DBU-promoted tandem Michael-addition/cyclization for the synthesis of polysubstituted pyrroles

Article abstract of DOI:10.1016/j.tet.2019.02.057

An efficient and transition-metal-free method for the synthesis of the structurally diversified pyrroles is described. Various α,β-unsaturated ynones reacted with N-substituted ethyl glycine ethyl ester hydrochlorides in the presence of DBU to form the co

Full text of DOI:10.1016/j.tet.2019.02.057

Accepted Manuscript
DBU-promoted tandem Michael-addition/cyclization for the synthesis of
polysubstituted pyrroles
Tianyu Yang, Ke-Hu Wang, Danfeng Huang, Pengfei Li, Zhoubin Deng, Yinpeng Su,
Yulai Hu
PII:
S0040-4020(19)30217-0
https://doi.org/10.1016/j.tet.2019.02.057
TET 30180
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 January 2019
Revised Date: 23 February 2019
Accepted Date: 25 February 2019
Please cite this article as: Yang T, Wang K-H, Huang D, Li P, Deng Z, Su Y, Hu Y, DBU-promoted
tandem Michael-addition/cyclization for the synthesis of polysubstituted pyrroles, Tetrahedron (2019),
doi: https://doi.org/10.1016/j.tet.2019.02.057.
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ACCEPTED MANUSCRIPT
Graphical Abstract
DBU-Promoted Tandem Michael-addition /
Cyclization for the Synthesis of
Polysubstituted Pyrroles
Leave this area blank for abstract info.
Tianyu Yang, Ke-Hu Wang, Danfeng Huang, Peifei Li, Zhoubin Deng, Yingpeng Su and Yulai Hu*
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, P. R. China.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
DBU-Promoted Tandem Michael-addition/Cyclization for the Synthesis of
Polysubstituted Pyrroles
Tianyu Yanga, Ke-Hu Wanga, Danfeng Huanga, Pengfei Lia, Zhoubin Denga, Yinpeng Sua and Yulai Hua,b,
a College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, P. R. China.
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient and transition-metal-free method for the synthesis of the structurally diversified
pyrroles is described. Various α,β-unsaturated ynones reacted with N-substituted ethyl glycine
ethyl ester hydrochlorides in the presence of DBU to form the corresponding products in good
yields. This protocol has the advantages of readily available starting materials, mild reaction
conditions and a wide scope of substrates, which provides a practical route for the synthesis of
polysubstituted pyrroles.
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved
.
α,β-unsaturated ynones
glycine ethyl ester
pyrroles
Michael addition
cyclization
tandem reaction
1. Introduction
in synthetic chemistry. The traditional methods for synthesis of
pyrroles are the Paal-Knorr7 or Hantazsch8 reactions. Transition-
metal-catalyzed methodologies are other important and efficient
approaches for construction of pyrrole derivatives in recent
years.9
Pyrroles represent an important class of nitrogen-containing
heterocycles, which show diverse pharmacological properties
such as anti-HIV-1,1 antitumor,2 antifungel3 and other
bioactivities.4 For examples, Atorvastatin, Lamellarin Q and
Porphobilinogen are prevalent pyrrole-derived clinical drugs
(Scheme 1).
On the other hand, α,β-unsaturated ynones are important
building blocks in the synthesis of heterocycles because of their
easy preparation and commercial availability.10 Till now, α,β-
unsaturated ynones have been successfully used in the synthesis
of pyridines,11 furfurans,12 and other heterocycles.13 As versatile
building blocks, they could also be applied for construction of
pyrrole derivatives. For instance, Cu-assisted cycloisomerisation
reactions of α,β-unsaturated ynone-derived alkynyl imines were
reported to provide pyrrole derivatives in good yields.14 One-pot
reactions of ynones with benzylamines could afford pyrrole
derivatives under metal free conditions, but amino acid esters
failed to give the corresponding pyrrole derivatives under the
same conditions.15 Meanwhile, there is an ester group at 2-
position of pyrrole ring of Lamellarin Q. In our research works,
we found that the reaction of ynones and amino acid esters
produced the ester group-containing pyrrole derivatives in good
yields when the reaction was performed in a two-step way in the
presence of DBU. Herein, we would like to disclose a practical
Scheme 1 Selected biological and pharmaceutical molecules
bearing highly substituted pyrrole
Pyrrole cores also appear frequently in natural products5 and
functional materials such as conducting materials.6 Due to their
wide applications, the development of new and more efficient
method for construction of pyrroles has long been an active topic
DBU-mediated
synthesis
of
ester
group-containing
Corresponding author. e-mail: huyl@nwnu.edu.cn

2
Tetrahedron
ACCEPTED MANUSCRIPT
Table 1 Optimization of Reaction Conditionsa
polysubstituted pyrroles from the reaction of amino acid esters
and ynones.
2. Results and discussion
We initiated our study with the reaction of 1,3-diphenylprop-
2-yn-1-one 1a (1 equiv), glycine ethyl ester hydrochloride 2a (1
equiv) and DBU (1 equiv) in DMSO at room temperature. After
12 h, the reaction mixture was then heated at 140 oC for another 4
h. The desired product 3a was obtained in 25% yield with
another compound 4a being formed in 32% yield (Table 1, entry
1). We envisioned that enaminone 4a would be the intermediate
for the desired product 3a. Based on literature reports about the
formation of enaminones, alcoholic solvent was beneficial to
generate the compound 4a.16 Thus, the mixture of 1,3-
diphenylprop-2-yn-1-one 1a (1 equiv), glycine ethyl ester
hydrochloride 2a (1 equiv) and DBU (1 equiv) were firstly stirred
in ethanol at room temperature for 12 h to form the compound
4a, and then the ethanol was replaced by DMSO. The reaction
mixture was heated at 140 oC for another 4 h to afford the
product 3a in 48% yield, but the compound 4a was still obtained
in 19% yield (Table 1, entry 2). When both two steps were
carried out in ethanol, there was no product 3a formed, and only
enaminone 4a was obtained in 45% yield (Table 1, entry 3).
