Preparation of 3-Iodoquinolines from N-Tosyl-2-propynylamines with Diaryliodonium Triflate and N-Iodosuccinimide

Article abstract of DOI:10.1021/acs.joc.7b01433

4-Aryl and 4-alkyl substituted 3-iodoquinolines could be smoothly obtained in one pot by treating N-tosyl-2-propynylamines with diaryliodonium triflate in the presence of K₃PO₄ and a catalytic amount of CuCl at room temperature, followed by treatment with N-iodosuccinimide and BF₃·OEt₂ at 0 °C, and then NaOH in methanol solution. The product, 3-iodo-4-phenylquinoline was smoothly transformed into 4-phenylquinoline with zinc; 4-phenyl-3-toluenesulfenylquinoline with toluenethiol, K₂CO₃, and CuI; 4-phenyl-3-phenylethynylquinoline with the Sonogashira coupling reaction; 4-phenyl-3-styrylquinoline with the Heck coupling reaction; 3,4-diphenylquinoline with the Suzuki-Miyaura coupling reaction; 2-cyclohexyl-3-iodo-4-phenylquinoline with cyclohexanecarboxylic acid, Ag₂CO₃, and K₂S₂O₈; and 3-iodo-2-(2′,5′-dioxan-1′-yl)-4-phenylquinoline with benzoyl peroxide in dioxane.

Full text of DOI:10.1021/acs.joc.7b01433

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Article
Preparation of 3-Iodoquinolines from N-Tosyl-2-propynylamines
with Diaryliodonium Triflate and N-Iodosuccinimide
Teppei Sasaki, Katsuhiko Moriyama, and Hideo Togo
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01433 • Publication Date (Web): 18 Jul 2017
Downloaded from http://pubs.acs.org on July 20, 2017
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Preparation of 3-Iodoquinolines from
N-Tosyl-2-propynylamines with
Diaryliodonium Triflate and
N-Iodosuccinimide
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Teppei Sasaki†, Katsuhiko Moriyama†‡, Hideo Togo*†
†Graduate School of Science and ‡Molecular Chirality Research Center,
Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
togo@faculty.chiba-u.jp
RECEIVED DATE (to be automatically inserted after your manuscript is accepted
if required according to the journal that you are submitting your paper to)
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ABSTRACT:
1) K3PO4, CuCl (cat.)
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N
2 I+
TfO-
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X
R
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NTs
H
X
I
2) NIS, BF3·OEt2
3) NaOH
R
23 examples
up to 89%
R = Aryl, Alkyl
X = H, CH3,Cl, Br, etc.
4-Aryl- and 4-alkyl substituted 3-iodoquinolines could be smoothly obtained in one pot
by treating N-tosyl-2-propynylamines with diaryliodonium triflate in the presence of
K3PO4 and a catalytic amount of CuCl at room temperature, followed by treatment with
N-iodosuccinimide and BF3•OEt2 at 0 °C, and then NaOH in methanol solution. The
product, 3-iodo-4-phenylquinoline was smoothly transformed into 4-phenylquinoline
with zinc; 4-phenyl-3-toluenesulfenylquinoline with toluenethiol, K2CO3, and CuI;
4-phenyl-3-phenylethynylquinoline with the Sonogashira coupling reaction;
4-phenyl-3-styrylquinoline with the Heck coupling reaction; 3,4-diphenylquinoline with
the Suzuki-Miyaura coupling reaction; 2-cyclohexyl-3-iodo-4-phenylquinoline with
cyclohexanecarboxylic
acid,
Ag2CO3,
and
K2S2O8;
and
3-iodo-2-(2’,5’-dioxan-1’-yl)-4-phenylquinoline with benzoyl peroxide in dioxane.
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INTRODUCTION
Quinoline derivatives, such as quinine, chloroquine, amodiaquine, primaquine, and
mefloquine, are one of the most well-known antimalarial drugs, as shown in Fig. 1.1a~1e)
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Other quinoline derivatives possessing anticancer,1f,1g)
antiasthmatic,1h) and
antibacterial1i) activities are also known. In addition, it is known that such quinoline
derivatives as 2-alkylquinolines and 2-arylquinolines exhibit a variety of biological
activities, including antiprotozoal activity, potent inhibitory activity toward human
immunodeficiency virus type-1 (HIV-1) integrase,1j) and anti-inflammatory activity.1k,1l)
Therefore, synthetic studies of quinoline skeleton have been actively carried out.2)
OH
N
HO
N
NH
N
HN
O
N
N
Cl
Cl
O
N
Quinine
Chloroquine
Amodiaquine
O
HO
N
O
H
O
N
N
HN
HN
NH2
N
N
CF3
CF3
Primaquine
Aablaquine
Mefloquine
Fig. 1. Biologically Active Quinolines
For the construction of the quinoline skeleton with transition metals, the preparation of
3-substituted 2-amino-4-chloroquinolines with o-alkynylanilines and isocyanides in the
presence of PdCl2 and LiCl at 120 °C,3a) the preparation of 2,3,4-trisubstituted
quinolines with o-acylanilines and alkenyliodides in the presence of CuI and glycine at
130 °C,3b) the preparation of 4-arylquinolines with β-arylacrolein and
O-(4-cyanobenzoyl)hydroxylamine in the presence of fac-Ir(ppy)3 and
p-chlorobenzenesulfonic acid under LED irradiation conditions,3c) and others3d~3e are
reported recently. On the other hand, for the construction of the quinoline skeleton
under transition-metal-free conditions, the preparation of 2,4-disubstituted
3-iodoquinolines with 1-(o-tosylamino)phenyl-2-propyn-1-ols with molecular iodine at
60 °C,4a)
the preparation of 3,4-disubstituted 2-thioalkoxyquinolines with
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arylisothiocyanate, alkyl triflate, and alkynes at 130 °C,4b) the preparation of
2-aroyl-4-arylquinolines with anilines, aryl methyl ketones, and styrene in the presence
of molecular iodine at 80 °C,4c) and others4d~4g are reported recently.
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Diaryliodonium salts are very useful for the C-arylation of active C-H groups, the
O-arylation of O-H groups, and the N-arylation of N-H groups.5) In particular, the
N-arylation of anilines, amides, phthalimides, morpholines, sulfonamides, O-protected
hydroxylamines, and nitrogen-containing heterocycles with diaryliodonium salts have
been actively studied recently.6) For the preparation of quinoline skeleton with
diaryliodoniym salts, the [2+2+2] cascade annulations with nitriles, alkynes, and
diaryliodonium salt in the presence of Cu(OTf)2 in 1,2-dichloroethane at 120 °C7a) and
with nitriles, 1-iodoalkynes, and diaryliodonium salt in the presence of Cu(OTf)2 in
1,2-dichloroethane at 100 °C7b) were recently reported to provide 2,3,4-trisubstituted
quinolines and 2,4-diaryl-3-iodoquinolines, respectively.
Here, as part of our ongoing investigation of the synthetic use of diaryliodonium salts
for heterocyclic compounds,8) we would like to report an efficient one-pot preparation
([4+2] annulation) of various 4-aryl-3-iodoquinolines and 4-alkyl-3-iodoquinolines by
treatment of N-tosyl 3-aryl-2-propynylamines and N-tosyl 3-alkyl-2-propynylamines,
respectively, with diaryliodonium triflate in the presence of a base, followed by the
reaction with N-iodosuccinimide (NIS) and then NaOH in methanol solution.
RESULTS AND DISCUSSION
First,
the
optimum
conditions
for
the
N-phenylation
of
N-tosyl
3-phenyl-2-propynylamine 1a with diphenyliodonium triflate A (1.2 equiv.) in the
presence of a base (1.2 equiv.), such as t-BuOK, NaH, K2CO3, or K3PO4, in toluene (3
mL) at 60 °C were examined and N-phenyl-N-tosyl 3-phenyl-2-propynylamine 2Aa was
obtained in 37%, 14%, 45%, and 41% yields, respectively, as shown in Table 1 (entries
1-4). When the same reaction was carried out in the presence of K3PO4 in
dichloromethane (3 mL) at 40 °C, N-phenyl-N-tosyl 3-phenyl-2-propynylamine 2Aa
was obtained in 5% (entry 5).
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Table 1. N-Phenylation of N-Tosyl 3-Phenyl-2-propynylamine 1a with
Diphenyliodonium Triflate A.
