Visible-Light-Induced Photocatalytic Aerobic Oxidative Csp3-H Functionalization of Glycine Derivatives: Synthesis of Substituted Quinolines

Article abstract of DOI:10.1021/acs.joc.6b02683

A visible-light induced photocatalytic aerobic oxidative dehydrogenative coupling/aromatization tandem reaction of glycine esters with unactivated alkenes has been accomplished. This visible light-driven protocol has been successfully applied to a broad s

Full text of DOI:10.1021/acs.joc.6b02683

Article
Visible-Light-Induced Photocatalytic Aerobic Oxidative Csp3-H
Functionalization of Glycine Derivatives: Synthesis of Substituted Quinolines
Xiaorong Yang, Liqi Li, Ying Li, and Yuan Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02683 • Publication Date (Web): 18 Nov 2016
Downloaded from http://pubs.acs.org on November 19, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Visible-Light-Induced Photocatalytic Aerobic Oxidative Csp3−H
Functionalization of Glycine Derivatives: Synthesis of Substituted
Quinolines
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
Xiaorong Yang, Liqi Li, Ying Li,* and Yuan Zhang*
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou
University, 222 Tianshui South Road, Lanzhou 730000, P. R. China
E-mail: zhangyuan@lzu.edu.cn; liying@lzu.edu.cn.
Abstract：
R4
R3
N
R3
0.5 mol% Ru(bpy)3Cl2·6H2O
10 mol% Cu(OTf)2
R4
O
R1
H
R1
OR2
CH3CN, rt, air
3W blue LED
OR2
N
H
O
38 examples, 18-84% yield
A visible-light induced photocatalytic aerobic oxidative dehydrogenative coupling/aromatization tandem reaction
of glycine esters with unactivated alkenes has been accomplished. This visible light-driven protocol has been
successfully applied to a broad scope of glycine esters and simple alkenes, giving rise to diverse substituted
quinoline derivatives in 18-84% yield under mild (at room temperature under air atmosphere) and operationally
simple reaction conditions.
Introduction
The direct oxidative cross-dehydrogenative coupling (CDC) of two C−H bonds has long been considered an
efficient and straightforward synthetic protocol for the construction of C−C bonds.1 This type of reaction is more
atom economical and environmentally friendly than traditional cross-coupling reactions, as it avoids the tedious
prefunctionalization and defunctionalization procedures, and thus largely reduces the number of reaction steps. In
this context, since the pioneering study of Li,2 the direct oxidative Csp3−H functionalization of glycine derivatives
has gained widespread attention from the chemists.3 In general, the active iminium ions are recognized to be the
key intermediates for these types of reactions (Scheme 1), which are subsequently trapped with appropriate
nucleophiles to furnish a large array of α-substituted α-amino acid derivatives (path a).3 Recently, an alternative
strategy has been disclosed whereby the iminium intermediates were captured by olefins (path b). This strategy
offers rapid access to the convenient synthesis of quinoline derivatives,4-7 which are common subunits in a wide
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 20
1
2
3
Scheme 1. Oxidative Functionalization of Glycine Derivatives.
4
5
6
7
H
Nu
R1
Nu
R1
[o]
R1
OR2
OR2
OR2
N
N
path a
N
H
H
O
O
O
R3
8
path b
9
R3
R3
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
[o]
R1
R1
OR2
OR2
N
N
H
O
O
range of bioactive natural products and pharmaceuticals.8 The first example of this oxidative dehydrogenative
coupling/aromatization tandem reaction was reported by Mancheño and coworkers in 2011,4 who synthesized a
variety of substituted quinolines from glycine derivatives using FeCl3 as the Lewis acid catalyst and a
stoichiometric amount of TEMPO oxoammonium salt as the oxidant. However, from economical and
environmental prospectives, the use of molecular oxygen as a “green” oxidant is undoubtedly more attractive. In
this regard, In 2012, Jia et al reported the same tandem process via an aerobic C−H functionalization of glycine
derivatives in the presence of radical cation salts and InCl3 using pure O2 as the sole oxidant.5a In 2014, Huo et al
developed an auto-oxidation coupling system for this reaction using air as the sole oxidant.6a However, under these
conditions, the substrate scope was limited to high electron-rich alkenes, and only moderate yield could be
obtained. Later, the same group disclosed that 1 equiv of CBr4 can also promote this transformation under air
atomosphere.6b Very recently, Liu et al reported the Cu(II)-catalyzed aerobic oxidative C−H functionalization of
glycine derivatives with olefins, employing NHPI as the co-catalyst and O2 as the oxidant.7 Though significant
progress have been made in this oxidative dehydrogenative coupling/aromatization tandem process, however, most
of the reactions employed stoichiometric amount of oxidants or pure O2 as the oxidant, and some of them were
undertaken at relative high temperature. Therefore, from environmental and practical standpoints, the development
of new sustainable and green catalytic versions and milder conditions (eg. under air atmosphere and at ambient
temperature) for this type of reaction, is still highly desired.
On the other hand, the application of visible light-induced photoredox catalysis in organic synthesis has
attracted great interest in recent years, because visible light is natural abundance, environmentally benign,
renewability, and ease of handle.9 In particular, photoredox catalysis recently has emerged as powerful tools to
initiate CDC reactions.9d,10 The majority of such photocatalytic CDC reactions are focused on the oxidative
coupling of C−H bonds in tertiary amines, such as tetrahydroisoquinolines,10 whereas only very few examples
have been reported involving the C−H functionalization of secondary amines,11 probably due to the relative higher
oxidation potential of the latter. Recently, efforts from the groups of Li,11a Rueping,11b and Wu11c have
2
ACS Paragon Plus Environment

Page 3 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
demonstrated that aerobic visible-light catalysis is capable for the formation of iminium intermediate from glycine
ester. Inspired by these results, we envisaged that this in situ generated iminium intermediate might be captured by
alkenes to give quinoline derivatives. Herein, we present a new direct photocatalytic aerobic oxidative
dehydrogenative coupling/aromatization tandem reaction of glycine esters and unactivated alkenes under mild
conditions.
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
Results and Discussion
We initiated our studies using glycine ester 1a and styrene 2a as model substrates to explore the reaction
conditions (Table 1, for details see supporting information). To our delight, the desired product 3a was obtained in
70% yield within 4h using 1 mol% Ru(bpy)3(PF6)2 as photocatalyst in combination with 10 mol% Cu(OTf)2 as the
Lewis acid cocatalyst in CH3CN under the irradiation of a 3W blue LED bulb (entry 1). A brief screen of several
photocatalysts revealed that Ru(bpy)3Cl2ꢀ6H2O was most effective in this protocol (entries 2–4), affording 3a in 75%
yield after 4h. We also examined other Lewis acids, and found that Cu(OTf)2 led to optimal yields (entries 5–8).
An evaluation of a variety of solvents identified CH3CN as the optimal medium (entries 9−11). Importantly, the
photocatalyst loading could be decreased to 0.5 mol% with no effect on the catalytic efficiency (entry 12), and this
level of efficiency was only slightly decreased with the photocatalyst loading further reduced to 0.1 mol% (entry
13). Tuning the light source to a 26 W fluorescent lamp, the reaction proceeded to completion, albeit at a slower
rate than reactions irradiated with blue LED (entry 14). Gratifyingly, this reaction also proceeded smoothly under
the irradiation of sun light, affording 3a in 74% yield after 6h (entry 15). This result demonstrates the potential
utility of this protocol. Moreover, molecular oxygen was found to play an important role in this system, and none
of the desired product 3a was observed when the reaction was carried out under Ar atmosphere (entry 16). Finally,
control studies indicated the essential roles of light, photocatalyst, and Cu catalyst in this transformation (entries
17–19).
Having identified the optimal conditions for this tandem protocol, we next focused on examining the scope of
the alkene component (Table 2). To our delight, an extensive range of electronically modified styrenes with
substituted groups at the ortho, meta, and para positions of benzene rings readily coupled with glycine esters 1a or
1b, affording the corresponding substituted quinoline derivatives 3b-3k in 64-82% yield. Notably, potentially
reactive chloro substituents at the benzene rings are well tolerated with this mild oxidation system, which afford a
handle for further modification. The use of naphthyl ethylenes as the substrates gave similar results (3l, 3l’).
Remarkably, 1,2-disubstituted alkenes were also suitable for this reaction, for example, 1,2-dihydronaphthalene
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 20
1
2
3
4
5
6
7
8
9
and propenylbenzene reacted smoothly with glycine esters, leading to trisubstituted quinolines 3m, 3m’ and 3n in
moderate yields, although a higher Lewis acid loading was required for optimal rate. To further demonstrate the
generality of this tandem protocol, we also examined other alkenes beyond the realm of styrene derivatives.
