A facile route to 5-methyl-5H-indeno[1,2-c]quinolones via palladium-catalyzed cyclization of 2-alkynylbromobenzenes with N,N-dimethyl-2-alkynylanilines

Article abstract of DOI:10.1039/c4ob00706a

A tandem reaction catalyzed by palladium is developed to provide a facile and simple route for the synthesis of 5-methyl-5H-indeno[1,2-c]quinolones, which can introduce diversity and complexity into the products from readily available starting materials. This transformation proceeds well with good functional group tolerance. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00706a

Organic &
Biomolecular Chemistry
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PAPER
A facile route to 5-methyl-5H-indeno[1,2-c]-
quinolones via palladium-catalyzed cyclization of
2-alkynylbromobenzenes with N,N-dimethyl-
2-alkynylanilines†
Cite this: Org. Biomol. Chem., 2014,
12, 5861
Xiaolin Pan,a Yong Luo,a Yunyan Kuang*a and Guangming Li*b
Received 5th April 2014,
Accepted 30th May 2014
A tandem reaction catalyzed by palladium is developed to provide a facile and simple route for the
synthesis of 5-methyl-5H-indeno[1,2-c]quinolones, which can introduce diversity and complexity into the
products from readily available starting materials. This transformation proceeds well with good functional
group tolerance.
DOI: 10.1039/c4ob00706a
www.rsc.org/obc
synthetic route. We hypothesize that our desired product can
also be synthesized by utilizing this easy-synthesizing substrate
1. Introduction
Cyclic compounds especially heterocycles have made a pro- with a C–N bond cleavage.
found impact on organic chemistry due to their special pro-
As part of our ongoing research, we wish to report herein
perties and potential biological activity.1 As a result, a series of that the cyclization reaction of N,N-dimethyl-2-alkynylaniline
strategies for access to heterocyclic skeletons such as indoles, with 2-alkynylbromobenzene takes place efficiently to afford
isoquinolines and benzofurans have been developed,2 among the multi-substituted 5H-indeno[1,2-c]quinoline 3 (Scheme 1).
which, the domino reaction has been utilized widely because This approach not only introduces more diversity and complex-
of its high efficiency and convenience.3 Recently, our group ity into the products, but also avoids the unexpected oxidative
focused intense attention on constructing fused polycycles via compounds 11H-indeno[1,2-c]quinolin-11-ol compared to the
palladium-catalyzed domino reactions involving double inser- previous work.4a,b The construction of versatile substituted
tion of triple bonds as the key step.4 In these protocols, 2-alky- 5H-indeno[1,2-c]quinolines will potentially help finding mole-
nylhalobenzenes as powerful electrophiles undergo cyclization cules with anticancer activity.6
with different alkynes as nucleophiles by a sequence of carbo-
palladation and reductive elimination to generate functiona-
lized polycyclic compounds.
