Direct alkenylation of alkylazaarenes with aldehydes through C(sp3)-H functionalization under catalytic InCl3 activation

Article abstract of DOI:10.1016/j.tet.2016.03.004

Under the influence of InCl₃ as a Lewis acid catalyst, a methodology on the C(sp³)-H functionalization of alkylazaarenes has been demonstrated through the activation of benzylic C-H bonds towards their addition reaction with the appropriate electrophiles. This methodology was chiefly applied in the direct alkenylation of primary and secondary benzylic C-H bonds of alkylazaarenes with aldehydes. A variety of alkenyl products were afforded in generally good yields including the starting alkenyl intermediate used in the synthesis of montelukast and other related molecules.

Full text of DOI:10.1016/j.tet.2016.03.004

Tetrahedron 72 (2016) 2132e2138
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Direct alkenylation of alkylazaarenes with aldehydes through
C(sp3)eH functionalization under catalytic InCl3 activation
*
Zaini Jamal, Yong-Chua Teo , Gina Shiyun Lim
Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616,
Singapore
a r t i c l e i n f o
a b s t r a c t
Under the influence of InCl3 as a Lewis acid catalyst, a methodology on the C(sp3)eH functionalization of
alkylazaarenes has been demonstrated through the activation of benzylic CeH bonds towards their
addition reaction with the appropriate electrophiles. This methodology was chiefly applied in the direct
alkenylation of primary and secondary benzylic CeH bonds of alkylazaarenes with aldehydes. A variety of
alkenyl products were afforded in generally good yields including the starting alkenyl intermediate used
in the synthesis of montelukast and other related molecules.
Article history:
Received 4 December 2015
Received in revised form 15 February 2016
Accepted 1 March 2016
Available online 8 March 2016
Keywords:
Aldehydes
Ó 2016 Elsevier Ltd. All rights reserved.
Alkylazaarenes
CeH functionalization
Indium
Lewis acid
1. Introduction
Previously, we reported an In-catalyzed methodology for the
C(sp3)eH functionalization of 2-methylazaarenes with tri-
The prevalent of the azaarene moiety among molecules in a di-
verse field of applications ensures that it occupies an important
position in organic synthesis.1 Unsurprisingly, a considerable de-
gree of attention has been focused on the development of synthetic
approaches towards various azaarene compounds.2
fluoromethyl ketones (Scheme 1).7
Since the direct functionalization of the azaarene core is tradi-
tionally cumbersome, an alternative approach that flourished
during the last few years is the C(sp3)eH functionalization of
alkylazaarenes.3 These recent developments also represent ad-
vances in the often imposing research on the direct functionaliza-
tion of C(sp3)eH bonds.4
Among the predominant recent examples are the catalytic
methodologies based on the CeH addition strategy.5 In the pres-
ence of an electrophilic species, the CeH addition is thought to
proceed through a characteristically nucleophilic enamide form of
the appropriate alkylazaarenes. Under either a Lewis acid or
Bronsted acid catalysis, the generation of this reactive enamide
intermediate is generally proposed as a consequence of the cata-
lytic benzylic CeH activation on the substrate.6
Scheme 1. In-catalyzed C(sp3)eH functionalization of 2-methylazaarenes with tri-
fluoromethyl ketones.
Similarly, upon the C(sp3)eH activation effect of the Lewis acid
catalyst, a reactive intermediate in the form of an In-enamide
species was proposed. This is believed to be a key in the success-
ful benzylic CeH addition to the electrophilic carbonyl carbon of
trifluoromethyl ketones.
Such catalytic applicability of trivalent indium for the activation
of chemical reactions is desirable due to their inherent lure of being
inexpensive, low toxic and high tolerance.8,9 However, the potential
of Lewis acidic trivalent indium for this class of C(sp3)eH func-
tionalization is still underdeveloped.
* Corresponding author. Tel.: þ65 6790 3846; fax: þ65 6896 9414; e-mail
address: yongchua.teo@nie.edu.sg (Y.-C. Teo).
http://dx.doi.org/10.1016/j.tet.2016.03.004
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

Z. Jamal et al. / Tetrahedron 72 (2016) 2132e2138
2133
Therefore, synchronizing with our interest in the development
of economical and benign metal-catalyzed organic reactions, we
subsequently envisioned a further development on In-catalyzed
C(sp3)eH functionalization of alkylazaarenes through addition re-
action with electrophiles.
2. Results and discussion
Through the cleavage of two C(sp3)eH bonds of alkylazaarenes,
synthesis of alkenyl products under neutral condensation condi-
tions with aldehydes was considered.
Henceforth, we began by the reaction between quinaldine 1a
and benzaldehyde 2a in which the incorporation of 10 mol % InCl3
was found to be vital in enriching yield of 3aa (Table 1, entries 1 and
2).10 This set of observations formed the basis to validate the acti-
vation role of catalytic InCl3 against several existing reports on
catalyst-free procedures for this class of C(sp3)eH functionaliza-
tion.11 It is also noteworthy that only a single isomer of 3aa as the
(E)-styrylquinoline was identified upon 1H NMR analysis of the
crude reaction mixture.
a General reaction conditions: 1b-1m (0.5 mmol), 2a (2.0 equiv.),
InCl3 (10 mol%), THF (0.3 mL), 120 oC, 24 h.
Scheme 2. Scope of alkylazaarenesa.
Table 1
and 2-phenethylquinoline were disappointingly found to be
unreactive with only the starting materials being recovered.
Besides 2-alkyl substituted quinolines, the functionalization of
a methyl group at the 4-position of the quinoline core was also
feasible. This was illustrated with our successful attempt using
lepidine in which a satisfactory 60% yield of 3ka was obtained.
Additionally, 3la and 3ma were also easily synthesized from the
corresponding 1-methylisoquinoline (1l) and 2-methylbenzo[d]
thiazole (1m) in 80% and 74% yields, respectively. However, at-
tempts with 3-methylisoquinoline, 2-picoline and 2,6-lutidine
were unsuccessful. Presumably, this could be attributed to the se-
vere aromaticity disruption on these substrates en route to the
generation of the respective In-enamide intermediates. An attempt
with 2-methylquinoxaline also failed due to substrate
decomposition.
Screening of conditions for the In-catalyzed C(sp3)eH alkenylation of 1a with 2aa
Entry
[In]
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
9
d
H2O
H2O
30
68
76
80
73
82
88
69
30
64
InCl3
InCl3
InCl3
InCl3
InCl3
InCl3
InBr3
In(OTf)3
In(CF3CO2)3
tBuOH
DCM
DCE
Toluene
THF
THF
THF
THF
Scope of aldehydes for this In-catalyzed C(sp3)eH functionali-
zation was next tested (Table 2).
10
a
General reaction conditions: 1a (0.5 mmol), 2a (2.0 equiv), [In] (10 mol %),
Solvent (0.3 mL), 120 ꢀC, 24 h.
b
Isolated yield.
Table 2
Scope of aldehydesa
After a series of attempts using several different solvents, the
reaction yield was subsequently further improved with the iso-
lation of 3aa in 88% yield (entry 7). The applicability of trivalent
indium was also concluded with InCl3 deemed as the best among
other In sources screened (entries 8e10).