Gratifyingly, aliphatic alkenes can be readily utilized in this procedure to build quinolines directly, albeit the yields
were decreased compared to those of the styrene derivatives (3o-3q). Interestingly, when vinyl acetate was used as
the substrate, a 4-unsubstituted quinoline was obtained (3q).12e However, alkenes with strong electron-withdrawing
substituents, such as methyl acrylate and acrylonitrile, were not suitable substrates for this tandem reaction. We
considered that the strong electron-withdrawing groups (-COOMe and -CN) would largely decrease the electron
density of the double bonds, accordingly, the iminium intermediate would be difficult to react with these
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
Table 1. Optimization of the Reaction Conditionsa
entry
photocatalyst
Ru(bpy)3(PF6)2
additive
Cu(OTf)2
solvent time (h) yield (%)b
1
CH3CN
CH3CN
CH3CN
CH3CN
4
4
4
4
4
4
4
4
4
4
4
5
6
15
6
4
4
4
4
70
75
61
57
nd
10
26
55
60
47
nd
78
68
76
74
nd
32
33
nd
2
Ru(bpy)3Cl2ꢀ6H2O
Eosin B
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
3
4
Rhodamine 6G
5
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Cu(OAc)2ꢀH2O CH3CN
6
CuSO4
CH3CN
CH3CN
CH3CN
DCE
7
In(OTf)3
Fe(OTf)3
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
8
9
10
11
12c
13d
14c,e
15c,f
16g
17h
18
19
DCM
DMF
Ru(bpy)3Cl2·6H2O Cu(OTf)2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
Ru(bpy)3Cl2ꢀ6H2O
－
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
－
Ru(bpy)3Cl2ꢀ6H2O
aReaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), photocatalyst (0.1-1 mol %), additive (10 mol%), solvent (1.0 mL), 3 W blue LED
4
ACS Paragon Plus Environment

Page 5 of 20
The Journal of Organic Chemistry
1
2
3
c
light irradiation under air at room temperature. bYield of the isolated product. 0.5 mol% of Ru(bpy)3Cl2ꢀ6H2O was used. d0.1 mol% of
4
5
Ru(bpy)3Cl2ꢀ6H2O was used. eUnder the irradiation of a 26 W fluorescent lamp. fUnder the irradiation of sun light. gReaction was carried
6
7
out under Ar. hReaction was carried out in the dark.
8
9
Table 2. Oxidative Dehydrogenative Coupling/Aromatization Tandem Reaction: Alkenes Scopea,b
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
R2
R1
H
Ru(bpy)3Cl2·6H2O(0.5 mol%)
R1
R3
O
H
Cu(OTf)2 (10 mol%)
R3
R2
OEt
N
H
OEt
CH3CN, rt, air
3W blue LED
N
O
3
2
1
OMe
OMe
MeO
OMe
OMe
R1
MeO
MeO
OEt
OEt
OEt
N
N
N
O
O
O
R1 = OMe, 3b, 76%
R1 = Me, 3b', 82%
3c, 64%
3d, 71%
Cl
F
R1
R1
R1
OEt
OEt
N
OEt
N
N
O
O
O
R1 = OMe, 3g, 72%
R1 = Me, 3g', 76%
R1 = OMe, 3f, 65%
1 = Me, 3f', 65%
R1 = OMe, 3e, 71%
R1 = Me, 3e', 80%
R
CF3
Cl
Cl
MeO
MeO
MeO
OEt
OEt
OEt
N
N
N
O
O
O
3j, 65%
3h, 69%
3i, 71%
Cl
Cl
O
R1
R1
MeO
OEt
OEt
OEt
N
N
N
O
O
R1 = OMe, 3m, 63%c
R1 = Me, 3m', 61%c
3k, 65%
R
1 = OMe, 3l, 83%
R1 = Me, 3l', 78%
Br
3
5
Me
MeO
MeO
OEt
OEt
OEt
N
N
N
O
O
O
3p, 18%c,d
3n, 53%c
3o, 36%c,d
MeO
MeO
MeO
OEt
OEt
OEt
N
N
N
O
O
O
3r, 61%d
3s, 26%d
3q, 44%c,d
aReaction conditions: 1 (0.1 mmol), 2 (0.2 mmol), Ru(bpy)3Cl2ꢀ6H2O (0.5 mol%), Cu(OTf)2 (10 mol%), CH3CN (1.0 mL), 3 W blue LED
light irradiation under air for 5-15h, rt. bYield of the isolated product. c20 mol% of Cu(OTf)2 was used. d0.5 mmol of alkenes were used.
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 20
1
2
3
electron-deficient alkenes. Furthermore, conjugated dienes, such as 1,3-cyclohexadiene and 1,3-pentadiene, were
4
5
also successfully utilized in this transformation to generate quinolines (3r, 3s).
6
7
8
9
We next explored the structural diversity of the glycine ester component in this tandem protocol (Table 3). We
first examined the electronic substituent effect on the aniline fragment. A variety of glycine esters bearing either
electron-donating or electron-withdrawing substituents at the para-position of the benzene rings were suitable
partners for this tandem reaction, affording the corresponding substituted quinolines in good yields (4a-4e).
Notably, a 3,5-dimethyl substituted substrate was also amenable to reaction with styrene, although a relatively
lower yield was obtained (4c). We then explored the scope of the ester fragment. The reaction proceeded readily
with a range of esters, such as methyl ester, isopropyl ester, tert-butyl ester, benzyl ester, phenyl ester, and allyl
ester, to afford the products 4f-4k with 61-76% yield. Furthermore, in addition to glycine esters, glycine amide as
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
Table 3. Oxidative Dehydrogenative Coupling/Aromatization Tandem Reaction: Glycine Esters Scopea,b
aReaction conditions: 1 (0.1 mmol), 2 (0.2 mmol), Ru(bpy)3Cl2ꢀ6H2O (0.5 mol%), Cu(OTf)2 (10 mol%), CH3CN (1.0 mL), 3 W blue LED
light irradiation under air for 5-15h, rt. bYield of the isolated product. c20 mol% of Cu(OTf)2 was used.
6
ACS Paragon Plus Environment

Page 7 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
well as glycine derived dipeptide were found to be viable substrates for this reaction, providing the corresponding
substituted quinolines in moderate yield (4l, 4m). Other α-amino carbonyls, such as ketones and nitriles were also
tried in this transformation, however, only trace products could be detected for α-amino ketones, while no reaction
occurred for α-amino nitriles.
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
The active species of oxygen in this photocatalytic reaction was detected by electron paramagnetic resonance
(EPR) studies (Figure S1). When the solution of 1a, Ru(bpy)3Cl2ꢀ6H2O and 5,5-dimethyl-1-pyrroline-N-oxide
(DMPO) in air-saturated CH3CN was irradiated with blue LED, a signal of the trapping radical was captured
(Figure S1a), the spectrum and hyperfine coupling constants of which are in good consistent with the literature
values for the adduct of O2 with DMPO.13 By contrast, only very weak EPR signal could be detected when
-ꢀ
1
2,2,6,6-tetramethylpiperidine (TEMP), an O2 scavenger, was used as a probe in the same air-saturated CH3CN
-ꢀ
solution (Figure S1b). These results illustrate that O2 generated from molecular oxygen is the active species in this
photocatalytic oxidative reaction.
Several control experiments were further conducted to probe the mechanism of this reaction (Scheme 2).
Upon irradiation of 1a with visible light in the presence of Ru(bpy)3Cl2ꢀ6H2O and Cu(OTf)2, the iminium
intermediate 5a could be isolated in 53% yield, along with some unknown byproducts. It should be noted that in
the tandem reaction, these byproducts could not be observed. While in the absence of Cu(OTf)2, the products of
this reaction were very complicated, and only trace of iminium 5a could be observed. The obtained iminium
intermediate 5a could readily react with styrene in the same reaction conditions, affording 3a in 86% yield.
Scheme 2. Control Experiments.
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 20
1
2
3
4
5
6
7
8
9
Interestingly, in the absence of photocatalyst, Cu(OTf)2 alone could also promote the coupling reaction of 5a with
styrene, however, in this case, the Povarov cyclization product tetrahydroquinoline 6a was obtained in 71% yield,
and only trace amount of 3a was observed. Strikingly, tetrahydroquinoline 6a could be almost quantitatively
transformed to 3a within 1h in the presence of Ru(bpy)3Cl2ꢀ6H2O under the irradiation of visible light. These
results suggest that photocatalyst plays a key role in both the iminium formation and the oxidative
dehydrogenation processes, while the Cu salt is responsible for the stabilization and the activation of the iminium
intermediate during the Povarov cyclization step.
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
Based upon these observations,
a
possible mechanism for this oxidative dehydrogenative
coupling/aromatization tandem reaction was proposed, as shown in scheme 3. It is well established that upon
irradiation with visible-light, [Ru(bpy)3]2+ is excited to the oxidizing excited state [Ru(bpy)3]2+*,9f which would
readily accept a single electron from 1a to produce [Ru(bpy)3]+ and the radical cation A. The photocatalyst may be
-ꢀ
regenerated by the molecular oxygen, and at the same time, an active species O2 may be formed during this
process.11c This active radical anion may abstract a hydrogen atom from A, to produce the iminium ion B. Then,
the in situ generated HOO- may abstract another hydrogen atom from B, to form the iminium intermediate, which
subsequently forms the active electrophile C under the influence of Cu(OTf)2. This active intermediate can be
captured by styrene to form the tetrahydroquinoline 6a, which is further dehydrogenated via photocatalysis to
afford 3a. Additionally, an α-amino radical is also likely to be generated from radical cation A, which may directly
react with alkenes. More details for the mechanism of this transform are currently under investigation.
