Copper-catalyzed double N-vinylation of aromatic amines: An efficient synthesis of various substituted N-arylpyrroies

Article abstract of DOI:10.1002/ejoc.201000665

A simple and efficient approach to various substituted N-arylpyrroles has been developed. The method is based on the copper-catalyzed sequential inter- and intramolecular Nvinylation of aromatic amines. The reactions proceed to afford substituted N-arylpyrroles in good-to-excellent yields using CuI as the precatalyst, iBuONa as the base, and N¹,N²dimethylethane- l,2-diamine (DMEDA) as the ligand. Ani-lines with electron-donating and -withdrawing substituents as well as a heteroaromatic amine performed very well under the conditions used. Tri- and tetrasubstituted dienyl diiodides also performed well under the reaction conditions and afforded the corresponding substituted N-arylpyrroles in good yields, Products were also obtained in high yields with CuBr or CuCl as precatalyst.

Full text of DOI:10.1002/ejoc.201000665

FULL PAPER
DOI: 10.1002/ejoc.201000665
Copper-Catalyzed Double N-Vinylation of Aromatic Amines: An Efficient
Synthesis of Various Substituted N-Arylpyrroles
Qian Liao,[a] Liyun Zhang,[a] Fei Wang,[a] Shutao Li,[a] and Chanjuan Xi*[a]
Keywords: Nitrogen heterocycles / Vinylation / Amines / Copper iodide
A simple and efficient approach to various substituted
N-arylpyrroles has been developed. The method is based on
the copper-catalyzed sequential inter- and intramolecular N-
vinylation of aromatic amines. The reactions proceed to af-
ford substituted N-arylpyrroles in good-to-excellent yields
using CuI as the precatalyst, tBuONa as the base, and N1,N2-
dimethylethane-1,2-diamine (DMEDA) as the ligand. Ani-
lines with electron-donating and -withdrawing substituents
as well as a heteroaromatic amine performed very well under
the conditions used. Tri- and tetrasubstituted dienyl diiodides
also performed well under the reaction conditions and af-
forded the corresponding substituted N-arylpyrroles in good
yields. Products were also obtained in high yields with CuBr
or CuCl as precatalyst.
of aromatic amines for the synthesis of a wide range of
structurally diverse pyrroles based on the reaction of
(1Z,3Z)-1,4-diiodo-1,3-dienes with aromatic amines
(Scheme 1), which includes N-vinylation of amines, which
is rarely described in the literature to the best of our knowl-
edge.
Introduction
Pyrroles are one of the most important classes of hetero-
cyclic compounds as they are the key structural subunits in
numerous natural products that exhibit interesting bio-
logical activities[1] and contribute to a variety of applica-
tions in pharmaceutical use.[2] In addition, substituted pyr-
roles are of significant interest because they are useful and
versatile synthetic intermediates for further structural elab-
oration.[3] Consequently, much attention has been paid to
the preparation of pyrrole derivatives. Classic methods for
their preparation include the Knorr,[4] Hantzsch,[5] and
Paal–Knorr condensation reactions.[1e,6,7] However, these
methods have some limitations with respect to regioselectiv-
ity and substitution patterns. Recently, great advances have
been made, particularly in transition-metal-catalyzed multi-
component processes and domino reactions.[8,9] In the past
few years, copper-catalyzed aryl C–N bond-forming reac-
tions through the coupling of aryl halides and N-nucleo-
philes have attracted considerable attention[10] and comple-
ment Pd-catalyzed reactions very well.[11] More recently,
coupling reactions between vinyl halides and amides have
also been reported.[12]
Scheme 1.
Results and Discussion
The requisite 1,4-diiodo-1,3-dienes were conveniently
prepared in high yields by the iodination of zirconacyclo-
pentadienes derived from intermolecular coupling of two
alkynes according to reported methods.[16] We began our
initial investigation with (3Z,5Z)-4,5-diethyl-3,6-diiodo-
octa-3,5-diene (1a) and p-methylaniline (2a), which was se-
lected as a typical case to screen the experimental conditions.
