Ionic diamine rhodium complex catalyzed reductive N-heterocyclization of 2-nitrovinylarenes

Article abstract of DOI:10.1021/jo200320k

Ionic diamine rhodium complex (1) catalyzes the reductive N-cyclization of 2-vinylnitroarenes using carbon monoxide as a reducing agent to afford functionalized indoles. The catalytic system allows direct access to indoles with ester and ketone groups at the 2- or 3-position, in good yields.

Full text of DOI:10.1021/jo200320k

NOTE
pubs.acs.org/joc
Ionic Diamine Rhodium Complex Catalyzed Reductive
N-Heterocyclization of 2-Nitrovinylarenes
Kazumi Okuro, Joanna Gurnham, and Howard Alper*
Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie,
Ottawa K1N 6N5, Canada
S Supporting Information
b
ABSTRACT: Ionic diamine rhodium complex (1) catalyzes the reductive
N-cyclization of 2-vinylnitroarenes using carbon monoxide as a reducing
agent to afford functionalized indoles. The catalytic system allows direct
access to indoles with ester and ketone groups at the 2- or 3-position, in
good yields.
ndole derivatives are recognized as important synthetic inter-
mediates for the design of pharmacologically active compounds.1
olefins20 and the inter- or intramolecular hydroaminomethylation21ꢀ23
of anilines containing an olefinic unit. Our interest in the catalytic
behavior of complex 1 led us to examine the possibility of effecting
the reductive intramolecular hydroaminomethylation of 2-nitro-
vinylarenes. We found that the reductive N-cyclization occurred
without any additives, affording indole derivatives instead of the
initially expected reductive hydroaminomethylation products. We
now describe our findings using the rhodium complex 1 (Figure1)
as the reaction catalyst.
I
Numerous synthetic methods for such compounds have been
developed. Some of the well-established methods include classic
organic syntheses such as the Fischer, Madelung, Reissert, Leim-
gruber-Batcho, and Gassman indole syntheses and others,2ꢀ6 all of
which are nonmetal-mediated approaches. Other attractive appli-
cations include the use of metal catalysts, in particular, transition
metals, which allows the preparation of functionalized indoles
from appropriate starting materials in a single step. Examples of
straightforward pathways to construct the indole skeleton involve
the Pd(II)-catalyzed intramolecular cyclization of 2-alkynylanilines7ꢀ9
and 2-alkenylanilines.10ꢀ14 Alternatively, reductive N-heterocy-
clization of 2-alkenylnitrobenzenes15ꢀ19 catalyzed by metal
complexes, where carbon monoxide can serve as a reducing
agent, can produce indoles. This reductive N-heterocyclization
methodology has received attention because of its avoidance of
the preparation of the corresponding aniline substrates that often
requires the chemoselective reduction of the nitro group when
the desired substrate has functional groups sensitive to the
reduction process. A stoichiometric amount of metal reducing
agent such as metallic Fe, Sn, or Zn can be used for this purpose;
however, the resulting metal waste originating from the metallic
reducing agents often makes it difficult or problematic to isolate
the aniline products effectively from the reaction mixture.
