Synthesis of highly substituted pyrroles via oxidative free radical reactions of β-aminocinnamates

Article abstract of DOI:10.1016/j.tet.2005.12.011

Oxidative free radical reactions of β-aminocinnamates are described. Imine radicals produced by tetra-n-butylammonium cerium(IV) nitrate (TBACN) oxidation of enamines undergo efficient addition to the C-C double bond of β-aminocinnamates. This TBACN media

Full text of DOI:10.1016/j.tet.2005.12.011

Tetrahedron 62 (2006) 2235–2239
Synthesis of highly substituted pyrroles via oxidative free
radical reactions of b-aminocinnamates
*
An-I Tsai and Che-Ping Chuang
Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan, ROC
Received 8 November 2005; revised 5 December 2005; accepted 6 December 2005
Available online 27 December 2005
Abstract—Oxidative free radical reactions of b-aminocinnamates are described. Imine radicals produced by tetra-n-butylammonium
cerium(IV) nitrate (TBACN) oxidation of enamines undergo efficient addition to the C–C double bond of b-aminocinnamates. This TBACN
mediated free radical reaction between b-aminocinnamates and enamines provides a novel method for the synthesis of highly substituted
pyrroles. The direct TBACN oxidation of b-aminocinnamates gave the dimerization products effectively.
q 2005 Elsevier Ltd. All rights reserved.
O
O
1. Introduction
O
O
O
R1
R2
OEt
2
EtO
Ar
R2
Free radical reactions have become increasingly impor-
tant in organic synthesis in the last two decades.1 The
oxidative addition of an electrophilic carbon-centered
radical to alkenes mediated by metal salts has received
considerable attention in the organic synthesis for the
construction of carbon–carbon bonds. Among these,
manganese(III) acetate and cerium(IV) ammonium nitrate
(CAN) have been used most efficiently.1d–f,2,3 Pyrrole
derivatives represent a class of compounds of great
important in heterocyclic chemistry primarily due to the
fact that pyrroles are important substructures of pharma-
ceutical agents and also of numerous natural products.4
Accordingly, substantial attention has been paid to
develop efficient methods for the synthesis of pyrroles.5
Earlier, we have reported that oxidative free radical
reactions between b-anilinocinnamate 1 and 1,3-dicarbo-
nyl compound 2 produced the desired pyrrole products 3
(29–54%) and dimerization product 4 (0–18%) (Eq. 1).6
Imine radical 6 can be generated from the oxidation of
enamine 5 by metal salts (Eq. 2) and it undergoes
efficient addition to the C–C double bond.7 We describe
here a much more effective method for the synthesis of
highly substituted pyrroles via the oxidative free radical
reaction between b-aminocinnamates and enamines.
CAN, MeOH
N
R1
Ar
+
NH
R
1
3 R
(1)
O
O
EtO
OEt
Ar
Ar
N
R
4
(1)
NH
O
NH2
O
Ce(IV) or Mn(III)
(2)
R1
R2
R1
R2
.
5
6
(2)
2. Results and discussion
The oxidative free radical reaction between b-anilino-
cinnamate 1 and enamine 5 was first examined (Eq. 3).
When b-anilinocinnamate 1a was treated with enamine 5a
and CAN in MeOH at room temperature, pyrrole 3a was
obtained in 54% yield and no dimerization product 4a could
be found (Table 1, entry 1). A plausible mechanism for this
reaction is shown in Scheme 1. Initiation occurs with CAN
oxidation of enamine 5a to produce imine radical 6a.
Keywords: Tetra-n-butylammonium cerium(IV) nitrate; Oxidative; Free
radical; b-Aminocinnamates.
