Synthesis of diversely substituted indoloquinolinones via Pd(II)/Cu(II)-mediated oxidative C-C bond formation and I(III)-mediated C-N bond formation

Article abstract of DOI:10.1021/jo4023292

A series of indoloquinolinones bearing different aromatic substitutents were readily synthesized starting from an aryl amine, a methyl 3-oxo-3-phenylpropanoate derivative, and methoxylamine through a series of reactions of coupling/enamination, oxidative

Full text of DOI:10.1021/jo4023292

Article
pubs.acs.org/joc
Synthesis of Diversely Substituted Indoloquinolinones via Pd(II)/
Cu(II)-Mediated Oxidative C−C Bond Formation and I(III)-Mediated
C−N Bond Formation
Xiang Zhang,† Daisy Zhang-Negrerie,† Jun Deng,†,‡ Yunfei Du,*,†,‡ and Kang Zhao*,†
†Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin
University, Tianjin 300072, China
‡Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
S
* Supporting Information
ABSTRACT: A series of indoloquinolinones bearing different aromatic substitutents were readily synthesized starting from an
aryl amine, a methyl 3-oxo-3-phenylpropanoate derivative, and methoxylamine through a series of reactions of coupling/
enamination, oxidative annulation, a one-pot sequence of N-alkylation, saponification and methoxyamidation, and final
intramolecular oxidative C−N bond formation. The underpinning of the strategy entails Pd(OAc)2/Cu(OAc)2-mediated
oxidative C(sp2)−C(sp2) bond formation and I(III)-mediated oxidative C(sp2)−N bond formation.
A literature survey indicates that there are a handful of
strategies that have been developed for the construction of the
indoloquinolinone skeleton. Arguably, the most commonly
used approach involves the reaction between a substituted
phenylhydrazine derivative and a 4-piperidinone derivative, a
method known as the Fisher indole synthesis (Figure 2, path
a).2b The indoloquinolinone skeleton can also be constructed
through an intramolecular displacement reaction involving an
aromatic fluorine (Figure 2, path b).4 The copper-catalyzed
cyclic antinucleometalation carboxylation of 2-alkynylanilines
followed by treatment with EDCI and detosylation is also an
effective approach to access this privileged molecule (Figure 2,
path c).5 The skeleton can also be assembled from an indole-3-
carboxylate derivative via intramolecular lactamization (Figure
2, path d).6 Furthermore, the target spatial arrangement of the
nuclei can be formed via a microwave-assisted thermal
electrocyclization of a phenyl isocyanate (Figure 2, path e).3c
The CuI-catalyzed photochemical or thermal reaction of 3-(2-
azidobenzylidene)-lactams (Figure 2, path f)7 and an
intermolecular condensation between 2-aminobenzylamine
and isatin can also provide the desired indoloquinolinone
skeleton (Figure 2, path g).8 Generally speaking, the main-
stream approach of the currently existing strategies remains at
the level of modification or functionalization of indole-,
indolinone-, or quinolinone-based compounds as starting
materials, which naturally limits the substituent pattern in the
INTRODUCTION
■
Indoloquinolinone derivatives exhibit potent practical value in
organic synthesis because of their wide occurrence in numerous
bioactive natural products.1 Indoloquinolinones (Figure 1, A1
Figure 1. Biologically active indoloquinolinones and their derivatives.
and A2), the structures of which belong to compounds that are
effective DNA intercalators, show cytotoxic ability against many
forms of cancer, such as leukemia and ovarian, breast, colon,
and central nervous system cancer.2 This coplanar tetracyclic
structure can also be utilized as useful building blocks for the
synthesis of many other potential antineoplastics (Figure 1,
B1−B4) as well as natural products such as isocryptolepine
(Figure 1, C).2b,3
Received: October 18, 2013
© XXXX American Chemical Society
A
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RESULTS AND DISCUSSION
■
Adopting the synthetic strategy described earlier, the simplest
substrate, 4a, with no substituent in either of the phenyl rings
was first prepared. The reaction of 3-oxo-3-phenyl propanoate
1a with aniline in glacial acetic acid provided N-phenyl enamine
2a in 79% yield. Following Glorius’ method by treating 2a with
Pd(OAc)2/Cu(OAc)2 under basic conditions, an oxidative C−
C bond formation occurred in 2a, leading to corresponding
indole product 3a in moderate yield.11a,c Similarly, the other
indole-3-carboxylates, 3b−o, could be readily obtained by this
transition-metal-mediated oxidative C−C bond-formation
approach (Table 1). Both electron-donating and electron-
withdrawing groups on the phenyl ring of the aniline moiety
could be well-tolerated in the process, with desired indoles 3b−
g being achieved in moderate to good yields (Table 1, entries
2−7). However, the electronic nature of the R1 substituents on
the phenyl ring significantly influenced the reaction yield
(Table 1, entries 8 and 9, 12 and 13). Specifically, when R1 was
an electron-withdrawing group, the reaction gave the desired
cyclized product in much lower yields relative to the substrate
bearing no substituent (R1 = H) (Table 1, entries 12 and 13).
The method could also be well-applied to the substrates
bearing substituents on both aromatic rings, affording the
corresponding indole products in moderate to good yields
(Table 1, entries 10 and 11, 14 and 15).
Figure 2. Existing strategies for the construction of the indoloquino-
linone skeleton.
phenyl ring(s). In this regard, it is highly desirable to develop
new approaches that would allow the construction of
indoloquinolinones bearing a versatile category of substituents
on either of the two phenyl rings.
Our retrosynthetic analysis for the synthesis of the
indoloquinolinone skeleton is illustrated in Figure 3. We
We also attempted to accomplish the conversion using the
iodobenzene diacetate (PIDA)-mediated oxidative cyclization
method developed in our own laboratory, but unfortunately
product 3a was achieved in only 20% yield.11b
Next, N-unsubstituted indole 3a was smoothly transformed
into intermediate 4a over a three-step sequence of methylation,
saponification, and methoxyamidation (Scheme 1). Adopting
the same strategy, the other N-methoxyamides, 4b−p, could be
conveniently achieved in 44−77% yield (see details in the
Experimental Section).
Scheme 1. Preparation of Intermediate 4a from Methyl 3-
a
Oxo-3-phenylpropanoate 1a
Figure 3. Retrosynthetic analysis.
envisaged that 5-methoxyindoloquinolinone 5 could be
accessed from N-methoxyamide 4 through intramolecular
oxidative C−N bond formation.9 Intermediate 4 could be
prepared from indole-3-carboxylic ester 3 through an N-
alkylation−hydrolysis−methoxyamidation sequence.10 The
preparation of intermediate 3 was attempted from N-aryl
enamine 2 through intramolecular oxidative C−C bond
formation mediated by either a transition metal or a
hypervalent iodine reagent.11 Key intermediate 2 could be
easily formed from the condensation between β-ketoesters 1
and the readily available correspondingly substituted anilines.12
The method ensures versatile functionalization of the target
indoloquinolinone compound, as the various substituents in the
phenyl ring of both 1 and anilines are expected to survive the
proposed reactions and to show up eventually in the final
product.
a
Reagents and conditions: (a) ArNH2, AvOH, 80 °C, 20 h, 79%; (b)
Pd(OAc)2, Cu(OAc)2, K2CO3, DMF, 80 °C, 15 h, 51%; (c) (1)
NaOH, CH3l, THF, rt, 2 h, (2) 2 N NaOH, EtOH, 80 °C, 9 h, then 4
N HCl, (3) SOCl2, DCM, rt, 2 h, then NH2OMe, TEA, DCM, −20 to
0 °C, 2 h (77% over three steps).
With N-methoxyamide 4a in hand, we set out to realize the
last step in the synthesis of the titled compound, namely, the
intramolecular ring-closure reaction to form cyclized product
5a. First, we found that the application of bis(trifluoroacetoxy)-
iodobenzene (PIFA) as oxidant in dichloroethane (DCE)
conveniently converted 4a to 5a in 76% yield (Table 2, entry
1). Later, we realized that the replacement of PIFA by PIDA
further improved the yield to a satisfactory 84% (Table 2, entry
B
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a
Table 1. Pd(OAc)2/Cu(OAc)2-Mediated Oxidative Indolization
a
Reaction conditions: N-aryl enamine 2 (10 mmol), Pd(OAc)2 (10 mol %), Cu(OAc)2 (30 mmol), and K2CO3 (30 mmol) were stirred in DMF
b
c
d
(125 mL) under an atmosphere of argon. The reaction was not stopped until the total consumption of N-aryl enamine 2. Isolated yields. Yield of
two separable regioisomers (3g/3g′ = 56:44).
2). Solvent-screening studies including THF, MeCN, TFE,
DMF, and TFA revealed that none of them were superior to
DCE (Table 2, entries 3−7). Parallel experiments indicated that
reactions run at a lower concentration of 4a (0.02 M) resulted
in a slightly improved yield (86%), whereas a higher
concentration (0.08 M) resulted in a decreased yield of the
product (Table 2, entries 8 and 9). Other hypervalent iodine
reagents (i.e., PhIO and PhICl2) were also tested. Results
showed that reactions using PhIO afforded the desired product
in only 17% yield, whereas PhICl2 was not effective for the
reaction (Table 2, entries 10 and 11).
