Synthesis of 2-and 3-indolylpyrroles via 1,3-dipolar cycloadditions of muenchnones and nitroalkenes

Article abstract of DOI:10.3987/COM-10-S(E)125

A series of 2-and 3-indolylpyrroles were generated via 1,3-dipolar cycloadditions between (2-nitrovinyl)indoles and symmetrical and unsymmetrical 1,3-oxazolium-5-olates (muenchnones). The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-10-S(E)125

HETEROCYCLES, Vol. 82, No. 2, 2011
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HETEROCYCLES, Vol. 82, No. 2, 2011, pp. 1617 - 1631. © The Japan Institute of Heterocyclic Chemistry
Received, 16th September, 2010, Accepted, 5th November, 2010, Published online, 18th November, 2010
DOI: 10.3987/COM-10-S(E)125
SYNTHESIS OF 2- AND 3-INDOLYLPYRROLES VIA 1,3-DIPOLAR
CYCLOADDITIONS OF MÜNCHNONES AND NITROALKENES †
Justin M. Lopchuk and Gordon W. Gribble*
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
ggribble@dartmouth.edu
Abstract – A series of 2- and 3-indolylpyrroles were generated via 1,3-dipolar
cycloadditions between (2-nitrovinyl)indoles and symmetrical and unsymmetrical
1,3-oxazolium-5-olates (münchnones).
INTRODUCTION
Methods for the synthesis of biheteroaryl compounds are of great importance due to the broad
applicability and privileged nature1 of these structures, which include natural products,2 pharmaceuticals,3
and materials such as polymers4 and dyes.5 Naturally occurring biheteroaryl structures exist as unfused2
or fused systems, examples of which are shown in Figure 1.2
H
N
O
O
H
H
N
N
O
MeO2C
CO2Me
O
NH
N
N
H
Cl
Cl
OH
O
N
H
N
N
H
N
H
OH
lycogarubin C
granulatimide
HO
MeO
rebeccamycin
Figure 1. Indolylpyrrole-based Natural Products
_____________________________________________________________________________________
† Dedicated to Professor Albert Eschenmoser in celebration of his 85th birthday and his many outstanding
contributions to synthetic organic chemistry.

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HETEROCYCLES, Vol. 82, No. 2, 2011
Currently, the most common way to synthesize these heterocycles is with transition metal catalyzed
cross-coupling.6 While these methods are rapidly improving, the direct cross-coupling of two heteroaryl
moieties remains a challenge.7 Few other methods exist for providing convenient access to simple
unfused indolylpyrrole core structures.
Mohanakrishnan and coworkers recently disclosed a
cycloaddition method based on tosylmethylisocyanide (TosMIC) which allows access to protected
indolylpyrrole structures.8 Our laboratory has long been interested in the use of 1,3-oxazolium-5-olates
(münchnones) for the synthesis of both fused heteroaromatics9 and caged systems.10 The 1,3-dipolar
cycloaddition of münchnones and nitroalkenes provides an orthogonal and transition metal-free
methodology that allows flexible access to these structures. As an extension of our work with 2- and 3-
nitroindoles,9 we endeavored to examine various 2- and 3-(2-nitrovinyl)indoles as substrates for
1,3-dipolar cycloadditions with symmetrical and unsymmetrical münchnones.
RESULTS AND DISCUSSION
The münchnone precursors were prepared as previously reported9 and the cyclized münchnones were
generated in situ (Scheme 1) with N,N’-diisopropylcarbodiimide (DIPC).
O
R2
R1
O
DIPC
R1
N
CO2H
O
N
THF, reflux
Bn
Bn
R2
1 (R1 = R2 = Ph)
2 (R1 = R2 = Me)
5 (R1 = R2 = Ph)
6 (R1 = R2 = Me)
1
2
1
2
3
4
7
8
(R = Ph, R = Me)
(R = Me, R = Ph)
(R = Ph, R = Me)
(R = Me, R = Ph)
1
2
1
2
Scheme 1. Generation of Münchnones 5-8
In lieu of the conventional Henry reaction approach, 3-(2-nitrovinyl)indoles 12 and 13 were synthesized
directly from indoles 9 and 10 by an addition-elimination reaction of 1-(dimethylamino)-2-nitroethylene11
(Scheme 2). However, the attempted synthesis of 14 using this route failed, presumably because
1-(phenylsulfonyl)indole 11 is too electron-deficient to undergo the requisite initial Michael addition
reaction.

