Generation of 11-fluoro-11H-indeno[1,2-c]quinolines via a palladium-catalyzed three-component reaction of 2-alkynylbromobenzenes, 2-alkynylanilines, and N-fluorobenzenesulfonimide

Article abstract of DOI:10.1002/adsc.201100582

A novel and efficient synthesis of 11-fluoro-11H-indeno[1,2-c]quinolines has been developed via a palladium-catalyzed three-component reaction of 2-alkynylbromobenzenes, 2-alkynylanilines, and N-fluorobenzenesulfonimide. The reaction works well with high

Full text of DOI:10.1002/adsc.201100582

FULL PAPERS
DOI: 10.1002/adsc.201100582
Generation of 11-Fluoro-11H-indeno[1,2-c]quinolines via a
G
Palladium-Catalyzed Three-Component Reaction of
2-Alkynylbromobenzenes, 2-Alkynylanilines, and
N-Fluorobenzenesulfonimide
Xiaolin Pan,a Yong Luo,a Gang Liu,a,b Shouzhi Pu,b,* and Jie Wua,*
a
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, Peopleꢀs Republic of China
Fax : (+86)-216-564-1740; e-mail: jie_wu@fudan.edu.cn
Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi
b
330013, Peopleꢀs Republic of China
E-mail: pushouzhi@yahoo.com.cn
Received: July 23, 2011; Revised: September 14, 2011; Published online: January 12, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100582.
Abstract: A novel and efficient synthesis of 11- materials. In the meantime, a fluorine atom could be
fluoro-11H-indenoACTHNUTRGNE[UNG 1,2-c]quinolines has been devel- incorporated into the scaffold during the reaction
oped via a palladium-catalyzed three-component re- process.
action of 2-alkynylbromobenzenes, 2-alkynylanilines,
and N-fluorobenzenesulfonimide. The reaction Keywords: 2-alkynylanilines; 2-alkynylbromoben-
works well with high selectivity. Additionally, the di- zenes; homogeneous catalysis; N-fluorobenzenesul-
versity and complexity could be easily introduced via fonimide;
11-fluoro-11H-indenoACTHNGUTERNNU[G 1,2-c]quinolines;
a simple operation from readily available starting palladium
Introduction
matory agents, antiasthamatic, antibacterial, antihy-
pertensive, and tyrosine kinase inhibiting agents).[7]
Molecules bearing a fluorine moiety are of great im- Additionally, quinolines have been utilized as valua-
portance in pharmaceuticals since the fluorinated ble synthons for the synthesis of nano- and mesostruc-
compounds can have significantly improved proper- tures with enhanced electronic and photonic proper-
ties (such as solubility, bioavailability, and metabolic ties.[8] The indene scaffold is another kind of privi-
stability).[1] In the last decade, effort continues to be leged structure, which can be observed in many drug
given to the methodological development for the syn- candidates.[9] Applications of indenes have been dem-
thesis of fluorinated molecules based on C F bond onstrated in materials science as well.[10] Inspired by
À
formation.[2–5] For instance, Liu and co-workers the advance of diversity-oriented synthesis of natural
À
achieved the generation of C F bond via transition product-like compounds, we conceived that a mole-
metal-catalyzed fluorination of unsaturated C C cule which incorporated both quinoline and indene
À
bonds recently.[5] In the meantime, novel and efficient skeletons would be attractive. If a fluorine atom could
methods for the formation of natural product-like be introduced to this scaffold, interesting biological
compounds are in great demand in the research on activities would be expected from the corresponding
chemical genetics.[6] It would be of high interest to focused library.
generate fluorinated natural product-like compounds
for the further evaluation of different biological route for the generation of indeno
assays.
via a palladium-catalyzed cascade reaction[11] of 2-alk-
Quinoline is regarded as a privileged fragment,
ynylhalobenzenes with 2-alkynylphenols.[12a] Encour-
Recently, we have described an efficient and novel
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
which is a ubiquitous subunit in many natural prod- aged by this result, we envisioned that 2-alkynylani-
ucts and pharmaceuticals showing remarkable biologi- lines would be a good partner as well in the above
cal activities (finding use as antimalarial, anti-inflam- transformation as a replacement for 2-alkynylphenols.
Adv. Synth. Catal. 2012, 354, 171 – 178
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Xiaolin Pan et al.
