Ru-Catalyzed Deoxygenative Regioselective C8-H Arylation of Quinoline N-Oxides

Article abstract of DOI:10.1021/acs.joc.9b01548

Regioselective C-H functionalization on quinolines is of high interest to lead to value-added products. Herein, we describe the development of Ru-catalyzed deoxygenative regioselective C8 arylation of quinoline N-oxides with arylboronic esters. Mechanistic studies revealed that it proceeds in a tandem process of arylation and then deoxygenation, wherein both steps were found to be catalytic with the ruthenium species.

Full text of DOI:10.1021/acs.joc.9b01548

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Note
Ru-Catalyzed Deoxygenative Regioselective
C8–H Arylation of Quinoline N-Oxides
Jinwoo Kim, Suhyeon Kim, Dongwook Kim, and Sukbok Chang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01548 • Publication Date (Web): 19 Jul 2019
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Ru-Catalyzed Deoxygenative Regioselective C8–H Arylation
of Quinoline N-Oxides
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Jinwoo Kim,†,‡ Suhyeon Kim,†,‡ Dongwook Kim,‡ and Sukbok Chang*,‡,†
†Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
‡Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon 34141, South Korea
E-mail: sbchang@kaist.ac.kr
Supporting Information
ABSTRACT: Regioselective C–H functionalization on quinolines is of high interest to lead to value-added products. Herein,
we describe the development of Ru-catalyzed deoxygenative regioselective C8 arylation of quinoline N-oxides with
arylboronic esters. Mechanistic studies revealed that it proceeds in a tandem process of arylation and then deoxygenation,
wherein both steps were found to be catalytic with the ruthenium species.
Quinoline is present in a broad range of natural and
Scheme 1. Regioselective C8–H functionalization of
pharmaceutical compounds,1 thus receiving special
quinolines and their N-oxides.
attention towards the introduction of functional groups in
a
more efficient and selective manner.2 In the
(a) Direct C8–H functionalization of quinolines
conventional approaches, the regioselective modifications
often depend on the pre-functionalization or the de novo
preparation of the core structure.3 On the other hand,
synthesis of quinoline derivatives via site-specific C–H
bond activation has been scrutinized in recent years.4 For
instance, direct C8–H-arylation and borylation of
quinolines were shown to be achieved by Rh and Ir
catalysis, respectively, albeit with limited substrate scope
(Scheme 1a).5
[Rh]
[Ir]
Ref. 5b
Ref. 5a
N
B(OR)2
N
N
H
Ar
(b) C8–H functionalizations of quinoline N-oxides
[Rh]
[Rh], [Ir]
N
N+
Ref. 9a
Ref. 11b,c
O
O-
Ph
Y
Ph
Y = NHR, Halogen
[Rh]
An alternative approach is to utilize quinoline N-oxides
as the substrates, where N-oxide serves as an effective
directing group to lead to the regioselective C–H bond
activation.6 While C2 functionalization of quinoline N-
oxides is governed mainly by the high electrophilicity of
C2 carbon and acidic nature of that C–H bond,7,8 C8–H
bond activation can be successfully carried out by the
facile formation of the corresponding metallacyclic
intermediates (Scheme 1b, left).9 In these procedures, an
additional deoxygenation step is often required after the
installation of the desired functional groups.10 A few
examples bypassing such a separate reduction process
have been reported.11 However, to our best knowledge,
deoxygenative C8 arylation is unprecedented to date
(Scheme 1b, right).
[Rh], [Ir], [Pd]
Ref. 9b,c,e
N
N+
N+
O-
Ref. 11d,e
Ar O-
H
R
[Rh]
[Rh], [Pd]
N+
O-
N
Ref. 9d,e,f
Ref. 11f
R
O
H
R
(c) This work: Ru-catalzyed deoxygenative C8–H arylation of quinoline N-oxides
Ar
B(OR)2
cat. [Ru]
cat. [Ru]
X
X
X
in situ
N+
O-
N
N+
Ar O-
H
Ar
N-oxide as a 'traceless' directing group
 Both steps are catalytic in Ru
Mild conditions / broad scope

 Excellent functional group tolerance

Interestingly, deoxygenative complexation occurred when
Ru-A is heated at 50 °C in THF/trifluoroethanol (TFE) to
give a Ru-quinoline complex Ru-B. Deoxygenation of 1a
also took place catalytically by in situ generated (p-
cymene)Ru(OTFA)2 species leading to quinoline 2a
(89%). The N–O bond distance of Ru-A is 1.345(4) Å,
being slightly longer than that of 1a (1.310 Å).12 In Ru-B,
the Ru–N bond is 2.151(2) Å, well consistent with the
reported values of the similar Ru complexes.13
Herein we present the first example of Ru-catalyzed
deoxygenative C8–H arylation of quinoline N-oxides by
using arylboronic esters. (p-Cymene)RuII was found to
effectively catalyze both C–H arylation and subsequent
deoxygenation. The reaction is featured to display broad
substrate scope and high functional group compatibility
under mild conditions.
At the outset of this study, we investigated reactivity of
quinoline N-oxide 1a with [(p-cymene)RuCl2]2 (Scheme
2). A stable adduct complex Ru-A was obtained in 93%
yield in the presence of silver trifluoroacetate (AgOTFA).
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Scheme 2. Deoxygenation of quinoline N-oxide with (p-
cymene)RuII.
Table 1. Reaction optimization for deoxygenative C8–H
arylation of quinoline N-oxide.a
6
7
8
9
[(p-cymene)RuCl2]2 (5 mol %)
[(p-cymene)RuCl2]2 (0.5 equiv)
O
AgOTs (20 mol %)
Ag2O (2.2 equiv)
N
AgOTFA (2.0 equiv)
O
O
O-
N+
Ru
CF3
N+
B
CH2Cl2 (0.05 M)
25 °C, 36 h, 93%
Cu(ClO4)2·6H2O (10 mol %)
O
O
O
+
O-
N+
O-
THF:TFE = 1:2 (0.2 M)
50 °C, 14 h
1a
F3C
CF3
Ru-A
1a
3a
(2.0 equiv)
CF3
10
11
12
13
14
15
16
17
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20
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53
54
55
56
57
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59
60
7aa
(p-cymene)Ru(OTFA)2
(10 mol %)
THF-d8:TFE = 1:2
50 °C, 2 h, 89%
THF:TFE = 5:1
50 °C, 24 h, 88%
O
O
B
O
B
BF3K
B
O
O
O
F3C
O
F3C
F3C
F3C
3a
4a
5a
6a
O
Ru
CF3
N
O
O
N
ent
ry
variation from the “standard”
conditions
yield
2a
2a
(%)b
(%)b
CF3
Ru-B
95
1
none
<5
(93)c
2
3
4
5
6
7
8
9
2a instead of 1a
0
39
70
0
99
59
30
75
49
81
30
41
74
71
Ru
4a instead of 3a
Ru
O1
O2
5a instead of 3a
N
O3
O2
N
O1
6a instead of 3a
No Cu(ClO4)2·6H2O
CuBr2 instead of Cu(ClO4)2·6H2O
51
6
C1
Ru-A
Estimates
Ru-B
Estimates
Cu(OTf)2 instead of Cu(ClO4)2·6H2O
Cu(OAc)2 instead of Cu(ClO4)2·6H2O
69
35
9
Ru–N
Ru–O1
2.151(2) Å
2.0796(19) Å
81.59(8)°
Ru–O1
Ru–O2
O1–N
2.095(3) Å
2.098(3) Å
1.345(4) Å
83.60(10)°
120.4(2) °
N–Ru–O1
C1–N–Ru
10 EtOH instead of TFE
O1–Ru–O2
Ru–O1–N
173.7(1)°
11 (CF3)2CHOH instead of TFE
7
[Cp*IrCl2]2 instead of [(p-
12
9
<5
cymene)RuCl2]2
We next wondered whether the facile deoxygenation
activity of Ru catalyst can be combined with an envisioned
C–H arylation to establish a tandem deoxygenative
arylation of quinoline N-oxides (Table 1).14 Pleasingly,
the (p-cymene)RuII catalyst system enabled a reaction of
1a with aryl ethyleneglycol boronic ester 3a to furnish C8-
arylated quinoline product 7aa in excellent yield along
with trace amount of quinoline 2a (2%) under optimized
conditions (entry 1). In this reaction, Ag2O (2.2 equiv)
serves as an oxidant and copper cocatalyst (10 mol %) is
proposed to facilitate a presumed aryl transmetalation
from boronates.15 On the other hand, quinoline 2a was not
reactive under the same conditions (entry 2).8a
Interestingly, the reaction efficiency was found to be
highly affected by the structure of boronic esters. For
instance, pinacol boronate (4a), neopentyl glycol boronate
(5a), and potassium trifluoroborate (6a) were much less
effective than glycolboronate 3a (entries 3–5). Likewise,
the type of copper cocatalyst significantly influenced the
product yields (entries 6–9).16,14 Trifluoroethanol (TFE)
was an exceptionally effective solvent in combination
with THF (entries 10 and 11). On the other hand,
[Cp*RhCl2]2 and [Cp*IrCl2]2 catalysts were unproductive
for the current deoxygenative arylation (entries 12 and 13).