Scheme 3. Proposed Mechanism for the Photocatalytic Oxidative Dehydrogenative Coupling/Aromatization
Tandem Reaction
MeO
MeO
H
H
SET
OEt
OEt
N
H
N
H
O
A
O
1a
[Ru(bpy)3]+
[Ru(bpy)3]2+
*
HO2
O2
MeO
h
v
O2
OEt
N
H
[Ru(bpy)3]2+
B
O
-H+ Cu(OTf)2
Ph
Ph
MeO
MeO
MeO
Ph
[O]
OEt
N
OEt
OEt
N
N
H
O
CuII
O
O
3a
6a
C
8
ACS Paragon Plus Environment

Page 9 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
In conclusion, we have developed a photocatalytic oxidative dehydrogenative coupling/aromatization tandem
reaction of glycine esters with unactivated alkenes. This visible-light-promoted method was shown to tolerate a
broad scope with regard to both the glycine ester and alkene substrates, affording a range of substituted quinolines
with moderate to good yields. Remarkably, this tandem protocol was conducted under very mild (at room
temperature under air atmosphere) and operationally simple reaction conditions, without the use of any other
oxidant. Given the diverse range of organic substrates, and the mild and operationally simple reaction conditions,
this visible-light-induced C−H functionalization/aromatization protocol should find broad application in organic
synthesis.
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
Experimental Section
General Experimental Methods. All reagents were used as received from commercial suppliers unless
otherwise indicated. All solvents were dried by standard techniques and freshly distilled before use. N-arylglycine
esters,3a 2-((4-methoxyphenyl)amino)-N-methylacetamide2b and ethyl 2-(2-((4-methoxyphenyl)amino)acetamido)
acetate2b were prepared according to literature procedures. All experiments were carried out under air atmosphere,
unless otherwise indicated. The silica gel (200-300 meshes) was used for column chromatography and TLC
1
inspections were taken on silica gel GF254 plates. H NMR, 13C NMR and 19F NMR spectra were measured on a
400 MHz spectrometer. The chemical shifts δ are given in ppm relative to tetramethylsilane and the coupling
constants J are given in Hz. The spectra were recorded with CDCl3 or d6-DMSO as solvent at room temperature.
EPR spectra were recorded at room temperature using an EPR spectrometer at 9.447 GHz. Typical spectrometer
parameters are shown as follows, sweep width: 100.0 G; center field set: 3365.2 G; time constant: 81.920 ms;
sweep time: 75.0 s; modulation amplitude: 1.0 G; modulation frequency: 100.0 kHz; receiver gain: 2.00×104;
microwave power: 24.590 mW. IR spectra were recorded on an FT-IR spectrometer. High resolution mass spectra
(HRMS) were obtained on a mass spectrometer by using electrospray ionization (ESI) analyzed by quadrupole
time of flight (QTof). Irradiation of photochemical reactions was carried out using a 3 W blue LED bulb.
General Procedure for the Visible-Light-Induced Photocatalytic Aerobic Oxidative Dehydrogenative
Coupling/Aromatization Tandem Reaction. To a solution of N-arylglycine esters 1 (0.1 mmol, 1 eq),
Ru(bpy)3Cl2·6H2O (0.5 mol%) and olefin 2 (0.2 mmol, 2 eq) in dry CH3CN (1.0 mL) was added Cu(OTf)2 (10
mol %). The mixed solution was irradiated with a 3 W blue LED under air atmosphere at room temperature. After
completion of the reaction as monitored by TLC, the solvent was concentrated in vacuo. The crude product was
purified by flash chromatography on silica gel (petroleum ether/EtOAc) to afford the products.
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 20
1
2
3
4
5
6
7
8
9
Ethyl 6-methoxy-4-phenylquinoline-2-carboxylate (3a).5a Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1 as eluent). White solid, 24.0 mg, 78% yield. 1H NMR (400 MHz, CDCl3): δ 8.27 (d,
J = 9.3 Hz, 1H), 8.09 (s, 1H), 7.58–7.48 (m, 5H), 7.43 (dd, J = 9.3, 2.8 Hz, 1H), 7.21 (d, J = 2.8 Hz, 1H), 4.55 (q, J
= 7.1 Hz, 2H), 3.80 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.6, 159.5, 148.0, 145.4,
144.3, 137.9, 132.7, 129.3, 129.1, 128.7, 128.6, 122.7, 121.8, 103.3, 62.0, 55.5, 14.4.
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
Ethyl 6-methoxy-4-(4-methoxyphenyl)quinoline-2-carboxylate (3b).12a Purified by flash column chromatography
1
(silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 25.7 mg, 76% yield. H NMR (400 MHz,
CDCl3): δ 8.26 (d, J = 9.3 Hz, 1H), 8.07 (s, 1H), 7.49 (d, J = 8.7 Hz, 2H), 7.42 (dd, J = 9.3, 2.8 Hz, 1H), 7.26 (d, J
= 2.8 Hz, 1H), 7.08 (d, J = 8.7 Hz, 2H), 4.55 (q, J = 7.1 Hz, 2H), 3.91 (s, 3H), 3.82 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 165.7, 159.9, 159.4, 147.7, 145.4, 144.3, 132.7, 130.6, 130.1, 129.3, 122.6, 121.7,
114.2, 103.3, 62.0, 55.5, 55.3, 14.4.
Ethyl 4-(4-methoxyphenyl)-6-methylquinoline-2-carboxylate (3b').5a Purified by flash column chromatography
(silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). Pale yellow solid, 26.3 mg, 82% yield. 1H NMR (400
MHz, CDCl3): δ 8.26 (d, J = 8.7 Hz, 1H), 8.07 (s, 1H), 7.75 (s, 1H), 7.61 (dd, J = 8.7, 1.5 Hz, 1H), 7.48 (d, J = 8.6
Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 4.56 (q, J = 7.1 Hz, 2H), 3.92 (s, 3H), 2.50 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H). 13
C
NMR (100 MHz, CDCl3): δ 165.7, 160.0, 148.6, 146.9, 146.86, 138.7, 132.2, 130.9, 130.8, 130.0, 128.0, 124.4,
121.3, 114.1, 62.1, 55.4, 22.0, 14.4.
Ethyl 4-(2,4-dimethoxyphenyl)-6-methoxyquinoline-2-carboxylate (3c). Purified by flash column
chromatography (silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). Pale yellow solid, 23.5 mg, 64% yield,
1
mp 112−114 °C. H NMR (400 MHz, CDCl3): δ 8.23 (d, J = 9.3 Hz, 1H), 8.06 (s, 1H), 7.39 (dd, J = 9.3, 2.7 Hz,
1H), 7.22 (d, J = 8.3 Hz, 1H), 6.92 (d, J = 2.7 Hz, 1H), 6.68–6.62 (m, 2H), 4.54 (q, J = 7.1 Hz, 2H), 3.91 (s, 3H),
3.78 (s, 3H), 3.71 (s, 3H), 1.47 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.8, 161.5, 159.1, 157.8,
145.34, 145.32, 144.1, 132.4, 131.7, 130.3, 122.9, 122.5, 119.3, 104.8, 103.8, 98.9, 61.9, 55.5, 55.4, 14.4. IR (KBr,
cm-1): ν 3441, 3077, 2956, 2836, 1732, 1681, 1583, 1471, 1364, 1265, 1104, 1025, 924, 830, 790. HRMS-ESI:
calcd for C21H22NO5 (M+H)+ 368.1492, found 368.1486.
Ethyl 4-(3,5-dimethoxyphenyl)-6-methoxyquinoline-2-carboxylate (3d). Purified by flash column
chromatography (silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 26.1 mg, 71% yield, mp
150−151 °C. 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 9.3 Hz, 1H), 8.10 (s, 1H), 7.43 (dd, J = 9.3, 2.8 Hz, 1H),
7.28 (d, J = 3.5 Hz, 1H), 6.67 (d, J = 2.3 Hz, 2H), 6.61-6,59(m, 1H), 4.55 (q, J = 7.1 Hz, 2H), 3.85 (s, 6H), 3.83 (s,
3H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.6, 161.0, 159.5, 147.9, 145.3, 144.3, 139.8,
10
ACS Paragon Plus Environment

Page 11 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
132.7, 129.1, 122.8, 121.5, 107.4, 103.3, 100.6, 62.1, 55.6, 55.5, 14.4. IR (KBr, cm-1): ν 3400, 3063, 2956, 2845,
1731, 1598, 1479, 1369, 1228, 1152, 1026, 826, 787. HRMS-ESI: calcd for C21H22NO5 (M+H)+ 368.1492, found
368.1497.
