Transition Metal-Free Oxidative Cross-Coupling Reaction of Activated Olefins with N-Alkyl Amides

Article abstract of DOI:10.1021/acs.joc.0c02837

The K2S2O8-mediated transition metal-free oxidative cross-coupling reaction of activated olefins with N-alkyl amides was developed, and the reaction gave N-allylic amides in moderate to good yield. This reaction protocol was suitable for different kinds o

Full text of DOI:10.1021/acs.joc.0c02837

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Article
Transition Metal-Free Oxidative Cross-Coupling Reaction of
Activated Olefins with N‑Alkyl Amides
Miaomiao Li, Lei Zheng, Li Ma, and Yunfeng Chen*
Cite This: J. Org. Chem. 2021, 86, 3989−3998
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ABSTRACT: The K2S2O8-mediated transition metal-free oxidative cross-coupling reaction of activated olefins with N-alkyl amides
was developed, and the reaction gave N-allylic amides in moderate to good yield. This reaction protocol was suitable for different
kinds of activated olefins.
In continuation of our research on metal-catalyzed cross-
coupling14 and oxidative cyclization reactions,15 herein, we
disclosed a transition metal-free oxidative coupling reaction of
activated olefins (including nitro-olefins, cinnamic acids, and
alkenyl sulfones) with N-alkyl amides.
INTRODUCTION
■
The oxidative cross-coupling reactions have been developed to
be a powerful tool for the construction of various chemical
bonds owing to high atom economy and sustainable chemical
process.1 Among them, oxidative R1−H/R2−H cross-dehydro-
genative coupling (CDC) reaction with air or O2 as the oxidant
is an ideal approach because C−H nucleophiles exist
extensively in nature and water is the only byproduct.2
However, oxidative R1−H/R2−X (or R2−M) cross-coupling
reaction is still an alternative strategy for some bond formation,
even though it generates considerable useless byproducts.3
N-alkyl amides are an important class of oxidative coupling
synthon,4 and this synthon has been successfully used in
construction of chemical bonds, such as C−C,5 C−N,6 and
C−O.7 In the presence of oxidants, N-alkyl amides could be
used as radical precursors to generate the α-amide radical or
radical cations via losing one or two electrons,5−8 and then, the
active amide radical couples with other reaction partners to
form diverse α-C functionalization amides. In spite of these
great achievements, the ideal oxidative CDC reaction between
sp2 C−H of terminal alkenes and α−C(sp3)−H of N-alkyl
amides to form allylic amides was still a challenge because of
the potential polymerization of terminal alkenes (Scheme 1a).
A compromise strategy was to utilize activated olefins as
radical acceptors, such as the reported cinnamic acids or
alkenyl sulfones, which couples with N-alkyl amides to form N-
allylic amides in the presence of metals9 or photocatalysts10
(Scheme 1b,c). Moreover, arylacetylene as a coupling partner
to react with amides was also developed, although this reaction
could give E/Z-N-allylic amides (Scheme 1d).11 N-allylic
amides are prevalent in natural products12 and as a synthetic
precursor for construction of other useful molecules.13 Hence,
more convenient and efficient methods (such as transition
metal-free and open-flask conditions) to access N-allylic
amides are still desired.
RESULTS AND DISCUSSION
■
(E)-(2-Nitrovinyl)benzene (1a) was chosen as an activated
olefin to react with N,N-dimethylacetamide (DMA, 2a) for our
initial study, and the results are summarized in Table 1. First,
the reaction was performed by using 3 equiv of tert-butyl
hydroperoxide (TBHP) as an oxidant,16 and the expected
product 3aa was obtained with 24% isolated yield (entry 1). In
general, the tert-butyl hydroperoxide (TBAI)/TBHP17 reac-
tion system was popular for oxidative C−H bond functional-
ization. However, 20 mol % TBAI along with TBHP had no
improvement for the yield of reaction (entry 2). Then, a
preliminary screening of the oxidants was conducted. Some
common oxidants such as di-tert-butyl peroxide (DTBP),
K2S2O8, PhI(OAc)2, (NH4)2S2O8, and radical initiators
including benzoic peroxyanhydride (BPO), azodiisobutyroni-
trile (AIBN), and 4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-
1,2-dicarbonitrile (DDQ) were tested (entries 3−9). Notably,
using K2S2O8 as an oxidant at 100 °C gave the best yield of 3aa
(entry 4, 87%). Altering the temperature of the reaction led no
further improvements (entries 10, 11). Different solvents such
as CH3CN, DCE, EtOH, toluene, DMSO, and EtOAc were
Received: November 28, 2020
Published: February 12, 2021
https://dx.doi.org/10.1021/acs.joc.0c02837
© 2021 American Chemical Society
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Scheme 1. Synthesis of N-Allylic Amides
a
Moreover, the addition of acidic or basic additives did not
improve the yield (entries 18, 19), and lowering the amount of
oxidants also led to a decreased yield of 3aa (entry 20).
With the optimized condition in hand (Table 1, entry 4), the
scope of this reaction was subsequently examined (Table 2). In
summary, all substrates proceeded fast and gave the target
products in moderate to good yields. First, an array of (E)-(2-
nitrovinyl)benzenes 1 with different electron-withdrawing
groups (−F, −Cl, −Br, and −CN) substituted on different
positions (ortho-, meta-, and para-) of the phenyl ring reacted
with DMA provided the corresponding products in good yields
(3ba−3ja, 81%−90%). Moreover, electron-donating group
(−Me and −OMe)-substituted nitroalkenes also gave moder-
ate yields (3fa, 71%; 3ja, 70%). Next, the scope of amides
including NMP, pyrrolidone, and DMF was also tested for this
reaction. As for NMP, the desired N-allylic amide was formed
in moderate yield and the amount of oxidants was increased to
4 equiv (3ab−3mb, 74−84%). Pyrrolidone was also suitable
for this reaction and gave the corresponding products with
good yield (up to 91% for 3id). However, lower yields were
observed, while DMF was used as an amide partner, probably
because of side reactions of the CHO group (3ac, 51%; 3bc,
53%).
On the other hand, α-alkyl nitroalkenes were also tested for
substrate scope (Table 3). It was found that the reactions were
completed within only 20 min by using (NH4)2S2O8 as
oxidants at 75 °C. However, the reactions yielded two isomer
products for all cases. For example, when (E)-(1-nitroprop-1-
en-2-yl)benzene (4a) was used to react with DMA, (E)-N-
methyl-N-(3-phenylbut-2-en-1-yl)acetamide 5a and N-methyl-
N-(3-phenylbut-3-en-1-yl)acetamide 5a′ were obtained in a
mixed yield of 88% with the ratio at 0.86−0.14 because there is
an equilibrium between 4a and 4a′, especially in polar DMF or
DMA solvent.18 Therefore, α-alkyl nitroalkenes (4/4′) with
different substitute groups were also tested, and the ratios of
the two isomeric products changed with different substituents
Table 1. Optimization of the Reaction Conditions
b
entry
1
2
3
4
5
6
7
8
9
oxidant
TBHP
TBHP
PhI(OAc)2
K2S2O8
DTBP
BPO
AIBN
DDQ
(NH4)2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
solvent
additive temp (°C) yield (%)
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
CH3CN
EtOH
DCE
toluene
EtOAc
DMSO
DMA
DMA
DMA
100
100
100
100
100
100
100
100
100
110
80
100
100
100
100
100
100
100
100
100
24
22
44
87
trace
61
21
n.r
82
73
59
51
n.r
19
26
25
21
17
81
59
c
c
TBAI
10
11
d
12
13
14
15
16
17
18
19
HOAc
K2CO3
e
20
a
Reaction Conditions: 1a (0.2 mmol), 2a (2 mL as solvent), oxidant
b
(0.6 mmol), additive (0.4 mmol), under air, and 0.5 h. Isolated yield
c
d
e
based on 1a. 20 mmol % of additives. Stirred for 2 h. 0.4 mmol
K2S2O8 was used, n.r = no reaction. TBHP: tert-Butyl hydroperoxide;
TBAI: tetrabutylammonium iodide; DTBP: di-tert-butyl peroxide;
BPO: benzoic peroxyanhydride; DDQ: 4,5-dichloro-3,6-dioxocyclo-
hexa-1,4-diene-1,2-dicarbonitrile; and AIBN: azodiisobutyronitrile.
introduced to reduce the amount of DMA (the ratio to DMA
was 1:1), but no better result was achieved (entries 12−17).
