Visible-light-promoted c2 selective arylation of quinoline and pyridine n-oxides with diaryliodonium tetrafluoroborate

Article abstract of DOI:10.1021/acs.joc.9b02933

A protocol of visible-light-promoted C2 selective arylation of quinoline and pyridine N-oxides, with diaryliodonium tetrafluoroborate as an arylation reagent, using eosin Y as a photocatalyst for the construction of N-heterobiaryls was presented. This met

Full text of DOI:10.1021/acs.joc.9b02933

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Note
Visible-Light Promoted C2 Selective Arylation of Quinoline
and Pyridine N-Oxides with Diaryliodonium Tetrafluoroborate
Dazhi Li, Ce Liang, Zaixing Jiang, JunZheng Zhang, Wang-Tao Zhuo,
Fan-Yue Zou, Wan-Peng Wang, Guo-Lin Gao, and Jinzhu Song
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02933 • Publication Date (Web): 07 Jan 2020
Downloaded from pubs.acs.org on January 7, 2020
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Visible-Light Promoted C2 Selective Arylation of Quinoline and Pyridine
N-Oxides with Diaryliodonium Tetrafluoroborate
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Dazhi Li,†,§ Ce Liang,‡,§ Zaixing Jiang,‡ Junzheng Zhang,‡ Wang-Tao Zhuo,‡ Fan-Yue Zou,‡
Wan-Peng Wang,‡ Guo-Lin Gao,*,‡ and Jinzhu Song*,†
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† School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, Heilongjiang, China.
‡
MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of
Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, Heilongjiang, China.
Eosin Y (10 mol%)
Cs2CO3 (1 equiv.)
R
R
+
Ar2IBF4
N
O
Ar
N
O
BQ or K2S2O8 (2 equiv.)
MeOH (1 mL), N2
5 W blue LEDs, 3 d.
ABSTRACT: A protocol of visible-light promoted C2 selective arylation of quinoline and
pyridine N-oxides, with diaryliodonium tetrafluoroborate as arylation reagent, using eosin Y as
photo-catalyst for the construction of N-heterobiaryls was presented. This methodology provided
an efficient way for the synthesis of 2-aryl substituted quinoline and pyridine N-oxides. And this
strategy advantaged of its specific regioselectivity, simple operation, good functional group
tolerance, and high to moderate yields under mild conditions.
Quinoline and pyridine motifs contained N-heterobiaryls are very important subunits widely existed in natural
products,1 bioactive compounds,2 pharmaceuticals,3 ligands,4 and functional materials.5 Therefore, significant
efforts had been made for the efficient synthesis of these functional molecules in the last decades. Conventional
methodologies commonly utilize transition-metal-catalyzed cross-coupling reactions, such as Stille,6 Suzuki,7
Negishi,8 Kumada,9 Hiyama10 and others.11 Among which, quinoline or pyridine coupling precursors usually
needed to be prefunctionalized by halogenation, boronation or metallization, which was neither step nor atom
Scheme 1. Selected direct arylation of N-heteroarenes.
Transition-metal catalyzed or metal-free arylation of N-heroarenes:
[M] cat.
+
Ar-L
Ar
(a)
or metal-free
N
O
N
O
L = halogen, metal, OTs, B(OH)2, BF3K, N2X, H, CO2H
Visible-light participated arylation of N-heteroarenes:
visible-light
+ Ar-X
Ar
(b)
(c)
N
N
X = N2BF4, halogen
This work:
Visible-light
+
Ar2IBF4
N
N
Ar
O
O
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economy. And the usage of air and moisture sensitive organometallic compounds in stoichiometric also bad for the
operation. All these defects limited their application in organic chemistry.
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Recently, direct selective arylation of quinoline and pyridine N-oxides have emerged as a powerful strategy to
build C-C bond between quinoline and pyridine N-oxide with arene for the construction of N-heterobiaryls, in
which various transition-metal catalysts were used, e.g. Pd,12 Cu,13 Ir,14 Ag,15 Rh,16 as well as metal-free processes
were employed (Scheme 1, a).17 All these protocols were very useful, but there were still some disadvantages, such
as high temperature,12b-d, 13b, c, 15 use of explosive diazonium compound,14, 16 use of water and moisture sensitive
organometallic compounds.13a, 17 To our best knowledge, there was no visible-light promoted or induced direct
arylation of quinoline or pyridine N-oxide was reported. Only rare of visible-light induced selective C-H arylation
of pyridine or quinoline was reported (Scheme 1, b).18 In these processes, there have some defects too, such as
explosive diazonium compounds were used,18a-e or bad regioselectivity were given.18a, 18d-f There’s still room for
inspiration in developing mild, efficient, regioselective and benign methods for the preparation of quinoline or
pyridine N-oxide contained N-heterobiaryls. Herein, we present visible-light promoted C2 selective arylation of
quinoline and pyridine N-oxides using diaryliodonium tetrafluoroborate as arylation reagent with simple operation
in room temperature to give C2 arylation products with good group tolerance (Scheme 1, c).
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Our initial investigation was carried out by using quinoline N-oxide (1a) as substrate, Ph2IBF4 (2a, 1 equiv.)
as arylation reagent, K2CO3 (1 equiv.) as base in the presence of Ru(bpy)3Cl2·6H2O (5 mol%), in 1 mL of MeCN
under N2 atmosphere, which led to the desired product 3a in 12% yield after irradiation with 5 W blue LEDs (light
emitting diodes) for 3 days (Table 1, entry 1). The preliminary result urges us for the further condition
optimization. Subsequently, different photo-catalysts were screened, and eosin Y gave the best result to give 3a in
20% yield (Table 1, entries 2 - 7). Other common bases were also tested, and Cs2CO3 was the ideal base for this
transformation in which the yield of 3a was increased to 25% (Table 1, entries 8 - 9). Further investigation showed
that methanol was the best solvent, and the yield of 3a was improved to 35% (Table 1, entry 10). When the
reaction time was shortened to 2 days, the yield of 3a was decreased to 24%, but if the reaction time was
prolonged to 7 days, the yield of the desired product was almost the same as 3 days (Table 1, entries 11 - 12).
Other diphenyliodonium salts, such as Ph2IPF6 (2b) and Ph2IOTf (2c) were also used as arylation reagents, but
failed to improve the yield of 3a (Table 1, entries 13 - 14). Furthermore, different additives were tested, and BQ
(1,4-benzoquinone) was helpful for improving the yield of 3a to 40% (Table 1, entries 15 - 18), probably with
deprotonation of intermediate. Different loadings of photo-catalyst, arylation reagent 2a and additive were
investigated, and the yield of 3a was improved up to 76% (Table 1, entries 19 - 21). When this reaction was run
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Table 1. Reaction conditions screening.a
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6
7
8
Photocatalyst
+
Ph2IX
N
O
N
O
Solvent, N2, rt
5 W blue LEDs
2a
: X = BF4;
2b
: X = PF6;
2c
: X = OTf.
1a
3a
Additive Time Yield
9
2
Photocatalyst
(mol%)
Base
Solvent
Entry
(equiv.) (1 equiv.) (1 mL)
(equiv.)
