Synthesis of indenoquinolinone through aryne-mediated Pd(II)-catalysed remote C–H activation

Article abstract of DOI:10.1007/s11164-020-04387-2

Abstract: [Figure not available: see fulltext.]Indenoquinolinones have been synthesized from 2-haloquinoline-3-carbaldehyde through Pd-mediated simultaneous C–H (aldehyde) and C–X bond activation. DFT studies were performed to investigate the mechanistic pathway, and in situ UV–Vis studies indicate the presence of Pd(II) intermediate species. Aryne ligated Pd complex is actual intermediate in these reactions. Ligation of reactive aryne to Pd reduces probability of side reactions. Graphic abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-020-04387-2

Research on Chemical Intermediates (2021) 47:2049–2061
https://doi.org/10.1007/s11164-020-04387-2
Synthesis of indenoquinolinone through aryne‑mediated
Pd(II)‑catalysed remote C–H activation
Anuj P. Patel1 · Mohammedumar M. Shaikh1 · Kamlesh K. Gurjar2 ·
Kishor H. Chikhalia3
Received: 26 September 2020 / Accepted: 23 December 2020 / Published online: 27 January 2021
© The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature 2021
Abstract
Indenoquinolinones have been synthesized from 2-haloquinoline-3-carbaldehyde
through Pd-mediated simultaneous C–H (aldehyde) and C–X bond activation. DFT
studies were performed to investigate the mechanistic pathway, and in situ UV–
Vis studies indicate the presence of Pd(II) intermediate species. Aryne ligated Pd
complex is actual intermediate in these reactions. Ligation of reactive aryne to Pd
reduces probability of side reactions.
Supplementary Information The online version contains supplementary material available at (https
://doi.org/10.1007/s11164-020-04387-2).
*
Kishor H. Chikhalia
chikhalia_kh@yahoo.com
1
2
3
Department of Chemistry, Gujarat University, Ahmedabad, Gujarat 380009, India
Chemical Department, VGEC, Ahmedabad, Gujarat 382424, India
Department of Chemistry, Veer Narmad South Gujarat University, Surat, Gujarat 395007, India
Vol.:(0123456789)
1 3

2050
A. P. Patel et al.
Graphic abstract
CHO
CsF
(dba)3
THF
O
N
Cl
OTf
TMS
R
Pd2
In situ
UV visible
N
R
R1
R1
14
examples
PyrOx
60-82%
yield
Confirmation of Mechanistic
pathway throgh
studies
DFT
Keywords C–H functionalization · Indenoquinoline · Aryne · DFT
Introduction
Among the signifcant novel synthetic protocols developed in organic chemistry,
transition metal-catalysed C–H functionalization is most interesting one [1–6]. It
has a great infuence in fascinating synthesis of numerous organic material as well
as therapeutically potent molecules [7]. In spite of various reported C–H activa-
tion protocols, aryne-mediated transformation has attracted remarkable attention
of organic chemists due to its numerous synthetic applications [8–13]. Two reac-
tive vicinal positions of benzene in aryne are responsible for reactivity of benzyne
towards innumerable substrates [13–16]. Recently, interesting studies are reported
on insertion and annulation of arynes with alkynes [17–19], aminoesters [20], alk-
enes [21], allenes [22], azides [23], hydrazones [24] and sydnones [25]. In addition
to this, σ-bond forming reaction between two similar or dissimilar elements such as
Si–Si [26], Sn–Sn [27] and C–Sn [28] has also been reported (Scheme 1).
Scheme 1 Biologically potent indenoquinolinone derivatives [30, 32]
1 3