7
8
9
Ethyl 4-mesityl-6-methoxyquinoline-2-carboxylate (3e). Purified by flash column chromatography (silica gel,
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
1
petroleum ether/EtOAc = 8/1 as eluent). White solid, 24.7 mg, 71% yield, mp 137−139 °C. H NMR (400 MHz,
CDCl3): δ 8.28 (d, J = 9.3 Hz, 1H), 7.96 (s, 1H), 7.42 (dd, J = 9.3, 2.8 Hz, 1H), 7.02 (s, 2H), 6.65 (d, J = 2.8 Hz,
1H), 4.54 (q, J = 7.1 Hz, 2H), 3.73 (s, 3H), 2.39 (s, 3H), 1.88 (s, 6H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 165.6, 159.6, 147.7, 145.7, 144.2, 137.8, 135.7, 133.7, 132.7, 130.0, 128.4, 122.9, 122.2, 102.6, 62.0,
55.5, 21.1, 20.1, 14.4. IR (KBr, cm-1): ν 3406, 2997, 2831, 1712, 1617, 1475, 1365, 1228, 1110, 1024, 849.
HRMS-ESI: calcd for C22H24NO3 (M+H)+ 350.1751, found 350.1756.
Ethyl 4-mesityl-6-methylquinoline-2-carboxylate (3e'). Purified by flash column chromatography (silica gel,
1
petroleum ether/EtOAc = 8/1 as eluent). Pale yellow solid, 26.8 mg, 80% yield, mp 113−115 °C. H NMR (400
MHz, CDCl3): δ 8.27 (d, J = 8.7 Hz, 1H), 7.96 (s, 1H), 7.60 (dd, J = 8.7, 1.7 Hz, 1H), 7.18 (s, 1H), 7.03 (s, 2H),
4.55 (q, J = 7.1 Hz, 2H), 2.44 (s, 3H), 2.40 (s, 3H), 1.86 (s, 6H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 165.6, 148.7, 147.3, 146.7, 139.1, 137.8, 135.9, 133.8, 132.5, 130.9, 128.5, 128.3, 123.8, 121.9, 62.1,
21.9, 21.1, 20.2, 14.4. IR (KBr, cm-1): ν 3395, 2921, 2859, 1718, 1613, 1556, 1444, 1373, 1250, 1109, 1023, 829,
755. HRMS-ESI: calcd for C22H24NO2 (M+H)+ 334.1802, found 334.1804.
Ethyl 4-(4-fluorophenyl)-6-methoxyquinoline-2-carboxylate (3f).12a Purified by flash column chromatography
1
(silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 21.2 mg, 65% yield. H NMR (400 MHz,
CDCl3): δ 8.27 (d, J = 9.3 Hz, 1H), 8.06 (s, 1H), 7.55–7.50 (m, 2H), 7.44 (dd, J = 9.3, 2.8 Hz, 1H), 7.29–7.22 (m,
2H), 7.15 (d, J = 2.7 Hz, 1H), 4.56 (q, J = 7.1 Hz, 2H), 3.82 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 165.5, 162.9 (d, JC-F = 247.0 Hz), 159.6, 146.9, 145.4, 144.3, 133.9 (d, JC-F = 3.4 Hz), 132.8, 131.0 (d,
JC-F = 8.1 Hz), 129.1, 122.8, 121.8, 115.9 (d, JC-F = 21.5 Hz), 103.1, 62.1, 55.5, 14.4. 19F NMR (376 MHz, CDCl3):
δ -112.8 (s, F).
Ethyl 4-(4-fluorophenyl)-6-methylquinoline-2-carboxylate (3f').5a Purified by flash column chromatography
1
(silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 20.2 mg, 65% yield. H NMR (400 MHz,
CDCl3): δ 8.27 (d, J = 8.6 Hz, 1H), 8.07 (s, 1H), 7.65–7.61 (m, 2H), 7.53–7.48 (m, 2H), 7.27–7.21 (m, 2H), 4.56
(q, J = 7.1 Hz, 2H), 2.50 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.5, 163.0 (d, JC-F
=
247.0 Hz), 147.8, 146.8 (d, JC-F = 10.6 Hz), 139.1, 133.7 (d, JC-F = 3.4 Hz), 132.4, 131.3, 131.2, 131.0, 127.8,
124.1, 121.4, 115.7 (d, JC-F = 21.5 Hz), 62.2, 22.0, 14.4. 19F NMR (376 MHz, CDCl3): δ -112.9 (s, F).
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 20
1
2
3
4
5
6
7
8
9
Ethyl 4-(4-chlorophenyl)-6-methoxyquinoline-2-carboxylate (3g).12a Purified by flash column chromatography
(silica gel, petroleum ether/EtOAc = 8/1 as eluent). White solid, 24.6 mg, 72% yield. 1H NMR (400 MHz, CDCl3):
δ 8.27 (d, J = 9.3 Hz, 1H), 8.06 (s, 1H), 7.54 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 7.44 (dd, J = 9.3, 2.8 Hz,
1H), 7.13 (d, J = 2.7 Hz, 1H), 4.55 (q, J = 7.1 Hz, 2H), 3.82 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (100 Hz,
CDCl3): δ 165.5, 159.7, 146.6, 145.3, 144.3, 136.3, 134.8, 132.8, 130.6, 129.0, 128.9, 122.9, 121.7, 102.9, 62.1,
55.5, 14.4.
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
Ethyl 4-(4-chlorophenyl)-6-methylquinoline-2-carboxylate (3g').5a Purified by flash column chromatography
(silica gel, petroleum ether/EtOAc = 8/1 as eluent). White solid, 24.8 mg, 76% yield. 1H NMR (400 MHz, CDCl3):
δ 8.28 (d, J = 9.2 Hz, 1H), 8.06 (s, 1H), 7.65–7.60 (m, 2H), 7.56–7.51 (m, 2H), 7.48–7.44 (m, 2H), 4.56 (q, J = 7.1
Hz, 2H), 2.50 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.4, 147.6, 146.9, 146.8, 139.2,
136.1, 134.8, 132.4, 131.0, 130.8, 128.9, 127.5, 124.0, 121.3, 62.2, 22.0, 14.4.
Ethyl 4-(2-chlorophenyl)-6-methoxyquinoline-2-carboxylate (3h).12b Purified by flash column chromatography
1
(silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 23.4 mg, 69% yield. H NMR (400 MHz,
CDCl3): δ 8.28 (d, J = 9.3 Hz, 1H), 8.07 (s, 1H), 7.58 (dd, J = 7.6, 1.6 Hz, 1H), 7.49–7.41 (m, 3H), 7.37 (dd, J =
7.2, 2.0 Hz, 1H), 6.76 (d, J = 2.7 Hz, 1H), 4.55 (m, 2H), 3.77 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 165.4, 159.6, 145.4, 145.3, 144.0, 136.5, 133.2, 132.7, 131.2, 130.0, 129.9, 129.3, 127.0, 123.0, 122.3,
103.2, 62.1, 55.5, 14.4.
Ethyl 4-(3-chlorophenyl)-6-methoxyquinoline-2-carboxylate (3i).12b Purified by flash column chromatography
(silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). Pale yellow solid, 24.3 mg, 71% yield. 1H NMR (400
MHz, CDCl3): δ 8.28 (d, J = 9.3 Hz, 1H), 8.07 (s, 1H), 7.55–7.54 (m, 1H), 7.51–7.41 (m, 4H), 7.14 (d, J = 2.7 Hz,
1H), 4.56 (q, J = 7.1 Hz, 2H), 3.83 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.4, 159.7,
146.3, 145.3, 144.3, 139.6, 134.8, 132.8, 130.0, 129.3, 128.8, 128.7, 127.5, 122.9, 121.7, 102.9, 62.1, 55.5, 14.4.
Ethyl 6-methoxy-4-(4-(trifluoromethyl)phenyl)quinoline-2-carboxylate (3j).12c Purified by flash column
chromatography (silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). Pale yellow solid, 24.2 mg, 65% yield. 1H
NMR (400 MHz, CDCl3): δ 8.29 (d, J = 9.3 Hz, 1H), 8.08 (s, 1H), 7.83 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.0 Hz,
2H), 7.46 (dd, J = 9.3, 2.8 Hz, 1H), 7.09 (d, J = 2.7 Hz, 1H), 4.56 (q, J = 7.1 Hz, 2H), 3.82 (s, 3H), 1.49 (t, J = 7.1
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.3, 159.8, 146.3, 145.3, 144.3, 141.6, 132.9, 130.8 (q, J = 32.5 Hz),
129.7, 128.7, 126.2 (q, J = 2.5 Hz), 125.8 (q, J = 3.8 Hz), 124.1 (q, J = 270.6 Hz), 123.0, 121.7, 102.8, 62.1, 55.6,
14.3. 19F NMR (376 MHz, CDCl3): δ -62.6 (s, 3F).
Ethyl 4-(2,4-dichlorophenyl)-6-methoxyquinoline-2-carboxylate (3k). Purified by flash column chromatography
12
ACS Paragon Plus Environment

Page 13 of 20
The Journal of Organic Chemistry
1
2
3
(silica gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). Pale yellow solid, 24.3 mg, 65% yield, mp 128−130 °C.
