Synthesis of Polysubstituted Quinolines from α-2-Aminoaryl Alcohols Via Nickel-Catalyzed Dehydrogenative Coupling

Article abstract of DOI:10.1021/acs.joc.7b03198

This study reports a nickel-catalyzed sustainable synthesis of polysubstituted quinolines from α-2-aminoaryl alcohols by a sequential dehydrogenation and condensation process that offers the advantages of a low catalyst loading and wide substrate scope. In contrast to earlier reported methods, this strategy allows the use of both primary as well as secondary α-2-aminoaryl alcohols in combination with either ketones or secondary alcohols for desired product formation. Using this methodology, 30 substituted quinoline derivatives were synthesized with up to 93% isolated yields.

Full text of DOI:10.1021/acs.joc.7b03198

Subscriber access provided by CORNELL UNIVERSITY LIBRARY
Article
Synthesis of Polysubstituted Quinolines from #-2-Aminoaryl
Alcohols Via Nickel-catalyzed Dehydrogenative Coupling
Sanju Das, Debabrata Maiti, and Suman De Sarkar
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03198 • Publication Date (Web): 18 Jan 2018
Downloaded from http://pubs.acs.org on January 18, 2018
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 10
The Journal of Organic Chemistry
1
2
3
4
5
6
Synthesis of Polysubstituted Quinolines from α-2-Aminoaryl Alco-
7
8
9
hols Via Nickel-catalyzed Dehydrogenative Coupling
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
Sanju Das, Debabrata Maiti, and Suman De Sarkar*
Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur-741246,
West Bengal, India
KEYWORDS: homogeneous catalysis. acceptorless dehydrogenation; nickel catalyst, quinoline, earth-abundant metal
ABSTRACT: This study reports a nickel catalyzed sustaina-
ble synthesis of polysubstituted quinolines from α-2-
aminoaryl alcohols by a sequential dehydrogenation and
condensation process that offers the advantages of low cat-
alyst loading and wide substrate scope. In contrast to earli-
er reported methods, this strategy allows the use of both
primary as well as secondary α-2-aminoaryl alcohols in
combination with either ketones or secondary alcohols for
desired product formation. Using this methodology, thirty
substituted quinoline derivatives were synthesized with up
to 93% isolated yield.
acceptorless dehydrogenation (AD) of alcohols7 have be-
come a prevailing tool for the sustainable synthesis of var-
INTRODUCTION
Quinolines1 are broadly found in natural products2 and
ious heterocyclic compounds. The key features of AD pro-
largely used in pharmaceutical industries, particularly as
cess are the generation of more reactive carbonyl com-
anticancer, antiviral, antimalarial and antituberculosis
pounds from alcohols by the release of dihydrogen as stoi-
agents (Figure 1).3 In addition, wide application of quino-
chiometric byproduct. The in situ generated carbonyl fur-
ther reacts with a suitable coupling partner to form the
lines and their derivatives are found in the preparation of
functional materials with improved physical properties.4
desired product in a sustainable manner. While significant
Consequently, there is an increasing demand for develop-
development in the field of C−C and C−N bond-forming
ing new methods towards the synthesis of highly function-
reactions has been reported using precious 4d and 5d
alized quinolines, preferably in an atom-economical and
transition metals,8 recent trend has drifted toward the us-
sustainable manner.5
age of earth-abundant, non-precious base metals like Mn,9
Fe,10 Co,11 and Ni.12
Scheme 1. Nickel Catalyzed Synthesis of Polysubstitut-
ed Quinolines by Acceptorless Dehydrogenation
Figure 1. Examples of bioactive quinoline derivatives
The traditional methods for constructing quinolines in-
clude the Combes synthesis from anilines and 1,3-
diketones, the Skraup synthesis from anilines and glycerin,
and the Friedländer synthesis from orthoacylanilines and
The catalytic synthesis of quinolines by indirect Fried-
lander reaction via an oxidative cyclization of 2-
α-methylene aldehydes/ketones.6 However, harsh reaction
conditions and undesired self-condensation of the starting
materials limits the scope and practicality of the quinoline
synthesis.5b
̈
aminobenzyl alcohol in combination with either ketones or
alcohols was described by the groups of Milstein,13 Shim,14
Yus,15 Verpoort,16 Kaneda17 and others18 employing Ru-
catalysis. Other precious metals like Ir19 and Pd20 has also
been used for similar transformations. In comparison, the
earth-abundant, eco-friendly and inexpensive first-row
In the recent years, the relatively stable α-2-aminoaryl
alcohols have been successfully employed for dehydro-
genative synthesis of quinolines. Especially, methods using
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 10
transition metals are much less explored in the synthesis
of quinoline derivatives.9e,21 In addition, most of the re-
ported methods are limited to the use 2-aminobenzyl alco-
hols as substrates with higher catalyst loading (5-8 mol %)
and superstoichiometric amount of base.22 Therefore, an
economical and universal synthetic strategy towards 4-
substituted quinoline derivatives employing variety of
different alcohols including secondary α-2-aminoaryl alco-
hols is highly desirable. In the present work, we have ad-
dressed the aforementioned issues by developing a gener-
alized and efficient nickel catalyzed dehydrogenative
method for the synthesis of polysubstituted quinolines
(Scheme 1). The used nickel catalyst 3 was first synthe-
sized by Jäger and Goedken23 and was readily prepared in
9
2
2
2
2
120 toluene
120 toluene
120 toluene
100 toluene
tBuOK
K2CO3
85
1
2
3
4
5
6
7
8
10
11d
12d
trace
92
tBuONa
tBuONa
45
aReaction conditions: 1a (0.3 mmol), 2a (0.25 mmol), 3 (2-5
mol %), solvent (1.5 mL), 16 h, under Ar. bIsolated yields.
cNiCl2 as catalyst. dSolvent (1.0 mL).
After establishing the optimal reaction condition, this
methodology was applied to other carbonyl derivatives
(Table 2). Differently substituted acetophenones smoothly
yielded 2-aryl quinolines (4ab-4ah) irrespective of the
electronic nature of the aryl group. Naphthyl and het-
eroaryl methyl ketones were also found to be the compe-
tent substrates (4ai-4ak). The method was successfully
utilized in the synthesis of the antibiotic agent 4al.26 The
reaction was not limited to the acetophenone derivatives.