Corresponding author. Fax: C886 6 2740552; e-mail: cpchuang@
mail.ncku.edu.tw
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.12.011

2236
A.-I. Tsai, C.-P. Chuang / Tetrahedron 62 (2006) 2235–2239
Table 1. Free radical reactions of b-aminocinnamates
Entry
b-Aminocinnamate
Enamine
Oxidant
Solvent
Product (yield
(%))
1
2
3
4
5
6
7
8
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1a: RZp-ClPh, ArZPh
1b: RZp-BrPh, ArZPh
1c: RZp-EtO2CPh, ArZPh
1d: RZPh, ArZPh
1e: RZCH2CN, ArZPh
11a: ArZPh
11a: ArZPh
11a: ArZPh
11a: ArZPh
11a: ArZPh
11a: ArZPh
11a: ArZPh
11a: ArZPh
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5b: R1ZEt, R2ZOMe
5b: R1ZEt, R2ZOMe
5c: R1ZiPr, R2ZOEt
5c: R1ZiPr, R2ZOEt
5d: R1ZPr, R2ZOEt
5e: R1ZMe, R2ZMe
5f: R1ZEt, R2ZEt
CAN
MeOH
HOAc
MeOH
MeCN
CHCl3
MeOH
CHCl3
MeOH
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
MeOH
MeOH
MeCN
CHCl3
MeOH
MeOH
MeOH
MeOH
3a (54)
3a (62)
3a (92)
3a (88)
3a (92)
3b (61) 7b (30)
3b (81)
3c (17) 7c (55)
3c (45) 7c (30)
3d (75)
3e (79)
3f (61)
3g (94)
3h (91)
3i (96)
3j (76)
7a (59)
7a (87)
Me(OAc)3
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
CAN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
TBACN
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5a: R1ZMe, R2ZOEt
5b: R1ZEt, R2ZOMe
5c: R1ZiPr, R2ZOEt
5e: R1ZMe, R2ZMe
5f: R1ZEt, R2ZEt
7a (92)
7a (89)
7b (89)
7c (84)
7d (69) 12a (14)
7e (72)
This radical intermediate 6a undergoes intermolecular
addition followed by oxidation to give 9a, which undergoes
nucleophilic addition of anilino group followed by
elimination of ammonia to produce pyrrole 3a (path a).
There is no trace of another expected pyrrole product 7a can
be detected, which is presumably derived from the
nucleophilic addition of amino group of 10a (path b).
With Mn(OAc)3 in HOAc, pyrrole 3a was obtained in 62%
yield (entry 2). It has been reported that tetra-n-
butylammonium cerium(IV) nitrate (TBACN) oxidized
1,3-dicarbonyl compounds more slowly than CAN.8 We
expected that pyrrole 3a could be generated in a better result
by using TBACN. Indeed, with TBACN, the reaction
between b-anilinocinnamate 1a and enamine 5a in MeOH
afforded pyrrole 3a in an impressive 92% yield (entry 3).9
With other enamines 5b and 5c, in addition to the formation
of products 3b and 3c, pyrroles 7b and 7c were also obtained
(entries 6 and 8). The ratios of 3/7 decrease as the size of
substituents (R1) on enamine 5 increases. This is pre-
sumably due to the steric effect exerted by R1 group—the
addition rate of anilino group (path a) was retarded by the
larger R1 and competitive nucleophilic addition of amino
group (path b) occurred. In attempt to investigate the range
of solvents compatible with this reaction, this reaction was
performed in various solvents. With enamine 5a, the change
of solvent to CH3CN or CHCl3 gave only pyrrole 3a in a
similar yield (entries 4 and 5). With enamine 5b, we are
surprised to found that pyrrole 3b was obtained in a much
better yield (81%) from 1a and no pyrrole 7b could be
isolated by using CHCl3 as solvent (entry 7). Since TBACN/
CHCl3 is the most effective reaction condition for the
formation of pyrrole 3, so the scope of this reaction was
explored with a variety of b-anilinocinnamate 1 and
enamine 5 using the TBACN/CHCl3 conditions. As shown
in Table 1, this method proved to be of general applicability
on b-anilinocinnamate 1 and enamine 5. In most cases,
b-anilinocinnamate 1 was smoothly converted to the
corresponding pyrrole 3 selectively in excellent to good
NH
O
O
R2
O
R2
O
O
O
R1
R2
R1
Ce(IV)
R1
.
OEt
EtO
Ar
EtO
Ar
6
.
NH
NH
Ar
NH
R
NH
R
NH
R
8
9
1
path a
O
O
R2
O
O
O
O
R1
R2
EtO
Ph
R2
path b
EtO
Ph
EtO
Ar
NH2
R1
N
R1
N
N
H
7
10
3
R
R
Scheme 1.

