Palladium-catalyzed synthesis of 3-acylated indoles involving oxidative cross-coupling of indoles with α-amino carbonyl compounds

Article abstract of DOI:10.1021/jo402215s

A new and selective C-N bond oxidative cleavage method to 3-acylated indoles by Pd-catalyzed oxidative cross coupling of indoles with α-amino carbonyl compounds has been developed; moreover, one-pot synthesis of 3-acylated indoles from 2-ethynylanilines and α-amino carbonyl compounds has also been established. Importantly, the products 3-acylated indoles can be used to construct polyheterocyclic compound, which can be employed as efficient probes for Hg²⁺ and Fe³⁺.

Full text of DOI:10.1021/jo402215s

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pubs.acs.org/joc
Palladium-Catalyzed Synthesis of 3‑Acylated Indoles Involving
Oxidative Cross-Coupling of Indoles with α‑Amino Carbonyl
Compounds
Ri-Yuan Tang,†,‡ Xiao-Kang Guo,‡ Jian-Nan Xiang,*,† and Jin-Heng Li*,†
†State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University,
Changsha 410082, China
‡College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
S
* Supporting Information
ABSTRACT: A new and selective C−N bond oxidative
cleavage method to 3-acylated indoles by Pd-catalyzed
oxidative cross coupling of indoles with α-amino carbonyl
compounds has been developed; moreover, one-pot synthesis
of 3-acylated indoles from 2-ethynylanilines and α-amino
carbonyl compounds has also been established. Importantly,
the products 3-acylated indoles can be used to construct
polyheterocyclic compound, which can be employed as efficient probes for Hg2+ and Fe3+.
conditions. However, the reaction could not be applied to
tertiary amines. As part of our continuing interest in this area,
we decided to explore a viable catalytic system and expand this
method to tertiary amines. After a series of trials, we found that
Pd(OAc)2 combined with Cu(OAc)2 and air was a viable
catalytic system for the reaction between indoles and tertiary
amines leading to 3-acylated indoles. Herein we report our
findings that indoles can undergo the oxidative cross coupling
with α-amino carbonyl compounds to afford 2-(1H-indol-3-yl)-
2-oxocarbonyl compounds in moderate to good yields using the
Pd(OAc)2/Cu(OAc)2/air system, wherein the carbonyl re-
sources is from α-amino carbonyl compounds through the C−
N bond cleavage (Scheme 1b);7 moreover, a one-pot synthesis
for the expected 3-acylated indoles from 2-ethynylanilines and
α-amino carbonyl compounds has also been established.1e,8
Importantly, the products, 2-(1H-indol-3-yl)-2-oxocarbonyl
compounds, can react with indoles to construct polyindoles,9
which can be used as efficient probes for Hg2+ and Fe3+.10
INTRODUCTION
■
Indoles, including 3-acylindoles, are ubiquitous in natural
products, pharmaceutical molecules, and functional materials, as
well as are valuable synthetic intermediates in organic
synthesis.1,2 Therefore, new, selective methods for their
synthesis are an important and popular topic of research,
particularly for 3-acylindole preparation due to wide
applications of its carbonyl group as a versatile intermediate
in the syntheses of a broad range of indole derivatives.1
Traditionally, Friedel−Crafts acylations,3a−e Vilsmeier−Haack
acylations,1a,3f and the reactions of indole salts with acyl
chlorides2e,3g−i are usually employed for the synthesis of 3-
acylindoles; however, the majority of these methods suffer from
the requirement of stoichiometric metal Lewis acids, harsh
reaction conditions (often strict exclusion of moisture),
unsatisfactory selectivity, and unwanted waste. Thus, the
development of new, catalytic routes to selectively accessing
3-acylindoles using readily available starting materials is highly
desirable.
Recently, Su’s group reported a convenient and general
method for acylation of indoles using secondary anilines as the
acyl resources by oxidative cleaving the C−N bond of
secondary anilines.4 Subsequently, Cheng’s group5 has also
developed a CuCl2/O2 system for efficient formylation of
indole with tertiary amines with a good functional group
tolerance. Very recently, we illustrated a mild route to the
selective synthesis of 2-(1H-indol-3-yl)-2-iminocarbonyls and
2-(1H-indol-3-yl)-2-oxocarbonyls via copper-catalyzed C−H
oxidation/cross-coupling of α-amino carbonyls with indoles in
the presence of TBHP (Scheme 1a).6 Interestingly, the
selectivity toward either 2-(1H-indol-3-yl)-2-iminocarbonyl
compounds or 2-(1H-indol-3-yl)-2-oxocarbonyl compounds
can be accessed by slight modification of the reaction
RESULTS AND DISCUSSION
■
Oxidative Cross-Coupling of Indoles with α-Amino
Carbonyl Compounds to 2-(1H-Indol-3-yl)-2-oxocarbon-
yl Compounds. Our investigation began with the oxidative
cross-coupling of indole 1a with 2-(methyl(phenyl)amino)-1-
phenylethanone 2a (Table 1). In the presence of 10 mol % of
Pd(OAc)2, treatment of indole 1a with substrate 2a in MeCN
at 80 °C under air atmosphere afforded a trace amount of the
expected product 3 (entry 1). To our delight, the presence of
Cu(OAc)2 oxidant was found to facilitate the reaction: the yield
of 3 was enhanced sharply to 53% with 1 equiv of Cu(OAc)2
Received: October 5, 2013
Published: October 22, 2013
© 2013 American Chemical Society
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Scheme 1. Synthesis and Applications of 3-Acylated Indoles
(entry 2) and to 62% using 2 equiv of Cu(OAc)2 (entry 3).
Results identical to those with 2 equiv of Cu(OAc)2 were
obtained when the reaction was carried out with 3 equiv of
Cu(OAc)2 (entry 4). Subsequently, a series of other oxidants,
including Cu(OTf)2, CuCl2, AgOAc, and TBHP, were
examined, and they were less effective than Cu(OAc)2 (entries
5−8); moreover, both Cu(OTf)2 and TBHP have no effect on
the reaction (entries 5 and 8). Extensive screening revealed that
the reaction between indole 1a and substrate 2a at 5 mol % of
Pd(OAc)2 worked well and gave the target product 3 in 60%
yield (entry 9); however, the yield was lowered to 54% using 2
mol % of Pd(OAc)2 (entry 10). Notably, in the presence of 2
equiv of Cu(OAc)2, the reaction could take place without Pd
catalysts, albeit with a lower yield (entry 11). Two other Pd
catalysts, PdCl2 and Pd(dba)2, were evaluated, and they were
less active than Pd(OAc)2 (entries 14 and 15). The reported
literature suggested that the presence of organic acids can
improve the C−N bond cleavage reaction.7 Therefore, a
number of acids, such as HOAc, CF3CO2H, PivOH, and
PhCO2H, were tested (entries 16−20). As expected, the
presence of 0.5 equiv of HOAc enhanced the yield of 3 to 80%
(entry 16) and 1 equiv of HOAc to 78% (entry 17). However,
PivOH has no obvious role in promoting the reaction (entry
19), and both CF3CO2H and PhCO2H suppressed the reaction.