HETEROCYCLES, Vol. 82, No. 2, 2011
1619
NO2
NO2
Me2N
N
TFA, CH2Cl2,
N
R
R
9 (R = H)
10 (R = Me)
11
12 (R = H) 92%
13 (R = Me) 79%
14
(R = SO2Ph)
(R = SO2Ph) no reaction
Scheme 2. Synthesis of 3-(2-nitrovinyl)indoles
Compound 14 was instead prepared by N-protection of indole-3-carboxaldehyde12 followed by
condensation with nitromethane in a standard Henry reaction13 (Scheme 3).
NO2
CHO
CHO
NH4OAc/AcOH
LDA
N
MeNO2
94%
PhSO2Cl
93%
N
N
SO2Ph
H
15
SO2Ph
11
14
Scheme 3. Synthesis of 3-(2-nitrovinyl)-1-(phenylsulfonyl)indole
The unprotected and methyl–protected 2-(2-nitrovinyl)indoles were generated in four and five steps,
respectively, from commercially available indole-2-carboxylic acid through a sequence of esterification,14
reduction,15 oxidation,15 protection16 (for the N-methyl derivative), and condensation with nitromethane17
(Scheme 4). Attempted generation of 20 from 19 with methyl iodide or dimethyl sulfate did not yield
an appreciable amount of the desired product.
(i, ii, iii)
(v)
NO2
CO2H
CHO
N
N
N
H
H
H
17
16
19
(iv)
NO2
(v)
CHO
N
N
Me
18
20
Me
(i) H2SO4, MeOH; (ii) DIBAL-H, THF; (iii) MnO2, MeCN, 94% over three steps; (iv) Aliquat 336, dimethyl sulfate,
50% aq. NaOH, CH2Cl2, 98%; (v) a) 50% aq. NaOH, MeNO2, MeOH, b) 20% aq. HCl (19, 87%; 20, 84%)
Scheme 4. Synthesis of 2-(2-nitrovinyl)indoles from indole-2-carboxylic acid

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HETEROCYCLES, Vol. 82, No. 2, 2011
Instead, 1-(phenylsulfonyl)indole derivative 21 was generated (Scheme 5) from indole via N-protection,18
C2-lithiation (quenching with DMF),19 and condensation with nitromethane.17
NO2
(ii)
(i)
(iii)
CHO
SO2Ph
N
N
N
N
H
SO2Ph
SO2Ph
23
11
21
22
(i) PhSO2Cl, NaOH, n-Bu4NHSO4, CH2Cl2, 97%; (ii) a) n-BuLi, THF, b) DMF, 69%; (iii) a) 50% aq. NaOH, MeNO2,
MeOH, b) 20% aq. HCl, 87%
Scheme 5. Synthesis of 2-(2-nitrovinyl)-1-(phenylsulfonyl)indole
With the nitroalkenes in hand, their reactivity with münchnones 5-8 was investigated. Gratifyingly,
3-(2-nitrovinyl)indoles 12-14 reacted smoothly with symmetrical münchnones 5 and 6 to give the
corresponding pyrrole products 24-29 in good yields (Table 1). It is proposed that the 1,3-dipolar
cycloadditions proceed though a bicyclic adduct which expels carbon dioxide and eliminates nitrous acid
to give the substituted N-benzyl-3-indolylpyrroles (Scheme 6).9 The protecting group on the indole (or
lack thereof) seemingly had no effect on the reaction.
Table 1. Reaction of 3-Nitroalkenes with Symmetrical Münchnones.
R1
NO2
Bn
R2
N
R1
H
O
DIPC
O
+
N
THF, reflux
Bn
R2
N
R3
N
R3
5: R1 = R2 = Ph
6: R1 = R2 = Me
12-14
24-29
Indole
12
Münchnone
R3
H
Product
Yielda
5
5
5
6
6
6
24
25
26
27
28
29
78%
62%
81%
84%
75%
68%
13
Me
14
SO2Ph
H
12
13
Me
14
SO2Ph
aYield refers to isolated products after column chromatography.

HETEROCYCLES, Vol. 82, No. 2, 2011
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Bn
R1
NO2
+
Bn
R2
R1
N
N
O2N
R1
O
H
O
- CO2
O
O
N
R2
Bn
- HNO2
R2
N
N
R
N
R
R
Scheme 6. Proposed Course of 1,3-Dipolar Cycloadditions
In a similar manner, 2-(2-nitrovinyl)indoles 19-21 were allowed to react with symmetrical münchnones 5
and 6. The corresponding 3-pyrrol-2-ylindoles were obtained in high yield and again, the various
protecting groups on the starting indoles had no effect on the outcome of the reaction (Table 2).
Table 2. Reaction of 2-Nitroalkenes with Symmetrical Münchnones.
H
NO2
R1
R2
O
DIPC
O
+
N
N
N
N
THF, reflux
Bn
Bn
R3
R2
R3 R1
19-21
30-35
5: R1 = R2 = Ph
1
2
6
: R = R = Me
Indole
19
Münchnone
R3
H
Product
30
Yielda
92%
90%
94%
92%
70%
86%
5
5
5
6
6
6
20
Me
31
21
SO2Ph
H
32
19
33
20
Me
34
21
SO2Ph
35
aYield refers to isolated products after column chromatography.
With the success of münchnones 5 and 6, we turned our attention to unsymmetrical münchnones 7 and 8
and tested them under the same reaction conditions. The reaction of münchnone 7 with
3-(2-nitrovinyl)indoles 12-14 gave the expected pyrrole products in moderate to good yield with
reasonably good regioselectivity (Table 3). The protecting group on the indole nitrogen did appear to

