General synthesis of pyrido[1,2-a]indoles via Pd-catalyzed cyclization of o-picolylbromoarenes

Article abstract of DOI:10.1016/j.jorganchem.2018.03.003

An efficient Pd-catalyzed cyclization of o-picolylbromoarenes into pyridoindoles has been developed. This novel transformation, which proceeds through a not common for Pd catalysis L-to X-type pyridine ligand swap, provides an efficient route to aryl-, as well as to cyanopyrido[1,2-a]indoles, not easily accessible by existing cyclization methods.

Full text of DOI:10.1016/j.jorganchem.2018.03.003

Journal of Organometallic Chemistry xxx (2018) 1e5
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
General synthesis of pyrido[1,2-a]indoles via Pd-catalyzed cyclization
of o-picolylbromoarenes
Padon Chuentragool, Zhou Li, Katrina Randle, Faraj Mahchi, Ishmael Ochir, Shadi Assaf,
Vladimir Gevorgyan*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient Pd-catalyzed cyclization of o-picolylbromoarenes into pyridoindoles has been developed.
This novel transformation, which proceeds through a not common for Pd catalysis L-to X-type pyridine
ligand swap, provides an efficient route to aryl-, as well as to cyanopyrido[1,2-a]indoles, not easily
accessible by existing cyclization methods.
Received 27 October 2017
Received in revised form
28 February 2018
Accepted 1 March 2018
Available online xxx
© 2018 Published by Elsevier B.V.
Dedicated to Prof. Beletskaya on the occa-
sion of her 85th birthday
Keywords:
pyrido[1,2-a]indole
Palladium-catalyzed
CeN coupling
Cyanopyridoindole
Picolyl L-X-type ligand
1. Introduction
to access the same core (Scheme 1D) [7]. Although appealing, this
method operates under harsh acidic conditions and is also limited
Pyrido[1,2-a]indole scaffold is an important heterocyclic motif
broadly found in organic materials [1] and biologically active
molecules [2] (Chart 1). Although, numerous methods toward as-
sembly of this essential core have been developed, synthesis of fully
aromatic pyrido[1,2-a]indoles still remains a challenging task [3,4].
One of the methods toward this skeleton relies on annulation of
pyridine derivatives with benzynes [4] or alkynes [5] (Scheme
1A,B). While the reaction with benzynes leads to formation of
pyridoindoles in moderate yields, employment of alkynes generally
results in pyrrolo[2,1-a]isoquinolines or tetrasubstituted pyr-
idoindoles. A presence of an activating group at C-3 position (R) is a
requisite for the success of the latter transformation. Klumpp and
co-workers [6a] developed an elegant synthesis of the pyridoindole
moiety using an acid-mediated aza-Nazarov type cyclization.
However, this transformation is limited to substrates possessing
hydroxyl- and aryl substituents at C-3 position (Scheme 1C) [6].
Later, Sekar reported Iron catalyzed CeH functionalization process
to substrates possessing aryl substituents at the C-3 position.
Herein, we report a novel efficient and general Pd-catalyzed cycli-
zation of o-picolyl haloarenes into pyrido[1,2-a]indoles (Scheme
1E). Notably, this transformation, which proceeds under basic
conditions, offers a practical synthetic route to fully aromatic pyr-
ido[1,2-a]indoles possessing aryl, or cyano groups at the C-3 posi-
tion [8]. Notably, picolyl group in this transformation serves as both
L- and X-type ligand, which is not common for Pd-catalyzed
intramolecular CeN coupling reactions [9e11].
2. Results & discussion
As a part of our on-going research program toward development
of general and efficient methods for synthesis of diverse fused
heterocyclic scaffolds [12], we turned our attention to synthesis of
pyrido[1,2-a]indoles. We thought that upon exposure to Pd(0)/L/
Base system,1 would be converted into a Pd(II) species 3, where the
picolyl group serves as an L-type ligand. Here, we hypothesized that
a subsequent deprotonation/etautomerization would convert the
latter into an X- type ligand (3 / 4) [9e11], thus setting up a stage
* Corresponding author.