Stimulated by Buchwald and Li and their co-workers’ obser-
vations,[13,14,17] CuI, DMEDA, Cs2CO3 or K3PO4, and tolu-
ene were selected as the catalytic system at 110 °C. Unfortu-
nately, no desired product was detected by GC analysis
(Table 1, entries 1 and 2). We thought that because aniline is
a weaker acid than amides, a stronger base should be em-
ployed to deprotonate the amino group. When a stronger
base, tBuOK, was used, the reaction gave a messy mixture
(entry 3). When tBuONa was used, the desired product was
obtained in 32% yield (by NMR; entry 4). Gratifyingly, when
the reaction temperature was raised to 140 °C, the yield dra-
Accordingly, the reactions of dienyl dihalides with
amides have provided a straightforward method for the con-
struction of N-acylpyrroles in a tandem process.[13,14] None-
theless, access to substituted N-arylpyrroles, as an impor-
tant class of pyrrole, has rarely been reported.[15] Herein we
would like to report a copper-catalyzed double N-vinylation
[a] Key Lab of Organic Optoelectronics & Molecular Engineering
of Ministry of Education, Department of Chemistry, Tsinghua
University,
Beijing, 100084, China
E-mail: cjxi@tsinghua.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000665.
View this journal online at
wileyonlinelibrary.com
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Copper-Catalyzed Double N-Vinylation of Aromatic Amines
Table 1. Optimization of base, solvent, copper salt, and tempera- CuCl as precatalyst gave the product in 73 and 89% yields,
ture in the reaction of 1a and 2a.
respectively (entries 11 and 12).
It has been demonstrated that certain ligands play impor-
tant roles in rate acceleration in copper-catalyzed C–N cou-
pling reactions.[10d,18] Next, the applicability of other li-
gands was screened under the optimized conditions. The
results are shown in Figure 1. DMEDA is the best ligand
in this reaction.
To investigate the scope of the reaction, other aromatic
amines were used in the reaction with (3Z,5Z)-4,5-diethyl-
3,6-diiodoocta-3,5-diene (1a) under the optimized condi-
tions. The reaction is applicable to various aromatic amines
and the results are summarized in Table 2. The reactions
Table 2. Reaction of (3Z,5Z)-4,5-diethyl-3,6-diiodoocta-3,5-diene
(1a) with aromatic amines.[a]
[a] 1H NMR yield using Cl2C=CHCl as the internal standard; iso-
lated yield is given in parentheses.
matically increased to 92% (entry 9). We also tested other
commonly used solvents in the copper-catalyzed C–N cou-
pling reactions. The results proved that 1,4-dioxane, DMF,
and NMP were not appropriate solvents for this reaction (en-
tries 5–7). A controlled experiment showed that copper is in-
dispensable to the reaction (entry 10). The effect of other cop-
per salts was also examined in the test reaction: CuBr and
[a] Reaction conditions: 1,4-diiodo-1,3-diene (1.0 equiv.), aromatic
amine (1.5 equiv.), CuI (10 mol-%), DMEDA (20 mol-%), tBuONa
(3 equiv.), toluene (2 mL), 140 °C. [b] 1H NMR yields using
Cl2C=CHCl as the internal standard; the isolated yields are given
in parentheses.
Figure 1. Comparison of ligands in the CuI-catalyzed double N-
vinylation of aromatic amines.
Eur. J. Org. Chem. 2010, 5426–5431
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Q. Liao, L. Zhang, F. Wang, S. Li, C. Xi
FULL PAPER
of anilines with both electron-donating and -withdrawing Table 3. Reaction of dienyl diiodide derivatives with aromatic
amines.[a]
substituents proceeded very well. For example, the reaction
of 1a with 4-methoxyaniline (2b) gives 3b in 78% yield by
NMR (70% isolated yield; entry 2). Similarly, the reaction
of 1a with 4-fluoroaniline (2d) gives the desired product in
high yield (entry 4). A Cl-substituted aniline is also a good
reagent for this reaction (entry 5). The heteroaromatic
amine 2-aminopyridine (2f) also performs well under the
conditions, giving a high yield of more than 95% (entry 6).
When 2,5-dimethylaniline (2g) and 1-naphthylamine (2h),
both of which have a large substituent at the orthoposition,
are used, the desired products are formed in moderate
yields after 72 h (entries 7 and 8). This may be attributed to
the steric hindrance effect of the bulky ethyl groups on the
pyrrole ring and the ortho substituent on the phenyl ring.
When alkyl-substituted amines, such as butyl- and hex-
ylamine were treated with 1a under similar reaction condi-
tions, the desired products were not observed.