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base (1.2 equiv)
Ph2I+-OTf (1.2 equiv)
Ph
Ph
additive
solvent, temp, time
1st step
NTs
H
NTs
Ph
1a
2Aa
Entry Base
Additive Solvent
Temp. Time Yield
(mol%)
(mL)
(ºC)
(h)
5
(%)
37
14
45
41
5
1
t-BuOK -
toluene (3.0) 60
toluene (3.0) 60
toluene (3.0) 60
toluene (3.0) 60
CH2Cl2 (3.0) 40
2
NaH
-
-
-
-
5
3
K2CO3
K3PO4
K3PO4
5
4
5
5
5
6
K3PO4 CuBr (20) CH2Cl2 (7.5) rt
K3PO4 CuI (20) CH2Cl2 (7.5) rt
3
92
91
88
99
90
1
7
3
8
K3PO4 CuCl (20) CH2Cl2 (7.5) rt
K3PO4 CuCl (5) CH2Cl2 (7.5) rt
K3PO4 CuCl (5) CH2Cl2 (3.0) rt
3
9
3
10
11
3
K3PO4
-
CH2Cl2 (7.5) rt
3
Then, based on a report for the effective N-phenylation of N-aryl arenesulfonamides
with diaryliodonium triflate,6b) the present N-phenylation of N-tosyl
3-phenyl-2-propynylamine 1a with diphenyliodonium triflate A in the presence of
K3PO4 and a catalyst (0.20 equiv.), such as CuBr, CuI, or CuCl, in dichloromethane (7.5
mL) at r.t. was carried out to form N-phenyl-N-tosyl 3-phenyl-2-propynylamine 2Aa in
92%, 91%, and 88% yields, respectively (entries 6-8). Finally, it was found that
treatment of N-tosyl 3-phenyl-2-propynylamine 1a with diphenyliodonium triflate A
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(1.2 equiv.) in the presence of K3PO4 (1.2 equiv.) and CuCl (0.05 equiv.) in
dichloromethane at room temperature for
3
h
gave N-phenyl-N-tosyl
9
3-phenyl-2-propynylamine 2Aa in 99% yield (entry 9). The yield of N-phenyl-N-tosyl
3-phenyl-2-propynylamine 2Aa was slightly decreased by reduction of the amount of
dichloromethane (3 mL) under same conditions (entry 10). Under the same reaction
conditions but without CuCl, N-phenylation did not proceed at all (entry 11).
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Table 2. Halocylization of N-Phenyl-N-Tosyl 3-Phenyl-2-propynylamine 2Aa to
3-Halo-4-phenylquinoline 3Aa.
NIS (1.5 equiv)
evaporation;
N
Ph
BF3·OEt2 (1.5 equiv)
NaOH (10.0 equiv)
NTs
X
Ph
CH2Cl2 (5.0 mL)
0 °C, 1 h
MeOH
temp, time
Ph
3Aa
2Aa
2nd step
3rd step
X = I, Br, Cl
Entry MeOH (mL) Temp. (ºC) Time (h) Yield (%)
1a,b
2a
3
5.0
60
60
60
60
50
60
60
19
19
19
19
19
19
19
72
85
87
95
90
73
15
5.0
5.0
4
10.0
5.0
5
6d
7e
10.0
10.0
a Under O2 (in a sealed tube). b Without evaporation. c Without BF3•OEt2.
d
e
NBS (1.5 equiv) was used instead of NIS. NCS (1.5 equiv) was used
instead of NIS.
Then, the preparation of the quinoline skeleton from N-phenyl-N-tosyl
3-phenyl-2-propynylamine 2Aa with NIS, followed by the reaction with NaOH was
carried out, as shown in Table 2.
Treatment of N-phenyl-N-tosyl
3-phenyl-2-propynylamine 2Aa with NIS and BF3•OEt2 in dichloromethane at 0 °C, the
evaporation of the solvent, and treatment of the residue with NaOH in methanol
solution provided 3-iodo-4-phenylquinoline 3Aa in good yields, as shown in Table 2.
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Finally, it was found that the treatment of N-phenyl-N-tosyl 3-phenyl-2-propynylamine
2Aa with NIS (1.5 equiv.) and BF3•OEt2 (1.5 equiv.) in dichloromethane at 0 °C for 1 h,
the evaporation of the solvent, followed by the treatment of the residue with NaOH in
methanol (10 mL) solution at 60 °C for 19 h provided 3-iodo-4-phenylquinoline 3Aa in
95% yield (entry 4). Under the same procedure and conditions, the treatment of
N-phenyl-N-tosyl 3-phenyl-2-propynylamine 2Aa with NIS alone did not generate
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iodocyclization
product.
The
2Aa
same
with
treatment
of
N-phenyl-N-tosyl
(NBS) and
3-phenyl-2-propynylamine
N-bromosuccinimide
N-chlorosuccinimide (NCS) instead of NIS under the same procedure and conditions
generated 3-bromo-4-phenylquinoline and 3-chloro-4-phenylquinoline in 73% and 15%
yields, respectively (entries 6 and 7).
Based on these results, a one-pot construction of the quinoline skeleton from N-tosyl
3-aryl-2-propynylamines 1 was carried out. Various N-tosyl 3-aryl-2-propynylamines
1 bearing phenyl (a), o-methylphenyl (b), m-methylphenyl (c), p-methylphenyl (d),
p-fluorophenyl (e), p-bromophenyl (f), p-chlorophenyl (g), o-chlorophenyl (h),
m-chlorophenyl (i), p-biphenyl (j), p-(methoxycarbonyl)phenyl (k), p-cyanophenyl (l),
2-naphthyl (m), 1-naphthyl (n), benzofuran-2-yl (o), and benzothiophen-2-yl (p) groups,
were treated with diphenyliodonium triflate A (1.2 equiv.) in the presence of K3PO4 (1.2
equiv. or 1.5 equiv.) and a catalytic amount of CuCl (5 mol%) in dichloromethane at
room temperature for 3 h, followed by the reaction with NIS (1.5 equiv. or 2.0 equiv.)
and BF3•OEt2 (1.5 equiv., 2.0 equiv., or 3.0 equiv.) at 0 °C for one hour. After the
reaction, the solvent was removed and the residue was treated with NaOH (10.0 equiv.)
Table 3. One-Pot Transformation of N-Tosyl 2-Propynylamines 1 into
3-Iodoquinolines 3 with Diphenyliodonium Triflate A
K3PO4 (1.2 equiv)
Ph2I+-OTf (1.2 equiv)
NIS (1.5 equiv)
BF3·OEt2 (1.5 equiv)
R
CuCl (5 mol%)
NTs
H
CH2Cl2 (7.5 mL)
rt, 3 h
0 °C, 1 h
1
evaporation;
N
NaOH (10.0 equiv)
I
MeOH (10.0 mL)
60 °C, 19 h
R
3A
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product, yield
N
N
N
N
I
I
I
10
11
12
13
14
15
16
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I
Me
Ph
Me
Me
3Aa (89%)
3Ab (85%)b
3Ac (87%)b
3Ad (84%)b
(87%)a
N
N
N
N
I
I
I
I
Cl
F
Br
Cl
3Ae (73%)
3Af (84%)
3Ag (80%)c,d
3Ah (82%)c
N
N
N
N
I
I
I
I
Cl
CO2Me
3Ak (65%)e,f
Ph
CN
3Ai (83%)c
3Aj (53%)c
3Al (43%)c,g
N
N
N
N
I
I
I
I
I
O
S
3Am (57%)b,c
3An (81%)
3Ao (45%)b,c
3Ap (53%)b,c
N
N
N
I
I
(CH2)2CH3
(CH2)6CH3
3Aq (60%)b,e
3Ar (56%)b,e
3As (57%)b,e
a
b
c
1a (6.0 mmol) was used. K3PO4 (1.5 equiv.) was used. NIS (2.0
d
equiv.) and BF3·OEt2 (2.0 equiv.) were used. The 3rd reaction step was
e
carried out at 50 °C. NIS (2.0 equiv.) and BF3·OEt2 (3.0 equiv.) were
used. f TMSCl (10.0 equiv.) was added and the mixture was stirred for 24
h at 60 °C after 3rd step. g DIH (2.0 equiv.) was used instead of NIS.