Among the effect of solvents examined, it turned out that
MeCN is the most efficient medium (entries 16 and 21−23). It
is noteworthy that the reaction is successful with 65% yield of 3
under N2 atmosphere (entry 24). Compared with the results
under air atmosphere, we deduced that the role of air was used
as an oxidant to improve the reaction (entry 16 vs entry 24).
Finally, the use of Cu(OAc)2/O2 as combined oxidants was
investigated: the Cu(OAc)2/O2 system was ineffective, and
only a 40% yield of product 3 was obtained (entry 25).
With the optimal reaction conditions in hand, we turned our
attention to exploring the viable substituents on the nitrogen
atom in amines (2) (Scheme 2). The reactivity of substrate 2b
with a free N−H bond, 1-phenyl-2-(phenylamino)ethanone,
was very low in terms of yield. Unfortunately, substrates 2c and
2d with two alkyl groups on the nitrogen atom were unsuitable
for the reaction. N-Benzyl-N-methylaniline (2e), the reported
efficient C−N cleavage reagent,7a was inert under the optimal
conditions.
Inspired by the results described above, we next set out to
investigate the scope of this oxidative cross coupling reaction
with respect to both indoles 1 and α-amino carbonyl
compounds 2 in the presence of 5 mol % of Pd(OAc)2, 2
equiv of Cu(OAc)2, 0.5 equiv of HOAc, and air (Table 2).
Gratifyingly, this protocol was general to a wide range of α-
amino carbonyl compounds 2. Initial screening on α-amino
ketones revealed that several substitiuents, including MeO, F,
Cl, CF3, and CN groups, on the aromatic ring of the 1-
arylethanone moiety were well-tolerated (products 4−8), and
the reactive order is electron-withdrawing groups > electron-
donating groups. While 1-(4-methoxyphenyl)-2-(methyl-
(phenyl)amino)ethanone gave the desired product 4 in 64%
yield, 2-(methyl(phenyl)amino)-1-(4-(trifluoromethyl)phenyl)-
ethanone and 4-(2-(methyl(phenyl)amino)acetyl)benzonitrile
furnished products 7 and 8 in 77% and 81% yields, respectively.
Unexpectedly, the reaction of CF3-containing substrate afforded
a mixture of 2- and 3-acylated indoles 7 with 1:4 ratio. Using 2-
(methyl(phenyl)amino)-1-(naphthalen-1-yl)ethanone, good
yield was still achieved (product 9). We were pleased to find
that the optimal conditions were compatible with 1-(methyl-
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a
Table 1. Screening of Optimal Conditions
entry
[Pd] (mol %)
[O] (equiv)
additive (equiv)
solvent
MeCN
T (°C)
yield (%)
1
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (5)
Pd(OAc)2 (2)
80
80
80
80
80
80
80
80
80
80
80
60
120
80
80
80
80
80
80
80
80
80
80
80
80
trace
53
2
Cu(OAc)2 (1)
Cu(OAc)2 (2)
Cu(OAc)2 (3)
Cu(OTf)2 (2)
CuCl2 (2)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
dioxane
CH2ClCH2Cl
DMSO
MeCN
MeCN
3
62
4
62
5
trace
15
6
7
AgOAc (2)
6
8
TBHP (2)
trace
60
9
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (2)
Cu(OAc)2 (0.2)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
54
12
Pd(OAc)2 (5)
Pd(OAc)2 (5)
PdCl2 (5)
41
59
52
Pd(dba)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
49
HOAc (0.5)
HOAc (1)
80
78
CF3CO2H (0.5)
PivOH (0.5)
PhCO2H (0.5)
HOAc (0.5)
HOAc (0.5)
HOAc (0.5)
HOAc (0.5)
HOAc (0.5)
trace
63
58
55
48
trace
65
b
24
c
25
40
a
b
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), [M], [O], additive, and solvent (2 mL) under air atmosphere for 12 h. Under N2
c
atmosphere. Under O2 (1 atm) atmosphere.
Scheme 2. Screening Scope of Viable Substituents on the
Nitrogen Atom in Amines (2)
Table 2. Pd-Catalyzed Cross-Coupling of Indoles (1) with α-
Amino Carbonyl Compounds (2)
a
(phenyl)amino)propan-2-one (product 10) but were ineffective
for α-amino ester (product 11). The reason might be that the
electron-withdrawing properties of ester group dramatically
decreased the reactivity of the α-CH2 group in α-amino ester
for the insertion of the active Pd species into the α-C−H bond,
resulting in the failure of the reaction.
The optimal conditions were subjected to a wide range of
indoles 1 (products 12−22). For example, indoles 1 with a
substituent, such as Me, MeO, F, Br, CN, and NO2, at the 5
position were consistent with the optimal conditions, providing
the corresponding products 12−17 in moderate to good yields.
a
Reaction conditions: 1 (0.2 mmol), 2 (0.24 mmol), Pd(OAc)2 (5
mol %), Cu(OAc)2 (2 equiv), HOAc (0.5 equiv), and MeCN (2 mL)
b
c
at 80 °C under air atmosphere. At 100 °C. A mixture of 2- and 3-
acylated indoles was obtained with 1:4 ratio.
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Importantly, F, Cl, or Br groups on the aryl ring of either
indoles 1 or α-amino carbonyl compounds 2 could be perfectly
tolerated, thereby facilitating possible additional modifications
at the halogenated positions (products 5, 6, 14, and 15). Using
7-Et-susbtituted indole, the expect product 18 was obtained in
67% yield from the reaction with 2-(methyl(phenyl)amino)-1-
phenylethanone 2a. Interestingly, indoles 1 with a substituent
at the 2 position displayed high activity, leading to the
corresponding products 19 and 20 in good yields. This
protocol could be applied to construct 2-acylated product 21
when 3-Me-substituted indole was used, albeit with a low yield.
It is noteworthy that 1-methyl-1H-indole is also viable for the
reaction with 2-(methyl(phenyl)amino)-1-phenylethanone 2a
in good yield (product 22).
be easily converted into the corresponding indoles, and cross
coupling with substrate 2a, Cu(OAc)2, and AcOH afforded the
expected products 28−31 in 72−84% yields. Interestingly,
aliphatic alkyne was also viable to react with substrate 2a,
offering product 32 in 83% yield.
