Iodocyclization of N-aryl-3-phenylpropiolamides by I2/CAN: A convenient route for the selective synthesis of quinolin-2-ones

Article abstract of DOI:10.1055/s-0030-1260101

A general method has been developed for the selective synthesis of 3-iodoquinolin-2-ones and spiro[4.5]trienes via intramolecular iodocyclization of N-(ortho-substituted aryl)-3-phenylpropiolamides using iodine/cerium(IV) ammonium nitrate reagent under mi

Full text of DOI:10.1055/s-0030-1260101

PAPER
2407
Iodocyclization of N-Aryl-3-phenylpropiolamides by I2/CAN: A Convenient
Route for the Selective Synthesis of Quinolin-2-ones
Synthesis of
Q
r
uinolin-
a
a
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India
X-ray Crystallography Center, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160921; E-mail: plikhar@iict.res.in
b
Received 28 February 2011; revised 31 May 2011
al. reported an alternative method for the electrophilic
ipso-cyclization of para-unactivated arylalkynes in the
presence of N-iodosuccinimide and acetic acid [Scheme 1
(B)].
Abstract: A general method has been developed for the selective
synthesis of 3-iodoquinolin-2-ones and spiro[4.5]trienes via in-
tramolecular iodocyclization of N-(ortho-substituted aryl)-3-phe-
nylpropiolamides using iodine/cerium(IV) ammonium nitrate
reagent under mild reaction conditions. The electronic effect of
ortho-substituents (electron-rich and electron-deficient group) trig-
gers the two different reaction pathways resulting to iodocyclized
quinolin-2-one and ipso-iodocyclized spiro-type compounds.
Ph
CF3
I2, CAN
N
MeO
(A)
O
MeCN, r.t.
Key words: iodocyclization, quinolin-2-ones, alkynes, heterocy-
cles, spiro compounds
I
N
CF3
Ph
R2
O
I
Y
NIS, AcOH
r.t.
The quinoline ring system is an important constituent of
natural products and is used in the design of many synthet-
ic compounds with pharmaceutical interest. Among the
known protocols, the electrophilic cyclization of aryl-sub-
stituted alkynes has provided an extremely useful route
for the construction of quinolines and isoquinolines under
mild condition.1 The pioneering work of Larock2 and
others3 on the electrophilic cyclization of functionally
substituted alkynes has proved that this protocol offers a
promising route to not only quinolines and isoquinolines,
but to a wide variety of heterocyclic and carbocyclic com-
pounds as well. In the reported methods, iodine
monochloride, iodine/sodium hydrogen carbonate, or N-
iodosuccinimide are usually employed as an iodine source
for the intramolecular electrophilic iodocyclization. Re-
cently, we have reported that 2-(perfluoroalkyl)quinolines
can be synthesized in good to excellent yield by electro-
philic cyclization of perfluoroalkyl propargyl imines us-
ing iodine/cerium(IV) ammonium nitrate in acetonitrile at
room temperature.4 In this report, interestingly the aryl
ring bearing active para-substituents (OMe), N-4-meth-
oxyphenyl perfluoroalkyl propargyl imines showed selec-
tive ipso-cyclization to an azaspiro compound in excellent
yield [Scheme 1 (A)]. Indeed, the same results were re-
ported by the groups of Fanghanel,5 Larock,6 and Li7 for
the iodocyclization of N-(para-substituted aryl)propiola-
mides to ipso-cyclized azaspiro compounds using iodine
and iodine monochloride as electrophiles. Thus, it was
generalized that the ipso-cyclization can be achieved from
arylalkynes bearing active para-substituents, such as
methoxy and N,N-dimethylamino groups. However, Li et
(B)
AcO
O
R1
R1
Y
O
R2
R3
N
Y = NMe2,O
O
I
R2
R1
R2
major
RfCH2OH, NXS
R1
(C)
+
molecular sieves
80 °C, X = I, Br, Cl
R2
N
O
R3
I
R1
N
O
R3
trace
R2
MeO
I2, CAN
no reaction
(D)
MeCN, r.t.
N
H
O
Scheme 1
In continuation of our previous investigation of the io-
docyclization of perfluoroalkyl propargyl imines/amines,4
we started to examine the iodocyclization of other sub-
strates (non-perfluoroalkyl-substituted compounds). We
first focused on the cyclization of N-(4-methoxyphenyl)-
3-phenylpropiolamide by iodine/cerium(IV) ammonium
nitrate in acetonitrile at room temperature, but no desired
product was obtained [Scheme 1 (D)]. Stimulated by our
previous observation and the unforeseen results of N-(4-
methoxyphenyl)-3-phenylpropiolamide prompted us to
study the electrophilic iodocyclization of N-(ortho-substi-
tuted and unsubstituted aryl)-3-phenylpropiolamides by
iodine/cerium(IV) ammonium nitrate reagents. In this
context, very recently Li et al. have reported the electro-
SYNTHESIS 2011, No. 15, pp 2407–2414
x
x.
x
x
.