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in methanol at 60 °C (50 °C for 3Ag) for 19 h to give the corresponding
4-aryl-3-iodoquinolines 3Aa~3Ap in one pot in good to moderate yields, respectively,
as shown in Table 3. For 3-iodoquinoline 3ak, the methyl ester group was hydrolyzed
by the treatment with NaOH in methanol at 3rd step reaction. Therefore, the formed
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carboxylate group was converted into methyl ester again by the treatment with TMSCl
in methanol after 3rd step reaction. A gram-scale experiment with 6.0 mmol of N-tosyl
3-phenyl-2-propynylamine 1a under the same procedure and conditions furnished
3-iodo-4-phenylquinoline
3Aa
in
87%
yield.
The
structure
of
4-(p-biphenyl)-3-iodoquinoline 3Aj was supported by X-ray crystallographic analysis
(see Supporting Information). N-Tosyl 3-alkyl-2-propynylamines 1 bearing propyl (q),
heptyl (r), and cyclohexyl (s) groups were also treated under the same procedure and
conditions to provide 4-alkyl-3-iodoquinolines 3Aq~3As in moderate yields,
respectively (Table 3).
Table 4. One-Pot Transformation of N-Tosyl 3-Phenyl-2-propynylamine 1a into
6-Substituted 3-Iodo-4-phenylquinolines 3a with Diaryliodonium Triflates B-E
X
2 I+
TfO-
(1.2 equiv)
K3PO4 (1.2 equiv)
CuCl (5 mol%)
NIS (2.0 equiv)
BF3·OEt2 (2.0 equiv)
Ph
NTs
H
CH2Cl2 (7.5 mL)
rt, 3 h
0 °C, 1 h
1a
evaporation;
N
NaOH (10.0 equiv)
X
I
MeOH (10.0 mL)
60 °C, 19 h
Ph
3a
A, X = H; B, X = Me; C, X = t-Bu; D, X = Cl; E, X = Br
product, yield
N
N
N
N
Me
I t-Bu
I Cl
I Br
I
Ph
Ph
Ph
Ph
3Ba (82%)
3Ca (81%)
3Da (52%)a,b
3Ea (61%)a
a
b
K3PO4 (1.5 equiv.) was used. NIS (2.0 equiv.) and BF3·OEt2 (3.0
equiv.) were used.
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Moreover, N-tosyl 3-phenyl-2-propynylamine 1a was treated with diaryliodonium
triflate (1.
2
equiv.), such as bis(p-methylphenyl)iodonium triflate B,
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bis(t-butylphenyl)iodonium triflate C, bis(p-chlorophenyl)iodonium triflate D, and
bis(p-bromophenyl)iodonium triflate E, instead of diphenyliodonium triflate A, in the
presence of K3PO4 (1.2 equiv.) and a catalytic amount of CuCl (5 mol%) in
dichloromethane at room temperature for 3 h, followed by the reaction with NIS (2.0
equiv.) and BF3•OEt2 (2.0 equiv.) at 0 °C for one hour. After the reaction, the solvent
was removed and the residue was treated with NaOH (10.0 equiv.) in methanol at 60 °C
for 19 h to give the corresponding 6-substituted 4-phenyl-3-iodoquinolines 3Ba-3Ea in
82%, 81%, 52%, and 61% yields, respectively, as shown in Table 4. Additionally,
when N-tosyl 3-phenyl-2-propynylamine 1a was treated with phenyl(mesityl)iodonium
triflate instead of diphenyliodonium triflate A under the same procedure and conditions,
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3-iodo-4-phenylquinoline was obtained in only 9% yield.
Thus,
phenyl(mesityl)iodonium triflate instead of diphenyliodonium triflate A is not effective
Scheme 1. Functionalization of 3-Iodo-4-Phenylquinoline
PdCl2(PPh3)2
K2CO3
N
Zn
N
Ph
EtOH, reflux
(92%)
DMF, 130 ˚C
(83%)
Ph
H
Ph
7Aa
Ph
4Aa
PdCl2(PPh3)2
PhB(OH)2
K2CO3
Tol SH
K2CO3
CuI
N
N
DMF, H2O
60 ˚C
(100%)
i-PrOH, 80 °C
N
S
Ph
Tol (71%)
Ph
5Aa
Ph
8Aa
I
Ph
3Aa
PdCl2(PPh3)2
CuI
C6H11 CO2H
Ag2CO3
K2S2O8
N
Ph
Et3N, rt
(99%)
H
N
TFA
I
Ph
Ph
Ph
6Aa
CH3CN/H2O,
70 °C
BPO
TFA
(62%)
9Aa
O
O
N
1,4-dioxane
80 °C
I
(55%)
Ph
10Aa
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for the present reaction, although phenyl(mesityl)iodonium triflate is an excellent
regioselective arylation reagent. This may be due to the steric hindrance of
phenyl(mesityl)iodonium triflate in the reaction with N-tosyl 3-phenyl-2-propynylamine
1a.
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The obtained 4-substituted 3-iodoquinolines could be transformed into various
quinoline derivatives, as shown in Scheme 1. For example, 3-iodo-4-phenylquinoline
3Aa was smoothly reduced to 4-phenylquinoline 4Aa in 92% yield with zinc in ethanol.
Treatment of 3-iodo-4-phenylquinoline 3Aa with toluenethiol and K2CO3 in the
presence of CuI gave 4-phenyl-3-toluenesulfenylquinoline 5Aa in 71% yield. The
Sonogashira coupling reaction, the Heck coupling reaction, and the Suzuki-Miyaura
coupling reaction of 3-iodo-4-phenylquinoline 3Aa with phenylacetylene, styrene, and
phenylboronic acid in the presence of PdCl2(Ph3P)2 gave the coupling products,
4-phenyl-3-phenylethynylquinoline 6Aa, 4-phenyl-3-styrylquinoline 7Aa, and
3,4-diphenylquinoline 8Aa in 99%, 83%, and 100% yields, respectively. The radical
decarboxylative alkylation reaction9) of 3-iodo-4-phenylquinoline 3Aa with
cyclohexanecarboxylic acid, Ag2CO3, and K2S2O8 in the presence of CF3CO2H gave
2-cyclohexyl-3-iodo-4-phenylquinoline 9Aa in 62% yield. Treatment of
3-iodo-4-phenylquinoline 3Aa with benzoyl peroxide (BPO) in 1,4-dioxane generated
2-(2’,5’-dioxan-1’-yl)-3-iodo-5-phenylquinoline 10Aa in 55% yield via radical
pathway.10)
The possible reaction pathway form N-tosyl 2-propynylamines 1 into 3-iodoquinolines
3 with diaryliodonium triflates A~E through iodocyclization of the formed
N-aryl-N-tosyl 2-propynylamines 2 onto the aromatic ring11) is proposed in Scheme 2.
Here, compound III, a precursor for qunoline 3, can be isolated before the treatment
with NaOH in methanol. Additionally, the present reaction with N-tosyl
3-phenyl-2-propynylamine 1a with diphenyliodonium triflate A in the presence of
TEMPO (0.5 equiv.) under the same procedure and conditions proceeded smoothly to
give 3-iodo-4-phenylquinoline 3Aa in 90% yield. Therefore, the present reaction does
not contain any radical pathway.
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TfO-
2 I+
X
X
X
NIS,
BF3
CuI (cat.)
NTs
NTs
NHTs
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N-Arylation
Iodocyclization
R
R
R
O
N
2
1
2
I
F3B
O
X
Ts
N
NTs
X
I
(-BF3)
O
HN
R
H
R
O
O
N
I
-
N
-
O
-
F3B
O
F3B
O
I
II
Ts
N
N
R
NaOH
(-TsH)
X
I
X
I
R
3
III
Scheme 2. Possible Reaction Pathway
In conclusion, 4-aryl- and 4-alkyl-3-iodoquinolines were smoothly obtained in one pot
by the treatment of N-tosyl 3-aryl-2-propynylamines and N-tosyl
3-alkyl-2-propynylamines with diaryliodonium triflate in the presence of K3PO4 and
CuCl, followed by the reaction with NIS and BF3•OEt2, and then with NaOH in
methanol solution. The obtained 3-iodoquinolines were easily transformed into
various functionalized quinoline derivatives bearing a C-C bond at 2- or 3-position
using Pd-catalyzed coupling reactions and radical coupling reactions.