Having established an effective catalytic system for the
coupling reactions, we next synthesized a variety of diiodo-
dienes[16] to explore the scope of double alkenylation under
the optimized conditions. The results are summarized in
Table 3.
As well as alkyl-substituted dienyl diiodides, aryl-substi-
tuted dienyl diiodides were also found to be suitable sub-
strates. The corresponding products were formed in high
yields (entries 3, 4, and 6). When a diiododiene fused with
a six-membered ring (1e) was used, the reaction proceeded
smoothly to afford bicyclic pyrrole 3n in 86% yield (en-
try 7). Diiodide 1f reacted with 2a to give the pyrrole 3o in
only 35% isolated yield after 48 h (entry 8). Furthermore,
this method is also effective for trisubstituted dienyl diio-
dide compounds. The reaction of (1Z,3Z)-1,4-diiodo-1,2,3-
triphenylbuta-1,3-diene (1g) with 2a led to the formation of
3p in 79% isolated yield (entry 9). The substrate 1h also
reacted with 2a to give the trisubstituted arylpyrrole 3q in
moderate yield (entry 10). When 1,4-diiodo-1,4-diphen-
ylbuta-1,3-diene was treated with p-methylaniline under the
same reaction conditions, the desired product was not ob-
served: A small amount of diyne was observed by GC–MS,
which underwent an E2-type elimination. The reactions of
(Z)-1-iodo-2-(1-iodo-1-phenylhex-1-en-2-yl)benzene
(1i)
and 2,2Ј-diiodobiphenyl (1j) were also examined. Both of
them proceeded smoothly under the conditions to afford
indole and carbazole in good yields, respectively (entries 11
and 12). Although the coupling reactions of these two sub-
strates with aniline are not tandem vinylations in the strict-
est sense of the term, they still demonstrate the generality
of our catalytic system.
[a] Reaction conditions: 1,4-diiodo-1,3-diene (1.0 equiv.), aromatic
amine (1.5 equiv.), CuI (10 mol-%), DMEDA (20 mol-%), tBuONa
(3 equiv.), toluene (2 mL) at 140 °C. [b] 1H NMR yields, using
Cl2C=CHCl as internal standard, the isolated yields are given in
parentheses.
Conclusions
appropriate base and diamine ligand to achieve reasonable
We have described an efficient copper-catalyzed tandem yields. The optimized reaction conditions are CuI as the
vinylation of anilines with dienyl diiodides. The methodol- precatalyst, tBuONa as the base, and N1,N2-dimethyleth-
ogy provides a facile route to di-, tri-, and tetrasubstituted ane-1,2-diamine (DMEDA) as the ligand. Further applica-
N-arylpyrroles in good-to-excellent yields. It is vital to use tion of the system to the synthesis of various heterocycles
a copper salt as the precatalyst with the assistance of an is under progress.
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Eur. J. Org. Chem. 2010, 5426–5431

Copper-Catalyzed Double N-Vinylation of Aromatic Amines
2,3,4,5-Tetraethyl-1-(p-fluorophenyl)-1H-pyrrole (3d): The crude
product was purified by column chromatography on basic alumina
with petroleum ether to give the desired product as a pale-yellow
oil (227 mg, 83%). Rf = 0.5 (petroleum ether). 1H NMR (300 MHz,
Experimental Section
General: All N-vinylation reactions were carried out in pre-dried
screw-capped test-tubes fitted with a Teflon®-lined septum. Tolu-
ene and 1,4-dioxane were distilled and stored over sodium. DMF
and NMP were freshly distilled. 1,4-Diiodo-1,3-dienes,[16a] 2,2Ј-di-
iodobiphenyl,[19] and (Z)-1-iodo-2-(1-iodo-1-phenylhex-1-en-2-yl)
benzene[20] were prepared according to literature procedures. Other
materials were commercially available and were used without fur-
ther purification. Thin-layer chromatography (TLC) was carried
out on silica gel purchased from commercial sources and compo-
nents were located by observation under UV light. 1H and 13C
NMR spectra were recorded with a JEOL AL-300 NMR spectrom-
eter at ambient temperature with CDCl3 as the solvent and TMS
as the internal standard. GC–MS spectra were recorded with a
Hewlett–Packard GC–MS system.