[Cp*RhCl2]2 instead of [(p-
13
0
0
cymene)RuCl2]2
aReaction conditions: 1a (0.10 mmol), boronic ester (2.0 equiv),
catalyst (5 mol %), AgOTs (20 mol %), Cu salt (10 mol %), and
Ag2O (2.2 equiv) in THF/TFE (1:2, 0.5 mL) for 14 h at 50 °C.
bYields were determined by 1H NMR spectroscopy using 1,1,2,2-
tetrachloroethane as the internal standard. cIsolated yield.
With the optimized conditions in hand, we then
explored the substrate scope of the Ru-catalyzed
deoxygenative C8-arylation of quinoline N-oxides (Table
2). Electronic variation on the quinoline skeleton did not
much alter the reaction efficiency (7b–7d). Halides and
nitro substituents were totally compatible with the present
conditions (7e–7k). Substrate scope was further examined
using polycyclic N-oxides. For instance, acridine N-oxide
was arylated albeit in moderate yield (7l). The arylation of
benzo[c]quinoline N-oxide and benzo[f]quinoline N-oxide
also proceeded smoothly (7m and 7n), and the
regioselectivity of 7n was confirmed by an XRD analysis.
We subsequently examined the compatibility of more
labile but synthetically versatile functional groups to the
current deoxygenative arylation conditions. A number of
carbonyl moieties such as acetyl, ester, and aldehyde were
all tolerated, and the arylation took place in high to
moderate yields (7o–7r). Protecting groups for aldehyde,
phenol, and amine were also well compatible with the
current conditions (7s–7u). In addition, the scope of
arylboronic esters was briefly surveyed to see that various
substituents could be incorporated on the aryl coupling
partner (7ab–7ag).14,17
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Table 2. Substrate scope of the deoxygenative C8–H arylation of quinoline N-oxides.a
6
7
8
9
[(p-cymene)RuCl2]2 (5 mol %)
AgOTs (20 mol %)
Ag2O (2.2 equiv)
Cu(ClO4)2·6H2O (10 mol %)
O
B
N
X
O
+
N+
O-
THF:TFE = 1:2 (0.2 M)
50 °C, 14 h
X
Y
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
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45
46
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49
50
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52
53
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57
58
59
60
Y
1
3
7
Electronic variation
Fucntional group tolerance
O
O
O
6
7
Br
Cl
O
O
Me
O
N
N
N
N
N
N
N
N
7aa
7c :
: 68%
6-Me
7-Me 7d
70%
7b
80%
7
7f
7o
79%
7p
75%
7q
52%
e
93%
90%
70%
(2.01 g, 74%)b
CF3
CF3
Cl
CF3
CF3
CF3
NO2
CF3
CF3
CF3
Cl
O
O
F
O2N
(iPr)3SiO
O
H
N
N
N
N
N
N
N
N
7g
72%
7h
75%
7i
79%
7j
74%
7k
57%
7r
74%
7s
67%
7t
58%
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
Polycyclic system
Boronic ester variation
AcHN
X = Br
Cl
7ab : 95%
7ac : 89%
N
N
N
N
7m
54%
CO2Et 7ad : 79%
N
NO2
Me
7ae : 75%
7af : 40%
7u
62%
7l
43%
7n
OMe 7ag : 39%
X
CF3
CF3
66%
CF3
CF3
aReaction conditions: 1 (0.10 mmol), 3 (2.0 equiv), [(p-cymene)RuCl2]2 (5 mol %), AgOTs (20 mol %), Cu(ClO4)2·6H2O (10 mol %), and
Ag2O (2.2 equiv) in THF/TFE (1:2, 0.5 mL) for 14 h at 50 °C. Isolation yields are reported. 1a (1.45 g, 10.0 mmol), 3a (2.0 equiv), [(p-
cymene)RuCl2]2 (5 mol %), AgOTs (20 mol %), Cu(ClO4)2·6H2O (10 mol %), and Ag2O (2.2 equiv) in THF/TFE (1:2, 60 mL) for 36 h at
50 °C.
b
To gain mechanistic insights, we first obtained a
reaction profile of the arylation of 1a (Scheme 3a). The
C8-arylated N-oxide intermediate 8aa was found to
initially form and then deoxygenation proceeded to afford
7aa, eventually reaching a full conversion after 10 h at 50
°C. No kinetic isotope effect (KIE) of the first C–H
arylation process was observed (kH/kD=1.02) from a
parallel rate comparison between 1a and 1a-d7 (Scheme
3b).
For more details on the subsequent deoxygenation step,
an isolated C8-arylated N-oxide 8aa was subjected to
various conditions (Scheme 4a). The deoxygenation was
enabled by the action of a cationic Ru(II) species, in situ
generated from [(p-cymene)RuCl2]2 and AgOTs (Scheme
4a). Neither Ag2O oxidant nor Cu additive mediated the
catalytic deoxygenation in the absence of Ru catalyst.10b,c
Moreover, the reaction was not thermally driven. We
further observed the formation of trifluoroethoxy
hemiacetal 10 from the reaction mixture, which was
assumed to be formed from trifluoroacetaldehyde 9 and
TFE (Scheme 4b),18 implying that TFE solvent is likely
involved in the catalysis as a reducing agent.
Scheme3. Kinetic study of the Ru-catalyzed
deoxygenative C8–H arylation
(a)
[(p-cymene)RuCl2]2 (5 mol %)
AgOTs (20 mol %)
N+
Ag2O (2.2 equiv)
O-
Cu(ClO4)·6H2O (10 mol %)
+
1a
3a
7aa
+
THF:TFE = 1:2 (0.2 M)
(2.0 equiv)
50 °C, 14 h
CF3
8aa
8aa
7aa
7aa 8aa
+
(b)
[(p-cymene)RuCl2]2 (5 mol %)
AgOTs (20 mol %)
Ag2O (2.2 equiv)
Cu(ClO4)·6H2O (10 mol %)
1a
or
1a-d7
8aa
or
8aa-d6
7aa
or
+
3a
THF:TFE = 1:2 (0.2 M)
7aa-d6
(2.0 equiv)
50 °C, 14 h
KIE = 1.02
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Scheme 4. Mechanistic investigations on the Ru-
catalyzed deoxygenation.
In conclusion, we have developed a Ru-catalyzed
deoxygenative C8-arylation of quinoline N-oxides for the
first time. The reaction was found to be a tandem process
consisted of an initial arylation and subsequent
deoxygenation, both of which is enabled by the ruthenium
catalyst. A broad range of substrates was successfully
applied with excellent functional group tolerance under
mild conditions.
(a)
N+
N
[(p-cymene)RuCl2]2 (5 mol %)
O-
AgOTs (20 mol %)
THF:TFE = 1:2
50 °C, 14 h
CF3
CF3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
99%
8aa
7aa
w/o Ru cat., 100 °C:
<5% conv.
(b)
[(p-cymene)RuCl2]2 (5 mol %)
EXPERIMENTAL SECTION
O
AgOTs (20 mol %)
9
7aa
8aa
+
General Information. Unless otherwise stated, all commercial
reagents were used without additional purifications. Quinoline N-
oxide (1a) was purchased from Tokyo Chemical Industry Co. and
used without further purification. The water content of N-oxides
was analyzed by Karl Fischer titration before use. All the
chemical reaction was performed under Ar atmosphere.
Analytical thin layer chromatography (TLC) was performed on
Merck pre-coated silica gel F254 plates. NMR spectra were
recorded on Bruker Ascend 400 (400 MHz) or Agilent
Technologies DD2 (600 MHz). 1H NMR chemical shifts were
quoted in parts per million (ppm) referenced to the residual
solvent peak or 0.0 ppm for tetramethylsilane. 13C{1H} NMR was
fully decoupled by broad band proton decoupling and the
chemical shifts were reported in ppm referenced to the residual
solvent peaks. All coupling constant (J) values are reported in
hertz. Multiplicities are reported as follows: singlet (s), doublet
(d), doublet of doublets (dd), doublet of doublets of doublets
(ddd), triplet (t), quartet (q), heptet (hept), and multiplet (m).
Infrared spectra were acquired on Bruker Alpha ATR FT-IR
spectrometer. Frequencies are given in wave numbers (cm-1) and
only selected peaks were reported. High resolution mass spectra
were obtained from the Korea Basic Science Institute (Daegu) by
EI and FAB method using Jeol JMS 700 high resolution mass
spectrometer with a quadrupole mass analyzer. The HRMS data
of 7d and 7ag were obtained from KAIST Analysis Center for
Research Advancement (Daejeon) by ESI method using Bruker
F3C
H
THF-d8:TFE = 10:1 (0.2 M)
(88%)
50 °C, 2 h
F3C
OH
OH
10
CF3
Detected by NMR
F3C
O
A plausible catalytic cycle of the present Ru-catalyzed
deoxygenative C8-arylation of quinoline N-oxides is
depicted in Scheme 5. The in situ-generated active species
A undergoes the C8–H bond activation to form a
ruthenacycle B. A subsequent transmetalation from
arylboronic ester, presumably through an aryl cuprate
species, is assumed to follow to give rise to a Ru aryl
intermediate C. The oxidation of C to the high-valent
Ru(III) species D by Ag+ oxidant is proposed to facilitate
the reductive elimination to afford C8-arylated quinoline
N-oxide 8aa.14 The resulting Ru(I) species E will be
subsequently oxidized to A to close the catalytic cycle.