A.-I. Tsai, C.-P. Chuang / Tetrahedron 62 (2006) 2235–2239
2237
yield (entries 9–15). In addition, when b-alkylaminocin-
namate 1e was reacted with enamine 5a under similar
conditions, pyrrole 3j was obtained in 76% yield (entry 16).
11a–11e was converted to the corresponding dimerization
product 12 in good yields (entries 1–5), the dimerization of
b-anilinocinnamate 1 was less productive (entries 7 and 8).
NH2
O
O
O
O
O
O
O
R1
R2
EtO
R2
OEt
5
EtO
OEt
TBACN
OEt
NH2
(5)
Ce(IV) or Mn(III)
Ar
+
NH
R
Ar
N
R1
Ar
N
Ar
Ar
1
3 R
(3)
11
12 H
O
O
(5)
EtO
R2
Table 2. Oxidative dimerization of b-aminocinnamates
Ar
N
H
R1
Entry
b-Aminocinnamate
Product (yield (%))
7
1
2
3
4
5
6
7
8
11a: ArZPh
11b: ArZp-Tolyl
11c: ArZp-BrPh
11d: ArZp-ClPh
11e: RZp-NO2Ph
1e: RZCH2CN, ArZPh
1a: RZp-ClPh, ArZPh
1c: RZp-EtO2CPh, ArZPh
12a (82)
12b (80)
12c (88)
12d (87)
12e (96)
4c (75)
(3)
The oxidative free radical reaction of b-aminocinnamate
11a was next studied (Eq. 4). Reaction of b-aminocin-
namate 11a with enamine 5a and CAN in MeOH afforded
pyrrole 7a in 59% yield (entry 17) and the reaction yield was
increased to 87% by replacing CAN with TBACN (entry
18). We also examined the effect of various solvents on the
yield of pyrrole 7a. Use MeCN or CHCl3 as solvent, pyrrole
7a was formed in a similar result (entries 19 and 20). Based
on these results, we also examined this TBACN mediated
reaction of b-aminocinnamate 11a with various enamines 5
in MeOH and the results were also summarized in Table 1
(entries 21–24). Again, the reaction worked well and pyrrole
7 was formed in good yield. For an unknown reason, with
enamine 5e, in addition to the desired pyrrole 7e, the
dimerization product 12a was also isolated (entry 23).
4a (41)
4b (46)
In conclusion, imine radical 6 generated from the TBACN
oxidation of enamine 5 undergoes efficient addition to the
C–C double bond of b-aminocinnamates. This free radical
reaction provides a novel method for the synthesis of highly
substituted pyrroles from readily available b-aminocinna-
mates and enamines. The dimerization product 12 can also
be synthesized effectively by the direct TBACN oxidation
of b-aminocinnamate 11.
O
O
NH2
O
O
3. Experimental
R2
R1
R2
EtO
OEt
5
Ar
N
H
R1
3.1. General considerations
Ce(IV)
Ar
+
NH2
11a
7
Ar = phenyl
(4)
Melting points are uncorrected. Infrared spectra were taken
with a Hitachi 260-30 spectrometer. The NMR spectra were
recorded on a Brucker AVANCE 300, AMX-400 or
AVANCE 500 spectrometer. Chemical shifts are reported
in ppm relative to TMS as internal reference. Elemental
analyses were performed with Heraeus CHN-Rapid Analy-
zer. Analytical thin-layer chromatography was performed
with precoated silica gel 60 F-254 plates (0.25 mm thick)
from EM Laboratories and visualized by UV light. The
reaction mixture was purified by column chromatography
over EM Laboratories silica gel (70–230 mesh). The
starting b-aminocinnamates 110b,11a and 1111b were syn-
thesized according to literature procedures. TBACN was
prepared with CAN and tetra-n-butylammonium hydrogen