3
CDCl3): δ = 7.25–7.21 (m, 2 H), 7.13–7.08 (m, 2 H), 2.46 (q, JHH
= 7.6 Hz, 4 H), 2.36 (q, 3JHH = 7.4 Hz, 4 H), 1.17 (t, 3JHH = 7.6 Hz,
3
6 H), 0.84 (t, JHH = 7.6 Hz, 6 H) ppm. 13C NMR (75 MHz,
1
4
CDCl3): δ = 161.9 (d, JFC = 247.1 Hz), 135.7 (d, JFC = 2.9 Hz),
3
2
130.8 (d, JFC = 8.7 Hz), 130.3, 119.6, 115.7 (d, JFC = 23.1 Hz),
18.0, 17.9, 17.1, 15.7 ppm. GC–MS (EI): m/z (%) = 273 (29) [M]+,
258 (100), 228 (13). HRMS: calcd. for C18H24FN 273.1893; found
273.1900.
1-(m-Chlorophenyl)-2,3,4,5-tetraethyl-1H-pyrrole (3e): The crude
product was purified by column chromatography on basic alumina
with petroleum ether to give the desired product as a pale-yellow
oil (251 mg, 87%). Rf = 0.5 (petroleum ether). 1H NMR (300 MHz,
CDCl3): δ = 7.36–7.34 (m, 2 H), 7.28 (s, 1 H), 7.20–7.16 (m, 1 H),
2.45 (q, 3JHH = 7.6 Hz, 4 H), 2.38 (q, 3JHH = 7.4 Hz, 4 H), 1.16 (t,
General Procedure for the Synthesis of 1-Aryl-1H-pyrroles: CuI
(19 mg, 0.1 mmol), 1,4-diiodo-1,3-diene (1.0 mmol), aniline
(1.5 mmol), and tBuONa (288 mg, 3.0 mmol) were added to a
screw-capped test-tube fitted with a Teflon®-lined septum. The
tube was then evacuated and backfilled with N2 (3 cycles). Aniline
(1.5 mmol), DMEDA (21.5 µL, 0.2 mmol), and toluene (2.0 mL)
were added by syringe at room temperature. The tube was then
sealed and the reaction mixture was stirred at 140 °C for the indi-
cated time. The reaction was cooled to room temperature. Ethyl
acetate (3 mL) was added and stirred for 15 min. The deposit was
separated and washed with ethyl acetate (3 mLϫ3). The organic
phase was combined. The solvent was removed under vacuum and
the residue was analyzed by 1H NMR spectroscopy. The crude
product was purified by column chromatography to give the corre-
sponding products.
3
3JHH = 7.6 Hz, 6 H), 0.85 (t, JHH = 7.4 Hz, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 141.0, 134.4, 130.1, 129.8, 129.4, 127.8,
127.4, 120.0, 18.0, 17.9, 17.0, 15.7 ppm. GC–MS (EI): m/z (%) =
289 (29) [M]+, 274 (100), 207 (11). HRMS: calcd. for C18H24ClN
289.1597; found 289.1587.
2,3,4,5-Tetraethyl-1-(2-pyridyl)-1H-pyrrole (3f): The crude product
was purified by column chromatography on silica gel with petro-
leum ether/EtOAc (15:1) to give the desired product as a pale-yel-
low oil (234 mg, 91%). Rf = 0.8 (petroleum ether/EtOAc = 5:1). 1H
3
NMR (300 MHz, CDCl3): δ = 8.60–8.57 (m, 1 H), 7.80 (td, JHH
4
3
= 7.9, JHH = 2.1 Hz, 1 H), 7.30–7.25 (m, 2 H), 2.48 (q, JHH
=
3
3
7.4 Hz, 4 H), 2.45 (q, JHH = 7.6 Hz, 4 H), 1.14 (t, JHH = 7.6 Hz,
6 H), 0.81 (t, JHH = 7.5 Hz, 6 H) ppm. 13C NMR (75 MHz,
3
2,3,4,5-Tetraethyl-1-(p-tolyl)-1H-pyrrole (3a): The crude product
was purified by column chromatography on basic alumina with
petroleum ether to give the desired product as colorless crystals
(237 mg, 88%). Rf = 0.6 (petroleum ether). 1H NMR (300 MHz,
CDCl3): δ = 152.8, 149.2, 137.7, 129.6, 122.4, 122.1, 120.4, 17.8,
17.7, 16.8, 15.2 ppm. GC–MS (EI): m/z (%) = 256 (41) [M]+, 241
(100), 227 (20). HRMS: calcd. for C17H24N2 256.1939; found
256.1933.