2
0
1
1
Advanced online publication: 08.07.2011
DOI: 10.1055/s-0030-1260101; Art ID: N23211SS
© Georg Thieme Verlag Stuttgart · New York

2408
P. R. Likhar et al.
PAPER
philic ipso-halocyclization of N-arylpropynamides with 47% isolated yield (Table 1, entry 1). Subsequently, the
polyfluoroalkyl alcohols and halosuccinimide as a nu- optimal conditions for iodine and cerium(IV) ammonium
cleophile and halide source respectively for the synthesis nitrate to afford the maximum product yield of 2b were
of 8-(polyfluoroalkoxy)azaspiro[4.5]trienes as the major identified. The highest yield (65%) was obtained with 2.0
product with trace amounts of phenylquinolin-2(1H)- equivalents of iodine and 2.0 equivalents of cerium(IV)
ones8 [Scheme 1 (C)]. Here, we wish to report that ortho- ammonium nitrate in 0.1 M acetonitrile at room tempera-
substituted (electron-rich group) and unsubstituted N- ture (entry 2). Iodocyclization was also carried out with
aryl-3-phenylpropiolamides can undergo electrophilic io- iodine (2.0 equiv) in acetonitrile at room temperature, no
docyclization with iodine/cerium(IV) ammonium nitrate cyclized product 2b was obtained whereas with a strong
to selectively yield 3-iodo-phenylquinolin-2-ones in good electrophile, when iodine monochloride was employed a
to excellent yields. Furthermore, we report that ortho-sub- negligible amount of product 2b was formed (entries 5
stituted (electron-deficient groups) N-aryl-3-phenylpro- and 6).
piolamides can afford selectively spiro[4.5]triene
compounds in the presence of iodine/cerium(IV) ammo-
nium nitrate in good to excellent yields. We assume that
To investigate the scope of the reaction, the effect of var-
ious ortho-substituted groups on the aniline moiety were
examined. The electron-donating and electron-withdraw-
the rational behind the adoption of two different reaction
ing behavior of the substituents has varying effect on the
pathways depends on the electronic environment in the ar-
product yields. The electron-donating substituents such as
omatic ring. The ortho-substituted phenylpropiolamides
the methoxy, and tert-butyl group afforded 2b–d good to
excellent yields (Table 2, entries 2–4) whereas strong
electron-withdrawing substituents such as trifluoromethyl
and N-aryl-3-phenylpropiolamides were prepared in good
to excellent yields from phenylpropiolic acid and substi-
tuted anilines using dicyclohexylcarbodiimide as cou-
and fluorine were found to be inactive in the cyclization
pling agent.9,10
reactions (entry 5). The effect of substituents on the alky-
To find the standard experimental procedure, as a model nyl phenyl was also examined for 1f–h and it was found
reaction, we selected N-(2-methoxyphenyl)-3-phenylpro- that they cyclized to give 2f–h in good yields (entries 6–
piolamide (1b) as the substrate and iodine monochloride, 8). Among the aliphatic alkynes, 1i and 1j, only methyl-
molecular iodine, and iodine/cerium(IV) ammonium ni- substituted alkyne 1i could undergo facile iodocyclization
trate as iodine source in acetonitrile at room temperature. in moderate yields (entry 9). We have also examined the
effect of meta-substituted group on the aniline moiety 1k;
Table 1 Screening of Iodine, Iodine Monochloride and Iodine/
however, no cyclization was observed in this reaction (en-
try 11).
Cerium(IV) Ammonium Nitrate in the Iodocyclization of Phenylpro-
piolamide 1ba
Interestingly, when phenyl, bromo, and chloro groups in
the ortho position of the aniline 1l–n were used,
spiro[4.5]triene products 3l–n were obtained in moderate
to good yields (Table 3, entries 1–3). Arylalkyne 1o hav-
ing methyl group at terminal alkyne was an unsuitable
substrate for the ipso-iodocyclization under our optimized
reaction conditions (entry 4).
Ph
Ph
I
I+
MeCN, r.t.