Both acyclic diaryl ketone and α-tetralone delivered the
desired quinolines in good yields (4am and 4an). Alicyclic
as well as open chain aliphatic ketones underwent efficient
dehydrogenative coupling to form the targeted heterocy-
clic motif. In case of unsymmetrically substituted dialkyl-
ketone, exclusive formation of the kinetic product (4ap)
was observed.27 Disubstituted quinoline (4aq) was pre-
pared by applying β-keto ester as the carbonyl partner.
Finally, an aldehyde was also used to synthesize 3-
substituted quinoline derivative (4ar) in moderate yield.
9
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
a
single step by improved method reported by
Niewahner.24
RESULTS AND DISCUSSION
We commenced our study by treating 2-aminobenzyl alco-
hol 1 (1.2 equiv) and acetophenone 2 (1.0 equiv) in vari-
ous solvents (1.5 mL) at 135 °C for 16 h in the presence of
nickel catalyst 3 (5 mol %) and tBuONa (1.0 equiv) under
argon atmosphere (Table 1). Reactions were performed in
a closed vial and no specialized setup for the removal of H2
from the reaction mixture was necessary for the progress
of the reaction.12b,25 Toluene was found as the optimal sol-
vent leading to excellent yield of the desired quinoline de-
rivative (entry 1). Reaction was completely shut down in
absence of the nickel catalyst (entry 6). Another nickel
catalyst (NiCl2) was also inefficient (entry 7). Lowering of
temperature to 120 °C did not affect the yield (entry 5) but
further lowering resulted a significant drop (entry 12). We
were pleased to find that only 2 mol % catalyst 3 is suffi-
cient for effective reaction proving high efficiency of the
nickel catalyst (entry 8). Notably, tBuOK was also found to
be active, while the weak carbonate base was inefficient
(entry 9 and 10), which indicates that an effective depro-
tonation of the alcohol is necessary for the dehydrogena-
tion process. Finally, reaction at higher substrate concen-
tration (0.25 M) using lower amount of toluene also
showed equal efficiency (entry 11).
Table 2. Substrate Scope Using 2-Aminobenzyl Alcohol
and Various Carbonyl Compoundsa,b
Table 1. Optimization of the Reaction Conditionsa, b
Entry
3
T
Solvent
Base
Yield
[%]b
[mol %] [°C]
1
2
3
4
5
6
7c
8
5
5
5
5
5
0
5
2
135 toluene
135 DMF
135 DCE
tBuONa
tBuONa
tBuONa
90
trace
trace
81
aReaction conditions: 1a (0.6 mmol), 2b-r (0.5 mmol), 3 (2
mol %), tBuONa (0.5 mmol) in toluene (2 mL), under Ar. bI-
solated yields are shown.
135 1,4-dioxane tBuONa
120 toluene
120 toluene
120 toluene
120 toluene
tBuONa
tBuONa
tBuONa
tBuONa
90
0
The catalytic behavior of the nickel complex was further
explored by coupling differently substituted 2-
aminobenzyl alcohols with acetophenone (Table 3). Both
electron rich and electron poor 2-aminobenzyl alcohols
trace
92
ACS Paragon Plus Environment

Page 3 of 10
The Journal of Organic Chemistry
underwent smooth oxidation followed by cyclization to the
corresponding quinolines (4ba-4fa). Disubstituted deriva-
1
2
3
4
5
6
7
8
tives also delivered the desired product in good yields
(4ga and 4ha). We were pleased to found that the accep-
torless dehydrogenation process is not limited to the pri-
mary benzyl alcohols. Both alkyl and aryl substituted sec-
ondary 2-aminoaryl alcohols are also competent sub-
strates and good to excellent yields were obtained in all
cases (4ia-4ma). However, elevated temperature and ex-
tended reaction time were required for dehydrative cy-
clization of the less reactive ketones formed by the initial
nickel catalyzed dehydrogenation.
9
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. Substrate Scope Using Substituted 2-
Aminoaryl Alcohols and Acetophenonea,b
aReaction conditions: 1 (0.6 mmol), 5 (0.5 mmol), 3 (2 mol
%), tBuONa (0.5 mmol) in toluene (2 mL), under Ar. Isolated
yields are shown. cReaction performed at 135 °C for 24 h.
b
Under similar reaction conditions as used for ketones, both
the alcohols smoothly dehydrogenated to the correspond-
ing carbonyls and follow-up condensation reaction yielded
the quinoline derivatives 4. Various functional groups in-
cluding halogens, alkoxy and heteroaryls were well toler-
ated in the reaction medium. Likewise, the ketone sub-
strates, for the secondary alcohols as well, all the reactions
were performed in a close vial under argon atmosphere
and removal of evolved H2 from the reaction vessel was
not required for effective coupling. Thus, this methodology
truly represents an operationally simple, sustainable and
high-yielding single step access to the quinoline deriva-
tives.
aReaction conditions: 1b-m (0.6 mmol), 2a (0.5 mmol), 3 (2
mol %), tBuONa (0.5 mmol) in toluene (2 mL), under Ar. bI-
Control experiments was performed to investigate the
mechanistic aspects of the reaction. An isotope labelled 1a-
d2 was treated with acetophenone derivative 2c under the
standard nickel catalysis (Scheme 2). Reaction was
quenched after partial conversion and the crude mixture
c
solated yields are shown. Reaction performed at 135 °C for
24 h.
In order to further demonstrate the potential of nickel cat-
alyst 3, a double dehydrogenative coupling was also stud-
ied by using 2-aminoaryl alcohols in combination with
various secondary alcohols 5 (Table 4).
1
was carefully analyzed by H NMR study. Major extent of
deuterium was found to be retained in the quinoline prod-
uct as well as in the unreacted 2-aminobenzyl alcohol (1a-
d2). Another interesting observation revealed the for-
mation of deuterated secondary alcohol (5c-d1). This indi-
cates that initially the used carbonyl partner (2c) acts as a
hydrogen acceptor which upon progress of the reaction
regenerates the ketone by reversible dehydrogenation.
The α,β-unsaturated ketone 628 was prepared and treated
under the standard reaction condition to check the mode
of cyclization after the initial aldol condensation.27 Only
15% yield of the corresponding quinoline was obtained
after 16 h, this is most likely due to the constricted cycliza-
tion arising from the trans-geometry of the double bond.
