Direct oxidative coupling of: N -acyl pyrroles with alkenes by ruthenium(ii)-catalyzed regioselective C2-alkenylation

Article abstract of DOI:10.1039/c9ob02421b

Ruthenium(ii)-catalyzed oxidative coupling by C2-alkenylation of N-acyl pyrroles with alkenes has been described. The acyl unit was found to be an effective chelating group for the activation of aryl C-H bonds ortho to the directing group. The alkenylation reaction of benzoyl pyrroles occurred regioselectively at the C2-position of the pyrrole ring, without touching the benzene ring. The reaction provides exclusively monosubstituted pyrroles under the optimized conditions. Disubstituted pyrroles could be obtained using higher loadings of the ruthenium(ii)-catalyst and the additives.

Full text of DOI:10.1039/c9ob02421b

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Direct oxidative coupling of N-acyl pyrroles with
alkenes by ruthenium(II)-catalyzed regioselective
Cite this: DOI: 10.1039/c9ob02421b
C2-alkenylation†
a,b
Weiqiang Chen,a Hui-Jing Li,*a,b Qin-Ying Lia,b and Yan-Chao Wu
*
Ruthenium(II)-catalyzed oxidative coupling by C2-alkenylation of N-acyl pyrroles with alkenes has been
described. The acyl unit was found to be an effective chelating group for the activation of aryl C–H bonds
ortho to the directing group. The alkenylation reaction of benzoyl pyrroles occurred regioselectively at
the C2-position of the pyrrole ring, without touching the benzene ring. The reaction provides exclusively
monosubstituted pyrroles under the optimized conditions. Disubstituted pyrroles could be obtained using
higher loadings of the ruthenium(II)-catalyst and the additives.
Received 9th November 2019,
Accepted 11th December 2019
DOI: 10.1039/c9ob02421b
rsc.li/obc
lyzed C2-alkenylation of unactivated indoles and pyrroles uti-
lizing hydroxy as a directing group.11d Meanwhile, aromatic
Introduction
Over the past few decades, transition-metal-catalyzed organic esters, aryl ketones, benzamides and acylsilanes were also
reactions through C–H bond cleavage have received consider- employed as chelating groups for the activation of aryl C–H
able interest1–4 as a powerful and straightforward approach for bonds at the ortho position under ruthenium or rhodium cata-
their synthetic applications in materials science,5 natural pro- lysis, according to ref. 12 and based on other reports.13 Prabhu
ducts and pharmaceuticals.6 Employing transition-metal-cata- reported a regioselective alkenylation of indole derivatives at
lyzed C–H activation in the synthesis of vinylarene derivatives the C2-position using the benzoyl group as a directing
has attracted much attention in recent years. Considering the group.14 Given the importance of the acyl group, which
subtle differences in the intrinsic reactivity of C–H bonds at behaves as
a directing group for ruthenium(II)-catalyzed
different positions of pyrroles, common solutions for control- functionalization, for the different behaviours of the directing
ling regioselectivity involve optimizing the electronic/steric groups,15 another very attractive platform for developing a new
properties,7 solvents,8 ligands,9 and directing groups.10,11 selective C–H activation strategy is the N-acyl pyrrole skeleton,
Among these protocols, utilization of the proximate effect by which widely exists in natural products and biomolecules
coordination of a functional group to the metal center is often
used as a promising activation strategy to achieve regio-
selective C–H bond functionalizations at the ortho-position.
For pyrrole derivatives, the use of directing groups on the
nitrogen atom has been effective for C2-alkenylation
(Scheme 1a). Carretero reported an efficient palladium(II)-cata-
lyzed regioselective C2-alkenylation of pyrroles bearing an N-
(2-pyridyl)sulfonyl protecting group.11a Song and Wang devel-
oped a selective ruthenium(II)-catalyzed direct C2-alkenylation
of indoles and pyrroles assisted by an N-dimethylcarbamoyl
group.11b,c Shortly afterwards, Sha reported a rhodium(III)-cata-
aSchool of Marine Science and Technology, Harbin Institute of Technology,
2 Weihai Road, Weihai 264209, P. R. China. E-mail: ycwu@iccas.ac.cn
bWeihai Institute of Marine Biomedical Industrial Technology, Wendeng District,
Weihai 264400, P. R. China
†Electronic supplementary information (ESI) available: Experimental pro-
cedures, characterization data, and copies of NMR spectra. CCDC 1915043. For
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c9ob02421b
Scheme 1 Directing
alkenylation.
group-controlled
regioselectivity
in
C2-
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Table 1 Optimization of the reaction conditions for 3aaa
Yieldb
(%)
Entry
[Ru] Cat.
Additive
Oxidant
1
2
3
4
5
6
7
Ru(PPh3)3Cl2
RuH2(PPh3)4
Ru(COD)Cl2
Ru3(CO)12
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
0
0
0
0
[RuCl2(CO)3]2
16
29
0
[RuCl2(p-cymene)]2
RuCl[(R,R)-Tsdpen]
(p-cymene)
Fig. 1 Selected medicinal and bioactive molecules containing N-acyl
pyrrole skeletons.
8
9
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
K2S2O8
PhI(OAc)2
<5
12
66
81
18
0
26
21
45
<5
69
0
10
11
12
13
14
15
16
17
18c
19
20
AgOTf
AgSbF6
Ag2CO3
AgNO3
Ag3PO4
AgF
AgBF4
AgOAc
AgSbF6
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
(Fig. 1),16 and organic compounds containing such pyrrole
functional groups are used in various organic reactions.17 In
light of the recent work on C–H functionalization under ruthe-
nium catalysis, it is highly desirable to extend the approach to
ruthenium-catalyzed C–H activation processes. With this back-
ground and based on previous reports on ruthenium catalysis,
we wanted to know whether the ruthenium-catalyzed oxidative
C2-alkenylation of benzoyl pyrroles takes place on the pyrrole
or benzene rings. We would like to report herein that the
above C2-alkenylation reaction occurred only on the pyrrole
rings and not on the benzene rings (Scheme 1b).
AgSbF6
Cu(OAc)2·H2O
0
a General conditions: [Ru] Cat. (0.01 mmol), additive (0.02 mmol),
oxidant (0.20 mmol), N-acyl pyrrole (1a, 0.20 mmol), and alkene (2a,
0.40 mmol) in toluene (2.0 mL) at 110 °C for 24 h under an argon
atmosphere (1 atm). b Isolated yields. c [Ru] Cat. (0.01 mmol), additive
(0.02 mmol), oxidant (0.30 mmol), in toluene (2.0 mL) at 110 °C for
24 h under an argon atmosphere (1 atm).
Results and discussion
The reaction of phenyl(1H-pyrrol-1-yl)methanone (1a) with
butyl acrylate (2a) was used as a probe for evaluating the reac- slightly decreased when the loading of Cu(OAc)2·H2O was
tion conditions, and the representative results are summarized increased from 1.0 equiv. to 1.5 equiv. (entry 18). In addition,
in Table 1. Initially, substrates 1a and 2a were reacted in the when substrates 1a and 2a were reacted in the presence of
presence of different ruthenium catalysts (0.05 equiv.) and Cu [RuCl2(p-cymene)]2 or a mixture of AgSbF6 and Cu(OAc)2·H2O,
(OAc)2·H2O (1.0 equiv.) in toluene at 110 °C for 24 h under an no C2-alkenylation product 3aa was obtained (entries 19 and
argon atmosphere (1 atm). No C2-alkenylation product 3aa was 20). However, AgSbF6 was chosen as the additive in our investi-
obtained with the use of Ru(PPh3)3Cl2, RuH2(PPh3)4, Ru(COD) gations because it gave the best yield. Therefore, the optimal
Cl2, Ru3(CO)12, and RuCl[(R,R)-Tsdpen](p-cymene) as the cata- reaction conditions were determined to be [RuCl2(p-cymene)]2
lyst in combination with Cu(OAc)2·H2O (entries 1–4, and 7). (0.05 equiv.), AgSbF6 (0.10 equiv.), and Cu(OAc)2·H2O (1.0
When [RuCl2(CO)3]2 and [RuCl2(p-cymene)]2 were used as the equiv.) in toluene at 110 °C for 24 h under an argon atmo-
catalyst under the same conditions, C2-alkenylation product sphere (1 atm).
3aa was obtained in 16% and 29% yields, respectively (entries
After establishing the optimal reaction conditions, the
5 and 6). Furthermore, other oxidants such as K2S2O8 and PhI scope and limitation of this ruthenium(II)-catalyzed direct oxi-
(OAc)2 did not promote the reaction (entries 8 and 9). In order dative C2-alkenylation reaction was subsequently investigated,
to further increase the yield, various silver salts were tested as and the representative results are summarized in Table 2.
additives in combination with [RuCl2(p-cymene)]2 and Cu Alkenes 2a–d reacted well with phenyl(1H-pyrrol-1-yl)metha-
(OAc)2·H2O under otherwise identical conditions. The C2-alke- none (1a) in the presence of [RuCl2(p-cymene)]2 (0.05 equiv.),
nylation product 3aa was obtained in low yields with the use of AgSbF6 (0.10 equiv.), and Cu(OAc)2·H2O (1.0 equiv.) in toluene
Ag2CO3, Ag3PO4, AgF, and AgOAc as the additives (entries 12, at 110 °C for 24 h under an argon atmosphere (1 atm) to afford
14, 15, and 17). No conversion was observed when AgNO3 was exclusively the C2-alkenylation products 3aa–ad in 71–81%
employed (entry 13). In contrast, AgOTf, AgSbF6 and AgBF4 yields. The C2-alkenylation product 3ae was obtained in only a
were the relatively effective additives for this oxidative coupling moderate yield with the use of a relatively sterically hindered
by C–H alkenylation (entries 10, 11, and 16). The yield of 3aa alkene 2e as the substrate, indicating that the steric factor may
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Table 2 Evaluation of alkenes for the C2-alkenylation reactiona,b
C2-alkenylation products 3an and 3ao in satisfactory yields.
When alkene 2p was reacted with phenyl(1H-pyrrol-1-yl)metha-
none (1a), C2-alkenylation product 3ap was not obtained
under the standard conditions.
Interestingly, 1,4-addition product 4aq was obtained in 56%
yield by treating N-acyl pyrrole 1a with pent-1-en-3-one (2q)
under the above-mentioned standard conditions (Scheme 2).