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HETEROCYCLES, Vol. 82, No. 2, 2011
alter the reaction; phenylsulfonyl deriviative 14 was optimal and yielded the major product in an 88:12
ratio and in 71% overall yield. However, münchnone 8 gave substantially different results (Table 3).
In each case, 8 was both less reactive (lower yielding) and less regioselective. Phenylsulfonyl
deriviative 14 still provided the highest yielding reaction (65%) but was completely nonselective, giving
essentially a 1:1 mixture of isomers.
Table 3. 3-Nitroalkenes with Unsymmetrical Münchnones
R2
R1
NO2
Bn
R1
Bn
R2
R1
N
N
O
H
H
DIPC
O
+
+
N
THF, reflux
Bn
R2
N
R3
12-14
7: R1 = Ph, R2 = Me
8: R1 = Me, R2 = Ph
N
R3
N
R3
36a-38a
36b-38b
Indole
Münchnone
R3
H
Products
Ratio (a:b)a
77 : 23
74 : 26
88 : 12
37 : 63
44 : 56
49 : 51
Yieldb
51%
86%
71%
20%
39%
65%
12
13
14
12
13
14
7
7
7
8
8
8
36a : 36b
37a : 37b
38a : 38b
36a : 36b
37a : 37b
38a : 38b
Me
SO2Ph
H
Me
SO2Ph
aRegiochemistry was determined by NOE interactions of the pyrrole ring proton with either the methyl or phenyl group of
the pyrrole.
bYield refers to isolated products after column chromatography.
Once again, 2-(2-nitrovinyl)indoles 19-21 proved more reactive then their isomeric counterparts. The
reactions with münchnone 7 proceeded in good to excellent yield with good regioselectivity (Table 4).
While phenylsulfonyl indole 21 gave the best yield, it also showed the lowest selectivity of the group.
Methyl–protected indole 20 exhibited a 9:1 selectivity with a 76% yield. As expected, münchnone 8
was less reactive in all cases; however, the selectivity was reasonably good in each case. Most
surprisingly, N-methylindole 20 afforded the opposite major product then what was expected based on the
other results in this study. The reason for this change is unknown and currently under investigation.
As has mostly been the case, N-phenylsulfonylindole 21 gave optimal results with a ratio of 91:9 in 78%
yield.

HETEROCYCLES, Vol. 82, No. 2, 2011
1623
Table 4. 2-Nitroalkenes with Unsymmetrical Münchnones
H
H
R1
R2
R1
NO2
O
DIPC
O
+
+
N
N
N
N
THF, reflux
N
N
Bn
Bn
Bn
R3
R2
R3 R1
R3 R2
19-21
39a-41a
39b-41b
1
2
7
: R = Ph, R = Me
8: R1 = Me, R2 = Ph
Indole
19
Münchnone
R3
H
Products
39a : 39b
40a : 40b
41a : 41b
39a : 39b
40a : 40b
41a : 41b
Ratio (a:b)a
87 : 13
90 : 10
79 : 21
26 : 74
70 : 30
9 : 91
Yieldb
7
7
7
8
8
8
89%
76%
95%
62%
45%
78%
20
Me
21
SO2Ph
H
19
20
Me
21
SO2Ph
aRegiochemistry was determined by NOE interactions of the pyrrole ring proton with either the methyl or phenyl group of
the pyrrole.
bYield refers to isolated products after column chromatography.
In summary, we report a reaction protocol that allows access to a variety of substituted 2- and 3-indolyl
pyrroles in moderate to high yields. In the case of unsymmetrical münchnones, the regioselectivity
varies substantially from being completely nonselective to where the major products are obtained in a 9:1
ratio. Extensions of this methodology to other heterocyclic systems as well as mechanistic and
computational studies designed to rationalize both the reactivity and regioselectivity are currently
underway and will be reported in due course.
EXPERIMENTAL
General: 1H NMR (300 MHz), 13C NMR (75 MHz), and NOE experiments were performed on a Varian
Unity spectrometer. Chemical shifts are reported in ppm with the solvent signal used as an internal
reference (CDCl3, 7.26 ppm). Coupling constants are reported in Hz and peak splittings are listed as
broad singlet (br s), singlet (s), doublet (d), doublet of doublets (dd), triplet (t), or multiplet (m).
Tetrahydrofuran (THF) was obtained by distillation from sodium benzophenone ketyl immediately prior
to use. All other commercial reagents were used as received.
3-(2-Nitrovinyl)-1H-indole11
1-(dimethylamino)-2-nitroethylene (1.06 g, 9.1 mmol, 1.2 eq.) and CH2Cl2 (25 mL). The flask was cooled
(12):
A
round
bottom
flask
was
charged
with