Entry
Aldehyde, R
Product
Yield (%)b
Utilizing the catalytic influence of InCl3 in THF as the general
reaction conditions, the C(sp3)eH alkenylation of various alkyla-
zaarenes with 2a was next demonstrated (Scheme 2).
1
2
3
4
5
6
7
8
2b, 4-BrC6H4
2c, 4-ClC6H4
2d, 4-FC6H4
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am
3an
3ao
82
84
83
80
80
70
60
75
83
80
85
82
60
20
2e, 4-F3CC6H4
2f, 4-PhC6H4
2g, 4-MeC6H4
2h, 4-OMeC6H4
2i, 2-pyridyl
2j, 3-pyridyl
2k, 4-pyridyl
2l, 2-furyl
We started off with the synthesis of several 2-styrylquinolines
(3bae3ga) from differently substituted quinaldines.12 Reasonably
good yields were obtained in all cases except in the example using
4-chloroquinaldine whereby only 25% yield of the 3ea was isolated.
The alkenylation of a higher order alkyl-substituted azaarene
was next attempted through the functionalization of secondary
benzylic CeH bonds of 2-ethylquinoline (1h) with 2a from which
3ha was obtained in 38% yield. Despite the modest yield from our
maiden attempt, studies with several other substrates bearing
similar secondary C(sp3)eH bonds were also considered. Gratify-
ingly, with 2,3-dihydro-1H-cyclopenta[b]quinoline (1i) and 1,2,3,4-
tetrahydroacridine (1j), the corresponding alkenyl products 3ia and
3ja were sumptuously yielded in 85% and 87%, respectively. How-
ever, other attempts with substrates possessing larger aliphatic ring
sizes (7- and 8-membered) as well as 2-(but-3-en-1-yl)quinoline
9
10
11
12
13
14
2m, 2-thienyl
2n, (E)-PhCH]CH
2o, (CH3)3C
a
General reaction conditions: 1a (0.5 mmol), 2be2o (2.0 equiv), InCl3 (10 mol %),
THF (0.3 mL), 120 ꢀC, 24 h.
b
Isolated yield.
Generally, with various substituted benzaldehydes, good yields
ranging from 60% to 84% of the corresponding 2-styrylquinolines

2134
Z. Jamal et al. / Tetrahedron 72 (2016) 2132e2138
were obtained (entries 1e7). Pyridinecarboxaldehydes 2i, 2j, and
2k were also compatible with the isolation of the respective
polynitrogen-containing alkenyl products in 75%, 83% and 80%
yields (entries 8e10). Other heteroaromatic aldehydes as 2l and 2m
also furnished the intended product in high yields (entries 11 and
12).
Comparatively, a slightly lower reactivity of cinnamaldehyde 2n
was observed as indicated by the moderate 60% yield of 3an (entry
13). However, with the aliphatic aldehyde 2o, a severely diminished
reactivity was evident with merely 20% yield of 3ao was obtainable
(entry 14).
Scheme 4. In-catalyzed C(sp3)eH functionalization of 1a with C]N and C]C
electrophiles.
The synthetic utility of this In-catalyzed C(sp3)eH functionali-
zation methodology was also demonstrated (Scheme 3).
proved to be significant as no intended product was formed when
the reaction was conducted in the absence of InCl3. Furthermore,
despite its low yielding, the In-catalyzed protocol exhibited only
a single C(sp3)eH bond cleavage and no addition to the carbonyl of
2r.
The unreactive nature of ketones was also observed in the cases
of our attempts with acetophenone and benzophenone. The elec-
trophilic C]C of trans-b-nitrostyrene was also insusceptible to-
wards the CeH addition.
3. Conclusion
Scheme 3. Preparation of 3dp.
In conclusion, an In-catalyzed C(sp3)eH functionalization of
alkylazaarenes with the appropriate electrophiles through the
benzylic CeH addition was successfully developed. Under the cat-
alytic C(sp3)eH activation effect of InCl3 Lewis acid, the synthesis of
various alkenyl products was described as the C(sp3)eH alkenyla-
tion of alkylazaarenes with aldehydes. A similar strategy using
representative electrophilic C]N and C]C was also successfully
demonstrated.
From a 2.0 mmol scaled reaction in the presence of 1.2 equiv 2p,
the intended product 3dp was obtained in a good yield of 68%.
Synthetically, 3dp is an important starting intermediate towards
montelukast and other related molecules.13
We next attempted the synthesis of several other alkenyl
products based on the secondary benzylic CeH functionalization.
On the additional ground related to the importance of 1i,14 the
application of this In-catalyzed methodology involving 1i with
several aldehydes was initiated (Fig. 1).
4. Experimental section
4.1. General
All commercially available chemicals and anhydrous solvents
were used directly upon purchase from suppliers. Analytical thin
layer chromatography (TLC) was performed using Merck 60 F254
precoated silica gel plates (0.2 mm thickness) and visualized using
UV radiation on Spectroline Model ENF-24061/F 254 nm. Flash
chromatography was performed using Merck silica gel 60 with AR
grade solvents. Melting points were determined using OptiMelt
automated melting point system and are uncorrected. IR spectra
were recorded using PerkineElmer Paragon 1000 FTIR spectro-
photometer on KBr plates. Nuclear magnetic resonance (NMR)
spectra were recorded on a Bruker Avance DPX 400 spectropho-
Fig. 1. In-catalyzed C(sp3)eH alkenylation of 1i with various aldehydes under the
general reaction conditions of 1i (0.5 mmol), aldehydes (2.0 equiv), InCl3 (10 mol %),
THF (0.3 mL), 120 ꢀC, 24 h.
tometer. Chemical shifts for 1H and 13C NMR are reported as
d in
units of parts per million (ppm) downfield from SiMe4 and relative
to the residual signal of CDCl3. Multiplicities are reported based on
apparent multiplicities and coupling constants (J values) are re-
ported in unit of Hertz (Hz). Elemental analysis was performed on
vario MICRO CUBE CHNS. Mass spectroscopy was performed using
Water Q-Tof Permies Mass Spectrometer.
High yields of the intended products were obtained from the
reaction with substituted benzaldehydes (82%e92%). 2-Substituted
benzaldehyde as 2-chlorobenzaldehyde also exemplified no effect
on the reaction efficiency as an excellent 92% yield of 3ic0 was ob-
tained. However, other aldehydes tested exhibited lower reactivity
with 2o noticeably affording only 24% yield of 3io.
4.2. Synthesis of alkylazaarenes 1hej
Under the general reaction conditions, the C(sp3)eH function-
alization with other electrophiles were also attempted (Scheme 4).
2q was firstly tested as a representative C]N electrophile from
which 3aa was obtained in essentially the same efficiency as the
analogous reaction between 1a and 2a.
4.2.1. 2-Ethylquinoline (1h). To an oven-dried RBF equipped with
a magnetic stir bar, quinaldine (5.0 mmol) and anhydrous ether
(5 mL) were added under an atmosphere of nitrogen. The mixture
was subsequently cooled to 0 ꢀC prior to the dropwise addition of
n-BuLi (1.2 equiv). The resulting reaction mixture was then stirred
at rt for 2 h followed by the dropwise addition of iodomethane
(2.0 equiv). After stirring for a further 5 h at rt, water (5 mL) was
However, with 2r as a potential C]C electrophile, only 20% of
the intended 3ar was isolated. Nonetheless, this observation

Z. Jamal et al. / Tetrahedron 72 (2016) 2132e2138
2135
slowly poured to the reaction mixture and the crude product was
extracted using EtOAc (3ꢁ10 mL). The combined organic layer was
then dried over Na2SO4 and concentrated under reduced pressure.
