Silver-catalyzed chemoselective annulation of propargyl amines with alkynes for access to pyridines and pyrroles

Article abstract of DOI:10.1016/j.tet.2017.09.002

The annulation of propargyl amines with electron-deficient alkynes in the presence of silver salts affording pyridines and pyrroles has been developed. The chemoselective [4+2] or [3+2] annulation approach to pyridines or pyrroles depends on the structure

Full text of DOI:10.1016/j.tet.2017.09.002

Accepted Manuscript
Silver-catalyzed chemoselective annulation of propargyl amines with alkynes for
access to pyridines and pyrroles
Tauqir A. Nizami, Ruimao Hua
PII:
S0040-4020(17)30915-8
10.1016/j.tet.2017.09.002
TET 28953
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 3 July 2017
Revised Date: 27 August 2017
Accepted Date: 4 September 2017
Please cite this article as: Nizami TA, Hua R, Silver-catalyzed chemoselective annulation of propargyl
amines with alkynes for access to pyridines and pyrroles, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.09.002.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Silver-catalyzed chemoselective annulation of propargyl amines with alkynes for access
to pyridines and pyrroles
1

ACCEPTED MANUSCRIPT
Silver-catalyzed chemoselective annulation of propargyl amines with alkynes for access
to pyridines and pyrroles
Tauqir A. Nizami and Ruimao Hua*
Department of Chemistry, Tsinghua University, Beijing 100084, China
Fax: +86-10-62771149
E-mail: ruimao@mail.tsinghua.edu.cn
Abstract: The annulation of propargyl amines with electron-deficient alkynes in the presence
of silver salts affording pyridines and pyrroles has been developed. The chemoselective [4+2]
or [3+2] annulation approach to pyridines or pyrroles depends on the structures of propargyl
amines and the different reaction conditions.
Keywords: annulation; alkynes; propargyl amines; pyridines; pyrroles; silver salts.
1. Introduction
Development of the synthetic methods for the formation of multi-substituted pyridines1
and pyrroles2 is one of the important and interesting research topics in the synthetic chemistry
and heterochemistry. Both pyridines and pyrroles are the most important kinds of
N-heterocyclic compounds, which have been applied in agrochemicals, pharmaceuticals, and
organic materials. On the other hand, propargyl amines with the π-nucleophilic character of
triple bond and vicinity of functional group have been used as the useful and versatile
reactants in the synthesis of various N-heterocycles via their annulation with other unsaturated
compounds.3 In our previous work, we have also developed the application of propargyl
alcohols, and propargyl amines in the synthesis of 2H-chromenes,4 4-vinyl-1,2,3-triazoles,5
1,2-dihydroquinolines,6 and 2,5-dimethylpyrazines.7 As a continuation of our interest in
developing synthetic methods for heterocyclic compounds via annulation process using
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alkynes as one of the reactants,8 and silver salts have been well applied in the synthesis of
heterocycles via the annulation of alkynes.9 We report here the highly selective formation of
multi-substituted pyridines and pyrroles via the annulation of propargyl amines with
electron-deficient alkynes catalyzed by silver salts under different conditions.
2. Results and discussion
The reaction of prop-2-yn-1-amine (1a) with the electron-deficient alkyne of
dimethylacetylenedicarboxylate (DMAD) (2a) was detailed studied to optimize the reaction
conditions. As shown in Table 1, in the presence of Ag2CO3, when a mixture of 1a and 2a (1.3
o
equiv.) in THF was heated at 100 C for 12 h, dimethyl pyridine-2,3-dicarboxylate (3aa)
could be isolated from the mixture in 39% yield (entry 1)10. Repeating the reaction in dioxane
for 10 h and using an increased amount of catalyst (10 mol%) resulted in the slight increase of
3aa yield (entry 2). Encouraged by this promising result, other silver salts such as silver
acetate (AgOAc), silver nitrate (AgNO3), silver iodide (AgI), silver tetrafluoroborate
(AgBF4), and silver hexafluoroantimonate (AgSbF6) were screened. It was found that either
3aa was formed in the fair yields or no reaction took place for the formation of 3aa due
maybe to their different solubility in dioxane (entries 3–7). However, 3aa yield could be
significantly increased to 62% when AgOTf was used as catalyst, and was further
considerably increased by using K2S2O8 as additive (entries 8–9). In addition, when toluene
was used as solvent, 3aa was obtained in 91% yield (entry 10). Although the decrease of the
catalyst amount to 5 mol% resulted in great decrease of 3aa yield (entry 11), the further
studies on the effect of reaction temperature and time in toluene were disclosed that the
o
reaction performed at 80 C for 6 h is the suitable choice for the formation of 3aa in a
satisfactory yield (entry 12), which were used as the optimal reaction conditions for the
studies of substrate scope.
