Unique chemoselective Clauson-Kass reaction of substituted aniline catalyzed by MgI2 etherate

Article abstract of DOI:10.1016/j.tet.2010.12.018

Clauson-Kass reaction of various substituted aniline, primary aryl amide, and sufonyl amide with 2,5-dimethoxytetrahydrofuran was realized in the presence of 10 mol % of MgI₂ etherate in a mild, efficient, and highly chemoselective manner. Iodide counterion and solvents (i.e., MeCN) played the critical roles for the unique reactivity of this catalytic system.

Full text of DOI:10.1016/j.tet.2010.12.018

Tetrahedron 67 (2011) 898e903
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Unique chemoselective ClausoneKass reaction of substituted aniline catalyzed by
MgI2 etherate
*
Xingxian Zhang , Junchen Shi
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 October 2010
Received in revised form 1 December 2010
Accepted 7 December 2010
Available online 10 December 2010
ClausoneKass reaction of various substituted aniline, primary aryl amide, and sufonyl amide with
2,5-dimethoxytetrahydrofuran was realized in the presence of 10 mol % of MgI2 etherate in a mild, ef-
ficient, and highly chemoselective manner. Iodide counterion and solvents (i.e., MeCN) played the critical
roles for the unique reactivity of this catalytic system.
Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
Keywords:
Chemoselective
Dimethoxytetrahydrofuran
Pyrrole
ClausoneKaas reaction
MgI2 etherate
1. Introduction
2. Results and discussion
Pyrrole derivatives are important species with remarkable bi-
ological activities1 and useful intermediates in the synthesis of nat-
ural products and heterocycles.2 Many methods for the synthesis of
pyrrole derivatives have been developed, which involve conjugate
addition,3 transition metal-mediated cyclization,4 aza-Michael ad-
dition,5 multi-components reactions,6 and other operations.7 Among
them, PaaleKnorr pyrrole synthesis and ClausoneKaas pyrrole syn-
thesis are the typical and commonly used protocols for the con-
struction of pyrroles framework. A number of catalysts have been
utilized into the condensation of ClausoneKass pyrrole synthesis,
such as glacial acetic acid,8 TfOH,9 P2O5,10 montmorillonite K-10,11
p-chloropyridine hydrochloride,12 FeCl3$7H2O,13 Bi(NO3)3$5H2O,14
and lanthanide triflate.15 Magnesium, a practically ideal main group
metal, which abundantly exists in nature, has been actively in-
vestigated as a catalyst in the field of CeC bond formation and
functional group transformation.16 In our previous papers,17 we have
demonstrated that MgI2 etherate could efficiently catalyze the
Mukaiyama aldol reaction of aldehydes with trimethylsilyl enolates,
allylation of aldehydes with allylstannane and cycloaddition of iso-
cyanates with oxiranes. In continuation of our research field, we will
wish to report a mild, efficient, and highly chemoselective Clau-
soneKass condensation of various primary amines with 2,5-dime-
thoxytetrahydrofuran catalyzed by 10% MgI2 etherate.
Initially, we have chosen aniline and 2,5-dimethoxytetrahy-
drofuran 1 as the model substrates for surveying the reaction pa-
rameters inthe modelreaction. The results are summarizedinTable 1.
Table 1
Optimization of reaction conditions for MgI2 etherate-catalyzed synthesis of pyrrole
from anilinea
10mol% MgX2
+
NH2
N
MeO
OMe
O
solvent
1
2a
3a
Entry
MgX2
Solvent
Time (h)
Temp (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
MgI2
MgI2
MgI2
MgI2
MgI2
MgI2
MgI2
MgI2
MgI2
MgBr2
MgCl2
MgClO4
DMF
CH2Cl2
EtOH
PhMe
THF
2-MeTHF
DMSO
Dioxane
CH3CN
CH3CN
CH3CN
CH3CN
6.0
6.0
6.0
6.0
7.0
6.5
5.5
6.0
6.0
6.0
6.5
7.0
100
40
75
100
65
80
100
100
80
80
80
Trace
Trace
Trace
35
25
55
55
65
85
65
9
10
11
12
60
75
80
a
The reaction was carried out by the condensation of aniline(5.0 mmol) and 2,5-
dimethoxytetrahydrofuran (6.0 mmol) in the presence of 10 mol % MgI2$(OEt2)n in
above solvent at indicated temperature.