(d)
(%)
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---
1
2
3
Ru(bpy)3Cl2
6H2O (5) 2a (1)
K2CO3
K2CO3
K2CO3
MeCN
MeCN
MeCN
3
12
2a
2a
---
---
fac-Ir(ppy)3 (5)
Ru(phen)3(PF6)2 (5)
(1)
(1)
3
3
17
12
2a
2a
2a
K2CO3
K2CO3
---
---
4
5
Ru(phen)3Cl2 (5)
(1)
(1)
(1)
MeCN
MeCN
3
3
12
13
Ru(bpz)3(PF6)2 (5)
---
---
---
---
6
7
[Ir(bpy)(ppy)2](PF6) (5)
Eosin Y (5)
K2CO3
K2CO3
MeCN
MeCN
MeCN
MeCN
MeOH
MeOH
MeOH
3
3
3
3
15
20
18
25
2a (1)
2a (1)
8
Eosin Y (5)
NEt3
9
2a
2a
Cs2CO3
Eosin Y (5)
(1)
(1)
10
11
12
Cs2CO3
Cs2CO3
Cs2CO3
Eosin Y (5)
---
---
3
2
7
3
3
3
3
3
3
35
24
34
33
20
29
38
32
40
Eosin Y (5)
2a (1)
2a
2b
2c
Eosin Y (5)
(1)
(1)
(1)
---
13 Eosin Y (5)
Cs2CO3 MeOH
---
14
15
Cs2CO3
MeOH
Eosin Y (5)
Eosin Y (5)
Eosin Y (5)
Eosin Y (5)
Eosin Y (5)
---
Ag2CO3 (1)
K2S2O8 (1)
DDQ (1)
BQ (1)
2a (1)
2a (1)
2a (1)
2a (1)
Cs2CO3 MeOH
Cs2CO3 MeOH
Cs2CO3 MeOH
Cs2CO3 MeOH
Cs2CO3 MeOH
Cs2CO3 MeOH
Cs2CO3 MeOH
16
17b
18c
BQ (2)
BQ (2)
BQ (2)
BQ (2)
BQ (2)
2a
2a
2a
3
3
50
65
19 Eosin Y (5)
20 Eosin Y (5)
(1)
(2)
(2)
21
22
Eosin Y (10)
---
3
3
76
Cs2CO3
MeCN
2a (2)
2a
trace
23d
(2)
Cs2CO3 MeCN
3
trace
Eosin Y (10)
a
1a
2
(0.1 mmol), , photocatalyst, base, additive, 1 mL solvent, N2
atmosphere, room temperature under the irradiation of 5 W blue LEDs for a certain time.
DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. BQ = 1,4-benzoquinone. In
Reaction condition:
b
c
d
darkness.
without light or photo-catalyst, only trace amount of product was detected (Table 1, entries 22 - 23), suggesting
either the photo-catalyst or light is necessary for the process. The best conditions that we got for this reaction were:
1a (1 equiv.) reacted with 2a (2 equiv.), in the presence of photo-catalyst eosin Y (10 mol%), with base Cs2CO3 (1
equiv.) and additive BQ (2 equiv.) in 1 mL of methanol under N2 atmosphere, with the irradiation of 5 W LEDs for
3 days.
With the optimized condition in hand, we investigated the scope of this reaction, and the results were
elucidated in Scheme 2. As depicted in Scheme 2, for all the quinoline N-oxide substrates investigated, desired
products were obtained in good to moderate yields, and substrates with electron-withdrawing group (Cl, Br, or
CO2Me) gave relatively higher yield than electron-donating group (Me or OMe). And the structure of 3a was
further established by X-ray crystallographic analysis (preparation and details in SI, CCDC: 1858700).19 As shown
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Scheme 2. Scope study of quinoline N-oxide.a
5
6
7
8
Eosin Y (10 mol%)
Cs2CO3 (1 equiv.)
R
R
+
Ph2IBF4
N
O
N
O
BQ (2 equiv.)
MeOH (1 mL), N2
5 W blue LEDs, 3 d.
2a
1
3
9
R1
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=
N
N
O
O
, R1 = Me, 70%
3a
, 76%
R1
3b
3c
3d
, R1 = Cl, 90%
R1
, R1 = Br, 89%
N
O
, R1 = Me, 68%
3g
3h
3i
3j
3k
N
O
, R1 = OMe, 70%
N
O
, R1 = Cl, 84%
, R1 = Br, 78%
, R1 = Me, 60%
, R1 = Cl, 78%
3e
3f
3l
, 67%
, R1 = CO2Me, 79%
Cl
N
O
N
O
Cl
N
O
3m
, 65%
3n
, 86%
3o
, 50%
a
1
Reaction conditions: (0.1 mmol), Ph2IBF4 (0.2 mmol, 2 equiv.), Cs2CO3
(0.1 mmol, 1 equiv.), BQ (0.2 mmol, 2 equiv.), MeOH (1 mL) under N2
atmosphere, irradiation with 5 W blue LEDs for 3 days.
in Scheme 2, substituted groups at C3 position of pyridine ring didn’t hinder the reaction, to form the final
products in good yields (Scheme 2, 3b - 3d). It’s also worth to notice that 3-chloroquinoline N-oxide gave the
expected product up to 90% yield (Scheme 2, 3c). C4 substituted quinoline N-oxides substrates could converted
into corresponding products smoothly in good yields (Scheme 2, 3e - 3f). Different substituents on the phenyl ring
fragment of the quinoline N-oxide were also tested, to give the corresponding products in good to moderate yields.
For example, substitution group at C6 or C8 position with Me, OMe, Cl, or Br group was tolerated with the
reaction conditions to produce the corresponding products in 67 - 84% yields (Scheme 2, 3g - 3j, 3l). Interestingly,
the ester group was suitable for the reaction conditions to furnish the desired product in 79% yield (Scheme 2, 3k).
In addition, when benzo[h]quinoline N-oxide and 4,7-dichloroquinoline N-oxide were submitted to the reaction,
desired products were isolated in 65% and 86% yield, respectively (Scheme 2, 3m - 3n). It was also worth noting
that when isoquinoline N-oxide submitted to this reaction, only 1-phenylisoquinoline N-oxide was isolated as the
main product in 50% yield, probably because of electronic effects (Scheme 2, 3o).
To extend the scope of the reaction, different substituted diaryliodonium tetrafluoroborate was subjected to
the reaction conditions (Scheme 3). As seen from Scheme 3, different substituents in para-position of the
diaryl-iodonium tetrafluoroborate, such as CF3, Cl, Me, and F, to give the desired products in 49-70% yields
(Scheme 3, 3p - 3s). Different substituents in meta-position of the diaryliodonium salts were also converted into
the final products in 62% and 50% yields, respectively (Scheme 3, 3t, 3u). It worth to noticed that, ortho-position
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Scheme 3. Scope study of diaryliodonium tetrafluoroborate.a
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6
7
8
Eosin Y (10 mol%)
Cs2CO3 (1 equiv.)
+
Ar2IBF4
N
O
Ar
N
O
BQ (2 equiv.)
MeOH (1 mL), N2
5 W blue LEDs, 3 d.
2
1a
3
9
R
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R
N
O
N
N
O
O
R
3p
3q
3r
3s
, R = CF3, 49%
, R = Me, 65%
, R = Cl, 52%
3t
3v
, R = Me, 48%
3w
, R = Cl, 47%
, R = Me, 62%
R = F, 50%
3u
,
, R = F, 70%
a
1a
Reaction conditions:
(0.1 mmol), Ar2IBF4 (0.2 mmol, 2 equiv.), Cs2CO3
(0.1 mmol, 1 equiv.), BQ (0.2 mmol, 2 equiv.), MeOH (1 mL) under N2
atmosphere, irradiation with 5 W blue LEDs for 3 days.
(2-Cl, 2-Me) substituted substrates didn’t hinder the reaction, to give the corresponding products in 48% and 47%
yield, respectively (3v, 3w). The yield were relative lower probably because the steric hindrance.
Then we tried this protocol for the arylation of pyridine N-oxide, and results were listed in Scheme 4. Further
investigation showed that K2S2O8 was a better additive for the arylation of pyridine N-oxide than BQ in the
reaction, probably with the oxidation of photo-catalyst. Pyridine N-oxide could convert to its corresponding
2-phenylpyridine N-oxide in 70% yield (Scheme 4, 5a). When pyridine N-oxides bearing strong withdrawing
groups, such as 4-nitro- or 4-cyanopyridine N-oxides, were also suitable for the reaction, to give the corresponding
products in 43% and 62% yield, respectively (Scheme 4, 5b, 5c). The yield of 5b was isolated in a relative lower
probably because the nitro group. Di- or tri-substituents on the pyridine ring did not hinder the reaction, to form
the desired products in acceptable yield (Scheme 4, 5d - 5i). 5g gave a lower yield probably because the steric
hindrance. It is worth to point out that the halogen substituted pyridine N-oxide, such as Br, Cl, that were normally
Scheme 4. Scope study of pyridine N-oxide.a
Eosin Y (10 mol%)
Cs2CO3 (1 equiv.)
