Synthesis of pyrrole-2,3,4,5-tetracarboxylates via a copper-catalyzed reaction of amine with but-2-ynedioate

Article abstract of DOI:10.1016/j.tet.2013.03.061

A copper-catalyzed reaction of amine with but-2-ynedioate gives rise to pyrrole-2,3,4,5-tetracarboxylates in moderate to good yields. The reaction proceeds in the presence of dioxygen with the formation of three bonds during the process.

Full text of DOI:10.1016/j.tet.2013.03.061

Tetrahedron 69 (2013) 3805e3809
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Synthesis of pyrrole-2,3,4,5-tetracarboxylates via a copper-catalyzed
reaction of amine with but-2-ynedioate
,
a
b
b,
Ling Zhang a , Xianbo Wang , Shaoyu Li , Jie Wu
*
*
a Department of Chemistry, Nanchang University, 999 Xuefu Road, Nanchang, Jiangxi 330031, China
b Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A copper-catalyzed reaction of amine with but-2-ynedioate gives rise to pyrrole-2,3,4,5-tetracarboxylates
in moderate to good yields. The reaction proceeds in the presence of dioxygen with the formation of
three bonds during the process.
Received 24 January 2013
Received in revised form 5 March 2013
Accepted 15 March 2013
Available online 20 March 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Amine
But-2-ynedioate
Copper acetate
Pyrrole-2,3,4,5-tetracarboxylate
NH2
EtO2C
N
1. Introduction
CO2Et
Cu(OAc)2 (10 mol %)
O2
CO2Et
+
+
N
It is well known that substituted pyrroles are an important class
of heterocyclic compounds due to their remarkable biological and
physical properties.1 The pyrrole core can be found in many natural
products (such as the lamellarin, ningalin, polycitone, lukianol, and
storniamide classes of natural products),2 as well as in agrochem-
icals (e.g., chlorfenapyr), pharmaceuticals (e.g., Lipitor), fluorescent
dyes (e.g., BODIPY derivatives),3 and conducting polymers (e.g.,
polypyrroles).4 So far, cyclization reactions, such as the Knorr,
PaaleKnorr, and Hantzsch reactions5 have been used as the most
common route to pyrrole derivatives. Other strategies were also
developed as alternative routes to pyrrole derivatives.6,7 Among the
family of pyrroles, the dihydropyrrolo[2,3-b]indole core A has
attracted much attention (Scheme 1), which is a widely distributed
structural framework presented in a number of biologically active
alkaloids8 (such as physostigmine,9 urchordamines,10 asperazine,11
chimonanthines,12 and leptosins13). Recently, we are interested in
the construction of natural product-like compounds for different
biological evaluations using tandem approaches.14 The interesting
biological activities of the compounds with a dihydropyrrolo[2,3-b]
indole core have made it as an attractive synthetic target. Therefore,
we initiated a program for the generation of dihydropyrrolo[2,3-b]
indole scaffold and its library construction.
N
K2CO3, toluene
CO2Et
°
C
100
1a
2a
A: not observed
EtO2C CO2Et
R5
R4
R3
A
N
R1
EtO2C
CO2Et
C6H4p-Me
3a, 38% yield
N
N
R2
Scheme 1. An unexpected reaction for the generation of pyrrole-2,3,4,5-
tetracarboxylate.
The proposed synthetic route was presented in Scheme 1.
Prompted by recent advances achieved in the [Cu]/O2 system,15,16
we conceived that the dihydropyrrolo[2,3-b]indole scaffold could
be constructed through a three-component reaction of indole,
amine, and but-2-ynedioate under oxidative conditions. At the be-
ginning, we studied a model reaction of 1-methylindole, p-toluidine
1a, with diethyl but-2-ynedioate 2a catalyzed by 10 mol % of
Cu(OAc)2 in the presence of dioxygen (Scheme 1). To our surprise, an
unexpected pyrrole-2,3,4,5-tetracarboxylate 3a was obtained in-
stead of the desired dihydropyrrolo[2,3-b]indole A. From this result,
we recognized that 1-methylindole was not involved in the reaction,
and the pyrrole product 3a came from the reaction of p-toluidine 1a
with 2.0 equiv of diethyl but-2-ynedioate 2a.