* Corresponding author. Tel.: þ86 571 88320320; fax: þ86 571 88320913;
b
Isolated yield by silica gel flash chromatography.
e-mail address: zhangxx@zjut.edu.cn (X. Zhang).
0040-4020/$ e see front matter Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.12.018

X. Zhang, J. Shi / Tetrahedron 67 (2011) 898e903
899
By screening various solvents we have found that untreated reagent-
gradeCH3CNisthebestsolventforthisreaction(Table 1, entry9). Poor
yields were given in toluene, THF, 2-MeTHF, DMSO, and dioxane
(Table 1, entries 4e8). No reaction was almost carried out in CH2Cl2,
EtOH, and DMF (Table 1, entries 1e3). To examine the halide anion
effect, halogen analogs of MgI2 etherate, MgCl2 etherate, MgBr2
etherate, and Mg(ClO4)2 were compared under parallel reaction
conditions (Table 1, entries 9e12), respectively. The best result has
been observed with MgI2 etherate as the catalyst. Good yield was also
given by using 10 mol % of MgClO4. However, MgCl2 etherate and
MgBr2 etherate are less effective in terms of substrate conversion.
With these optimal conditions in hand, we further explored the
scope and limitation of this simple process by reaction of elec-
tronically, sterically and functionally diverse amines under the
same conditions. The results are listed in Table 2. As shown in Table
2, the reaction proceeded smoothly in MeCN at 80 ꢀC and provided
a single product without any side-products in good to excellent
yields. Furthermore, we have observed the following delicate
electronic effects: (1) anilines bearing an electron-donating group
(i.e., OMe, Me) reacted much faster than aniline and provided the
corresponding products in excellent yields (Table 2. entries 2 and
3). In addition, the reaction of less sterically hindered 2-methyl-
aniline 2c with 2,5-dimethoxytetrahydrofuran could give a good
yield (Table 2. entry 4). However, the more sterically hindered 2,6-
diisopropylaniline gave a moderate yield (Table 2, entry 5). (2)
anilines bearing electron-withdrawing group (i.e., Cl, Br, F, NO2, CF3)
deactivated aryl amine remarkably and afforded the corresponding
pyrrole derivatives in moderate yields (Table 2. entries 6e12).
Seemingly, this reactivity of aromatic amine is principally de-
pendent on the electron density of the amino group, which is fur-
Table 2
Synthesis of N-aryl pyrrole derivatives catalyzed by MgI2 etheratea
.
10%MgI2
(OEt2)n
NH2
N
+
untreated CH3CN
MeO
OMe
O
R
2a-2o
R
3a-3o
1
Entry
1
Amine
Time (h)
Product
Yieldb (%)
85
NH2
N
6.0
2.0
3a
3b
2a
2b
MeO
Me
NH2
MeO
N
2
3
98
94
NH2
Me
N
2.0
6.0
3c
2c
Me
Me
4
5
84
70
NH2
N
2d
3d
CHMe2
NH2
CHMe2
N
10.0
CHMe2
3e
CHMe2
2e
Br
NH2
Br
N
6
7
6.0
6.0
66
73
3f
2f
F
F
NH2
NH2
F
F
N
N
2g
3g
8
6.0
8.0
65
77
65
F
F
2h
3h
F3C
F3C
9
NH2
N
2i
3i
NO2
NO2
10
12.0
NH2
N
2j
3j

900
X. Zhang, J. Shi / Tetrahedron 67 (2011) 898e903
Table 2 (continued)
Entry
Amine
Time (h)
12.0
Product
Yieldb (%)
62
O2N
N
N
O2N
NH2
NH2
11
12
3k
2k
O2N
H2N
O2N
H2N
12.0
70
3l
2l
N
N
N
NH2
13
14
12.0
10.0
68
65
2m
3m
H2N
NH2
H2N
N
3n
2n
H2N
H2N
15
10.0
63
NH2
N
2o
3o
a
Thereactionwascarriedoutbythecondensationofaniline(5.0 mmol)and2,5-dimethoxytetrahydrofuran(6.0 mmol)inthepresenceof10 mol%MgI2$(OEt2)n inMeCNat80ꢀC.