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Table 1
Optimizing the reaction conditions for the formation of 3aaa
COOMe
Ag salt
COOMe
COOMe
+
solvent, additive
N
100 or 80 oC, 10 h
COOMe
NH2
1a
2a
3aa
1.3 equiv
Entry
Catalyst (mol%)
Solvent
Additiveb
Yield (%)c
1
2
3
Ag2CO3 (5)
Ag2CO3 (10)
AgOAc (10)
THF
39
43
47
dioxane
dioxane
dioxane
dioxane
4
5
AgNO3 (10)
AgI (10)
28
15
6
AgBF4 (10)
dioxane
dioxane
0
0
AgSbF6 (10)
7
8
9
dioxane
dioxane
AgOTf (10)
AgOTf (10)
62
74
91
56
93
K2S2O8
10
toluene
toluene
toluene
K2S2O8
K2S2O8
K2S2O8
AgOTf (10)
AgOTf (5)
AgOTf (10)
11
12d
a Reactions were carried out using 1.0 mmol of 1a, 1.3 mmol of 2a and silver
salt in 5 mL of solvent.
b 1 equiv.
c Isolated yield based on the amount of 1a used.
at 80 oC for 6 h
d
Several substituted pyridines could be synthesized in mild to good yields as summarized
in Table 2 under the optimized conditions. Notably, when unsymmetric alkynes were used, the
[4+2] cycloaddition reactions occurred with an excellent regioselective manner to afford
3ab–3ae bearing electron-withdrawing group at 3-position of pyridine ring, as the sole
regioisomer due to the first step of Michael addition of N-H bond of 1a to alkynes taking
place with excellent regioselectvity as shown in the proposed mechanism (vide infra). In
addition, the reaction of but-3-yn-2-one (2c) with 1a had to be carried out at room
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temperature to decrease the self-dimerization of 2c affording the corresponding pyridine
derivative 3ac in a relatively low yield. In the case of 3-butyn-2-amine (1b) used, the
annulation with 2a also occurred to afford the corresponding pyridine derivative 3ba in 46%
yield. However, under the similar reaction conditions, the reactions of 3-substituted propargyl
amines, such as 3-phenyl-2-propyn-1-amine and 2-heptyn-1-amine with 2a could not produce
the corresponding pyridine derivatives at all.
Table 2
The synthesis of pyridine derivatives
The reaction manner of N-substituted propargyl amines is expected to be different from
1a, since the reaction must be unfavorable for the formation of pyridine ring due to the
substituent at the nitrogen atom. Interestingly, as shown in Table 3, when a mixture of 1.5
equivalent of N-methyl propargyl amine (1c) and 2a in toluene in the presence of 10 mol% of
o
AgOTf was heated at 80 C for 8 h, the four-substituted pyrrole ring 4ca could be isolated in
13% yield from the reaction mixture (Table 3, entry 1). Although a [3+2] cycloaddition of
N-propargylamines with activated alkynes by base-catalyzed reaction affording a variety of
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multi-substituted pyrroles was reported by Jin and co-worker,3f in continuation of our previous
work on the synthesis of pyrroles8d,8l,8q,8r and with the purpose of providing an alternative
catalyst system for the construction of pyrrole ring, we further optimized the reaction
conditions for the synthesis of 4ca. As concluded in Table 3, DMF is found the suitable
solvent for the formation of 4ca, and AgOAc shows higher catalytic activity than AgOTf and
Ag2CO3. Moreover, the use of base is the key factor to promote the transformation, and DBU
(1,8-diazabicyclo[5.4.0]undec-7-ene), an organic base is the better choice than inorganic bases,
such as KOAc and KOtBu. After optimizing the reaction conditions, the yield of 4ca could be
improved to 84% in DMF at 80 oC for 2 h.