Alternatively, a direct reductive elimination from a neutral
Ru(II) intermediate C cannot be completely excluded at
the present. The second deoxygenation process is
proposed also to be catalyzed by (p-cymene)Ru(OTs)2
species A, wherein trifluoroethanol cosolvent acts as a
reducing agent.
microQTOF-QII with
a quadrupole mass analyzer. X-ray
diffraction data was collected on a Bruker D8 QUEST coated
with Parabar oil under a stream of N2 (g) at 173 K. The PAL
BL2D-SMDC program was used for data collection (detector
distance is 66 mm, omega scan; Δω = 3°, exposure time is 0.7 sec
per frame) and HKL3000sm (Ver 716.7) was used for cell
refinement, reduction and absorption correction.
Scheme 5. A plausible pathway of the current Ru-
catalyzed deoxygenative arylation.
[(p-cymene)RuCl2]2
3a
RuII
1a
O
OTs
N
2 AgOTs
Synthesis of an Ru-Quinoline N-oxide Adduct (Scheme 2,
Ru-A). To a mixture of quinoline N-oxide (284 mg, 1.96 mmol),
silver trifluoroacetate (432 mg, 1.96 mmol), and Li2CO3 (144 mg,
1.95 mmol) in CH2Cl2 (40 mL) was added [(p-cymene)RuCl2]2
(600 mg, 0.978 mmol) and the mixture was stirred at 25 °C. After
12 h, additional portion of silver trifluoroacetate (432 mg, 1.96
mmol) was added and the reaction mixture was further stirred at
25 °C for 24 h. The suspension was filtered through a pad of celite
and the filtrate was concentrated under reduced pressure. The
residue was recrystallized in CH2Cl2/n-hexane to obtain Ru-A.
Orange crystal (874 mg, 93%); decompose at >250 °C; 1H NMR
(600 MHz, CD2Cl2) δ 8.61 (d, J = 8.8 Hz, 1H), 8.53 (d, J = 6.1
Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.98 – 7.91 (m, 2H), 7.76 –
7.71 (m, 1H), 7.26 (dd, J = 8.4, 6.2 Hz, 1H), 6.06 (d, J = 5.9 Hz,
2H), 5.82 (d, J = 5.8 Hz, 2H), 2.98 (hept, J = 7.0 Hz, 1H), 2.26 (s,
3H), 1.34 (d, J = 7.0 Hz, 6H); 13C{1H} NMR (150 MHz, CD2Cl2)
δ 162.4 (q, J = 35.9 Hz), 143.6, 141.3, 135.8, 132.6, 130.2, 129.4,
128.7, 120.3, 119.4, 115.4 (q, J = 291.8 Hz), 99.9, 95.9, 80.0, 77.7,
31.6, 22.5, 18.5; 19F NMR (564 MHz, CD2Cl2) δ -75.56; IR (cm-
1) 3122, 3075, 2969, 2934, 2880, 1713, 1697, 1397, 1181; HRMS
(FAB) m/z calcd. for C23H21F6NO5Ru [M]+: 607.0374, found:
B
2 Ag+
2 Ag0
RuII
O
C
N
RuII
A
OTs
TsO
Ag0
CF3
Ag+
8aa
Ag0
Ag+
+
RuIII
RuI
O
TsO
N
E
CF3
D
RuII
N+
N
O-
OTs
TsO
+ H2O
CF3
O
OH
CF3
7aa
8aa
CF3
H
CF3
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607.0371.
Synthesis of Ru-B (Scheme 2). A solution of Ru-A (30.4 mg,
RF = 0.3). White solid (91.4 mg, 45%); mp 89 – 91 °C; δ 8.68 (d,
J = 9.4 Hz, 1H), 8.43 (d, J = 5.7 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H),
7.64 (d, J = 2.4 Hz, 2H), 7.48 (d, J = 9.4 Hz, 1H), 7.33 – 7.28 (m,
2H), 2.35 (s, 3H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 169.4,
150.8, 140.1, 135.5, 131.7, 125.7, 125.1, 122.5, 121.8, 119.5, 21.3;
IR (cm-1) 3073, 3053, 2994, 2923, 1748, 1572, 1371, 1199;
HRMS (EI) m/z calcd. for C11H9NO3 [M]+: 203.0582, found:
203.0581
0.0500 mmol) in THF-d8/TFE=5:1 (0.5 mL) was heated in a
preheated oil bath at 50 °C for 24 h. The mixture was filtered and
the filtrate was concentrated under reduced pressure. The residue
was recrystallized in CH2Cl2/n-hexane to obtain Ru-B. Yellow
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crystal (25.9 mg, 88%); decompose at >250 °C; H NMR (600
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MHz, CD2Cl2) δ 9.16 (dd, J = 5.3, 1.5 Hz, 1H), 8.67 (dd, J = 8.8,
1.0 Hz, 1H), 8.32 (d, J = 8.1 Hz, 1H), 7.91 (dd, J = 8.0, 1.5 Hz,
1H), 7.85 (ddd, J = 8.7, 6.9, 1.5 Hz, 1H), 7.67 (ddd, J = 8.1, 6.9,
1.0 Hz, 1H), 7.51 (dd, J = 8.2, 5.3 Hz, 1H), 6.22 (d, J = 5.7 Hz,
2H), 5.78 (d, J = 5.9 Hz, 2H), 2.77 (hept, J = 6.9 Hz, 1H), 1.85 (s,
3H), 1.21 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (150 MHz, CD2Cl2)
δ 163.6 (q, J = 36.3 Hz), 156.2, 148.3, 140.2, 131.6, 130.2, 129.4,
129.1, 128.1, 121.9, 115.3 (q, J = 291.3 Hz), 103.7, 97.7, 82.4,
79.6, 31.5, 22.4, 18.6; 19F NMR (376 MHz, CD2Cl2) δ -75.34; IR
(cm-1) 3080, 3057, 2974, 1696, 1681, 1181, 1126; HRMS (FAB)
m/z calcd. for C23H21F6NO4Ru [M]+: 591.0425, found: 591.0415.
6-(1,3-Dioxolan-2-yl)quinoline 1-oxide (Table 2, 1s). The
same procedure for the synthesis of 1l was followed by using 6-
(1,3-dioxolan-2-yl)quinoline5a (503 mg, 2.50 mmol) as the
starting material (acetone, RF = 0.1). Yellow solid (395 mg, 73%);
1
mp 81 – 83 °C; H NMR (400 MHz, CD2Cl2) δ 8.67 (d, J = 9.0
Hz, 1H), 8.46 (dd, J = 6.1, 0.9 Hz, 1H), 7.99 (d, J = 1.4 Hz, 1H),
7.83 (dd, J = 9.0, 1.8 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.30 (dd,
J = 8.4, 6.1 Hz, 1H), 5.96 (s, 1H), 4.19 – 4.03 (m, 4H); 13C{1H}
NMR (100 MHz, CD2Cl2) δ 142.4, 139.4, 136.0, 130.7, 128.7,
126.6, 125.7, 121.9, 120.3, 103.1, 66.9; IR (cm-1) 3096, 3049,
2939, 2887, 1716, 1571, 1507, 1275; HRMS (EI) m/z calcd. for
C12H11NO3 [M]+: 217.0739, found 217.0738.
6-[(Triisopropylsilyl)oxy]quinoline N-oxide (Table 2, 1t). The
same procedure for the synthesis of 1l was followed by using 6-
[(triisopropylsilyl)oxy]quinoline5a (302 mg, 1.00 mmol) as the
starting material (CH2Cl2/acetone = 4:1, RF = 0.2). Yellow solid
(317 mg, 91%); mp 63 – 65 °C; 1H NMR (400 MHz, CD2Cl2) δ
8.54 (d, J = 9.5 Hz, 1H), 8.30 (dd, J = 6.0, 1.0 Hz, 1H), 7.56 (d, J
= 8.5 Hz, 1H), 7.33 (dd, J = 9.4, 2.6 Hz, 1H), 7.23 – 7.18 (m, 2H),
1.39 – 1.24 (m, J = 7.5 Hz, 3H), 1.11 (d, J = 7.6 Hz, 18H); 13C{1H}
NMR (100 MHz, CD2Cl2) δ 156.5, 137.8, 134.0, 132.5, 126.2,
124.5, 121.9, 121.7, 114.9, 18.0, 13.1; 29Si NMR (79 MHz,
CD2Cl2) δ 17.87; IR (cm-1) 3063, 2941, 2892, 2863, 1617, 1205;
HRMS (FAB) m/z calcd. for C18H28NO2Si [M]+ 318.1889, found:
318.1892.
