DOI: 10.1002/ajoc.

201700267 Full Paper

Synthetic Methods

Regioselective Metal-Free C2@H Arylation of Quinoline N-Oxides

with Aryldiazonium Salts/Anilines under Ambient Conditions
Rakesh Kumar,[a, b] Rakesh Kumar,[a] Ankit Kumar Dhiman,[a] and Upendra Sharma*[a, b]
Dedicated to our mentor Dr. Bikram Singh on the occasion of his retirement

Abstract: Herein, a base-promoted direct C2@H arylation of
quinoline N-oxides with aryldiazonium salts under metal-free
conditions is reported. This reaction avoids the need for an
oxidant, metal catalyst, or inert atmosphere and proceeds
through a highly regioselective C@H bond functionalization
to provide a series of C2-arylated quinoline N-oxides. Abun-
dantly available amines (anilines and heteroaryl amines) can
also be employed as arylating agents through an in situ di-
azotization process, thereby affording a library of diverse 2-
arylquinoline N-oxides in moderate-to-good yields. The syn-
thesized 2-arylated quinoline N-oxides were further convert-
ed into C8-substituted quinolines to demonstrate the applic-
ability of this catalytic approach. A radical pathway is pro-
posed for the C2 arylation, based on a preliminary mechanis-
tic study.

Introduction Quinolines represent a privileged class of heterocycles[7] and,

Bi(hetero)aryl compounds are ubiquitous motifs in natural
products,[1] pharmaceuticals,[2] agrochemicals,[2] and functional
organic materials.[3] The most-common strategy for the con-
struction of such scaffolds is transition-metal-catalyzed cross-
coupling reactions.[4] Although highly efficient and widely used
in industrial applications, this approach suffers from certain
limitations, such as the necessary prefunctionalization of the
(hetero)aryl partner and the use of stoichiometric amounts of
toxic metals, which produce waste byproducts that are difficult
to treat.[4] Recently, the direct functionalization of C@H bonds
has emerged as an atom-economical alternative for generating
such building blocks without the requisite activated precur-
sors.[5] However, traditional C@H activations typically involve
transition-metal catalysis, so alternative routes that enhance
the cost effectiveness and decrease the toxicity of this process
are highly desirable.[6] Thus, metal-free methods for the synthe-
sis of bi(hetero)aryls systems offer exciting possibilities for ad-
dressing these economic and environmental issues.
amongst the various quinoline scaffolds, C2-functionalized qui-
nolines are of particular interest for applications in pharma-
ceuticals and functional materials (Figure 1).[8] For example,
DDQ107498 (A) has recently been shown to exhibit excellent
antimalarial activity and is currently undergoing clinical trials
for approval as a potential antimalarial drug.[9] 6-Arylinde-
no[1,2c]quinoline derivatives (B) have been found to be potent
against the growth of human cancer cell lines.[10a, b] Compound
C is known to be a selective COX-2 inhibitor,[10c] and com-
pound D is used as phosphorescent dopant and a poly(N-vinyl-
carbazole)/polybutadine (PVK/PBD) blend in polymer light-
emitting diode (PLED) devices.[10d]
Owing to the importance of C2-arylated quinolines, various
methods have been developed for their synthesis, including
SuzukiMiyaura cross-coupling reactions of quinoline halides[11]

[a] R. Kumar, Dr. R. Kumar, A. K. Dhiman, Dr. U. Sharma

Department of Natural Product Chemistry and Process Development
(NPCPD)
CSIRInstitute of Himalayan Bioresource Technology, Palampur
Himachal Pradesh 176061 (India)
E-mail: upendra@ihbt.res.in
upendraihbt@gmail.com
[b] R. Kumar, Dr. U. Sharma
Academy of Scientific and Innovative Research
Anusandhan Bhawan, 2 Rafi Marg
New Delhi 110001 (India)
Supporting information and the ORCID identification number(s) for the au-
thor(s) of this article can be found under https://doi.org/10.1002/
ajoc.201700267. Figure 1. Examples of important 2-arylquinoline scaffolds.

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and the metal-catalyzed C@H functionalization of quinoline N-
oxide.[1214]
A metal-free synthesis of 2-arylquinolines was reported that
proceeded through the deoxygenative coupling of quinoline
N-oxides with arylboronic acids.[15] Although this method was
environmentally benign, its narrow substrate scope for the ar-
ylboronic acid and the need for an inert atmosphere and high
temperatures needed further improvement. Heteroaryl N-
oxides are also known to undergo metal-free, radical-mediated
reactions for functionalization at the C2 position.[16] When the
work reported herein was in progress, a KMnO4-mediated
cross-coupling reaction between quinoline N-oxides and aro-
matic hydrazines was reported for the C2 arylation of quinoline
Full Paper
Results and Discussion
Our preliminary studies focused on the optimization of the re-
action conditions for the C2 arylation of quinoline N-oxides
with commercially available aryl diazonium tetrafluoroborates.
First, we reacted quinoline N-oxide (1 a) with 4-methoxyphenyl
diazonium tetrafluoroborate (2 a) in various solvents at room
temperature in the presence of different bases. The reaction
with NaOAc in water as a green solvent only provided trace
amounts of C2-arylated product 3 a (Table 1, entry 1). The addi-
Table 1. Optimization of the reaction conditions.[a]

N-oxides.[17] This reaction proceeded through a radical pathway

in which an aryl radical that was generated in situ from an aryl
hydrazine reacted with the quinoline N-oxide to furnish the
substituted quinoline. However, this reaction was not applica-
ble to quinoline N-oxides that were substituted with strongly
electron-withdrawing substituents, such as nitro groups.[17]
Aryldiazonium salts are versatile intermediates that can gen-
Entry 1 a 2a Base Solvent Yield [%][b]
erate aryl radicals through photoinduced electron transfer,[18] [mmol] [mmol]
base-mediated reactions,[19] or other mechanisms.[20] In addition 3a 4a
to metal-catalyzed reactions,[18, 20] metal-free transformations 1 0.1 0.2 NaOAc water trace trace
with aryl diazonium salts have also been reported.[17, 18bd] In 2 0.1 0.2 NaOAc water/MeOH 24 6
a recent report, aryl diazonium salts that were generated (1:1)
3 0.1 0.2 NaOAc DMSO 26 7
in situ from anilines were utilized for the C2 arylation of quino-
4 0.1 0.2 NaOAc MeCN 36 5
line N-oxides under metal-free conditions.[21] However, this re- 5[c] 0.1 0.2 NaOAc MeCN 36 6
action required an inert atmosphere, exhibited longer reaction 6 0.1 0.15 NaOAc MeCN 21 5
times, and had limited substrate scope, thereby providing low- 7 0.2 0.1 NaOAc MeCN 43 trace
8[d] 0.3 0.1 NaOAc MeCN 71 (65)[e] n.d.
to-moderate yields of the products (Scheme 1 b).
9[d] 0.3 0.1 NaOMe MeCN 70 n.d.
Herein, we report the metal- and oxidant-free C2 arylation of 10 0.5 0.1 NaOAc MeCN 48 n.d.
quinoline N-oxide with diazonium salts under mild reaction 11[f] 0.3 0.1 NaOAc MeCN 60 n.d.
conditions (Scheme 1 c). This operationally simple method 12[f] 0.3 0.1 NaOMe MeCN 72 (66)[e] n.d.
13[f] 0.2 0.1 NaOMe MeCN 52 trace
avoids the need for an inert atmosphere and demonstrates
14[f] 0.3 0.1 MeCN n.d. n.d.
a wide substrate scope with short reaction times.
[a] Reaction conditions: compound 1 a (0.10.3 mmol), compound 2 a
(0.10.2 mmol), base (1.52.0 equiv), solvent (1 mL), RT, 12 h; [b] based on
1
H NMR analysis of the crude reaction mixture, by using tetrachloroethane
(TCE) as an internal standard; [c] base (1.5 equiv); [d] 6 h; [e] yield of the
isolated product is given in parentheses; [f] 70 8C for 10 min. n.d. = not
detected.

tion of 50 % (v/v) MeOH in water was found to be beneficial,

Scheme 1. Approaches for the C2 arylation of quinoline N-oxides. Ts = 4-tol-
uenesulfonyl.
thereby leading to the formation of compound 3 a in 24 %
yield (Table 1, entry 2). In addition to compound 3 a, a double-
arylation side product (4 a) was also obtained in 6 % yield. The
yields of compounds 3 a and 4 a remained unchanged on
changing the solvent to DMSO (Table 1, entry 3). Performing
the reaction in pure MeCN resulted in a slight increase in the
yield of compound 3 a to 36 % (Table 1, entry 4), whilst de-
creasing the quantity of the base or compound 2 a was not
beneficial (Table 1, entries 5 and 6). Gratifyingly, an increase in
the yield was observed with complete selectivity for C2 aryla-
tion when the reaction was performed with an excess of com-
pound 1 a at room temperature for 6 h (Table 1, entries 710).
Furthermore, increasing the temperature to 70 8C provided
similar yields within a shorter reaction time (10 min; Table 1,