E-mail address: vlad@uic.edu (V. Gevorgyan).
https://doi.org/10.1016/j.jorganchem.2018.03.003
0022-328X/© 2018 Published by Elsevier B.V.
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P. Chuentragool et al. / Journal of Organometallic Chemistry xxx (2018) 1e5
Chart 1. Selected examples of important molecules containing pyrido[1,2-a]indole
fragment.
for a reductive elimination into the targeted product 2 (Scheme 1E)
[13]. In order to test this hypothesis, o-picolyl bromobenzene 1a
was first subjected to the Pd(PPh3)4 complex and a base, which
resulted in the formation of pyrido[1,2-a]indole product 2a in good
yield. (Table 1, entry 1). The combination of palladium(II) catalysts
and triphenylphosphine ligand resulted in lower yields (entries 2,
3). DPEphos was found to be the best ligand, providing nearly
quantitative yield of 2a, while dppf was less efficient (entries 4, 5).
Further screening indicated potassium phosphate and toluene as
the optimal combination of a base and a solvent (entries 6e10). In
addition, two transition metal-catalyzed conditions, that were
employed for synthesis of pyridoindole by Sekar [7] and pyr-
idobenzimidazoles by Maes [14] were inefficient (entries 11, 12).
The control experiment indicated that palladium catalyst is crucial
for this transformation (entry 13).
With the optimized conditions in hand, the generality of this
method was examined (Table 2). Tolyl-substituted derivative
reacted well producing the cyclized product 2b in good yield.
Picolylarenes 1c,d, possessing electron-withdrawing substituents,
such as chloride and fluoride at the benzene ring, were competent
substrates producing the fused indole products in high yields.
Presence of an electron-releasing methoxy substituent (1e) did not
hamper the reaction, as well. Likewise, substituents at the pyridine
ring did not affect the reaction outcome. Thus, fluorine-containing
heteroarene, which was previously shown to react inefficiently [7],
produced the tricyclic product 2f in good yield. Cyclization of the
methyl-substituted substrate 1g proceeded uneventfully to pro-
duce the corresponding pyridoindole in 96% yield. Notably, not only
aryl-substituted reactants, but also a substrate possessing the
nitrile group at the benzylic position (1h) was a capable reactant for
this cyclization reaction, producing 2h in excellent yield. Impor-
tantly, this substitution motif at pyrido[1,2-a]indoles is not easily
accessible via existing synthetic methods (vide supra). Moreover,
o-picolyl bromonaphthalene (1i), reacted efficiently producing
tetracyclic benzopyrido[1,2-a]indole 2i in nearly quantitative yield.
Notably, selective cyclization of unsymmetrical substrates 1e, i
highlights the superiority of this method vs reported protocols
leading to the mixtures of the regioisomers (Scheme 1D [7]).
Scheme 1. Synthesis of pyrido[1,2-a]indole.
3. Conclusions
In summary, we have developed a practical synthesis of phenyl-
and cyanopyrido[1,2-a]indoles via the Pd-catalyzed cyclization re-
action of o-picolylbromoarenes. This reaction is quite general with
respect to the substitution pattern at both, benzene and pyridine
rings. In contrast to the existing transition metal-catalyzed cycli-
zation methods toward this core, which operate under strong acidic
conditions, this complementary method proceeds under basic
conditions. The reaction underwent efficient cyclization providing
this tricyclic scaffold in excellent yields. It is believed that this
approach may be extended to other heterocyclic cores, and, thus,
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P. Chuentragool et al. / Journal of Organometallic Chemistry xxx (2018) 1e5
3
Table 1
(anhydrous sodium sulfate), filtered (celite plug), and concentrated
under a reduced pressure. A silica gel column chromatography
(20:1 Hexanes/EtOAc) afforded the product 1a-g,i.
