Metal-Free Synthesis of Pyrrolo[1,2- a ]quinoxalines Mediated by TEMPO Oxoammonium Salts

Article abstract of DOI:10.1055/s-0037-1610131

We herein describe a novel TEMPO oxoammonium salt initiated Pictet-Spengler reaction of imines, generated in situ from carbonyl compounds and pyrrole- or indole-containing substrates, to afford 4,5-dihydropyrrolo[1,2- a ]quinoxalines or 5,6-dihydroindolo[1,2- a ]quina-oxalines in good to excellent yields. Moreover, a one-pot synthesis of a biologically important quinoxaline is achieved via a cyclization-dehydrogenation process using one equivalent of the oxoammonium salt.

Full text of DOI:10.1055/s-0037-1610131

SYNTHESIS
0
0
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9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–N
paper
A
en
H.-r. Huo et al.
Paper
Synthesis
Metal-Free Synthesis of Pyrrolo[1,2-a]quinoxalines Mediated by
TEMPO Oxoammonium Salts
Heng-rui Huo
Xiang-Ying Tang*
R
CHO
R CHO
Yue-fa Gong*
0
0
0
0
0-
0
0
1
9-
9
4
4
4-
0
5
5
1b (1.0 mol%)
1b (100 mol%)
N
N
N
N
CH3CN, rt
CH3CN, rt
School of Chemistry and Chemical Engineering, Huazhong
University of Science and Technology, 1037 Luoyu Road,
Wuhan 430074, P. R. of China
NH2
N
H
R
R
=
1b
30 examples
12 examples
gongyf@mail.hust.edu.cn
N
O
xytang@hust.edu.cn
up to 98% yield
up to 94% yield
PF6
Received: 29.10.2017
Accepted after revision: 08.04.2018
Published online: 13.06.2018
rolyl/indolyl rings, which provides a metal-free and envi-
ronmentally friendly construction of 4,5-dihydroquinoxal-
ines and 5,6-dihydroquinoxalines.
DOI: 10.1055/s-0037-1610131; Art ID: ss-2017-h0698-op
At the outset, we investigated the model cyclocondensa-
tion reaction between 2-(1H-pyrrol-1-yl)aniline (2a) and
benzaldehyde (3a) at room temperature in the presence of
different oxoammonium salt initiators and solvents (Table
1). When 3.0 mol% of initiator 1a was used, the reaction
was complete within 12 hours and gave product dihydro-
quinazolinone 4aa in 87% yield (Table 1, entry 1). On reduc-
ing the amount of 1a to 1.0 mol%, the reaction proceeded
readily to give a slightly higher yield of 4aa, whereas a fur-
ther reduction to 0.5 mol% of 1a led to a detectable decline
in the reaction rate (Table 1, entries 2 and 3). To our delight,
Abstract We herein describe a novel TEMPO oxoammonium salt initi-
ated Pictet–Spengler reaction of imines, generated in situ from carbon-
yl compounds and pyrrole- or indole-containing substrates, to afford
4,5-dihydropyrrolo[1,2-a]quinoxalines or 5,6-dihydroindolo[1,2-a]quin-
oxalines in good to excellent yields. Moreover, a one-pot synthesis of a
biologically important quinoxaline is achieved via a cyclization–dehy-
drogenation process using one equivalent of the oxoammonium salt.
Key words TEMPO oxoammonium salts, Pictet–Spengler reaction,
imines, dihydroquinoxalines, quinoxalines
Among nitrogen-containing heterocyclic natural prod-
ucts, dihydropyrrolo-/indolo[1,2-a]quinoxalines and their
derivatives are very important scaffolds due to their pres-
ence in a wide range of natural products and pharmaceuti-
cally active compounds.1 As shown in Figure 1, cannabinoid
receptor antagonist A is a CB1R antagonist,2 playing a spe-
cial role in energy homeostasis and in reducing human
body weight. The 5-HT3 receptor antagonist B shows im-
portant activity in the treatment of postoperative nausea
and vomiting.3 Compound C is reported to have anti-HIV
activity,4 whilst compound D demonstrates antiprolifera-
tive activity.5
N
N
N
F
N
N
Cl
O
Cl
NH2
N
N
COOH
O
A
B
CB1R antagonist
5-HT3 receptor antagonist
Thus, numerous efforts have been devoted to construct
these fused ring systems. Dihydroquinoxalines and quinox-
alines are usually synthesized via the Pictet–Spengler reac-
tion6 of 2-(1H-pyrrol-1-yl)aniline or 2-(1H-indol-1-yl)ani-
lines with carbonyl compounds under aerobic heating,7 or
under the catalysis of Lewis acids,8 Brønsted acids9 or I2.9g,10
Considering their important pharmacological activity,
herein, we report a novel TEMPO oxoammonium salt initi-
ated intramolecular cyclization of imines possessing pyr-
N
N
N
NH
N
N
H
O
O
N
C
D
Figure 1 Examples of biologically active dihydroquinoxalines and quin-
oxalines
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

B
H.-r. Huo et al.
Paper
Synthesis
other oxoammonium salts such as 1b–d were effective in
this reaction and delivered the desired product 4aa in excel-
lent yields; among these salts, 1b proved to be the best (Ta-
ble 1, entries 4–6). Next, the effect of the reaction time was
assessed in the presence of 1.0 mol% of 1b (Table 1, entries 7
and 8). Shortening the time to 6 hours reduced the conver-
sion significantly, while extending the reaction time to 18
hours resulted in complete consumption of the substrate,
but the yield was slightly reduced. Next, the effect of other
solvents such as dichloromethane (CH2Cl2), dichloroethane
(DCE), tetrahydrofuran (THF), dimethyl sulfoxide (DMSO)
and ethanol on the reaction was examined (Table 1, entries
9–13), with the results indicating that acetonitrile was still
the most appropriate solvent in terms of the product yield.
No reaction occurred when oxoammonium salt 1 was not
present (Table 1, entry 14). In addition, we found that 4a
could be further oxidized by oxoammonium salt 1 or air to
produce a small amount of 5a.
products 4ab–ai in high yields (Scheme 1). Heteroaromatic
aldehydes were also tolerated under the reaction condi-
tions, and products 4aj and 4ak were obtained in 96% and
91% yields, respectively. For cinnamaldehyde, the cyclocon-
densation was sluggish, providing 4al in a slightly lower
yield (72%), probably due to the chemical instability of cin-
namaldehyde under the reaction conditions. Notably, the
aliphatic aldehyde n-propyl aldehyde was also suitable for
this cyclization, giving 4am in 76% yield. When 1,4-phthal-
aldehyde was employed as the substrate, the double Pictet–
Spengler reaction readily took place to give 4an in 80%
yield.
Further investigation of the Pictet–Spengler reactions of
aldehydes with 2-(1H-indol-1-yl)anilines 2b and 2c was
conducted. As can be seen in Scheme 2, the reactions of ar-
omatic aldehydes with 2-(1H-indol-1-yl)anilines 2b or 2c
all proceeded well to provide the desired products 4ba–cn
in good to excellent yields. For heteroaromatic aldehydes
such as furaldehyde and picolinaldehyde, the reactions pro-
ceeded smoothly to furnish products 4cj and 4ck in 98%
and 92% yields, respectively. Treatment of chromone-3-car-
boxaldehyde and isopropyl aldehyde under the standard re-
action conditions led to the desired products 4cl and 4cm
in isolated yields of 86% and 80%, respectively. Interestingly,
when 1,4-phthalaldehyde was employed as the substrate
the expected product 4cn was obtained in 93% yield. Fur-
thermore, treatment of 2-(1-methyl-1H-indol-3-yl)aniline
(2d) with benzaldehyde (3a) provided the corresponding
product 4da in 85% yield (Scheme 3).
Using the above optimized conditions, we next turned
our efforts to determining the substrate scope of this meth-
odology. The reactions of 2a with different aromatic alde-
hydes all proceeded smoothly to give the corresponding
N
N
1b (1.0 mol%)
R
CHO
+
CH3CN, rt
N
H
R
NH2
2a
3
4a
4aa: R = H, 12 h, 93%
Since the cyclized products could be further oxidized
into the corresponding biologically active quinoxalines, we
performed the cyclization using oxoammonium salt 1b (1.0
equiv). As shown in Scheme 4, four representative sub-
strates 2a–d were chosen to investigate this tandem cy-
clization–dehydrogenation process. The corresponding
products 5aa–ae, 5ba, 5ca–5ce and 5da were obtained in
good to excellent yields.
Based on the above observations, we next synthesized
biologically active compound 4ea, which possesses antican-
cer activity,11 by treating 2e with acetone in the presence of
1.0 mol% of 1b. Gratifyingly, the desired product 4ea was
successfully isolated in 86% yield (Scheme 5). The opera-
tional simplicity, metal-free and mild conditions of this
method make this protocol practical for the synthesis of
such drug candidates.
N
4ab: R = CH3, 18 h, 90%
4ac: R = OCH3, 18 h, 94%
4ad: R = Cl, 18 h, 86%
4ae: R = NO2, 18 h, 88%
N
OCH3
N
H
N
H
R
4af: 18 h, 92%
N
N
N
Cl
O
O
N
H
N
H
N
H
Cl
4ag: 18 h, 92%
4ah: 18 h, 89%
4ai: 18 h, 93%
N
N
N
N
H
N
N
N
H
O
4aj: 18 h, 96%
4ak: 12 h, 91%
4al: 24 h, 72%
Although the actual mechanism for the above transfor-
mations remains to be elucidated, the two reaction path-
ways outlined in Scheme 6 are postulated to explain the
role of the TEMPO oxoammonium salt. In order to verify
whether the interaction between the imine (formed from
amine 2 and aldehyde 3) and the TEMPO oxoammonium
salt promoted the reaction, we determined the chemical
shifts of the protons of the imine and the mixture of
imine/TEMPO oxoammonium salt, respectively. However,
no detectable change was observed in the chemical shift of
N
HN
N
NH
N
N
H
4am: 18 h, 76%
4an: 18 h, 80%a
Scheme 1 Substrate scope of the methodology. Reagents and condi-
tions: 2a (0.5 mmol), 3 (0.6 mmol), 1b (1.0 mol%), CH3CN (2.5 mL), rt. a
Reagents and conditions: 2a (1.2 mmol), 3n (0.5 mmol), 1b (1.0 mol%),
CH3CN (2.5 mL), rt, 18 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