EXPERIMENTAL SECTION
1
General: H NMR spectra were measured on 500 MHz spectrometers. Chemical shifts
were recorded as follows: chemical shift in ppm from internal tetramethylsilane on the δ
scale, multiplicity (s = singlet; d = doublet; t = triplet; q = quartet; m = multiplet; br =
13
broad), coupling constant (Hz), integration, and assignment. C NMR spectra were
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measured on 125 MHz spectrometers. Chemical shifts were recorded in ppm from the
solvent resonance employed as the internal standard (deuterochloroform at 77.0 ppm).
Characteristic peaks in the infrared (IR) spectra were recorded in wave numbers, cm-1.
High-resolution mass spectra were recorded by Thermo Fisher Scientific Exactive
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Orbitrap mass spectrometers.
Melting points were uncorrected. Thin-layer
chromatography (TLC) was performed using 0.25 mm silica gel plates (60F-254). The
products were purified by column chromatography on silica gel 60 (63–200 mesh).
Diaryliodonium triflates: Diaryliodonium triflates A~E were prepared by the
literature method in 51~84% yields.12)
Diphenyliodonium triflate (A): white solid; Mp: 178-179 °C (lit.12a) Mp 177-178 °C);
IR (neat) 1566, 1472, 1444 cm-1; 1H-NMR (400 MHz, CDCl3): δ = 7.49 (dd, 4H, J = 7.9,
7.5 Hz), 7.64 (dd, 2H, J = 7.9, 7.5 Hz), 7.98 (d, 4H, J = 7.5 Hz); C{1H}NMR (100
13
MHz, DMSO-d6): δ = 116.6, 121.8 (q, JC-F = 315.9 Hz), 131.8, 132.1, 135.2.
Bis(4-methylphenyl)iodonium triflate (B): gray solid; Mp: 131 °C (decomposition)
(lit.12a) Mp 182-184 °C); IR (neat) 3061, 1581, 1480, 1397 cm-1; H-NMR (400 MHz,
1
CDCl3): δ = 2.42 (s, 6H), 7.27 (d, 4H, J = 8.4 Hz) , 7.81 (d, 4H, J = 8.4 Hz);
13C{1H}NMR (100 MHz, CDCl3): δ = 21.4, 109.8, 121.6 (q, JC-F = 367.8 Hz), 132.9,
135.0, 143.5; HRMS (ESI) Calcd for C14H14I [M]+ = 309.0135, Found = 309.0128;
HRMS (ESI) Calcd for CO3F3S [M]+ = 148.9515, Found = 148.9515.
Bis(4-tert-butylphenyl)iodonium triflate (C): white solid; Mp: 162-163 °C (lit.12a) Mp
164-165 °C); IR (neat) 2960, 1580, 1481, 1396 cm-1; 1H-NMR (400 MHz, CDCl3): δ =
1.30 (s, 18H), 7.47 (d, 4H, J = 8.8 Hz) , 7.89 (d, 4H, J = 8.8 Hz); C{1H}NMR (100
13
MHz, CDCl3): δ = 30.9, 35.2, 109.4, 121.8 (q, JC-F = 316.5 Hz), 129.5, 134.85, 156.47.
Bis(4-chlorophenyl)iodonium triflate (D): white solid; Mp: 177-178 °C (lit.12a) Mp
175-176 °C); IR (neat) 1557, 1471, 1390 cm-1; 1H-NMR (400 MHz, CDCl3): δ = 7.41 (d,
4H, J = 8.8 Hz) , 7.93 (d, 4H, J = 8.8 Hz); 13C{1H}NMR (100 MHz, CDCl3): δ =111.1,
121.8 (q, JC-F = 316.4 Hz), 132.3, 136.7, 139.6.
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Bis(4-bromophenyl)iodonium triflate (E): white solid; Mp: 201-202 °C (lit.12b) Mp
198 °C); IR (neat) 1555, 1471, 1384 cm-1; 1H-NMR (400 MHz, CDCl3): δ = 7.55 (d, 4H,
J = 8.8 Hz) , 7.87 (d, 4H, J = 8.8 Hz); 13C{1H}NMR (100 MHz, DMSO-d6): δ = 115.4,
121.8 (q, JC-F = 316.5 Hz), 126.4, 134.7, 137.1.
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Typical procedure for one-pot conversion of N-tosyl-2-propynylamines 1 into
3-iodo-4-phenylquinolines 3
To a mixture of N-tosyl-3-phenyl-2-propynylamine 1a (0.5 mmol, 142.7 mg), CuCl (5
mol%, 2.6 mg), and K3PO4·nH2O (0.6 mmol, 172.1 mg) in CH2Cl2 (7.5 mL) was added
diphenyliodonium trifluoromethanesulfonate (0.6 mmol, 258.1 mg). The obtained
mixture was stirred for 3 h at room temperature, and the flask was flushed by argon gas.
Then, NIS (0.75 mmol, 172.2 mg) and BF3·OEt2 (0.75 mmol, 94 µL) were added at
0 °C, and the obtained mixture was stirred for 1 h at 0 °C. Then, the solvent was
removed, and NaOH (5.0 mmol, 206.1 mg) and MeOH (10 mL) were added to the
residue, and the obtained mixture was stirred for 19 h at 60 °C. Saturated Na2SO3
aqueous solution (10 mL) was added to the reaction mixture, and the product was
extracted with CHCl3 (15 mL × 3). The organic layer was dried over Na2SO4. After
removal of the solvent under reduced pressure, the residue was purified by silica-gel
column chromatography (eluent: n-hexane
:
EtOAc
=
8:1) to give
3-iodo-4-phenylquinolin (3Aa) (147.7 mg, 89% yield).
3-Iodo-4-phenylquinolin (3Aa): Yield: 147.7 mg (89%); white solid; Mp: 131-132 °C;
IR (neat) 3062, 1499, 1485 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.27 (d, 2H, J = 7.5
Hz), 7.41-7.49 (m, 2H), 7.51-7.59 (m, 3H), 7.73 (t, 1H, J = 7.5 Hz), 8.12 (d, 1H, J = 8.6
Hz), 9.25 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 96.3, 126.7, 127.3, 128.6 (2C),
128.9, 129.0, 129.4, 129.6, 140.3, 147.1, 152.3, 156.5; HRMS (ESI) Calcd for C15H11NI
[M+H]+ = 331.9931, Found = 331.9927.
3-Iodo-4-(2’-methylphenyl)quinoline (3Ab): Yield: 146.2 mg (85%); white solid; Mp:
1
83-84 °C; IR (neat) 3017, 1499, 1482 cm-1; H NMR (400 MHz, CDCl3): δ = 1.96 (s,
3H), 7.07 (d, 1H, J = 7.6 Hz), 7.31-7.47 (m, 5H), 7.73 (t, 1H, J = 7.6 Hz), 8.13 (d, 1H, J
= 8.3 Hz), 9.25 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 19.5, 96.7, 126.2, 126.3,
127.5, 128.6 (2C), 128.8, 129.5, 129.7, 130.3, 135.4, 139.9, 147.0, 152.4, 156.5; HRMS
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(ESI) Calcd for C16H13NI [M+H]+ = 346.0087, Found = 346.0082.
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3-Iodo-4-(3’-methylphenyl)quinoline (3Ac): Yield: 150.3 mg (87%); pale yellow
solid; Mp: 83-84 °C; IR (neat) 3060, 1498, 1482 cm-1; 1H NMR (400 MHz, CDCl3): δ =
2.45 (s, 3H), 7.06 (d, 1H, J = 6.8 Hz), 7.07 (s, 1H), 7.34 (d, 1H, J = 7.5 Hz), 7.40-7.52
(m, 3H), 7.72 (t, 1H, J = 7.5 Hz), 8.11 (d, 1H, J = 8.4 Hz), 9.24 (s, 1H); 13C{1H}NMR
(100 MHz, CDCl3): δ = 21.5, 96.2, 126.0, 126.7, 127.2, 128.4, 128.8, 129.2, 129.3,
129.4, 129.5, 138.2, 140.1, 147.0, 152.4, 156.4; HRMS (ESI) Calcd for C16H13NI
[M+H]+ = 346.0087, Found = 346.0084.