Catalytic Deoxygenation of 1a with (p-cymene)RuII Species
(Scheme 2). A mixture of [(p-cymene)RuCl2]2 (3.1 mg, 0.0050
mmol) and silver trifluoroacetate (4.4 mg, 0.020 mmol) in THF-
d8/TFE=10:1 (0.5 mL) was stirred at 25 °C for 30 min. The
mixture was filtered through syringe filter and 1a (14.5 mg, 0.100
mmol) was added to the filtrate. The mixture was taken into J-
Young NMR tube and heated in a preheated oil bath at 50 °C for
24 h. The crude yield of deoxygenated product 2a was determined
1
by H NMR spectroscopy using 1,1,2,2-tetrachloroethane as the
internal standard (89%).
General Procedure for the Reaction Condition Screening
(Table 1). A mixture of catalyst (0.0050 mmol) and AgOTs (5.8
mg, 0.020 mmol) in solvents (0.5 mL) was stirred at 25 °C for 30
min. To the solution were added 1a (14.5 mg, 0.100 mmol),
boronic ester (0.200 mmol), Ag2O (51.0 mg, 0.220 mmol), and
Cu salt (0.010 mmol) and the reaction mixture was stirred in a
preheated heating mantle at 50 °C for 14 h. The mixture was
cooled to 25 °C, diluted with EtOAc (30 mL), quenched with sat.
aq. Na2CO3 (20 mL), and extracted with EtOAc (20 mL x 3). The
combined organic layer was dried over MgSO4, concentrated, and
the crude yield of 7aa was determined by 1H NMR spectroscopy
using 1,1,2,2-tetrachloroethane as the internal standard.
6-Formylquinoline N-oxide (Table 2, 1r).5a To a solution of 6-
(1,3-dioxolan-2-yl)quinoline N-oxide (217 mg, 1.00 mmol) in
THF (4 mL) were added formaldehyde (2.1 mL, 37 wt. % in water)
and p-toluenesulfonic acid monohydrate (190 mg, 1.00 mmol).
The resulting mixture was stirred at room temperature for 36 h.
The solution was quenched with sat. aq. NaHCO3 solution (20 mL)
and then extracted with dichloromethane (20 mL x 3). The
solution was dried over MgSO4 and evaporated under reduced
pressure. The residue was purified by SiO2 column
chromatography (acetone, RF = 0.2) to obtain the product. Yellow
1
solid (139 mg, 80%); mp 169 – 171 °C; H NMR (400 MHz,
Preparation of Quinoline N-Oxides (Table 2). Quinoline N-
oxides 1b–1k, 1m–1p, and 1u were prepared following the
reference procedures.9a,11b
CD2Cl2) δ 10.19 (d, J = 0.8 Hz, 1H), 8.78 (d, J = 9.0 Hz, 1H), 8.55
(dd, J = 6.1, 1.0 Hz, 1H), 8.40 (d, J = 1.7 Hz, 1H), 8.17 (dd, J =
9.0, 1.7 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.40 (dd, J = 8.5, 6.1
Hz, 1H); 13C{1H} NMR (100 MHz, CD2Cl2) δ 191.3, 144.4, 137.7,
136.4, 133.5, 130.9, 127.7, 126.2, 122.9, 121.4; IR (cm-1) 3104,
3046, 3010, 2923, 2852, 1679, 1573, 1450, 1356, 1268; HRMS
(EI) m/z calcd. for C10H7NO2 [M]+: 173.0477, found 173.0474.
Acridine N-oxide (Table 2, 1l).19 To a mixture of acridine (300
mg, 1.67 mmol) and MeReO3 (12.5 mg, 0.050 mmol) was added
50% aqueous solution of H2O2 (227 mg, 3.34 mmol) and the
reaction mixture was stirred at 25 °C for 12 h. The mixture was
diluted with CH2Cl2 (50 mL) and H2O (20 mL) was added. The
aqueous layer was extracted with CH2Cl2 (20 mL x 3). The
combined organic layer was washed with brine (5 mL), dried over
Na2SO4, concentrated, and the residue was purified by SiO2
column chromatography (CH2Cl2/acetone = 3:1, RF = 0.3) to
obtain the product. The spectral data was well matched with the
Preparation of Arylboronic Esters (Table 1 and Table 2).
Arylboronic esters 3a,20 4a,21 5a,22 6a,23 and 3b–3g20 were
prepared according to the reference procedure.
General Procedure for the Ru-Catalyzed Tandem
Deoxygenative C–H Arylation (Table 2). A mixture of [(p-
cymene)RuCl2]2 (3.1 mg, 0.0050 mmol) and AgOTs (5.8 mg,
0.020 mmol) in THF/TFE (1:2, 0.5 mL) was stirred at 25 °C for
30 min. To the solution were added 1 (0.100 mmol), 3 (0.200
mmol), Ag2O (51.0 mg, 0.220 mmol), and Cu(ClO4)2·6H2O (3.7
mg, 0.010 mmol) and the reaction mixture was stirred in a
preheated heating mantle at 50 °C for 14 h. The mixture was
cooled to 25 °C, diluted with EtOAc (30 mL), quenched with sat.
aq. Na2CO3 (20 mL), and extracted with EtOAc (20 mL x 3). The
1
previous report.9a Yellow solid (201 mg, 62%); H NMR (400
MHz, CD2Cl2) δ 8.79 (dd, J = 9.1, 0.6 Hz, 2H), 8.25 (s, 1H), 8.00
(d, J = 8.5 Hz, 2H), 7.76 (ddd, J = 9.0, 6.7, 1.2 Hz, 2H), 7.58 (ddd,
J = 8.0, 6.7, 0.9 Hz, 2H); 13C{1H} NMR (100 MHz, CD2Cl2) δ
140.0, 130.9, 129.1, 128.2, 127.5, 123.5, 119.9; IR (cm-1) 3048,
2920, 2851, 1620, 1560, 1530, 1471, 1435, 1401, 1327.
6-Acetoxyquinoline N-oxide (Table 2, 1q). The same procedure
for the synthesis of 1l was followed by using 6-acetoxyquinoline
(187 mg, 1.00 mmol) as starting material (CH2Cl2/acetone = 2:1,
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combined organic layer was dried over MgSO4, concentrated, and
= 2.3 Hz, 1H), 7.48 (dd, J = 8.3, 4.1 Hz, 1H); 13C{1H} NMR (150
MHz, CD2Cl2) δ 151.0, 144.8, 142.6, 141.6, 135.9, 132.2, 131.5,
131.1, 129.92 (q, J = 32.3 Hz), 129.92, 127.2, 125.1 (q, J = 3.8
Hz), 124.9 (q, J = 272.0 Hz), 122.6; 19F NMR (564 MHz, CD2Cl2)
δ -62.78; IR (cm-1) 3057, 3034, 2959, 2920, 2849, 1615, 1315,
1105; HRMS (EI) m/z calcd. for C16H9ClF3N [M]+: 307.0376,
found: 307.0371.
purified by SiO2 column chromatography to obtain the product.
8-[4-(Trifluoromethyl)phenyl]quinoline (Table 2, 7aa).
EtOAc/n-hexane = 1:4, RF = 0.4; White solid (25.3 mg, 93%); mp
115 – 117 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.90 (dd, J = 4.1,
1.8 Hz, 1H), 8.26 (dd, J = 8.3, 1.8 Hz, 1H), 7.91 (dd, J = 8.2, 1.5
Hz, 1H), 7.83 (d, J = 8.0 Hz, 2H), 7.79 – 7.73 (m, 3H), 7.67 –
7.63 (m, 1H), 7.46 (dd, J = 8.3, 4.1 Hz, 1H); 13C{1H} NMR (150
MHz, CD2Cl2) δ 150.8, 146.2, 144.0, 139.7, 136.7, 131.6, 130.6,
129.4 (q, J = 32.2 Hz), 129.2, 128.9, 126.7, 125.01 (q, J = 271.8
Hz), 124.99 (q, J = 3.7 Hz), 121.8; 19F NMR (564 MHz, CD2Cl2)
δ -62.66; IR (cm-1) 3069, 3046, 2953, 2918, 2849, 1586, 1322,
1107; HRMS (EI) m/z calcd. for C16H10F3N [M]+: 273.0765,
found: 273.0761.
6-Methoxy-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2,
7b). EtOAc/n-hexane = 1:4, RF = 0.5; White solid (24.1 mg, 80%);
mp 85 – 87 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.73 (dd, J = 4.1,
1.7 Hz, 1H), 8.14 (dd, J = 8.3, 1.6 Hz, 1H), 7.81 (d, J = 8.0 Hz,
2H), 7.74 (d, J = 8.1 Hz, 2H), 7.43 – 7.37 (m, 2H), 7.18 (d, J =
2.8 Hz, 1H), 3.97 (s, 3H); 13C{1H} NMR (100 MHz, CD2Cl2) δ
157.6, 148.2, 143.5, 142.5, 141.1, 135.4, 131. 5, 130.4, 129.5 (q,
J = 32.2 Hz), 124.98 (q, J = 3.8 Hz), 124.94 (q, J = 271.9 Hz),
123.1, 122.1, 106.1, 56.0; 19F NMR (564 MHz, CD2Cl2) δ -62.69;
IR (cm-1) 3077, 3022, 2938, 2836, 1608, 1597, 1322, 1212, 1148,
1105; HRMS (EI) m/z calcd. for C17H12F3NO [M]+: 303.0871,
found: 303.0868.