Screening of reaction conditions.
1a, 33% yield over 2 steps: 1H NMR (400 MHz, CDCl3)
d ppm 8.62
(d, J ¼ 3.80 Hz, 1 H), 7.68e7.50 (m, 2 H), 7.37e7.28 (m, 2 H),
7.28e7.19 (m, 3 H), 7.19e7.06 (m, 4 H), 7.06e6.92 (m, 2 H), 6.09 (s,
1 H). 13C NMR (100 MHz, CDCl3)
d
ppm 161.99,149.71,142.12,141.59,
136.43, 133.08, 131.31, 129.58, 128.50, 128.20, 127.27, 126.70, 125.58,
124.08, 121.50, 58.37. 13C-DEPT 135 NMR (100 MHz, CDCl3)
ppm
d
Entry
Catalyst,
Ligand
Base/Acid
Solvent
Yield(%)a
149.71, 136.43, 133.08, 131.31, 129.58, 128.50, 128.20, 127.28, 126.70,
124.08, 121.50, 58.37.
1b, 46% yield over 2 steps: 7: 1, ortho: para; 1H NMR (400 MHz,
1
2
Pd(PPh3)4
Pd(OAc)2,
PPh3
PdCl2(PPh3)2,
PPh3
K3PO4
K3PO4
CH3Ph
CH3Ph
72
45
CDCl3):
d
ppm 8.62 (d, J ¼ 4.38 Hz,1H), 7.63e7.56 (m, 2H), 7.28e7.00
(m, 9H), 6.07 (s, 1H), 2.34 (s, 3H). 13C NMR (101 MHz, CDCl3):
d
ppm
3
K3PO4
K3PO4
K3PO4
Cs3CO3
DIPEA
K3PO4
K3PO4
K3PO4
CH3Ph
CH3Ph
CH3Ph
CH3Ph
CH3Ph
DMF
31
68
96
22
41
19
51
21
21.11, 58.07, 121.42, 124.03, 125.59, 127.27, 128.14, 129.25, 129.47,
131.30, 133.07, 136.25, 136.39, 138.60, 142.33, 149.69, 162.28.
4
Pd(OAc)2,
dppf
1c, 53% yield over 2 steps: 1H NMR (400 MHz, CDCl3):
d
ppm
8.66e8.57 (m, 1H), 7.66e7.57 (m, 1H), 7.35e6.98 (m, 10H), 6.05(s,
1H). 13C NMR (101 MHz, CDCl3):
ppm 57.77, 121.67, 124.12, 125.70,
5
Pd(OAc)2,
DPEphos
Pd(OAc)2,
DPEphos
Pd(OAc)2,
DPEphos
Pd(OAc)2,
DPEphos
Pd(OAc)2,
DPEphos
Pd(OAc)2,
DPEphos
FeCl2, FeCl3
Cu(OAc)2
No [Pd],
d
6
126.92, 127.52, 128.62, 129.47, 132.11, 132.56, 133.12, 136.56, 140.88,
149.75, 161.46.
7
1d, 32% yield over 2 steps: 1H NMR (400 MHz, CDCl3):
d ppm
8
8.64 (d, J ¼ 4.03 Hz, 1H), 7.60 (t, J ¼ 7.70 Hz, 1H), 7.38e7.29 (m, 3H),
7.29e7.22 (m, 1H), 7.20e7.11 (m, 3H), 7.11e7.04 (m, 2H), 6.99e6.92
9
MeCN
dioxane
(m, 1H), 6.09(s, 1H). 13C NMR (101 MHz, CDCl3):
d ppm 57.65, 114.35,
10
120.08, 121.67, 124.13, 125.32, 126.91, 128.66, 129.52, 132.22, 136.58,
138.26, 141.58, 149.78, 160.09, 161.76, 162.07. 19F NMR (376 MHz,
11
12
13
PivOH
3,4,5-TFBA
K3PO4
xylene
DMSO
CH3Ph
0b
0c
0b
CDCl3):
d
ppm ꢀ114.6.