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H.-r. Huo et al.
Paper
Synthesis
1b (1.0 mol%)
R1
R1
R
CHO
+
N
N
CH3CN, rt
N
H
R
NH2
2b (R1 = H)
2c (R1 = CH3)
3
4b/c
4ca: R = H, 12 h, 92%
4cb: R = CH3, 12 h, 96%
4cc: R = OCH3, 12 h, 95%
4cd: R = Cl, 12 h, 97%
4ce: R = NO2, 12 h, 98%
N
N
N
N
H
N
H
N
H
R
OCH3
4cf: 15 h, 95%
4ba: 12 h, 84%
N
N
N
Cl
O
O
N
H
N
H
N
H
Cl
4cg: 15 h, 97%
4ch: 18 h, 87%
4ci: 18 h, 96%
N
N
N
O
N
H
N
H
N
N
H
O
O
4cj: 15 h, 98%
4ck: 12 h, 92%
4cl: 9 h, 86%
N
N
HN
NH
N
N
H
4cn: 12 h, 93%a
4cm: 18 h, 80%
Scheme 2 Further investigations of the substrate scope. Reagents and conditions: 2b or 2c (0.5 mmol), 3 (0.6 mmol), 1b (1.0 mol%), CH3CN (2.5 mL),
rt. a Reagents and conditions: 2c (1.2 mmol), 3n (0.5 mmol), 1b (1.0 mol%), CH3CN (2.5 mL), rt, 12 h.
the proton of the CH=N group. This observation provided
negative evidence for the direct activation of an imine by
the TEMPO oxoammonium salt through the formation of
complex 8 (path a). On the other hand, we found that the
TEMPO oxoammonium salts can be readily reduced by aro-
matic amines such as 2a, and the reaction mixture was sub-
jected to flash chromatography to afford a little amount of
TEMPO. Hence, the proton could be simultaneously re-
leased during oxidation of the aromatic amine. Thus, we
postulate that the above cyclization process might be cata-
lyzed by the proton generated in situ.
In conclusion, we have described TEMPO oxoammoni-
um salts as environmentally friendly and efficient reagents
for initiating the intramolecular Pictet–Spengler reactions
of imines possessing pyrrolyl/indolyl rings. The easy to han-
dle and metal-free conditions for this process are beneficial
CHO
N
N
1b (1.0 mol%)
+
CH3CN, rt
N
Ph
NH2
H
2d
3a
4da: 18 h, 85%
Scheme 3 Reagents and conditions: 2d (0.5 mmol), 3a (0.6 mmol), 1b
(1.0 mol%), CH3CN (2.5 mL), rt, 18 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

D
H.-r. Huo et al.
Paper
Synthesis
for the practical production of biologically important 4,5-
dihydropyrrolo[1,2-a]quinoxalines and 5,6-dihydroindo-
lo[1,2-a]quinoxalines.
3 (1.2 equiv)
1b (1.0 equiv)
N
N
N
CH3CN, rt
R1
N
H
R1
N
NH2
All reagents and solvents were purchased from Reagent Co. and were
used without further purification. Reactions were monitored by TLC
analysis using Yantai Jiangyou Silicone Development Co., Ltd. silica gel
60 Å F-254 thin-layer plates. Flash column chromatography was per-
formed on Qingdao Haiyang Chemical Co., Ltd. silica gel 60 Å, 10–40
μm. Melting points were determined with an Electrothermal melting
point apparatus and are uncorrected. IR spectra were recorded as thin
films between KBr plates using a Bruker FT-IR spectrophotometer. 1H
NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on a
Bruker AV 400 spectrometer. Chemical shifts are reported in ppm rel-
ative to tetramethylsilane with the solvent resonance as the internal
2
4
5
5aa: R = H, 90%
5ab: R = CH3, 83%
5ac: R = OCH3, 75%
5ad: R = Cl, 92%
N
N
N
5ae: R = NO2, 87%
N
Ph
R
5ba: 86%
5ca: R = H, 92%
5cb: R = CH3, 89%
5cc: R = OCH3, 81%
5cd: R = Cl, 94%
5ce: R = NO2, 90%
N
N
N
N
Ph
N
N
1b (1.0 mol%)
O
5da: 90%
+
R
MeO
MeO
CH3CN, rt
NH2
N
H
Scheme 4 One-pot synthesis of quinoxalines. Reagents and conditions:
2 (0.5 mmol), 3 (0.6 mmol), 1b (1.0 mol%), CH3CN (2.5 mL), 12–18 h,
then 1b (0.5 mmol) was added and the mixture stirred for an additional
6 h at rt.
O
O
2e
4ea: 18 h, 86%
Scheme 5 Synthesis of biologically active compound 4ea
Table 1 Optimization of the Reaction Conditionsa
Y– = BF4 (1a)
–
N
Ph CHO (3a)
N
–
N
PF6 (1b)
+
N
O
–
ClO4 (1c)
Cat. (x mol%)
Y–
TfO– (1d)
Ph
N
H
Ph
NH2
N
solvent, rt, time
2a
4aa
5aa
Entry
Cat. (x)
Solvent
Time (h)
Yield of 4aa (%)b
Yield of 5aa (%)b
1
2
1a (3.0)
1a (1.0)
1a (0.5)
1b (1.0)
1c (1.0)
1d (1.0)
1b (1.0)
1b (1.0)
1b (1.0)
1b (1.0)
1b (1.0)
1b (1.0)
1b (1.0)
–
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
DCE
12
12
12
12
12
12
6
87
90
68
93
89
85
62
85
88
89
35
46
74
NDc
8
<5
<5
<5
<5
<5
<5
11
<5
<5
<5
<5
<5
NDc
3
4
5
6
7
8
18
12
12
12
12
12
12
9
10
11
12
13
14
THF
DMSO
EtOH
CH3CN
a Unless otherwise specified, all reactions were carried out using 2a (0.5 mmol), 3a (0.6 mmol), 1 (x mol%) in the indicated solvent (2.5 mL) at rt for the given
time.
b Yield of isolated product.
c ND = not detected.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

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H.-r. Huo et al.
Paper
Synthesis
O
N
N
N
N
+
Ph CHO
N
O
N
Ph
path a
NH2
N
Ph
8
2a
3a
6
O
N
path b
H+
H+
N
N
N
H
7
Ph
N
H
Ph
4aa
Scheme 6 A proposed mechanism for the catalytic process
standard. Data are reported as follows: chemical shift, multiplicity (s:
singlet, d: doublet, t: triplet, q: quartet, m: multiplet, and br s: broad
singlet), coupling constant(s) (Hz), integration. 13C NMR spectra were
recorded with complete proton decoupling. Chemical shifts are re-
ported in ppm relative to tetramethylsilane with the solvent reso-
nance as internal standard. High-resolution mass spectrometry was
performed using a TOF-Q mass spectrometer equipped with an ESI
source.
HRMS (ESI): m/z [M2 – ClO4]+ calcd for C18H36N2O6Cl: 411.2256;
found: 411.2248.
TEMPO+OTf– (1d)
The same procedure with TfOH instead of 50% HBF4 provided
TEMPO+OTf– (1d) (9.1 g, 29.7 mmol, 58%) as a yellow solid; mp 147–
148 °C.
HRMS (ESI): m/z [M2 – OTf]+ calcd for C18H36N2O3Tf: 461.2292; found:
461.2270.
TEMPO+BF4– (1a); Typical Procedure (Scheme 7)
2-(1H-Pyrrol-1-yl)aniline (2a)13 (Scheme 8)
–
Y– = BF4 (1a)
HY
–
PF6 (1b)
NaOCl
+
–
N
O
N
O
ClO4 (1c)
Y–
O
NH2
NO2
TfO– (1d)
O
N
N
CuSO4·5H2O
NaBH4, EtOH
AcOH
O
+
Scheme 7
reflux, 1 h
NO2
NH2
Scheme 8
–
Synthesis of TEMPO+BF4 (1a). Tetrafluoroboric acid (HBF4) (50% in
H2O, 7.8 mL, 61.4 mmol, 1.2 equiv) was added dropwise to a solution
of TEMPO (8.0 g, 51.2 mmol, 1 equiv) in Et2O (40 mL) over 0.5 h at
0 °C. After the solution had become amber in color, NaOCl (18.0 mL,
25.6 mmol) was added over 1 h at 0 °C and the mixture was stirred
for an additional 1 h at 0 °C. The formed yellow precipitate was fil-
tered and washed with ice-cold 5% NaHCO3 (15 mL), H2O (30 mL) and
Et2O (100 mL). The solid was dried in vacuo at 50 °C over 24 h to yield
TEMPO+BF4– (1a) (9.0 g, 36.9 mmol, 72%) as a bright yellow solid; mp
155–156 °C (Lit.12 162–163 °C).
A mixture of o-nitroaniline (3.45 g, 25.00 mmol) and 2,5-dimethoxy-
tetrahydrofuran (3.2 mL, 25.00 mmol) in AcOH was refluxed for 1 h
with vigorous stirring. The reaction mixture was cooled to ambient
temperature and then poured into H2O. The precipitate was filtered,
washed with H2O, dissolved in EtOAc, dried over Na2SO4 and evapo-
rated to dryness under reduced pressure. The residue was filtered
through a short pad of silica gel (hexane/EtOAc, 20:1), to afford 1-(2-
nitrophenyl)-1H-pyrrole, which was used directly in the next step
without any further purification.
HRMS (ESI): m/z [M2 – BF4]+ calcd for C18H36N2O2BF4: 399.2800;
Yield: 4.42 g (94%); brown oil.
found: 399.2790.
1H NMR (400 MHz, CDCl3): δ = 7.85 (dd, J = 8.4, 1.2 Hz, 1 H), 7.67–7.63
(m, 1 H), 7.49 (dd, J = 1.2, 1.2 Hz, 1 H), 7.47–7.44 (m, 1 H), 6.79 (dd, J =
2.0, 2.0 Hz, 2 H), 6.37–6.36 (dd, J = 2.0, 2.0 Hz, 2 H).
TEMPO+PF6– (1b)
The same procedure with 60% HPF6 instead of 50% HBF4 provided
TEMPO+PF6– (1b) (11.4 g, 37.9 mmol, 74%) as a yellow solid; mp 144–
145 °C.
2-(1H-Pyrrol-1-yl)aniline (2a)
HRMS (ESI): m/z [M2 – PF6]+ calcd for C18H36N2O2PF6: 457.2413;
found: 457.2385.
To a solution of 1-(2-nitrophenyl)-1H-pyrrole (3.76 g, 20 mmol) in
EtOH (80 mL) was added CuSO4·5H2O (6.24 g, 25 mmol). NaBH4 (1.51
g, 40 mmol) was then added portionwise at 0 °C and the reaction
mixture was stirred at room temperature for 1 h. The mixture was fil-
tered through a short pad of silica gel using EtOAc (3 × 40 mL) as elu-
ent. The solvent was evaporated in vacuo and the residue was sub-
jected to flash chromatography (petroleum ether/EtOAc, 20:1) to af-
ford 2-(1H-pyrrol-1-yl)aniline (2a).
TEMPO+ClO4– (1c)
The same procedure with 70% HClO4 instead of 50% HBF4 provided
TEMPO+ClO4– (1c) (8.9 g, 34.8 mmol, 68%) as a yellow solid; mp 125–
126 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