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to 0 °C. Trifluoroacetic acid (2.02 g, 17.7 mmol, 2.3 eq.) was added slowly, followed by a solution of
indole (2.00 g, 7.6 mmol, 1.0 eq.) in CH2Cl2 (15 mL). The resulting solution was stirred at 0 °C for 65
min then poured into ice water (100 mL) and the layers separated. The aqueous layer was extracted with
CH2Cl2 (2 x 60 mL) and the combined organic extracts were washed with saturated aqueous NaHCO3 (1 x
60 mL), brine (1 x 60 mL), dried over Na2SO4, and concentrated in vacuo. The crude product was
purified by flash chromatography over silica gel (30% EtOAc in hexanes) to give 12 as a light brown
solid (1.32 g, 92%). 1H NMR (CDCl3) δ 8.74 (br s, 1H), 8.30 (d, 1H, J = 13.4 Hz), 7.83-7.78 (m, 2H),
7.68 (d, 1H, J = 2.9 Hz), 7.50-7.46 (m, 1H), 7.39-7.32 (m, 2H).
1-Methyl-3-(2-nitrovinyl)-1H-indole11 (13):
A
round bottom flask was charged with
1-(dimethylamino)-2-nitroethylene (2.12 g, 18.2 mmol, 1.2 eq.) and CH2Cl2 (50 mL). The flask was
cooled to 0 °C. Trifluoroacetic acid (4.04 g, 35.4 mmol, 2.3 eq.) was added slowly, followed by a
solution of 1-methylindole (2.00 g, 15.2 mmol, 1.0 eq.) in CH2Cl2 (30 mL). The resulting solution was
stirred at 0 °C for 45 min then poured into ice water (150 mL) and the layers separated. The aqueous
layer was extracted with CH2Cl2 (2 x 100 mL) and the combined organic extracts were washed with
saturated aqueous NaHCO3 (1 x 100 mL), brine (1 x 100 mL), dried over Na2SO4, and concentrated in
vacuo. The crude product was purified by flash chromatography over silica gel (30% EtOAc in
hexanes) to give 13 as an orange solid (2.43 g, 79%). 1H NMR (CDCl3) δ 8.25 (d, 1H, J = 13.4 Hz),
7.78-7.73 (m, 2H), 7.52 (s, 1H), 7.42-7.31 (m, 3H), 3.87 (s, 3H).
3-(2-Nitrovinyl)-1-(phenylsulfonyl)-1H-indole20 (14): A round bottom flask was charged with
ammonium acetate (2.14 g, 27.8 mmol, 2.4 eq.), nitromethane (4.87 g, 79.8 mmol, 6.9 eq.), and acetic
acid (25 mL). 1-(phenylsulfonyl)indole-3-carboxaldehyde (3.30 g, 11.6 mmol, 1 eq.) was added and the
mixture was heated to 100 °C for 6 h, cooled to room temperature, and stirred overnight. The reaction
mixture was poured into distilled water (100 mL) and 2M NaOH was added with stirring until the pH = 7.
The aqueous solution was extracted with EtOAc (4 x 50 mL); the combined organic extracts were washed
with brine (1 x 50 mL), dried over Na2SO4, and concentrated in vacuo. The crude product was purified
by flash chromatography over silica gel (30% EtOAc in hexanes) to give 14 as a tan solid (3.58 g, 94%).
1H NMR (CDCl3) δ 8.15 (s, 1H), 8.05-7.94 (m, 2H), 7.77-7.37 (m, 9H).
Representative procedure for the synthesis of 19-21: A round bottom flask was charged with
indole-2-carboxaldehyde (1.0 g, 6.89 mmol, 1.0 eq.), nitromethane (1.5 g, 24.6 mmol, 3.6 eq), and
methanol (25 mL). The flask was cooled to 0 °C (ice bath) and 50% aqueous sodium hydroxide (7.5
mL) was added slowly dropwise with vigorous stirring. After 90 min, an ice-water mixture (25 mL) was

HETEROCYCLES, Vol. 82, No. 2, 2011
1625
added. The resulting mixture was poured slowly into ice cold 20% aqueous HCl (150 mL) under stirring.
After 5 min, the crude 19 which precipitated was collected by vacuum filtration over sintered glass and
dried in air.
2-(2-Nitrovinyl)-1H-indole17 (19): The crude product was purified by flash chromatography over silica
gel (30% EtOAc in hexanes) to give 19 as a light brown solid (1.13 g, 87%). 1H NMR (CDCl3) δ 8.31 (br
s, 1H), 8.05 (d, 1H, J = 13.4 Hz), 7.66 (d, 1H, J = 8.1 Hz), 7.50 (d, 1H, J = 13.7 Hz), 7.42-7.32 (m, 2H),
7.20-7.15 (m, 1H), 7.07 (s, 1H).
1-Methyl-2-(2-nitrovinyl)-1H-indole21 (20): The crude product was purified by flash chromatography
over silica gel (30% EtOAc in hexanes) to give 20 as an orange solid (1.17 g, 84%). 1H NMR (CDCl3) δ
8.17 (d, 1H, J = 13.4 Hz), 7.71-7.63 (m, 2H), 7.35 (d, 2H, J = 5.6 Hz), 7.19-7.13 (m, 1H), 7.10 (s, 1H),
3.88 (s, 3H).
2-(2-Nitrovinyl)-1-(phenylsulfonyl)-1H-indole (21): The crude product was purified by flash
1
chromatography over silica gel (30% EtOAc in hexanes) to give 21 as a yellow solid (0.91 g, 87%). H
NMR (CDCl3) δ 8.81 (d, 1H, J = 13.4 Hz), 8.26 (d, 1H, J = 8.6 Hz), 7.76 (d, 1H, J = 9.5 Hz), 7.59-7.26
(m, 8H), 7.11 (s, 1H); HRMS (ESI+) m/z calculated for C16H13N2O4S (MH+) 329.0596, found 329.0602.
Representative procedure for the reaction of nitroalkenes and münchnones (24-41): A round bottom
flask was charged with the 3-(2-nitrovinyl)indole (94 mg, 0.50 mmol, 1 eq.), münchnone precursor 1 (518
mg, 1.5 mmol, 3 eq.) and THF (20 mL). DIPC (233 µL, 1.5 mmol, 3 eq.) was added and the mixture was
heated to reflux under nitrogen for 18-24 h. Once TLC indicated complete consumption of the nitroalkene,
the mixture was cooled to room temperature and concentrated in vacuo. The residue was purified directly
by flash chromatography over silica gel (1:3 CH2Cl2:hexanes) to yield pure 24.
3-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)-1H-indole (24): White solid, 78% yield; 1H NMR (CDCl3) δ
7.87 (d, 2H, J = 7.1 Hz), 7.52-7.11 (m, 16H), 6.81 (s, 1H), 6.76 (d, 2H, J = 7.6 Hz), 6.70 (s, 1H), 5.20 (s,
2H); 13C NMR (CDCl3) δ 139.7, 136.2, 135.7, 133.9, 133.8, 132.3, 132.1, 131.6, 131.1, 129.3, 129.1,
129.0, 128.9, 128.7, 128.5, 128.5, 128.0, 127.6, 127.2, 127.0, 126.3, 122.0, 120.6, 119.7, 117.0, 112.2,
111.2, 110.4, 48.8; HRMS (ESI+) m/z calculated for C31H25N2 (MH+) 425.2018, found 425.2026.
1
3-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (25): White solid, 62% yield; H NMR
(CDCl3) δ 7.79 (d, 1H, J = 7.8 Hz), 7.48 (d, 2H, J = 6.8 Hz), 7.38-7.06 (m, 15H), 6.75-6.72 (m, 3H), 6.57