Synthesis of indenoquinolinone through aryne-mediated…
2051
Indenoquinolinone, a biologically potent molecule of azafourenone class, has
been found to possess excellent biological profle [29–33]. Indenoquinolinones have
been synthesized through diferent protocols by diferent research groups. Diferent
synthetic strategies for indenoquinolinone involve palladium-catalysed intramolecu-
lar arylation (Scheme 2, route a) [34], TBHP promoted intramolecular carbonyla-
tion (Scheme 2, route b) [35], poly(4-vinylpyridinium)hydrogen sulphate-catalysed
three-component strategy (Scheme 2, route c) [36], iron/AcOH prompted intra-
molecular cyclization (Scheme 2, route d) [37] and Cu-catalysed double C(sp3)–H
bond functionalization (Scheme 2, route e) [38]. Assembling signifcances of aryne
chemistry, therapeutical importance of indenoquinolinones as well as our continu-
ous interest in transition metal-catalysed C–H functionalization [39–44], we were
encouraged to synthesize indenoquinolinone using Pd catalyst from halo-substituted
quinolinecarbaldehyde and aryne precursor. Palladium-catalysed current proto-
col ofers single-step, one-pot synthesis of indenoquinolinones. Proposed protocol
afords good to excellent yields and wide range of functional group tolerance. Mech-
anistic studies were also performed to develop understanding of protocol. DFT stud-
ies reveal that aryne frst ligated to Pd complex (S) and resulting species (A) under-
goes oxidative addition with halo-substituted quinolinecarbaldehyde (C–X bond).
Proposed path is according to previous studies. However, previous studies do not
provide signifcant evidences (experimental or computational) in favour of proposed
mechanistic paths [45, 46].
Result and discussion
Extensive studies were performed to fnd the suitable Pd/ligand system, fuoride
source and solvent (Table 1). Pd(OAc)2 and PdCl2 were found inefective system
(entry no. 3 and 4). Pd2(dba)3 is the most suitable candidate in the present method.
Scheme 2 Synthetic protocols towards indenoquinolinone
1 3

2052
A. P. Patel et al.
Table 1 Optimization of the reaction conditionsa
Sr. no
Catalyst
Ligand
Solvent
Fluoride source
Yield (%)b
1
Pd2(dba)3
Pd(PPh3)4
Pd(OAc)2
PdCl2
PyrOx
PyrOx
PyrOx
PyrOx
P(o-tolyl)3
Xantphos
BINAP
PyrOx
PyrOx
PyrOx
PyrOx
PyrOx
PyrOx
PyrOx
–
THF
THF
THF
THF
THF
THF
THF
Toluene
DMF
MeCN
THF
THF
THF
THF
THF
THF
CsF
80
64
05
0
2
CsF
3
4
5
6
7
8
9
10
11
12
13
14
15
16
CsF
CsF
CsF
CsF
CsF
CsF
CsF
CsF
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
–
70
51
72
47
12
67
16
11
25
0
TBAF
KF+18- Crown-6
TBAT
–
CsF
0
0
PyrOx
CsF
aReaction conditions:1a (1.57 mmol, 1.0 equiv.), 2a (3.14 mmol, 2.0 equiv.), Pd catalyst (5.0 mol%),
ligand (5.0 mol%), fuoride source (7.85 mmol, 5 equiv.), THF (5.0 mL) at 80 °C for 3−4 h
bIsolated yield. Reaction at 80 °C. Reaction in dry THF. One-pot reaction
Further, exchange of Pd(PPh3)4 with Pd2(dba)3 decreases the yield (entry no. 2).
Notably, Pd source plays crucial role in the reaction. Nominal efect was noticed
in case of ligands. Employing BINAP and P(o-tolyl)3 ligands, 72% and 70% yield
was noticed, respectively. Yield was found highest (81%) in case of PyrOx{4-(tert-
butyl)-2-(5-(trifuoromethyl)pyridin-2-yl)-4,5-dihydrooxazole}ligand (L) (entry no.
1).
Furthermore, replacement of CsF with other fuoride sources like TBAF,
KF+18-crown-6 and TBAT signifcantly decreases the yield. Toluene and DMF
were not found suitable solvent, while MeCN aforded reasonable yield. In the cur-
rent investigation, THF was observed to be excellent solvent compared to others.
Desired product was not noticed in blank tests those were conducted in the absence
of Pd catalyst, ligand and fuoride source in separate reactions (entry no. 14–16).
Blank reactions indicate that all the three components (Pd, ligand and fuoride
source) play vital roles. In the next step, protocol was optimized for Pd/ligand (1:1)
system. Initially yield % is increased with increasing Pd/ligand loading up to 5%, but
1 3