Watanabe et al. have demonstrated that the Pd complex in
combination with SnCl2 could catalyze reductive N-cyclization
of 2-vinylnitrobenzenes in the presence of carbon monoxide to
afford indole derivatives.16,17 The Pd-catalyzed reaction was
applied to the synthesis of 3-indolecarboxylic acid derivatives,
which are useful as pharmaceuticals or synthetic intermediates.18
Sonoda et al. also demonstrated the use of a selenium catalyst
with carbon monoxide as a reducing agent.19
Treatment of 2-isopropenylnitrobenzene (2a) with 5 mol % of
1 in THF at 100 °C under CO/H2 (100/700 psi), optimal
conditions for the hydroaminomethylation of 2-allylanilines,23
afforded 3-methylindole (3a) in 27% yield (Table 1, entry 1). A
dramatic increase in the yield of 3a resulted when the partial
pressure of H2 was reduced, and the best results were obtained
using 100 psi of CO (entries 2 and 3). No reaction took place at
80 °C (entry 4). Decreased CO pressure to 28 psi still induced
the reaction to some extent, giving 3a in 51% yield, with 2a being
recovered in 36% yield (entry 5). The reactions in toluene or
CH3CN were inferior to those in THF (entries 6 and 7). In order
to clarify the effectiveness of complex 1, the use of [Rh(COD)-
Cl]2, a synthetic precursor of 1,20 alone or in combination with
standard phosphine ligands, was evaluated. The indole 3a was
formed in only 4% yield when [Rh(COD)Cl]2 was used as the
catalyst. Similarly, any combined catalytic system of [Rh(COD)-
Cl]2 and phosphines was totally ineffective, with no 3a being
formed (entries 8ꢀ14).
Our catalytic system is also versatile for reactions with
functionalized 2-nitrovinylarenes under optimized conditions
(Table 2). Substrates bearing an ester group on the double bond
gave the corresponding indole derivatives in good to excellent
yields (Table 2, entries 6ꢀ9), regardless of the position of an
ester group (i.e., terminal or internal carbons). It is surprising that
2-nitrocinnamaldehyde (2k) also underwent the cyclization to
We have previously reported the synthesis of a novel, air-stable
ionic diamine rhodium complex [Rh(CO)2(Me2NCH2CH2-
NMe2)]þ[RhCl2(CO)2]ꢀ (1).20 This complex exhibits excellent
catalytic activity for the highly regioselective hydroformylation of
Received: March 2, 2011
Published: May 04, 2011
r
2011 American Chemical Society
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|

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NOTE
While the mechanism for the reaction remains to be eluci-
dated, the present reaction may conceivably involve a nitreneꢀ
rhodium intermediate, which would be formed by deoxygenation
of the nitro group by carbon monoxide under the influence of the
rhodium complex as proposed for the Pd-catalyzed reaction.17
It is possible that the coordination environment around the
nitrene species affects the reaction course, giving rise to the
different behavior for 2e and 2k by the Pd-catalyzed reaction.
In summary, we have demonstrated that the reductive N-cy-
clization of 2-vinylnitroarenes catalyzed by the ionic diamine
rhodium complex using carbon monoxide as a reducing agent
affords functionalized indoles usually in good yields. This catalyst
system is particularly useful for the synthesis of indoles with ester
and ketone groups.
Figure 1. Structure of 1.
Table 1. Optimization of the Ionic Diamine Complex Cata-
lyzed N-Reductive Cyclization of 2aa
yieldb (%)
’ EXPERIMENTAL SECTION
entry
catalyst system
CO/H2 (psi)
2a
3a
Typical Procedure for the Reductive N-Heterocyclization
of 2. The 2-nitrovinylarenes (1.0 mmol), complex 120 (0.05 mmol, 25.6
mg), and THF (3 mL) were placed into a glass liner equipped with a
magnetic stirring bar. The glass liner was then inserted into a 45 mL
autoclave. The autoclave was flushed five times with carbon monoxide
and pressurized to 100 psi. The autoclave was heated at 100 °C with
stirring. After the reaction, the autoclave was cooled to rt prior to the
release of carbon monoxide. The solvent was evaporated under reduced
pressure, and the product was purified by silica gel column chromatog-
raphy with n-hexane and diethyl ether as the eluant.