6-Methyl-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7c).
EtOAc/n-hexane = 1:4, RF = 0.7; White solid (20.1 mg, 70%); mp
103 – 105 °C; 1H NMR (400 MHz, CD2Cl2) δ 8.82 (dd, J = 4.1,
1.8 Hz, 1H), 8.16 (dd, J = 8.3, 1.8 Hz, 1H), 7.82 (d, J = 8.0 Hz,
2H), 7.74 (d, J = 8.1 Hz, 2H), 7.70 – 7.65 (m, 1H), 7.60 (d, J =
2.0 Hz, 1H), 7.41 (dd, J = 8.3, 4.1 Hz, 1H), 2.59 (s, 3H); 13C{1H}
NMR (100 MHz, CD2Cl2) δ 149.9, 144.8, 144.1, 139.3, 136.6,
136.0, 132.9, 131.5, 129.3 (q, J = 32.3 Hz), 129.2, 127.6, 125.00
(q, J = 271.8 Hz), 124.95 (q, J = 3.8 Hz), 121.7, 21.7; 19F NMR
(564 MHz, CD2Cl2) δ -62.66; IR (cm-1) 2959, 2922, 2854, 1739,
1616, 1593, 1574, 1486, 1321, 1160; HRMS (EI) m/z calcd. for
C17H12F3N [M]+: 287.0922, found: 287.0920.
6-Fluoro-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7g).
EtOAc/n-hexane = 1:10, RF = 0.4; White solid (20.9 mg, 72%);
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mp 100 – 102 °C; H NMR (600 MHz, CD2Cl2) δ 8.86 (dd, J =
4.0, 1.8 Hz, 1H), 8.21 (dd, J = 8.4, 1.8 Hz, 1H), 7.82 (d, J = 8.0
Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.58 – 7.51 (m, 2H), 7.47 (dd,
J = 8.4, 4.1 Hz, 1H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 160.2
(d, J = 247.5 Hz), 150.1 (d, J = 2.8 Hz), 143.5, 142.7, 142.5 (d, J
= 8.9 Hz), 136.2 (d, J = 5.5 Hz), 131.5, 130.1 (d, J = 10.2 Hz),
129.9 (q, J = 32.4 Hz), 125.1 (q, J = 3.8 Hz), 124.9 (q, J = 271.9
Hz), 122.5, 120.5 (d, J = 26.5 Hz), 111.4 (d, J = 21.3 Hz); 19F
NMR (564 MHz, CD2Cl2) δ -62.79 (s, 3F), -114.01 – -114.37 (m,
1F); IR (cm-1) 3080, 2922, 1610, 1497, 1395, 1318, 1164, 1118,
1067, 841; HRMS (EI) m/z calcd. for C16H9F4N [M]+: 291.0671,
found: 291.0668.
5-Chloro-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7h).
EtOAc/n-hexane = 1:4, RF = 0.7; White solid (22.9 mg, 75%); mp
94 – 96 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.95 (dd, J = 4.1, 1.7
Hz, 1H), 8.67 (dd, J = 8.5, 1.7 Hz, 1H), 7.79 (d, J = 8.1 Hz, 2H),
7.78 – 7.72 (m, 3H), 7.68 (d, J = 7.8 Hz, 1H), 7.57 (dd, J = 8.6,
4.1 Hz, 1H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 151.3, 146.8,
143.2, 139.1, 133.4, 131.8, 131.6, 130.3, 129.6 (q, J = 32.3 Hz),
127.0, 126.8, 125.1 (q, J = 3.8 Hz), 124.9 (q, J = 271.8 Hz), 122.5;
19F NMR (564 MHz, CD2Cl2) δ -62.73; IR (cm-1) 3069, 3049,
2959, 2920, 2851, 1615, 1320, 1120; HRMS (EI) m/z calcd. for
C16H9ClF3N [M]+: 307.0376, found: 307.0371.
4-Chloro-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7i).
EtOAc/n-hexane = 1:4, RF = 0.7; White solid (24.1 mg, 79%); mp
97 – 99 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.76 (d, J = 4.7 Hz,
1H), 8.34 (dd, J = 8.5, 1.5 Hz, 1H), 7.81 (dd, J = 7.2, 1.5 Hz, 1H),
7.79 (d, J = 8.3 Hz, 2H), 7.77 – 7.73 (m, 3H), 7.56 (d, J = 4.5 Hz,
1H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 150.1, 147.2, 143.7,
143.1, 140.3, 131.6, 131.6, 129.6 (q, J = 32.5 Hz), 127.7, 127.3,
125.0 (q, J = 3.8 Hz), 124.94 (q, J = 271.8 Hz), 124.94 (s), 121.9;
19F NMR (564 MHz, CD2Cl2) δ -62.71; IR (cm-1) 3112, 3073,
2918, 2851, 1496, 1317, 1107; HRMS (EI) m/z calcd. for
C16H9ClF3N [M]+: 307.0376, found: 307.0377.
6-Nitro-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7j).
EtOAc/n-hexane = 1:4, RF = 0.3; White solid (23.5 mg, 74%); mp
170 – 172 °C; 1H NMR (600 MHz, CD2Cl2) δ 9.08 (d, J = 2.5 Hz,
1H), 8.85 (s, 1H), 8.51 (d, J = 2.2 Hz, 1H), 8.46 (d, J = 8.3 Hz,
1H), 7.86 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.63 (dd,
J = 8.3, 4.1 Hz, 1H); 13C{1H} NMR (100 MHz, CD2Cl2) δ 154.1,
148.3, 145.5, 142.0, 141.8, 138.7, 131.6, 130.3 (q, J = 32.4 Hz),
128.2, 125.3 (q, J = 3.8 Hz), 125.0, 124.8 (q, J = 272.0 Hz), 123.6,
123.4; 19F NMR (564 MHz, CD2Cl2) -62.85; IR (cm-1) 3085, 1803,
1610, 1533, 1484, 1349, 1318, 1161, 1120, 1107; HRMS (EI) m/z
calcd. for C16H9F3N2O2 [M]+: 318.0616, found: 318.0617.
5-Nitro-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7k).
EtOAc/n-hexane = 1:4, RF = 0.5; Yellow solid (18.1 mg, 57%);
mp 161 – 163 °C; 1H NMR (600 MHz, CD2Cl2) δ 9.03 (d, J = 8.9
Hz, 1H), 9.01 (dd, J = 4.2, 1.5 Hz, 1H), 8.42 (d, J = 8.0 Hz, 1H),
7.84 (d, J = 8.0 Hz, 1H), 7.83 – 7.77 (m, 4H), 7.69 (dd, J = 8.9,
4.0 Hz, 1H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 151.8, 146.5,
146.2, 145.8, 142.4, 132.3, 131.6, 130.5 (q, J = 32.3 Hz), 128.8,
125.2 (q, J = 3.9 Hz), 124.8 (q, J = 271.9 Hz), 124.5, 124.3, 122.1;
19F NMR (564 MHz, CD2Cl2) δ -62.88; IR (cm-1) 3067, 2959,
2920, 2851, 1617, 1322, 1095; HRMS (EI) m/z calcd. for
C16H9F3N2O2 [M]+: 318.0616, found: 318.0613.
7-Methyl-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7d).
EtOAc/n-hexane = 1:10, RF = 0.4; White solid (19.6 mg, 68%);
1
mp 114 – 116 °C; H NMR (400 MHz, CD2Cl2) δ 8.77 (dd, J =
4.2, 1.8 Hz, 1H), 8.19 (dd, J = 8.2, 1.8 Hz, 1H), 7.82 (d, J = 8.4
Hz, 1H), 7.76 (d, J = 7.9 Hz, 2H), 7.53 (d, J = 8.4 Hz, 1H), 7.45
(d, J = 7.8 Hz, 2H), 7.36 (dd, J = 8.2, 4.2 Hz, 1H), 2.31 (s, 3H);
13C{1H} NMR (100 MHz, CD2Cl2) δ 150.5, 147.4, 144.0, 138.6,
137.8, 136.1, 131.4, 129.8, 129.1 (q, J = 32.2 Hz), 127.8, 127.0,
125.2 (q, J = 3.7 Hz), 125.0 (q, J = 271.8 Hz), 120.7, 21.1; 19F
NMR (564 MHz, CD2Cl2) δ -62.58; IR (cm-1) 3053, 3006, 2923,
2853, 1607, 1318, 1106; HRMS (ESI) m/z calcd. for C17H12F3N
[M+H]+: 288.0995, found: 288.0993.
6-Bromo-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7e).