R
R
Ph2IBF4
+
K2S2O8 (2 equiv.)
MeOH (1 mL), N2
5 W LEDs, 3 d
N
O
N
O
4
5
R1
R1
N
Ph
N
O
Ph
NC
N
O
Ph
O
N
O
Ph
, R1 = CN, 50%
, R1 = Cl, 43%
5d
5e
, R1 = H, 70%
5a
5f
, 55%
5g
, 40%
, R1 = NO2, 43%
5b
5c
, R1 = CN, 62%
R1
Cl
Cl
Ph
N
O
Ph
N
O
Ph
N
O
Ph
R2
N
O
Ph
5j'
, 24%
5k
, 30%
5j
, 39%
, R1 = Br, R2 = Me, 46%
, R1 = Me, R2 = Br, 50%
5h
5i
a
4
Reaction conditions: (0.1 mmol), Ph2IBF4 (0.2 mmol, 2 equiv.),
Cs2CO3 (0.1 mmol, 1 equiv.), K2S2O8 (0.2 mmol, 2 equiv.), MeOH (1
mL) under N2 atmosphere, irradiation with 5 W LEDs for 3 days.
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sensitive to the metal catalytic arylation reaction conditions, could be suitable for this protocol. The yield of 5e
was not so good probably because of electron effect. The yield of 5h was a bit low probably as electron and steric
effects. It was not surprise that 3-chloropyridine N-oxide gave the expected products in two structure isomers (5j
and 5j') in 63% yield, and the ratio is 13:8. Interestingly, when the product 2-phenylpyridine N-oxide (5a) was
subjected to the standard conditions, the expected product 2,6-diphenylpyridine N-oxide was obtained in 30%
yield (Scheme 4, 5k).
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Cs2CO3 (1 equiv.)
Eosin Y (10 mol%)
Ph2IBF4
(1)
+
+
N
O
N
O
N
O
BQ (2 equiv.)
MeOH (1 mL)
5 W LEDs, N2, rt., 3 d
1a
(1 equiv.)
2a
(2 equiv.)
TEMPO
(2 equiv.)
0% yield
Cs2CO3 (1 equiv.)
Eosin Y (10 mol%)
Ph2IBF4
(2)
+
N
N
BQ (2 equiv.)
2a
(2 equiv.)
MeOH (1 mL)
(1 equiv.)
5 W LEDs, N2, rt., 3 d
0% yield
Cs2CO3 (1 equiv.)
Eosin Y (10 mol%)
(3)
Ph2IBF4
+
N
N
K2S2O8 (2 equiv.)
MeOH (1 mL)
5 W LEDs, N2, rt., 3 d
2a
(2 equiv.)
(1 equiv.)
0% yield
To give further insight into the reaction mechanism, the control experiment was conducted by addition of 2
equiv. of TEMPO ((2,2,6,6-Tetramethylpiperidin-1-yl)oxyl) into the reaction, and no desired product was isolated
(eq. 1), and with HRMS (high resolution mass spectrometer) test for the reaction mixture, Ph-OTEMP was
detected. And in our reaction mixture without TEMPO, diphenyl was also detected by GC-Mass, which suggested
that radical pathway involved in the process. We also tried the same condition use quinoline and pyridine as
substrates, but to find no reaction (eq. 2 and 3), that means the N-oxide group was essential for this reaction. And
Stern-Volmer experiments were carried out with 1a, 2a, and BQ (details in SI).
Scheme 5. Proposed reaction mechanism.
H
Cs2CO3
N
O
Ar
N
O
Ar
or
-H+
3
5
C
Eosin Y
Visible light
SET
H
Oxidative quenching
N
O
Ar
B
Eosin Y+
Eosin Y*
N
O
SET
1
4
or
-
Ar2IBF4
Ar + ArI + BF4
2
A
Accordingly the reaction mechanism was proposed based upon the above results and previous literatures as
depicted in Scheme 5.20 Firstly, eosin Y was activated by visible light to its excited state eosin Y* under the
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irradiation of 5 W blue LEDs, which was oxidized by Ar2IBF4 (2) through a SET (single electron transfer)
reaction, to give eosin Y+ and phenyl radical (A).21 Subsequently the radical intermediate A was selectively added
to C2 position of quinoline or pyridine N-oxide (1 or 4) to generate intermediate B which went through another
SET reaction to give intermediate C and regenerated photo-catalyst. Finally, intermediate C loss one proton with
the assistant of base (Cs2CO3) to afford the final products 3 or 5. The additives, BQ probably help with the
deprotonation of intermediate C to give final product 3, and K2S2O8 probably with the oxidation of photo-catalyst
in pyridine N-oxide examples.
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In summary, we have developed a strategy of visible-light promoted C2 selective arylation of quinoline and
pyridine N-oxides under mild reaction conditions. Compared with previous methodologies, this strategy has
attracted special attention due to its operational simplicity, good functional group tolerance, good regioselectivity,
and high to moderate yields under mild conditions.
EXPERIMENTAL SECTION
1. General information:
1H and 13C NMR spectra were obtained on Bruker AV-400 or AV-600 instrument in CDCl3 or DMSO-d6 with
TMS (SiMe4) as internal standard. And chemical shift values were reported in ppm relative to dimethyl TMS (δ =
1
0.00 ppm) or DMSO (δ = 2.50 ppm) for H NMR, chloroform (δ = 77.0 ppm) or DMSO (δ = 39.5 ppm) for 13C
NMR. The reported δ of 13C NMR were 13C{1H} proton-decoupled carbons data. The following abbreviations (or
combinations thereof) were used to explain multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, and m =
multiplet. HRMS (ESI) spectra were recorded on a 1200-6520 Q-TOF/Agilent mass spectrometer using
electrospray ionization. The single crystal data was collected on an Agilent Technology Super Nova Eos Dual
system with a (Mo-Kα, λ = 0.71073 Å) micro focus source and focusing multilayer mirror optics. All materials and
solvents were used as received from commercial sources without further purification. Flash column
chromatography was performed using 200-300 mesh silica gel. The 5W LEDs tape lights were made by NVC
lighting CO., LTD, the wave length is 450-480 nm, the distance from light source to vessel is about 5 cm, no filters
was used.
2. Preparation and characterization of substrates
2.1. Preparation of substituted quinoline or pyridine N-oxide.
Quinoline and pyridine N-oxides were synthesized according previous report. 22
2.2. Preparation of diaryliodonium tetrafluoroborate.
Diaryliodonium tetrafluoroborates were synthesized according previous report.23
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2.3. Preparation of diphenyliodonium hexafluorophosphate.
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Diphenyliodonium hxeaflurophosphates was synthesized according previous report.24
2.4. Preparation of diphenyliodonium trifluoromethanesulfonate.
Diphenyliodonium trifluoromethanesulfonate was synthesized according previous report.25
2.5. Characterization of substrates.
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1a, quinoline N-oxide, white solid. H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 8.8 Hz, 1H), 8.55 (d, J = 5.9 Hz,
1H), 7.88 (d, J = 8.2 Hz, 1H), 7.78 –7.74 (m, 2H), 7.65 (t, J = 7.5 Hz, 1H), 7.30 (t, J = 7.2 Hz, 1H). 13C{1H} NMR
(151 MHz, CDCl3) δ 141.4, 135.5, 130.4, 130.3, 128.7, 128.0, 126.0, 120.9, 119.6.
1b, 3-methylquinoline N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.68 (d, J = 8.7 Hz, 1H), 8.41 (s, 1H),
7.76 (d, J = 8.2 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H), 7.59 (t, J = 7.0 Hz, 1H), 7.51 (s, 1H), 2.43 (s, 3H). 13C{1H}
NMR (151 MHz, CDCl3) δ 139.5, 136.8, 131.1, 130.1, 129.2, 128.6, 127.3, 125.4, 119.4, 18.6.
1c, 3-chloroquinoline N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 8.7 Hz, 1H), 8.51 (d, J = 1.7
Hz, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.76 – 7.72 (m, 2H), 7.68 – 7.65 (m, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ
140.3, 135.2, 130.2, 129.8, 129.6, 127.4, 127.3, 124.3, 119.7.
