Access to fused pyrroles via the reaction of spiro-dienyl ethers with amines involving a chemoselective skeletal rearrangement

Article abstract of DOI:10.1016/j.tet.2014.05.084

Under metal-free conditions, the reaction of spiro-dienyl ethers, derived from furan derivatives, with aromatic amines provided fused pyrroles. The reaction proceeded through an interesting and chemoselective skeletal rearrangement and provided an alternative protocol for the construction of pyrrole rings from furan derivatives.

Full text of DOI:10.1016/j.tet.2014.05.084

Tetrahedron xxx (2014) 1e7
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Access to fused pyrroles via the reaction of spiro-dienyl ethers
with amines involving a chemoselective skeletal rearrangement
,b,
Xiaoyu Zhang a, Li Huang a, Hui Peng a, Fanghua Ji a, Xuehui Li a, Biaolin Yin a
*
a School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, Guangdong, China
b State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510640, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Under metal-free conditions, the reaction of spiro-dienyl ethers, derived from furan derivatives, with
aromatic amines provided fused pyrroles. The reaction proceeded through an interesting and chemo-
selective skeletal rearrangement and provided an alternative protocol for the construction of pyrrole
rings from furan derivatives.
Received 6 March 2014
Received in revised form 20 May 2014
Accepted 22 May 2014
Available online xxx
Ó 2014 Published by Elsevier Ltd.
Keywords:
Fused pyrroles
Spiro-dienyl ethers
Furan derivatives
Skeletal rearrangement
1. Introduction
R2
R
Pyrrole derivatives 1 are prevalent in a wide variety of bi-
ologically and medicinally important compounds1 and used as
building blocks for the construction of pharmaceutical agents2 and
electronic materials.3 Consequently, numerous methods for their
synthesis have been developed over the years, including the Knorr
reaction,4 Hantzsch reaction,5 Clauson-Kass reaction,6 PaaleKnorr
reaction,4c,7 transition-metal-mediated reaction,8 and other oper-
ations.9 Among these methods, the PaaleKnorr and Clauson-Kass
reactions are the most commonly used, albeit multi-step syn-
thetic operations are required. A similar protocol based on the furan
ring opening-pyrrole closure strategy is also extensively used
(Scheme 1).10 Due to the fact that furan derivatives have attracted
great attentions as green, renewable building blocks in organic
synthesis,11 it is highly desirable to develop access to structurally
novel pyrroles starting from furan derivatives.
R''
NR
RO
OR
O
O
3
5
OH
O
R1NH2
Paal-Knorr
R2
R
R
O
R
R1NH2
Clauson-Kass
R1NH2
N
R1
This work
1
O
6
O
NR
R''
O
2
furan ring opening-
pyrrole closure
R1NH2
R
4
O
2. Results and discussion
Scheme 1. Strategy to synthesize pyrroles from furan or its derivatives.
Acid-catalyzed rearrangement of suitable 2-furylcarbinols 7
into 4-hydroxycyclopentenone derivatives 8 (namely Piancatelli
rearrangement)12 has been well used as a key step in the con-
struction of a series of natural products and biologically relevant
cyclopentenones.13 The overall transformation is considered to
proceed through a cascade sequence that terminates with a 4p-
electrocyclic ring closure of a pentadienyl cation (Scheme 2). Re-
cently we and other groups explored the Piancatelli rearrange-
ment in an intramolecular fashion and developed an access to
spiro-componds.14 More recently, we disclosed an approach to
a class of spiro-dienyl ethers 6 from 2-furylcarbinol 5 and explored
* Corresponding author. E-mail address: blyin@scut.edu.cn (B. Yin).
0040-4020/$ e see front matter Ó 2014 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2014.05.084
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2
X. Zhang et al. / Tetrahedron xxx (2014) 1e7
H2O
R
H+
a
R
O
b
O
A
O
B
OH
H2O
OH2
R
7
HO
R
HO
c
4π conr.
HO
C
d
HO
R
R
O
8
OH
D
Scheme 2. Proposed mechanism of the Piancatelli reaction. conr.¼conrotatory.
the thermal rearrangement of 6 into cyclopentenone.15 Given that
the highly strained 6 is readily synthesized from furans and it
contains multiple reactive sites, it is anticipated that further
modification of the spiro-dienyl enol segment of 6 would provide
access to a variety of structurally novel heterocycles and thus ex-
pand the synthetic application of sustainable material from furan
derivatives.
Fig. 1. X-ray crystal structure of compound 11n.
Table 1
Optimization of the reaction conditionsa
Owing to the importance of spirooxindoles 10a bearing a 2,5-
dihydro-pyrrole subunit in medicinal significance, we attempted
to synthesize 10a via the reaction of 6a in the presence of p-tolui-
dine, assuming that the thermal rearrangement of 6a into 9a could
be suppressed. However, upon heating 6a with 4-methylaniline in
DCE at 100 ꢀC for 5 h, no expected spirooxindoles 10a was pro-
duced. Instead, a fused pyrrole 11a was formed in 58% yield
(Scheme 3). The structure of 11a was unambiguously determined
by X-ray crystallography (Fig. 1).16 This unexpected result none-
theless provided an unprecedented access to fused pyrroles with
structural novelty from dienyl ether. The reaction of dienyl ether
with nucleophiles, such as amine, has never been reported. Ex-
ploring such a reaction would expand the synthetic applications of
furan derivatives.
O
OMe
NEt
MeO
OMe
Bn
Me
NH2
N
OMe
OMe
O
catalyst, T, solvent,
16 h
Ph
OMe
NEt
O
6a
11a
Me
Entry
Catalyst
T (ꢀC)
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
d
100
80
DCE
DCE
DCE
DCE
58
0
d
d
105
110
130
105
105
105
105
105
105
105
105
65
50
15
ND
ND
54
59
66
75
84
80
d
d
DCE
d
Toluene
DMF
Dioxane
THF
d
d
OMe
MeO
OMe
9
d
10
11
12
13
CSA
ZnCl2
p-TsOH
DCE
DCE
DCE
DCE
O
NEt
ꢀ
MS 4 A
Ph
O
9a
Bold values signify optimized reaction conditions.
a
OMe
MeO
All reactions were performed on a 0.3 mmol scale. Unless otherwise noted, the
amount of the catalyst was 20 mol %. ND: not detected. NR: no reaction.
OMe
OMe
b
MeO
Isolated yield.
OMe
p-toluidine
DCE, 100 oC,
5h
N
Ph
NEt
10a
O
O
increasing the temperature to 110 ꢀC lowered the yield to 50%
(entry 4), accompanied by a small amount of rearranged product
9a, which could be isolated in 62% yield when conducting the re-
action at 130 ꢀC, and the yield of 11a decreased to 15% (entry 5).