* Corresponding authors. E-mail address: jie_wu@fudan.edu.cn (J. Wu).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.061

3806
L. Zhang et al. / Tetrahedron 69 (2013) 3805e3809
Table 2
2. Results/discussion
Synthesis of pyrrole-2,3,4,5-tetracarboxylates 3 via Cu(OAc)2-catalyzed reaction of
amine 1 with but-2-ynedioate 2a
With this interesting result in hand, we started to explore the
optimal conditions for this transformation (Table 1). Initially, the
reaction was screened in various solvents in the presence of K2CO3
as base under reflux (Table 1, entries 1e5). The reaction worked
efficiently in acetonitrile at 85 ꢀC, which afforded the correspond-
ing product 3a in 41% yield (Table 1, entry 4). Different bases were
examined subsequently (Table 1, entries 6e12). It seemed that the
reaction using cesium carbonate gave a better result (58% yield)
compared with other bases employed, although a comparable yield
(57%) was obtained when t-BuONa was used in the reaction (Table
1, entry 12). The yield was increased to 74% when the reaction
occurred at 70 ꢀC (Table 1, entry 13). No better yields were obtained
by evaluation of other copper salts (Table 1, entries 15e20). A
control experiment without the addition of copper catalyst resulted
in no reaction (Table 1, entry 21). The efficiency was retarded when
the amount of copper(II) acetate was reduced to 5 mol % or the
reaction was performed in air (Table 1, entries 22 and 23).
CO2R2
R2O2C
R2O2C
CO2R2
CO2R2
Cu(OAc)2 (10 mol %)
Cs2CO3, MeCN, 70
O2
R1 NH2
1
+
°
C
N
CO2R2
2
R1
3
EtO2C
EtO C
CO2Et
EtO2C
CO2Et
EtO2C
EtO2C
CO2Et
CO2Et EtO2C
CO2Et
CO2Et
C6H4p-Me
3a, 74% yield
2
N
N
N
C6H4p-OMe
C6H4m-OMe
3c, 61% yield
3b, 76% yield
EtO2C
EtO2C
CO2Et
EtO2C
EtO2C
CO2Et
EtO2C
EtO2C
CO2Et
CO2Et
N
C6H4p-Cl
CO2Et
N
CO2Et
N
i
C6H5
C6H4p- Pr
3e, 70% yield
3f, 61% yield
3d, 72% yield
Table 1
Initial studies for the copper-catalyzed reaction of p-toluidine 1a with diethyl but-2-
ynedioate 2a
EtO2C
EtO2C
CO2Et
EtO2C CO2Et
EtO2C CO2Et
EtO2C
EtO2C
3a
CO2Et
CO2Et
CO2Et EtO2C
C6H3p-F-o-Br
3g, 45% yield
EtO2C CO2Et
CO2Et EtO2C
C6H4p-F
3h, 50% yield
EtO2C CO2Et
CO2Et
C6H4p-Br
3i, 45% yield
EtO2C CO2Et
NH2
N
N
N
[Cu] (10 mol %)
+
CO2Et
C6H4p-Me
base, solvent
N
O2
CO2Et
2a
1a
Entry
[Cu]
Base
Solvent
Temp (ꢀC)
Yielda (%)
EtO2C
CO2Et EtO2C
C6H4p-CO2Et
3j, 26% yield
CO2Et EtO2C
CO2Et
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OTf)2
CuBr
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
Cs2CO3
CsOAc
NaOH
Toluene
DMF
1,4-Dioxane
MeCN
DCE
100
100
100
85
85
85
85
85
85
85
85
85
70
50
70
70
70
70
70
70
70
70
70
38
25
27
41
37
48
58
35
54
30
54
57
74
56
33
44
47
19
Trace
21
NR
42
25
N
N
N
C6H22,4,6-Me3
benzylp-Me
3l, 55% yieldb
EtO2C CO2Et
CO2Et
3k, 45% yield
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtO2C
EtO2C
CO2Et
EtO2C
EtO2C
CO2Et
CO2Et
CO2Et EtO2C
benzylp-F
3n, 42% yieldb
EtO2C CO2Me
9
N
N
n
Bu
N
10
11
12
13
14
15
16
17
18
19
20
21
22b
23c
DBU
Bn
DABCO
t-BuONa
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
3o, 44% yieldb
3m, 58% yieldb
MeO2C CO2Me
EtO2C
CO2Me
C6H4p-OMe
3q, 36% yield
MeO2C
CO2Me
CuI
CuCl
CuCl2
CuBr2
d
N
N
C6H4p-OMe
3p, 55% yield
a Isolated yield based on amine 1. b K3PO4 was used as the base.
