Ligand promoted and controlled palladium-catalyzed intramolecular Heck reaction of homoallyl alcohols: A facile synthesis of cyclopentaannulated quinolines

Article abstract of DOI:10.1016/j.tet.2012.08.088

Bidentate phosphine ligands in palladium-catalyzed intramolecular Heck reactions of 2-chloroquinolin-3-yl-(1-homoallyl)alcohols are described to afford facile synthesis of 3-methylene-2,3-dihydro-1H-cyclopenta[b]quinolines in improved yields. We further observed using bulky aromatic phosphine ligand in Pd-catalyzed intermolecular Heck coupling reaction at olefinic centers with iodobenzene also favored exclusively Heck products in excellent yield.

Full text of DOI:10.1016/j.tet.2012.08.088

Tetrahedron 68 (2012) 9206e9210
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ligand promoted and controlled palladium-catalyzed intramolecular Heck
reaction of homoallyl alcohols: a facile synthesis of cyclopentaannulated
quinolines
,
a
,
,
Radhey M. Singh a , Atish Chandra b, Neha Sharma a, Bhawana Singh a c, Ritush Kumar a
*
a Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India
b Centre of Biomedical Magnetic Resonance, SGPGI Campus, Lucknow 226 014, India
c Division of Organic Chemistry, National Chemical Laboratory, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 June 2012
Received in revised form 18 August 2012
Accepted 28 August 2012
Available online 1 September 2012
Bidentate phosphine ligands in palladium-catalyzed intramolecular Heck reactions of 2-chloroquinolin-
3-yl-(1-homoallyl)alcohols are described to afford facile synthesis of 3-methylene-2,3-dihydro-1H-cy-
clopenta[b]quinolines in improved yields. We further observed using bulky aromatic phosphine ligand in
Pd-catalyzed intermolecular Heck coupling reaction at olefinic centers with iodobenzene also favored
exclusively Heck products in excellent yield.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Ligand promoted
Homoallyl alcohol
Palladium-catalyzed
Heck cyclization
Quinoline
1. Introduction
bromobenzene.7 It is well established that these Pd-catalyzed Heck
coupling reactions illustrate same catalytic cycle with all ligands on
Transition metal-catalyzed cyclization reactions have been used
in the preparation of carbocycles and heterocycles.1 Amongst var-
ious metal-catalyzed reactions, palladium-catalyzed intra-
molecular reactions across alkenes and alkynes have been
extensively used by both cyclic carbopalladation and annulation
processes in the synthesis of carbo- and heterocyclic compounds.2
Kundig et al. have reported Pd-catalyzed intramolecular Heck re-
action of 2-chlorophenyl-1-homoallyl alcohol complexes to the
synthesis of Heck product, methylene indane complex.3 Similarly,
Zhai et al. have also reported the synthesis of 1-hydroxy-3-
Pd(0), but there are no mechanistic consequences of ligands vari-
ations along these lines. However, there was report in 1986 that
bulky aromatic phosphine ligands favored both stereoselectivity
and high yields of the desired product formation.8 Lipshutz et al.
have also reported the stereoselectivity and high yields of Negishi
couplings at olefinic centers by ligand variations.9 Similarly, ligand-
controlled Pd-catalyzed intramolecular and intermolecular re-
actions favoring Heck products have been reported in high yields.10
Recently, Buchwald et al. have reported the ligands-controlled
transformation favoring synthesis of various five, six, and seven
membered heterocycles from N-(o-vinylphenyl)-o-chloroaryl
amines by Pd-catalyzed intramolecular cyclization.11
Previously, we reported Pd-catalyzed intramolecular Heck re-
actions of 2-chloroquinolin-3-yl-(1-homoallyl)alcohols 1.12 In this
study, monodentate Ph3P ligand with Pd(OAc)2 afforded moderate
yields of Heck products. We envisioned that the improved yields of
Heck products could be obtained from bulky aromatic phosphine
ligands in combination with Pd(OAc)2. Therefore, we initially
evaluated commercially available bulky aromatic phosphine li-
gands with Pd(OAc)2 for intramolecular Heck reactions of com-
pounds 1 under similar reaction conditions. In an initial study, it
was found that bidentate phosphine ligands were effective to afford
exclusively Heck products in high yields. Thus, herein we report
methylene-cyclopent[c]pyridine
from
3-bromopyridyl-4-
homoallyl alcohol.4 In contrast, Ray et al. have reported Heck-
isomerization products from 2-bromovinyl-1-allyl alcohols and 2-
bromovinyl-1-homoallyl alcohols, respectively, via Pd-catalyzed
intramolecular Heck reactions.5 The tandem Heck-isomerization
reactions are well documented in the coupling of allylic and
homoallylic alcohols with aryl halides.6 However, Crawley et al.