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entries 11 and 12). Reactions with 3 equivalents of compound
1 a at 70 8C in the presence of NaOMe provided compound 3 a
in 66 % yield, without the formation of an observable amount
of compound 4 a (Table 1, entry 12). Therefore, we selected
NaOAc and NaOMe as suitable bases for this reaction at room
temperature and at 70 8C, respectively. No product formation
was observed without a base, thus indicating the importance
of a base for the completion of the reaction (Table 1, entry 14).
With the optimized reaction conditions in hand, we investi-
gated the substrate scope of this reaction with various quino-
line N-oxides and aryldiazonium tetrafluoroborates (Scheme 2).
Scheme 2. Substrate scope with quinoline N-oxides and aryldiazonium tetra-
fluoroborates. Reaction conditions: a) compound 1 (1.5 mmol), compound 2
(0.5 mmol), NaOMe (1.0 mmol), MeCN (5 mL), 70 8C, 10 min; b) compound
1 (1.5 mmol), compound 2 (0.5 mmol), NaOAc (1.0 mmol), MeCN (5 mL), RT,
6 h. NaOAc = sodium acetate.
Thus, the reactions of compound 1 a with commercially avail-
able phenyldiazonium salts that contained electron-donating
OMe and electron-withdrawing NO2 para substituents provided
compounds 3 a and 3 d in 66 % and 67 % yield, respectively.
Halide-substituted phenyl diazonium salt also reacted efficient-
ly with compound 1 a to furnish the C2-arylated products
(3 b, c) in good yields. Furthermore, substituted quinoline N-
oxides were also reacted with aryldiazonium tetrafluorobo-
rates. Reactions of 6-methoxy- and 6-methyl quino-
line N-oxides with p-nitro- and p-methoxy phenylte-
trafluoroborates provided the corresponding prod-
ucts (3 e, f) in good yields, whilst sterically demand-
ing 3-substituted quinoline N-oxides provided the
corresponding products in moderate yields (3 g, h).
Polyaromatic phenanthridine N-oxide also reacted
successfully to regioselectively provide the C2-arylat-
ed product (3 i). Gratifyingly, this method was also Scheme 3. C2 arylation of quinoline N-oxide with aniline.
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applicable to the selective C2 arylation of 4-nitropyridine N-
oxide, albeit in low yield (3 j). Comparatively lower yields of
the products were observed at room temperature for all of
these substrates (3 ag, i).
After studying commercially available aryl diazonium salts,
we turned our attention towards utilizing anilines as an aryl
source. Because a large variety of aryl amines are commercially
available and can be readily converted into diazonium salts,
a one-pot procedure would constitute an attractive strategy
for accessing 2-aryl quinoline N-oxides. Thus, aniline (5 a) was
first reacted with tert-butyl nitrite (TBNO; 2.0 equiv) and HCl
(1.5 equiv) to generate phenyldiazonium chloride, which was
then reacted with 1.03.0 molar equivalents of compound 1 a
in MeCN in the same pot in the presence of different bases
(for details of the optimization study, see the Supporting Infor-
mation, Table S2). The highest yield of compound 3 k was ob-
served with compound 5 a (0.1 mmol), compound 1 a
(3.0 equiv), and NaOAc (2.0 equiv) at room temperature after
30 min (Scheme 3). Furthermore, compound 3 k has been un-
ambiguously characterized by single-crystal X-ray diffraction.
Next, a wide range of arylamines was subjected to diazotiza-
tion/arylation reactions with compound 1 a (Scheme 4). Ani-
lines that contained different functional groups at different po-
sitions reacted well to furnish 2-aryl quinoline N-oxides (3 k
3 w). Halide substituents at the ortho, meta, or para positions
of the anilines did not affect the outcome of the reaction and
provided the desired products in good yields, except for com-
pound 3 l, for which a low yield of the product was obtained
(3 l, m, qu). The tolerance towards halide substituents provid-
ed further opportunities for functionalization by using cou-
pling reactions. Anilines that were substituted with important
functional groups, such as SCF3, SO3CH3, and CF3 groups, at dif-
ferent position reacted well under the reaction conditions
(3 o, p, v). Next, various substituted quinoline N-oxides were
subjected to arylation with aniline under our reaction condi-
tions. Both electron-withdrawing and electron-donating
groups, as well as further-modifiable halide substituents, at dif-
ferent positions of the quinoline ring were well-tolerated and
afforded a library of 2-phenyl quinoline N-oxides (3 x3 zi) in
5575 % yields. Yun et al. failed to achieve the C2 arylation of
nitro-substituted quinoline N-oxide with phenylhydrazine,[17]
whereas these substrates reacted successfully under our reac-
tion conditions to provide the corresponding products in good
yields (3 z and 3 zb). The mildness of the reaction conditions
was further exhibited by its tolerance to sensitive functional
groups, such as ester and hydroxy groups, at the C6 and
C8 positions of quinoline N-oxide (3 zg and 3 zi).
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Scheme 4. Substrate scope for the quinoline N-oxides and anilines. Reaction
conditions: 1) compound 5 (0.5 mmol), HCl (2.0 equiv), tBuONO (1.5 equiv),
MeCN (2.5 mL), 0 8C to RT, 20 min; 2) compound 1 (1.5 mmol), NaOAc
(2.0 equiv), MeCN (2.5 mL), RT, 30 min.
These methods were also applicable for the heteroarylation
of quinoline N-oxides (Scheme 5). Thus, two heteroaryl diazoni-
Scheme 6. Further elaboration of the 2-arylated quinoline N-oxide scaffold.
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Scheme 5. Substrate scope with heteroaryl amines. Reaction conditions:
1) compound 5 (0.5 mmol), HBF4 (2.0 equiv), isoamyl nitrite (1.5 equiv),
MeCN (2.5 mL), 0 8C, 5 min; 2) compound 1 (1.5 mmol), NaOAc (2.0 equiv),
MeCN (2.5 mL), 70 8C, 10 min.
um tetrafluoroborates that were generated in situ from the
corresponding amines (see the Supporting Information) also
reacted successfully with compound 1 a to produce the de-
sired cross-coupled products, albeit in low yields. 2-Aminoben-
zothiazole and 2-bromopyridin-4-amine provided the isolated
compounds 3 zj and 3 zk in 42 % and 46 % yield, respectably.
Notably, the retained N-oxide functionality in the products
also provided an opportunity for the further functionalization
of the quinoline scaffold.
Synthetic Applications
These synthesized 2-phenyl quinoline N-oxides could be fur-
ther elaborated into a range of multisubstituted quinolines
(Scheme 6). Deoxy product 6 was obtained in 50 % yield by re-
acting compound 3 k with CuI and Zn dust under previously
reported conditions.[22] The C8 iodination,[23] alkenylation,[24]
and alkylation[25] of 2-phenyl quinoline N-oxide (3 k) were also
1046 T 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