Cu(OAc)2
Cu(OAc)2
a
Isolated yield based on p-toluidine 1a.
In the presence of 5 mol % of Cu(OAc)2.
The reaction occurred in air.
b
c
be compatible under the standard conditions although the yield was
low (3j, 26% yield). We also examined the steric bulky 2,4,6-
trimethylaniline in the reaction with diethyl but-2-ynedioate 2a,
which produced the corresponding product 3k in 45% yield. The
yields were very low when aliphatic amines were utilized in the
reactions. We thus re-explored the optimal conditions of aliphatic
amines with but-2-ynedioate 2. Finally, we identified the reactions
worked efficiently when K3PO4 was used as the base. For instance,
pyrrole-2,3,4,5-tetracarboxylate 3m was formed in 58% yield when
benzyl amine was involved in the reaction of diethyl but-2-
ynedioate 2a. n-Butyl amine was also a good reactant in this trans-
formation, which gave rise to the expected product 3o in 44% yield.
4-Methoxybenzenamine reacted with dimethyl but-2-ynedioate
leading to the desired pyrrole 3p in 55% yield. The structure of tet-
ramethyl 1-(4-methoxyphenyl)-pyrrole-2,3,4,5-tetracarboxylate
3p was unambiguously illustrated by X-ray diffraction analysis
The scope of this copper(II)-catalyzed tandem reaction of amines
1 with but-2-ynedioates 2 was then investigated under the opti-
mized conditions (10 mol % of Cu(OAc)2, Cs2CO3, MeCN, O2 (balloon),
70 ꢀC). The results are exemplified in Table 2. A range of pyrrole-
2,3,4,5-tetracarboxylates 3 were obtained in moderate to good
yields. Various anilines 1 were demonstrated to be tolerated in
the transformation. However, the nature of the substituents on the
aromatic ring of anilines 1 had effects for the final outcome.
For instance, compound 3b was furnished in 76% yield when
4-methoxybenzenamine was used in the reaction of diethyl but-2-
ynedioate 2a, while pyrrole-2,3,4,5-tetracarboxylate 3i was gener-
ated in 45% yield when 4-bromobenzenamine was employed as
a replacement. The ester group attached on the aniline was found to

L. Zhang et al. / Tetrahedron 69 (2013) 3805e3809
3807
reaction as indicated by TLC, the solvent was evaporated and the
residue was purified by flash column chromatography on silica gel
to provide the products 3 (eluted with PE/EA¼4:1).
4.1.1. Tetraethyl 1-p-tolyl-1H-pyrrole-2,3,4,5-tetracarboxylate
(3a). Yield: 74%; Yellow liquid; 1H NMR (400 MHz, CDCl3)
d 1.08
(t, J¼6.4 Hz, 6H), 1.34 (t, J¼6.9 Hz, 6H), 2.38 (s, 3H), 4.10 (q, J¼6.4 Hz,
4H), 4.33 (q, J¼6.9 Hz, 4H), 7.14 (d, J¼6.9 Hz, 2H), 7.20 (d, J¼7.6 Hz,
2H); 13C NMR (100 MHz, CDCl3)
d 13.8, 14.2, 21.4, 61.5, 61.7, 119.3,
127.2, 128.2, 129.4, 134.4, 139.7, 159.6, 163.4; HRMS (ESI) calcd for
C23H27NO8: 468.1634 (MþNaþ), found: 468.1671.
4.1.2. Tetraethyl 1-(4-methoxyphenyl)-1H-pyrrole-2,3,4,5-tetracar-
boxylate (3b). Yield: 76%; Yellow liquid; 1H NMR (400 MHz, CDCl3)
d
1.10 (t, J¼6.8 Hz, 6H), 1.34 (t, J¼6.9 Hz, 6H), 3.82 (s, 3H), 4.10 (q,
Fig. 1. X-ray ORTEP illustration of tetramethyl 1-(4-methoxyphenyl)-pyrrole-2,3,4,5-
tetracarboxylate 3p (30% probability ellipsoids).