sulfate.12 Spectra data of pyrroles 3a–j and dimerization
products 4a–c have been reported.6
O
O
EtO
OEt
Ar
12a
N
H
Ar
(4)
The preparation of highly substituted C2-symmetric
pyrroles by the oxidative dimerization of enamino esters
has been reported.6,10 On the basis of the generation of
dimerization product 12a in the reaction between b-amino-
cinnamate 11a and enamine 5e, we expected that the direct
TBACN oxidation of b-aminocinnamate 11 would produce
dimerization product 12 effectively (Eq. 5). Indeed, the
formation of dimerization product 12a (82%) was achieved
by the oxidation of b-aminocinnamate 11a with TBACN in
methanol. Analogous results were obtained with other
b-aminocinnamates 11 and were summarized in Table 2
(entries 1–5). The N-alkyl substituted b-aminocinnamate 1e
also underwent the direct TBACN oxidation reaction,
producing pyrrole 4c in a much better yield than that
performed with CAN (entry 6).6 The TBACN mediated
oxidative dimerization of b-anilinocinnamates 1 was also
studied. As shown in Table 2, while b-aminocinnamate
3.2. Typical experimental procedure for the free radical
reaction between b-aminocinnamates and enamines
A solution of 132 mg (0.69 mmol) of ethyl 3-amino-
cinnamate (11a), 446 mg (3.46 mmol) of ethyl 3-amino-
crotonate (5a) and 1.39 g (1.39 mmol) of TBACN in 10 mL
of MeOH was stirred at room temperature for 30 min and
another 1.39 g (1.39 mmol) of TBACN was added. After

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A.-I. Tsai, C.-P. Chuang / Tetrahedron 62 (2006) 2235–2239
stirred for another 30 min, the reaction mixture was diluted
with EtOAc (100 mL), washed with aq satd NaHSO3
(50 mL) and H2O (3!50 mL), dried (Na2SO4), and
concentrated in vacuo. The residue was chromatographed
over 15 g of silica gel (EtOAc/hexane, 1:4) followed by
recrystallization (EtOAc–hexane) to give 182 mg (87%) of
pyrrole 7a.
(400 MHz, CDCl3) d 1.16 (t, JZ7.3 Hz, 3H, CH3), 1.18
(t, JZ7.1 Hz, 3H, CH3), 1.26 (t, JZ7.6 Hz, 3H, CH3), 2.77
(q, JZ7.3 Hz, 2H, CH2), 2.82 (q, JZ7.6 Hz, 2H, CH2), 4.21
(q, JZ7.1 Hz, 2H, OCH2), 7.33–7.43 (m, 3H, ArH),
7.46–7.52 (m, 2H, ArH), 8.32 (br s, 1H, NH); 13C NMR
(100.6 MHz, CDCl3) d 8.6 (q), 13.9 (2q), 20.2 (t), 35.9 (t),
60.7 (t), 112.4 (s), 122.2 (s), 128.26 (3d), 128.30 (2d), 131.3
(s), 133.6 (s), 138.1 (s), 166.0 (s), 201.0 (s). Anal. Calcd for
C18H21NO3: C, 72.22; H, 7.07; N, 4.68. Found: C, 72.32; H,
7.13; N, 4.64.
3.2.1. 3,4-Diethoxycarbonyl-2-methyl-5-phenylpyrrole
(7a). White crystals; mp 100–101 8C; IR (CHCl3) 3455,
3305, 2990, 1700, 1445, 1285, 1095 cmK1 1H NMR
;
(300 MHz, CDCl3) d 1.26 (t, JZ7.1 Hz, 3H, CH3), 1.33
(t, JZ7.2 Hz, 3H, CH3), 2.51 (s, 3H, CH3), 4.27 (q, JZ
7.1 Hz, 2H, OCH2), 4.28 (q, JZ7.2 Hz, 2H, OCH2),
7.27–7.42 (m, 3H, ArH), 7.42–7.50 (m, 2H, ArH), 8.37
(br s, 1H, NH); 13C NMR (125.7 MHz, CDCl3) d 12.7 (q),
14.0 (q), 14.2 (q), 59.9 (t), 61.0 (t), 112.1 (s), 114.5 (s),
126.9 (2d), 127.8 (d), 128.5 (2d), 130.6 (s), 130.9 (s), 135.4
(s), 164.7 (s), 167.1 (s). Anal. Calcd for C17H19NO4: C,
67.76; H, 6.36; N, 4.65. Found: C, 67.76; H, 6.35; N, 4.64.
