Facile assembly of cyclopenta[c]quinolin-3-ols via a palladium-catalyzed reaction of 2-alkynylaniline with 2-alkynylvinyl bromide

Article abstract of DOI:10.1016/j.tet.2012.08.093

A palladium-catalyzed tandem reaction of 2-alkynylaniline with 2-alkynylvinyl bromide provides an efficient route for the assembly of cyclopenta[c]quinolin-3-ols. A double insertion of triple bonds is the key step during the transformation.

Full text of DOI:10.1016/j.tet.2012.08.093

Tetrahedron 68 (2012) 9004e9008
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Facile assembly of cyclopenta[c]quinolin-3-ols via a palladium-catalyzed reaction
of 2-alkynylaniline with 2-alkynylvinyl bromide
,
b,
*
Chao Ye a, Guanyinsheng Qiu b, Xiaolin Pan b, Yiyuan Peng a , Jie Wu
*
a Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi
330022, China
b Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 June 2012
Received in revised form 21 August 2012
Accepted 28 August 2012
Available online 4 September 2012
A palladium-catalyzed tandem reaction of 2-alkynylaniline with 2-alkynylvinyl bromide provides an
efficient route for the assembly of cyclopenta[c]quinolin-3-ols. A double insertion of triple bonds is the
key step during the transformation.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
2-Alkynylaniline
2-Alkynylvinyl bromide
Cyclopenta[c]quinolin-3-ol
Palladium-catalyzed reaction
1. Introduction
reaction of 2-alkynylaniline 1 with aryl/alkenyl halide is known,9
which proceeds through an intermediate a to afford the indole
Currently, small molecule modulators used for the systematic
perturbation of gene products are of high demand in the field of
chemical biology.1 Therefore, efficient and facile approaches for the
collection of novel drug-like small molecules are needed.2 In the
past decade, diversity-oriented synthesis has been used as an at-
tractive strategy for the preparation of natural product-like com-
pounds.3,4 Among the synthetic approaches applied, tandem
reactions have been demonstrated as a powerful method for the
generation of molecular diversity and complexity.5 The importance
of nitrogen-containing heterocycles embedded with privileged
substructures is well-known, due to their remarkable biological
properties.6 Thus, continuous efforts have been underway for the
methods development for the rapid access to privileged scaffold-
based N-heterocycles.
compound (Scheme 1, Eq 1). We envisioned that 2-alkynylvinyl
H
NH2
X
N
Pd(0)
ref. 8
R1
R2
R1
R1
+
(1)
R3
R2
1
NH2 R4
PdII
N
R4
R3
NH2
R1
R1
R3
HO
B
R2
R3
a
R2
R3 Pd
NH2
X
R2
R3
base
R4
E
H
N
R4
O2
R1
R1
Pd(0)
?
Br
R3
+
(2)
R3
R3
R2
D
1
2
R2
R3
The quinoline core is a well-known privileged structural motif
presented in a number of natural and synthetic products with in-
teresting pharmacological or physical properties.7 To construct the
novel molecular frameworks via a tandem process, we aimed to
develop a practical synthetic route for unique polyheterocycles
containing a quinoline substructure. Recently, we are interested in
the palladium-catalyzed tandem reactions of 2-alkynylanilines 1
for the generation of N-heterocycles.8 The palladium-catalyzed
Scheme 1. A proposed palladium-catalyzed tandem reaction of 2-alkynylaniline with
2-alkynylvinyl bromide.
bromide 2 might be a good reactant as well in the palladium-
catalyzed reaction of 2-alkynylaniline 1 (Scheme 1, Eq. 2). The
presence of an additional alkynyl moiety would enable its double
insertion of triple bonds (intermediate B), and the generation of
a fused quinoline D or E would be expected. Recently, the highly
selective intramolecular or intermolecular double insertion of tri-
ple bonds has been successfully applied in the construction of
heterocyclic or carbocyclic compounds.10 Encouraged by these
* Corresponding authors. E-mail address: jie_wu@fudan.edu.cn (J. Wu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.093

C. Ye et al. / Tetrahedron 68 (2012) 9004e9008
9005
Table 1
results, we envisioned that the hypothesis presented in Scheme 1
was possible although the competitive pathway for the formation
of indole seemed inevitable. If the transformation proceeded
smoothly as expected, the fused quinoline compounds would be
generated and the formation of three bonds in a tandem one-pot
procedure would be anticipated.