F
H.-r. Huo et al.
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Synthesis
Yield: 2.69 g (85%); white crystalline solid; mp 94–95 °C.
2-(1H-Indol-1-yl)aniline (2b)
1H NMR (400 MHz, DMSO-d6): δ = 7.17–7.13 (m, 2 H), 6.83–6.78 (m, 4
H), 6.34 (d, J = 2.0 Hz, 2 H), 3.53 (br s, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 137.3, 123.8, 122.8, 122.4, 117.0,
Yield: 3.17 g (95%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.69 (dd, J = 7.2, 1.2 Hz, 1 H), 7.18 (m, 6
H), 6.82 (dd, J = 7.6, 7.6 Hz, 2 H), 6.68 (d, J = 3.2 Hz, 1 H), 3.41 (br s, 2
H).
113.7, 111.4, 104.7.
13C NMR (100 MHz, CDCl3): δ = 143.1, 136.4, 129.1, 128.60, 128.57,
2-(1H-Indol-1-yl)aniline (2b) and 2-(3-Methyl-1H-indol-1-yl)ani-
124.9, 122.2, 120.9, 120.1, 118.5, 116.2, 110.7, 103.2.
line (2c)9d (Scheme 9)
2-(3-Methyl-1H-indol-1-yl)aniline (2c)
Yield: 3.46 g (95%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.63 (dd, J = 6.8, 2.4 Hz, 1 H), 7.23–7.15
(m, 4 H), 7.14–7.09 (m, 1 H), 6.98 (d, J = 0.8 Hz, 1 H), 6.85–6.79 (m, 2
H), 3.41 (br s, 2 H), 2.38 (d, J = 1.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.1, 136.7, 129.0, 128.9, 128.6,
126.1, 125.2, 122.2, 119.5, 119.1, 118.6, 116.3, 112.4, 110.6, 9.7.
F
NaOH
DMSO
CuSO4·5H2O
NaBH4, EtOH
N
+
N
NO2
H
N
NO2
NH2
2b,c
2-(1-Methyl-1H-indol-3-yl)aniline (2d)14 (Scheme 10)
Scheme 9
Br
To a well-stirred solution of 1H-indole (2.34 g, 20 mmol) or 3-methyl-
1H-indole (2.62 g, 20 mmol) in DMSO (40 mL) were added slowly
NaOH (0.80 g, 20 mmol) and 1-fluoro-2-nitrobenzene (2.1 mL, 20
mmol). The reaction mixture was stirred vigorously for 1–1.5 h at
room temperature until no more starting material was detectable by
TLC analysis. The reaction mixture was extracted with EtOAc and the
combined organics washed with H2O and dried over Na2SO4. The sol-
vent was evaporated in vacuo and the obtained solid was purified by
column chromatography on silica gel (petroleum ether/EtOAc, 20:1)
to afford 1-(2-nitrophenyl)-1H-indole or 3-methyl-1-(2-nitrophe-
nyl)-1H-indole.
NO2
CH3I, NaH
THF
Pd(OAc)2, PPh3
TBAB, K2CO3
N
N
N
H
NO2
Scheme 10
To a solution of 1H-indole (1.41 g, 12 mmol) in THF (30 mL) at 0 °C
was added NaH (60% in mineral oil, 720 mg, 18 mmol). The reaction
was warmed to room temperature and allowed to stir for 30 min as a
dark blue color developed. After 30 min, the reaction flask was cooled
to 0 °C and iodomethane (0.93 mL, 15 mmol) was added dropwise.
The mixture was warmed to room temperature and allowed to stir
until all the starting material had been consumed. The mixture was
cooled to 0 °C and quenched with saturated NH4Cl. The product was
extracted with Et2O (3 × 30 mL) and washed with H2O (60 mL) and
sat. NaCl (60 mL). The organic phase was concentrated in vacuo to
give a yellow liquid, which was purified via flash chromatography on
silica gel (petroleum ether/EtOAc, 60:1) to give 1-methyl-1H-indole.
1-(2-Nitrophenyl)-1H-indole
Yield: 3.81 g (80%); yellow crystalline solid; mp 84–85 °C.
1H NMR (400 MHz, CDCl3): δ = 7.97 (dd, J = 8.4, 1.6 Hz, 1 H), 7.67–7.63
(m, 2 H), 7.50 (m, 2 H), 7.19–7.14 (m, 2 H), 7.13–7.10 (m, 2 H), 6.70 (d,
J = 3.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 146.3, 136.7, 133.8, 132.9, 129.8,
129.0, 128.4, 128.1, 125.5, 123.0, 121.4, 121.0, 109.6, 105.1.
3-Methyl-1-(2-nitrophenyl)-1H-indole
Yield: 4.14 g (82%); brown crystalline solid; mp 56–57 °C.
1-Methyl-1H-indole
1H NMR (400 MHz, CDCl3): δ = 7.96 (dd, J = 8.0, 1.2 Hz, 1 H), 7.64 (ddd,
J = 8.0, 8.0, 1.6 Hz, 1 H), 7.62–7.57 (m, 1 H), 7.51 (dd, J = 8.0, 1.2 Hz, 1
H), 7.48–7.43 (m, 1 H), 7.20–7.14 (m, 2 H), 7.13–7.08 (m, 1 H), 6.90 (d,
J = 0.8 Hz, 1 H), 2.35 (d, J = 1.2 Hz, 3 H).
Yield: 1.54 g (98%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.62 (dd, J = 8.0, 2.4 Hz, 1 H), 7.29 (d,
J = 8.4 Hz, 1 H), 7.23–7.18 (m, 1 H), 7.11–7.07 (m, 1 H), 7.00 (dd, J =
2.8, 1.6 Hz, 1 H), 6.47 (dd, J = 2.4, 2.4 Hz, 1 H), 3.72 (d, J = 0.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 146.0, 136.8, 133.6, 133.1, 129.7,
1-Methyl-1H-indole (1.31 g, 10 mmol), Pd(OAc)2 (225 mg, 1.0 mmol),
PPh3 (197 mg, 0.75 mmol), K2CO3 (4.15 g, 30 mmol) and TBAB (739
mg, 2 mmol) were added to an oven-dried 100 mL round-bottom
flask. The flask was closed with a septum, evacuated and backfilled
with argon. Next, a solution of 2-bromo-1-nitrobenzene (2.02 g, 10
mmol) in dry DMF (50 mL) was added under an inert atmosphere at
room temperature. The resulting mixture was heated at 115 °C under
an argon atmosphere. After completion of the reaction, the mixture
was washed with H2O (2 × 30 mL) and extracted with EtOAc. The
combined organic layers were dried and evaporated. The residue was
purified by column chromatography (hexanes/EtOAc, 60:1) to afford
pure 1-methyl-3-(2-nitrophenyl)-1H-indole.
129.5, 127.8, 125.5, 125.3, 123.0, 120.5, 119.5, 114.5, 109.4, 9.7.
CuSO4·5H2O (4.49 g, 18 mmol) and NaBH4 (0.85 g, 22.5 mmol) were
added portionwise at 0 °C to a solution of 1-(2-nitrophenyl)-1H-in-
dole (3.57 g, 15 mmol) or 3-methyl-1-(2-nitrophenyl)-1H-indole
(3.78 g, 15 mmol) in EtOH (50 mL). The reaction mixture was then
stirred at room temperature for 1 h. The mixture was filtered through
a short pad of silica gel using EtOAc (3 × 30 mL) as the eluent. The sol-
vent was evaporated in vacuo and the residue was subjected to flash
chromatography (petroleum ether/EtOAc, 15:1) to afford the expect-
ed indole.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

G
H.-r. Huo et al.
Paper
Synthesis
1-Methyl-3-(2-nitrophenyl)-1H-indole
pressure. The crude residue was purified by flash column chromatog-
raphy (petroleum ether/EtOAc, 20:1) to afford methyl 3-amino-4-(in-
dolin-1-yl)benzoate.
Yield: 0.78 g (31%); brown solid; mp 128–130 °C.
1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 7.6 Hz, 1 H), 7.71 (ddd, J =
7.6, 7.6, 1.2 Hz, 1 H), 7.63 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H), 7.58 (d, J = 7.6
Hz, 1 H), 7.46 (dd, J = 7.6, 1.2 Hz, 1 H), 7.33 (d, J = 8.0 Hz, 1 H), 7.29–
7.25 (m, 2 H), 7.15 (dd, J = 7.6, 7.6 Hz, 1 H), 3.51 (s, 3 H).
Methyl 3-Amino-4-(indolin-1-yl)benzoate
Yield: 1.85 g (86%); off-white solid; mp 102–103 °C.
1H NMR (400 MHz, CDCl3): δ = 7.52 (d, J = 1.6 Hz, 1 H), 7.45 (dd, J = 8.4,
2.0 Hz, 1 H), 7.22 (d, J = 8.0 Hz, 1 H), 7.19 (d, J = 7.2 Hz, 1 H), 7.03 (dd,
J = 7.6, 7.6 Hz, 1 H), 6.76 (dd, J = 6.8, 6.8 Hz, 1 H), 6.35 (d, J = 7.6 Hz, 1
H), 3.89 (m, 5 H), 3.80 (br s, 2 H), 3.14 (t, J = 8.2 Hz, 2 H).
2-(1-Methyl-1H-indol-3-yl)aniline (2d) (Scheme 11)
13C NMR (100 MHz, CDCl3): δ = 167.1, 149.0, 142.5, 135.9, 130.7,
127.7, 127.2, 124.8, 123.1, 120.4, 119.2, 117.0, 109.5, 53.8, 52.0, 28.9.
CuSO4·5H2O
N
N
NaBH4, EtOH
Methyl 3-Amino-4-(1H-indol-1-yl)benzoate (2e) (Scheme 13)
NO2
NH2
Scheme 11
To a solution of 1-methyl-3-(2-nitrophenyl)-1H-indole (757 mg, 3
mmol) in EtOH (12 mL) was added CuSO4·5H2O (899 mg, 3.6 mmol).
NaBH4 (170 mg, 4.5 mmol) was then added portionwise at 0 °C and
the mixture was stirred at room temperature for 1 h. The reaction
mixture was filtered through a short pad of silica gel using EtOAc
(3 × 15 mL) as the eluent. The solvent was evaporated in vacuo and
the residue was subjected to flash chromatography (petroleum
ether/EtOAc, 20:1) to afford 2-(1-methyl-1H-indol-3-yl)aniline (2d).
DDQ
N
N
EtOAc, rt, 4 h
MeO2C
NH2
MeO2C
NH2
Scheme 13
A mixture of methyl 3-amino-4-(indolin-1-yl)benzoate (1.00 g, 3.7
mmol) and DDQ (1.70 g, 7.5 mmol) in EtOAc (15 mL) was stirred at
room temperature for 4 h. Upon completion of the reaction, the mix-
ture was partitioned between 1 M NaOH and EtOAc. The aqueous lay-
er was extracted with EtOAc (3 × 20 mL) and the combined organic
layers were dried over Na2SO4 and concentrated in vacuo. The residue
was purified by flash column chromatography (petroleum ether/EtOAc,
20:1) to furnish methyl 3-amino-4-(1H-indol-1-yl)benzoate (2e).
Yield: 433 mg (65%); yellow crystalline solid; mp 127–128 °C.
1H NMR (400 MHz, CDCl3): δ = 7.61 (d, J = 8.0 Hz, 1 H), 7.36 (d, J = 8.0
Hz, 1 H), 7.30–7.24 (m, 2 H), 7.16–7.12 (m, 3 H), 6.81 (dd, J = 13.2, 7.2
Hz, 2 H), 3.81 (s, 3 H), 3.69 (br s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 144.8, 137.1, 131.3, 127.8, 127.7,
127.0, 122.1, 120.7, 120.5, 119.7, 118.4, 115.5, 113.3, 109.6, 32.9.
Yield: 542 mg (55%); off-white solid; mp 63–64 °C.
Methyl 3-Amino-4-(1H-indol-1-yl)benzoate (2e)15 (Scheme 12)
1H NMR (400 MHz, CDCl3): δ = 7.68 (dd, J = 8.0, 1.2 Hz, 1 H), 7.55 (d,
J = 1.6 Hz, 1 H), 7.49 (dd, J = 8.0, 1.6 Hz, 1 H), 7.24–7.11 (m, 5 H), 6.70
(d, J = 3.2 Hz, 1 H), 3.91 (s, 3 H), 3.54 (br s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 166.8, 142.8, 136.0, 130.6, 128.8,
128.7, 128.4, 128.1, 122.6, 121.2, 120.6, 119.6, 117.5, 110.8, 104.0,
52.3.
To a stirred solution of indoline (941 μL, 8.4 mmol) in dry CH2Cl2 (20
mL) was added methyl 4-fluoro-3-nitrobenzoate (1.84 g, 9.2 mmol)
and K2CO3 (2.32 g, 16.8 mmol) under an argon atmosphere, and the
resulting mixture was refluxed for 4 h. Upon completion of the reac-
tion, the solvent was removed, and the crude product was partitioned
between H2O and EtOAc. The aqueous layer was extracted with EtOAc
(3 × 30 mL) and the combined organic layers were dried over Na2SO4
and concentrated in vacuo to furnish methyl 4-(indolin-1-yl)-3-nitro-
benzoate as a red solid (2.38 g, 95%). The crude product was used for
further transformation without further purification.
4,5-Dihydroquinoxalines 4; General Procedure
A mixture of arylamine 2 (0.5 mmol) and aldehyde 3 (0.6 mmol) in
CH3CN (2.5 mL, 0.2 M) was stirred for 15 min at room temperature.
TEMPO oxoammonium salt 1b (1.0 mol%) was then introduced. The
mixture was stirred at room temperature and the reaction progress
was monitored by TLC. Upon completion, the mixture was directly
purified by flash column chromatography (petroleum ether/EtOAc,
80:1–20:1) to afford the desired 4,5-dihydroquinoxaline 4.
A mixture of methyl 4-(indolin-1-yl)-3-nitrobenzoate (2.10 g, 7.0
mmol), ammonium formate (2.2 g, 35.2 mmol) and Zn powder (4.6 g,
70.4 mmol) in dry MeOH (50 mL) was stirred at room temperature for
15 min. Upon completion of the reaction, the mixture was filtered
through a short pad of silica gel and the solvent was evaporated. The
product was dissolved in CH2Cl2 (75 mL), precipitated ammonium for-
mate was filtered off and the solvent was evaporated under reduced
4-Phenyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (4aa)9d
Yield: 115 mg (93%); pale yellow solid; mp 89–90 °C.
F
K2CO3, DCM
Zn, HCOONH4
N
N
+
reflux, 4 h
MeOH, rt, 15 min
MeO2C
N
MeO2C
NO2
H
MeO2C
NO2
NH2
Scheme 12
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