4
5
1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 9.3 Hz, 1H), 8.04 (s, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.46–7.42 (m, 2H),
6
7
7.32 (d, J = 8.2 Hz, 1H), 6.72 (d, J = 2.7 Hz, 1H), 4.58–4.53 (m, 2H), 3.80 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H). 13
C
8
9
NMR (100 MHz, CDCl3): δ 165.3, 159.8, 145.2, 144.2, 144.0, 135.4, 135.1, 134.1, 132.8, 132.0, 129.9, 129.1,
127.5, 123.2, 122.3, 102.9, 62.1, 55.6, 14.4. IR (KBr, cm-1): ν 3352, 2928, 1699, 1619, 1479, 1378, 1276, 1224,
1143, 1106, 1033, 866, 840, 791. HRMS-ESI: calcd for C19H16Cl2NO3 (M+H)+ 376.0502, found 376.0507.
Ethyl 4-(2-Naphthyl)-6-methoxyquinoline-2-carboxylate (3l). Purified by flash column chromatography (silica
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
1
gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 29.5 mg, 83% yield, mp 94−95 °C. H NMR (400
MHz, CDCl3): δ 8.30 (d, J = 9.3 Hz, 1H), 8.20 (s, 1H), 8.04–7.99 (m, 2H), 7.97–7.91 (m, 2H), 7.65 (dd, J = 8.4,
1.7 Hz, 1H), 7.60–7.55 (m, 2H), 7.45 (dd, J = 9.3, 2.8 Hz, 1H), 7.25 (d, J = 2.8 Hz, 1H), 4.56 (q, J = 7.1 Hz, 2H),
3.75 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.6, 159.6, 147.9, 145.4, 144.3, 135.4,
133.3, 133.1, 132.7, 129.3, 128.6, 128.3, 128.2, 127.8, 126.9, 126.8, 126.7, 122.8, 122.0, 103.3, 62.1, 55.5, 14.4.
IR (KBr, cm-1): ν 3406, 2980, 2849, 1715, 1620, 1478, 1368, 1227, 1111, 1024, 833, 750. HRMS-ESI: calcd for
C23H20NO3 (M+H)+ 358.1438, found 358.1442.
Ethyl 4-(2-Naphthyl)-6-methylquinoline-2-carboxylate (3l').4b Purified by flash column chromatography (silica
gel, petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 26.7 mg, 78% yield. 1H NMR (400 MHz, CDCl3): δ
8.30 (d, J = 8.7 Hz, 1H), 8.19 (s, 1H), 8.04–8.00 (m, 2H), 7.99–7.91 (m, 2H), 7.74 (s, 1H), 7.66–7.56 (m, 4H), 4.57
(q, J = 7.1 Hz, 2H), 2.47 (s, 3H), 1.50 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.6, 148.9, 146.9,
146.8, 139.0, 135.3, 133.2, 133.1, 132.4, 130.9, 128.8, 128.3, 128.2, 128.0, 127.8, 127.2, 126.8, 126.7, 124.5,
121.6, 62.2, 22.0, 14.4.
Ethyl 2-methoxy-7,8-dihydrobenzo[k]phenanthridine-6-carboxylate (3m). Purified by flash column
chromatography (silica gel, petroleum ether/EtOAc = 8/1 as eluent). Pale yellow solid, 20.9 mg, 63% yield, mp
134−135 °C. 1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 9.2 Hz, 1H), 8.00–7.94 (m, 1H), 7.78 (d, J = 2.7 Hz, 1H),
7.44–7.36 (m, 4H), 4.53 (q, J = 7.1 Hz, 2H), 3.91 (s, 3H), 3.14–3.06 (m, 2H), 2.86–2.79 (m, 2H), 1.47 (t, J = 7.1
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 166.9, 159.2, 146.6, 143.4, 140.3, 140.2, 132.3, 131.9, 130.4, 128.9,
128.4, 128.0, 126.3, 126.27, 121.5, 103.4, 61.9, 55.5, 28.7, 25.6, 14.3. IR (KBr, cm-1): ν 3395, 2929, 2844, 1709,
1619, 1500, 1350, 1211, 1170, 1035, 821, 752. HRMS-ESI: calcd for C21H20NO3 (M+H)+ 334.1438, found
334.1429.
Ethyl 2-methyl-7,8-dihydrobenzo[k]phenanthridine-6-carboxylate (3m'). Purified by flash column
chromatography (silica gel, petroleum ether/EtOAc = 8/1 as eluent). White solid, 19.4 mg, 61% yield, mp
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 20
1
2
3
4
5
6
7
8
9
100−102 °C. 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H), 8.13 (d, J = 8.6 Hz, 1H), 7.94–7.89 (m, 1H), 7.55 (dd, J
= 8.6, 1.7 Hz, 1H), 7.45–7.37 (m, 3H), 4.54 (q, J = 7.1 Hz, 2H), 3.12–3.04 (m, 2H), 2.87–2.78 (m, 2H), 2.55 (s,
3H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 167.0, 148.3, 145.9, 140.9, 140.3, 138.1, 131.8,
131.1, 130.4, 129.7, 129.3, 128.9, 127.9, 126.3, 125.1, 124.1, 62.0, 28.8, 25.6, 22.2, 14.3. IR (KBr, cm-1): ν3387,
2925, 2367, 1721, 1601, 1561, 1458, 1372, 1305, 1242, 1177, 1073, 754. HRMS-ESI: calcd for C21H20NO2
(M+H)+ 318.1489, found 318.1487.
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
Ethyl 3,6-dimethyl-4-phenylquinoline-2-carboxylate (3n).4b Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1 as eluent). White solid, 16.3 mg, 53% yield. 1H NMR (400 MHz, CDCl3): δ 8.08 (d,
J = 8.6 Hz, 1H), 7.57–7.48 (m, 4H), 7.26–7.21 (m, 2H), 7.11 (s, 1H), 4.54 (q, J = 7.1 Hz, 2H), 2.39 (s, 3H), 2.29 (s,
3H), 1.47 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 167.5, 150.5, 147.9, 144.3, 137.8, 136.9, 131.3,
129.6, 129.2, 128.6, 128.2, 128.0, 126.3, 124.7, 61.9, 21.9, 16.8, 14.3.
Ethyl 4-hexyl-6-methoxyquinoline-2-carboxylate (3o). Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1 as eluent). Pale yellow solid, 11.2 mg, 36% yield, mp 51−52 °C. 1H NMR (400 MHz,
CDCl3): δ 8.21 (d, J = 9.3 Hz, 1H), 8.00 (s, 1H), 7.41 (dd, J = 9.3, 2.7 Hz, 1H), 7.25 (d, J = 2.7 Hz, 1H), 4.54 (q, J
= 7.1 Hz, 2H), 3.97 (s, 3H), 3.05 (t, J = 7.8 Hz, 2H), 1.84–1.76 (m, 2H), 1.49 (t, J = 7.1 Hz, 3H), 1.45–1.23 (m,
6H), 0.90 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.9, 159.1, 148.2, 145.4, 143.7, 133.0, 129.9,
122.1, 120.8, 101.3, 61.9, 55.5, 32.3, 31.6, 29.32, 29.27, 22.5, 14.4, 14.0. IR (KBr, cm-1): ν 2930, 2857, 1715, 1621,
1510, 1477, 1372, 1280, 1253, 1228, 1175, 1144, 1109, 1025, 951, 863, 834, 790, 732. HRMS-ESI: calcd for
C19H26NO3 (M+H)+ 316.1907, found 316.1903.
Ethyl 4-(3-bromopropyl)-6-methoxyquinoline-2-carboxylate (3p). Purified by flash column chromatography
(silica gel, petroleum ether/EtOAc = 8/1 as eluent). Pale yellow solid, 6.4 mg, 18% yield, mp 79−81 °C. 1H NMR
(400 MHz, CDCl3): δ 8.22 (d, J = 9.3 Hz, 1H), 8.03 (s, 1H), 7.43 (dd, J = 9.3, 2.7 Hz, 1H), 7.33 (d, J = 2.7 Hz, 1H),
4.54 (q, J = 7.1 Hz, 2H), 3.99 (s, 3H), 3.53 (t, J = 6.1 Hz, 2H), 3.30–3.24 (m, 2H), 2.39– 2.30 (m, 2H), 1.49 (t, J =
7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.7, 159.5, 146.2, 145.4, 143.8, 133.1, 129.7, 122.7, 121.2, 101.1,
62.0, 55.7, 33.3, 32.4, 30.6, 14.4. IR (KBr, cm-1): ν 3076, 2987, 1710, 1619, 1510, 1480, 1438, 1369, 1345, 1261,
1232, 1109, 1022, 954, 837, 788. HRMS-ESI: calcd for C16H19BrNO3 (M+H)+ 352.0543, found 352.0545.