To elucidate the mechanism, some control experiments were
carried out (Scheme 3).9 In the presence of H218O , 55% of
Scheme 3. Control Experiments
One-Pot Tandem Route to 2-(1H-Indol-3-yl)-2-oxo-
carbonyl Compounds. It is known that indoles can be readily
prepared from 2-ethynylanilines 23 in the presence of transition
metals (for example, Pd).8 Thus, we next investigated the
feasibility of one-pot synthesis of 2-(1H-indol-3-yl)-2-oxocar-
bonyl compounds from the reaction of 2-ethynylanilines 23
with α-amino carbonyl compounds 2, which will make this
methodology more useful in organic synthesis (Table 3). After
Table 3. One-Pot Tandem Route to 2-(1H-Indol-3-yl)-2-
a
oxocarbonyl Compounds
product 3 contained the 18O atom, suggesting that the oxygen
of the new formed carbonyl group was from water (Scheme 3,
eq 1). In the absence of indoles, substrate 2a was converted to
N-methyl-2-oxo-N,2-diphenylacetamide 33 in 67% yield
(Scheme 3, eq 2), and the GC−MS analysis results showed
that intermediate A was in situ formed and disappeared after
the reaction finished (Figure S1, Supporting Information).
Notably, intermediate B was also in situ determined from the
reaction of indole 1a with substrate 2a by HRMS analysis
(Scheme 3, eq 2, and Figure S2, Supporting Information). The
results showed that N-methyl-2-oxo-N,2-diphenylacetamide 33
was not suitable to react with indole 1a under the optimal
conditions (Scheme 3, eq 3).
Consequently, possible mechanisms outlined in Scheme 4
are proposed.4−7 Initially, α-amino carbonyl compound 2 reacts
with the Pd active species to produce intermediate C, followed
by reaction with indoles to afford intermediate D. It is noted
that intermediate C can be readily oxidized to iminium ion A in
the presence of Cu(OAc)2 and air.4−7 Reductive elimination of
intermediate D takes place leading to intermediate E.
Alternately, iminium ion A can simply react with indole to
give intermediate E directly. Intermediate E can be quickly
converted into intermediate B in the presence of oxidants.
Hydrolysis of intermediate B gives the desired 3-acylated
indoles and N-methylaniline.
Gratifyingly, the obtained indolyl diketone products could be
used to construct conjugated polyheterocyclic compounds,
which have good electronic chemistry and fluorescence
properties: in the presence of PTFA, polyheterocyclic
compounds 34−37 were prepared from the reaction of indolyl
1,2-diketones with 1H-indoles (Scheme 5).9
a
Reaction conditions: (1) 1 (0.2 mmol), PdCl2 (5 mol %), and MeCN
(2 mL) at 80 °C for 4 h under air atmosphere; (2) 2 (0.24 mmol),
Cu(OAc)2 (2 equiv), and HOAc (0.5 equiv) at 80 °C for 12 h. For
24 h.
b
a series of trials (Table S1 in Supporting Information), we
found that 2-phenylindole could be in situ generated in the
presence of 2-(phenylethynyl)aniline 23a and PdCl2, and
addition of 2-(methyl(phenyl)amino)-1-phenylethanone 2a,
Cu(OAc)2, and AcOH resulted in the expected 1-phenyl-2-
(2-phenyl-1H-indol-3-yl)ethane-1,2-dione 20 in 81% yield.
Encouraged by these results, the other four α-amino carbonyl
compounds 2 were employed to react with 2-(phenylethynyl)-
aniline 23a: they are all suitable substrates for the one-pot
reaction with substrate 23a, giving the corresponding products
24−27 in high yields. Subsequently, a variety of 2-ethynylani-
lines were examined in the presence of 2-(methyl(phenyl)-
amino)-1-phenylethanone 2a (products 28−32). 2-
(Phenylethynyl)anilines with a substituents, such as Me, F,
Br, and CF3 groups, on the aryl ring of the aniline moiety could
Generally, highly conjugated polyheterocyclic molecules
usually serve as metal ion probes because they have good
fluorescence properties.10 As expected, preliminary experiments
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Scheme 4. Possible Mechanisms
Scheme 5. Application of 3-Acylated Indoles
Figure 1. Fluorescence emission spectra of compound 34 in the
presence of different metal ions Ag+, Ba2+, Bi2+, Co+, Cr3+, Cu2+, Fe3+,
Hg2+, Ni2+, and Zn2+ in CH3CN/H2O (100:1). λex = 370 nm, [35] =
2.5 × 10−4 M, [Mn+] = 1 × 10−3 M.
were conducted to investigate the probe functionality of
compound 34 (Figure 1). As shown in Figure 1, 4 equiv of Mn+
ion (including Ag+, Ba2+, Bi3+, Co2+, Cr3+, Cu2+, Fe3+, Hg2+,
Ni2+, and Zn2+) was introduced to a solution of 34 in CH3CN/
H2O to test the change of fluorescence emission intensity. We
found that Hg2+, Fe3+, and Cu2+ could distinctly depress the
fluorescence. In particular, both Hg2+ and Fe3+ quenched the
fluorescence completely, implying that compound 34 is a good
probe for Hg2+ and Fe3+ ions.
EXPERIMENTAL SECTION
■
1
General Considerations. The H and 13C NMR spectra were
recorded in CDCl3 or DMSO solvent on a NMR spectrometer using
TMS as internal standard. LRMS was performed on a GC-MS
instrument and HRMS was measured on an electrospray ionization
(ESI) apparatus using time-of-flight (TOF) mass spectrometry.
Melting points are uncorrected.
CONCLUSIONS
■
In summary, we have described a novel and general palladium-
catalyzed C−H oxidative/cross-coupling of indoles with α-
amino carbonyl compounds to furnish 3-acylated indoles via a
selectively C−N bond cleavage process. Notablely, the present
system allows the tandem reaction of 2-(phenylethynyl)aniline
with α-amino carbonyls to afford diversified 2-arylindolyl
diketones which should be significant for the construction of
indole libraries. Moreover, these indolyl diketones can be
transformed to highly polyheterocyclic compounds, which serve
as excellent probes for metal ions, such as Hg2+ and Fe3+.
Preparation of α-Amino Carbonyl Compounds (2) and 2-
Ethynylanilines (23). Both α-amino carbonyl compounds (1)11 and
2-ethynylanilines (23)8 were prepared according to the known
procedures.