3.3. Typical procedure for the oxidative dimerization
reaction of b-aminocinnamates
A solution of 138 mg (0.72 mmol) of ethyl 3-amino-
cinnamate (11a), and 722 mg (0.72 mmol) of TBACN in
10 mL of MeOH was stirred at room temperature for
30 min. After the work-up as described for the preparation
of pyrrole 7a, the residue was chromatographed over 15 g of
silica gel (EtOAc/hexane, 1:6) followed by recrystallization
(EtOAc–hexane) to give dimerization product 12a (107 mg,
82%).
3.2.2. 4-Ethoxycarbonyl-2-ethyl-3-methoxycarbonyl-5-
phenylpyrrole (7b). White crystals; mp 88–89 8C; IR
(CHCl3) 3455, 3310, 2985, 1690, 1450, 1285, 1100 cmK1
;
3.3.1. 3,4-Diethoxycarbonyl-2,5-diphenylpyrrole (12a).
White crystals; mp 149–150 8C; IR (CHCl3) 3450, 2990,
1715, 1490, 1225, 1125 cmK1; 1H NMR (400 MHz, CDCl3)
d 1.25 (t, JZ7.1 Hz, 6H, 2CH3), 4.24 (q, JZ7.1 Hz, 4H,
2OCH2), 7.39–7.44 (m, 6H, ArH), 7.51–7.59 (m, 4H, ArH),
8.59 (br s, 1H, NH); 13C NMR (100.6 MHz, CDCl3) d 14.0
(2q), 60.7 (2t), 114.5 (2s), 128.1 (4d), 128.5 (6d), 130.9 (2s),
134.2 (2s), 165.2 (2s). Anal. Calcd for C22H21NO4: C,
72.71; H, 5.82; N, 3.85. Found: C, 72.63; H, 5.83; N, 3.83.
1H NMR (400 MHz, CDCl3) d 1.26 (t, JZ7.1 Hz, 6H,
2CH3), 2.93 (q, JZ7.6 Hz, 2H, CH2), 3.80 (s, 3H, OCH3),
4.26 (q, JZ7.1 Hz, 2H, OCH2), 7.28–7.39 (m, 3H, ArH),
7.43–7.49 (m, 2H, ArH), 8.50 (br s, 1H, NH); 13C NMR
(100.6 MHz, CDCl3) d 13.6 (q), 14.0 (q), 20.2 (t), 51.1 (q),
61.0 (t), 111.3 (s), 114.6 (s), 127.1 (2d), 127.9 (d), 128.6
(2d), 130.8 (s), 130.9 (s), 140.9 (s), 165.0 (s), 166.8 (s).
Anal. Calcd for C17H19NO4: C, 67.76; H, 6.36; N, 4.65.
Found: C, 67.72; H, 6.38; N, 4.63.
3.3.2. 3,4-Diethoxycarbonyl-2,5-di-(p-tolyl)pyrrole
(12b). White crystals; mp 137–138 8C; IR (KBr) 3265,
2980, 1725, 1680, 1220 cmK1; 1H NMR (400 MHz, CDCl3)
d 1.25 (t, JZ7.1 Hz, 6H, 2CH3), 2.37 (s, 6H, 2CH3), 4.23 (q,
JZ7.1 Hz, 4H, 2OCH2), 7.20 (d, JZ8.1 Hz, 4H, ArH), 7.44
(d, JZ8.1 Hz, 4H, ArH), 8.54 (br s, 1H, NH); 13C NMR
(75.4 MHz, CDCl3) d 14.0 (2q), 21.3 (2q), 60.6 (2t), 114.0
(2s), 128.0 (4d), 129.1 (4d), 134.2 (2s), 138.4 (2s), 165.3
(2s). Anal. Calcd for C24H25NO4: C, 73.64; H, 6.44; N, 3.57.
Found: C, 73.61; H, 6.41; N, 3.55.
3.2.3.