1e, 47% yield over 2 steps: 1H NMR (400 MHz, CDCl3):
d
ppm
DPEphos
8.60 (d, J ¼ 4.97 Hz, 1H), 7.60 (t, J ¼ 7.60 Hz, 1H), 7.32e7.09 (m, 7H),
6.74e6.79 (m, 3H), 5.68(s, 1H), 3.74 (s, 3H). 13C NMR (101 MHz,
a
GC yields.
No reaction.
Decomposition.
b
c
CDCl3):
126.57, 128.43, 129.37, 136.44, 142.55, 144.31, 149.54, 159.65, 160.64.
1f, 42% yield over 2 steps: 1H NMR (400 MHz, CDCl3):
ppm
d ppm 55.13, 59.37, 111.67, 115.50, 121.45, 121.89, 123.75,
d
7.73e7.66 (m, 1H), 7.60 (d, J ¼ 7.89 Hz, 1H), 7.37e7.22 (m, 4H),
will find broad applications for synthesis of important polycyclic
molecules.
7.19e7.07 (m, 4H), 6.91e6.97 (m, 1H), 6.83e6.77 (m, 1H), 6.06 (s,
1H). 13C NMR (101 MHz, CDCl3):
d
ppm 57.71, 107.30, 121.42, 125.54,
126.96, 127.42, 128.47, 128.62, 129.56, 131.32, 133.15, 141.00, 141.38,
160.64, 162.00, 164.39. 19F NMR (376 MHz, CDCl3):
ppm ꢀ66.7.
1g, 39% yield over 2 steps: 1H NMR (400 MHz, CDCl3):
ppm
4. Experimental section
d
d
4.1. Synthesis and characterization of starting materials
8.52 (d, J ¼ 5.13 Hz, 1H), 7.61 (d, J ¼ 8.07 Hz, 1H), 7.36e7.30 (m, 2H),
7.27e7.19 (m, 4H), 7.18e7.14 (m, 1H), 7.11e7.06 (m, 1H), 7.00e6.93
4.1.1. 2-((2-bromophenyl)(phenyl)methyl)pyridine (1a-1f)
(m, 2H), 6.17 (s, 1H), 2.26 (s, 3H). 13C NMR (101 MHz, CDCl3):
d ppm
To an argon-charged flask, 0.34 mL of 2-bromopyridine
(3.6 mmol) and 10 mL of THF were added under a positive pres-
sure of argon, and cooled at ꢀ78 ꢁC for 5 min 1.4 mL of n-BuLi so-
lution in hexane (2.5 M, 3.5 mmol) was added. The metal-halogen
exchange step completed in 30 min according to TLC. 3.6 mL of
corresponding 2-bromobenzaldehyde was added to 2-pyridyl
lithium solution at ꢀ78 ꢁC. Reaction was kept at this temperature
for 2 h, then stirred at an ambient temperature for another 6 h.
Afterwards, the reaction was quenched by adding 50 mL of satu-
rated aqueous ammonium chloride solution, then extracted by
30 mL of ethyl acetate. The combined organic extract was dried
(anhydrous sodium sulfate), filtered (celite plug), and concentrated
under a reduced pressure. The crude alcohol was submitted to next
step without purification.
To the crude alcohol, 4 mL benzene (44 mmol) was added under
an argon atmosphere, and stirred until the alcohol was completely
dissolved. This benzene solution was cooled at 0 ꢁC for 5 min, and
2 mL of trifluoromethanesulfonic acid was added. The flask was
removed from ice bath, and reaction mixture was stirred at room
temperature for 12 h. The reaction mixture was added to 20 mL of
cooled saturated sodium bicarbonate solution, and extracted by
20 mL of ethyl acetate. The combined organic extract was dried
21.22, 58.36, 122.69, 125.08, 125.69, 126.77, 127.39, 128.29, 128.58,
129.70, 131.54, 133.11, 141.86, 142.35, 147.63, 149.50, 161.79.