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1d, 3-bromoquinoline N-oxide, white solid. H NMR (600 MHz, CDCl3) δ 8.66 (d, J = 8.8 Hz, 1H), 8.65 (d, J =
1.5 Hz, 1H), 7.90 (s, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.78 – 7.75 (m, 1H), 7.68 – 7.65 (m, 1H). 13C{1H} NMR (151
MHz, CDCl3) δ 140.3, 137.1, 130.5, 130.1, 129.7, 127.8, 127.3, 119.7, 114.2.
1e, 4-methylquinoline N-oxide, brown solid. 1H NMR (400 MHz, CDCl3) δ 8.81 (d, J = 8.7 Hz, 1H), 8.43 (d, J =
6.1 Hz, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.77 (t, J = 7.4 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H), 7.12 (d, J = 6.1 Hz, 1H),
2.66 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 140.8, 134.8, 134.5, 130.0, 129.7, 128.4, 124.6, 121.3, 120.2,
18.2.
1f, 4-chloroquinoline N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 8.7 Hz, 1H), 8.44 (d, J = 6.5
Hz, 1H), 8.20 (d, J = 8.3 Hz, 1H), 7.83 (t, J = 7.8 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.38 (d, J = 6.5 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3) δ 142.0, 135.0, 131.1, 129.9, 129.6, 127.9, 125.1, 120.9, 120.2.
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1g, 6-methylquinoline N-oxide, white solid. H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 8.9 Hz, 1H), 8.46 (d, J =
6.0 Hz, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.61 (s, 1H), 7.58 (dd, J = 8.9, 1.7 Hz, 1H), 7.25 (dd, J = 8.4, 6.0 Hz, 1H),
2.54 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 139.8, 138.8, 134.8, 132.4, 130.5, 126.8, 125.4, 120.8, 119.3,
21.3.
1h, 6-methoxyquinoline N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.65 (d, J = 9.5 Hz, 1H), 8.39 (dd, J
= 6.0, 0.7 Hz, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.37 (dd, J = 9.5, 2.7 Hz, 1H), 7.24 (dd, J = 8.5, 6.0 Hz, 1H), 7.10 (d,
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J = 2.6 Hz, 1H), 3.94 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 159.3, 137.1, 133.7, 131.9, 124.9, 122.7, 121.4,
121.3, 105.6, 55.6.
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1i, 6-chloroquinoline N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J = 9.3 Hz, 1H), 8.50 (d, J = 6.0
Hz, 1H), 7.85 (d, J = 2.1 Hz, 1H), 7.69 – 7.63 (m, 2H), 7.33 (dd, J = 8.5, 6.1 Hz, 1H). 13C{1H} NMR (151 MHz,
CDCl3) δ 139.9, 135.5, 134.9, 131.1, 131.0, 126.7, 124.6, 122.1, 121.6.
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1j, 6-bromoquinoline N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 9.3 Hz, 1H), 8.51 (d, J = 6.0
Hz, 1H), 8.04 (d, J = 1.5 Hz, 1H), 7.82 (dd, J = 9.3, 1.7 Hz, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.32 (dd, J = 8.4, 6.2
Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 140.3, 135.7, 133.6, 131.5, 130.0, 124.5, 123.2, 122.1, 121.7.
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1k, 6-(methoxycarbonyl)quinoline N-oxide, white solid. H NMR (400 MHz, CDCl3) δ 8.79 (d, J = 9.1 Hz, 1H),
8.62 – 8.59 (m, 2H), 8.32 (dd, J = 9.1, 1.6 Hz, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.39 (dd, J = 8.4, 6.1 Hz, 1H), 4.01 (s,
3H). 13C{1H} NMR (151 MHz, CDCl3) δ 165.6, 143.1, 137.0, 130.9, 130.3, 129.8, 129.7, 126.5, 121.8, 120.3,
52.6.
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1l, 8-methylquinoline N-oxide, white solid. H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 6.0 Hz, 1H), 7.64 – 7.61
(m, 2H), 7.43 – 7.39 (m, 2H), 7.16 (dd, J = 8.3, 6.1 Hz, 1H), 3.19 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ
141.2, 137.1, 133.4, 133.2, 132.3, 127.9, 126.7, 126.3, 120.5, 24.8.
1m, benzo[h]quinoline N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 10.85 (d, J = 7.6 Hz, 1H), 8.65 (d, J =
6.2 Hz, 1H), 7.92 – 7.89 (m, 1H), 7.83 – 7.71 (m, 4H), 7.61 (d, J = 8.8 Hz, 1H), 7.37 (dd, J = 7.9, 6.4 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3) δ 139.2, 138.3, 133.9, 131.1, 130.4, 128.9, 128.2 (d, J = 7.6 Hz), 127.9, 127.6,
125.9, 125.7, 124.9, 121.1.
1n, 4,7-dichloroquinoline N-oxide, white solid. 1H NMR (600 MHz, CDCl3) δ 8.77 (d, J = 2.0 Hz, 1H), 8.43 (d, J
= 6.6 Hz, 1H), 8.14 (d, J = 8.9 Hz, 1H), 7.69 (dd, J = 8.9, 2.0 Hz, 1H), 7.38 (d, J = 6.6 Hz, 1H). 13C{1H} NMR
(151 MHz, CDCl3) δ 142.2, 138.1, 135.8, 130.7, 129.6, 126.7, 126.4, 121.2, 119.8.
1o, isoquinoline N-oxide, white solid. 1H NMR (600 MHz, CDCl3) δ 8.77 (s, 1H), 8.15 (dd, J = 7.1, 1.6 Hz, 1H),
7.80 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 7.1 Hz, 1H), 7.64 – 7.58 (m, 2H). 13C{1H} NMR
(151 MHz, CDCl3) δ 136.6, 136.0, 129.4, 129.3, 128.9, 128.6, 126.5, 124.8, 124.1.
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2a, diphenyliodonium tetrafluoroborate, off-white solid. H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J = 7.5 Hz,
4H), 7.66 (t, J = 7.4 Hz, 2H), 7.53 (t, J = 7.8 Hz, 4H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 135.2, 132.1, 131.8,
116.6.
2b, diphenyliodonium hexafluorophosphate, off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 7.7 Hz,
4H), 7.63 (t, J = 7.3 Hz, 2H), 7.50 (t, J = 7.5 Hz, 4H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 135.1, 131.7, 131.6,
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2c, diphenyliodonium trifluoromethanesulfonate, off-white solid. H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J =
7.8 Hz, 4H), 7.67 (t, J = 7.4 Hz, 2H), 7.53 (t, J = 7.8 Hz, 4H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 135.2,
132.1, 131.8, 116.6.
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2d, bis[4-(trifluoromethyl)phenyl]iodonium tetrafluoroborate, white solid. 1H NMR (600 MHz, DMSO-d6) δ 8.52
(d, J = 7.3 Hz, 4H), 7.94 (d, J = 7.4 Hz, 4H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 136.3, 132.1 (q, J = 32.7
Hz), 128.6 (d, J = 2.9 Hz), 123.4 (q, J = 273.7 Hz), 121.0. 19F NMR (376 MHz, DMSO-d6) δ -61.77, -148.19 (d, J
= 19.9 Hz).
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2e, di-p-tolyliodonium tetrafluoroborate, white solid. H NMR (600 MHz, DMSO-d6) δ 8.09 (d, J = 8.1 Hz, 4H),
7.32 (d, J = 8.0 Hz, 4H), 2.33 (s, 6H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 142.5, 135.0, 132.3, 113.1, 20.9.
2f, bis(4-chlorophenyl)iodonium tetrafluoroborate, white solid. 1H NMR (600 MHz, DMSO-d6) δ 8.26 (d, J = 7.3
Hz, 4H), 7.59 (d, J = 7.3 Hz, 4H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 137.5, 137.1, 131.8, 115.1.
2g, bis(4-fluorophenyl)iodonium tetrafluoroborate, gray solid.26 1H NMR (600 MHz, DMSO-d6) δ 8.32 (dd, J =
8.0, 5.2 Hz, 4H), 7.42 (d, J = 8.6 Hz, 4H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 164.0 (d, J = 251.6 Hz), 138.0
(d, J = 9.1 Hz), 119.3 (d, J = 22.8 Hz), 111.2. 19F NMR (376 MHz, DMSO-d6) δ -106.57, -148.12 (d, J = 21.8 Hz).