Isolated yield by silica gel flash chromatography.
b
Table 3
thered suggested by the exclusively regioselective condensation of
2-nitro-benzene-1,4-diamine 2l (Table 2, entry 12). Moreover, we
examined the reactivity of heteroaromatic amines, such as 2-ami-
nopyridine 2m, with 2,5-dimethoxytetrahydrofuran 1 in the pres-
ence of 10 mol % MgI2 etherate. Moderate yield was also obtained
by prolonging the reaction time (Table 2, entry 13). Additionally, the
ClausoneKass reaction of aromatic diamine with 2,5-dimethox-
ytetrahydrofuran 1 was selectively conducted (Table 2, entries 14
and 15). Moreover, we also studied the condensation of aliphatic
amines with 2,5-dimethoxytetrahydrofuran 1. Unfortunately, ali-
phatic amines are inert in the presence of MgI2 etherate.
Synthesis of N-acyl pyrrole derivatives catalyzed by MgI2 etheratea
O
C
O
C
.
10%MgI2
(OEt2)n
NH2
+
N
untreated CH3CN
MeO
OMe
O
R
R
4a-4e
5a-5e
1
Entry
Substrate
Time (h)
6.0
Product
Yieldb (%)
71
O
O
C
N
C
NH2
1
2
To expand the scope of this reaction we investigated the one-
step preparation of N-acyl pyrroles from primary aryl amides
using MgI2 etherate. N-Acyl pyrroles can be regarded as activated
carboxylic acid equivalents and are usually prepared by the ad-
dition of pyrrolyl anion with the appropriate acylating agents.18,19
However, the harsh reaction conditions and strict avoidance from
moisture limited this method. Recently, Azizi et al. reported
a simple, practical and economical procedure for synthesis of N-
acyl pyrrole catalyzed by FeCl3$7H2O in water.13 Herein, we
attempted to examined the scope and generality of our protocol
using different substituted amides with 2,5-dimethoxytetrahy-
drofuran 1. The results are summarized in Table 3. As shown in
Table 3, the results showed that aryl amides are also good sub-
strates in this catalytic system, and the desired acyl pyrroles are
formed in moderate to good yield. We have also observed the
same delicate electronic effects: (1) the reactivity of primary aryl
amides with an electron-donating substitution (i.e., OMe, Me) is
much better than primary benzamide (Table 3, entries 2 and 3). (2)
An electron-withdrawing substitution (i.e., F, Cl, NO2,) deactivated
aryl amides remarkably (Table 3, entries 4 and 5). For example,
primary aromatic amides with electronic-rich functionality, such
as 4-methylbenzamide 4b, underwent efficiently condensation
with 2,5-dimethoxytetrahydrofuran 1 to afford the corresponding
N-acyl pyrroles 5b in 82% yields. The condensation of primary
aromatic amides with electronic-poor functionality, such as
4-fluorobenzamide 4d and 2-chlorobenzamide 4e, with 2,5-
dimethoxytetrahydrofuran 1 afforded the corresponding N-acyl
pyrroles in moderate yields. Especially, 4-nitrobenzamide could
4a
5a
O
C
O
C
Me
NH2
Me
N
6.0.
82
4b
5b
O
C
O
C
N
NH2
3
4
6.0
78
65
OCH3
5c
OMe
4c
O
O
F
C N
F
C NH2
10.0
4d
5d
O
C
O
C
NH2
N
5
10.0
62
Cl
Cl
4e
5e
a
The reaction was carried out by the condensation of aryl amide (5.0 mmol) and
2,5-dimethoxytetrahydrofuran (6.0 mmol) in the presence of 10 mol % MgI2$(OEt2)n
in MeCN at 80 ꢀC.
b
Isolated yield by silica gel flash chromatography.
not reacted with 2,5-dimethoxytetrahydrofuran 1 under the same
condition. Apparently, the reactivity of these substituted aromatic
amides is dependent on the inherent nucleophilicity of the amino
group.