Purification by silica gel chromatography (hexane/EtOAc) then
afforded 1h as a yellow oil in 81% yield. 1h is a known
compound.6n
127.1,127.4,128.2,128.5,128.7,128.9,135.2,135.5,136.1,136.3,148.7,
156.9; HRMS (ESI) calcd for C17H13ClN [MþH]: 266.0736, found:
266.0737.
4.3.5. (E)-4-Chloro-2-styrylquinoline (3ea).16 Light yellow solid
(25%, 33.7 mg); Rf (20% EtOAc/hexane) 0.57; 1H NMR (400 MHz,
CDCl3):
7.63e7.70 (m, 3H), 7.73e7.77 (m, 2H), 8.90 (d, J¼8.5 Hz, 1H),
8.17e8.20 (m, 1H); 13C NMR (100 MHz, CDCl3):
119.3, 124.0, 125.5,
127.1,127.4,128.0,128.9,129.0,129.6,130.7,135.4,136.2,142.7,149.1,
156.0; HRMS (ESI) calcd for C17H13ClN [MþH]: 266.0736, found:
266.0737.
d 7.31e7.36 (m, 2H), 7.39e7.43 (m, 2H), 7.56e7.60 (m, 1H),
4.2.2. 2,3-Dihydro-1H-cyclopenta[b]quinoline (1i) and 1,2,3,4-
tetrahydroacridine (1j). To an oven-dried RBF equipped with
a magnetic stir bar, 2-nitrobenzaldehyde (5.0 mmol) was dissolved
in EtOH (15 mL). Iron powder (4.0 equiv) and 0.1 N HCl (5.0 mol %,
2.5 mL) were next added after which the resulting mixture was
then stirred at 95 ꢀC for 40 min. Upon cooling, cyclopentanone or
cyclohexanone (1.0 equiv) was added followed by the portionwise
addition of powdered KOH (1.2 equiv). Heating was continued at
95 ꢀC for another 30 min. The reaction mixture was then filtered
through a pad of Celite with the resulting filtrate subsequently
washed with water and extracted using dichloromethane
(3ꢁ10 mL). The combined organic layers were further washed with
brine, dried over Na2SO4 and concentrated under reduced pressure.
Purification by silica gel chromatography (hexane/EtOAc) then
afforded 1i or 1j as yellow solid in 87% or 90% yield, respectively. 1i
and 1j are known compounds.15
d
4.3.6. (E)-6-Methyl-2-styrylquinoline (3fa).10 White solid (85%,
104.3 mg); Rf (20% EtOAc/hexane) 0.43; 1H NMR (400 MHz, CDCl3):
d
7.32e7.34 (m, 1H), 2.54 (s, 3H), 7.38e7.42 (m, 3H), 7.53e7.55 (m,
2H), 7.63e7.68 (m, 4H), 7.97 (d, J¼8.0 Hz, 1H), 8.04 (d, J¼9.0 Hz, 1H);
13C NMR (100 MHz, CDCl3):
21.6, 119.3, 126.5, 127.2, 127.4, 128.5,
d
128.8, 128.9, 129.2, 132.0, 133.9, 135.7, 136.1, 136.7, 146.9, 155.2; El-
emental Anal. calcd (%) for C18H15N: C 88.13, H 6.16, N 5.71; found: C
87.99, H 6.18, N 5.71.
4.3.7. (E)-6-Methoxy-2-styrylquinoline (3ga).10 White solid (75%,
98.1 mg); Rf (20% EtOAc/hexane) 0.34; 1H NMR (400 MHz, CDCl3):
4.3. General procedure for InCl3-catalyzed C(sp3)eH
functionalization
d
3.94 (s, 3H), 7.07 (d, J¼3.0 Hz, 1H), 7.31e7.42 (m, 5H), 7.60e7.65
(m, 4H), 7.98 (d, J¼9.0 Hz, 1H), 8.03 (d, J¼8.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3):
d 55.6, 105.3, 119.6, 122.3, 127.1, 128.3, 128.8,
To a screw-capped reaction vial equipped with a magnetic stir
bar, InCl3 (10 mol %), alkylazaarene (0.5 mmol), aldehyde (2.0 equiv)
and THF (0.3 mL) were sequentially added. The resulting reaction
vial was then placed into a preheated oil bath at 120 ꢀC with vig-
orous stirring. After 24 h, the reaction vial was taken out of the oil
bath and allowed to cool to room temperature. The reaction mix-
ture was next concentrated under reduced pressure and the
remaining residue was purified by silica gel chromatography
(hexane/EtOAc) to afford the desired product.
129.1, 130.7, 133.2, 135.1, 136.7, 144.3, 153.7, 157.7; HRMS (ESI) calcd
for C18H16NO [MþH]: 262.1232, found: 262.1225.
4.3.8. (E)-2-(1-Phenylprop-1-en-2-yl)quinoline (3ha).17 White solid
(38%, 46.0 mg); Rf (20% EtOAc/hexane) 0.52; 1H NMR (400 MHz,
CDCl3):
d
2.54 (d, J¼1.0 Hz, 3H), 7.31 (t, J¼7.5 Hz, 1H), 7.43 (t,
J¼7.5 Hz, 2H), 7.49e7.53 (m, 4H), 7.70e7.74 (m, 1H), 7.76 (d,
J¼8.5 Hz, 1H), 7.81 (dd, J1¼8.0 Hz, J2¼1.5 Hz, 1H), 8.14 (d, J¼8.5 Hz,
2H); 13C NMR (100 MHz, CDCl3):
d 16.1, 118.7, 126.1, 127.0, 127.1,
127.3, 128.2, 129.46, 129.48, 129.6, 131.7, 136.1, 137.7, 137.9, 147.8,
160.1; HRMS (ESI) calcd for C18H16N [MþH]: 246.1282, found:
246.1284.
4.3.1. (E)-2-Styrylquinoline (3aa).10 White solid (88%, 101.8 mg); Rf
(20% EtOAc/hexane) 0.51; 1H NMR (400 MHz, CDCl3):
d 7.41e7.35 (m,
1H), 7.39e7.44 (m, 3H), 7.50 (t, J¼7.5 Hz, 1H), 7.64e7.73 (m, 5H),
7.79 (d, J¼8.0 Hz, 1H), 8.08, (d, J¼9.0 Hz, 1H), 8.14 (d, J¼8.5 Hz, 1H);
4.3.9. (E)-3-Benzylidene-2,3-dihydro-1H-cyclopenta[b]quinoline
(3ia). Light yellow solid (85%, 109.8 mg); mp 138e140 ꢀC; Rf
(20% EtOAc/hexane) 0.54; nmax (KBr) 3047, 2880, 1604, 1565,
1496, 1444, 1404, 1277, 1239, 1199, 1148, 957, 911, 877, 859,
13C NMR (100 MHz, CDCl3):
d 119.3, 126.2, 127.3, 127.4, 127.5, 128.7,
128.8, 129.1, 129.2, 129.8, 134.5, 136.4, 136.6, 148.3, 156.0; Elemental
Anal. calcd (%) for C17H13N: C 88.28, H 5.67, N 6.06; found: C 87.90, H
5.70, N 6.02.