2. Results and discussion
In our attempt to synthesize N-substituted 5H-indeno[1,2-c]-
quinolones with our previously reported method,4a we found
We investigated the model reaction of 1-bromo-2-(phenylethy-
that the substrates N-mono-alkylated-2-alkynylaniline were very
difficult to synthesize. The direct Buchwald cross coupling of
aryl bromide and amine usually suffers from low yields.5 The
alkylation of the 2-alkynylaniline would generate a large
amount of undesired N,N-disubstituted products. So a long
synthetic route including protection–alkylation–deprotection is
typically needed.5 However, the recently reported chemistry of
N,N-dimethyl 2-alkynylaniline gives us a new insight into this
nyl)benzene 1a and N,N-dimethyl-2-(phenylethynyl)aniline 2a
in the presence of 5 mol% palladium catalyst at 102 °C under
various reaction conditions (Table 1). Our initial attempt
focused on screening ligands. The transformation did not
occur in the use of PCy3 (entry 1), and a trace amount of the
desired product 3a was detected under the conditions of P
(tBu)3·HBF4 (entry 2). Several other ligands, such as DPPF
(1,1′-bis(diphenylphosphino)ferrocene), DPPM (bis(diphenyl-
phosphino)methane), DPE Phos (bis[2-(diphenylphosphino)-
phenyl] ether) and L1, utilized as the replacement of the above
ligands could improve the final outcome to moderate yields
(entries 3–6). Interestingly, the reaction gave rise to 3a in 53%
yield without the addition of the ligand (entry 7). L2 was
proved to be the most effective ligand improving the yield to
67% and PPh3 afforded the desired product in similar yield of
62% (entries 8–9). Subsequently, the examination of bases
aDepartment of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433,
China. E-mail: yykuang@fudan.edu.cn; Fax: +86 21 6564 1740;
Tel: +86 21 6564 2796
bDepartment of Gastroenterology, Xinhua Hospital, Medical School of Shanghai
Jiaotong University, Shanghai, China. E-mail: ligm68@126.com
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4ob00706a
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(1j) serve as viable substrates for synthesizing indeno[1,2-c]qui-
nolones. The reaction was also smoothly performed with mod-
erate yields for N,N-dimethyl-2-alkynylanilines 2 bearing either
electron-rich or electron-poor groups in the R3 or R4 position.
A plausible reaction pathway is depicted in Scheme 2. The
active intermediate (R-PdIIX), generated from the oxidative
addition of 2-alkynylbromobenzene 1 to Pd0, reacted with
N,N-dimethyl-2-alkynylaniline 2 via intermolecular insertion of
the triple bond to provide A. The subsequent intramolecular
insertion of the triple bond occurred to give rise to B, which
went through intramolecular C–N bond formation to afford
the quaternary ammonium intermediate C. In the presence of
TBAI, N-demethylation by SN2 attack of I− to C proceeded,7 fol-
lowed by reductive elimination to furnish the desired product
3 and Pd0.
In conclusion, we have disclosed a simple and convenient
access to 5-methyl-5H-indeno[1,2-c]quinolones via a palla-
dium-catalyzed tandem reaction of 2-alkynylbromobenzenes
with N,N-dimethyl-2-alkynylanilines. The conversion tolerates
different functional groups, and more diverse substituents can
be easily introduced from readily available starting materials
to promote the diversity and complexity of the substrates.
3. Experimental section
General experimental procedure for palladium-catalyzed reac-
tion of 2-alkynylbromobenzene 1, N,N-dimethyl-2-alkynylani-
line 2: N,N-dimethyl-2-alkynylaniline (0.20 mmol) was added
to a mixture of Pd(OAc)2 (5 mol%), L2 (10 mol%), t-BuONa
(0.4 mmol), TBAI (0.24 mmol) in a test tube. This test tube was
vacuumed and filled with N2. Then a solution of 2-alkynyl-
bromobenzene (0.24 mmol) in 1,4-dioxane (2.0 mL) was added
to the system. The mixture was heated under reflux. After
N,N-dimethyl-2-alkynylaniline was consumed completely as
indicated by TLC, the reaction was cooled and the solvent was
diluted with EtOAc (10 mL), washed with saturated brine (2 ×
10 mL), and dried using anhydrous Na2SO4. Evaporation of the
solvent followed by purification on silica gel provides the pro-
ducts 3a–3r.
Scheme 1 Palladium-catalyzed tandem reaction of 2-alkynylbromo-
benzene 1 with N,N-dimethyl-2-alkynylaniline 2. Isolated yield based on
N,N-dimethyl-2-alkynylaniline 2.
showed that t-BuONa was the best choice and the others could
not increase yields (entries 10–13). Further screening of sol-
vents showed that the reaction proceeded most efficiently in
1,4-dioxane (entries 14–17). Various palladium sources were
explored only to find that Pd2dba3 could give a similar yield
while other palladium catalysts lowered the yield of 3a (entries
18–20). Further exploration proved that an additive was necess-
ary and TBAI (n-Bu4NI) was the best choice. No other additives
could enhance the isolated yield (entries 21–25). Subsequently,
the reaction did not proceed well when the temperature was
lowered, while higher temperatures could not promote the
conversion obviously (entries 26–29).