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HETEROCYCLES, Vol. 82, No. 2, 2011
13
(s, 1H), 5.18 (s, 2H), 3.64 (s, 3H); C NMR (CDCl3) δ 139.7, 137.0, 135.6, 134.0, 133.8, 132.1, 131.5,
129.3, 128.6, 128.4, 128.4, 127.7, 127.5, 127.2, 126.9, 126.7, 126.3, 121.5, 120.8, 119.1, 110.7, 110.5,
109.2, 74.0, 48.8, 32.9; HRMS (ESI+) m/z calculated for C32H27N2 (MH+) 439.2174, found 439.2172.
3-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (26): Light orange solid, 81%
1
yield; H NMR (CDCl3) δ 8.05 (d, 1H, J = 8.3 Hz), 7.78 (d, 1H, J = 7.8 Hz), 7.67 (d, 2H, J = 7.8 Hz),
7.52-7.17 (m, 18H), 7.13 (s, 1H), 6.77-6.74 (m, 3H), 5.22 (s, 2H), 13C NMR (CDCl3) δ 139.3, 138.3,
136.0, 135.4, 133.7, 133.5, 132.9, 131.4, 131.2, 129.4, 129.3, 128.8, 128.7, 128.6, 127.9, 127.4, 127.2,
124.8, 123.5, 123.0, 121.3, 118.9, 114.5, 113.9, 110.1, 48.9; HRMS (ESI+) m/z calculated for
C37H29N2O2S (MH+) 565.1950, found 565.1942.
1
3-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)- 1H-indole (27): Light yellow solid, 84% yield; H NMR
(CDCl3) δ 8.07 (br s, 1H), 7.80 (d, 1H, J = 7.8 Hz), 7.41-7.14 (m, 7H), 7.00 (d, 2H, J = 7.6 Hz), 6.23 (s,
1H), 5.13 (s, 2H), 2.26 (s, 6H); 13C NMR (CDCl3) δ 138.9, 136.4, 129.0, 127.7, 127.3, 126.0, 122.1,
121.6, 120.7, 119.6, 113.5, 113.3, 111.2, 107.6, 47.3, 12.6, 11.4; HRMS (ESI+) m/z calculated for
C21H21N2 (MH+) 301.1705, found 301.1703.
1
3-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (28): Yellow solid, 75% yield; H
NMR (CDCl3) δ 7.82 (d, 1H, J = 7.8 Hz), 7.39-7.26 (m, 5H), 7.18 (t, 1H, J = 6.8 Hz), 7.15-7.01 (m, 3H)
6.24 (s, 1H), 5.15 (s, 2H)3.84 (s, 3H), 2.28 (s, 6H); 13C NMR (CDCl3) δ 138.9, 137.1, 129.0, 128.1, 127.6,
127.3, 126.4, 126.0, 124.5, 121.7, 120.9, 119.1, 113.4, 112.0, 109.3, 107.6, 47.3, 33.0, 12.6, 11.5; HRMS
(ESI+) m/z calculated for C22H23N2 (MH+) 315.1861, found 315.1856.
3-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (29): Orange solid, 68%
yield; 1H NMR (CDCl3) δ 8.09 (d, 2H, J = 8.3 Hz), 7.96-7.90 (m, 3H), 7.74 (d, 2H, J = 7.8 Hz), 7.54-7.25
13
(m, 6H), 6.98 (d, 2H, J = 8.0 Hz), 6.19 (s, 1H), 5.12 (s, 2H), 2.23 (s, 6H); C NMR (CDCl3) δ 138.4,
138.3, 135.6, 133.9, 131.6, 129.4, 129.1, 128.4, 127.7, 127.0, 125.9, 125.4, 123.5, 122.2, 121.4, 120.0,
113.9, 111.0, 107.1, 47.3, 12.6, 11.4; HRMS (ESI+) m/z calculated for C27H25N2O2S (MH+) 441.1637,
found 441.1631.
2-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)-1H-indole (30): White solid, 92% yield; 1H NMR (CDCl3) δ
7.73 (br s, 1H), 7.56-7.36 (m, 11H), 7.20-7.07 (m, 6H), 6.77-6.75 (m, 3H), 6.47 (s, 1H), 5.12 (s, 2H); 13C
NMR (CDCl3) δ 139.1, 136.3, 136.0, 134.7, 133.3, 132.9, 131.9, 131.6, 129.4, 129.3, 129.1, 129.0, 128.8,
128.6, 127.8, 127.2, 126.2, 121.2, 120.0, 119.9, 115.6, 110.5, 108.3, 98.7, 48.7; HRMS (ESI+) m/z