N
H
O
N
O
H
OMe
OMe
1b
2b
These results are contradictory to the results obtained by
Li et al. in which N-(4-methoxyphenyl)-N-methyl-3-phe-
nylpropynamide underwent ipso-iodocyclization but gave
the 1-azaspiro[4.5]decane-2,8-dione devoid of the trifluo-
romethyl group in the spirocyclic motif.8 The role of
2,2,2-trifluoroethanol ascribed by Li et al. in the reaction
was as a strong nucleophile that attacked the para position
of aniline and assisted in ipso-cyclization. However, in the
present study, the source of oxygen was ascertained by
conducting a controlled reaction with (2-bromophenyl)-3-
phenylpropiolamide and iodine/cerium(IV) ammonium
nitrate in dry acetonitrile under identical experimental
Entry
I+ (equiv)
I2 (2.0)
I2 (2.0)
I2 (3.0)
I2 (2.0)
I2 (1.0)
ICl
CAN (equiv) Time (h) Yieldb (%)
1
2
3
4
5
6
1.0
2.0
2.0
2.0
0
6
4
47
65
65
43
0
3
6
24
24
0
trace
a Reaction conditions: 1b (0.25 mmol), I2 and CAN, 0.1 M MeCN, r.t.
b Isolated yield of 2b.
conditions
and
found
that
bromo-substituted
spiro[4.5]trienes formed in only 7% yield. This observa-
tion suggests that water may be the possible source of ox-
ygen. To confirm the role of water, the reaction was
conducted in the presence of acetic acid (2 equiv) with N-
(2-bromophenyl)-3-phenylpropiolamide using iodine/
cerium(IV) ammonium nitrate in dry acetonitrile and this
gave the 8-acetoxy-substituted spiro[4.5]triene in 72%
(cis/trans 40:60) (Scheme 2).
With the recent success in iodocyclization of the perfluo-
roalkyl propargyl imines,4 the iodocyclization of N-(2-
methoxyphenyl)-3-phenylpropiolamide (1b) was exam-
ined using iodine (2.0 equiv)/cerium(IV) ammonium ni-
trate (1.0 equiv) in 0.1 M acetonitrile at room temperature
and the desired product quinolin-2-one 2b was obtained in
Synthesis 2011, No. 15, 2407–2414 © Thieme Stuttgart · New York

PAPER
Synthesis of Quinolin-2-ones
2409
Table 2 Iodocyclization of N-Aryl-3-phenylpropiolamides 1a–ka
R1
R1
I2, CAN
MeCN
I
N
H
O
N
H
O
R2
R2
1a–k
2a–i
Entry
Arylalkyne 1
Product 2
Time (h)
Yieldb (%)
Ph
Ph
I
1
2
1a
2a
4
4
62
N
O
N
O
O
Me
Me
Ph
Ph
I
1b
2b
65
N
H
N
H
O
OMe
OMe
1b
N
N
3
4
1c
2c
3
3
88
93
O
Ph
O
Ph
I
Ph
Ph
I
1d
2d
N
H
O
N
H
O
Ph
c
5
6
1e
1f
–
24
0
N
H
O
CF3
2f
3
75
I
N
H
O
N
H
O
OMe
OMe
I
7
1g
2g
3
84
N
H
O
N
H
O
Synthesis 2011, No. 15, 2407–2414 © Thieme Stuttgart · New York

2410
P. R. Likhar et al.
PAPER
Table 2 Iodocyclization of N-Aryl-3-phenylpropiolamides 1a–ka (continued)
R1
R1
I2, CAN
MeCN
I
N
H
O
N
H
O
R2
R2
1a–k
2a–i
Entry
Arylalkyne 1
Product 2
Time (h)
Yieldb (%)
OMe
OMe
8
9
1h
2h
3
78
I
N
H
O
N
H
O
I
1i
2i
4
66
N
H
O
N
H
O
O
c
10
11
1j
–
–
24
24
0
0
N
H
Ph
c
1k
MeO
N
O
H
a Reaction conditions: 1a–k (0.25 mmol), I2 (0.5 mmol), CAN (0.5 mmol), MeCN (5 mL), r.t.
b Isolated yield. All products are characterized by NMR spectroscopy and mass spectrometry.
c No reaction.
The N-methyl substrate, N-methyl-N,3-diphenylpropiola- for the formation of spiro[4.5]trienes can be explained
mide (1a), also underwent clean cyclization and this result with the initial formation of an iodonium intermediate I
provided an interesting contrast to the substrates that do by electrophilic attack of the iodine cation which is gener-
not bear a meta- or para-methoxy group and have an un- ated in situ by activation with cerium(IV) ammonium ni-
substituted NH group that do not cyclize under the same trate, on the C≡C bond of the propargylic aniline
conditions [Table 2, entry 1 vs. entry 11, and Scheme 1 (Scheme 3). The presence of an electron-withdrawing
(D)]. The ortho groups in combination with the NH group group in the ortho position activates the para position and
have a pronounced effect on the cyclization reaction facilitates nucleophilic OH substitution at the para posi-
which may be attributed to the steric size of the ortho
Ph
group, which imposes a conformational change on the
amide and brings it closer to the arene ring for cyclization.