Preparation of the 2-Vinylnitroarenes 2. 2-Isopropenylni-
trobenzene (2a). To a suspension of methyltriphenylphosphonium
bromide (72 mmol, 25.7 g) in THF (50 mL) was added dropwise
NaHMDS (1.0 M THF, 72 mL) at ꢀ78 °C. The resulting solution was
stirred at this temperature for 15 min, and then a solution of 2-nitro-
benzaldehyde (60 mmol, 9.06 g) in THF (20 mL) was added, and the
resulting reaction mixture was further stirred at rt for 14 h. The reaction
was quenched using saturated NH4Cl (aq), and the crude product was
extracted twice with diethyl ether. The combined organic layers were
dried over Na2SO4 and concentrated in vacuo. The residue was purified
by silica gel column chromatography with n-hexane/diethyl ether (90/
10) as the eluant to obtain the product (9.28 g, 95%): 1H NMR (400
MHz, CDCl3) δ 2.07 (s, 3 H), 4.92 (d, J = 4.0 Hz, 1 H), 5.16 (d, J = 4.0
Hz, 1 H), 7.24ꢀ7.32 (m, 1 H), 7.37ꢀ7.38 (m, 1 H), 7.50ꢀ7.53 (m, 1
H), 7.83ꢀ7.85 (d, 1 H); 13C NMR δ 23.3, 53.5, 115.4, 124.0, 127.9,
130.6, 132.7, 139.0, 142.8, 148.3; HRMS (EI) calcd for C9H9NO2
163.0633, found 163.0607.
2-Isopropenyl-4-methoxynitrobenzene (2b). A mixture of 5-hydro-
xy-2-nitroacetophenone (17.5 mmol, 3.16 g), K2CO3 (30 mmol, 4.14 g),
and MeI (60 mmol, 8.46 g) in DMSO (30 mL) was stirred at rt for 20 h.
The reaction mixture was poured into water, and the product was
extracted three times with diethyl ether. The combined organic layers
were washed with brine, dried over Na2SO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica gel with n-
hexane/diethyl ether (80/20) as the eluant to give 4-methoxy-2-
nitroacetophenone (2.89 g, 85%).
To a suspension of methyltriphenylphosphonium bromide (7.2
mmol, 2.57 g) in THF (30 mL) was added dropwise NaHMDS (1.0
M THF, 7.2 mL) at 0 °C, and then the solution was stirred at rt for 30
min. To the above reaction mixture was added a solution of 4-methoxy-
2-nitroacetophenone (6.0 mmol, 1.17 g) in THF (30 mL) at 0 °C.
Thereafter, the resulting reaction mixture was further stirred at rt for 15
h. The reaction was quenched using saturated NH4Cl (aq), and the
crude product was extracted twice with diethyl ether. The combined
organic layers were dried over Na2SO4 and concentrated in vacuo. The
residue was purified by silica gel column chromatography with n-
1
2
1
100/700
100/100
100/0
100/0
28/0
0
27
67
81
0
1
0
10
87
36
12
33
55
100
72
84
47
83
68
3
4c
1
1
5
1
51
59
28
4
6d
7e
8
1
100/0
100/0
100/100
100/0
100/0
100/0
100/0
100/0
100/0
1
[Rh(COD)Cl]2
[Rh(COD)Cl]2/2PPh3
[Rh(COD)Cl]2/2PCy3
[Rh(COD)Cl]2/1dppe
[Rh(COD)Cl]2/1dppp
[Rh(COD)Cl]2/1dppb
[Rh(COD)Cl]2/1dppf
9
0
10
11
12
13
14
0
0
0
0
0
a Reaction conditions: 2a (1 mmol), Rh catalyst (0.05 mmol), monopho-
sphine (0.20 mmol) or bisphosphine (0.1 mmol), solvent 3 mL. b Yield
determined by 1H NMR using tert-butyl acetate as an internal standard.
c Reaction at 80 °C. d Reaction in toluene. e Reaction in acetonitrile.
produce 2-formylindole (3k) in 52% yield (entry 10), whereas it
was reported that the palladium-catalyzed cyclization of the same
substrate afforded quinoline but 3k was not formed at al.17 It
should also be noted that R,β-unsaturated ketones can be used
for the present cyclization, affording indoles substituted by acetyl
or benzoyl groups in good yields, without the formation of the
corresponding quinoline derivatives (entries 11ꢀ16). Along
with the results for 2-nitrocinnamaldehyde (2k) described above,
the reaction of 2-(2-methyl-1-propenyl)nitrobenzene (2e) gave
distinct results compared to the Pd catalyst.17 The reaction
catalyzed by the Pd complex gave 2,3-dimethylindole in which
[1,5]-sigmatropic rearrangement of the terminal methyl group
took place during the reaction. In contrast, the current catalytic
system resulted in a complex mixture, with no 2,3-dimethylindole
being detected.