Meanwhile, the toluene and 1,4-dioxane were used as the
solvents for the second step, the desired product 3a was not
formed in both of the solvents. When DMF was used, the 3a was
obtained in 35% yield with the compound 4a being formed in
13% yield (Table 1, entry 4−6). The result indicated that DMSO
is the suitable solvent for the second step. When the reaction
temperature in the second step was decreased, the yield of the
desired product 3a decreased (Table 1, entries 7−10). Further
studies showed that the yield of product 3a reached to 85% when
4 equiv of glycine ethyl ester hydrochloride 2a and 4 equiv of
DBU in step one were used (Table 1, entry 17). The other bases
such as KOH, NaOH, K3PO4, Na3PO4, K2CO3, Cs2CO3, Et3N, and
DABCO were also examined, but DBU gave the best result.
Thus, the best reaction conditions were the treatment of 1 equiv
of 1,3-diphenylprop-2-yn-1-one with 4 equiv of glycine ethyl
ester hydrochloride and 4 equiv of DBU in ethanol at room
temperature for 12 h, and then the ethanol was vaporized. The
residue was redissolved in DMSO, and another 1 equiv of DBU
Step 1
DBU
Step 2
Yield (%)b
3a/4a
Entry
1a/2a
Temp
(oC)
140
DBU
1c
2
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:2
1:3
1:4
1:4
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
2 equiv.
3 equiv.
4 equiv.
4 equiv.
4 equiv.
4 equiv.
4 equiv.
/
/
/
/
/
/
/
/
/
/
25/32
48/19
0/45
0/27
0/36
35/13
37/21
28/30
23/25
10/43
54/15
58/12
60/8
140
reflux
reflux
reflux
140
120
100
50
3d
4e
5f
6g
7
8
9
10
11
12
13
14
15
16
17
18
r.t.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
1 equiv.
140
140
140
140
140
140
140
140
69/0
71/0
82/0
85/0
1.5 equiv.
76/0
a Reaction conditions: 1a (0.5 mmol), 2a (1.0−4.0 equiv) and DBU (1.0−4.0
equiv) were mixed in EtOH (5 mL), and stirred at r.t. for 12 h. EtOH was
vaporized, and then another portion of DBU (0−1.5 equiv) and DMSO (5 mL)
was added. The mixture was stirred at 140 oC for 4 h. b Isolated yields. c Step
d
e
1: using DMSO as solvent. Step 2: using EtOH as solvent. Step 2: using
toluene as solvent. f Step 2: using 1,4-dioxane as solvent. g Step 2: using DMF
as solvent.
Table 2 Reaction of N-Substituted Glycine Ethyl Ester
Hydrochlorides 2a−2g with Ynones 1a−1ca
Entry R1
R2
R3
Product Yield (%)b
1
2
3
4
5
6
7
8
9
C6H5 (1a)
C6H5 (1a) H (2a)
3a
3b
3c
3d
3e
3f
85
0
C6H5 (1a)
C6H5 (1a)
C6H5 (1a)
C6H5 (1a)
C6H5 (1a) C6H5 (2b)
C6H5 (1a) Boc (2c)
C6H5 (1a) Benzyl (2d)
C6H5 (1a) Methyl (2e)
0 (62c)
65
76
57
65
0
o
was added. The mixture was heated at 140 C for another 4 h.
The target product 3a was then obtained.
4-CH3C6H4 (1b) C6H5 (1b) Methyl (2e)
With the optimal reaction conditions in hand, the scope of the
reaction was investigated. First, glycine ethyl ester hydrochloride
and its N-substituted derivatives 2a−2g were reacted with ynones
1a−1c. As shown in Table 2, the substituents on nitrogen atom of
glycine ethyl ester had great influence on the reaction. When N-
phenyl glycine ethyl ester was used in the reaction, no product 3b
was obtained (Table 2, entry 2). When N-Boc glycine ethyl ester
was applied in the reaction, the deprotected product 3a was
formed instead of Boc-protected product 3c (Table 2, entry 3). N-
Alkyl glycine ethyl ester could also be applied in the reaction to
afford the corresponding products (Table 2, entries 5−9), but the
yields were lower. When the bulky t-butyl group was attached to
the nitrogen atom, no product was formed (Table 2, entry 8).
These results indicated that the electronic properties and steric
hindrance at the N atom disfavored this reaction.
4-ClC6H4 (1c)
C6H5 (1a)
C6H5 (1a)
C6H5 (1c) Methyl (2e)
C6H5 (1a) t-Butyl (2f)
C6H5 (1a) n-Butyl (2g) 3i
3g
3h
37
aReaction conditions: 1a−1c (0.5 mmol, 1 equiv), 2a−2g (4.0 equiv) and DBU
(4.0 equiv) were mixed in EtOH (5 mL) and then stirred at r.t. for 12 h, EtOH
was vaporized, and then another portion of DBU (1.0 equiv) and DMSO (5
o
b
mL) was added. The mixture was stirred at 140 C for 4 h. Isolated yields.
cYield of 3a.
not influence the transformation obviously. For instance, when
the substituents on aromatic ring of R1 group were methyl or
chlorine group, the para-, ortho- and meta-substituted products
3j−3n were obtained in almost the same yields (Table 3, entries
1−5). Meanwhile, the electronic properties of the substituents on
phenyl rings of aromatic ynones had influence on the product
yields. For examples, when both substituents on aromatic rings of
R1 and R2 groups were methyl group, the yield of 3u was 67%
(Table 3, entry 12). However, when the substituent on aromatic
rings of R1 group was chlorine and the substituent on aromatic
rings of R2 group was methyl group, the yield of 3v decreased to
49% (Table 3, entry 13). When the R1 or/and R2 groups were
aliphatic substituents, the corresponding products were produced
in low yields (Table 3, entries 15−26). Especially, no product
Afterward, various ynones 1b−1aa were investigated in the
reaction. As shown in Table 3. Both electrodonating and
electrowithdrawing groups on phenyl rings of 1,3-diarylynones
were well tolerated and provided the corresponding products in
good yields (Table 3, entries 1−14). Further observation showed
that the steric hindrance on phenyl rings of aromatic ynones did

3
ACCEPTED MANUSCRIPT
was formed if R1 was t-butyl group (Table 3, entry 18). When R1
was trifluoromethyl group, only intermediate 4ai was obtained
instead of the corresponding pyrrole in the yield of 92% (Table
3, entry 26).
which was depicted in Scheme 3. First, glycine ethyl ester
hydrochloride 2a was neutralized by DBU to give glycine ethyl
ester 5a, which performed 1,4-addition reaction with ynone 1a to
provide the enaminone 4a. Deprotonation of the enaminone 4a
by DBU generated the anion intermediate 6a, which conducted
1,2-addition to carbonyl group to generate intermediate 7a.