1i, 31% yield over 2 steps: 1H NMR (400 MHz, CDCl3):
d ppm 8.63
(d, J ¼ 4.97 Hz, 1H), 8.35 (d, J ¼ 8.48 Hz, 1H), 7.79 (d, J ¼ 7.89 Hz, 1H),
7.72 (d, J ¼ 8.77 Hz, 1H), 7.65e7.55 (m, 2H), 7.53e7.47 (m, 1H),
7.34e7.22 (m, 4H), 7.19e7.10 (m, 4H), 6.49 (s, 1H). 13C NMR
(101 MHz, CDCl3):
d ppm 59.02, 121.54, 124.24, 125.40, 126.41,
126.70, 127.39, 127.77, 128.06, 128.25, 128.52, 129.57, 132.65, 133.48,
136.47, 149.73, 162.09.
4.1.2. Synthesis of 2-(2-bromophenyl)-2-(pyridin-2-yl)acetonitrile
(1h)
A 100 mL round bottom flask was evacuated and back-filled by
argon 3 times, and charged with 0.84 mL of o-bromophenylaceto-
nitrile (6.5 mmol) and 25 mL of toluene under a positive pressure of
argon. After being cooled in an ice bath for 5 min, 7.5 mL of a so-
lution of NaHMDS in THF (1 M, 7.5 mmol) was added to this toluene
solution, and the ice bath was removed. After 30 min, 0.47 mL of 2-
chloropyridine (5.0 mmol) was added, and the mixture was heated
in a 70 ꢁC oil bath for 6 h. The progress of reaction was monitored by
TLC. Upon completion, reaction was quenched by adding 50 mL of
saturated aqueous ammonium chloride solution reaction, then
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P. Chuentragool et al. / Journal of Organometallic Chemistry xxx (2018) 1e5
Table 2
Pd-catalyzed synthesis of pyrido[1,2-a]indoles.a
extracted by 30 mL of ethyl acetate for three times. The combined
organic extract was dried (anhydrous sodium sulfate), filtered
(celite plug), and concentrated under a reduced pressure. A silica
gel column chromatography purification (9:1 Hexanes/EtOAc)
afforded 0.84 g of 1h in 64% yield.
conical vial was closed by a cap equipped with a pressure release
valve, removed from glovebox, and placed in a metal bath over a
stirring plate preheated to designated temperature. The progress of
reaction was monitored by TLC and GC-MS. Upon complete, the
reaction mixture was cooled down and filtered (celite plug), under
a pressure of argon, and rinsed by 10 mL dicholormethane. The
filtrate was concentrated under a reduced pressure, and purified by
a neutralized (by trimethylamine) silica gel column (20:1 Hexanes/
EtOAc) packed under argon.
1h: 1H NMR (400 MHz, CDCl3)
d
ppm 8.63e8.62 (1H, m),
7.70e7.59 (m, 3H), 7.59e7.35 (m, 1H), 7.38e7.20 (m, 3H), 5.80 (s,
1H). 13C NMR (101 MHz, CDCl3)
ppm 153.95, 150.23, 137.38, 134.17,
133.40, 130.44, 130.26, 128.40, 123.70, 123.27, 122.51, 118.53, 44.74.