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3-Iodo-4-(4’-methylphenyl)quinoline (3Ad): Yield: 145.2 mg (84%); white solid; Mp:
155-156 °C; IR (neat) 2959, 1491, 1375 cm-1; 1H NMR (400 MHz, CDCl3): δ = 2.49 (s,
3H), 7.16 (d, 2H, J = 7.7 Hz) , 7.37 (d, 2H, J = 7.7 Hz) , 7.42 (t, 1H, J = 7.6 Hz), 7.50 (d,
1H, J = 7.6 Hz), 7.71 (t, 1H, J = 7.6 Hz), 8.11 (d, 1H, J = 8.4 Hz), 9.24 (s, 1H);
13C{1H}NMR (100 MHz, CDCl3): δ =21.4, 96.5, 126.7, 127.2, 128.8, 129.0, 129.2,
129.3, 129.5, 137.2, 138.4, 147.1, 152.4, 156.5; HRMS (ESI) Calcd for C16H13NI
[M+H]+ = 346.0087, Found = 346.0084.
4-(4’-Fluorophenyl)-3-iodoquinoline (3Ae): Yield: 128.2 mg (73%); white solid; Mp:
1
105-106 °C; IR (neat) 3063, 1509, 1493 cm-1; H NMR (400 MHz, CDCl3): δ =
7.25-7.27 (m, 4H), 7.45 (d, 2H, J = 8.3 Hz), 7.71-7.78 (m, 1H), 8.13 (d, 1H, J = 8.3 Hz),
9.25 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 96.6, 115.7 (d, JC-F = 21.6 Hz),
126.3, 127.4, 128.8, 129.5, 129.7, 130.9 (d, JC-F = 8.5 Hz), 136.0 (d, JC-F = 3.8 Hz),
147.0, 151.2, 156.4, 162.7 (d, JC-F = 249.0 Hz); HRMS (ESI) Calcd for C15H10NFI
[M+H]+ = 349.9836, Found = 349.9832.
4-(4’-Bromophenyl)-3-iodoquinoline (3Af): Yield: 172.0 mg (84%); pale yellow
1
solid; Mp: 162-163 °C; IR (neat) 3064, 1500, 1483 cm-1; H NMR (400 MHz, CDCl3):
δ = 7.17 (d, 2H, J = 8.3 Hz), 7.43-7.48 (m, 2H), 7.70-7.78 (m, 3H), 8.13 (d, 1H, J = 8.3
Hz), 9.24 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 96.1, 113.0, 126.2, 127.6,
128.5, 129.5, 129.8, 130.7, 131.9, 139.0, 147.0, 151.0, 156.5; HRMS (ESI) Calcd for
C15H10NBrI [M+H]+ = 409.9036, Found = 409.9034.
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4-(4’-Chlorophenyl)-3-iodoquinoline (3Ag): Yield: 145.4 mg (80%); white solid; Mp:
146-147 °C; IR (neat) 2924, 1500, 1484 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.23 (d,
2H, J = 8.5 Hz), 7.43-7.47 (m, 2H), 7.55 (d, 2H, J = 8.5 Hz), 7.71-7.78 (m, 1H), 8.13 (d,
1H, J = 8.3 Hz), 9.24 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 96.2, 126.2, 127.5,
128.6, 128.9, 129.5, 129.7, 130.4, 134.7, 138.4, 147.0, 150.9, 156.4; HRMS (ESI) Calcd
for C15H10NClI [M+H]+ = 365.9541, Found = 365.9541.
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4-(2’-Chlorophenyl)-3-iodoquinoline (3Ah): Yield: 150.4 mg (82%); white solid; Mp:
136-137 °C; IR (neat) 3010, 1501, 1472 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.21 (d,
1H, J = 7.6 Hz), 7.32 (d, 1H, J = 7.6 Hz), 7.44-7.53 (m, 3H), 7.61 (d, 1H, J = 7.7 Hz),
7.75 (t, 1H, J = 7.6 Hz), 8.15 (d, 1H, J = 8.4 Hz), 9.26 (s, 1H); 13C{1H}NMR (100 MHz,
CDCl3): δ = 96.4, 125.9, 127.1, 127.6, 128.4, 129.6, 129.8, 129.9, 130.2, 130.5, 132.8,
138.9, 146.9, 149.9, 156.4; HRMS (ESI) Calcd for C15H10NClI [M+H]+ = 365.9541,
Found = 365.9541.
4-(3’-Chlorophenyl)-3-iodoquinoline (3Ai): Yield: 152.2 mg (83%); white solid; Mp:
1
115-116 °C; IR (neat) 3045, 1500, 1473 cm-1; H NMR (400 MHz, CDCl3): δ =
7.14-7.20 (m, 1H), 7.27-7.29 (m, 1H), 7.43-7.53 (m, 4H), 7.74 (t, 1H, J = 7.3 Hz) , 8.13
(d, 1H, J = 8.4 Hz), 9.24 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 96.0, 126.3,
127.3, 127.6, 128.5, 128.9, 129.1, 129.6, 129.9, 130.0, 134.6, 141.8, 147.0, 150.7,
156.5; HRMS (ESI) Calcd for C15H10NClI [M+H]+ = 365.9541, Found = 365.9539.
4-(Biphenyl-4’-yl)-3-iodoquinoline (3Aj): Yield: 108.2 mg (53%); white solid; Mp:
165-166 °C; IR (neat) 3033, 1565, 1483 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.38 (d,
2H, J = 8.4 Hz ), 7.39-7.57 (m, 5H), 7.72-7.76 (m, 3H), 7.78 (d, 2H, J = 8.4 Hz), 8.13 (d,
1H, J = 8.6 Hz), 9.27 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 96.4, 126.7, 127.1,
127.2, 127.4, 127.7, 128.9 (2C), 129.5, 129.6, 129.7, 139.1, 140.3, 141.4, 147.2, 152.1,
156.6; HRMS (ESI) Calcd for C21H15NI [M+H]+ = 408.0244, Found = 408.0244.
3-Iodo-4-(4’-methoxycarbonylphenyl)quinoline (3Ak): Yield: 126.9 mg (65%); white
1
solid; Mp: 133-134 °C; IR (neat) 2956, 1717, 1493 cm-1; H NMR (400 MHz, CDCl3):
δ = 4.00 (s, 3H), 7.36-7.40 (m, 3H), 7.45 (t, 1H, J = 7.6 Hz), 7.75 (t, 1H, J = 7.6 Hz),
8.14 (d, 1H, J = 8.5 Hz), 8.25 (d, 2H, J = 8.5 Hz), 9.25 (s, 1H); 13C{1H}NMR (100 MHz,
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CDCl3): δ = 52.3, 95.5, 126.2, 127.6, 128.4, 129.2, 129.5, 129.9, 129.9, 130.4, 144.7,
147.0, 151.2, 156.4, 166.5; HRMS (ESI) Calcd for C17H13O2NI [M+H]+ = 389.9985,
Found = 389.9985.
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4-(4’-Cyanophenyl)-3-iodoquinoline (3Al): Yield: 78.5 mg (43%); white solid; Mp:
139-140 °C; IR (neat) 3033, 2228, 1493 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.33 (d,
1H, J = 8.0 Hz), 7.42 (d, 2H, J = 8.4 Hz), 7.47 (t, 1H, J = 7.8 Hz), 7.77 (t, 1H, J = 7.7
Hz), 7.88 (d, 2H, J = 8.4 Hz), 8.15 (d, 1H, J = 8.4 Hz), 9.23 (s, 1H); 13C{1H}NMR (100
MHz, CDCl3): δ = 95.2, 124.1, 125.7, 128.0 (2C), 129.8, 130.1 (2C), 130.4, 146.6,
147.0, 148.0, 149.9, 156.5; HRMS (ESI) Calcd for C16H10N2I [M+H]+ = 356.9883,
Found = 356.9879.
3-Iodo-4-(naphthalen-2’-yl)quinoline (3Am): Yield: 109.3 mg (57%); white solid;
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Mp: 163-164 °C; IR (neat) 3057, 1565, 1496 cm-1; H NMR (400 MHz, CDCl3): δ =
7.36-7.43 (m, 2H), 7.49 (d, 1H, J = 7.9 Hz), 7.57-7.63 (m, 2H), 7.73 (t, 1H, J = 7.6 Hz),
7.77 (s, 1H), 7.89-8.00 (m, 2H) ,8.04 (d, 1H, J = 8.4 Hz), 8.15 (d, 1H, J = 8.4 Hz), 9.29
(s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 96.4, 126.66, 126.69, 126.7, 126.8, 127.4,
127.9, 128.3, 128.39, 128.42, 129.0, 129.5, 129.7, 133.0, 133.1, 137.6, 147.1, 152.2,
156.6; HRMS (ESI) Calcd for C19H13NI [M+H]+ = 382.0087, Found = 382.0088.