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a
Table 2. Substrate Scope of Nitroalkenes and Amides
a
Reaction conditions: 1 (0.2 mmol), 2 (3 mL as solvent), K2S2O8 (0.6 mmol), 100 °C for 0.5 h, when NMP used as a reactant, the amount of
K2S2O8 is 0.8 mmol.
a
Table 3. Substrate Scope of α-Nitroalkenes and DMA
a
b
Reaction conditions: 4 (0.2 mmol), 2 (2 mL as solvent), (NH4)2S2O8 (0.6 mmol), 75 °C for 0.5 h. The ratio of isomers of reactants. 4b:4b′ =
c
d
1
87%:13%. 4c:4c′ = 93%:7%. 4d:4d′ (4e:4e′) = 99%:1%; all the ratios were detected by H NMR.
on the α-alkyl nitroalkenes and ratios of the isomers of
reactants.
partner under optimal reaction conditions, fast polymerization
of styrene happened and only trace product was detected
(Scheme 2a). In the presence of 2,2,6,6-tetramethylpiperidine-
1-oxyl, a radical scavenger, the formation of products was
totally inhibited, which revealed that the reaction might
undergo a radical process (Scheme 2b). If β-methylstyrene
served as the reaction partner, the corresponding product 5a or
5a′ was hard to be detected (Scheme 2c). At the same time,
the reaction of isomeric α-alkyl nitro-olefin (4a′) could give
product 5a′ as the major product under standard reaction
conditions (Scheme 2d), and prolongation of the reaction time
did not change the ratio of the products, which revealed that
the formation of the regioisomers (5a) could be started from
Because −SO2Ar and −COOH are also good leaving
groups,19,20 we further expanded this transition metal-free
oxidative condition to cinnamic acids and alkenyl sulfones.
Pleasantly, the expected N-allylic amides could be obtained
from both cinnamic acids and alkenyl sulfones. In this case, an
appropriate amount of base such as sodium carbonate or t-
BuOK must be added to improve the reactions, and the
reaction results are summarized in Table 4.
To gain insights into mechanism of this oxidative cross-
coupling reaction, some control experiments were conducted
(Scheme 2). First, when styrene was chosen as the reaction
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Table 4. Scope of Other Activated Olefins
a
Reaction Conditions: 5 (0.2 mmol), 2 (2 mmol), K2CO3 (0.6 mmol), K2S2O8 (0.6 mmol), toluene (2.5 mL), and H2O (0.5 mL), stirred at 90 °C
b
for 0.5 h under air. Reaction Conditions: 5 (0.2 mmol), 2 (2 mL as solvent), t-BuOK (0.8 mmol), and (NH4)2S2O8 (0.6 mmol), stirred at 110 °C
for 0.5 h under air.
Scheme 2. Control Experiments
Scheme 3. Plausible Mechanism
the original isomers of starting materials. When using (E)-(2-
nitroprop-1-en-1-yl)benzene (3o) as a reactant, no product
was detected (Scheme 2e).
Based on abovementioned experiments and previous
results,13 a plausible mechanism was proposed (Scheme 3).
Potassium peroxodisulfate generated peroxodisulfate radicals
first and subsequently abstracted a hydrogen atom from the α−
C−H bond of DMA to form amide radical species A. Then, the
amide radical addition to olefins resulted in formation of the
alkyl radical species B. If there was an alkyl group, it was easy
to be formed, which was in accordance with lower reaction
temperature and shorter reaction time. Finally, B was
converted to the product 3 with the departure of the leaving
group.
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mmol). The reaction mixture was allowed to stir at 90 °C (oil bath)
for 0.5 h. After the reaction was completed (as monitored by TLC),
the mixture was quenched with water and extracted with EtOAc (3 ×
15 mL). The organic layer was washed with saturated brine (3 × 5
mL), dried over anhydrous Na2SO4, and concentrated under reduced
pressure to give the crude products, which was purified by flash
column chromatography using 100−200 mesh silica gel and a mixture
of petroleum ether and EA (v/v = 3:1) as eluents to afford the desired
products 3aa.
In conclusion, we developed a transition metal-free oxidative
coupling reaction between activated olefins and N-alkyl
amides. Besides simple and mild reaction conditions, the
method could give N-allylic amides in moderate to good yields.
This protocol was suitable for different activated olefins, which
supplied some alternative strategies for the accomplishment of
N-allylic amides.
Gram Scale for the Synthesis of N-Allylic Amides 3aa. A
mixture of (E)-(2-nitrovinyl)benzene 1a (1.04 g, 7 mmol) and
K2S2O8 (5.68 g, 21 mmol) in 20 mL of DMA was stirred under air in
a 50 mL flask at 100 °C (oil bath) for 40 min. Refer to the general
procedure above to get 3aa (0.97 g, 72.8%) as a pale-yellow oil.
Characterization Data. N-cinnamyl-N-methylacetamide (3aa)11
was obtained as pale-yellow oil (32.9 mg, 87%); purification by silica
gel chromatography (Rf = 0.19 eluent: PE/EA = 1:1); 1H NMR (400
MHz, CDCl3-d): δ 7.41−7.19 (m, 5H), 6.48 (dd, J = 15.8, 9.8 Hz,
1H), 6.20−6.07 (m, 1H), 4.18−4.12 (m, 1H), 4.08−4.05 (m, 1H),
2.99 (s, 1.4H), 2.98 (s, 1.6H), 2.14 (s, 1.4H), 2.13 (s, 1.6H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 170.8, 170.4, 136.5, 136.0,
132.7, 131.7, 128.6, 128.5, 127.9, 127.6, 126.3, 126.0, 124.5, 123.6,
52.5, 49.2, 35.4, 33.4, 21.8, 21.2 ppm.
EXPERIMENTAL SECTION
■
General Information. Unless otherwise stated, all chemicals used
in the experiments were obtained from commercial sources and used
directly without further treatment. Thin-layer chromatography (TLC)
was performed with the detection of compounds with UV light. Flash
column chromatography purification of the products was accom-
plished on silica gel (200−300 mesh). Petroleum ether (PE) (60−90
°C) and ethyl acetate (EA) were used as eluents for silica gel
chromatography. Melting points for all solid products were measured
on an X-4A melting point apparatus without correction. H and 13C
NMR spectra were recorded at 22 °C on a Bruker AV 400 and 600
MHz spectrometers with tetramethylsilane as an internal standard,
respectively. 1H and 13C chemical shifts in NMR spectra were
1
1
referenced, relative to signals of CDCl3 (δ 7.26 ppm for H and 77.0
(E)-N-(3-(4-chlorophenyl)allyl)-N-methylacetamide (3ba)9 was
obtained as pale-yellow oil (39.8 mg, 89%); purification by silica gel
ppm for 13C). High-resolution mass spectra (HRMS) were acquired
on Waters Acquity UPLC Class I/Xevo G2Q-TOF. The activated
olefins were synthesized according to the literatures: α-alkyl
nitroalkenes,18 nitroalkenes,21a and vinyl sulfones.21b
1
chromatography (Rf = 0.14 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.28 (s, 2H), 7.26 (d, J = 1.6 Hz, 2H), 6.41 (dd, J
= 16.0, 8.5 Hz, 1H), 6.16−6.04 (m, 1H), 4.14−4.11 (m, 1H), 4.06−
4.03 (m, 1H), 2.98 (s, 1.7H), 2.96 (s, 1.3H), 2.12 (s, 1.3H), 2.12 (s,
1.7H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 170.7, 170.5,
135.0, 134.5, 133.6, 133.2, 131.3, 130.4, 128.8, 128.6, 127.6, 127.5,
125.3, 124.4, 52.5, 49.2, 35.5, 33.5, 21.8, 21.3 ppm.