Interestingly, inclusion of water was found to accelerate
the annulation process supposedly by eliminating the ge-
ometric constrain via a reversible oxa-Michael addition to
the double bond (Scheme 3).
Table 4. Double Dehydrogenative Coupling Using 2-
Aminoaryl Alcohols and Secondary Alcoholsa,b
Scheme 2. Mechanistic Studies
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 10
dride and freshly distilled under argon. Nickel catalyst 3
was prepared following reported procedure.24 The follow-
ing starting materials were synthesized according to pre-
viously described methods: α-2-aminoaryl alcohols 1b-
1c,29 1d-h,30 1i-m;30b,31 ketones 2l,32 2m;9g secondary alco-
hol 5,30b isotope labelled 1a-d230b,33 and aldol product 6.28
Other substrates were obtained from commercial sources
and were used without further purification. Yields refer to
isolated compounds, estimated to be >95% pure as deter-
mined by1HNMR. Thin layer chromatography (TLC) was
performed on Merck precoated silica gel 60 F254 alumi-
num sheets, detection under UV light at 254nm. Chromato-
graphic separations were carried out on Chempure Silica
gel (100–200 mesh). Melting point (M. p.): Labtronics LT-
110 capillary melting point apparatus was used. Nuclear
magnetic resonance (NMR) spectroscopy was performed
using JEOL 400 MHz and Bruker 500 MHz spectrometers. If
not otherwise specified, chemical shifts (δ) are provided in
ppm.
1
2
3
4
5
6
7
8
9
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
A probable catalytic cycle is depicted in Scheme 3 based on
the literature reports and afore mentioned mechanistic
studies. Dehydrogenation of the 2-aminobenzyl alcohol 1
generates reactive amino aldehyde 9 and nickel-hydride 8
via an alkoxy nickel species 7. The generated nickel-
hydride 8 either reacts with another molecule of 1 to re-
generate 7 with the liberation of dihydrogen or hydrogen-
ate the ketone to form secondary alcohols 5. The nickel
catalyzed reversible interconversion between 2 and 5 is
associated with the follow-up aldol reaction with the ami-
no aldehyde 9. As the aldol reaction proceeds the equilib-
rium shifts towards the ketone following the Le Chatelier's
principle with the generation of dihydrogen. Finally, dehy-
drative cyclization of the aldol product 10 resulted in the
formation of quinoline 4.
Optimization studies for the direct synthesis of quinolines
(Table 1):
The 2-aminobenzyl alcohol 1a (37 mg, 0.3 mmol, 1.2
equiv), acetophenone 2a (30 mg, 0.25 mmol, 1 equiv),
nickel catalyst 3 (2-5 mg, 0.01 mmol, 2-5 mol %) and base
(0.25 mmol, 1 equiv) were placed in a pre-dried 15 mL
sealed tube. The tube was degassed and purged with argon
for three times. Solvent (1.0-1.5 mL) was then added and
the mixture was stirred at variable temperature (110-135
°C) for 16 h. At ambient temperature, EtOAc (8 mL) was
added, and the reaction mixture was washed with brine (5
mL), dried over sodium sulfate, concentrated under vacu-
um and purified by silica gel column chromatography us-
ing 1% ethyl acetate in hexane to deliver 4aa.
Scheme 3. Proposed Mechanism
General procedure for the synthesis of quinolines by dehy-
drogenative coupling of α-2-aminoaryl alcohols and car-
bonyl compounds (GP 1):
The α-2-aminoaryl alcohol 1 (0.60 mmol, 1.2 equiv), car-
bonyl compound 2 (0.50 mmol, 1 equiv), nickel catalyst 3
(4 mg, 0.01 mmol, 2 mol %) and tBuONa (48 mg, 0.50
mmol, 1 equiv) were placed in a pre-dried 15 mL sealed
tube. The tube was degassed and purged with argon for
three times. Toluene (2.0 mL) was then added and the mix-
ture was stirred at 120 °C or 135 °C for 16-24 h. At ambi-
ent temperature, EtOAc (8 mL) was added, and the reac-
tion mixture was washed with brine (5 mL), dried over
sodium sulfate, concentrated under vacuum and purified
by silica gel column chromatography using 0.5−15% ethyl
acetate in hexanes to deliver the quinoline 4.
CONCLUSION
In summary, an atom efficient and versatile nickel cata-
lyzed practical synthesis of polysubstituted quinolines
from α-2-aminoaryl alcohols in combination with either
ketones or secondary alcohols is reported. The sequential
dehydrogenation and condensation process result in the
selective formation of C−C and C−N bonds with the libera-
tion of dihydrogen and water. A major highlight of this
strategy is the use of secondary α-2-aminoaryl alcohols,
leading to the synthesis of various 4-substituted quino-
lines. This methodology represents an operationally sim-
ple, sustainable synthetic method and offers future oppor-
tunities for method developments based on earth-
abundant metals.
General procedure for the synthesis of quinolines by dehy-
drogenative coupling of α-2-aminoaryl alcohols and sec-
ondary alcohols (GP 2):
The α-2-aminoaryl alcohol 1 (0.60 mmol, 1.2 equiv), sec-
ondary alcohol 5 (0.50 mmol, 1 equiv), nickel catalyst 3 (4
mg, 0.01 mmol, 2 mol %) and tBuONa (48 mg, 0.50 mmol, 1
equiv) were placed in a pre-dried 15 mL sealed tube. The
tube was degassed and purged with argon for three times.
Toluene (2.0 mL) was then added and the mixture was
stirred at 120 °C for 16-24 h. At ambient temperature,
EtOAc (8 mL) was added and the reaction mixture was
washed with brine (5 mL), dried over sodium sulfate, con-
EXPERIMENTAL SECTION
General Information. Catalytic reactions were performed
under argon atmosphere using pre-dried glassware and
standard sealed tube. Toluene was dried with calcium hy-
ACS Paragon Plus Environment

Page 5 of 10
The Journal of Organic Chemistry
centrated under vacuum and purified by silica gel column
chromatography using 0.5−15% ethyl acetate in hexanes
ethyl acetate in hexanes yielded 4ad (98 mg, 82%) as a
white solid (M. p.: 111–112°C). H NMR (400 MHz, CDCl3)
1
1
2
3
4
5
6
7
8
9
to deliver the quinoline 4.