Ethyl 6-methoxyquinoline-2-carboxylate (3q).12e Purified by flash column chromatography (silica gel, petroleum
ether/EtOAc = 8/1 as eluent). White solid, 10.1 mg, 44% yield. 1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 9.3 Hz,
1H), 8.16 (s, 2H), 7.43 (dd, J = 9.3, 2.8 Hz, 1H), 7.10 (d, J = 2.8 Hz, 1H), 4.55 (q, J = 7.1 Hz, 2H), 3.96 (s, 3H),
1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.5, 159.3, 145.7, 143.7, 135.5, 132.2, 130.7, 123.3,
14
ACS Paragon Plus Environment

Page 15 of 20
The Journal of Organic Chemistry
1
2
3
121.5, 104.6, 62.0, 55.6, 14.3.
4
5
Ethyl (E)-6-methoxy-4-(prop-1-en-1-yl)quinoline-2-carboxylate (3r). Purified by flash column chromatography
6
7
1
(silica gel, petroleum ether/EtOAc = 8/1 as eluent). White solid, 16.5 mg, 61% yield, mp 113−114 °C. H NMR
8
9
(400 MHz, CDCl3): δ 8.18 (t, J = 4.6 Hz, 2H), 7.40 (dd, J = 9.3, 2.7 Hz, 1H), 7.32–7.28 (m, 1H), 7.01 (d, J = 15.6
Hz, 1H), 6.66–6.54 (m, 1H), 4.55 (q, J = 7.1 Hz, 2H), 3.97 (s, 3H), 2.06 (dd, J = 6.7, 1.5 Hz, 3H), 1.49 (t, J = 7.1
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.8, 159.1, 145.5, 144.1, 143.1, 133.6, 132.7, 128.4, 125.6, 122.5,
117.7, 101.2, 62.0, 55.5, 19.1, 14.4. IR (KBr, cm-1): ν 3352, 2976, 2933, 1717, 1620, 1584, 1474, 1416, 1367, 1254,
1224, 1144, 1112, 1022, 960, 916, 896, 856, 832, 785. HRMS-ESI: calcd for C16H18NO3 (M+H)+ 272.1281, found
272.1278.
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
Ethyl 2-methoxy-7,8-dihydrophenanthridine-6-carboxylate (3s). Purified by flash column chromatography
(silica gel, petroleum ether/EtOAc = 8/1 as eluent). Pale yellow oil, 7.4 mg, 26% yield. 1H NMR (400 MHz,
CDCl3): δ 8.04 (d, J = 9.2 Hz, 1H), 7.34 (dd, J = 9.2, 2.7 Hz, 1H), 7.24 (d, J = 2.6 Hz, 1H), 7.17 (dt, J = 9.8, 1.6
Hz, 1H), 6.57–6.50 (m, 1H), 4.52 (q, J = 7.1 Hz, 2H), 3.95 (s, 3H), 3.15 (t, J = 8.0 Hz, 2H), 2.45–2.39 (m, 2H),
1.47 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 167.0, 158.8, 146.5, 142.6, 136.9, 134.9, 132.1, 126.1,
125.7, 121.81, 121.78, 100.0, 61.8, 55.5, 23.3, 22.5, 14.3. IR (KBr, cm-1): ν 3405, 2936, 2833, 1720, 1621, 1500,
1467, 1428, 1301, 1227, 1179, 1105, 1031, 863, 831, 754. HRMS-ESI: calcd for C17H18NO3 (M+H)+ 284.1281,
found 284.1277.
Ethyl 6-hydroxy-4-phenylquinoline-2-carboxylate (4a).5a Purified by flash column chromatography (silica gel,
1
petroleum ether/EtOAc = 4/1–2/1 as eluent). White solid, 21.7 mg, 74% yield. H NMR (400 MHz, d6-DMSO): δ
10.38 (brs, 1H), 8.11 (d, J = 9.1 Hz, 1H), 7.87 (s, 1H), 7.62–7.53 (m, 5H), 7.43 (dd, J = 9.1, 2.6 Hz, 1H), 7.16 (d, J
= 2.6 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, d6-DMSO): δ 164.9, 157.9,
146.5, 144.1, 142.8, 137.4, 132.3, 129.1, 128.8, 128.7, 128.6, 123.2, 120.8, 105.9, 61.2, 14.2.
Ethyl 6-methyl-4-phenylquinoline-2-carboxylate (4b).5a Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1 as eluent). White solid, 24.5 mg, 84% yield. 1H NMR (400 MHz, CDCl3): δ 8.28 (d,
J = 8.7 Hz, 1H), 8.09 (s, 1H), 7.70 (s, 1H), 7.62 (dd, J = 8.7, 1.7 Hz, 1H), 7.57–7.50 (m, 5H), 4.56 (q, J = 7.1 Hz,
2H), 2.49 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.6, 148.9, 146.9, 146.8, 138.9,
137.7, 132.3, 130.8, 129.5, 128.6, 128.5, 127.8, 124.3, 121.4, 62.1, 22.0, 14.4.
Ethyl 5,7-dimethyl-4-phenylquinoline-2-carboxylate (4c).4b Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1–4/1 as eluent). Pale yellow solid, 12.3 mg, 40% yield. 1H NMR (400 MHz, CDCl3):
δ 8.05 (s, 1H), 7.92 (s, 1H), 7.49–7.42 (m, 3H), 7.35–7.31 (m, 2H), 7.22 (s, 1H), 4.54 (q, J = 7.1 Hz, 2H), 2.52 (s,
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 20
1
2
3
4
5
3H), 2.00 (s, 3H), 1.47 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.5, 150.0, 149.7, 146.4, 142.0,
139.7, 135.0, 134.1, 128.9, 128.7, 127.9, 125.4, 122.6, 62.1, 24.2, 21.3, 14.4.
6
7
8
9
Ethyl 6-chloro-4-phenylquinoline-2-carboxylate (4d).5a Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1 as eluent). White solid, 22.5 mg, 72% yield. 1H NMR (400 MHz, CDCl3): δ 8.32 (d,
J = 9.0 Hz, 1H), 8.15 (s, 1H), 7.93 (d, J = 2.3 Hz, 1H), 7.72 (dd, J = 9.0, 2.3 Hz, 1H), 7.59–7.50 (m, 5H), 4.57 (q, J
= 7.1 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.2, 149.1, 148.0, 146.6, 136.9, 134.8,
132.7, 131.1, 129.4, 129.0, 128.9, 128.5, 124.5, 122.0, 62.4, 14.4.
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
Ethyl 6-bromo-4-phenylquinoline-2-carboxylate (4e).5a Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 26.0 mg, 73% yield. 1H NMR (400 MHz, CDCl3): δ 8.25
(d, J = 9.0 Hz, 1H), 8.14 (s, 1H), 8.11 (d, J = 2.1 Hz, 1H), 7.86 (dd, J = 9.0, 2.2 Hz, 1H), 7.60–7.50 (m, 5H), 4.57
(q, J = 7.1 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.2, 149.0, 148.1, 146.8, 136.9,
133.6, 132.8, 129.4, 129.0, 128.9, 128.87, 127.9, 123.3, 122.0, 62.4, 14.4.
Methyl 6-methoxy-4-phenylquinoline-2-carboxylate (4f).12d Purified by flash column chromatography (silica gel,
petroleum ether/EtOAc = 8/1–4/1 as eluent). White solid, 21.4 mg, 73% yield. 1H NMR (400 MHz, CDCl3): δ 8.27
(d, J = 9.3 Hz, 1H), 8.11 (s, 1H), 7.55–7.49 (m, 5H), 7.44 (dd, J = 9.3, 2.7 Hz, 1H), 7.23 (d, J = 2.7 Hz, 1H), 4.08
(s, 3H), 3.81 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 166.1, 159.6, 148.1, 145.0, 144.2, 137.8, 132.6, 129.3, 129.2,
128.7, 128.6, 122.8, 121.8, 103.3, 55.5, 53.0.
Isopropyl 6-methoxy-4-phenylquinoline-2-carboxylate (4g). Purified by flash column chromatography (silica gel,
1
petroleum ether/EtOAc = 8/1 as eluent). Pale yellow solid, 23.0 mg, 72% yield, mp 151−152 °C. H NMR (400
MHz, CDCl3): δ 8.28 (d, J = 9.3 Hz, 1H), 8.04 (s, 1H), 7.57–7.50 (m, 5H), 7.43 (dd, J = 9.3, 2.8 Hz, 1H), 7.20 (d, J
= 2.8 Hz, 1H), 5.44–5.35 (m, 1H), 3.80 (s, 3H), 1.47 (s, 3H), 1.45 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 165.0,
159.4, 147.9, 145.7, 144.4, 138.0, 132.8, 129.3, 129.0, 128.7, 128.6, 122.6, 121.7, 103.2, 69.6, 55.5, 21.9. IR (KBr,
cm-1): ν 3432, 2972, 1729, 1619, 1474, 1373, 1223, 1104, 1027, 841, 707. HRMS-ESI: calcd for C20H20NO3
(M+H)+ 322.1438, found 322.1442.