have recently reported poor yields of Heck isomerization products
from Heck coupling reactions of aryl homoallyl alcohol with
* Corresponding author. Tel.: þ91 542 6702482; fax: þ91 542 2368127; e-mail
address: rmohan@bhu.ac.in (R.M. Singh).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.088

R.M. Singh et al. / Tetrahedron 68 (2012) 9206e9210
9207
Table 2
bidentate phosphine ligands promoted intramolecular Heck re-
Selective intramolecular cyclization of 1 using BINAP ligand
actions that aid facile synthesis of 1-hydroxy-3-methylene-2,3-
dihydro-1H-cyclopenta[b]quinolines in improved yields.
S. No.
1
Substrate
Time (h)
Yield of 2 (%)
OH
2. Results and discussion
2
83
86
79
80
78
76
Cl
N
1a
2-Chloro-3-(1-hydroxy-but-3-en-1-yl)-quinoline (1a) was cho-
sen as the model substrate for Pd-catalyzed intramolecular Heck
reactions. In our previous study, PPh3 (10 mol %) ligand in combi-
nation with Pd(OAc)2 (5 mol %), and Et3N (2 equiv) in acetonitrile at
80 ꢀC provided the Heck product 2a in a moderate yield of 46%
along with other side product 3a (Scheme 1, Table 1, entry 1). This
observation prompted us further to evaluate the reactions with the
commercially available bulky phosphine ligand under similar re-
action conditions to improve the yield of Heck product (Table 1,
entries 2e6). Using bulky monodentate ligands, such as Cy3P and
(o-tol)3P also provided the mixture of the products but with the
improvement in the yield of Heck product (entries 2e3). All avail-
able bidentate ligands tested (5 mol %) led to exclusively Heck
product (entries 4e6). BINAP was found to be best ligand, which
gave best yield of Heck product 2a (83% entry 4). We further
screened various bases with this catalytic system (entries 7e10).
Changing the base from Et3N to DBU the yield decreased signifi-
cantly (entry 7). Reactions with other bases, such as DABCO, Cs2CO3,
and K2CO3 gave only traces or none of the product, respectively
(entries 8e10). Finally, we probed various solvents (entries 10e13).
DMF and DMA solvents led to slower reaction rate with lower yields
(entries 11e12). Reactions in DCE and dioxane gave only traces of
the product (entries 13e14). Thus, the optimal conditions for
intramolecular Heck reaction was found as 1 mmol substrate 1a in
combination with 5 mol % Pd(OAc)2, 5 mol % BINAP and 2 equiv of
Et3N base in 5 mL acetonitrile at 80 ꢀC for 2 h.
OH
2
3
4
5
6
1.5
1.5
1
Cl
N
1b
OH
O
N
1c
Cl
OH
Cl
N
1d
OH
4
Cl
N
1e
OH
4
Cl
N
1f
OH
Table 1
Optimization of the reaction conditions
7
2.5
89
40
79
82
S. No Catalyst
Ligand
Base
Solvent
Time (h) Yield (%)
Cl
N
1g
Cl
2a
3a
1
2
3
4
Pd(OAc)2 10% PPh3
Pd(OAc)2 10% Cy3P
Pd(OAc)2 10%(o-Tol)3P
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%DPPE
TEA
TEA
TEA
TEA
TEA
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
4
3
3
2
8
46
62
65
83
65
70
Trace
20
Trace
d
16
15
13
d
d
d
d
d
d
d
d
d
d
d
OH
Br
8
8
Cl
N
1h
5
6
Pd(OAc)2 5%XanthPhos TEA
3
7
8
9
10
11
12
13
14
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%BINAP
Pd(OAc)2 5%BINAP
DBU
DABCO CH3CN
Cs2CO3 CH3CN
K2CO3
TEA
TEA
24
24
24
24
15
15
24
OH
9
3
CH3CN
DMF
DMA
DCE
Cl
N
1i
66
68
Trace
Trace
TEA
TEA
O
Dioxane 24
10
2
Bold values signify optimized reaction condition.