performed with a rhodium catalyst according to previously re-
ported conditions by Chang and co-workers and ourselves.
Mechanistic Investigation
To understand the mechanism of the C2 arylation of quinoline
N-oxides with aryldiazonium salts, we performed several con-
trol experiments (Scheme 7). No product was formed when 2-
Scheme 7. Control experiments.
methyl quinoline was reacted with compound 2 a (Scheme 7 a),
whilst an intermolecular competition experiment between
compound 1 a and deuterated analogue [D7]-1 a revealed a ki-
netic isotopic effect, kH/kD = 1.1 (Scheme 7 b), thus in-
dicating that the cleavage of a C@H bond in quino-
line N-oxide might not be involved in the rate-deter-
mining step. When the reaction of compound 1 a
with 4-nitrophenyldiazonium tetrafluoroborate was
performed in the presence of radical scavenger
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), the de-
sired product was observed in only 25 % yield, thus
indicating the involvement of a radical pathway
(Scheme 7 c). LCMS and GCMS analysis of this reac-
tion mixture revealed the presence of a molecular
ion peak at m/z = 262, which corresponded to a 4-ni-
trophenyl@TEMPO adduct (E; Scheme 7 c).[26] Further- Scheme 8. Proposed reaction mechanism.
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more, a competition experiment between 4-methyl- and 4-ni-
troquinoline N-oxides with diazonium salt 2 a provided the C2-
arylated products, compounds 3 z (Me) and 3 za (NO2), in
a 1:1.7 ratio (Scheme 7 d). On the other hand, a competition
experiment between 4-methyl- and 4-nitrodiazonium salts with
compound 1 a provided compounds 3 a and 3 d in a 1:2.5
ratio. These experiments indicated that quinoline N-oxides and
diazonium salts with electron-withdrawing groups favored the
C-2 arylation reactions.
Based on these preliminary mechanistic experi-
ments and previous literature reports, a plausible re-
action mechanism for the C2 arylation of quinoline
N-oxide is proposed in Scheme 8.[17, 19, 21] The reaction
may proceed through the initial formation of acetox-
yazo or methoxyazo intermediate B from the diazo-
nium salt and an acetate or methoxy ion.[17] Decom-
position of intermediate B would lead to the genera-
tion of nucleophilic phenyl radical C,[27] which would
attack at the C2 position of quinoline N-oxide, there-
by leading to the formation of intermediate D.
Single-electron transfer (SET) would then provide in-
termediate E and an aryl radical. Finally, proton ab-
straction by an anion (OAc@ , OMe@ , or X@) would
result in the formation of the product.
Conclusion
In conclusion, a simple, cost-effective, and environ-
mentally friendly method for the direct C2 arylation
of quinoline N-oxides with aryldiazonium salts under
oxidant- and metal-free conditions has been devel-
oped. Abundantly available anilines were also suc-
cessfully employed in the two-step, one-pot C2 ary-
lation of quinoline N-oxides. This regioselective
cross-coupling reaction was promoted by the base
under mild reaction conditions and provided the de-
sired products in moderate-to-good yields with
broad substrate scope. The formation of TEMPO@
aryl adducts suggested the involvement of a free-
radical pathway. The N-oxide functionality was ame-
nable to further modification of the heteroaryl
moiety. The main advantages of this method include short re-
action times, ambient reaction conditions (room temperature
in air), and broad substrate scope.
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Experimental Section
General
High-grade solvents were used in all of the reactions. Column chro-
matography was performed on silica gel (230400 mesh) and
monitored by using TLC on silica gel 60F254 plates. 1H and 13C NMR
spectra were recorded on 300 and 600 MHz instruments. Chemical
shifts (d) are reported in parts per million (ppm), downfield of an
internal standard. Mass spectra were recorded on an electrospray
ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometer.
IR spectra were recorded on a Shimadzu IR Prestige-21 FTIR spec-
trometer with a ZnSe single-reflection ATR accessory. Melting
points were recorded on an Electrothermal 9100 apparatus.
General Procedure for the C2 Arylation of Quinoline N-Oxides
with Aryldiazonium Tetrafluoroborates
Method (a): Aryldiazonium tetrafluoroborate salt (0.5 mmol), quino-
line N-oxide (3 equiv), NaOAc (2 equiv), and MeCN (5 mL) were
added to an oven-dried screw-capped vial that was charged with
a magnetic stirrer bar and the mixture was stirred for 6 h at RT.
After completion of the reaction (by TLC), the mixture was extract-
ed with EtOAc and washed with brine. The organic layer was dried
over anhydrous Na2SO4 and evaporated under reduced pressure.
The residue was purified by column chromatography on silica gel
(n-hexane/EtOAc).
Method (b): Quinoline N-oxide (1.5 mmol), NaOMe (1 mmol), and
MeCN (2.5 mL) were added to an oven-dried screw-capped vial
that was charged with a magnetic stirrer bar. Then, a solution of
the aryldiazonium tetrafluoroborate salt (0.5 mmol) in MeCN
(2.5 mL) was slowly added at 70 8C and the mixture was stirred for
10 min. After completion of the reaction (by TLC), the mixture was
extracted with EtOAc and washed with brine. The organic layer
was dried over anhydrous Na2SO4 and evaporated under reduced
pressure. The residue was purified by column chromatography on
silica gel (n-hexane/EtOAc).
2-(4-Methoxyphenyl)quinoline 1-Oxide (3 a)[17]
1
Yellow solid; 66 % yield; m.p. 110 8C; H NMR (600 MHz, CDCl3): d =
8.85 (d, J = 9.0 Hz, 1 H; ArH), 8.02 (d, J = 8.4 Hz, 2 H; ArH), 7.84 (d,
J = 7.8 Hz, 1 H; ArH), 7.797.77 (m, 1 H; ArH), 7.73 (d, J = 8.4 Hz, 1 H;
ArH), 7.647.61 (m, 1 H; ArH), 7.51 (d, J = 8.4 Hz, 1 H; ArH), 7.03 (d,
J = 9.0 Hz, 2 H; ArH), 3.89 ppm (s, 3 H; OCH3); 13C NMR (150 MHz,
CDCl3): d = 160.7, 145.0, 142.5, 131.4, 130.7, 129.4, 128.3, 128.0,
125.8, 125.5, 123.2, 120.4, 113.9, 55.5 ppm; FTIR: n = 3078, 2953,
2920, 2831, 1598, 1560, 1500, 1450, 1440, 1344, 1292, 1247, 1176,
1026, 808, 748, 603 cm@1; HRMS (ESI): m/z calcd for C16H14NO2 :
252.1019 [M+ +H]+; found: 252.1008.
2-(4-Bromophenyl)quinoline 1-Oxide (3 b)[17]
Brown crystals; 67 % yield; m.p. 167169 8C; 1H NMR (600 MHz,
CDCl3): d = 8.82 (d, J = 8.4 Hz, 1 H; ArH), 7.887.85 (m, 3 H; ArH),
7.807.78 (m, 1 H; ArH), 7.75 (d, J = 8.4 Hz, 1 H; ArH), 7.667.63 (m,
3 H; ArH), 7.47 ppm (d, J = 8.4 Hz, 1 H; ArH); 13C NMR (150 MHz,
CDCl3): d = 144.0, 142.4, 132.4, 131.6, 131.31, 130.9, 129.8, 128.7,
128.2, 125.5, 124.0, 123.0, 120.3 ppm; FTIR: n = 3039, 3059, 2920,
2820, 2850, 1587, 1558, 1483, 1398, 1336, 1323, 1242, 1219, 1132,
1097, 804, 736, 567, 482 cm@1; HRMS (ESI): m/z calcd for
C15H11BrNO: 300.0019 [M+ +H]+; found: 300.0011.
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2-(3,5-Dichlorophenyl)quinoline 1-Oxide (3 c)
Brown solid; 68 % yield; m.p. 148150 8C; 1H NMR (600 MHz,
CDCl3): d = 8.81 (d, J = 9.0 Hz, 1 H; ArH), 7.897.88 (m, 3 H; ArH),
7.827.80 (m, 1 H; ArH), 7.75 (d, J = 8.4 Hz, 1 H; ArH), 7.697.67 (m,
1 H; ArH), 7.467.45 ppm (m, 2 H; ArH); 13C NMR (150 MHz, CDCl3):
d = 142.6, 142.4, 136.2, 135.1, 131.1, 130.0, 129.7, 129.2, 128.2,
128.2, 125.6, 122.8, 120.4 ppm; FTIR: n = 3072, 1672, 1566, 1427,
1411, 1332, 1234, 1120, 1068, 854, 800, 758, 665, 555 cm@1; HRMS
(ESI): m/z calcd for C15H10Cl2NO2 : 290.0134 [M+ +H]+; found:
290.0130.
2-(4-Nitrophenyl)quinoline 1-Oxide (3 d)
Brown solid; 67 % yield; m.p. 210212 8C; 1H NMR (600 MHz,
CDCl3): d = 8.84 (d, J = 9.0 Hz, 1 H; ArH), 8.38 (d, J = 9.0 Hz, 2 H;
ArH), 8.18 (d, J = 8.4 Hz, 2 H; ArH), 7.92 (d, J = 7.8 Hz, 1 H; ArH),
7.857.82 (m, 2 H; ArH), 7.71 (t, J = 7.2 Hz, 1 H; ArH), 7.52 ppm (d,
J = 8.4 Hz, 1 H; ArH); 13C NMR (150 MHz, CDCl3): d = 148.2, 143.0,
142.5, 139.8, 131.3, 130.8, 130.2, 129.4, 128.3, 125.8, 123.6, 122.8,
120.4 ppm; FTIR: n = 3076, 2920, 2848, 1598, 1562, 1512, 1489,
1342, 1292, 1103, 842, 808, 754, 565 cm@1; HRMS (ESI): m/z calcd
+H]+; found: 267.0754.
for C15H11N2O3 : 267.0764 [M+
6-Methoxy-2-(4-nitrophenyl)quinoline 1-Oxide (3 e)
Yellow solid; 60 % yield; m.p. 232240 8C; 1H NMR (600 MHz,
CDCl3): d = 8.71 (d, J = 9.6 Hz, 1 H; ArH), 8.32 (d, J = 8.4 Hz, 2 H;
ArH), 8.14 (d, J = 8.4 Hz, 2 H; ArH), 7.70 (d, J = 9.0 Hz, 1 H; ArH), 7.47
(d, J = 8.4 Hz, 1 H; ArH), 7.42 (dd, J = 9.6, 1.8 Hz, 1 H; ArH), 7.13 (s,
1 H; ArH), 3.96 ppm (s, 3 H; OCH3); 13C NMR (150 MHz, CDCl3): d =
160.0, 147.9, 141.2, 139.91, 137.9, 131.7, 130.8, 125.0, 123.5, 123.4,
123.3, 122.1, 106.1, 55.9 ppm; FTIR: n = 3107, 3078, 2922, 2850,
1718, 1618, 1595, 1508, 1467, 1213, 1107, 850, 748, 692 cm@1;
HRMS (ESI): m/z calcd for C16H13N2O4 : 297.0870 [M+ +H]+; found:
297.0860.
2-(4-Methoxyphenyl)-6-methylquinoline 1-Oxide (3 f)
Yellow solid; 70 % yield; m.p. 131133 8C; 1H NMR (300 MHz,
CDCl3): d = 8.71 (d, J = 9.3 Hz, 1 H; ArH), 7.99 (d, J = 9.0 Hz, 2 H;
ArH), 7.647.56 (m, 3 H; ArH), 7.45 (d, J = 8.7 Hz, 1 H; ArH), 7.01 (d,
J = 9.0 Hz, 2 H; ArH), 3.86 (s, 3 H; OCH3), 2.53 ppm (s, 3 H; CH3);
13
C NMR (75 MHz, CDCl3): d = 160.5, 144.2, 140.9, 138.4, 132.7,
131.3, 129.5, 127.0, 125.9, 125.0, 123.2, 120.1, 113.8, 55.5, 21.4 ppm;
FTIR: n = 2997, 2916, 2839, 1597, 1575, 1566, 1516, 1492, 1436,
1330, 1292, 1180, 1028, 848, 817, 804, 628, 557 cm@1; HRMS (ESI):
m/z calcd for C17H16NO2 : 266.1176 [M+ +H]+; found: 266.1166.
3-(1,3-Dioxolan-2-yl)-2-(4-methoxyphenyl)quinoline 1-Oxide
(3 g)
Brown crystals; 42 % yield; m.p. 160162 8C; 1H NMR (600 MHz,
CDCl3): d = 8.77 (d, J = 9.0 Hz, 1 H; ArH), 8.07 (s, 1 H; ArH), 7.91 (d,
J = 8.4 Hz, 1 H; ArH), 7.797.76 (m, 1 H; ArH), 7.667.64 (m, 1 H;
ArH), 7.507.47 (m, 2 H; ArH), 7.077.05 (m, 2 H; ArH), 5.56 (s, 1 H;
CH), 4.154.13 (m, 2 H), 3.953.93 (m, 2 H), 3.88 ppm (s, 3 H; OCH3);
13
C NMR (150 MHz, CDCl3): d = 160.3, 146.2, 142.0, 132.0, 131.6,
131.1, 129.0, 128.7, 128.7, 123.6, 123.4, 120.5, 114.1, 100.7, 65.7,
55.5 ppm; FTIR: n = 3057, 2966, 2885, 1610, 1570, 1492, 1450, 1388,
1303, 1240, 1215, 1184, 1016, 977, 756, 831, 516 cm@1; HRMS (ESI):
m/z calcd for C19H18NO4 : 324.1230 [M+ +H]+; found: 324.1219.
T 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