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1627
calculated for C31H25N2 (MH+) 425.2018, found 425.2018.
1
2-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (31): Pale yellow solid, 90% yield; H
NMR (CDCl3) δ 7.53-7.03 (m, 17H), 6.72 (d, 2H, J = 7.8 Hz), 6.49 (s, 1H), 6.34 (s, 1H), 5.23 (s, 2H),
13
3.44 (s, 3H); C NMR (CDCl3) δ 139.2, 132.0, 130.7, 130.0, 129.4, 129.0, 128.7, 128.6, 128.5, 128.4,
127.7, 127.6, 127.1, 126.2, 120.7, 120.1, 119.4, 112.1, 109.4, 101.7, 49.1, 30.9; HRMS (ESI+) m/z
calculated for C32H27N2 (MH+) 439.2174, found 439.2176.
2-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (32): White solid, 94% yield;
1H NMR (CDCl3) δ 8.32 (d, 1H, J = 8.3 Hz), 7.62 (d, 2H, J = 9.5 Hz), 7.51-7.11 (m, 17H), 6.95 (dd, 2H, J
13
= 1.5, 8.1 Hz), 6.75-6.72 (m, 2H), 6.51 (s, 1H), 6.25 (s, 1H), 5.20 (s, 2H); C NMR (CDCl3) δ 139.6,
139.1, 137.9, 136.8, 136.3, 135.2, 133.5, 133.4, 132.2, 130.9, 130.4, 129.4, 129.0, 128.7, 128.5, 128.2,
127.7, 127.5, 127.2, 126.4, 124.2, 123.8, 120.5, 116.0, 114.1, 113.9, 113.0, 49.1; HRMS (ESI+) m/z
calculated for C37H29N2O2S (MH+) 565.1950, found 565.1945.
2-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-1H-indole (33): White solid, 92% yield; 1H NMR (CDCl3) δ
8.11 (br s, 1H), 7.64 (d, 1H, J = 6.6 Hz), 7.40-7.30 (m, 4H), 7.20-7.14 (m, 2H), 7.00 (d, 2H, J = 7.6 Hz),
13
6.49 (s, 1H), 6.19 (s, 1H), 5.12 (s, 2H), 2.41 (s, 3H), 2.25 (s, 3H); C NMR (CDCl3) δ 138.2, 136.0,
135.7, 130.0, 129.1, 128.7, 127.5, 126.1, 125.9, 121.0, 119.9, 119.9, 112.7, 110.5, 105.1, 98.5, 47.2, 25.7,
12.6, 11.7; HRMS (ESI+) m/z calculated for C21H21N2 (MH+) 301.1705, found 301.1706.
1
2-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (34): Pale yellow solid, 70% yield; H
NMR (CDCl3) δ 7.66 (d, 1H, J = 7.8 Hz), 7.42-7.15 (m, 6H), 7.03 (d, 2H, J = 7.3 Hz), 6.45 (s, 1H), 6.10
13
(s, 1H), 5.15 (s, 2H), 3.78 (s, 3H), 2.28 (s, 3H), 2.25 (s, 3H); C NMR (CDCl3) δ 138.4, 137.8, 129.1,
128.6, 128.1, 127.7, 127.5, 125.9, 120.8, 120.0, 119.5, 111.6, 109.4, 108.0, 101.0, 47.4, 31.0, 12.6, 11.3;
HRMS (ESI+) m/z calculated for C22H23N2 (MH+) 315.1861, found 315.1864.
2-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (35): Light orange solid, 86%
1
yield; H NMR (CDCl3) δ 8.39 (d, 1H, J = 8.3), 7.50-7.07 (m, 13H), 6.40 (s, 1H), 6.09 (s, 1H), 5.08 (s,
2H), 2.26 (s, 3H), 1.92 (s, 3H); 13C NMR (CDCl3) δ 138.8, 138.4, 138.1, 138.0, 133.4, 130.9, 129.1,
128.7, 127.5, 127.1, 127.0, 126.1, 124.1, 124.1, 120.3, 116.5, 112.4, 111.1, 110.1, 47.4, 12.6, 11.1;
HRMS (ESI+) m/z calculated for C27H25N2O2S (MH+) 441.1637, found 441.1641.
3-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)-1H-indole (36a): White solid, 51% (obtained as the