Cl
N
1j
OH
O
OH
Pd(OAc)2/Ligand/Base
Solvent, 80oC
+
N
1a
Cl
N
N
R
R
R
CH3
However, vice-versa with small variations in yields are found with
electron donating and withdrawing substituents at position-7, re-
spectively (entries 3, 4, 7). No significant variations in yields were
observed with electron donating substituents at position-8, how-
ever, the longer reaction periods could be attributed to electronic
effects (entries 5, 6). To generalize the scope of reaction and effect
of fused-benzene ring, pyridine analogue with phenyl group at
position-6 tested led to slower reaction rate with no significant
change in the yield (entry 9), indicating benzene-fused pyridine
ring enhanced rate of Heck reactions.
2a
3a
R = H, Me,Et, OMe, Cl, Br
Scheme 1. Intramolecular Heck cyclization of 1a.
With an optimized catalytic system for intramolecular Heck
reaction with substrate 1a in hand, the scope of optimized catalytic
system for Heck reaction was evaluated with other substrates 1bei
affording the cyclized products 2bei in good yields. Results are
summarized in Table 2. The electron donating substituent at
position-6 enhances the yield (entry 2) where as with electron
withdrawing substituent the yield decreases significantly (entry 8).
To further understand the effect of hydroxyl group of compound
1a in Heck reaction, hydroxy group in substrate 1a was first

9208
R.M. Singh et al. / Tetrahedron 68 (2012) 9206e9210
transformed into methoxy group using NaH and CH3I in THF at
room temperature to afford the substrate 1j and tested under op-
timized intramolecular Heck reaction using BINAP and PPh3 li-
gands, respectively, to afford Heck-product 2j. BINAP ligand led to
no variation in yield and reaction time (Scheme 2, Table 2, entry 10),
however, PPh3 ligand provided same yield in shorter reaction time
Scheme 2. We assume this as an indication that with smaller PPh3
ligand OH group in 1a competes for the same Pd-coordination site
as alkene affording mixture of products with longer reaction time
and found absent with bulky BINAP ligand.
a. Intramolecular coordination of the quinolineepalladium a with
the carbonecarbon double bond yields the complex b, which in-
tramolecularly adds across the carbonecarbon double bond pro-
ducing the annulated palladium intermediate c. Subsequent
hydride elimination from the intermediate c affords complex d,
which contains the tricyclic exo-methylene as -bonded ligand. The
dissociation of -bonded HPdLnCl from d affords Heck product 2
(Path A). While addition of -bonded HPdLnCl across exo-methy-
b-
p
p
p
lene bond in d affords intermediate e, which subsequently trans-
form to isomerized product 3 (Path B).
3
O
O
OH
O
Et3NHCl
NaH/CH3I
THF, RT
Pd(OAc)2/L/TEA
Pd0Ln
1
CH3CN, 80oC
N
1a
Cl
3
Et3N
N
1j
Cl
N
OH
L
2j
BINAP 2h 82%
PPh3 1h 80%
PdLnHCl
OH
PdHClLn-1
OH
N
Pdl
Scheme 2. Intramolecular Heck cyclization of 1j.
a
g
Path A
During the course of our investigation to improve the yield of
Heck products we characterized low yield product 3a as 3-methyl-
2,3-dihydro-1H-cyclopenta[b]quinoline-1-one from its spectral
and analytical data and could be an isomerized Heck product. It
would be formed via an intermediate compound 2a. To evaluate the
substrate 3a as an isomerized Heck product, substrate 2a was tested
using Ph3P ligand under optimized conditions led to complete
conversion in 1 h with 40% yield and characterized as Heck isom-
erization product 3a Scheme 3. This result is clearly consistent with
olefin migration via hydropalladation and dehydropalladation
mechanism and leads to enol formation, which tautomerizes to
ketone affording 3a. Failing similar reaction with BINAP could be
attributed to larger size of the ligand.