δ 8.21 (d, J = 8.7 Hz, 1H), 8.16 (d, J = 8.3 Hz, 1H), 8.12 (d, J =
8.4 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.76 – 7.71 (m, 1H),
7.56 – 7.51 (m, 1H), 7.49 (d, J = 8.4 Hz, 2H). 13C NMR (126
MHz, CDCl3) δ 156.1, 148.4, 138.2, 137.0, 135.7, 129.9,
129.8, 129.1, 128.9, 127.6, 127.3, 126.6, 118.6.
2-(4-Bromophenyl)quinoline (4ae):19a The GP 1 was
followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and 4-
bromoacetophenone 2e (100 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 1% ethyl
acetate in hexanes yielded 4ae (128 mg, 91%) as a white
solid (M. p.: 118–119 °C). 1H NMR (400 MHz, CDCl3) δ 8.19
(d, J = 8.6 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 8.05 (d, J = 8.7
Hz, 2H), 7.81 (d, J = 8.6 Hz, 2H), 7.73 (m,1H), 7.65 (d, J = 8.5
Hz, 2H), 7.54 (dd, J = 11.1, 4.1 Hz, 1H). 13C NMR (126 MHz,
CDCl3) δ 156.1, 148.4, 138.6, 137.0, 132.1, 129.9, 129.8,
129.2, 127.6, 127.4, 126.6, 124.0, 118.6.
2-(2-Bromophenyl)quinoline (4af):34 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
phenyl)-methanol 1a (74 mg, 0.6 mmol) and 2-
bromoacetophenone 2f (100 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 1% ethyl
acetate in hexanes yielded 4af (111 mg, 79%) as a yellow
solid (M.p.: 74-75°C). 1H NMR (500 MHz, CDCl3) δ 8.22 (d, J
= 8.6 Hz, 1H), 8.19 (d, J = 8.6 Hz, 1H), 7.87 (d, J = 8.1 Hz,
1H), 7.77 – 7.73 (m, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.64 (dd, J
= 7.6, 1.6 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.45 (m, 1H), 7.30
(m, 1H). 13C NMR (126 MHz, CDCl3) δ 158.9, 148.1, 141.8,
135.8, 133.4, 131.7, 130.1, 129.8, 127.8, 127.7, 127.3,
126.9, 122.8, 122.0.
2-Phenylquinoline (4aa):19a The GP 1 was followed using
nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-phenyl)-
methanol 1a (74 mg, 0.6 mmol) and acetophenone 2a (60
mg, 0.5 mmol). After 16 h, purification by column chroma-
tography using 1% ethyl acetate in hexanes yielded 4aa
(94 mg, 92%).
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol)
and 1-(phenyl)ethanol 5a (61 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 1% ethyl
acetate in hexanes yielded 4aa (71 mg, 69%) as a white
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
solid (M. p.: 81–82°C). H NMR (400 MHz, CDCl3) δ 8.23 –
8.17 (m, 4H), 7.87 (d, J = 8.8 Hz, 1H), 7.82 (d, J = 8.5 Hz,
1H), 7.74 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.58 – 7.45 (m, 4H).
13C NMR (126 MHz, CDCl3) δ 157.5, 148.4, 139.8, 136.8,
129.9, 129.7, 129.4, 128.9, 127.7, 127.6, 127.3, 126.4,
119.1.
2-(4-Methoxyphenyl)quinoline (4ab):19a The GP 1 was
followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and 4-
methoxyacetophenone 2b (75 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 2% ethyl
acetate in hexanes yielded 4ab (86 mg, 73%).
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol)
and 1-(4-methoxyphenyl)ethanol 5b (76 mg, 0.5 mmol).
After 16 h, purification by column chromatography using
2% ethyl acetate in hexanes yielded 4ab (85 mg, 72%) as a
1
white solid (M. p.: 123–124 °C). H NMR (400 MHz, CDCl3)
2-(3-Chlorophenyl)quinoline (4ag):35 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
phenyl)-methanol 1a (74 mg, 0.6 mmol) and 3-
chloroacetophenone 2g (77 mg, 0.5 mmol). After 16 h, pu-
rification by column chromatography using 1% ethyl ace-
tate in hexanes yielded 4ag (97 mg, 81%) as a pale-yellow
δ 8.24 – 8.06 (m, 4H), 7.83 (d, J = 8.6 Hz, 1H), 7.80 (d, J =
7.7 Hz, 1H), 7.71 (ddd, J = 8.3, 7.0, 1.2 Hz, 1H), 7.50 (t, J =
7.7 Hz, 1H), 7.05 (d, J = 8.9 Hz, 2H), 3.89 (s, 3H). 13C NMR
(126 MHz, CDCl3) δ 161.0, 157.1, 148.5, 136.7, 132.4,
129.7, 129.0, 127.6, 127.1, 126.0, 118.7, 114.4, 55.5.
2-p-Tolylquinoline (4ac):19a The GP 1 was followed using
nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-phenyl)-
methanol 1a (74 mg, 0.6 mmol) and 4-
methylacetophenone 2c (67 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 1% ethyl
acetate in hexanes yielded 4ac (101 mg, 92%) as a white
solid (M. p.: 82–83°C). 1 H NMR (400 MHz, CDCl3) δ 8.19 (d,
J = 4.5 Hz, 1H), 8.17 (d, J = 4.5 Hz, 1H), 8.09 (d, J = 8.2 Hz,
2H), 7.86 (d, J = 8.9 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.72
(m, 1H), 7.51 (t, J = 6.9 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H), 2.45
(s, 3H). 13C NMR (126 MHz, CDCl3) δ 157.3, 148.3, 139.4,
136.9, 136.6, 129.6, 129.5, 127.4, 127.4, 127.1, 126.0,
118.8, 21.3.
2-(4-Chlorophenyl)quinoline (4ad):19a The GP 1 was
followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and 4-
chloroacetophenone 2d (77 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 1% ethyl
acetate in hexanes yielded 4ad (111 mg, 93%).
1
solid (M.p.: 66-68°C). H NMR (400 MHz, CDCl3) δ 8.23 –
8.16 (m, 3H), 8.04 – 8.00 (m, 1H), 7.81 (d, J = 8.4 Hz, 2H),
7.74 (t, J = 7.4 Hz, 1H), 7.57 – 7.51 (m, 1H), 7.44 (dd, J = 4.8,
1.4 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 155.8, 148.4,
141.6, 137.1, 135.1, 130.1, 130.0, 129.9, 129.4, 127.8,
127.6, 127.5, 126.7, 125.7, 118.8.