13C-DEPT 135 NMR (101 MHz, CDCl3)
ppm 150.23, 137.37, 133.39,
d
d
2b, 86% yield:: 7: 1, ortho: para; 1H NMR (500 MHz, CDCl3):
130.43, 130.24, 128.39, 123.26, 122.50, 44.72.
d
ppm 8.34 (d, J ¼ 7.34 Hz, 1H), 8.05 (d, J ¼ 8.44 Hz, 1H), 7.91 (d,
J ¼ 8.44 Hz, 1H), 7.72 (d, J ¼ 9.17 Hz, 1H), 7.62 (d, J ¼ 8.07 Hz, 2H),
7.44 (t, J ¼ 8.07 Hz, 1H), 7.39e7.32 (m, 4H), 6.94e6.89 (m, 1H), 6.51
4.2. General procedure for palladium-catalyzed synthesis of pyrido
[1,2-a]indole
(t, J ¼ 6.24 Hz, 1H), 2.47 (s, 3H). 13C NMR (126 MHz, CDCl3):
d ppm
21.28, 108.23, 110.24, 118.18, 119.38, 120.13, 122.60, 123.17, 124.33,
127.64,128.49,128.73,129.27,129.60,132.23,133.85,135.25. HRMS-
(þ)EI calcd. for C19H15N [M]þ: 257.12045, found: 257.12008.
0.3 mmol of the corresponding o-picolylbromobenzene was
added to a screw-thread vial, which was evacuated and back-filled
by argon three times on a double bank Schlenk manifold. To this
vial, 2.5 mL of dry toluene was added under a flow of argon. The vial
was closed by a cap, and swirled gently till all solid particles are
dissolved. This vial and an oven-dried Wheaton conical vial were
transferred into an argon filled glovebox. To this conical vial, a
stirring bar, 0.015 mmol of Pd(OAc)2, 0.03 mmol of a ligand, and
0.6 mmol of a designated base were added. The toluene solution of
substrate was added to this conical vial using a glass pipette. This
2c, 76% yield: 1H NMR (400 MHz, CDCl3):
d
ppm 8.24 (d, J ¼ 7.02 Hz,
1H), 7.94e7.90 (m, 2H), 7.71e7.63 (m, 3H), 7.52 (t, J ¼ 7.31 Hz, 2H),
7.40e7.30 (m, 2H), 6.95e6.90 (m, 1H), 6.54 (t, J ¼ 7.02 Hz, 1H). 13C NMR
(101 MHz, CDCl3): d ppm 106.20, 108.98, 110.30, 118.30, 120.30, 123.05,
123.96, 125.89, 129.01, 129.45, 133.72, 134.69. HRMS-(þ)EI calcd. for
C
18H12ClN [M-H]þ: 277.06582, found: 277.06622.
2d, 94% yield: 1H NMR (400 MHz, CDCl3):
d ppm 8.14 (d,
J ¼ 7.02 Hz, 1H), 7.97 (dd, J ¼ 8.77, 5.26 Hz, 1H), 7.69 (d, J ¼ 8.18 Hz,
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P. Chuentragool et al. / Journal of Organometallic Chemistry xxx (2018) 1e5
5
3H), 7.59e7.51 (m, 3H), 7.36 (t, J ¼ 7.31 Hz, 1H), 7.25e7.18 (m, 1H),
References
6.90e6.83 (m, 1H), 6.49 (t, J ¼ 6.43 Hz, 1H). 13C NMR (101 MHz,
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CDCl3):
d ppm 96.41, 106.05, 108.69, 112.31, 112.56, 118.39, 120.37,
122.36, 124.03, 125.89, 128.96, 133.57, 134.91, 157.52, 159.62. 19F
NMR (376 MHz, CDCl3):
ppm ꢀ121.3. HRMS-(þ)EI calcd. for
18H12FN [M-H]þ: 261.09537, found: 261.09551.