After screening a wide range of solvents, DCE was turned out to be
the best (entries 6e9). Several catalysts, such as CSA, ZnCl2, p-TsOH,
O
NEt
Ph
6a
Me
O
NEt
N
OMe
OMe
Ph
ꢀ
and molecular sieves 4 A, were examined (entries 10e13) and p-
OMe
TsOH (20 mol %) provided the best yield (84%, entry 11). Therefore,
the optimized combination for this reaction was to use DCE as the
solvent, p-TsOH (20 mol %) as the catalyst, and 105 ꢀC as the re-
action temperature.
11a (58%)
Me
Scheme 3. The reaction of 6a with p-toluidine.
With our optimized reaction conditions, a range of R2NH2 with
different 6 containing various Ar and R1 group were tested to in-
vestigate the reaction scope as demonstrated in Table 2. The amine
structure was critical to the success of this reaction. When R2 was
aromatic, the reaction proceeded well, giving the desired 11 in
moderate-to-good yields. In contrast, no desired product was
produced when R2 was an alkyl group (11f). Complicated reaction
mixtures were obtained, when using phenylhydrazine as the
amine, and the yields were lower (11e and 11r). It is worth
We then screened a variety of catalysts, solvents, and reaction
temperatures to optimize the reaction as shown in Table 1. The
reaction outcome was greatly influenced by the temperature. For
instance, lowering the reaction temperature to 80 ꢀC shut down the
reaction completely (entry 2). In contrast, a slight increase of
temperature to 105 ꢀC enhanced the yield to 65% (entry 3). Further
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X. Zhang et al. / Tetrahedron xxx (2014) 1e7
3
Table 2
R1
Synthesis of 11a,b
O
O
R1
5
4
NEt
3
NEt
Ar
O
p-TsOH (20 mol %)
DCE, 105 oC, 16 h
2
9
6
in the absence
of R2NH2
N
O
Ar
Ar
R2NH2
NEt
R2
R1
R1
11
6
O
R1
R1
Ar
Ar
O
O
R2NH2
H+
+
NEt
+
+
O
NEt
6
Ar
NEt
N
O
NEt
NEt
NEt
O
12
R2
14
O
O
13
N
R2
N
R2
OMe
OMe
2-Br-C6H4
OMe
OMe
Ph
O
MeO
11g, R2 = Ph, 77%
MeO
+
11a, R2 = 4-Me-C6H4, 82%
11b, R2 = 3-MeO-C6H4, 75%
11c, R2 = 3,5-di-MeO-C6H3, 65%
11d, R2 = 3-Me-C6H4, 82%
11e, R2 = PhNH, 45%
11h, R2 = 4-Me-C6H4, 80%
11i, R2 = 3-MeO-C6H4, 74%
11j, R2 = 3,5-di-MeO-C6H3, 60%
11k, R2 = 4-NO2-C6H4, 81%
R1
11
N
R2
Ar
R1
16 (favored)
+
N
R1
R1
NEt
Ar R2
O
11f, R2 = Bn, 0%
+
O
15
NEt
O
NEt
NEt
N
NEt
N
Ar
Ar
O
O
R2
N
R2
OMe
Ph
18
R2
(disfavored)
17
N
R2
OMe
OMe
MeO
2-Cl-C6H4
11n, R2 = 4-Me-C6H4, 80%
Scheme 4. A plausible reaction mechanism.
MeO
O
11l, R2 = 4-Me-C6H4, 82%
11m, R2 = 3-MeO-C6H4, 77%
NEt
O
then undergoes two possible types of heterolytic CeC
bond cleavage to give open chain intermediate 16 or 17. Accord-
ing to the observation, the formation of 16 is favored over in-
termediate 17, presumably because the formation of phenyl
carbocation is more difficulty than the aminoacylium cation. An
intramolecular acylation of pyrrole at C-3 from 16 generates the
product 11. In the absence of amines, the reaction would undergo
a rearrangement to generate product 9 straightly from in-
termediate 13.
To further demonstrate the synthetic utility of this protocol,
tricyclic pyrroles 11 were transformed to pentacyclic pyrroles
19gei and 19k in moderate-to-good yields via two notable ap-
proaches: either the Pd-catalyzed intramolecular direct arylation
N
OMe
4-Me-C6H4
NEt
R2
MeO
11t, R2 = 4-Me-C6H4, 83%
N
R2
OMe
2-Cl-C6H4
O
MeO
11o, R2 = Ph, 66%
NEt
11p, R2 = 4-Me-C6H4, 80%
11q, R2 = 3-Me-C6H4, 72%
11r, R2 = PhNH, 48%
N
OMe
4-NO2-C6H4
R2
MeO
11u, R2 = 4-Me-C6H4, 78%
11s, R2 = 3,5-di-Me-C6H3, 62%
11v, R2 = H, 73%
O
O
NEt
NEt
of the pyrrole ring at its
b-position or a regio-selective intra-
molecular dehydrogenative coupling reaction using Cu(OAc)2 as the
oxidant. Both two approaches led to the products in good yields
(Scheme 5).
N
N
R2
OMe
OMe
2,6-di-Me-C6H4
2-Cl-C6H4
R2
OMe
OMe
11x, R2 = 4-Me-C6H4, 75%
11y, R2 = PhCONH, 0%
11z, R2 = HCONH, 0%
11w, R2 = 4-Me-C6H4, 55%
Et
N
Et
N
1
1
R
R
O
Pd(OAc) (10 mol %),
O
aAll reactions were performed on a 0.3-mmol scale.
bIsolated yield.
2
PPh (20 mol %)
3
K CO (2 equiv)
2
3
Br
N
o
N
toluene, N , 120 C,
2
16 h
2
2
R
R
11g
19g (64%)
19h (85%)
19i (60%)
19k (51%)
11h
11i
highlighting that when NH3$H2O was used as the nucleophile, the
desired product was produced in good yield (11v). Notably, due to
their weak nucleophilicity, benzoyl amide, and formamide as the
nucleophiles resulted in no reaction (11y and 11z). The electronic
properties of the substituents on the Ar rings did not apparently
influence the reaction.
11k
Et
N
Et
N
1
1
R
R
O
O
Pd(OAc) (10 mol %),
2
Cu(OAc) (2 equiv)
2
H
H
On the basis of the experimental results shown above, a ten-
tative mechanistic interpretation is proposed in Scheme 4. Pro-
tonation of 6 gave oxocarbonium ion 12, which would then
undergo the ring-opening process to provide the intermediate 13.
The condensation of 13 with R3NH2 gave the intermediate 14. An
electro-cyclization is preceded to give the intermediate 15, which
toluene, PivOH,
110 C, 20 h
N
N
o
2
2
R
R
11a
11b
19h (67%)
19i (73%)
Scheme 5. Synthesis of pentacyclic pyrroles 19.