3-Iodo-4-(naphthalen-1’-yl)quinoline (3An): Yield: 154.9 mg (81%); pale yellow
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solid; Mp: 162-163 °C; IR (neat) 3048, 1565, 1496 cm-1; H NMR (400 MHz, CDCl3):
δ = 7.15 (d, 1H, J = 8.4 Hz), 7.23 (d, 1H, J = 8.4 Hz), 7.31-7.37 (m, 3H), 7.53 (t, 1H, J
= 7.0 Hz), 7.66 (t, 1H, J = 7.6 Hz), 7.77 (t, 1H, J = 7.6 Hz) , 7.99 (d, 1H, J = 8.2 Hz),
8.05 (d, 1H, J = 8.2 Hz), 8.18 (d, 1H, J = 8.4 Hz), 9.32 (s, 1H); 13C{1H}NMR (100 MHz,
CDCl3): δ = 97.6, 125.2, 125.4, 126.3, 126.7, 126.8, 127.0, 127.5, 128.5, 129.0, 129.5
(2C), 129.8, 130.6, 133.5, 137.9, 147.0, 151.2, 156.6; HRMS (ESI) Calcd for C19H13NI
[M+H]+ = 382.0087, Found = 382.0086.
4-(Benzofuran-2’-yl)-3-iodoquinoline (3Ao): Yield: 83.6 mg (45%); white solid; Mp:
133-134 °C; IR (neat) 3062, 1558, 1493 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.11 (s,
1H), 7.37 (t, 1H, J = 7.7 Hz), 7.43 (t, 1H, J = 8.2 Hz), 7.53 (t, 1H, J = 7.9 Hz), 7.63 (d,
1H, J = 8.2 Hz), 7.74-7.82 (m, 3H), 8.15 (d, 1H, J = 8.4 Hz), 9.30(s, 1H); 13C{1H}NMR
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(100 MHz, CDCl3): δ = 96.3, 109.2, 111.7, 121.6, 123.4, 125.3, 125.8, 127.9, 128.0,
128.7, 129.7, 130.1, 141.6, 147.1, 152.5, 155.1, 156.9; HRMS (ESI) Calcd for
C17H11ONI [M+H]+ =371.9880, Found = 371.9876.
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4-(Benzo[b]thiophen-2’-yl)-3-iodoquinoline (3Ap): Yield: 103.2 mg (53%); white
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solid; Mp: 191-192 °C; IR (neat) 3052, 1490, 1454 cm-1; H NMR (400 MHz, CDCl3):
δ = 7.33 (s, 1H), 8.14 (d, 1H, J = 8.2 Hz), 7.43-4.50 (m, 3H), 7.75 (d, 1H, J = 7.9 Hz),
7.77 (d, 1H, J = 7.5 Hz), 7.90-7.96 (m, 2H), 9.27 (s, 1H); 13C{1H}NMR (100 MHz,
CDCl3): δ = 98.0, 122.4, 124.2, 124.8, 125.0, 125.5, 126.4, 127.8, 129.5 (2C), 130.0,
139.5, 140.6, 140.7, 145.7, 147.0, 156.5; HRMS (ESI) Calcd for C17H11NIS [M+H]+
=387.9651, Found = 387.9648.
3-Iodo-4-propylquinoline (3Aq): Yield: 89.7 mg (60%); colorless oil; IR (neat) 3068,
2958, 1501 cm-1; 1H NMR (400 MHz, CDCl3): δ = 1.13 (t, 3H, J = 7.4 Hz), 5.03 (s, 2H),
1.66-1.76 (m, 2H), 3.22 (t, 2H, J = 8.3 Hz), 7.57 (t, 1H, J = 8.8 Hz), 7.72 (t, 1H, J = 8.8
Hz), 8.04 (d, 1H, J = 9.4 Hz), 8.07 (d, 1H, J = 8.8 Hz), 9.10 (s, 1H); 13C{1H}NMR (100
MHz, CDCl3): δ =14.4, 22.8, 38.8, 97.4, 124.0, 127.2, 128.4, 129.4, 130.1, 147.3, 151.0,
157.0; HRMS (ESI) Calcd for C12H13NI [M+H]+ =298.0087, Found = 298.0085.
4-Heptyl-3-iodoquinoline (3Ar): Yield: 94.9 mg (56%); colorless oil; IR (neat) 3069,
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1505, 1480 cm-1; H NMR (400 MHz, CDCl3): δ = 0.90 (t, 3H, J = 6.9 Hz), 1.30-1.42
(m, 6H), 1.50-1.58 (m, 2H), 1.62-1.70 (m, 2H), 3.22 (t, 2H, J = 7.9 Hz), 7.57 (t, 1H, J =
7.8 Hz), 7.72 (t, 1H, J = 7.6 Hz), 8.06 (t, 2H, J = 8.8 Hz), 9.09 (s, 1H); 13C{1H}NMR
(100 MHz, CDCl3): δ = 14.1, 22.6, 29.0, 29.3, 29.9, 31.8, 37.1, 97.4, 124.0, 127.2,
128.3, 129.4, 130.1, 147.3, 151.2, 157.0; HRMS (ESI) Calcd for C16H21NI [M+H]+
=354.0713, Found = 354.0711.
4-Cyclohexyl-3-iodoquinoline (3As): Yield: 96.5 mg (57%); colorless oil; IR (neat)
3064, 1495, 1473 cm-1; 1H NMR (400 MHz, CDCl3): δ = 1.40-1.59 (m, 3H), 1.92 (d, 5H,
J = 12.9 Hz), 2.23 (q, 2H, J = 12.7 Hz), 3.55 (t, 1H, J = 12.7 Hz), 6.96 (d, 1H, J = 8.3
Hz), 7.52 (t, 1H, J = 7.7 Hz), 7.69 (t, 1H, J = 7.5 Hz), 8.39 (d, 1H, J = 8.6 Hz), 9.15 (s,
1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 26.0, 27.1, 30.8, 52.9, 99.3, 125.3, 125.7,
128.2, 129.0, 130.6, 148.6, 153.6, 157.6; HRMS (ESI) Calcd for C15H17NI [M+H]+
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=338.0400, Found = 338.0398.
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3-Iodo-6-methyl-4-phenylquinoline (3Ba): Yield: 141.7 mg (82%); white solid; Mp:
136-137 °C; IR (neat) 3044, 1563, 1488 cm-1; 1H NMR (400 MHz, CDCl3): δ = 2.41 (s,
3H), 7.19 (s, 1H), 7.23-7.28 (m, 2H), 7.52-7.60 (m, 4H), 8.01 (d, 1H, J = 8.6 Hz), 9.17
(s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ =21.7, 96.4, 125.3, 128.5, 128.6, 128.9,
129.0, 129.1, 131.9, 137.7, 140.5, 145.7, 151.5, 155.6; HRMS (ESI) Calcd for C16H13NI
[M+H]+ = 346.0087, Found = 346.0085.
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6-(tert-Butyl)-3-iodo-4-phenylquinoline (3Ca): Yield: 157.0 mg (81%); pale yellow
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solid; Mp: 115-116 °C; IR (neat) 2958, 2362, 1990 cm-1; H NMR (400 MHz, CDCl3):
δ = 1.25 (s, 9H), 7.28 (d, 2H, J = 7.9 Hz), 7.37 (d, 1H, J = 2.0 Hz), 7.53-7.58 (m, 3H),
7.81 (d, 1H, J = 8.9 Hz), 8.05 (d, 1H, J = 8.8 Hz), 9.18 (s, 1H); 13C{1H}NMR (100 MHz,
CDCl3): δ = 30.9, 35.0, 96.2, 121.6, 128.5 (2C), 128.5, 128.6, 128.9, 129.0, 140.4, 145.6,
150.3, 152.1, 155.9; HRMS (ESI) Calcd for C19H19NI [M+H]+ = 388.0557, Found =
388.0557.