General Procedure for Oxidative Coupling Reaction
between Amides and Nitroalkenes. A mixture of (E)-(2-
nitrovinyl)benzene (1a) (0.2 mmol) and K2S2O8 (0.6 mmol) in 2
mL of DMA was stirred under air in a 10 mL dried tube at 100 °C (oil
bath). After the reaction was completed (as monitored by TLC), the
mixture was quenched with water and extracted with EtOAc (3 × 15
mL). The organic layer was washed with saturated brine (3 × 5 mL),
dried over anhydrous Na2SO4, and concentrated under reduced
pressure to give the crude products, which was purified by flash
column chromatography using 100−200 mesh silica gel and a mixture
of petroleum ether and EA (v/v = 1:1) as eluents to afford the desired
products.
General Procedure for Oxidative Coupling Reaction
between Amides and α-Alkyl Nitroalkenes. To a 10 mL dried
tube with a magnetic bar, (E)-(1-nitroprop-1-en-2-yl)benzene (4a)
(0.2 mmol) was loaded and 2 mL of DMA was added, followed by the
addition of (NH4)2S2O8 (0.6 mmol). The reaction mixture was
allowed to stir at 75 °C (oil bath) for 0.5 h. After the reaction was
completed (as monitored by TLC), the mixture was quenched with
water and extracted with EtOAc (3 × 15 mL). The organic layer was
washed with saturated brine (3 × 5 mL), dried over anhydrous
Na2SO4, and concentrated under reduced pressure to give the crude
products, which was purified by flash column chromatography using
100−200 mesh silica gel and a mixture of petroleum ether and EA (v/
v = 3:1) as eluents to afford the desired products 3aa.
General Procedure for Oxidative Coupling Reaction
between Amides and Vinyl Sulfones. To a 10 mL dried tube
with a magnetic bar, (E)-1-methyl-4-(styrylsulfonyl)benzene 6a (0.2
mmol) and t-BuOK (0.6 mmol) were loaded and 2 mL of DMA was
added, followed by the addition of (NH4)2S2O8 (0.6 mmol). The
mixture was stirred at 110 °C (oil bath) for 0.5 h. After the reaction
was completed (as monitored by TLC), the mixture was quenched
with water and extracted with EtOAc (3 × 15 mL). The organic layer
was washed with saturated brine (3 × 5 mL), dried over anhydrous
Na2SO4, and concentrated under reduced pressure to give the crude
products, which was purified by flash column chromatography using
100−200 mesh silica gel and a mixture of petroleum ether and EA (v/
v = 3:1) as eluents to afford the desired products 3aa.
(E)-N-(3-(4-bromophenyl)allyl)-N-methylacetamide (3ca) was
obtained as pale-yellow oil (43.4 mg, 81%); purification by silica gel
1
chromatography (Rf = 0.19 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.46−7.40 (m, 2H), 7.24−7.20 (m, 2H), 6.40 (dd,
J = 16.0, 8.3 Hz, 1H), 6.18−6.07 (m, 1H), 4.15−4.09 (m, 1H), 4.07−
4.01 (m, 1H), 2.97 (d, J = 8.0 Hz, 3H), 2.12 (d, J = 1.2 Hz, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 170.7, 170.4, 135.5, 135.0,
131.7, 131.6, 131.3, 130.4, 127.8, 127.8, 125.4, 124.5, 121.7, 121.3,
52.4, 49.2, 35.5, 33.4, 21.7, 21.2 ppm. HRMS (ESITOF) m/z: [M +
H]+ calcd for C12H15BrNO, 268.0332; found, 268.0330.
(E)-N-(3-(4-fluorophenyl)allyl)-N-methylacetamide (3da)9 was
obtained as colorless oil (37.3 mg, 90%); purification by silica gel
1
chromatography (Rf = 0.19 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.36−7.28 (m, 2H), 7.03−6.96 (m, 2H), 6.43 (dd,
J = 15.8, 9.6 Hz, 1H), 6.08−6.00 (m, 1H), 4.12 (d, J = 6.4 Hz, 1H),
4.04 (d, J = 4.2 Hz, 1H), 2.98 (s, 1.6H), 2.96 (s, 1.4H), 2.13 (s,
1.4H), 2.11 (s, 1.6H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ
170.7, 170.4, 161.0, 132.7, 132.3, 131.5, 130.5, 127.9 (d, J = 6.3 Hz),
127.8 (d, J = 6.3 Hz), 124.3 (d, J = 2.2 Hz), 123.4 (d, J = 2.2 Hz),
115.6 (d, J = 15.1 Hz), 115.4 (d, J = 15.0 Hz), 52.5, 49.2, 35.5, 33.4,
21.8, 21.3 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for
C12H15FNO, 208.1132; found, 208.1128.
(E)-N-(3-(4-cyanophenyl)allyl)-N-methylacetamide (3ea)9 was
obtained as yellow oil (34.7 mg, 81%); purification by silica gel
1
chromatography (Rf = 0.21 eluent: PE/EA = 1:3); H NMR (400
MHz, CDCl3-d): δ 7.59−7.54 (m, 2H), 7.42 (t, J = 8.0 Hz, 2H), 6.45
(dd, J = 16.0, 5.5 Hz, 1H), 6.31−6.24 (m, 1H), 4.16−4.12 (m, 1H),
4.10−4.08 (m, 1H), 2.99 (s, 1.8H), 2.95 (s, 1.2H), 2.11 (s, 1.8H),
2.10 (s, 1.2H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 170.7,
170.5, 140.9, 140.4, 132.4, 132.3, 130.5, 129.6, 128.7, 127.9, 126.8,
126.7, 118.8, 118.7, 111.0, 110.6, 52.3, 49.1, 35.7, 33.6, 21.7, 21.2
ppm.
(E)-N-(3-(4-methoxyphenyl)allyl)-N-methylacetamide (3fa)9 was
obtained as pale-yellow oil (31.1 mg, 71%); purification by silica gel
General Procedure for Oxidative Coupling Reaction
between Amides and Cinnamic Acids. To a 10 mL dried tube
with a magnetic bar, cinnamic acid 7a (0.2 mmol) and Na2CO3 (0.6
mmol) were loaded and 1.5 mL of toluene, DMA (2.0 mmol), and 0.7
mL of water were added, followed by the addition of K2S2O8 (0.6
1
chromatography (Rf = 0.18 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.32−7.27 (m, 2H), 6.85 (t, J = 8.2 Hz, 2H), 6.41
(dd, J = 16.0, 12.0 Hz, 1H), 6.05−5.91 (m, 1H), 4.13−4.10 (m, 1H),
4.04−4.01 (m, 1H), 3.80 (s, 1.5H), 3.79 (s, 1.5H), 2.97 (s, 1.5H),
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2.96 (s, 1.5H), 2.13 (s, 1.5H), 2.11 (s, 1.5H) ppm; 13C{1H} NMR
(100 MHz, CDCl3-d): δ 170.7, 170.4, 159.4, 159.2, 132.3, 131.2,
129.3, 128.8, 127.6, 127.5, 122.3, 121.3, 114.1, 113.9, 55.3, 55.2, 52.6,
49.3, 35.3, 33.4, 21.8, 21.3 ppm.