Initial studies for the palladium-catalyzed reaction of 2-(2-phenylethynyl)benzen-
amine 1a with 2-alkynylvinyl bromide 2aa
Ph
N
Ph
NH2
[Pd] (5 mol %)
ligand (10 mol %)
Br
n
+
Pr
base, solvent
n
n
OH
100 °C
Pr
Pr
Ph
n
3a
1a
2a
Ph
Pr
2. Results/discussion
H
N
N
Ph
Ph
Initially, a model reaction of 2-(2-phenylethynyl)benzenamine
1a with 2-alkynylvinyl bromide 2a in the presence of a palladium
catalyst (5 mol %) was studied (Table 1). At the outset, the reaction
was catalyzed by Pd(OAc)2 (5 mol %) and PPh3 (10 mol %) in the
presence of t-BuONa (2.0 equiv) in 1,4-dioxane at 100 ꢀC (Table 1,
entry 1). Disappointingly, only a trace amount of product was
detected. A similar outcome was observed when the ligand was
replaced by DPPP (Table 1, entry 2). No reaction occurred when N-
heterocyclic carbene (IPr) was used in the reaction (Table 1, entry
3). To our delight, a product was isolated in 26% yield when X-
phos was utilized as the ligand (Table 1, entry 4). However, the
structural illustration revealed that this product was cyclopenta[c]
quinolin-3-ol 3a instead of the expected compound D or E (Fig. 1).
This unexpected result was reasonable, since the cyclopenta[c]
quinoline D could be easily converted to cyclopenta[c]quinolin-3-
ol 3 in the presence of a base under air.11 This promising result
prompted us for further investigation. The yield was increased to
43% when PCy3 was employed as the ligand (Table 1, entry 5). A
better yield was obtained by evaluation of other palladium sour-
ces (Table 1, entries 6 and 7). Interestingly, cyclopenta[c]quinolin-
3-ol 3a could be isolated in 60% yield without the addition of
a phosphine ligand (Table 1, entry 8). In light of this result, we
further screened different bases (Table 1, entries 9e12). The yield
was lower when t-BuOK was employed in the reaction (Table 1,
entry 9). The reaction was inert when K2CO3, Cs2CO3, or NaOMe
was utilized. Furthermore, the reaction was retarded when the
temperature was lower (data not shown in Table 1). The trans-
formation afforded the corresponding product 3a in 51% yield
when the reaction took place in toluene (Table 1, entry 13). The
reaction failed when the solvent was changed to DMF, DMSO, or
NMP (Table 1, entries 14e16).
n
n
Pr
Pr
not observed
HO
Ph
n
n
Ph
Pr
Pr
D1
E1
Entry
[Pd]
Ligand
Base
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PPh3
DPPP
IPr
X-Phos
PCy3
PCy3
PCy3
d
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
Toluene
Trace
Trace
nr
26
43
17
47
60
36
Trace
Trace
Trace
51
Trace
Trace
nr
9
d
10
11
12
13
14
15
16
d
K2CO3
Cs2CO3
d
d
NaOMe
t-BuONa
t-BuONa
t-BuONa
t-BuONa
d
d
DMF
DMSO
NMP
d
d
a
Reaction conditions: 2-(2-phenylethynyl)benzenamine 1a (1.0 equiv), 2-
alkynylvinyl bromide 2a (1.2 equiv), palladium catalyst (5 mol %), ligand
(10 mol %), base (2.0 equiv), 100 ꢀC.
b
Isolated yield based on 2-(2-phenylethynyl)benzenamine 1a.
After establishing the optimized conditions (5 mol % of
PdCl2(PPh3)2, 2.0 equiv of t-BuONa, 1,4-dioxane, 100 ꢀC), we next
explored the generality of this palladium-catalyzed tandem re-
action of 2-alkynylanilines 1 with 2-alkynylvinyl bromides 2. The
results are summarized in Table 2. We found that the reactions
worked well leading to a range of cyclopenta[c]quinolin-3-ols 3
in moderate yields. Various 2-alkynylanilines 1 were demon-
strated to be good reactants in the transformation. The sub-
stituents attached to the triple bond were all tolerated under the
standard conditions. 2-Alkynylanilines 1 with different sub-
stituents on the aromatic ring were examined as well, which
reacted with 2-alkynylvinyl bromides 2 affording the corre-
sponding products. During the reaction process, only a trace
amount of indole was detected, which demonstrated the high
selectivity of the double insertion of triple bonds. Subsequently,
several 2-alkynylvinyl bromides 2 were employed in the re-
actions of 2-alkynylanilines 1, and the desired products were
afforded as expected.
Fig. 1. X-ray ORTEP illustration of cyclopenta[c]quinolin-3-ol 3a (30% probability
ellipsoids).
3. Conclusions
The possible mechanism was proposed in Scheme 2. An oxida-
tive addition of Pd(0) to vinyl bromide 2 would occur first, which
would then coordinate with the triple bond of 2-alkynylanilines 1.