When the reaction was performed in the absence of [RuCl2(p-
cymene)]2, under otherwise same conditions, 1,4-addition
product 4aq was obtained only in trace amounts, indicating
that the transformation occurs via a transition-metal-mediated
C–H activation reaction. α,β-Unsaturated ketone 2r reacted
uneventfully with N-acyl pyrrole 1a to afford adduct 4ar in 51%
yield. When a deactivated α,β-unsaturated ketone 2s was used,
trace amounts of 1,4-addition product 4as were obtained and
the starting materials were recovered.18
Next, the scope of the direct oxidative alkenylation of differ-
ently substituted N-acyl pyrroles 1 was investigated, and the
results are shown in Table 3. This coupling reaction turned
out to be a versatile reaction, as the alkenylation could tolerate
various functional groups. N-Acyl pyrroles 1b–d, each bearing
an electron-donating group, smoothly underwent oxidative
coupling by the alkenylation reaction in the presence of
[RuCl2(p-cymene)]2 (0.05 equiv.), AgSbF6 (0.10 equiv.), and Cu
(OAc)2·H2O (1.0 equiv.) in toluene at 110 °C for 24 h under an
argon atmosphere (1 atm) to generate C2-alkenylation products
3ba–da in 69%–73% yields. With their meta/para-position
bearing sensitive functional groups such as I, Br, Cl and F,
N-acyl pyrroles 1e–i were well-tolerated substrates for the oxi-
a General conditions: [RuCl2(p-cymene)]2 (0.01 mmol), AgSbF6
(0.02 mmol), Cu(OAc)2·H2O (0.20 mmol,), phenyl(1H-pyrrol-1-yl)metha-
none (1a, 0.20 mmol), and alkene (2a, 0.40 mmol) in toluene (2.0 mL)
at 110 °C for 24 h under an argon atmosphere (1 atm). b Isolated
yields.
effect the complexation of the double bond to the metal
center. Alkenes 2f and 2g reacted with 1a under the standard
conditions to give C2-alkenylation products 3af and 3ag in
69% and 66% yields, respectively. Some other types of alkenes
2h–l have also been investigated, and the C2-alkenylation pro-
ducts 3ah–al were obtained in moderate to good yields under
the standard reaction conditions. Unfortunately, the reaction
was complex when styrene (2m) was used as the substrate, and
the expected pyrrole product was not obtained, indicating that
non-activated styrene derivatives are not suitable substrates.
Electrophilic alkenes including sulfone, nitrile, and phospho-
nate were investigated next, and alkenes 2n and 2o reacted
Scheme 2 1,4-Addition reaction of N-acyl pyrrole 1a with
smoothly with phenyl(1H-pyrrol-1-yl)methanone (1a) to give α,β-unsaturated ketones 2q–s.
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Table 3 Evaluation of N-acyl pyrroles for the C2-alkenylation
reactiona,b
standard conditions, C2-alkenylation product 3qa was
obtained exclusively. 2,3,4-Trisubstituted pyrrole 1r has also
been investigated, which reacted with 2a to give C2-alkenyla-
tion product 3ra in 73% yield, without being influenced by the
steric factor effect.
To our delight, when alkene 2a reacted with cyclohexyl(1H-
pyrrol-1-yl)methanone (1s) under the optimized reaction con-
ditions, the desired C2-alkenylation product 3sa was obtained
in 71% yield (Scheme 3), indicating the great synthetic value of
this protocol. Subsequently, several other N-acyl pyrroles 1t–v
were also investigated, affording C2-alkenylation products 3ta–
va in good yields.
To further evaluate the regioselectivity of the C2-alkenyla-
tion reaction, 2,5-disubstituted N-acyl pyrrole 1w was subjected
to the procedure and no reaction occurred, reflecting an excel-
lent regioselectivity of the alkenylation at the pyrrole C2-posi-
tion (Scheme 4). The product outcome of the catalysis indi-
cates that the C–H bond functionalization occurring in pyrrole
is due to the fact that the C–H bond in the pyrrole ring is more
acidic than in the benzene ring.19
The C2,C5-double alkenylated product 6aa was also
obtained in 61% yield using higher loadings of [RuCl2(p-
cymene)]2, AgSbF6 and Cu(OAc)2·H2O (i.e., 10 mol% versus
5 mol%, 20 mol% versus 10 mol%, and 2.0 equiv. versus 1.0
equiv., respectively, Scheme 5 and Table 2). We were pleased to
find that the current catalytic system could be successfully
applied to N-benzoyl indole (Scheme 6). Under the optimized
conditions, indole cleanly produced the C2-alkenylation
product 8aa in 80% yield.
To demonstrate the further utility of our synthesis, we
attempted elaboration of the alkenylated product 3ab. As can
a General conditions: [RuCl2(p-cymene)]2 (0.01 mmol), AgSbF6
(0.02 mmol), Cu(OAc)2·H2O (0.20 mmol), N-acyl pyrrole (1a,
0.20 mmol), and alkene (2a, 0.40 mmol) in toluene (2.0 mL) at 110 °C
for 24 h under an argon atmosphere (1 atm). b Isolated yields.
dative alkenylation reaction to afford C2-alkenylation products
3ea–ia in good yields. The reaction of butyl acrylate (2a) with
N-acyl pyrroles 1j and 1k, each bearing an electron-withdraw-
ing group, CF3 or NO2, on the aromatic ring proceeded well
under the standard conditions to generate C2-alkenylation pro-
ducts 3ja and 3ka in 76% and 79% yields, respectively. N-Acyl
pyrroles 1l and 1m, each bearing a naphthyl group, reacted
smoothly with butyl acrylate (2a) to give C2-alkenylation pro-
ducts 3la and 3ma in 74% and 73% yields, respectively. From
the experimental results, it was found that electron-withdraw-
ing or electron-donating groups on the benzene ring do not
have a significant impact on the reactivity. Thiophene- and
furan-containing N-acyl pyrroles 1n and 1o have also been
investigated, and only substrate 1n could convert to the corres-
ponding product 3na in a low yield. The reaction of butyl acry-
late (2a) with 2-substituted pyrrole 1p proceeded well under
the standard conditions to generate C2-alkenylation product
3pa in 75% yield, and no C4-alkenylation product was
Scheme 3 Substrate scope with respect to N-acyl pyrroles.
Scheme 4 Investigation of the alkenylation reaction of 2,5-di-
obtained. When 2,3-disubstituted pyrrole 1q was subjected to substituted N-acyl pyrrole 1w with alkene 2a.
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Scheme 5 The coupling of pyrrole 1a with butyl acrylate (2a).
Scheme 6 The coupling of indole 7 with butyl acrylate (2a).
Scheme 7 Deprotection and hydrolysis of the C2-alkenylation product
3ab.
Scheme 8 Verification experiments.
On the basis of these experimental results and previous
reports,10–15,21 a plausible mechanism for oxidative coupling
by the C2-alkenylation reaction of N-acyl pyrroles 1 with
alkenes 2 is illustrated in Scheme 9. First, the catalytically
active species [Ru(OAc)(L)][SbF6] is generated from the reaction
of [RuCl2(p-cymene)]2, AgSbF6 and Cu(OAc)2·H2O by the elim-
be seen from Scheme 7, deprotection and hydrolysis was
readily achieved by heating 3ab with NaOH to furnish the
debenzoylated pyrrole derivative of acrylic acid 9. This product
9 is a very useful intermediate, which can be transformed into
a variety of bioactive molecules.20
The reaction mechanism of this oxidative coupling by the
C2-alkenylation reaction was studied next, and the representa-
tive results are illustrated in Scheme 8. In order to check
whether the reaction was a Friedel–Crafts alkylation or not,
phenyl(1H-pyrrol-1-yl)methanone (1a) was reacted with butyl
acrylate (2a) in the presence of AlCl3, H2SO4, or In(OTf)3 (0.50
equiv.) in toluene at 110 °C for 6 h under an argon atmosphere
(1 atm), but C2-alkenylation product 3aa was not obtained
(Scheme 8a). When 1-benzyl-1H-pyrrole 10 was reacted with
butyl acrylate (2a) under standard conditions, no reaction
occurred, indicating that the mechanism is chelation-con-
trolled with an acyl unit as the directing group (Scheme 8b).
The inter-molecular competition experiment was also con-
ducted using different pyrroles 1a and 1q. Alkenylation of 1a
and 1q with alkene 2a in a one-pot fashion revealed the elec-
tron-rich substrate 1a to be preferentially functionalized
(Scheme 8c), which is in good agreement with the electrophilic
activation mode. Considering the remarkable activity of the
cationic ruthenium(II) catalyst, its mode of action in this alke-
nylation reaction was studied next. When N-acyl pyrrole 1a was
subjected to standard conditions in the presence of D2O, H/D
scrambling was observed in 1a, thereby indicating a reversible
C–H cyclometalation reaction (Scheme 8d).
Scheme 9 Mechanism for the oxidative coupling by C2-alkenylation of
N-acyl pyrroles with alkenes.
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ination of chloride ions. Intramolecular C–H bond activation The reaction mixture was then diluted with Et2O, washed with
at the ortho-position of the pyrrole ring occurs to give a five- 1 M HCl (30 mL), saturated aqueous NaHCO3 (30 mL) and
membered ruthenacycle intermediate A accompanied by the brine (30 mL), dried over Na2SO4 and filtered. The volatiles
release of acetic acid. The coordination of the intermediate A were removed in vacuo and the residue was subjected to flash
with alkene 2 produces intermediate B, and further intra- column chromatography to give N-acyl pyrroles.
molecular insertion of alkene 2 into the Ru–C bond generates
Phenyl(1H-pyrrol-1-yl)methanone (1a). Synthesis was carried
intermediate C. Subsequently, β-hydride elimination of the out according to the general procedure, and compound 1a was
intermediate C occurs to give the desired C2-alkenylation obtained in 91% yield as a yellow oil after purification by silica
product 3. Finally, a catalytically active species is regenerated gel column chromatography. 1H NMR (400 MHz, CDCl3)
in the presence of a copper(II) salt, which is then used in δ (ppm): 7.75 (d, J = 7.6 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.51 (t,
another catalytic cycle.
J = 7.4 Hz, 2H), 7.29 (d, J = 1.6 Hz, 2H), 6.35 (d, J = 1.6 Hz, 2H).