3-Acetyl-2-(4-methoxyphenyl)quinoline 1-Oxide (3 h)
Light-brown solid; 52 % yield; m.p. 166168 8C; 1H NMR (600 MHz,
CDCl3): d = 8.80 (d, J = 8.4 Hz, 1 H; ArH), 7.94 (d, J = 7.8 Hz, 1 H;
ArH), 7.88 (s, 1 H), 7.867.84 (t, J = 7.8 Hz, 1 H; ArH), 7.707.68 (m,
1 H; ArH), 7.57 (d, J = 8.4 Hz, 2 H; ArH), 7.06 (d, J = 8.4 Hz, 2 H; ArH),
3.89 (s, 3 H; OCH3), 1.97 ppm (s, 3 H; COCH3); 13C NMR (150 MHz,
CDCl3): d = 200.6, 161.0, 143.1, 142.7, 137.2, 132.1, 132.0, 129.3,
129.2, 128.5, 124.5, 124.1, 120.5, 114.4, 55.6, 30.1 ppm; FTIR: n =
2968, 2908, 2837, 1680, 1517, 1487, 1463, 1421, 1319, 1240, 1180,
1024, 783, 759, 551 cm@1; HRMS (ESI): m/z calcd for C18H16NO3 :
294.1125 [M+ +H]+; found: 294.1114.
6-(4-Methoxyphenyl)phenanthridine 5-Oxide (3 i)
White solid; 57 % yield; m.p. 238240 8C; 1H NMR (600 MHz, CDCl3):
d = 8.99 (dd, J = 8.4, 1.2 Hz, 1 H; ArH), 8.628.61 (m, 1 H; ArH), 8.56
(d, J = 8.4 Hz, 1 H; ArH), 7.857.79 (m, 2 H; ArH), 7.727.69 (m, 1 H;
ArH), 7.58 (d, J = 7.2 Hz, 1 H; ArH), 7.557.52 (m, 3 H; ArH), 7.17
7.10 (m, 2 H; ArH), 3.92 ppm (s, 3 H; OCH3); 13C NMR (150 MHz,
CDCl3): d = 160.3, 144.3, 139.8, 131.7, 129.8, 129.1, 128.8, 128.5,
127.8, 127.3, 126.9, 126.2, 124.1, 122.6, 122.1, 121.4, 114.4,
55.6 ppm; FTIR: n = 3072, 2970, 2910, 1656, 1608, 1519, 1510, 1485,
1458, 1392, 1300, 1249, 1215, 1026, 817, 759, 719, 563 cm@1; HRMS
(ESI): m/z calcd for C20H16NO2 : 302.1176 [M+ +H]+; found: 302.1160.
6-(4-Methoxyphenyl)-4-nitro-2,3-dihydropyridine 1-Oxide (3 j)
Yellow crystals; 40 % yield; m.p. 144146 8C; 1H NMR (600 MHz,
CDCl3): d = 8.35 (d, J = 7.2 Hz, 1 H; ArH), 8.28 (d, J = 3.0 Hz, 1 H;
ArH), 7.98 (dd, J = 7.2, 3.0 Hz, 1 H; ArH), 7.84 (d, J = 9.0 Hz, 2 H;
ArH), 7.04 (d, J = 8.4 Hz, 2 H; ArH), 3.89 ppm (s, 3 H; OCH3); 13C NMR
(150 MHz, CDCl3): d = 161.6, 150.1, 142.3, 141.5, 130.9, 122.9, 121.1,
117.9, 114.2, 55.6 ppm; FTIR: n = 3111, 3076, 2960, 2937, 2841,
1604, 1504, 1460, 1406, 1332, 1298, 1271, 1236, 1184, 1093, 823,
655, 528, 460 cm@1; HRMS (ESI): m/z calcd for C12H13N2O4 : 249.0870
[M++H]+; found: 249.0702.
General Procedure for the C2 Arylation of Quinoline N-Oxides
with Anilines
Aniline (0.5 mmol), HCl 11 m aqueous solution (2 equiv), and MeCN
(2.5 mL) were added to an oven-dried screw-capped vial that was
charged with a magnetic stirrer bar. tert-Butyl nitrite (1.5 equiv)
was slowly added at 0 8C and the mixture was stirred for 20 min at
RT. Then, the as-formed aryldiazonium chloride salt was slowly
added to a solution of the quinoline N-oxide (1.5 mmol) and
NaOAc (1 mmol) in MeCN (2.5 mL) at RT and the mixture was
stirred for 30 min. After completion of the reaction (by TLC), the
mixture was extracted with EtOAc and washed with brine. The or-
ganic layer was dried over anhydrous Na2SO4 and evaporated
under reduced pressure. The residue was purified by column chro-
matography on silica gel (n-hexane/EtOAc).
2-Phenylquinoline 1-Oxide (3 k)[17]
1
Light-brown crystals; 77 % yield; m.p. 135138 8C; H NMR
(600 MHz, CDCl3): d = 8.86 (d, J = 9.0 Hz, 1 H; ArH), 7.97 (d, J =
7.2 Hz, 2 H; ArH), 7.86 (d, J = 7.8 Hz, 1 H; ArH), 7.807.77 (m, 1 H;
ArH), 7.75 (d, J = 9.0 Hz, 1 H; ArH), 7.657.62 (m, 1 H; ArH), 7.53
7.50 (m, 3 H; ArH), 7.487.45 ppm (m, 1 H; ArH); 13C NMR (150 MHz,
CDCl3): d = 145.1, 142.4, 133.6, 130.7, 129.7, 129.6, 128.5, 128.4,
128.1, 125.3, 123.4, 120.4 ppm; FTIR: n = 3047, 1598, 1560, 1490,
1450, 1350, 1325, 1309, 1244, 815, 765, 700, 607, 570 cm@1; HRMS
(ESI): m/z calcd for C15H12NO: 222.0913 [M+ +H]+; found: 222.0905.
Asian J. Org. Chem. 2017, 6, 1043 1053 www.AsianJOC.org
Full Paper
2-(4-Fluorophenyl)quinoline 1-Oxide (3 l)[17]
Light-yellow solid; 33 % yield; m.p. 155157 8C; 1H NMR (600 MHz,
CDCl3): d = 8.84 (d, J = 9.0 Hz, 1 H; ArH), 8.028.00 (m, 2 H; ArH),
7.86 (d, J = 8.4 Hz, 1 H; ArH), 7.807.78 (m, 1 H; ArH), 7.75 (d, J =
8.4 Hz, 1 H; ArH), 7.667.63 (m, 1 H; ArH), 7.49 (d, J = 9.0 Hz, 1 H;
ArH), 7.227.19 ppm (t, J = 8.7 Hz, 2 H; ArH); 13C NMR (150 MHz,
CDCl3): d = 164.4 (d, J(C,F) = 249.0 Hz), 144.16, 142.45, 131.9 (d,
J(C,F) = 9.0 Hz), 130.82, 129.70, 129.6 (d, J(C,F) = 4.5 Hz), 128.64,
128.12, 125.42, 123.15, 120.37, 115.52 ppm (d, J(C,F) = 22.5 Hz);
FTIR: n = 3064, 2962, 1759, 1597, 1562, 1517, 1500, 1452, 1325,
1300, 1222, 1203, 1095, 802, 736, 605, 513 cm@1. HRMS (ESI): m/z
calcd for C15H11FNO: 240.0819 [M+ +H]+; found: 240.0812.
2-(4-Iodophenyl)quinoline 1-Oxide (3 m)
Yellow solid; 65 % yield; m.p. 178179 8C; 1H NMR (600 MHz,
CDCl3): d = 8.83 (d, J = 8.4 Hz, 1 H; ArH), 7.887.86 (m, 3 H; ArH),
7.817.78 (m, 1 H; ArH), 7.777.74 (m, 3 H; ArH), 7.687.64 (m, 1 H;
ArH), 7.48 ppm (d, J = 8.4 Hz, 1 H; ArH); 13C NMR (150 MHz, CDCl3):
d = 144.2, 142.5, 137.6, 133.0, 131.4, 130.9, 129.8, 128.8, 128.2,
125.5, 123.0, 120.4, 96.1 ppm; FTIR: n = 3034, 2920, 2850, 1583,
1562, 1479, 1450, 1394, 1336, 1247, 1002, 804, 744, 570, 480 cm@1;
HRMS (ESI): m/z calcd for C15H11INO: 347.9880 [M+ +H]+; found:
347.9863.
2-(4-(tert-Butyl)phenyl)quinoline 1-Oxide (3 n)[21]
Light-yellow crystals; 70 % yield; m.p. 159160 8C; 1H NMR
(600 MHz, CDCl3): d = 8.86 (d, J = 9.0 Hz, 1 H; ArH), 7.95 (d, J =
8.4 Hz, 2 H; ArH), 7.83 (d, J = 8.4 Hz, 1 H; ArH), 7.777.75 (m, 1 H;
ArH), 7.72 (d, J = 9.0 Hz, 1 H; ArH), 7.627.60 (m, 1 H; ArH), 7.54 (d,
J = 8.4 Hz, 2 H; ArH), 7.51 (d, J = 9.0 Hz, 1 H; ArH), 1.37 ppm (s, 9 H;
C(CH3)3); 13C NMR (150 MHz, CDCl3): d = 152.9, 145.1, 142.4, 130.6,
130.6, 129.5, 129.4, 128.3, 128.0, 125.4, 125.2, 123.4, 120.4, 35.0,
31.3 ppm; FTIR: n = 3057, 2960, 2866, 1598, 1575, 1500, 1452, 1338,
1307, 1265, 1205, 1120, 1020, 889, 806, 758, 569 cm@1; HRMS (ESI):
m/z calcd for C19H20NO: 278.1539 [M+ +H]+; found: 278.1515.
2-(4-((Trifluoromethyl)thio)phenyl)quinoline 1-Oxide (3 o)
Yellow solid; 63 % yield; m.p. 104108 8C; 1H NMR (600 MHz,
CDCl3): d = 8.84 (d, J = 9.0 Hz, 1 H), 8.05 (d, J = 8.4 Hz, 2 H), 7.89 (d,
J = 8.4 Hz, 1 H), 7.827.78 (m, 4 H), 7.697.66 (m, 1 H), 7.51 ppm (d,
J = 9.0 Hz, 1 H); 13C NMR (150 MHz, CDCl3): d = 143.8, 142.5, 136.1,
136.0, 131.0, 130.8, 130.7, 130.0, 129.0, 128.2, 125.9, 125.5, 123.0,
120.4 ppm; FTIR: n = 3070, 2926, 1726, 1564, 1556, 1489, 1450,
1338, 1114, 1038, 1014, 819, 754, 605, 570 cm@1. HRMS (ESI): m/z
calcd for C16H11F3NOS: 322.0508 [M+ +H]+; found: 322.0497.
2-(4-(Methylsulfonyl)phenyl)quinoline 1-Oxide (3 p)
Light-yellow solid; 74 % yield; m.p. 236 8C; 1H NMR (600 MHz,
CDCl3): d = 8.83 (d, J = 9.0 Hz, 1 H; ArH), 8.18 (d, J = 8.4 Hz, 2 H;
ArH), 8.10 (d, J = 8.4 Hz, 2 H; ArH), 7.91 (d, J = 8.4 Hz, 1 H; ArH),
7.847.82 (m, 2 H), 7.727.69 (m, 1 H; ArH), 7.51 (d, J = 8.4 Hz, 1 H;
ArH), 3.11 ppm (s, 3 H; CH3); 13C NMR (150 MHz, CDCl3): d = 143.3,
142.4, 141.1, 139.0, 131.2, 130.8, 130.1, 129.3, 128.3, 127.6, 125.8,
122.9, 120.4, 44.7 ppm; FTIR: n = 3041, 2993, 2914, 1726, 1562,
1342, 1301, 1139, 1083, 815, 777, 615, 555 cm@1; HRMS (ESI): m/z
calcd for C16H14NO3S: 300.0689 [M+ +H]+; found: 300.0671.
1049 T 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