Typical Experimental Procedure for the Oxidative Cross
Coupling of Indoles (1) with α-Amino Carbonyl Compounds
(2). To a Schlenk tube were added indoles 1 (0.2 mmol), α-amino
carbonyl compounds 2 (0.24 mmol), Pd(OAc)2 (5 mol %), Cu(OAc)2
(2 equiv), HOAc (0.5 equiv), and MeCN (2 mL). Then the tube was
charged with air and stirred at 80 °C (oil bath temperature) for the
indicated time until complete consumption of starting material as
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monitored by TLC and GC−MS analysis. After the reaction was
finished, the reaction mixture was washed with brine. The aqueous
phase was re-extracted with ethyl acetate. The combined organic
extracts were dried over Na2SO4 and concentrated in vacuum, and the
resulting residue was purified by silica gel column chromatography
(only hexane) to afford the desired product.
Typical Experimental Procedure for the One-Pot Tandem
Route to 2-(1H-Indol-3-yl)-2-oxocarbonyl Compounds from
Oxidative Cross-Coupling of 2-Ethynylanilines (23) and α-
Amino Carbonyl Compounds (2). A mixture of 2-ethynylanilines
23 (0.2 mmol), PdCl2 (5 mol %), and MeCN (2 mL) was stirred at 80
°C (oil bath temperature) for 4 h, and then α-amino carbonyl
compounds 2 (0.24 mmol), Cu(OAc)2 (2 equiv), and HOAc (0.5
equiv) were added. The mixture was stirred at 80 °C for 12 h until
complete consumption of the starting material as monitored by TLC
and GC−MS analysis. After the reaction was finished, the reaction
mixture was washed with brine. The aqueous phase was re-extracted
with ethyl acetate. The combined organic extracts were dried over
Na2SO4 and concentrated in vacuum, and the resulting residue was
purified by silica gel column chromatography (only hexane) to afford
the desired product.
(m, 1H), 7.24−7.20 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 192.0,
186.8, 136.4, 136.2, 135.9, 135.3 (q, J = 32.5 Hz, 1C), 130.7, 128.9,
125.7 (q, J = 3.7 Hz, 1C), 125.5, 124.8, 123.4 (q, J = 271.3 Hz, 1C),
123.7, 122.5, 114.3, 111.8; IR (neat, cm−1) 1731, 1685, 1332, 1267,
1204; HRMS (ESI) calcd for C17H11F3NO2 [M + H]+ 318.0736,
found 318.0715.
4-(2-(1H-Indol-3-yl)-2-oxoacetyl)benzonitrile (8): 81% yield (44.3
mg), yellow solid; mp 178−180 °C; 1HNMR (500 MHz, DMSO-d6) δ
12.55 (brs, 1H), 8.32 (s, 1H), 8.28−8.26 (m, 1H), 8.16 (d, J = 7.0 Hz,
2H), 8.10 (d, J = 7.0 Hz, 2H), 7.63−7.60 (m, 1H), 7.39−7.34 (m,
2H); 13C NMR (125 MHz, DMSO-d6) δ 191.2, 185.7, 137.5, 135.9,
135.1, 131.9, 129.1, 123.9, 122.9, 121.9, 120.1, 116.8, 115.1, 111.7,
111.2; IR (neat, cm−1) 1716, 1617, 1516, 1269, 1129; HRMS (ESI)
calcd for C17H11N2O2 [M + H]+ 275.0815, found 275.0796.
1-(1H-Indol-3-yl)-2-(naphthalen-2-yl)ethane-1,2-dione (9):6 70%
1
yield (41.8 mg), yellow solid; H NMR (500 MHz, acetone-d6) δ
11.29 (brs, 1H), 8.51 (s, 1H), 8.29 (m, 1H), 8.02−7.87 (m, 5H), 7.56
(t, J = 7.4 Hz, 1H), 7.49−7.46 (m, 2H), 7.24−7.20 (m, 2H); 13C NMR
(125 MHz, acetone-d6) δ 194.8, 189.6, 138.2, 137.9, 137.1, 134.0,
133.5, 131.9, 130.8, 130.2, 129.7, 128.8, 128.0, 126.6, 125.0, 124.9,
123.7, 122.7, 114.6, 113.3; IR (neat, cm−1) 1731, 1695, 1268, 1208,
1029; HRMS (ESI) calcd for C20H14NO2 [M + H]+ 300.1019, found
300.0992.
Typical Experimental Procedure for the Synthesis of
Polyheterocyclic Compounds 34−37 from 2-(1H-Indol-3-yl)-
2-oxocarbonyl Compounds. To a Schlenk tube were added 2-(1H-
indol-3-yl)-2-oxocarbonyl compounds (0.1 mmol), indole 1a (0.2
mmol), PTFA (0.5 equiv), and toluene (1 mL). Then the tube was
charged with argon and stirred at 120 °C (oil bath temperature) for
the indicated time until complete consumption of starting material as
monitored by TLC and GC−MS analysis. After the reaction was
finished, the reaction mixture was washed with brine. The aqueous
phase was re-extracted with ethyl acetate. The combined organic
extracts were dried over Na2SO4 and concentrated in vacuum, and the
resulting residue was purified by silica gel column chromatography
(only hexane) to afford the desired product.
1-(1H-Indol-3-yl)propane-1,2-dione (10):6 61% yield (22.8 mg),
pale yellow solid; 1H NMR (500 MHz, DMSO-d6) δ 12.28 (brs, 1H),
8.34 (d, J = 3.0 Hz, 1H), 8.20 (d, J = 6.5 Hz, 1H), 7.54 (d, J = 6.5 Hz,
1H), 7.29−7.24 (m, 2H), 2.44 (s, 3H); 13C NMR (125 MHz, DMSO-
d6) δ 201.7, 185.5, 138.4 (2C), 137.1, 126.4, 124.2, 123.2, 121.8, 111.1,
26.1; IR (KBr, cm−1) 1704, 1593; HRMS (ESI) for C11H10NO2 [M +
H]+ calcd 188.0706, found 188.0690.
1-(5-Methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (12): 61%
1
yield (32.0 mg), yellow solid, mp 175−177 °C; H NMR (300 MHz,
DMSO-d6) δ 12.32 (brs, 1H), 8.11 (s, 1H), 8.06 (s, 1H), 7.96 (d, J =
7.2 Hz, 2H), 7.74 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.6 Hz, 2H), 7.44 (d,
J = 8.3 Hz, 1H), 7.15 (d, J = 7.3 Hz, 1H), 3.37 (s, 3H); 13C NMR (125
MHz, DMSO-d6) δ 194.0, 188.5, 137.8, 135.3, 134.6, 133.0, 131.9,
129.7, 129.1, 125.3, 125.2, 120.9, 112.4, 112.2, 21.3; IR (neat, cm−1)
3054, 1269, 1205, 1024, 993; HRMS (ESI) calcd for C17H14NO2 [M +
H]+ 264.1019, found 264.1023.