After insertion, a vinyl Pd(II) B would be generated, which would
subsequently undergo an intramolecular insertion of another triple
bond to produce intermediate C. Further CeN coupling and base-
promoted hydroxylation in the presence of dioxygen would afford
the unexpected cyclopenta[c]quinolin-3-ol 3.
In conclusion, we have described a novel and efficient pathway
for the preparation of cyclopenta[c]quinolin-3-ols via a palladium-
catalyzed tandem reaction of 2-alkynylaniline with 2-alkynylvinyl
bromide. The complexity could be easily introduced with the for-
mation of three bonds in a one-pot procedure. During the reaction
process, the double insertion of triple bonds was highly selective,
and the competitive pathway for the formation of indole was
minimized. Currently, application of the strategy of double

9006
C. Ye et al. / Tetrahedron 68 (2012) 9004e9008
Table 2
thin-layer chromatography was performed using glass plates pre-
coated with 0.25 mm 230e400 mesh silica gel impregnated with
a fluorescent indicator (254 nm). Thin-layer chromatography plates
were visualized by exposure to ultraviolet light. Organic solutions
were concentrated on rotary evaporators at w20 Torr at 25e35 ꢀC.
Nuclear magnetic resonance (NMR) spectra are recorded in parts
Synthesis of cyclopenta[c]quinolin-3-ols 3 via a palladium-catalyzed reaction of 2-
alkynylaniline 1 with 2-alkynylvinyl bromide 2a
R4
N
R4
R3
OH
R3
NH2
Ph
Pd(PPh3)2Cl2
(5 mol %)
R1
R1
Br
R3
+
t-BuONa, 1,4-dioxane
per million from internal tetramethylsilane on the
d
scale. 1H and
R3
°
100
N2
C
R2
R2
1
2
3
13C NMR spectra were recorded in CDCl3 on a Bruker DRX-400
spectrometer operating at 400 MHz and 100 MHz, respectively.
All chemical shift values are quoted in parts per million and cou-
pling constants quoted in hertz. High-resolution mass spectrome-
try (HRMS) spectra were obtained on a microTOF II Instrument.
air
N
N
Ph
N
C6H4
n
p
-Cl
N
C6H4
n
Pr
p
-Me
Et
OH
Pr
n
Pr
OH
n
OH
OH
n
Ph
3b, 62% yield
Ph
n
Ph
Ph
Ph
Pr
Et
Pr
3d, 47% yield
C6H4
Pr
3c, 55% yield
Ph
3a, 60% yield
Ph
4.2. General procedure for the palladium-catalyzed tandem
reaction of 2-alkynylaniline with 2-alkynylvinyl bromide
N
N
N
N
p
-Me
n
n
n
n
Pr
Pr
Pr
Pr
OH
n
Pr
OH
OH
n
Pr
OH
n
Pr
2-Alkynylvinyl bromide 2 (0.2 mmol) was added to a mixture of
PdCl2(PPh3)2 (5 mol %), t-BuONa (0.6 mmol), and 2-alkynylaniline
(0.2 mmol) in 1,4-dioxane (2.0 mL) under nitrogen atmosphere.
The mixture was heated at 100 ꢀC. After consumption of the
starting material as indicated by TLC, the reaction mixture was
stirred in air. After 1 h, the reaction was quenched by water (10 mL).
The mixture was extracted with ethyl acetate (10 mLꢁ3), and the
combined organic layers were washed with brine (15 mL), dried
over Na2SO4. The solvent was evaporated under reduced pressure
and the residue was purified by column chromatography on silica
gel (eluted with PE/EA¼5:1) to provide the compound 3.
n
p
-ClC6H4
p
-MeC6H4
Ph
Pr
3g, 61% yield
3e, 50% yield
Ph
3f, 52% yield
3h, 57% yield
N
N
Ph
N
Ph
N
C6H4p-Cl
n
Pr
n
n
n
Pr
Pr
Pr
OH
n
Pr
OH
n
Pr
OH
n
OH
n
Pr
p-MeC6H4
p
-ClC6H4
Ph
3k, 51% yield
Ph
Ph
Pr
3i, 61% yield
3j, 48% yield
3l, 50% yield
N
Ph
Et
N
Ph
N
n
n
Pr
Pr
Cl
Cl
Cl
OH
Et
OH
n
OH
n
p
-MeC6H4
3o, 43% yield
p
-MeC6H4
3m, 43% yield
Ph
3n, 46% yield
Pr
Pr
4.2.1. 1,4-Diphenyl-2,3-dipropyl-3H-cyclopenta[c]quinolin-3-ol
3a. 1H NMR (400 MHz, CDCl3):
d
0.61 (t, J¼6.9 Hz, 3H), 0.83 (t,
J¼6.9 Hz, 3H), 1.40e1.49 (m, 2H), 1.52e1.62 (m, 2H), 1.77e1.74 (m,
2H), 1.87 (br, 1H), 2.06e2.15 (m, 2H), 2.17e2.22 (m, 2H), 7.09e7.15
(m, 1H), 7.19 (d, J¼8.0 Hz, 1H), 7.22e7.30 (m, 1H), 7.36e7.55 (m, 8H),
7.72 (d, J¼6.4 Hz, 2H), 8.10 (d, J¼8.2 Hz, 1H); 13C NMR (100 MHz,
a
Isolated yield based on 2-alkynylaniline 1.