2-(3-Chlorophenyl)quinoline 1-Oxide (3 q)
Light-yellow solid; 76 % yield; m.p. 141144 8C; 1H NMR (600 MHz,
CDCl3): d = 8.82 (d, J = 9.0 Hz, 1 H; ArH), 8.00 (s, 1 H; ArH), 7.85 (d,
J = 8.4 Hz, 1 H; ArH), 7.837.81 (m, 1 H; ArH), 7.797.76 (m, 1 H;
ArH), 7.74 (d, J = 9.0 Hz, 1 H; ArH), 7.657.62 (m, 1 H; ArH), 7.45 (d,
J = 8.4 Hz, 1 H; ArH), 7.437.42 ppm (m, 2 H; ArH); 13C NMR
(150 MHz, CDCl3): d = 143.7, 142.3, 135.2, 134.3, 130.8, 129.8, 129.7,
129.7, 129.6, 128.8, 128.1, 127.8, 125.4, 123.0, 120.3 ppm; FTIR: n =
3072, 1593, 1571, 1562, 1479, 1448, 1336, 1242, 1205, 1064, 817,
754, 694, 570 cm@1; HRMS (ESI): m/z calcd for C15H11ClNO: 256.0524
[M++H]+; found: 256.0516.
2-(3-Bromophenyl)quinoline 1-Oxide (3 r)
Light-yellow solid; 70 % yield; m.p. 140141 8C; 1H NMR (600 MHz,
CDCl3): d = 8.83 (d, J = 9.0 Hz, 1 H; ArH), 8.15 (t, J = 1.8 Hz, 1 H; ArH),
7.89 (d, J = 7.8 Hz, 1 H; ArH), 7.86 (d, J = 8.4 Hz, 1 H; ArH), 7.807.77
(m, 1 H; ArH), 7.75 (d, J = 8.4 Hz, 1 H; ArH), 7.667.63 (m, 1 H; ArH),
7.597.58 (m, 1 H; ArH), 7.46 (d, J = 9.0 Hz, 1 H; ArH), 7.38 ppm (t,
J = 7.8 Hz, 1 H; ArH); 13C NMR (150 MHz, CDCl3): d = 143.6, 142.4,
135.5, 132.6, 132.6, 130.9, 129.9, 129.8, 128.8, 128.3, 128.2, 125.5,
123.1, 122.4, 120.4 ppm; FTIR: n = 3068, 3030, 1512, 1566, 1475,
1478, 1336, 1205, 1062, 817, 740, 669, 569, 430 cm@1; HRMS (ESI):
m/z calcd for C15H11BrNO: 300.0019 [M+ +H]+; found: 300.0009.
2-(2-Fluorophenyl)quinoline 1-Oxide (3 s)[17]
Brown solid; 59 % yield; m.p. 132136 8C; 1H NMR (600 MHz,
CDCl3): d = 8.84 (d, J = 8.4 Hz, 1 H; ArH), 7.89 (d, J = 7.8 Hz, 1 H;
ArH), 7.79 (dd, J = 7.2, 1.2 Hz, 1 H; ArH), 7.76 (d, J = 8.4 Hz, 1 H;
ArH), 7.70 (td, J = 7.2, 1.8 Hz, 1 H; ArH), 7.677.65 (m, 1 H; ArH),
7.507.46 (m, 1 H; ArH), 7.45 (d, J = 8.4 Hz, 1 H; ArH), 7.307.28 (m,
1 H; ArH), 7.23 ppm (t, J = 9.0, 1 H; ArH); 13C NMR (150 MHz, CDCl3):
d = 161.3 (d, J(C,F) = 249.0 Hz), 142.3, 141.5, 131.6 (d, J(C,F) = 9.0 Hz)
131.4 (d, J(C,F) = 1.5 Hz), 130.7, 130.1, 128.9, 128.2, 125.0, 124.3 (d,
J(C,F) = 3.0 Hz), 123.9 (d, J(C,F) = 1.5 Hz) 121.8 (d, J(C,F) = 13.5 Hz),
120.4, 116.2 ppm (d, J(C,F) = 22.5 Hz); FTIR: n = 3072, 3041, 2962,
1726, 1614, 1579, 1560, 1487, 1456, 1342, 1253, 1217, 1091, 808,
675, 611, 572 cm@1; HRMS (ESI): m/z calcd for C15H11FNO: 240.0819
[M++H]+; found: 240.0811.
2-(2-Bromophenyl)quinoline 1-Oxide (3 t)[17]
1
Sticky orange liquid, 55 %; H NMR (600 MHz, CDCl3): d = 8.84 (d,
J = 8.4 Hz, 1 H; ArH), 7.92 (d, J = 7.8 Hz, 1 H; ArH), 7.80 (dd, J = 14.4,
8.4 Hz, 2 H; ArH), 7.74 (d, J = 8.4 Hz, 1 H; ArH), 7.707.68 (m, 1 H;
ArH), 7.507.46 (m, 2 H; ArH), 7.397.35 ppm (m, 2 H; ArH); 13C NMR
(150 MHz, CDCl3): d = 145.4, 142.2, 135.4, 133.1, 131.2, 130.8, 130.7,
130.3, 128.9, 128.3, 127.7, 125.0, 123.7, 123.4, 120.5 ppm; FTIR: n =
3059, 2927, 1730, 1598, 1560, 1514, 1475, 1340, 1325, 1242, 1193,
1072, 1022, 893, 810, 756, 736, 611, 569, 493 cm@1; HRMS (ESI): m/z
calcd for C15H11BrNO: 300.0019 [M+ +H]+; found: 300.0008.
2-(3-Chloro-4-methylphenyl)quinoline 1-Oxide (3 u)[17]
Brown crystals; 66 % yield; m.p. 144 8C; 1H NMR (600 MHz, CDCl3):
d = 8.83 (d, J = 9.0 Hz, 1 H; ArH), 8.03 (d, J = 1.8 Hz, 1 H; ArH), 7.86
(d, J = 8.4 Hz, 1 H; ArH), 7.807.77 (m, 2 H; ArH), 7.74 (d, J = 8.4 Hz,
1 H; ArH), 7.657.63 (m, 1 H; ArH), 7.48 (d, J = 8.4 Hz, 1 H; ArH), 7.37
(d, J = 8.4 Hz, 1 H; ArH), 2.45 ppm (s, 3 H; CH3); 13C NMR (150 MHz,
CDCl3): d = 143.8, 142.4, 137.9, 134.5, 132.6, 130.9, 130.8, 130.1,
129.7, 128.7, 128.1, 127.9, 125.4, 123.1, 120.4, 20.2 ppm; FTIR: n =
3057, 2924, 2850, 1689, 1687, 1598, 1560, 1490, 1346, 1305, 1280,
Asian J. Org. Chem. 2017, 6, 1043 1053 www.AsianJOC.org 1050
Full Paper
1259, 1199, 1143, 1026, 825, 769, 553, 487 cm@1; HRMS (ESI): m/z
+H]+; found: 270.0666.
calcd for C16H13ClNO: 270.0680 [M+
2-(3,5-Bis(trifluoromethyl)phenyl)quinoline 1-Oxide (3 v)
Yellow solid; 55 % yield; m.p. 108110 8C; 1H NMR (600 MHz, CDCl3):
d = 8.84 (d, J = 9.0 Hz, 1 H; ArH), 8.48 (s, 2 H; ArH), 7.98 (s, 1 H; ArH),
7.93 (d, J = 7.8 Hz, 1 H; ArH), 7.877.83 (m, 2 H; ArH), 7.737.71 (m,
1 H; ArH), 7.54 ppm (d, J = 9.0 Hz, 1 H; ArH); 13C NMR (150 MHz,
CDCl3): d = 142.3, 142.2, 135.5, 131.92 (q, J(C,F) = 33.0 Hz), 131.4,
130.2, 130.1, 129.5, 128.4, 126.2, 124.2, 123.35 (q, J(C,F) = 3.0 Hz),
122.6, 122.4, 120.3 ppm; FTIR: n = 3116, 3059, 2926, 1691, 1564,
1473, 1382, 1346, 1273, 1168, 1118, 1070, 898, 812, 678 cm@1; HRMS
(ESI): m/z calcd for C17H10F6NO: 358.0661 [M+ +H]+; found: 358.0649.
2-(Benzo[d][1,3]dioxol-5-yl)quinoline 1-Oxide (3 w)
Red solid; 38 % yield; m.p. 194197 8C; 1H NMR (600 MHz, CDCl3):
d = 8.84 (d, J = 9.0 Hz, 1 H; ArH), 7.85 (d, J = 8.4 Hz, 1 H; ArH), 7.79
7.67 (m, 1 H; ArH), 7.72 (d, J = 8.4 Hz, 1 H; ArH), 7.67 (d, J = 1.2 Hz,
1 H; ArH), 7.647.62 (m, 1 H; ArH), 7.48 (d, J = 9.0 Hz, 1 H; ArH),
7.417.40 (m, 1 H; ArH), 6.95 (d, J = 8.4 Hz, 1 H; ArH), 6.04 ppm (s,
2 H; CH2); 13C NMR (150 MHz, CDCl3): d = 148.8, 147.6, 144.8, 142.5,
130.7, 129.5, 128.4, 128.1, 127.3, 125.3, 124.4, 123.4, 120.4, 110.2,
108.4, 101.6 ppm; FTIR: n = 3070, 2908, 2789, 1598, 1562, 1500,
1483, 1454, 1355, 1311, 1253, 1228, 1207, 1116, 1031, 812, 773, 565,
441 cm@1; HRMS (ESI): m/z calcd for C16H12NO3 : 266.0812 [M+ +H]+;
found: 266.0801.
3-Methyl-2-phenylquinoline 1-Oxide (3 x)
Light-yellow crystals; 55 % yield; m.p. 140143 8C; 1H NMR
(600 MHz, CDCl3): d = 8.73 (d, J = 8.4 Hz, 1 H; ArH), 7.79 (d, J =
8.4 Hz, 1 H; ArH), 7.727.69 (m, 1 H; ArH), 7.63 (s, 1 H; ArH), 7.62
7.60 (m, 1 H; ArH), 7.567.54 (m, 2 H; ArH), 7.497.47 (m, 1 H; ArH),
7.437.41 (m, 2 H; ArH), 2.24 ppm (s, 3 H; CH3); 13C NMR (150 MHz,
CDCl3): d = 147.4, 140.6, 133.3, 131.5, 129.9, 129.6, 129.3, 129.0,
129.0, 128.6, 127.3, 125.8, 120.4, 20.7 ppm; FTIR: n = 3057, 2958,
2852, 1726, 1568, 1485, 1444, 1305, 1209, 1089, 758, 698, 570 cm@1;
HRMS (ESI): m/z calcd for C16H14NO: 236.1070 [M+ +H]+; found:
236.1054.
4-Methyl-2-phenylquinoline 1-Oxide (3 y)
Red crystals; 67 % yield; m.p. 105107 8C; 1H NMR (600 MHz,
CDCl3): d = 8.92 (d, J = 9.0 Hz, 1 H; ArH), 7.997.96 (m, 3 H), 7.81
7.79 (m, 1 H; ArH), 7.697.67 (m, 1 H; ArH), 7.537.50 (m, 2 H; ArH),
7.487.45 (m, 1 H; ArH), 7.35 (s, 1 H; ArH), 2.69 ppm (s, 3 H; CH3);
13
C NMR (150 MHz, CDCl3): d = 144.6, 141.9, 139.1, 133.7, 130.4,
129.8, 129.6, 129.3, 128.4, 128.3, 124.7, 123.9, 121.0, 18.4 ppm;
FTIR: n = 3057, 2962, 2926, 1722, 1600, 1560, 1496, 1448, 1382,
1336, 1145, 1132, 765, 729, 694, 551, 472 cm@1; HRMS (ESI): m/z
calcd for C16H14NO: 236.1070 [M+ +H]+; found: 236.1060.
4-Nitro-2-phenylquinoline 1-Oxide (3 z)[28]
Yellow solid; 75 % yield; m.p. 128130 8C; 1H NMR (600 MHz,
CDCl3): d = 8.878.85 (m, 1 H; ArH), 8.838.82 (m, 1 H; ArH), 8.44 (s,
1 H; ArH), 7.967.95 (m, 2 H; ArH), 7.907.84 (m, 2 H; ArH), 7.58
7.52 ppm (m, 3 H; ArH); 13C NMR (150 MHz, CDCl3): d = 144.2, 143.9,
139.7, 131.7, 131.7, 131.4, 130.7, 129.5, 128.8, 124.7, 121.5, 121.2,
120.9 ppm; FTIR: n = 3078, 2920, 1581, 1556, 1519, 1502, 1490,
1438, 1294, 1145, 997, 738, 686, 557 cm@1; HRMS (ESI): m/z calcd
+H]+; found: 267.0754.
for C15H11N2O3 : 267.0764 [M+
T 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

