), 131.8 (C), 138.2 (C), 162.4 (C).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 0.89 (t, J = 7.2, 3H), 1.06 (t, J = 7.2 Hz, 3H), 1.34–
1.50 (m, 4H), 2.18 (td, J = 7.2, 2.0 Hz, 2H), 2.32 (s, 3H), 4.31 (q, J = 7.2 Hz, 2H), 4.61 (dt, J
= 10.0 Hz, 2.0 Hz, 1H), 5.26 (d, J = 10.0 Hz, 1H), 7.12 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.4
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Hz, 2H); C NMR (100 MHz, CDCl3) δ 13.5 (CH3), 13.9 (CH3), 18.4 (CH2), 21.0 (CH3),
21.8 (CH2), 30.1 (CH2), 39.1 (CH), 63.1 (CH2), 75.1 (C), 87.1 (C), 92.4 (CH), 128.0 (CH),
130.0 (CH), 132.7 (C), 138.2 (C), 162.6 (C). IR (ATR) 1307, 1559, 1749, 2337 cm-1; HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd. for C18H23NO4Na 340.1519; Found 340.1506.
Ethyl 6,6-dimethyl-3-(4-methylphenyl)-2-nitro-4-heptynoate (9Ad) (dr = 1 : 1.1)
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Colorless oil (146 mg, 0.46 mmol, 92%). Major isomer: H NMR (400 MHz, CDCl3) δ 1.08
(dd, J = 7.2, 7.2 Hz, 3H), 1.19 (s, 9H), 2.32 (s, 3H), 4.02–4.11 (m, 2H), 4.60 (d, J = 9.6 Hz,
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1H), 5.24 (d, J = 9.6 Hz, 1H), 7.14 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H); C NMR
(100 MHz, CDCl3) δ 13.6 (CH3), 21.1 (CH3), 27.5 (C), 30.8 (CH3), 39.2 (CH), 62.9 (CH2),
74.3 (C), 92.6 (CH), 94.9 (C), 128.4 (CH), 129.5 (CH), 132.8 (C), 138.2 (C), 162.4 (C).
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Minor isomer: H NMR (400 MHz, CDCl3) δ 1.19 (s, 9H), 1.34 (dd, J = 7.2, 7.2 Hz, 3H),
2.31 (s, 3H), 4.27–4.36 (m, 2H), 4.60 (d, J = 9.6 Hz, 1H), 5.22 (d, J = 9.6 Hz, 1H), 7.13 (d, J
= 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H);13C NMR (100 MHz, CDCl3) δ 13.9 (CH3), 21.1
(CH3), 27.5 (C), 30.8 (CH3), 39.0 (CH), 63.1 (CH2), 73.6 (C), 92.5 (CH), 95.4 (C), 128.0
(CH), 129.5 (CH), 131.8 (C), 138.2 (C), 162.6 (C). IR (NaCl) 1307, 1361, 1566, 1752, 2245
cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for C18H23NO4Na 340.1519; Found 340.1507.