base
H
CDCl3):
d 13.8, 14.8, 16.4, 21.7, 27.9, 36.8, 86.1, 122.5, 124.5, 125.4,
N
R4
OH
R3
R3
Br
R3
R4
N
R4
O2
R3
O2
base
R1
127.9, 128.1, 128.7, 129.0, 129.2, 136.3, 136.6, 139.3, 140.3, 148.6,
149.0, 154.7, 155.3; HRMS calcd for C30H30NOþ [MþH]þ: 420.2322,
found: 420.2309. IR: 3322.1, 3044.8, 2958.8, 2930.7, 2870.9, 1560.9,
R1
D
R4
R2
1490.9, 1442.6, 1417.0 cmꢂ1
.
3
R2
R3
C-N
Pd(0)
coupling
4.2.2. 2,3-Diethyl-1,4-diphenyl-3H-cyclopenta[c]quinolin-3-ol
3b. 1H NMR (400 MHz, CDCl3):
2
base
R3
d
0.36 (t, J¼7.3 Hz, 3H), 1.03 (t,
J¼7.3 Hz, 3H),1.66e1.71 (m,1H),1.79e1.86 (m,1H), 2.16 (q, J¼7.3 Hz,
2H), 2.18 (q, J¼7.3 Hz, 2H), 7.12 (d, J¼7.8 Hz,1H), 7.21 (d, J¼7.8 Hz,1H),
7.29e7.30 (m, 1H), 7.41e7.56 (m, 8H), 7.75 (d, J¼7.8 Hz, 2H), 8.11 (d,
II
NH2
Pd
X
R4
R3
R1
IIPd
R3
J¼8.2 Hz,1H); 13C NMR (100 MHz, CDCl3):
d
7.49,13.1,18.5, 27.3, 87.0,
A
R3
R2
124.2,127.9,128.1,128.4,128.7,128.8,129.0,129.1,129.2,129.3,129.8,
135.6, 136.5, 139.3, 140.2, 149.0, 155.3, 155.6; HRMS calcd for
C
NH2 R4
II
Pd
R3
NH2
R1
C
28H26NOþ [MþH]þ: 392.2009, found: 392.2001. IR: 3356.8, 3047.5,
R1
2966.8, 2933.2, 2873.5, 1554.0, 1491.2, 1442.8, 1375.2 cmꢂ1
.
1
B
R2
R2
R3
R3
4.2.3. 1-Phenyl-2,3-dipropyl-4-p-tolyl-3H-cyclopenta[c]quinolin-3-
ol 3c. 1H NMR (400 MHz, CDCl3):
d
0.62 (t, J¼6.9 Hz, 3H), 0.82 (t,
Scheme 2. A proposed mechanism for the generation of cyclopenta[c]quinolin-3-ol 3.
J¼6.9 Hz, 3H), 1.40e1.46 (m, 1H), 1.51e1.59 (m, 1H), 1.62e1.67 (m,
1H), 1.71e1.77 (m, 1H), 2.03 (br, 1H), 2.04e2.14 (m, 2H), 2.15e2.22
(m, 2H), 2.44 (s, 3H), 7.09e7.13 (m, 1H), 7.19 (d, J¼8.2 Hz, 1H), 7.29
(d, J¼8.2 Hz, 2H), 7.41 (d, J¼6.8 Hz, 1H), 7.48e7.55 (m, 4H), 7.60 (d,
J¼8.0 Hz, 2H), 8.09 (d, J¼8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
insertion of triple bonds for the generation of other N-heterocycles
is ongoing in our laboratory.