Having established the optimal reaction conditions (5 mol%
of Pd(OAc)2, 10 mol% of L2, 2.0 equiv. of t-BuONa, 1.2 equiv.
of TBAI, 1,4-dioxane, under reflux), we then focused on the
scope of this palladium-catalyzed tandem reaction of 2-alkynyl-
bromobenzenes 1 with N,N-dimethyl-2-alkynylanilines 2. The
results are summarized in Scheme 1. With respect to the scope
of 2-alkynylbromobenzenes 1, various electron-donating or
electron-withdrawing substituents attached on the aromatic
ring (R1 group) or the triple bond (R2 group) were well toler-
ated. It is notable that 1-bromo-2-(phenylethynyl)-benzene
derivatives with heterocyclic (1n), alkyl (1m), and bulky groups
5-Methyl-6,11-diphenyl-5H-indeno[1,2-c]quinoline (3a)
1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 7.9 Hz, 1H), 7.59–7.50
(m, 7H), 7.46–7.31 (m, 6H), 7.23 (t, J = 7.2 Hz, 1H), 7.08 (t, J =
7.4 Hz, 1H), 6.88 (t, J = 7.3 Hz, 1H), 6.31 (d, J = 7.8 Hz, 1H),
3.47 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.1, 142.5, 138.7,
136.1, 135.5, 130.6, 129.5, 129.0, 128.8, 126.6, 125.6, 125.4,
124.3, 123.0, 120.6, 120.4, 120.0, 118.3, 116.2, 115.5, 36.2.
HRMS (ESI) calcd for C29H22N+: 384.1747 (M + H+), found:
384.1753.
11-(4-Methoxyphenyl)-5-methyl-6-phenyl-5H-indeno[1,2-c]-
quinoline (3b)
1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.1 Hz, 1H), 7.64–7.36
(m, 10H), 7.25–7.20 (m, 1H), 7.14–7.08 (m, 3H), 6.90–6.86 (m,
1H), 6.32 (d, J = 7.9 Hz, 1H), 3.91 (s, 3H), 3.56 (s, 3H). 13C NMR
5862 | Org. Biomol. Chem., 2014, 12, 5861–5865
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Table 1 Palladium-catalyzed domino reaction of 2-alkynylbromobenzene 1a, N,N-dimethyl-2-(phenylethynyl)aniline 2aa
Entry
Ligand
Pd
Base
Solvent
Additive
Yield (%)
1
2
3
4
5
6
7
8
PCy3
P(t-Bu)3 HBF4
DPPF
DPPM
DPEPhos
L1
—
PPh3
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PhCN)2
Pd2dba3
PdCl2(PPh3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuOK
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
DMSO
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
—
n.r
Trace
47
40
45
43
53
62
67
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
n.r.
40
60
Cs2CO3
K3PO4
KOH
56
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
n.r.
Trace
21
45
Trace
61
DMF
Toluene
Diglyme
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
L2
L2
L2
L2
44
n.r.
n.r.
n.r.
38
43
50
63
68
64
TBAB
KI
L2
TBAC
nBu4OAc
TBAI
TBAI
TBAI
TBAI
L2
L2b
L2c
L2d
L2e
a Isolated yield based on 2-alkynylaniline 2. b, c, d, e The reaction was performed at 90 °C, 100 °C, 105 °C, and 110 °C.
(100 MHz, CDCl3): δ 158.4, 143.9, 142.7, 136.2, 135.6, 132.7, 1H), 3.54 (s, 3H), 2.22 (s, 3H). 13C NMR (100 MHz, CDCl3):
131.6, 130.8, 129.5, 129.1, 126.5, 125.6, 125.4, 124.3, 123.2, δ 143.9, 142.3, 138.8, 135.6, 134.1, 132.5, 130.6, 129.5, 129.1,
123.0, 120.6, 120.3, 119.8, 118.3, 116.2, 115.4, 114.3, 113.9, 128.6, 127.7, 126.5, 125.8, 125.5, 124.2, 123.0, 120.6, 120.2,
55.3, 36.3. HRMS (ESI) calcd for C30H24NO+: 414.1852 (M + 119.7, 118.3, 116.0, 115.4, 36.3, 21.0. HRMS (ESI) calcd for
H+), found: 414.1870.