Under the optimal conditions, a series of enamides 4,
prepared via the approach described in Scheme 1, was
converted to the corresponding cyclized products in satisfactory
to high yields (Table 3). The electronic nature of the R group
on the phenyl ring of the indole moiety, electron-donating or
electron-withdrawing, exhibited no effect on the efficacy of the
reaction, with the desired indoloquinolinones 5b−g achieved in
similar good to excellent yields (Table 3, entries 2−7).
However and as expected, the electronic nature of the R1
substituents on the phenyl ring to which the N-atom cyclizes
did influence the reaction yield to a certain degree. Specifically,
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a
Table 2. Optimization of Reaction Conditions
b
c
entry
oxidant (equiv)
solvent
c (mol/L)
T (°C)
time (h)
yield (%)
1
2
3
4
5
6
7
PIFA (1.2)
PIDA (1.2)
PIDA (1.2)
PIDA (1.2)
PIDA (1.2)
PIDA (1.2)
PIDA (1.2)
PIDA (1.2)
PIDA (1.2)
PhlO (1.2)
PhlCI2 (1.2)
DCE
DCE
THF
MeCN
TFE
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.02
0.08
0.05
0.05
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0.08
0.5
76
84
68
51
65
82
78
86
80
17
ND
0.5
0.17
0.08
0.5
DMF
TFA
0.08
1
d
8
DCE
DCE
DCE
DCE
e
9
0.08
12
10
11
16
a
b
Reaction conditions: 4a (0.2 mmol) and oxidant (0.24 mmol) in solvent (4 mL) unless otherwise stated. The reaction was not stopped until the
c
d
e
total consumption of substrate 4a. Isolated yields. DCE (10 mL) was used. DCE (2.5 mL) was used.
when R1 was an electron-donating group, the reaction gave the
desired cyclized product in slightly higher yields relative to that
CONCLUSIONS
■
We have disclosed an alternative approach to construct the
with no substituent (Table 3, entries 8−11); the opposite was
true when R1 was an electron-withdrawing group (Table 3,
entries 12−13). It is worth noting that PIDA was not effective
for the conversion of substrate 4n or 4o. Desired products 5n
and 5o were obtained in 75 and 82% yields, respectively, when
PIFA was used as the oxidant instead (Table 3, entries 14−15).
Entry 16 shows that the method is also applicable to substrates
where a benzyl substituent is attached to the N-atom of the
indole moiety. This result adds another dimension to the
versatility of the indoloquinolinones that can be obtained
through this method (Table 3, entry 16).
Finally, it is worth mentioning that the N-methoxy moiety in
the final product can be conveniently removed by known
procedures to afford the NH-free indoloquinolinone product.13
For example, compound 5a, upon treatment with NaH in DMF
at 120 °C for 1 h, can be converted to product D in 87% yield
(Scheme 2, eq 1). Moreover, N-benzylated 5p can be converted
to bioactive product A1 in moderate yield under the same
reaction conditions, with both the N-methoxy and the N-benzyl
moieties being effectively removed (Scheme 2, eq 2).
synthetically and biologically important indoloquinolinone
compounds from readily available 3-oxo-3-phenylpropanoate
derivatives and substituted anilines that involves Pd/Cu-
catalyzed C−C bond formation and I(III)-mediated oxidative
C−N bond formation. By starting from simple starting
materials and constructing the skeleton in four steps, the
strategy allows for the various substituents in the starting
materials to be carried through, which neatly provides
convenient access to a variety of biologically active
indolequinolinone derivatives containing different substituents
on the two phenyl rings.
EXPERIMENTAL SECTION
■
General Information. 1H and 13C NMR spectra were recorded on
a 600 MHz (150 MHz for 13C NMR) spectrometer at 25 °C.
Chemical-shift values are given in ppm and referenced to the internal
standard, TMS (tetramethylsilane). The peak patterns are indicated as
follows: s, singlet; d, doublet; t, triplet; q, quadruplet; m, multiplet; dd,
doublet of doublets, and br s, broad singlet. The coupling constants (J)
are reported in Hertz (Hz). High-resolution mass spectrometry
(HRMS) was obtained on a Q-TOF microspectrometer. Melting
points were determined with a National micromelting point apparatus
without corrections. DCM, DCE, CH3CN, toluene, DMF, and THF
were dried by CaH2 before use. Flash column chromatography was
performed over silica gel 200−300 mesh, and the eluent was a mixture
of DCM and MeOH.
Scheme 2. Deprotection of 5-Methoxy Indoloquinolinone 5a
and 5p
General Procedure for the Preparation of N-Aryl Enamines
2.11b A mixture of β-ketone ester (20.0 mmol), substituted aniline
(30 mmol), and glacial acetic acid (30 mmol) was stirred at 80 °C
under a nitrogen atmosphere until TLC indicated the total
consumption of the β-ketone ester. Then, the resulting mixture was
purified by column chromatography using a mixture of petroleum
ether (PE) and EtOAc as eluent to afford N-aryl enamines 2 as a single
Z configuration.
Following this general procedure, known N-aryl enamines 2a,14,15
2b,11b 2c,12b,15 2d,15 2f,12b 2g,12a 2h,16 2i,11c and 2m16 were prepared
in 79, 87, 86, 40, 80, 58, 66, 57, and 81% yields, respectively. The
1
properties and H NMR data of 2a−d, 2f−i, and 2m were consistent
with those in the literature. Novel N-aryl enamines 2e, 2j−l, 2n, and
2o thus obtained were characterized as follows:
D
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a
Table 3. I(III)-Mediated Synthesis of Indoloquinolinones
a
b
c
Optimal reaction conditions: 4 (0.2 mmol, 1 equiv), PIDA (0.24 mmol, 1.2 equiv), DCE (10 mL), room temperature. Isolated yields. Yield of
d
two inseparable regioisomers (5l/5l′ = 10:1). The reaction was carried out using 1.1 equiv of PIFA in DCM at room temperature.
(Z)-Methyl 3-((2-Chlorophenyl)amino)-3-phenylacrylate (2e).
Following the general procedure for 40 h, 2e was isolated as a light
6.29 (d, J = 7.9 Hz, 1H), 5.12 (s, 1H), 3.76 (s, 3H). 13C NMR (150
MHz, CDCl3) δ 170.1, 158.0, 137.5, 135.7, 129.7, 129.6, 128.6, 128.0,
126.4, 125.8, 123.5, 123.4, 93.0, 50.9. HRMS (ESI) m/z calcd for
1
yellow solid. Yield: 1.26 g, 22%, mp 52−58 °C. H NMR (600 MHz,
+
CDCl3) δ 10.34 (br s, 1H), 7.35−7.27 (m, 6H), 6.82−6.78 (m, 2H),
C16H14ClNNaO2 [M + Na+], 310.0605; found, 310.0592.
E
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(Z)-Methyl 3-((4-Chlorophenyl)amino)-3-(p-tolyl)acrylate (2j).
Following the general procedure for 18 h, 2j was isolated as a white
solid. Yield: 3.31 g, 55%, mp 91−92 °C. 1H NMR (600 MHz, CDCl3)
δ 10.23 (br s, 1H), 7.21 (d, J = 7.8 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H),
7.04 (d, J = 9.0 Hz, 2H), 6.59 (d, J = 9.0 Hz, 2H), 6.02 (s, 1H), 3.74
(s, 3H), 2.34 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 170.5, 158.9,
139.9, 139.2, 132.6, 129.3, 128.7, 128.2, 128.1, 123.3, 90.1, 50.7, 21.4.
J = 8.8 Hz, 1H), 3.91 (s, 3H), 3.81 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 166.0, 155.8, 144.9, 132.2, 130.3, 129.5, 129.1, 128.5, 128.1,
113.5, 111.9, 104.1, 103.7, 55.8, 50.8. HRMS (ESI) m/z calcd for
+
C17H16NO3 [M + H+], 282.1125; found, 282.1123.
Methyl 7-Methyl-2-phenyl-1H-indole-3-carboxylate (3d). Follow-
ing the general procedure at 110 °C for 4 h, 3d was isolated as a white
solid. Yield: 1.96 g, 74%, mp 152−153 °C. 1H NMR (600 MHz,
CDCl3) δ 8.55 (br s, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.62 (dd, J = 8.0,
1.9 Hz, 2H), 7.41−7.38 (m, 3H), 7.18 (t, J = 7.5 Hz, 1H), 7.05 (d, J =
7.5 Hz, 1H), 3.78 (s, 3H), 2.47 (s, 3H). 13C NMR (150 MHz, CDCl3)
δ 166.1, 144.6, 134.9, 132.2, 129.6, 129.1, 128.1, 127.2, 123.9, 122.3,
120.5, 119.8, 104.9, 50.9, 16.6. HRMS (ESI) m/z calcd for
+
HRMS (ESI) m/z calcd for C17H16ClNNaO2 [M + Na+], 324.0762;
found, 324.0759.