J¼6.8 Hz, 4H), 4.33 (q, J¼6.9 Hz, 4H), 6.90 (d, J¼7.8 Hz, 2H), 7.18 (d,
J¼7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 13.8, 14.2, 55.5, 61.5, 61.7,
113.8, 119.2, 128.4, 128.7, 129.6, 159.6, 160.2, 163.3; HRMS (ESI) calcd
for C23H27NO9: 484.1584 (MþNaþ), found: 484.1571.
(Fig. 1, also see the Supplementary data). A three-component re-
action of 4-methoxybenzenamine, dimethyl but-2-ynedioate, and
diethyl but-2-ynedioate was examined subsequently. Interestingly,
the expected product 3q was generated in 36% yield.
4.1.3. Tetraethyl 1-(3-methoxyphenyl)-1H-pyrrole-2,3,4,5-
tetracarboxylate (3c). Yield: 61%; Yellow liquid; 1H NMR
A possible mechanism is proposed, which is presented in
Scheme 2. Prompted by the advancement of an oxygenecopper
catalytic system applied in the oxidation reactions,15,16 we envi-
sioned that a double Michael addition would occur to furnish
compound a. Then an oxidation would take place in the presence of
a copper catalyst and dioxygen to produce intermediate c, which
would undergo further transformation to afford the pyrrole-
2,3,4,5-tetracarboxylate 3.
(400 MHz, CDCl3)
d
1.07 (t, J¼6.9 Hz, 6H), 1.33 (t, J¼6.9 Hz, 6H), 3.77
(s, 3H), 4.10 (q, J¼6.9 Hz, 4H), 4.33 (q, J¼6.9 Hz, 4H), 6.79 (s, 1H),
6.85 (d, J¼7.8 Hz, 1H), 8.23 (d, J¼8.2 Hz, 1H), 7.30 (t, J¼8.2 Hz, 1H);
13C NMR (100 MHz, CDCl3)
d 13.8, 14.2, 55.5, 61.5, 61.7, 113.3, 115.4,
119.4, 119.8, 128.1, 129.4, 138.0, 159.4, 159.7, 163.3; HRMS (ESI) calcd
for C23H27NO9: 484.1584 (MþNaþ), found: 484.1566.
4.1.4. Tetraethyl 1-(4-isopropylphenyl)-1H-pyrrole-2,3,4,5-tetracar-
boxylate (3d). Yield: 72%; Yellow liquid; 1H NMR (400 MHz,
CDCl3)
d
0.99 (t, J¼6.0 Hz, 6H), 1.20e1.34 (m, 12H), 2.90e2.95 (m,
Cu(II)
O2
1H), 4.06 (q, J¼6.0 Hz, 4H), 4.31 (q, J¼6.4 Hz, 4H), 7.15 (d, J¼7.4 Hz,
2H), 8.23 (d, J¼7.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 13.7, 14.1,
R2O2C
R1
R2O2C
CO2R2
CO2R2
R2O2C
R1
CO2R2
b
CO2R2
Cu(III)
23.9, 33.9, 61.5, 61.6, 119.3, 126.7, 127.3, 128.3, 134.7, 150.4, 159.6,
163.3; HRMS (ESI) calcd for C25H31NO8: 496.1947 (MþNaþ), found:
496.1935.
R1 NH2
1
+
N
N
-e
CO2R2
2
R2O2C
CO2R2
a
4.1.5. Tetraethyl 1-phenyl-1H-pyrrole-2,3,4,5-tetracarboxylate (3e).
Yield: 70%; Yellow liquid;
1H NMR (400 MHz, CDCl3)
d 1.04 (t,
R2O2C
R2O2C
R2O2C
R1
R2O2C
H
CO2R2
CO2R2
CO2R2
CO2R2
J¼6.9 Hz, 6H), 1.33 (t, J¼6.9 Hz, 6H), 4.06 (q, J¼6.9 Hz, 4H), 4.32 (q,
- H+
- H+
-e
R1
R2O2C
N
R1
R2O2C
N
J¼6.9 Hz, 4H), 7.21 (d, J¼6.9 Hz, 2H), 7.40e7.42 (m, 3H); 13C NMR
N
3
CO2R2
e
CO2R2
d
(100 MHz, CDCl3)
d 13.7, 14.2, 61.5, 61.7, 119.5, 127.5, 128.1, 128.7,
H
c
129.6, 137.1, 159.5, 163.3; HRMS (ESI) calcd for C22H25NO8: 454.1478
(MþNaþ), found: 454.1465.