2h, di-m-tolyliodonium tetrafluoroborate, white solid. 1H NMR (600 MHz, DMSO-d6) δ 8.11 (s, 2H), 8.05 (d, J =
8.0 Hz, 2H), 7.47 (d, J = 7.6 Hz, 2H), 7.41 (t, J = 7.8 Hz, 2H), 2.33 (s, 6H). 13C{1H} NMR (151 MHz, DMSO-d6)
δ 141.8, 135.4, 132.7, 132.3, 131.5, 116.2, 20.8.
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2i, bis(3-fluorophenyl)iodonium tetrafluoroborate, gray solid. H NMR (600 MHz, DMSO-d6) δ 8.32 (d, J = 5.3
Hz, 2H), 8.12 (d, J = 5.8 Hz, 2H), 7.63 (d, J = 5.9 Hz, 2H), 7.55 (t, J = 7.4 Hz, 2H). 13C{1H} NMR (151 MHz,
DMSO-d6) δ 161.8 (d, J = 252.3 Hz), 133.6 (d, J = 7.9 Hz), 131.6, 122.4 (d, J = 24.8 Hz), 119.6 (d, J = 21.0 Hz),
116.4 (d, J = 7.7 Hz). 19F NMR (376 MHz, DMSO-d6) δ -107.44, -148.23 (d, J = 21.8 Hz).
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2j, di-o-tolyliodonium tetrafluoroborate, white solid. H NMR (600 MHz, DMSO-d6) δ 8.33 (d, J = 7.9 Hz, 2H),
7.59 – 7.55 (m, 4H), 7.32 – 7.29 (m, 2H), 2.61 (s, 6H). 13C{1H} NMR (151 MHz, DMSO-d6) δ 140.6, 137.2,
132.8, 131.6, 129.3, 120.6, 25.0. HRMS (ESI) m/z calcd for C14H14I+ [M-BF4]+ 309.0140, found 309.0145.
2k, bis(4-chlorophenyl)iodonium tetrafluoroborate, white solid. 1H NMR (600 MHz, DMSO-d6) δ 8.53 (d, J = 8.0
Hz, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.70 (t, J = 7.7 Hz, 2H), 7.50 (t, J = 7.7 Hz, 2H). 13C{1H} NMR (151 MHz,
DMSO-d6) δ 139.0, 136.0, 134.8, 130.5, 130.3, 119.6.
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4a, pyridine N-oxide, colourless oil. H NMR (400 MHz, CDCl3) δ 8.25 – 8.22 (m, 2H), 7.30 (s, 3H). 13C{1H}
NMR (151 MHz, CDCl3) δ 139.3, 126.1, 125.9.
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4b, 4-nitropyridine N-oxide, pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 6.3 Hz, 2H), 8.13 (d, J =
6.4 Hz, 2H). 13C{1H} NMR (151 MHz, CDCl3) δ 142.1, 140.1, 120.8.
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4c, 4-cyanopyridine N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 6.1 Hz, 2H), 7.53 (d, J = 6.0
Hz, 2H). 13C{1H} NMR (151 MHz, CDCl3) δ 140.2, 128.9, 115.8, 107.6.
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4d, 2-cyano-3-methylpyridine N-oxide, white solid. H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 6.5 Hz, 1H), 7.40
(dd, J = 7.8, 6.7 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 2.56 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 142.4, 137.3,
127.9, 126.3, 126.2, 111.0, 19.0.
4e, 2-chloro-3-methylpyridine N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 6.4 Hz, 1H), 7.17 –
7.11 (m, 2H), 2.44 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 142.2, 138.0, 136.0, 127.2, 122.3, 19.9.
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4f, 2-cyano-4-methylpyridine N-oxide, white solid. H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 6.8 Hz, 1H), 7.49
(d, J = 1.9 Hz, 1H), 7.30 (dd, J = 6.4, 2.2 Hz, 1H), 2.41 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 139.4, 136.6,
131.4, 130.0, 125.1, 111.7, 20.0.
4g, 2,3,5-trimethylpyridine N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 6.90 (s, 1H), 2.46 (s,
3H), 2.30 (s, 3H), 2.23 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.1, 136.9, 134.0, 132.1, 128.7, 19.3, 17.7,
13.3.
4h, 5-bromo-2-methylpyridine N-oxide, white solid. 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 1.1 Hz, 1H), 7.31
(dd, J = 8.4, 1.5 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 2.46 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 147.9, 140.5,
128.2, 126.4, 117.2, 17.3.
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4i, 2-bromo-5-methylpyridine N-oxide, white solid. H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H), 7.54 (d, J = 8.3
Hz, 1H), 6.97 (d, J = 8.3 Hz, 1H), 2.30 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 140.2, 135.5, 129.9, 129.6,
127.5, 17.9.
4j, 3-chloropyridine N-oxide, white solid. 1H NMR (600 MHz, CDCl3) δ 8.27 (s, 1H), 8.14 (d, J = 6.3 Hz, 1H),
7.30 (d, J = 8.3 Hz, 1H), 7.29 – 7.23 (m, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 138.6, 137.6, 133.2, 125.7,
125.7.
3. Preparation and characterization of products
3.1 The preparation of products.
To a 10 mL vial, magnetic stir bar, substrate 1 (0.1 mmol), Ph2IBF4 (0.2 mmol, 2 equiv.), BQ or K2S2O8 (0.2
mmol, 2 equiv.), Cs2CO3 (0.1 mmol, 1 equiv.), eosin Y (0.01 mmol, 10 mol%), MeOH (1 mL) were added in
sequence and sealed the flask. Evacuated and backfilled it with nitrogen (3 cycles) under -78 oC. Then the vial was
irradiated by 5 W blue LEDs at room temperature for 3 days. After the substrate was consumed (monitored by
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TLC), the mixture was filtered and the filtrate concentrated in vacuo. The residue was purified by precipitation
thin-layer chromatography (PTLC) using hexanes: ethyl acetate (10:1 to 1:1 depending on the substrates) as the
eluant to afford the desired products 3 and 5.
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3a, 2-phenylquinoline N-oxide, 16.8 mg, yield 76%, white solid.27 1H NMR (600 MHz, CDCl3) δ 8.86 (d, J = 8.8
Hz, 1H), 7.97 (d, J = 7.3 Hz, 2H), 7.85 (d, J = 8.1 Hz, 1H), 7.78 (t, J = 7.5 Hz, 1H), 7.74 (d, J = 8.7 Hz, 1H), 7.63
(t, J = 7.4 Hz, 1H), 7.53 – 7.49 (m, 3H), 7.46 (t, J = 7.4 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 144.9, 142.2,
133.4, 130.5, 129.5, 129.5, 129.4, 128.3, 128.2, 127.9, 125.2, 123.2, 120.2. HRMS (ESI) m/z calcd for C15H12NO+
[M+H]+ 222.0919, found 222.0919.
3b, 3-methyl-2-phenylquinoline N-oxide, 16.5 mg, yield 70%, white solid.28 1H NMR (400 MHz, CDCl3) δ 8.73
(d, J = 8.7 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.72 – 7.68 (m, 1H), 7.63 – 7.59 (m, 2H), 7.57 – 7.53 (m, 2H), 7.49 –
7.45 (m, 1H), 7.43 – 7.41 (m, 2H), 2.23 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 147.2, 140.4, 133.1, 131.3,
129.5, 129.2, 128.9, 128.8 (2C), 128.5, 127.2, 125.6, 120.2, 20.6. HRMS (ESI) m/z calcd for C16H14NO+ [M+H]+
236.1075, found 236.1078.
3c, 3-chloro-2-phenylquinoline N-oxide, 23.0 mg, yield 90%, white solid. 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J
= 8.7 Hz, 1H), 7.88 (s, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.76 (t, J = 7.8 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.58 – 7.49
(m, 5H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.4, 141.1, 131.4, 130.5, 129.5 (3C), 128.6, 128.6, 128.5, 127.2,
124.9, 120.4. HRMS (ESI) m/z calcd for C15H11ClNO+ [M+H]+ 256.0529, found 256.0530.