21.2 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for C13H15N2O,
215.1179; found, 215.1180.
(E)-N-(3-(3-methoxyphenyl)allyl)-N-methylacetamide (3na)9 was
obtained as pale-yellow oil (28.5 mg, 65%); purification by silica gel
1
(E)-N-(3-(2-chlorophenyl)allyl)-N-methylacetamide (3ga) was
obtained as pale-yellow oil (37.6 mg, 84%); purification by silica gel
chromatography (Rf = 0.23 eluent: PE/EA = 1:3); H NMR (400
MHz, CDCl3-d): δ 7.25−7.19 (m, 1H), 6.99−6.92 (m, 1H), 6.90 (s,
1H), 6.85−6.75 (m, 1H), 6.44 (dd, J = 15.6, 12.2 Hz, 1H), 6.19−6.06
(m, 1H), 4.14 (d, J = 6.4 Hz, 1H), 4.05 (d, J = 4.8 Hz, 1H), 3.81 (d, J
= 5.2 Hz, 3H), 2.98 (d, J = 2.8 Hz, 3H), 2.13 (d, J = 4.4 Hz, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 170.8, 170.4, 159.8,
159.8, 138.0, 137.5, 132.6, 131.5, 129.6, 129.5, 124.9, 124.0, 119.0,
118.9, 113.6, 113.5, 111.7, 111.4, 55.2, 55.2, 52.5, 49.2, 35.4, 33.5,
21.8, 21.3 ppm.
1
chromatography (Rf = 0.25 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.53−7.46 (m, 1H), 7.34 (t, J = 7.8 Hz, 1H),
7.27−7.12 (m, 2H), 6.86 (d, J = 15.8 Hz, 1H), 6.16−6.04 (m, 1H),
4.17 (d, J = 6.4 Hz, 1H), 4.08 (d, J = 5.6 Hz, 1H), 3.01 (s, 1.7H), 2.99
(s, 1.3H), 2.15 (s, 1.3H), 2.13 (s, 1.7H) ppm; 13C{1H} NMR (100
MHz, CDCl3-d): δ 170.7, 170.5, 134.7, 132.8, 129.7, 129.6, 128.9,
128.8, 128.6, 128.5, 127.5, 126.9, 126.9, 126.8, 126.7, 52.7, 49.3, 35.5,
33.4, 21.8, 21.3 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for
C12H15ClNO, 224.0837; found, 224.0839.
(E)-N-(3-(2-bromophenyl)allyl)-N-methylacetamide (3ha) was
obtained as pale-yellow oil (45.6 mg, 85%); purification by silica gel
chromatography (Rf = 21 eluent: PE/EA = 1:1); 1H NMR (400 MHz,
CDCl3-d): δ 7.57−7.42 (m, 2H), 7.25 (d, J = 10.0 Hz, 1H), 7.15−
7.03 (m, 1H), 6.80 (dd, J = 15.8, 4.4 Hz, 1H), 6.11−5.97 (m, 1H),
4.19−4.13 (m, 1H), 4.10−4.04 (m, 1H), 3.00 (s, 1.7H), 2.98 (s,
1.3H), 2.14 (s, 1.3H), 2.12 (s, 1.7H) ppm; 13C{1H} NMR (100 MHz,
CDCl3-d): δ 170.7, 170.5, 136.4, 136.2, 132.8, 132.8, 131.3, 131.0,
129.1, 128.9, 127.6, 127.5, 127.5, 127.1, 127.1, 126.8, 123.5, 123.4,
52.5, 49.2, 35.4, 33.4, 21.7, 21.3 ppm. HRMS (ESITOF) m/z: [M +
H]+ calcd for C12H15BrNO, 268.0332; found, 268.0332.
(E)-1-methyl-5-styrylpyrrolidin-2-one (3ab)9 was obtained as
colorless oil (33.0 mg, 82%); purification by silica gel chromatography
1
(Rf = 0.18 eluent: PE/EA = 1:1); H NMR (400 MHz, CDCl3-d): δ
7.42−7.25 (m, 5H), 6.56 (d, J = 15.8 Hz, 1H), 6.01 (dd, J = 15.8, 8.6
Hz, 1H), 4.14−4.02 (m, 1H), 2.78 (s, 3H), 2.55−2.24 (m, 3H),
1.89−1.77 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ
175.1, 135.9, 133.0, 128.9, 128.7, 128.2, 126.5, 63.0, 30.0, 27.9, 25.7
ppm.
(E)-5-(4-chlorostyryl)-1-methylpyrrolidin-2-one (3bb) was ob-
tained as pale-yellow oil (38.2 mg, 81%); purification by silica gel
1
chromatography (Rf = 0.13 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.28 (d, J = 12.4 Hz, 4H), 6.51 (d, J = 15.8 Hz,
1H), 5.99 (dd, J = 15.8, 8.5 Hz, 1H), 4.14−4.02 (m, 1H), 2.77 (s,
3H), 2.54−2.23 (m, 3H), 1.87−1.76 (m, 1H) ppm; 13C{1H} NMR
(100 MHz, CDCl3-d): δ 175.0, 134.3, 133.8, 131.7, 129.5, 128.8,
127.7, 62.8, 29.9, 27.9, 25.6 ppm. HRMS (ESITOF) m/z: [M + H]+
calcd for C13H15ClNO, 236.0837; found, 236.0840.
(E)-N-(3-(2-fluorophenyl)allyl)-N-methylacetamide (3ia) was ob-
tained as pale-yellow oil (34.4 mg, 83%); purification by silica gel
1
chromatography (Rf = 0.21 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.41 (q, J = 7.2, 6.8 Hz, 1H), 7.18 (d, J = 11.8 Hz,
1H), 7.13−6.98 (m, 2H), 6.61 (t, J = 14.8 Hz, 1H), 6.27−6.14 (m,
1H), 4.15 (d, J = 6.4 Hz, 2H), 4.06 (d, J = 5.2 Hz, 1H), 2.98 (s,
1.6H), 2.97 (s, 1.4H), 2.13 (s, 1.4H), 2.12 (s, 1.6H) ppm; 13C{1H}
NMR (100 MHz, CDCl3-d): δ 170.7, 170.5, 161.3, 158.8, 129.2 (d, J
= 8.5 Hz), 128.9 (d, J = 8.5 Hz), 127.6 (d, J = 3.6 Hz), 127.3 (d, J =
3.6 Hz), 127.2 (d, J = 4.6 Hz), 126.5 (d, J = 5.4 Hz), 124.9 (d, J = 3.8
Hz), 124.6, 124.3, 124.1 (d, J = 3.6 Hz), 124.0 (d, J = 3.5 Hz), 115.9,
115.7, 115.7, 115.5, 52.8, 49.5, 35.5, 33.4, 21.7, 21.3 ppm. HRMS
(ESITOF) m/z: [M + H]+ calcd for C12H15FNO, 208.1132; found,
208.1132.
(E)-5-(4-bromostyryl)-1-methylpyrrolidin-2-one (3cb) was ob-
tained as pale-yellow oil (44.8 mg, 80%); purification by silica gel
1
chromatography (Rf = 0.13 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.45 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H),
6.49 (d, J = 15.8 Hz, 1H), 6.01 (dd, J = 15.8, 8.4 Hz, 1H), 4.16−3.97
(m, 1H), 2.77 (s, 3H), 2.53−2.24 (m, 3H), 1.91−1.75 (m, 1H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 175.0, 134.8, 131.8), 131.7,
129.7, 128.0, 122.0, 62.8, 29.9, 28.0, 25.6 ppm. HRMS (ESITOF) m/
z: [M + H]+ calcd for C13H15BrNO, 280.0332; found, 280.0333.