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Scheme 1. A proposed synthetic route for the palladium-catalyzed three-component reaction of 2-alkynylbromobenzenes 1,
2-alkynylanilines 2, and N-fluorobenzenesulfonimide 3.
Therefore, 5H-indeno
ACHTUNGTRENNUNG
tained which incorporated both quinoline and indene PdAHCTUNGTRENNUNG
skeletons as mentioned above. The proposed synthet- generated the desired product 4a in 73% yield. An-
ic route is shown in Scheme 1. An oxidative addition other fluorinating reagent (such as Selectfluor) was
of 2-alkynylbromobenzenes 1 to Pd(0) would occur to employed in the above reaction as well. However, the
generate an intermediate A, which then coordinated reaction gave rise to the corresponding product 4a in
with the triple bond of 2-alkynylanilines 2. After a lower yield. The reaction was retarded when the
double triple bond insertion, a vinyl Pd(II) species C temperature was decreased or the catalytic amount of
would be formed, which subsequently undergoes an palladium acetate was reduced.
À
intramolecular C N bond formation to afford 5H-
With the optimized reaction conditions in hand, we
indeno
trophilic fluorine source (such as N-fluorobenzenesul- ferent types of 2-alkynylbromobenzenes and 2-
fonimide 3, NSFI), the fluorinated 11H-indeno[1,2- alkynylanilines. As shown in Table 2, this reaction
ACHTUNGTRENNUNG[1,2-c]quinoline D. In the presence of an elec- next investigated the scope of the reaction using dif-
A
ACHTUNGTRENNUNG
c]quinoline 4 would be furnished. Although several proceeded with high selectivity to afford the desired
competitive reactions exist,[13] the attractiveness of 11- products in moderate to good yields. 2-Alkynylani-
fluoro-11H-indenoACTHNUTRGNE[NUG 1,2-c]quinoline 4 and the challenge lines with both electron-donating and electron-with-
of the synthetic route described in Scheme 1 prompt- drawing substituents could be smoothly converted
ed us to explore the feasibility of this transformation. into the desired products. For instance, 2-alkynylbro-
mobenzene 1a reacted with 2-alkynylaniline 2b and
N-fluorobenzenesulfonimide 3 leading to the corre-
sponding product 4b in 55% yield (Table 2, entry 2).
A similar yield was obtained when 2-alkynylaniline 2c
Results and Discussion
To begin our study, 2-alkynylbromobenzene 1a was with a p-methoxyphenyl group at the R4 position was
first reacted with 2-alkynylaniline 2a and N-fluoro- used as a replacement in the above reaction (50%
benzenesulfonimide 3 catalyzed by palladium acetate yield, Table 2, entry 3). When 2-alkynylaniline 2d with
(Table 1). A trace amount of the desired product 4a a p-chlorophenyl group at the R4 position was utilized
was detected when PCy3 was employed as the ligand as a substrate, its reaction of 2-alkynylbromobenzene
in the presence of Na2CO3 in 1,4-dioxane (Table 1, 1a with N-fluorobenzenesulfonimide 3 gave rise to
entry 1). No reaction occurred when t-BuOK was the expected product 4d in a lower yield (Table 2,
used as a replacement for the base (Table 1, entry 2). entry 4). Compared with the result from the reaction
Fortunately, the reaction proceeded as expected when of 5-methyl-2-alkynylaniline 2e (75% yield, Table 2,
NaOMe was utilized as base, albeit in low yield entry 5), an inferior yield was afforded when 5-
(Table 1, entry 3). With this promising preliminary chloro-2-alkynylaniline 2f was employed as the sub-
result in hand, different ligands, bases, and solvents strate in the above reaction under the standard condi-
were screened. Finally, we realized that this reaction tions (51% yield, Table 2, entry 6). Further explora-
172
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Generation of 11-Fluoro-11H-indenoACTHNURGTNE[UNG 1,2-c]quinolines via a Palladium-Catalyzed Three-Component Reaction
Table 1. Initial studies for the palladium-catalyzed three-component reaction of 2-alkynylbromobenzene 1a, 2-alkynylaniline
2a, and N-fluorobenzenesulfonimide 3.
Entry
Ligand
Base
Solvent
Yield [%][a]
1
2
3
4
5
6
7
8
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
Na2CO3
t-BuOK
NaOMe
DABCO
KOH
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
nr
12
33
64
62
52
73
64
42
trace
nr
nr
nr
K3PO4
Cs2CO3
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
9
PCy3
PCy3
10
11
12
13
14
15
16
DMF
DPPF[b]
DPEphos
XantPhos
L1
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
L2
XPhos
nr
trace
[a]
Isolated yield based on 2-alkynylaniline 2a.