6-Chloro-3-iodo-4-phenylquinoline (3Da): Yield: 95.6 mg (52%); pale yellow solid;
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Mp: 169-170 °C; IR (neat) 3045, 1601, 1480 cm-1; H NMR (400 MHz, CDCl3): δ =
7.23-7.29 (m, 2H), 7.43 (d, 1H, J = 2.5 Hz), 7.52-7.61 (m, 3H), 7.65 (dd, 1H, J = 9.1,
2.5 Hz) , 8.05 (d, 1H, J = 8.8 Hz), 9.23 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ =
97.5, 125.4, 128.8, 128.9, 129.0, 129.4, 130.7, 131.1, 133.3, 139.6, 145.5, 151.5, 156.8;
HRMS (ESI) Calcd for C15H10NClI [M+H]+ = 365.9541, Found = 365.9539.
6-Bromo-3-iodo-4-phenylquinoline (3Ea): Yield: 125.2 mg (61%); white solid; Mp:
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183-184 °C; IR (neat) 3045, 1597, 1474 cm-1; H NMR (400 MHz, CDCl3): δ =
7.22-7.29 (m, 2H), 7.55-7.61 (m, 4H), 7.78 (d, 1H, J = 9.0 Hz), 7.98 (d, 1H, J = 9.1 Hz),
9.24 (s, 1H); 13C{1H}NMR (100 MHz, CDCl3): δ = 97.5, 121.6, 128.7, 128.8, 128.9,
129.0, 129.8, 131.2, 133.2, 139.6, 145.7, 151.4, 157.0; HRMS (ESI) Calcd for
C15H10NBrI [M+H]+ = 409.9036, Found = 409.9034.
N-Tosyl-1,2-dihydro-3-iodo-4-phenylquinoline (IIIAa): Without treatment with
NaOH in methanol: pale yellow solid; Mp: 181-182 °C; IR (neat) 1595, 1491, 1449
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cm-1; H NMR (400 MHz, CDCl3): δ = 2.41 (s, 3H), 4.88 (s, 2H), 6.42 (d, 2H, J = 6.3
Hz), 6.53 (dd, 1H, J = 7.9, 1.4 Hz), 7.07 (td, 1H, J = 7.7, 1.4, Hz), 7.18 (d, 2H, J = 8.2
Hz), 7.25-7.36 (m, 4H) , 7.43 (d, 2H, J = 8.2 Hz) , 7.77 (dd, 1H, J = 8.0, 1.1, Hz);
13C{1H}NMR (100 MHz, CDCl3): δ = 21.4, 56.8, 92.6, 126.6, 126.9, 127.3, 127.5,
128.0, 128.2, 128.4, 129.1, 129.4, 130.9, 134.1, 135.6, 140.0, 143.0, 143.8; HRMS
(APCI) Calcd for C22H19INO2S [M+H]+ = 488.0174, Found = 488.0176.
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Preparation of 4-phenylquinoline (4Aa)
To a mixture of 3-iodo-4-phenylquinoline (3Aa) (0.5 mmol, 165.6 mg) in EtOH (7.5
mL) was added Zn powder (5 mmol, 363.3 mg). Under the argon atmosphere, the
obtained mixture was stirred for 16 h at refluxing temperature. The cooled mixture was
filtered through celite, and then the filtrate was concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel (eluent:
n-hexane:AcOEt = 5:1) to afford 4-phenylquinoline (4Aa) (94.4 mg, 92% yield).
4-Phenylquinoline (4Aa): Yield: 94.4 mg (92%); pale yellow oil; IR (neat) 3059, 1508,
1490 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.34 (d, 1H, J = 4.3 Hz), 7.47-7.55(m, 6H),
7.73 (t, 1H, J = 7.7 Hz), 7.92 (d, 1H, J = 8.4 Hz), 8.18 (d, 1H, J = 8.4 Hz) , 8.95 (d, 1H,
J = 4.3 Hz); C{1H}NMR (100 MHz, CDCl3): δ = 121.2, 125.7, 126.5, 126.6, 128.3,
13
128.4, 129.2, 129.4, 129.7, 137.8, 148.3, 148.5, 149.8; HRMS (ESI) Calcd for C15H12N
[M+H]+ = 206.0964, Found = 206.0965.
Preparation of 4-phenyl-3-p-toluenesulfenylquinoline (5Aa)
To a mixture of 3-iodo-4-phenylquinoline (3Aa) (0.5 mmol, 165.7 mg), CuI (0.025
mmol, 4.8 mg), K2CO3 (0.1 mmol, 138.2 mg), and p-Tol-SH (0.55 mmol, 68.4 mg) in
iPrOH (5.0 mL) was added ethylene glycol (1.0 mmol, 56 µL). Under the argon
atmosphere, the obtained mixture was stirred for 48 h at 80°C. H2O (5.0 mL) was added
to the reaction mixture, and the product was extracted with EtOAc (15 mL × 3), and
washed with brine (15 mL). The organic layer was dried over Na2SO4. After removal of
the solvent under reduced pressure, the residue was purified by silica-gel column
chromatography
(eluent:
n-hexane
:
EtOAc
=
8:1)
to
give
4-phenyl-3-p-toluenesulfenylquinoline (5Aa) (116.6 mg, 71% yield).
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4-Phenyl-3-p-toluenesulfenylquinoline (5Aa): Yield: 116.6 mg (71%); white solid;
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Mp: 128-129 °C; IR(neat) 3060, 1563, 1486 cm-1; H NMR (400 MHz, CDCl3): δ =
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2.33 (s, 3H), 7.10 (d, 2H, J = 8.1 Hz) , 7.21 (d, 2H, J = 8.1 Hz), 7.32-7.36 (m, 2H),
7.41-7.56 (m, 5H), 7.66 (t, 1H, J = 7.5 Hz) , 8.08 (d, 1H, J = 8.3 Hz), 8.67 (s, 1H);
13C{1H}NMR (100 MHz, CDCl3): δ = 21.1, 126.0, 127.1, 127.5, 128.4, 128.5, 129.0,
129.4, 129.5, 129.6, 130.2, 130.6, 132.2, 136.0, 137.9, 146.5, 147.3, 151.7; HRMS
(ESI) Calcd for C22H18NS [M+H]+ = 328.1154, Found = 328.1152.
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Preparation of 4-phenyl-3-phenylethynylquinoline (6Aa)
To a mixture of 3-iodo-4-phenylquinoline (3Aa) (0.5 mmol, 165.7 mg), CuI (0.010
mmol, 1.9 mg), and PdCl2(PPh3)2 (0.010 mmol, 7.0 mg) in Et3N (2.5 mL) was added
ethynylbenzene (0.6 mmol, 66 µL). Under the argon atmosphere, the obtained mixture
was stirred for 3 h at 60°C. H2O (2.5 mL) was added to the reaction mixture, and the
product was extracted with EtOAc (15 mL × 3), and washed with brine (15 mL). The
organic layer was dried over Na2SO4. After removal of the solvent under reduced
pressure, the residue was purified by silica-gel column chromatography (eluent:
n-hexane : EtOAc = 5:1) to give 4-phenyl-3-phenylethynylquinoline (6Aa) (151.1 mg,
99% yield).
4-Phenyl-3-phenylethynylquinoline (6Aa): Yield: 151.1 mg (99%); pale yellow solid;
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Mp: 148-149 °C; IR (neat) 3050, 2199, 1488 cm-1; H NMR (400 MHz, CDCl3): δ =
7.24-7.31 (m, 5H), 7.48-7.61 (m, 6H), 7.69-7.76 (m, 2H), 8.16 (d, 1H, J = 8.7 Hz), 9.08
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(s, 1H); C{1H}NMR (100 MHz, CDCl3): δ = 86.8, 95.2, 116.4, 122.7, 126.2, 126.5,
127.1, 128.1, 128.2, 128.4, 128.5, 129.57, 129.61, 130.0, 131.4, 136.0, 147.1, 149.9,
152.0; HRMS (ESI) Calcd for C23H16N [M+H]+ = 306.1277, Found = 306.1273.
Preparation of (E)-4-phenyl-3-styrylquinoline (7Aa)
To a mixture of 3-iodo-4-phenylquinoline (3Aa) (0.5 mmol, 165.7 mg), K2CO3 (1.0
mmol, 138.2 mg), and PdCl2(PPh3)2 (0.010 mmol, 7.0 mg) in DMF (5.0 mL) was added
styrene (1.0 mmol, 57 µL). Under the argon atmosphere, the obtained mixture was
stirred for 3 h at 60°C. Saturated NaHCO3 aqueous solution (5.0 mL) was added to the
reaction mixture, and the product was extracted with EtOAc (15 mL × 3), and washed
with brine (15 mL). The organic layer was dried over Na2SO4. After removal of the
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solvent under reduced pressure, the residue was purified by silica-gel column
chromatography
(eluent:
n-hexane
:
EtOAc
=
5:1)
to
give
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(E)-4-phenyl-3-styrylquinoline (7Aa) (126.9 mg, 83% yield).