726 cmꢂ1 1H NMR (400 MHz, CDCl3):
; d 3.21e3.25 (m, 4H),
7.28e7.32 (m, 1H), 7.41e7.47 (m, 3H), 7.62e7.67 (m, 3H), 7.72 (d,
J¼8.0 Hz, 1H), 7.83e7.84 (m, 1H), 7.93 (s, 1H), 8.12 (d, J¼9.0 Hz,
4.3.2. (E)-6-Bromo-2-styrylquinoline (3ba).10 White solid (77%,
119.4 mg); Rf (20% EtOAc/hexane) 0.51; 1H NMR (400 MHz, CDCl3):
1H); 13C NMR (100 MHz, CDCl3):
d 27.9, 29.1, 124.8, 125.8, 127.38,
d
7.32e7. 43 (m, 4H), 7.63e7.73 (m, 4H), 7.77 (dd, J¼2.0, 9.0 Hz, 1H),
127.4, 128.3, 128.5, 128.8, 129.2, 129.5, 131.3, 137.0, 137.5, 140.8,
148.3, 162.2; HRMS (ESI) calcd for C19H16N [MþH]: 258.1282,
found: 258.1284.
7.93e7.95 (m, 2H), 8.04 (d, J¼9.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3):
d 119.9, 120.3, 127.4, 128.4, 128.6, 128.9, 129.6, 130.9, 133.2,
135.0, 135.3, 136.4, 146.9, 156.4; HRMS (ESI) calcd for C17H13BrN
[MþH]: 310.0231, found: 310.0231.
4.3.10. (E)-4-Benzylidene-1,2,3,4-tetrahydroacridine (3ja). Yellow
solid (87%, 117.5 mg); mp 105e107 ꢀC; Rf (20% EtOAc/hexane) 0.60;
nmax (KBr) 3049, 2947, 2871, 1584, 1489, 1442, 1409, 1309, 1253,
4.3.3. (E)-6-Chloro-2-styrylquinoline (3ca).10 White solid (71%,
94.4 mg); Rf (20% EtOAc/hexane) 0.51; 1H NMR (400 MHz, CDCl3):
1161, 911, 855, 749 cmꢂ1 1H NMR (400 MHz, CDCl3):
; d 1.90e1.96
d
7.32e7.43 (m, 4H), 7.63e7.72 (m, 5H), 7.77 (d, J¼2.0 Hz, 1H), 8.01
(m, 2H), 3.00e3.05 (m, 4H), 7.29 (t, J¼7.0 Hz,1H), 7.39e7.47 (m, 3H),
7.51e7.53 (m, 2H), 7.62e7.66 (m, 1H), 7.71 (d, J¼8.0 Hz, 1H), 7.84 (s,
1H), 8.09 (d, J¼8.5 Hz, 1H), 8.24 (s, 1H); 13C NMR (100 MHz, CDCl3):
(d, J¼9.0 Hz, 1H), 8.05 (d, J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
120.3, 126.2, 127.3, 127.9, 128.6, 128.8, 128.9, 130.7, 130.8, 131.8,
134.9, 135.4, 136.4, 146.7, 156.3; HRMS (ESI) calcd for C17H13ClN
d 23.1, 28.5, 30.3, 125.9, 126.7, 127.0, 127.7, 128.1, 128.7, 129.3, 129.4,
[MþH]: 266.0736, found: 266.0736.
129.9, 131.4, 134.7, 135.9, 137.9, 147.2, 154.4; HRMS (ESI) calcd for
20H18N [MþH]: 272.1439, found: 272.1441.
C
4.3.4. (E)-7-Chloro-2-styrylquinoline (3da).10 White solid (73%,
97.0 mg); Rf (20% EtOAc/hexane) 0.61; 1H NMR (400 MHz, CDCl3):
4.3.11. (E)-4-Styrylquinoline (3ka).17 Light yellow solid (60%,
68.9 mg); Rf (20% EtOAc/hexane) 0.23; 1H NMR (400 MHz, CDCl3):
d 7.31e7.38 (m, 2H), 7.41e7.45 (m, 2H), 7.57e7.64 (m, 4H), 7.71e7.75
d
7.32e7.46 (m, 5H), 7.65 (d, J¼8.5 Hz, 3H), 7.70e7.74 (m, 2H),
8.08e8.11 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
119.6, 119.7, 125.7,

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Z. Jamal et al. / Tetrahedron 72 (2016) 2132e2138
(m, 1H), 7.81 (d, J¼16.5 Hz, 1H), 8.15 (d, J¼8.5 Hz, 1H), 8.21 (d,
J¼8.5 Hz, 1H), 8.90 (d, J¼3.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
141.4, 148.3, 156.0; HRMS (ESI) calcd for C23H18N [MþH]: 308.1439,
found: 308.1442.
d
117.1, 122.9, 123.5, 126.5, 127.1, 128.8, 128.9, 129.3, 130.2, 135.1,
136.6, 142.9, 148.7, 150.2; HRMS (ESI) calcd for C17H14N [MþH]:
4.3.19. (E)-2-(4-Methylstyryl)quinoline (3ag).10 White solid (70%,
86.0 mg); Rf (20% EtOAc/hexane) 0.52; 1H NMR (400 MHz, CDCl3):
232.1126, found: 232.1127.
d
2.39 (s, 3H), 7.22 (d, J¼8.0 Hz, 2H), 7.37 (d, J¼16.5 Hz, 1H), 7.49 (t,
4.3.12. (E)-1-Styrylisoquinoline (3la).10 Light yellow solid (80%,
92.0 mg); Rf (20% EtOAc/hexane) 0.40; 1H NMR (400 MHz, CDCl3):
J¼7.5 Hz, 1H), 7.55 (d, J¼8.0 Hz, 2H), 7.65e7.72 (m, 3H), 7.78 (d,
J¼8.0 Hz, 1H), 8.07 (d, J¼8.5 Hz, 1H), 8.12 (d, J¼9.0 Hz, 1H); 13C NMR
d
7.32e7.36 (m, 1H), 7.41e7.44 (m, 2H), 7.54 (d, J¼5.5 Hz, 1H),
(100 MHz, CDCl3): d 21.4, 119.2, 126.1, 127.2, 127.3, 127.5, 128.1, 129.2,
7.58e7.72 (m, 4H), 7.80 (d, J¼8.5 Hz, 1H), 8.01 (s, 2H), 8.37 (d,
129.6, 129.7, 133.8, 134.4, 136.3, 138.8, 148.3, 156.2; Elemental Anal.
calcd (%) for C18H15N: C 88.13, H 6.16, N 5.71; found: C 87.92, H 6.20,
N 5.72.
J¼8.0 Hz, 1H), 8.57 (d, J¼5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
119.9, 122.8, 124.4, 126.7, 127.1, 127.2, 127.4, 128.5, 128.7, 129.8,
135.8, 136.6, 136.9, 142.4, 154.4; HRMS (ESI) calcd for C17H14
[MþH]: 232.1126, found: 232.1120.