Table 3
Optimizing the reaction conditions for the formation of pyrrole derivative 4caa
The substrate scope for the formation of four-substituted pyrroles 4 was further
investigated under the reaction conditions indicated in entry 6 of Table 3. As summarized in
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Table 4, it was found that the use of terminal alkyne of 2b resulted in the relatively low yields
of 4cb, 4db and 4eb owing to the self-dimerization of 2b as the side-reaction under the
reaction conditions. When internal alkynes, such as 2a, 2f and 2g were employed, the
corresponding pyrroles 4cf, 4da, 4dg, 4ea and 4eg were obtained in good yields. In addition,
the formation of substituted pyrroles occurred with excellent regioselectivity to give the
regioisomer having electron-withdrawing group at 3-position when unsymmetric internal
alkynes were used. The excellent regioselective manner is similar to the formation of
substituted pyridines ring, which can be reasonably explained by the proposed mechanism
(vide infra).
Table 4
The synthesis of pyrrole derivatives
R"
Me
R"
AgOAc (10 mol%)
+
R
DBU (1.0 equiv)
DMF. 80 oC, 2 h
R'
N
R
N
H
1
R'
2
4
1.5 equiv
R = Me, 1c; R = cyclohexyl, 1d; R = benzyl, 1e
R' = Ph, R" = COOMe, 2f; R' = Me, R" = COOEt 2g
Me
COOMe
COOEt
Me
COOEt Me
COOMe
Me
Ph
COOMe
N
N
N
N
Me
Me
4cb 61%
Me
COOEt
4cf 72%
4da 73%
4db 59%
Me
COOEt
Me
COOMe
Me
Ph
COOEt
Me
N
Me
COOMe
N
N
N
Ph
Ph
4dg 76%
4ea 78%
4eb 64%
4eg 81%
Rasagiline (N-propargyl-1(R)-aminoindan) is a commercial drug, which has been applied
as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in
6

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more advanced cases.11 Moreover, under the similar reaction conditions, rac-rasagiline also
underwent the annulation with 2a to afford the expected pyrrole derivative 5 in 72% yield
(eq.1).
Ag+
EWG
H
EWG
regioselective
Michael reaction
H
R
+
N
R
R'
N
..
R'
1
2
adduct
EWG: ester, acetyl
carbocyclization
Ag
EWG
Ag
EWG
R'
R'
N
R
N
R
base
aromatization
R = H
Ag+
oxidant
aromatization
R = H
Ag+
Me
EWG
EWG
R'
N
R'
N
R
4
3
Scheme 1. Proposed reaction mechanism
The proposed mechanism for the present silver-catalyzed chemoselective [4+2] and [3+2]
annulation of propargyl amines with alkynes respectively affording pyridines and pyrroles is
shown in Scheme 1. It involves the Michael addition of propargyl amine to α,β-unsaturated
carbonyl compound, and the carbocyclization forming six-membered or five-membered
7

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nitrogen-heterocyclic intermediates to then chemoselectively give pyridines 3 or pyrroles 4
via further aromatization under different conditions. The first step of Michael addition
occurring with high regioselectivity to yield N-propargylic β-enaminones or β-enamino esters
is the key step to afford the pyridines and pyrroles bearing electron-withdrawing group at
3-position.12
3. Conclusion
In conclusion, we have studied the annulation of propargyl amine or N-methyl
propargylamine with electron-deficient alkynes in the presence of silver salts as catalysts and
K2S2O8 or DBU as additives to develop the chemoselective [4+2] and [3+2] cycloadditions
affording pyridines and pyrroles. The present procedures have the advantages of high atom
economy and high chemoselectivity with the use of easily available starting materials.