The reaction of 6-methoxy-2-isopropenylnitrobenzene (2c)
did not take place, and 2c was recovered unchanged, suggesting
that the nitro group cannot access to the coordination sphere of
the rhodium center because of the steric bulkiness of a methoxy
group. The allylic alcohol (2r), allylic acetate (2s), and con-
jugated diene derivatives (2n) also gave unsatisfactory results
(entries 17ꢀ19). The nonconjugated diene 2u also afforded
2-(1-propenyl)indole (3u) in low yield.
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NOTE
Table 2. Results of the Ionic Diamine Rhodium Complex Catalyzed N-Heterocyclization of a Variety of 2-Nitrovinylarenes 2.a
a Reaction conditions: 2 (1.0 mmol), 1 (0.05 mmol), THF 3 mL, CO 100 psi, 100 °C, 20 h. b Isolated yield after column chromatography. c The starting
material 2c was completely recovered.
hexane/diethyl ether (80/20) as the eluant to obtain the product (1.06 g,
92%): 1H NMR (400 MHz, CDCl3) δ 2.05 (d, J = 1.2 Hz, 3 H), 3.86 (s, 3
H), 4.89 (dd, J = 1.2, 1.5 Hz, 1 H), 5.12 (d, J = 1.5 Hz, 1 H), 6.72 (d, J =
2.8 Hz, 1 H), 6.83 (dd, J = 2.8, 9.1 Hz, 1 H), 7.97 (d, J = 9.1 Hz, 1 H); 13C
NMR δ 23.3, 55.9, 112.8, 114.6, 115.7, 127.0, 140.9, 142.4, 144.0, 163.0;
HRMS (EI) calcd for C10H11NO3 193.0739, found 193.0726.
2-Isopropenyl-6-methoxynitrobenzene (2c). A mixture of 3-hydro-
xy-2-nitroacetophenone (1.8 mmol, 0.33 g), K2CO3 (10 mmol, 1.38 g),
and MeI (20 mmol, 2.84 g) in DMSO (30 mL) was stirred at 50 °C for
20 h. The reaction mixture was poured into water, and the product was
extracted three times with diethyl ether. The combined organic layers
were washed with brine, dried over Na2SO4, and concentrated in vacuo.
The residue was purified by silica gel column chromatography with
n-hexane/diethyl ether (75/25) as the eluant to give 3-methoxy-2-nitroa-
cetophenone (0.32 g, 91%).
(1.6 mmol, 0.32 g) in THF (10 mL) at 0 °C. Thereafter, the resulting
reaction mixture was further stirred at rt for 15 h. The reaction was
quenched using saturated NH4Cl (aq), and the crude product was
extracted twice with diethyl ether. The combined organic layers were
dried over Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography with n-hexane/diethyl
ether (80/20) as the eluant to give 0.24 g (64%) of 2c: 1H NMR (400
MHz, CDCl3) δ 2.04 (d, J = 1.0 Hz, 3H), 3.87 (s, 3 H), 5.00 (dd, J = 1.0,
1.6 Hz, 1 H), 5.17 (d, J = 1.6 Hz, 1 H), 6.85ꢀ6.87 (m, 2 H), 7.32ꢀ7.36
(m, 1 H); 13C NMR (100 MHz, CDCl3) δ 23.5, 56.4, 111.0, 117.0,
120.4, 130.6, 137.4, 140.5, 150.6; HRMS (EI) calcd for C10H11NO3
193.0739, found 193.0741.