C30H24N+: 398.1903 (M + H+), found: 398.1904.
11-(4-Chlorophenyl)-5-methyl-6-phenyl-5H-indeno[1,2-c]-
quinoline (3c)
2-Chloro-5-methyl-6,11-diphenyl-5H-indeno[1,2-c]quinoline (3e)
1H NMR (400 MHz, CDCl3): δ 7.99–7.98 (m, 1H), 7.65–7.53 (m,
1H NMR (400 MHz, CDCl3): δ 8.06–8.03 (m, 1H), 7.67–7.66 (m, 7H), 7.47–7.45 (m, 4H), 7.38–7.36 (m, 1H), 7.30–7.21 (m, 2H),
3H), 7.56–7.50 (m, 7H), 7.46–7.40 (m, 2H), 7.26–7.22 (m, 1H), 6.91 (t, J = 7.6 Hz, 1H), 6.32 (d, J = 8.0 Hz, 1H), 3.52 (s, 3H). 13
C
7.19–7.15 (m, 1H), 6.90 (d, J = 7.1 Hz, 1H), 6.32 (d, J = 8.0 Hz, NMR (100 MHz, CDCl3): δ 143.9, 142.3, 137.8, 135.2, 134.7,
1H), 3.62 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.3, 142.2, 131.5, 130.3, 129.7, 129.6, 129.0, 128.9, 128.5, 127.0, 126.4,
137.3, 136.1, 135.5, 132.3, 132.1, 130.6, 129.7, 129.6, 129.1, 124.8, 124.6, 124.3, 124.2, 121.3, 120.9, 120.7, 118.6, 116.8,
126.8, 125.8, 125.6, 124.5, 123.2, 122.9, 120.7, 120.5, 118.5, 116.4, 36.4. HRMS (ESI) calcd for C29H21ClN+: 418.1357
118.0, 116.3, 115.7, 36.4. HRMS (ESI) calcd for C29H21ClN+: (M + H+), found: 418.1351.
418.1357 (M + H+), found: 418.1361.
2-Fluoro-5-methyl-6,11-diphenyl-5H-indeno[1,2-c]quinoline (3f)
1H NMR (400 MHz, CDCl3): δ 7.71–7.64 (m, 4H), 7.59–7.44 (m,
2,5-Dimethyl-6,11-diphenyl-5H-indeno[1,2-c]quinoline (3d)
1H NMR (400 MHz, CDCl3): δ 7.86 (s, 1H), 7.63–7.38 (m, 12H), 9H), 7.26–7.22 (m, 1H), 7.12–7.07 (m, 1H), 6.93–6.89 (m, 1H),
7.24–7.19 (m, 2H), 6.87 (t, J = 7.6 Hz, 1H), 6.32 (d, J = 8.0 Hz, 6.33 (d, J = 8.0 Hz, 1H), 3.91 (s, 3H), 3.56 (s, 3H). 13C NMR
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6.42 (d, J = 7.9 Hz, 1H), 3.56 (s, 3H), 2.55 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 144.4, 142.4, 139.5, 138.8, 136.2, 132.6,
130.7, 130.2, 129.2, 128.9, 128.8, 126.5, 125.7, 125.5, 124.3,
123.1, 123.0, 120.7, 120.3, 119.9, 118.3, 116.3, 115.5, 36.3, 21.6.
HRMS (ESI) calcd for C30H24N+: 398.1903 (M + H+), found:
398.1884.