Synthesis of indenoquinolinone through aryne-mediated…
2053
87
85
86
85
84
84
80
64
60
36
40
20
9
5
0
1
2
3
4
5
6
7
8
9
10
%Catalytic system (Pd/Ligand)
Fig. 1 Optimization of catalyst and ligand loading
Scheme 3 Substrate scopea
afterwards reaction, it was found independent to amount of catalyst. These observa-
tions indicate that generation of benzyne is rate-determining step (Fig. 1). Reaction
was monitored with TLC, and optimal time for complete conversion of 1a was 4 h.
This optimized condition was used for further investigations.
The present annulation reaction was extended for a variety of 2-haloquino-
line-3-carbaldehyde (1a–1j), and aryne precursors (2a–2c) were investigated
(Scheme 3). It was observed that –CH3/-OCH3 groups on 2-chloroquinoline-3-car-
baldehyde favour the conversion into the corresponding indenoquinolinone (3b–f).
Conversely, –NO2 and –F substitution showed moderate conversion (3d, 3 g and
3 h). Other aryne precursors (2b and 2c) were also investigated; the reaction of pre-
cursor 2b (4,5-dimethyl-2-(trimethylsilyl)phenyl trifuoromethanesulfonate) with
substrate 1a delivers only 60% conversion. Another precursor 2c (4,5-dimethoxy-
2-(trimethylsilyl)phenyl trifuoromethanesulfonate) was found slightly more efec-
tive than 2b. Iodo derivatives, 2-iodoquinoline-3-carbaldehydes, were also found
equally good substrates with aryne and deliver desired products in good yield (entry
no. 2, 10, 12 and 14).
To investigate the broader role of Pd/ligand system in the present protocol, theo-
retical mechanistic studies were performed. Possibly, indenoquinolinone synthesis
proceeds through two diferent pathways (path I and II) as shown in Fig. 2. In path
I, Pd/ligand complex coordinates with benzyne and forms species A [47, 48], which
further participates in oxidative addition (OA) with 1a to deliver intermediate B.
Eventually, B transforms into the intermediate C.
In path II, S undergoes oxidative addition with 1a and resulting spe-
cies G coordinate with benzyne intermediate and deliver C. Intermediate C is
1 3

2054
A. P. Patel et al.
Fig. 2 Proposed mechanistic pathway
common in both pathways. In view of calculated free energy barrier for OA,
path I (17.40 kcal mol−1) is more favourable than path II (32.41 kcal mol−1). It is
appropriate to state that S coordinates with benzyne before to participate in OA.
Presumably, S species hold reactive diradical benzyne species and prevent the
side reactions. However, in reductive elimination (RE) intermediate C can deliver
product through intermediates D or E. Formation of D (14.71 kcal mol−1) is more
favoured than formation of E (28.64 kcal mol−1) from species C. In the formation
of D, arylpalladium intermediate C coordinates with aldehyde group to produce a
palladium(II) alkoxide D [49, 50]. Free energy barrier for TS4 (1.82 kcal mol−1)
indicates that palladium plays a vital role in remote activation of C–H bond (alde-
hyde group) and in the elimination of HCl from intermediate D.
Alternatively, intermediate C can undergo oxidative addition of the aldehyde
C–H bond to form palladium(IV) intermediate E [51]. However, formation of
E(28.64 kcal mol−1) is not favoured by free energy. Overall oxidative addition
step controls the rate of reaction, and path I (17.40 kcal mol−1) is more favourable
than path II (32.41 kcal mol−1).
These mechanistic studies reveal that Pd/ligand system (S) plays three roles in
these reactions. Firstly, Pd holds the benzyne intermediate and possibly guides
site-specifc installation. Further, Pd/ligand helps in C–X and C–H bond (alde-
hyde) activation.
1 3

Synthesis of indenoquinolinone through aryne-mediated…
2055
Computational studies
DFT studies were performed to fnd favourable pathway on the basis of calculated
Gibb’s free energy. All the calculations were performed with Gaussian 09 package
at the hybrid functional B3LYP. CPCM solvent model was implemented for THF
solvent. LANL2DZ pseudo-potential was used for Pd and 6-311G basis set for other
atoms. Accordingly, all the geometries were optimized without constraint. All the
energy values mentioned here are Gibb’s free energy. For all species, single point
energy and vibration frequencies were calculated on optimized geometry and ther-
mal correction was adjusted. Transition states were confrmed by single imaginary
frequency (Figs. 3 and 4).
To validate the DFT results, in situ UV–visible spectroscopy studies were per-
formed (Fig. 5). In situ recorded spectrum indicates the presence of tetra-coordinated
Pd(II) species. Experimental spectrum shows the similarity with DFT calculated
spectrum for species C (experimental λmax =462 nm and calculated λmax =461 nm).
On the basis of in situ recorded spectrum, we can predict that Pd(IV) species are not
intermediate and RE does not follow through E species (path II). In situ recorded
spectrum serves the direct evidence of intermediate Pd(II) species.
Conclusion
Herein, a simple, efective and rapid synthetic method is investigated for indenoqui-
nolinones. Mechanistic studies explain broader role of Pd. It plays triple role, facili-
tates OA, C–H activation (aldehyde group) and holds benzyne species (minimize
side reactions) in these reactions. Mechanistic studies will be helpful for further
development. Work is under pipeline for the synthesis of other biologically potent
heterocycles as well as carbocycles aimed at the extension of this transformation for
the synthesis of other biologically potent heterocycles as well as carbocycles.
Fig. 3 DFT calculated free energy profle of possible mechanistic paths
1 3