3,4-Diethoxycarbonyl-2-isopropyl-5-phenyl-
pyrrole (7c). White crystals; mp 118–119 8C; IR (CHCl3)
3460, 3315, 2980, 1700, 1445, 1280, 1230 cmK1; 1H NMR
(400 MHz, CDCl3) d 1.25 (t, JZ7.2 Hz, 3H, CH3), 1.29 (d,
JZ7.0 Hz, 6H, 2CH3), 1.31 (t, JZ7.1 Hz, 3H, CH3), 3.70
(septet, JZ7.0 Hz, 1H, CH), 4.24 (q, JZ7.2 Hz, 2H,
OCH2), 4.25 (q, JZ7.1 Hz, 2H, OCH2), 7.28–7.39 (m,
3H, ArH), 7.43–7.49 (m, 2H, ArH), 8.52 (br s, 1H, NH); 13C
NMR (100.6 MHz, CDCl3) d 14.0 (q), 14.2 (q), 21.9 (2q),
25.8 (d), 60.0 (t), 60.9 (t), 111.1 (s), 114.5 (s), 127.3 (2d),
128.0 (d), 128.6 (2d), 130.7 (s), 131.1 (s), 144.3 (s), 164.5
(s), 166.6 (s). Anal. Calcd for C19H23NO4: C, 69.28; H,
7.04; N, 4.25. Found: C, 69.23; H, 7.10; N, 4.25.
3.3.3. 2,5-Di-(p-bromophenyl)-3,4-diethoxycarbonyl-
pyrrole (12c). White crystals; mp 211–212 8C; IR (KBr)
1
3290, 2980, 1700, 1485, 1285 cmK1; H NMR (400 MHz,
CDCl3) d 1.26 (t, JZ7.1 Hz, 6H, 2CH3), 4.25 (q, JZ7.1 Hz,
4H, 2OCH2), 7.40–7.46 (m, 4H, ArH), 7.52–7.57 (m, 4H,
ArH), 8.55 (br s, 1H, NH); 13C NMR (100.6 MHz, CDCl3) d
14.0 (2q), 60.9 (2t), 115.0 (2s), 123.0 (2s), 129.5 (2s), 129.7
(4d), 131.8 (4d), 133.3 (2s), 164.9 (2s). Anal. Calcd for
C22H19Br2NO4: C, 50.70; H, 3.68; N, 2.69. Found: C, 50.83;
H, 3.66; N, 2.68.
3.2.4. 3-Acetyl-4-ethoxycarbonyl-2-methyl-5-phenyl-
pyrrole (7d). White crystals; mp 92–93 8C; IR (CHCl3)
3450, 3280, 3000, 1705, 1655, 1420, 1120 cmK1; 1H NMR
(500 MHz, CDCl3) d 1.21 (t, JZ7.1 Hz, 3H, CH3), 2.42 (s,
3H, CH3), 2.43 (s, 3H, CH3), 4.22 (q, JZ7.1 Hz, 2H,
OCH2), 7.31–7.40 (m, 3H, ArH), 7.46 (d, JZ7.4 Hz, 2H,
ArH), 8.60 (br s, 1H, NH); 13C NMR (100.6 MHz, CDCl3) d
13.2 (q), 13.9 (q), 30.3 (q), 60.9 (t), 113.3 (s), 122.8 (s),
127.9 (2d), 128.2 (d), 128.4 (2d), 131.0 (s), 132.8 (s), 133.7
(s), 166.4 (s), 196.5 (s). Anal. Calcd for C16H17NO3: C,
70.83; H, 6.32; N, 5.16. Found: C, 70.71; H, 6.36; N, 5.17.
3.3.4. 2,5-Di-(p-chlorophenyl)-3,4-diethoxycarbonyl-
pyrrole (12d). White crystals; mp 222–223 8C; IR (KBr)
1
3295, 2980, 1700, 1485, 1450 cmK1; H NMR (400 MHz,
CDCl3) d 1.27 (t, JZ7.1 Hz, 6H, 2CH3), 4.26 (q, JZ7.1 Hz,
4H, 2OCH2), 7.40 (d, JZ8.5 Hz, 4H, ArH), 7.51 (d, JZ
8.5 Hz, 4H, ArH), 8.48 (br s, 1H, NH); 13C NMR
(100.6 MHz, CDCl3) d 14.1 (2q), 60.9 (2t), 115.0 (2s),
128.9 (4d), 129.1 (2s), 129.5 (4d), 133.3 (2s), 134.8 (2s),
3.2.5. 3-Ethoxycarbonyl-5-ethyl-2-phenyl-4-propionyl-
pyrrole (7e). White crystals; mp 113–114 8C; IR (CHCl3)
3450, 3300, 2985, 1700, 1450, 1270 cmK1 1H NMR
;

A.-I. Tsai, C.-P. Chuang / Tetrahedron 62 (2006) 2235–2239
2239
5. (a) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1999, 2849.