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4
X. Zhang et al. / Tetrahedron xxx (2014) 1e7
3. Conclusion
Ion-trap-HRMS (ESI) calcd for C30H31N2O5 [MþH]þ 499.2233, found
499.2246.
In summary, we have developed a novel access to fused pyr-
roles via the unprecedented reaction of dienyl ethers derived from
furans with amines under metal-free conditions. We have dis-
closed for the first time that the thermal rearrangement of dienyl
ether into cyclopentenone can be suppressed in the presence of
suitable nucleophiles, such as amine, under suitable conditions.
The involved mechanism of dienoneephenol-like rearrangement
is also interesting and may open a new avenue to further design
new reactions, owing to the ready availability of dienyl ethers from
furans.
4.2.3. 2-Benzyl-1-(3,5-dimethoxyphenyl)-5-ethyl-7,8,9-trimethoxy-
1H-pyrrolo[3,2-c]quinolin-4(5H)-one (11c). Yellow solid (105 mg,
65%), mp¼101e103 ꢀC; IR (KBr) 2926, 1608, 1480, 1286, 755 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d 7.19e7.13 (m, 2H), 7.10e7.07 (m, 1H),
6.99e6.97 (m, 2H), 6.65e6.62 (m, 2H), 6.35 (s, 1H), 6.10 (s, 2H), 4.38
(q, J¼7.2 Hz, 2H), 3.88 (s, 3H), 3.77 (s, 2H), 3.59 (s, 3H), 3.55 (s, 3H),
3.22 (s, 3H), 1.35 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
160.6, 159.3, 152.8, 148.4, 143.7, 139.5, 138.9, 137.0, 134.1, 133.9,
128.7, 128.3, 126.2, 116.3, 106.6, 105.0, 103.8, 99.7, 94.0, 89.3, 61.0,
60.2, 56.0, 55.4, 37.4, 34.4, 12.9; Ion-trap-HRMS (ESI) calcd for
C
31H33N2O6 [MþH]þ 529.2339, found 529.2353.
4. Experimental section
4.2.4. 2-Benzyl-5-ethyl-7,8,9-trimethoxy-1-(m-tolyl)-1H-pyrrolo
4.1. General
[3,2-c]quinolin-4(5H)-one (11d). Brown syrup (114 mg, 82%): IR
(KBr) 2924, 1644, 1505, 1252, 1256, 754 cmꢁ1 1H NMR (400 MHz,
;
IR spectra were recorded with FTIR as a thin film or using KBr
CDCl3)
d
7.22e7.16 (m, 5H), 7.11 (d, J¼7.6 Hz, 1H), 7.02e7.01 (m, 2H),
pellets and are expressed in cmꢁ1 1H (400 MHz) and 13C
.
6.87 (d, J¼7.6 Hz,1H), 6.71 (s,1H), 6.69 (s,1H), 4.46 (q, J¼7.2 Hz, 2H),
(100 MHz) NMR spectra were recorded using CDCl3 as a solvent.
Chemical shifts are reported in parts per million downfield to
tetramethylsilane. Coupling constants are reported and expressed
in Hertz; splitting patterns are designated as s (singlet), d (dou-
blet), t (triplet), q (quartet), m (multiplet), dd (double doublet), dt
(double triplet), dq (double quartet). Infrared (IR) spectra were
obtained on a Bruker Vector 22 spectrometer. Mass spectra
were obtained from high resolution ESI mass spectrometer. All
reactions were carried out using freshly distilled and dry
solvents. Column chromatography was performed over silica gel
(100e200 mesh) using petroleum ether and ethyl acetate as the
eluent.
3.95 (s, 3H), 3.74 (s, 2H), 3.62 (s, 3H), 3.17 (s, 3H), 2.27 (s, 3H), 1.42 (t,
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 159.3,152.8,148.3,142.1,
139.8, 138.7, 138.4, 137.0, 134.1, 133.9, 128.8, 128.3, 128.2, 127.8,
127.2, 126.1, 123.4, 116.4, 106.4, 103.8, 94.0, 60.9, 59.8, 56.0, 37.4,
34.5, 21.1, 12.9; Ion-trap-HRMS (ESI) calcd for C30H31N2O4 [MþH]þ
483.2284, found 483.2269.
4.2.5. 2-Benzyl-5-ethyl-7,8,9-trimethoxy-1-(phenylamino)-1H-pyr-
rolo[3,2-c]quinolin-4(5H)-one (11e). Yellow solid (65 mg, 45%),
mp¼94e96 ꢀC; IR (KBr) 3446, 2923, 1642, 1456, 1267, 754 cmꢁ1; 1H
NMR (400 MHz, CDCl3)
d 7.34e7.31 (m, 3H), 7.22e7.16 (m, 3H),
7.04e7.00 (m, 4H), 6.70 (s, 1H), 6.69 (s, 1H), 4.46 (q, J¼7.2 Hz, 2H),
3.94 (s, 3H), 3.78 (s, 2H), 3.61 (s, 3H), 3.18 (s, 3H), 1.42 (t, J¼7.2 Hz,
4.2. General procedure for the synthesis of 11 from 6
3H); 13C NMR (100 MHz, CDCl3)
d 159.3, 152.8, 148.3, 142.3, 139.8,
138.6, 137.1, 134.1, 134.0, 128.7, 128.5, 128.2, 127.1, 126.4, 126.2, 116.4,
106.5, 103.8, 94.1, 60.9, 59.8, 56.0, 37.4, 34.4, 12.9; Ion-trap-HRMS
(ESI) calcd for C29H30N3O4 [MþH]þ 484.2236, found 484.2249.
The mixture of 6 (0.3 mmol), amine (0.3 mmol), DCE (5 mL), and
p-TsOH (10.3 mg, 0.06 mmol) was stirred at 105 ꢀC under nitrogen
atmosphere for w16 h. After the disappearance of material 6
according to TLC, the mixture was cooled to room temperature.
Removal of the organic solvent provided the crude product, which
then was purified by flash chromatography on silica gel (eluent:
EtOAc/PE¼1:3) to give 11.