DPPF: 1,1’-bis(diphenylphosphino)ferrocene.
[b]
tion indicated that various 2-alkynylbromobenzenes 1 formation works well with high selectivity, and diver-
were suitable reactants in the transformation. The sity and complexity could be easily introduced via a
structure of compound 4j was unambiguously deter- simple operation from readily available starting mate-
mined by X-ray crystallography analysis in the mean- rials. During the reaction process, a fluorine atom
time (see the Supporting Information). We also ex- could be incorporated into the scaffold. We believe
plored the reaction of 1-chloro-2-(2-phenylethynyl)- that the interesting biological activities would be ex-
benzene 1g, 2-alkynylaniline 2a and N-fluorobenzene- pected from the corresponding focused library. Fur-
sulfonimide 3 under the standard conditions shown in ther application of this strategy to explore new cas-
Table 2. This reaction worked well to afford the ex- cade reactions with the introduction of a fluorine
pected product 4a in 61% yield (Table 2, entry 18), atom is in progress.
which indicated aryl chloride was effective as well in
this transformation.
Experimental Section
Conclusions
General Experimental Procedure for the Palladium-
Catalyzed Three-Component Reaction of 2-
Alkynylbromobenzenes, 2-Alkynylanilines and N-
Fluorobenzenesulfonimide
In conclusion, we have described a novel and efficient
route for the generation of 11-fluoro-11H-indenoACTHUNTGRNEUNG[1,2-
c]quinolines via a palladium-catalyzed three-compo-
nent reaction of 2-alkynylbromobenzenes, 2-alkynyl-
2-Alkynylbromobenzene 1 (0.24 mmol) was added to a mix-
ACHTUNGTRENNUNGanilines, and N-fluorobenzenesulfonimide. This trans- ture of PdAHCUTNGTREN(NUNG OAc)2 (5 mol%), tricyclohexylphosphine
Adv. Synth. Catal. 2012, 354, 171 – 178
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Xiaolin Pan et al.
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Table 2. Scope investigation for the palladium-catalyzed three-component reaction of 2-alkynylbromobenzenes 1, 2-alkynyla-
nilines 2, and N-fluorobenzenesulfonimide 3.
Entry
1
2-Alkynylhalobenzene
2-Alkynylaniline
Product
Yield [%][a]
73
4a
4b
4c
4d
4e
4f
4g
2
3
4
5
6
7
1a
1a
1a
1a
1a
1a
55
50
40
75
51
45
8
1a
4h
4i
38
57
67
9
2a
2a
10
4j
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Generation of 11-Fluoro-11H-indeno
Table 2. (Continued)
ACHTUNGERTN[NUNG 1,2-c]quinolines via a Palladium-Catalyzed Three-Component Reaction
Entry
2-Alkynylhalobenzene
2-Alkynylaniline
Product
Yield [%][a]
56
11
2a
4k
4l
12
13
14
15
16
17
1d
1d
2b
2c
2a
2b
2a
2e
2a
41
43
86
54
38
42
61
4m
4n
4a
4p
4q
4r
1e
1f
18
[a]
Isolated yield based on 2-alkynylaniline 2.
(10 mol%), t-BuONa (0.8 mmol), and 2-alkynylaniline
(0.20 mmol) in 1,4-dioxane (2.0 mL). The mixture was
heated at 1008C. After 2-alkynylaniline 2 was consumed
completely, N-fluorobenzenesulfonimide (0.3 mmol) was
added to the mixture. After completion of the reaction as
indicated by TLC, the solvent was diluted by EtOAc
(10 mL), washed with saturated brine (2ꢂ10 mL), and dried
by anhydrous Na2SO4. Evaporation of the solvent followed
by purification on silica gel provides the product 4.
129.7, 129.1, 128.8, 128.7, 128.5, 128.4, 127.4, 125.0, 124.3,
124.2, 123.3, 101.5 (d, JC,F =183.6 Hz): HR-MS (ESI): m/z=
388.1500, calcd. for C28H18FN (M+H+): 388.1502.