2-(1-Pentenyl)nitrobenzene (2d). A mixture of 2-nitrobenzyl bro-
mide (20 mmol, 4.32 g) and triphenylphosphine (20 mmol, 5.24 g) in
toluene (50 mL) was heated at 100 °C for 24 h. The precipitated
(2-nitrobenzyl)triphenylphosphonium bromide was collected by filtra-
tion (9.44 g, 99%).
To a suspension of methyltriphenylphosphonium bromide (1.9 mmol, 0.69
g) in THF (10 mL) was added dropwise NaHMDS (1.0 M THF, 1.9 mL)
at 0 °C, and then the solution was stirred at rt for 30 min. To the above reaction
mixture was added a solution of 4-methoxy-2-nitroacetophenone
A
mixture of (2-nitrobenzyl)triphenylphosphonium bromide
(10 mmol, 4.78 g) and K2CO3 (20 mmol, 2.76 g) in DMSO (30 mL)
4717
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NOTE
was stirred at rt for 2 h, and then butyraldehyde (20 mmol, 1.40 g) was
added. The resulting mixture was further stirred at rt for 18 h. The
mixture was poured into water, and the product was extracted three
times with diethyl ether. The combined organic layers were washed with
brine, dried over Na2SO4, and concentrated in vacuo. The residue was
purified by silica gel column chromatography with n-hexane/diethyl
(m, 3 H), 7.54ꢀ7.56 (m, 2 H), 7.66ꢀ7.70 (m, 1 H), 7.91ꢀ7.93 (m, 2
H), 8.13ꢀ8.15 (m, 1 H); 13C NMR δ 124.9, 127.9, 128.3, 129.49, 123.0,
132.5, 132.9, 134.0, 134.2, 137.2, 146.8, 147.2, 195.0; HRMS (EI) calcd
for C15H11NO3 253.0739, found 253.0696.
1-(Nitrophenyl)-buten-3-one (2m). The product was prepared ac-
cording to the literature method.30
ether (90/10) as the eluant to give 1.67 g (88%) of 2d. The 1H and 13
C
4-(5-Methoxy-2-nitrophenyl)buten-2-one (2n). A mixture of 4-(5-
hydroxy-2-nitrophenyl)buten-3-one (6 mmol, 1.24 g), which was pre-
pared from 4-hydroxy-2-nitrobenzaldehyde with 1-(triphenylphosph-
oranylidene)-2-propanone in a similar manner to 2m (77%),30 KOH
(24 mmol, 1.34 g), and MeI (24 mmol, 3.40 g) in DMSO was stirred at rt
for 16 h. The resulting solution was poured into water, and the product
was extracted three times with diethyl ether. The combined organic
layers were washed with water, dried over Na2SO4, and concentrated in
vacuo. The residue was purified by silica gel column chromatography
with n-hexane/diethyl ether (80/20) as the eluant to give 0.90 g (68%)
of 2n: mp 118ꢀ121 °C; 1H NMR (400 MHz, CDCl3) δ 2.42 (s, 3 H),
3.90 (s, 3 H), 6.48 (d, J = 16.0 Hz, 1 H), 6.96ꢀ6.99 (m, 2 H), 8.07 (d, J =
16.0 Hz, 1 H), 8.13 (m, 1 H); 13C NMR δ 26.9, 56.1, 114.0, 115.2, 127.9,
131.9, 134.0, 140.4, 163.6, 198.4; HRMS (EI) calcd for C9H8NO3 [M ꢀ
Ac] 178.0504, found 178.0500.