2056
A. P. Patel et al.
Fig. 4 Optimized geometries of transition states
Experimental section
General information
Catalysts, ligands and aryne precursors were purchased from Sigma-Aldrich and
directly used without further purifcation. All reactions were monitored by thin-layer
chromatography using Merck 60 F254 precoated silica gel plates (0.25 mm thickness).
Column chromatography was performed using 60–120 and 200–400 mess silica from
Spectrochem PVT., LTD., Mumbai, India. 1H and 13C NMR spectra were recorded on
a Bruker AM400 (400 MHz for 1H NMR, 100 MHz for 13C NMR) instrument. NMR
spectra were processed with the MestReNova program. Data for 1H NMR are reported
as chemical shift (δ ppm), multiplicity (s=singlet, d=doublet, t=triplet, q=quartet,
1 3

Synthesis of indenoquinolinone through aryne-mediated…
2057
Fig. 5 a In situ recorded UV–Vis spectra of intermediate species; spectrum of C was recorded by refux-
ing of S and 1a under N2 and spectrum of C was recorded after addition of 2a and CsF in refuxing solu-
tion of C. b Computed UV–Vis spectra of C
m=multiplet), coupling constant (Hz), integration and assignment. Data for 13C NMR
are reported as chemical shift. HRMS spectra were recorded on XEVO G2-XS QTOF
spectrophotometer. All liquid reactants and solvents were distilled before use. UV–visi-
ble detection was monitored at appropriate wavelength, respectively, using Jasco V-570
UV spectrophotometer in the range of 200 – 800 nm.
General procedure for the synthesis of N‑(o‑tolyl)acetamide
An equimolar amount of o-toluidine (5 g, 0.33 mol), acetic anhydride (3.41 ml.
0.33 mol), acetic acid (0.5 ml) was stirred for 30 min at room temperature. The temper-
ature was gradually raised to 80 °C and further stirred for 2 h. Progress of the reaction
was monitored by TLC using ethyl acetate: hexane (7:3) as eluent. After the completion
of the reaction, it was poured into cold water. Precipitates were fltered and washed
with water and recrystallized from methanol to get titled compound. M.P. 109–112 ºC.
General procedure for the synthesis
of 2‑chloro‑8‑methylquinoline‑3‑carbaldehyde
The formylating reagent was prepared from phosphorus oxytrichloride, and N,N-
dimethylformamide (12:3) at 0–5 °C was added to N-(o-tolyl)acetamide (1.49 g,
10 mmol). The mixture was heated at 80 °C for 14 h. Progress of reaction was
1 3