Scheme 2. A possible mechanism for the Cu(OAc)2-catalyzed reaction of amine 1 with
but-2-ynedioate 2.
4.1.6. Tetraethyl 1-(4-chlorophenyl)-1H-pyrrole-2,3,4,5-tetracar-
boxylate (3f). Yield: 61%; Yellow liquid; 1H NMR (400 MHz,
3. Conclusions
CDCl3)
4H), 4.33 (q, J¼7.2 Hz, 4H), 7.21 (d, J¼8.0 Hz, 2H), 7.39 (d, J¼8.4 Hz,
2H); 13C NMR (100 MHz, CDCl3)
13.8, 14.2, 61.6, 61.9, 119.8, 128.0,
d
1.10 (t, J¼6.8 Hz, 6H),1.33 (t, J¼7.2 Hz, 6H), 4.11 (q, J¼6.8 Hz,
In conclusion, we have described a novel and efficient route
for the preparation of pyrrole-2,3,4,5-tetracarboxylates via a cop-
per(II)-catalyzed reaction of amine with but-2-ynedioate in the
presence of dioxygen. Three bonds are formed during the reaction
process. Currently, using the strategy for the formation of other
heterocyclic compounds is ongoing in our laboratory.
d
128.9, 129.0, 135.5, 135.7, 159.4, 163.1; HRMS (ESI) calcd for
C22H24ClNO8: 466.1269 (MþHþ), found: 466.1255.
4.1.7. Tetraethyl 1-(2-bromo-4-fluorophenyl)-1H-pyrrole-2,3,4,5-
tetracarboxylate (3g). Yield: 45%; Yellow liquid; 1H NMR
4. Experimental section
(400 MHz, CDCl3)
d
1.11 (t, J¼6.8 Hz, 6H), 1.34 (t, J¼6.8 Hz, 6H), 4.12
(q, J¼6.8 Hz, 4H), 4.33 (q, J¼6.8 Hz, 4H), 7.08e7.10 (m, 1H),
4.1. General procedure of the synthesis of pyrrole-2,3,4,5-
tetracarboxylates 3 via Cu(OAc)2-catalyzed reaction of amine 1
with but-2-ynedioate 2
7.28e7.31 (m, 1H), 7.38 (d, J¼7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
13.8, 14.1, 61.6, 61.9, 115.0 (d, 2JCF¼21.9 Hz), 120.3 (d, 2JCF¼25.7 Hz),
120.5, 123.6 (d, 3JCF¼10.5 Hz), 127.4, 130.5 (d, 3JCF¼9.5 Hz), 133.3 (d,
4JCF¼3.8 Hz),159.0,162.5 (d, 1JCF¼253.6 Hz),163.0; HRMS (ESI) calcd
for C22H23BrFNO8: 528.0669 (MþHþ), found: 528.0656.
Amine 1 (0.30 mmol), Cu(OAc)2 (0.03 mmol, 10 mol %), and
Cs2CO3 (0.03 mmol, 10 mol %) were added to a solution of but-2-
ynedioates 2 (0.66 mmol) in CH3CN (1.5 mL). The mixture was
stirred at 70 ꢀC under O2 atmosphere. After completion of the
4.1.8. Tetraethyl 1-(4-fluorophenyl)-1H-pyrrole-2,3,4,5-tetracar-
boxylate (3h). Yield: 50%; Yellow liquid; 1H NMR (400 MHz,

3808
L. Zhang et al. / Tetrahedron 69 (2013) 3805e3809
CDCl3)
d
1.09 (t, J¼7.4 Hz, 6H),1.33 (t, J¼7.4 Hz, 6H), 4.10 (q, J¼7.4 Hz,
(400 MHz, CDCl3) d 3.68 (s, 6H), 3.84 (s, 3H), 3.89 (s, 6H), 6.93
4H), 4.33 (q, J¼7.4 Hz, 4H), 7.08e7.12 (m, 2H), 7.23e7.26 (m, 2H); 13C
(d, J¼8.2 Hz, 2H), 7.19 (d, J¼8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3)
NMR (100 MHz, CDCl3)
d
3
13.8,14.1, 61.6, 61.8,115.8 (d, 2JCF¼22.9 Hz),
d 52.7, 55.5, 113.9, 119.1, 128.3, 128.5, 129.3, 160.0, 160.2, 163.7;
4
119.6, 128.2, 129.5(d, JCF¼8.6 Hz), 132.9 (d, JCF¼2.9 Hz), 159.4,
162.9 (d, 1JCF¼247.9 Hz), 164.2; HRMS (ESI) calcd for C22H24FNO8:
472.1384 (MþNaþ), found: 472.1373.