Tert-butyl 6-methoxy-4-phenylquinoline-2-carboxylate (4h). Purified by flash column chromatography (silica
1
gel, petroleum ether/EtOAc = 8/1 as eluent). Pale yellow solid, 22.2 mg, 66% yield, mp 156−158 °C. H NMR
(400 MHz, CDCl3): δ 8.26 (d, J = 9.3 Hz, 1H), 7.98 (s, 1H), 7.56–7.50 (m, 5H), 7.42 (dd, J = 9.3, 2.8 Hz, 1H),
7.18 (d, J = 2.8 Hz, 1H), 3.80 (s, 3H), 1.68 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 164.3, 159.3, 147.8, 146.5,
144.4, 138.1, 132.8, 129.3, 128.9, 128.7, 128.5, 122.5, 121.6, 103.2, 82.3, 55.5, 28.2. IR (KBr, cm-1): ν 3444, 2972,
1734, 1622, 1490, 1367, 1266, 1239, 1144, 1032, 828, 710. HRMS-ESI: calcd for C21H22NO3 (M+H)+ 336.1594,
16
ACS Paragon Plus Environment

Page 17 of 20
The Journal of Organic Chemistry
1
2
3
found 336.1597.
4
5
Benzyl 6-methoxy-4-phenylquinoline-2-carboxylate (4i). Purified by flash column chromatography (silica gel,
6
7
1
petroleum ether/EtOAc = 8/1 as eluent). White solid, 26.6 mg, 72% yield, mp 140−142 °C. H NMR (400 MHz,
8
9
CDCl3): δ 8.27 (d, J = 9.3 Hz, 1H), 8.07 (s, 1H), 7.55–7.49 (m, 7H), 7.42 (dd, J = 9.3, 2.8 Hz, 1H), 7.39–7.32 (m,
3H), 7.19 (d, J = 2.8 Hz, 1H), 5.52 (s, 2H), 3.79 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 165.3, 159.5, 147.9,
145.0, 144.4, 137.8, 135.8, 132.7, 129.2, 129.16, 128.7, 128.6, 128.5, 128.3, 122.8, 121.8, 103.2, 67.5, 55.4. IR
(KBr, cm-1): ν 3391, 2966, 1708, 1619, 1476, 1355, 1224, 1126, 1025, 828, 734. HRMS-ESI: calcd for C24H20NO3
(M+H)+ 370.1438, found 370.1443.
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
Phenyl 6-methoxy-4-phenylquinoline-2-carboxylate (4j). Purified by flash column chromatography (silica gel,
1
petroleum ether/EtOAc = 8/1–4/1 as eluent). Pale yellow solid, 21.6 mg, 61% yield, mp 187−188 °C. H NMR
(400 MHz, CDCl3): δ 8.32 (d, J = 9.3 Hz, 1H), 8.22 (s, 1H), 7.57 (d, J = 3.9 Hz, 4H), 7.49–7.43 (m, 3H), 7.33–
7.28 (m, 3H), 7.27–7.20 (m, 2H), 3.82 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 164.3, 159.8, 151.1, 148.2, 144.5,
137.8, 132.8, 129.4, 129.3, 128.8, 128.7, 126.0, 123.0, 122.2, 121.8, 103.3, 55.5. IR (KBr, cm-1): ν 3108, 2931,
2362, 1751, 1619, 1587, 1492, 1373, 1216, 1195, 1100, 1031, 936, 917, 832, 758, 731. HRMS-ESI: calcd for
C23H18NO3 (M+H)+ 356.1281, found 356.1285.
Allyl 6-methoxy-4-phenylquinoline-2-carboxylate (4k). Purified by flash column chromatography (silica gel,
1
petroleum ether/EtOAc = 8/1 as eluent). Pale yellow solid, 24.4 mg, 76% yield, mp 139−141 °C. H NMR (400
MHz, CDCl3): δ 8.27 (d, J = 9.3 Hz, 1H), 8.10 (s, 1H), 7.59–7.50 (m, 5H), 7.43 (dd, J = 9.3, 2.2 Hz, 1H), 7.22 (d, J
= 2.1 Hz, 1H), 6.17–6.07 (m, 1H), 5.47 (d, J = 17.2 Hz, 1H), 5.33 (d, J = 10.4 Hz, 1H), 4.99 (d, J = 5.8 Hz, 2H),
3.80 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 165.2, 159.5, 148.0, 145.1, 144.3, 137.8, 132.7, 131.9, 129.3,129.2,
128.7, 128.6, 122.8, 121.8, 119.0, 103.3, 66.6, 55.5. IR (KBr, cm-1): ν 3440, 2945, 1732, 1619, 1473, 1358, 1221,
1110, 1030, 945, 842, 708. HRMS-ESI: calcd for C20H18NO3 (M+H)+ 320.1287, found 320.1285.
6-Methoxy-N-methyl-4-phenylquinoline-2-carboxamide (4l).5b Purified by flash column chromatography (silica
gel, petroleum ether/EtOAc = 4/1 as eluent). White solid, 15.9 mg, 54% yield. 1H NMR (400 MHz, CDCl3): δ 8.23
(brs, 1H), 8.21 (s, 1H), 8.03 (d, J = 9.2 Hz, 1H), 7.56–7.52 (m, 4H), 7.51–7.46 (m, 1H), 7.40 (dd, J = 9.2, 2.8 Hz,
1H), 7.24 (d, J = 2.8 Hz, 1H), 3.80 (s, 3H), 3.11 (d, J = 5.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.4, 158.9,
148.3, 147.2, 143.1, 138.0, 131.4, 129.3, 128.9, 128.7, 128.5, 122.6, 119.4, 103.5, 55.5, 26.2.
Ethyl N-[(6-Methoxy-4-phenylquinolin-2-yl)carbonyl] aminoacetate (4m).5b Purified by flash column
1
chromatography (silica gel, petroleum ether/EtOAc = 4/1 as eluent). Pale yellow solid, 23.7 mg, 65% yield. H
NMR (400 MHz, CDCl3): δ 8.69 (t, J = 5.4 Hz, 1H), 8.19 (s, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.55–7.47 (m, 5H),
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 20
1
2
3
4
5
6
7.41 (dd, J = 9.2, 2.8 Hz, 1H), 7.23 (d, J = 2.7 Hz, 1H), 4.33 (d, J = 5.7 Hz, 2H), 4.28 (q, J = 7.1 Hz, 2H), 3.80 (s,
3H), 1.33 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 169.9, 165.0, 159.0, 148.2, 146.4, 143.2, 138.0,
131.7, 129.3, 129.0, 128.6, 128.5, 122.6, 119.4, 103.4, 61.5, 55.4, 41.5, 14.2.
7
8
9
Procedure for the Synthesis of Tetrahydroquinoline. To a solution of iminium 5a (0.1 mmol, 1.0 eq) and
olefin 2a (0.2 mmol, 2.0 eq) in dry CH3CN (1.0 mL) was added Cu(OTf)2 (10 mol%). The mixed solution was
stirred under air atmosphere at room temperature. After completion of the reaction as monitored by TLC, the
reaction solvent was concentrated in vacuo. The crude product was purified by flash chromatography on silica gel
(petroleum ether/EtOAc = 8:1) to afford the product.
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
Ethyl 6-methoxy-4-phenyl-1,2,3,4-tetrahydroquinoline-2-carboxylate (6a). Pale yellow oil, 22.0 mg, 71% yield.
1H NMR (400 MHz, CDCl3): δ 7.33–7.17 (m, 6H), 6.69–6.62 (m, 2 H), 6.22 (d, J = 2.4 Hz, 1H), 4.19–4.12 (m,
4H), 3.57 (s, 3H), 2.58–2.53 (m, 1H), 2.16–2.08 (m, 1H), 1.24 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ
172.7, 152.2, 144.5, 137.5, 128.7, 128.5, 126.7, 125.5, 115.9, 115.0, 113.5, 61.3, 55.6, 54.4, 44.0, 35.1, 14.1.
HRMS-ESI: calcd for C19H22NO3 (M+H)+ 312.1594, found 312.1594.
Supporting Information
Details for the optimization of the reaction conditions, the EPR spectra, and copies of NMR spectra of the products.
This material is available free of charge via the Internet at http:// pubs.acs.org.
Acknowledgments
We gratefully acknowledge the National Natural Science Foundation of China (No. 21572092, 21472078), the
Fundamental Research Funds for the Central Universities (No. lzujbky-2016-56) for financial support. We thank
professor Qiang Liu (Lanzhou University) for helpful discussion.
References
1. For selected reviews, see: (a) Li, C.-J.; Li, Z. Pure Appl.Chem. 2006, 78, 935. (b) Li, C.-J. Acc. Chem. Res.
2009, 42, 335. (c) Scheuermann, C. J. Chem.-Asian J. 2010, 5, 436. (d) Yeung, C. S.; Dong, V. M. Chem. Rev.
2011, 111, 1215. (e) Liu, C.; Zhang, H.; Shi, W.; Lei, A. W. Chem. Rev. 2011, 111, 1780. (f) Zhang, C.; Tang,
C. H.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3464. (g) Girard, S. A.; Knauber, T.; Li, C.-J. Angew. Chem., Int.