4-Chloro-2-phenyl-7-(trifluoromethyl)quinoline 1-Oxide (3 za)
1
Brown solid; 70 % yield; m.p. 7780 8C; H NMR (600 MHz, CDCl3):
d = 9.20 (s, 1 H; ArH), 8.33 (d, J = 8.4 Hz, 1 H; ArH), 7.977.96 (m,
2 H; ArH), 7.927.90 (m, 1 H; ArH), 7.72 (s, 1 H; ArH), 7.557.50 ppm
(m, 3 H; ArH); 13C NMR (150 MHz, CDCl3): d = 146.0, 142.7, 133.2 (q,
J(C,F) = 33.0 Hz), 132.7, 131.9, 130.5, 129.5, 128.9, 128.8, 128.7,
126.7, 125.2, 125.2, 119.3 ppm (q, J(C,F) = 4.5 Hz). FTIR: n = 3064,
2918, 2850, 1625, 1589, 1554, 1494, 1390, 1313, 1300, 1220, 1124,
1072, 900, 881, 740, 690, 659, 630, 432 cm@1; HRMS (ESI): m/z calcd
for C16H10ClF3NO: 324.0398 [M+ +H]+; found: 324.0377.
5-Nitro-2-phenylquinoline 1-Oxide (3 zb)
Yellow solid; 75 % yield; m.p. 222223 8C; 1H NMR (600 MHz,
CDCl3): d = 9.25 (d, J = 8.4 Hz, 1 H; ArH), 8.51 (d, J = 9.0 Hz, 1 H;
ArH), 8.43 (d, J = 7.8 Hz, 1 H; ArH), 7.99 (d, J = 7.2 Hz, 2 H; ArH),
7.887.85 (m, 1 H; ArH), 7.74 (d, J = 9.0 Hz, 1 H; ArH), 7.577.51 ppm
(m, 3 H; ArH);13C NMR (150 MHz, CDCl3): d = 146.1, 145.9, 143.5,
132.4, 130.4, 129.6, 128.7, 127.1, 126.5, 126.3, 123.2, 120.3 ppm;
FTIR: n = 3095, 3041, 1620, 1552, 1519, 1492, 1435, 1336, 1301,
1251, 819, 763, 686, 642, 565 cm@1; HRMS (ESI): m/z calcd for
C15H11N2O3 : 267.0764 [M++H]+; found: 267.0755.
6-Methyl-2-phenylquinoline 1-Oxide (3 zc)
Yellow solid; 66 % yield; m.p. 129130 8C; 1H NMR (600 MHz,
CDCl3): d = 8.74 (d, J = 9.0 Hz, 1 H; ArH), 7.987.96 (m, 2 H; ArH),
7.67 (d, J = 8.4 Hz, 1 H; ArH), 7.63 (s, 1 H; ArH), 7.627. 60 (m, 1 H;
ArH), 7.537.51 (m, 2 H; ArH), 7.487.46 (m, 2 H; ArH), 2.56 ppm (s,
3 H; CH3); 13C NMR (150 MHz, CDCl3): d = 144.5, 140.9, 138.8, 133.7,
132.8, 129.9, 129.7, 129.5, 128.4, 127.0, 124.9, 123.4, 120.2,
21.5 ppm. FTIR: n = 3039, 2918, 2854, 1726, 1658, 1566, 1487, 1444,
1348, 1305, 1269, 1195, 881, 823, 773, 694, 553, 514, 486 cm@1.
HRMS (ESI): m/z calcd for C16H14NO: 236.1070 [M+ +H]+; found:
236.1066.
6-Isopropyl-2-phenylquinoline 1-Oxide (3 zd)
1
Black solid; 71 % yield; m.p. 7882 8C; H NMR (600 MHz, CDCl3):
d = 8.77 (d, J = 9.0 Hz, 1 H; ArH), 7.96 (d, J = 7.8 Hz, 2 H; ArH), 7.71
(d, J = 8.4 Hz, 1 H; ArH), 7.69 (dd, J = 9.0, 1.8 Hz, 1 H; ArH), 7.65 (s,
1 H; ArH). 7.537.46 (m, 4 H; ArH), 3.153.10 (m, 1 H; CH(CH3)2), 1.37
(s, 3 H; CH3), 1.36 ppm (s, 3 H; CH3); 13C NMR (150 MHz, CDCl3): d =
149.5, 144.5, 141.1, 133.8, 130.6, 129.9, 129.7, 129.5, 128.4, 125.3,
124.3, 123.4, 120.4, 34.1, 23.9 ppm; FTIR: n = 2954, 2924, 2850,
1691, 1598, 1568, 1489, 1460, 1446, 1348, 1307, 1249, 750, 696,
688, 565 cm@1; HRMS (ESI): m/z calcd for C18H18NO: 264.1383
[M++H]+; found: 264.1366.
6-Fluoro-2-phenylquinoline 1-Oxide (3 ze)
Brown solid; 74 % yield; m.p. 148150 8C; 1H NMR (600 MHz,
CDCl3): d = 8.84 (dd, J = 9.6, 4.8 Hz, 1 H; ArH), 7.92 (d, J = 7.2 Hz, 2 H;
ArH), 7.64 (d, J = 8.4 Hz, 1 H; ArH), 7.50- 7.48 (m, 4 H; ArH), 7.46
7.43 ppm (m, 2 H; ArH); 13C NMR (150 MHz, CDCl3): d = 161.7 (d,
J(C,F) = 249.0 Hz), 144.6, 139.3, 133.2, 130.7 (d, J(C,F) = 9.0 Hz),
129.7, 129.5, 128.4, 124.6, 124.5 (d, J(C,F) = 4.5 Hz), 123.4 (d, J(C,F) =
9.0 Hz), 120.2 (d, J(C,F) = 25.5 Hz), 111.5 ppm (d, J(C,F) = 22.5 Hz);
FTIR: n = 3057, 2924, 2850, 1689, 1687, 1598, 1560, 1490, 1346,
1305, 1282, 1259, 1199, 1143, 1026, 825, 769, 553, 487 cm@1; HRMS
(ESI): m/z calcd for C15H11FNO: 240.0819 [M+ +H]+; found: 240.0812.
Asian J. Org. Chem. 2017, 6, 1043 1053 www.AsianJOC.org 1051
Full Paper
6-Chloro-2-phenylquinoline 1-Oxide (3 zf)
Brown solid; 72 % yield; m.p. 141143 8C; 1H NMR (600 MHz,
CDCl3): d = 8.79 (d, J = 9.6 Hz, 1 H; ArH), 7.94 (d, J = 7.2 Hz, 2 H;
ArH), 7.84 (s, 1 H; ArH), 7.69 (d, J = 9.0 Hz, 1 H; ArH), 7.65 (d, J =
8.4 Hz, 1 H; ArH), 7.537.50 (m, 3 H; ArH), 7.47 ppm (t, J = 7.2 Hz,
1 H; ArH); 13C NMR (150 MHz, CDCl3): d = 145.4, 140.9, 134.8, 133.1,
131.4, 130.4, 129.9, 129.6, 128.5, 126.8, 124.7, 124.3, 122.4 ppm;
FTIR: n = 3061, 2920, 2850, 1678, 1591, 1487, 1365, 1274, 1072, 825,
758, 694, 528, 511 cm@1; HRMS (ESI): m/z calcd for C15H11ClNO:
256.0524 [M+ +H]+; found: 256.0516.
6-(Methoxycarbonyl)-2-phenylquinoline 1-Oxide (3 zg)
Yellow needle-like crystals; 72 % yield; m.p. 141145 8C; 1H NMR
(600 MHz, CDCl3): d = 8.89 (d, J = 9.0 Hz, 1 H; ArH), 8.61 (d, J =
1.2 Hz, 1 H; ArH), 8.368.34 (m, 1 H; ArH), 7.997.97 (m, 2 H; ArH),
7.83 (d, J = 9.0 Hz, 1 H; ArH), 7.58 (d, J = 9.0 Hz, 1 H; ArH), 7.547.52
(m, 2 H; ArH), 7.49 (t, J = 7.2 Hz, 1 H; ArH), 4.01 ppm (s, 3 H;
COOCH3); 13C NMR (150 MHz, CDCl3): d = 166.1, 146.8, 144.2, 133.1,
130.9, 130.2, 130.1, 129.7, 129.1, 128.5, 126.0, 124.4, 121.0, 120.0,
52.8 ppm; FTIR: n = 3290, 3053, 2951, 1716, 1660, 1622, 1598, 1487,
1435, 1348, 1282, 1230, 1215, 1180, 1099, 813, 765, 752, 696,
497 cm@1; HRMS (ESI): m/z calcd for C17H14NO3 : 280.0968 [M+ +H]+;
found: 280.0955.
8-Methyl-2-phenylquinoline 1-Oxide (3 zh)
Brown solid; 58 % yield; m.p. 97101 8C; 1H NMR (600 MHz, CDCl3):
d = 7.867.84 (m, 2 H; ArH), 7.657.63 (m, 2 H; ArH), 7.527.49 (m,
2 H; ArH), 7.467.41 (m, 3 H; ArH), 7.38 (d, J = 8.4 Hz, 1 H; ArH),
3.21 ppm (s, 3 H; CH3); 13C NMR (150 MHz, CDCl3): d = 146.5, 142.3,
134.3, 134.3, 133.9, 131.8, 129.6, 129.3, 128.4, 128.0, 126.9, 125.6,
123.3, 25.7 ppm; FTIR: n = 3080, 2962, 2924, 1658, 1564, 1489,
1438, 1411, 1336, 1303, 1255, 1219, 1043, 976, 827, 758, 696,
516 cm@1; HRMS (ESI): m/z calcd for C16H14NO: 236.1070 [M+ +H]+;
found: 236.1055.
8-Hydroxy-2-phenylquinoline 1-Oxide (3 zi)
Brown solid; 60 % yield; m.p. 98100 8C; 1H NMR (600 MHz, CDCl3):
d = 7.877.85 (m, 2 H; ArH), 7.797.76 (m, 1 H; ArH), 7.547.44 (m,
4 H; ArH), 7.387.36 (m, 1 H; ArH), 7.217.19 (m, 1 H; ArH), 7.07
7.05 ppm (m, 1 H; ArH); 13C NMR (150 MHz, CDCl3): d = 154.6, 144.2,
132.2, 131.5, 130.4, 130.1, 129.6, 129.4, 128.5, 123.0, 116.7,
115.4 ppm; FTIR: n = 2922, 2852, 1600, 1566, 1462, 1446, 1336,
1292, 1153, 1051, 825, 750, 696, 663, 482 cm@1; HRMS (ESI): m/z
+H]+; found: 238.0864.
calcd for C15H12NO2 : 238.0863 [M+
General Procedure for the Two-Step C2 Arylation of Quinoline
N-Oxides with Heteroaryl Anilines through Aryldiazonium Tet-
rafluoroborates
Aniline (0.5 mmol), HBF4 (2.0 equiv), and MeCN (2.5 mL) were
added to an oven-dried screw-capped vial that was charged with
a magnetic stirrer bar. Isoamyl nitrite (1.2 equiv) was slowly added
at 0 8C and the mixture was stirred for 5 min. Then, the as-formed
aryldiazonium tetrafluoroborate was slowly added to a solution of
the quinoline N-oxide (1.5 mmol) and NaOAc (2 equiv) in MeCN
(2.5 mL) at 70 8C and the mixture was stirred for a further 10 min.
After completion of the reaction (by TLC), the mixture was extract-
ed with EtOAc and washed with brine. The organic layer was dried
over anhydrous Na2SO4 and evaporated under reduced pressure.
T 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