(Z)-Methyl 3-((2,4-Dimethylphenyl)amino)-3-(4-methoxyphenyl)-
acrylate (2k). Following the general procedure for 18 h, 2k was
1
isolated as a white solid. Yield: 2.80 g, 45%, mp 93−95 °C. H NMR
+
C17H16NO2 [M + H+], 266.1176; found, 266.1165.
(600 MHz, CDCl3) δ 10.04 (br s, 1H), 7.20 (d, J = 8.4 Hz, 2H), 6.93
(s, 1H), 6.75 (d, J = 8.4 Hz, 2H), 6.62 (d, J = 8.4 Hz, 1H), 6.29 (d, J =
8.4 Hz, 1H), 4.96 (s, 1H), 3.76 (s, 3H), 3.73 (s, 3H), 2.35 (s, 3H),
2.19 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 170.8, 160.4, 160.2,
136.6, 133.2, 131.1, 130.4, 129.6, 128.4, 126.5, 124.3, 113.7, 88.7, 55.2,
Methyl 7-Chloro-2-phenyl-1H-indole-3-carboxylate (3e). Follow-
ing the general procedure at 80 °C for 4 h, 3e was isolated as a white
solid. Yield: 2.24 g, 78%, mp 164−166 °C. 1H NMR (600 MHz,
CDCl3) δ 8.78 (br s, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.62 (m, 2H), 7.40
(br s, 3H), 7.24 (d, J = 7.5 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 3.80 (s,
3H).13C NMR (150 MHz, CDCl3) δ 165.4, 145.1, 132.5, 131.4, 129.6,
129.5, 129.0, 128.2, 122.8, 122.6, 120.8, 116.5, 105.5, 51.1. HRMS
+
50.6, 20.7, 18.1. HRMS (ESI) m/z calcd for C19H21NNaO3 [M +
Na+], 334.1414; found, 334.1403.
(Z)-Methyl 3-(3-Chlorophenyl)-3-(phenylamino)acrylate (2l). Fol-
+
(ESI) m/z calcd for C16H13ClNO2 [M + H+], 286.0629; found,
lowing the general procedure for 8 h, 2l was isolated as a light yellow
1
oil. Yield: 4.65 g, 81%. H NMR (600 MHz, CDCl3) δ 10.22 (br s,
286.0614.
1H), 7.38 (s, 1H), 7.31 (d, J = 6.8 Hz, 1H), 7.22−7.16 (m, 2H), 7.11
(t, J = 7.5 Hz, 2H), 6.94 (t, J = 7.2 Hz, 1H), 6.67 (d, J = 7.8 Hz, 2H),
4.99 (s, 1H), 3.74 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 170.3,
157.6, 139.9, 137.8, 134.5, 129.7, 129.6, 128.8, 128.2, 126.5, 123.4,
122.4, 91.3, 50.9. HRMS (ESI) m/z calcd for C16H14ClNNaO2+ [M +
Na+], 310.0605; found, 310.0598.
Methyl 6-Methoxy-2-phenyl-1H-indole-3-carboxylate (3f). Fol-
lowing the general procedure at 100 °C for 12 h, 3f was isolated as a
light yellow solid. Yield: 1.60 g, 57%, mp 147−149 °C. 1H NMR (600
MHz, CDCl3) δ 8.88 (br s, 1H), 8.02 (d, J = 9.0 Hz, 1H), 7.52−7.29
(5H), 6.79 (d, J = 9.0 Hz, 1H), 6.71 (s, 1H), 3.74 (s, 3H), 3.71 (s,
3H). 13C NMR (150 MHz, CDCl3) δ 166.2, 157.0, 143.8, 136.1, 132.0,
129.4, 128.9, 128.1, 122.8, 121.8, 111.9, 104.0, 94.6, 55.6, 50.9. HRMS
(Z)-Methyl 3-((3,4-Dimethoxyphenyl)amino)-3-(p-tolyl)acrylate
(2n). Following the general procedure for 18 h, 2n was isolated as a
+
(ESI) m/z calcd for C17H16NO3 [M + H+], 282.1125; found,
1
light yellow solid. Yield: 4.25 g, 65%, mp 84−85 °C. H NMR (600
282.1117.
MHz, CDCl3) δ 10.23 (br s, 1H), 7.21 (d, J = 8.1 Hz, 2H), 7.07 (d, J =
8.0 Hz, 2H), 6.60 (d, J = 8.6 Hz, 1H), 6.29 (dd, J = 8.6, 2.5 Hz, 1H),
6.20 (d, J = 2.5 Hz, 1H), 4.94 (s, 1H), 3.77 (s, 3H), 3.73 (s, 3H), 3.55
(s, 3H), 2.31 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 170.6, 159.9,
148.6, 145.2, 139.4, 133.9, 133.2, 129.0, 128.2, 114.6, 111.1, 107.5,
Methyl 6-Fluoro-2-phenyl-1H-indole-3-carboxylate (3g) and
Methyl 4-Fluoro-2-phenyl-1H-indole-3-carboxylate (3g′). Following
the general procedure at 60 °C for 12 h, 3g and 3g′ were isolated as
two regioisomers. Yield: 1.51 g, 56% (3g/3g′ = 56:44). 3g: white solid,
mp 202−205 °C. 1H NMR (600 MHz, DMSO-d6) δ 12.24 (br s, 1H),
8.04 (dd, J = 9.0, 5,4 Hz, 1H), 7.70 (d, J = 6.6 Hz, 2H), 7.52−7.48 (m,
3H), 7.22 (dd, J = 9.0, 1.8 Hz, 1H), 7.08 (ddd, J = 9.6, 9.0, 1.8 Hz,
1H), 3.74 (s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 164.6, 159.1 (d,
J = 235.6 Hz), 145.2 (d, J = 2.7 Hz), 135.5 (d, J = 2.7 Hz), 131.5,
129.8, 129.0, 127.9, 123.8, 122.5 (d, J = 9.8 Hz), 109.8 (d, J = 23.6
Hz), 102.7, 97.8 (d, J = 25.4 Hz), 50.5. HRMS (ESI) m/z calcd for
+
88.9, 55.9, 55.5, 50.6, 21.3. HRMS (ESI) m/z calcd for C19H21NNaO4
[M + Na+], 350.1363; found, 350.1358.
(Z)-Methyl 3-(4-Methoxyphenyl)-3-((3-(trifluoromethyl)phenyl)-
amino)acrylate (2o). Following the general procedure for 18 h, 2o
was isolated as a colorless oil. Yield: 3.23 g, 46%. 1H NMR (600 MHz,
CDCl3) δ 10.32 (br s, 1H), 7.27 (d, J = 8.7 Hz, 2H), 7.21−7.05 (m,
2H), 6.93 (s, 1H), 6.83 (d, J = 8.7 Hz, 2H), 6.77 (d, J = 7.8 Hz, 1H),
5.06 (s, 1H), 3.79 (s, 3H), 3.74 (s, 3H). 13C NMR (150 MHz, CDCl3)
δ 170.4, 161.0, 158.1, 141.3, 131.1 (q, J = 32.4 Hz), 129.6, 129.1,
127.3, 124.7, 123.7 (q, J = 272.4 Hz), 119.1 (q, J = 3.6 Hz), 118.4 (q, J
= 3.4 Hz), 114.1, 91.8, 55.3, 50.8. HRMS (ESI) m/z calcd for
+
C16H1319FNO2 [M + H+], 270.0925; found, 270.0922. 3g′: light
1
yellow solid, mp 162−164 °C. H NMR (600 MHz, CDCl3) δ 8.83
(br s, 1H), 7.53 (dd, J = 6.1, 2.7 Hz, 2H), 7.44−7.33 (m, 3H), 7.16−
7.12 (m, 2H), 6.90 (dd, J = 11.2, 7.6 Hz, 1H), 3.76 (s, 3H).13C NMR
(150 MHz, CDCl3) δ 165.6, 156.1 (d, J = 251.8 Hz), 143.3, 139.43,
137.8 (d, J = 10.1 Hz), 131.5, 129.2, 129.1, 128.3, 123.9 (d, J = 8.2
Hz), 115.6 (d, J = 19.1 Hz), 107.8 (d, J = 21.4 Hz), 104.0 (d, J = 2.4
+
C18H1619F3NNaO3 [M + Na+], 374.0974; found, 374.0963.
General Procedure for the Preparation of Indole-3-carbox-
ylates 3.11a,c N-Aryl enamine 2 (10 mmol) was stirred in DMF (125
mL) together with Pd(OAc)2 (10 mol %), Cu(OAc)2 (30 mmol), and
K2CO3 (30 mmol) at 60−140 °C under an atmosphere of argon. After
completion of the reaction (as indicated by TLC), the reaction mixture
was cooled to room temperature, diluted with EtOAc (150 mL), and
filtered through a short pad of silica, which was then washed with
EtOAc (600 mL). Removal of the solvent in vacuo and purification of
the residue by column chromatography using a mixture of PE and
EtOAc as eluent provided indole-3-carboxylate 3 as a white to light
yellow solid.