Dehydration of 7a gave the product 3a.
Table 3 Reaction of Glycine Ethyl Ester Hydrochlorides 2a
with Various Ynones 1b−1aaa
Entry R1
R2
Product
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
3u
3v
3w
3x
3y
Yield (%)b
74
76
67
73
64
72
69
75
84
70
65
67
49
78
64
38
1
4-CH3C6H4 (1b)
C6H5 (1b)
C6H5 (1c)
C6H5 (1d)
C6H5 (1e)
C6H5 (1f)
C6H5 (1g)
C6H5 (1h)
C6H5 (1i)
2
3
4
5
6
7
4-ClC6H4 (1c)
2-CH3C6H4 (1d)
3-ClC6H4 (1e)
2-ClC6H4 (1f)
4-CH3OC6H4 (1g)
4-FC6H4 (1h)
8
9
4-CF3C6H4 (1i)
3,5-Cl2C6H3 (1j)
2-Naphthyl (1k)
1-Naphthyl (1l)
4-CH3C6H4 (1m)
4-ClC6H5 (1n)
3,5-Cl2C6H3 (1o)
Benzyl (1p)
Methyl (1q)
i-Propyl (1r)
t-Butyl (1s)
Cyclohexyl (1t)
Cinnamyl (1u)
4-CH3C6H4 (1v)
3,5-Cl2C6H3 (1w)
C6H5 (1j)
C6H5 (1k)
C6H5 (1l)
10
11
12
13
14
15
16
17
18
19
20
21
22
Scheme 3 Proposed mechanism
4-CH3C6H4 (1m)
4-CH3C6H4 (1n)
4-CH3C6H4 (1o)
C6H5 (1p)
C6H5 (1q)
C6H5 (1r)
C6H5 (1s)
C6H5 (1t)
C6H5 (1u)
3. Conclusions
In summary, we have developed an effective and practical
tandem Michael addition/cyclization of α,β-unsaturated ynones
with N-substituted glycine ethyl ester hydrochlorides for the
synthesis of polysubstituted pyrroles under transition-metal-free
conditions. A series of polysubstituted pyrroles were obtained in
good yields. This protocol overcomes some literature limitations,
and makes the glycine ethyl ester hydrochlorides applicable for
the preparation of polysubstituted pyrroles.
3z
30
0
13
58
45
60
3aa
3ab
3ac
Cyclopropyl (1v) 3ad
Cyclopropyl
3ae
(1w)
23
24
25
26
C6H5 (1x)
C6H5 (1y)
Methyl (1z)
Trifluoromethyl
(1aa)
t-Butyl (1x)
Cyclohexyl (1y)
H (1z)
3af
10
15
3ag
3ah
3ai
4. Experimental Section
19
C6H5 (1aa)
0 (92c)
All of the commercially available reagents and solvents were
used without further purification. α,β-unsaturated ynones and
compounds 2f and 2g were prepared according to the literature
procedure.10e,17 Flash chromatography was performed using silica
gel 60 (230-400 mesh). Analytical thin layer chromatography
(TLC) was conducted using silica gel GF254. TLC plates were
analysed by an exposure to ultraviolet (UV) light and/or
submersion in a phosphomolybdic acid solution or in iodine
(4ai)
a
Reaction conditions: 1b−1aa (0.5 mmol), 2a (4.0 equiv), DBU (4.0 equiv)
were mixed in EtOH (5 mL), and then stirred at r.t. for 12 h, EtOH was
vaporized, and then another portion of DBU (1.0 equiv) and DMSO (5 mL)
was added. The mixture was stirred at 140 oC for 4 h. b Isolated yields. c Yield
of 4ai.
In order to further demonstrate the utilities of this process in
synthesis of pyrrole derivatives, a gram-scale experiment was
conducted (Scheme 2). When 1.03 gram of 1,3-diphenylprop-2-
yn-1-one 1a reacted with 2.79 gram of glycine ethyl ester
hydrochloride 2a under the standard reaction conditions. The
product 3a was obtained in 80% yield. This result showed this
process was an efficient and practical method to prepare pyrrole
derivatives
1
vapour. H NMR spectra were measured on 600 MHz and 400
MHz spectrometers. Chemical shifts were recorded as follows:
chemical shift in parts per million from internal tetramethylsilane
on the δ scale, multiplicity (s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; br, broad), coupling constant (hertz),
integration, and assignment. 13C NMR spectra were measured on
150 MHz and 100 MHz spectrometers. Chemical shifts were
recorded in parts per million from the solvent resonance
employed as the internal standard (deuterochloroform at 77.0
ppm).
Ph
Ph
COOEt
+
Ph
COOEt
NH2•HCl
N
H
Ph
O
4.1. General experimental procedure for the synthesis of
compounds 3
3a, 1.16 g
(80% yield)
1a, 1.03 g
2a, 2.79 g
α,β-Unsaturated ynones (1; 0.5 mmol, 1 equiv), N-substituted
glycine ethyl ester hydrochlorides (2; 2.0 mmol, 4 equiv) and
DBU (2.0 mmol, 4 equiv) were mixed in ethanol (5 mL) and
stirred at room temperature for 12 h. When TLC showed
intermediate 4 was generated, ethanol was evaporated. DBU (0.5
mmol, 1 equiv) and DMSO (5 mL) were then added, the mixture
was stirred at 140 oC for 4 h. After completion of the reaction, the
under standard conditions
Scheme 2 Gram-scale synthesis of ethyl 3,5-diphenyl-1H-
pyrrole-2-carboxylate 3a
On the basis of the literature,12a,16 and our experimental
results, a tentative mechanism for the reaction was proposed,

4
Tetrahedron
ACCEPTED MANUSCRIPT
mixture was diluted with ethyl acetate (3 × 10 mL) and washed
0.77 (t, J = 7.2 Hz, 3H).13C NMR (150 MHz, CDCl3) δ = 162.0,
with brine (3 × 10 mL). The organic phase was dried over
anhydrous Na2SO4 and filtered. The solvents were vaporized, and
the residue was purified by silica gel column chromatography
with EtOAc/petroleum ether (1 : 5−1 : 3) as the eluent to afford
the products 3.
140.0, 137.0, 133.7, 132.5, 129.6, 129.4, 128.4, 128.0, 127.4,
126.4, 119.1, 111.7, 59.8, 46.0, 33.9, 19.7, 13.7, 13.6.HRMS
(ESI): m/z [M + H]+ calcd for C23H26NO2: 348.1958; found
348.1954.