H
H.-r. Huo et al.
Paper
Synthesis
IR (KBr): 3433, 3346, 3059, 2923, 1605, 1512, 1487, 1384, 1332, 1281,
1059, 1029, 752, 702, 627 cm–1
4-(3-Methoxyphenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline
.
(4af)9o
1H NMR (400 MHz, CDCl3): δ = 7.44 (dd, J = 8.0, 1.6 Hz, 2 H), 7.38–7.29
(m, 4 H), 7.17 (dd, J = 2.4, 1.2 Hz, 1 H), 6.94 (ddd, J = 7.6, 7.6, 1.2 Hz, 1
H), 6.82 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H), 6.69 (dd, J = 7.6, 1.2 Hz, 1 H),
6.23 (dd, J = 3.2, 3.2 Hz, 1 H), 5.57–5.56 (m, 1 H), 5.49 (s, 1 H), 4.12 (br
s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 141.5, 136.2, 130.0, 128.7, 128.3,
128.0, 125.5, 124.7, 119.4, 115.4, 114.8, 114.4, 110.2, 105.9, 56.2.
Yield: 127 mg (92%); white solid; mp 129–130 °C.
IR (KBr): 3326, 3060, 2960, 1600, 1513, 1485, 1467, 1336, 1263, 1028,
755, 714, 635, 555 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.30 (d, J = 8.0 Hz, 1 H), 7.26 (dd, J = 8.4,
8.4 Hz, 1 H), 7.16 (dd, J = 2.4, 1.2 Hz, 1 H), 7.02–7.00 (m, 2 H), 6.94
(ddd, J = 7.6, 7.6, 0.8 Hz, 1 H), 6.87–6.79 (m, 2 H), 6.69 (dd, J = 8.0, 0.8
Hz, 1 H), 6.23 (dd, J = 3.2, 3,2 Hz, 1 H), 5.61–5.60 (m, 1 H), 5.47 (s, 1 H),
4.14 (br s, 1 H), 3.75 (s, 3 H).
4-(p-Tolyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (4ab)
Yield: 116 mg (90%); colorless oil.
13C NMR (100 MHz, CDCl3): δ = 159.9, 143.1, 136.1, 129.8, 129.7,
125.5, 124.7, 120.3, 119.4, 115.4, 114.8, 114.4, 114.0, 113.2, 110.3,
105.9, 56.2, 55.3.
IR (KBr): 3447, 3345, 2924, 2854, 1743, 1655, 1626, 1597, 1384, 1216,
1160, 1117, 1034, 636, 507 cm–1
.
HRMS (ESI): m/z [M + H]+ calcd for C18H17N2O: 277.1335; found:
1H NMR (400 MHz, CDCl3): δ = 7.31–7.26 (m, 3 H), 7.15–7.12 (m, 3 H),
6.91 (dd, J = 7.6, 7.6 Hz, 1 H), 6.79 (dd, J = 7.6, 7.6 Hz, 1 H), 6.64 (d, J =
8.0 Hz, 1 H), 6.21 (dd, J = 3.2, 3.2 Hz, 1 H), 5.56 (dd, J = 2.0, 1.2 Hz, 1 H),
5.42 (s, 1 H), 4.05 (br s, 1 H), 2.33 (s, 3 H).
277.1361.
4-(2,4-Dichlorophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline
(4ag)9d
13C NMR (100 MHz, CDCl3): δ = 138.6, 138.0, 136.4, 130.3, 129.4,
Yield: 145 mg (92%); white solid; mp 138–139 °C.
127.9, 125.6, 124.7, 119.4, 115.4, 114.8, 114.4, 110.3, 105.9, 56.0, 21.3.
HRMS (ESI): m/z [M + H]+ calcd for C18H17N2: 261.1386; found:
IR (KBr): 3438, 3312, 3134, 2924, 2830, 1588, 1513, 1469, 1384, 1332,
1041, 778, 748, 714, 665, 578 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.39 (s, 1 H), 7.33 (dd, J = 8.0, 0.8 Hz, 1
H), 7.22 (dd, J = 2.8, 1.6 Hz, 1 H), 7.11 (d, J = 1.2 Hz, 2 H), 6.93 (ddd, J =
7.6, 7.6, 1.2 Hz, 1 H), 6.83 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H), 6.67 (dd, J =
7.6, 1.2 Hz, 1 H), 6.30 (dd, J = 3.2, 3.2 Hz, 1 H), 6.02 (s, 1 H), 5.81–5.80
(m, 1 H), 4.33 (br s, 1 H).
261.1381.
4-(4-Methoxyphenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline
(4ac)9d
Yield: 130 mg (94%); white solid; mp 125–126 °C.
13C NMR (100 MHz, CDCl3): δ = 138.3, 134.9, 134.2, 133.3, 130.2,
129.3, 127.7, 126.9, 125.3, 124.9, 119.7, 115.7, 114.7, 114.6, 110.5,
106.1, 51.5.
IR (KBr): 3431, 3332, 2932, 2801, 1606, 1511, 1484, 1336, 1287, 1238,
1173, 1155, 1022, 778, 751, 708, 674, 603 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 8.8 Hz, 2 H), 7.31 (dd, J = 7.6,
1.2 Hz, 1 H), 7.17 (dd, J = 2.4, 1.2 Hz, 1 H), 6.95 (ddd, J = 7.6, 7.6, 1.2 Hz,
1 H), 6.89 (d, J = 8.8 Hz, 2 H), 6.82 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H), 6.70
(dd, J = 7.6, 1.2 Hz, 1 H), 6.23 (dd, J = 3.2, 3.2 Hz, 1 H), 5.56 (dd, J = 1.6,
0.8 Hz, 1 H), 5.44 (s, 1 H), 4.09 (br s, 1 H), 3.79 (s, 3 H).
4-(Benzo[d][1,3]dioxol-5-yl)-4,5-dihydropyrrolo[1,2-a]quinoxal-
ine (4ah)9p
Yield: 129 mg (89%); colorless oil.
13C NMR (100 MHz, CDCl3): δ = 159.6, 136.4, 133.5, 130.5, 129.2,
125.6, 124.7, 119.3, 115.4, 114.8, 114.3, 114.0, 110.2, 105.8, 55.7, 55.3.
IR (KBr): 3362, 3139, 3066, 2893, 1609, 1512, 1484, 1444, 1336, 1248,
1038, 932, 746, 705 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.20 (d, J = 6.8 Hz, 1 H), 7.07–7.06 (m, 1
H), 6.86–6.82 (m, 2 H), 6.78 (dd, J = 8.0, 1.6 Hz, 1 H), 6.74–6.70 (m, 1
H), 6.67 (d, J = 8.0 Hz, 1 H), 6.60 (d, J = 8.0 Hz, 1 H), 6.14 (dd, J = 3.2, 3.2
Hz, 1 H), 5.82 (s, 2 H), 5.52 (d, J = 3.2 Hz, 1 H), 5.32 (s, 1 H), 4.02 (br s,
1 H).
13C NMR (100 MHz, CDCl3): δ = 148.0, 147.6, 136.1, 135.5, 130.0,
125.4, 124.7, 121.3, 119.4, 115.4, 114.7, 114.4, 110.2, 108.3, 108.1,
105.9, 101.2, 55.9.
4-(4-Chlorophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (4ad)9k
Yield: 121 mg (86%); white crystalline solid; mp 176–177 °C.
IR (KBr): 3433, 3343, 3044, 2923, 2853, 1592, 1473, 1421, 1340, 1088,
1039, 826, 749, 712, 595 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.29 (m, 5 H), 7.17–7.16 (m, 1 H),
6.97–6.93 (m, 1 H), 6.86–6.81 (m, 1 H), 6.71 (dd, J = 7.6, 1.2 Hz, 1 H),
6.24–6.22 (m, 1 H), 5.55–5.54 (m, 1 H), 5.47 (s, 1 H), 4.09 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.0, 135.9, 134.1, 129.4, 129.3,
128.9, 125.5, 124.8, 119.6, 115.4, 114.8, 114.5, 110.3, 106.0, 55.6.
HRMS (ESI): m/z [M + H]+ calcd for C18H15N2O2: 291.1128; found:
291.1158.
4-(Naphthalen-1-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (4ai)
Yield: 137 mg (93%); white crystalline solid; mp 114–115 °C.
IR (KBr): 3415, 3333, 3053, 2869, 1597, 1514, 1475, 1331, 1290, 1231,
4-(4-Nitrophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (4ae)9d
Yield: 128 mg (88%); yellow solid; mp 132–133 °C.
IR (KBr): 3340, 3133, 3102, 3070, 1601, 1514, 1487, 1344, 1286, 1154,
1160, 806, 771, 702, 671, 636, 566, 519 cm–1
.
783, 751, 704, 660 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 8.4 Hz, 1 H), 7.88–7.85 (m, 1
H), 7.81 (d, J = 8.0 Hz, 1 H), 7.60 (d, J = 6.8 Hz, 1 H), 7.46–7.39 (m, 3 H),
7.35 (dd, J = 8.0, 0.8 Hz, 1 H), 7.20 (dd, J = 2.8, 1.6 Hz, 1 H), 6.93 (ddd,
J = 7.6, 7.6, 1.2 Hz, 1 H), 6.83 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H), 6.65 (dd, J =
7.6, 1.2 Hz, 1 H), 6.24 (s, 1 H), 6.18 (dd, J = 3.2, 3.2 Hz, 1 H), 5.49–5.48
(m, 1 H), 4.14 (br s, 1 H).
1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 8.4 Hz, 2 H), 7.55 (d, J = 8.4
Hz, 2 H), 7.30 (dd, J = 7.6, 0.8 Hz, 1 H), 7.18 (dd, J = 2.8, 1.2 Hz, 1 H),
6.97 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H), 6.85 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H),
6.75 (dd, J = 8.0, 1.2 Hz, 1 H), 6.24 (dd, J = 3.2, 3.2 Hz, 1 H), 5.61 (s, 1
H), 5.56–5.55 (m, 1 H), 4.25 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 148.9, 147.7, 135.3, 128.6, 128.0,
125.2, 125.0, 123.9, 119.9, 115.6, 114.9, 110.5, 106.3, 55.4.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