N
4.3.20. (E)-2-(4-Methoxystyryl)quinoline (3ah).10 Yellow solid (60%,
78.8 mg); Rf (20% EtOAc/hexane) 0.36; 1H NMR (400 MHz, CDCl3):
18
4.3.13. (E)-2-Styrylbenzo[d]thiazole (3ma).
Yellow solid (74%,
d
3.85 (s, 3H), 6.94 (d, J¼9.0 Hz, 2H), 7.28 (d, J¼17.0 Hz, 1H), 7.48 (t,
88.4 mg); Rf (20% EtOAc/hexane) 0.54; 1H NMR (400 MHz, CDCl3):
J¼7.5 Hz, 1H), 7.57e7.72 (m, 5H), 7.77 (d, J¼8.0 Hz, 1H), 8.06 (d,
d
7.34e7.43 (m, 5H), 7.45e7.50 (m, 1H), 7.51e7.59 (m, 3H), 7.86 (d,
J¼8.5 Hz, 1H), 8.11 (d, J¼9.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
J¼8.0 Hz, 1H), 8.01 (d, J¼8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 55.4, 114.3, 119.2, 126.0, 126.9, 127.3, 127.5, 128.7, 129.1, 129.4,
d
121.5, 122.1, 123.0, 125.4, 126.3, 127.4, 129.0, 129.4, 134.4, 135.4,
129.7, 134.1, 136.3, 148.3, 156.4, 160.2; HRMS (ESI) calcd for
18H16NO [MþH]: 262.1232, found: 262.1222.
137.7,153.9,167.0; HRMS (ESI) calcd for C15H12NS [MþH]: 238.0690,
C
found: 238.0689.
4.3.21. (E)-2-(2-(Pyridin-2-yl)vinyl)quinoline (3ai).10 Light yellow
solid (75%, 87.3 mg); Rf (20% EtOAc/hexane) 0.17; 1H NMR (400 MHz,
4.3.14. (E)-2-(4-Bromostyryl)quinoline (3ab).10 Light yellow solid
(82%, 127.2 mg); Rf (20% EtOAc/hexane) 0.51; 1H NMR (400 MHz,
CDCl3):
d
7.21 (ddd, J1¼7.0 Hz, J2¼5.0 Hz, J3¼1.0 Hz, 1H); 7.51 (t,
CDCl3):
2H), 7.70 (t, J¼7.5 Hz, 1H), 7.76 (d, J¼8.0 Hz, 1H), 8.08 (d, J¼8.5 Hz,
2H); 13C NMR (100 MHz, CDCl3):
119.4, 122.6, 126.3, 127.4, 127.5,
128.7, 129.3, 129.7, 129.9, 132.0, 133.1, 135.5, 136.5, 148.3, 155.6;
d
7.35 (d, J¼16.5 Hz, 1H), 7.45e7.51 (m, 5H), 7.58e7.62 (m,
J¼7.5 Hz, 1H), 7.58 (d, J¼8.0 Hz, 1H), 7.67e7.74 (m, 3H), 7.79e7. 88
(m, 3H), 8.10 (d, J¼9.0 Hz, 1H), 8.15 (d, J¼8.5 Hz, 1H), 8.65e8.66 (m,
d
1H); 13C NMR (100 MHz, CDCl3):
d 120.3, 122.78, 122.8, 126.4, 127.5,
127.6, 129.4, 129.8, 132.6, 133.7, 136.5, 136.6, 148.3, 149.8, 155.1,
155.3; HRMS (ESI) calcd for C16H13N2 [MþH]: 233.1078, found:
233.1075.
HRMS (ESI) calcd for
310.0234.
C
17H13BrN [MþH]: 310.0231, found:
4.3.15. (E)-2-(4-Chlorostyryl)quinoline (3ac).10 White solid (84%,
111.7 mg); Rf (20% EtOAc/hexane) 0.43; 1H NMR (400 MHz, CDCl3):
4.3.22. (E)-2-(2-(Pyridin-3-yl)vinyl)quinoline (3aj).10 Light yellow
solid (83%, 96.4 mg); Rf (20% EtOAc/hexane) 0.36; 1H NMR
d
7.35e7.39 (m, 3H), 7.51 (t, J¼7.5 Hz, 1H), 7.57 (d, J¼9.0 Hz, 2H),
(400 MHz, CDCl3):
d
7.30 (dd, J1¼5.0 Hz, J2¼8.0 Hz 1H), 7.42 (d,
7.63e7.67 (m, 2H), 7.71 (t, J¼7.5 Hz, 1H), 7.79 (d, J¼8.0 Hz, 1H), 8.08
J¼16.5 Hz, 1H), 7.50 (t, J¼7.5 Hz, 1H), 7.61e7.78 (m, 4H), 7.92 (d,
J¼8.0 Hz, 1H), 8.10 (dd, J1¼8.5 Hz, J2¼12.0 Hz, 2H), 8.54 (s, 1H), 8.83
(d, J¼8.5 Hz, 1H), 8.14 (d, J¼9.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
119.4, 126.3, 127.4, 127.6, 128.4, 129.0, 129.3, 129.6, 129.9, 133.1,
(s, 1H); 13C NMR (100 MHz, CDCl3):
d 119.4, 123.7, 126.5, 127.52,
134.3, 135.1, 136.5, 148.3, 155.6; HRMS (ESI) calcd for C17H13ClN
[MþH]: 266.0736, found: 266.0730.
127.55, 129.3, 129.9, 130.6, 130.9, 132.3, 133.3, 136.6, 148.2, 149.2,
149.4, 155.2; HRMS (ESI) calcd for C16H13N2 [MþH]: 233.1078,
found: 233.1075.
4.3.16. (E)-2-(4-Fluorostyryl)quinoline (3ad).10 White solid (83%,
103.5 mg); Rf (20% EtOAc/hexane) 0.40; 1H NMR (400 MHz,
4.3.23. (E)-2-(2-(Pyridin-4-yl)vinyl)quinoline (3ak).10 Yellow solid
(80%, 93.1 mg); Rf (50% EtOAc/hexane) 0.23; 1H NMR (400 MHz,
CDCl3):
J¼7.0 Hz, 1H), 7.59e7.79 (m, 6H), 8.10 (dd, J1¼8.5 Hz, J2¼19.0 Hz,
2H); 13C NMR (100 MHz, CDCl3):
d
7.09 (t, J¼8.5 Hz, 2H), 7.32 (d, J¼16.0 Hz, 1H), 7.50 (t,
CDCl3):
d
7.48e7.83 (m, 8H), 8.10 (d, J¼9.0 Hz, 1H), 8.18 (d, J¼9.0 Hz,
d
115.9 (d, J¼22.0 Hz), 119.3,
1H), 8.64 (d, J¼5.5 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 119.6,
126.2, 127.4, 128.8 (d, J¼2.5 Hz), 127.5, 128.9 (d, J¼8.0 Hz), 129.2,
129.8, 132.8 (d, J¼3.5 Hz), 133.2, 136.4, 148.3, 155.8, 163.0 (d,
J¼249.0 Hz); HRMS (ESI) calcd for C17H13FN [MþH]: 250.1042,
found: 250.1029.
121.4, 126.8,127.6,127.7, 129.4,130.0,131.5, 133.3, 136.7, 143.8,149.7,
150.4, 154.7; HRMS (ESI) calcd for C16H13N2 [MþH]: 233.1078,
found: 233.1078.