3
3
CDCl3): δ = 7.21 (d, JHH = 7.9 Hz, 2 H), 7.13 (d, JHH = 7.9 Hz,
3
3
1-(2,5-Dimethylphenyl)-2,3,4,5-tetraethyl-1H-pyrrole (3g): The
crude product was purified by column chromatography on basic
alumina with petroleum ether to give the desired product as a col-
orless oil (163 mg, 58%). Rf = 0.5 (petroleum ether). 1H NMR
(300 MHz, CDCl3): δ = 7.14 (d, 3JHH = 7.6 Hz, 1 H), 7.01 (d, 3JHH
2 H), 2.47 (q, JHH = 7.6 Hz, 4 H), 2.40 (s, 3 H), 2.36 (q, JHH
=
3
3
7.6 Hz, 4 H), 1.17 (t, JHH = 7.6 Hz, 6 H), 0.85 (t, JHH = 7.6 Hz,
6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.3, 137.0, 130.2,
129.5, 129.0, 119.2, 21.3, 18.1, 18.0, 17.1, 15.8 ppm. GC–MS (EI):
m/z (%) = 269 (41) [M]+, 254 (100), 224 (20). HRMS: calcd. for
C19H27N 269.2143; found 269.2153.
3
= 7.9 Hz, 1 H), 7.06 (s, 1 H), 2.45 (q, JHH = 7.4 Hz, 4 H), 2.40–
2.30 (m, 2 H), 2.33 (s, 3 H), 2.18–2.06 (m, 2 H), 1.82 (s, 3 H), 1.15
2,3,4,5-Tetraethyl-1-(p-methoxyphenyl)-1H-pyrrole (3b): The crude
product was purified by column chromatography on basic alumina
with petroleum ether/EtOAc (10:1) to give the desired product as
a pale-yellow oil (201 mg, 70%). Rf = 0.3 (petroleum ether/EtOAc
= 50:1). 1H NMR (300 MHz, CDCl3): δ = 7.19–7.16 (m, 2 H),
3
3
(t, JHH = 7.5 Hz, 6 H), 0.84 (t, JHH = 7.5 Hz, 6 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 138.7, 135.8, 134.4, 130.4, 130.2,
129.2, 128.8, 119.3, 21.0, 18.1, 18.0, 17.3, 16.9, 15.7 ppm. GC–MS
(EI): m/z (%) = 283 (34) [M]+, 268 (100), 254 (13). HRMS: calcd.
for C20H29N 283.2300; found 283.2301.
3
6.96–6.92 (m, 2 H), 3.85 (s, 3 H), 2.46 (q, JHH = 7.6 Hz, 4 H),
3
3
2,3,4,5-Tetraethyl-1-(1-naphthyl)-1H-pyrrole (3h): The crude prod-
uct was purified by column chromatography on silica gel with pe-
troleum ether to give the desired product as colorless crystals
(162 mg, 53%). Rf = 0.5 (petroleum ether). 1H NMR (300 MHz,
CDCl3): δ = 7.87 (d, 3JHH = 7.6 Hz, 2 H), 7.54–7.36 (m, 4 H), 7.05
2.35 (q, JHH = 7.6 Hz, 4 H), 1.16 (t, JHH = 7.4 Hz, 6 H), 0.86 (t,
3JHH = 7.5 Hz, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.8,
132.4, 130.4, 130.2, 119.1, 113.9, 55.5, 18.1, 18.0, 17.1, 15.8 ppm.
GC–MS (EI): m/z (%) = 285 (29) [M]+, 270 (100). HRMS: calcd.
for C19H27NO 285.2093; found 285.2090.
3
3
(d, JHH = 8.6 Hz, 1 H), 2.53 (q, JHH = 7.6 Hz, 4 H), 2.39–2.27
2,3,4,5-Tetraethyl-1-phenyl-1H-pyrrole (3c): The crude product was
purified by column chromatography on silica gel with petroleum
ether to give the desired product as a colorless oil (165 mg, 65%).
Rf = 0.4 (petroleum ether). 1H NMR (300 MHz, CDCl3): δ = 7.43–
3
(m, 2 H), 2.15–2.02 (m, 2 H), 1.22 (t, JHH = 7.4 Hz, 6 H), 0.72 (t,
3JHH = 7.4 Hz, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 136.6,
134.1, 133.0, 131.1, 128.3, 127.9, 127.1, 127.0, 126.5, 125.3, 124.1,
119.5, 18.3, 18.1, 17.3, 16.1 ppm. GC–MS (EI): m/z (%) = 305 (48)
[M]+, 290 (100), 246 (23). HRMS: calcd. for C22H27N 305.2143;
found 305.2142.