4.8. Ethyl 5-phenyl-3-(p-tolyl)-1H-pyrrole-2-carboxylate18 (3j)
4.2. Ethyl 3,5-diphenyl-1H-pyrrole-2-carboxylate18 (3a)
White solid (74%, 112.8 mg); m. p. 169−170oC; Rf = 0.5 (EA/
PE = 1/5). H NMR (600 MHz, CDCl3) δ = 9.40 (s, 1H), 7.60
1
1
Yellow oil (85%, 123.6 mg); Rf = 0.5 (EA/ PE = 1/5). H
NMR (600 MHz, CDCl3) δ = 9.66 (s, 1H), 7.61 (d, J = 7.8 Hz,
2H), 7.58 (d, J = 7.2 Hz, 2H), 7.41−7.36 (m, 4H), 7.31 (d, J = 7.2
Hz, 1H), 7.29 (d, J = 7.2 Hz, 1H), 6.61 (d, J = 3.0 Hz, 1H), 4.24
(q, J = 7.2 Hz, 2H), 1.22 (t, J = 7.2 Hz, 3H). 13C NMR (150
MHz, CDCl3) δ = 161.4, 135.5, 135.2, 133.4, 131.1, 129.5, 128.9,
127.8, 127.6, 127.0, 124.8, 118.6, 109.9, 60.4, 14.1.
(d, J = 7.2 Hz, 2H), 7.50 (d, J = 7.8 Hz, 2H), 7.42 (t, J = 7.2 Hz,
2H), 7.31 (t, J = 7.8 Hz, 1H), 7.19 (d, J = 7.8 Hz, 2H), 6.61 (d, J
= 3.0 Hz, 1H), 4.28 (q, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.27 (t, J =
7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ = 161.2, 136.8,
135.3, 133.5, 132.1, 131.1, 129.4, 129.0, 128.4, 127.9, 124.8,
118.5, 109.9, 60.3, 21.2, 14.3.
4.3. Ethyl 1-benzyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (3d).
4.9. Ethyl 3-(4-chlorophenyl)-5-phenyl-1H-pyrrole-2-carboxylate
19 (3k).
1
Yellow oil (65%, 123.8 mg); Rf = 0.4 (EA/ PE = 1/5). H
o
White solid (76%, 123.8 mg ); m. p. 184−185 C; Rf = 0.4
NMR (600 MHz, CDCl3) δ = 7.46 (d, J = 7.2 Hz, 2H), 7.35−7.33
(m, 7H), 7.28 (t, J = 7.2 Hz, 1H), 7.24 (t, J = 8.4 Hz, 2H), 7.17 (t,
J = 7.8 Hz, 1H), 6.92 (t, J = 7.2 Hz, 2H), 6.34 (d, J = 2.4 Hz,
1H), 5.60 (s, 2H), 4.00 (q, J = 7.2 Hz, 2H), 0.93 (t, J = 7.2 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ = 161.7, 140.5, 139.4, 136.6,
134.0, 132.0, 129.5, 129.4, 128.5, 128.4, 128.2, 127.5, 126.7,
126.6, 125.7, 119.7, 112.0, 59.8, 49.6, 13.6. HRMS (ESI): m/z
[M + Na]+ calcd for C26H23NO2Na: 404.1621; found 404.1621.
(EA/ PE = 1/5). 1H NMR (600 MHz, DMSO-d6) δ = 12.0 (s, 1H),
7.90 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.43−7.40 (m,
4H), 7.30 (t, J = 7.2 Hz, 1H), 6.77 (d, J = 2.4 Hz, 1H), 4.20 (q, J
= 7.2 Hz, 2H), 1.21 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz,
DMSO-d6) δ = 165.3, 140.8, 139.1, 136.3, 136.0, 135.9, 135.8,
133.6, 132.4, 132.4, 130.4, 123.6, 114.7, 64.6, 19.1.
4.10. Ethyl 5-phenyl-3-(o-tolyl)-1H-pyrrole-2-carboxylate (3l).
4.4. Ethyl 1-methyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (3e).
o
White solid (67%, 102.2 mg); m. p. 157−158 C; Rf = 0.5
1
(EA/ PE = 1/5). H NMR (600 MHz, CDCl3) δ = 9.54 (br, 1H),
7.61 (d, J = 7.8 Hz, 2H), 7.41 (t, J = 7.8 Hz, 2H), 7.31 (t, J = 7.2
Hz, 1H), 7.25−7.23 (m, 3H), 7.20−7.17 (m, 1H), 6.49 (d, J = 3.0
Hz, 1H), 4.14 (q, J = 7.2 Hz, 2H), 2.24 (s, 3H), 1.07 (t, J = 7.2
Hz, 3H). 13C NMR (150 MHz, CDCl3) δ = 161.3, 136.6, 135.6,
135.3, 132.6, 131.2, 130.1, 129.4, 129.0, 127.8, 127.2, 124.9,
124.7, 120.0, 110.2, 60.1, 20.3, 14.0. HRMS (ESI): m/z [M + H]+
calcd for C20H20NO2: 306.1489; found 306.1486.
Pale yellow oil (76%, 116.0 mg); Rf = 0.6 (EA/ PE = 1/5). H
NMR (600 MHz, CDCl3) δ = 7.43−7.40 (m, 6H), 7.38−7.32 (m,
3H), 7.27 (t, J = 7.2 Hz, 1H), 6.24 (d, J = 1.8 Hz, 1H), 4.14 (q, J
= 7.2 Hz, 2H), 3.85 (s, 3H), 1.06 (t, J = 7.8 Hz, 3H). 13C NMR
(150 MHz, CDCl3) δ = 162.0, 140.2, 136.7, 133.4, 131.9, 129.5,
129.3, 128.4, 128.0, 127.4, 126.5, 120.3, 111.3, 59.7, 35.0, 13.8.
HRMS (ESI): m/z [M + Na]+ calcd for C20H19NO2Na: 328.1308;
found 328.1313.