4.2.6. 2-(2-Bromo-benzyl)-5-ethyl-7,8,9-trimethoxy-1-phenyl-1,5-
dihydro-pyrrolo[3,2-c]quinolin-4-one (11g). Brown solid (126 mg,
77%), mp¼246e248 ꢀC; IR (KBr) 2932, 1645, 1554, 1458, 1277, 1023,
754 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.53 (dd, J¼0.8 Hz, J¼8.0 Hz,
1H), 7.23e7.08 (m, 3H), 7.05 (br, 1H), 7.03e6.99 (m, 4H), 6.72 (s, 1H),
6.51 (s, 1H), 4.46 (q, J¼7.2 Hz, 1H), 3.98 (s, 3H), 3.84 (s, 2H), 3.68 (s,
3H), 2.42 (s, 3H), 1.44 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
4.2.1. 2-Benzyl-5-ethyl-7,8,9-trimethoxy-1-(p-tolyl)-1H-pyrrolo[3,2-
c]quinolin-4(5H)-one (11a). Brown solid (118 mg, 82%),
mp¼157e159 ꢀC; IR (film) 2927, 1645, 1509, 1453, 1252,
d
159.3, 152.9, 148.4, 139.1, 138.7, 138.3, 137.1, 136.9, 134.2, 134.1,
755 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.23e7.18 (m, 3H), 7.12 (d,
132.8, 131.0, 129.3, 128.2, 127.4, 126.0, 124.7, 116.4, 106.5, 103.9, 94.1,
61.0, 59.9, 56.1, 37.4, 35.0, 21.2, 12.9; Ion-trap-HRMS (ESI) calcd for
J¼8.0 Hz, 2H), 7.04e7.02 (m, 2H), 6.91 (d, J¼8.0 Hz, 2H), 6.69 (s,
1H), 6.67 (s, 1H), 4.45 (q, J¼7.2 Hz, 2H), 3.94 (s, 3H), 3.75 (s, 2H),
3.64 (s, 3H), 3.20 (s, 3H), 2.39 (s, 3H), 1.41 (t, J¼7.2 Hz, 3H); 13C
C
29H28BrN2O4 [MþH]þ 547.1232, found 547.1259.
NMR (100 MHz, CDCl3)
d
159.3, 152.7, 148.4, 140.1, 139.7, 138.7,
4.2.7. 2-(2-Bromo-benzyl)-5-ethyl-7,8,9-trimethoxy-1-p-tolyl-1,5-
dihydro-pyrrolo[3,2-c]quinolin-4-one (11h). Yellow solid (134 mg,
80%), mp¼255e257 ꢀC; IR (KBr) 2930, 1621, 1545, 1447, 1257, 1024,
137.0, 136.8, 134.1, 134.0, 129.1, 128.8, 128.6, 128.2, 126.2, 126.1,
116.3, 106.3, 94.1, 61.0, 59.9, 56.0, 37.4, 34.4, 21.1, 12.9; Ion-trap-
HRMS (ESI) calcd for
483.2270.
C
30H31N2O4 [MþH]þ 483.2284, found
752 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.54 (dd, J¼1.2 Hz, J¼7.6 Hz,
1H), 7.27e7.08 (m, 5H), 7.03 (br, 1H), 7.00 (br, 1H), 6.72 (s, 1H), 6.51
(s, 1H), 4.47 (q, J¼7.6 Hz, 2H), 3.98 (s, 3H), 3.94 (s, 2H), 3.68 (s, 3H),
3.24 (s, 3H), 2.42 (s, 3H), 1.44 (t, J¼7.6 Hz, 3H); 13C NMR (100 MHz,
4.2.2. 2-Benzyl-5-ethyl-7,8,9-trimethoxy-1-(3-methoxyphenyl)-1H-
pyrrolo[3,2-c]quinolin-4(5H)-one (11b). Brown solid (112 mg, 75ꢁ%1),
CDCl3) d 159.5, 152.9, 148.9, 140.0, 138.5, 138.4, 137.1, 137.0, 134.1,
mp¼124e126 ꢀC; IR (KBr) 2927, 1645, 1456, 1325, 1256, 755 cm
;
133.9, 132.5, 130.9, 129.3, 127.9, 127.2, 125.9, 124.4, 116.1, 106.3,
103.7, 94.3, 60.8, 56.1, 37.4, 35.0, 21.0, 12.9; Ion-trap-HRMS (ESI)
calcd for C30H30BrN2O4 [MþH]þ 561.1389, found 561.1374.
1H NMR (400 MHz, CDCl3)
d 7.24e7.14 (m, 4H), 7.04e7.02 (m, 2H),
6.87e6.85 (m, 1H), 6.72 (s, 1H), 6.69 (s, 1H), 6.68e6.66 (m, 1H),
6.51e6.50 (m, 1H), 4.46 (q, J¼7.2 Hz, 2H), 3.95 (s, 3H), 3.80 (d,
J¼16 Hz, 2H), 3.64 (s, 3H), 3.63 (s, 3H), 3.23 (s, 3H), 1.42 (t, J¼7.2 Hz,
4.2.8. 2-(2-Bromo-benzyl)-5-ethyl-7,8,9-trimethoxy-1-(3-methoxy-
phenyl)-1,5-dihydro-pyrrolo[3,2-c]quinolin-4-one (11i). Brown solid
(128 mg, 74%), mp¼298e300 ꢀC; IR (KBr) 2921, 1630, 1528, 1430,
3H); 13C NMR (100 MHz, CDCl3)
d 159.8, 159.3, 152.8, 148.3, 143.3,
139.7, 138.7, 137.0, 134.1, 133.9, 129.1, 128.7, 128.3, 126.2, 118.9, 116.3,
113.3, 112.0, 106.6, 103.8, 94.0, 61.0, 60.0, 56.0, 55.3, 37.4, 34.4, 12.9;
1241, 1038, 754 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.50 (d, J¼8.0 Hz,
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X. Zhang et al. / Tetrahedron xxx (2014) 1e7
5
1H), 7.28e7.60 (m, 4H), 6.88 (dd, J¼8.4 Hz, 1H), 6.71 (br, 1H), 6.70
(br, 1H), 6.62 (br, 1H), 6.55 (br, 1H), 4.45 (q, J¼6.8 Hz, 2H), 3.96 (s,
3H), 2.39 (s, 3H), 1.39 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
159.7, 159.5, 155.2, 140.3, 139.4, 139.3, 138.8, 136.5, 134.7, 128.9,
3H), 3.71 (s, 3H), 3.66 (s, 3H), 3.25 (s, 3H), 1.42 (t, J¼7.2 Hz, 3H); 13
C
128.8, 128.2, 126.4, 126.1, 115.5, 106.1, 100.3, 92.1, 91.6, 55.3, 53.8,
37.5, 34.4, 21.1, 12.9; Ion-trap-HRMS (ESI) calcd for C29H29N2O3
[MþH]þ 453.2178, found 453.2159.
NMR (100 MHz, CDCl3)
d 160.0, 159.3, 153.0, 148.4, 143.3, 138.3,
137.1,134.2,134.0,132.8,130.9,129.4,128.2,127.4,124.6,118.8,116.5,
11.3, 116.9, 113.3, 111.9, 106.8, 103.8, 94.1, 61.0, 60.0, 56.1, 55.4, 37.5,
34.9, 12.9; Ion-trap-HRMS (ESI) calcd for C30H30BrN2O5 [MþH]þ
577.1388, found 577.1362.