EtOAc/n-hexane = 1:4, RF = 0.6; White solid (31.7 mg, 90%); mp
110 – 112 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.90 (dd, J = 4.1,
1.8 Hz, 1H), 8.17 (dd, J = 8.3, 1.7 Hz, 1H), 8.07 (d, J = 2.2 Hz,
1H), 7.84 (d, J = 2.2 Hz, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.76 (d, J
= 8.2 Hz, 2H), 7.48 (dd, J = 8.3, 4.1 Hz, 1H); 13C{1H} NMR (150
MHz, CD2Cl2) δ 151.1, 145.0, 142.5, 141.7, 135.8, 133.6, 131.5,
130.6, 130.4, 129.9 (q, J = 32.3 Hz), 125.1 (q, J = 3.8 Hz), 124.9
(q, J = 272.0 Hz), 122.6, 120.3; 19F NMR (564 MHz, CD2Cl2) δ -
62.77; IR (cm-1) 3071, 2925, 1615, 1586, 1482, 1415, 1322, 1158,
1105, 1066; HRMS (EI) m/z calcd. for C16H9BrF3N [M]+:
350.9870, found: 350.9866.
6-Chloro-8-[4-(trifluoromethyl)phenyl]quinoline (Table 2, 7f).
EtOAc/n-hexane = 1:4, RF = 0.6; White solid (21.5 mg, 70%); mp
115 – 117 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.89 (dd, J = 4.1,
1.8 Hz, 1H), 8.17 (dd, J = 8.3, 1.8 Hz, 1H), 7.89 (d, J = 2.4 Hz,
1H), 7.81 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.1 Hz, 2H), 7.71 (d, J
4-[4-(Trifluoromethyl)phenyl]acridine (Table 2, 7l). EtOAc/n-
hexane = 1:5, RF = 0.6; Yellow solid (13.8 mg, 43%); mp 147 –
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149 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.88 (s, 1H), 8.12 – 8.10
141.3, 136.5, 131.5, 129.8 (q, J = 32.3 Hz), 129.6, 125.8, 125.1
(q, J = 3.8 Hz), 124.9 (q, J = 271.8 Hz), 122.3, 119.3, 21.4; 19F
NMR (564 MHz, CD2Cl2) δ -62.76; IR (cm-1) 3051, 2918, 1683,
1609, 1576, 1318, 1248, 1157, 1103, 1060; HRMS (EI) m/z calcd.
for C18H12F3NO2 [M]+: 331.0820, found: 331.0821.
(m, 2H), 8.07 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 7.9 Hz, 2H), 7.84
(d, J = 6.8 Hz, 1H), 7.82 – 7.75 (m, 3H), 7.66 – 7.63 (m, 1H), 7.59
– 7.57 (m, 1H); 13C{1H} NMR (100 MHz, CD2Cl2) δ 149.3, 147.0,
144.0, 139.3, 136.6, 131.7, 131.3, 130.6, 130.2, 129.34 (q, J =
32.1 Hz), 129.33, 128.5, 127.3, 126.9, 126.5, 125.8, 125.1 (q, J =
272.0 Hz), 125.0 (q, J = 3.8 Hz); 19F NMR (564 MHz, CD2Cl2) -
62.62; IR (cm-1) 3054, 3039, 2930, 1929, 1613, 1525, 1409, 1326,
1164, 1106; HRMS (EI) m/z calcd. for C20H12F3N [M]+: 323.0922,
found: 323.0924.
4-[4-(Trifluoromethyl)phenyl]phenanthridine (Table 2, 7m).
EtOAc/n-hexane = 1:4, RF = 0.7; White solid (17.6 mg, 54%); mp
163 – 165 °C; 1H NMR (600 MHz, CD2Cl2) δ 9.26 (s, 1H), 8.73
– 8.67 (m, 2H), 8.08 (dd, J = 7.9, 1.4 Hz, 1H), 7.92 (ddd, J = 8.4,
7.1, 1.3 Hz, 1H), 7.83 (d, J = 8.0 Hz, 2H), 7.81 – 7.74 (m, 5H);
13C{1H} NMR (150 MHz, CD2Cl2) δ 153.7, 144.7, 142.2, 140.5,
132.9, 131.7, 131.5, 130.2, 129.3 (q, J = 32.3 Hz), 129.1, 128.3,
127.1, 126.7, 125.0 (q, J = 271.8 Hz), 124.93 (q, J = 4.0 Hz),
124.93 (s), 123.1, 122.5; 19F NMR (564 MHz, CD2Cl2) δ -62.62;
IR (cm-1) 3089, 3036, 2959, 2925, 2851, 1613, 1315, 1118;
HRMS (EI) m/z calcd. for C20H12F3N [M]+: 323.0922, found:
323.0918.
5-[4-(Trifluoromethyl)phenyl]benzo[f]quinoline (Table 2, 7n).
EtOAc/n-hexane = 1:4, RF = 0.4; White solid (21.4 mg, 66%); mp
95 – 97 °C; 1H NMR (600 MHz, CD2Cl2) δ 9.10 – 9.05 (m, 1H),
8.93 (dd, J = 4.2, 1.6 Hz, 1H), 8.71 (d, J = 8.2 Hz, 1H), 8.04 (s,
1H), 8.01 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 –
7.74 (m, 3H), 7.74 – 7.69 (m, 1H), 7.63 (dd, J = 8.4, 4.2 Hz, 1H);
13C{1H} NMR (100 MHz, CD2Cl2) δ 149.7, 146.5, 144.1, 138.1,
131.8, 131.6, 131.49, 131.47, 130.2, 129.4 (q, J = 32.2 Hz), 129.3,
128.2, 127.9, 126.2, 125.01 (q, J = 3.9 Hz), 124.99 (q, J = 271.9
Hz), 123.0, 121.9; 19F NMR (564 MHz, CD2Cl2) -62.65; IR (cm-
1) 3066, 2960, 2926, 2849, 2088, 1919, 1703, 1686, 1615, 1321;
HRMS (EI) m/z calcd. for C20H12F3N [M]+: 323.0922, found:
323.0917.
1-{8-[4-(Trifluoromethyl)phenyl]quinolin-3-yl)ethan-1-one
(Table 2, 7o). EtOAc/n-hexane = 1:4, RF = 0.2; White solid (24.9
mg, 79%); mp 141 – 143 °C; 1H NMR (600 MHz, CD2Cl2) δ 9.38
(d, J = 2.2 Hz, 1H), 8.78 (d, J = 2.3 Hz, 1H), 8.04 (dd, J = 8.1, 1.5
Hz, 1H), 7.88 (dd, J = 7.2, 1.5 Hz, 1H), 7.82 (d, J = 8.0 Hz, 2H),
7.76 (d, J = 8.1 Hz, 2H), 7.73 (dd, J = 8.2, 7.1 Hz, 1H), 2.73 (s,
3H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 197.0, 149.4, 147.6,
143.3, 139.8, 137.9, 133.0, 131.5, 130.3, 129.8, 129.6 (q, J = 32.2
Hz), 127.8, 127.7, 125.1 (q, J = 3.8 Hz), 124.9 (q, J = 272.0 Hz),
27.1; 19F NMR (564 MHz, CD2Cl2) δ -62.72; IR (cm-1) 3050,
2922, 2852, 1682, 1607, 1574, 1317, 1248, 1159, 1107; HRMS
(EI) m/z calcd. for C18H12F3NO [M]+: 315.0871, found: 315.0869.
Methyl 8-[4-(trifluoromethyl)phenyl]quinoline-6-carboxylate
(Table 2, 7p). EtOAc/n-hexane = 1:4, RF = 0.3; White solid (24.9
mg, 75%); mp 164 – 166 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.98
(dd, J = 4.1, 1.9 Hz, 1H), 8.63 (d, J = 2.0 Hz, 1H), 8.36 (dd, J =
8.3, 1.8 Hz, 1H), 8.33 (d, J = 2.0 Hz, 1H), 7.84 (d, J = 7.9 Hz,
2H), 7.76 (d, J = 7.9 Hz, 2H), 7.52 (dd, J = 8.3, 4.1 Hz, 1H), 4.00
(s, 3H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 166.7, 152.8, 148.0,
143.2, 140.1, 138.1, 131.6, 131.5, 129.9, 129.7 (q, J = 32.5 Hz),
128.5, 128.3, 125.1 (q, J = 3.9 Hz), 124.9 (q, J = 271.7 Hz), 122.5,
52.8; 19F NMR (564 MHz, CD2Cl2) δ -62.73; IR (cm-1) 3067,
2954, 2846, 1725, 1613, 1490, 1328, 1249, 1169, 1096, 1067;
HRMS (EI) m/z calcd. for C18H12F3NO2 [M]+: 331.0820, found:
331.0816.