1-(1H-Indol-3-yl)-2-phenylethane-1,2-dione (3):6 80% yield (39.8
mg), yellow solid; 1H NMR (300 MHz, CDCl3) δ 8.90 (brs, 1H), 8.50
(d, J = 8.7 Hz, 1H), 8.11 (d, J = 8.7 Hz, 1H), 7.95 (d, J = 3.2 Hz, 1H),
7.65−7.37 (m, 5H), 7.15 (d, J = 8.7 Hz, 1H), 6.83 (d, J = 8.8 Hz, 1H);
13C NMR (125 MHz, CDCl3) δ 193.5, 188.3, 136.4, 135.4, 134.3,
1-(5-Methoxy-1H-indol-3-yl)-2-phenylethane-1,2-dione (13):6
133.4, 130.3, 128.8, 127.8, 124.6, 123.5, 122.6, 114.1, 111.6; IR (neat,
cm−1): 1735, 1682, 1384, 1271, 1208; HRMS (ESI) calcd for
C16H11NO2Na [M + Na]+ 272.0682, found 272.0689.
1
48% yield (26.7 mg), yellow solid; H NMR (300 MHz, DMSO-d6)
δ 12.32 (brs, 1H), 8.10 (s, 1H), 7.98−7.96 (m, 2H), 7.77−7.72 (m,
2H), 7.60 (t, J = 7.6 Hz, 2H), 7.46 (d, J = 8.8 Hz, 1H), 6.95 (dd, J =
8.8, 2.5 Hz, 1H), 3.83 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ
194.5, 188.9, 156.7, 138.2, 135.1, 133.5, 132.2, 130.2, 129.6, 126.4,
114.1, 114.0, 113.0, 103.6, 55.9; IR (neat, cm−1)1733, 1634, 1486,
1266, 1213; HRMS (ESI) calcd for C17H14NO3 [M + H]+ 280.0968,
found 280.0974.
1-(1H-Indol-3-yl)-2-(4-methoxyphenyl)ethane-1,2-dione (4):6
1
64% yield (35.7 mg), yellow solid; H NMR (500 MHz, DMSO-d6)
δ 12.37 (brs, 1H), 8.21−8.20 (m, 1H), 8.12 (s, 1H), 7.94 (d, J = 9.0
Hz, 2H), 7.56−7.54 (m, 1H), 7.34−7.27 (m, 2H), 7.11(d, J = 9.0 Hz,
2H), 3.87 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 193.2, 189.6,
164.8, 138.1, 137.4, 132.7, 126.3, 125.5, 124.3, 123.3, 121.7, 115.0,
113.2, 56.3; IR (neat, cm−1) 1714, 1596, 1516, 1436, 1269; HRMS
(ESI) calcd for C17H14NO3 [M + H]+ 280.0968, found 280.0973.
1-(4-Fluorophenyl)-2-(1H-indol-3-yl)ethane-1,2-dione (5):6 64%
yield (34.2 mg), yellow solid; 1H NMR (300 MHz, DMSO-d6) δ 12.44
(brs, 1H), 8.23−8.20 (m, 2H), 8.08−8.04 (m, 2H), 7.57−7.28 (m,
5H); 13C NMR (125 MHz, DMSO-d6) δ 192.9, 188.6, 166.3 (d, J =
252.9 Hz, 1C), 138.6, 137.5, 133.5, 133.4, 130.3 (d, J = 2.5 Hz, 1C),
125.6, 124.4, 123.4, 121.7, 116.8 (d, J = 22.1 Hz, 1C), 113.2 (d, J =
30.4 Hz, 1C); IR (neat, cm−1) 1776, 1418, 1232, 1013, 854; HRMS
(ESI) calcd for C16H11FNO2 [M + H]+ 268.0768, found 268.0775.
1-(4-Chlorophenyl)-2-(1H-indol-3-yl)ethane-1,2-dione (6):6 73%
1-(5-Fluoro-1H-indol-3-yl)-2-phenylethane-1,2-dione (14):6 58%
yield (30.9 mg), yellow solid; 1H NMR (500 MHz, DMSO-d6) δ 12.52
(brs, 1H), 8.25 (s, 1H), 7.98−7.96 (m, 2H), 7.90 (d, J = 10.0 Hz, 1H),
7.75−7.72 (m, 1H), 7.60−7.57 (m, 3H), 7.20−7.16 (m, 1H); 13C
NMR (125 MHz, DMSO-d6) δ 194.2, 188.8, 159.7 (d, J = 234.9 Hz,
1C), 139.7, 135.2, 134.1, 133.4, 130.3, 129.6, 126.3 (d, J = 11.0 Hz,
1C), 114.7 (d, J = 9.75 Hz, 1C), 113.1 (d, J = 4.4 Hz, 1C), 112.5 (d, J
= 25.8 Hz, 1C), 106.7 (d, J = 24.6 Hz, 1C); IR (neat, cm−1) 1756,
1426, 1268, 1007, 973; HRMS (ESI) calcd for C16H11FNO2 [M + H]+
268.0768, found 268.0776.
1-(5-Bromo-1H-indol-3-yl)-2-phenylethane-1,2-dione (15): 49%
yield (32.0 mg), yellow solid; mp 216−217 °C; 1H NMR (300
MHz, DMSO-d6) δ 12.60 (brs, 1H), 8.37 (s, 1H), 8.26 (s, 1H), 7.99−
7.96 (m, 2H), 7.80−7.23 (m, 1H), 7.63−7.42 (m, 4H); 13C NMR
(125 MHz, DMSO-d6) δ 193.5, 188.3, 138.9, 135.7, 134.8, 132.8,
129.8, 129.1, 126.8, 126.5, 123.3, 115.6, 114.8, 112.0; IR (neat, cm−1)
1715, 1517, 1269, 1209, 993; HRMS (ESI) calcd for C16H11BrNO2 [M
+ H]+ 327.9968 and 329.9948, found 327.9978 and 329.9957.
3-(2-Oxo-2-phenylacetyl)-1H-indole-5-carbonitrile (16): 35% yield
(19.2 mg), yellow solid; mp 188−190 °C; 1H NMR (500 MHz,
DMSO-d6) δ 12.87 (brs, 1H), 8.60 (s, 1H), 8.44 (s, 1H), 7.99 (d, J =
8.3 Hz, 2H), 7.79−7.73 (m, 3H), 7.62 (t, J = 7.8 Hz, 2H); 13C NMR
1
yield (41.3 mg), yellow solid; H NMR (500 MHz, acetone-d6) δ
11.31 (brs, 1H), 8.25−8.22 (m, 1H), 8.01 (d, J = 3.2 Hz, 1H), 7.92 (d,
J = 8.5 Hz, 2H), 7.48−7.44 (m, 3H), 7.21−7.17 (m, 2H); 13C NMR
(125 MHz, acetone-d6) δ 193.3, 188.7, 141.0, 138.1, 138.1, 133.2,
132.5, 130.0, 126.6, 124.9, 123.8, 122.7, 114.3, 113.4; IR (neat, cm−1)
1715, 1507, 1266, 1207, 704; HRMS (ESI) Calcd for C16H11ClNO2
[M + H]+ 284.0473, found 284.0464.