AcO
Ph
I2, CAN, AcOH
anhyd MeCN
Similarly, the ortho effect must be more than an electronic
effect, as if this were the case the meta- and para-methoxy
compounds would also cyclize.
I
N
O
HN
Br
H
Br
O
The phenyl-substituted spiro[4.5]triene 3l (Table 3, entry
1) was fully characterized by various spectroscopic tools
and the structure was confirmed by a single-crystal X-ray
diffraction study (Figure 1).11 The plausible mechanism
72% (cis/trans = 40:60)
Scheme 2 ipso-Iodocyclization of N-(2-bromophenyl)-3-phenyl-
propiolamide in the presence of iodine/cerium(IV) ammonium nitrate
and acetic acid
Synthesis 2011, No. 15, 2407–2414 © Thieme Stuttgart · New York

PAPER
Synthesis of Quinolin-2-ones
2411
Table 3 ipso-Iodocyclization of N-Aryl-3-phenylpropiolamides
1l–na
R2
R2
O
I2, CAN
MeCN
I
N
H
O
HN
R1
R1
O
1l–o
3l–n
Entry
1
R1
Ph
Br
Cl
Br
R2
3
Time (h) Yieldb (%)
1
2
3
4
1l
Ph
Ph
Ph
Me
3l
3m
3n
–
3
3
89
91
67
0
1m
1n
1o
5
24
Figure 1 ORTEP diagram of phenyl-substituted spiro[4.5]triene 3l
a Reaction conditions: 1l–o (0.25 mmol), I2 (0.5 mmol), CAN (0.5
mmol), MeCN (5 mL), r.t.
Ph
b Isolated yield of 31–n. All products are characterized by NMR and
mass spectroscopy.
Ph
I+
Ph
I
I+
N
H
O
N
O
tion of the aryl moiety in II. As discussed earlier, the trace
amounts of water present in the reaction system plays an
important role in this step. The subsequent oxidation of
the hydroxy group in 4 to the carbonyl group affords
spiro[4.5]triene-type compounds 3. It is believed that ce-
rium(IV) ammonium nitrate acts as an efficient and con-
venient activator for iodine during the activation process
through the reduction of Ce(IV) to Ce(III).4,12
N
O
H
H
R
R
R
1
2
I
I2 + CAN = I+
R = electron-donating group
Scheme 4 Plausible mechanism for the formation of 3-iodoquino-
lin-2(1H)-ones
clization of the aniline aromatic ring with the activated tri-
ple bond results in the formation of corresponding 3-
iodoquinolin-2(1H)-one 2.
The one-electron oxidizing property of cerium(IV) am-
monium nitrate is well-illustrated in the oxidative addition
reactions of electrophilic radicals to alkenes, enabling in- From the above studies, it can be generalized that under
termolecular and intramolecular carbon–carbon and the experimental conditions, the electron-donating group
carbon–heteroatom bond formation.13 Cerium(IV) ammo- at the ortho position of arylalkynes or unsubstituted phe-
nium nitrate also oxidizes secondary alcohols into ketones nylalkyne can selectively undergo iodocyclization to 3-io-
and benzylic alcohols into aldehydes.14 The oxidation of a doquinolin-2-one compounds whereas with electron-
carbonyl group to corresponding radical cation is also withdrawing group at the ortho position of arylalkynes
well established through one-electron transfer by ceri- they can undergo cyclization to afford 3-iodo-
um(IV) ammonium nitrate.14
spiro[4.5]triene compounds.
The plausible mechanism for iodocyclization of N-aryl-3- The presence of the iodide functional group at the 3-posi-
phenylpropiolamide 1 presented herein is outlined in tion of the quinoline ring provides an opportunity to ex-
Scheme 4 and can be explained with initial formation of plore the scope of the chemistry. 3-Iodoquinolin-2(1H)-
iodonium intermediate I. The intramolecular ortho cy- one 2d underwent facile Suzuki coupling with phenylbo-
ronic acid catalyzed by bis(triphenylphosphine)palladi-
um(II) dichloride to afford highly substituted 8-tert-butyl-
3,4-diphenylquinolin-2(1H)-one (5) in good yield (80%)
(Scheme 5).
Ph
Ph
Ph
I
+
I
I+
+
N
O
N
O
N
H
O
H
H
R
R
R
I2 + CAN = I+
Ph
1
I
II
Ph
B(OH)2
Ph
I
Ph
O
Ph
'Pd', K2CO3, DMF
N2, 100 °C
I
I
+
H2O
– H+
oxidation
CAN
HO
O
N
H
O
N
H
N
H
N
H
O
O
R
R
5 80%
2d
4
3
Scheme 3 Plausible mechanism for the formation of spiro-type
compounds
Scheme 5 Suzuki coupling of 3-iodoquinol-2(1H)-one with boronic
acid
Synthesis 2011, No. 15, 2407–2414 © Thieme Stuttgart · New York

2412
P. R. Likhar et al.
PAPER
IR (KBr): 1631 cm–1.