5-Methyl-11-phenyl-6-(o-tolyl)-5H-indeno[1,2-c]quinoline (3j)
1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.1 Hz, 1H), 7.63–7.36
(m, 12H), 7.23 (t, J = 7.2 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.90
(t, J = 7.5 Hz, 1H), 6.27 (d, J = 7.9 Hz, 1H), 3.58 (s, 3H), 2.15 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 143.5, 142.5, 138.7, 136.8,
136.1, 135.0, 130.9, 130.7, 129.9, 129.2, 129.0, 128.8, 127.1,
126.5, 125.8, 125.3, 124.3, 123.2, 123.0, 120.5, 120.2, 120.1,
118.3, 115.9, 115.5, 35.4, 19.3. HRMS (ESI) calcd for C30H24N+:
398.1903 (M + H+), found: 398.1904.
6-(4-Chlorophenyl)-5-methyl-11-phenyl-5H-indeno[1,2-c]-
quinoline (3k)
1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 8.1 Hz, 1H), 7.65–7.39
(m, 12H), 7.28–7.23 (m, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.95 (t, J =
7.6 Hz, 1H), 6.42 (d, J = 7.8 Hz, 1H), 3.58 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 142.7, 142.6, 138.5, 136.1, 135.8, 134.0,
130.7, 130.6, 130.0, 128.8, 126.7, 125.8, 125.4, 124.6, 123.2,
123.0, 120.6, 120.5, 118.5, 116.5, 115.5, 36.4. HRMS (ESI) calcd
for C29H21ClN+: 418.1357 (M + H+), found: 418.1345.
Scheme 2 Plausible reaction pathway.
(100 MHz, CDCl3): δ 158.4 (d, JCF = 241.1 Hz), 144.0, 142.2,
137.9, 135.3, 132.7, 130.5, 129.7, 129.6, 129.1, 128.9, 127.0,
3
124.6, 124.5, 121.0, 120.7 (d, JCF = 6.5 Hz), 118.6, 117.1 (d,
2
2
3JCF = 8.7 Hz), 115.5, 114.0 (d, JCF = 24.0 Hz), 110.8 (d, JCF
=
6-(4-Fluorophenyl)-5-methyl-11-phenyl-5H-indeno[1,2-c]-
quinoline (3l)
23.6 Hz), 36.6. HRMS (ESI) calcd for C29H21FN+: 402.1653
(M + H+), found: 402.1656.
1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.1 Hz, 1H), 7.60–7.20
(m, 13H), 7.11 (t, J = 7.4 Hz, 1H), 6.93 (t, J = 7.6 Hz, 1H), 6.35
(d, J = 7.9 Hz, 1H), 3.52 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
163.3 (d, JCF = 248.8 Hz), 142.9, 142.6, 138.5, 136.1, 131.5,
131.2, 131.1, 130.6, 129.0, 128.8, 126.7, 125.7, 125.4, 124.5,
123.1, 123.0, 120.5 (d, 3JCF = 7.7 Hz), 120.4, 118.5, 116.8 (d, 2JCF
= 21.6 Hz), 116.7, 115.5, 36.2. HRMS (ESI) calcd for C29H21FN+:
402.1653 (M + H+), found: 402.1648.
6-(4-Methoxyphenyl)-5-methyl-11-phenyl-5H-indeno[1,2-c]-
quinoline (3g)
1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 8.0 Hz, 1H), 7.61–7.59
(m, 2H), 7.55–7.51 (m, 2H), 7.48–7.35 (m, 6H), 7.26–7.22
(m, 1H), 7.12–7.08 (m, 3H), 6.93 (t, J = 7.8 Hz, 1H), 6.47 (d, J =
7.4 Hz, 1H), 3.93 (s, 3H), 3.54 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 160.4, 144.1, 142.4, 138.8, 136.2, 130.6, 130.4, 129.2,
128.8, 127.6, 126.5, 125.6, 125.4, 124.3, 123.0, 122.9, 120.7,
120.4, 119.9, 118.3, 116.6, 115.6, 114.9, 55.4, 36.2. HRMS (ESI)
calcd for C30H24NO+: 414.1852 (M + H+), found: 414.1850.