2
OH
OH
OH
PdHClLn-1
PdHClLn-1
f
OH
d
PdLn-1Cl
OH
-
h
Path B
y
b
d
e
r
l
i
m
i
d
e
i
n
a
t
i
o
PdClLn-1
n
c
PdClLn-1
Scheme 5. Tentative mechanism.
3. Conclusion
O
In conclusion, we have developed bulky aromatic phosphine
ligand-promoted and controlled Pd-catalyzed intramolecular Heck
reaction conditions affording facile synthesis of 3-methylene-2,3-
dihydro-1H-cyclopenta[b]quinolines in good yields. We also dem-
onstrated that bulky phosphine ligand favored exclusively Heck
products in coupling reaction of olefinic center with iodobenzene.
O
Pd(OAc)2/BINAP/Et3N
CH3CN, 80 0C, 1h
Pd(OAc)2/PPh3/Et3N
CH3CN, 80 0C, 1h
2a
N
N
CH3
CH3
3a
3a
Not Formed
Scheme 3. Palladium-catalyzed isomerization of 2.
4. Experimental section
4.1. General
To further understand the scope and limitation of ligands, in-
termolecular Heck coupling reactions was undertaken. Thus, Heck
coupling reactions of olefinic center of aryl homoallyl alcohols 2a
with iodobenzene using both bidentate BINAP and monodentate
Ph3P ligands were tested under optimized reaction conditions
Schemes 4 and 5. BINAP ligand afforded exclusively Heck product in
2 h with 85% yield while Ph3P ligand yielded a mixture of Heck and
Heck-isomerized products in 4 h with 72% and 7% yields, re-
spectively. This further evidenced that bulky aromatic phosphine
ligands favored Heck products exclusively in both inter- and
intramolecular Heck coupling reactions.
All reactions were performed under nitrogen atmosphere. All
commercially available reagents were used without further purifi-
cation. Acetonitrile was fractionally distilled from CaH2 under ni-
trogen. Column chromatography was performed with silica gel
(60e120 mesh) obtained from Qualigens fine chemicals. The
combined organic layers were dried over MgSO4. Solvents were
evaporated under reduced pressure. All yields given refer to as
isolated yields. Melting points are uncorrected. NMR spectra were
recorded on 300 MHz and 75 MHz spectrometers. Chemical shifts
are reported in parts per million. Coupling constants (J values) are
reported in hertz. IR spectra recorded on FT-IR spectrometer.
PhI/Pd(OAc)2
O
OH
OH
/PPh3/TEA
/CH3CN/
PhI/Pd(OAc)2/BINAP
+
2a
80 oC, 4h
TEA/CH3CN/80 o
2 h
C
N
N
85%
N
Ph
Ph
5
4
Ph
4
7%
72%
4.2. General procedure for palladium-catalyzed intra-
molecular cyclization of compounds 1aej using BINAP as
ligand
Scheme 4. Intermolecular Heck reaction on 2a.
A plausible mechanism for this Pd(0)-catalyzed intramolecular
cyclization of alkenes 1 to products 2 and 3 is shown in Scheme 5.
The oxidative addition of Pd(0) species to the 3-substituted alkenyl-
2-chloroquinoline 1 leads to the quinolineepalladium intermediate
To a suspension of Pd(OAc)2 (5 mol %), BINAP (5 mol %) and
alkenyl quinoline 1aej (1 mmol) in CH3CN (5 mL) was added Et3N
(2 equiv) and stirred at 80 ꢀC. After completion of the reaction (as
monitored by TLC), the mixture was cooled and solvent was

R.M. Singh et al. / Tetrahedron 68 (2012) 9206e9210
9209
evaporated under reduced pressure. The products obtained were
separated by column chromatography on silica gel using ethyl ac-
etate and hexane (1:9) as eluent gave the pure products 2aej.
126.0, 126.1, 128.1, 128.2, 132.7, 137.5, 143.2, 145.2, 147.8, 157.8; IR
(KBr): 3427, 3298 cmꢁ1
.