11-Fluoro-6-phenyl-11-(p-tolyl)-11H-indenoACHTNUTRGNE[NUG 1,2-c]quino-
line (4b): 1H NMR (400 MHz, CDCl3): d=8.19 (d, J=
8.8 Hz, 1H), 7.78–7.76 (m, 3H), 7.67–7.59 (m, 4H), 7.43–
7.39 (m, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.32–7.30 (m, 2H),
7.20–7.10 (m, 4H), 6.97 (d, J=7.6 Hz, 1H), 2.33 (s, 3H);
19F NMR (376 MHz, CDCl3): d=À165.9; 13C NMR
11-Fluoro-6,11-diphenyl-11H-indenoACTHNUTRGNEUNG[1,2-c]quinoline (4a):
3
(100 MHz, CDCl3): d=155.6, 150.0 (d, JC,F =6.6 Hz), 148.1,
1H NMR (400 MHz, CDCl3): d=8.20 (d, J=8.8 Hz, 1H),
7.79–7.76 (m, 3H), 7.67–7.58 (m, 4H), 7.44–7.40 (m, 3H),
7.39–7.31 (m, 4H), 7.21–7.13 (m, 2H), 6.98 (d, J=7.6 Hz,
1H); 19F NMR (376 MHz, CDCl3): d=À166.7; 13C NMR
2
146.9 (d, 2JC,F =20.0 Hz), 139.9, 138.1, 136.4 (d, JC,F
=
4
27.5 Hz), 131.8, 130.1, 129.8 (d, JC,F =1.9 Hz), 129.7, 129.5,
3
129.1, 128.9, 128.8, 128.5, 127.3, 124.9, 124.4, 124.2 (d, JC,F
=
2
7.4 Hz), 123.4, 123.3, 101.6 (d, JC,F =183.0 Hz), 21.2; HR-MS
(ESI): m/z=402.1663, calcd. for C29H20FN (M+H+):
402.1658.
(100 MHz, CDCl3): d=155.7, 149.9 (d, JC,F =17.3 Hz), 146.7
2
2
(d, JC,F =19.8 Hz), 139.9, 139.4 (d, JC,F =27.4 Hz), 139.2 (d,
4JC,F =3.0 Hz), 131.9 (d, 4JC,F =3.4 Hz), 130.1, 129.9, 129.8,
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Xiaolin Pan et al.
FULL PAPERS
11-Fluoro-2-methoxy-6,11-diphenyl-11H-indeno
quinoline (4c): H NMR (400 MHz, CDCl3): d=8.19 (d, J=
[1,2-c]-
11-Fluoro-11-(4-methoxyphenyl)-2-methyl-6-phenyl-11H-
1
indenoACHTUNGTRNEUNG
[1,2-c]quinoline (4h): 1H NMR (400 MHz, CDCl3):
8.4 Hz, 1H), 7.80–7.76 (m, 3H), 7.68–7.64 (m, 1H), 7.61–
7.57 (m, 3H), 7.44–7.40 (m, 1H), 7.37–7.33 (m, 3H), 7.21–
7.17 (m, 1H), 7.14–7.10 (m, 1H), 6.97 (d, J=7.6 Hz, 1H),
6.87 (d, J=8.4 Hz, 2H), 3.78 (s, 3H); 19F NMR (376 MHz,
CDCl3): d=À164.7; 13C NMR (100 MHz, CDCl3): d=159.5,
d=8.08 (d, J=8.4 Hz, 1H), 7.77–7.75 (m, 2H), 7.59–7.58 (m,
3H), 7.54–7.48 (m, 2H), 7.35–7.33 (m, 3H), 7.20–7.17 (m,
1H), 7.13–7.10 (m, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.88 (d, J=
8.8 Hz, 2H), 3.79 (s, 3H), 2.41 (s, 3H); 19F NMR (376 MHz,
CDCl3): d=À166.4; 13C NMR (100 MHz, CDCl3): d=159.4,
2
2
155.7, 150.0, 148.2, 146.9 (d, JC,F =20.2 Hz), 140.0, 138.0 (d,
154.7, 148.9, 146.9, 140.1, 138.2, 137.3, 132.2, 131.5 (d, JC,F
=
4
4JC,F =3.1 Hz), 131.4 (d, 2JC,F =28.0 Hz), 129.7 (d, JC,F
=
28.1 Hz), 129.8, 129.7, 129.0, 128.9, 128.7, 128.3, 125.6 (d,
1.9 Hz), 129.7, 129.1, 128.8, 128.7, 128.4 (d, 4JC,F =1.6 Hz),
127.3, 125.6 (d, 3JC,F =7.5 Hz), 124.9, 124.4, 123.4, 123.3,
114.2, 101.5 (d, JC,F =182.6 Hz), 55.2; HR-MS (ESI): m/z=
418.1607, calcd. for C29H20FNO (M+H+): 418.1607.