NMR spectra were in accordance with literature data.24
2-(2-Methyl-1-propenyl)nitrobenzene (2e). To a solution of isopro-
pyltriphenylphosphonium iodide (18 mmol, 7.78 g) in THF (30 mL)
was added n-BuLi (2.5 M in hexane, 7.2 mL) at 0 °C, and then the
resulting solution was further stirred at this temperature for 30 min. A
solution of 2-nitrobenzaldehyde (15 mmol, 2.27 g) in THF (10 mL) was
then added to the above solution, and the resulting mixture was stirred
again at 0 °C for 3 h. The reaction was quenched using saturated NH4Cl
(aq), and the crude product was extracted twice with diethyl ether. The
combined organic layers were dried over Na2SO4 and concentrated in
vacuo. The residue was purified by silica gel column chromatography
with n-hexane/diethyl ether (90/10) as the eluant to form 1.27 g (48%)
of 2e. The 1H and 13C NMR spectra were in accordance with literature
data.25
1-(5-Chloro-2-nitrophenyl)buten-2-one (2o). The product was pre-
pared from 5-chloro-2-nitrobenzaldehyde in a manner similar to that for
2-Nitrostilbene (2f). The product was prepared from 2-nitrobenzyl-
triphenylphosphonium bromide and benzaldehyde in a manner similar
to that for 2d (100%). The 1H and 13C NMR spectra were in accordance
with literature data.26
Methyl 2-Nitrocinnamate (2g). The product was prepared by acid
(concd H2SO4)-catalyzed esterification of commercially available 2-ni-
trocinnamic acid in MeOH (92%). The 1H and 13C NMR spectra were
in accordance with literature data.27
1
the synthesis of 2m (81%):30 mp 147ꢀ148 °C; H NMR (400 MHz,
CDCl3) δ 2.41 (s, 3 H), 6.54 (d, J = 16.0 Hz, 1 H), 7.24ꢀ7.51 (m, 1 H),
7.58ꢀ7.59 (m, 1H), 7.93 (d, J = 16.0 Hz, 1 H), 8.04ꢀ8.06 (m, 1 H); 13C
NMR δ 27.4, 126.6, 126.7, 129.1, 129.1, 130.3, 132.6, 137.8, 140.3,
197.6; HRMS (EI) calcd for C8H5NO2 [M ꢀ Ac] 182.0009, found
182.0015.
Methyl 2-(2-Nitrophenyl)acrylate (2h). The product was prepared
3-(2-Nitrophenyl)buten-2-one (2q). To a solution of 2-nitropheny-
lacetic acid (50 mmol, 9.08 g) in Ac2O (25 mL) was added 1-methy-
limidazole (25 mmol, 2.0 mL). After the mixture was allowed to react for
12 h, it was poured into water. The crude product was extracted three
times with diethyl ether. The combined organic layers were washed with
brine, dried over Na2SO4, and concentrated in vacuo. The crude
2-nitrophenylacetone thus obtained was used for the next step without
purification.
A mixture of crude 2-nitrophenylacetone, morpholine (12.5 mmol,
1.09 g), and 37% HCHO (aq) (12.5 mL) in AcOH (50 mL) was heated
at 100 °C for 20 h. After the solvent was removed under reduced
pressure, diethyl ether and water were added. The organic layer was
separated, dried over Na2SO4, and evaporated in vacuo. The residue was
purified by silica gel column chromatography with n-hexane/diethyl
ether (80/20) as the eluant, giving 3.20 g (67%) of 2q: 1H NMR (400
MHz, CDCl3) δ 2.45 (s, 3 H), 6.00 (s, 1 H), 6.27 (s, 1 H), 7.28ꢀ7.31 (m,
1 H), 7.46ꢀ7.50 (m, 1 H), 7.59ꢀ7.63 (m, 1 H), 8.05ꢀ8.09 (m, 1 H);
13C NMR δ 26.3, 124.5, 125.6, 129.3, 129.3, 132.1, 133.4, 133.7, 148.3,
197.3; HRMS (EI) calcd for C8H6NO2 [M ꢀ Ac] 148.0399, found
148.0376.