4.2.7. 6-Chloro-3-methylene-2,3-dihydro-1H-cyclopenta[b]quinolin-
4.2.1. 3-Methylene-2,3-dihydro-1H-cyclopenta[b]quinolin-1-ol
1-ol (2g). White solid; yield: 89%; mp 125e126 ꢀC; 1H NMR
(2a). White solid; yield: 83%; mp 145 ꢀC; 1H NMR (300 MHz,
(300 MHz, CDCl3):
d
¼2.09 (d, J¼6.6, 1H, OH), 2.83 (d, J¼16.8 Hz, 1H,
CDCl3):
d
¼2.09 (d, J¼7.0 Hz, 1H, OH), 2.81 (d, J¼17.0 Hz, 1H, CH2),
CH2), 3.38 (dd, J¼16.8, 7.5 Hz, 1H, CH2), 5.42 (s, 1H, ]CH2), 5.47 (br
s, 1H, CHOH), 6.34 (s, 1H, ]CH2), 7.59 (s, 1H, H-5), 7.69 (d, J¼7.2 Hz,
1H, H-7), 8.04 (d, J¼7.2 Hz, 1H, H-8), 8.65 (s, 1H, H-9); 13C NMR
3.36 (dd, J¼17.0, 7.0 Hz, 1H, CH2), 5.37 (s, 1H, ]CH2), 5.42 (m, 1H,
CH), 6.31 (s, 1H, ]CH2), 7.50 (t, J¼8.0 Hz, 1H, H-6), 7.70 (t, J¼8.0 Hz,
1H, H-7), 7.81 (d, J¼8.1 Hz, 1H, H-5), 8.01 (d, J¼8.4 Hz, 1H, H-8), 8.21
(75 MHz, CDCl3):
d
¼41.1, 70.5, 111.2, 126.5, 127.2, 128.1, 129.1, 132.6,
(s, 1H, H-4); 13C NMR (75 MHz, CDCl3):
d¼41.3, 70.8, 110.4, 126.3,
132.6, 135.6, 138.6, 144.3, 160.0; HRMS calcd for C13H11NOCl
128.1, 128.2, 129.4, 129.7, 132.7, 138.2, 144.7, 149.2, 159.1; IR (KBr):
3605, 3410 cmꢁ1; MS: m/z¼198 [MþH]þ, 180. HRMS calcd for
C13H12NO [MþH]þ 198.0918, found 198.0912.
[MþH]þ 232.0529, found 232.0532.
4.2.8. 7-Bromo-3-methylene-2,3-dihydro-1H-cyclopenta[b]quinolin-
1-ol (2h). Brown solid; yield: 40%; mp 149e150 ꢀC; 1H NMR
4.2.2. 7-Methyl-3-methylene-2,3-dihydro-1H-cyclopenta[b]quinolin-
(300 MHz, CDCl3):
d
¼2.07 (d, J¼6.9 Hz, 1H, OH), 2.84 (d, J¼17.1 Hz,
1-ol (2b). White solid; yield: 86%; mp 144 ꢀC; 1H NMR (300 MHz,
1H, CH2), 3.38 (dd, J¼17.1, 7.5 Hz, 1H, CH2), 5.40 (m, 2H, CHOH and
]CH2), 6.32 (s, 1H, ]CH2), 7.75 (d, J¼6.9 Hz, 1H, H-5), 7.95 (m, 2H,
CDCl3):
d
¼2.01 (d, J¼7.2 Hz, 1H, OH), 2.53 (s, 3H, CH3), 2.81 (d,
J¼17.0 Hz, 1H, CH2), 3.37 (dd, J¼17.0, 7.5 Hz, 1H, CH2), 5.35 (s, 1H, ]
CH2), 5.41 (m, 1H, CHOH), 6.28 (s, 1H, ]CH2), 7.54 (d, J¼8.7 Hz, 1H,
H-6), 7.57 (s, 1H, H-8), 8.01 (d, J¼8.4 Hz, 1H, H-5), 8.12 (s, 1H, H-9);
H-6 and H-8), 8.12 (s, 1H, H-9); 13C NMR (75 MHz, CDCl3):
d¼41.2,
70.6, 110.9, 120.1, 129.2, 130.0, 130.9, 131.6, 133.1, 139.1, 144.3, 147.7,
159.5.