3JC,F =7.4 Hz), 124.8, 123.4, 123.2, 123.1, 114.2, 110.8, 101.6
(d,
432.1759, calcd. for C30H22FNO (M+H+): 432.1764.
11-Fluoro-8-methyl-6,11-diphenyl-11H-indeno[1,2-c]quin-
JC,F =183.0 Hz), 55.2, 22.0; HR-MS (ESI): m/z=
AHCTUNGTRENNUNG
1
11-(4-Chlorophenyl)-11-fluoro-2-methyl-6-phenyl-11H-
oline (4i): H NMR (400 MHz, CDCl3): d=8.22 (dd, J=8.4,
2.6 Hz, 1H), 7.78–7.76 (m, 3H), 7.61–7.59 (m, 4H), 7.51–
7.22 (m, 7H), 7.04–6.99 (m, 1H), 6.77–6.76 (m, 1H), 2.16 (s,
3H); 19F NMR (376 MHz, CDCl3): d=À165.5; 13C NMR
(100 MHz, CDCl3): d=158.8 (d, 2JC,F =31.8 Hz), 153.4,
148.6, 148.1 (d, 3JC,F =8.1 Hz), 144.0 (d, 2JC,F =20.1 Hz),
indenoACHTUNGTRENNUNG
[1,2-c]quinoline (4d): 1H NMR (400 MHz, CDCl3):
d=8.09 (d, J=8.8 Hz, 1H), 7.77–7.75 (m, 2H), 7.60–7.58 (m,
3H), 7.51–7.49 (m, 1H), 7.46 (s, 1H), 7.38–7.30 (m, 5H),
7.22–7.12 (m, 2H), 6.97 (d, J=7.6 Hz, 1H), 2.42 (s, 3H);
19F NMR (376 MHz, CDCl3): d=À166.5; 13C NMR
2
139.9, 138.6, 135.9, 130.3, 130.1, 129.6 (d, 3JC,F =10.8 Hz),
(100 MHz, CDCl3): d=154.7, 147.0, 146.3 (d, JC,F
=
19.8 Hz), 140.0, 138.3 (d, 2JC,F =19.8 Hz), 140.0, 138.3 (d,
3
129.4, 129.1, 128.8 (d, 2JC,F =19.5 Hz), 128.2 (d, JC,F
=
4
4JC,F =2.8 Hz), 138.1, 137.6, 134.1, 132.3, 130.0 (d, JC,F
=
=
3
10.9 Hz), 127.3, 127.0, 126.7, 125.1 (d, JC,F =11.0 Hz), 124.8,
124.3, 123.3, 122.8, 101.3 (d, JC,F =183.3 Hz), 21.7; HR-MS
(ESI): m/z=402.1662, calcd. for C29H20FN (M+H+):
402.1658.
4
1.9 Hz), 129.9, 129.1, 129.0, 128.9, 128.8, 128.5 (d, JC,F
3
1.8 Hz), 125.8 (d, JC,F =7.6 Hz), 124.9, 123.4, 122.7, 101.3 (d,
J
C,F =184.5 Hz), 22.0; HR-MS (ESI): m/z=436.1262, calcd.
for C29H19ClFN (M+H+): 436.1268.