1H NMR (300 MHz): d = 7.55–7.45 (m, 3 H), 7.30–7.26 (m, 1 H),
In conclusion, we have developed an efficient and simple
methodology for the selective synthesis of quinolin-
2(1H)-ones and spiro[4.5]trienes using two different elec- 7.19 (dd, J = 7.55, 1.7 Hz, 2 H), 6.95–6.90 (m, 2 H), 4.33 (t,
tronic environments at the ortho-position of arylalkynes
using the iodine/cerium(IV) ammonium nitrate system.
The iodocyclization by iodine/cerium(IV) ammonium ni-
trate showed considerable synthetic advantages, in terms
of mild reaction conditions, simplicity of the reaction pro-
cess and good-to-excellent yields.
J = 5.85, 2 H), 8.04 (t, J = 6.23 Hz, 2 H), 2.24–2.14 (d, J = 6.04 Hz,
2 H).
13C NMR (75.5 MHz): d = 158.52, 156.07, 141.36, 136.17, 130.22,
128.59, 128.40, 128.26, 126.73, 124.77, 121.82, 121.24, 101.09,
44.47, 27.66, 20.77.
MS (ESI): m/z = 388 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C18H15INO: 388.0198; found:
388.0202.
All chemicals were purchased from Aldrich and were used as re-
ceived. All solvents used were analytical grade and were used as re-
ceived from Merck India Pvt. Ltd. 1H and 13C spectra were recorded
on a Bruker, Avance 300 (300 MHz 1H and 75 MHz 13C) spectrom-
eter at r.t. with respect to TMS and CDCl3 for 1H and 13C NMR, re-
spectively; residual CHCl3 (1H: d = 7.25 ppm; 13C: d = 77 ppm).
Acme silica gel (60–120 mesh) was used for column chromatogra-
phy and TLC was performed on Merck precoated silica gel 60-F254
plates.
8-tert-Butyl-3-iodo-4-phenylquinolin-2(1H)-one (2d)
Yield: 94 mg (93%); white solid; mp 210–212 °C.
IR (KBr): 3274, 1651 cm–1.
1H NMR (300 MHz): d = 9.16 (br s, 1 H), 7.56–7.46 (m, 4 H), 7.22–
7.18 (m, 2 H), 6.98–6.93 (m, 2 H), 4.61 (s, 9 H).
13C NMR (75.5 MHz): d = 158.91, 158.65, 141.51, 135.77, 134.04,
128.71, 128.55, 128.51, 128.13, 127.11, 122.30, 121.53, 99.38,
34.12, 30.59.
Iodocyclization of N-Arylpropiolamides 1; General Procedure
N-Arylpropiolamide (0.25 mmol), I2 (2 equiv), and CAN (2 equiv)
were added to a reaction vessel containing MeCN (5 mL). The mix-
ture was stirred at r.t. for the required time and was then diluted with
EtOAc (30 mL), and washed with sat. aq Na2S2O3 (25 mL). The or-
ganic layer was separated and the aqueous layer was extracted with
fresh EtOAc (2 × 30 mL). The combined organic layers were dried
(anhyd Na2SO4). The solvent was evaporated under reduced pres-
sure and the products were purified by column chromatography (sil-
ica gel, hexane–EtOAc, 10:1) to afford pure product.
MS (ESI): m/z = 404 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C19H19INO: 404.0511; found:
404.0509.
8-tert-Butyl-3-iodo-4-naphthalen-1-ylquinolin-2(1H)-one (2f)
Yield: 85 mg (75%); white solid; mp 286–288 °C.
IR (KBr): 3274, 1650 cm–1.
1H NMR (300 MHz): d = 9.24 (br s, 1 H), 7.96 (dd, J = 8.31, 3.78
Hz, 1 H), 7.61 (t, J = 7.58 Hz, 1 H), 7.54–7.46 (m, 2 H), 7.38 (d,
J = 3.59 Hz, 2 H), 7.30 (d, J = 6.79 Hz, 1 H), 6.85 (t, J = 7.55 Hz, 1
H), 6.75 (d, J = 8.12 Hz, 1 H), 1.65 (s, 9 H).
13C NMR (75.5 MHz): d = 158.74, 154.75, 147.62, 138.99, 134.16,
133.57, 132.20, 128.99, 128.66, 128.53, 127.18, 126.86, 126.58,
126.43, 126.20, 125.52, 125.05, 122.5, 100.77.
3-Iodo-1-methyl-4-phenylquinolin-2(1H)-one (2a)
Yield: 55 mg (62%); white solid; mp 172–174 °C.