13C NMR (75 MHz, CDCl3):
d
¼21.5, 41.4, 70.8, 109.8, 126.9, 128.2,
129.0, 131.9, 132.1, 136.2, 138.2, 144.7, 147.8, 158.2; IR (KBr): 3410,
3275 cmꢁ1; MS: m/z¼212 [MþH]þ, 194. HRMS calcd for C14H14NO
[MþH]þ 212.1075, found 212.1081.
4.2.9. 7-Methylene-3-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridin-
5-ol (2i). White solid; yield: 79%; mp 80e81 ꢀC; 1H NMR (300 MHz,
CDCl3):
d
¼2.01 (d, J¼6.9, 1H, OH), 2.75 (d, J¼17.1 Hz, 1H, CH2), 3.33
(dd, J¼17.1, 7.5 Hz, 1H, CH2), 5.25 (s, 1H, ]CH2), 5.35 (br s, 1H,
CHOH), 6.07 (s, 1H, ]CH2), 7.40e7.50 (m, 3H, phenyl), 7.58 (m, 2H,
phenyl), 7.97 (s, 1H, H-5), 8.80 (s, 1H, H-7); 13C NMR (75 MHz,
4.2.3. 6-Methoxy-3-methylene-2,3-dihydro-1H-cyclopenta[b]quino-
lin-1-ol (2c). White solid; yield: 79%; mp 135 ꢀC; 1H NMR
(300 MHz, CDCl3):
d
¼2.01 (d, J¼7.0 Hz, 1H, OH), 2.81 (d, J¼17.0 Hz,
CDCl3):
d
¼41.1, 70.9, 108.1, 127.0, 128.1, 129.0, 131.8, 136.5, 137.6,
1H, CH2), 3.35 (dd, J¼17.0, 7.5 Hz, 1H, CH2), 3.96 (s, 3H, OCH3), 5.35
(s, 1H, ]CH2), 5.41 (m, 1H, CHOH), 6.27 (s, 1H, ]CH2), 7.15 (d,
J¼9.0 Hz, 1H, H-7), 7.43 (s, 1H, H-5), 7.68 (d, J¼9.0 Hz, 1H, H-8), 8.14
140.4, 144.5, 149.4, 157.0; HRMS calcd for C15H14NO [MþH]þ
224.1075, found 224.1075.
(s, 1H, H-9); 13C NMR (75 MHz, CDCl3):
d
¼41.3, 55.5, 70.7, 107.1,
4.2.10. 1-Methoxy-3-methylene-2,3-dihydro-1H-cyclopenta[b]quino-
109.9, 119.6, 123.5, 129.0, 132.6, 136.3, 144.9, 151.0, 159.1, 161.0; IR
(KBr): 3435 cmꢁ1; MS: m/z¼228 [MþH]þ, 210. HRMS calcd for
C14H14NO2 [MþH]þ 228.1024, found 228.1023.
line (2j). Liq.; yield: 82%; 1H NMR (300 MHz, CDCl3):
d
¼2.9 (d,
J¼16.8 Hz, 1H, CH2), 3.2 (dd, J¼16.8, 5.1 Hz, 1H, CH2), 3.5 (s, 3H,
OCH3), 5.0 (t, J¼3.0 Hz, 1H, CHOCH3), 5.4 (s, 1H, ]CH), 6.3 (s, 1H, ]
CH2), 7.5 (t, J¼7.8 Hz, 1H), 7.7 (t, J¼8.4 Hz, 1H), 7.8 (d, J¼8.1 Hz, 1H),
4.2.4. 6-Methyl-3-methylene-2,3-dihydro-1H-cyclopenta[b]quinolin-
8.1 (d, J¼8.7 Hz, 1H), 8.2 (s, 1H); 13C NMR (75 MHz, CDCl3):
¼37.4,
d
1-ol (2d). White solid; yield: 80%; mp 148 ꢀC; 1H NMR (300 MHz,
56.1, 78.8, 110.1, 126.2, 128.0, 128.1, 129.4, 129.6, 133.0, 135.9, 145.0,
CDCl3):
d
¼2.00 (d, J¼6.9, 1H, OH), 2.56 (s, 3H, CH3), 2.82 (d,
149.3, 159.5; IR (KBr): 2926, 1109 cmꢁ1
.