(E)-5-(4-fluorostyryl)-1-methylpyrrolidin-2-one (3db) was ob-
tained as pale-yellow oil (36.8 mg, 84%); purification by silica gel
(E)-N-(3-(2-methoxyphenyl)allyl)-N-methylacetamide (3ja)9 was
obtained as pale-yellow oil (30.7 mg, 70%); purification by silica gel
1
chromatography (Rf = 0.15 eluent: PE/EA = 1:1); H NMR (400
1
chromatography (Rf = 0.22 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.37−7.33 (m, 2H), 7.01 (t, J = 8.8 Hz, 2H), 6.52
(d, J = 15.8 Hz, 1H), 5.92 (dd, J = 15.8, 8.4 Hz, 1H), 4.12−4.02 (m,
1H), 2.77 (s, 3H), 2.51−2.24 (m, 3H), 1.88−1.77 (m, 1H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 175.0, 163.8, 161.3, 132.0,
131.7, 128.6 (d, J = 2.2 Hz), 128.1 (d, J = 8.1 Hz), 115.6 (d, J = 21.6
Hz), 62.8, 29.9, 27.9, 25.7 ppm. HRMS (ESITOF) m/z: [M + H]+
calcd for C13H15FNO, 220.1132; found, 220.1131.
(E)-4-(2-(1-methyl-5-oxopyrrolidin-2-yl)vinyl)benzonitrile (3eb)
was obtained as a pale-yellow solid (37.1 mg, 82%); mp 88−91 °C;
purification by silica gel chromatography (Rf = 0.14 eluent: PE/EA =
1:3); 1H NMR (400 MHz, CDCl3-d): δ 7.58 (d, J = 8.0 Hz, 2H), 7.44
(d, J = 8.4 Hz, 2H), 6.54 (d, J = 15.8 Hz, 1H), 6.15 (dd, J = 15.8, 8.4
Hz, 1H), 4.15−4.07 (m, 1H), 2.76−2.74 (m, 3H), 2.48−2.24 (m,
3H), 1.87−1.75 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d):
δ 174.9, 140.2, 132.8, 132.4, 131.0, 126.9, 118.6, 111.2, 62.4, 29.6,
27.9, 25.3 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for
C14H15N2O, 227.1179; found, 227.1180.
(E)-5-(4-methoxystyryl)-1-methylpyrrolidin-2-one (3fb) was ob-
tained as a pale-yellow solid (35.2 mg, 76%); mp 56−59 °C;
purification by silica gel chromatography (Rf = 0.13 eluent: PE/EA =
1:1) 1H NMR (400 MHz, CDCl3-d): δ 7.30 (d, J = 8.8 Hz, 2H), 6.85
(d, J = 8.8 Hz, 2H), 6.49 (d, J = 15.6 Hz, 1H), 5.84 (dd, J = 15.6, 8.6
Hz, 1H), 4.07−3.99 (m, 1H), 3.79 (d, J = 1.2 Hz, 3H), 2.75 (s, 3H),
2.48−2.23 (m, 3H), 1.87−1.73 (m, 1H) ppm; 13C{1H} NMR (100
MHz, CDCl3-d): δ 175.0, 159.5, 132.4, 128.6, 127.7, 126.5, 114.0,
63.0, 55.2, 30.0, 27.8, 25.8 ppm. HMSR (ESITOF) m/z: [M + H]+
calcd for C14H18NO2, 232.1332; found, 232.1321.
MHz, CDCl3-d): δ 7.41 (d, J = 7.8 Hz, 1H), 7.26−7.17 (m, 1H),
6.99−6.82 (m, 2H), 6.81 (dd, J = 16.0, 12.4 Hz, 1H), 6.19−6.08 (m,
1H), 4.18−4.12 (m, 1H), 4.08−4.02 (m, 1H), 3.84 (d, J = 1.6 Hz,
3H), 2.97 (d, J = 2.0 Hz, 3H), 2.13 (d, J = 10.8 Hz, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 170.7, 170.4, 156.7, 156.5,
129.0, 128.7, 127.7, 127.1, 127.0, 126.8, 125.5, 125.1, 125.0, 124.2,
120.6, 110.8, 110.8, 55.4, 55.4, 53.1, 49.6, 35.3, 33.3, 21.8, 21.3 ppm.
(E)-N-methyl-N-(3-(p-tolyl)allyl)acetamide (3ka)9 was obtained
as colorless oil (31.3 mg, 77%); purification by silica gel
1
chromatography (Rf = 0.22 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.29−7.23 (m, 2H), 7.12 (t, J = 8.2 Hz, 2H), 6.44
(dd, J = 15.8, 10.8 Hz, 1H), 6.13−6.03 (m, 1H), 4.13 (d, J = 6.4 Hz,
1H), 4.04 (d, J = 5.2 Hz, 1H), 2.97 (s, 3H), 2.34 (s, 1.6H), 2.33 (s,
1.4H), 2.14 (s, 1.5H), 2.12 (s, 1.5H) ppm; 13C{1H} NMR (100 MHz,
CDCl3-d): δ 170.8, 170.4, 137.8, 137.5, 133.7, 133.2, 132.7), 131.6,
129.3, 129.2, 126.2, 126.2, 123.4, 122.5, 52.6, 49.2, 35.3, 33.4, 21.8,
21.3, 21.1 ppm.
(E)-N-(3-(3-cyanophenyl)allyl)-N-methylacetamide (3ma) was
obtained as pale-yellow oil (35.1 mg, 82%); purification by silica gel
1
chromatography (Rf = 0.22 eluent: PE/EA = 1:3); H NMR (400
MHz, CDCl3-d): δ 7.62−7.37 (m, 4H), 6.43 (dd, J = 16.0, 4.0 Hz,
1H), 6.26−6.14 (m, 1H), 4.16−4.13 (m, 1H), 4.10−4.07 (m, 1H),
2.99 (s, 1.8H), 2.96 (s, 1.2H), 2.12 (s, 1.8H), 2.11 (s, 1.2H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 170.7, 170.6, 137.7, 137.3,
131.1, 130.8, 130.5, 130.4, 130.1, 129.8, 129.7, 129.5, 129.3, 129.3,
127.5, 126.8, 118.6, 118.5, 112.8, 112.6, 52.3, 49.1, 35.7, 33.5, 21.7,
3994
https://dx.doi.org/10.1021/acs.joc.0c02837
J. Org. Chem. 2021, 86, 3989−3998

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(E)-5-(2-chlorostyryl)-1-methylpyrrolidin-2-one (3gb) was ob-
tained as pale-yellow oil (34.9 mg, 74%); purification by silica gel
chromatography (Rf = 0.18 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.55−7.46 (m, 1H), 7.37−7.34 (m, 1H), 7.25−
7.13 (m, 2H), 6.95 (d, J = 15.6 Hz, 1H), 5.99 (dd, J = 15.6, 8.6 Hz,
1H), 4.22−4.02 (m, 1H), 2.79 (s, 3H), 2.57−2.23 (m, 3H), 1.92−
1.77 (m, 1H). ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 175.0,
134.1, 133.1, 131.7, 129.8, 129.3), 129.1, 126.9, 126.9, 62.8, 29.9,
27.9, 25.5 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for
C13H15ClNO, 236.0837; found, 236.0840.
NMR (100 MHz, CDCl3-d): δ 174.9, 137.1, 131.8, 131.2, 130.5,
130.5, 129.9, 129.5, 118.4, 112.8, 62.5, 29.7, 28.0, 25.4 ppm. HRMS
(ESITOF) m/z: [M + H]+ calcd for C14H15N2O, 227.1179; found,
227.1176.