6-Butyl-5-methyl-11-phenyl-5H-indeno[1,2-c]quinoline (3m)
1H NMR (400 MHz, CDCl3): δ 8.03–8.95 (m, 2H), 7.59–7.51 (m,
5H), 7.44–7.28 (m, 5H), 7.04 (t, J = 7.2 Hz, 1H), 3.78 (s, 3H),
3.38 (m, 2H), 1.92–1.84 (m, 2H), 1.72–1.63 (m, 2H), 1.07 (t, J =
7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 146.5, 142.4, 138.9,
136.3, 130.8, 128.8, 128.3, 126.5, 126.4, 125.7, 125.4, 123.9,
122.9, 122.7, 120.9, 120.7, 119.1, 118.8, 115.3, 115.0, 34.4, 30.5,
30.2, 23.1, 13.9. HRMS (ESI) calcd for C27H26N+: 364.2060
(M + H+), found: 364.2038.
6-(4-(tert-Butyl)phenyl)-5-methyl-11-phenyl-5H-indeno[1,2-c]-
quinoline (3h)
1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.1 Hz, 1H), 7.62 (d,
J = 8.2 Hz, 4H), 7.55–7.49 (m, 3H), 7.45–7.39 (m, 5H), 7.25–7.21
(m, 1H), 7.11 (t, J = 7.8 Hz, 1H), 6.88 (t, J = 7.8 Hz, 1H), 6.33 (t,
J = 7.9 Hz, 1H), 3.58 (s, 3H), 1.47 (s, 9H). 13C NMR (100 MHz,
CDCl3): δ 152.8, 144.4, 142.4, 138.8, 136.2, 132.5, 130.7, 129.2,
128.7, 128.7, 126.5, 126.4, 125.7, 125.4, 124.2, 123.1, 123.0,
120.7, 120.3, 119.9, 118.2, 116.4, 115.5, 36.4, 35.0, 31.4. HRMS
(ESI) calcd for C33H30N+: 440.2373 (M + H+), found: 440.2370.
5-Methyl-11-phenyl-6-(thiophen-3-yl)-5H-indeno[1,2-c]-
quinoline (3n)
1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 8.1 Hz, 1H), 7.68–7.66
(m, 1H), 7.61–7.59 (m, 2H), 7.55–7.37 (m, 7H), 7.28–7.24
(m, 1H), 7.21–7.20 (m, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.98 (t, J =
7.5 Hz, 1H), 6.49 (d, J = 7.9 Hz, 1H), 3.61 (s, 3H). 13C NMR
5-Methyl-11-phenyl-6-(p-tolyl)-5H-indeno[1,2-c]quinoline (3i)
1H NMR (400 MHz, CDCl3): δ 8.07–8.05 (m, 1H), 7.62–7.36 (m, (100 MHz, CDCl3): δ 142.5, 139.2, 138.6, 136.2, 135.3, 130.6,
12H), 7.26–7.19 (m, 1H), 7.12–7.09 (m, 1H), 6.93–6.89 (m, 1H), 129.0, 128.8, 128.0, 127.8, 126.6, 126.0, 125.7, 125.2, 124.5,
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123.1, 123.0, 120.6, 120.4, 120.3, 118.4, 117.2, 115.5, 36.2.
HRMS (ESI) calcd for C27H20NS+: 390.1311 (M + H+), found:
390.1335.
40, 339; (c) M. D. Burke and S. L. Schreiber, Angew. Chem.,
Int. Ed., 2004, 43, 46; (d) S. L. Schreiber, Nature, 2009, 457,
153; (e) D. S. Tan, Nat. Chem. Biol., 2005, 1, 74;
(f) D. P. Walsh and Y.-T. Chang, Chem. Rev., 2006, 106, 2476;
(g) C. Cordier, D. Morton, S. Murrison, A. Nelson and
C. O’Leary-Steele, Nat. Prod. Rep., 2008, 25, 719.
5,9-Dimethyl-6,11-diphenyl-5H-indeno[1,2-c]quinoline (3o)
1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.1 Hz, 1H), 7.63–7.35
(m, 12H), 7.23 (s, 1H), 7.09 (t, J = 7.9 Hz, 1H), 6.73 (d, J =
8.0 Hz, 1H), 6.21 (d, J = 8.0 Hz, 1H), 3.56 (s, 3H), 2.36 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 143.3, 142.9, 138.9, 136.1, 135.7,
134.2, 130.7, 129.5, 129.2, 128.8, 126.8, 126.5, 126.4, 125.7,
123.0, 122.9, 121.9, 120.4, 119.9, 118.4, 116.3, 115.4, 36.3, 21.8.