1-(1H-Indol-3-yl)-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione
1
(7): 77% yield (48.8 mg), yellow solid; mp 174−175 °C; H NMR
(500 MHz, acetone-d6) δ 11.36 (brs, 1H), 8.25−8.23 (m, 1H), 8.13
(d, J = 8.1 Hz, 2H), 8.10 (s, 1H), 7.82 (d, J = 8.2 Hz, 2H), 7.49−7.46
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(125 MHz, DMSO-d6) δ 193.3, 188.4, 140.2, 138.8, 134.9, 132.6,
129.8, 129.1, 126.8, 126.1, 124.9, 119.8, 114.3, 112.6, 105.1; IR (neat,
cm−1) 1639, 1269, 1186, 796, 665; HRMS (ESI) calcd for
C17H11N2O2 [M + H]+ 275.0815, found 275.0809.
148.9, 139.1, 136.0, 131.8, 130.9, 130.4, 130.2, 129.8, 129.0, 127.9,
126.8, 123.9, 122.9, 121.1, 112.3, 110.2; IR (neat, cm−1) 1716, 1682,
1272, 1186, 1024, 820; HRMS (ESI) calcd for C22H14ClNO2Na [M +
Na]+ 382.0605, found 382.0604.
1-(5-Nitro-1H-indol-3-yl)-2-phenylethane-1,2-dione (17): 70%
yield (41.1 mg), yellow solid; mp 190−191 °C. 1H NMR (300
MHz, DMSO-d6) δ 12.99 (brs, 1H), 9.09 (s, 1H), 8.51 (s, 1H), 8.28−
8.19 (m, 1H), 8.04−7.99 (m, 2H), 7.81−7.74 (m, 2H), 7.64−7.59 (m,
2H); 13C NMR (125 MHz, DMSO-d6) δ 193.2, 188.4, 143.3, 141.3,
140.3, 134.9, 132.6, 129.9, 129.2, 124.6, 119.2, 117.4, 113.7, 113.6; IR
(neat, cm−1)1716, 1507, 1326, 1209; HRMS (ESI) calcd for
C16H11N2O4 [M + H]+ 295.0713, found 295.0721.
4-(2-Oxo-2-(2-phenyl-1H-indol-3-yl)acetyl)benzonitrile (26): 82%
yield (57.4 mg), yellow solid; mp 210−211 °C; H NMR (500 MHz,
1
acetone-d6) δ 11.41 (brs, 1H), 8.25−8.23 (m, 1H), 7.76−7.72 (m,
4H), 7.46−7.44 (m, 1H), 7.24−7.23 (m, 5H), 7.08 (t, J = 7.8 Hz, 2H);
13C NMR (125 MHz, acetone-d6) δ 193.0, 190.6, 149.9, 137.7, 137.2,
133.4, 131.73, 131.3, 130.8, 130.6, 129.0, 128.3, 125.0, 124.0, 122.7,
118.6, 117.5, 112.9, 112.1; IR (neat, cm−1) 1769, 1715, 1559, 1270,
1192; HRMS (ESI) calcd for C23H15N2O2 [M + H]+ 351.1128, found
351,1131.
1-(7-Ethyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (18):6 67%
1
yield (37.1 mg), yellow solid; H NMR (300 MHz, CDCl3) δ 9.80
1-(Naphthalen-2-yl)-2-(2-phenyl-1H-indol-3-yl)ethane-1,2-dione
1
(brs, 1H), 8.29 (d, J = 7.9 Hz, 1H), 8.07 (d, J = 7.2 Hz, 2H), 7.76 (d, J
= 2.9 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.31
(m, 1H), 7.18 (d, J = 7.3 Hz, 1H), 2.89 (q, J = 7.6 Hz, 2H), 1.33 (t, J =
7.6 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ 194.5, 189.1, 137.9,
136.2, 135.1, 133.6, 130.2, 129.6, 129.1, 125.6, 123.7, 123.3, 119.3,
113.5, 24.0, 15.2; IR (neat, cm−1) 1674, 1594, 1268, 1155, 791; HRMS
(ESI) calcd for C18H15NO2Na [M + Na]+ 300.0995, found 300.0989.
1-(2-Methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (19):6 92%
(27): 80% yield (60.0 mg), yellow solid; mp 172−173 °C; H NMR
(300 MHz, acetone-d6) δ 11.42 (brs, 1H), 8.66 (s, 1H), 8.45−8.42 (m,
1H), 8.17−8.01 (m, 7H), 7.74−7.60 (m, 4H), 7.40−7.30 (m, 3H); 13C
NMR (125 MHz, acetone-d6) δ 194.8, 189.7, 138.0, 137.7, 137.1,
134.0, 133.4, 131.9, 130.8, 130.2, 129.7, 128.8, 128.0, 126.6, 125.0,
124.9, 123.7, 122.7, 114.6, 113.3; IR (neat, cm−1) 1668, 1596, 1450,
1181, 831; HRMS (ESI) calcd for C26H18NO2 [M + H]+ 376.1332,
found 376.1333.
1
yield (48.3 mg), yellow solid; H NMR (500 MHz, acetone-d6) δ
1-(5-Methyl-2-phenyl-1H-indol-3-yl)-2-phenylethane-1,2-dione
1
(28): 72% yield (48.8 mg), yellow solid; mp 167−169 °C; H NMR
11.11 (brs, 1H), 7.88−7.83 (m, 3H), 7.56 (m, 1H), 7.43 (t, J = 7.8 Hz,
2H), 7.30−7.29 (m, 1H), 7.07−7.01 (m, 2H), 2.42 (s, 3H); 13C NMR
(125 MHz, acetone-d6) δ 196.4, 191.0, 148.0, 136.5, 135.4, 134.4,
130.5, 130.1, 127.9, 123.9, 123.3, 121.5, 112.4, 111.4, 14.7; IR (neat,
cm−1) 1762, 1388, 1268, 1207, 1030; HRMS (ESI) calcd for
C17H14NO2 [M + H]+ 264.1019, found 264.1023.