1
N-cinnamyl-N-methylformamide (3ac)10 was obtained as colorless
oil (17.9 mg, 51%); purification by silica gel chromatography (Rf =
1
0.36 eluent: PE/EA = 1:1); H NMR (400 MHz, CDCl3-d): δ 8.13
(d, J = 21.0 Hz, 1H), 7.41−7.24 (m, 5H), 6.54 (dd, J = 16.0, 4.4 Hz,
1H), 6.14−6.05 (m, 1H), 4.11 (d, J = 6.6 Hz, 1H), 4.00 (d, J = 6.2
Hz, 1H), 2.91 (d, J = 23.2 Hz, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3-d): δ 162.7, 162.3, 136.2, 135.8, 133.6, 128.7, 128.6, 128.1,
127.8, 126.4, 126.4, 123.9, 123.2, 51.6, 46.1, 34.1, 29.5 ppm.
(E)-5-(2-bromostyryl)-1-methylpyrrolidin-2-one (3hb) was ob-
tained as pale-yellow oil (43.7 mg, 78%); purification by silica gel
1
chromatography (Rf = 0.18 eluent: PE/EA = 1:1); H NMR (400
(E)-N-(3-(4-chlorophenyl)allyl)-N-methylformamide (3bc) was
obtained as colorless oil (22.2 mg, 53%); purification by silica gel
MHz, CDCl3): δ 7.59−7.44 (m, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.17−
7.07 (m, 1H), 6.91 (d, J = 15.6 Hz, 1H), 5.95 (dd, J = 15.6, 8.6 Hz,
1H), 4.22−4.02 (m, 1H), 2.80 (s, 3H), 2.51−2.27 (m, 3H), 1.91−
1.78 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 175.0,
135.9, 133.0, 131.9, 131.9, 129.4, 127.6, 127.1, 123.6, 62.7, 29.9,
278.0, 25.5 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for
C13H15BrNO, 280.0332; found, 280.0333.
1
chromatography (Rf = 0.29 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 8.12 (d, J = 18.0 Hz, 1H), 7.28 (s, 2H), 7.27 (s,
2H), 6.48 (dd, J = 16.0, 5.6 Hz, 1H), 6.12−6.02 (m, 1H), 4.12−4.06
(m, 1H), 4.01−3.95 (m, 1H), 2.93 (s, 1.4H), 2.87 (s, 1.6H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 162.7, 162.4, 134.7, 134.4,
133.8, 133.4, 132.3, 132.2, 128.8, 128.7, 127.6, 127.6, 124.6, 123.9,
51.5, 46.1, 34.2, 29.6 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd
for C11H13ClNO, 210.0680; found, 210.0676.
(E)-5-(2-fluorostyryl)-1-methylpyrrolidin-2-one (3ib) was ob-
tained as pale-yellow oil (35.1 mg, 80%); purification by silica gel
1
(E)-5-styrylpyrrolidin-2-one (3ad)9 was obtained as a white solid,
(33.3 mg, 89%); mp 71−75 °C; purification by silica gel
chromatography (Rf = 0.18 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.44 (d, J = 7.8 Hz, 1H), 7.29−7.19 (m, 1H),
7.15−7.00 (m, 2H), 6.71 (d, J = 15.8 Hz, 1H), 6.10 (dd, J = 15.8, 8.6
Hz, 1H), 4.13−4.07 (m, 1H), 2.78 (s, 3H), 2.54−2.25 (m, 3H),
1.89−1.78 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ
175.0, 161.5, 159.0, 131.6 (d, J = 5.0 Hz), 129.4 (d, J = 8.4 Hz), 127.6
(d, J = 3.5 Hz), 125.5 (d, J = 3.4 Hz), 124.2 (d, J = 3.6 Hz), 123.7 (d,
J = 12.2 Hz), 115.8 (d, J = 22.0 Hz), 63.2, 29.9, 27.9, 25.6. ppm.
HRMS (ESITOF) m/z: [M + H]+ calcd for C13H15FNO, 220.1132;
found, 220.1148.
1
chromatography (Rf = 0.25 eluent: PE/EA = 1:3); H NMR (400
MHz, CDCl3-d): δ 7.39−7.29 (m, 4H), 7.29−7.20 (m, 1H), 6.53 (d, J
= 15.8 Hz, 2H), 6.12 (dd, J = 15.8, 7.4 Hz, 1H), 4.32 (q, J = 6.4 Hz,
1H), 2.45−2.32 (m, 3H), 1.97−1.86 (m, 1H) ppm; 13C{1H} NMR
(100 MHz, CDCl3-d): δ 178.4, 136.0, 131.0, 129.8, 128.6, 127.9,
126.4, 56.5, 30.0, 28.4 ppm.
(E)-5-(4-chlorostyryl)pyrrolidin-2-one (3bd) was obtained as a
white solid (39.9 mg, 90%); mp 106−108 °C; purification by silica gel
1
(E)-5-(2-methoxystyryl)-1-methylpyrrolidin-2-one (3jb) was ob-
tained as pale-yellow oil (32.8 mg, 71%); purification by silica gel
chromatography (Rf = 0.29 eluent: PE/EA = 1:5); H NMR (400
MHz, CDCl3-d): δ 7.31−7.26 (m, 2H), 6.49 (d, J = 15.8 Hz, 1H),
6.25 (s, 1H), 6.10 (dd, J = 15.8, 7.2 Hz, 1H), 4.32 (q, J = 6.8 Hz, 1H),
2.47−2.30 (m, 3H), 2.00−1.84 (m, 1H) ppm; 13C{1H} NMR (100
MHz, CDCl3-d): δ 178.5, 134.5, 133.6, 130.5, 129.8, 128.8, 127.7,
56.4, 30.0, 28.3 ppm. HRMS (ESITOF) m/z: [M + Na]+ calcd for
C12H12ClNNaO, 244.0500; found, 244.0499.
(E)-4-(2-(5-oxopyrrolidin-2-yl)vinyl)benzonitrile (3ed) was ob-
tained as a white solid (35.7 mg, 84%); mp 73−76 °C; purification by
silica gel chromatography (Rf = 0.19 eluent: PE/EA = 1:3); 1H NMR
(400 MHz, CDCl3-d): δ 7.55 (d, J = 7.2 Hz, 2H), 7.41 (d, J = 8.0 Hz,
2H), 7.26 (s, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.25 (dd, J = 16.0 6.8
Hz, 1H), 4.40−4.29 (m, 1H), 2.45−2.28 (m, 3H), 1.89 (q, J = 8.8, 6.8
Hz, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 178.7, 140.6,
133.9, 132.3, 129.0, 126.9, 118.7, 110.9, 56.0, 29.8, 27.9 ppm. HRMS
(ESITOF) m/z: [M + H]+ calcd for C13H13N2O, 213.1022; found,
213.1021.
1
chromatography (Rf = 0.18 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.44−7.40 (m, 1H), 7.29−7.19 (m, 1H), 6.97−
6.84 (m, 3H), 6.02 (dd, J = 15.6, 8.7 Hz, 1H), 4.14−4.00 (m, 1H),
3.85 (s, 3H), 2.78 (s, 3H), 2.51−2.23 (m, 3H), 1.90−1.76 (m, 1H)
ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 175.0, 156.8, 129.4,
129.2, 127.9, 127.0, 124.8, 120.6, 110.9, 63.4, 55.4, 30.1, 27.8, 25.8
ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for C14H18NO2,
232.1332; found, 232.1321.