4.2.14. 2-(2-Chlorobenzyl)-5-ethyl-7,9-dimethoxy-1-phenyl-1H-pyr-
rolo[3,2-c]quinolin-4(5H)-one (11o). Brown solid (93 mg,ꢁ61 6%),
mp¼152e153 ꢀC; IR (KBr) 2923, 1645, 1456, 1254, 755 cm
;
1H
4.2.9. 2-(2-Bromo-benzyl)-1-(3,5-dimethoxy-phenyl)-5-ethyl-7,8,9-
trimethoxy-1,5-dihydro-pyrrolo[3,2-c]quinolin-4-one (11j). Brown
solid (109 mg, 60%), mp¼294e296 ꢀC; IR (KBr) 2918, 1635, 1523,
NMR (400 MHz, CDCl3) d 7.39e7.28 (m, 4H), 7.15e7.07 (m, 5H), 6.56
(s, 1H), 6.55 (s, 1H), 6.07 (s, 1H), 4.43 (d, J¼7.2 Hz, 2H), 3.86 (s, 3H),
3.81 (s, 2H), 2.99 (s, 3H), 1.39 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
1442, 1235, 1039, 755 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.43 (d,
CDCl3) d 159.6, 159.6, 155.2, 142.8, 139.3, 137.7, 136.5, 134.7, 133.9,
J¼7.6 Hz, 2H), 7.15e6.98 (m, 3H), 6.62 (s, 1H), 6.50 (s, 1H), 6.36 (t,
J¼2.4 Hz, 1H), 6.16 (d, J¼2.0 Hz, 2H), 4.37 (q, J¼7.2 Hz, 2H), 3.88 (s,
3H), 3.84 (s, 2H), 3.60 (s, 3H), 3.59 (s, 6H), 3.24 (s, 3H), 1.36 (t,
d 161.0,159.5,152.9,148.5,
143.9, 138.7, 138.2, 137.1, 134.3, 134.2, 132.7, 130.9, 128.2, 127.4,
124.6, 116.4,106.9,104.9,103.8, 99.8, 97.1, 94.3, 60.9, 60.0, 55.9, 55.5,
130.9, 129.3, 128.6, 127.8, 126.9, 126.7, 126.5, 115.7, 106.4, 100.2, 92.2,
91.6, 55.3, 53.8, 37.6, 32.0, 12.8; Ion-trap-HRMS (ESI) calcd for
C
28H26N2O3 [MþH]þ 473.1632, found 473.1644.
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
4.2.15. 2-(2-Chlorobenzyl)-5-ethyl-7,9-dimethoxy-1-(p-tolyl)-1H-
pyrrolo[3,2-c]quinolin-4(5H)-one (11p). Brown solid (117 mg, 80ꢁ%1),
37.5, 35.1, 12.9; Ion-trap-HRMS (ESI) calcd for
C31H32BrN2O6
mp¼161e163 ꢀC; IR (KBr) 2924, 1644, 1457, 1263, 1080, 755 cm
;
[MþH]þ 607.1444, found 607.1495.
1H NMR (400 MHz, CDCl3)
d 7.31e7.28 (m, 1H), 7.18e7.11 (m, 5H),
6.97e6.95 (m, 2H), 6.55 (s, 1H), 6.50 (s, 1H), 6.08 (s, 1H), 4.42 (q,
J¼7.2 Hz, 2H), 3.86 (s, 3H), 3.79 (s, 2H), 2.96 (s, 3H), 2.39 (s, 3H), 1.39
4.2.10. 2-(2-Bromo-benzyl)-5-ethyl-7,8,9-trimethoxy-1-(4-nitro-
phenyl)-1,5-dihydro-pyrrolo[3,2-c]quinolin-4-one
(11k). Brown
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 159.6, 159.6, 155.2,
solid (144 mg, 81%), mp¼315e317 ꢀC; IR (KBr) 2922, 1625, 1538,
140.3,139.3,137.8,136.6,134.7,134.0,131.0,129.3,129.1,127.8,126.7,
126.2, 115.5, 106.1, 100.3, 92.1, 91.6, 55.3, 53.8, 37.5, 32.1, 21.0, 12.8;
Ion-trap-HRMS (ESI) calcd for C29H28ClN2O3 [MþH]þ 487.1788,
found 487.1769.
1450, 1241, 1045, 756 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 8.23 (d,
J¼8.8 Hz, 2H), 7.49 (d, J¼7.6 Hz, 1H), 7.24 (d, J¼8.8 Hz, 3H), 7.19 (d,
J¼6.8 Hz, 2H), 7.09 (d, J¼7.6 Hz,1H), 6.73 (s,1H), 6.64 (s,1H), 4.46 (q,
J¼7.2 Hz, 2H), 3.97 (s, 3H), 3.90 (s, 2H), 3.64 (s, 3H), 3.28 (s, 3H), 1.43
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
162.3, 159.0, 153.5,
4.2.16. 2-(2-Chlorobenzyl)-5-ethyl-7,9-dimethoxy-1-(m-tolyl)-1H-
147.9,147.7,146.5,137.8,137.4, 134.3,134.2,132.9,130.6,128.5,128.7,
126.7, 134.4, 134.2, 117.3, 108.1, 103.3, 94.6, 61.2, 60.1, 56.1, 37.6, 34.6,
pyrrolo[3,2-c]quinolin-4(5H)-one (11q). Brown solid (105 mg, 72ꢁ%1),
mp¼136e137 ꢀC; IR (KBr) 2923, 1639, 1459, 1266, 1080, 755 cm
;
12.9; Ion-trap-HRMS (ESI) calcd for
592.1083, found 592.1067.
C
29H27BrN3O6 [MþH]þ
1H NMR (400 MHz, CDCl3)
d 7.32e7.28 (m, 1H), 7.24e7.22 (m, 2H),
7.14e7.09 (m, 4H), 6.84 (s, 1H), 6.58 (s, 1H), 6.56 (s, 1H), 6.08 (s, 1H),
4.44 (q, J¼7.2 Hz, 2H), 3.86 (s, 3H), 3.82 (s, 2H), 2.93 (s, 3H), 2.31 (s,
4.2.11. 2-(2-Chlorobenzyl)-5-ethyl-7,8,9-trimethoxy-1-(p-tolyl)-1H-
3H), 1.40 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 159.6, 159.6,
pyrrolo[3,2-c]quinolin-4(5H)-one (11l). Yellow solid (118 mgꢁ, 182%),
155.2, 139.3, 138.5, 137.7, 136.6, 130.9, 130.1, 129.3, 129.3,128.8,
128.3, 127.7, 127.6, 127.5, 127.1, 126.7, 123.5, 115.6, 106.4, 92.1, 91.7,
55.3, 53.8, 37.6, 31.9, 21.1, 12.8; Ion-trap-HRMS (ESI) calcd for
mp¼164e166 ꢀC; IR (KBr) 2924, 1647, 1456, 1263, 755 cm
;
1H
NMR (400 MHz, CDCl3)
d 7.31e7.29 (m, 1H), 7.16e7.11 (m, 5H),
6.98e6.97 (m, 2H), 6.69 (s, 1H), 6.50 (s, 1H), 4.42 (d, J¼7.2 Hz, 2H),
C
29H28ClN2O3 [MþH]þ 487.1788, found 487.1999.