2f, 78% yield: 1H NMR (500 MHz, CDCl3):
d
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d
ppm 8.26 (dd, J ¼ 8.44,
3.67 Hz, 1H), 8.02 (d, J ¼ 8.44 Hz, 1H), 7.70 (d, J ¼ 6.97 Hz, 2H),
7.57e7.44 (m, 4H), 6.93e6.86 (m, 1H), 6.14 (t, J ¼ 6.97 Hz, 1H). 13C
NMR (126 MHz, CDCl3):
d ppm 87.92, 107.95, 113.13, 115.21, 117.89,
118.91, 120.99, 123.07, 123.71, 126.14, 128.30, 128.89, 133.69, 134.19,
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2743e2755;
152.35, 154.45. 19F NMR (376 MHz, CDCl3):
d
ppm ꢀ106.7. HRMS-(þ)
EI calcd. for C18H12FN [M ꢀ H]þ: 261.09537, found: 261.09552.
2g, 96% yield: 1H NMR (500 MHz, CDCl3):
d ppm 8.24 (d,
b) I.L. Nikonov, D.S. Kopchuk, I.S. Kovalev, G.V. Zyryanov, A.F. Khasanov,
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6427e6429;
J ¼ 7.34 Hz, 1H), 8.04 (d, J ¼ 8.07 Hz, 1H), 7.88 (d, J ¼ 8.44 Hz, 1H),
7.74 (d, J ¼ 8.07 Hz, 1H), 7.55 (t, J ¼ 7.70 Hz, 2H), 7.50e7.48 (m, 1H),
7.43 (t, J ¼ 6.97 Hz, 1H), 7.37e7.29 (m, 2H), .6.36 (d, J ¼ 7.34 Hz, 1H),
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Ed. 48 (2009) 1138e1143;
2.34 (s, 3H). 13C NMR (126 MHz, CDCl3):
d ppm 21.69, 104.48, 110.08,
b) S. Samala, P. Pallavi, R. Kumar, R.K. Arigela, G. Singh, R.S. Ampapathi,
A. Priya, S. Datta, A. Patra, B. Kundu, Chem. Eur J. 20 (2014) 14344
e24350;
c) H. Sun, C. Wang, Y.-F. Yang, P. Chen, Y.-D. Wu, X. Zhang, Y. Huang, J. Org.
Chem. 79 (2014) 11863e11872;
111.27, 115.52, 118.99, 119.66, 123.14, 123.76, 125.41, 128.04, 128.83,
129.27, 133.52, 133.79, 135.58. HRMS-(þ)EI calcd. for C19H15
N
[M ꢀ H]þ: 257.12045, found: 257.12062.
2h, 95% yield: 1H NMR (400 MHz, CDCl3)
d ppm 8.46 (d,
d) B. Zhou, J. Du, Y. Yang, Y. Li, Chem. Eur J. 20 (2014) 12768e12772.
[6] a) R.R. Naredla, C. Zheng, S.O. Nilsson Lill, D.A. Klumpp, J. Am. Chem. Soc. 133
(2011) 13169e13175;
J ¼ 7.09 Hz, 1H), 7.91 (d, J ¼ 8.62 Hz, 2H), 7.74 (dd, J ¼ 9.13, 1.02 Hz,
1H), 7.58e7.48 (m, 1H), 7.46e7.37 (m, 1H), 7.36e7.28 (m, 1H), 6.83
(td, J ¼ 6.83, 1.10 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d ppm 141.85,
b) I. Karthikeyan, D. Arunprasath, G. Sekar, G. Chem, Commun. Now. 51 (2015)
1701e1704.
129.37, 128.98, 127.25, 125.49, 125.18, 122.07, 119.66, 118.12, 116.75,
[7] I. Karthikeyan, G. Sekar, Eur. J. Org Chem. (2014) 8055e8063.
[8] For synthesis of alkylpyrido[1,2-a]indoles via pyrolysis at 800 oC, see O. Akio,
K. Takayuki, I. Hiroshi, Chem. Lett. vol. 10 (1981) 1737e1738. For synthesis of
pyrrolo[2,1-a]isoquinolines containing akyl- and cyano groups at C-3 position
see: ref 5a.