4. Experimental section
4.1. General methods
d 13.8, 14.8, 16.5, 21.3, 21.7, 27.9, 36.8, 86.2, 122.4, 124.2, 125.2, 127.9,
128.7, 128.8, 128.9, 129.2, 129.9, 136.4, 136.6, 137.4, 138.1, 139.2,
148.5, 149.0, 154.6, 155.4; HRMS calcd for C31H32NOþ [MþH]þ:
434.2478, found: 434.2471. IR: 3390.6, 3057.2, 2959.2, 2928.4,
Unless otherwise stated, all commercial reagents were used as
received. All solvents were dried and distilled according to standard
1674.8, 1602.3, 1544.3, 1510.5, 1485.5 cmꢂ1
.
procedures. Flash column chromatography was performed using
4.2.4. 4-(4-Chlorophenyl)-1-phenyl-2,3-dipropyl-3H-cyclopenta[c]
quinolin-3-ol 3d. 1H NMR (400 MHz, CDCl3):
0.60 (t, J¼7.2 Hz, 3H),
ꢀ
silica gel (60-A pore size, 32e63
mm, standard grade). Analytical
d

C. Ye et al. / Tetrahedron 68 (2012) 9004e9008
9007
0.83 (t, J¼7.3 Hz, 3H), 1.40e1.44 (m, 1H), 1.50e1.57 (m, 1H),
1.62e1.69 (m, 1H), 1.74e1.78 (m, 1H), 1.99 (s, 1H), 2.11e2.15 (m, 1H),
2.19e2.27 (m, 1H), 7.13e7.15 (m, 1H), 7.19 (d, J¼8.0 Hz, 1H), 7.26 (d,
J¼8 Hz, 1H), 7.40 (d, J¼8.0 Hz, 1H), 7.45e7.55 (m, 7H), 7.76 (d,
J¼8.4 Hz, 2H), 8.07 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
147.6, 148.0, 154.0, 154.5; HRMS calcd for C32H34NOþ [MþH]þ:
448.2635, found: 448.2621. IR: 3407.0, 2958.6, 1910.9, 1708.6,
1633.0, 1552.2, 1444.3 cmꢂ1
.
4.2.10. 1-(4-Chlorophenyl)-8-methyl-4-phenyl-2,3-dipropyl-3H-cy-
clopenta[c]quinolin-3-ol 3j. 1H NMR (400 MHz, CDCl3):
0.60 (t,
d
14.0, 14.9, 16.5, 21.9, 28.0, 36.3, 86.3, 122.6, 124.3, 125.0, 125.7,
d
128.1, 128.3, 128.5, 128.9, 129.3, 129.9, 130.7, 131.0, 134.7, 136.3,
136.5, 138.8, 139.4, 149.1, 149.2, 154.3, 155.0; HRMS calcd for
J¼6.8 Hz, 3H), 0.84 (t, J¼7.3 Hz, 3H), 1.37e1.47 (m, 2H), 1.52e1.60
(m, 2H), 1.72e1.78 (m, 2H), 1.96 (s, 1H), 2.04e2.14 (m, 1H), 2.22 (s,
3H), 6.94 (s, 1H), 7.23e7.25 (m, 1H), 7.37e7.42 (m, 3H), 7.48e7.53
(m, 5H), 7.69 (d, J¼7.2 Hz, 2H), 7.99 (d, J¼8.8 Hz, 1H); 13C NMR
C
30H29ClNOþ [MþH]þ: 454.1932, found: 454.1930. IR: 3445.8,
3050.8, 2955.7, 1612.8, 1496.1, 1455.8 cmꢂ1
.
(100 MHz, CDCl3): d 13.8, 14.8, 16.5, 21.8, 21.9, 27.9, 36.9, 86.2, 122.2,
4.2.5. 1-(4-Chlorophenyl)-4-phenyl-2,3-dipropyl-3H-cyclopenta[c]
quinolin-3-ol 3e. 1H NMR (400 MHz, CDCl3):
122.9, 128.1, 128.4, 128.9, 129.0, 129.7, 130.7, 131.4, 133.9, 135.3,
136.2, 138.1, 140.3, 147.3, 147.6, 154.5, 154.9; HRMS calcd for
d
0.60 (t, J¼7.2 Hz, 3H),
0.81 (t, J¼7.2 Hz, 3H), 1.37e1.46 (m, 1H), 1.53e1.61 (m, 2H),
1.72e1.79 (m, 2H), 1.94 (s, 1H), 2.06e2.13 (m, 1H), 2.16e2.22 (m,
1H), 7.18e7.24 (m, 3H), 7.38 (d, J¼8.0 Hz, 1H), 7.43e7.52 (m, 5H),
7.57 (t, J¼6.8 Hz, 1H), 7.70 (d, J¼6.8 Hz, 2H), 8.10 (d, J¼8.8 Hz, 1H);
C
31H31ClNOþ [MþH]þ: 468.2089, found: 448.2079. IR: 3398.5,
3058.7, 2958.6, 2927.3, 2870.7, 1550.4, 1489.6 cmꢂ1
.