+
Hz), 51.47. HRMS (ESI) m/z calcd for C16H1319FNO2 [M + H+],
270.0925; found, 270.0916.
Methyl 5-Chloro-2-(p-tolyl)-1H-indole-3-carboxylate (3j). Follow-
ing the general procedure at 90 °C for 15 h, 3j was isolated as a yellow
solid. Yield: 2.06 g, 69%, mp 194−196 °C. 1H NMR (600 MHz,
CDCl3) δ 8.76 (br s, 1H), 8.12 (s, 1H), 7.44 (d, J = 7.8 Hz, 2H),
7.21−7.15 (m, 2H), 7.13 (d, J = 7.8 Hz, 2H), 3.80 (s, 3H), 2.32 (s,
3H).13C NMR (150 MHz, CDCl3) δ 165.6, 146.2, 139.7, 133.5, 129.2,
128.9, 128.7, 128.4, 127.8, 123.4, 121.6, 112.1, 103.8, 51.0, 21.3.
+
HRMS (ESI) m/z calcd for C17H15ClNO2 [M + H+], 300.0786;
Following this general procedure, known indole-3-carboxylates
3a,17,18 3b,11b 3h,6 and 3i11c,19 were prepared in 51, 48, 53, and 46%
found, 300.0785.
1
yields, respectively. The properties and H NMR data of 3a−b and
Methyl 2-(4-Methoxyphenyl)-5,7-dimethyl-1H-indole-3-carboxy-
late (3k). Following the general procedure at 90 °C for 10 h, 3k was
isolated as a light yellow solid. Yield: 2.50 g, 81%, mp 148−149 °C. 1H
NMR (600 MHz, CDCl3) δ 8.42 (br s, 1H), 7.80 (s, 1H), 7.55 (d, J =
8.7 Hz, 2H), 6.97−6.82 (m, 3H), 3.82 (s, 3H), 3.78 (s, 3H), 2.46 (s,
3H), 2.35 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 166.2, 160.3,
144.6, 133.0, 131.7, 130.9, 127.5, 125.4, 124.5, 119.8, 119.3, 113.6,
3h−i were consistent with those in the literature. Novel indole-3-
carboxylates 3c−g and 3j−o thus obtained were characterized as
follows:
Methyl 5-Methoxy-2-phenyl-1H-indole-3-carboxylate (3c). Fol-
lowing the general procedure at 140 °C for 8 h, 3c was isolated as a
1
yellow solid. Yield: 2.44 g, 87%, mp 104−106 °C. H NMR (600
+
MHz, CDCl3) δ 8.42 (br s, 1H), 7.72 (d, J = 2.4 Hz, 1H), 7.63 (dd, J =
7.6, 2.4 Hz, 2H), 7.50−7.41 (m, 3H), 7.27 (d, J = 8.8 Hz, 1H), 6.92 (d,
104.0, 55.3, 50.8, 21.7, 16.5. HRMS (ESI) m/z calcd for C19H20NO3
[M + H+], 310.1438; found, 310.1434.
F
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Methyl 2-(3-Chlorophenyl)-1H-indole-3-carboxylate (3l). Follow-
ing the general procedure at 90 °C for 10 h, 3l was isolated as a white
solid. Yield: 1.21 g, 42%, mp 157−158 °C. 1H NMR (600 MHz,
CDCl3) δ 8.79 (br s, 1H), 8.18 (d, J = 6.7 Hz, 1H), 7.58 (s, 1H), 7.48
(d, J = 7.1 Hz, 1H), 7.32 (d, J = 7.0 Hz, 2H), 7.29−7.24 (m, 3H), 3.83
(s, 3H). 13C NMR (150 MHz, CDCl3) δ 165.8, 142.8, 135.2, 134.0,
133.6, 129.4, 129.4, 129.2, 127.9, 127.3, 123.6, 122.3, 122.2, 111.3,
column chromatography using a mixture of PE and EtOAc as eluent
gave substrate 4 as a solid.
N-Methoxy-1-methyl-2-phenyl-1H-indole-3-carboxamide (4a).
Following general procedure A, 4a was isolated as a white solid.
Yield: 215.6 mg, 77%, mp 131−134 °C. 1H NMR (600 MHz, CDCl3)
δ 8.29 (d, J = 7.8 Hz, 1H), 7.73 (br s, 1H), 7.61−7.52 (m, 3H), 7.46
(dd, J = 6.3, 2.7 Hz, 2H), 7.35 (d, J = 7.9 Hz, 1H), 7.33 (t, J = 7.4 Hz,
1H), 7.29 (t, J = 7.1 Hz, 1H), 3.66 (s, 3H), 3.54 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ 164.6, 141.4, 136.9, 130.8, 130.4, 130.0, 129.3,
126.8, 123.2, 122.0, 121.7, 109.7, 106.3, 64.4, 30.9. HRMS (ESI) m/z
+
104.9, 51.1. HRMS (ESI) m/z calcd for C16H13ClNO2 [M + H+],
286.0629; found, 286.0627.
Methyl 2-(4-Fluorophenyl)-1H-indole-3-carboxylate (3m). Fol-
lowing the general procedure at 100 °C for 18 h, 3m was isolated
+
calcd for C17H16N2NaO2 [M + Na+], 303.1104; found, 303.1102.
1
N-Methoxy-1,5-dimethyl-2-phenyl-1H-indole-3-carboxamide
(4b). Following general procedure A, 4b was isolated as a white solid.
Yield: 129.4 mg, 44%, mp 171−174 °C. 1H NMR (600 MHz, CDCl3)
δ 8.09 (s, 1H), 7.71 (br s, 1H), 7.60−7.52 (m, 3H), 7.48−7.42 (m,
2H), 7.23 (d, J = 8.3 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H), 3.66 (s, 3H),
3.50 (s, 3H), 2.50 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 164.8,
141.3, 135.4, 131.5, 130.9, 130.4, 129.9, 129.2, 127.0, 124.7, 121.3,
109.3, 105.8, 64.4, 30.9, 21.6. HRMS (ESI) m/z calcd for
as a white solid. Yield: 0.78 g, 29%, mp 158−159 °C. H NMR (600
MHz, CDCl3) δ 8.80 (br s, 1H), 8.16 (d, J = 7.2 Hz, 1H), 7.59−7.50
(m, 2H), 7.31 (d, J = 7.4 Hz, 1H), 7.28−7.24 (m, 2H), 7.03 (t, J = 8.5
Hz, 2H), 3.80 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 166.1, 163.2
(d, J = 249.7 Hz), 143.7, 135.2, 131.5 (d, J = 8.4 Hz), 127.9, 127.4,
123.4, 122.3, 122.1, 115.2 (d, J = 21.8 Hz), 111.2, 104.4, 51.0. HRMS
+
(ESI) m/z calcd for C16H1319FNO2 [M + H+], 270.0925; found,
270.0921.
+
C18H18N2NaO2 [M + Na+], 317.1260; found, 317.1257.
Methyl 5,6-Dimethoxy-2-(p-tolyl)-1H-indole-3-carboxylate (3n).
Following the general procedure at 80 °C for 18 h, 3n was isolated as a
white solid. Yield: 1.79 g, 55%, mp 148−151 °C. 1H NMR (600 MHz,
DMSO-d6) δ 11.77 (br s, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.55 (s, 1H),
7.28 (d, J = 8.0 Hz, 2H), 6.96 (s, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.72
(s, 3H), 2.38 (s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 165.1, 147.1,
145.9, 142.6, 137.9, 129.9, 129.5, 129.3, 128.4, 120.4, 103.4, 102.3,
N,5-Dimethoxy-1-methyl-2-phenyl-1H-indole-3-carboxamide
(4c). Following general procedure A, 4c was isolated as a light yellow
1
solid. Yield: 142.6 mg, 46%, mp 145−148 °C. H NMR (600 MHz,
CDCl3) δ 7.75 (d, J = 2.5 Hz, 1H), 7.60 (br s, 1H), 7.51−7.46 (m,
3H), 7.37−7.35 (m, 2H), 7.13 (d, J = 8.9 Hz, 1H), 6.87 (dd, J = 8.8,
2.5 Hz, 1H), 3.81 (s, 3H), 3.56 (s, 3H), 3.41 (s, 3H). 13C NMR (150
MHz, CDCl3) δ 164.9, 155.9, 141.3, 132.0, 130.9, 130.4, 130.1, 129.3,
127.7, 113.9, 110.5, 105.8, 102.9, 64.3, 55.8, 30.9. HRMS (ESI) m/z
+
94.9, 55.8, 55.6, 50.3, 20.9. HRMS (ESI) m/z calcd for C19H20NO4
[M + H+], 326.1387; found, 326.1382.
+
calcd for C18H18N2NaO3 [M + Na+], 333.1210; found, 333.1202.