2-(3-Methoxyphenyl)quinoline (4ah):36 The GP 1 was
followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and 3-
methoxyacetophenone 2h (75 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 2% ethyl
acetate in hexanes yielded 4ah (99 mg, 84%).
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol)
and 1-(3-methoxyphenyl)ethanol 5h (76 mg, 0.5 mmol).
After 16 h, purification by column chromatography using
2% ethyl acetate in hexanes yielded 4ah (99 mg, 84%) as a
1
brown liquid. H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.5
Hz, 2H), 7.86 (d, J = 8.5 Hz, 1H), 7.83 – 7.78 (m, 2H), 7.73
(m, 2H), 7.55 – 7.49 (m, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.03
(dd, J = 8.4, 2.0 Hz, 1H), 3.94 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ 160.3, 157.2, 148.3, 141.3, 136.8, 129.9, 129.9,
129.7, 127.5, 127.4, 126.4, 120.1, 119.2, 115.5, 112.9, 55.5.
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol)
and 1-(4-chlorophenyl)ethanol 5d (76 mg, 0.5 mmol). Af-
ter 16 h, purification by column chromatography using 1%
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 10
2-(Naphthalen-2-yl)quinoline (4ai):19a The GP 1 was
16 h, purification by column chromatography using 8%
1
2
3
4
5
6
7
8
followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and 1-
naphthalen-2-yl-ethanone 2i (85 mg, 0.5 mmol). After 16
h, purification by column chromatography using 1% ethyl
acetate in hexanes yielded 4ai (106 mg, 83%).
ethyl acetate in hexanes yielded 4al (60 mg, 44%) as a
1
viscous liquid. H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.5
Hz, 1H), 8.16 (s, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.81 (ddd, J =
8.3, 7.0, 1.2 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.56 (s, 1H),
7.41 – 7.33 (m, 5H), 7.12 (s, 1H), 6.93 (s, 1H). 13C NMR (126
MHz, CDCl3)
δ 155.0, 147.7, 137.7, 137.4, 133.2,
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol)
and 1-naphthalen-2-yl-ethanol 5i (86 mg, 0.5 mmol). After
16 h, purification by column chromatography using 1%
ethyl acetate in hexanes yielded 4ai (106 mg, 83%) as a
130.9,129.9, 129.8, 129.4, 128.8, 128.5, 127.9, 127.5, 127.0,
120.9.
3-Benzyl-2-(4-methoxy-phenyl)-quinoline (4am):38 The
GP 1 was followed using nickel catalyst 3 (4 mg, 2.0 mol
%), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and
1-(4-methoxy-phenyl)-3-phenyl-propane-1-one 2m (120
mg, 0.5 mmol). After 16 h, purification by column chroma-
tography using 2% ethyl acetate in hexanes yielded 4am
(135 mg, 83%) as a yellow solid. 1H NMR (400 MHz, CDCl3)
δ 8.12 (d, J = 8.4 Hz, 1H), 7.89 (s, 1H), 7.72 (d, J = 8.3 Hz,
1H), 7.69 – 7.61 (m, 1H), 7.50 – 7.46 (m, 1H), 7.45 (d, J =
8.5 Hz, 2H), 7.29 – 7.15 (m, 3H), 7.04 – 7.00 (m, 2H), 6.96
(d, J = 8.9 Hz, 2H), 4.15 (s, 2H), 3.85 (s, 3H). 13C NMR (126
MHz, CDCl3) δ 160.5, 159.8, 146.8, 140.2, 137.2, 133.3,
132.7, 130.4, 129.3, 129.2, 129.1, 128.6, 127.5, 127.2,
126.4, 126.4, 113.9, 55.5, 39.3.
9
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
white solid (M. p.: 161-162 °C). H NMR (400 MHz, CDCl3)
δ 8.63 (s, 1H), 8.39 (dd, J = 8.7, 1.8 Hz, 1H), 8.26 (d, J = 8.5
Hz, 1H), 8.22 (d, J = 8.8 Hz, 1H), 8.04 – 7.97 (m, 3H), 7.91
(dd, J = 5.9, 3.4 Hz, 1H), 7.83 (d, J = 8.2 Hz, 1H), 7.76 (m,
1H), 7.58 – 7.51 (m, 3H). 13C NMR (126 MHz, CDCl3) δ
157.3, 148.5, 137.1, 136.9, 134.0, 133.7, 130.0, 129.8,
129.0, 128.7, 127.8, 127.6, 127.4, 127.3, 126.8, 126.5,
125.2, 119.3.
2-(Thiophen-2-yl)quinoline (4aj):37 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
phenyl)-methanol 1a (74 mg, 0.6 mmol) and 1-thiophen-2-
yl-ethanone 2j (63 mg, 0.5 mmol). After 16 h, purification
by column chromatography using 1% ethylacetate in hex-
anes yielded 4aj (91 mg, 86%).
5,6-Dihydrobenzo[c]acridine (4an):19a The GP 1 was
followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and α-
tetralone 2n (73 mg, 0.5 mmol). After 16 h, purification by
column chromatography 2% ethyl acetate in hexanes
yielded 4an (100 mg, 87%) as a white solid (M. p.: 64-65
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol)
and 1-thiophen-2-yl-ethanol 5J (64 mg, 0.5 mmol). After
16 h, purification by column chromatography using 1%
ethyl acetate in hexanes yielded 4aj (93 mg, 88%) as a
white solid (M. p.: 130-131°C). 1H NMR (500 MHz, CDCl3) δ
8.13 (d, J = 8.6 Hz, 1H), 8.09 (d, J = 8.5 Hz, 1H), 7.79 (d, J =
8.6 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H), 7.74 (dd, J = 3.6, 0.7 Hz,
1H), 7.71 – 7.66 (m, 1H), 7.51 – 7.45 (m, 2H), 7.16 (dd, J =
4.9, 3.8 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 152.5, 148.3,
145.6, 136.7, 129.9, 129.4, 128.7, 128.2, 127.6, 127.3,
126.2, 126.0, 117.8.