3
7.35 (m, 3 H), 7.26–7.24 (m, 2 H), 2.47 (q, JHH = 7.6 Hz, 4 H),
3
3
2.38 (q, JHH = 7.6 Hz, 4 H), 1.17 (t, JHH = 7.6 Hz, 6 H), 0.84 (t,
3JHH = 7.5 Hz, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 139.7,
130.1, 129.2, 128.8, 127.5, 119.4, 18.05, 17.96, 17.1, 15.7 ppm. GC–
2,3,4,5-Tetrapropyl-1-(p-tolyl)-1H-pyrrole (3i): The crude product
MS (EI): m/z (%) = 255 (31) [M]+, 240 (100), 210 (13). HRMS: was purified by column chromatography on basic alumina with
calcd. for C18H25N 255.1987; found 255.1982.
petroleum ether to give the desired product as a pale-yellow oil
Eur. J. Org. Chem. 2010, 5426–5431
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Q. Liao, L. Zhang, F. Wang, S. Li, C. Xi
FULL PAPER
(230 mg, 71%). Rf = 0.6 (petroleum ether). 1H NMR (300 MHz,
21.7, 21.2, 18.1, 14.6 ppm. GC–MS (EI): m/z (%) = 267 (33) [M]+,
252 (100). HRMS: calcd. for C19H25N 267.1987; found 267.1996.
3
3
CDCl3): δ = 7.18 (d, JHH = 8.2 Hz, 2 H), 7.08 (d, JHH = 8.3 Hz,
3
2 H), 2.39–2.34 (m, 7 H), 2.29 (t, JHH = 7.9 Hz, 4 H), 1.52 (sext,
4,5,6,7-Tetrahydro-2-(p-tolyl)-2H-isoindole (3o):[21] The crude prod-
uct was purified by column chromatography on basic alumina with
petroleum ether to give the desired product as a colorless crystal.
(74 mg, 35%) Rf = 0.5 (petroleum ether). 1H NMR (300 MHz,
3
3
3JHH = 7.9 Hz, 4 H), 1.20 (sext, JHH = 7.9 Hz, 4 H), 0.98 (t, JHH
= 7.4 Hz, 6 H), 0.70 (t, JHH = 7.4 Hz, 6 H) ppm. 13C NMR
3
(75 MHz, CDCl3): δ = 137.2, 137.0, 129.4, 129.0, 128.9, 118.4, 27.6,
27.3, 25.6, 24.1, 21.3, 14.9, 14.3 ppm. GC–MS (EI): m/z (%) = 325
(23) [M]+, 296 (100), 238 (10). HRMS: calcd. for C23H35N
325.2770; found 325.2781.
3
3
CDCl3): δ = 7.22 (d, JHH = 8.2 Hz, 2 H), 7.17 (d, JHH = 8.2 Hz,
2 H), 6.76 (s, 2 H), 2.64 (br., 4 H), 2.34 (s, 3 H), 1.76 (br., 4 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 138.8, 134.6, 130.1, 121.9, 120.0,
114.8, 24.2, 22.2, 20.9 ppm. GC–MS (EI): m/z (%) = 211 (66)
[M]+, 183 (100), 168 (13). HRMS: calcd. for C15H17N 211.1361;
found 211.1352.
2,3,4,5-Tetraphenyl-1-(p-tolyl)-1H-pyrrole (3j): CH2Cl2 was used to
dilute the reaction mixture and wash the deposit. The crude prod-
uct was purified by column chromatography on silica gel with pe-
troleum ether/CH2Cl2 (10:1) to give the desired product as colorless
crystals (352 mg, 76%). Rf = 0.7 (petroleum ether/CH2Cl2 = 5:1).