4.2.11. 8-Methyl-1,4-diphenyl-2,3-dipropyl-3H-cyclopenta[c]quino-
lin-3-ol 3k. 1H NMR (400 MHz, CDCl3):
13C NMR (100 MHz, CDCl3):
d
13.7, 14.8, 16.3, 21.6, 28.1, 36.4, 86.0,
d
0.60 (t, J¼6.8 Hz, 3H), 0.83 (t,
124.2, 126.2, 128.1, 129.1, 129.3, 130.6, 130.7, 134.2, 134.6, 136.8,
137.7, 139.2, 139.7, 149.9, 150.6, 153.8, 154.6; HRMS calcd for
J¼7.3 Hz, 4H), 1.39e1.47 (m, 1H), 1.54e1.60 (m, 2H), 1.72e1.78 (m, 1H),
1.99 (s, 1H), 2.07e2.12 (m, 1H), 2.15 (s, 3H), 2.19e2.25 (m, 1H), 6.89 (s,
1H), 7.26e7.27 (m, 1H), 7.37e7.49 (m, 8H), 7.70 (d, J¼6.4 Hz, 2H), 7.98
C
30H29ClNOþ [MþH]þ: 454.1932, found: 454.1930. IR: 3352.9,
3049.9, 2929.9, 2849.6, 1668.5, 1489.0 cmꢂ1
.
(d, J¼8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 13.8, 14.8, 16.5, 21.7,
27.9, 36.8, 86.2,122.4,123.2,127.8,128.1,128.3,128.6,129.1,129.3,129.5,
131.2, 134.9, 136.2, 136.7, 139.4, 140.4, 147.6, 147.9, 154.1, 154.3; HRMS
calcd for C31H32NOþ [MþH]þ: 434.2478, found: 434.2471. IR: 3356.1,
4.2.6. 4-Phenyl-2,3-dipropyl-1-p-tolyl-3H-cyclopenta[c]quinolin-3-
ol 3f. 1H NMR (400 MHz, CDCl3):
0.59e0.60 (m, 3H), 0.83 (t,
d
J¼6.4 Hz, 3H), 1.40e1.43 (m, 1H), 1.55e1.68 (m, 2H), 1.72e1.76 (m,
1H), 1.97 (s, 1H), 2.04e2.11 (m, 1H), 2.18e2.25 (m, 1H), 2.49 (s, 3H),
7.15 (d, J¼6.8 Hz, 2H), 7.26e7.31 (m, 3H), 7.48e7.55 (m, 4H), 7.72 (d,
J¼6.0 Hz, 2H), 8.10 (d, J¼8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
3057.0, 2958.8, 2930.1, 2871.0, 1552.3, 1492.3, 1442.8, 1377.5 cmꢂ1
.
4.2.12. 4-(4-Chlorophenyl)-8-methyl-1-phenyl-2,3-dipropyl-3H-cy-
clopenta[c]quinolin-3-ol 3l. 1H NMR (400 MHz, CDCl3):
0.59 (t,
d
d
13.9, 14.9, 16.6, 21.5, 21.9, 28.0, 36.9, 86.2,122.7, 124.4, 125.4, 128.2,
J¼7.2 Hz, 3H), 0.83 (t, J¼7.6 Hz, 3H),1.39e1.44 (m, 2H),1.51e1.56 (m,
1H), 1.60e1.67 (m, 1H), 1.72e1.80 (m, 1H), 2.07e2.11 (m, 1H), 2.15 (s,
3H), 2.19e2.24 (m, 2H), 6.87 (s, 1H), 7.25e7.26 (m, 2H), 7.36e7.39
(m, 1H), 7.43 (d, J¼8.4 Hz, 1H), 7.46e7.50 (m, 3H), 7.74 (d, J¼8.0 Hz,
128.5, 129.1, 129.2, 129.5, 129.6, 130.0, 133.6, 136.4, 137.7, 139.5,
140.5, 148.9, 149.1, 149.2, 154.8, 155.4; HRMS calcd for C31H32NOþ
[MþH]þ: 434.2478, found: 434.2473. IR: 3352.0, 3057.2, 2958.5,
2929.3, 2870.6, 1547.1, 1491.0, 1370.3 cmꢂ1
.
2H), 7.96 (d, J¼8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 14.0, 14.9,
16.5, 21.9, 22.0, 28.0, 36.3, 86.3, 122.5, 123.3, 128.0, 128.1, 128.2,
128.8,129.4,130.7,131.0,131.6,134.6,135.3,136.3,136.7,139.5,147.7,
4.2.7. 1-Cyclopropyl-4-phenyl-2,3-dipropyl-3H-cyclopenta[c]quino-
lin-3-ol 3g. 1H NMR (400 MHz, CDCl3):
d
0.52 (t, J¼6.9 Hz, 3H), 1.03
148.4, 153.3, 154.5; HRMS calcd for
C
31H31ClNOþ [MþH]þ:
(t, J¼7.2 Hz, 3H), 1.14e1.17 (m, 2H), 1.39e1.41 (m, 2H), 1.59e1.65 (m,
2H), 1.72e1.77 (m, 2H), 1.94e2.02 (m, 2H), 2.24e2.32 (m, 2H),
2.39e2.42 (m, 1H), 2.46e2.52 (m, 1H); 13C NMR (100 MHz, CDCl3):
468.2089, found: 468.2080. IR: 3342.7, 2959.1, 2929.8, 2870.7,
1591.4, 1551.2, 1490.9, 1441.7 cmꢂ1
.