3-(2-Nitrophenyl)buten-1-ol (2r). To a solution of 2-nitrocinnamal-
dehyde (30 mmol, 5.31 g) in MeOH (30 mL) was added NaBH4 (15
mmol, 0.57 g) in one portion at rt, and the mixture was stirred for 10 min.
The reaction mixture was poured into water, and the crude product was
extracted with diethyl ether. After the organic layer was dried over
Na2SO4 and concentrated in vacuo, the crude product was recrystallized
from n-hexane/AcOEt (1/1, v/v) to form 1.3 g (24%) of 2r. The 1H and
13C NMR spectra were in accordance with literature data.31
1-Acetoxy-3-(2-nitrophenyl)-2-butene (2s). To a solution of 2u
(15 mmol, 2.69 g) and dimethylaminopyridine (15 mg) in pyridine
(10 mL) was added Ac2O (20 mmol, 2.04 g) at 0 °C, and the resulting
mixture was stirred at rt for 15 h. The reaction solution was poured into
water, and the product was extracted three times with diethyl ether. After
the combined organic layers were washed with 10% HCl and then water,
the organic layer was dried (Na2SO4) and concentrated in vacuo. The
according to the literature method.28
Methyl 2-(5-Methoxy-2-nitrophenyl)acrylate (2i). The product was
prepared according to the literature method.29
Methyl 2-(5-Chloro-2-nitrophenyl)acrylate (2j). A solution of tert-
butyl 2-(5-chloro-2-nitrophenyl)acetic acid (8 mmol, 2.2 g) prepared by
the literature method18 was heated in the presence of concd H2SO4 (a
few drops) for 20 h. The solution was evaporated in vacuo, and the
resulting crude methyl 2-(5-chloro-2-nitrophenyl)acetate was further
transformed by the literature method28 to obtain the product (82%): mp
61ꢀ63 °C; 1H NMR (400 MHz, CDCl3) δ 3.67 (s, 3 H), 5.85 (d, J = 0.6
Hz, 1 H), 6.50 (d, J = 0.6 Hz, 1 H), 7.33 (dd, J = 2.3, 8.7 Hz, 1 H), 7.44
(dd, J = 0.2, 8.7 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 52.4, 126.1,
128.1, 129.4, 132.0, 134.6, 138.8, 139.9, 146.1, 164.8; HRMS (EI) calcd
for C10H8ClNO4 241.0142, found 241.0112.
2-(2-Nitrophenyl)-1-phenylpropen-1-one (2l). To a solution of
2-nitrophenylacetic acid (15 mmol, 2.72 g) in CH2Cl2 (30 mL) were
added DMF (a few drops) and oxalyl chloride (30 mmol, 3.81 g), and the
resulting solution was stirred at rt for 20 h. The organic solvent was
removed under reduced pressure, and then benzene (30 mL) and AlCl3
(22 mmol, 2.94 g) were added to the residue. The mixture was allowed
to react at rt for 45 min. The reaction was quenched using cold 10% HCl
(20 mL), and the organic layer was separated, dried over Na2SO4, and
concentrated in vacuo. The residue was purified by silica gel column
chromatography with n-hexane/diethyl ether (80/20) as the eluant to
give 2-nitrobenzyl phenyl ketone (1.91 g, 53%).