2-(Pyridin-3-yl)quinoline (4ak):21a The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
phenyl)-methanol 1a (74 mg, 0.6 mmol ), and 1-pyridine-
3-yl-ethanone 2k (60.5 mg, 0.5 mmol). After 16 h, purifica-
tion by column chromatography using 15% ethyl acetate in
hexanes yielded 4ak (79 mg, 77%).
1
°C). H NMR (500 MHz, CDCl3) δ 8.59 (d, J = 7.7 Hz, 1H),
8.14 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H), 7.74 (d, J = 8.1 Hz, 1H),
7.65 (dd, J = 8.2, 7.1 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.43 (t,
J = 7.5 Hz, 1H), 7.37 (t, J = 7.3 Hz, 1H), 7.28 (d, J = 7.4 Hz,
1H), 3.13 (t, J = 6.8 Hz, 2H), 3.03 – 3.00 (m, 2H). 13C NMR
(126 MHz, CDCl3) δ 153.5, 147.8, 139.5, 134.9, 133.8,
130.7, 129.8, 129.6, 128.7, 128.0, 128.0, 127.5, 127.0,
126.2, 126.2, 29.0, 28.6.
1,2,3,4-Terahydro-acridine (4ao):39 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
phenyl)-methanol 1a (62 mg, 0.5 mmol) and cyclohexa-
none 2o (74 mg, 0.75 mmol). After 16 h, purification by
column chromatography using 1% ethyl acetate in hexanes
1
yielded 4ao (62 mg, 68%) as a colorless oil. H NMR (400
MHz, CDCl3) δ 7.96 (d, J = 8.4 Hz, 1H), 7.72 (s, 1H), 7.64 (d, J
= 8.3 Hz, 1H), 7.61 – 7.53 (m, 1H), 7.44 – 7.36 (m, 1H), 3.10
(t, J = 6.5 Hz, 2H), 2.91 (t, J = 6.3 Hz, 2H), 2.00 – 1.92 (m,
2H), 1.85 (qd, J = 6.2, 2.9 Hz, 2H), 13C NMR (126 MHz,
CDCl3) δ 159.3, 146.7, 135.0, 131.0, 128.5, 128.3, 127.3,
126.9, 125.5, 33.6, 29.3, 23.3, 22.9.
2-Isobutyl-quinoline (4ap):39 The GP 1 was followed us-
ing nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-phenyl)-
methanol 1a (62 mg, 0.5 mmol) and 4-methylpentan-2-one
2p (75 mg, 0.75 mmol). After 16 h, purification by column
chromatography 1% ethyl acetate in hexanes yielded 4ap
(57 mg, 62%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ
8.06 (d, J = 3.1 Hz, 1H), 8.04 (d, J = 3.0 Hz, 1H), 7.77 (d, J =
8.4 Hz, 1H), 7.67 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.51 – 7.44
(m, 1H), 7.26 (d, J = 8.4 Hz, 1H), 2.85 (d, J = 7.3 Hz, 2H),
2.28 – 2.14 (m, 1H), 0.98 (d, J = 6.7 Hz, 6H). 13C NMR (101
MHz, CDCl3) δ 162.4, 148.0, 136.0, 129.4, 129.0, 127.6,
126.8, 125.8, 122.2, 48.5, 29.6, 22.7.
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-methanol 1a (74 mg, 0.6 mmol)
and 1-pyridine-3-yl-ethanol 5k (62 mg, 0.5 mmol). After
16 h, purification by column chromatography using 15%
ethyl acetate in hexanes yielded 4ak (78 mg, 76%) as a
1
brown solid (M.p.: 66-67 °C). H NMR (400 MHz, CDCl3) δ
9.36 (d, J = 2.1 Hz, 1H), 8.70 (dd, J = 4.8, 1.6 Hz, 1H), 8.52
(dt, J = 7.7, 1.7 Hz, 1H), 8.28 (d, J = 8.6 Hz, 1H), 8.18 (d, J =
8.6 Hz, 1H), 7.89 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H),
7.76 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.60 – 7.53 (m, 1H), 7.46
(dd, J = 7.8, 4.8 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 154.8,
150.3, 149.0, 148.5, 137.3, 135.3, 135.1, 130.1, 129.9,
127.7, 127.5, 126.9, 123.8, 118.7.
3-(Imidazol-1-yl-2-phenyl)quinoline (4al):26 The GP 1
was followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-phenyl)-methanol 1a (74 mg, 0.6 mmol) and 2-
imidazol-1-yl-phenyl-ethanone 2l (93 mg, 0.5 mmol). After
ACS Paragon Plus Environment

Page 7 of 10
The Journal of Organic Chemistry
2-Methyl-quinoline-3-carboxylic acid ethyl ester The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
(4aq):40 The GP 1 was followed using nickel catalyst 3 (4
mg, 2.0 mol %), (2-amino-phenyl)-methanol 1a (62 mg, 0.5
mmol) and ethylacetoacetate 2q (98 mg, 0.75 mmol). After
16 h, purification by column chromatography 3% ethyl
acetate in hexanes yielded 4aq (63 mg, 59%) as a yellow
oil. 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.04 (d, J = 8.6
Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.82 – 7.75 (m, 1H), 7.54
(dd, J = 11.2, 4.1 Hz, 1H), 4.44 (q, J = 7.2 Hz, 2H), 2.99 (s,
3H), 1.46 (t, J = 7.2 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ
166.7, 158.6, 148.8, 140.0, 131.8, 128.7, 128.6, 126.6,
125.9, 124.2, 61.5, 25.8, 14.47.
mol %), (2-amino-3-methylphenyl)methanol 1d (82 mg,
0.6 mmol) and 1-phenylethanol 5a (61 mg, 0.5 mmol). Af-
ter 16 h, purification by column chromatography using 2%
ethyl acetate in hexanes yielded 4da (89 mg, 81%) as a
1
2
3
4
5
6
7
8
1
pale-yellow oil. H NMR (400 MHz, CDCl3) δ 8.30 (dd, J =
7.1, 1.4 Hz, 2H), 8.18 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 8.5 Hz,
1H), 7.67 (d, J = 8.2 Hz, 1H), 7.61 – 7.57 (m, 1H), 7.55 (d, J =
7.8 Hz, 2H), 7.49 (ddd, J = 8.5, 4.4, 1.4 Hz, 1H), 7.45 – 7.40
(m, 1H), 2.94 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 155.6,
147.3, 140.0, 137.8, 137.0, 129.8, 129.3, 128.9, 127.6,
127.2, 126.1, 125.5, 118.3, 18.0.