d
8.7, 9.2,10.3,13.8,14.9,16.4, 22.1, 27.9, 36.4, 85.7,125.1,128.1,128.3,
4.2.13. 1-(4-Chlorophenyl)-8-methyl-4-phenyl-2,3-dipropyl-3H-cy-
clopenta[c]quinolin-3-ol 3m. 1H NMR (400 MHz, CDCl3):
0.60 (t,
129.0, 130.0, 137.9, 140.4, 149.0, 149.9, 155.1, 155.5; HRMS calcd for
d
C
27H30NOþ [MþH]þ: 384.2322, found: 384.2316. IR: 3368.2, 3059.4,
J¼6.4 Hz, 3H), 0.83 (t, J¼6.8 Hz, 3H), 1.38e1.48 (m, 2H), 1.54e1.60
(m, 2H), 1.72e1.78 (m, 1H), 1.95 (br, 1H), 2.06e2.14 (m, 1H),
2.19e2.26 (m, 1H), 2.49 (s, 3H), 7.12e7.16 (m, 2H), 7.28e7.36 (m,
3H), 7.46e7.48 (m, 4H), 7.71 (d, J¼6.4 Hz, 2H), 8.00 (d, J¼8.8 Hz,1H);
2958.5, 2929.5, 2870.4, 1560.8, 1491.0, 1453.8 cmꢂ1
.
4.2.8. 8-Methyl-1-phenyl-2,3-dipropyl-4-p-tolyl-3H-cyclopenta[c]
quinolin-3-ol 3h. 1H NMR (400 MHz, CDCl3):
d
0.61 (t, J¼7.2 Hz, 3H),
13C NMR (100 MHz, CDCl3):
d 13.9, 14.9, 16.5, 21.5, 21.8, 28.0, 36.9,
0.83 (t, J¼7.2 Hz, 3H),1.39e14.5 (m,1H),1.59e1.66 (m,1H),1.72e1.78
(m,1H),1.98 (s,1H), 2.15 (s, 3H), 2.19e2.23 (m,1H), 2.43 (s, 3H), 6.87
(s,1H), 7.29 (d, J¼7.6 Hz, 2H), 7.37 (d, J¼8.4 Hz,1H), 7.41 (d, J¼6.8 Hz,
1H), 7.48e7.49 (m, 3H), 7.59 (d, J¼7.6 Hz, 2H), 7.97 (d, J¼8.8 Hz, 1H);
86.2, 123.4, 128.3, 128.7, 129.1, 129.6, 129.7, 130.0, 131.1, 131.4, 132.8,
137.2, 138.1139.1, 140.1, 147.5, 148.3, 155.0, 155.6; HRMS calcd for
C
31H31ClNOþ [MþH]þ: 468.2089, found: 468.2082. IR: 3376.2,
3057.2, 2959.3, 2930.5, 2871.1, 1616.8, 1560.9, 1493.7, 1418.9 cmꢂ1
.
13C NMR (100 MHz, CDCl3):
d 13.9, 14.8, 16.5, 21.3, 21.7, 27.9, 36.9,
86.2, 122.3, 123.2, 127.8, 128.6, 128.8, 128.9, 129.3, 129.4, 129.5, 131.1,
134.8,136.3,136.8,137.5,138.0,139.4,147.6,147.8,154.0,154.6; HRMS
calcd for C32H34NOþ [MþH]þ: 448.2635, found: 448.2624. IR:
4.2.14. 8-Chloro-1,4-diphenyl-2,3-dipropyl-3H-cyclopenta[c]quino-
lin-3-ol 3n. 1H NMR (400 MHz, CDCl3):
(t, J¼7.3 Hz, 3H), 1.42e1.47 (m, 1H), 1.56e1.62 (m, 2H), 1.74e1.80 (m,
1H), 1.97 (br, 1H), 2.04e2.15 (m, 1H), 2.21e2.25 (m, 1H), 7.09e7.10
(m, 1H), 7.26e7.30 (m, 2H), 7.41e7.53 (m, 7H), 7.71e7.72 (m, 2H),
d
0.60 (t, J¼6.8 Hz, 3H), 0.84
3386.9, 2958.2, 2921.8, 2870.4, 1554.0, 1496.0, 1442.8 cmꢂ1
.