3d, 3-bromo-2-phenylquinoline N-oxide, 26.7 mg, yield 89%, white solid.29 1H NMR (400 MHz, CDCl3) δ 8.70 (d,
J = 8.7 Hz, 1H), 8.08 (s, 1H), 7.81 – 7.74 (m, 2H), 7.68 – 7.64 (m, 1H), 7.58 – 7.47 (m, 5H). 13C{1H} NMR (151
MHz, CDCl3) δ 146.3, 141.3, 133.3, 130.6, 129.4, 129.4, 129.3, 129.2, 128.6, 128.2, 127.1, 120.5, 117.2. HRMS
(ESI) m/z calcd for C15H11BrNO+ [M+H]+ 300.0024, found 300.0023.
3e, 4-methyl-2-phenylquinoline N-oxide, 14.1 mg, yield 60%, brown solid.28 1H NMR (400 MHz, CDCl3) δ 8.92
(d, J = 8.7 Hz, 1H), 7.97 (d, J = 7.3 Hz, 3H), 7.79 (t, J = 7.8 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 7.2 Hz,
2H), 7.46 (t, J = 7.2 Hz, 1H), 7.34 (s, 1H), 2.69 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 144.4, 141.7, 133.7,
133.5, 130.3, 129.6, 129.4, 129.1, 128.2, 128.2, 124.6, 123.8, 120.8, 18.3. HRMS (ESI) m/z calcd for C16H14NO+
[M+H]+ 236.1075, found 236.1076.
3f, 4-chloro-2-phenylquinoline N-oxide, 19.9 mg, yield 78%, white solid.30 1H NMR (400 MHz, CDCl3) δ 8.89 (d,
J = 8.7 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.97 (d, J = 6.9 Hz, 2H), 7.86 (t, J = 7.4 Hz, 1H), 7.76 (t, J = 7.6 Hz,
1H), 7.62 (s, 1H), 7.55 – 7.47 (m, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.0, 142.9, 132.4, 131.4, 130.0,
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129.5 (2C), 129.2, 128.4, 127.1, 125.0, 123.1, 120.8. HRMS (ESI) m/z calcd for C15H11ClNO+ [M+H]+ 256.0529,
found 256.0523.
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3g, 6-methyl-2-phenylquinoline N-oxide, 16.0 mg, yield 68%, white solid.28 1H NMR (400 MHz, CDCl3) δ 8.74
(d, J = 8.8 Hz, 1H), 7.97 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 8.6 Hz, 1H), 7.61 (d, J = 10.4 Hz, 2H), 7.52 (t, J = 7.2
Hz, 2H), 7.46 (t, J = 7.9 Hz, 2H), 2.56 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 144.3, 140.7, 138.6, 133.6,
132.7, 129.7, 129.6, 129.4, 128.2, 126.9, 124.8, 123.3, 120.1, 21.4. HRMS (ESI) m/z calcd for C16H14NO+ [M+H]+
236.1075, found 236.1076.
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3h, 6-methoxy-2-phenylquinoline N-oxide, 17.6 mg, yield 70%, brown solid.22 1H NMR (400 MHz, CDCl3) δ 8.75
(d, J = 9.5 Hz, 1H), 7.94 (d, J = 7.4 Hz, 2H), 7.65 (d, J = 8.7 Hz, 1H), 7.52 – 7.43 (m, 4H), 7.39 (dd, J = 9.5, 2.6
Hz, 1H), 7.11 (d, J = 2.5 Hz, 1H), 3.95 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 159.2, 143.3, 137.7, 133.5,
+
130.9, 129.5, 129.3, 128.2, 124.5, 123.8, 122.6, 121.9, 105.8, 55.7. HRMS (ESI) m/z calcd for C16H14NO2
[M+H]+ 252.1025, found 252.1025.
3i, 6-chloro-2-phenylquinoline N-oxide, 21.5 mg, yield 84%, white solid.28 1H NMR (400 MHz, CDCl3) δ 8.80 (d,
J = 9.3 Hz, 1H), 7.96 (d, J = 7.6 Hz, 2H), 7.85 (s, 1H), 7.70 (d, J = 9.3 Hz, 1H), 7.66 (d, J = 8.7 Hz, 1H), 7.55 –
7.46 (m, 4H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.2, 140.8, 134.6, 133.0, 131.2, 130.3, 129.7, 129.5, 128.4,
126.6, 124.6, 124.0, 122.3. HRMS (ESI) m/z calcd for C15H11ClNO+ [M+H]+ 256.0529, found 256.0527.
3j, 6-bromo-2-phenylquinoline N-oxide, 23.4 mg, yield 78%, brown solid.31 1H NMR (400 MHz, CDCl3) δ 8.72
(d, J = 9.3 Hz, 1H), 8.03 (d, J = 1.9 Hz, 1H), 7.96 (d, J = 7.0 Hz, 2H), 7.84 (dd, J = 9.3, 1.9 Hz, 1H), 7.65 (d, J =
8.7 Hz, 1H), 7.54 – 7.46 (m, 4H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.2, 141.1, 133.8, 133.0, 130.7, 129.9,
129.8, 129.5, 128.3, 124.5, 123.9, 122.8, 122.3. HRMS (ESI) m/z calcd for C15H11BrNO+ [M+H]+ 300.0024,
found 300.0029.
3k, 6-(methoxycarbonyl)-2-phenylquinoline N-oxide, 22.1 mg, yield 79%, brown solid.28 1H NMR (400 MHz,
CDCl3) δ 8.90 (d, J = 9.1 Hz, 1H), 8.61 (s, 1H), 8.35 (d, J = 9.1 Hz, 1H), 7.99 (d, J = 7.4 Hz, 2H), 7.84 (d, J = 8.7
Hz, 1H), 7.59 (d, J = 8.7 Hz, 1H), 7.56 – 7.48 (m, 3H), 4.02 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 165.9,
146.6, 144.1, 133.0, 130.8, 130.1, 130.0, 129.9, 129.5, 129.0, 128.4, 125.8, 124.2, 120.9, 52.7. HRMS (ESI) m/z
calcd for C17H14NO3+ [M+H]+ 280.0974, found 280.0974.
3l, 8-methyl-2-phenylquinoline N-oxide, 15.8 mg, yield 67%, white solid.28 1H NMR (400 MHz, CDCl3) δ 7.86 –
7.84 (m, 2H), 7.66 – 7.63 (m, 2H), 7.53 – 7.49 (m, 2H), 7.46 – 7.41 (m, 3H), 7.38 (d, J = 8.6 Hz, 1H), 3.21 (s, 3H).
13C{1H} NMR (151 MHz, CDCl3) δ 146.3, 142.1, 134.2, 134.2, 133.8, 131.6, 129.4, 129.1, 128.3, 127.9, 126.8,
125.5, 123.1, 25.6. HRMS (ESI) m/z calcd for C16H14NO+ [M+H]+ 236.1075, found 236.1075.
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3m, 2-phenylbenzo[h]quinoline N-oxide, 17.7 mg, yield 65%, brown solid.27 1H NMR (400 MHz, CDCl3) δ 10.92
– 10.88 (m, 1H), 7.98 – 7.94 (m, 1H), 7.90 – 7.87 (m, 3H), 7.81 (d, J = 8.3 Hz, 1H), 7.79 – 7.72 (m, 2H), 7.69 (d, J
= 8.8 Hz, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.57 – 7.53 (m, 2H), 7.51 – 7.47 (m, 1H). 13C{1H} NMR (151 MHz,
CDCl3) δ 148.6, 139.0, 134.5, 134.4, 130.6, 130.4, 129.6, 129.2, 128.9, 128.6 (d, J = 6.5 Hz), 128.3, 128.2, 127.6,
126.6, 125.1 (2C), 123.5. HRMS (ESI) m/z calcd for C19H14NO+ [M+H]+ 272.1075, found 272.1071.