HRMS (ESI) calcd for C30H24N+: 398.1903 (M + H+), found:
398.1884.
2 For selected examples for the synthesis of heterocycles, see:
(a) G. Zeni and R. C. Larock, Chem. Rev., 2006, 106, 4644;
(b) M. Alvarez-Corral, M. Munoz-Dorado and I. Rodrıguez-
Garcıa, Chem. Rev., 2008, 108, 3174; (c) H. Cao, L. McNamee
and H. Alper, Org. Lett., 2008, 10, 5281; (d) A. Minatti and
K. Muniz, Chem. Soc. Rev., 2007, 36, 1142;
(e) M. A. P. Martins, C. P. Frizzo, D. N. Moreira, L. Buriol
and P. Machado, Chem. Rev., 2009, 109, 4140;
(f) A. Armstrong and J. C. Collins, Angew. Chem., Int. Ed.,
2010, 49, 2282; (g) A. R. Katritzky and S. Rachwal, Chem.
Rev., 2010, 110, 1564; (h) Z.-Y. Tang and Q.-S. Hu, Adv. Synth.
Catal., 2006, 348, 846; (i) N. Halland, M. Nazaré, O. Rkyek,
J. Alonso, M. Urmann and A. Lindenschmidt, Angew. Chem.,
Int. Ed., 2009, 48, 6879; ( j) Z.-Y. Tang and Q.-S. Hu, Adv.
Synth. Catal., 2006, 348, 846; (k) H. Siebeneicher,
I. Bytschkov and S. Doye, Angew. Chem., Int. Ed., 2003, 42,
3042.
8-Chloro-5-methyl-6,11-diphenyl-5H-indeno[1,2-c]quinoline (3p)
1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.1 Hz, 1H), 7.65–7.49
(m, 8H), 7.44–7.39 (m, 5H), 7.13 (t, J = 7.7 Hz, 1H), 6.82 (d, J =
8.4 Hz, 1H), 6.18 (d, J = 8.5 Hz, 1H), 3.57 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 144.6, 143.5, 138.0, 136.0, 135.1, 130.6,
130.3, 129.8, 129.6, 128.9, 127.2, 126.9, 126.8, 126.7, 125.8,
123.4, 122.9, 121.5, 120.3, 119.1, 117.8, 115.7, 115.6, 36.4.
HRMS (ESI) calcd for C29H21ClN+: 418.1357 (M + H+), found:
418.1331.
3 For reviews, see: (a) J. Panteleev, L. Zhang and M. Lautens,
Angew. Chem., Int. Ed., 2011, 50, 9089; (b) L. F. Tietze,
M. A. Düfert, T. Hungerland, K. Oum and T. Lenzer, Chem. –
Eur. J., 2011, 17, 8452; (c) S. H. Kim, S. H. Park, J. H. Choi
9-Fluoro-5-methyl-6,11-diphenyl-5H-indeno[1,2-c]quinoline (3q)
1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.0 Hz, 1H), 7.66–7.39
(m, 12H), 7.15–7.06 (m, 2H), 6.62–6.57 (m, 1H), 6.23–6.19 (m,
and S. Chang, Chem.