1H NMR (300 MHz, CDCl3): δ = 7.10–7.01 (m, 12 H), 6.95–6.89
2,3,4-Triphenyl-1-(p-tolyl)-1H-pyrrole (3p): CH2Cl2 was used to di-
lute the reaction mixture and wash the deposit. The crude product
was purified by column chromatography on silica gel with petro-
leum ether/CH2Cl2 (7:1) to give the desired product as yellow crys-
tals (305 mg, 79%). Rf = 0.5 (petroleum ether/CH2Cl2 = 5:1). 1H
NMR (300 MHz, CDCl3): δ = 7.20–6.94 (m, 20 H), 2.30 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.7, 136.5, 135.6,
135.5, 132.1, 131.6, 131.2, 129.6, 128.5, 128.2, 127.9, 127.8, 126.7,
125.9, 125.8, 124.7, 122.9, 121.5, 21.1 ppm. GC–MS (EI): m/z (%)
= 385 (100) [M]+, 267 (18), 252 (7). HRMS: calcd. for C29H23N
385.1830; found 385.1817.
3
(m, 10 H), 6.80 (d, JHH = 8.2 Hz, 2 H), 2.25 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 136.6, 136.1, 135.5, 132.5, 131.8,
131.5, 131.2, 129.03, 128.96, 127.7, 127.6, 126.5, 125.4, 122.8,
21.2 ppm. GC–MS (EI): m/z (%) = 461 (100) [M]+, 281 (22), 165
(25). HRMS: calcd. for C35H27N 461.2143; found 461.2156.
3,5-Diethyl-2,4-diphenyl-1-(p-tolyl)-1H-pyrrole (3k): The crude
product was purified by column chromatography on silica gel with
petroleum ether/EtOAc (25:1) to give the desired product as a yel-
low oil (223 mg, 60%). Rf = 0.4 (petroleum ether/EtOAc = 50:1).
1H NMR (300 MHz, CDCl3): δ = 7.41–7.05 (m, 14 H), 2.55–2.48
2,3,5-Triphenyl-1-(p-tolyl)-1H-pyrrole (3q):[22] CH2Cl2 was used to
dilute the reaction mixture and wash the deposit. The crude prod-
uct was purified by column chromatography on basic alumina with
petroleum ether/CH2Cl2 (10:1) to give the desired product as a
3
3
(m, 4 H), 2.31 (s, 3 H), 0.85 (t, JHH = 7.5 Hz, 3 H), 0.77 (t, JHH
= 7.4 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.4, 136.9,
136.8, 133.5, 133.1, 130.7, 130.5, 130.1, 129.3, 128.7, 128.1, 127.7,
126.1, 125.9, 122.5, 122.2, 21.2, 18.4, 18.2, 16.2, 15.2 ppm. GC–MS
(EI): m/z (%) = 365 (73) [M]+, 350 (100), 320 (13). HRMS: calcd.
for C27H27N 365.2143; found 365.2131.
white solid (165 mg, 43%). Rf = 0.45 (petroleum ether/CH2Cl2
=
1
5:1). H NMR (300 MHz, CDCl3): δ = 7.26–7.03 (m, 15 H), 6.95
3
3
(d, JHH = 7.9 Hz, 2 H), 6.85 (d, JHH = 7.9 Hz, 2 H), 6.69 (s, 1
H), 2.26 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.0,
136.35, 136.30, 134.9, 133.1, 132.9, 132.4, 131.6, 129.2, 128.9,
128.7, 128.3, 128.2, 128.1, 128.0, 127.0, 126.4, 125.5, 123.5, 110.0,
21.2 ppm. GC–MS (EI): m/z (%) = 385 (100) [M]+, 267 (8), 165
(15). HRMS: calcd. for C29H23N 385.1830; found 385.1824.
2,3,4,5-Tetrapropyl-1-(2-pyridyl)-1H-pyrrole (3l): The crude product
was purified by column chromatography on silica gel with petro-
leum ether/EtOAc (50:1) to give the desired product as a pale-yel-
low oil (198 mg, 63%). Rf = 0.7 (petroleum ether/EtOAc = 20:1).