4.11. Ethyl 3-(3-chlorophenyl)-5-phenyl-1H-pyrrole-2-
4.5. Ethyl 1-methyl-5-phenyl-3-(p-tolyl)-1H-pyrrole-2-
carboxylate (3m).
carboxylate (3f).
o
1
White solid (73%, 119 mg); m. p. 178−179 C; Rf = 0.5 (EA/
Pale yellow oil (57%, 91.0 mg); Rf = 0.6 (EA/ PE = 1/5). H
PE = 1/4). 1H NMR (400 MHz, CDCl3) δ = 9.71 (s, 1H),
7.62−7.60 (m, 3H), 7.46−7.39 (m, 3H), 7.34−7.29 (m, 3H), 6.60
(d, J = 2.4 Hz, 1H), 4.26 (q, J = 7.2 Hz, 2H), 1.25 (t, J = 6.8 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ = 161.3, 137.0, 135.7, 133.4,
131.7, 130.9, 129.7, 129.0, 128.8, 128.0, 127.7, 127.0, 124.9,
118.8, 109.7, 60.6, 14.1. HRMS (ESI): m/z [M + H]+ calcd for
C19H17ClNO2: 326.0942; found 326.0938.
NMR (600 MHz, CDCl3) δ = 7.41−7.37 (m, 4H), 7.34−7.32 (m,
3H), 7.14 (d, J = 7.8 Hz, 2H), 6.22 (d, J = 1.2 Hz, 1H), 4.15 (q, J
= 7.2 Hz, 2H), 3.83 (s, 3H), 2.35 (s, 3H), 1.10 (t, J = 7.2 Hz, 3H).
13C NMR (150 MHz, CDCl3) δ = 162.0, 140.1, 136.0, 133.6,
133.3, 131.9, 129.3, 129.3, 128.4, 128.1, 127.9, 120.2, 111.3,
59.7, 34.9, 21.1, 13.8. HRMS (ESI): m/z [M + Na]+ calcd for
C21H21NO2Na: 342.1465; found 342.1469.
4.12. Ethyl 3-(2-chlorophenyl)-5-phenyl-1H-pyrrole-2-
4.6. Ethyl 3-(4-chlorophenyl)-1-methyl-5-phenyl-1H-pyrrole-2-
carboxylate (3n).
carboxylate (3g).
o
Dark yellow oil (65%, 55.1 mg); Rf = 0.5 (EA/ PE = 1/5).1H
NMR (600 MHz, CDCl3) δ = 7.43−7.40 (m, 4H), 7.38−7.34 (m,
3H), 7.30 (d, J = 8.4 Hz, 2H), 6.20 (d, J = 1.8 Hz, 1H), 4.15 (q, J
= 7.2 Hz, 2H), 3.85 (s, 3H), 1.10 (t, J = 7.2 Hz, 3H).13C NMR
(150 MHz, CDCl3) δ = 162.0, 140.3, 135.2, 132.4, 132.0, 131.7,
130.8, 129.3, 128.5, 128.1, 127.5, 120.2, 111.2, 60.0, 35.0, 14.0.
HRMS (ESI): m/z [M + Na]+ calcd for C20H18ClNO2Na:
362.0918; found 362.0910.
White solid (64%, 104.4 mg); m. p. 184−185 C; Rf = 0.5
1
(EA/ PE = 1/4). H NMR (400 MHz, CDCl3) δ = 9.93 (br, 1H),
7.64 (d, J = 7.6 Hz, 2H), 7.45−7.38 (m, 4H), 7.31−7.24 (m, 3H),
6.57 (d, J = 2.8, 1H), 4.16 (q, J = 7.2, 2H), 1.07 (t, J = 6.8 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ = 161.4, 135.5, 135.0,
133.9, 131.8, 131.1, 129.7, 129.0, 128.9, 128.3, 127.8, 125.9,
124.9, 120.4, 110.2, 60.4, 13.9. HRMS (ESI): m/z [M + H]+ calcd
for C19H17ClNO2: 326.0942; found 326.0937.
4.13. Ethyl 3-(4-methoxyphenyl)-5-phenyl-1H-pyrrole-2-
4.7. Ethyl 1-butyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (3i).
carboxylate18 (3o).
Dark yellow oil (37%, 64.2 mg); Rf = 0.5 (EA/ PE = 1/10).1H
NMR (600 MHz, CDCl3) δ = 7.42−7.41 (m, 6H), 7.39−7.36 (m,
1H), 7.33 (t, J = 7.2 Hz, 2H), 7.26 (t, J = 7.2 Hz, 1H), 6.19 (d, J =
1.8 Hz, 1H), 4.33 (t, J = 6.0 Hz, 2H), 4.14 (q, J = 7.2 Hz, 2H),
1.64−1.59 (m, 2H), 1.18−1.11 (m, 2H), 1.05(t, J = 7.2 Hz, 3H),
White solid (72%, 115.6 mg); m.p. 133−134 oC; Rf = 0.5 (EA/
1
PE = 1/5). H NMR (400 MHz, CDCl3) δ = 9.46 (br, 1H), 7.60
(d, J = 7.6 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.41 (t, J = 7.2 Hz,
2H), 7.31 (t, J = 7.6 Hz, 1H), 6.93 (t, J = 8.8 Hz, 2H), 6.59 (d, J =

5
ACCEPTED MANUSCRIPT
3.2 Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H), 3.84 (s, 3H), 1.27 (t, J =
7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ = 161.2, 158.9,
135.4, 133.3, 131.1, 130.6, 129.0, 127.8, 127.5, 124.8, 118.3,
113.1, 109.8, 60.3, 55.3, 14.3.
125.4, 124.9, 124.8, 120.8, 111.2, 60.1, 13.5. HRMS (ESI): m/z
[M + H]+ calcd for C23H20NO2: 342.1489; found 342.1485.
4.19. Ethyl 3,5-di-p-tolyl-1H-pyrrole-2-carboxylate (3u).
o
White solid (67%, 106.8 mg); m. p. 173−175 C; Rf = 0.6
(EA/ PE = 1/5). H NMR (600 MHz, CDCl3) δ = 9.46(br, 1H),
4.14. Ethyl 3-(4-fluorophenyl)-5-phenyl-1H-pyrrole-2-
1
carboxylate (3p).
7.40 (d, J = 7.2 Hz, 4H), 7.10 (d, J = 8.4 Hz, 4H), 6.45 (d, J = 3.6
Hz, 1H), 4.16 (q, J = 7.2 Hz, 2H), 2.28 (s, 3H), 2.26 (s, 3H), 1.15
(t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ = 161.3,
137.7, 136.6, 135.6, 133.5, 132.2, 129.6, 129.4, 128.3, 124.7,
124.6, 118.1, 109.5, 60.3, 21.2, 21.1, 14.2. HRMS (ESI): m/z [M
+ H]+ calcd for C21H22NO2: 320.1645; found 320.1648.