3.94 (s, 3H), 3.81 (s, 2H), 3.64 (s, 3H), 3.21 (s, 3H), 2.38 (s, 3H), 1.40
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
159.2, 152.8, 148.4,
4.2.17. 2-(2-Chlorobenzyl)-5-ethyl-7,9-dimethoxy-1-(phenylamino)-
1H-pyrrolo[3,2-c]quinolin-4(5H)-one (11r). Yellow solid (70 mg,
48%), mp¼162e164 ꢀC; IR (KBr) 3450, 2923, 1642, 1519, 1268, 1039,
139.7, 138.6, 137.0, 136.9, 136.5, 134.1, 134.0, 134.0, 130.9, 129.4,
129.3, 127.9, 126.7, 125.9, 116.3, 106.3, 103.9, 94.1, 61.0, 59.9, 56.0,
37.4, 32.2, 21.1, 12.9; Ion-trap-HRMS (ESI) calcd for C30H30ClN2O4
[MþH]þ 517.1894, found 517.1906.
755 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.39e7.28 (m, 4H), 7.15e7.07
(m, 5H), 6.56 (s, 1H), 6.55 (s, 1H), 6.08 (s, 1H), 4.43 (d, J¼7.2 Hz, 2H),
3.86 (s, 3H), 3.81 (s, 2H), 2.93 (s, 3H), 1.39 (t, J¼7.2 Hz, 3H); 13C NMR
4.2.12. 2-(2-Chlorobenzyl)-5-ethyl-7,8,9-trimethoxy-1-(3-
methoxyphenyl)-1H-pyrrolo[3,2-c]quinolin-4(5H)-one
(11m). Brown solid (123 mg, 77%), mp¼182e184 ꢀC; IR (KBr) 2926,
(100 MHz, CDCl3) d 159.6, 159.6, 155.2, 142.8, 139.3, 137.7, 136.5,
134.7, 133.9, 130.9, 129.3, 128.6, 127.8, 126.9, 126.7, 126.5, 115.7,
106.4, 100.2, 92.2, 91.6, 55.4, 53.8, 37.6, 32.0, 12.8; Ion-trap-HRMS
(ESI) calcd for C28H27ClN3O3 [MþH]þ 488.1741, found 488.1756.
1646, 1457, 1263, 1098, 755 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
7.32e7.30 (m, 2H), 7.16e7.10 (m, 3H), 6.89e6.86 (m, 1H), 6.71 (s,
1H), 6.69 (s, 1H), 6.61 (s, 1H), 6.59 (s, 1H), 4.45 (q, J¼7.2 Hz, 2H), 3.95
4.2.18. 2-(2-Chlorobenzyl)-1-(3,5-dimethylphenyl)-5-ethyl-7,9-
dimethoxy-1H-pyrrolo[3,2-c]quinolin-4(5H)-one (11s). Brown solid
(93 mg, 62%), mp¼167e168 ꢀC; IR (KBr) 2924, 1647, 1457, 1286,
(s, 3H), 3.88e3.87 (br, 2H), 3.68 (s, 3H), 3.65 (s, 3H), 3.25 (s, 3H),1.42
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 159.9, 159.2, 152.9,
148.3, 143.2, 138.2, 137.0, 136.5, 134.1, 134.0, 133.9, 130.8, 129.3,
127.9, 126.8, 118.7, 116.4, 113.2, 111.8, 106.6, 103.7, 94.0, 61.0, 60.0,
56.0, 55.3, 37.4, 32.1, 12.9; Ion-trap-HRMS (ESI) calcd for
1080, 754 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 7.29e7.26 (m, 1H),
7.13e7.11 (m, 4H), 6.92 (s, 1H), 6.62 (s, 1H), 6.60 (s, 1H), 6.56 (s, 1H),
6.09 (s, 1H), 4.44 (d, J¼7.2 Hz, 2H), 3.82 (s, 2H), 2.94 (s, 3H), 2.26 (s,
C
30H30ClN2O5 [MþH]þ 533.1843, found 533.1857.
6H), 1.40 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 159.6, 159.6,
155.3, 142.5, 139.3, 138.2, 137.7, 136.7, 134.6, 133.8, 130.8, 129.2,
128.4, 127.6, 126.6, 124.2, 115.5, 106.4, 100.4, 92.1, 91.7, 55.3, 53.7,
37.5, 31.9, 21.0, 12.8; Ion-trap-HRMS (ESI) calcd for C30H30ClN2O3
[MþH]þ 501.1945, found 501.1962.
4.2.13. 2-Benzyl-5-ethyl-7,9-dimethoxy-1-(p-tolyl)-1H-pyrrolo[3,2-
c]quinolin-4(5H)-one (11n). Yellow solid (108 mg, ꢁ81 0%),
mp¼107e109 ꢀC; IR (KBr) 2925, 1644, 1454, 1208, 753 cm
;
1H
NMR (400 MHz, CDCl3)
d
7.20e7.16 (m, 3H), 7.14 (d, J¼8.0 Hz, 2H),
7.02e7.01 (m, 2H), 6.89 (d, J¼8.0 Hz, 2H), 6.67 (s, 1H), 6.55 (s, 1H),
4.2.19. 5-Ethyl-7,9-dimethoxy-2-(4-methylbenzyl)-1-(p-tolyl)-1H-
pyrrolo[3,2-c]quinolin-4(5H)-one (11t). Brown syrup (116 mg, 83%);
6.06 (s, 1H), 4.43 (q, J¼7.2 Hz, 2H), 3.85 (s, 3H), 3.73 (s, 2H), 2.94 (s,
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6
X. Zhang et al. / Tetrahedron xxx (2014) 1e7
IR (KBr) 2925, 1624, 1512, 1456, 1082, 754 cmꢁ1; 1H NMR (400 MHz,
CDCl3)
extracts were washed with brine, dried over Na2SO4, filtered, and
concentrated. The residue was purified by flash column chroma-
tography (using petroleum ether/ethyl acetate (3:1) as the eluent)
to give 19.
d
7.15 (d, J¼8.0 Hz, 2H), 7.02 (d, J¼8.0 Hz, 2H), 6.93e6.89 (m,
4H), 6.64 (s, 1H), 6.55 (s, 1H), 6.07 (s, 1H), 4.43 (q, J¼7.2 Hz, 2H), 3.86
(s, 3H), 3.67 (s, 2H), 2.94 (s, 3H), 2.39 (s, 3H), 2.29 (s, 3H), 1.39 (t,
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 159.7,159.5,155.2,140.4,
139.7, 139.3, 136.5, 135.7, 135.6, 134.7, 128.9, 128.7, 128.6, 126.4,
115.5, 106.0, 100.4, 92.1, 91.6, 55.3, 53.8, 37.5, 33.9, 21.0, 21.0, 12.8;
Ion-trap-HRMS (ESI) calcd for C30H31N2O3 [MþH]þ 467.2335, found
467.2351.