HRMS (ESI) calcd for C19H19NO9: 428.0958 (MþNaþ), found:
428.0941.
4.1.17. 2,3-Diethyl 4,5-dimethyl 1-(4-methoxyphenyl)-1H-pyrrole-
4.1.9. Tetraethyl 1-(4-bromophenyl)-1H-pyrrole-2,3,4,5-tetracarbox-
2,3,4,5-tetracarboxylate (3q). Yield: 36%; Yellow liquid; 1H NMR
ylate (3i). Yield: 45%; Yellow solid; 1H NMR (400 MHz, CDCl3)
(400 MHz, CDCl3)
d
1.10 (t, J¼7.3 Hz, 3H),1.34 (t, J¼6.8 Hz, 3H), 3.66 (s,
d
1.10 (t, J¼6.9 Hz, 6H), 1.33 (t, J¼6.4 Hz, 6H), 4.10 (q, J¼6.9 Hz, 4H),
4.32 (q, J¼6.4 Hz, 4H), 7.14 (d, J¼7.3 Hz, 2H), 7.55 (d, J¼7.3 Hz, 2H);
13C NMR (100 MHz, CDCl3)
13.8, 14.1, 61.6, 61.9, 119.8, 123.8, 128.0,
3H), 3.82 (s, 3H), 3.87 (s, 3H), 4.10 (q, J¼7.3 Hz, 2H), 4.33 (q, J¼6.8 Hz,
2H), 6.91 (d, J¼8.3 Hz, 2H), 7.18 (d, J¼7.8 Hz, 2H); 13C NMR (100 MHz,
d
CDCl3) d 13.8,14.2, 52.6, 52.7, 55.5, 61.5, 61.8,113.9,119.0,119.3,127.8,
129.2, 132.0, 136.1, 159.3, 163.1; HRMS (ESI) calcd for C22H24BrNO8:
128.6,128.8,129.5,159.6,160.0,160.2,163.2,163.9; HRMS (ESI) calcd
510.0764 (MþHþ), found: 510.0743.
for C21H23NO9: 456.1271 (MþNaþ), found: 456.1288.
4.1.10. Tetraethyl 1-(4-(ethoxycarbonyl)phenyl)-1H-pyrrole-2,3,4,5-
Acknowledgements
tetracarboxylate (3j). Yield: 26%; Yellow liquid; 1H NMR
(400 MHz, CDCl3)
d
1.08 (t, J¼6.9 Hz, 6H), 1.32e1.38 (m, 9H), 4.09 (q,
Financial support from National Natural Science Foundation of
China (No. 21032007) is gratefully acknowledged.
J¼6.9 Hz, 4H), 4.33e4.37 (m, 6H), 7.34 (d, J¼7.8 Hz, 2H), 8.11 (d,
J¼7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 13.8,14.2,14.4, 61.5, 61.6,
61.9, 119.2, 120.0, 127.7, 127.9, 130.1, 140.8, 159.3, 163.1, 165.5; HRMS
Supplementary data
(ESI) calcd for C25H29NO10: 526.1689 (MþNaþ), found: 526.1669.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.03.061.
These data include MOL file and InChiKey of the most important
compound described in this article.