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HETEROCYCLES, Vol. 82, No. 2, 2011
major isomer – 77:23 ratio of 36a:36b); 1H NMR (CDCl3) δ 7.80 (d, 1H, J = 7.6 Hz), 7.45-7.08 (m, 11H),
13
7.00 (d, 2H, J = 7.1 Hz), 6.69 (d, 1H, J = 2.4 Hz), 6.49 (s, 1H), 5.09 (s, 2H), 2.27 (s, 3H); C NMR
(CDCl3) δ 139.4, 136.2, 133.9, 131.4, 129.1, 129.0, 128.9, 128.7, 128.5, 127.3, 127.1, 126.0, 122.3, 121.9,
121.9, 120.7, 119.6, 115.3, 112.6, 111.2, 108.4, 47.9, 12.8; HRMS (EI+) m/z calculated for C26H22N2
(M+) 362.17830, found 362.17707.
3-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)-1H-indole (36b): Clear oil, 20% (obtained as the
major isomer – 63:37 ratio of 36b:36a); 1H NMR (CDCl3) δ 8.09 (s, 1H), 7.85 (d, 1H, J = 7.8), 7.43-7.06
(m, 14H), 6.62 (s, 1H), 5.26 (s, 2H), 2.26 (s, 3H); 13C NMR (CDCl3) δ 139.3, 136.4, 134.4, 129.0, 128.9,
128.9, 128.7, 127.3, 127.3, 127.0, 126.0, 122.3, 121.9, 121.8, 120.7, 119.8, 115.1, 113.0, 111.3, 109.7,
48.3, 11.7; HRMS (EI+) m/z calculated for C26H22N2 (M+) 362.17830, found 362.17743.
3-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (37a): Orange solid, 86%
1
(obtained as the major isomer – 74:26 ratio of 37a:37b); H NMR (CDCl3) δ 7.73 (d, 1H, J = 8.1 Hz),
7.41-7.18 (m, 9H), 7.09 (t, 2H, J = 6.8 Hz), 7.00 (d, 2H, J = 7.6), 6.59 (s, 1H), 6.45 (s, 1H), 5.08 (s, 2H),
13
3.65 (s, 3H), 2.26 (s, 3H); C NMR (CDCl3) δ 139.5, 137.0, 134.0, 131.3, 129.0, 128.9, 128.5, 127.3,
127.1, 126.6, 126.0, 121.4, 120.9, 119.0, 115.4, 111.2, 109.2, 108.5, 47.9, 32.8, 12.8; HRMS (ESI+) m/z
calculated for C27H25N2 (MH+) 377.2018, found 377.2021.
3-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (37b): Orange oil, 39% (obtained
as the major isomer – 56:44 ratio of 37b:37a); 1H NMR (CDCl3) δ 7.91 (d, 1H, J = 7.8 Hz), 7.50-7.12 (m,
13
14H), 6.67 (s, 1H), 5.31 (s, 2H), 3.87 (s, 3H), 2.32 (s, 3H); C NMR (CDCl3) δ 139.4, 137.1, 134.3,
131.4, 129.2, 128.9, 128.7, 127.2, 126.9, 126.5, 126.0, 121.8, 120.8, 119.3, 115.3, 111.1, 109.8, 109.4,
48.3, 33.0, 11.7; HRMS (ESI+) m/z calculated for C27H25N2 (MH+) 377.2018, found 377.2021.
3-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (38a): Pale orange
solid, 71% (obtained as the major isomer – 88:12 ratio of 38a:38b); 1H NMR (CDCl3) δ 8.02 (d, 1H, J =
8.3 Hz), 7.67 (d, 2H, J = 7.8 Hz), 7.50-7.19 (m, 13H), 7.08 (s, 1H), 6.96 (d, 2H, J = 7.1 Hz), 6.39 (s, 1H),
13
5.07 (s, 2H), 2.24 (s, 3H); C NMR (CDCl3) δ 138.9, 138.3, 135.4, 133.7, 133.1, 131.7, 131.2, 129.7,
129.3, 129.1, 129.0, 128.7, 127.9, 127.3, 127.0, 126.0, 124.7, 123.6, 122.8, 121.3, 119.4, 113.8, 112.8,
108.2, 48.0, 12.8; HRMS (ESI+) m/z calculated for C32H27N2O2S (MH+) 503.1793, found 503.1789.
3-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (38b): Orange solid,
1
65% (obtained as the major isomer – 51:49 ratio of 38b:38a); H NMR (CDCl3) δ 8.10 (d, 2H, J = 8.3