4.3.1. 5-Ethyl-2,3,4-trimethoxy-12-phenyl-11,12-dihydro-5H-5,12-
diaza-benzo[5,6]pentaleno[2,1-b]naphthalen-6-one
(19g). Brown
solid (33 mg, 64%), mp¼192e193 ꢀC; IR (KBr) 2928, 1646, 1552,
1458, 1223, 1049, 745 cmꢁ1; IR (KBr) 2928, 1646, 1552, 1458, 1223,
1049, 745 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
8.39 (d, J¼7.6 Hz, 1H),
4.2.20. 5-Ethyl-7,9-dimethoxy-2-(4-nitrobenzyl)-1-(p-tolyl)-1H-pyr-
7.44 (t, J¼8.0 Hz, 2H), 7.38e7.33 (m, 4H), 7.30e7.27 (m, 2H), 7.12 (t,
J¼8.4 Hz,1H), 6.74 (s,1H), 4.52 (q, J¼8.0 Hz, 2H), 3.98 (s, 3H), 3.70 (s,
3H), 3.57 (s, 2H), 3.26 (s, 3H), 1.49 (t, J¼7.2 Hz, 2H); 13C NMR
rolo[3,2-c]quinolin-4(5H)-one (11u). Brown syrup (111 mg, 78%); IR
(KBr) 2922, 1640, 1531, 1435, 1268, 755 cmꢁ1 1H NMR (400 MHz,
;
CDCl3)
d
8.01 (d, J¼8.0 Hz, 2H), 7.12e7.08 (m, 4H), 6.82 (d, J¼8.0 Hz,
(100 MHz, CDCl3) d 159.6, 153.1, 148.1, 147.8, 143.1, 142.8, 138.6,
2H), 6.78 (s, 1H), 6.56 (s, 1H), 6.07 (s, 1H), 4.44 (q, J¼7.2 Hz, 2H), 3.88
(s, 3H), 3.86 (s, 2H), 2.93 (s, 3H), 2.38 (s, 3H), 1.40 (t, J¼7.2 Hz, 3H);
137.2, 136.0, 134.4, 129.1, 127.3, 126.9, 126.8, 124.3, 123.6, 122.3,
112.1, 104.2, 94.2, 61.2, 60.0, 56.2, 37.6, 32.3, 13.0; Ion-trap-HRMS
(ESI) calcd for C29H27N2O4 [MþH]þ 467.1971, found 467.1982.
13C NMR (100 MHz, CDCl3)
d 159.8, 159.6, 155.3, 146.6, 146.5, 140.1,
139.5,137.1,136.9,135.1,129.4,129.0,126.4,123.3,115.4,106.8,100.1,
92.2, 91.7, 55.3, 53.8, 37.6, 34.2, 21.0, 12.8; Ion-trap-HRMS (ESI)
calcd for C29H28N3O5 [MþH]þ 498.2029, found 498.2047.
4.3.2. 5-Ethyl-2,3,4-trimethoxy-12-p-tolyl-11,12-dihydro-5H-5,12-
diaza-benzo[5,6]pentaleno[2,1-b]naphthalen-6-one
(19h). Brown
solid (44 mg, 85%), mp¼195e196 ꢀC; IR (KBr) 2919, 1642, 1559,
4.2.21. 5-Ethyl-7,9-dimethoxy-2-(4-nitrobenzyl)-1H-pyrrolo[3,2-c]
quinolin-4(5H)-one (11v). Brown syrup (89 mg, 73%); IR (KBr) 2940,
1642, 1556, 1437, 1245, 1012, 754 cmꢁ1; 1H NMR (400 MHz, CDCl3)
1460, 1265, 1040, 749 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 8.39 (d,
J¼7.6 Hz, 1H), 7.37e7.34 (m, 2H), 7.22 (d, J¼8.0 Hz, 2H), 7.17e7.10
(m, 3H), 6.73 (s, 1H), 4.51 (q, J¼7.2 Hz, 2H), 3.98 (s, 3H), 3.72 (s, 3H),
3.53 (s, 2H), 3.27 (s, 3H), 2.42 (s, 3H), 1.49 (t, J¼7.2 Hz, 3H); 13C NMR
d
7.32e7.30 (m, 1H),
d
9.34 (s, 1H), 8.15 (d, J¼8.4 Hz, 2H), 7.38 (d,
J¼8.4 Hz, 2H), 6.62 (s, 1H), 6.57 (s, 1H), 6.38 (s, 1H), 4.41 (q, J¼7.2 Hz,
(100 MHz, CDCl3) d 159.6, 153.1, 148.2, 147.9, 142.8, 140.6, 138.7,
2H), 4.21 (s, 2H), 3.99 (s, 3H), 3.91 (s, 3H), 1.36 (t, J¼7.2 Hz, 3H); 13
C
137.3, 136.5, 136.0, 134.4, 129.6, 127.2, 126.6, 124.3, 123.7, 123.4,
122.3, 111.9, 104.4, 94.2, 61.3, 60.1, 56.2, 37.6, 32.3, 21.1, 13.0; Ion-
trap-HRMS (ESI) calcd for C30H29N2O4 [MþH]þ 481.2127, found
481.2135.
NMR (100 MHz, CDCl3)
d 159.8, 159.6, 156.3, 146.3, 138.7, 133.5,
131.2, 129.3, 123.8, 113.0, 104.7, 98.9, 92.5, 92.1, 56.0, 55.5, 37.3, 34.1,
12.9; Ion-trap-HRMS (ESI) calcd for C22H22N3O5 [MþH]þ 408.1559,
found 408.1577.