1-Phenyl-2-(2-phenyl-1H-indol-3-yl)ethane-1,2-dione (20): 85%
yield (55.2 mg), yellow solid; mp 190−191 °C; 1H NMR (300
MHz, acetone-d6) δ 11.49 (brs, 1H), 8.36−8.33 (m, 1H), 7.74 (d, J =
7.5 Hz, 2H), 7.66−7.56 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.41−7.33
(m, 5H), 7.19 (t, J = 7.7 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ
193.8, 191.1, 148.0, 135.5, 133.8, 133.7, 130.5, 130.0, 129.9, 129.6,
128.4, 128.2, 127.3, 124.4, 123.5, 122.5, 111.9, 111.2; IR (neat,
cm−1)1668, 1596, 1450, 1181, 831; HRMS (ESI) calcd for C22H16NO2
[M + H]+ 326.1176, found 326.1175.
(300 MHz, CDCl3) δ 9.13 (brs, 1H), 8.25 (s, 1H), 7.68 (d, J = 7.7 Hz,
2H), 7.52 (t, J = 7.4 Hz, 1H), 7.33−7.04 (m, 9H), 2.52 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 193.9, 191.1, 148.2, 133.9, 133.8, 133.7,
133.2, 130.6, 130.0, 129.8, 129.5, 128.4, 128.1, 127.5, 125.8, 122.2,
111.5, 111.0, 21.7; IR (neat, cm−1) 1675, 1449, 1269, 1208, 859;
HRMS (ESI) calcd for C23H18NO2 [M + H]+ 340.1332, found
340.1353.
1-(5-Fluoro-2-phenyl-1H-indol-3-yl)-2-phenylethane-1,2-dione
1
(29): 74% yield (50.7 mg), yellow solid; mp 211−212 °C; H NMR
(500 MHz, acetone-d6) δ 11.46 (brs, 1H), 7.90 (d, J = 9.8 Hz, 1H),
7.59 (d, J = 8.2 Hz, 2H), 7.51−7.44 (m, 2H), 7.32−7.19 (m, 5H),
7.05−6.99 (m, 3H); 13C NMR (125 MHz, acetone-d6) δ 194.2, 191.7,
160.6 (d, J = 234.9 Hz, 1C), 134.8, 134.7, 131.5, 131.1, 130.7, 130.2,
129.5, 129.5, 129.4, 128.9, 114.1 (d, J = 9.71 Hz, 1C), 112.8 (d, J =
26.1 Hz, 1C), 107.7 (d, J = 25.2 Hz, 1C); IR (neat, cm−1) 1716, 1364,
1270, 1226, 1192; HRMS (ESI) calcd for C22H15FNO2 [M + H]+
344.1081, found 344.1061.
1-(3-Methyl-1H-indol-2-yl)-2-phenylethane-1,2-dione (21): 30%
1
yield (15.7 mg), yellow solid; mp 53−54 °C; H NMR (300 MHz,
CDCl3) δ 8.59 (d, J = 7.6 Hz, 1H), 8.08 (d, J = 7.7 Hz, 2H), 7.72 (t, J
= 7.2 Hz, 1H), 7.59−7.54 (m, 3H), 7.50−7.39 (m, 2H), 6.99 (br s,
1H), 2.25 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 187.6, 162.8,
134.4, 134.3, 131.6, 131.0, 129.2, 128.2, 124.7, 123.8, 120.7, 119.7,
118.1, 115.9, 8.6; IR (neat, cm−1): 1673, 1445, 1397, 1208, 843, 671;
HRMS (ESI) calcd for C17H14NO2 [M + H]+ 264.1019, found
264.1038.
1-(5-Bromo-2-phenyl-1H-indol-3-yl)-2-phenylethane-1,2-dione
1
(30): 84% yield (67.7 mg), yellow solid; mp 212−213 °C; H NMR
(500 MHz, acetone-d6) δ 11.47 (brs, 1H), 8.42 (s, 1H), 7.59−7.03 (m,
12H); 13C NMR (125 MHz, acetone-d6) δ 194.1, 191.7, 134.8, 134.7,
131.3, 131.1, 130.8, 130.2, 129.6, 129.5, 129.4, 128.9, 127.6, 125.1,
123.8, 116.8, 114.7, 113.9; IR (neat, cm−1) 1696, 1391, 1341, 1268,
1208; HRMS (ESI) calcd for C22H15BrNO2 [M + H]+ 404.0281 and
406.0261, found 404.0288 and 406.0278.
1-(1-Methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (22):6 73%
yield (38.4 mg), yellow solid; 1H NMR (500 MHz, acetone-d6) δ 8.23
(d, J = 8.0, 2H), 7.97 (d, J = 8.0, 1H), 7.47 (m, 1H), 7.63−7.58 (m,
3H), 7.41−7.35 (m, 2H), 3.87 (s, 3H); 13C NMR (125 MHz, acetone-
d6) δ 194.5, 188.6, 141.7, 138.2, 135.3, 133.4, 130.3, 129.7, 125.9,
124.5, 123.8, 121.8, 111.9, 111.8, 34.0; IR (neat, cm−1) 3643, 1716,
1457, 1267, 1173; HRMS (ESI) calcd for C17H14NO2 [M + H]+
264.1019, found 264.1013.
1-Phenyl-2-(2-phenyl-5-(trifluoromethyl)-1H-indol-3-yl)ethane-
1,2-dione (31): 84% yield (66.0 mg), yellow solid; mp 201−203 °C;
1H NMR (500 MHz, DMSO-d6) δ 13.02 (brs, 1H), 8.58 (s, 1H),
7.74−7.66 (m, 5H), 7.48 (t, J = 7.8 Hz, 2H), 7.40−7.37 (m, 3H), 7.21
(t, J = 7.7 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) δ 193.0, 190.6,
150.8, 134.3, 132.9, 130.1, 130.0, 129.2, 128.8, 127.9, 126.4, 125.1 (q, J
= 270.0, 1C), 124.0, 123.6, 123.3, 120.4, 118.3, 113.3, 110.6; IR (neat,
cm−1) 1713, 1269, 1111, 862, 823; HRMS (ESI) calcd for
C23H15F3NO2 [M + H]+ 394.1049, found 394.1054.
1-(4-Methoxyphenyl)-2-(2-phenyl-1H-indol-3-yl)ethane-1,2-
1
dione (24): 85% yield (60.3 mg), yellow solid; mp 159−161 °C; H
NMR (500 MHz, acetone-d6) δ 11.26 (brs, 1H), 8.17 (d, J = 7.0 Hz,
1H), 7.56 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 7.0 Hz, 1H), 7.27−7.25 (m,
2H), 7.21−7.15 (m, 3H), 7.06 (t, J = 7.7 Hz, 2H), 6.82 (d, J = 8.0,
2H), 3.73 (s, 3H); 13C NMR (125 MHz, acetone-d6) δ 193.4, 192.2,
165.2, 132.6, 132.5, 131.1, 130.4, 130.2, 128.8, 128.4, 128.0, 127.9,
124.7, 123.6, 122.6, 115.1, 114.8, 112.8, 56.1; IR (neat, cm−1) 1716,
1596, 1451, 1267, 1169; HRMS (ESI) calcd for C23H18NO3 [M + H]+
356.1281, found 3561288.