HETEROCYCLES, Vol. 82, No. 2, 2011
1629
Hz), 7.94 (d, 2H, J = 7.6 Hz), 7.77 (d, 2H, J = 7.6 Hz), 7.66 (d, 2H, J = 7.6 Hz), 7.54-7.18 (m, 10H), 7.04
13
(d, 2H, J = 7.1 Hz), 6.55 (s, 1H), 5.24 (s, 2H), 2.24 (s, 3H); C NMR (CDCl3) δ 138.9, 138.3, 135.4,
133.6, 133.0, 131.4, 131.3, 129.7, 129.3, 129.1, 129.0, 128.7, 127.9, 127.3, 127.0, 125.9, 124.6, 123.4,
122.5, 121.3, 119.4, 113.8, 112.7, 108.2, 48.0, 11.7; HRMS (ESI+) m/z calculated for C32H27N2O2S
(MH+) 503.1793, found 503.1795.
2-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)-1H-indole (39a): Off-white solid, 89% (obtained as
1
the major isomer – 87:13 ratio of 39a:39b); H NMR (CDCl3) δ 7.68 (br s, 1H), 7.53-7.25 (m, 8H),
7.15-7.03 (m, 3H), 6.94 (d, 2H, J = 7.1 Hz), 6.43 (s, 1H), 6.40 (d, 1H, J = 1.7 Hz), 4.98 (s, 2H), 2.24 (s,
3H); 13C NMR (CDCl3) δ 138.8, 135.9, 135.1, 133.1, 131.6, 130.2, 130.1, 129.2, 129.1, 129.0, 128.9,
128.8, 127.4, 125.9, 125.9, 120.9, 119.8, 119.7, 114.0, 110.4, 106.4, 98.3, 47.7, 12.7; HRMS (ESI+) m/z
calculated for C26H23N2 (MH+) 363.1861, found 363.1862.
2-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)-1H-indole (39b): Off-white solid, 62% (obtained as
the major isomer – 74:26 ratio of 39b:39a); 1H NMR (CDCl3) δ 8.16 (br s, 1H), 7.64 (d, 2H, J = 7.1 Hz),
13
7.38-7.02 (m, 12H), 6.54-6.52 (m, 2H), 5.23 (s, 2H), 2.41 (s, 3H); C NMR (CDCl3) δ 138.7, 136.1,
135.1, 133.3, 131.6, 129.9, 129.2, 129.1, 129.0, 128.9, 128.8, 127.6, 127.5, 125.9, 125.9, 121.3, 120.1,
119.8, 114.3, 110.6, 107.1, 99.0, 48.2, 11.9; HRMS (ESI+) m/z calculated for C26H23N2 (MH+) 363.1861,
found 363.1859.
2-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (40a): Yellow solid, 76%
1
(obtained as the major isomer – 90:10 ratio of 40a:40b); H NMR (CDCl3) δ 7.55 (d, 1H, J = 7.8 Hz),
7.39-6.99 (m, 13H), 6.34 (s, 1H), 6.23 (s, 1H), 5.15 (s, 2H), 3.40 (s, 3H), 2.23 (s, 3H); 13C NMR (CDCl3)
δ 139.0, 137.6, 132.9, 130.5, 129.8, 129.1, 129.1, 128.8, 128.6, 128.6, 127.5, 127.4, 125.9, 120.6, 120.0,
119.3, 113.5, 110.1, 109.4, 101.5, 48.1, 30.8, 12.8; HRMS (ESI+) m/z calculated for C27H25N2 (MH+)
377.2018, found 377.2019.
2-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)-1-methyl-1H-indole (40b): Yellow oil, 45% (obtained
as the minor isomer – 30:70 ratio of 40b:40a); 1H NMR (CDCl3) δ 7.66 (d, 1H, J = 7.6 Hz), 7.40-7.00 (m,
13H), 6.49 (s, 1H), 6.44 (s, 1H), 5.26 (s, 2H), 3.80 (s, 3H), 2.24 (s, 3H); 13C NMR (CDCl3) δ 138.9, 137.6,
132.8, 130.5, 129.8, 129.1, 129.0, 128.8, 128.7, 128.6, 127.5, 127.4, 125.9, 120.9, 120.1, 119.6, 113.4,
110.1, 109.5, 101.3, 48.4, 31.0, 11.5; HRMS (ESI+) m/z calculated for C27H25N2 (MH+) 377.2018, found
377.2018.

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2-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (41a): Tan solid, 95%
1
(obtained as the major isomer – 79:21 ratio of 41a:41b); H NMR (CDCl3) δ 8.26 (d, 1H, J = 8.5 Hz),
13
7.63-7.12 (m, 13H), 7.02-6.97 (m, 5H), 6.28 (s, 1H), 6.23 (s, 1H), 5.09 (s, 2H), 2.24 (s, 3H); C NMR
(CDCl3) δ 139.6, 138.9, 137.8, 137.5, 134.2, 133.5, 132.5, 130.8, 129.1, 129.0, 129.0, 128.9, 128.8, 128.8,
128.3, 127.4, 127.2, 127.1, 124.1, 123.8, 120.5, 116.0, 113.0, 111.7, 48.1, 12.8; HRMS (ESI+) m/z
calculated for C32H27N2O2S (MH+) 503.1793, found 503.1801.
2-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H-indole (41b): Tan solid, 78%
1
(obtained as the major isomer – 91:9 ratio of 41b:41a); H NMR (CDCl3) δ 8.40 (d, 1H, J = 8.1 Hz),
13
7.53-7.10 (m, 18H), 6.49 (s, 1H), 6.39 (s, 1H), 5.22 (s, 2H), 1.97 (s, 3H); C NMR (CDCl3) δ 138.8,
138.8, 138.1, 137.4, 133.5, 131.5, 130.8, 129.1, 129.1, 128.9, 128.9, 128.7, 128.7, 128.3, 127.5, 127.3,
127.1, 126.1, 124.3, 124.1, 120.4, 116.5, 112.6, 112.2, 48.3, 11.5; HRMS (ESI+) m/z calculated for
C32H27N2O2S (MH+) 503.1793, found 503.1797.
ACKNOWLEDGEMENTS
This work was supported by the Donors of the Petroleum Research Fund (PRF), administered by the
American Chemical Society, and by Wyeth.
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