(b) Borger, D. L.; Boyce, C. W.; Labroli, M. A.; Sehon, C. A.;
Jin, Q. J. Am. Chem. Soc. 1999, 121, 54. (c) Lee, C.-F.; Yang,
L.-M.; Hwu, T.-Y.; Feng, A.-S.; Tseng, J.-C.; Luh, T.-Y.
J. Am. Chem. Soc. 2000, 122, 4992. (d) Kelin, A. V.; Sromek,
A. W.; Gevorgyan, V. J. Am. Chem. Soc. 2001, 123, 2074. (e)
Ferreira, P. M. T.; Maia, H. L. S.; Monteiro, L. S. Tetrahedron
Lett. 2002, 43, 4491. (f) Bashiardes, G.; Safir, I.; Barbot, F.;
Laduranty, J. Tetrahedron Lett. 2003, 44, 8417. (g) Minetto,
G.; Raveglia, L. F.; Taddei, M. Org. Lett. 2004, 6, 389. (h)
Alongi, M.; Minetto, G.; Taddei, M. Tetrahedron Lett. 2005,
46, 7069. (i) Demir, A. S.; Emrullahoglu, M. Tetrahedron
2005, 61, 10482.
164.8 (2s). Anal. Calcd for C22H19Cl2NO4: C, 61.12; H,
4.43; N, 3.24. Found: C, 61.13; H, 4.42; N, 3.23.
3.3.5. 3,4-Diethoxycarbonyl-2,5-di-(p-nitrophenyl)-
pyrrole (12e). Yellow crystals; mp 217–218 8C; IR (KBr)
1
3230, 1740, 1680, 1345, 1225 cmK1; H NMR (400 MHz,
CDCl3) d 1.29 (t, JZ7.1 Hz, 6H, 2CH3), 4.30 (q, JZ7.1 Hz,
4H, 2OCH2), 7.76 (d, JZ8.8 Hz, 4H, ArH), 8.29 (d, JZ
8.8 Hz, 4H, ArH), 9.01 (br s, 1H, NH); 13C NMR
(100.6 MHz, CDCl3) d 14.0 (2q), 61.4 (2t), 117.1 (2s),
123.9 (4d), 128.8 (4d), 132.7 (2s), 136.5 (2s), 147.6 (2s),
164.3 (2s). Anal. Calcd for C22H19N3O8: C, 58.28; H, 4.22;
N, 9.27. Found: C, 58.37; H, 4.23; N, 9.30.
6. Chuang, C.-P.; Wu, Y.-L. Tetrahedron 2004, 60, 1841.
7. (a) Cossy, J.; Bouzide, A. J. Chem. Soc., Chem.
Commun. 1993, 1218. (b) Cossy, J.; Bouzide, A.;
Leblanc, C. Synlett 1993, 202. (c) Cossy, J.; Bouzide,
A. Tetrahedron Lett. 1993, 34, 5583. (d) Cossy, J.;
Bouzide, A. Tetrahedron 1999, 55, 6483. (e) Cossy, J.;
Bouzide, A.; Leblanc, C. J. Org. Chem. 2000, 65, 7257.
(f) Chuang, C.-P.; Wu, Y.-L. Tetrahedron Lett. 2001, 42,
1719. (g) Zhang, Y.; Raines, A. J.; Flowers, R. A., II
J. Org. Chem. 2004, 69, 6267.
Acknowledgements
We are grateful to the National Science Council of ROC for
financial support. (Grant No. NSC-93-2113-M-006-004)
References and notes
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