(E)-1-methyl-5-(4-methylstyryl)pyrrolidin-2-one (3kb) was ob-
tained as pale-yellow oil (33.6 mg, 78%); purification by silica gel
1
chromatography (Rf = 0.21 eluent: PE/EA = 1:1); H NMR (400
MHz, CDCl3-d): δ 7.27 (d, J = 8.2 Hz, 2H), 7.17−7.10 (m, 2H), 6.52
(d, J = 15.8 Hz, 1H), 5.95 (dd, J = 15.8, 8.4 Hz, 1H), 4.12−3.99 (m,
1H), 2.76 (s, 3H), 2.33 (d, J = 5.8 Hz, 6H), 1.88−1.73 (m, 1H) ppm;
13C{1H} NMR (100 MHz, CDCl3-d): δ 175.0, 138.0, 133.0, 132.8,
129.3, 127.7, 126.4, 63.0, 30.0, 27.8, 25.7, 21.1 ppm. HRMS
(ESITOF) m/z: [M + H]+ calcd for C14H18NO, 216.1383; found,
216.1380.
(E)-5-(2-bromostyryl)pyrrolidin-2-one (3hd) was obtained as
colorless oil (39.8 mg, 88%); purification by silica gel chromatography
1
(Rf = 0.18 eluent: PE/EA = 1:1); H NMR (400 MHz, CDCl3-d): δ
(E)-5-(3,4-dimethoxystyryl)-1-methylpyrrolidin-2-one (3lb) was
obtained as a pale-yellow solid (43.9 mg, 84%); mp 66−70 °C;
purification by silica gel chromatography (Rf = 0.18 eluent: PE/EA =
7.58−7.45 (m, 2H), 7.29 (d, J = 8.4 Hz, 1H), 7.17−7.08 (m, 1H),
6.89 (d, J = 15.8 Hz, 1H), 6.08 (dd, J = 15.8, 7.6 Hz, 1H), 5.91 (s,
1H), 4.44−4.34 (m, 1H), 2.48−2.33 (m, 3H), 2.02−1.90 (m, 1H)
ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 178.6, 135.9, 132.9,
132.7, 129.9, 129.2, 127.5, 127.1, 123.6, 56.4, 30.0, 28.2 ppm. HRMS
(ESITOF) m/z: [M + Na]+ calcd for C12H12BrNNaO, 287.9994;
found, 287.9998.
1
1:3); H NMR (400 MHz, CDCl3-d): δ 6.90 (d, J = 6.4 Hz, 2H),
6.82−6.78 (m, 1H), 6.47 (d, J = 15.6 Hz, 1H), 5.85 (dd, J = 16.0, 8.6
Hz, 1H), 4.09−3.99 (m, 1H), 3.88 (d, J = 1.2 Hz, 3H), 3.85 (d, J =
1.2 Hz, 3H), 2.75 (s, 3H), 2.48−2.23 (m, 3H), 1.87−1.74 (m, 1H)
ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 174.9, 149.1, 149.0,
132.6, 128.8, 126.7, 119.8, 111.0, 108.7, 62.9, 55.8, 55.8, 29.9, 27.8,
25.7 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for C15H20NO3,
262.1438; found, 262.1430.
(E)-3-(2-(1-methyl-5-oxopyrrolidin-2-yl)vinyl)benzonitrile (3mb)
was obtained as a pale-yellow solid (32.1 mg, 71%); mp 57−60 °C;
purification by silica gel chromatography (Rf = 0.18 eluent: PE/EA =
1:3); 1H NMR (400 MHz, CDCl3-d): δ 7.63 (s, 1H), 7.59 (d, J = 7.8
Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 6.53 (d, J
= 15.8 Hz, 1H), 6.10 (dd, J = 15.6, 8.2 Hz, 1H), 4.16−4.06 (m, 1H),
2.76 (s, 3H), 2.50−2.26 (m, 3H), 1.88−1.78 (m, 1H) ppm; 13C{1H}
(E)-5-(2-fluorostyryl)pyrrolidin-2-one (3id) was obtained as a
white solid (37.4 mg, 91%); mp 108−111 °C; purification by silica gel
1
chromatography (Rf = 0.27 eluent: PE/EA = 1:3); H NMR (400
MHz, CDCl3-d): δ 7.45−7.37 (m, 1H), 7.24−7.16 (m, 1H), 7.12−
6.97 (m, 2H), 6.67 (d, J = 16.0 Hz, 2H), 6.21 (dd, J = 16.0, 7.4 Hz,
1H), 4.37−4.30 (m, 1H), 2.45−2.30 (m, 3H), 1.92 (d, J = 4.2 Hz,
1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 178.4, 161.4,
159.0, 132.6 (d, J = 5.0 Hz), 129.2 (d, J = 8.4 Hz), 127.5 (d, J = 3.6
Hz), 124.1 (d, J = 3.6 Hz), 123.8 (d, J = 12.1 Hz), 123.5, 115.7 (d, J =
22.1 Hz), 56.7, 29.9, 28.3 ppm. HRMS (ESITOF) m/z: [M + H]+
calcd for C12H13FNO, 206.0976; found, 206.0972.
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Article
(E)-5-(2-methoxystyryl)pyrrolidin-2-one (3jd) was obtained as
pale-yellow oil (33.5 mg, 77%); purification by silica gel
chromatography (Rf = 0.13 eluent: PE/EA = 1:1); H NMR (400
chromatography (Rf = 0.09 eluent: PE/EA = 3:1); the ratio of vinyl/
allyl is about 0.62:0.38; 1H NMR (400 MHz, CDCl3-d): δ 7.35 (d, J =
8.2 Hz, 0.7H), 7.28 (m, 2.5H), 7.14 (q, J = 8.7, 7.9 Hz, 3.2H), 5.73−
5.63 (m, 1H), 5.36−5.33 (m, 0.6H), 5.06 (s, 0.6H), 4.20 (d, J = 7.0
Hz, 1H), 4.07 (d, J = 6.4 Hz, 1H), 3.47−3.41 (m, 0.6H), 3.38−3.32
(m, 0.6H), 2.96 (d, J = 7.5 Hz, 3H), 2.91 (d, J = 1.6 Hz, 1.8H), 2.78−
2.70 (m, 1.2H), 2.37−2.31 (m, 4.8H), 2.12 (d, J = 13.0 Hz, 3H),
2.09−2.06 (m, 3H), 2.03 (s, 0.8H), 1.92 (s, 1H) ppm; 13C{1H} NMR
(100 MHz, CDCl3-d): δ 170.4, 170.3, 145.4, 144.3, 139.9, 139.5,
138.3, 138.1, 137.7, 137.3, 136.9, 129.3, 129.1, 129.0, 128.9, 125.8,
125.7, 125.5, 125.5, 122.1, 121.8, 114.1, 113.1, 49.7, 49.2, 47.7, 45.0,
37.0, 35.4, 34.2, 33.2, 33.1, 33.0, 21.9, 21.8, 21.5, 21.1, 21.1, 21.0,
21.0, 16.0, 15.9 ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for
C14H20NO, 218.1539; found, 218.1539.
1
MHz, CDCl3-d): δ 7.40 (d, J = 6.0 Hz, 1H), 7.28−7.19 (m, 1H),
6.94−6.80 (m, 3H), 6.13 (dd, J = 16.0, 7.6 Hz, 1H), 6.04 (s, 1H),
4.39−4.27 (m, 1H), 3.84 (s, 3H), 2.45−2.31 (m, 3H), 2.00−1.87 (m,
1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 178.2, 156.7,
130.4, 129.1, 127.0, 126.1, 124.9, 120.6, 110.8, 57.0, 55.4, 30.0, 28.6
ppm. HRMS (ESITOF) m/z: [M + H]+ calcd for C13H16NO2,
218.1176; found, 218.1152.