The residue was purified by column chromatography on silica gel
(n-hexane/EtOAc).
2-(2-Bromopyridin-4-yl)quinoline 1-Oxide (3 zj)
1 Ackermann, Acc. Chem. Res. 2014, 47, 281 295; c) W. Liu, L. Ackermann,
Orange solid; 46 % yield; m.p. 176178 8C; H NMR (600 MHz,
CDCl3): d = 8.81 (d, J = 9.0 Hz, 1 H; ArH), 8.54(d, J = 4.8 Hz, 1 H; ArH),
8.13 (d, J = 1.2 Hz, 1 H; ArH), 7.91 (d, J = 7.8 Hz, 1 H; ArH), 7.89 (dd,
J = 4.8, 1.8 Hz, 1 H; ArH), 7.85- 7.82 (m, 1 H; ArH), 7.81 (d, J = 9.0 Hz,
1 H; ArH), 7.737.70 (m, 1 H; ArH), 7.50 ppm (d, J = 9.0 Hz, 1 H; ArH);
13
C NMR (150 MHz, CDCl3): d = 150.4, 143.7, 142.7, 142.5, 141.1,
131.3, 130.3, 129.6, 128.4, 128.1, 125.7, 122.8, 122.3, 120.4 ppm;
FTIR: n = 3059, 3022, 1936, 1722, 1581, 1562, 1533, 1442, 1427,
1381, 1330, 1246, 1205, 817, 740, 669, 569, 430 cm@1; HRMS (ESI):
m/z calcd for C14H10BrN2O: 300.9971 [M+ +H]+; found: 300.9960.
2-(Benzo[d]thiazol-2-yl)quinoline 1-Oxide (3 zk)
1
Yellow solid; 44 % yield; m.p. 128131 8C; H NMR (600 MHz,
CDCl3): d = 8.86 (d, J = 9.0 Hz, 1 H; ArH), 8.77 (d, J = 9.0 Hz, 1 H;
ArH), 8.16 (d, J = 8.4 Hz, 1 H; ArH), 8.07 (d, J = 8.4 Hz, 1 H; ArH), 7.90
(d, J = 8.4 Hz, 1 H; ArH), 7.86 (d, J = 9.0 Hz, 1 H; ArH), 7.847.81 (m,
1 H; ArH), 7.707.68 (m, 1 H; ArH), 7.597.56 (m, 1 H; ArH), 7.51
7.48 ppm (m, 1 H; ArH); 13C NMR (150 MHz, CDCl3): d = 157.3, 152.2,
141.4, 136.6, 131.0, 129.9, 129.6, 128.4, 126.8, 126.2, 125.9, 123.5,
122.1, 120.9, 120.1 ppm; FTIR: n = 3454, 3377, 3244, 3061, 2960,
1660, 1598, 1568, 1552, 1359, 827, 756, 727 cm@1; HRMS (ESI): m/z
calcd for C16H11N2OS: 279.0587 [M+ +H]+; found: 279.0568.
CCDC 1538310 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
Acknowledgements
The authors thank the Director of the CSIR-IHBT, SERB, India
(EMR/2014/001023, YSS/2015/001893; CSIR-IHBT communica-
tion no.: 4136) and the UGC, New Delhi for their support
during this activity.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: arylation C@H functionalization quinolines
regioselectivity synthetic methods
[1] a) M. C. Kozlowski, B. J. Morgan, E. C. Linton, Chem. Soc. Rev. 2009, 38,
3193 3207; b) G. Bringmann, C. Gunther, M. Ochse, O. Schupp, S. Tasler,
Prog. Chem. Org. Nat. Prod. 2001, 82, 1 249.
[2] a) D. A. Horton, G. T. Bourne, M. L. Smyte, Chem. Rev. 2003, 103, 893
930; b) L. Ackermann, R. Vicente, A. R. Kapdi, Angew. Chem. Int. Ed.
2009, 48, 9792 9826; Angew. Chem. 2009, 121, 9976 10011.
[3] a) A. Mishra, M. K. R. Fischer, P. B-uerle, Angew. Chem. Int. Ed. 2009, 48,
2474 2499; Angew. Chem. 2009, 121, 2510 2536; b) J. Wiberg, T. Mari-
nado, D. P. Hagberg, L. Sun, A. Hagfeldt, B. Albinsson, J. Phys. Chem.
2009, 113, 3881 3886; c) L.-Y. Lin, C.-H. Tsai, K.-T. Wong, T.-W. Huang, L.
Hsieh, S.-H. Liu, H.-W. Lin, C.-C. Wu, S. H. Chou, S.-H. Chen, A.-I. Tsai, J.
Org. Chem. 2010, 75, 4778 4785.
[4] a) A. de Meijere, F. Diederich, Metal-Catalyzed Cross-Coupling Reactions,
Wiley-VCH, Weinheim, 2004; b) J. P. Corbet, G. Mignani, Chem. Rev.
2006, 106, 2651 2710; c) M. Beller, C. Bolm, Transition Metals for Organ-
ic Synthesis, Wiley-VCH, Weinheim, 2004; d) G. Bringmann, A. J. Price,
Asian J. Org. Chem. 2017, 6, 1043 1053 www.AsianJOC.org 1052
Full Paper
P. A. Mortimer, M. J. Keller, J. Gresser, M. Garner, A. Breuning, Angew.
Chem. Int. Ed. 2005, 44, 5384 5427; Angew. Chem. 2005, 117, 5518
5563; e) L. Anastasia, E. Negishi, Handbook of Organopalladium Chemis-
try for Organic Synthesis, Wiley, New York, 2002.
[5] a) M. Moselage, J. Li, L. Ackermann, ACS Catal. 2016, 6, 498 525; b) L.
ACS Catal. 2016, 6, 3743 3752; d) T. Gensch, M. N. Hopkinson, F. Glo-
rius, J. Wencel-Delord, Chem. Soc. Rev. 2016, 45, 2900 2936; e) J.
Wencel-Delord, T. Droege, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40,
4740 4761; f) B. Liu, F. Hu, B.-F. Shi, ACS Catal. 2015, 5, 1863 1881;
g) Y. Segawa, T. Maekawa, K. Itami, Angew. Chem. Int. Ed. 2015, 54, 66
81; Angew. Chem. 2015, 127, 68 83; h) G. Rouquet, N. Chatani, Angew.
Chem. Int. Ed. 2013, 52, 11726 11743; Angew. Chem. 2013, 125, 11942
11959.
[6] J. C. Hermann, Y. S. Chen, C. Wartchow, J. Menke, L. Gao, S. K. Gleason,
N. E. Haynes, N. Scott, A. Petersen, S. Gabriel, B. Vu, K. M. George, A.
Narayanan, S. H. Li, H. Qian, N. Beatini, L. H. Niu, Q. F. Gan, ACS Med.
Chem. Lett. 2013, 4, 197 200.
[7] a) J. P. Michael, Nat. Prod. Rep. 2008, 25, 166 187; b) V. R. Solomon, H.
Lee, Curr. Med. Chem. 2011, 18, 1488 1508; c) Y. Tokoro, A. Nagai, K.
Kokado, Y. Chujo, Macromolecules 2009, 42, 2988 2993.
[8] a) A. E. M. Saeed, S. A. Elhadi, Synth. Commun. 2011, 41, 1435 1443;
b) L. Chen, H. You, C. Yang, X. Zhang, J. Qin, D. Ma, J. Mater. Chem.
2006, 16, 3332 3339; c) R. Kumar, R. Sharma, I. Kumar, U. Sharma, Org.
Biomol. Chem. 2016, 14, 2613 2617; d) J. C. Lewis, R. G. Bergman, J. A.
Ellman, Acc. Chem. Res. 2008, 41, 1013 1025.
[9] B. Baragaa, I. Hallyburton, M. C. S. Lee, N. R. Norcross, R. Grimaldi, T. D.
Otto, W. R. Proto, A. M. Blagborough, S. Meister, G. Wirjanata, A. Rueck-
er, L. M. Upton, T. S. Abraham, M. J. Almeida, A. Pradhan, A. Porzelle,
M. S. Martinez, J. M. Bolscher, A. Woodland, S. Norval, F. Zuccotto, J.
Thomas, F. Simeons, L. Stojanovski, M. Osuna-Cabello, P. M. Brock, T. S.
Churcher, K. A. Sala, S. E. Zakutansky, M. B. Jimenez-Daz, L. M. Sanz, J.
Riley, R. Basak, M. Campbell, V. M. Avery, R. J. Sauerwein, K. J. Dechering,