4. Experimental section
4.1 General methods
All commercial reagents are analytically pure and used without further purification. All
reactions were carried out without any particular precautions to moisture or oxygen. Nuclear
magnetic resonance (NMR) spectra were recorded on a JEOL ECA-400 or JEOL ECA-600 by
using CDCl3 as solvent at 298 K. 1H NMR (400 MHz and 600 MHz) chemical shifts (δ) were
1
13
referenced to internal standard TMS (for H, δ = 0.00 ppm). C NMR (101 MHz and 125
13
MHz) chemical shifts were referenced to internal solvent CDCl3 (for C, δ = 77.16 ppm).
GC-MS were obtained on a Shimadzu GCMS-QP2010S, and high-resolution mass spectra
(ESI) were obtained with a microTOF-Q 10142 spectrometer.
4.2 A typical experiment procedure for synthesis of substituted pyridine 3aa
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A mixture of propargylamine (1a, 1.0 mmol, 55.1 mg), dimethyl acetylenedicarboxylate
(2a, 1.3 mmol, 185.0 mg), AgOTf (25.7 mg, 0.1 mmol) and K2S2O8 (270.0 mg, 1.0 mmol) in
toluene (20 mL) in a thick-walled screw-capped Pyrex tube was stirred with a magnetic stirrer
o
at 80 C for 6 h. After removal of the solvent under reduced pressure, purification was
performed by flash column chromatography on silica gel with petroleum ether/ethyl acetate
(8:2) as eluent to afford 3aa in 93% yield (181.3 mg, 0.93 mmol).
4.3 A typical experiment procedure for synthesis of substituted pyrrole 4ca
A mixture of N-methylprop-2-yn-1-amine (1c, 1.5 mmol, 103.6 mg), dimethyl
acetylenedicarboxylate (2a, 1.0 mmol, 142.1 mg), AgOAc (16.7 mg, 0.1 mmol) and DBU
(152 mg, 1.0 mmol) in DMF (7 mL) in a thick-walled screw-capped Pyrex tube was stirred
o
with a magnetic stirrer at 80 C for 2 h. After cooling to room temperature, the reaction
mixture was diluted with saturated aq. NH4Cl (10 mL) and extracted with ethyl acetate (5 x
10.0 mL). The combined organic phrase was washed with brine (2 x 15.0 mL) and dried over
anhydrous Na2SO4. After removal of solvent under reduced pressure, purification was
performed by flash column chromatography on silica gel with petroleum ether/ethyl acetate
(7:3) as eluent to afford 4ca in 84% yield (177.2 mg, 0.84 mmol).
4.4 Characterization data of product
All the products were characterized by 1H-NMR, 13C-NMR, GCMS, and HRMS (ESI, for
new products). The copies of NMR charts were reported in supplementary data.
Dimethyl pyridine-2,3-dicarboxylate (3aa)13: yellow solid (181.3 mg, 0.93 mmol, 93%); m.p.
o
o
1
52.5-53.8 C (known 52.0-53.5 C) H-NMR (400 MHz, CDCl3) δ 8.77 (1H, d, J = 7.2 Hz),
8.19 (1H, d, J = 7.6 Hz), 7.53-7.50 (1H, m), 4.00 (3H, s), 3.94 (3H, s); 13C-NMR (100 MHz,
CDCl3) δ 166.5, 165.6, 151.7, 150.6, 137.5, 126.3, 125.0, 53.0, 52.8; GC−MS m/z (% rel.
inten.) 195 (M+, 10), 164 (74), 136 (80), 107 (85), 79 (100).