2058
A. P. Patel et al.
monitored by TLC using ethyl acetate: hexane (7:3) as eluent. After the completion
of reaction, it was poured into cold water. The precipitates were fltered and washed
with water and recrystallized from methanol to get the titled compound.
General procedure for the synthesis
of 2‑iodo‑8‑methylquinoline‑3‑carbaldehyde
To sodium iodide (20.0 g), hydrochloric acid (1.3 mL, 55% w/v aqueous solu-
tion), and acetonitrile (200 mL), 2-chloro-3-formyl-8-methylquinoline (10.0 g,
0.49 mol) was added and the mixture was stirred under refux for 4.5 h. Most of the
solvent was removed under pressure and water (ca. 150 mL), and saturated aque-
ous sodium carbonate was added to render the mixture alkaline. The crude prod-
uct (13.5 g, 93%) was fltered of, washed well with water, and dried in air, and
was pure enough for further use. A sample was recrystallized from ethanol to get
2-iodo-8-methylquinoline-3-carbaldehyde.
General procedure for the synthesis of 11H‑indeno[1,2‑b]
quinolin‑11‑one
The 2-chloroquinoline-3-carbaldehyde (1.57 mmol), the 2-(trimethylsilyl)aryl tri-
fate (3.14 mmol), CsF (5 equiv.), Pd2(dba)3 (5 mol%), PyrOx(5 mol%), and 5 mL of
THF were placed in a vial, and the vial was sealed. The reaction mixture was stirred
frst at room temperature for 1 min and then heated to 80° C for 4 h. The mixture
was allowed to cool to room temperature diluted with diethyl ether, washed with
brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The
product was isolated by column chromatography using 200–400 mess silica.
11H‑indeno[1,2‑b]quinolin‑11‑one (3a) Yellow Powder; 297 mg, 80% iso-
1
lated yield; H NMR (400 MHz, CDCl3): δ 8.76 (s, 1H), 8.12–8.06 (m, 2H),
7.90(d, J=7.2 MHz, 1H), 7.85(d, J=8.4 MHz, 1H), 7.70–7.55(m, 4H); 13C NMR
(100 MHz, CDCl3): δ 197.74, 160.27, 150.28, 140.32, 134.57, 133.96, 132.48,
130.57, 130.20, 129.10, 128.68, 126.91, 126.23, 125.15, 122.10; Anal. Calcd.
For C16H9NO: C: 83.10; H: 3.92; N: 6.06. Found: C: 83.12; H: 3.91; N: 6.09. mp
173 °C. HRMS-ESI (m/z) calcd for C16H9NO [M+H]+231.0684, found231.0687.
C16H9NO.
6‑Methyl‑11H‑indeno[1,2‑b]quinolin‑11‑one (3b) Yellow Powder; 260 mg,
1
70% isolated yield; H NMR (400 MHz, CDCl3): δ 8.73 (s, 1H), 8.06–7.90 (m,
2H), 7.70–7.66(m, 2H), 7.55(dd, J=8.1 MHz, 1H), 7.44–7.42(m, 2H), 2.65(s, 1H);
13C NMR (100 MHz, CDCl3): δ 191.74, 163.29, 150.79, 140.32, 137.66, 134.57,
133.96, 132.48, 131.20, 130.41, 127.63, 126.98, 125.92, 125.34, 125.15, 122.10,
19.45; Anal. Calcd. For C17H11NO: C: 83.25; H: 4.52; N: 5.71. Found: C: 83.22; H:
4.53; N: 5.73. mp178 °C. HRMS-ESI (m/z) calcd for C17H8NO [M+H]+245.0841,
found 245.0847.
1 3