(E)-N-methyl-N-(3-phenylbut-2-en-1-yl)acetamide (5a) was ob-
tained as colorless oil (35.8 mg, 88%); purification by silica gel
chromatography (Rf = 0.08 eluent: PE/EA = 3:1); the ratio of vinyl/
allyl is about 0.86:0.14; 1H NMR (400 MHz, CDCl3-d): δ 7.48−7.26
(m, 5.6H), 5.75−5.66 (m, 1H), 5.38−5.35 (m, 0.2H), 5.11 (s, 0.2H),
4.21 (d, J = 6.9 Hz, 1H), 4.08 (d, J = 6.5 Hz, 1H), 3.49−3.43 (m,
0.2H), 3.39−3.34 (m, 0.2H), 2.97 (d, J = 9.2 Hz, 3H), 2.91 (s, 0.5H),
2.78 (s, 0.4H), 2.15−2.07 (m, 6H), 2.02 (s, 0.3H), 1.91 (s, 0.3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 170.4, 142.9, 142.4,
138.5, 138.4, 128.6, 128.4, 128.2, 127.5, 127.1, 125.9, 125.9, 125.7,
125.6, 123.0, 122.6, 49.2, 45.1, 35.4, 33.2, 21.8, 21.5, 16.0, 15.9 ppm.
HRMS (ESITOF) m/z: [M + H]+ calcd for C3H18NO, 204.1383;
found, 204.1384.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02837.
■
sı
Optimization of the reaction Conditions for α-alkyl
nitroalkenes, vinyl sulfones, and cinnamic acids with
DMA, coupling constants of all compounds, ratio of
vinyl/allyl of compounds 5, and 1H and 13C NMR
spectra (PDF)
(E)-N-(3-(3-bromophenyl)but-2-en-1-yl)-N-methylacetamide (5b)
was obtained as colorless oil (48.5 mg, 86%); purification by silica gel
chromatography (Rf = 0.08 eluent: PE/EA = 3:1); ratio of vinyl/allyl
1
is about 0.52:0.48; H NMR (400 MHz, CDCl3-d): δ 7.60−7.46 (m,
2H), 7.44−7.27 (m, 4H), 7.25−7.13 (m, 2H), 5.75−5.64 (m, 1H),
5.36 (d, J = 10.8 Hz, 0.9H), 5.13 (s, 0.9H), 4.18 (d, J = 6.9 Hz, 1H),
4.06 (d, J = 6.4 Hz, 1H), 3.46−3.41 (m, 1H), 3.37−3.32 (m, 0.8H),
2.96 (d, J = 14.3 Hz, 3H), 2.90 (d, J = 7.1 Hz, 2.7H), 2.76−2.68 (m,
2H), 2.11 (d, J = 9.5 Hz, 3H), 2.06 (s, 3H), 2.02 (s, 1.8H), 1.92 (s,
1H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 170.4, 170.4,
144.9, 144.3, 143.3, 142.6, 142.0, 137.1, 130.8, 130.4, 130.3, 130.1,
130.0, 129.9, 129.8, 129.7, 129.0, 128.8, 124.6, 124.4, 124.3, 124.2,
123.9, 122.8, 122.5, 122.4, 116.1, 115.1, 49.5, 49.1, 47.4, 45.1, 36.8,
35.6, 34.0, 33.2, 33.1, 32.7, 21.8, 21.8, 21.5, 21.0, 16.0, 15.8 ppm.
HRMS (ESITOF) m/z: [M + Na]+ calcd for C13H16BrNNaO,
304.0307; found, 304.0307.
AUTHOR INFORMATION
Corresponding Author
■
Yunfeng Chen − School of Chemistry and Environmental
Engineering, Wuhan Institute of Technology, Wuhan 430205,
P. R. China; orcid.org/0000-0002-6220-5015;
Email: yfchen@wit.edu.cn
Authors
Miaomiao Li − School of Chemistry and Environmental
Engineering, Wuhan Institute of Technology, Wuhan
430205, P. R. China
(E)-N-(3-(4-fluorophenyl)but-2-en-1-yl)-N-methylacetamide (5c)
was obtained as colorless oil (36.7 mg, 83%); purification by silica gel
chromatography (Rf = 0.06 eluent: PE/EA = 3:1); the ratio of vinyl/
allyl is about 0.70:0.30; 1H NMR (400 MHz, CDCl3-d): δ 7.45−7.39
(m, 0.8H), 7.33 (m, 2.4H), 7.04−6.96 (m, 3H), 5.69−5.58 (m, 1H),
5.29 (d, J = 1.2 Hz, 0.4H), 5.09 (d, J = 4.2 Hz, 0.4H), 4.18 (d, J = 7.0
Hz, 1H), 4.09−4.02 (m, 1H), 3.49−3.29 (m, 0.8H), 2.98 (s, 2H),
2.94 (s, 1H), 2.90 (d, J = 9.9 Hz, 1.2H), 2.77−2.65 (m, 0.8H), 2.13
(s, 1.3H), 2.10 (s, 1.7H), 2.08−2.06 (m, 3H), 2.02 (s, 0.6H), 1.90 (s,
0.6H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 170.5, 163.2,
160.8, 137.4, 127.6, 127.5, 127.2 (d, J = 1.5 Hz), 127.1 (d, J = 1.5
Hz), 122.8, 122.4, 115.3, 115.2, 115.1, 115.0 (d, J = 1.9 Hz), 114.8,
83.8, 49.1, 47.6, 45.2, 36.8, 35.5, 34.2, 33.7, 33.2, 33.0, 21.8, 21.7,
21.4, 16.2, 16.0 ppm. HRMS (ESITOF) m/z: [M + Na]+ calcd for
C13H16FNNaO, 244.1108; found, 244.1108.
(E)-N-(3-(4-bromophenyl)but-2-en-1-yl)-N-methylacetamide (5d)
was obtained as colorless oil (46.3 mg, 82%); purification by silica gel
chromatography (Rf = 0.06 eluent: PE/EA = 3:1); the ratio of vinyl/
allyl is about 0.85:0.15; 1H NMR (400 MHz, CDCl3-d): δ 7.49−7.38
(m, 2.4H), 7.32 (d, J = 8.6 Hz, 0.2H), 7.27−7.22 (m, 2.3 H), 5.74−
5.63 (m, 1H), 5.35 (d, J = 9.1 Hz, 0.2H), 5.15−5.11 (m, 0.2H), 4.18
(d, J = 6.9 Hz, 1H), 4.05 (d, J = 6.4 Hz, 1H), 3.46−3.38 (m, 0.2H),
3.37−3.31 (m, 0.2H), 2.96 (d, J = 14.0 Hz, 3H), 2.90 (d, J = 9.7 Hz,
0.6H), 2.75−2.65 (m, 0.4H), 2.15−2.04 (m, 6H), 1.98 (s, 0.4H), 1.91
(s, 0.2H) ppm; 13C{1H} NMR (100 MHz, CDCl3-d): δ 170.4, 141.7,
141.2, 137.3, 131.7, 131.4, 131.4, 131.2, 127.6, 127.5, 127.3, 127.3,
123.6, 123.2, 121.4, 121.0, 35.6, 33.2, 21.8, 21.5, 15.9, 15.8 ppm.
HRMS (ESITOF) m/z: [M + Na]+ calcd for C13H16BrNNaO,
304.0307; found, 304.0307.
Lei Zheng − School of Chemistry and Environmental
Engineering, Wuhan Institute of Technology, Wuhan
430205, P. R. China
Li Ma − School of Chemistry and Environmental Engineering,
Wuhan Institute of Technology, Wuhan 430205, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02837
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (21002076), the Scientific Research Foundation for the
Returned Overseas Chinese Scholars for financial support. We
also thank Graduate Innovative Fund of Wuhan Institute of
Technology (CX2019165) for support.
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