X. Zhang, J. Shi / Tetrahedron 67 (2011) 898e903
901
This interesting chemoselectivity was further evaluated by
crossover experiments of various aniline with 2,5-dimethoxyte-
trahydrofuran 1, respectively. The MgI2 etherate catalysis shows
high levels of aromatic amines discrimination in the competitive
reactions with 2,5-dimethoxytetrahydrofuran 1 (Table 4). Firstly, the
catalyst can differentiate the steric difference in aromatic amines to
much higher extents (Table 4, entries 1 and 2). Secondly, the MgI2
etherate catalyst can uniquely recognize the delicate difference in
electronic effect involved in aniline. Interestingly enough, 4-nitro-
aniline is much less reactive than aniline, 4-methylaniline, and 4-
methoxyaniline in the MgI2 etherate-catalyzed process. Only the
ClausoneKass condensation product of aniline, 4-methylaniline,
and 4-methoxyaniline was obtained, respectively. In crossover-re-
action of 4-nitroaniline with 4-bromoaniline or 4-fluoroaniline, the
former is also less reactive than the latter (Table 4, entries 6 and 7)
and the reaction exclusively gave the 1-(4-bromophenyl)-1H-pyr-
role or 1-(4-fluorophenyl)-1H-pyrrole. More significantly, the MgI2
etherate catalyst shows the remarkable preference for 4-methox-
yaniline or 4-methylaniline over aniline, 4-bromoaniline, and 4-
fluoroaniline (Table 4, entries 8e12). These results suggest that the
relative reactivity of aromatic amines in the MgI2 etherate-catalyzed
process is determined almost solely by nucleophilicity of aromatic
amines themselves.
To the best of our knowledge, commonly used strong Lewis acids,
i.e., FeCl3$7H2O,13 Bi(NO3)3$5H2O,14 and Sc(OTf)3,15 are usually non- or
poor-chemoselective. Thus, MgI2 etherate represents a novel type of
main group Lewis acid catalyst, which selectively activates the elec-
tron-rich functionality aromatic amines. The uniqueness of MgI2
etherate is attributed to the dissociative character of iodide counter-
ion, which is cooperating with the coordination of Lewis basic oxygen
atom of acetal function with Mg(II) leading to a more Lewis acidic
cationic Mg-coordinate as a result of Lewis base activation of Lewis
acid.20 The reactive intermediate 6 on reaction with amines 2 can lead
to pyrroles 3 following a nucleophilic addition and subsequent ex-
pulsion of MeOH, dehydration, and aromatization steps as shown in
the proposed catalytic cycle (Scheme 1). This reaction suggests the
capability of MgI2 etherate to serve as Lewis acid activator.
In conclusion, we have developed a mild, convenient, and en-
vironmentally friendly procedure for efficient synthesis of N-aryl
pyrroles and N-acyl pyrroles by the condensation of amines with
2,5-dimethoxytetrahydrofuran in the presence of 10 mol % of MgI2
etherate. Furthermore, we have demonstrated that the MgI2
etherate catalysis system has unique chemoselectivity to the sub-
strates. Exploitation of this protocol for generation of novel multi-
cyclic structures is actively pursued in our lab.
3. Experimental section
Table 4
Crossover condensation of 1 with aromatic aminesa
3.1. General procedure for the synthesis of N-aryl pyrroles 3aeo
.
(OEt2)n
10 mol% MgI2
A Schlenk reaction tube was charged with primary aromatic
amine (5.0 mmol), 2,5-dimethoxytetrahydrofuran (6.0 mmol), MgI2
etherate (10% mmol), and acetonitrile (10 mL). The reaction mix-
ture was stirred at 80 ꢀC for several hours and then concentrated in
vacuo. The residue was purified by flash column chromatography
on a silica gel to give the desired product.