4.3.24. (E)-2-(2-(Furan-2-yl)vinyl)quinoline (3al).10 Brown solid
(85%, 94.4 mg); Rf (20% EtOAc/hexane) 0.51; 1H NMR (400 MHz,
4.3.17. (E)-2-(4-(Trifluoromethyl)styryl)quinoline
solid (80%, 119.7 mg); Rf (20% EtOAc/hexane) 0.40; 1H NMR
(3ae).10 White
CDCl3):
d
6.47 (dd, J1¼3.0 Hz, J2¼1.5 Hz, 1H), 6.55 (d, J¼3.5 Hz,
(400 MHz, CDCl3):
d
7.46e7.55 (m, 2H), 7.65e7.75 (m, 7H), 7.81 (d,
1H), 7.28 (d, J¼16.5 Hz, 1H), 7.46e7.58 (m, 4H), 7.69 (t, J¼7.5 Hz,
1H), 7.77 (d, J¼8.0 Hz, 1H), 8.06 (d, J¼8.5 Hz, 1H), 8.10 (d,
J¼8.0 Hz, 1H), 8.09 (d, J¼8.5 Hz, 1H), 8.17 (d, J¼8.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3):
d
119.5, 124.1 (q, J¼272.0 Hz), 125.8 (q, J¼3.5 Hz),
J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 111.1, 112.0, 119.9,
126.6, 127.3, 127.6, 129.3, 130.0, 130.2 (q, J¼32.5 Hz), 131.4, 132.7,
136.6, 140.01, 140.02, 148.3, 155.2; HRMS (ESI) calcd for C18H13F3N
[MþH]: 300.1000, found: 300.0988.
121.7, 126.0, 126.8, 127.3, 127.5, 129.2, 129.7, 136.3, 143.2, 148.3,
152.8, 155.6; HRMS (ESI) calcd for C15H12NO [MþH]: 222.0919,
found: 222.0914.
4.3.18. (E)-2-(2-([1,10-Biphenyl]-4-yl)vinyl)quinoline (3af).10 Light
yellow solid (80%, 123.2 mg); Rf (20% EtOAc/hexane) 0.51; 1H NMR
4.3.25. (E)-2-(2-(Thiophen-2-yl)vinyl)quinoline
solid (82%, 97.2 mg); Rf (20% EtOAc/hexane) 0.53; 1H NMR (400 MHz,
CDCl3):
(d, J¼5.0 Hz,1H), 7.47e7.51 (m,1H), 7.58 (d, J¼9.0 Hz,1H), 7.68e7.72
(m, 1H), 7.77 (d, J¼8.5 Hz, 1H), 7.85 (d, J¼16.0 Hz, 1H), 8.06 (d,
J¼8.5 Hz, 1H), 8.11 (d, J¼9.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
(3am).10 Yellow
(400 MHz, CDCl3):
d
7.35e7.39 (m, 1H), 7.44e7.53 (m, 4H),
d
7.05 (dd, J1¼5.0 Hz, J2¼3.5 Hz, 1H), 7.19e7.24 (m, 2H), 7.29
7.64e7.81 (m, 10H), 8.09 (d, J¼8.5 Hz, 1H), 8.14 (d, J¼8.5 Hz, 1H); 13
C
NMR (100 MHz, CDCl3):
d 119.3, 126.2, 127.0, 127.4, 127.47, 127.53,
127.7, 128.8, 128.9, 129.0, 129.2, 129.8, 134.0, 135.6, 136.4, 140.5,

Z. Jamal et al. / Tetrahedron 72 (2016) 2132e2138
2137
d
119.4, 126.0, 126.1, 127.3, 127.5, 127.8, 128.1, 128.2, 129.1, 129.7,
136.0, 137.0, 143.1, 148.4, 161.7; HRMS (ESI) calcd for C19H15ClN
136.3, 142.1, 148.3, 155.5; HRMS (ESI) calcd for C15H12NS [MþH]:
[MþH]: 292.0893, found: 292.0891.
238.0690, found: 238.0685.
4.3.32. (E)-3-(4-(Trifluoromethyl)benzylidene)-2,3-dihydro-1H-cy-
clopenta[b]quinoline (3ie). Yellow solid (92%, 150.4 mg); mp
156e159 ꢀC; Rf (20% EtOAc/hexane) 0.53; nmax (KBr) 3067, 2930,
1614, 1565, 1498, 1445, 1412, 1327, 1246, 1116, 1071, 1013, 897, 833,
4.3.26. 2-((1E,3E)-4-Phenylbuta-1,3-dien-1-yl)quinoline
(3an).10 Yellow solid (60%, 77.0 mg); Rf (20% EtOAc/hexane) 0.51;
1H NMR (400 MHz, CDCl3):
d
6.87 (d, J¼15.5 Hz, 1H), 6.95 (d,
J¼15.5 Hz, 1H), 7.07 (dd, J1¼15.5 Hz, J2¼11.0 Hz, 1H), 7.26e7.29 (m,
1H), 7.36 (t, J¼7.5 Hz, 2H), 7.46e7.59 (m, 5H), 7.69 (t, J¼8.0 Hz, 1H),
7.77 (d, J¼8.0 Hz, 1H), 8.05 (d, J¼8.5 Hz, 1H), 8.10 (d, J¼8.5 Hz, 1H);
756 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d 3.21 (s, br s, 4H), 7.45e7.49
(m, 1H), 7.62e7.72 (m, 6H), 7.81 (s, 1H), 7.93 (m, 1H), 8.11 (d,
J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 27.8, 29.1, 123.1, 124.2
13C NMR (100 MHz, CDCl3):
d
119.5, 126.1, 126.8, 127.3, 127.5, 128.2,
(q, J¼272.0 Hz), 125.4 (q, J¼4.0 Hz), 126.1, 127.5, 128.5, 128.7, 129.0,
129.3, 129.4, 131.5, 137.0, 140.9, 143.4, 148.3, 161.5; HRMS (ESI) calcd
for C20H15F3N [MþH]: 326.1156, found: 326.1157.
128.6, 128.8, 129.2, 129.7, 132.9, 134.9, 136.0, 136.2, 137.0, 148.4,
156.0; HRMS (ESI) calcd for C19H16N [MþH]: 258.1282, found:
258.1272.