1
Ethyl nicotinate (3ab)14: light reddish oil (95.1 mg, 0.63 mmol, 63%); H-NMR (400 MHz,
CDCl3) δ 9.32 (1H, s), 8.19 (1H, d, J = 7.2 Hz), 7.85 (1H, d, J = 7.6 Hz), 7.78 (1H, dd, J = 7.2
9

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13
Hz, 1.2 Hz), 4.75 (2H, q, J = 7.4 Hz), 1.61 (3H, t, J = 7.4 Hz Hz); C-NMR (100 MHz,
CDCl3) δ 165.5, 150.5, 148.0, 136.3, 129.2, 123.8, 59.8, 14.3; GC−MS m/z (% rel. inten.) 151
(M+, 5), 128 (30), 94 (100), 68 (45).
1-(Pyridin-3-yl)ethanone (3ac)15: light yellow oil (67.8 mg, 0.56 mmol, 56%); 1H-NMR (400
MHz, CDCl3) δ 9.18 (1H, s), 8.75 (1H, d, J = 8.7 Hz), 8.20 (1H, d, J = 8.1 Hz), 7.37 (1H, dd,
13
J = 7.9, 1.3 Hz), 2.07 (3H, s); C-NMR (100 MHz, CDCl3) δ 203.0, 157.8, 149.9, 139.5,
128.9, 120.7, 36.0; GC−MS m/z (% rel. inten.) 121 (M+, 50), 106 (85), 78 (100), 51 (45), 94
(30).
1
1-(2-Ethylpyridin-3-yl)ethanone (3ad)16: yellow oil (106.5 mg, 0.71 mmol, 71%); H-NMR
(400 MHz, CDCl3) δ 8.88 (1H, d, J = 6.4), 7.98 (1H, m), 7.59 (1H, 1H, d, J = 6.4), 3.31 (2H,
13
q, J = 7.7 Hz), 2.27 (3H, s), 1.43 (3H, t, J = 7.7 Hz); C-NMR (100 MHz, CDCl3) δ 202.9,
172.9, 150.2, 136. 8, 131.8, 121.8, 33.2, 27.4, 14.3; GC−MS m/z (% rel. inten.) 149 (M+, 25),
120 (100), 92 (95), 65 (40), 51 (10).
1-(2-Phenylpyridin-3-yl)ethanone (3ae)12: light yellow oil (143.8 mg, 0.73 mmol, 73%);
1H-NMR (400 MHz, CDCl3) δ 8.67-8.62 (1H, m), 8.05 (2H, d, J = 7.7 Hz), 7.79-7.76 (1H, m),
13
7.53-7.44 (4H, m), 1.41 (3H, s); C-NMR (100 MHz, CDCl3) δ 203.8, 151.0, 148.6, 136.5,
136.4, 131.5, 129.2, 128.9, 128.7, 122.0, 30.4; GC−MS m/z (% rel. inten.) 197 (M+, 60), 182
(100), 154 (50), 127 (45), 77 (25), 51 (20).
Dimethyl 6-methylpyridine-2,3-dicarboxylate (3ba)17: light yellow solid (96.2 mg, 0.46 mmol,
46%); m.p. 67.8-68.2 °C (known 68.0-69.0 oC); 1H-NMR (400 MHz, CDCl3) δ 8.10 (1H, d, J
13
= 8.4 Hz), 7.32 (1H, d, J =8.4 Hz), 3.97 (3H, s), 3.91 (3H, s), 2.58 (3H, s); C-NMR (100
MHz, CDCl3) δ 167.3, 166.1, 160.9, 148.1, 138.2, 133.7, 123.7, 53.1, 52.8, 22.8; GC−MS m/z
(% rel. inten.) 209 (M+, 20), 166 (30), 137 (45), 107 (45), 93 (25), 77 (20).
Dimethyl 1,4-dimethyl-1H-pyrrole-2,3-dicarboxylate (4ca): light yellow oil (177.2 mg, 0.84
mmol, 84%); 1H-NMR (400 MHz, CDCl3) δ 6.32 (1H, s), 4.24 (3H, s), 3.57 (6H, s), 2.24 (3H,
13
s); C-NMR (100 MHz, CDCl3) δ 167.5, 165.3, 127.5, 121.7, 121.4, 114.2, 59.9, 59.1, 36.3,
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14.5; IR (KBr): ν(C=O) 1695, 1680 cm-1; HRMS (ESI): m/z calcd. for C10H13NO4 [M - H]+
210.0772; found 210.0767.