–
Asian J., 2011, 6, 2618;
1H), 3.58 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 161.4 (d, JCF
=
(d) J. Montgomery, Angew. Chem., Int. Ed., 2004, 43, 3890;
(e) D. Enders, C. Grondal and M. R. M. Hüttl, Angew. Chem.,
Int. Ed., 2007, 46, 1570; (f) K. C. Nicolaou, D. J. Edmonds
and P. G. Bulger, Angew. Chem., Int. Ed., 2006, 45, 7134;
(g) L. F. Tietze, G. Brasche and K. Gericke, Domino Reactions
in Organic Synthesis, Wiley-VCH, Weinheim, Germany, 2006;
(h) L. F. Tietze, A. Düfert, F. Lotz, L. Sölter, K. Oum,
T. Lenzer, T. Beck and R. Herbst-Irmer, J. Am. Chem. Soc.,
2009, 131, 17879; (i) E. Negishi, C. Coperet, S. Ma, S. Liou
and Y. F. Liu, Chem. Rev., 1996, 96, 365.
4 (a) Y. Luo, X. Pan and J. Wu, Org. Lett., 2011, 13, 1150;
(b) X. Pan, Y. Luo and J. Wu, Chem. Commun., 2011, 47,
8967; (c) Y. Luo, X. Pan and J. Wu, Adv. Synth. Catal., 2012,
354, 3071; (d) Y. Luo and J. Wu, Org. Lett., 2012, 14, 1592;
(e) Y. Luo and J. Wu, Chem. Commun., 2011, 47, 11137;
(f) Y. Luo, L. Hong and J. Wu, Chem. Commun., 2011, 47,
5298.
239.5 Hz), 143.9, 143.8, 138.5, 136.0, 135.3, 130.5, 129.7, 129.6,
129.0, 128.9, 127.1, 126.9, 126.8, 125.8, 125.2, 123.2, 122.6,
121.6 (d, 3JCF = 9.4 Hz), 119.5, 115.7, 115.6, 108.1 (d, 2JCF = 24.0
2
Hz), 103.7 (d, JCF = 22.7 Hz), 36.4. HRMS (ESI) calcd for
C29H21FN+: 402.1653 (M + H+), found: 402.1663.
8-Chloro-6-(4-methoxyphenyl)-5-methyl-11-phenyl-5H-indeno-
[1,2-c]quinoline (3r)
1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.0 Hz, 1H), 7.58–7.51
(m, 5H), 7.45–7.33 (m, 6H), 7.19–7.10 (m, 4H), 6.38 (s, 1H),
3.97 (s, 3H), 3.60 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.7,
145.1, 140.5, 138.3, 136.2, 130.6, 130.3, 130.2, 128.8, 127.1,
126.8, 126.7, 125.9, 125.6, 124.3, 123.4, 123.1, 120.5, 119.3,
119.1, 115.8, 115.1, 55.6, 36.4. HRMS (ESI) calcd for
C30H23ClNO+: 448.1463 (M + H+), found: 448.1461.
5 See in ESI†: T. Ishida, S. Kikuchi, T. Tsubo and T. Yamada,
Org. Lett., 2013, 15, 848.
Acknowledgements
6 (a) B.-C. Hong, Z.-Y. Chen and W.-H. Chen, Org. Lett., 2000,
2, 2647; (b) J. J. Eisch, H. Gopal and C. T. Kuo, J. Org. Chem.,
1978, 43, 2190; (c) V. N. Gogte, A. G. Namjoshi and
B. D. Tilak, Tetrahedron Lett., 1971, 45, 4305.
Financial support from the National Natural Science Foun-
dation of China (no. 21202022).
7 (a) B. Yao, Q. Wang and J. Zhu, Angew. Chem., Int. Ed., 2013,
52, 12992; (b) B. Yao, Q. Wang and J. Zhu, Angew. Chem., Int.
Ed., 2012, 51, 5170; (c) B. Yao, Q. Wang and J. Zhu, Angew.
Chem., Int. Ed., 2012, 51, 12311.
Notes and references
1 (a) S. L. Schreiber, Science, 2000, 287, 1964; (b) P. Arya,
D. T. H. Chou and M.-G. Baek, Angew. Chem., Int. Ed., 2001,
This journal is © The Royal Society of Chemistry 2014
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