4.3.33. (E)-3-(4-Methylbenzylidene)-2,3-dihydro-1H-cyclopenta[b]
quinoline (3ig). Yellow solid (86%, 116.5 mg); mp 164e166 ꢀC; Rf
(20% EtOAc/hexane) 0.57; nmax (KBr) 3033, 2919, 2858, 1596, 1561,
4.3.27. (E)-2-(3,3-Dimethylbut-1-en-1-yl)quinoline (3ao).6c Light
yellow oil (20%, 21.2 mg); Rf (20% EtOAc/hexane) 0.60; 1H NMR
(400 MHz, CDCl3):
d
1.20 (s, 9H), 6.66 (d, J¼16.5 Hz, 1H), 6.83 (d,
1510, 1496, 1403, 1275, 1153, 1134, 894, 806, 754 cmꢂ1 1H NMR
;
J¼16.5 Hz, 1H), 7.46e7.48 (m, 1H), 7.57 (d, J¼8.5 Hz, 1H), 7.65e7.67
(400 MHz, CDCl3):
d
2.39 (s, 3H), 3.22 (s, br s, 4H), 7.23 (d, J¼8.0 Hz,
(m, 1H), 7.74e7.76 (m, 1H), 8.05 (t, J¼9.5 Hz, 2H); 13C NMR
2H), 7.44e7.46 (m, 1H), 7.53 (d, J¼8.0 Hz, 2H), 7.64e7.65 (m, 1H),
(100 MHz, CDCl3): d 29.5, 33.9, 118.6, 125.6, 126.5, 127.2, 127.4, 129.1,
7.71 (d, J¼8.0 Hz, 1H), 7.81 (s, 1H), 7.92 (s, 1H), 8.11 (d, J¼8.5 Hz, 1H);
129.5, 136.2, 148.1, 148.3, 156.9; HRMS (ESI) calcd for C15H18
N
13C NMR (100 MHz, CDCl3):
d 21.4, 27.9, 29.0, 124.8, 125.7, 127.4,
[MþH]: 212.1439, found: 212.1437.
128.2, 128.7, 129.1, 129.3,129.5,131.2, 134.7, 137.0, 137.4, 139.7, 148.3,
162.4; HRMS (ESI) calcd for C20H18N [MþH]: 272.1439, found:
272.1434.
4.3.28. (E)-3-(2-(7-Chloroquinolin-2-yl)vinyl)benzaldehyde
(3dp).10 Yellow solid (68%, 402 mg); Rf (20% EtOAc/hexane) 0.36; 1H
NMR (400 MHz, CDCl3):
d
7.42e7.47 (m, 2H), 7.58 (t, J¼8.0 Hz, 1H),
4.3.34. (E)-3-(4-Methoxybenzylidene)-2,3-dihydro-1H-cyclopenta[b]
quinoline (3ih). Yellow solid (82%, 117.6 mg); mp 129e130 ꢀC; Rf
(20% EtOAc/hexane) 0.46; nmax (KBr) 3076, 2924, 2838, 1597, 1564,
7.62 (d, J¼8.5 Hz, 1H), 7.72 (d, J¼9.0 Hz, 1H), 7.78 (d, J¼16.5 Hz, 1H),
7.84 (d, J¼7.5 Hz,1H), 7.88 (d, J¼7.5 Hz,1H), 8.08e8.13 (m, 3H),10.07
(s, 1H); 13C NMR (100 MHz, CDCl3):
d
120.0, 125.9, 127.4, 128.2,
1509, 1428, 1304, 1249, 1173, 1027, 894, 831, 755 cmꢂ1 1H NMR
;
128.3, 128.7, 129.6, 129.8, 130.2, 133.0, 133.5, 135.8, 136.4, 137.0,
137.4, 148.7, 156.2, 192.1; HRMS (ESI) calcd for C18H13ClNO [Mþ1]:
294.0685, found: 294.0681.
(400 MHz, CDCl3): d 3.22 (s, br s, 4H), 3.85 (s, 3H), 6.95e6.97 (m,
2H), 7.44e7.46 (m, 1H), 7.58 (d, J¼9.0 Hz, 2H), 7.61e7.64 (m, 1H),
7.71 (d, J¼8.0 Hz,1H), 7.78 (s, 1H), 7.92 (s, 1H), 8.09 (d, J¼8.5 Hz,1H);
13C NMR (100 MHz, CDCl3):
d 27.9, 29.0, 55.3, 114.1, 124.5, 125.6,
4.3.29. (E)-3-(4-Bromobenzylidene)-2,3-dihydro-1H-cyclopenta[b]
quinoline (3ib). Yellow solid (88%, 147.9 mg); mp 191e193 ꢀC; Rf
(20% EtOAc/hexane) 0.54; nmax (KBr) 3087, 2915, 1599, 1564, 1487,
127.4, 128.2, 128.7, 129.1, 130.4, 130.9, 131.2, 136.9, 138.3, 148.3,
159.0, 162.6; HRMS (ESI) calcd for C20H18NO [MþH]: 288.1388,
found: 288.1387.
1426, 1406, 1275, 1153, 1135, 1073, 1005, 893, 824, 759 cmꢂ1 1H
;
NMR (400 MHz, CDCl3):
d
3.18e3.22 (m, 4H), 7.45e7.48 (m, 3H),
4.3.35. (E)-3-(Pyridin-3-ylmethylene)-2,3-dihydro-1H-cyclopenta[b]
quinoline (3ij). Yellow solid (63%, 81.4 mg); mp 132e135 ꢀC; Rf (50%
EtOAc/hexane) 0.29; nmax (KBr) 3058, 2919, 1604, 1582, 1565, 1497,
1419, 1313, 1273, 1220, 1151, 1129, 1021, 943, 891, 740 cmꢂ1; 1H NMR
7.52e7.54 (m, 2H), 7.65 (t, J¼7.5 Hz, 1H), 7.72e7.74 (m, 2H), 7.96 (s,
1H), 8.10 (d, J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 27.9, 29.1,
121.3, 123.5, 126.0, 127.5, 128.4, 128.9, 129.3, 130.9, 131.4, 131.7,
136.4, 137.0, 141.6, 148.4, 161.9; HRMS (ESI) calcd for C19H15BrN
[MþH]: 336.0388, found: 336.0389.
(400 MHz, CDCl3):
d 3.19e3.25 (m, 4H), 7.33 (s, br s, 1H), 7.44e7.48
(m, 1H), 7.63e7.67 (m, 1H), 7.71e7.56 (m, 2H), 7.86 (d, J¼8.0 Hz, 1H),
7.95 (s, 1H), 8.10 (d, J¼8.5 Hz, 1H), 8.52 (s, br s, 1H), 8.90 (s, br s, 1H);
4.3.30. (E)-3-(4-Chlorobenzylidene)-2,3-dihydro-1H-cyclopenta[b]
quinoline (3ic). Yellow solid (91%, 132.6 mg); mp 142e144 ꢀC; Rf
(20% EtOAc/hexane) 0.51; nmax (KBr) 3042, 2915, 1603, 1563, 1497,
13C NMR (100 MHz, CDCl3):
d 27.8, 29.1, 120.9, 126.1, 127.5, 128.4,
129.0, 129.3, 131.5, 135.7, 136.9, 143.2, 147.9, 148.3, 150.7, 161.4;
HRMS (ESI) calcd for C18H15N2 [MþH]: 259.1235, found: 259.1239.
1489, 1428, 1406, 1272, 1134, 1095, 1011, 895, 829, 749 cmꢂ1 1H
;
NMR (400 MHz, CDCl3):
d
3.17e3.25 (m, 4H), 7.35e7.38 (m, 2H),
4.3.36. (E)-3-(Furan-2-ylmethylene)-2,3-dihydro-1H-cyclopenta[b]
quinoline (3il). Yellow solid (77%, 95.6 mg). Mp 147e150 ꢀC; Rf (20%
EtOAc/hexane) 0.51; nmax (KBr) 3076, 2927, 1598, 1560, 1481, 1404,
7.44e7.48 (m, 1H), 7.53 (d, J¼8.5 Hz, 2H), 7.63e7.67 (m, 1H),
7.71e7.76 (m, 2H), 7.94 (s, 1H), 8.10 (d, J¼8.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3):
d
27.9, 29.0, 123.5, 125.9, 127.5, 128.4, 128.7,
1275, 1135, 1021, 931, 878, 735 cmꢂ1 1H NMR (400 MHz, CDCl3):
;
128.9, 129.2, 130.6, 131.4, 133.1, 136.0, 136.9, 141.4, 148.3, 161.9;
d 3.21 (s, br s, 4H), 6.49e6.53 (m, 2H), 7.41e7.45 (m, 1H), 7.51e7.52
HRMS (ESI) calcd for
292.0892.