+ Ar'NH2
+
ArNH2
3
+
3'
MeO
OMe
CH3CN
O
1
Entry
Ar
Ar0
Ratio (3/30)b
Yieldc (%)
1
2
3
4
5
6
7
8
C6H5
2-MeC6H4
C6H5
2,6-(CH3)2CHC6H3
2,6-(CH3)2CHC6H3
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
C6H5
80:20
70:30
90
88
84
93
98
65
71
98
97
97
92
95
86
The physical and spectra data of the compounds 3aeo are
shown as follows.
>99/<1
>99/<1
>99/<1
>99/<1
>99/<1
92/8
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-MeC6H4
C6H5
3.1.1. 1-Phenyl-1H-pyrrole (3a). White solid;13 mp 60.0e62.0 ꢀC
(lit. 62 ꢀC); Rf 0.64 (100% petroleum ether); 1H NMR (500 MHz,
CDCl3):
d
¼6.35 (t, J¼2.0 Hz, 2H), 7.09 (t, J¼2.0 Hz, 2H), 7.22e7.25
9
4-BrC6H4
4-FC6H4
4-BrC6H4
97/3
95/5
(m, 1H), 7.37e7.43 (m, 4H) ppm.
10
11
12
13
85/15d
75/25d
74/26d
3.1.2. 1-(4-Methoxyphenyl)-1H-pyrrole (3b). White solid;13 mp
112.1e112.9 ꢀC; Rf 0.18 (100% petroleum ether); 1H NMR(500 MHz,
C6H5
4-BrC6H4
a
Reactions were run with a mixture of 5.0 mmol of each aromatic amine,
5.0 mmol of 2,5-dimethoxytetrahydrofuran 1 and 10 mol % of MgI2 etherate in
MeCN at 80 ꢀC.
CDCl3):
d
¼3.83 (s, 3H), 6.32 (t, J¼2.0 Hz, 2H), 6.94 (d, J¼9.0 Hz, 2H),
7.0 (t, J¼2.0 Hz, 2H), 7.31 (d, J¼9.0 Hz, 2H) ppm.
b
The ratio was determined by flash column chromatography.
3.1.3. 1-(4-Tolyl)-1H-pyrrole (3c). Pale yellowish solid;13 mp
82.9e83.1 ꢀC (lit. 81.5e83.0 ꢀC); Rf 0.59 (100% petroleum ether);
c
Isolated overall yield.
d
The ratio was determined by GC analysis.
OMe
O
MgI2 (OEt2)n
R-NH2
2
I
+ H2O
6
N
R
3
MgI(OMe) (OEt2)n
H
(OEt2)n
MgI
I
O
H
OMe
OMe
MeO
N
R
HN
R
O
O
1
H
(OEt2)n
MgI
(OEt2)n
MgI2
O
MeOH
I
N
R
H
Scheme 1. The proposed mechanism of MgI2 etherate-catalyzed pyrrole synthesis.

902
X. Zhang, J. Shi / Tetrahedron 67 (2011) 898e903
1H NMR: (500 MHz, CDCl3):
d
¼2.40 (s, 3H), 6.36 (t, J¼2.0 Hz,
6.78 (dd, J¼1.5, 8.0 Hz, 1H), 7.05 (t, J¼2.0 Hz, 2H), 7.18 (t, J¼2.0 Hz,
1H) ppm.
2H), 7.09 (t, J¼2.0 Hz, 2H), 7.25 (s, 2H), 7.31 (d, J¼8.5 Hz,
2H) ppm.
3.2. General procedure for preparation of N-acyl pyrrole 5aee
3.1.4. 1-(2-Tolyl)-1H-pyrrole (3d). Yellowish oil;13 Rf 0.79 (100%
petroleum ether); 1H NMR (500 MHz, CDCl3):
d
¼2.25 (s, 3H),
A Schlenk reaction tube was charged with primary aromatic
amide (5.0 mmol), 2,5-dimethoxytetrahydrofuran (6.0 mmol), MgI2
etherate (10% mmol), and acetonitrile (10 mL). The reaction mix-
ture was stirred at 80 ꢀC for several hours and then concentrated in
vacuo. The residue was purified by flash column chromatography
on a silica gel to give the desired product.