13C NMR (100 MHz, CDCl3) δ (ppm): 167.7, 133.2, 132.2,
129.4, 128.4, 121.2, 113.1. These spectral data correspond to
previously reported data.22a
(4-Ethylphenyl)(1H-pyrrol-1-yl)methanone (1b). Synthesis
was carried out according to the general procedure, and com-
pound 1b was obtained in 90% yield as a yellowish oil after
purification by silica gel column chromatography. 1H NMR
(400 MHz, CDCl3) δ (ppm): 7.69 (d, J = 7.6 Hz, 2H), 7.34–7.30
(m, 4H), 6.34 (s, 2H), 2.75 (q, J = 7.4 Hz, 2H), 1.29 (t, J = 7.4 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 167.7, 149.2, 130.5,
129.8, 127.9, 121.3, 112.9, 28.9, 15.2. These spectral data
correspond to previously reported data.22c
(4-Methoxyphenyl)(1H-pyrrol-1-yl)methanone (1c). Synthesis
was carried out according to the general procedure, and com-
pound 1c was obtained in 93% yield as a yellowish oil after
purification by silica gel column chromatography. 1H NMR
(400 MHz, CDCl3) δ (ppm): 7.76 (d, J = 8.4 Hz, 2H), 7.29 (t, J =
2.0 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 6.34 (t, J = 2.0 Hz, 2H),
3.89 (s, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 167.1, 163.0,
132.0, 125.2, 121.3, 113.8, 112.7, 55.5. These spectral data
correspond to previously reported data.22b
(1H-Pyrrol-1-yl)(o-tolyl)methanone (1d). Synthesis was
carried out according to the general procedure, and compound
1d was obtained in 90% yield as a yellowish oil after purifi-
cation by silica gel column chromatography. 1H NMR
(400 MHz, CDCl3) δ (ppm): 7.44–7.39 (m, 2H), 7.30 (t, J =
6.6 Hz, 2H), 7.15 (s, 2H), 6.31 (d, J = 1.2 Hz, 2H), 2.34 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm): 168.2, 136.4, 133.7, 130.8,
130.7, 127.8, 125.5, 120.6, 113.4, 19.3. These spectral data
correspond to previously reported data.22b
Conclusions
In summary, we have developed a ruthenium(II)-catalyzed
regioselective C–H activation of the pyrrole C2-position with
alkenes leading to the formation of 2-substituted alkenylation
pyrrole derivatives. The regioselectivity of the current alkenyla-
tion reaction has been achieved by employing acyl as the
directing group. This protocol provides a straightforward
method for the preparation of valuable vinyl pyrroles, a struc-
tural motif for a large number of functional materials, natural
products, and biomolecules. Further mechanistic investi-
gations on the applications of this method are in progress.
Experimental
General information
All reactions were carried out under an argon atmosphere
unless otherwise noted. Dichloromethane and toluene were
distilled prior to use under a nitrogen atmosphere. Silica gel
(200–300 mesh) was used for flash chromatography. N-acyl pyr-
roles were prepared according to the literature procedures.1
Formyl chloride, alkenes, and other reagents were purchased
from commercial sources and used directly. High-resolution
mass spectra (HRMS) were recorded using an Electrothermal
LTQ-Orbitrap mass spectrometer. Melting points were
measured using Gongyi X-5 microscopy digital melting point
apparatus and were uncorrected. H and 13C-NMR spectra were
1
recorded with a Bruker Avance III 400 MHz NMR spectrometer
with CDCl3 as the solvent. The chemical shifts are reported in
ppm relative to CDCl3 (δ = 7.26) for1H NMR and relative to the
central CDCl3 resonance (δ = 77.0) for 13C NMR. Coupling con-
stants (J) are quoted in Hz. NMR data of the known compounds
are in agreement with the literature values. Multiplicities are
reported as follows: singlet (s), doublet (d), doublet of doublets
(dd), triplet (t), quartet (q), and multiplet (m).
(4-Iodophenyl)(1H-pyrrol-1-yl)methanone (1e). Synthesis was
carried out according to the general procedure, and compound
1e was obtained in 87% yield as a white solid after purification
1
by silica gel column chromatography. mp 69–70 °C. H NMR
(400 MHz, CDCl3) δ (ppm): 7.87 (d, J = 8.4 Hz, 2H), 7.47 (d, J =
8.4 Hz, 2H), 7.25 (t, J = 1.8 Hz, 2H), 6.36 (t, J = 2.2 Hz, 2H).
13C NMR (100 MHz, CDCl3) δ (ppm): 166.9, 137.7, 132.5, 130.9,
121.1, 113.4, 99.6. These spectral data correspond to previously
reported data.22d
General procedure for the synthesis of N-acyl pyrroles22
(4-Bromophenyl)(1H-pyrrol-1-yl)methanone (1f). Synthesis
Benzoyl chloride (20.0 mmol) was added dropwise to a stirred was carried out according to the general procedure, and com-
solution of pyrrole (1.71 g, 25.6 mmol), triethylamine (2.60 g, pound 1f was obtained in 86% yield as a white solid after puri-
25.6 mmol) and DMAP (260 mg, 2.1 mmol) in dry dichloro- fication by silica gel column chromatography. mp 68–69 °C.
methane (30 mL) at 0 °C. The solution was allowed to warm to 1H NMR (400 MHz, CDCl3) δ (ppm): 7.70–7.64 (m, 4H), 7.27 (t,
room temperature and stirred until the end of the reaction. J = 2.2 Hz, 2H), 6.38 (t, J = 2.4 Hz, 2H). 13C NMR (100 MHz,
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CDCl3) δ (ppm): 166.7, 132.0, 131.8, 131.0, 127.2, 121.1, 113.4. 131.4, 131.2, 130.4, 128.4, 127.6, 126.9, 126.7, 125.0, 124.4,
These spectral data correspond to previously reported data.22e
121.0, 113.4. These spectral data correspond to previously
(3-Bromophenyl)(1H-pyrrol-1-yl)methanone (1g). Synthesis reported data.22g
was carried out according to the general procedure, and com-
Naphthalen-2-yl(1H-pyrrol-1-yl)methanone (1m). Synthesis
pound 1g was obtained in 87% yield as a yellowish oil after was carried out according to the general procedure, and com-
purification by silica gel column chromatography. 1H NMR pound 1m was obtained in 83% yield as a white solid after
(400 MHz, CDCl3) δ (ppm): 7.91 (s, 1H), 7.77–7.68 (m, 2H), purification by silica gel column chromatography. mp
7.42 (t, J = 7.8 Hz, 1H), 7.28 (s, 2H), 6.39 (s, 2H). 13C NMR 85–87 °C. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.27 (s, 1H),
(100 MHz, CDCl3) δ (ppm): 166.1, 135.2, 135.1, 132.3, 130.0, 7.98–7.92 (m, 3H), 7.82 (d, J = 8.4 Hz, 1H), 7.66–7.58 (m, 2H),
127.9, 122.6, 121.1, 113.6. These spectral data correspond to 7.36 (s, 2H), 6.39 (s, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm):
previously reported data.22c
167.8, 134.9, 132.2, 130.7, 130.4, 129.1, 128.5, 128.4, 127.9,
(4-Chlorophenyl)(1H-pyrrol-1-yl)methanone (1h). Synthesis 127.1, 125.5, 121.4, 113.1. These spectral data correspond to
was carried out according to the general procedure, and com- previously reported data.22c
pound 1h was obtained in 83% yield as a yellowish oil after
(1H-Pyrrol-1-yl)(thiophen-2-yl)methanone (1n). Synthesis
purification by silica gel column chromatography. 1H NMR was carried out according to the general procedure, and com-
(400 MHz, CDCl3) δ (ppm): 7.70 (d, J = 8.4 Hz, 2H), 7.49 (d, J = pound 1n was obtained in 80% yield as a yellowish oil after
8.8 Hz, 2H), 7.25 (t, J = 2.4 Hz, 2H), 6.36 (t, J = 2.4 Hz, 2H). 13
C
purification by silica gel column chromatography. 1H NMR
NMR (100 MHz, CDCl3) δ (ppm): 166.6, 138.7, 131.5, 130.9, (400 MHz, CDCl3) δ (ppm): 7.77–7.76 (m, 1H), 7.72–7.71 (m,
128.8, 121.1, 113.4. These spectral data correspond to pre- 1H), 7.47 (t, J = 2.4 Hz, 2H), 7.20–7.18 (m, 1H), 6.38 (t, J = 2.2
viously reported data.22c
Hz, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 160.6, 135.8,
(3-Fluorophenyl)(1H-pyrrol-1-yl)methanone (1i). Synthesis 134.0, 133.3, 127.7, 121.0, 113.2. These spectral data corres-
was carried out according to the general procedure, and com- pond to previously reported data.22c
pound 1i was obtained in 80% yield as a yellowish oil after
Furan-2-yl(1H-pyrrol-1-yl)methanone (1o). Synthesis was
purification by silica gel column chromatography. 1H NMR carried out according to the general procedure, and compound
(400 MHz, CDCl3) δ (ppm): 7.54–7.44 (m, 3H), 7.33–7.28 (m, 1o was obtained in 82% yield as a yellowish oil after purifi-
1H), 7.27 (t, J = 2.2 Hz, 2H), 6.36 (t, J = 2.2 Hz, 2H). 13C NMR cation by silica gel column chromatography. 1H NMR
(100 MHz, CDCl3) δ (ppm): 166.2, 163.5, 161.0, 135.2, 135.1, (400 MHz, CDCl3) δ (ppm): 7.69–7.66 (m, 3H), 7.43–7.42 (m,
130.3, 130.2, 125.2, 125.1, 121.1, 119.4, 119.2, 116.7, 116.4, 1H), 6.63–6.62 (m, 1H), 6.36 (t, J = 2.4 Hz, 2H). 13C NMR
113.5. These spectral data correspond to previously reported (100 MHz, CDCl3) δ (ppm): 155.5, 146.7, 146.5, 121.2, 120.7,
data.22c
113.2, 112.4. These spectral data correspond to previously
(1H-Pyrrol-1-yl)(4-(trifluoromethyl)phenyl)methanone (1j). reported data.22c
Synthesis was carried out according to the general procedure,
Methyl 1-benzoyl-1H-pyrrole-2-carboxylate (1p). Synthesis
and compound 1j was obtained in 80% yield as a yellow solid was carried out according to the general procedure, and com-
after purification by silica gel column chromatography. 1H pound 1p was obtained in 81% yield as a yellowish oil after
NMR (400 MHz, CDCl3) δ (ppm): 7.86 (d, J = 8.4 Hz, 2H), 7.79 purification by silica gel column chromatography. 1H NMR
(d, J = 8.4 Hz, 2H), 7.25 (t, J = 2.2 Hz, 2H), 6.38 (t, J = 2.2 Hz, (400 MHz, CDCl3) δ (ppm): 7.74 (d, J = 6.8 Hz, 2H), 7.60 (t, J =
2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 166.4, 136.6, 134.0, 7.4 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.23–7.22 (m, 1H),
133.7, 129.7, 125.6, 125.5, 124.8, 122.1, 121.1, 113.8. HRMS 7.07–7.06 (m, 1H), 6.30 (t, J = 3.2 Hz, 1H), 3.57 s, (3H). 13C
(ESI) m/z: calcd for C12H8F3NNaO [M + Na]+: 262.0450, found: NMR (100 MHz, CDCl3) δ (ppm): 168.2, 160.6, 133.5, 133.3,
262.0456.