Ethyl 3-(4-methylphenyl)-5-trimethylsilyl-2-nitro-4-pentynoate (9Ae) (dr = 1 : 1.1)
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Colorless oil (132 mg, 0.40 mmol, 79%). Major isomer: H NMR (400 MHz, CDCl3) δ 0.15
(s, 9H), 1.08 (dd, J = 7.2, 7.2 Hz, 3H), 2.33 (s, 3H), 3.91–4.13 (m, 2H), 4.65 (d, J = 10.0 Hz,
1H), 5.28 (d, J = 10.0 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H); 13C NMR
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(100 MHz, CDCl3) δ -0.2 (CH3), 13.7 (CH3), 21.2 (CH3), 40.1 (CH), 63.1 (CH2), 91.1 (C),
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92.1 (CH), 101.3 (C), 128.6 (CH), 129.7 (CH), 131.0 (C), 138.5 (C), 162.3 (C). Minor
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isomer: H NMR (400 MHz, CDCl3) δ 0.15 (s, 9H), 1.35 (dd, J = 7.2, 7.2 Hz, 3H), 2.32 (s,
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3H), 4.27–4.39 (m, 2H), 4.66 (d, J = 10.0 Hz, 1H), 5.27 (d, J = 10.0 Hz, 1H), 7.14 (d, J = 8.0
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Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H); C NMR (100 MHz, CDCl3) δ -0.2 (CH3), 14.0 (CH3),
21.2 (CH3), 39.9 (CH), 63.3 (CH2), 91.7 (C), 92.1 (CH), 100.5 (C), 128.2 (CH), 129.8 (CH),
132.0 (C), 138.5 (C), 162.5 (C). IR (ATR) 1564, 1751, 2180 cm-1; HRMS (ESI-TOF) m/z: [M
+ Na]+ Calcd. for C17H23NO4SiNa 356.1289; Found 356.1290.
Ethyl 3-(4-methoxyphenyl)-2-nitro-5-phenyl-4-pentynoate (9Ba) (dr = 1 : 1.1)
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Colorless oil (147 mg, 0.42 mmol, 83%). Major isomer: H NMR (400 MHz, CDCl3) δ 1.12
(dd, J = 7.2, 7.2 Hz, 3H), 3.80 (s, 3H), 4.05–4.17 (m, 2H), 4.86 (d, J = 9.6 Hz, 1H), 5.37 (d, J
= 9.6 Hz, 1H), 6.89 (d, J = 8.0 Hz, 2H), 7.32-7.45 (m, 7H); 13C NMR (100 MHz, CDCl3) δ
13.7 (CH3), 39.4 (CH), 55.3 (CH3), 63.1 (CH2), 84.9 (C), 85.7 (C), 92.0 (CH), 114.4 (CH),
122.3 (C), 126.0 (C), 128.3 (CH), 128.6 (CH), 129.8 (CH), 131.8 (CH), 159.8 (C), 162.3 (C).
Minor isomer: 1H NMR (400 MHz, CDCl3) δ 1.31 (t, J = 7.2 Hz, 3H), 3.78 (s, 3H), 4.34 (q, J
= 7.2 Hz, 2H), 4.86 (d, J = 9.6 Hz, 1H), 5.36 (d, J = 9.6 Hz, 1H), 6.88 (d, J = 8.0 Hz, 2H),
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7.32–7.45 (m, 7H); C NMR (100 MHz, CDCl3) δ 13.9 (CH3), 39.2 (CH), 55.3 (CH3) 63.3
(CH2), 84.3 (C), 86.4 (C), 91.9 (CH), 114.5 (CH), 126.9 (C), 128.3 (CH), 128.7 (CH), 129.5
(CH), 131.7 (CH), 131.8 (C), 159.8 (C), 162.3 (C). IR (ATR) 1560, 1749, 2355 cm-1; HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd. for C20H19NO5Na 376.1155; Found 376.1141.
Ethyl -2-nitro-3,5-diphenyl-4-pentynoate (9Ca) (dr = 1 : 1.1)
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Colorless oil (152 mg, 0.47 mmol, 94%). Major isomer: H NMR (400 MHz, CDCl3) δ 1.07
(dd, J = 7.2, 7.2 Hz, 3H), 4.02–4.14 (m, 2H), 4.91 (d, J = 9.6 Hz, 1H), 5.42 (d, J = 9.6 Hz,
1H), 7.27–7.48 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 13.6 (CH3), 40.1 (CH), 63.2 (CH2),
84.7 (C), 85.9 (C), 91.9 (CH), 122.2 (C), 134.2 (C), 162.3 (C). Minor isomer: 1H NMR (400
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5.41 (d, J = 9.6 Hz, 1H), 7.27–7.48 (m, 10H); C NMR (100 MHz, CDCl3) δ 13.9 (CH3),
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addition, other signals were observed as follows, however, they could not be assigned to
which isomers although 30 signals were totally observed. 128.3 (CH), 128.3 (CH), 128.4
(CH), 128.7 (CH), 128.7 (CH), 128.7 (CH), 129.0 (CH), 129.0 (CH), 129.1 (CH), 131.7 (CH),
131.9 (CH), 131.9 (CH). IR (NaCl) 1562, 1749, 2357 cm-1; HRMS (ESI-TOF) m/z: [M +
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Na]+ Calcd. for C19H17NO4Na 346.1050; Found 346.1044.