3n, 4,7-dichloro-2-phenylquinoline N-oxide, 24.9 mg, yield 86%, white solid. 1H NMR (400 MHz, CDCl3) δ 8.90
(s, 1H), 8.15 (d, J = 8.9 Hz, 1H), 7.95 (d, J = 7.2 Hz, 2H), 7.69 (d, J = 8.9 Hz, 1H), 7.61 (s, 1H), 7.55 – 7.48 (m,
3H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.8, 143.2, 138.2, 132.0, 130.3 (2C), 129.4, 129.1, 128.5, 126. 6,
125.6, 123.2, 120.4. HRMS (ESI) m/z calcd for C15H10Cl2NO+ [M+H]+ 290.0139, found 290.0138.
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3o, 1-phenylisoquinoline N-oxide, 11.1 mg, yield 50%, brown solid.27 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J =
7.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 7.2 Hz, 1H), 7.61 – 7.45 (m, 8H). 13C{1H} NMR (151 MHz,
CDCl3) δ 146.2, 137.4, 130.9, 130.1, 129.6, 129.4, 129.1, 129.0, 128.8, 128.3, 126.8, 125.7, 123.3. HRMS (ESI)
m/z calcd for C15H12NO+ [M+H]+ 222.0919, found 222.0918.
3p, 2-(4-(trifluoromethyl)phenyl)quinoline N-oxide, white solid, 14.1 mg, yield 49%.31 1H NMR (600 MHz,
CDCl3) δ 8.85 (d, J = 8.7 Hz, 1H), 8.10 (d, J = 7.8 Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.83 – 7.78 (m, 4H), 7.69 (t, J
= 7.4 Hz, 1H), 7.51 (d, J = 8.6 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 143.6, 142.2, 137.0, 131.2 (q, J = 32.7
Hz), 130.9, 130.0, 129.8, 128.9, 128.1, 125.5, 125.3 (q, J = 3.7 Hz), 123.9 (q, J = 272.7 Hz), 122.9, 120.2. 19
NMR (376 MHz, CDCl3) δ -62.86. HRMS (ESI) m/z calcd for C16H11F3NO+ [M+H]+ 290.0793, found 290.0784.
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3q, 2-p-tolylquinoline N-oxide, light yellow solid, 15.2mg, yield 65%.32 1H NMR (600 MHz, CDCl3) δ 8.86 (d, J =
8.8 Hz, 1H), 7.90 (d, J = 7.9 Hz, 2H), 7.85 (d, J = 8.1 Hz, 1H), 7.79 – 7.76 (m, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.63
(t, J = 7.5 Hz, 1H), 7.50 (d, J = 8.7 Hz, 1H), 7.33 (d, J = 7.9 Hz, 2H), 2.43 (s, 3H). 13C{1H} NMR (151 MHz,
CDCl3) δ 145.1, 142.2, 139.7, 130.5, 130.5, 129.4, 129.4, 128.9, 128.2, 127.9, 125.2, 123.2, 120.2, 21.5. HRMS
(ESI) m/z calcd for C16H14NO+ [M+H]+ 236.1075, found 236.1073.
3r, 2-(4-chlorophenyl)quinoline N-oxide, white solid, 13.3 mg, yield 52%.29 1H NMR (600 MHz, CDCl3) δ 8.84
(d, J = 8.8 Hz, 1H), 7.96 (d, J = 8.3 Hz, 2H), 7.88 (d, J = 8.1 Hz, 1H), 7.80 (t, J = 7.8 Hz, 1H), 7.77 (d, J = 8.7 Hz,
1H), 7.66 (t, J = 7.5 Hz, 1H), 7.51 – 7.48 (m, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 143.9, 142.2, 135.5, 131.8,
131.0, 130.7, 129.6, 128.6, 128.5, 128.0, 125.4, 122.9, 120.2. HRMS (ESI) m/z calcd for C15H11ClNO+ [M+H]+
256.0529, found 256.0519.
3s, 2-(4-fluorophenyl)quinoline N-oxide, light yellow solid, 16.7 mg, yield 70%.15 1H NMR (600 MHz, CDCl3) δ
8.85 (d, J = 8.8 Hz, 1H), 8.03 –8.00 (m, 2H), 7.88 (d, J = 8.1 Hz, 1H), 7.81 – 7.79 (m, 1H), 7.76 (d, J = 8.7 Hz,
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1H), 7.67 – 7.64 (m, 1H), 7.50 (d, J = 8.7 Hz, 1H), 7.21 (t, J = 8.7 Hz, 2H). 13C{1H} NMR (151 MHz, CDCl3) δ
163.2 (d, J = 250.7 Hz), 144.0, 142.2, 131.8 (d, J = 8.5 Hz), 130.7, 129.5, 129.4 (d, J = 3.5 Hz), 128.5, 128.0,
125.4, 123.0, 120.2, 115.4 (d, J = 21.9 Hz). 19F NMR (376 MHz, CDCl3) δ -110.53. HRMS (ESI) m/z calcd for
C15H11FNO+ [M+H]+ 240.0825, found 240.0817.
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3t, 2-m-tolylquinoline N-oxide, light yellow solid, 14.6 mg, yield 62%.29 1H NMR (600 MHz, CDCl3) δ 8.86 (d, J
= 8.7 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.83 (s, 1H), 7.79 (t, J = 7.8 Hz, 1H), 7.75 (d, J = 8.6 Hz, 1H), 7.71 (d, J =
7.7 Hz, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.50 (d, J = 8.6 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H),
2.45 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.3, 142.2, 137.9, 133.4, 130.5, 130.3, 130.1, 129.5, 128.3,
128.2, 127.9, 126.6, 125.2, 123.4, 120.3, 21.5. HRMS (ESI) m/z calcd for C16H14NO+ [M+H]+ 236.1075, found
236.1077.
3u, 2-(3-fluorophenyl)quinoline N-oxide, light yellow solid, 12.0 mg, yield 50%.31 1H NMR (600 MHz, CDCl3) δ
8.85 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.82 – 7.77 (m, 3H), 7.72 (d, J = 7.7 Hz, 1H), 7.67 (t, J = 7.5 Hz,
1H), 7.52 – 7.48 (m, 2H), 7.18 (td, J = 8.4, 2.4 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 162.4 (d, J = 246.1
Hz), 143.7, 142.3, 135.3 (d, J = 8.5 Hz), 130.8, 129.9 (d, J = 8.3 Hz), 129.7, 128.7, 128.0, 125.4, 125.3(d, J = 3.0
Hz), 123.0, 120.3, 116.7 (d, J = 23.6 Hz), 116.6 (d, J = 21.1 Hz). 19F NMR (376 MHz, CDCl3) δ -112.66. HRMS
(ESI) m/z calcd for C15H11FNO+ [M+H]+ 240.0825, found 240.0816.
3v, 2-o-tolylquinoline N-oxide, light yellow solid, 11.3 mg, yield 48%.22 1H NMR (600 MHz, CDCl3) δ 8.84 (d, J
= 8.7 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.79 (t, J = 7.5 Hz, 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H),
7.41 – 7.38 (m, 1H), 7.37 – 7.31 (m, 4H), 2.27 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 146.7, 142.1, 137.7,
133.9, 130.4, 130.1, 129.8, 129.3, 129.1, 128.4, 128.0, 125.9, 124.6, 123.8, 120.3, 19.6. HRMS (ESI) m/z calcd for
C16H14NO+ [M+H]+ 236.1075, found 236.1076.
3w, 2-(2-chlorophenyl)quinoline N-oxide, white solid, 12.1 mg, yield 47%.22 1H NMR (600 MHz, CDCl3) δ 8.84
(d, J = 8.7 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.81 – 7.78 (m, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.70 – 7.67 (m, 1H),
7.57 – 7.55 (m, 1H), 7.53 – 7.52 (m, 1H), 7.46 – 7.41 (m, 2H), 7.39 (d, J = 8.6 Hz, 1H). 13C{1H} NMR (151 MHz,
CDCl3) δ 143.9, 142.0, 133.8, 133.2, 131.0, 130.6, 130.5, 130.1, 129.8, 128.8, 128.1, 126.9, 124.6, 123.6, 120.3.
HRMS (ESI) m/z calcd for C15H11ClNO+ [M+H]+ 256.0529, found 256.0522.