11-Fluoro-11-phenyl-6-(p-tolyl)-11H-indenoACHTNUTRGNE[NUG 1,2-c]quino-
11-Fluoro-2-methyl-6,11-diphenyl-11H-indenoACTHNUTRGNE[UNG 1,2-c]quin-
line (4j): 1H NMR (400 MHz, CDCl3): d=8.18 (d, J=
8.4 Hz, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.68–7.62 (m, 3H),
7.43–7.39 (m, 5H), 7.36–7.30 (m, 4H), 7.20–7.12 (m, 2H),
7.07 (d, J=7.6 Hz, 1H), 2.51 (s, 3H); 19F NMR (376 MHz,
CDCl3): d=À166.3; 13C NMR (100 MHz, CDCl3): d=155.8,
148.2, 146.8, 139.5 (d, 2JC,F =27.3 Hz), 139.0, 138.4, 137.0,
oline (4e): 1H NMR (400 MHz, CDCl3): d=8.08 (d, J=
8.8 Hz, 1H), 7.77–7.75 (m, 2H), 7.59–7.57 (m, 3H), 7.51–
7.46 (m, 2H), 7.44–7.42 (m, 2H), 7.35–7.32 (m, 4H), 7.19–
7.10 (m, 2H), 6.97 (d, J=7.6 Hz, 1H), 2.38 (s, 3H);
19F NMR (376 MHz, CDCl3): d=À166.8; 13C NMR
(100 MHz, CDCl3): d=154.7, 149.1 (d, 2JC,F =17.2 Hz),
4
134.3, 130.1, 129.8 (d, JC,F =1.7 Hz), 129.6, 129.4, 128.8 (d,
2
4
146.9, 146.7, 140.0, 139.5 (d, JC,F =27.4 Hz), 138.3 (d, JC,F
=
=
=
=
3JC,F =5.9 Hz), 128.3 (d, 2JC,F =18.3 Hz), 127.2, 125.0, 124.3
3
2.8 Hz), 137.4, 132.2, 129.8, 129.0, 128.9, 128.7 (d, JC,F
(d, 3JC,F =7.6 Hz), 124.2, 123.4, 123.2, 101.5 (d, JC,F
=
4
3
5.9 Hz), 128.3 (d, JC,F =1.6 Hz), 128.2, 124.9, 124.2 (d, JC,F
183.5 Hz); HR-MS (ESI): m/z=402.1652, calcd. for
7.6 Hz), 123.3, 123.1 (d, 2JC,F =30.4 Hz), 101.6 (d, JC,F
C29H20FN (M+H+): 402.1658.
183.6 Hz), 21.9; HR-MS (ESI): m/z=402.1652, calcd. for
11-Fluoro-8-methoxy-6,11-diphenyl-11H-indenoACTHNUGRTNEUNG[1,2-c]-
C29H20FN (M+H+): 402.1658.
1
quinoline (4k): H NMR (400 MHz, CDCl3): d=8.18 (d, J=
8.8 Hz, 1H), 7.75–7.73 (m, 3H), 7.66–7.62 (m, 1H), 7.44–
7.33 (m, 7H), 7.20–7.16 (m, 2H), 7.14–7.11 (m, 3H), 3.94 (s,
3H); 19F NMR (376 MHz, CDCl3): d=À166.3; 13C NMR
2-Chloro-11-fluoro-6,11-diphenyl-11H-indenoACTHNUTRGNE[NUG 1,2-c]quino-
line (4f): 1H NMR (400 MHz, CDCl3): d=8.12 (d, J=
9.2 Hz, 1H), 7.77–7.72 (m, 3H), 7.61–7.60 (m, 4H), 7.40–
7.36 (m, 6H), 7.23–7.13 (m, 2H), 7.00 (d, J=7.26 Hz, 1H);
19F NMR (376 MHz, CDCl3): d=À167.4; 13C NMR
(100 MHz, CDCl3): d=155.9, 146.7, 146.6, 139.6, 139.0,
138.7, 137.7 (d, 4JC,F =3.0 Hz), 134.0, 133.2, 131.7, 130.7,
130.0 (d, 4JC,F =1.8 Hz), 129.1 (d, 2JC,F =31.8 Hz), 128.8,
128.7, 128.5, 125.1, 124.2 (d, 3JC,F =7.6 Hz), 123.9, 123.5,
(100 MHz, CDCl3): d=160.4, 155.4, 150.0, 148.2, 146.7 (d,
4
2JC,F =19.8 Hz), 139.5 (d, 2JC,F =27.3 Hz), 138.4 (d, JC,F
=
4
3.0 Hz), 132.3, 131.9 (d, JC,F =3.2 Hz), 130.2, 130.0, 129.9 (d,
4JC,F =1.9 Hz), 129.8 (d, JC,F =29.5 Hz), 128.8, 128.4, 128.2,
2
127.2, 125.0, 124.3 (d, 3JC,F =7.1 Hz), 123.4, 123.2, 114.1,
101.5 (d,
JC,F =183.5 Hz), 55.4; HR-MS (ESI): m/z=
123.0, 101.4 (d,
JC,F =184.1 Hz); HR-MS (ESI): m/z=
418.1601, calcd. for C29H20FNO (M+H+): 418.1607.
422.1096, calcd. for C28H17ClFN (M+H+): 422.1112.