4.2.9. 8-Methyl-4-phenyl-2,3-dipropyl-1-p-tolyl-3H-cyclopenta[c]
quinolin-3-ol 3i. 1H NMR (400 MHz, CDCl3):
8.02 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 13.9, 14.9, 16.6,
d
0.59 (t, J¼7.2 Hz, 3H),
21.8, 28.0, 36.9, 86.3, 120.2, 123.1, 128.3, 128.7, 129.0, 129.1, 129.2,
130.0, 131.2, 131.5, 133.2, 135.9, 139.1, 140.0, 147.8, 148.1, 155.1, 155.6;
HRMS calcd for C30H29ClNOþ [MþH]þ: 454.1932, found: 454.1930.
IR: 3361.7, 3052.3, 2959.3, 2930.5, 2817.2, 1543.9, 1485.6, 1464.6,
0.83 (t, J¼7.2 Hz, 3H), 1.38e1.44 (m, 1H), 1.54e1.60 (m, 2H),
1.71e1.76 (m, 1H), 1.99 (s, 1H), 2.06e2.13 (m, 1H), 2.17 (s, 3H),
2.20e2.26 (m, 1H), 2.48 (s, 3H), 6.96 (s, 1H), 7.15 (d, J¼8.0 Hz, 1H),
7.28e7.31 (m, 3H), 7.38 (d, J¼8.8 Hz, 1H), 7.44e7.49 (m, 3H), 7.71 (d,
J¼7.2 Hz, 2H), 7.98 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
1377.3 cmꢂ1
.
d
13.8, 14.8, 16.4, 21.3, 21.8, 27.9, 36.8, 86.1, 122.4, 123.3, 128.0, 128.2,
4.2.15. 8-Chloro-2,3-diethyl-4-phenyl-1-p-tolyl-3H-cyclopenta[c]
quinolin-3-ol 3o. 1H NMR (400 MHz, CDCl3):
0.35 (t, J¼7.3 Hz, 3H),
129.1, 129.2, 129.5, 131.2, 133.6, 134.8, 136.2, 137.4, 139.4, 140.4,
d

9008
C. Ye et al. / Tetrahedron 68 (2012) 9004e9008
2010, 53, 7405; (c) Oh, S.; Nam, H. J.; Park, J.; Beak, S. H.; Park, S. B. Chem-
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1.06 (t, J¼7.3 Hz, 3H), 1.67e1.70 (m, 2H), 1.82e1.87 (m, 1H), 2.01 (s,
1H), 2.15e2.21 (m, 1H), 2.29e2.34 (m, 1H), 2.50 (s, 3H), 7.16e7.19
(m, 2H), 7.30e7.38 (m, 3H), 7.48e7.50 (m, 4H), 7.75 (d, J¼7.3 Hz,
5. For reviews, see: (a) Montgomery, J. Angew. Chem., Int. Ed. 2004, 43, 3890; (b)
Negishi, E.; Coperet, C.; Ma, S.; Liou, S. Y.; Liu, F. Chem. Rev. 1996, 96, 365; (c)
Tietze, L. F. Chem. Rev. 1996, 96, 115; (d) Grigg, R.; Sridharan, V. J. Organomet.
Chem. 1999, 576, 65; (e) Miura, T.; Murakami, M. Chem. Commun. 2007, 217; (f)
Malacria, M. Chem. Rev. 1996, 96, 289; (g) Nicolaou, K. C.; Montagnon, T.;
Snyder, S. A. Chem. Commun. 2003, 551; (h) Nicolaou, K. C.; Edmonds, D. J.;
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2H), 8.02 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 7.48, 13.2,
18.5, 21.4, 27.4, 87.0, 123.0, 123.3, 128.2, 128.5, 129.0, 129.6, 129.7,
129.9, 131.0, 131.3, 132.7, 136.5, 138.0, 139.0, 140.0, 147.4, 148.4,
155.4, 155.8; HRMS calcd for C29H27ClNOþ [MþH]þ: 440.1776,
found: 440.1765. IR: 3371.2, 2967.5, 2932.8, 2875.0, 1542.7, 1484.9,
€
Huttl, M. R. M. Angew. Chem., Int. Ed. 2007, 46, 1570; (j) Tietze, L. F.; Brasche, G.;
1457.3, 1379.2 cmꢂ1
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Gericke, K. Domino Reactions in Organic Synthesis; Wiley-VCH: Weinheim,
€
Germany, 2006; (k) Tietze, L. F.; Dufert, M. A.; Hungerland, T.; Oum, K.; Lenzer,
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Financial support from National Natural Science Foundation of
China (No. 20972030) is gratefully acknowledged.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.08.093.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
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