Ethyl 1,4-dimethyl-1H-pyrrole-3-carboxylate (4cb)18: light yellow oil (102.0 mg, 0.61 mmol,
61%); 1H-NMR (400 MHz, CDCl3) δ 7.16 (1H, s), 6.32 (1H, s), 4.24 (2H, q, J = 5.2 Hz), 3.57
13
(3H, s), 2.24 (3H, s), 1.31 (3H, t, J = 5.2 Hz); C-NMR (100 MHz, CDCl3) δ 165.4, 127.5,
121.7, 121.4, 114.27, 59.15, 36.30, 14.52, 11.63; GC−MS m/z (% rel. inten.) 167 (M+, 60),
138 (55), 122 (100), 94 (20), 82 (12), 53 (18).
Methyl 1,4-dimethyl-2-phenyl-1H-pyrrole-3-carboxylate (4cf): light yellow oil (165.0 mg,
1
0.72 mmol, 72%); H-NMR (400 MHz, CDCl3) δ 7.40-7.30 (5H, m), 6.39 (1H, s), 3.59 (3H,
13
s), 3.25 (3H, s), 2.22 (3H, s); C-NMR (100 MHz, CDCl3) δ 165.1, 132.2, 130.6, 129.1,
128.0, 127.8, 121.7, 120.0, 111.5, 50.5, 31.4, 12.3; IR (KBr): ν(C=O) 1695 cm-1; HRMS (ESI):
m/z calcd. for C14H15NO2 [M + H]+ 230.1176; found 230.1173.
Dimethyl 1-cyclohexyl-4-methyl-1H-pyrrole-2,3-dicarboxylate (4da)3f: yellow oil (203.7 mg,
0.73 mmol, 73%); 1H-NMR (400 MHz, CDCl3) δ 6.66 (1H, s), 4.45 (1H, s), 3.81 (3H, s), 3.79
(3H, s), 2.12 (3H, s), 2.01-0.96 (10H, m); 13C-NMR (100 MHz, CDCl3) δ 166.0, 161.9, 123.1,
120.2, 119.5, 119.2, 56.6, 51.7, 51.3, 34.3, 25.6, 25.2, 10.7. GC−MS m/z (% rel. inten.) 279
(M+, 25), 247 (50), 215 (40), 165 (100), 134 (35), 107 (30), 79 (10), 55 (25).
Ethyl 1-cyclohexyl-4-methyl-1H-pyrrole-3-carboxylate (4db): light yellow oil (139.4 mg, 0.59
1
mmol, 59%); H-NMR (400 MHz, CDCl3) δ 7.28 (1H, s), 6.65 (1H, s), 4.45 (2H, q, J = 7.6
13
Hz), 3.79-3.73 (1H, m), 2.20 (3H, s), 2.0-1.44 (10H, m), 1.27 (3H, t, J = 7.6 Hz); C-NMR
(100 MHz, CDCl3) δ 165.6, 124.5, 121.0, 118.5, 113.6, 61.0, 59.2, 34.4, 27.8, 25.6, 14.6, 11.9;
IR (KBr): ν(C=O) 1687 cm-1; HRMS (ESI): m/z calcd. for C14H21NO2 [M + H]+ 236.1645;
found 236.1642.
Ethyl 1-cyclohexyl-2,4-dimethyl-1H-pyrrole-3-carboxylate (4dg): light yellow oil (190.1 mg,
1
0.76 mmol, 76%); H-NMR (400 MHz, CDCl3) δ 6.29 (1H, s), 4.23 (2H, q, J = 7.2),
13
3.98-3.95 (1H, m), 2.27 (3H, s), 2.21-1.29 (13H, m); C-NMR (100 MHz, CDCl3) δ 165.8,
11

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135.5, 127.7, 120.2, 114.8, 60.4, 59.1, 32.0, 27.8, 26.6, 14.6, 12.9, 9.8; IR (KBr): ν(C=O)
1699 cm-1; HRMS (ESI): m/z calcd. for C15H25NO2 [M + H]+ 250.1802; found 250.1797.