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8-[4-(Trifluoromethyl)phenyl]quinoline-6-carbaldehyde
(Table 2, 7r). EtOAc/n-hexane = 1:4, RF = 0.3; White solid (22.4
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mg, 74%); mp 100 – 102 °C; H NMR (400 MHz, CD2Cl2) δ
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10.23 (s, 1H), 9.03 (dd, J = 4.2, 1.8 Hz, 1H), 8.42 (dd, J = 8.3, 1.8
Hz, 2H), 8.21 (d, J = 1.8 Hz, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.77
(d, J = 8.1 Hz, 2H), 7.57 (dd, J = 8.3, 4.1 Hz, 1H); 13C{1H} NMR
(100 MHz, CD2Cl2) δ 191.7, 153.4, 148.8, 143.0, 141.0, 138.2,
134.4, 134.2, 131.6, 129.9 (q, J = 32.3 Hz), 128.8, 127.4, 125.1
(q, J = 3.8 Hz), 124.9 (q, J = 271.9 Hz), 122.8; 19F NMR (376
MHz, CD2Cl2) -62.68; IR (cm-1) 3042, 2928, 2853, 1738, 1687,
1616, 1492, 1422, 1324, 1104; HRMS (EI) m/z calcd. for
C17H10F3NO [M]+: 301.0714, found: 301.0709.
6-(1,3-Dioxolan-2-yl)-8-[4-(trifluoromethyl)phenyl]quinoline
(Table 2, 7s). EtOAc/n-hexane = 1:4, RF = 0.3; White solid (23.2
mg, 67%); mp 112 – 114 °C; 1H NMR (400 MHz, CD2Cl2) δ 8.91
(dd, J = 4.1, 1.8 Hz, 1H), 8.28 (dd, J = 8.3, 1.7 Hz, 1H), 8.00 (d,
J = 1.7 Hz, 1H), 7.89 – 7.81 (m, 3H), 7.76 (d, J = 8.2 Hz, 2H),
7.47 (dd, J = 8.3, 4.2 Hz, 1H), 6.01 (s, 1H), 4.22 – 4.05 (m, 4H);
13C{1H} NMR (100 MHz, CD2Cl2) δ 151.2, 146.6, 143.8, 140.1,
137.0, 136.6, 131.6, 129.5 (q, J = 32.3 Hz), 128.8, 128.7, 126.9,
124.99 (q, J = 3.8 Hz), 124.98 (q, J = 271.9 Hz), 122.0, 103.7,
66.0; 19F NMR (376 MHz, CD2Cl2) δ -62.62; IR (cm-1) 3066,
2986, 2954, 2926, 2899, 2876, 1616, 1492, 1323, 1158; HRMS
(EI) m/z calcd. for C19H14F3NO2 [M]+: 345.0977, found: 345.0972.
8-[4-(Trifluoromethyl)phenyl]-6-
[(triisopropylsilyl)oxy]quinoline (Table 2, 7t). EtOAc/n-hexane =
1
1:4, RF = 0.8; Yellow oil (25.9 mg, 58%); H NMR (600 MHz,
CD2Cl2) δ 8.74 (dd, J = 4.1, 1.8 Hz, 1H), 8.09 (dd, J = 8.3, 1.8
Hz, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.75 (d, J = 8.0 Hz, 2H), 7.41
(d, J = 2.7 Hz, 1H), 7.38 (dd, J = 8.3, 4.1 Hz, 1H), 7.26 (d, J = 2.8
Hz, 1H), 1.37 (hept, J = 7.5 Hz, 3H), 1.17 (d, J = 7.5 Hz, 18H);
13C{1H} NMR (150 MHz, CD2Cl2) δ 154.1, 148.5, 143.7, 142.4,
141.2, 135.4, 131.5, 130.5, 129.5 (q, J = 32.2 Hz), 126.5, 125.02
(q, J = 3.8 Hz), 124.94 (q, J = 271.8 Hz), 121.9, 114.8, 18.2, 13.2;
19F NMR (564 MHz, CD2Cl2) δ -62.69; 29Si NMR (119 MHz,
CD2Cl2) δ 17.22; IR (cm-1) 2946, 2867, 1610, 1597, 1487, 1460,
1323, 1219, 1166, 1122; HRMS (EI) m/z calcd. for
C25H30F3NOSi [M]+: 445.2049, found: 445.2047.
N-{8-[4-(Trifluoromethyl)phenyl]quinolin-6-yl}acetamide
(Table 2, 7u). EtOAc/n-hexane = 1:1, RF = 0.2; White solid (20.4
mg, 62%); mp 95 – 97 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.79
(dd, J = 4.0, 1.9 Hz, 1H), 8.32 (d, J = 2.4 Hz, 1H), 8.15 (dd, J =
8.3, 1.8 Hz, 1H), 7.95 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.69 (d, J
= 8.0 Hz, 2H), 7.64 (d, J = 2.4 Hz, 1H), 7.41 (dd, J = 8.3, 4.1 Hz,
1H), 2.21 (s, 3H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 169.2,
149.6, 143.5, 143.3, 140.4, 136.4, 136.3, 131.4, 129.8, 129.6 (q,
J = 32.3 Hz), 125.0 (q, J = 3.9 Hz), 124.9 (q, J = 271.9 Hz), 124.2,
122.2, 116.7, 24.8; 19F NMR (564 MHz, CD2Cl2) δ -62.72; IR
(cm-1) 3272, 3075, 1669, 1542, 1370, 1321, 1158, 1109, 1064,
839; HRMS (EI) m/z calcd. for C18H13F3N2O [M]+: 330.0980,
found: 330.0977.
8-(4-Bromophenyl)quinoline (Table 2, 7ab). EtOAc/n-hexane
= 1:4, RF = 0.5; Off-white solid (21.5 mg, 95%); mp 97 – 99 °C;
1H NMR (600 MHz, CD2Cl2) δ 8.91 (dd, J = 4.1, 1.8 Hz, 1H),
8.24 (dd, J = 8.2, 1.8 Hz, 1H), 7.88 (dd, J = 8.2, 1.5 Hz, 1H), 7.73
(dd, J = 7.2, 1.5 Hz, 1H), 7.68 – 7.60 (m, 3H), 7.59 (d, J = 10.7
Hz, 2H), 7.45 (dd, J = 8.2, 4.1 Hz, 1H); 13C{1H} NMR (150 MHz,
CD2Cl2) δ 150.6, 146.2, 139.9, 139.1, 136.6, 132.9, 131.2, 130.3,
129.1, 128.4, 126.7, 121.7, 121.6; IR (cm-1) 3046, 2927, 2846,
1590, 1489, 1070, 1002, 958, 818, 792; HRMS (EI) m/z calcd.
for C15H10BrN [M]+: 282.9997, found: 282.9995.
8-[4-(Trifluoromethyl)phenyl]quinolin-6-yl acetate (Table 2,
7q). EtOAc/n-hexane = 1:4, RF = 0.3; White solid (17.3 mg, 52%);
mp 78 – 80 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.88 (dd, J = 4.0,
1.7 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.9 Hz, 2H),
7.75 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 1.4 Hz, 1H), 7.52 (d, J = 1.3
Hz, 1H), 7.47 (dd, J = 8.5, 4.1 Hz, 1H), 2.37 (s, 3H); 13C{1H}
NMR (150 MHz, CD2Cl2) δ 169.7, 150.6, 148.5, 144.3, 143.0,
8-(4-Chlorophenyl)quinoline (Table 2, 7ac). EtOAc/n-hexane
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= 1:4, RF = 0.5; White solid (21.3 mg, 89%); mp 95 – 97 °C; 1H
NMR (600 MHz, CD2Cl2) δ 8.91 (dd, J = 4.1, 1.8 Hz, 1H), 8.25
(dd, J = 8.3, 1.8 Hz, 1H), 7.88 (dd, J = 8.2, 1.5 Hz, 1H), 7.73 (dd,
J = 7.2, 1.5 Hz, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.64 – 7.61 (m,
1H), 7.47 (d, J = 8.4 Hz, 2H), 7.45 (dd, J = 8.7, 4.5 Hz, 1H);
13C{1H} NMR (150 MHz, CD2Cl2) δ 150.6, 146.3, 139.9, 138.7,
136.6, 133.5, 132.5, 130.4, 129.2, 128.4, 128.3, 126.7, 121.6; IR
(cm-1) 3044, 1594, 1577, 1489, 1458, 1185, 1083, 1013, 960, 819,
789; HRMS (EI) m/z calcd. for C15H10ClN [M]+: 239.0502, found:
239.0499.
Ethyl 4-(quinolin-8-yl)benzoate (Table 2, 7ad). EtOAc/n-
hexane = 1:4, RF = 0.5; White solid (21.8 mg, 79%); mp 91 –
93 °C; 1H NMR (600 MHz, CD2Cl2) δ 8.92 (dd, J = 4.1, 1.8 Hz,
1H), 8.26 (dd, J = 8.2, 1.9 Hz, 1H), 8.15 (d, J = 8.4 Hz, 2H), 7.91
(dd, J = 8.2, 1.5 Hz, 1H), 7.81 – 7.75 (m, 3H), 7.65 (dd, J = 8.2,
7.1 Hz, 1H), 7.46 (dd, J = 8.3, 4.1 Hz, 1H), 4.42 (q, J = 7.1 Hz,
2H), 1.43 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (150 MHz, CD2Cl2)
δ 166.8, 150.7, 146.3, 144.8, 140.2, 136.6, 131.2, 130.6, 129.7,
129.2, 129.1, 128.7, 126.6, 121.7, 61.3, 14.6; IR (cm-1) 3045,
2977, 2900, 1712, 1612, 1495, 1362, 1266, 1190, 1101, 792 ;
HRMS (EI) m/z calcd. for C18H15NO2 [M]+: 277.1103, found:
277.1102.