I
H.-r. Huo et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3): δ = 136.7, 136.4, 134.2, 131.3, 129.3,
128.90, 128.86, 126.2, 125.83, 125.78, 125.6, 125.5, 124.8, 124.1,
119.5, 115.6, 114.8, 114.3, 110.3, 106.3, 53.4.
HRMS (ESI): m/z [M + H]+ calcd for C21H17N2: 297.1386; found:
297.1390.
1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.0 Hz, 1 H), 7.13–7.12 (m, 1
H), 6.94–6.90 (m, 1 H), 6.79–6.75 (m, 1 H), 6.70 (dd, J = 7.6, 1.2 Hz, 1
H), 6.29 (dd, J = 3.2, 3.2 Hz, 1 H), 5.98–5.97 (m, 1 H), 4.36 (dd, J = 6.4,
5.6 Hz, 1 H), 3.96 (br s, 1 H), 1.94–1.83 (m, 1 H), 1.81–1.70 (m, 1 H),
1.02 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 136.0, 129.6, 125.5, 124.6, 119.0,
115.3, 114.6, 114.1, 110.0, 104.0, 52.3, 28.3, 9.9.
4-(Furan-2-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (4aj)
Yield: 113 mg (96%); pale yellow oil.
1,4-Bis(4,5-dihydropyrrolo[1,2-a]quinoxalin-4-yl)benzene (4an)9d
Yield: 165 mg (80%); white solid; mp >300 °C.
IR (KBr): 3364, 3116, 2920, 2805, 1613, 1516, 1482, 1425, 1337, 1289,
1177, 1011, 742, 710, 602, 531 cm–1
.
IR (KBr): 3463, 3340, 3266, 3136, 2926, 2788, 1607, 1513, 1471, 1418,
1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 0.8 Hz, 1 H), 7.28–7.27 (m, 1
H), 7.16 (dd, J = 2.8, 1.2 Hz, 1 H), 6.91 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H),
6.80 (dd, J = 7.6, 1.2 Hz, 1 H), 6.69–6.66 (m, 1 H), 6.29 (dd, J = 3.2, 3.2
Hz, 1 H), 6.22 (dd, J = 3.2, 2.0 Hz, 1 H), 6.04 (d, J = 3.2 Hz, 1 H), 5.99 (d,
J = 2.8 Hz, 1 H), 5.65 (s, 1 H), 4.32 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 154.6, 142.4, 134.9, 125.9, 125.4,
124.8, 119.6, 115.8, 114.7, 114.6, 110.4, 110.3, 107.1, 105.8, 49.3.
1335, 1286, 1215, 1157, 1049, 1021, 765, 745, 704, 624, 507 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 7.48 (d, J = 7.6 Hz, 2 H), 7.42 (s, 2
H), 7.31 (s, 4 H), 6.91 (dd, J = 7.2, 7.2 Hz, 2 H), 6.85 (d, J = 7.2 Hz, 2 H),
6.70 (dd, J = 7.2, 7.2 Hz, 2 H), 6.60 (s, 2 H), 6.17 (dd, J = 3.2, 3.2 Hz, 2
H), 5.62 (d, J = 2.0 Hz, 2 H), 5.54 (s, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 142.6, 137.0, 129.4, 127.6, 125.1,
124.7, 118.1, 115.5, 115.0, 110.4, 105.5, 54.2.
HRMS (ESI): m/z [M + H]+ calcd for C28H23N4: 415.1917; found:
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2O: 237.1022; found:
237.1031.
415.1889.
4-(Pyridin-2-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (4ak)16
Yield: 112 mg (91%); pale yellow solid; mp 125–126 °C.
6-Phenyl-5,6-dihydroindolo[1,2-a]quinoxaline (4ba)9d
Yield: 124 mg (84%); yellow solid; mp 118–119 °C.
IR (KBr): 3455, 3267, 3059, 2985, 2929, 1611, 1589, 1513, 1469, 1429,
1338, 1288, 752, 712, 684, 648 cm–1
.
IR (KBr): 3446, 3335, 3057, 2924, 2853, 1685, 1654, 1598, 1508, 1454,
1386, 1214, 1156, 765, 744, 702, 648, 506 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.52–8.50 (m, 1 H), 7.48 (ddd, J = 7.6,
7.6, 2.0 Hz, 1 H), 7.26 (dd, J = 7.6, 1.2 Hz, 1 H), 7.19 (dd, J = 3.2, 1.2 Hz,
1 H), 7.11 (d, J = 8.0 Hz, 1 H), 7.07 (ddd, J = 7.6, 5.2, 1.2 Hz, 1 H), 6.88
(ddd, J = 7.6, 7.6, 1.2 Hz, 1 H), 6.75 (ddd, J = 8.0, 8.0, 1.2 Hz, 1 H), 6.68
(dd, J = 7.6, 1.2 Hz, 1 H), 6.30 (dd, J = 3.2, 3.2 Hz, 1 H), 5.92–5.91 (m, 1
H), 5.67 (s, 1 H), 4.93 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 161.3, 149.2, 137.0, 135.2, 126.8,
125.3, 124.8, 122.7, 121.6, 119.2, 115.9, 114.6, 114.5, 110.4, 106.5,
56.6.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.4 Hz, 1 H), 7.93–7.89 (m, 1
H), 7.51–7.48 (m, 3 H), 7.42–7.37 (m, 3 H), 7.25 (dd, J = 7.6, 7.6 Hz, 1
H), 7.13 (dd, J = 7.6, 7.6 Hz, 1 H), 7.02–6.98 (m, 2 H), 6.84–6.79 (m, 1
H), 5.86 (s, 1 H), 5.47 (s, 1 H), 4.13 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.1, 139.3, 137.7, 134.2, 129.7,
128.8, 128.6, 128.4, 127.4, 124.0, 122.5, 121.1, 120.9, 120.2, 116.9,
116.1, 111.7, 100.2, 57.2.
7-Methyl-6-phenyl-5,6-dihydroindolo[1,2-a]quinoxaline (4ca)9d
Yield: 142 mg (92%); yellow crystalline solid; mp 152–153 °C.
IR (KBr): 3453, 3378, 3032, 2908, 1624, 1593, 1505, 1451, 1384, 1358,
HRMS (ESI): m/z [M + H]+ calcd for C16H14N3: 248.1182; found:
248.1174.
4-Phenethylpyrrolo[1,2-a]quinoxaline (4al)17
1320, 1283, 1253, 1229, 1202, 1155, 746, 693, 618, 518 cm–1
.
Yield: 98 mg (72%); yellow solid; mp 48–49 °C.
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.4 Hz, 1 H), 7.81–7.78 (m, 1
H), 7.47 (d, J = 7.6 Hz, 1 H), 7.21–7.17 (m, 1 H), 7.16–7.08 (m, 6 H),
6.88–6.81 (m, 2 H), 6.65–6.60 (m, 1 H), 5.55 (s, 1 H), 4.18 (s, 1 H), 1.93
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 141.8, 135.7, 133.5, 132.7, 130.8,
128.8, 128.0, 127.4, 127.2, 123.7, 122.6, 120.4, 119.9, 119.0, 116.5,
116.2, 111.8, 107.5, 55.2, 8.4.
IR (KBr): 3434, 3138, 3026, 2926, 2858, 1608, 1528, 1480, 1452, 1424,
1376, 1100, 1036, 753, 705 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.95 (dd, J = 7.6, 1.6 Hz, 1 H), 7.87 (dd,
J = 2.8, 1.2 Hz, 1 H), 7.79 (dd, J = 8.0, 1.6 Hz, 1 H), 7.47–7.39 (m, 2 H),
7.34–7.28 (m, 4 H), 7.23–7.18 (m, 1 H), 6.88 (dd, J = 4.0, 1.2 Hz, 1 H),
6.82 (dd, J = 3.6, 2.4 Hz, 1 H), 3.34–3.29 (m, 2 H), 3.25–3.20 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 156.3, 141.8, 136.0, 129.5, 128.5,
127.3, 127.0, 126.1, 125.9, 125.1, 114.3, 113.7, 113.6, 106.2, 37.5, 34.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H17N2: 273.1386; found:
7-Methyl-6-(p-tolyl)-5,6-dihydroindolo[1,2-a]quinoxaline (4cb)9f
Yield: 156 mg (96%); yellow solid; mp 55–56 °C.
273.1413.
IR (KBr): 3437, 3369, 3048, 2920, 2856, 1627, 1510, 1455, 1384, 1363,
1226, 1156, 738, 633, 507 cm–1
.
4-Ethyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (4am)9d
Yield: 75 mg (76%); white solid; mp 54–55 °C.
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.4 Hz, 1 H), 7.88–7.86 (m, 1
H), 7.56 (d, J = 8.0 Hz, 1 H), 7.27 (dd, J = 7.6, 7.6 Hz, 1 H), 7.18 (dd, J =
7.6, 7.6 Hz, 1 H), 7.09 (d, J = 8.0 Hz, 2 H), 7.03 (d, J = 8.0 Hz, 2 H), 6.93–
6.90 (m, 2 H), 6.71–6.68 (m, 1 H), 5.61 (s, 1 H), 4.23 (br s, 1 H), 2.26 (s,
3 H), 2.02 (s, 3 H).
IR (KBr): 3368, 3060, 2964, 2929, 1612, 1516, 1483, 1424, 1342, 1295,
1175, 1090, 743, 701 cm–1
.
13C NMR (100 MHz, CDCl3): δ = 138.9, 137.7, 135.8, 133.5, 132.9,
130.8, 129.5, 127.5, 127.1, 123.7, 122.5, 120.4, 119.8, 119.0, 116.4,
116.2, 111.8, 107.3, 54.9, 21.2, 8.4.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