4.1.11. Tetraethyl 1-mesityl-1H-pyrrole-2,3,4,5-tetracarboxylate
(3k). Yield: 45%; Yellow liquid; 1H NMR (400 MHz, CDCl3)
d 1.06
(t, J¼6.8 Hz, 6H), 1.34 (t, J¼6.8 Hz, 6H), 1.95 (s, 6H), 2.28 (s, 3H), 4.07
(q, J¼6.8 Hz, 4H), 4.32 (q, J¼6.8 Hz, 4H), 6.88 (s, 2H); 13C NMR
(100 MHz, CDCl3) d 13.7, 14.2, 17.6, 21.2, 61.5, 61.6, 119.5, 127.2, 128.7,
References and notes
133.3, 135.7, 139.2, 159.5, 163.4; HRMS (ESI) calcd for C25H31NO8:
474.2128 (MþHþ), found: 474.2103.
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boxylate (3l). Yield: 55%; Yellow liquid; 1H NMR (400 MHz,
CDCl3)
d
1.21 (t, J¼6.9 Hz, 6H), 1.31 (t, J¼6.9 Hz, 6H), 2.27 (s, 3H),
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4.22 (q, J¼6.9 Hz, 4H), 4.29 (q, J¼6.9 Hz, 4H), 5.66 (s, 2H), 6.96 (d,
J¼7.4 Hz, 2H), 7.06 (d, J¼7.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
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d
13.9, 14.2, 21.2, 49.9, 61.4, 61.9, 120.1, 126.8, 126.9, 129.3, 133.4,
137.5, 160.3, 163.4; HRMS (ESI) calcd for C24H29NO8: 482.1791
(MþNaþ), found: 482.1778.
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(3m). Yield: 58%; Yellow liquid; 1H NMR (400 MHz, CDCl3)
d 1.20
(t, J¼6.9 Hz, 6H),1.31 (t, J¼6.9 Hz, 6H), 4.22 (q, J¼6.9 Hz, 4H), 4.27 (q,
J¼6.9 Hz, 4H), 5.71 (s, 2H), 7.06 (d, J¼6.9 Hz, 2H), 7.23e7.26 (m, 3H);
13C NMR (100 MHz, CDCl3)
d 13.9, 14.2, 50.1, 61.4, 62.0, 120.2, 126.8,
126.9, 127.8, 128.7, 136.4, 160.3, 163.4; HRMS (ESI) calcd for
C23H27NO8: 468.1634 (MþNaþ), found: 468.1626.
4.1.14. Tetraethyl 1-(4-fluorobenzyl)-1H-pyrrole-2,3,4,5-tetracar-
boxylate (3n). Yield: 42%; Yellow liquid; 1H NMR (400 MHz,
CDCl3)
d
1.23 (t, J¼6.9 Hz, 6H), 1.31 (t, J¼7.3 Hz, 6H), 4.21e4.32 (m,
8H), 5.66 (s, 2H), 6.95 (d, J¼8.2 Hz, 2H), 7.08 (d, J¼8.2 Hz, 2H); 13C
NMR (100 MHz, CDCl3)
d 13.9, 14.2, 49.4, 61.5, 62.0, 115.5 (d,
2JCF¼21.9 Hz), 120.3, 126.6, 128.9 (d, JCF¼8.6 Hz), 132.2 (d,
4JCF¼2.9 Hz),160.3,163.3 (d, 1JCF¼245.0 Hz),164.2; HRMS (ESI) calcd
for C23H26FNO8: 486.1540 (MþNaþ), found: 486.1510.
3
4.1.15. Tetraethyl 1-butyl-1H-pyrrole-2,3,4,5-tetracarboxylate
(3o). Yield: 44%; Yellow liquid; 1H NMR (400 MHz, CDCl3)
d
0.90
(t, J¼6.9 Hz, 3H), 1.23e1.32 (m, 16H), 1.69 (d, J¼6.0 Hz, 2H),
4.27e4.33 (m, 8H); 13C NMR (100 MHz, CDCl3)
13.7, 14.0, 14.2, 19.9,
d
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33.6, 47.6, 61.3, 61.9, 119.8, 126.3, 160.4, 163.5; HRMS (ESI) calcd for
C20H29NO8: 434.1791 (MþNaþ), found: 434.1783.
4.1.16. Tetramethyl 1-(4-methoxyphenyl)-1H-pyrrole-2,3,4,5-
tetracar-boxylate (3p). Yield: 55%; Yellow solid; 1H NMR

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