(3-Nitrophenyl)(1H-pyrrol-1-yl)methanone (1k). Synthesis calcd for C13H11NNaO3 [M + Na]+: 252.0631, found: 252.0636.
was carried out according to the general procedure, and com- Ethyl 1-benzoyl-2-methyl-1H-pyrrole-3-carboxylate (1q).
129.8, 128.6, 127.7, 126.0, 121.2, 110.6, 51.5. HRMS (ESI) m/z:
pound 1k was obtained in 80% yield as a yellow oil after purifi- Synthesis was carried out according to the general procedure,
cation by silica gel column chromatography. 1H NMR and compound 1q was obtained in 75% yield as a white solid
(400 MHz, CDCl3) δ (ppm): 8.63 (s, 1H), 8.49 (d, J = 8.0 Hz, after purification by silica gel column chromatography. mp
1
1H), 8.11 (d, J = 7.6 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.27 (s, 56–58 °C. H NMR (400 MHz, CDCl3) δ (ppm): 7.73 (d, J = 7.2
2H), 6.44 (s, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 165.2, Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 6.75 (d,
148.0, 134.9, 134.8, 129.9, 126.7, 124.3, 121.0, 114.2. These J = 3.6 Hz, 1H), 6.55 (d, J = 3.6 Hz, 1H), 4.31 (q, J = 7.0 Hz, 2H),
spectral data correspond to previously reported data.22f
2.81 (s, 3H), 1.36 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz,
Naphthalen-1-yl(1H-pyrrol-1-yl)methanone (1l). Synthesis CDCl3) δ (ppm): 169.3, 164.9, 139.1, 133.4, 133.1, 130.1, 128.6,
was carried out according to the general procedure, and com- 121.9, 117.2, 111.2, 60.0, 14.4, 13.4. HRMS (ESI) m/z: calcd for
pound 1l was obtained in 80% yield as a yellowish oil after C15H15NNaO3 [M + Na]+: 280.0944, found: 280.0941.
purification by silica gel column chromatography. 1H NMR
Ethyl 1-benzoyl-2,4-dimethyl-1H-pyrrole-3-carboxylate (1r).
(400 MHz, CDCl3) δ (ppm): 8.03 (d, J = 8.0 Hz, 1H), 7.96–7.92 Synthesis was carried out according to the general procedure,
(m, 2H), 7.67–7.65 (m, 1H), 7.59–7.52 (m, 3H), 7.22 (s, 2H), and compound 1r was obtained in 79% yield as a yellowish oil
6.33 (s, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 167.6, 133.4, after purification by silica gel column chromatography.
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1H NMR (400 MHz, CDCl3) δ (ppm): 7.72 (d, J = 7.2 Hz, 2H), (t, J = 7.0 Hz, 1H), 7.35 (d, J = 6.8 Hz, 1H), 7.31 (d, J = 3.6 Hz,
7.61 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 6.53 (s, 1H), 1H), 6.63 (d, J = 3.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
4.31 (q, J = 7.0 Hz, 2H), 2.77 (s, 3H), 2.16 (s, 3H), 1.37 (t, J = 7.2 (ppm): 168.6, 135.9, 135.0, 131.8, 130.7, 129.1, 128.5, 127.5,
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 169.1, 165.6, 124.8, 123.9, 120.8, 116.3, 108.5. HRMS (ESI) m/z: calcd for
139.6, 133.7, 132.8, 129.9, 128.5, 121.6, 120.2, 117.2, 59.8, 14.3, C15H11NNaO [M + Na]+: 244.0733, found: 244.0737.
13.9, 12.5. HRMS (ESI) m/z: calcd for C16H17NNaO3 [M + Na]+:
General procedure for direct oxidative coupling between N-acyl
pyrroles and alkenes
294.1101, found: 294.1106.
Cyclohexyl(1H-pyrrol-1-yl)methanone (1s). Synthesis was
carried out according to the general procedure, and compound A Schlenk reaction tube equipped with a magnetic stir bar was
1s was obtained in 80% yield as a white solid after purification charged with [RuCl2(p-cymene)]2 (0.05 equiv., 0.01 mmol),
1
by silica gel column chromatography. mp 54–55 °C. H NMR AgSbF6 (0.10 equiv., 0.02 mmol), Cu(OAc)2·H2O (1.0 equiv.,
(400 MHz, CDCl3) δ (ppm): 7.33 (t, J = 2.0 Hz, 2H), 6.29 (t, J = 0.20 mmol), N-acyl pyrroles 1 (1.0 equiv., 0.2 mmol) and
2.4 Hz, 2H), 2.96–2.89 (m, 1H), 1.97–1.85 (m, 4H), 1.76–1.58 alkenes 2 (2.0 equiv., 0.4 mmol) in toluene (2.0 mL). The tube
(m, 3H), 1.43–1.24 (m, 3H). 13C NMR (100 MHz, CDCl3) was sealed under argon and heated to 110 °C with stirring for
δ (ppm): 173.8, 118.9, 112.9, 42.8, 29.6, 25.6, 25.5. These spec- 24 h. After cooling down, the solvent was removed under
tral data correspond to previously reported data.22e
Cyclopentyl(1H-pyrrol-1-yl)methanone (1t). Synthesis was atography (ethyl acetate/petroleum ether mixtures).
carried out according to the general procedure, and compound Butyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate (3aa). Synthesis
reduced pressure, and the residue was purified by flash chrom-
1t was obtained in 81% yield as a yellowish oil after purifi- was carried out according to the general procedure, and com-
cation by silica gel column chromatography. 1H NMR pound 3aa was obtained in 81% yield as a colorless oil after
(400 MHz, CDCl3) δ (ppm): 7.34(s, 2H), 6.29 (t, J = 2.4 Hz, 2H), purification by silica gel column chromatography. 1H NMR
3.42–3.34 (m, 1H), 2.02–1.97 (m, 4H), 1.84–1.75 (m, 2H), (400 MHz, CDCl3) δ (ppm): 8.05 (d, J = 16.0 Hz, 1H), 7.75 (d, J
1.72–1.63 (m, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 173.8, = 7.2 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H),
119.2, 112.8, 43.0, 30.5, 26.1. HRMS (ESI) m/z: calcd for 7.02–7.01 (m, 1H), 6.84 (d, J = 3.2 Hz, 1H), 6.28–6.24 (m, 2H),
C10H13NNaO [M + Na]+: 186.0889, found: 186.0891.
4.16 (t, J = 6.6 Hz, 2H), 1.68–1.61 (m, 2H), 1.45–1.35 (m, 2H),
1-(1H-Pyrrol-1-yl)ethan-1-one (1u). Synthesis was carried out 0.93 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm):
according to the general procedure, and compound 1u was 168.7, 167.0, 134.1, 133.3, 133.1, 132.2, 130.1, 128.6, 126.6,
obtained in 82% yield as a yellowish oil after purification by 116.8, 115.7, 111.9, 64.2, 30.7, 19.2, 13.7. HRMS (ESI) m/z:
1
silica gel column chromatography. H NMR (400 MHz, CDCl3) calcd for C18H19NNaO3 [M + Na]+: 320.1257, found 320.1263.
δ (ppm): 7.29 (s, 2H), 6.30 (t, J = 2.2 Hz, 2H), 2.53 (s, 3H). 13C
Methyl
NMR (100 MHz, CDCl3) δ (ppm): 167.7, 119.3, 113.2, 22.3. Synthesis was carried out according to the general procedure,
These spectral data correspond to previously reported data.22h
and compound 3ab was obtained in 76% yield as a colorless
(E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate
(3ab).
2-Methyl-1-(1H-pyrrol-1-yl)prop-2-en-1-one (1v). Synthesis oil after purification by silica gel column chromatography.
was carried out according to the general procedure, and com- 1H NMR (400 MHz, CDCl3) δ (ppm): 8.09 (d, J = 16.0 Hz, 1H),
pound 1v was obtained in 80% yield as a yellowish oil after 7.76 (d, J = 8.0 Hz, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.51 (t, J = 7.4
purification by silica gel column chromatography. 1H NMR Hz, 2H), 7.02 (s, 1H), 6.85 (s, 1H), 6.29–6.25 (m, 2H), 3.76 (s,
(400 MHz, CDCl3) δ (ppm): 7.30 (t, J = 2.2 Hz, 2H), 6.31 (t, J = 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.7, 167.3, 134.4,
2.4 Hz, 2H), 5.70 (d, J = 1.2 Hz, 1H), 5.52 (s, 1H), 2.11 (t, J = 1.4 133.2, 133.1, 132.1, 130.1, 128.6, 126.7, 116.3, 115.8, 111.9,
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.5, 138.6, 51.5. HRMS (ESI) m/z: Calcd for C15H13NNaO3 [M + Na]+:
123.0, 120.5, 113.1, 19.8. HRMS (ESI) m/z: calcd for C8H9NNaO 278.0788, found 278.0791.
[M + Na]+: 158.0576, found: 158.0573.
Ethyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate (3ac). Synthesis
(2,5-Dimethyl-1H-pyrrol-1-yl)(phenyl)methanone
(1w). was carried out according to the general procedure, and com-
Synthesis was carried out according to the general procedure, pound 3ac was obtained in 79% yield as a colorless oil after
and compound 1w was obtained in 80% yield as a yellowish oil purification by silica gel column chromatography. 1H NMR
after purification by silica gel column chromatography. (400 MHz, CDCl3) δ (ppm): 8.06 (d, J = 16.0 Hz, 1H), 7.76 (d,
1H NMR (400 MHz, CDCl3) δ (ppm): 7.69 (d, J = 8.0 Hz, 2H), J = 7.6 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H),
7.59 (t, J = 8.0 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 5.87 (s, 2H), 7.02 (d, J = 2.8 Hz, 1H), 6.85 (d, J = 3.6 Hz, 1H), 6.28–6.24 (m,
2.07 (s, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm): 171.1, 135.6, 2H), 4.22 (q, J = 7.2 Hz, 2H), 1.3 (t, J = 7.0 Hz, 3H). 13C NMR
133.1, 130.3, 130.1, 128.6, 110.1, 14.6. HRMS (ESI) m/z: calcd (100 MHz, CDCl3) δ (ppm): 168.8, 166.9, 134.2, 133.4, 133.1,
for C13H13NNaO [M + Na]+: 222.0889, found: 222.0893.