11-Fluoro-2-methyl-6-phenyl-11-(p-tolyl)-11H-indenoCATHNUGTNRE[NUG 1,2-
11-Fluoro-6-(4-methoxyphenyl)-11-(p-tolyl)-11H-indeno-
AHCTUNGTRENNUNG
[1,2-c]quinoline (4l): 1H NMR (400 MHz, CDCl3): d=8.18
c]quinoline (4g): 1H NMR (400 MHz, CDCl3): d=8.08 (d,
J=8.4 Hz, 1H), 7.77–7.75 (m, 2H), 7.59–7.54 (m, 4H), 7.49–
(d, J=8.4 Hz, 1H), 7.78–7.72 (m, 3H), 7.66–7.62 (m, 1H),
7.41–7.35 (m, 2H), 7.31–7.29 (m, 2H), 7.19–7.11 (m, 7H),
3.94 (s, 3H), 2.33 (s, 3H); 19F NMR (376 MHz, CDCl3): d=
À165.8; 13C NMR (100 MHz, CDCl3): d=160.4, 155.4, 148.2,
7.47ACHTUNGTRENNUNG(m, 1H), 7.35–7.30 (m, 3H), 7.19–7.09 (m, 4H), 6.96 (d,
J=7.6 Hz, 1H), 2.40 (s, 3H), 2.33 (s, 3H); 19F NMR
(376 MHz, CDCl3): d=À166.5; 13C NMR (100 MHz,
CDCl3); d=154.7, 146.9, 140.1, 138.2 (d, 4JC,F =2.3 Hz),
2
4
146.9 (d, JC,F =20.1 Hz), 138.3 (d, JC,F =2.9 Hz),138.0, 136.5
(d, 2JC,F =27.2 Hz), 134.2, 132.4, 131.9 (d, 4JC,F =3.3 Hz),
130.3, 129.9, 129.7 (d, 4JC,F =1.8 Hz), 129.6, 129.5, 128.4,
127.1, 124.9, 124.4, 124.2 (d, 3JC,F =7.4 Hz), 123.3, 123.2,
114.1, 101.6 (d, JC,F =182.8 Hz), 55.4, 21.2; HR-MS (ESI):
m/z=432.1771, calcd. for C30H22FNO (M+H+): 432.1764.
2
137.9, 137.3, 136.5 (d, JC,F =27.5 Hz), 132.1, 129.8, 129.7 (d,
4JC,F =1.8 Hz), 129.5, 129.0, 128.9, 128.7, 128.3, 124.9, 124.2
3
2
(d, JC,F =7.3 Hz), 123.4, 123.1 (d, JC,F =18.1 Hz), 101.7 (d,
C,F =183.1 Hz), 21.9, 21.2; HR-MS (ESI): m/z=416.1803,
calcd. for C30H22FN (M+H+): 416.1815.
J
176
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 171 – 178

Generation of 11-Fluoro-11H-indenoACTHNURGTNE[UNG 1,2-c]quinolines via a Palladium-Catalyzed Three-Component Reaction
11-Fluoro-6,11-bis(4-methoxyphenyl)-11H-indeno
quinoline (4m): H NMR (400 MHz, CDCl3): d=8.18 (d, J=
G
JC,F =183.1 Hz), 37.5, 30.7, 23.0, 21.8, 14.1; HR-MS (ESI):
m/z=382.1960, calcd. for C27H24FN (M+H+): 382.1971.
Crystallographic data for the structure 4j have been de-
posited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 827084. These data
can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif or on application to CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK [fax.: (internat.) +44-1223/336-033;
e-mail: deposit@ccdc.cam.ac.uk].
1
8.4 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.73 (d, J=8.8 Hz,
2H), 7.66–7.63 (m, 2H), 7.42–7.33 (m, 4H), 7.20–7.10 (m,
5H), 6.87 (d, J=8.8 Hz, 1H), 3.94 (s, 3H), 3.78 (s, 3H);
19F NMR (376 MHz, CDCl3): d=À164.7; 13C NMR
(100 MHz, CDCl3): d=160.4, 159.5, 155.4, 148.2, 146.9 (d,
2
2JC,F =20.2 Hz), 138.2, 134.3, 131.4 (d, JC,F =28.1 Hz), 130.3,
4
130.0, 129.7 (d, JC,F =1.8 Hz), 129.6, 128.4, 127.1, 125.7 (d,
3JC,F =7.3 Hz), 125.3, 124.9, 124.4, 123.3, 123.2, 114.1 (d,
3JC,F =5.1 Hz), 101.5 (d, JC,F =182.4 Hz), 55.4, 55.2; HR-MS
(ESI): m/z=448.1708, calcd. for C30H22FNO2 (M+H+):
448.1713.