9
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
3-Phenylquinoline (4ar):35 The GP 1 was followed using
8-Chloro-2-phenylquinoline (4ea):42 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
3- chlorophenyl)methanol 1e (94 mg, 0.6 mmol) and ace-
tophenone 2a (60 mg, 0.5 mmol). After 16 h, purification
by column chromatography 2% ethyl acetate in hexanes
nickel catalyst
3 (4 mg, 2.0 mol %), (2-amino-
phenyl)methanol 1a (74 mg, 0.6 mmol) and phenylacetal-
dehyde 2r (60 mg, 0.5 mmol). After 16 h, purification by
column chromatography 1% ethyl acetate in hexanes
yielded 4ar (44 mg, 43%) as a pale-yellow solid (M. p.: 49-
51 °C). 1H NMR (400 MHz, CDCl3) δ 9.19 (d, J = 2.3 Hz, 1H),
8.31 (d, J = 2.2 Hz, 1H), 8.15 (d, J = 8.6 Hz, 1H), 7.92 – 7.87
(m, 1H), 7.76 – 7.68 (m, 3H), 7.62 – 7.51 (m, 3H), 7.47 –
7.41 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 150.1, 138.1,
134.0, 133.4, 129.5, 129.4, 129.3, 128.3, 128.2, 128.2,
128.1, 127.6, 127.2.
6-Bromo-2-phenylquinoline (4ba):34 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
5-bromophenyl)methanol 1b (121 mg, 0.6 mmol) and ace-
tophenone 2a (60 mg, 0.5 mmol). After 16 h, purification
by column chromatography 2% ethyl acetate in hexanes
yielded 4ba (131 mg, 92%) as a colorless solid (M. p.: 114-
115 °C). 1H NMR (500 MHz, CDCl3) δ 8.16 (d, J = 7.9 Hz,
2H), 8.10 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 8.9 Hz, 1H), 7.97 (s,
1H), 7.88 (d, J = 8.6 Hz, 1H), 7.78 (d, J = 8.9 Hz, 1H), 7.53 (t,
J = 7.5 Hz, 2H), 7.49 (d, J = 6.8 Hz, 1H). 13C NMR (126 MHz,
CDCl3) δ 157.8, 147.0, 139.3, 135.8, 133.2, 131.6, 129.7,
129.6, 129.0, 128.4, 127.7, 120.2, 119.9.
1
yielded 4ea (98 mg, 82%) as a viscous oil. H NMR (400
MHz, CDCl3) δ 8.32 – 8.26 (m, 2H), 8.23 (d, J = 8.5 Hz, 1H),
7.97 (d, J = 8.4 Hz, 1H), 7.85 (dd, J = 7.6, 1.4 Hz, 1H), 7.76 –
7.73 (m, 1H), 7.54 (dd, J = 8.3, 6.5 Hz, 2H), 7.51 – 7.46 (m,
1H), 7.45 – 7.40 (m, 1H). 13C NMR (126 MHz, CDCl3) δ
157.6, 144.5, 139.2, 137.3, 134.2, 129.9, 129.0, 128.6,
127.8, 126.7, 126.2, 119.5.
7-Fluoro-2-phenylquinoline (4fa):43 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
4-fluorophenyl)methanol 1f (85 mg, 0.6 mmol ) and aceto-
phenone 2a (60 mg, 0.5 mmol). After 16 h, purification by
column chromatography 2% ethyl acetate in hexanes
1
yielded 4fa (94 mg, 84%) as a white solid. H NMR (400
MHz, CDCl3) δ 8.20 (d, J = 8.5 Hz, 1H), 8.16 (d, J = 7.3 Hz,
2H), 7.85 (d, J = 8.7 Hz, 1H), 7.80 (dd, J = 9.5, 2.7 Hz, 2H),
7.57 – 7.45 (m, 3H), 7.32 (td, J = 8.6, 2.6 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ 163.4 (d, J = 249.6 Hz), 158.5, 149.4 (d,
J = 13.0 Hz), 139.4, 136.8, 129.7, 129.6 (d, J = 10.0 Hz),
129.0, 127.7, 124.3, 118.5 (d, J = 2.0 Hz), 116.9 (d, J = 25.5
Hz), 113.4 (d, J = 20.2 Hz). 19F NMR (376 MHz, CDCl3) δ -
109.5 (dd, J = 8.4, 8.4 Hz).
6,8-Dibromo-2-phenylquinoline (4ga):44 The GP 1 was
followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-3,5-dibromophenyl)methanol 1g (169 mg, 0.6
mmol) and acetophenone 2a (60 mg, 0.5 mmol). After 16 h,
purification by column chromatography 2% ethyl acetate
in hexanes yielded 4ga (158 mg, 87%).
6-Iodo-2-phenylquinoline (4ca):41 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
5-iodophenyl)methanol 1c (149 mg, 0.6 mmol) and aceto-
phenone 2a (60 mg, 0.5 mmol). After 16 h, purification by
column chromatography 2% ethyl acetate in hexanes
yielded 4ca (146 mg, 88%).
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-5-iodophenyl)methanol 1c (149 mg, 0.6
mmol) and 1-phenylethanol 5a (61 mg, 0.5 mmol). After
16 h, purification by column chromatography using 2%
ethyl acetate in hexanes yielded 4ca (108 mg, 65%) as a
white solid. 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 1.7 Hz,
1H), 8.15 (d, J = 6.9 Hz, 2H), 8.09 (d, J = 8.7 Hz, 1H), 7.95
(dd, J = 8.9, 2.0 Hz, 1H), 7.89 (dd, J = 8.9, 3.8 Hz, 2H), 7.56 –
7.45 (m, 3H). 13C NMR (126 MHz, CDCl3) δ 158.0, 147.4,
139.4, 138.5, 136.4, 135.6, 131.6, 129.8, 129.0, 129.0,
127.7, 119.7, 91.7.
8-Methyl-2-phenylquinoline (4da):19a The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-amino-
3-methylphenyl)methanol 1d (82 mg, 0.6 mmol) and ace-
tophenone 2a (60 mg, 0.5 mmol). After 16 h, purification
by column chromatography 2% ethyl acetate in hexanes
yielded 4da (93 mg, 85%).