R. Noviyanti, B. Campo, J. A. Frearson, I. Angulo-Barturen, S. Ferrer-
Bazaga, F. J. Gamo, P. G. Wyatt, D. Leroy, P. Siegl, M. J. Delves, D. E. Kyle,
S. Wittlin, J. Marfurt, R. N. Price, R. E. Sinden, E. A. Winzeler, S. A. Char-
man, L. Bebrevska, D. W. Gray, S. Campbell, A. H. Fairlamb, P. A. Willis,
J. C. Rayner, D. A. Fidock, K. D. Read, I. H. Gilbert, Nature 2015, 522,
315 320.
[10] a) C. H. Tseng, Y. L. Chen, P. J. Lu, C. N. Yang, C. C. Tzeng, Bioorg. Med.
Chem. 2008, 16, 3153 3162; b) C. H. Tseng, Y. L. Chen, K. Y. Chung, C. M.
Cheng, C. H. Wang, C. C. Tzeng, Bioorg. Med. Chem. 2009, 17, 7465
7476; c) A. Zarghi, S. ArfaeiIranian, J. Pharm. Res. 2011, 10, 655 683.
[11] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457 2483; b) A. J. Suzuki,
Organomet. Chem. 2002, 653, 83 90; c) J. Hassan, M. S8vignon, C.
Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 2002, 102, 1359 1470; d) F. I.
Wu, H. J. Su, C. F. Shu, L. Luo, W. G. Diau, C.-H. Cheng, J. Mater. Chem.
2005, 15, 1035 1042.
[12] a) Y. Liu, J. Kim, J. Chae, Curr. Org. Chem. 2014, 18, 2049 2071; b) G.
Yan, A. J. Borah, M. Yang, Adv. Synth. Catal. 2014, 356, 2375 2394; c) L.
Ackermann, S. Fenner, Chem. Commun. 2011, 47, 430 432; d) X. Chen,
C. Zhu, X. Cui, Y. Wu, Chem. Commun. 2013, 49, 6900 6902; e) H. Wang,
X. Cui, Y. Pei, Q. Zhang, J. Bai, D. Wei, Y. Wu, Chem. Commun. 2014, 50,
14409 14411; f) J. Wu, X. Cui, L. Chen, G. Jiang, Y. Wu, J. Am. Chem. Soc.
2009, 131, 13888 13889; g) F. Gosselin, S. J. Savage, N. Blaquiere, S. T.
Staben, Org. Lett. 2012, 14, 862 865; h) Z. Wu, H. Song, X. Cui, C. Pi, W.
Du, Y. Wu, Org. Lett. 2013, 15, 1270 1273; i) C. Zhu, M. Yi, D. Wei, X.
Chen, Y. Wu, X. Cui, Org. Lett. 2014, 16, 1840 1843; j) G. Li, C. Jia, K.
Sun, Org. Lett. 2013, 15, 5198 5201; k) Z. Wu, C. Pi, X. Cui, J. Bai, Y. Wu,
Adv. Synth. Catal. 2013, 355, 1971 1976.
[13] a) L.-C. Campeau, S. Rousseaux, K. Fagnou, J. Am. Chem. Soc. 2005, 127,
18020 18021; b) L.-C. Campeau, D. R. Stuart, J.-P. Leclerc, M. Bertrand-
Laperle, E. Villemure, H.-Y. Sun, S. Lasserre, N. Guimond, M. Lecavallier,
K. Fagnou, J. Am. Chem. Soc. 2009, 131, 3291 33069.
[14] a) S. H. Cho, S. J. Hwang, S. Chang, J. Am. Chem. Soc. 2008, 130, 9254
9256; b) W. Sun, M. Wang, Y. Zhang, L. Wang, Org. Lett. 2015, 17, 426
429; c) J. W. Yuan, S. N. Liu, L. B. Qu, Tetrahedron 2017, 73, 2267 2275.
[15] L. Bering, A. P. Antonchick, Org. Lett. 2015, 17, 3134 3137.
[16] a) G. Deng, K. Ueda, S. Yanagisawa, K. Itami, C.-J. Li, Chem. Eur. J. 2009,
15, 333 337; b) W. Sun, Z. Xie, J. Liu, L. Wang, Org. Biomol. Chem. 2015,
13, 4596 4604.
T 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
 Full Paper
[17] J. W. Yuan, W. J. Li, Y. M. Xiao, Tetrahedron 2017, 73, 179 186. Am. Chem. Soc. 2015, 137, 3213 3216; k) B. Verbelen, S. Boodts, J. Hof-
[18] a) A. Roglans, A. Pla-Quintana, M. Moreno-Manas, Chem. Rev. 2006, 106, kens, N. Boens, W. Dehaen, Angew. Chem. Int. Ed. 2015, 54, 4612 4616;
4622 4643; b) C. Galli, Chem. Rev. 1988, 88, 765 792; c) D. P. Hari, B. Angew. Chem. 2015, 127, 4695 4699; l) K. Shin, S.-W. Park, S. Chang, J.
Knig, Angew. Chem. Int. Ed. 2013, 52, 4734 4743; Angew. Chem. 2013, Am. Chem. Soc. 2015, 137, 8584 8592.
125, 4832 4842; d) F. Mo, G. Dong, Y. Zhang, J. Wang, Org. Biomol. [21] A. P. Colleville, A. J. Richard, R. A. J. Horan, S. Olazabal, N. C. O. Tomkin-
Chem. 2013, 11, 1582 1593. son, Org. Process Res. Dev. 2016, 20, 1283 1296.
[19] U. M. V. Basavanag, A. D. Santos, L. E. Kaim, R. Gamez-Montano, L. Gri- [22] S. K. Singh, M. S. Reddy, M. Mangle, K. R. Gnesh, Tetrahedron 2007, 63,
maud, Angew. Chem. Int. Ed. 2013, 52, 7194 7197; Angew. Chem. 2013, 126 130.
125, 7335 7338. [23] H. Hwang, J. Kim, J. Jeong, S. Chang, J. Am. Chem. Soc. 2014, 136,
[20] For recent examples of arylation reactions that use aryldiazonium salts, 10770 10776.
see: a) D. Kalyani, K. B. McMurtrey, S. R. Neufeldt, M. S. Sanford, J. Am. [24] R. Sharma, R. Kumar, I. Kumar, U. Sharma, Eur. J. Org. Chem. 2015,
Chem. Soc. 2011, 133, 18566 18569; b) E. W. Werner, M. S. Sigman, J. 7519 7528.
Am. Chem. Soc. 2011, 133, 9692 9695; c) E. W. Werner, T.-S. Mei, A. J. [25] U. Sharma, Y. Park, S. Chang, J. Org. Chem. 2014, 79, 9899 9906.
Burckle, M. S. Sigman, Science 2012, 338, 1455 1458; d) D. P. Hari, P. [26] Y. Qu, Z. Li, H. Xiang, X. Zhou, Adv. Synth. Catal. 2013, 355, 3141 3146.
Schroll, B. Konig, J. Am. Chem. Soc. 2012, 134, 2958 2961; e) M. Hart- [27] F. De Vleeschouwer, V. Van Speybroeck, M. Waroquier, P. Gerrlings, F. D.
mann, Y. Li, A. Studer, J. Am. Chem. Soc. 2012, 134, 16516 16519; f) B. Proft, Org. Lett. 2007, 9, 2721 2724.
Sahoo, M. N. Hopkinson, F. Glorius, J. Am. Chem. Soc. 2013, 135, 5505 [28] F. Zhang, X. F. Duan, Org. Lett. 2011, 13, 6102 6105.
5508; g) F. P. Crisjstomo, T. Mart&n, R. Carrillo, Angew. Chem. Int. Ed.
2014, 53, 2181 2185; Angew. Chem. 2014, 126, 2213 2217; h) X.-Z.
Shu, M. Zhang, Y. He, H. Frei, F. D. Toste, J. Am. Chem. Soc. 2014, 136,
Manuscript received: May 9, 2017
58445847; i) C. C. Oliveira, M. V. Marques, M. N. Godoi, T. Regiani, V. G.
Santos, E. A. F. dos Santos, M. N. Eberlin, M. M. Sa, C. R. D. Correia, Org. Accepted manuscript online: May 15, 2017
Lett. 2014, 16, 5180; j) H. M. Nelson, B. D. Williams, J. Miro, F. D. Toste, J. Version of record online: June 22, 2017

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