J¼17.0 Hz, 1H, CH2), 3.36 (dd, J¼17.0, 7.5 Hz, 1H, CH2), 5.35 (s, 1H, ]
CH2), 5.40 (br s, 1H, CHOH), 6.29 (s, 1H, ]CH2), 7.35 (d, J¼8.1 Hz,1H,
H-7), 7.71 (d, J¼8.1 Hz, 1H, H-8), 7.89 (s, 1H, H-5), 8.16 (s, 1H, H-9);
4.2.11. 3-Methyl-2,3-dihydro-1H-cyclopenta[b]quinolin-1-one
(3a). White solid; yield: 16%; mp 125 ꢀC; 1H NMR (300 MHz,
13C NMR (75 MHz, CDCl3):
d
¼21.8, 41.3, 70.8, 110.0, 126.3, 127.7,
CDCl3):
d¼1.58 (d, J¼7.2 Hz, 3H, CH3), 2.50 (dd, J¼19.2, 4.2 Hz, 1H,
128.3, 128.6, 132.4, 137.5, 140.1, 144.7, 149.4, 159.0; IR (KBr):
3610 cmꢁ1; MS: m/z¼212 [MþH]þ, 194. HRMS calcd for C14H14NO
[MþH]þ 212.1075, found 212.1083.
CH2), 3.15 (dd, J¼19.2, 8.4 Hz, 1H), 3.66 (m, 1H), 7.59 (t, J¼7.2 Hz,
1H), 7.85 (t, J¼7.5 Hz, 1H), 7.98 (d, J¼8.1 Hz, 1H), 8.15 (d, J¼8.4 Hz,
1H), 8.55 (s, 1H). 13C NMR (75 MHz, CDCl3):
d¼20.4, 35.5, 45.5,
126.8, 126.9, 127.2, 129.2, 130.4, 132.5, 133.2, 151.9, 174.6, 204.4; IR
(KBr): cmꢁ1. 2962, 1711, 1610; MS: m/z¼198 [MþH]þ. HRMS (EI): m/
z calcd for C13H11NO: 197.0841; found: 197.0844. HRMS calcd for
C13H12NO [MþH]þ 198.0918, found 198.0926.
4.2.5. 5-Methyl-3-methylene-2,3-dihydro-1H-cyclopenta[b]quinolin-
1-ol (2e). White solid; yield: 78%; mp 164 ꢀC; 1H NMR (300 MHz,
CDCl3):
d
¼1.96 (d, J¼7.2 Hz, 1H, OH), 2.80 (d, J¼17.0 Hz, 1H, CH2),
2.85 (s, 3H, CH3), 3.41 (dd, J¼17.0, 7.5 Hz, 1H, CH2), 5.35 (s, 1H, ]
CH2), 5.45 (m, 1H, CHOH), 6.36 (s, 1H, ]CH2), 7.49 (t, J¼7.5 Hz, 1H,
H-7), 7.55 (d, J¼7.0 Hz, 1H, H-6), 7.66 (d, J¼8.0 Hz, 1H, H-8), 8.18 (s,
4.3. General procedure for palladium-catalyzed in-
termolecular reaction on compound 2
1H, H-9); 13C NMR (75 MHz, CDCl3):
d¼17.9, 41.3, 71.0, 109.7, 126.0,
126.1, 128.1, 129.8, 132.6, 137.4, 137.6, 145.1, 148.4, 157.9; IR (KBr):
3692, 3410 cmꢁ1; HRMS calcd for C14H14NO [MþH]þ 212.1075,
found 212.1083.
To a suspension of Pd(OAc)2 (5 mol %), PPh3 (10 mol %) or BINAP
(5 mol %), 3 (1 mmol), and iodobenzene (1.1 mmol) in CH3CN
(10 mL) was added Et3N (2 mmol) and stirred at 80 ꢀC till com-
pletion of the reaction (as monitored by TLC). The mixture was
cooled and solvent was evaporated under reduced pressure. The
products obtained were separated by column chromatography on
silica gel using ethyl acetate and hexane (1:9) as eluent gave the
pure product.