(1H-Indol-1-yl)(phenyl)methanone (7). Synthesis was carried HRMS (ESI) m/z: calcd for C16H15NNaO3 [M + Na] : 292.0944,
out according to the general procedure, and compound 7 was found 292.0951.
132.2, 130.1, 128.6, 126.6, 116.9, 115.7, 111.9, 60.3, 14.3.
+
obtained in 82% yield as a white solid after purification by
Cyclohexyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate (3ad).
silica gel column chromatography. mp 56–58 °C. 1H NMR Synthesis was carried out according to the general procedure,
(400 MHz, CDCl3) δ (ppm): 8.45 (d, J = 8.4 Hz, 1H), 7.75 (d, J = and compound 3ad was obtained in 71% yield as a colorless
1
6.8 Hz, 2H), 7.62 (t, J = 8.0 Hz, 2H), 7.54 (t, J = 7.4 Hz, 2H), 7.41 oil after purification by silica gel column chromatography. H
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NMR (400 MHz, CDCl3) δ (ppm): 8.02 (d, J = 16.0 Hz, 1H), 7.76 (ppm): 168.7, 166.8, 134.6, 133.3, 133.1, 132.2, 130.1, 128.6,
(d, J = 7.6 Hz, 2H), 7.63 (t, J = 7.6 Hz, 1H), 7.51 (t, J = 7.8 Hz, 126.7, 116.4, 115.9, 111.9, 70.7, 69.8, 69.3, 66.7, 63.6, 15.1.
2H), 7.02 (d, J = 2.0 Hz, 1H), 6.84 (d, J = 3.2 Hz, 1H), 6.28–6.24 HRMS (ESI) m/z: calcd for C20H23NNaO5 [M + Na]+: 380.1468,
(m, 2H), 1.89–1.86 (m, 2H), 1.75–1.72 (m, 2H), 1.56–1.23 (m, found 380.1491.
7H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.8, 166.3, 133.8,
2-Methoxyethyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate (3ai).
133.4, 133.1, 132.3, 130.1, 128.6, 126.5, 117.5, 115.6, 111.9, Synthesis was carried out according to the general procedure,
72.5, 31.7, 25.5, 23.8. HRMS (ESI) m/z: calcd for C20H21NNaO3 and compound 3ai was obtained in 73% yield as a pale yellow
[M + Na]+: 346.1414, found 346.1409.
solid after purification by silica gel column chromatography.
1
(1S,4S)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-yl(E)-3-(1-benzoyl- Mp: 95–96 °C. H NMR (400 MHz, CDCl3) δ (ppm): 8.09 (d, J =
1H-pyrrol-2-yl)acrylate (3ae). Synthesis was carried out accord- 16.0 Hz, 1H), 7.76 (d, J = 7.2 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H),
ing to the general procedure, and compound 3ae was obtained 7.51 (t, J = 7.6 Hz, 2H), 7.03–7.01 (m, 1H), 6.85 (d, J = 3.2 Hz,
in 51% yield as a colorless oil after purification by silica gel 1H), 6.32 (d, J = 16.0 Hz, 1H), 6.28 (t, J = 3.4 Hz, 1H), 4.33 (t, J =
1
column chromatography. H NMR (400 MHz, CDCl3) δ (ppm): 4.8 Hz, 2H), 3.65 (t, J = 4.6 Hz, 2H), 3.41 (s, 3H). 13C NMR
8.03 (d, J = 16.0 Hz, 1H), 7.76 (d, J = 7.2 Hz, 2H), 7.63 (t, J = (100 MHz, CDCl3) δ (ppm): 168.7, 166.9, 134.7, 133.3, 133.1,
7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.03–7.02 (m, 1H), 6.85 (d, 132.1, 130.1, 128.6, 126.7, 116.3, 115.9, 111.9, 70.6, 63.4, 59.0.
J = 3.2 Hz, 1H), 6.28–6.22 (m, 2H), 4.78–4.75 (m, 1H), 1.87–1.77 HRMS (ESI) m/z: calcd for C17H17NNaO4 [M + Na]+: 322.1050,
(m, 2H), 1.74–1.71 (m, 1H), 1.60–1.52 (m, 2H), 1.25–1.21 (m, found 322.1054.
2H), 1.03 (s, 3H), 0.87 (s, 3H), 0.84 (s, 3H). 13C NMR (100 MHz,
2-Phenoxyethyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate (3aj).
CDCl3) δ (ppm): 168.7, 166.4, 133.8, 133.5, 133.0, 132.2, 130.0, Synthesis was carried out according to the general procedure,
128.6, 126.6, 117.5, 115.6, 111.9, 80.9, 48.9, 47.0, 45.1, 38.8, and compound 3aj was obtained in 82% yield as a colorless oil
33.7, 27.1, 20.1, 20.0, 11.5. HRMS (ESI) m/z: calcd for after purification by silica gel column chromatography. 1H
C23H25NNaO3 [M + Na]+: 386.1727, found 386.1731.
Phenyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate
NMR (400 MHz, CDCl3) δ (ppm): 8.10 (d, J = 16.0 Hz, 1H), 7.76
(3af). (d, J = 7.2 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz,
Synthesis was carried out according to the general procedure, 2H), 7.28 (t, J = 8.0 Hz, 2H), 7.04–7.03 (m, 1H), 6.97–6.93 (m,
and compound 3af was obtained in 69% yield as a colorless oil 3H), 6.86 (d, J = 3.2 Hz, 1H), 6.32 (d, J = 16.0 Hz, 1H), 6.28 (t,
1
after purification by silica gel column chromatography. H NMR J = 3.4 Hz, 1H), 4.53 (t, J = 5.0 Hz, 2H), 4.22 (t, J = 4.8 Hz, 2H).
(400 MHz, CDCl3) δ (ppm): 8.29 (d, J = 16.0 Hz, 1H), 7.78 (d, J = 13C NMR (100 MHz, CDCl3) δ (ppm): 168.6, 166.8, 158.7, 134.9,
6.8 Hz, 2H), 7.65 (t, J = 7.6 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.39 133.2, 133.1, 132.1, 130.1, 129.5, 128.6, 126.7, 121.1, 116.0,
(t, J = 7.8 Hz, 2H), 7.23 (t, J = 7.4 Hz, 1H), 7.15 (d, J = 7.6 Hz, 2H), 114.6, 111.9, 65.9, 62.7. HRMS (ESI) m/z: calcd for
7.09–7.07 (m, 1H), 6.97 (d, J = 3.2 Hz, 1H), 6.46 (d, J = 16.0 Hz, C22H19NNaO4 [M + Na]+: 384.1206, found 384.1201.
1H), 6.33 (t, J = 3.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm):
(Tetrahydrofuran-2-yl)methyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)
168.7, 165.3, 150.8, 135.9, 133.2, 133.1, 131.9, 130.1, 129.3, 128.7, acrylate (3ak). Synthesis was carried out according to the
127.1, 125.6, 121.7, 116.5, 115.6, 112.1. HRMS (ESI) m/z: calcd for general procedure, and compound 3ak was obtained in 80%
C20H15NNaO3 [M + Na]+: 340.0944, found 340.0941.
Benzyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acrylate
yield as a colorless oil after purification by silica gel column
(3ag). chromatography. H NMR (400 MHz, CDCl3) δ (ppm): 8.09 (d,
1
Synthesis was carried out according to the general procedure, J = 16.0 Hz, 1H), 7.75 (d, J = 7.2 Hz, 2H), 7.63 (t, J = 7.4 Hz,
and compound 3ag was obtained in 66% yield as a colorless 1H), 7.50 (t, J = 7.4 Hz, 2H), 7.02–7.01 (m, 1H), 6.85 (d, J = 3.6
1
oil after purification by silica gel column chromatography. H Hz, 1H), 6.32 (d, J = 16.0 Hz, 1H), 6.27 (t, J = 3.4 Hz, 1H),
NMR (400 MHz, CDCl3) δ (ppm): 8.11 (d, J = 16.0 Hz, 1H), 7.76 4.26–4.23 (m, 1H), 4.20–4.08 (m, 2H), 3.93–3.88 (m, 1H),
(d, J = 6.8 Hz, 2H), 7.63 (t, J = 7.6 Hz, 1H), 7.51 (t, J = 7.8 Hz, 3.82–3.78 (m, 1H), 2.06–1.86 (m, 3H), 1.69–1.60 (m, 1H). 13C
2H), 7.38–7.33 (m, 5H), 7.04–7.03 (m, 1H), 6.86 (d, J = 3.2 Hz, NMR (100 MHz, CDCl3) δ (ppm): 168.6, 166.8, 134.6, 133.3,
1H), 6.32 (d, J = 16.0 Hz, 1H), 6.28 (t, J = 3.4 Hz, 1H), 5.22 (s, 133.1, 132.1, 130.0, 128.6, 126.7, 116.3, 115.8, 111.9, 76.6, 68.4,
2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.7, 166.7, 136.2, 66.4, 28.0, 25.6. HRMS (ESI) m/z: calcd for C19H19NNaO4 [M +
134.7, 133.3, 133.1, 132.1, 130.1, 128.6, 128.5, 128.2, 128.1, Na]+: 348.1206, found 348.1210.
126.7, 116.3, 115.9, 111.9, 66.1. HRMS (ESI) m/z: calcd for
2,5-Dioxopyrrolidin-1-yl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acry-
late (3al). Synthesis was carried out according to the general
C21H17NNaO3 [M + Na]+: 354.1101, found 354.1106.