5a, 2-phenylpyridine N-oxide, 12.0 mg, white solid, yield 70%.13c 1H NMR (400 MHz, CDCl3) δ 8.32 (dd, J = 6.4,
0.8 Hz, 1H), 7.82 – 7.79 (m, 2H), 7.50 – 7.40 (m, 4H), 7.29 (td, J = 7.8, 1.2 Hz, 1H), 7.23 – 7.19 (m, 1H). 13C{1H}
NMR (151 MHz, CDCl3) δ 149.1, 140.3, 132.5, 129.4, 129.1, 128.1, 127.3, 125.6, 124.4. HRMS (ESI) m/z calcd
for C11H10NO+ [M+H]+ 172.0762, found 172.0764.
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5b, 4-nitro-2-phenylpyridine N-oxide, 9.3 mg, brown solid, yield 43%.12a 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J
= 7.2 Hz, 1H), 8.30 (d, J = 2.8 Hz, 1H), 8.04 (dd, J = 7.1, 2.8 Hz, 1H), 7.82 – 7.80 (m, 2H), 7.54 – 7.53 (m, 3H).
13C{1H} NMR (151 MHz, CDCl3) δ 150.3, 142.0, 141.4, 130.8, 130.6, 129.1, 128.7, 121.6, 118.5. HRMS (ESI)
m/z calcd for C11H9N2O3+ [M+H]+ 217.0613, found 217.0615.
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5c, 4-cyano-2-phenylpyridine N-oxide, 12.2 mg, white solid, yield 62%.33 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J
= 6.8 Hz, 1H), 7.78 – 7.74 (m, 2H), 7.69 (d, J = 2.4 Hz, 1H), 7.52 – 7.50 (m, 3H), 7.45 (dd, J = 6.8, 2.5 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3) δ 150.6, 141.4, 130.6, 130.5, 130.0, 129.1, 128.6, 126.6, 116.0, 107.7. HRMS
(ESI) m/z calcd for C12H9N2O+ [M+H]+ 197.0715, found 197.0722.
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5d, 2-cyano-3-methyl-6-phenylpyridine N-oxide, 10.6 mg, white solid, yield 50%. H NMR (400 MHz, CDCl3) δ
7.80 – 7.78 (m, 2H), 7.52 – 7.48 (m, 4H), 7.21 (d, J = 8.2 Hz, 1H), 2.57 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3)
δ 147.5, 141.0, 130.9, 130.2, 129.1, 128.9, 128.4, 127.4, 126.0, 111.5, 19.0. HRMS (ESI) m/z calcd for
C13H11N2O+ [M+H]+ 211.0871, found 211.0875.
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5e, 2-chloro-3-methyl-6-phenylpyridine N-oxide, 9.5 mg, white solid, yield 43%. H NMR (400 MHz, CDCl3) δ
7.80 – 7.77 (m, 2H), 7.49 – 7.42 (m, 3H), 7.26 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 2.47 (s, 3H). 13C{1H}
NMR (151 MHz, CDCl3) δ 148.3, 143.3, 134.4, 132.7, 129.6, 129.3, 128.2, 126.4, 123.7, 20.2. HRMS (ESI) m/z
calcd for C12H11ClNO+ [M+H]+ 220.0529, found 220.0527.
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7.80 – 7.78 (m, 2H), 7.49 – 7.48 (m, 3H), 7.43 (d, J = 2.6 Hz, 2H), 2.42 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3)
δ 149.5, 135.9, 130.9, 130.9, 130.4, 130.2, 129.2, 128.4, 126.3, 112.2, 20.2. HRMS (ESI) m/z calcd for
C13H11N2O+ [M+H]+ 211.0871, found 211.0872.
5g, 2,3,5-trimethyl-6-phenylpyridine N-oxide, 8.6 mg, white solid, yield 40%. 1H NMR (400 MHz, CDCl3) δ 7.49
– 7.45 (m, 2H), 7.42 – 7.38 (m, 1H), 7.31 – 7.29 (m, 2H), 7.00 (s, 1H), 2.49 (s, 3H), 2.34 (s, 3H), 2.04 (s, 3H).
13C{1H} NMR (151 MHz, CDCl3) δ 147.2, 146.0, 133.3, 132.6, 131.3, 129.2, 129.0, 128.6, 128.4, 19.5, 19.4, 14.1.
HRMS (ESI) m/z calcd for C14H16NO+ [M+H]+ 214.1232, found 214.1232.
5h, 3-bromo-6-methyl-2-phenylpyridine N-oxide, 12.1 mg, white solid, yield 46%. 1H NMR (400 MHz, CDCl3) δ
7.53 – 7.44 (m, 4H), 7.39 (d, J = 7.6 Hz, 2H), 7.15 (d, J = 8.4 Hz, 1H), 2.49 (s, 3H). 13C{1H} NMR (151 MHz,
CDCl3) δ 150.1, 148.9, 133.1, 129.3, 129.2, 128.7, 128.5, 125.0, 119.2, 18.2. HRMS (ESI) m/z calcd for
C12H11BrNO+ [M+H]+ 264.0024, found 264.0024.
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5i, 6-bromo-3-methyl-2-phenylpyridine N-oxide, 13.2 mg, white solid, yield 50%. H NMR (400 MHz, CDCl3) δ
7.56 (d, J = 8.4 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 7.44 (t, J = 7.0 Hz, 1H), 7.32 (d, J = 7.7 Hz, 2H), 7.03 (d, J = 8.4
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Hz, 1H), 2.09 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 151.1, 134.6, 132.4, 130.9, 129.1, 129.0, 128.7, 128.5,
127.1, 19.7. HRMS (ESI) m/z calcd for C12H11BrNO+ [M+H]+ 264.0024, found 264.0026.
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5j, 5-chloro-2-phenylpyridine N-oxide, white solid, 8.0 mg, yield 39%. White solid.33 1H NMR (600 MHz, CDCl3)
δ 8.38 (s, 1H), 7.78 (d, J = 7.1 Hz, 2H), 7.50 – 7.46 (m, 3H), 7.37 (d, J = 8.5 Hz, 1H), 7.31 (d, J = 8.5 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3) δ 148.0, 139.65, 131.59, 131.56, 129.91, 129.17, 128.41, 127.06, 125.92.
HRMS (ESI) m/z calcd for C11H9ClNO+ [M+H]+ 206.0373, found 206.0377.
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5j', 3-chloro-2-phenylpyridine N-oxide, white solid, 4.9 mg, yield 24%. White solid. 1H NMR (600 MHz, CDCl3)
δ 8.29 (d, J = 6.5 Hz, 1H), 7.53 (t, J = 7.3 Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.45 (d, J = 7.5 Hz, 2H), 7.40 (d, J =
8.3 Hz, 1H), 7.19 (t, J = 7.4 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 149.2, 138.8, 133.5, 130.3, 129.7, 129.5,
128.6, 126.6, 124.0. HRMS (ESI) m/z calcd for C11H9ClNO+ [M+H]+ 206.0373, found 206.0366.
5k, 2,6-diphenylpyridine N-oxide, 7.4 mg, white solid, yield 30%.27 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 7.5
Hz, 4H), 7.48 – 7.41 (m, 8H), 7.33 (t, J = 8.0 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 150.0, 133.3, 129.6,
129.3, 128.1, 126.1, 125.0. HRMS (ESI) m/z calcd for C17H14NO+ [M+H]+ 248.1075, found 248.1072.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
1H and 13C NMR spectra of starting materials and products
X-ray crystal structure data for 3a
AUTHOR INFORMATION
Corresponding Authors
*E-mail: songjinzhulab@hit.edu.cn
*E-mail:gaoguol@hit.edu.cn
ORCID
Junzheng Zhang: 0000-0002-1989-7714
Guo-Lin Gao: 0000-0001-5177-9139
Author Contributions
§ D. L. and C. L. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful for financial support from China NSFC (No. 21302029, 21372055, 21472030 and 21672047),
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the Fundamental Research Funds for the Central Universities (HIT.NSRIF.2014064) and the Heilongjiang
Postdoctoral Science Foundation (No.LBH-Z14104).
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