J
H.-r. Huo et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C23H21N2: 325.1699; found:
325.1723.
13C NMR (100 MHz, CDCl3): δ = 159.9, 143.4, 135.8, 133.5, 132.6,
130.8, 129.8, 127.4, 123.8, 122.6, 120.4, 119.9, 119.5, 119.0, 116.5,
116.3, 113.3, 112.8, 111.8, 107.5, 55.2, 55.1, 8.4.
HRMS (ESI): m/z [M + H]+ calcd for C23H21N2O: 341.1648; found:
341.1672.
6-(4-Methoxyphenyl)-7-methyl-5,6-dihydroindolo[1,2-a]quinox-
aline (4cc)9f
Yield: 161 mg (95%); pale yellow crystalline solid; mp 130–131 °C.
6-(2,4-Dichlorophenyl)-7-methyl-5,6-dihydroindolo[1,2-a]quin-
oxaline (4cg)
IR (KBr): 3447, 3326, 3052, 2910, 2841, 1607, 1511, 1457, 1383, 1363,
1282, 1240, 1179, 1021, 790, 741, 601, 539 cm–1
.
Yield: 184 mg (97%); pale yellow crystalline solid; mp 135–136 °C.
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.4 Hz, 1 H), 7.89–7.86 (m, 1
H), 7.55 (d, J = 7.6 Hz, 1 H), 7.27 (dd, J = 7.6, 7.6 Hz, 1 H), 7.18 (dd, J =
7.6, 7.6 Hz, 1 H), 7.12 (d, J = 8.4 Hz, 2 H), 6.95–6.89 (m, 2 H), 6.75 (d,
J = 8.8 Hz, 2 H), 6.70–6.68 (m, 1 H), 5.57 (s, 1 H), 4.20 (br s, 1 H), 3.70
(s, 3 H), 1.99 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.3, 135.9, 134.0, 133.5, 133.1,
130.8, 128.5, 127.4, 123.7, 122.6, 120.4, 119.8, 119.0, 116.4, 116.2,
114.1, 111.8, 107.3, 55.3, 54.7, 8.4.
IR (KBr): 3448, 3377, 2922, 2854, 1628, 1593, 1510, 1458, 1384, 1229,
1157, 1041, 862, 818, 796, 746, 690, 639, 542 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.4 Hz, 1 H), 7.89 (d, J = 7.6
Hz, 1 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.38 (d, J = 1.6 Hz, 1 H), 7.32 (dd, J =
7.6, 7.6 Hz, 1 H), 7.23 (dd, J = 7.6, 7.6 Hz, 1 H), 7.94–6.86 (m, 3 H), 6.66
(d, J = 7.2 Hz, 1 H), 6.59 (d, J = 8.4 Hz, 1 H), 6.10 (s, 1 H), 4.71 (br s, 1 H),
2.11 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C23H21N2O: 341.1648; found:
341.1625.
13C NMR (100 MHz, CDCl3): δ = 137.0, 134.5, 134.3, 133.6, 133.0,
130.9, 130.5, 130.1, 129.6, 127.5, 127.3, 124.0, 122.9, 120.7, 120.3,
119.3, 116.7, 116.4, 111.9, 107.9, 50.7, 8.2.
HRMS (ESI): m/z [M + H]+ calcd for C22H17Cl2N2: 379.0763; found:
379.0790.
6-(4-Chlorophenyl)-7-methyl-5,6-dihydroindolo[1,2-a]quinoxal-
ine (4cd)9d
Yield: 167 mg (97%); pale yellow solid; mp 59–60 °C.
6-(Benzo[d][1,3]dioxol-5-yl)-7-methyl-5,6-dihydroindolo[1,2-
a]quinoxaline (4ch)
IR (KBr): 3415, 3370, 3052, 2920, 2856, 1598, 1509, 1487, 1455, 1384,
1362, 1227, 1156, 1089, 739, 627, 509 cm–1
.
Yield: 154 mg (87%); yellow solid; mp 144–145 °C.
1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.4 Hz, 1 H), 7.90–7.87 (m, 1
H), 7.57 (d, J = 8.0 Hz, 1 H), 7.30 (dd, J = 8.0, 8.0 Hz, 1 H), 7.23–7.19 (m,
3 H), 7.14 (d, J = 8.4 Hz, 2 H), 6.98–6.92 (m, 2 H), 6.75–6.73 (m, 1 H),
5.64 (s, 1 H), 4.26 (br s, 1 H), 2.04 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 140.3, 135.2, 133.7, 133.5, 132.2,
130.6, 129.0, 128.5, 127.4, 123.8, 122.8, 120.5, 120.1, 119.1, 116.5,
116.3, 111.8, 107.5, 54.4, 8.4.
IR (KBr): 3446, 3375, 3049, 2902, 2782, 1599, 1500, 1454, 1391, 1367,
1291, 1236, 1157, 1037, 929, 861, 797, 734, 699, 609, 528 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.4 Hz, 1 H), 7.88–7.86 (m, 1
H), 7.56 (d, J = 7.6 Hz, 1 H), 7.29–7.25 (m, 1 H), 7.20–7.16 (m, 1 H),
6.95–6.89 (m, 2 H), 6.71–6.64 (m, 4 H), 5.83 (s, 2 H), 5.54 (s, 1 H), 4.18
(br s, 1 H), 2.03 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 148.1, 147.3, 135.9, 135.6, 133.5,
132.7, 130.8, 127.3, 123.8, 122.6, 120.6, 120.5, 119.9, 119.0, 116.5,
116.2, 111.9, 108.3, 107.7, 107.4, 101.1, 54.9, 8.4.
7-Methyl-6-(4-nitrophenyl)-5,6-dihydroindolo[1,2-a]quinoxaline
(4ce)9f
HRMS (ESI): m/z [M + H]+ calcd for C23H19N2O2: 355.1441; found:
Yield: 174 mg (98%); yellow solid; mp 102–103 °C.
355.1413.
IR (KBr): 3421, 3369, 3053, 2921, 2855, 1597, 1512, 1344, 1227, 1156,
741, 705, 506 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.02–7.98 (m, 3 H), 7.88–7.85 (m, 1 H),
7.58 (d, J = 7.6 Hz, 1 H), 7.33–7.27 (m, 3 H), 7.22 (dd, J = 7.6, 7.6 Hz, 1
H), 6.98–6.92 (m, 2 H), 6.75–6.73 (m, 1 H), 5.72 (s, 1 H), 4.26 (br s, 1
H), 2.10 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 148.9, 147.4, 134.5, 133.6, 131.1,
130.5, 127.8, 127.3, 124.1, 123.1, 120.8, 120.5, 119.2, 116.6, 116.5,
111.9, 107.9, 53.8, 8.4.
7-Methyl-6-(naphthalen-1-yl)-5,6-dihydroindolo[1,2-a]quinoxal-
ine (4ci)
Yield: 173 mg (96%); yellow solid; mp 134–135 °C.
IR (KBr): 3447, 3376, 3047, 2917, 2853, 1623, 1597, 1508, 1454, 1385,
1362, 1227, 1157, 780, 738, 697, 634, 536 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.29 (d, J = 8.0 Hz, 1 H), 8.07 (d, J = 8.4
Hz, 1 H), 7.95 (d, J = 8.0 Hz, 1 H), 7.88 (d, J = 7.6 Hz, 1 H), 7.73 (d, J = 8.0
Hz, 1 H), 7.56–7.48 (m, 3 H), 7.31 (dd, J = 7.6, 7.6 Hz, 1 H), 7.23–7.18
(m, 2 H), 7.06 (d, J = 6.8 Hz, 1 H), 6.93 (dd, J = 7.6, 7.6 Hz, 1 H), 6.83
(dd, J = 7.6, 7.6 Hz, 1 H), 6.55 (d, J = 7.6 Hz, 1 H), 6.45 (s, 1 H), 4.31 (br
s, 1 H), 1.82 (s, 3 H).
6-(3-Methoxyphenyl)-7-methyl-5,6-dihydroindolo[1,2-a]quinox-
aline (4cf)
Yield: 162 mg (95%); pale yellow solid; mp 138–139 °C.
13C NMR (100 MHz, CDCl3): δ = 136.0, 135.8, 134.3, 133.5, 132.5,
130.9, 130.8, 129.4, 128.8, 127.3, 126.8, 126.3, 125.9, 125.5, 123.7,
123.0, 122.6, 120.5, 120.1, 119.1, 116.5, 116.4, 111.9, 107.8, 52.7, 8.1.
HRMS (ESI): m/z [M + H]+ calcd for C26H21N2: 361.1699; found:
361.1691.
IR (KBr): 3449, 3373, 3052, 2922, 2855, 1597, 1509, 1488, 1454, 1384,
1361, 1224, 1155, 1041, 737, 703, 637, 508 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 8.0 Hz, 1 H), 7.80–7.77 (m, 1
H), 7.47 (d, J = 7.6 Hz, 1 H), 7.19 (dd, J = 7.6, 7.6 Hz, 1 H), 7.12–7.04 (m,
2 H), 6.86–6.81 (m, 2 H), 6.71 (d, J = 7.6 Hz, 1 H), 6.68–6.64 (m, 2 H),
6.64–6.61 (m, 1 H), 5.51 (s, 1 H), 4.14 (br s, 1 H), 3.55 (s, 3 H), 1.96 (s, 3
H).
6-(Furan-2-yl)-7-methyl-5,6-dihydroindolo[1,2-a]quinoxaline
(4cj)8b
Yield: 147 mg (98%); brilliant yellow solid; mp 95–96 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