6.36 (t, J¼2.0 Hz, 2H), 6.83 (t, J¼2.0 Hz, 2H), 7.28e7.33 (m,
4H) ppm.
3.1.5. 1-(2,6-Diisopropylphenyl)-1H-pyrrole (3e). White crystalline
solid;21 mp 62.2e63.0 ꢀC; Rf 0.84 (100% petroleum ether); 1H NMR
(500 MHz, CDCl3):
2H), 6.31 (t, J¼2.0 Hz, 2H), 6.63 (t, J¼2.0 Hz, 2H), 7.21 (d, J¼8.0 Hz,
2H), 7.38 (t, J¼8.0 Hz, 1H) ppm.
d
¼1.123 (s, 6H), 1.137 (s, 6H), 2.401e2.456 (m,
The physical and spectra data of the compounds 5aee are as
follows.
3.2.1. 1-Benzoyl-1H-pyrrole (5a). Yellowish oil;13 Rf 0.65 (10% EtOAc
3.1.6. 1-(4-Bromophenyl)-1H-pyrrole (3f). White solid;13 mp
96.0e97.0 ꢀC; Rf 0.68 (100% petroleum ether); 1H NMR (500 MHz,
in petroleum ether); 1H NMR (500 MHz, CDCl3):
d
¼6.35 (t,
J¼2.5 Hz, 2H), 7.29 (t, J¼2.5 Hz, 2H), 7.51 (t, J¼7.5 Hz, 2H), 7.60 (d,
CDCl3):
d
¼6.38 (t, J¼2.0 Hz, 2H), 7.01 (t, J¼2.0 Hz, 2H), 7.28 (d,
J¼7.5 Hz, 1H), 7.74e7.76 (m, 2H) ppm.
J¼9.0 Hz, 2H), 7.55 (t, J¼7.0 Hz, 2H) ppm.
3.2.2. 1-(4-Methylbenzoyl)-1H-pyrrole (5b). Yellowish oil;13 Rf 0.70
3.1.7. 1-(4-Fluorophenyl)-1H-pyrrole (3g). Pale yellowish solid;22
mp 50.6e51.7 ꢀC; Rf 0.68 (100% petroleum ether); 1H NMR
(CDCl3, 500 MHz):
7.15 (t, J¼8.5 Hz, 2H), 7.36e7.39 (m, 2H) ppm.
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
(s, 3H), 6.33 (t, J¼2.5 Hz, 2H), 7.29 (dd, J¼2.5, 4.0 Hz, 4H), 7.65 (d,
J¼8.5 Hz, 2H) ppm.
d¼2.44
d¼6.38 (t, J¼2.0 Hz, 2H), 7.05 (t, J¼2.0 Hz, 2H),
3.2.3. 1-(2-Methoxybenzoyl)-1H-pyrrole (5c). Yellowish oil; Rf 0.55
3.1.8. 1-(2,4-Difluorophenyl)-1H-pyrrole (3h). Pale yellowish oil;23
Rf 0.33 (100% petroleum ether); 1H NMR (CDCl3, 500 MHz):
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
d¼3.81
(s, 3H), 6.28 (t, J¼2.5 Hz, 2H), 7.02e7.08 (m, 2H), 7.17 (s, 2H), 7.39
(dd, J¼2.0, 8.0 Hz, 1H), 7.47e7.51 (m, 1H). 13C NMR (125 MHz,
d¼6.34 (t, J¼2.0 Hz, 2H), 6.91e6.99 (m, 4H), 7.31e7.36 (m, 1H) ppm.
CDCl3):
132.29, 156.79, 166.35 ppm.
d
¼55.78, 111.50, 113.06, 120.49, 120.61, 123.66, 129.22,
3.1.9. 1-(3-Trifluoromethylphenyl)-1H-pyrrole (3i). White solid;11
mp 49.7e50.0 ꢀC; Rf 0.67 (100% petroleum ether); 1H NMR
(CDCl3, 500 MHz):
3.2.4. 1-(4-Fluorobenzoyl)-1H-pyrrole (5d). Yellowish oil;27 Rf 0.70
d¼6.38 (t, J¼2.0 Hz, 2H), 7.11 (t, J¼2.0 Hz, 2H),
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
d
¼6.35
7.48e7.58 (m, 3H), 7.63 (s, 1H) ppm.