Ethyl 3-(4-chlorophenyl)-2-nitro-5-phenyl-4-pentynoate (9Da) (dr = 1 : 1.1)
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Colorless oil (164 mg, 0.46 mmol, 92%). Major isomer: H NMR (400 MHz, CDCl3) δ 1.12
(dd, J = 7.2, 7.2 Hz, 3H), 4.06–4.19 (m, 2H), 4.89 (d, J = 9.6 Hz, 1H), 5.39 (d, J = 9.6 Hz,
1H), 7.27–7.43 (m, 9H); 13C NMR (100 MHz, CDCl3) δ 13.7 (CH3), 39.4 (CH), 63.4 (CH2),
84.1 (C), 86.3 (C), 91.6 (CH), 122.0 (C), 128.3 (CH), 128.8 (CH), 129.2 (CH), 130.1 (CH),
131.8 (CH), 132.8 (C), 134.7 (C), 162.1 (C). Minor isomer: 1H NMR (400 MHz, CDCl3) δ
1.30 (t, J = 7.2 Hz, 3H), 4.34 (q, J = 7.2 Hz, 2H), 4.89 (d, J = 9.6 Hz, 1H), 5.38 (d, J = 9.6 Hz,
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1H), 7.30–7.41 (m, 9H); C NMR (100 MHz, CDCl3) δ 13.9 (CH3), 39.2 (CH), 63.5 (CH2),
83.5 (C), 86.9 (C), 91.5 (CH), 122.0 (C), 128.4 (CH), 128.9 (CH), 129.2 (C), 129.3 (CH),
129.8 (CH), 131.7 (CH), 133.6 (C), 162.2 (C). IR (NaCl) 1562, 1751, 2364 cm-1; HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd. for C19H16NO4ClNa 380.0660; Found 380.0641.
Ethyl 3-(2-furyl)-2-nitro-5-phenyl-4-pentynoate (9Ea) (dr = 1 : 1.1)
Pale yellow oil (28 mg, 0.09 mmol, 18%). Major isomer: 1H NMR (400 MHz, CDCl3) δ 1.23
(dd, J = 7.2, 7.2 Hz, 3H), 4.19–4.30 (m, 2H), 5.05 (d, J = 8.8 Hz, 1H), 5.58 (d, J = 8.8 Hz,
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1H), 6.35–6.39 (m, 1H), 6.44 (d, J = 3.2 Hz, 1H), 7.28–7.44 (m, 6H); C NMR (100 MHz,
CDCl3) δ 13.8 (CH3), 34.1 (CH), 63.4 (CH2), 81.7 (C), 85.5 (C), 89.2 (CH), 109.5 (CH),
110.8 (CH), 122.0 (C), 128.3 (CH), 128.8 (CH), 131.9 (CH), 143.2 (CH), 146.9 (C), 162.1
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(C). Minor isomer: 1.30 (t, J = 7.2 Hz, 3H), 4.33 (q, J = 7.2 Hz, 2H), 5.08 (d, J = 8.8 Hz, 1H),
5.55 (d, J = 8.8 Hz, 1H), 6.35–6.39 (m, 1H), 6.42 (d, J = 3.2 Hz, 1H), 7.28–7.44 (m, 6H). 13C
NMR (100 MHz, CDCl3) δ 13.9 (CH3), 33.9 (CH), 63.4 (CH2), 81.1 (C), 86.1 (C), 88.7 (CH),
109.3 (CH), 110.8 (CH), 121.9 (C), 128.3 (CH), 128.9 (CH), 131.8 (CH), 143.2 (CH), 147.4
(C), 162.1 (C). IR (KBr) 1567, 1753, 2354 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd.