C
19H15ClN [MþH]: 292.0893, found:
(m, 1H), 7.60e7.65 (m, 2H), 7.69 (d, J¼8.0 Hz, 1H), 7.90 (s, 1H), 8.06
(d, J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 27.5, 28.7, 111.3,
111.9, 112.2, 125.7, 127.4, 128.2, 128.8, 129.1, 131.1, 137.7, 138.9, 142.8,
4.3.31. (E)-3-(2-Chlorobenzylidene)-2,3-dihydro-1H-cyclopenta[b]
quinoline (3ic0). Yellow solid (92%, 133.7 mg); mp 142e144 ꢀC; Rf
(20% EtOAc/hexane) 0.51; nmax (KBr) 3048, 2880, 1630, 1554, 1500,
1604,1438,1408,1240,1152,1037, 946, 880, 832, 734 cmꢂ1; 1H NMR
148.3, 154.0, 161.7; HRMS (ESI) calcd for
248.1075, found: 248.1074.
C
17H14NO [MþH]:
4.3.37. (E)-3-(2,2-Dimethylpropylidene)-2,3-dihydro-1H-cyclopenta
[b]quinoline (3io). Yellow solid (24%, 28.9 mg); mp 112e114 ꢀC; Rf
(20% EtOAc/hexane) 0.63; nmax (KBr) 3059, 2985, 2945, 1652, 1608,
(400 MHz, CDCl3): d 3.10e3.18 (m, 4H), 7.20e7.24 (m,1H), 7.27e7.31
(m, 1H), 7.44e7.47 (m, 2H), 7.59e7.61 (m, 1H), 7.63e7.67 (m, 1H),
7.71 (d, J¼8.0 Hz, 1H), 7.92 (s, 1H), 8.06e8.07 (m, 1H), 8.14 (d,
1564, 1496, 1402, 1360, 1265, 1231, 1199, 1134, 954, 884, 756 cmꢂ1
;
J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
27.9, 29.0, 121.2, 126.0,
1H NMR (400 MHz, CDCl3):
3.11e3.14 (m, 2H), 6.95e6.96 (m, 1H), 7.39e7.43 (m, 1H), 7.58e7.62
d 1.28 (s, 9H), 3.01e3.05 (m, 2H),
126.4, 127.4, 128.41, 128.43, 128.8, 129.46, 129.53, 129.8, 131.3, 134.7,

2138
Z. Jamal et al. / Tetrahedron 72 (2016) 2132e2138
(m,1H), 7.69 (d, J¼8.5 Hz,1H), 7.89 (s,1H), 8.04 (d, J¼8.5 Hz,1H); 13
C
2146e2159; (c) Yan, G.; Wu, X.; Yang, M. Org. Biomol. Chem. 2013, 11,
5558e5578.
NMR (100 MHz, CDCl3):
d 26.8, 27.7, 30.3, 33.4, 125.4, 127.3, 128.1,
6. For selected examples on the proposed reactive enamide, see (a) Zhu, Z.-Q.; Bai,
P.; Huang, Z.-Z. Org. Lett. 2014, 16, 4881e4883; (b) Wang, F.-F.; Luo, C.-P.; Deng,
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Y.; Uozumi, Y.; Zou, K. RSC Adv. 2014, 4, 57875e57884; (d) Gao, X.; Zhang, F.;
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Y.; Chavan, S. S. RSC Adv. 2013, 3, 20281e20286; (f) Li, Y.; Guo, F.; Zha, Z.; Wang,
Z. Chem.dAsian J. 2013, 8, 534e537; (g) Graves, V. B.; Shaikh, A. Tetrahedron
Lett. 2013, 54, 695e698; (h) Qian, B.; Shi, D.; Yang, L.; Huang, H. Adv. Synth.
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128.5, 129.2, 131.1, 136.2, 136.9, 137.0, 148.2, 162.8; HRMS (ESI) calcd
for C17H20N [MþH]: 238.1595, found: 238.1595.
4.3.38. 1,3-Diphenyl-4-(quinolin-2-yl)butan-1-one
yellow solid (20%, 35.2 mg): Rf (20% EtOAc/hexane) 0.29; 1H NMR
(400 MHz, CDCl3): 3.32e3.49 (m, 4H), 4.05e4.11 (m, 1H),
(3ar).19 Light
d
7.11e7.29 (m, 6H), 7.31e7.36 (m, 2H), 7.39e7.49 (m, 2H), 7.61e7.65
(m, 1H), 7.71 (d, J¼8.0 Hz, 1H), 7.82e7.84 (m, 2H), 7.95e7.99 (m,
2H); 13C NMR (100 MHz, CDCl3):
d 41.4, 44.4, 45.8, 121.9, 125.8,
126.5, 126.8, 127.5, 127.6, 128.0, 128.38, 128.43, 128.9, 129.2, 132.8,
136.0, 137.2, 144.1, 147.9, 160.4, 198.7; HRMS (ESI) Calcd for
7. Jamal, Z.; Teo, Y.-C. RSC Adv. 2015, 5, 26949e26953.
C
25H22NO [MþH]: 352.1701, found: 352.1703.
8. For selected reviews on indium catalysis, see (a) Yadav, J. S.; Antony, A.; George,
J.; Subba Reddy, B. V. Eur. J. Org. Chem. 2010, 591e605; (b) Lee, P. H. Bull. Korean
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Acknowledgements
We would like to thank the National Institute of Education,
Nanyang Technological University (RP 5/13 TYC) for their generous
financial support.
Supplementary data
Supplementary data (copies of 1H and 13C NMR spectra of all
new compounds) associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2016.03.004.
10. Co Lewis acid was previously studied for the catalytic direct alkenylation of 2-
methylquinolines with aldehydes, see Jamal, Z.; Teo, Y.-C. Synlett 2014,
2049e2053.
11. For selected catalyst-free procedures, see (a) Xu, L.; Shao, Z.; Wang, L.; Zhao, H.;
Xiao, J. Tetrahedron Lett. 2014, 55, 6856e6860; (b) Xu, L.; Shao, Z.; Wang, L.;
Xiao, J. Org. Lett. 2014, 16, 796e799; (c) Nageswara Rao, N.; Meshram, H. M.
Tetrahedron Lett. 2013, 54, 5087e5090; (d) Li, H.-Y.; Xing, L.-J.; Xu, T.; Wang, P.;
Liu, R.-H.; Wang, B. Tetrahedron Lett. 2013, 54, 858e860; (e) Yan, Y.; Xu, K.; Fang,
Y.; Wang, Z. J. Org. Chem. 2011, 76, 6849e6855; (f) Staderini, M.; Cabezas, N.;
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