2-(2-Ethoxyethoxy)ethyl (E)-3-(1-benzoyl-1H-pyrrol-2-yl)acry- procedure, and compound 3al was obtained in 54% yield as a
late (3ah). Synthesis was carried out according to the general colorless oil after purification by silica gel column chromato-
1
procedure, and compound 3ah was obtained in 61% yield as a graphy. H NMR (400 MHz, CDCl3) δ (ppm): 8.36 (d, J = 16.0
colorless oil after purification by silica gel column chromato- Hz, 1H), 7.76 (d, J = 6.8 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.53 (t,
1
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 8.09 (d, J = 16.0 J = 7.8 Hz, 2H), 7.11–7.10 (m, 1H), 7.02 (d, J = 3.6 Hz, 1H), 6.41
Hz, 1H), 7.76 (d, J = 6.8 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, (d, J = 16.0 Hz, 1H), 6.33 (t, J = 3.4 Hz, 1H), 2.86 (s, 4H). 13C
J = 7.8 Hz, 2H), 7.03–7.02 (m, 1H), 6.85 (d, J = 3.2 Hz, 1H), NMR (100 MHz, CDCl3) δ (ppm): 169.4, 168.5, 162.0, 139.1,
6.33–6.27 (m, 2H), 4.34 (t, J = 5.0 Hz, 2H), 3.76 (t, J = 4.8 Hz, 133.3, 133.0, 131.4, 130.1, 128.7, 128.1, 117.8, 112.3, 109.2,
2H), 3.69–3.67 (m, 2H), 3.61–3.59 (m, 2H), 3.53 (q, J = 7.2 Hz, 25.6. HRMS (ESI) m/z: calcd for C18H14N2NaO5 [M + Na]+:
2H), 1.20 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 361.0795, found 361.0800.
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(E)-Phenyl(2-(3-(phenylsulfonyl)prop-1-en-1-yl)-1H-pyrrol-1-yl) 2H), 6.81 (t, J = 2.8 Hz, 2H), 6.27 (d, J = 16.0 Hz, 1H), 6.22 (t, J =
methanone (3an). Synthesis was carried out according to the 3.4 Hz, 1H), 4.17 (t, J = 6.6 Hz, 2H), 2.34 (s, 3H), 1.70–1.63 (m,
general procedure, and compound 3an was obtained in 70% 2H), 1.46–1.37 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR
yield as a colorless oil after purification by silica gel column (100 MHz, CDCl3) δ (ppm): 169.4, 167.0, 136.9, 134.3, 133.9,
1
chromatography. H NMR (400 MHz, CDCl3) δ (ppm): 7.89 (d, 132.0, 131.2, 131.0, 128.2, 126.1, 125.7, 117.2, 116.0, 112.3,
J = 7.2 Hz, 2H), 7.69 (d, J = 7.2 Hz, 2H), 7.63–7.59 (m, 2H), 7.54 64.2, 30.7, 19.4, 19.1, 13.7. HRMS (ESI) m/z: calcd for
(t, J = 7.4 Hz, 2H), 7.48 (t, J = 7.6 Hz, 2H), 6.90 (d, J = 15.6 Hz, C19H21NNaO3 [M + Na]+: 334.1414, found 334.1410.
1H), 6.85–6.84 (m, 1H), 6.57 (d, J = 3.2 Hz, 1H), 6.19 (t, J = 3.4
Butyl (E)-3-(1-(4-iodobenzoyl)-1H-pyrrol-2-yl)acrylate (3ea).
Hz, 1H), 6.00–5.93 (m, 1H), 3.95–3.93 (m, 2H). 13C NMR Synthesis was carried out according to the general procedure,
(100 MHz, CDCl3) δ (ppm): 169.0, 138.5, 133.7, 133.6, 133.2, and compound 3ea was obtained in 72% yield as a colorless
1
132.8, 129.9, 129.6, 129.1, 128.5, 128.4, 124.7, 114.3, oil after purification by silica gel column chromatography. H
113.0, 111.5, 60.6. HRMS (ESI) m/z: calcd for C20H17NNaO3S NMR (400 MHz, CDCl3) δ (ppm): 8.02 (d, J = 16.0 Hz, 1H), 7.87
[M + Na]+: 374.0821, found 374.0823.
(d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 6.98–6.97 (m, 1H),
(E)-3-(1-Benzoyl-1H-pyrrol-2-yl)acrylonitrile (3ao). Synthesis 6.84 (d, J = 3.2 Hz, 1H), 6.29–6.24 (m, 2H), 4.17 (t, J = 6.8 Hz,
was carried out according to the general procedure, and com- 2H), 1.69–1.62 (m, 2H), 1.45–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz,
pound 3ao was obtained in 66% yield as a colorless oil after 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.0, 166.9, 137.9,
purification by silica gel column chromatography. 1H NMR 133.8, 132.6, 132.2, 131.3, 126.2, 117.1, 115.8, 112.2, 100.8,
(400 MHz, CDCl3) δ (ppm): 7.91 (d, J = 16.4 Hz, 1H), 7.75 (d, 64.3, 30.7, 19.1, 13.7. HRMS (ESI) m/z: Calcd for C18H18INNaO3
J = 7.2 Hz, 2H), 7.66 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), [M + Na]+: 446.0224, found 446.0220.
7.06–7.05 (m, 1H), 6.86 (d, J = 3.6 Hz, 1H), 6.29 (t, J = 3.4 Hz,
Butyl (E)-3-(1-(4-bromobenzoyl)-1H-pyrrol-2-yl)acrylate (3fa).
1H), 5.70 (d, J = 16.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) Synthesis was carried out according to the general procedure,
δ (ppm): 168.7, 140.0, 133.3, 132.9, 131.2, 130.0, 128.7, 127.5, and compound 3fa was obtained in 70% yield as a yellow oil
118.5, 116.0, 112.1, 94.0. HRMS (ESI) m/z: calcd for after purification by silica gel column chromatography. 1H
C14H10N2NaO [M + Na]+: 245.0685, found 245.0689.
NMR (400 MHz, CDCl3) δ (ppm): 8.02 (d, J = 16.0 Hz, 1H),
Butyl (E)-3-(1-(4-ethylbenzoyl)-1H-pyrrol-2-yl)acrylate (3ba). 7.67–7.62 (m, 4H), 6.97 (d, J = 2.4 Hz, 1H), 6.84 (d, J = 3.2 Hz,
Synthesis was carried out according to the general procedure, 1H), 6.29–6.24 (m, 2H), 4.16 (t, J = 6.6 Hz, 2H), 1.69–1.62 (m,
and compound 3ba was obtained in 73% yield as a colorless 2H), 1.45–1.35 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H). 13C NMR
1
oil after purification by silica gel column chromatography. H (100 MHz, CDCl3) δ (ppm): 167.7, 166.9, 133.8, 132.2, 132.1,
NMR (400 MHz, CDCl3) δ (ppm): 8.04 (d, J = 16.0 Hz, 1H), 7.69 132.0, 131.5, 128.2, 126.2, 117.1, 115.8, 112.2, 64.3, 30.7, 19.1,
(d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 1.6 Hz, 13.7. HRMS (ESI) m/z: calcd for C18H18BrNNaO3 [M + Na]+:
1H), 6.83 (d, J = 2.8 Hz, 1H), 6.27–6.23 (m, 2H), 4.16 (t, J = 6.6 398.0362, found 398.0366.
Hz, 2H), 2.74 (q, J = 7.6 Hz, 2H), 1.68–1.61 (m, 2H), 1.45–1.35
Butyl (E)-3-(1-(3-bromobenzoyl)-1H-pyrrol-2-yl)acrylate (3ga).
(m, 2H), 1.28 (t, J = 7.6 Hz, 3H), 0.93 (t, J = 7.4 Hz, 3H). 13C Synthesis was carried out according to the general procedure,
NMR (100 MHz, CDCl3) δ (ppm): 168.6, 167.0, 150.2, 134.1, and compound 3ga was obtained in 73% yield as a pale yellow
1
132.0, 130.6, 130.4, 128.1, 126.6, 115.5, 111.6, 64.1, 30.7, oil after purification by silica gel column chromatography. H
28.9, 19.1, 15.1, 13.7. HRMS (ESI) m/z: calcd for C20H23NNaO3 NMR (400 MHz, CDCl3) δ (ppm): 8.03 (d, J = 16.0 Hz, 1H), 7.89
[M + Na]+: 348.1570, found 348.1573.
(t, J = 1.8 Hz, 1H), 7.77–7.74 (m, 1H), 7.67 (d, J = 8.0 Hz, 1H),
(E)-3-(1-(4-methoxybenzoyl)-1H-pyrrol-2-yl)acrylate 7.39 (t, J = 8.0 Hz, 1H), 6.99–6.98 (m, 1H), 6.85 (d, J = 3.6 Hz,
Butyl
(3ca). Synthesis was carried out according to the general pro- 1H), 6.30–6.25 (m, 2H), 4.17 (t, J = 6.6 Hz, 2H), 1.69–1.62 (m,
cedure, and compound 3ca was obtained in 69% yield as a 2H), 1.45–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H). 13C NMR
pale yellow oil after purification by silica gel column chromato- (100 MHz, CDCl3) δ (ppm): 167.1, 166.9, 136.0, 135.2, 133.8,
1
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 7.97 (d, J = 16.0 132.8, 132.3, 130.1, 128.5, 126.2, 122.7, 117.2, 116.0, 112.4,
Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 2.0 Hz, 1H), 6.98 64.3, 30.7, 19.1, 13.7. HRMS (ESI) m/z: calcd for
(d, J = 8.4 Hz, 2H), 6.84 (d, J = 3.2 Hz, 1H), 6.28–6.23 (m, 2H), C18H18BrNNaO3 [M + Na]+: 398.0362, found 398.0360.
4.16 (t, J = 6.6 Hz, 2H), 3.89 (s, 3H), 1.68–1.61 (m, 2H),
Butyl (E)-3-(1-(4-chlorobenzoyl)-1H-pyrrol-2-yl)acrylate (3ha).
1.44–1.35 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, Synthesis was carried out according to the general procedure,
CDCl3) δ (ppm): 168.0, 167.1, 163.7, 134.0, 132.7, 132.0, 126.5, and compound 3ha was obtained in 78% yield as a colorless
1
125.3, 116.4, 115.3, 113.9, 111.5, 64.2, 55.6, 30.7, 19.1, 13.7. oil after purification by silica gel column chromatography. H
HRMS (ESI) m/z: calcd for C19H21NNaO4 [M + Na]+: 350.1363, NMR (400 MHz, CDCl3) δ (ppm): 8.01 (d, J = 16.0 Hz, 1H), 7.71
found 350.1366.
(d, J = 8.8 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 6.99–6.98 (m, 1H),
Butyl (E)-3-(1-(2-methylbenzoyl)-1H-pyrrol-2-yl)acrylate (3da). 6.85 (d, J = 3.2 Hz, 1H), 6.30–6.24 (m, 2H), 4.17 (t, J = 6.8 Hz,
Synthesis was carried out according to the general procedure, 2H), 1.69–1.62 (m, 2H), 1.45–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz,
and compound 3da was obtained in 71% yield as a yellow oil 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 167.6, 166.9, 139.7,
after purification by silica gel column chromatography. 1H 133.8, 132.2, 131.6, 131.5, 129.0, 126.2, 117.1, 115.8, 112.2,
NMR (400 MHz, CDCl3) δ (ppm): 8.19 (d, J = 16.0 Hz, 1H), 64.3, 30.7, 19.1, 13.7. HRMS (ESI) m/z: calcd for
7.45–7.41 (m, 1H), 7.37 (d, J = 6.8 Hz, 1H), 7.29 (t, J = 6.6 Hz, C18H18ClNNaO3 [M + Na]+: 354.0867, found 354.0863.