Synthesis of indenoquinolinone through aryne-mediated…
2059
7‑Methyl‑11H‑1indeno[1,2‑b]quinolin‑11‑one (3c) Yellow Powder; 260 mg, 70%
isolated yield; H NMR (400 MHz, CDCl3): δ 8.60 (s, 1H), 8.06(d, J=7.6 MHz,
1H), 7.90–7.70(m, 4H), 7.56–7.52(m, 2H), 2.47(s, 1H); 13C NMR (100 MHz,
CDCl3): δ191.74, 161.48, 151.49, 141.54, 140.32, 134.57, 133.96, 133.19, 132.48,
130.68, 129.47, 128.99, 127.91, 127.67, 125.25, 122.10, 21.69; Anal. Calcd. For
C17H11NO: C: 83.25; H: 4.52; N: 5.71. Found: C: 83.22; H: 4.53; N: 5.73. mp182
°C. HRMS-ESI (m/z) calcd for C17H8NO [M+H]+245.0841, found 245.0846.
8‑Nitro‑11H‑indeno[1,2‑b]quinolin‑11‑one (3d) Yellow Powder; 223 mg, 60%
1
isolated yield; H NMR (400 MHz, CDCl3): δ 8.92 (s, 1H), 8.72 (s, 1H), 8.67(d,
J=8.4 MHz, 1H), 8.07–7.84(m, 3H), 7.71–7.57(m, 2H); 13C NMR (100 MHz,
CDCl3): δ191.74, 158.41, 149.28, 144.50, 140.32, 134.57, 133.96, 133.68,
132.63, 132.48, 130.83, 129.13, 126.67, 125.15, 124.88, 122.10; Anal. Calcd. For
C16H8N2O3: C: 69.57; H: 2.92; N: 10.14. Found: C: 69.59; H: 2.93; N: 10.12. mp163
°C. HRMS-ESI (m/z) calcd for C16H8N2O3 [M+H]+276.0535, found 276.0540.
6‑Methoxy‑11H‑indeno[1,2‑b]quinolin‑11‑one (3e) Yellow Powder; 305 mg,
82% isolated yield; 1H NMR (400 MHz, CDCl3): δ 8.61 (s, 1H), 8.05(d, J=8.1 MHz,
1H), 7.90(d, J=8.4 MHz, 1H), 7.70–7.55(m, 2H), 7.33(dd, J=MHz, 1H), 7.29(d,
J=7.6 MHz, 1H), 6.86(d, J=7.4 MHz, 1H), 3.92(s, 1H); 13C NMR (100 MHz,
CDCl3): δ 191.74, 162.14, 158.36, 146.81, 140.32, 134.57, 133.96, 132.48, 131.42,
127.65, 127.61, 126.81, 125.15, 122.10, 120.93, 109.87, 57.09; Anal. Calcd. For
C17H11NO2: C: 78.15; H: 4.24; N: 5.36. Found: C: 78.11; H: 4.24; N: 5.35. mp170
°C. HRMS-ESI (m/z) calcd for C17H11NO2 [M+H]+261.0790, found 261.0792.
7‑Methoxy‑11H‑indeno[1,2‑b]quinolin‑11‑one (3f) Yellow Powder; 297 mg,
80% isolated yield; 1H NMR (400 MHz, CDCl3): δ 8.65 (s, 1H), 8.06–7.90(m, 2H),
7.70–7.56(m, 3H), 7.48(d, J=7.8 MHz, 1H), 7.35(s, 1H), 3.84(s, 1H); 13C NMR
(100 MHz, CDCl3): δ191.74, 163.15, 162.86, 149.43, 134.57, 133.96, 132.48,
130.65, 129.97, 129.39, 125.63, 125.15, 122.10, 116.60, 108.29, 56.04; Anal.
Calcd. For C17H11NO2: C: 78.15; H: 4.24; N: 5.36. Found: C: 78.11; H: 4.24; N:
5.35. mp159 °C. HRMS-ESI (m/z) calcd for C17H11NO2 [M+H]+261.0790, found
261.0793.
6‑Fluoro‑11H‑indeno[1,2‑b]quinolin‑11‑one (3 g) Yellow Powder; 260 mg,
1
70% isolated yield; H NMR (400 MHz, CDCl3): δ 8.74(s, 1H), 8.06–7.89(m,
2H), 7.70–7.47(m, 4H), 7.29(d, J=8.4 MHz, 1H); 13C NMR (100 MHz, CDCl3):
δ191.74,162.84, 162.23, 140.32, 134.57, 133.96, 132.48, 130.16, 127.45, 126.69,
126.39, 125.15, 123.88, 122.10, 114.42; Anal. Calcd. For C16H8FNO: C: 77.10;
H: 3.24; F: 7.62; N: 5.62. Found: C: 77.13; H: 3.24; F: 7.61; N: 5.63. mp159 °C.
HRMS-ESI (m/z) calcd for C16H8NOF [M+H]+249.0590, found 249.0594.
8‑Fluoro‑11H‑indeno[1,2‑b]quinolin‑11‑one (3 h) Yellow Powder; 241 mg, 65%
isolated yield; 1H NMR (400 MHz, CDCl3): δ 8.74(s, 1H), 8.15–8.05(m, 2H), 7.90–
7.55(m, 3H), 7.50(s, 1H), 7.45(d, J=7.6 MHz, 1H); 13C NMR (100 MHz, CDCl3):
1 3