IR (KBr): 1633 cm–1.
1H NMR (300 MHz): d = 7.58–7.46 (m, 4 H), 7.38 (d, J = 8.5 Hz, 1
H), 7.20 (d, J = 7.6 Hz, 2 H), 7.11 (d, J = 7.7 Hz, 1 H), 7.08–7.00
(m, 1 H), 3.89 (s, 3 H).
13C NMR (75.5 MHz): d = 159.07, 156.29, 141.14, 139.48, 131.03,
128.86, 128.71, 128.58, 128.36, 122.34, 121.41, 114.16, 101.40,
31.69.
MS (ESI): m/z = 454 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H21INO: 454.0667; found:
454.0660.
MS (ESI): m/z = 362 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C16H13INO: 362.0041; found:
8-tert-Butyl-3-iodo-4-(2-methoxyphenyl)quinolin-2(1H)-one
(2g)
Yield: 91 mg (84%); white solid; mp 196–198 °C.
IR (KBr): 3303, 1642 cm–1.
362.0036.
3-Iodo-8-methoxy-4-phenylquinolin-2(1H)-one (2b)
Yield: 61 mg (65%); yellow solid; mp 124–126 °C.
IR (KBr): 3411, 1729 cm–1.
1H NMR (300 MHz): d = 9.11 (br s, 1 H), 7.74 (dd, J = 9.07, 2.27
Hz, 1 H), 7.51–7.48 (m, 1 H), 7.34 (d, J = 2.27 Hz, 1 H), 7.06–6.92
(m, 3 H), 6.82 (d, J = 9.07 Hz, 1 H), 3.76 (s, 3 H), 1.61 (s, 9 H).
13C NMR (75.5 MHz): d = 158.59, 155.66, 154.99, 139.00, 138.98,
137.64, 135.74, 134.10, 132.49, 128.51, 128.50, 126.31, 122.44,
113.85, 82.48, 55.87, 34.11, 30.59.
1H NMR (300 MHz): d = 8.58 (d, J = 8.88 Hz, 1 H), 8.2 (br s, 1 H),
7.93 (dd, J = 9.07, 2.27 Hz, 1 H), 7.76 (d, J = 2.27 Hz, 1 H), 7.62 (s,
1 H), 7.60 (d, J = 1.32 Hz, 1 H), 7.49–7.35 (m, 3 H), 4.07 (s, 3 H).
MS (ESI): m/z = 434 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C20H21INO2: 434.0617; found:
13C NMR (75.5 MHz): d = 166.04, 150.85, 147.24, 143.57, 133.12,
132.72, 130.68, 128.65, 119.48, 119.03, 117.63, 105.31, 83.08,
56.46.
434.0618.
MS (ESI): m/z = 378 [M + H]+.
8-tert-Butyl-3-iodo-4-(4-methoxyphenyl)quinolin-2(1H)-one
(2h)
Yield: 84 mg (78%); white solid; mp 199–201 °C.
HRMS (ESI): m/z [M + H]+ calcd for C16H13INO2: 377.9913; found:
377.9902.
IR (KBr): 3295 cm–1.
1H NMR (300 MHz): d = 9.17 (br s, 1 H), 7.53–7.42 (m, 1 H), 7.13–
6.88 (m, 6 H), 3.84 (s, 3 H), 1.51 (s, 9 H).
6-Iodo-7-phenyl-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinolin-5-
one (2c)
Yield: 85 mg (88%); white solid; mp 174–176 °C.
Synthesis 2011, No. 15, 2407–2414 © Thieme Stuttgart · New York

PAPER
Synthesis of Quinolin-2-ones
2413
13C NMR (75.5 MHz): d = 159.61, 158.80, 158.70, 139.00, 137.11,
135.40, 134.01, 129.53, 128.43, 127.20, 122.24, 114.03, 100.00,
55.29, 34.11, 30.59.
MS (ESI): m/z = 434 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C20H21INO2: 434.0617; found:
8-tert-Butyl-3,4-diphenylquinolin-2(1H)-one (5)
Yield: 71 mg (80%); white solid; mp 259–260 °C.
IR (KBr): 3257, 1650 cm–1.
1H NMR (300 MHz): d = 9.15 (br s, 1 H), 7.47 (d, J = 7.55 Hz, 1 H),
7.37–7.18 (m, 3 H), 7.18–7.02 (m, 8 H), 7.02–6.92 (m, 1 H), 1.64
(s, 9 H).
434.0597.
13C NMR (75.5 MHz): d = 161.13, 150.42, 136.7, 135.82, 134.93,
133.71, 131.23, 130.58, 129.70, 128.77, 127.89, 127.71, 127.62,
127.48, 126.97, 126.79, 121.71, 34.14, 30.64.