1
Yellow oil (69%, 106.6 mg); Rf = 0.5 (EA/ PE = 1/4). H
NMR (400 MHz, CDCl3) δ = 9.56 (s, 1H), 7.61−7.53 (m, 4H),
7.41 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.6 Hz, 1H), 7.06 (t, J = 8.8
Hz, 2H), 6.58 (d, J = 3.2 Hz, 1H), 4.26 (q, J = 7.2 Hz, 2H), 1.24
(t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ = 162.1 (d, J
= 247.5 Hz), 161.2, 135.5, 132.4, 131.1, 131.1 (d, J = 9.0 Hz),
131.0, 129.0, 128.0, 124.8, 118.6, 114.5 (d, J = 21.0 Hz), 109.8,
60.5, 14.2. 19F NMR (376 MHz, CDCl3) δ = −61.25. HRMS
(ESI): m/z [M + H]+ calcd for C19H17FNO2 : 310.1238; found
310.1234.
4.20. Ethyl 5-(4-chlorophenyl)-3-(p-tolyl)-1H-pyrrole-2-
carboxylate (3v).
o
White solid (49%, 83.2 mg); m. p. 176−177 C; Rf = 0.4 (EA/
PE = 1/5). 1H NMR (600 MHz, CDCl3) δ = 9.44 (s, 1H), 7.45 (d,
J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz,
2H), 7.11 (d, J = 7.8 Hz, 2H), 6.49 (d, J = 3.0 Hz, 1H), 4.18 (q, J
= 7.2 Hz, 2H), 2.31 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H). 13C NMR
(150 MHz, CDCl3) δ = 161.3, 136.9, 134.2, 133.6, 133.5, 131.9,
129.7, 129.3, 129.2, 128.4, 126.0, 118.8, 110.2, 60.5, 21.2, 14.2.
HRMS (ESI): m/z [M + H]+ calcd for C20H19ClNO2: 340.1099;
found 340.1096.
4.15. Ethyl 5-phenyl-3-(4-(trifluoromethyl) phenyl)-1H-pyrrole-
2-carboxylate (3q).
1
Yellow oil (75%, 134.6 mg); Rf = 0.5 (EA/ PE = 1/4). H
NMR (600 MHz, DMSO-d6) δ = 12.12 (s, 1H), 7.90 (d, J = 7.8
Hz, 2H), 7.75, (d, J = 8.4 Hz ,2H), 7.70 (d, J = 8.4 Hz, 2H), 7.41
(t, J = 7.8 Hz, 2H), 7.30 (t, J = 7.8 Hz, 1H), 6.82 (d, J = 3.0 Hz,
1H), 4.19 (q, J = 7.2 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H). 13C NMR
(150 MHz, DMSO-d6) δ = 160.4, 139.7, 136.1, 131.0, 130.8,
130.1, 128.7, 127.7, 127.2 (q, JC-F = 31.5 Hz), 125.6, 124.6 (q, JC-
F = 270.0 Hz), 124.4 (q, JC-F = 4.5 Hz, ), 119.1, 109.9, 59.9, 14.1.
19F NMR (376 MHz, DMSO-d6) δ = −61.25. HRMS (ESI): m/z
[M + H]+ calcd for C20H17F3NO2: 360.1206; found 360.1201.
4.21. Ethyl 3-(3,5-dichlorophenyl)-5-(p-tolyl)-1H-pyrrole-2-
carboxylate (3w).
o
White solid (78%, 158.4 mg); m. p. 182−183 C; Rf = 0.4
1
(EA/ PE = 1/5). H NMR (600 MHz, DMSO-d6) δ = 12.04 (s,
1H), 7.79 (d, J = 6.0 Hz, 2H), 7.58 (s, 2H), 7.48 (s, 1H), 7.21 (d,
J = 6.0 Hz, 2H), 6.81 (s, 1H), 4.21 (q, J = 6.0 Hz, 2H), 2.31 (s,
3H), 1.21 (t, J = 6.0 Hz, 3H). 13C NMR (150 MHz, DMSO-d6) δ
= 160.7, 139.3, 137.4, 136.7, 133.6, 129.6, 129.5, 128.5, 128.4,
126.4, 125.9, 119.1, 109.9, 60.2, 21.2, 14.4. HRMS (ESI): m/z
[M + H]+ calcd for C20H18Cl2NO2: 374.0709; found 374.0711.
4.16. Ethyl 3-(3,5-dichlorophenyl)-5-phenyl-1H-pyrrole-2-
carboxylate (3r).
1
Yellow oil (84%, 151.2 mg); Rf = 0.5 (EA/ PE = 1/4). H
NMR (600 MHz, CDCl3) δ = 9.91 (s, 1H), 7.51 (d, J = 7.2 Hz,
2H), 7.35 (d, J = 1.8 Hz, 2H), 7.28 (t, J = 7.8 Hz, 2H), 7.22−7.18
(m, 2H), 6.45 (d, J = 3.0 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H), 1.14
(t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ = 161.3,
138.1, 136.1, 133.9, 130.7, 130.1, 128.9, 128.0, 128.0, 126.7,
125.0, 119.0, 109.6, 60.8, 14.0. HRMS (ESI): m/z [M + H]+
calcd for C20H16Cl2NO2 : 360.0553; found 360.0549.
4.22. Ethyl 3-benzyl-5-phenyl-1H-pyrrole-2-carboxylate (3x).
o
White solid (64%, 97.6 mg); m. p. 165−166 C; Rf = 0.5 (EA/
PE = 1/4). 1H NMR (600 MHz, CDCl3) δ = 9.15 (s, 1H), 7.50 (d,
J = 7.2 Hz, 2H), 7.37 (t, J = 7.2 Hz, 2H), 7.29−7.25 (m, 5H),
7.21−7.18 (m, 1H), 6.31 (d, J = 3.0 Hz, 1H), 4.35 (q, J = 6.6 Hz,
2H), 4.19 (s, 2H), 1.35 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ = 161.6, 141.2, 135.3, 131.2, 129.5, 128.9, 128.8,
128.7, 128.3, 127.7, 125.9, 124.6, 109.7, 60.2, 33.2, 14.5. HRMS
(ESI): m/z [M + H]+ calcd for C20H20NO2: 306.1489; found
306.1485.