2060
A. P. Patel et al.
δ191.74, 162.34, 161.48, 149.63, 140.32, 134.57, 133.96, 132.89, 132.48, 131.68,
130.27, 127.80, 125.15, 122.10, 117.62, 114.44; Anal. Calcd. For C16H8FNO: C:
77.10; H: 3.24; F: 7.62; N: 5.62. Found: C: 77.13; H: 3.24; F: 7.61; N: 5.63. mp161
°C. HRMS-ESI (m/z) calcd for C16H8NOF [M+H]+249.0590, found 249.0591.
2,3‑Dimethyl‑11H‑indeno[1,2‑b]quinolin‑11‑one (3i) Yellow Powder; 233 mg,
1
60% isolated yield; H NMR (400 MHz, CDCl3): δ 8.76(s, 1H), 8.12–8.00(m, 2H),
7.85–7.55(m, 4H), 2.42(s, 6H); 13C NMR (100 MHz, CDCl3): δ191.24, 160.13,
150.22, 144.61, 143.54, 139.24, 130.89, 130.57, 130.27, 129.89, 129.10, 127.92,
126.91, 126.21, 126.18, 125.56, 20.37; Anal. Calcd. For C18H13NO: C: 83.37; H:
5.05; N: 5.40. Found: C: 83.40; H: 5.04; N: 5.42. mp187 °C. HRMS-ESI (m/z) calcd
for C18H13NO [M+H]+259.0997, found 259.1002.
2,3‑Dimethoxy‑11H‑indeno[1,2‑b]quinolin‑11‑one (3j)
Yellow Powder;
1
260 mg, 70% isolated yield; H NMR (400 MHz, CDCl3): δ 8.76(s, 1H), 8.12–
8.00(m, 2H), 7.85–7.55(m, 4H), 3.83(s, 6H); 13C NMR (100 MHz, CDCl3): δ192.24,
160.13, 155.13, 153.67, 150.22, 134.70, 130.57, 130.20, 129.89, 129.10, 127.92,
126.91, 126.21, 107.80, 107.26, 56.79; Anal. Calcd. For C18H13NO3: C: 74.22; H:
4.50; N: 4.81. Found: C: 74.25; H: 4.49; N: 4.83. mp193 °C. HRMS-ESI (m/z) calcd
for C18H13NO3 [M+H]+291.0895, found 291.0892.
Acknowledgements Authors are thankful to Dr. N.K.Shah, Head, Department of Chemistry, Gujarat
University, for laboratory facilities and Department of Chemistry, PDPU, for providing computational
facilities and NFDD Centre, Rajkot, for spectral analysis.
References
1. B. Niea, W. Wua, Y. Zhangb, H. Jiang, J. Zhang. Org. Chem. Front. 7, 3067 (2020)
2. G. Li, Q. Liu, L. Vasamsetty, W. Guo, J. Wang. Angew. Chemie-Int. 9, 3503 (2020)
3. Y.F. Yang, X. Hong, J.Q. Yu, K.N. Houk, Acc. Chem. Res. 50, 2853 (2017)
4. X. Chen, K.M. Engle, D.H. Wang, J.Q. Yu, Angew. Chemie - Int. 48, 5094 (2009)
5. Z. Li, Z. Liang, Y. Wang, P. Yu, Res Chem Intermed. 39, 1917 (2013)
6. W.L. Chen, Y.Y. Jhang, Res Chem Intermed. 43, 3517 (2017)
7. J. Yamaguchi, A.D. Yamaguchi, K. Itami, Angew. Chemie-Int. 51, 8960 (2012)
8. M. Asamdi, K.H. Chikhalia, Asian. J. Org. Chem. 6, 1331 (2017)
9. S.S. Bhojgude, A. Bhunia, A.T. Biju, Acc. Chem. Res. 49, 1658 (2016)
10. J. Shi, Y. Li, Y. Li, Chem. Soc. Rev. 46, 1707 (2017)
11. R. Karmakar, D. Lee, Chem. Soc. Rev. 45, 4459 (2016)
12. C. Wu, F. Shi, Asian. J. Org. Chem. 2, 116 (2013)
13. S. Yoshida, T. Hosoya, Chem. Lett. 44, 1450 (2015)
14. D. Peña, A. Cobas, D. Pérez, E. Guitián, L. Castedo, Org. Lett. 2, 1629 (2000)
15. R.M. Patel, N.P. Argade, Org. Lett. 15, 14 (2013)
16. D. Peña, D. Pérez, E. Guitián, L. Castedo, Org. Lett. 1, 1555 (1999)
17. D. Peña, D. Pérez, E. Guitián, L. Castedo, Eur. J. Org. Chem. 7, 1238 (2003)
18. D. Peña, D. Pérez, E. Guitián, L. Castedo, J. Am. Chem. Soc. 121, 5827 (1999)
19. Y. Sato, T. Tamura, M. Mori, Angew. Chemie - Int. 43, 2436 (2004)
20. K. Okuma, N. Matsunaga, N. Nagahora, K. Shioji, Y. Yokomori, Chem. Commun. (Camb). 47,
5822 (2011)
21. T.T. Jayanth, M. Jeganmohan, C.H. Cheng, J. Org. Chem. 69, 8445 (2004)
1 3