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for C17H15NO5Na 336.0842; Found 336.0859.
Conversion of ethynylated product 9 to enynes 10
To a solution of adduct 9Aa (144 mg, 0.43 mmol) in acetonitrile (0.5 mL), triethylamine (126
µL, 0.9 mmol) was added, and the resultant mixture was stirred at room temperature for 18 h.
After removal of the solvent under reduced pressure, 1 M hydrochloric acid (1 mL, 1 mmol)
was added, and the mixture was extracted with dichloromethane (50 mL ´ 3). The organic
layer was dried over magnesium sulfate, and concentrated. The residue was subjected to the
column chromatography on silica gel to afford enyne 10Aa (eluted with hexane/ethyl acetate
= 9/1, 116 mg, 0.40 mmol, 93%) as a colorless solid. When other adducts were used, the
experiments were conducted in a similar way.
Ethyl (Z)-3-(4-methyphenyl)-5-phenyl-2-penten-4-ynoate (10Aa)
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Colorless oil (116 mg, 0.40 mmol, 93%). H NMR (400 MHz, CDCl3) δ 1.35 (t, J = 7.2 Hz,
3H), 2.39 (s, 3H), 4.30 (q, J = 7.2 Hz, 2H), 6.57 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.36-7.38
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(m, 3H), 7.63 (dd, J = 2.4 Hz, 6.0 Hz, 2H), 7.69 d, J = 8.0 Hz, 2H); C NMR (100 MHz,
CDCl3) δ 14.4 (CH3), 21.3 (CH3), 60.3 (CH2), 87.0 (C), 101.9 (C), 121.9 (CH), 122.9 (C),
127.2 (CH), 128.4 (CH), 129.2 (CH), 129.4 (CH), 132.1 (CH), 134.4 (C), 136.2 (C), 140.2
(C), 165.5 (C); IR (ATR) 1587, 1715, 2203 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C20H19O2 291.1380; Found 291.1369.
Ethyl (Z)-3-(4-methyphenyl)-5-(4-trifluoromethyl)phenyl-2-penten-4-ynoate (10Ab)
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Pale yellow oil (150 mg, 0.42 mmol, 98%). 1H NMR (400 MHz, CDCl3) δ 1.35 (t, J = 7.2 Hz,
3H), 2.40 (s, 3H), 4.30 (q, J = 7.2 Hz, 2H), 6.61 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.62 (d, J =
8.0 Hz, 2H), 7.67 (dd, J = 2.4 Hz, 8.0 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz,
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CDCl3) δ 14.4 (CH3), 21.3 (CH3), 60.4 (CH2), 88.9 (C), 99.7 (C), 122.9 (CH), 123.9 (q, JCF
271 Hz, CH), 125.3 (q, JCF = 3.6 Hz, CH), 125.4 (C), 127.1 (CH), 129.5 (CH), 130.7 (q, JCF
=
=
32 Hz, C), 132.2 (CH), 133.9 (C), 135.6 (C), 140.5 (C), 165.3 (C); IR (ATR) 1323, 1593,
1716, 2206 cm-1; HRMS (EI, [M]+) Calcd. for C21H17F3O2 358.1181; Found 358.1181.