(t, J¼2.5 Hz, 2H), 7.19 (t, J¼8.5 Hz, 2H), 7.26 (t, J¼2.5 Hz, 2H), 7.78
3.1.10. 1-(2-Nitrophenyl)-1H-pyrrole (3j). Yellowish oil;15 Rf 0.38
(dd, J¼5.5, 8.5 Hz, 2H) ppm.
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
3.2.5. 1-(2-Chlorobenzoyl)-1H-pyrrole (5e). Yellowish oil;15 Rf 0.60
d
¼6.37 (t, J¼2.0 Hz, 2H), 6.80 (t, J¼2.0 Hz, 2H), 7.48 (dd, J¼5.0,
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
J¼2.5 Hz, 2H), 7.12 (s, 2H), 7.37e7.40 (m, 1H), 7.45e7.50 (m, 3H) ppm.
d
¼6.33 (t,
8.0 Hz, 2H), 7.65 (dd, J¼1.5, 8.0 Hz, 1H), 7.86 (dd, J¼2.0, 7.0 Hz,
1H) ppm.
3.1.11. 1-(4-Nitrophenyl)-1H-pyrrole (3k). Yellowish solid;15 mp
183.1e184.4 ꢀC; Rf 0.50 (10% EtOAc in petroleum ether); 1H NMR
3.3. General procedure for crossover reaction
(500 MHz, CDCl3):
d
¼6.45 (t, J¼2.0 Hz, 2H), 7.20 (t,
A
Schlenk reaction tube was charged with each amine
J¼2.0 Hz, 2H), 7.54 (dd, J¼9.0, 7.0 Hz, 2H), 8.33 (dd, J¼2.0, 7.0 Hz,
(5.0 mmol), 2,5-dimethoxytetrahydrofuran (6.0 mmol), MgI2
etherate (10% mmol), and acetonitrile (10 mL). The reaction mix-
ture was stirred at 80 ꢀC for several hours and then concentrated in
vacuo. Flash column chromatography afforded the desired prod-
ucts. The ratio of each product was determined by column chro-
matography isolation or GC analysis.
2H) ppm.
3.1.12. 1-(3-Nitro-4-aminophenyl)-1H-pyrrol (3l). Red-brown solid;24
mp 178.8e179.7 ꢀC; Rf 0.42 (17% EtOAc in petroleum ether); 1H NMR
(500 MHz, CDCl3):
J¼9.0 Hz, 1H), 7.02(t, J¼2.0 Hz, 2H), 7.48 (dd, J¼2.0, 6.5 Hz, 1H), 8.16
(d, J¼3.0 Hz, 1H) ppm.
d
¼6.11 (s, 2H), 6.36 (t, J¼2.0 Hz, 2H), 6.91 (d,
Acknowledgements
3.1.13. 1-(2-Pyridinyl)-1H-pyrrol (3m). Yellowish oil;14 Rf 0.33 (2.5%
Financial support from the Zhejiang Province Natural Science
Foundation of China (Project Y4100692).
EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
d¼6.36 (s,
2H), 7.10 (t, J¼6.0 Hz, 1H), 7.32 (d, J¼8.0 Hz, 2H), 7.52 (s, 2H), 7.74 (t,
J¼8.0 Hz, 1H), 8.43 (d, J¼4.0 Hz, 1H) ppm.
Supplementary data
3.1.14. 1-(4-Aminophenyl)-1H-pyrrol (3n). Pale yellowish solid;25
mp 155.5e156.5 ꢀC; Rf 0.32 (17% EtOAc in petroleum ether); 1H
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.12.018.
NMR (500 MHz, CDCl3):
6.5 Hz, 2H), 6.97 (t, J¼2.0 Hz, 2H), 7.18 (dd, J¼2.0, 6.5 Hz, 2H), 8.16
(d, J¼3.0 Hz, 1H) ppm.
d
¼6.30 (t, J¼2.0 Hz, 2H), 6.72 (dd, J¼2.0,
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