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(E)-4-Phenyl-3-styrylquinoline (7Aa): Yield: 126.9 mg (83%); white solid; Mp:
174-175 °C; IR (neat) 3057, 1631, 1489 cm-1; 1H NMR (400 MHz, CDCl3): δ = 6.96 (d,
1H, J = 16.6 Hz), 7.21-7.39 (m, 8H), 7.44 (t, 1H, J = 7.6 Hz), 7.51-7.60 (m, 4H), 7.67 (t,
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1H, J = 7.6 Hz), 8.14 (d, 1H, J = 8.3 Hz), 9.35 (s, 1H); C{1H}NMR (100 MHz,
CDCl3): δ = 124.6, 126.5, 126.6, 126.8, 127.3, 127.8, 128.0, 128.2, 128.5, 128.7, 128.9,
129.4, 130.1, 131.0, 135.8, 136.9, 145.1, 147.2, 148.4; HRMS (ESI) Calcd for C23H18N
[M+H]+ = 308.1434, Found = 308.1431.
Preparation of 3,4-diphenylquinoline (8Aa)
To a mixture of 3-iodo-4-phenylquinoline (3Aa) (0.5 mmol, 167.1 mg) and PhB(OH)2
(1.0 mmol, 121.9 mg) in DMF (10 mL) was added PdCl2(PPh3)2 (0.025 mmol, 17.5 mg).
Under the argon atmosphere, the obtained mixture was stirred for 30 min at room
temperature. Then, K2CO3 (1.0 mmol, 138.2 mg) in H2O (2 mL) was added to the
mixture, and the obtained mixture was stirred for 1.5 h at 60°C. H2O (5 mL) was added
to the reaction mixture, and the product was extracted with CH2Cl2 (15 mL × 3), and
washed with brine (15 mL × 2). The organic layer was dried over Na2SO4. After
removal of the solvent under reduced pressure, the residue was purified by silica-gel
column chromatography (eluent: n-hexane : EtOAc = 5:1) to give 3,4-diphenylquinoline
(8Aa) (140.1 mg, 100% yield).
3,4-Diphenylquinoline (8Aa): Yield: 140.1 mg (100%); white solid; Mp: 137-138 °C;
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IR (neat) 3061, 1566, 1484 cm-1; H NMR (400 MHz, CDCl3): δ = 7.16-7.29 (m, 7H),
7.33-7.39 (m, 3H), 7.49 (t, 1H, J = 7.7 Hz), 7.67-7.76 (m, 2H), 8.20 (d, 1H, J = 8.4 Hz),
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9.01 (s, 1H); C{1H}NMR (100 MHz, CDCl3): δ = 126.4, 126.7, 126.9, 127.0, 127.6,
127.9, 128.0, 128.8, 129.4, 130.0, 130.3, 132.9, 136.1, 138.0, 145.3, 147.4, 151.7;
HRMS (ESI) Calcd for C21H16N [M+H]+ = 282.1277, Found = 282.1277.
Preparation of 2-cyclohexyl-3-iodo-4-phenylquinoline (9Aa)
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To a mixture of 3-iodo-4-phenylquinoline (3Aa) (0.5 mmol, 165.7 mg),
cyclohexanecarboxylic acid (1.0 mmol, 124 µL), Ag2CO3 (0.1 mmol, 17.0 mg), and
K2S2O8 (1.0 mmol, 270.4 mg) in MeCN/H2O (5:1, 12 mL) was added trifluoroacetic
acid (0.65 mmol, 50 µL). Under the argon atmosphere, the obtained mixture was stirred
for 6 h at 70°C. Saturated NaHCO3 aqueous solution (5.0 mL) was added to the reaction
mixture, and the product was extracted with EtOAc (15 mL × 3), and washed with brine
(15 mL). The organic layer was dried over Na2SO4. After removal of the solvent under
reduced pressure, the residue was purified by silica-gel column chromatography (eluent:
n-hexane : EtOAc = 30:1) to give 2-cyclohexyl-3-iodo-4-phenylquinoline (9Aa) (127.8
mg, 62% yield).
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2-Cyclohexyl-3-iodo-4-phenylquinoline (9Aa): Yield: 127.8 mg (62%); white solid;
Mp: 101-102 °C; IR (neat) 3056, 1499 cm-1; 1H NMR (400 MHz, CDCl3): δ = 1.35-1.57
(m, 3H), 1.73-1.85 (m, 3H), 1.92 (d, 2H, J = 12.9 Hz), 2.05 (d, 2H, J = 11.8 Hz), 3.46 (t,
1H, J = 11.6 Hz), 7.22 (d, 2H, J = 7.7 Hz), 7.28-7.34 (m, 2H), 7.48-7.58 (m, 3H) 7.67 (t,
1H, J = 7.3 Hz), 8.07 (d, 1H, J = 8.38 Hz); 13C{1H}NMR (100 MHz, CDCl3): δ = 26.1,
26.5, 32.1, 49.1, 101.5, 126.3, 126.7, 127.2, 128.2, 128.5, 129.0, 129.1, 129.5, 142.6,
147.0, 153.6, 165.3; HRMS (ESI) Calcd for C21H21NI [M+H]+ = 414.0713, Found =
414.0713.
Preparation of 2-(1’,4’-dioxan-2’-yl)-3-iodo-4-phenylquinoline (10Aa)
To a solution of 3-iodo-4-phenylquinoline (3Aa) (0.5 mmol, 167.1 mg) and
trifluoroacetic acid (0.65 mmol, 50 µL) in 1,4-dioxane (4.0 mL) was added benzoyl
peroxide (1.0 mmol, 323.0 mg) at room temperature, and the flask was flushed by argon
gas. Then, the mixture was stirred for 4 h at 80 °C. Saturated NaHCO3 aqueous
solution (5.0 mL) was added to the reaction mixture, and the product was extracted with
EtOAc (15 mL × 3), and washed with brine (15 mL). The organic layer was dried over
Na2SO4. After filtration, the solvent was removed under reduced pressure, the residue
was purified by silica-gel column chromatography (eluent: n-hexane:EtOAc = 5:1) to
give 2-(1’,4’-dioxan-2’-yl)-3-iodo-4-phenylquinoline (10Aa) (115.1 mg, 55% yield).
2-(1’,4’-Dioxan-2’-yl)-3-iodo-4-phenylquinoline (10Aa): Yield: 115.1 mg (55%);
1
white solid; Mp: 119-120 °C; IR (neat) 2956, 1502, 1180 cm-1; H NMR (400 MHz,
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CDCl3): δ = 3.83-3.97 (m, 2H), 4.02-4.12 (m, 3H), 4.25 (dd, 1H, J = 11.6, 2.5 Hz), 5.39
(d, 1H, J = 9.6 Hz), 7.18-7.24 (m, 2H), 7.32-7.43 (m, 2H), 7.50-7.59 (m, 3H), 7.71 (t,
9
13
1H, J = 7.6 Hz), 8.21 (d, 1H, J = 8.4 Hz); C{1H}NMR (100 MHz, CDCl3): δ = 66.3,
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67.7, 69.9, 80.8, 98.6, 126.7, 127.6, 128.0, 128.51, 128.54, 128.7, 128.9, 129.1, 129.6,
129.9, 141.8, 146.7, 154.6, 156.1; HRMS (ESI) Calcd for C19H17O2NI [M+H]+ =
418.0298, Found = 418.0299.
AUTHOR INFORMATION
Corresponding Author
*E-mail: togo@faculty.chiba-u.jp
ORCID
Katsuhiko Moriyama: 0000-0001-8443-3599
ACKNOWLEDGEMENTS
Financial support in the form of a Grant-in–Aid for Scientific Research (No. 15K05418)
from the Ministry of Education, Culture, Sports, Science, and Technology in Japan is
gratefully acknowledged.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website
at DOI: http://pubs.acs.org. NMR charts of all quinolines 3, IIIAa, 4Aa~10Aa, and
diaryliodonium triflates A~E, and X-ray analytical data of 3Aj.
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