K
H.-r. Huo et al.
Paper
Synthesis
IR (KBr): 3451, 2924, 2854, 1635, 1458, 1384, 1215, 1157, 1039, 843,
743, 640, 506 cm–1
1,4-Bis(7-methyl-5,6-dihydroindolo[1,2-a]quinoxalin-6-yl)ben-
zene (4cn)
.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.4 Hz, 1 H), 7.84–7.81 (m, 1
H), 7.60 (d, J = 7.6 Hz, 1 H), 7.30–7.26 (m, 2 H), 7.20 (dd, J = 7.6, 7.6 Hz,
1 H), 6.95–6.91 (m, 2 H), 6.79–6.77 (m, 1 H), 6.12 (dd, J = 3.2, 2.0 Hz, 1
H), 5.80 (d, J = 3.2 Hz, 1 H), 5.75 (s, 1 H), 4.49 (br s, 1 H), 2.24 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 153.9, 142.3, 135.3, 133.6, 130.5,
130.2, 127.4, 123.7, 122.7, 120.5, 120.2, 119.2, 116.5, 111.8, 110.4,
107.7, 107.2, 48.3, 8.1.
Yield: 254 mg (93%); pale yellow solid.
IR (KBr): 3388, 3049, 2912, 2857, 1629, 1599, 1510, 1454, 1386, 1364,
1325, 1289, 1252, 1230, 1202, 1156, 1049, 1017, 735, 624, 532 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 8.00 (d, J = 8.0 Hz, 2 H), 7.83–7.80
(m, 2 H), 7.55 (d, J = 7.6 Hz, 2 H), 7.23 (dd, J = 7.6, 7.6 Hz, 2 H), 7.15
(dd, J = 7.6, 7.6 Hz, 2 H), 7.10 (d, J = 3.2 Hz, 4 H), 6.90–6.89 (m, 4 H),
6.81 (s, 4 H), 5.74 (d, J = 3.2 Hz, 2 H), 2.12 (d, J = 3.6 Hz, 6 H).
13C NMR (100 MHz, DMSO-d6): δ = 142.1, 137.1, 133.33, 133.31,
133.27, 130.5, 127.1, 126.6, 124.3, 122.9, 120.7, 119.3, 118.8, 116.5,
116.3, 112.0, 106.3, 52.2, 8.49, 8.47.
7-Methyl-6-(pyridin-2-yl)-5,6-dihydroindolo[1,2-a]quinoxaline
(4ck)
Yield: 143 mg (92%); white solid; mp 156–157 °C.
HRMS (ESI): m/z [M + H]+ calcd for C38H31N4: 543.2543; found:
IR (KBr): 3450, 3263, 3066, 2925, 1628, 1591, 1507, 1460, 1388, 1362,
543.2518.
1322, 1282, 1228, 1157, 1042, 997, 840, 792, 743, 671, 624 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.55 (d, J = 4.4 Hz, 1 H), 8.00 (d, J = 8.0
Hz, 1 H), 7.82–7.80 (m, 1 H), 7.62 (d, J = 7.6 Hz, 1 H), 7.36–7.27 (m, 2
H), 7.22 (dd, J = 7.6, 7.6 Hz, 1 H), 7.02 (dd, J = 7.2, 5.6 Hz, 1 H), 6.88–
6.83 (m, 2 H), 6.79–6.73 (m, 2 H), 5.79 (s, 1 H), 5.30 (br s, 1 H), 2.23 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 160.2, 149.6, 136.9, 135.7, 133.8,
130.8, 130.5, 127.5, 123.8, 122.8, 122.5, 121.4, 120.5, 119.8, 119.2,
116.9, 116.3, 111.9, 108.5, 55.1, 8.3.
7-Methyl-6-phenyl-6,7-dihydro-5H-indolo[2,3-c]quinoline (4da)
Yield: 132 mg (85%); pale yellow solid; mp 159–160 °C.
IR (KBr): 3421, 3057, 3030, 2925, 2852, 1603, 1580, 1547, 1503, 1471,
1453, 1374, 1325, 1281, 1238, 1160, 743, 698 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.56 (dd, J = 7.6, 1.2 Hz, 1 H), 7.34–7.32
(m, 2 H), 7.21–7.14 (m, 4 H), 7.07–7.02 (m, 1 H), 6.93 (ddd, J = 7.6, 7.6,
1.2 Hz, 1 H), 6.86–6.80 (m, 2 H), 6.67 (ddd, J = 7.6, 7.6, 1.2 Hz, 1 H),
6.47 (d, J = 8.0 Hz, 1 H), 5.91 (s, 1 H), 4.21 (br s, 1 H), 3.91 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 144.6, 144.4, 139.4, 131.9, 128.7,
128.2, 127.9, 127.4, 124.7, 122.5, 121.9, 119.6, 118.8, 117.9, 115.7,
114.4, 111.2, 109.2, 57.3, 32.9.
HRMS (ESI): m/z [M + H]+ calcd for C21H18N3: 312.1495; found:
312.1469.
3-(7-Methyl-5,6-dihydroindolo[1,2-a]quinoxalin-6-yl)-4H-
chromen-4-one (4cl)
HRMS (ESI): m/z [M + H]+ calcd for C22H19N2: 311.1543; found:
311.1545.
Yield: 163 mg (86%); pale yellow solid; mp 117–118 °C.
IR (KBr): 3349, 3060, 2920, 1636, 1607, 1509, 1459, 1389, 1351, 1231,
Methyl 6,6-Dimethyl-5,6-dihydroindolo[1,2-a]quinoxaline-3-car-
1154, 762, 734, 700, 540 cm–1
.
boxylate (4ea)11
1H NMR (400 MHz, CDCl3): δ = 8.23 (d, J = 7.6 Hz, 1 H), 8.02 (d, J = 8.4
Hz, 1 H), 7.87–7.84 (m, 1 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.58 (dd, J = 7.6,
7.6 Hz, 1 H), 7.39–7.30 (m, 2 H), 7.28–7.22 (m, 2 H), 7.13 (s, 1 H),
6.92–6.85 (m, 2 H), 6.77–6.74 (m, 1 H), 6.04 (s, 1 H), 5.44 (br s, 1 H),
2.26 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 177.9, 156.5, 154.0, 135.2, 134.0,
133.9, 130.3, 128.9, 126.9, 125.7, 125.4, 124.1, 123.8, 122.9, 122.4,
120.6, 120.0, 119.3, 118.3, 117.1, 116.4, 111.8, 107.7, 47.1, 8.2.
Yield: 131 mg (86%); yellow solid; mp 151–152 °C.
IR (KBr): 3441, 3339, 3044, 2957, 2853, 1710, 1620, 1601, 1492, 1452,
1386, 1315, 1289, 1228, 1111, 1006, 892, 766, 732, 649 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.4
Hz, 1 H), 7.61 (dd, J = 8.4, 2.0 Hz, 1 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.48 (d,
J = 2.0 Hz, 1 H), 7.23–7.19 (m, 1 H), 7.14 (d, J = 7.6 Hz, 1 H), 6.34 (s, 1
H), 3.84 (s, 3 H), 1.51 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 166.8, 143.0, 135.8, 134.1, 130.6,
130.1, 125.4, 122.8, 121.8, 121.5, 121.1, 117.3, 116.0, 111.9, 97.4, 52.1,
51.9, 28.6.
HRMS (ESI): m/z [M + H]+ calcd for C25H19N2O2: 379.1441; found:
379.1440.
HRMS (ESI): m/z [M + H]+ calcd for C19H19N2O2: 307.1441; found:
307.1441.
6-Isopropyl-7-methyl-5,6-dihydroindolo[1,2-a]quinoxaline (4cm)
Yield: 111 mg (80%); pale yellow oil.
IR (KBr): 3386, 3052, 2959, 2921, 2866, 1625, 1598, 1509, 1456, 1383,
Quinoxalines 5; General Procedure
1363, 1287, 1232, 1049, 738, 702 cm–1
.
A mixture of arylamine 2 (0.5 mmol) and aldehyde 3 (0.6 mmol) in
CH3CN (2.5 mL, 0.2 M) was treated with TEMPO oxoammonium salt
1b (1.0 mol%). The resulting mixture was stirred at room temperature
for 12–18 h until the reaction was complete (as indicated by TLC).
Next, additional salt 1b (0.5 mmol) was added and the mixture was
stirred for 6 h at room temperature. The mixture was dissolved in
DCM (50 mL) and washed with saturated Na2CO3, water, dried over
sodium sulfate. The solvent was evaporated and the residue was puri-
fied by flash column chromatography (petroleum ether/EtOAc, 20:1)
to afford the product 5.
1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.0 Hz, 1 H), 7.79 (dd, J = 7.6,
1.6 Hz, 1 H), 7.58–7.56 (m, 1 H), 7.26–7.16 (m, 2 H), 6.96–6.88 (m, 2
H), 6.75–6.72 (m, 1 H), 4.26 (br s, 1 H), 4.05 (d, J = 9.2 Hz, 1 H), 2.25 (s,
3 H), 1.93–1.84 (m, 1 H), 0.89 (d, J = 6.8 Hz, 3 H), 0.84 (d, J = 6.8 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 136.1, 133.7, 133.4, 130.7, 127.9,
123.8, 122.4, 120.3, 119.5, 118.9, 116.8, 116.0, 111.4, 106.8, 56.4, 32.6,
19.6, 19.1, 9.0.
HRMS (ESI): m/z [M + H]+ calcd for C19H21N2: 277.1699; found:
277.1703.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