Methyl 2-(4-Methoxyphenyl)-6-(trifluoromethyl)-1H-indole-3-
carboxylate (3o). Following the general procedure at 80 °C for 15
h, 3o was isolated as a light yellow solid. Yield: 1.32 g, 53%, mp 191−
192 °C. 1H NMR (600 MHz, DMSO-d6) δ 12.48 (br s, 1H), 8.21 (d, J
= 8.4 Hz, 1H), 7.73 (s, 1H), 7.70 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 8.5
Hz, 1H), 7.10 (d, J = 8.6 Hz, 2H), 3.86 (s, 3H), 3.77 (s, 3H). 13C
NMR (150 MHz, DMSO-d6) δ 164.5, 160.2, 147.3, 134.3, 131.3,
130.0, 125.9 (q, J = 271.4 Hz), 123.1, 122.7 (q, J = 31.4 Hz), 121.9,
117.5 (q, J = 2.5 Hz), 113.4, 108.8 (q, J = 2.7 Hz), 102.4, 55.2, 50.7.
N-Methoxy-1,7-dimethyl-2-phenyl-1H-indole-3-carboxamide
(4d). Following general procedure A, 4d was isolated as a white solid.
Yield: 144.1 mg, 49%, mp 169−172 °C. 1H NMR (600 MHz, CDCl3)
δ 8.12 (d, J = 8.0 Hz, 1H), 7.68 (br s, 1H), 7.55−7.54 (m, 3H), 7.45−
7.39 (m, 2H), 7.11 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 7.1 Hz, 1H), 3.73
(s, 3H), 3.60 (s, 3H), 2.76 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
164.6, 142.1, 136.0, 131.1, 130.6, 130.0, 129.3, 127.7, 126.2, 121.9,
121.3, 119.6, 106.6, 64.3, 34.3, 20.3. HRMS (ESI) m/z calcd for
+
C18H18N2NaO2 [M + Na+], 317.1260; found, 317.1254.
+
HRMS (ESI) m/z calcd for C18H1519F3NO3 [M + H+], 350.0999;
7-Chloro-N-methoxy-1-methyl-2-phenyl-1H-indole-3-carboxa-
found, 350.0995.
mide (4e). Following general procedure A, 4e was isolated as a white
Preparation of Indole-3-carboxamides 4.10−12 To a solution
of indole 3 (2.5 mmol) in THF (25 mL) was added NaOH (25 mmol)
followed by the addition of iodomethane (5.0 mmol) (for substrate
4m, benzyl bromide (2.5 mmol) was used instead). The solution was
stirred for at room temperature for 2 h. After the completion of the
reaction, the reaction mixture was evaporated in vacuum. Then, water
(20 mL) and ethanol (20 mL) were added to the mixture, and the
mixture was heated at 80 °C for 15 h. After the mixture was cooled and
acidified with HCl(aq) (4 N), the precipitate was collected, washed
with water, and dried in the air overnight to afford carboxylic acid.
Method A. To a solution of the carboxylic acid intermediate (1
mmol) in DCM (10 mL) was added thionyl chloride (2 mmol)
dropwise at room temperature. After stirring at room temperature for
1 h, the dark mixture was added dropwise to a solution of
methoxamine (4 mmol) in DCM (10 mL) at −20 to 0 °C. The
reaction mixture was stirred at room temperature for 2 h, diluted with
water (50 mL), extracted with DCM (50 mL × 3), and washed with
brine (30 mL × 1). The combined organic phases were dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the
crude amide. Purification by column chromatography using a mixture
of PE and EtOAc as eluent gave substrate 4 as a white to yellow solid.
Method B. To a solution of the carboxylic acid intermediate (1
mmol) in DCM (10 mL) were added 1-ethyl-3-(3-dimethylamino-
propyl) carbodiimide hydrochloride (EDCI, 1.1 mmol) and N-
hydroxybenzotriazole (HOBT, 1.1 mmol). The mixture was stirred
at room temperature for 1 h. Methoxamine (4 mmol) was then added.
The reaction mixture was diluted with water (50 mL), extracted with
DCM (50 mL × 3), and washed with brine (30 mL × 1). The
combined organic phases were dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo to afford the crude amide. Purification by
1
solid. Yield: 211.1 mg, 67%, mp 147−148 °C. H NMR (600 MHz,
CDCl3) δ 8.15 (d, J = 8.0 Hz, 1H), 7.79 (br s, 1H), 7.61−7.53 (m,
3H), 7.43−7.42 (m, 2H), 7.22 (d, J = 7.8 Hz, 1H), 7.11 (t, J = 7.8 Hz,
1H), 3.83 (s, 3H), 3.59 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
163.9, 142.9, 132.5, 130.5, 130.4, 130.2, 129.8, 129.4, 125.0, 122.3,
120.4, 117.0, 107.0, 64.2, 34.3. HRMS (ESI) m/z calcd for
+
C17H15ClN2NaO2 [M + Na+], 337.0714; found, 337.0710.
4,N-Dimethoxy-1-methyl-2-phenyl-1H-indole-3-carboxamide
(4f). Following general procedure A, 4f was isolated as a white solid.
Yield: 226.3 mg, 73%, mp 159−161 °C. 1H NMR (600 MHz, CDCl3)
δ 8.12 (d, J = 8.8 Hz, 1H), 7.80 (br s, 1H), 7.61−7.48 (m, 3H), 7.43−
7.42 (m, 2H), 6.90 (dd, J = 8.8, 2.2 Hz, 1H), 6.75 (d, J = 2.2 Hz, 1H),
3.86 (s, 3H), 3.62 (s, 3H), 3.45 (s, 3H). 13C NMR (150 MHz, CDCl3)
δ 164.7, 157.1, 140.3, 137.8, 130.9, 130.5, 129.9, 129.2, 122.4, 121.0,
111.5, 100.0, 93.2, 64.3, 55.7, 30.9. HRMS (ESI) m/z calcd for
+
C18H18N2NaO3 [M + Na+], 333.1210; found, 333.1203.
6-Fluoro-N-methoxy-1-methyl-2-phenyl-1H-indole-3-carboxa-
mide (4g). Following general procedure A, 4g was isolated as a light
1
yellow solid. Yield: 172.8 mg, 58%, mp 166−168 °C. H NMR (600
MHz, CDCl3) δ 8.24 (dd, J = 8.7, 5.5 Hz, 1H), 7.71 (br s, 1H), 7.65−
7.52 (m, 3H), 7.51−7.38 (m, 2H), 7.07−6.99 (m, 2H), 3.64 (s, 3H),
3.49 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 164.2, 160.4 (d, J =
240.3 Hz), 159.6, 141.5 (d, J = 3.3 Hz), 137.1 (d, J = 12.1 Hz), 130.5,
130.4, 130.2, 129.4, 123.0 (d, J = 9.7 Hz), 123.0, 110.6 (d, J = 23.8
Hz), 96.1 (d, J = 26.4 Hz), 64.4, 31.0. HRMS (ESI) m/z calcd for
+
C17H1519FN2NaO2 [M + Na+], 321.1010; found, 321.1006.
N-Methoxy-1-methyl-2-(p-tolyl)-1H-indole-3-carboxamide (4h).
Following general procedure A, 4h was isolated as a light yellow
1
solid. Yield: 194.0 mg, 66%, mp 170−172 °C. H NMR (600 MHz,
CDCl3) δ 8.29 (d, J = 7.7 Hz, 1H), 7.83 (br s, 1H), 7.35 (d, J = 7.7 Hz,
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2H), 7.33−7.21 (m, 5H), 3.65 (s, 3H), 3.48 (s, 3H), 2.46 (s, 3H). 13
C
116.9 (d, J = 3.1 Hz), 113.8, 108.3 (q, J = 3.7 Hz), 107.34, 62.9, 55.2,
+
NMR (150 MHz, CDCl3) δ 164.8, 141.5, 140.2, 136.9, 130.3, 130.0,
31.1. HRMS (ESI) m/z calcd for C19H1719F3N2NaO3 [M + Na+],
127.6, 126.9, 123.0, 121.9, 121.7, 109.6, 106.1, 64.4, 30.8, 21.5. HRMS
401.1083; found, 401.1082.
+
(ESI) m/z calcd for C18H18N2NaO2 [M + Na+], 317.1260; found,
1-Benzyl-N-methoxy-2-phenyl-1H-indole-3-carboxamide (4p).
Following general procedure A, 4p was isolated as a white solid.
Yield: 249.2 mg, 70%, mp 154−155 °C. 1H NMR (600 MHz, CDCl3)
δ 8.33 (d, J = 7.9 Hz, 1H), 7.75 (br s, 1H), 7.51− 7.50 (m, 1H), 7.48−
7.44 (m, 2H), 7.39−7.35 (m, 2H), 7.31−7.25 (m, 1H), 7.24−7.18 (m,
5H), 6.86 (dd, J = 7.0, 2.5 Hz, 2H), 5.15 (s, 2H), 3.65 (s, 3H). 13C
NMR (150 MHz, CDCl3) δ 164.5, 141.4, 136.9, 136.6, 130.4, 130.1,
129.2, 128.8, 127.5, 127.1, 126.0, 123.5, 122.2, 121.9, 110.5, 107.1,
317.1258.