MS (ESI): m/z = 354 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C25H24NO: 354.1857; found:
8-tert-Butyl-3-iodo-4-methylquinolin-2(1H)-one (2i)
Yield: 56 mg (66%); white solid; mp 206–208 °C.
IR (KBr): 1640, 3303 cm–1.
1H NMR (300 MHz): d = 9.02 (br s, 1 H), 7.66 (d, J = 8.309 Hz, 1
H), 7.52 (dd, J = 7.554, 1.511 Hz, 1 H), 7.15–7.08 (m, 1 H), 2.82 (s,
3 H), 1.57 (s, 9 H).
354.1875.
13C NMR (75.5 MHz): d = 158.36, 153.57, 135.2, 134.35, 128.35,
124.15, 122.42, 120.57, 100.45, 34.09, 30.6, 26.69.
Acknowledgment
MS (ESI): m/z = 342 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C14H17INO: 342.0354; found:
S.S.R. and M.V.K. thank CSIR and UGC for providing research fel-
lowships.
342.0343.
References
3-Iodo-4,6-diphenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione
(3l)
(1) (a) Jia, C.; Piao, D.; Kitamura, T.; Fujiwara, Y. J. Org.
Chem. 2000, 65, 7516. (b) Fischer, D.; Tomeba, H.; Pahadi,
N. K.; Patil, N. T.; Yamamoto, Y. Angew. Chem. Int. Ed.
2007, 46, 4764. (c) Ding, Q.; Wang, Z.; Wu, J. J. Org.
Chem. 2009, 74, 921. (d) Yao, T.; Larock, R. C. J. Org.
Chem. 2005, 70, 1432. (e) Zhang, X.; Yao, T.; Campo, M.
A.; Larock, R. C. Tetrahedron 2010, 66, 1177.
Yield: 98 mg (89%); white solid; mp 190–192 °C.
IR (KBr): 3322, 1716, 1657 cm–1.
1H NMR (300 MHz): d = 7.57 (br s, 1 H), 7.42–7.27 (m, 7 H), 7.26
(dd, J = 5.86, 1.46 Hz, 1 H), 7.18 (s, 1 H), 7.16 (s, 1 H), 6.57 (dd,
J = 10.26, 1.46 Hz, 1 H), 6.42–6.37 (m, 2 H).
13C NMR (75.5 MHz): d = 184.93, 170.23, 160.35, 154.31, 145.85,
135.69, 131.48, 130.44, 130.20, 129.95, 128.63, 128.60, 127.77,
127.40, 97.62, 68.69, 29.64.
MS (ESI): m/z = 462 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C21H14INNaO2: 461.9967;
(2) (a) Zhang, X.; Campo, M. A.; Yao, T.; Larock, R. C. Org.
Lett. 2005, 7, 763. (b) Larock, R. C. Pure Appl. Chem. 1999,
71, 1435. (c) Huang, Q.; Larock, R. C. J. Org. Chem. 2003,
68, 980. (d) Huang, Q.; Larock, R. C. Tetrahedron Lett.
2002, 43, 3557. (e) Huang, Q.; Hunter, J. A.; Larock, R. C.
J. Org. Chem. 2002, 67, 3437. Selected recent papers on
other heterocycles and carbocycles: (f) Yue, D.; Larock, R.
C. J. Org. Chem. 2002, 67, 1905. (g) Yao, T.; Larock, R. C.
Tetrahedron Lett. 2002, 43, 7401. (h) Yao, T.; Larock, R. C.
J. Org. Chem. 2005, 70, 1432. (i) Yao, T.; Campo, M. A.;
Larock, R. C. J. Org. Chem. 2005, 70, 3511. (j) Yue, D.;
Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 10292.
(k) Pattarozzi, M.; Zonta, C.; Broxterman, Q. B.; Kaptein,
B.; Zorzi, R. D.; Randaccio, L.; Scrimin, P.; Licini, G. Org.
Lett. 2007, 9, 2365. (l) Ciochina, R.; Grossman, R. B. Chem
Rev. 2006, 106, 3963. (m) Bi, H.-P.; Guo, L.-N.; Duan, X.-
H.; Gou, F.-R.; Huang, S.-H.; Liu, X.-Y.; Liang, Y.-M. Org.
Lett. 2007, 9, 397. (n) Barluenga, J.; Villa, H. V.;
found: 461.9959.
6-Bromo-3-iodo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3m)
Yield: 100 mg (91%); brown solid; mp 196–198 °C.
IR (KBr): 3305, 1723, 1653 cm–1.
1H NMR (300 MHz): d = 7.45–7.35 (m, 3 H), 7.32–7.24 (m, 2 H),
7.03 (br s, 1 H), 6.83–6.75 (m, 2 H), 6.39 (d, J = 9.82 Hz, 1 H).