8-(4-Nitrophenyl)quinoline (Table 2, 7ae). EtOAc/n-hexane =
1:4, RF = 0.5; Yellow solid (18.7 mg, 75%); mp 167 – 169 °C; 1H
NMR (600 MHz, CD2Cl2) δ 8.91 (dd, J = 4.1, 1.8 Hz, 1H), 8.32
(d, J = 8.7 Hz, 2H), 8.28 (dd, J = 8.2, 1.8 Hz, 1H), 7.95 (dd, J =
8.1, 1.5 Hz, 1H), 7.90 (d, J = 8.7 Hz, 2H), 7.79 (dd, J = 7.1, 1.6
Hz, 1H), 7.69 – 7.65 (m, 1H), 7.49 (dd, J = 8.3, 4.1 Hz, 1H);
13C{1H} NMR (150 MHz, CD2Cl2) δ 150.9, 147.4, 147.0, 146.0,
138.8, 136.7, 132.1, 130.7, 129.4, 129.2, 126.7, 123.2, 121.9; IR
(cm-1) 3101, 3049, 2920, 1596, 1511, 1337, 1107, 965, 852, 796;
HRMS (EI) m/z calcd. for C15H10N2O2 [M]+: 250.0742, found:
250.0740.
8-(p-Tolyl)quinoline (Table 2, 7af). EtOAc/n-hexane = 1:4, RF
= 0.5; Yellow oil (8.8 mg, 40%); 1H NMR (600 MHz, CD2Cl2) δ
8.90 (dd, J = 4.1, 1.8 Hz, 1H), 8.23 (dd, J = 8.3, 1.8 Hz, 1H), 7.85
(dd, J = 8.2, 1.5 Hz, 1H), 7.72 (dd, J = 7.1, 1.5 Hz, 1H), 7.61 (dd,
J = 8.2, 7.1 Hz, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.43 (dd, J = 8.3,
4.1 Hz, 1H), 7.30 (d, J = 7.7 Hz, 2H), 2.45 (s, 3H); 13C{1H} NMR
(150 MHz, CD2Cl2) δ 150.4, 146.6, 141.3, 137.4, 137.3, 136.5,
131.0, 130.3, 129.1, 128.8, 127.7, 126.6, 121.4, 21.3; IR (cm-1)
3048, 3025, 3003, 2920, 2861, 1594, 1495, 1465, 1379, 818, 792;
HRMS (EI) m/z calcd. for C16H13N [M]+: 219.1048, found:
219.1044.
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Procedure for the Reaction Profile Investigation on the Ru-
Catalyzed Deoxygenative C8-Arylation (Scheme 3a).
A
mixture of 3a (216 mg, 1.00 mmol), Ag2O (255 mg, 1.10 mmol),
and Cu(ClO4)2·6H2O (18.5 mg, 0.500 mmol) in THF/TFE (1:2,
2.5 mL) was stirred at 25 °C for 30 min. In another flask, a
mixture of [(p-cymene)RuCl2]2 (15.5 mg, 0.0250 mmol) and
AgOTs (29.0 mg, 0.100 mmol) in THF/TFE=1:2 (2.5 mL) was
stirred at 25 °C for 30 min. To the first mixture were added 1a
(72.5 mg, 0.500 mmol) and the solution from the second flask
were added sequentially. The reaction mixture was stirred in a
preheated oil bath at 50 °C. At selected time points, 100 μL of the
reaction mixture was sampled and the reaction progress was
determined by 19F NMR spectroscopy using 3,5-
bis(trifluoromethyl)benzamide as the internal standard.
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Procedure for the Kinetic Isotope Effect Experiment
(Scheme 3b). A mixture of 3a (216 mg, 1.00 mmol), Ag2O (255
mg, 1.10 mmol), and Cu(ClO4)2·6H2O (18.5 mg, 0.500 mmol) in
THF/TFE (1:2, 2.5 mL) was stirred at 25 °C for 30 min. In another
flask, a mixture of [(p-cymene)RuCl2]2 (15.5 mg, 0.0250 mmol)
and AgOTs (29.0 mg, 0.100 mmol) in THF/TFE (1:2, 2.5 mL)
was stirred at 25 °C for 30 min. To the first mixture were
sequentially added 1a (72.5 mg, 0.500 mmol) or 1a-d7 (76.0 mg,
0.500 mmol) and the solution from the second flask. The reaction
mixture was stirred in a preheated oil bath at 50 °C. 100 μL
portion of the reaction mixture was sampled every 5 minutes for
2.5 h. The initial reaction progress was monitored by 19F NMR
spectroscopy using 3,5-bis(trifluoromethyl)benzamide as the
internal standard. The sum of 7aa and 8aa (or 7aa-d6 and 8aa-d6)
was plotted and the initial rate of the arylation on 1a and 1a-d7
was determined by linear fitting of the initial five points from
each reaction profile. The initial rate for the C–H arylation was
found to be 1.57 mM/min and 1.54 mM/min for 1a and 1a-d7,
respectively, yielding KIE value 1.02.
General Procedure for the Condition Screening on Ru-
Catalyzed Deoxygenation (Scheme 4a). A mixture of [(p-
cymene)RuCl2]2 (3.1 mg, 0.0050 mmol) and AgOTs (5.8 mg,
0.020 mmol) in THF/TFE (1:2, 0.5 mL) was stirred at 25 °C for
30 min. To the solution was added 8aa (28.9 mg, 0.100 mmol)
and the reaction mixture was stirred in a preheated heating mantle
at 50 °C for 14 h. The mixture was cooled to 25 °C and
concentrated under reduced pressure. The yield of 7aa was
determined by 1H NMR spectroscopy using 1,1,2,2-
tetrachloroethane as the internal standard.
8-(4-Methoxyphenyl)quinoline (Table 2, 7ag). EtOAc/n-
1
hexane = 1:3, RF = 0.5; Colorless oil (9.1 mg, 39%); H NMR
(400 MHz, CD2Cl2) δ 8.90 (d, J = 4.1 Hz, 1H), 8.23 (d, J = 8.2
Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 7.1 Hz, 1H), 7.66
– 7.56 (m, 3H), 7.43 (dd, J = 8.3, 4.1 Hz, 1H), 7.03 (d, J = 8.5 Hz,
2H), 3.88 (s, 3H); 13C{1H} NMR (150 MHz, CD2Cl2) δ 159.5,
150.3, 146.5, 140.8, 136.6, 132.5, 132.2, 130.2, 129.2, 127.5,
126.7, 121.4, 113.6, 55.7; IR (cm-1) 3034, 3002, 2936, 2898, 2834,
1609, 1513; HRMS (ESI) m/z calcd. for C16H13NO [M+Na]+:
258.0889, found: 258.0889.
Procedure for the Reaction Byproduct Analysis (Scheme
4b). A mixture of [(p-cymene)RuCl2]2 (3.1 mg, 0.0050 mmol)
and AgOTs (5.8 mg, 0.020 mmol) in THF-d8/TFE (10:1, 0.5 mL)
was stirred at 25 °C for 30 min. The solution was added to 8aa
(28.9 mg, 0.100 mmol) placed in a J-Young tube. The reaction
mixture was heated in a preheated oil bath at 50 °C for 2 h. The
1H and 19F crude NMR was compared with 10, which was
separately prepared by dissolving 918 in THF-d8/TFE (10:1, 0.5
mL).
General Procedure for the Gram-Scale Arylation.
A
mixture of [(p-cymene)RuCl2]2 (306 mg, 0.500 mmol) and
AgOTs (558 mg, 2.00 mmol) in THF/TFE (1:2, 60 mL) was
stirred at 25 °C for 30 min. To the solution were added 1a (1.45
g, 10.0 mmol), 3a (4.32 g, 20.0 mmol), Ag2O (5.10 g, 22.0 mmol),
and Cu(ClO4)2·6H2O (371 mg, 1.00 mmol) and the reaction
mixture was stirred in a preheated heating mantle at 50 °C for 36
h. The mixture was cooled to 25 °C, diluted with EtOAc (100 mL),
quenched with sat. aq. Na2CO3 (100 mL), and extracted with
EtOAc (100 mL x 3). The combined organic layer was dried over
MgSO4, concentrated, and purified by SiO2 column
chromatography to obtain the product (2.01 g, 74%).
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publication website
NMR spectra for products, and detailed experimental
procedure for the mechanistic studies (PDF)
Crystallographic data of Ru-A, Ru-B, and 7n (CIF)
AUTHOR INFORMATION
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Corresponding Authors
*sbchang@kaist.ac.kr
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Quinoline N-Oxides: Insights into the Electronic, Steric, and
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ORCID
Sukbok Chang: 0000-0001-9069-0946
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGEMENTS
This research was supported by the Institute for Basic Science
(IBS-R010-D1) in Korea.
Single crystal x-ray diffraction experiment with synchrotron
radiation were performed at the BL2D-SMC in Pohang
Accelerator Laboratory.
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