4.2.6. 5-Ethyl-3-methylene-2,3-dihydro-1H-cyclopenta[b]quinolin-
1-ol (2f). White solid; yield: 76%; mp 104 ꢀC; 1H NMR (300 MHz,
CDCl3):
d
¼1.40 (t, J¼7.5 Hz, 3H, CH3), 1.94 (d, J¼7.2 Hz, 1H, OH), 2.83
(d, J¼17.0 Hz, 1H, CH2), 3.31e3.41 (m, 3H, CH2, CH2CH3), 5.34 (s, 1H,
]CH2), 5.43 (m, 1H, CHOH), 6.35 (s, 1H, ]CH2), 7.42 (t, J¼7.5 Hz,1H,
H-7), 7.55 (d, J¼6.6 Hz, 1H, H-6), 7.65 (d, J¼8.0 Hz, 1H, H-8), 8.17 (s,
4.3.1. 3-Benzylidene-2,3-dihydro-1H-cyclopenta[b]quinolin-1-ol
1H, H-9); 13C NMR (75 MHz, CDCl3):
d¼15.1, 24.5, 41.2, 70.9, 109.5,
(4). White solid; yield: 85%; mp 219e220 ꢀC; 1H NMR (300 MHz,

9210
R.M. Singh et al. / Tetrahedron 68 (2012) 9206e9210
2. (a) Negishi, E.; Coperet, C.; Ma, S.; Liou, S. Y.; Liu, F. Chem. Rev. 1996, 96, 365; (b)
CDCl3):
d
¼2.27 (d, J¼7.5 Hz, 1H, OH), 3.10 (d, J¼17.1 Hz, 1H, CH2),
Li, J. J.; Gribble, G. W. Palladium in Heterocyclic Chemistry; Pergamon: Oxford,
2000; (c) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644; (d) Zeni, G.; Larock,
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Org. Chem. 2007, 72, 1538; (f) Larock, R. C. J. Organomet. Chem. 1999, 576, 111; (g)
Collins, I. J. Chem. Soc., Perkin Trans. 1 2000, 2845; (h) Liang, Z.; Ma, S.; Yu, J.; Xu,
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A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2007, 129, 6880; (j)
Alberico, D.; Rudolph, A.; Lautens, M. J. Org. Chem. 2007, 72, 775; (k) Patil, N. T.;
Wu, H.; Yamamoto, Y. J. Org. Chem. 2007, 72, 6577; (l) Doi, T.; Iijima, Y.; Takasaki,
M.; Takahashi, T. J. Org. Chem. 2007, 72, 3667; (m) Thansandote, P.; Raemy, M.;
Rudolph, A.; Lautens, M. Org. Lett. 2007, 9, 5255.
3.66 (dd, J¼17.0, 7.5 Hz, 1H, CH2), 5.51 (br s, 1H, CH), 7.30e7.44 (m,
4H, Ph H), 7.56 (m, 2H, ArH), 7.70 (t, J¼7.2 Hz, 1H, H-7), 7.73e7.81
(m, 2H, ArH), 8.12 (d, J¼8.4 Hz, 1H, H-8), 8.20 (s, 1H, H-4); IR (KBr):
1604, 2930, 3190 cmꢁ1
.
4.3.2. 3-Benzyl-2,3-dihydro-cyclopenta[b]quinolin-1-one (5). Light
brown solid; yield: 7%; mp 123e124 ꢀC; 1H NMR (300 MHz, CDCl3):
d
¼2.61 (d, J¼7.2 Hz,1H), 2.83e2.88 (m, 2H), 3.70 (dd,1 Hz,1H), 3.94
(m, 1H), 7.24e7.44 (m, 2H), 7.60e7.64 (m, 3H), 7.91 (t, J¼7.8 Hz, 1H),
7.98 (m, 2H), 8.21 (d, J¼8.4 Hz,1H), 8.54 (s,1H). IR (KBr): cmꢁ1 2925,
1714, 1611.
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Acknowledgements
A.C. andB.S. thanktoDST forInspireFacultyFellowship. N.S. isalso
thankful to UGC, New Delhi for SRF and R.S. would also like to thank
BHU for CRET Fellowship. We are also thankful to Prof. A.K. Singh,
Department of Chemistry, IIT Roorkee for providing HRMS data.
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