13C NMR (75.5 MHz): d = 182.15, 170.14, 159.81, 143.89, 143.62,
135.71, 130.93, 130.41, 128.79, 127.57, 98.74, 70.20.
MS (ESI): m/z = 464 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C15H9BrINNaO2: 463.8759;
Ballesteros, A.; González, J. M. J. Am. Chem. Soc. 2003,
125, 9028. (o) Barluenga, J.; Trincado, M.; Rubio, E.;
Gonzalez, J. M. Angew. Chem. Int. Ed. 2003, 42, 2406.
(p) Barluenga, J.; Trincado, M.; Rubio, E.; Gonzalez, J. M.
Angew. Chem. Int. Ed. 2006, 45, 3140. (q) Barluenga, J.;
Palomas, D.; Rubio, E.; Gonzalez, J. M. Org. Lett. 2007, 9,
2823.
found: 463.8739.
6-Chloro-3-iodo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3n)
Yield: 66 mg (67%); white solid; mp 188–190 °C.
IR (KBr): 3184, 1702, 1663 cm–1.
1H NMR (300 MHz): d = 8.12 (br s, 1 H), 7.55–7.35 (m, 3 H), 7.32–
7.21 (m, 2 H), 6.74 (d, J = 9.82 Hz, 1 H), 6.53 (d, J = 1.51 Hz, 1 H),
6.40 (dd, J = 9.82, 1.51 Hz, 1 H).
13C NMR (75.5 MHz): d = 182.93, 159.56, 150.47, 143.54, 131.56,
130.91, 130.572, 130.42, 128.83, 127.47, 98.62, 69.64, 29.66.
(3) (a) Guimond, N.; Fagnou, K. J. Am. Chem. Soc. 2009, 131,
12050. (b) Halim, R.; Scammells, P. J.; Flynn, B. L. Org.
Lett. 2008, 10, 1967. (c) Huo, Z.; Gridnev, I. D.; Yamamoto,
Y. J. Org. Chem. 2010, 75, 1266. (d) Sun, Q.; LaVoie, E. J.
Heterocycles 1996, 43, 737. (e) Sashida, H.; Kawamukai,
A. Synthesis 1999, 1145. (f) Amii, H.; Kishikawa, Y.;
Uneyama, K. Org. Lett. 2001, 3, 1109. (g) Sangu, K.;
Fuchibe, K.; Akiyama, T. Org. Lett. 2004, 6, 353.
(h) Mahanty, J. S.; De, P.; Das, P.; Kundu, N. G.
MS (ESI): m/z = 420 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C15H9ClNNaO2: 419.9264;
Tetrahedron 1997, 53, 13397.
found: 419.9244.
(4) Likhar, P. R.; Subhas, M. S.; Roy, S.; Kantam, M. L.;
Sridhar, B.; Seth, R. K.; Biswas, S. Org. Biomol. Chem.
2009, 7, 85.
Synthesis 2011, No. 15, 2407–2414 © Thieme Stuttgart · New York

2414
P. R. Likhar et al.
PAPER
(5) Appel, T. R.; Yehia, N. A. M.; Baumeister, U.; Hartung, H.;
Kluge, R.; Strohl, D.; Fanghanel, E. Eur. J. Org. Chem.
2003, 47.
(11) CCDC-806430 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
(6) Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2005, 127,
12230.
(12) (a) Togo, H.; Iida, S. Synlett 2006, 2159; and references cited
therein. (b) Lin, C.; Lai, P.-T.; Liao, S. K.-S.; Hung, W.-T.;
Yang, W.-B.; Fang, J.-M. J. Org. Chem. 2008, 73, 3848.
(13) Kim, S. S.; Jung, H. C. Synthesis 2003, 2135.
(14) (a) Ho, T.-L. Organic Syntheses by Oxidation with Metal
Compounds; Mijs, W. J.; de Jonge, C. R. H. I., Eds.; Plenum:
NewYork, 1986, 569. (b) Molander, G. A. Chem. Rev. 1992,
92, 29.
(7) Yu, Q. F.; Zhang, Y. H.; Yin, Q.; Tang, B. X.; Tang, R. Y.;
Zhong, P.; Li, J. H. J. Org. Chem. 2008, 73, 3658.
(8) Wang, Z. Q.; Tang, B. X.; Zhang, H. P.; Wang, F.; Li, J. H.
Synthesis 2009, 891.
(9) Pinto, A.; Neuville, L.; Retailleau, P.; Zhu, J. Org. Lett.
2006, 8, 4927.
(10) Kolarovic, A.; Faberova, Z. J. Org. Chem. 2009, 74, 7199.
Synthesis 2011, No. 15, 2407–2414 © Thieme Stuttgart · New York