4.17. Ethyl 3-(naphthalen-2-yl)-5-phenyl-1H-pyrrole-2-
carboxylate (3s).
o
White solid (70%, 119.4 mg ); m. p. 174−176 C; Rf = 0.5
(EA/ PE = 1/5). H NMR (400 MHz, CDCl3) δ = 9.65 (s, 1H),
1
8.05 (s, 1H), 7.86−7.82 (m, 3H), 7.74−7.71 (m, 1H), 7.63 (d, J =
7.2 Hz, 2H), 7.48−7.39 (m, 4H), 7.31 (t, J = 10.8 Hz, 1H), 6.72
(d, J = 3.2 Hz, 1H), 4.26 (q, J = 7.2 Hz, 2H), 1.20 (t, J = 6.8 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ = 161.4, 135.6, 133.3, 133.2,
132.7, 132.6, 131.1, 129.0, 128.2, 128.1, 128.0, 127.9, 127.6,
126.9, 125.9, 125.7, 124.8, 118.9, 110.2, 60.5, 14.2. HRMS
(ESI): m/z [M + H]+ calcd for C23H20NO2: 342.1489; found
342.1482.
4.23. Ethyl 3-methyl-5-phenyl-1H-pyrrole-2-carboxylate (3y).
Yellow oil (38%, 43.5 mg); Rf = 0.5 (EA/ PE = 1/4). 1H NMR
(600 MHz, CDCl3) δ = 9.41 (s, 1H), 7.55 (d, J = 7.8 Hz, 2H),
7.37 (t, J = 7.8 Hz, 2H), 7.26 (t, J = 7.2 Hz, 1H), 6.37 (d, J = 3.0
Hz, 1H), 4.32 (q, J = 7.2 Hz, 2H), 2.38 (s, 3H), 1.36 (t, J = 7.2
Hz, 3H). 13C NMR (150 MHz, CDCl3) δ = 162.0, 135.3, 131.4,
129.3, 128.8, 127.5, 124.7, 119.9, 110.2, 60.1, 14.5, 13.0.HRMS
(ESI): m/z [M + Na]+ calcd for C14H15NO2Na: 252.0995; found
252.1000.
4.18. Ethyl 3-(naphthalen-1-yl)-5-phenyl-1H-pyrrole-2-
carboxylate (3t).
o
4.24. Ethyl 3-isopropyl-5-phenyl-1H-pyrrole-2-carboxylate (3z).
White solid (65%, 110.8 mg ); m. p. 178−179 C; Rf = 0.5
1
1
(EA/ PE = 1/5). H NMR (600 MHz, CDCl3) δ = 9.69 (br, 1H),
Pale yellow oil (38%, 48.8 mg); Rf = 0.5 (EA/ PE = 1/4). H
7.91−7.83 (m, 3H), 7.65 (d, J = 7.2 Hz, 2H), 7.50 (d, J = 4.8 Hz,
2H), 7.47−7.38 (m, 4H), 7.32 (t, J = 7.2 Hz, 1H), 6.67 (d, J = 3.0
Hz, 1H), 3.97 (q, J = 7.2 Hz, 2H), 0.70 (t, J = 7.2 Hz, 3H). 13C
NMR (150 MHz, CDCl3) δ = 161.5, 135.5, 133.8, 133.4, 132.6,
131.2, 130.9, 129.0, 128.0, 127.9, 127.5, 127.4, 126.4, 125.6,
NMR (400 MHz, CDCl3) δ = 9.56 (s, 1H), 7.59 (d, J = 8.4 Hz,
2H), 7.36 (t, J = 7.6 Hz, 2H), 7.25 (d, J = 7.2 Hz, 1H), 6.48 (d, J
= 3.2 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.59−3.52 (m, 1H), 1.35
(t, J = 6.8 Hz, 3H), 1.27 (d, J = 7.2 Hz, 6H). 13C NMR (150

6
Tetrahedron
1
MHz, CDCl3) δ = 161.8, 141.3, 135.5, 131.5, 128.8, 127.4,
Pale yellow oil (15%, 11.1 mg); Rf = 0.4 (EA/ PE = 1/5). H
NMR (600 MHz, CDCl3) δ = 9.29 (br, 1H), 7.55 (d, J = 7.2 Hz,
2H), 7.33 (t, J = 7.8 Hz, 2H), 7.26 (t, J =7.8 Hz, 1H), 6.07 (d, J =
3.0 Hz, 1H), 4.23 (q, J = 6.6 Hz, 2H), 2.63−2.59 (m, 1H), 2.02 (d,
J = 15.0 Hz, 2H), 1.82 (d, J = 13.2 Hz, 2H), 1.73−1.70 (m, 1H),
1.45−1.32 (m, 4H), 1.28−1.24 (m, 1H) 1.22 (t, J = 6.6 Hz, 3H).
13C NMR (150 MHz, CDCl3) δ = 161.5, 142.7, 135.7, 132.4,
129.5, 127.4, 126.7, 116.1, 108.3, 60.0, 36.8, 32.7, 26.1, 26.0,
14.2. HRMS (ESI): m/z [M + Na]+ calcd for C19H23NO2Na:
320.1621; found 320.1630.
ACCEPTED MANUSCRIPT
124.7, 118.5, 105.9, 60.0, 25.7, 23.7, 14.4. HRMS (ESI): m/z [M
+ Na]+ calcd for C16H19NO2Na: 280.1308; found 280.1310.
4.25. Ethyl 3-cyclohexyl-5-phenyl-1H-pyrrole-2-carboxylate
(3ab).
1
Pale yellow oil (13%, 19.3 mg); Rf = 0.5 (EA/ PE = 1/4). H
NMR (600 MHz, CDCl3) δ = 9.30 (s, 1H), 7.56 (d, J = 7.2 Hz,
2H), 7.37 (t, J = 8.4 Hz, 2H), 7.26 (t, J = 7.2 Hz, 1H), 6.46 (d, J =
3.0 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.20−3.15 (m, 1H), 1.95 (d,
J = 9.6 Hz, 2H), 1.83 (d, J = 12.0 Hz, 2H), 1.75 (d, J = 14.4 Hz,
1H), 1.43−1.40 (m, 4H), 1.37 (t, J = 6.6 Hz, 3H), 1.29−1.25 (m,
1H). 13C NMR (150 MHz, CDCl3) δ = 161.7, 140.6, 135.3, 131.5,
128.8, 127.4, 124.7, 118.5, 106.4, 60.0, 35.9, 34.2, 26.9, 26.3,
14.4. HRMS (ESI): m/z [M + Na]+ calcd for C19H23NO2Na:
320.1621; found 320.1624.