Ethyl (Z)-3-(4-methylphenyl)-2-nonen-4-ynoate (10Ac)
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Colorless oil (131 mg, 0.43 mmol, 99%). H NMR (400 MHz, CDCl3) δ 0.95 (t, J = 7.2 Hz,
3H), 1.32 (t, J = 7.2 Hz, 3H),1.50 (tq, J = 7.2 Hz, 7.6 Hz, 2H),1.66 (tt, J = 7.2 Hz, 7.6 Hz,
2H), 2.36 (s, 3H) 2.56 (t, J = 7.2 Hz, 2H), 4.25 (q, J = 7.2 Hz, 2H), 6.47 (s, 1H), 7.17 (d, J =
7.6 Hz, 2H), 7.60 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 13.6 (CH3), 14.3 (CH3),
19.8 (CH2), 21.2 (CH3), 22.1 (CH2), 30.6 (CH2), 60.1 (CH2), 78.2 (C), 104.7 (C), 121.1 (CH),
127.1 (CH), 129.2 (CH), 135.0 (C), 137.1 (C), 139.9 (C), 165.7 (C); IR (NaCl) 1595, 1720,
2207 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H23O2 271.1698; found 271.1682.
Ethyl (Z)-6,6-dimethyl-3-(4-methylphenyl)-2-hepten-4-ynoate (10Ad)
Colorless oil (117 mg, 0.43 mmol, quant.). 1H NMR (400 MHz, CDCl3) δ 1.33 (t, J = 7.2 Hz,
3H), 1.37 (s, 9H), 2.37 (s, 3H), 4.26 (q, J = 7.2 Hz, 2H), 6.45 (s, 1H), 7.18 (d, J = 8.0 Hz, 2H),
13
7.60 (d, J = 8.0 Hz, 2H); C NMR (100 MHz, CDCl3) δ 14.4 (CH3), 21.2 (CH3), 28.7 (C),
30.7 (CH3), 60.9 (CH2), 112.2 (C), 121.1 (CH), 121.1(C), 127.1 (CH), 129.2 (CH), 135.1 (C),
136.7 (C), 139.9 (C), 165.7 (C); IR (NaCl) 1595, 1721, 2215 cm-1; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd. for C18H23O2 271.1693; Found 271.1687.
Ethyl (Z)-3-(4-methylphenyl)-5-trimethylsilyl-2-penten-4-ynoate (10Ae)
Colorless oil (121 mg, 0.42 mmol, 98%). 1H NMR (400 MHz, CDCl3) δ 0.09 (s, 9H), 1.14 (t,
J = 7.2 Hz, 3H), 2.17 (s, 3H), 4.07 (q, J = 7.2 Hz, 2H), 6.30 (s, 1H), 6.99 (d, J = 8.4 Hz, 2H),
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7.40 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 0.00 (CH3), 14.6 (CH3), 21.5 (CH3),
60.6 (CH2), 101.7 (C), 108.9 (C), 123.2 (CH), 127.4 (CH), 129.5 (CH), 134.5 (C), 135.9 (C),
140.4 (C), 165.6 (C); IR (NaCl) 1698, 1724, 2149 cm-1; HRMS (ESI-TOF) m/z: [M + H]+
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Calcd. for C17H23O2Si 287.1462; Found 287.1467.
Ethyl (Z)-3-(4-metoxhyphenyl)-5-phenyl-2-penten-4-ynoate (10Ba)
1
Colorless oil (114 mg, 0.37 mmol, 86%). H NMR (400 MHz, CDCl3) δ 1.35 (t, J = 7.2 Hz,
3H), 4.29 (q, J = 7.2 Hz, 2H), 6.52 (s, 1H), 6.93 (d, J = 8.8 Hz, 2H), 7.36–7.38 (m, 3H), 7.63
(dd, J = 2.4 Hz, 8.8 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 14.4
(CH3), 55.4 (CH3), 60.3 (CH2), 87.0 (C), 101.8 (C), 114.0 (CH), 120.6 (CH), 122.8 (C), 128.4
(CH), 128.7 (CH), 129.2 (CH), 129.5 (C), 132.1 (CH), 135.8 (C), 161.2 (C), 165.6 (C); IR
(KBr) 1601, 1731, 2201 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C20H19O3
307.1329; Found 307.1318.