N-Methoxy-1-methyl-2-(4-methoxyphenyl)-1H-indole-3-carboxa-
mide (4i). Following general procedure A, 4i was isolated as a light
yellow solid. Yield: 161.2, 52%, mp 169−172 °C. 1H NMR (600 MHz,
CDCl3) δ 8.30 (d, J = 7.4 Hz, 1H), 7.81 (br s, 1H), 7.37 (d, J = 8.7 Hz,
2H), 7.35−7.24 (m, 3H), 7.08 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H), 3.68
(s, 3H), 3.51 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 164.8, 160.9,
141.4, 136.9, 131.8, 126.9, 123.0, 122.5, 121.9, 121.7, 114.8, 109.6,
+
64.4, 47.6. HRMS (ESI) m/z calcd for C23H20N2NaO2 [M + Na+],
+
106.2, 64.4, 55.5, 30.8. HRMS (ESI) m/z calcd for C18H18N2NaO3
379.1417; found, 379.1412.
[M + Na+], 333.1210; found, 333.1204.
General Procedure for the Conversion of Indole-3-carbox-
amides 4 to Indoloquinolinone 5.20 To a solution of indole-3-
carboxamide 4 (0.2 mmol) in DCE (10 mL) was added PIDA (0.24
mmol) gradually at room temperature for 1 h. Then, the mixture was
treated with saturated NaHCO3 (40 mL) and extracted with CH2Cl2
(20 mL × 3). The combined organic phases were dried over
anhydrous Na2SO4 and evaporated under reduced pressure to remove
the solvent. The given residue was purified by flash chromatography
using a mixture of DCM and MeOH as eluent to provide desired
indoloquinolinone 5.
5-Chloro-N-methoxy-1-methyl-2-(p-tolyl)-1H-indole-3-carboxa-
mide (4j). Following general procedure A, 4j was isolated as a white
solid. Yield: 246.0 mg, 75%, mp 169−170 °C. H NMR (600 MHz,
CDCl3) δ 8.30 (s, 1H), 7.76 (br s, 1H), 7.38 (d, J = 7.9 Hz, 2H), 7.33
(d, J = 7.9 Hz, 2H), 7.24−7.17 (m, 2H), 3.65 (s, 3H), 3.49 (s, 3H),
2.48 (s, 3H).13C NMR (150 MHz, CDCl3) δ 164.2, 142.4, 140.6,
135.3, 130.2, 130.2, 128.0, 127.7, 127.2, 123.4, 121.3, 110.6, 105.8,
1
+
64.4, 31.0, 21.5. HRMS (ESI) m/z calcd for C18H17ClN2NaO2 [M +
Na+], 351.0871; found, 351.0869.
N-Methoxy-2-(4-methoxyphenyl)-1,5,7-trimethyl-1H-indole-3-
carboxamide (4k). Following the general procedure, 4k was isolated
as a light yellow solid. Yield: 260.3 mg, 77%, mp 199−200 °C. H
5-Methoxy-11-methyl-5H-indolo[3,2-c]quinolin-6(11H)-one (5a).
Following the general procedure, 5a was isolated as a yellow solid.
1
1
Yield: 48 mg, 86%, mp 208−210 °C. H NMR (600 MHz, CDCl3) δ
NMR (600 MHz, CDCl3) δ 7.96 (s, 1H), 7.69 (br s, 1H), 7.33 (d, J =
8.5 Hz, 2H), 7.06 (d, J = 8.5 Hz, 2H), 6.84 (s, 1H), 3.89 (s, 3H), 3.70
(s, 3H), 3.65 (s, 3H), 2.72 (s, 3H), 2.42 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 165.0, 160.7, 142.0, 134.4, 131.9, 131.3, 128.1, 127.8, 122.9,
120.8, 119.2, 114.8, 106.0, 64.4, 55.4, 34.1, 21.2, 20.1. HRMS (ESI) m/
8.54 (d, J = 7.8 Hz, 1H), 8.34 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 8.4 Hz,
1H), 7.61 (t, J = 7.8 Hz, 1H), 7.46−7.41 (m, 2H), 7.36−7.34 (m, 2H),
4.25 (s, 3H), 4.17 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 155.7,
139.7, 138.2, 136.7, 129.2, 124.7, 124.3, 122.9, 122.2, 122.1, 121.9,
113.2, 113.0, 109.0, 108.0, 63.0, 33.5. HRMS (ESI) m/z calcd for
+
z calcd for C20H22N2NaO3 [M + Na+], 361.1523; found, 361.1514.
+
C17H15N2O2 [M + H+], 279.1128; found, 279.1125.
2-(3-Chlorophenyl)-N-methoxy-1-methyl-1H-indole-3-carboxa-
mide (4l). Following the general procedure, 4l was isolated as a light
yellow solid. Yield: 175.8 mg, 56%, mp 98−99 °C. H NMR (600
5-Methoxy-8,11-dimethyl-5H-indolo[3,2-c]quinolin-6(11H)-one
(5b). Following the general procedure, 5b was isolated as a yellow
1
1
solid. Yield: 50 mg, 85%, mp 245−246 °C. H NMR (600 MHz,
MHz, CDCl3) δ 8.15 (br s, 1H), 8.06 (d, J = 7.9 Hz, 1H), 7.47 (t, J =
8.1 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 7.40 (s, 1H), 7.34−7.27 (m,
3H), 7.22 (t, J = 7.2 Hz, 1H), 3.64 (s, 3H), 3.49 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ 164.4, 140.1, 136.9, 134.8, 132.4, 130.5, 130.3,
129.8, 128.8, 126.2, 123.3, 122.0, 121.2, 109.9, 106.6, 64.3, 31.0.
HRMS (ESI) m/z calcd for C17H15ClN2NaO2+ [M + Na+], 337.0714;
found, 337.0708.
CDCl3) δ 8.30 (s, 1H), 8.28 (d, J = 8.2 Hz, 1H), 7.75 (d, J = 8.4 Hz,
1H), 7.57 (t, J = 7.8 Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 8.4
Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 4.17 (s, 3H), 4.16 (s, 3H), 2.50 (s,
3H). 13C NMR (150 MHz, CDCl3) δ 155.8, 138.1, 138.0, 136.7, 131.5,
129.0, 126.2, 124.4, 122.8, 122.1, 121.7, 113.2, 113.2, 108.6, 107.5,
+
63.0, 33.5, 21.4. HRMS (ESI) m/z calcd for C18H17N2O2 [M + H+],
293.1285; found, 293.1277.
2-(4-Fluorophenyl)-N-Methoxy-1-methyl-1H-indole-3-carboxa-
5,8-Dimethoxy-11-methyl-5H-indolo[3,2-c]quinolin-6(11H)-one
mide (4m). Following the general procedure, 4m was isolated as a
(5c). Following the general procedure, 5c was isolated as a yellow
1
1
light yellow solid. Yield: 226.5 mg, 76%, mp 157−158 °C. H NMR
solid. Yield: 53 mg, 86%, mp 203−204 °C. H NMR (600 MHz,
(600 MHz, CDCl3) δ 8.18 (d, J = 7.8 Hz, 1H), 7.83 (br s, 1H), 7.49−
7.41 (m, 2H), 7.36−7.23 (m, 5H), 3.69 (s, 3H), 3.53 (s, 3H). 13C
NMR (150 MHz, CDCl3) δ 164.65, 163.5 (d, J = 250.9 Hz), 140.7,
136.9, 132.5 (d, J = 8.4 Hz), 126.6, 126.3, 126.6 (d, J = 3.6 Hz), 123.3,
122.1, 121.4, 116.4 (d, J = 21.7 Hz), 116.3, 109.8, 106.4, 64.5, 30.9.
HRMS (ESI) m/z calcd for C17H1519FN2NaO2+ [M + Na+], 321.1010;
found, 321.1008.
CDCl3) δ 8.23 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 2.4 Hz, 1H), 7.72 (d, J
= 8.6 Hz, 1H), 7.59−7.53 (m, 1H), 7.33−7.28 (m, 1H), 7.26 (d, J =
8.2 Hz, 1H), 7.00 (dd, J = 8.6, 2.4 Hz, 1H), 4.15 (s, 3H), 4.13 (s, 3H),
3.92 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 155.9, 155.6, 138.1,
136.6, 134.5, 129.0, 124.8, 122.7, 122.1, 115.2, 113.2, 109.9, 107.5,
102.9, 63.0, 55.8, 33.5 (one carbon signal missing because of peak
+
overlap). HRMS (ESI) m/z calcd for C18H17N2O3 [M + H+],
N,5,6-Trimethoxy-1-methyl-2-(p-tolyl)-1H-indole-3-carboxamide
(4n). Following the general procedure, 4n was isolated as a white solid.
Yield: 240.7 mg, 68%, mp 188−200 °C. 1H NMR (600 MHz, CDCl3)
δ 7.87 (s, 1H), 7.74 (br s, 1H), 7.37 (d, J = 7.2 Hz, 2H), 7.32 (d, J =
7.2 Hz, 2H), 6.77 (s, 1H), 3.98 (s, 3H), 3.95 (s, 3H), 3.66 (s, 3H),
3.47 (s, 3H), 2.47 (s, 3H).13C NMR (150 MHz, CDCl3) δ 165.1,
147.6, 146.5, 140.1, 139.4, 131.2, 130.4, 130.1, 127.9, 120.1, 105.6,
103.1, 92.7, 64.4, 56.2, 30.9, 21.5 (one carbon signal missing because
309.1234; found, 309.1232.