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Butyl (E)-3-(1-(3-fluorobenzoyl)-1H-pyrrol-2-yl)acrylate (3ia). and compound 3ma was obtained in 73% yield as a colorless
Synthesis was carried out according to the general procedure, oil after purification by silica gel column chromatography.
and compound 3ia was obtained in 80% yield as a colorless oil 1H NMR (400 MHz, CDCl3) δ (ppm): 8.28 (s, 1H), 8.10 (d, J =
after purification by silica gel column chromatography. 1H 16.0 Hz, 1H), 7.97–7.92 (m, 3H), 7.84–7.81 (m, 1H), 7.67–7.58
NMR (400 MHz, CDCl3) δ (ppm): 8.04 (d, J = 16.0 Hz, 1H), (m, 2H), 7.10–7.09 (m, 1H), 6.89 (d, J = 2.8 Hz, 1H), 6.32–6.28
7.56–7.46 (m, 3H), 7.37–7.32 (m, 1H), 7.01–7.00 (m, 1H), 6.86 (m, 2H), 4.16 (t, J = 6.6 Hz, 2H), 1.67–1.60 (m, 2H), 1.43–1.34
(d, J = 3.2 Hz, 1H), 6.31–6.25 (m, 2H), 4.18 (t, J = 6.6 Hz, 2H), (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ
1.70–1.63 (m, 2H), 1.46–1.37 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). (ppm): 168.8, 167.0, 135.3, 134.1, 132.3, 132.1, 131.7, 130.4,
13C NMR (100 MHz, CDCl3) δ (ppm): 167.4, 166.9, 163.6, 161.1, 129.2, 128.8, 128.6, 127.9, 127.2, 126.7, 125.6, 116.8, 115.7,
135.4, 135.3, 133.9, 132.3, 130.5, 130.4, 126.3, 125.8, 125.7, 111.9, 64.2, 30.7, 19.1, 13.7. HRMS (ESI) m/z: calcd for
120.3, 120.1, 117.2, 117.1, 116.9, 116.0, 112.3, 64.3, 30.8, 19.2, C22H21NNaO3 [M + Na]+: 370.1414, found 370.1411.
13.7. HRMS (ESI) m/z: calcd for C18H18FNNaO3 [M + Na]+:
338.1163, found 338.1160.
Butyl (E)-3-(1-(thiophene-2-carbonyl)-1H-pyrrol-2-yl)acrylate
(3na). Synthesis was carried out according to the general pro-
Butyl
(E)-3-(1-(4-(trifluoromethyl)benzoyl)-1H-pyrrol-2-yl) cedure, and compound 3na was obtained in 36% yield as a
acrylate (3ja). Synthesis was carried out according to the pale orange oil after purification by silica gel column chrom-
general procedure, and compound 3ja was obtained in 76% atography. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.99 (d, J =
yield as a pale yellow solid after purification by silica gel 16.0 Hz, 1H), 7.78–7.77 (m, 1H), 7.71–7.70 (m, 1H), 7.34–7.33
column chromatography. Mp: 38–39 °C. 1H NMR (400 MHz, (m, 1H), 7.20–7.18 (m, 1H), 6.85 (d, J = 3.6 Hz, 1H), 6.32 (t, J =
CDCl3) δ (ppm): 8.08 (d, J = 16.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 3.6 Hz, 1H), 6.26 (d, J = 16.0 Hz, 1H), 4.17 (t, J = 6.8 Hz, 2H),
2H), 7.79 (d, J = 8.0 Hz, 2H), 6.94–6.93 (m, 1H), 6.86 (d, J = 3.2 1.69–1.63 (m, 2H), 1.45–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H).
Hz, 1H), 6.31–6.27 (m, 2H), 4.18 (t, J = 6.8 Hz, 2H), 1.70–1.62 13C NMR (100 MHz, CDCl3) δ (ppm): 167.0, 161.7, 136.6, 135.2,
(m, 2H), 1.46–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H). 13C NMR 134.8, 133.7, 132.0, 128.0, 126.0, 116.8, 115.5, 112.0, 64.3, 30.7,
(100 MHz, CDCl3) δ (ppm): 167.5, 166.8, 136.7, 134.6, 134.3, 19.2, 13.7. HRMS (ESI) m/z: calcd for C16H17NNaO3S [M + Na]+:
133.8, 132.5, 130.2, 126.1, 125.7, 125.7, 125.6, 125.6, 124.7, 326.0821, found 326.0823.
122.0, 117.5, 116.1, 112.6, 64.3, 30.7, 19.2, 13.7. HRMS (ESI) m/
z: calcd for C19H18F3NNaO3 [M + Na]+: 388.1131, found pyrrole-2-carboxylate (3pa). Synthesis was carried out accord-
388.1133. ing to the general procedure, and compound 3pa was obtained
Methyl
(E)-1-benzoyl-5-(3-butoxy-3-oxoprop-1-en-1-yl)-1H-
Butyl (E)-3-(1-(3-nitrobenzoyl)-1H-pyrrol-2-yl)acrylate (3ka). in 75% yield as a colorless oil after purification by silica gel
1
Synthesis was carried out according to the general procedure, column chromatography. H NMR (400 MHz, CDCl3) δ (ppm):
and compound 3ka was obtained in 79% yield as a yellow oil 7.63–7.59 (m, 3H), 7.45 (t, J = 7.8 Hz, 2H), 7.39 (d, J = 15.6 Hz,
after purification by silica gel column chromatography. 1H 1H), 7.03 (d, J = 4.0 Hz, 1H), 6.77 (d, J = 4.0 Hz, 1H), 6.33 (d, J =
NMR (400 MHz, CDCl3) δ (ppm): 8.60 (t, J = 1.8 Hz, 1H), 15.6 Hz, 1H), 4.11 (t, J = 6.8 Hz, 2H), 3.61 (s, 3H), 1.64–1.57 (m,
8.51–8.48 (m, 1H), 8.11–8.09 (m, 1H), 8.04 (d, J = 16.0 Hz, 1H), 2H), 1.39–1.30 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H). 13C NMR
7.75 (d, J = 8.0 Hz, 1H), 6.95–6.94 (m, 1H), 6.89 (d, J = 3.2 Hz, (100 MHz, CDCl3) δ (ppm): 169.5, 166.2, 160.1, 135.1, 134.6,
1H), 6.35 (t, J = 3.4 Hz, 1H), 6.30 (d, J = 16.0 Hz, 1H), 4.18 (t, J = 133.8, 130.9, 129.8, 129.0, 127.4, 119.9, 118.3, 111.5, 64.5, 51.8,
6.8 Hz, 2H), 1.70–1.62 (m, 2H), 1.46–1.36 (m, 2H), 0.94 (t, J = 30.6, 19.0, 13.6. HRMS (ESI) m/z: calcd for C20H21NNaO5 [M +
7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 166.8, 166.3, Na]+: 378.1312, found 378.1316.
148.1, 135.4, 135.0, 133.5, 132.6, 130.0, 127.4, 125.8, 124.8,
117.8, 116.3, 113.1, 64.4, 30.7, 19.2, 13.7. HRMS (ESI) m/z: 1H-pyrrole-3-carboxylate (3qa). Synthesis was carried out
calcd for C18H18N2NaO5 [M + Na]+: 365.1108, found 365.1106.
according to the general procedure, and compound 3qa was
Ethyl (E)-1-benzoyl-5-(3-butoxy-3-oxoprop-1-en-1-yl)-2-methyl-
Butyl (E)-3-(1-(1-naphthoyl)-1H-pyrrol-2-yl)acrylate (3la). obtained in 79% yield as a yellow oil after purification by silica
Synthesis was carried out according to the general procedure, gel column chromatography. 1H NMR (400 MHz, CDCl3) δ
and compound 3la was obtained in 74% yield as a colorless oil (ppm): 7.68–7.64 (m, 3H), 7.48 (t, J = 7.8 Hz, 2H), 7.15 (d, J =
after purification by silica gel column chromatography. 1H 15.6 Hz, 1H), 7.09 (s, 1H), 6.06 (d, J = 16.0 Hz, 1H), 4.30 (q, J =
NMR (400 MHz, CDCl3) δ (ppm): 8.29 (d, J = 16.0 Hz, 1H), 8.05 7.0 Hz, 2H), 4.04 (t, J = 6.6 Hz, 2H), 3.45 (s, 3H), 1.58–1.51 (m,
(d, J = 8.0 Hz, 1H), 7.98–7.92 (m, 2H), 7.67–7.65 (m, 1H), 2H), 1.36 (t, J = 7.0 Hz, 3H), 1.32–1.25 (m, 2H), 0.88 (t, J = 7.4
7.57–7.52 (m, 3H), 6.86 (d, J = 3.2 Hz, 1H), 6.81–6.80 (m, 1H), Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 169.8, 166.6,
6.31 (d, J = 16.0 Hz, 1H), 6.20 (t, J = 3.4 Hz, 1H), 4.18 (t, J = 6.6 164.3, 139.9, 135.1, 133.2, 132.1, 130.7, 129.3, 129.2, 115.9,
Hz, 2H), 1.70–1.63 (m, 2H), 1.46–1.37 (m, 2H), 0.95 (t, J = 7.4 115.6, 113.8, 64.1, 60.1, 30.6, 19.0, 14.3, 13.6, 13.0. HRMS (ESI)
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.9, 166.9, m/z: calcd for C22H25NNaO5 [M + Na]+: 406.1625, found
134.4, 133.5, 132.3, 132.2, 131.4, 130.5, 128.5, 127.8, 127.7, 406.1629.