Ethyl (Z)-3,5-diphenyl-2-penten-4-ynoate (10Ca)
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1
Pale yellow oil (117 mg, 0.42 mmol, 98%). H NMR (400 MHz, CDCl3) δ H NMR (400
MHz, CDCl3, TMS) δ 1.35 (t, J = 7.2 Hz, 3H), 4.31 (q, J = 7.2 Hz, 2H), 6.59 (s, 1H), 7.3–7.4
(m, 3H), 7.4–7.5 (m, 3H), 7.6–7.7 (m, 2H), 7.75–7.85 (m, 2H); 13C NMR (100MHz, CDCl3)
δ 14.4 (CH3), 60.4 (CH3), 86.9 (C), 102.1 (C), 122.7 (C), 122.8 (CH), 127.2 (CH), 128.4
(CH), 128.7 (CH), 129.2 (CH), 129.9 (CH), 132.1 (CH), 136.3 (C), 137.2 (C), 165.4 (C);
HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C19H17O2 277.1223, Found 277.1215.
Ethyl (Z)-3-(4-chlorophenyl)-5-phenyl-2-penten-4-ynoate (10Da)
1
Colorless oil (130 mg, 0.42 mmol, 97%). H NMR (400 MHz, CDCl3) δ 1.35 (t, J = 7.2 Hz,
3H), 4.30 (q, J = 7.2 Hz, 2H), 6.56 (s, 1H), 7.36–7.41 (m, 5H), 7.61–7.63 (m, 3H), 7.72 (d, J
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= 8.8 Hz, 1H); C NMR (100 MHz, CDCl3) δ 14.4 (CH3), 60.5 (CH2), 86.5 (C), 102.4 (C),
122.5 (CH), 130.0 (CH), 128.5 (CH), 128.9 (CH), 128.9 (C), 129.4 (CH), 132.1 (CH), 135.0
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(C), 135.6 (C), 136.0 (C), 165.2 (C); IR (NaCl) 1588, 1717, 2203 cm-1; HRMS (ESI-TOF)
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m/z: [M + H]+ Calcd. for C19H16O2Cl 311.0833; Found 311.0821.
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Ethyl (Z)-3-(2-furyl)-5-phenyl-2-penten-4-ynoate (10Ea)
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Pale yellow oil (113 mg, 0.43 mmol, 99%). 1H NMR (400 MHz, CDCl3) δ 1.34 (t, J = 7.2 Hz,
3H), 4.28 (q, J = 7.2 Hz, 2H), 6.56 (s, 1H), 6.50 (dd, J = 1.6 Hz, 3.2 Hz, 1H), 6.63 (s, 1H),
6.92 (d, J = 3.2 Hz, 1H), 7.37–7.38 (m, 3H), 7.47 (d, J = 1.6 Hz, 1H), 7.60–7.63 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 14.4 (CH3), 60.3 (CH2), 84.4 (C), 99.0 (C), 112.3 (CH), 113.7
(CH), 118.2 (CH), 122.5 (C), 124.8 (C), 128.4 (CH), 129.3 (CH), 132.1 (CH), 144.4 (CH),
151.8 (C), 165.5 (C); IR (KBr) 1732, 2205 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C17H15O3 266.0943; Found 266.0946.
Cyanation of cinnamate 2A using potassium cyanide
Grinded potassium cyanide (7.1 mg, 0.1 mmol) was dissolved into a methanol (50 µL), and
then diluted with acetonitrile (1 mL). The solution was added to a solution of nitrocinnamate
2A (24 mg, 0.1 mmol) in acetonitrile (2.4 mL) at room temperature for over 3 min., and the
resultant mixture was stirred for further 1 hour. Triethylamine (28 µL, 0.2 mmol) was added,
and the mixture was stirred at room temperature for further 1 h. After removal of the solvent,
1 M hydrochloric acid (2 mL, 2 mmol) was added, and the mixture was extracted with
dichloromethane (20 mL ´ 3). The organic layer was dried over magnesium sulfate, and
concentrated. The residue was treated with silica gel column chromatography to afford
cyanoalkene 13a (18.5 mg, 0.09 mmol, 86%) as a pale yellow solid. When other nitroalkenes
2 were used, the experiments were conducted in a similar way.