1-(2-Hexyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (32): 83%
yield (55.2 mg), yellow solid; mp 155−156 °C; 1H NMR (500
MHz, acetone-d6) δ 11.15 (brs, 1H), 7.91−7.89 (m, 2H), 7.82 (d, J =
7.5 Hz, 1H), 7.62−7.59 (m, 1H), 7.49−7.46 (m, 2H), 7.32−7.31 (m,
1H), 7.09−7.02 (m, 2H), 2.85 (t, J = 8.0 Hz, 2H), 1.16−1.13 (m, 8H),
0.70 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 195.1, 190.3,
151.1, 134.9, 134.4, 130.1, 129.7, 128.9, 128.5, 126.8, 123.3, 122.9,
122.5, 110.9, 31.4, 29.2, 29.1, 28.6, 22.5, 14.0; IR (neat, cm−1) 3689,
3643, 1734, 1457, 1268; HRMS (ESI) calcd for C22H24NO2 [M + H]+
334,1802, found 334.1825.
1-(4-Chlorophenyl)-2-(2-phenyl-1H-indol-3-yl)ethane-1,2-dione
1
(25): 91% yield (65.3 mg), yellow solid; mp 180−182 °C; H NMR
(500 MHz, DMSO-d6) δ 12.66 (brs, 1H), 8.21 (d, J = 7.1 Hz, 1H),
7.68 (d, J = 8.5, 2H), 7.57−7.54 (m, 3H), 7.39−7.32 (m, 5H), 7.23 (t,
J = 7.7 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) δ 192.3, 189.8,
N-Methyl-2-oxo-N,2-diphenylacetamide (33):12 67% yield (32.0
mg), yellow solid; 1H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz,
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Featured Article
2H), 7.52−7.41 (m, 1H), 7.40−7.36 (m, 3H), 7.19−7.08 (m, 2H),
7.06 (d, J = 7.5 Hz,2H), 3.43 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
190.8, 167.1, 141.2, 134.2, 133.6, 130.1, 129.5, 129.4, 128.7, 128.4,
128.1, 126.7, 36.2; IR (neat, cm−1) 1736, 1508, 1467, 1265; HRMS
(ESI) calcd for C15H14NO2 [M + H]+ 240.1019, found 240.1013.
6-(1H-Indol-3-yl)-7-phenyl-5,8-dihydroindolo[2,3-c]carbazole
(34): 50% yield (22.3 mg), gray solid; mp 116−117 °C; 1H NMR (300
MHz, DMSO-d6) δ 11.84 (brs, 1H), 11.07 (brs, 1H), 10.55 (br s, 1H),
8.71 (d, J = 7.4 Hz, 1H), 7.64−7.06 (m, 14H), 6.84 (t, J = 7.4 Hz, 1H),
6.49 (t, J = 8.7 Hz, 1H), 6.51 (d, J = 8.2, 1H); 13C NMR (125 MHz,
DMSO-d6) δ 140.9, 139.6, 139.4, 139.1, 135.9, 135.0, 132.8, 130.4,
129.1, 128.0, 127.8, 127.6, 126.6, 125.7, 123.8, 123.7, 122.9, 121.5,
120.9, 120.7, 120.0, 119.2, 118.5, 118.3, 113.6, 111.4, 110.8, 110.5,
110.0, 105.2; IR (neat, cm−1) 1773, 1714, 1684, 1387, 1270; HRMS
(ESI) calcd for C32H22N3 [M + H]+ 448.1808, found 448.1813.
6-(1-Methyl-1H-indol-3-yl)-7-phenyl-5,8-dihydroindolo[2,3-c]-
carbazole (35): 45% yield (20.7 mg), gray solid; mp 118−119 °C; 1H
NMR (500 MHz, CDCl3) δ 8.78 (brs, 1H), 8.24 (d, J = 7.4 Hz, 1H),
8.03 (brs, 1H), 7.84 (brs, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.59 (d, J =
8.0 Hz, 1H), 7.40−6.96 (m, 14H), 1.95 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 140.2, 139.7, 139.2, 138.6, 136.6, 135.4, 133.9, 133.5, 130.3,
129.8, 128.0, 127.5, 126.8, 124.4, 123.7, 122.4, 121.3, 121.2, 120.5,
119.7, 119.6, 119.5, 119.1, 114.9, 110.9, 110.5, 110.3, 109.5,108.7,
105.5, 12.5; IR (neat, cm−1) 1743, 1682, 1384, 1270, 1030; HRMS
(ESI) calcd for C33H24N3 [M + H]+ 462.1965, found 462.1973.
6-(1H-Indol-3-yl)-2,11-dimethoxy-7-phenyl-5,8-dihydroindolo-
[2,3-c]carbazole (36): 35% yield (17.7 mg), gray solid; mp 116−118
20120161110041), and Hunan Provincial Natural Science
Foundation of China (No. 13JJ2018) for financial support.
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°C; H NMR (500 MHz, acetone-d6) δ 10.81 (brs, 1H), 10.10 (brs,
1H), 9.63 (brs, 1H), 7.98 (brs, 1H), 7.42 (d, J = 7.7 Hz, 1H), 7.31−
7.01 (m, 10H), 6.95 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 8.7 Hz, 1H), 6.79
(t, J = 7.4 Hz, 1H), 6.70 (d, J = 8.7 Hz, 1H), 3.81 (s, 3H), 3.32 (s,
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4-(7-(1H-Indol-3-yl)-5,8-dihydroindolo[2,3-c]carbazol-6-yl)-
benzonitrile (37): 34% yield (16.0 mg), gray solid; mp 201−202 °C;
1H NMR (500 MHz, CDCl3) δ 8.88 (brs, 1H), 8.25 (d, J = 7.6 Hz,
1H), 8.20 (brs, 1H), 8.18 (brs, 1H), 7.70−7.68 (m, 2H), 7.60 (d, J =
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110.6, 109.9, 106.3; IR (neat, cm−1) 1774, 1683, 1378, 1332, 1269;
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ASSOCIATED CONTENT
■
S
* Supporting Information
J.-H. Angew. Chem., Int. Ed. 2012, 51, 3453.
Optimization of two reactions, in situ HRMS and GC−MS
analysis, and copies of NMR spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: jnxiang@hnu.edu.cn.
*E-mail: jhli@hnu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Natural Science Foundation of China (Nos.
21202121 and 21172060), Specialized Research Fund for the
Doctoral Program of Higher Education (No.
11170
dx.doi.org/10.1021/jo402215s | J. Org. Chem. 2013, 78, 11163−11171

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