1H NMR (300 MHz, CDCl3): δ = 8.59–8.57 (m, 1 H), 7.78 (td,
3JHH = 7.7, 4JHH = 2.0 Hz, 1 H), 7.29–7.23 (m, 2 H), 2.50–2.33 (m,
3-Butyl-2-phenyl-1-(p-tolyl)-1H-indole (3r): The crude product was
purified by column chromatography on silica gel with petroleum
ether/EtOAc (100:1) to give the desired product as a colorless oil
(320 mg, 94%). Rf = 0.5 (petroleum ether/EtOAc = 50:1). 1H NMR
(300 MHz, CDCl3): δ = 7.69 (dd, 3JHH = 5.9, 4JHH = 3.1 Hz, 1 H),
3
3
8 H), 1.50 (sext, JHH = 7.6 Hz, 4 H), 1.12 (sext, JHH = 7.6 Hz, 4
H), 0.97 (t, 3JHH = 7.2 Hz, 6 H), 0.69 (t, 3JHH = 7.4 Hz, 6 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 153.0, 149.1, 137.6, 128.5, 122.4,
122.0, 119.5, 27.2, 26.9, 25.2, 23.7, 14.7, 14.1 ppm. GC–MS (EI):
m/z (%) = 312 (31) [M]+, 283 (100), 225 (20). HRMS: calcd. for
C21H32N2 312.2565; found 321.2555.
3
3
7.30–7.15 (m, 8 H), 7.10 (d, JHH = 8.3 Hz, 2 H), 7.03 (d, JHH
=
3
8.3 Hz, 2 H), 2.81 (t, JHH = 7.9 Hz, 2 H), 2.32 (s, 3 H), 1.70 (qui,
3JHH = 7.7 Hz, 2 H), 1.36 (sext, JHH = 7.4 Hz, 2 H), 0.88 (t, JHH
= 7.4 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.9, 137.2,
136.4, 136.1, 132.5, 130.7, 129.7, 128.4, 128.0, 127.8, 127.3, 122.3,
119.9, 119.3, 115.8, 110.7, 33.5, 24.6, 23.0, 21.2, 14.1 ppm. GC–MS
(EI): m/z (%) = 339 (33) [M]+, 296 (100), 207 (18). HRMS: calcd.
for C25H25N 339.1987; found 339.1997.
3
3
1-(m-Chlorophenyl)-2,3,4,5-tetraphenyl-1H-pyrrole (3m): CH2Cl2
was used to dilute the reaction mixture and wash the deposit. The
crude product was purified by column chromatography on silica
gel with petroleum ether/CH2Cl2 (5:1) to give the desired product
as colorless crystals (365 mg, 76%). Rf = 0.4 (petroleum ether/
1
CH2Cl2 = 5:1). H NMR (300 MHz, CDCl3): δ = 7.11–6.78 (m, 24
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 139.7, 134.9, 133.7,
131.7, 131.5, 131.3, 131.0, 129.3, 129.1, 127.7, 127.6, 127.3, 127.0,
126.7, 125.5, 123.1 ppm. HRMS: calcd. for C34H24ClN 481.1597;
found 481.1602.
1-(p-Tolyl)carbazole (3s):[23] The crude product was purified by col-
umn chromatography on silica gel with petroleum ether/CH2Cl2
(30:1) to give the desired product as colorless crystals (186 mg,
1
72%). Rf = 0.45 (petroleum ether). H NMR (300 MHz, CDCl3):
δ = 8.09 (d, 3JHH = 7.9 Hz, 2 H), 7.37–7.33 (m, 6 H), 7.29–7.19 (m,
4 H), 2.37 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.1,
137.4, 135.1, 130.5, 127.0, 126.0, 123.3, 120.4, 119.8, 109.9,
21.3 ppm. Our NMR spectroscopic data were consistent with the
corresponding literature.
1,3-Diethyl-4,5,6,7-tetrahydro-2-(p-tolyl)-2H-isoindole (3n): The
crude product was purified by column chromatography on basic
alumina with petroleum ether to give the desired product as a pale-
yellow oil (214 mg, 80%). Rf = 0.5 (petroleum ether). 1H NMR
(300 MHz, CDCl3): δ = 7.22 (d, 3JHH = 8.1 Hz, 2 H), 7.13 (d, 3JHH
= 8.4 Hz, 2 H), 2.55 (m, 4 H), 2.41 (s, 3 H), 2.34 (q, 3JHH = 7.5 Hz,
3
4 H), 1.78 (m, 4 H), 0.88 (t, JHH = 7.5 Hz, 6 H) ppm. 13C NMR Supporting Information (see also the footnote on the first page of
(75 MHz, CDCl3): δ = 137.2, 136.5, 129.4, 128.6, 128.5, 114.6, 24.1,
this article): NMR spectra for 3a–3r.
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5426–5431

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Received: May 10, 2010
Published Online: August 16, 2010
Eur. J. Org. Chem. 2010, 5426–5431
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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