4.31. Ethyl 3-methyl-1H-pyrrole-2-carboxylate (3ah).
1
Pale yellow oil (19%, 14.5 mg); Rf = 0.3 (EA/ PE = 1/3). H
NMR (400 MHz, CDCl3) δ = 9.47 (br, 1H), 6.82 (t, J = 4.2 Hz,
1H), 5.94(t, J = 4.2 Hz, 1H), 4.31 (q, J = 10.2 Hz, 2H), 2.31 (s,
3H), 1.35 (t, J = 10.8 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ =
161.4, 133.9, 121.3, 116.0, 108.8, 60.0, 14.5, 13.1. HRMS (ESI):
m/z [M + Na]+ calcd for C8H11NO2Na: 176.0682; found
176.0686.
4.26. Ethyl 5-phenyl-3-styryl-1H-pyrrole-2-carboxylate (3ac).
Yellow oil (58%, 91.9 mg); Rf = 0.5 (EA/ PE = 1/4). 1H NMR
(600 MHz, DMSO-d6) δ = 11.85 (s, 1H), 7.91 (d, J = 7.8 Hz,
2H), 7.79 (d, J = 16.2 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 7.42 (t, J
= 7.8 Hz, 2H), 7.38 (t, J = 7.8 Hz, 2H), 7.31 (d, J = 7.2 Hz, 1H)
,7.25 (d, J = 7.8 Hz, 1H), 7.15 (d, J = 16.2 Hz, 1H), 7.12 (d, J =
1.8 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H), 1.40 (t, J = 6.6 Hz, 3H).
13C NMR (150 MHz, DMSO-d6) δ = 160.8, 137.6, 136.6, 131.1,
129.3, 128.8, 128.6, 128.6, 127.5, 127.3, 126.0, 125.5, 121.3,
120.1, 104.9, 59.8, 14.5. HRMS (ESI): m/z [M + H]+ calcd for
C21H20NO2: 318.1489; found 318.1485.
4.32. Ethyl (3-oxo-1,3-diphenylprop-1-en-1-yl) carbamate20 (4a)
Yellow solid (92%, 142 mg); Rf = 0.3 (EA/ PE = 1/5); m. p.
o
1
79−80 C. H NMR (600 MHz, CDCl3): δ = 11.43 (s, 1H), 7.91
(d, J = 7.8 Hz, 2H), 7.43−7.37 (m, 8H), 5.87 (s, 1H), 4.17 (q, J =
6.0 Hz, 2H), 3.95 (d, J = 6.6 Hz, 2H), 1.23 (t, J = 8.4 Hz, 3H).
13C NMR (150 MHz, CDCl3) δ = 190.0, 169.2, 165.7, 139.8,
135.0, 130.7, 129.5, 128.5, 128.0, 127.5, 127.0, 94.5, 61.3, 46.2,
13.9.
4.27. Ethyl 5-cyclopropyl-3-(p-tolyl)-1H-pyrrole-2-carboxylate
4.33. Ethyl 4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl glycinate
(3ad).
(4ai).
Yellow oil (45%, 60.5 mg); Rf = 0.5 (EA/ PE = 1/4). 1H NMR
(600 MHz, CDCl3) δ = 8.89 (s, 1H), 7.43 (d, J = 7.8 Hz, 2H),
7.15 (d, J = 7.8 Hz, 2H), 5.95 (d, J = 3.0 Hz, 1H), 4.24 (q, J = 7.2
Hz, 2H), 2.36 (s, 3H), 1.87−1.82 (m, 1H), 1.25 (t, J = 7.2 Hz,
3H), 0.96−0.93 (m, 2H), 0.74−0.72 (m, 2H). 13C NMR (150
MHz, CDCl3) δ = 160.9, 139.0, 136.5, 132.8, 132.3, 129.3, 128.3,
116.1, 108.2, 60.0, 21.2, 14.3, 8.4, 7.4. HRMS (ESI): m/z [M +
H]+ calcd for C17H20NO2: 270.1489; found 270.1487.
1
Pale yellow oil (92%, 138.4 mg); Rf = 0.3 (EA/ PE = 1/3). H
NMR (600 MHz, CDCl3) δ = 11.10 (s, 1H), 7.43−7.37 (m, 3H),
7.28 (d, J = 6.6 Hz, 2H), 5.41 (s, 1H), 4.12 (q, J = 7.2 Hz, 2H),
3.95 (d, J = 6.0 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR (150
MHz, CDCl3) δ = 177.0 (q, JC-F = 33.0 Hz), 170.2, 168.3,
133.4,130.6, 129.0, 127.2, 117.3 (q, JC-F = 288.0 Hz ), 91.0, 61.8,
46.6, 14.0.19F NMR (376 MHz, CDCl3) δ = −77.11. HRMS
(ESI): m/z [M + Na]+ calcd for C14H14F3NO3Na: 324.0818; found
324.0817.
4.28. Ethyl 5-cyclopropyl-3-(3,5-dichlorophenyl)-1H-pyrrole-2
carboxy-late (3ae).
Acknowledgements
Yellow oil (60%, 96.9 mg); Rf = 0.5 (EA/ PE = 1/4). 1H NMR
(600 MHz, CDCl3) δ = 9.20 (br, 1H), 7.34 (d, J = 2.4 Hz, 2H),
7.19 (t, J = 1.8 Hz, 1H), 5.86 (d, J = 3.0 Hz, 1H), 4.18 (q, J = 7.2
Hz, 2H), 1.80−1.76 (m, 1H), 1.20 (t, J = 6.6 Hz, 3H), 0.90−0.87
(m, 2H), 0.66 (q, J = 6.6 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ
= 160.9, 139.6, 138.4, 133.9, 129.4, 128.0, 126.6, 116.7, 108.8,
60.4, 14.1, 8.4, 7.6. HRMS (ESI): m/z [M + H]+ calcd for
C16H16Cl2NO2: 324.0553; found 324.0555.
We are thankful for financial support from the National
Natural Science Foundation of China (Grant No. 21662030 and
21861033), Key Laboratory Polymer Materials of Gansu
Province (Northwest Normal University); Key Laboratory of
Polymer Materials of Ministry of Education of Ecological
Environment; and State Key Laboratory of Applied Organic
Chemistry, Lanzhou University.
4.29. Ethyl 5-(tert-butyl)-3-phenyl-1H-pyrrole-2-carboxylate
(3af).
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