Ed. 2014, 53, 74.
2. (a) Zhao, L.; Li, C.-J. Angew. Chem., Int. Ed. 2008, 47, 7075. (b) Zhao, L.; Basle, O.; Li, C.-J. Proc. Natl.
Acad. Sci. U. S. A. 2009, 106, 4106.
3. For selected examples, see: (a) Xie, J.; Huang, Z. Z. Angew. Chem., Int. Ed. 2010, 49, 10181. (b) Zhang, G.;
Zhang, Y.; Wang, R. Angew. Chem., Int. Ed. 2011, 50, 10429. (c) Li, K.; Tan, G.; Huang, J.; Song, F.; You, J.
18
ACS Paragon Plus Environment

Page 19 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Angew. Chem., Int. Ed. 2013, 52, 12942. (d) Huo, C. D.; Wang, C.; Wu, M. X.; Jia, X. D.; Xie, H. S.; Yuan, Y.
Adv. Synth. Catal. 2014, 356, 411. (e) Zhu, Z. Q.; Bai, P.; Huang, Z. Z. Org. Lett. 2014, 16, 4881. (f) Wei,
X.-H.; Wang, G.-W.; Yang, S.-D. Chem. Commun. 2015, 51, 832. (g) Huo, C. D.; Chen, F. J.; Yuan, Y.; Xie, H.
S.; Wang, Y. J. Org. Lett. 2015, 17, 5028. (h) Xie, Z.; Liu, X.; Liu, L. Org. Lett. 2016. 18, 2982. (i) Jia, X.;
Zhu, Y.; Yuan, Y.; Zhang, X.; Lü, S.; Zhang, L.; Luo, L. ACS Catal. 2016, 6, 6033.
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
4. (a) Richter, H.; Mancheño, O. G. Org. Lett. 2011, 13, 6066. (b) Rohlmann, R.; Stopka, T.; Richter, H.;
Mancheño, O. G. J. Org. Chem. 2013, 78, 6050.
5. (a) Jia, X. D.; Peng, F. F.; Qing, C.; Huo, C. D.; Wang, X. C. Org. Lett. 2012, 14, 4030. (b) Jia, X. D.; Wang,
Y. X.; Peng, F. F.; Huo, C. D.; Yu, L. L.; Liu, J.; Wang, X. C. J. Org. Chem. 2013, 78, 9450. (c) Liu, J.; Wang,
Y. X.; Yu, L. L.; Huo, C. D.; Wang, X. C.; Jia, X. D. Adv. Synth. Catal. 2014, 356, 3214. (d) Liu, J.; Liu, F.;
Zhu, Y. Z.; Ma, X. G.; Jia, X. D. Org. Lett. 2015, 17, 1409. (e) Wang, Y. X.; Peng, F. F.; Liu, J.; Huo, C. D.;
Wang, X. C.; Jia, X. D. J. Org. Chem. 2015, 80, 609.
6. (a) Huo, C.; Yuan, Y.; Wu, M.; Jia, X.; Wang, X.; Chen, F.; Tang, J. Angew. Chem., Int. Ed. 2014, 53, 13544.
(b) Huo, C. D.; Xie, H. S.; Wu, M. X.; Jia, X. D.; Wang, X. C.; Chen, F. J.; Tang, J. Chem.-Eur. J. 2015, 21,
5723.
7. Xie, Z. Y.; Jia, J.; Liu, X. G.; Liu, L. Adv. Synth. Catal. 2016, 358, 919.
8. Musiol, R.; Serda, M.; Hensel-Bielowka, S.; Polanski, J. Curr. Med. Chem. 2010, 17, 1960.
9. For selected reviews, see: (a) Zeitler, K. Angew. Chem., Int. Ed. 2009, 48, 9785. (b) Yoon, T. P.; Ischay, M. A.;
Du, J. N. Nat. Chem. 2010, 2, 527. (c) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40,
102. (d) Shi, L.; Xia, W. J. Chem. Soc. Rev. 2012, 41, 7687. (e) Xuan, J.; Xiao, W. J. Angew. Chem., Int. Ed.
2012, 51, 6828. (f) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322. (g)
Corrigan, N.; Shanmugam, S.; Xu, J.; Boyer, C. Chem. Soc. Rev. 2016, DOI: 10.1039/C6CS00185H.
10. For selected examples, see: (a) Condie, A. G.; Gonzalez-Gomez, J. C.; Stephenson, C. R. J. J. Am. Chem. Soc.
2010, 132, 1464. (b) Rueping, M.; Vila, C.; Koenigs, R. M.; Poscharny, K.; Fabry, D. C. Chem. Commun.
2011, 47, 2360. (c) Rueping, M.; Zhu, S. Q.; Koenigs, R. M. Chem. Commun. 2011, 47, 8679. (d) Liu, Q.; Li,
Y.-N.; Zhang, H.-H.; Chen, B.; Tung, C.-H.; Wu, L.-Z. Chem.-Eur. J. 2012, 18, 620. (e) Meng, Q.-Y.; Zhong,
J.-J.; Liu, Q.; Gao, X.-W.; Zhang, H.-H.; Lei, T.; Li, Z.-J.; Feng, K.; Chen, B.; Tung, C.-H.; Wu, L.-Z. J. Am.
Chem. Soc. 2013, 135, 19052. (f) Zhong, J.-J.; Meng, Q.-Y.; Liu, B.; Li, X.-B.; Gao, X.-W.; Lei, T.; Wu, C.-J.;
Li, Z.-J.; Tung, C.-H.; Wu, L.-Z. Org. Lett. 2014, 16, 1988. (g) Wu, C.-J.; Zhong, J.-J.; Meng, Q.-Y.; Lei, T.;
Gao, X.-W.; Tung, C.-H.; Wu, L.-Z. Org. Lett. 2015, 17, 884. (h) Xu, G. Q.; Li, C. G.; Liu, M. Q.; Cao, J.;
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 20
1
2
3
4
5
6
Luo, Y. C.; Xu, P. F. Chem. Commun. 2016, 52, 1190. (i) Liu, X.; Ye, X.; Bureš, F.; Liu, H.; Jiang, Z. Angew.
Chem., Int. Ed. 2015, 54, 11443. (j) Wei, G.; Zhang, C.; Bureš, F.; Ye, X.; Tan, C.-H.; Jiang, Z. ACS Catal.
2016, 6, 3708.
7
8
9
11. (a) Wang, Z. Q.; Hu, M.; Huang, X. C.; Gong, L. B.; Xie, Y. X.; Li, J. H. J. Org. Chem. 2012, 77, 8705. (b)
Zhu, S. Q.; Rueping, M. Chem. Commun. 2012, 48, 11960. (c) Gao, X. W.; Meng, Q. Y.; Xiang, M.; Chen, B.;
Feng, K.; Tung, C. H.; Wu, L. Z. Adv. Synth. Catal. 2013, 355, 2158. (d) Gao, X. W.; Meng, Q. Y.; Li, J. X.;
Zhong, J. J.; Lei, T.; Li, X. B.; Tung, C. H.; Wu, L. Z. ACS Catal. 2015, 5, 2391. (e) Tan, Y.; Yuan, W.; Gong,
L.; Meggers, E. Angew. Chem., Int. Ed. 2015, 54, 13045. (f) Upon the submission of this manuscript, we
noticed that a visible-light-induced photocatalytic intramolecular Povarov cyclization reaction for the
construction of quinoline-fused lactones had just been reported: Dong, W. H.; Hu, B.; Gao, X. S.; Li, Y. Y.;
Xie, X. M.; Zhang, Z. G. J. Org. Chem. 2016, 81, 8770.
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
12. (a) Huang, H.; Jiang, H.; Chen, K.; Liu, H. J. Org. Chem. 2009, 74, 5476. (b) McNulty, J.; Vemula, R.;
Bordon, C.; Yolken, R.; Jones-Brando, L. Org. Biomol. Chem. 2014, 12, 255. (c) Bharate, J. B.; Wani, A.;
Sharma, S.; Reja, S. I.; Kumar, M.; Vishwakarma, R. A.; Kumar, A.; Bharate, S. B. Org. Biomol. Chem. 2014,
12, 6267. (d) Wu, Y. C.; Liu, L.; Li, H. J.; Wang, D.; Chen, Y. J. J. Org. Chem. 2006, 71, 6592. (e) Isambert,
N.; Cruz, M.; Arevalo, M. J.; Gomez, E.; Lavilla, R. Org. Lett. 2007, 9, 4199.
13. (a) Villamena, F. A.; Liu, Y. P.; Zweier, J. L. J. Phys. Chem. A 2008, 112, 12607. (b) Ou, Z. Z.; Chen, J. R.;
Wang, X. S.; Zhang, B. W.; Cao, Y. New. J. Chem. 2002, 26, 1130. (c) Ma, J. H.; Zhao, J. Q.; Jiang, L. J.
Photochem. Photobiol. 2001, 74, 143.
20
ACS Paragon Plus Environment