126.9, 126.6, 124.7, 124.4, 117.3, 116.1, 112.3, 64.3, 30.7, 19.1,
13.7. HRMS (ESI) m/z: calcd for C22H21NNaO3 [M + Na]+: dimethyl-1H-pyrrole-3-carboxylate (3ra). Synthesis was carried
370.1414, found 370.1410. out according to the general procedure, and compound 3ra
Ethyl (E)-1-benzoyl-5-(3-butoxy-3-oxoprop-1-en-1-yl)-2,4-
Butyl (E)-3-(1-(2-naphthoyl)-1H-pyrrol-2-yl)acrylate (3ma). was obtained in 73% yield as a yellow oil after purification by
1
Synthesis was carried out according to the general procedure, silica gel column chromatography. H NMR (400 MHz, CDCl3)
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δ (ppm): 7.67–7.63 (m, 3H), 7.46 (t, J = 7.8 Hz, 2H), 7.36 (d, J = 116.7, 115.8, 111.8, 64.3, 30.8, 19.4, 19.2, 13.7. HRMS (ESI) m/
16.0 Hz, 1H),5.69 (d, J = 16.4 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), z: calcd for C15H19NNaO3 [M + Na]+: 284.1257, found 284.1254.
4.04 (t, J = 6.6 Hz, 2H), 2.43 (d, J = 2.8 Hz, 6H), 1.59–1.52 (m,
1-(1-Benzoyl-1H-pyrrol-2-yl)pentan-3-one (4aq). Synthesis
2H), 1.38 (t, J = 7.0 Hz, 3H), 1.34–1.27 (m, 2H), 0.89 (t, J = 7.4 was carried out according to the general procedure, and com-
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 170.8, 167.0, pound 4aq was obtained in 56% yield as a colorless oil after
165.2, 140.3, 135.0, 133.3, 131.4, 130.6, 129.2, 127.8, 119.1, purification by silica gel column chromatography. 1H NMR
115.5, 115.3, 64.2, 60.0, 30.6, 19.1, 14.4, 13.7, 13.2, 12.1. HRMS (400 MHz, CDCl3) δ (ppm): 7.72 (d, J = 7.2 Hz, 2H), 7.59 (t, J =
(ESI) m/z: calcd for C23H27NNaO5 [M + Na]+: 420.1781, found 7.4 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 6.77 (t, J = 2.4 Hz, 1H), 6.11
420.1787.
(d, J = 2.8 Hz, 2H), 3.24 (t, J = 7.4 Hz, 2H), 2.82 (t, J = 7.4 Hz,
Butyl (E)-3-(1-(cyclohexanecarbonyl)-1H-pyrrol-2-yl)acrylate 2H), 2.45 (q, J = 7.2 Hz, 2H), 1.06 (t, J = 7.4 Hz, 3H). 13C NMR
(3sa). Synthesis was carried out according to the general pro- (100 MHz, CDCl3) δ (ppm): 210.6, 169.3, 136.0, 134.3, 132.3,
cedure, and compound 3sa was obtained in 71% yield as a 129.7, 128.4, 123.4, 112.8, 110.6, 42.1, 35.9, 23.0, 7.8. HRMS
colorless oil after purification by silica gel column chromato- (ESI) m/z: calcd for C16H17NNaO2 [M + Na]+: 278.1151, found
1
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 8.28 (d, J = 16.0 278.1154.
Hz, 1H), 7.28–7.27 (m, 1H), 6.70 (d, J = 4.0 Hz, 1H), 6.28 (t, J =
3-(1-Benzoyl-1H-pyrrol-2-yl)-1-cyclohexylpropan-1-one (4ar).
3.4 Hz, 1H), 6.20 (d, J = 16.0 Hz, 1H), 4.18 (t, J = 6.6 Hz, 2H), Synthesis was carried out according to the general procedure,
2.96–2.91 (m, 1H), 1.98–1.94 (m, 2H), 1.89–1.85 (m, 2H), and compound 4ar was obtained in 51% yield as a colorless
1
1.69–1.64 (m, 4H), 1.44–1.39 (m, 6H), 0.95 (t, J = 7.4 Hz, 3H). oil after purification by silica gel column chromatography. H
13C NMR (100 MHz, CDCl3) δ (ppm): 175.5, 167.1, 135.5, 132.1, NMR (400 MHz, CDCl3) δ (ppm): 7.72 (d, J = 6.8 Hz, 2H), 7.59
123.0, 117.3, 115.3, 112.5, 64.2, 44.1, 30.8, 29.6, 25.6, 25.5, (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 6.77 (t, J = 2.6 Hz,
19.2, 13.7. HRMS (ESI) m/z: calcd for C18H25NNaO3 [M + Na]+: 1H), 6.10 (d, J = 2.8 Hz, 2H), 3.21 (t, J = 7.4 Hz, 2H), 2.85 (t, J =
326.1727, found 326.1730.
7.4 Hz, 2H), 2.39–2.32 (m, 1H), 1.85–1.75 (m, 4H), 1.38–1.19
Butyl (E)-3-(1-(cyclopentanecarbonyl)-1H-pyrrol-2-yl)acrylate (m, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm): 213.1, 169.3,
(3ta). Synthesis was carried out according to the general pro- 136.2, 134.3, 132.3, 129.7, 128.4, 123.4, 112.8, 110.5, 50.8, 40.4,
cedure, and compound 3ta was obtained in 73% yield as a 28.4, 25.8, 25.7, 22.9. HRMS (ESI) m/z: calcd for C20H23NNaO2
colorless oil after purification by silica gel column chromato- [M + Na]+: 332.1621, found 332.1616.
1
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 8.31 (d, J = 16.0
Dibutyl 3,3′-(1-benzoyl-1H-pyrrole-2,5-diyl)(2E,2′E)-diacrylate
Hz, 1H), 7.30–7.29 (m, 1H), 6.69 (d, J = 3.6 Hz, 1H), 6.27 (t, J = (6aa). Synthesis was carried out according to the general pro-
3.4 Hz, 1H), 6.20 (d, J = 16.0 Hz, 1H), 4.17 (t, J = 6.8 Hz, 2H), cedure, and compound 6aa was obtained in 61% yield as a
3.43–3.35 (m, 1H), 2.01–1.96 (m, 4H), 1.83–1.75 (m, 2H), colorless oil after purification by silica gel column chromato-
1.70–1.63 (m, 4H), 1.46–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H). graphy. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.70–7.65 (m, 3H),
13C NMR (100 MHz, CDCl3) δ (ppm): 175.5, 167.0, 135.5, 132.2, 7.49 (t, J = 7.8 Hz, 2H), 7.27 (d, J = 16.0 Hz, 2H), 6.82 (s, 2H),
123.3, 117.2, 115.2, 112.4, 64.2, 44.3, 30.8, 30.6, 26.1, 19.1, 6.18 (d, J = 16.0 Hz, 2H), 4.08 (t, J = 6.6 Hz, 4H), 1.61–1.54 (m,
13.7. HRMS (ESI) m/z: calcd for C17H23NNaO3 [M + Na]+: 4H), 1.37–1.28 (m, 4H), 0.91 (t, J = 7.4 Hz, 6H). 13C NMR
312.1570, found 312.1573.
(100 MHz, CDCl3) δ (ppm): 169.2, 166.5, 135.0, 134.0, 133.6,
Butyl (E)-3-(1-acetyl-1H-pyrrol-2-yl)acrylate (3ua). Synthesis 132.0, 130.8, 129.1, 117.4, 114.0, 64.3, 30.6, 19.1, 13.7. HRMS
was carried out according to the general procedure, and com- (ESI) m/z: calcd for C25H29NNaO5 [M + Na]+: 446.1938, found
pound 3ua was obtained in 76% yield as a colorless oil after 446.1932.
purification by silica gel column chromatography. 1H NMR
Butyl (E)-3-(1-benzoyl-1H-indol-2-yl)acrylate (8aa). Synthesis
(400 MHz, CDCl3) δ (ppm): 8.32 (d, J = 16.0 Hz, 1H), 7.21–7.20 was carried out according to the general procedure, and com-
(m, 1H), 6.71 (d, J = 3.2 Hz, 1H), 6.28 (t, J = 3.4 Hz, 1H), 6.22 (d, pound 8aa was obtained in 80% yield as a colorless oil after
J = 16.0 Hz, 1H), 4.18 (t, J = 6.8 Hz, 2H), 2.59 (s, 3H), 1.71–1.63 purification by silica gel column chromatography. 1H NMR
(m, 2H), 1.47–1.38 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR (400 MHz, CDCl3) δ (ppm): 7.73 (d, J = 7.6 Hz, 2H), 7.67–7.60
(100 MHz, CDCl3) δ (ppm): 169.2, 167.0, 135.1, 132.2, 123.8, (m, 2H), 7.52–7.47 (m, 3H), 7.34 (d, J = 8.0 Hz, 1H), 7.26–7.18
117.6, 115.4, 112.8, 64.3, 30.8, 24.2, 19.2, 13.7. HRMS (ESI) m/z: (m, 2H), 7.10 (s, 1H), 6.33 (d, J = 16.0 Hz, 1H), 4.12 (t, J = 6.8
calcd for C13H17NNaO3 [M + Na]+: 258.1101, found 258.1103.
Butyl (E)-3-(1-methacryloyl-1H-pyrrol-2-yl)acrylate
Hz, 2H), 1.64–1.57 (m, 2H), 1.41–1.31 (m, 2H), 0.94 (t, J = 7.4
(3va). Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 169.2, 166.2,
Synthesis was carried out according to the general procedure, 138.2, 136.1, 134.8, 134.3, 133.4, 130.1, 128.9, 128.7, 125.4,
and compound 3va was obtained in 79% yield as a colorless 123.4, 121.3, 119.0, 114.6, 110.7, 64.4, 30.6, 19.1, 13.7. HRMS
1
oil after purification by silica gel column chromatography. H (ESI) m/z: calcd for C22H21NNaO3 [M + Na]+: 370.1414, found:
NMR (400 MHz, CDCl3) δ (ppm): 8.04 (d, J = 16.0 Hz, 1H), 370.1410.
7.18–7.17 (m, 1H), 6.80 (d, J = 3.2 Hz, 1H), 6.25 (t, J = 3.4 Hz,
1H), 6.22 (d, J = 16.0 Hz, 1H), 5.80 (d, J = 1.6 Hz, 1H), 5.59 (s,
1H), 4.18 (t, J = 6.8 Hz, 2H), 2.12 (s, 3H), 1.71–1.63 (m, 2H),
Conflicts of interest
1.47–1.37 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ (ppm): 169.7, 167.0, 139.5, 134.2, 131.7, 125.9, 125.5, There are no conflicts to declare.
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Acknowledgements
We thank the Natural Science Foundation of Shandong
Province (ZR2019MB009), the Key Research and Development
Program of Shandong Province (2019GSF108089), the National
Natural Science Foundation of China (21672046 and
21372054), and the Fund from the Huancui District of Weihai
City.
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