5-Methoxy-10,11-dimethyl-5H-indolo[3,2-c]quinolin-6(11H)-one
(5d). Following the general procedure, 5d was isolated as a yellow
1
solid. Yield: 51 mg, 88%, mp 234−237 °C. H NMR (600 MHz,
CDCl3) δ 8.37 (d, J = 7.7 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 7.69 (d, J
= 8.4 Hz, 1H), 7.53 (t, J = 7.7 Hz, 1H), 7.29−7.26 (m, 1H), 7.14 (t, J
= 7.3 Hz, 1H), 7.03 (d, J = 7.3 Hz, 1H), 4.27 (s, 3H), 4.13 (s, 3H),
2.73 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 155.6, 139.5, 139.4,
136.7, 129.0, 128.2, 125.2, 123.3, 122.1, 122.0, 120.8, 120.1, 113.1,
112.8, 108.3, 63.0, 36.8, 20.7. HRMS (ESI) m/z calcd for
+
of peak overlap). HRMS (ESI) m/z calcd for C20H22N2NaO4 [M +
Na+], 377.1472; found, 377.1469.
+
C18H17N2O2 [M + H+], 293.1285; found, 293.1279.
N-Methoxy-2-(4-methoxyphenyl)-1-methyl-6-(trifluoromethyl)-
1H-indole-3-carboxamide (4o). Following general procedure A, 4o
was isolated as a white solid. Yield: 245.7 mg, 65%, mp 163−164 °C.
1H NMR (600 MHz, DMSO-d6) δ 10.75 (br s, 1H), 8.00 (s, 1H), 7.93
10-Chloro-5-methoxy-11-methyl-5H-indolo[3,2-c]quinolin-6-
(11H)-one (5e). Following the general procedure, 5e was isolated as a
yellow solid. Yield: 52 mg, 84%, mp 237−240 °C. H NMR (600
MHz, CDCl3) δ 8.49 (d, J = 7.8 Hz, 1H), 8.29 (d, J = 8.3 Hz, 1H),
7.79 (d, J = 8.3 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H), 7.36 (t, J = 7.8 Hz,
2H), 7.24 (t, J = 7.8 Hz, 1H), 4.58 (s, 3H), 4.16 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ 155.3, 140.4, 137.1, 135.7, 129.7, 127.8, 126.9,
1
(d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 8.6 Hz, 2H),
7.11 (d, J = 8.6 Hz, 2H), 3.85 (s, 3H), 3.70 (s, 3H), 3.59 (s, 3H). 13
C
NMR (150 MHz, DMSO-d6) δ 162.4, 159.9, 144.2, 135.3, 131.9,
128.1, 125.2 (t, J = 271.6 Hz), 122.5 (d, J = 30.9 Hz), 121.6, 120.5,
H
dx.doi.org/10.1021/jo4023292 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
123.6, 122.9, 122.3, 121.0, 116.6, 113.4, 112.6, 108.4, 63.1, 36.8.
122.1, 114.6, 113.9, 109.1, 108.6, 63.2, 33.4. HRMS (ESI) m/z calcd
+
+
HRMS (ESI) m/z calcd for C17H14ClN2O2 [M + H+], 313.0738;
for C17H14ClN2O2 [M + H+], 313.0738; found, 313.0732.
found, 313.0735.
3-Fluoro-5-methoxy-11-methyl-5H-indolo[3,2-c]quinolin-6(11H)-
one (5m). Following the general procedure, 5m was isolated as a
5,9-Dimethoxy-11-methyl-5H-indolo[3,2-c]quinolin-6(11H)-one
(5f). Following the general procedure, 5f was isolated as a yellow solid.
Yield: 56 mg, 91%, mp 213−215 °C. H NMR (600 MHz, CDCl3) δ
1
yellow solid. Yield: 47 mg, 79%, mp 224−225 °C. H NMR (600
1
MHz, CDCl3) δ 8.43 (d, J = 7.8 Hz, 1H), 8.23 (dd, J = 8.7, 5.7 Hz,
1H), 7.41−7.38 (m, 1H), 7.38−7.34 (m, 2H), 7.30 (t, J = 6.9 Hz, 1H),
7.05 (dd, J = 11.5, 5.2 Hz, 1H), 4.15 (s, 3H), 4.14 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ 163.2 (d, J = 254.8 Hz), 155.7, 139.4, 138.4 (d, J
= 10.9 Hz), 137.8, 124.9 (d, J = 9.9 Hz), 124.7, 124.0, 122.1, 121.8,
110.2 (d, J = 23.3 Hz), 109.5 (d, J = 2.4 Hz), 109.0, 106.9, 100.2 (d, J
8.33 (d, J = 8.6 Hz, 1H), 8.21 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 8.1 Hz,
1H), 7.53(t, J = 7.8 Hz, 1H), 7.29 (t, J = 7.8 Hz, 1H), 6.91 (dd, J = 8.6,
2.1 Hz, 1H), 6.76 (d, J = 2.1 Hz, 1H), 4.14 (s, 3H), 4.09 (s, 3H), 3.87
(s, 3H). 13C NMR (150 MHz, CDCl3) δ 158.3, 155.6, 140.8, 137.5,
136.1, 128.6, 122.7, 122.4, 122.1, 118.1, 113.1, 111.0, 108.0, 99.9, 93.0,
+
+
63.0, 55.6, 33.5. HRMS (ESI) m/z calcd for C18H17N2O3 [M + H+],
= 27.8 Hz), 63.2, 33.4. HRMS (ESI) m/z calcd for C17H1419FN2O2
309.1234; found, 309.1228.
[M + H+], 297.1034; found, 297.1029.
9-Fluoro-5-methoxy-11-methyl-5H-indolo[3,2-c]quinolin-6(11H)-
5,8,9-Trimethoxy-3,11-dimethyl-5H-indolo[3,2-c]quinolin-6-
(11H)-one (5n). Following the general procedure except that 1.1 equiv
of PIFA and DCM were employed instead of PIDA and DCE, 5n was
isolated as a gray solid. Yield: 53 mg, 75%, mp 191−192 °C. 1H NMR
(600 MHz, CDCl3) δ 7.93 (d, J = 8.2 Hz, 1H), 7.82 (s, 1H), 7.40 (s,
1H), 7.03 (d, J = 8.2 Hz, 1H), 6.64 (s, 1H), 4.12 (s, 3H), 3.98 (s, 3H),
3.93 (s, 3H), 3.91 (s, 3H), 2.48 (s, 3H). 13C NMR (150 MHz, CDCl3)
δ 155.9, 148.4, 146.1, 138.8, 136.7, 135.7, 133.8, 123.4, 122.0, 116.7,
112.9, 110.8, 106.6, 102.5, 92.1, 63.0, 56.2, 56.0, 33.3, 21.9. HRMS
one (5g). Following the general procedure, 5g was isolated as a yellow
1
solid. Yield: 48 mg, 81%, mp 198−200 °C. H NMR (600 MHz,
CDCl3) δ 8.38 (dd, J = 8.5, 5.6 Hz, 1H), 8.24 (d, J = 8.2 Hz, 1H), 7.72
(d, J = 8.4 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.32 (t, J = 7.7 Hz, 1H),
7.05−7.00 (m, 2H), 4.14 (s, 3H), 4.13 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 161.3 (d, J = 243.8 Hz), 155.4, 140.1 (d, J = 11.6 Hz), 136.4,
135.6, 129.2, 123.0 (d, J = 9.3 Hz), 122.6, 122.3, 120.5, 113.2, 112.8,
110.4 (d, J = 23.9 Hz), 107.8 (d, J = 3.6 Hz), 96.0 (d, J = 27.7 Hz),
+
+
63.1, 33.7. HRMS (ESI) m/z calcd for C17H1419FN2O2 [M + H+],
(ESI) m/z calcd for C20H21N2O4 [M + H+], 353.1496; found,
297.1034; found, 297.1027.
5-Methoxy-3,11-dimethyl-5H-indolo[3,2-c]quinolin-6(11H)-one
(5h). Following the general procedure, 5h was isolated as a yellow
solid. Yield: 53 mg, 91%, mp 184−185 °C. H NMR (600 MHz,
353.1494.
3,5-Dimethoxy-11-methyl-9-(trifluoromethyl)-5H-indolo[3,2-c]-
quinolin-6(11H)-one (5o). Following the general procedure except
that 1.1 equiv of PIFA and DCM were employed instead of PIDA and
DCE, 5o was isolated as a gray solid. Yield: 62 mg, 82%, mp > 250 °C.