4.3.3. 5-Ethyl-2,3,4-trimethoxy-12-(3-methoxy-phenyl)-11,12-
dihydro-5H-5,12-diaza-benzo[5,6]pentaleno[2,1-b]naphthalen-6-one
(19i). Brown solid (48 mg, 60%), mp¼201e203 ꢀC; IR (KBr) 2936,
1626, 1545, 1438, 1271, 1046, 735 cmꢁ1; 1H NMR (400 MHz, CDCl3)
4.2.22. 2-(2,6-Dimethylbenzyl)-5-ethyl-7,8-dimethoxy-1-(p-tolyl)-
1H-pyrrolo[3,2-c]quinolin-4(5H)-one (11w). Yellow solid (79 mg,
55%), mp¼119e121 ꢀC; IR (KBr) 2923, 1642, 1519, 1452, 1208,
755 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.48 (d, J¼8.0 Hz, 2H), 7.42
d
8.39 (d, J¼7.6 Hz, 1H), 7.38e7.31 (m, 3H), 7.12 (t, J¼7.6 Hz, 1H),
(d, J¼8.0 Hz, 2H), 7.09e7.01 (m, 3H), 6.87 (s, 1H), 6.33 (s, 1H), 6.15 (s,
1H), 4.42 (q, J¼7.2 Hz, 2H), 3.93 (s, 3H), 3.64 (s, 2H), 3.33 (s, 3H), 2.51
(s, 3H), 2.21 (s, 6H),1.35 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
6.90e6.88 (m, 2H), 6.81 (s, 1H), 6.73 (s, 1H), 4.51 (q, J¼6.8 Hz, 2H),
3.98 (s, 3H), 3.79 (s, 3H), 3.72 (s, 3H), 3.59 (s, 2H), 3.32 (s, 3H); 13C
NMR (100 MHz, CDCl3)
d 160.3, 159.6, 153.3, 148.4, 147.7, 144.3,
d
159.1, 148.5, 143.7, 139.7, 137.1, 136.7, 136.4, 134.6, 131.6, 130.7,
142.9, 138.8, 137.4, 136.0, 134.6, 129.8, 127.4, 126.7, 124.3, 123.8,
122.3, 116.1, 112.3, 112.1, 111.3, 104.2, 100.0, 94.2, 61.3, 60.4, 56.3,
55.6, 37.7, 32.5, 13.1; Ion-trap-HRMS (ESI) calcd for C30H29N2O5
[MþH]þ 497.2076, found 497.2058.
128.9, 128.1, 126.6, 114.4, 107.8, 103.9, 103.4, 98.9, 56.0, 54.9, 37.0,
27.6, 21.2, 19.7, 13.0; Ion-trap-HRMS (ESI) calcd for C31H33N2O3
[MþH]þ 481.2491, found 481.2479.
4.2.23. 2-(2-Chlorobenzyl)-5-ethyl-7,8-dimethoxy-1-(p-tolyl)-1H-
pyrrolo[3,2-c]quinolin-4(5H)-one (11x). Brown solid (109 mg, 75%),
mp¼184e186 ꢀC; IR (KBr) 2925, 1641, 1577, 1465, 1268, 1039,
4.3.4. 5-Ethyl-2,3,4-trimethoxy-12-(4-nitro-phenyl)-11,12-dihydro-
5H-5,12-diaza-benzo[5,6]pentaleno[2,1-b]naphthalen-6-one
(19k). Brown syrup (48 mg, 60%), mp¼243e245 ꢀC; IR (KBr) 2935,
1625, 1553, 1427, 1252, 1022, 748 cmꢁ1; 1H NMR (400 MHz, CDCl3)
755 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.34 (d, J¼8.0 Hz, 2H),
7.29e7.28 (m, 1H), 7.22 (d, J¼8.0 Hz, 2H), 7.16e7.14 (m, 3H), 6.87 (s,
1H), 6.59 (s,1H), 6.27 (s, 1H), 4.45 (q, J¼7.2 Hz, 2H), 3.93 (s, 3H), 3.89
(s, 2H), 3.29 (s, 3H), 2.45 (s, 3H), 1.38 (t, J¼7.2 Hz, 3H); 13C NMR
d
8.40 (d, J¼8.0 Hz,1H), 8.32 (d, J¼9.2 Hz, 2H), 7.44 (d, J¼9.2 Hz, 2H),
7.16 (t, J¼6.4 Hz, 1H), 6.77 (s, 1H), 4.52 (q, J¼7.2 Hz, 2H), 4.00 (s, 3H),
3.73 (s, 3H), 3.61 (s, 2H), 3.34 (s, 3H), 1.50 (t, J¼7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3)
d
159.1, 148.6, 143.7, 139.6, 136.7, 136.2, 135.9,
(100 MHz, CDCl3) d 159.4, 153.7, 148.5, 147.6, 146.6, 146.0, 142.3,
134.0,134.0,131.7,130.8,130.4,129.3,129.0,127.9,126.7,114.4,107.8,
105.5, 103.4, 98.9, 56.0, 54.8, 37.1, 30.7, 21.2, 13.0; Ion-trap-HRMS
(ESI) calcd for C29H28ClN2O3 [MþH]þ 487.1788, found 487.1799.
137.9, 137.7, 136.1, 134.7, 128.2, 127.5, 124.8, 124.4, 122.9, 122.6, 113.0,
103.7, 94.8, 61.5, 60.3, 56.2, 37.7, 32.4, 13.0; Ion-trap-HRMS (ESI)
calcd for C29H26N3O6 [MþH]þ 512.1822, found 512.1810.
4.3. General procedure for the synthesis of 19 from 11 via
direct arylation
4.4. General procedure for the synthesis of 19 from 11 via
a dehydrogenative coupling
K2CO3 (0.2 mmol), Pd(OAc)2 (10 mol %), and PPh3 (20 mol %)
were subsequently added to the stirred solution of 11 (0.1 mmol) in
dry toluene (2 mL) in a Schlenk flask under nitrogen atmosphere.
The reaction mixture was heated at 120 ꢀC until the disappearance
of the starting material (approximately 16 h) according to TLC. H2O
(5 mL) was then added to the reaction mixture. The resulting
mixture was extracted with AcOEt (3ꢂ5 mL). The combined organic
Pd(OAc)2 (11.2 mg, 0.05 mmol, 5.0 mol %), Cu(OAc)2$(182 mg,
1.0 mmol), PivOH (250 mg, 2.5 mmol), and 11 (0.5 mmol) in dry
toluene(3 mL) were stirred in a sealed tube at 140 ꢀC for 20 h. H2O
(50 mL) was added at ambient temperature, and the resulting
mixture was extracted with EtOAc(3ꢂ50 mL). The combined or-
ganic layers were washed with satd aq NH4Cl (50 mL), H2O (50 mL),
and brine (50 mL), dried over Na2SO4, filtered, and concentrated in
Please cite this article in press as: Zhang, X.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.05.084

X. Zhang et al. / Tetrahedron xxx (2014) 1e7
7
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vacuo. The residue was purified by flash column chromatography
(using petroleum ether/ethyl acetate¼10:1 as the eluent) to
give 19.
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This work was supported by the National Natural Science
Foundation of China (No. 21072062, 21272078, 21336002), the
Fundamental Research Funds for the Central Universities
(2014ZG0027), the Natural Science Foundation of Guangdong
Province, China (10351064101000000), the Program for New Cen-
tury Excellent Talents in Universities (NCET-12-0189), and the Open
Funds for the State Key Laboratory of Pulp and Paper Engineering of
China.
Supplementary data
Details on CIF information of 11n, scanned photocopies of 1H
and 13C NMR spectral data were supported. Supplementary data
related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2014.05.084.
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Please cite this article in press as: Zhang, X.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.05.084