Dimethyl 1-benzyl-4-methyl-1H-pyrrole-2,3-dicarboxylate (4ea)3f: light yellow oil (224.0 mg,
1
0.78 mmol, 78%); H-NMR (400 MHz, CDCl3) δ 7.35-7.28 (5H, m), 7.05 (1H, s), 4.97 (2H,
s), 4.32 (3H, s), 4.31 (3H, s), 2.47 (3H, s); 13C-NMR (100 MHz, CDCl3) δ 165.8, 161.9, 135.0,
128.8, 128.2, 127.9, 127.4,125.9, 124.7, 120.3, 53.9, 53.1, 51.0, 12.3; GC−MS m/z (% rel.
inten.) 287 (M+, 15), 255 (10), 223 (55), 164 (25), 196 (20), 91 (100).
Ethyl 1-benzyl-4-methyl-1H-pyrrole-3-carboxylate (4eb)19: light yellow oil (156.0 mg, 0.64
1
mmol, 64%); H-NMR (400 MHz, CDCl3) δ 7.33-7.13 (6H, m), 6.38 (1H, s), 4.86 (2H, s),
4.22 (2H, q, J = 6.0 Hz), 2.24 (3H, s), 1.30 (3H, t, J = 6.0 Hz); 13C-NMR (100 MHz, CDCl3) δ
165.4, 136.9, 128.9, 128.0, 127.3, 127.0, 122.0, 120.7, 114.6, 59.2, 53.6, 14.54 11.8; GC−MS
m/z (% rel. inten.) 243 (M+, 25), 214 (10), 198 (15), 170 (5), 106 (5), 91 (100), 65 (15).
Ethyl 1-benzyl-2,4-dimethyl-1H-pyrrole-3-carboxylate (4eg)20: light yellow oil (208.2 mg,
0.81 mmol, 81%); 1H-NMR (400 MHz, CDCl3) δ 7.26-6.84 (6H, m), 4.90 (2H, s), 4.24 (2H, q,
J = 7.2), 2.39 (3H, s), 2.38 (3H, s), 1.31 (3H, t, J = 7.2); 13C-NMR (100 MHz, CDCl3) δ 166.1,
137.1, 136.0, 128.6, 127.3, 126.2, 120.4, 119.5, 111.4, 58.8, 49.89, 14.3, 12.6, 11.36; GC−MS
m/z (% rel. inten.) 257 (M+, 30), 228 (6), 212 (14), 184 (8), 91 (100), 65 (15).
Dimethyl 1-(2,3-dihydro-1H-inden-1-yl)-4-methyl-1H-pyrrole-2,3-dicarboxylate (5): light
1
yellow oil (226.1 mg, 0.72 mmol, 72%); H-NMR (600 MHz, CDCl3) δ 7.27-7.24 (4H, m),
6.99 (1H, d, J = 7.2 Hz), 6.27 (1H, s), 3.78 (6H, s), 3.18-2.72 (4H, m), 2.15 (3H, s); 13C-NMR
(125 MHz, CDCl3) δ 166.2, 162.9, 143.9, 141.1, 128.2, 126.5, 124.9, 124.2, 121.8, 120.4,
62.2, 51.5, 30.9, 30.3, 10.8; IR (KBr): ν(C=O) 1730, 1707 cm-1; HRMS (ESI): m/z calcd. for
C18H19NO4 [M + H]+ 314.1387; found 314.1385.
Acknowledgements
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This project was supported by the National Natural Science Foundation of China (Nos.
21273125 and 21473097). Mr. Nizami, Tauqir A. thanks the China Scholarship Council (CSC)
for generous support for his study in Tsinghua University as PhD candidate.
Supplementary data
Copies of 1H-NMR, 13C-NMR charts of all products associated with this article can be found
in the online version, at http://dx.doi.org/10.1016/j.tet.xxxx.
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