1H NMR (600 MHz, DMSO) δ 8.51 (d, J = 8.9 Hz, 1H), 8.39 (d, J =
1
CDCl3) δ 8.41 (d, J = 7.7 Hz, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.39 (s,
1H), 7.31−7.26 (m, 1H), 7.26−7.20 (m, 2H), 7.01 (dd, J = 8.3, 0.9
Hz, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 2.43 (s, 3H). 13C NMR (150
MHz, CDCl3) δ 155.7, 139.8, 139.4, 138.3, 136.6, 124.3, 124.2, 123.4,
122.6, 121.7, 121.6, 112.9, 110.4, 108.8, 107.0, 62.9, 33.2, 21.9. HRMS
7.9 Hz, 1H), 8.22 (s, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.20 (s, 1H), 7.05
(d, J = 8.6 Hz, 1H), 4.34 (s, 3H), 4.07 (s, 3H), 3.95 (s, 3H).
Unfortunately, the poor solubility of 5o prevented 13C NMR
+
(ESI) m/z calcd for C18H17N2O2 [M + H+], 293.1285; found,
characterization. HRMS (ESI) m/z calcd for C19H1619F3N2O3 [M +
+
H+], 377.1108; found, 377.1103.
293.1282.
3,5-Dimethoxy-11-methyl-5H-indolo[3,2-c]quinolin-6(11H)-one
(5i). Following the general procedure, 5i was isolated as a yellow solid.
Yield: 58 mg, 94%, mp 231−232 °C. H NMR (600 MHz, CDCl3) δ
11-Benzyl-5-methoxy-5H-indolo[3,2-c]quinolin-6(11H)-one (5p).
Following the general procedure, 5p was isolated as a yellow solid.
Yield: 60 mg, 85%, mp > 250 °C. H NMR (600 MHz, CDCl3) δ
1
1
8.44 (d, J = 7.7 Hz, 1H), 8.14 (d, J = 9.0 Hz, 1H), 7.37−7.32 (m, 2H),
7.32−7.28 (m, 1H), 7.15 (d, J = 2.5 Hz, 1H), 6.87 (dd, J = 9.0, 2.5 Hz,
1H), 4.14 (s, 3H), 4.10 (s, 3H), 3.92 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 160.7, 155.9, 155.6, 138.1, 136.6, 134.5, 129.0, 124.8, 122.7,
122.1, 115.2, 113.2, 109.9, 107.5, 102.9, 63.0, 55.8, 33.5. HRMS (ESI)
8.62−8.52 (m, 1H), 7.86 (d, J = 8.2 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H),
7.46 (t, J = 7.8 Hz, 1H), 7.31−7.30 (m, 3H), 7.26 (t, J = 7.3 Hz, 2H),
7.22 (t, J = 7.3 Hz, 1H), 7.11−7.06 (m, 3H), 5.76 (s, 2H), 4.14 (s,
3H). 13C NMR (150 MHz, CDCl3) δ 155.7, 140.0, 138.1, 136.7, 136.0,
129.3, 129.2, 127.9, 125.7, 125.1, 124.4, 123.0, 122.4, 122.4, 122.1,
113.1, 112.3, 109.3, 108.5, 63.1, 49.2. HRMS (ESI) m/z calcd for
+
m/z calcd for C18H17N2O3 [M + H+], 309.1234; found, 309.1230.
+
C23H19N2O2 [M + H+], 355.1441; found, 355.1439.
8-Chloro-5-methoxy-3,11-dimethyl-5H-indolo[3,2-c]quinolin-6-
(11H)-one (5j). Following the general procedure, 5j was isolated as a
yellow solid. Yield: 61 mg, 93%, mp > 250 °C. H NMR (600 MHz,
CDCl3) δ 8.32 (s, 1H), 8.05 (d, J = 8.2 Hz, 1H), 7.43 (s, 1H), 7.19 (m,
2H), 7.11 (d, J = 8.2 Hz, 1H), 4.11 (s, 3H), 4.09 (s, 3H), 2.51 (s, 3H).
13C NMR (150 MHz, CDCl3) δ 155.4, 140.4, 139.0, 137.7, 136.7,
127.4, 125.0, 124.5, 123.7, 122.7, 121.0, 113.1, 110.2, 109.9, 106.3,
General Procedure for the Preparation of Bioactive
Indoloquinolinones A1 and D.13 To a solution of 5a or 5p (0.5
mmol) in DMF was added NaH (60% in mineral oil, 5 mmol)
gradually. The reaction mixture was heated at 120 °C for 1 h. After
cooling to room temperature, the reaction mixture was diluted with
water (50 mL), extracted with EtOAc (50 mL × 3), and washed with
brine (30 mL). The combined organic phases were dried over
anhydrous Na2SO4 and evaporated under reduced pressure to remove
the solvent. The residue was purified by flash chromatography using a
mixture of PE and EtOAc as eluent.
1
+
63.0, 33.5, 22.0. HRMS (ESI) m/z calcd for C18H16ClN2O2 [M +
H+], 327.0895; found, 327.0891.
3,5-Dimethoxy-8,10,11-trimethyl-5H-indolo[3,2-c]quinolin-6-
(11H)-one (5k). Following the general procedure, 5k was isolated as a
yellow solid. Yield: 58 mg, 86%, mp 226−227 °C. H NMR (600
1
Following this general procedure, indoloquinolinones A121 and D7
were prepared in 87 and 52% yields, respectively. The properties and
1H NMR data of A1 and D were in consistent with those in the
MHz, CDCl3) δ 8.16 (s, 1H), 8.08 (d, J = 9.0 Hz, 1H), 7.20 (s, 1H),
6.90 (s, 1H), 6.89 (d, J = 9.0 Hz, 1H), 4.29 (s, 3H), 4.15 (s, 3H), 3.95
(s, 3H), 2.74 (s, 3H), 2.45 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
160.4, 155.9, 139.9, 138.5, 137.4, 131.4, 129.3, 125.5, 124.7, 120.2,
119.3, 109.9, 106.6, 105.9, 96.8, 62.8, 55.6, 36.6, 21.1, 20.6. HRMS
literature.
+
(ESI) m/z calcd for C20H21N2O3 [M + H+], 337.1547; found,
ASSOCIATED CONTENT
■
337.1546.
S
* Supporting Information
2-Chloro-5-methoxy-11-methyl-5H-indolo[3,2-c]quinolin-6(11H)-
one (5l) and 4-Chloro-5-methoxy-11-methyl-5H-indolo[3,2-c]-
quinolin-6(11H)-one (5l′). Following the general procedure, an
inseparable mixture of 5l and 5l′ was obtained as a yellow solid.
Yield: 52 mg, 83% (5l/5l′ = 10:1), mp 199−200 °C. 5l: 1H NMR (600
MHz, CDCl3) δ 8.53 (d, J = 7.8 Hz, 1H), 8.28 (s, 1H), 7.74 (d, J = 8.9
Hz, 1H), 7.56 (d, J = 8.9 Hz, 1H), 7.49−7.45 (m, 2H), 7.37 (t, J = 6.8
Hz, 1H), 4.26 (s, 3H), 4.17 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
155.3, 139.6, 136.7, 135.1, 129.2, 127.7, 125.1, 123.9, 122.3, 122.2,
1H and 13C NMR spectra for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: duyunfeier@tju.edu.cn (Y.D.).
*E-mail: kangzhao@tju.edu.cn (K.Z.).
I
dx.doi.org/10.1021/jo4023292 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
2009, 74, 6802. (f) Johansson, H.; Jorgensen, T. B.; Gloriam, D. E.;
Braeuner-Osborne, H.; Pedersen, D. S. RSC Adv. 2013, 3, 945.
Notes
The authors declare no competing financial interest.
(11) (a) Wurtz, S.; Rakshit, S.; Neumann, J. J.; Droge, T.; Glorius, F.
̈
̈
Angew. Chem., Int. Ed. 2008, 47, 7230. (b) Yu, W. Q.; Du, Y. F.; Zhao,
ACKNOWLEDGMENTS
K. Org. Lett. 2009, 11, 2417. (c) Neumann, J. J.; Rakshit, S.; Droge, T.;
̈
■
Wurtz, S.; Glorius, F. Chem.Eur. J. 2011, 17, 7298.
̈
Y.D. acknowledges the National Natural Science Foundation of
China (21072148), the Foundation (B) for Peiyang Scholar−
Young Core Faculty of Tianjin University (2013XR-0144), and
the Innovation Foundation of Tianjin University (2013XJ-
0005) for financial support.
(12) (a) Rao, V. V. R.; Wentrup, C. J. Chem. Soc., Perkin Trans. 1
2002, 10, 1232. (b) Zheng, H. J.; Chen, W. B.; Deng, J. G.; Lin, W. Q.;
Yuan, W. C.; Zhang, X. M.; Wu, Z. J. Chem.Eur. J. 2008, 14, 9864.
(c) Zhao, M.; Wang, F.; Li, X. M. Org. Lett. 2012, 14, 1412.
(13) Zhong, H. B.; Yang, D.; Wang, S. Q.; Huang, J. H. Chem.
Commun. 2012, 48, 3236.
(14) Fustero, S.; Torre, M. G.; Jofre,
́
V.; Carlon, R. P.; Navarro, A.;
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