Synthesis of indenoquinolinone through aryne-mediated…
2061
22. J.C. Hsieh, D.K. Rayabarapu, C.H. Cheng, Chem. Commun. (Camb) 5, 532 (2004)
23. F. Shi, J.P. Waldo, Y. Chen, R.C. Larock, Org. Lett. 10, 2409 (2008)
24. C. Spiteri, S. Keeling, J.E. Moses, Org. Lett. 12, 3368 (2010)
25. C. Wu, Y. Fang, R.C. Larock, F. Shi, Org. Lett. 12, 2234 (2010)
26. H. Yoshida, J. Ikadai, M. Shudo, J. Ohshita, A. Kunai, J. Am. Chem. Soc. 125, 6638 (2003)
27. H. Yoshida, K. Tanino, J. Ohshita, A. Kunai, Angew. Chemie - Int. Ed. 43, 5052 (2004)
28. H. Yoshida, Y. Honda, E. Shirakawa, T. Hiyama, Chem. Commun. 2, 1880 (2001)
29. C.D. Huford, S. Liu, A.M. Clark, B.O. Oguntimein, J. Nat. Prod. 50, 961 (1987)
30. I. Akritopoulou-Zanze, S.W. Djuric, Top Heterocycl Chem. 25, 231 (2010)
31. M. Manpadi, P.Y. Uglinskii, S.K. Rastogi, K.M. Cotter, Y.S.C. Wong, L.A. Anderson, A.J. Ortega,
S. Van slambrouck, W.F.A. Steelant, S. Rogelj, Org. Biomol. Chem. 5, 3865 (2007)
32. C. Tseng, C. Tzeng, C. Yang, P. Lu, Y. Liu, H. Chen, C. Chen, C. Yang, Y. Chen, Mol Divers. 17,
781 (2013)
33. S. Narwal, K.S. Kumar, P.K. Verma, Res Chem Intermed. 43, 2765 (2017)
34. N. Marquise, P.J. Harford, F. Chevallier, T. Roisnel, V. Dorcet, A.L. Gagez, S. Sable, L. Picot, V.
Thiery, A.E.H. Wheatley, Tetrahedron 69, 10123 (2013)
35. K. Mishra, A.K. Pandey, J.B. Singh, R.M. Singh, Org. Biomol. Chem. 14, 6328 (2016)
36. N.G. Khaligh, Chinese. J. Catal. 35, 474 (2014)
37. R.R. Rajawinslin, S.D. Gawande, V. Kavala, Y.-H. Huang, C.-W. Kuo, T.-S. Kuo, M.L. Chen, C.H.
He, C.F. Yao, RSC Adv. 4, 3780 (2014)
38. Z. Wang, G. Chen, X. Zhang, X. Fan, Org. Chem. Front. 4, 612 (2017)
39. S.S. Mudaliar, S.N. Zala, K.H. Chikhalia, J. Organomet. Chem. 848, 142 (2017)
40. M.U.M. Shaikh, S.S. Mudaliar, K.H. Chikhalia, RSC Adv. 6, 50780 (2016)
41. P.K. Patel, J.P. Dalvadi, K.H. Chikhalia, Tetrahedron Lett. 56, 6585 (2015)
42. J.P. Dalvadi, P.K. Patel, K.H. Chikhalia, Tetrahedron 70, 9394 (2014)
43. S.S. Mudaliar, M.M. Shaikh, K.H. Chikhalia, ChemistrySelect. 2, 1689 (2017)
44. S.S. Mudaliar, A.P. Patel, J.J. Patel, K.H. Chikhalia, Tetrahedron Lett. 59, 734 (2018)
45. J.P. Waldo, X. Zhang, F. Shi, R.C. Larock, J. Org. Chem. 73, 6679 (2008)
46. X. Zhang, R.C. Larock, Org. Lett. 7, 3973 (2005)
47. T. Matsubara, Organometallics 22, 4297 (2003)
48. M. Retbøll, A.J. Edwards, A.D. Rae, A.C. Willis, M.A. Bennett, E. Wenger, J. Am. Chem. Soc. 124,
8348 (2002)
49. V. Gevorgyan, L.G. Quan, Y. Yamamoto, Tetrahedron Lett. 40, 4089 (1999)
50. L.G. Quan, V. Gevorgyan, Y. Yamamoto, J. Am. Chem. Soc. 121, 3545 (1999)
51. L.L. Wei, L.M. Wei, W.-B. Pan, M.-J. Wu, Synlett 9, 1497 (2004)
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional afliations.
1 3