L
H.-r. Huo et al.
Paper
Synthesis
4-Phenylpyrrolo[1,2-a]quinoxaline (5aa)9d
13C NMR (100 MHz, CDCl3): δ = 151.8, 148.6, 144.5, 136.0, 130.5,
129.7, 128.4, 127.2, 125.7, 124.8, 123.8, 115.2, 114.5, 113.8, 108.3.
Yield: 110 mg (90%); brilliant yellow solid; mp 98–99 °C.
IR (KBr): 3136, 3061, 1603, 1595, 1522, 1472, 1444, 1414, 1368, 1319,
1244, 1165, 1094, 1071, 1032, 1006, 931, 910, 880, 751, 710, 695, 620
6-Phenylindolo[1,2-a]quinoxaline (5ba)9l
cm–1
.
Yield: 127 mg (86%); yellow solid; mp 170–171 °C.
1H NMR (400 MHz, CDCl3): δ = 8.04 (dd, J = 7.6, 1.2 Hz, 1 H), 8.01–7.98
(m, 3 H), 7.86 (dd, J = 8.0, 0.8 Hz, 1 H), 7.56–7.51 (m, 3 H), 7.50 (dd, J =
8.0, 1.6 Hz, 1 H), 7.45 (ddd, J = 8.0, 8.0, 1.6 Hz, 1 H), 6.99 (dd, J = 4.0,
1.2 Hz, 1 H), 6.88 (dd, J = 4.0, 2.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 154.4, 138.5, 136.3, 130.3, 129.8,
128.7, 128.6, 127.5, 127.2, 125.4, 125.3, 114.6, 114.0, 113.6, 108.7.
IR (KBr): 3106, 3058, 2957, 1604, 1517, 1480, 1426, 1380, 1342, 1318,
1285, 1250, 1211, 1174, 1090, 1042, 979, 925, 887, 861, 751, 719, 641
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.51–8.46 (m, 2 H), 8.09 (dd, J = 8.0, 1.2
Hz, 1 H), 8.03–8.00 (m, 2 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.62–7.52 (m, 5
H), 7.46–7.40 (m, 2 H), 7.24 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 156.3, 138.2, 136.2, 133.1, 130.5,
130.2, 130.1, 129.2, 129.1, 128.68, 128.66, 128.4, 124.4, 124.2, 122.8,
122.7, 114.7, 114.6, 102.6.
4-(p-Tolyl)pyrrolo[1,2-a]quinoxaline (5ab)10a
Yield: 107 mg (83%); pale yellow oil.
IR (KBr): 3138, 3062, 3032, 2920, 1612, 1529, 1511, 1476, 1445, 1422,
1367, 1347, 1320, 1250, 1211, 1183, 1162, 1100, 1041, 931, 824, 755,
7-Methyl-6-phenylindolo[1,2-a]quinoxaline (5ca)9d
722, 652, 618 cm–1
.
Yield: 142 mg (92%); yellow solid; mp 159–160 °C.
1H NMR (400 MHz, CDCl3): δ = 8.05 (dd, J = 7.6, 1.2 Hz, 1 H), 7.99–7.98
(m, 1 H), 7.93 (d, J = 8.0 Hz, 2 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.52–7.43 (m,
2 H), 7.36 (d, J = 8.0 Hz, 2 H), 7.01 (dd, J = 4.0, 0.8 Hz, 1 H), 6.89 (dd, J =
3.6, 2.8 Hz, 1 H), 2.47 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 154.4, 139.9, 136.3, 135.7, 130.2,
129.3, 128.6, 127.3, 127.2, 125.4, 125.2, 114.5, 113.9, 113.6, 108.7,
21.5.
IR (KBr): 3042, 3029, 2921, 2855, 1611, 1540, 1479, 1447, 1399, 1372,
1332, 1313, 1255, 1207, 1122, 1105, 1072, 988, 941, 913, 848, 732,
967, 645, 608 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.47 (dd, J = 8.4, 3.6 Hz, 2 H), 8.02–8.00
(m, 1 H), 7.89 (d, J = 8.4 Hz, 1 H), 7.66–7.61 (m, 2 H), 7.57 (dd, J = 7.6,
7.6 Hz, 2 H), 7.54–7.52 (m, 3 H), 7.44 (dd, J = 7.6, 7.6 Hz, 1 H), 7.39 (dd,
J = 7.6, 7.6 Hz, 1 H), 2.05 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.7, 139.5, 135.6, 132.1, 130.6,
130.3, 130.1, 129.3, 128.6, 128.5, 128.3, 125.7, 124.8, 123.8, 122.1,
120.8, 114.4, 111.0, 11.1.
4-(4-Methoxyphenyl)pyrrolo[1,2-a]quinoxaline (5ac)9l
Yield: 103 mg (75%); white crystalline solid; mp 111–112 °C.
IR (KBr): 3147, 3102, 3063, 3037, 2993, 2965, 2834, 1610, 1532, 1509,
1476, 1423, 1371, 1324, 1298, 1249, 1180, 1098, 1032, 935, 830, 807,
7-Methyl-6-(p-tolyl)indolo[1,2-a]quinoxaline (5cb)9d
787, 756, 737, 706, 652, 620 cm–1
.
Yield: 143 mg (89%); brilliant yellow solid; mp 156–157 °C.
1H NMR (400 MHz, CDCl3): δ = 8.04–7.98 (m, 4 H), 7.87 (d, J = 7.6 Hz, 1
H), 7.52–7.43 (m, 2 H), 7.07 (d, J = 8.4 Hz, 2 H), 7.01 (dd, J = 4.0, 1.2 Hz,
1 H), 6.90 (dd, J = 3.6, 2.8 Hz, 1 H), 3.91 (s, 3 H).
IR (KBr): 3273, 3226, 3063, 2919, 1615, 1543, 1480, 1452, 1400, 1379,
1328, 1325, 1225, 1213, 1187, 1158, 1120, 1083, 1033, 994, 815, 782,
747, 635, 610 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 8.72 (d, J = 8.4 Hz, 2 H), 8.00 (d, J =
8.0 Hz, 1 H), 7.91 (d, J = 7.6 Hz, 1 H), 7.73–7.65 (m, 2 H), 7.59 (d, J = 8.0
Hz, 2 H), 7.53–7.47 (m, 2 H), 7.43 (d, J = 7.6 Hz, 2 H), 2.46 (s, 3 H), 2.04
(s, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 157.2, 140.3, 132.4, 130.2, 130.1,
129.9, 129.4, 129.2, 128.0, 126.8, 125.1, 124.9, 123.1, 121.6, 115.6,
115.3, 21.6, 11.6.
13C NMR (100 MHz, CDCl3): δ = 161.0, 153.9, 136.3, 131.1, 130.1,
127.2, 127.1, 125.4, 125.2, 114.5, 114.0, 113.9, 113.6, 108.6, 55.4.
4-(4-Chlorophenyl)pyrrolo[1,2-a]quinoxaline (5ad)10a
Yield: 128 mg (92%); pale yellow solid; mp 174–175 °C.
IR (KBr): 3142, 3105, 3078, 3045, 1613, 1595, 1531, 1475, 1445, 1422,
1398, 1371, 1348, 1319, 1275, 1245, 1166, 1090, 1039, 1011, 933,
849, 827, 788, 749, 714, 648, 613 cm–1
.
6-(4-Methoxyphenyl)-7-methylindolo[1,2-a]quinoxaline (5cc)10a
1H NMR (400 MHz, CDCl3): δ = 8.03 (dd, J = 8.0, 0.8 Hz, 1 H), 8.00–7.95
(m, 3 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.54–7.51 (m, 3 H), 7.47 (ddd, J = 8.0,
8.0, 0.8 Hz, 1 H), 6.96–6.95 (m, 1 H), 6.91–6.89 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 153.1, 136.9, 136.1, 135.9, 130.3,
123.0, 128.8, 127.7, 127.1, 125.4, 125.1, 114.8, 114.1, 113.7, 108.5.
Yield: 137 mg (81%); brilliant yellow solid; mp 202–203 °C.
IR (KBr): 3279, 3227, 3175, 3069, 2923, 2840, 1607, 1579, 1534, 1511,
1479, 1452, 1395, 1330, 1310, 1255, 1211, 1180, 1118, 1081, 1029,
992, 946, 835, 762, 742, 678, 608 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 8.79 (d, J = 8.4 Hz, 2 H), 8.09 (d, J =
8.0 Hz, 1 H), 7.96 (d, J = 8.0 Hz, 1 H), 7.79–7.72 (m, 4 H), 7.59–7.53 (m,
2 H), 7.23 (d, J = 8.4 Hz, 2 H), 3.91 (s, 3 H), 2.15 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 162.0, 156.8, 133.1, 131.5, 130.5,
130.3, 123.0, 128.1, 125.3, 124.9, 123.6, 122.0, 116.0, 115.4, 114.5,
56.0, 11.9.
4-(4-Nitrophenyl)pyrrolo[1,2-a]quinoxaline (5ae)9l
Yield; 126 mg (87%); brilliant yellow solid; mp 220–221 °C.
IR (KBr): 3150, 3105, 3079, 1601, 1512, 1476, 1424, 1373, 1350, 1318,
1249, 1173, 1102, 1038, 1009, 938, 858, 835, 752, 721, 698, 648, 609
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 8.8 Hz, 2 H), 8.20 (d, J = 8.8
Hz, 2 H), 8.06–8.04 (m, 2 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.61–7.56 (m, 1
H), 7.53–7.49 (m, 1 H), 6.97–6.95 (m, 2 H).
6-(4-Chlorophenyl)-7-methylindolo[1,2-a]quinoxaline (5cd)
Yield: 161 mg (94%); orange-yellow solid; mp 226–227 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

M
H.-r. Huo et al.
Paper
Synthesis
IR (KBr): 3271, 3225, 3176, 3068, 2913, 1616, 1596, 1533, 1483, 1455,
1400, 1330, 1255, 1214, 1192, 1159, 1086, 1017, 994, 942, 860, 824,
Supporting Information
786, 749, 728, 678, 612 cm–1
.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610131.
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1H NMR (400 MHz, DMSO-d6): δ = 8.75–8.71 (m, 2 H), 8.01 (d, J = 8.0
Hz, 1 H), 7.93 (dd, J = 8.0, 1.6 Hz, 1 H), 7.73–7.63 (m, 6 H), 7.54–7.47
(m, 2 H), 2.06 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 156.2, 137.9, 134.9, 134.7, 132.0,
131.1, 130.12, 130.07, 129.74, 129.72, 128.9, 126.0, 125.2, 124.7,
122.9, 121.3, 115.4, 115.2, 11.5.
References
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HRMS (ESI): m/z [M + H]+ calcd for C22H16N2Cl: 343.0997; found:
343.1006.
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7-Methyl-6-(4-nitrophenyl)indolo[1,2-a]quinoxaline (5ce)
Yield: 159 mg (90%); red solid; mp 259–260 °C.
IR (KBr): 3151, 3097, 3066, 2946, 2905, 2861, 1597, 1566, 1542, 1520,
1479, 1450, 1408, 1379, 1347, 1312, 1256, 1214, 1194, 1158, 1104,
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1H NMR (400 MHz, DMSO-d6): δ = 8.75 (dd, J = 8.4, 6.0 Hz, 2 H), 8.44
(d, J = 8.8 Hz, 2 H), 8.03–7.93 (m, 4 H), 7.75–7.70 (m, 1 H), 7.66 (dd, J =
7.6, 7.6 Hz, 1 H), 7.54–7.47 (m, 2 H), 2.05 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 162.7, 157.4, 145.7, 135.3, 133.1,
131.9, 130.8, 130.3, 130.2, 130.0, 125.9, 124.7, 124.0, 123.0, 121.3,
115.5, 115.2, 110.4, 11.6.
HRMS (ESI): m/z [M + H]+ calcd for C22H16N3O2: 354.1237; found:
354.1252.
7-Methyl-6-phenyl-7H-indolo[2,3-c]quinoline (5da)
Yield: 139 mg (90%); white solid; mp 112–113 °C.
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1640. (b) Xu, H.; Fan, L.-L. Eur. J. Med. Chem. 2011, 46, 1919.
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IR (KBr): 3053, 2925, 2854, 1611, 1557, 1512, 1489, 1472, 1442, 1419,
1377, 1333, 1306, 1262, 1227, 1199, 1157, 1128, 1088, 1024, 999,
943, 918, 856, 796, 761, 741, 701, 642, 611 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.73 (d, J = 8.0 Hz, 1 H), 8.60 (d, J = 8.0
Hz, 1 H), 8.32 (d, J = 8.0 Hz, 1 H), 7.71–7.62 (m, 4 H), 7.59 (dd, J = 7.6,
7.6 Hz, 1 H), 7.55–7.51 (m, 3 H), 7.49 (d, J = 8.4 Hz, 1 H), 7.41 (dd, J =
7.6, 7.6 Hz, 1 H), 3.45 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 148.0, 142.2, 141.8, 140.2, 132.3,
130.3, 129.4, 128.8, 128.5, 126.9, 125.9, 124.2, 123.3, 122.9, 122.5,
121.9, 120.7, 110.4, 33.2.
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HRMS (ESI): m/z [M + H]+ calcd for C22H17N2: 309.1386; found:
309.1392.
Funding Information
This project received financial support from the National Natural Sci-
ence Foundation of China (21472053, 21172082).
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Acknowledgment
We are grateful for the financial support from the National Natural
Science Foundation of China. The Center of Analysis and Testing of
Huazhong University of Science and Technology is acknowledged for
characterization of the new compounds.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N

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H.-r. Huo et al.
Paper
Synthesis
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