A mixture of 2-nitrobenzyl phenyl ketone (4.0 mmol, 0.359 g), 37%
HCHO (aq) (62 mmol, 5 mL), and morpholine (4.0 mmol, 0.35 g) in
AcOH (20 mL) was refluxed for 20 h. After being cooled to rt, water was
added, and the product was extracted three times with diethyl ether. The
combined organic layers were washed with water, dried over Na2SO4,
and concentrated in vacuo to give the crude product, which was purified
by silica gel column chromatography with n-hexane/diethyl ether (80/
20) as the eluant to obtain the product (0.95 g, 48%): mp 122ꢀ123 °C;
1H NMR (400 MHz, CDCl3) δ 5.99 (s, 1 H), 6.19 (s, 1 H), 7.46ꢀ7.48
4718
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NOTE
residue was purified by silica gel column chromatography with
n-hexane/diethyl ether (85/15) as the eluant to obtain 3.13 g (95%) of
2s. The 1H and 13C NMR spectra were in accord with literature data.32
1-(2-Nitrophenyl)-1,3-butadiene (2t). To a suspension of allyltriphe-
nylphosphonium bromide (22 mmol, 8.43 g) in diethyl ether (120 mL)
was added t-BuOK (24 mmol, 2.69 g) at rt, and the resulting solution
was stirred for 15 min. Thereafter, a solution of 2-nitrobenzaldehyde
(20 mmol, 3.02 g) in diethyl ether (20 mL) was added, and the solution
was allowed to react for 7 h. The reaction was quenched using saturated
NH4Cl (aq), and the crude product was extracted twicewith diethyl ether.
The combinedorganiclayers were dried over Na2SO4 and concentratedin
vacuo. The residue was purified by silica gel column chromatography with
n-hexane/diethyl ether (90/10) as the eluant to form 0.66 g (19%) of 2t.
The 1H and 13C NMR spectra were in accord with literature data.33
1-(2-Nitrophenyl)-1,4-pentadiene (2u). A mixture of 3-butenylpho-
sphonium bromide (12 mmol, 4.79 g), K2CO3 (12 mmol, 1.66 g), and
18-crown-6 (21 mg) in CH2Cl2 (40 mL) was stirred at rt for 20 h.
Thereafter, a solution of 2-nitrobenzaldehyde (8.0 mmol, 1.21 g) was
added, and the resulting solution was further stirred for 15 h. The
reaction was quenched using saturated NH4Cl (aq), and the organic
layer was separated. The organic layers were dried over Na2SO4 and
concentrated in vacuo, and the residue was purified by silica gel column
chromatography with n-hexane/diethyl ether (90/10) as the eluant to
form 1.37 g (91%) of 2u: 1H NMR (400 MHz, CDCl3) (a mixture of a
trans and cis isomer) the major isomer δ 2.79ꢀ2.83 (m, 2 H), 5.01ꢀ5.09
(m, 2 H), 5.82ꢀ5.86 (m, 2 H), 6.77ꢀ6.78 (m, 1 H), 7.36ꢀ7.39 (m, 2
H), 7.54ꢀ7.56 (m, 1 H), 7.98ꢀ8.00 (m, 1H), the minor isome δ
2.99ꢀ3.00 (m, 1 H), 5.01ꢀ5.09 (m, 2 H), 5.01ꢀ5.09 (m, 2 H),
6.23ꢀ6.24 (m, 2 H), 6.80ꢀ6.81 (m, 1 H), 7.36ꢀ7.39 (m, 2 H),
7.54ꢀ7.56 (m, 1 H), 7.81ꢀ7.83 (m, 1 H); 13C NMR (a mixture of a
trans and cis isomer) δ 32.6, 37.1, 115.7, 116.4, 124.4, 124.6, 126.1,
126.5, 127.6, 128.0, 128.5, 131.2, 131.6, 132.8, 132.9, 136.0, 148.3;
HRMS (EI) calcd for C11H11NO2 189.0790, found 189.0728.
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1
3u50are known compounds, and the H NMR spectra were in accor-
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2-Acetyl-5-chloroindole (3o): mp 205 °C dec; 1H NMR (400 MHz,
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9.23 (brs, 1 H); 13C NMR δ 25.9, 108.9, 113.3, 122.2, 126.6, 126.9,
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’ ASSOCIATED CONTENT
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Supporting Information.
General procedures and 1H
S
b
and/or 13C NMR spectra for obtained compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
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’ AUTHOR INFORMATION
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Corresponding Author
*E-mail: howard.alper@uottawa.ca.
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’ ACKNOWLEDGMENT
We are grateful to the Natural Sciences and Engineering
Research Council of Canada (NSERC) for financial support of
this research.
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