Supporting Information
Experimental procedure, characterization data as well as
1 H, 19F and 13C NMR spectra of compounds 4 are available
as Supporting Information.
6-(4-Chlorophenyl)-11-fluoro-11-phenyl-11H-indenoACTHNUTRGNEU[GN 1,2-
c]quinoline (4n): 1H NMR (400 MHz, CDCl3): d=8.16 (d,
J=8.4 Hz, 1H), 7.77–7.73 (m, 3H), 7.67–7.63 (m, 1H), 7.59–
7.57 (m, 1H), 7.42–7.40 (m, 3H), 7.38–7.31 (m, 4H), 7.22–
7.15 (m, 2H), 7.06–7.04 (m, 1H), 2.87 (s, 1H); 19F NMR
(376 MHz, CDCl3): d=À166.2; 13C NMR (100 MHz,
2
Acknowledgements
CDCl3): d=154.3, 150.1 (d, JC,F =17.3 Hz), 148.2, 146.7 (d,
2JC,F =19.9 Hz), 139.3 (d, 4JC,F =27.4 Hz), 138.4, 137.9 (d,
4JC,F =3.0 Hz), 135.2, 130.4, 130.1, 129.9 (d, 4JC,F =1.8 Hz),
129.8, 129.0, 128.8, 128.7, 128.6, 128.3, 127.6, 125.2, 124.3,
Financial support from National Natural Science Foundation
of China (No. 21032007) is gratefully acknowledged.
124.4 (d, 3JC,F =7.7 Hz), 123.3, 123.1, 101.4 (d, JC,F
183.7 Hz); HR-MS (ESI): m/z=422.1107, calcd. for
C28H17ClFN (M+H+): 422.1112.
References
6-(4-Chlorophenyl)-11-fluoro-11-(p-tolyl)-11H-indenoACTHNUTRGNEU[GN 1,2-
c]quinoline (4o): 1H NMR (400 MHz, CDCl3): d=8.16 (d,
J=8.4 Hz, 1H), 7.79–7.73 (m, 3H), 7.68–7.63 (m, 1H), 7.59–
7.57 (m, 2H), 7.43–7.36 (m, 2H), 7.31–7.28 (m, 2H), 7.21–
7.19 (m, 1H), 7.17–7.14 (m, 3H), 7.04 (d, J=7.2 Hz, 1H),
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(4p): 1H NMR (400 MHz, CDCl3): d=8.10 (d, J=8.4 Hz,
1H), 7.82 (d, J=7.6 Hz, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.63–
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1.62 (m, 2H), 1.06 (t, J=7.6 Hz, 3H); 19F NMR (376 MHz,
CDCl3): d=À167.9; 13C NMR (100 MHz, CDCl3): d=158.0,
149.2 (d, 2JC,F =17.1 Hz), 148.1, 146.9 (d, 2JC,F =20.0 Hz),
À
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=
3
10.7 Hz), 126.6, 125.3, 124.3, 124.2, 124.1, 123.1, 123.0, 101.4
(d, JC,F =183.2 Hz), 37.6, 30.6, 23.0, 14.1; HR-MS (ESI):
m/z=368.1825, calcd. for C26H22FN (M+H+): 368.1815.
6-Butyl-11-fluoro-2-methyl-11-phenyl-11H-indenoACTHNUGTRNEUNG[1,2-c]-
1
quinoline (4q): H NMR (400 MHz, CDCl3): d=7.99 (d, J=
8.4 Hz, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.45–7. 43 (m, 3H),
7.39–7.38 (m, 1H), 7.33–7.21 (m, 6H), 3.41–3.36 (m, 2H),
2.35 (s, 3H), 1.95–1.89 (m, 2H), 1.66–1.61ACTHUNRTGNEUNG(m, 2H), 1.05 (t,
J=7.2 Hz, 3H); 19F NMR (376 MHz, CDCl3): d=À169.1;
13C NMR (100 MHz, CDCl3): d=157.0, 146.7, 139.6 (d,
2JC,F =27.3 Hz), 138.5 (d, 4JC,F =3.1 Hz), 136.5, 131.8, 130.3
(d, 4JC,F =1.6 Hz), 128.9, 128.8, 128.7, 128.2, 128.1, 125.2,
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