Ethyl 3-cyano-3-(4-methylphenyl)-2-propenoate (13a)
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Pale yellow solid (18.5 mg, 0.09 mmol, 86%), 56.6–57.5 ℃. H NMR (400 MHz, CDCl3,
TMS) δ 1.38 (t, J = 7.2 Hz, 3H), 4.35 (q, J = 7.2 Hz, 2H), 6.83 (s, 1H), 7.27 (d, J = 6.8 Hz,
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2H), 7.61 (d, J = 6.8 Hz, 2H); C NMR (100 MHz, CDCl3) δ 14.1 (CH3), 21.4 (CH3), 61.2
(CH2), 115.1 (C), 126.0 (C), 127.0 (CH), 128.2 (CH), 129.2 (C), 130.0 (CH), 142.3 (C),
163.4 (C); IR (ATR, cm-1) 2363, 1717, 1566; HRMS (ESI/TOF) m/z: [M + H]+ Calcd.for
C13H14NO2 216.1019, Found 216.1015.
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Ethyl 3-cyano-3-(4-methoxyphenyl)-2-propenoate (13b)
Pale yellow solid (21 mg, 0.09 mmol, 90%), 105.8–106.4 °C. 1H NMR (400 MHz, CDCl3) δ
1.37 (t, J = 7.2 Hz, 3H), 3.87 (s, 3H), 4.45 (q, J = 7.2 Hz, 2H), 6.76 (s, 1H), 6.96 (d, J = 8.8
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Hz, 2H), 7.68 (d, J = 8.8 Hz, 2H); C NMR (100 MHz, CDCl3) δ 14.1 (CH3), 55.6 (CH3),
61.6 (CH2), 114.7 (CH), 115.2 (C), 124.3 (C), 125.6 (C), 126.5 (CH), 128.7 (CH), 162.4 (C),
163.6 (C); IR (ATR) 1593, 1707, 2357 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C13H14NO3 232.0968; Found 232.0959.
Ethyl 3-cyano-3-phenyl-2-propenoate (13c)
Pale yellow oil (19 mg, 0.09 mmol, 92%). 1H NMR (400 MHz, CDCl3, TMS) δ 1.38 (t, J =
7.2 Hz, 3H), 4.36 (q, J = 7.2 Hz, 2H), 6.88 (s, 1H), 7.4–7.6 (m, 3H), 7.7–7.8 (dd, J = 7.0, 2.0
Hz, 2H); 13C NMR (100MHz, CDCl3) δ 14.1 (CH3), 61.8 (CH2), 115.1 (C), 126.1 (C), 127.0
(CH), 129.3 (CH), 129.5 (CH), 131.5 (CH), 131.9 (CH), 163.2 (C); HRMS (ESI/TOF) m/z:
[M + H]+ Calcd. for C12H11NO2 202.0863, Found 202.0859.
Ethyl 3-(4-chlorophenyl)-3-cyano-2-propenoate (13d)
Pale yellow oil (20 mg, 0.085mmol, 85%). 1H NMR (400 MHz, CDCl3, TMS) δ 1.38 (t, J =
7.2 Hz, 3H), 4.36 (q, J = 7.2 Hz, 2H), 6.85 (s, 1H), 7.44 (d, J = 8.7 Hz, 2H), 7.65 (d, J = 8.7
Hz, 2H); 13C NMR (100MHz, CDCl3) δ 14.1 (CH3), 61.9 (CH2), 114.7 (C), 124.9 (C), 128.3
(CH), 129.6 (CH), 129.8 (CH), 130.4 (C), 138.0 (C), 163.0 (C); HRMS (ESI/TOF) m/z: [M +
H]+ Calcd. for C12H11ClNO2: 236.0473, Found: 236.0470.