111.16, 110.83, 74.45. 13C NMR DEPT-135 (101 MHz, CDCl3)
127.25, 125.49, 125.18, 122.07, 119.66, 118.12, 111.16, 110.83.
d ppm
2i, 98% yield: 1H NMR (500 MHz, CDCl3)
d ppm 9.17 (d,
J ¼ 7.34 Hz, 1H), 8.66 (d, J ¼ 8.44 Hz, 1H), 8.08 (d, J ¼ 8.80 Hz, 2H),
7.91 (d, J ¼ 9.17 Hz, 1H), 7.81e7.70 (m, 4H), 7.60 (t, J ¼ 7.34 Hz, 2H),
7.54 (t, J ¼ 6.97 Hz, 1H), 7.43 (t, J ¼ 7.70 Hz, 1H), 7.04e6.97 (m, 1H),
[9] For this type of cyclizations under Iridium-catalysis, see Z.-P. Yang, Q.-F. Wu,
S.-L. You, Angew. Chem. Int. Ed. 53 (2014) 6986e6989.
[10] a) I.P. Beletskaya, A.N. Kashin, N.B. Karlstedt, A.V. Mitin, A.V. Cheprakov,
G.M. Kazankov, J. Organomet. Chem. 622 (2001) 89e96;
b) I.P. Beletskaya, Pure Appl. Chem. 77 (2005), 2021-2027.
[11] a) D. Chernyak, V. Gevorgyan, Org. Lett. 12 (2010) 5558e5560;
b) Z. Li, D. Chernyak, V. Gevorgyan, Org. Lett. 14 (2012) 6056e6059.
[12] a) I.V. Seregin, V. Gevorgyan, J. Am. Chem. Soc. 128 (2006) 12050e12051;
b) S. Chuprakov, V. Gevorgyan, Org. Lett. 9 (2007) 4463e4466;
c) S. Chuprakov, F.W. Hwang, V. Gevorgyan, Angew. Chem. Int. Ed. 46 (2007)
4757e4759;
6.79 (t, J ¼ 7.34 Hz, 1H). 13C NMR (126 MHz, CDCl3):
d ppm 108.92,
110.43, 118.39, 119.41, 119.71, 120.14, 121.99, 123.21, 123.80, 125.05,
125.80, 126.14, 126.29, 126.60, 128.58, 128.91, 129.77, 129.95, 130.72,
133.17, 134.91. HRMS-(þ)EI calcd. for C22H15N [M]þ: 293.12045,
found: 293. 11987.
d) I.V. Seregin, A.W. Schammel, V. Gevorgyan, Org. Lett.
9 (2007) 3433
e3436;
Acknowledgements
e) R.K. Shiroodi, V. Gevorgyan, Chem. Soc. Rev. 42 (2013) 4991e5001;
f) A.V. Gulevich, A.S. Dudnik, N. Chernyak, V. Gevorgyan, V. Chem, Rev. 133
(2013) 3084e3213.
We thank National Science Foundation (CHE-1362541, CHE-
1663779) for support of this work.
[13] For palladium-catalyzed CeN coupling reaction of bromoarenes towards
synthesis of pyridobenzimidazoles, see): a) T. Sakamoto, J. Chem. Soc., Perkin
Trans. 1 (1999) 1505e1510;
b) T. Xu, H. Alper, Org. Lett. 17 (2015) 1569e1572.
[14] For synthesis of pyridobenzimidazoles via the copper-catalyzed CeN coupling
reaction of chloroarenes, see K.-S. Masters, T.R.M. Rauws, A.K. Yadav,
W.A. Herrebout, B. Van der Veken, B.U.W. Maes, Chem. Eur J. 17 (2011)
6315e6320.
Appendix A. Supplementary data
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.jorganchem.2018.03.003
Please cite this article in press as: P. Chuentragool, et al., Journal of Organometallic Chemistry (2018), https://doi.org/10.1016/
j.jorganchem.2018.03.003