Ethyl 3-cyano-3-(2-furyl)-2-propenoate (13e)
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Brown oil (13 mg, 0.07 mmol, 66%). 1H NMR (400 MHz, CDCl3) δ 1.36 (t, J = 7.2 Hz, 3H),
4.35 (q, J = 7.2 Hz, 2H), 6.57 (dd, J = 3.2, 1.6 Hz, 1H), 6.79 (s, 1H), 6.98 (d, J = 3.2 Hz, 1H),
7.54 (d, J = 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1 (CH3), 61.6 (CH2), 113.1 (CH),
113.5 (C), 114.9 (C), 116.1 (CH), 124.3 (CH), 146.2 (CH), 147.9 (C), 163.4 (C); IR (ATR)
1586, 2326 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for C10H9NO3Na 214.0475;
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Found 214.0472.
2-(4-Methylphenyl)-4-oxo-4-phenyl-2-butenenitrile (13g)
Pale yellow oil (20 mg, 0.08 mmol, 80%). 1H NMR (400 MHz, CDCl3, TMS) δ 2.43 (s, 3H),
7.31 (d, J = 8.0 Hz, 2H), 7.5–7.6 (m, 2H), 7.6–7.7 (m, 1H), 7.7–7.8 (m, 2H), 7.88 (s, 1H),
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8.04 (d, J = 8.0 Hz, 2H); C NMR (100MHz, CDCl3) δ 21.1 (CH3), 116.1 (C), 124.8 (C),
127.2 (CH), 128.6 (CH), 129.0 (CH), 129.8 (C), 130.1 (CH), 131.7 (CH), 133.9 (CH), 136.9
(C), 142.4 (C), 187.0 (C); HRMS (ESI/TOF) m/z: [M + H]+ Calcd. for C17H14NO 248.1070,
found 248.1065.
Ethyl 3-cyano-3-(4-methylphenyl)-2-nitro-2-propanoate (12a) (dr = 1 : 1.4)
Yellow oil (16 mg, 0.06 mmol, 60%). The diastereomeric ratio was determined by 1H NMR
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of the reaction mixture. Major isomer: H NMR (400 MHz, CDCl3) δ 1.18 (dd, J = 7.2, 7.2,
Hz, 3H), 2.35 (s, 3H), 4.18–4.24 (m, 2H), 4.77 (d, J = 8.0 Hz, 1H), 5.43 (d, J = 8.0 Hz, 1H),
7.21 (d, J = 6.4 Hz, 2H), 7.26 (d, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 13.6 (CH3),
21.1 (CH3), 40.0 (CH), 64.2 (CH2), 88.5 (CH), 116.2 (C), 125.4 (C), 128.1 (CH), 130.3 (CH),
140.1 (C), 161.2 (C). Minor isomer: 1H NMR (400 MHz, CDCl3) δ 1.34 (t, J = 7.2 Hz, 3H),
2.35 (s, 3H), 4.38 (q, J = 7.2 Hz, 2H), 4.78 (d, J = 8.0 Hz, 1H) 5.42 (d, J = 8.0 Hz, 1H), 7.21
(d, J = 6.4 Hz, 2H), 7.26 (d, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 13.8 (CH3), 21.1
(CH3), 37.8 (CH), 64.3 (CH2), 88.6 (CH), 115.9 (C), 126.0 (C), 128.1 (CH), 130.4 (CH),
140.2 (C), 161.2 (C); IR (KBr) 1756, 2252 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd.
for C13H14N2O4Na 285.0846; Found 285.0848.
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