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-3,5-dibromophenyl)methanol (169 mg,
0.6 mmol) and 1-phenylethanol 5a (61 mg, 0.5 mmol). Af-
ter 16 h, purification by column chromatography using 2%
ethyl acetate in hexanes yielded 4ga (136 mg, 75%) as a
1
white solid (M. p.: 95-97 °C). H NMR (400 MHz, CDCl3) δ
8.31 – 8.26 (m, 2H), 8.15 (d, J = 2.3 Hz, 1H), 8.10 (d, J = 8.8
Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.93 (d, J = 2.1 Hz, 1H),
7.57 – 7.47 (m, 3H). 13C NMR (126 MHz, CDCl3) δ 157.8,
143.9, 138.5, 136.3, 136.0, 130.2, 129.4, 129.0, 128.9,
127.7, 126.6, 120.0, 119.4.
6,7-Dimethoxy-2-phenylquinoline (4ha):35 The GP 1
was followed using nickel catalyst 3 (4 mg, 2.0 mol %), (2-
amino-4,5-dimethoxyphenyl)methanol 1h (110 mg, 0.6
mmol) and acetophenone 2a (60 mg, 0.5 mmol). After 16 h,
purification by column chromatography 15% ethyl acetate
in hexanes yielded 4ha (106 mg, 76%) as a pale-yellow
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 10
solid (M.p.: 132-134 °C). 1H NMR (400 MHz, CDCl3) δ 8.13 –
(d, J = 8.4 Hz, 1H), 8.21 (d, J = 7.3 Hz, 2H), 7.92 (d, J = 8.4
1
2
3
4
8.08 (m, 2H), 8.06 (d, J = 8.5 Hz, 1H), 7.73 (d, J = 8.4 Hz,
1H), 7.54 – 7.48 (m, 3H), 7.47 – 7.39 (m, 1H), 7.07 (s, 1H),
4.06 (s, 3H), 4.03 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
155.6, 152.7, 149.8, 145.4, 140.2, 135.1, 129.0, 128.9,
127.4, 122.9, 117.5, 108.5, 105.0, 56.3, 56.2.
Hz, 1H), 7.84 (s, 1H), 7.78 – 7.72 (m, 1H), 7.60 – 7.52 (m,
7H), 7.51 – 7.45 (m, 2H). 13C NMR (101 MHz, CDCl3) δ
157.0, 149.3, 148.9, 139.8, 138.5, 130.3, 129.7, 129.6,
129.5, 129.0, 128.7, 128.5, 127.7, 126.5, 125.9, 125.8,
119.5.
5
6
7
8
9
4-Methyl-2-phenylquinoline (4ia):34 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), 1-(2-
amino-phenyl)ethanol 1i (82 mg, 0.6 mmol) and acetophe-
none 2a (60 mg, 0.5 mmol). After 16 h, purification by col-
umn chromatography 2% ethyl acetate in hexanes yielded
4ia (73 mg, 67%).
4-(4-Methoxyphenyl)-2-phenylquinoline (4ma):47 The
GP 1 was followed using nickel catalyst 3 (4 mg, 2.0 mol
%), (2-aminophenyl)-(4-methoxyphenyl)methanol 1m
(137 mg, 0.6 mmol) and acetophenone 2a (60 mg, 0.5
mmol). After 24 h, purification by column chromatography
5% ethyl acetate in hexanes yielded 4ma (87 mg, 56%) as
a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.4 Hz,
1H), 8.19 (d, J = 7.1 Hz, 2H), 7.95 (d, J = 8.2 Hz, 1H), 7.80 (s,
1H), 7.76 – 7.68 (m, 1H), 7.58 – 7.43 (m, 6H), 7.09 (d, J =
8.5 Hz, 2H), 3.92 (s, 3H). 13C NMR (126 MHz, CDCl3) δ
160.1, 157.1, 149.1, 149.0, 140.0, 131.0, 130.9, 130.3,
129.6, 129.4, 129.0, 127.7, 126.4, 126.2, 125.8, 119.5,
114.3, 55.6.
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 GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), (2-amino-phenyl)-ethanol 1a (82 mg, 0.6 mmol)
and 1-phenylethanol 5a (61 mg, 0.5 mmol). After 16 h,
purification by column chromatography using 2% ethyl
acetate in hexanes yielded 4ia (63 mg, 58%) as a yellow
1
viscous liquid. H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.5
Hz, 1H), 8.17 – 8.14 (m, 2H), 8.01 (d, J = 8.3 Hz, 1H), 7.75 –
7.69 (m, 2H), 7.58 – 7.50 (m, 3H), 7.46 (dd, J = 8.4, 6.1 Hz,
1H), 2.78 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 157.2, 148.3,
145.0, 140.0, 130.4, 129.5, 129.3, 128.9, 127.7, 127.4,
126.2, 123.8, 119.9, 19.1.
4-Ethyl-2-phenylquinoline (4ja):45 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), 1-(2-
aminophenyl)propanol 1j (91 mg, 0.6 mmol) and aceto-
phenone 2a (60 mg, 0.5 mmol). After 24 h, purification by
column chromatography 2% ethyl acetate in hexanes
yielded 4ja (52 mg, 45%) as a viscous liquid. 1H NMR (400
MHz, CDCl3) δ 8.19 (d, J = 8.3 Hz, 1H), 8.17 – 8.14 (m, 2H),
8.05 (d, J = 8.3 Hz, 1H), 7.75 – 7.68 (m, 2H), 7.54 (m, 3H),
7.48 – 7.43 (m, 1H), 3.18 (q, J = 7.6 Hz, 2H), 1.46 (t, J = 7.6
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 157.4, 150.6, 148.5,
140.2, 130.6, 129.3, 129.3, 128.9, 127.7, 126.5, 126.1,
123.4, 118.0, 25.5, 14.4.
4-Butyl-2-phenylquinoline (4ka):46 The GP 1 was fol-
lowed using nickel catalyst 3 (4 mg, 2.0 mol %), 1-(2-
aminophenyl)pentanol 1k (107 mg, 0.6 mmol) and aceto-
phenone 2a (60 mg, 0.5 mmol). After 24 h, purification by
column chromatography 1% ethyl acetate in hexanes
yielded 4ka (87 mg, 67%) as a viscous liquid. 1H NMR (400
MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 1H), 8.16 (dd, J = 5.5, 3.5
Hz, 2H), 8.05 (d, J = 8.3 Hz, 1H), 7.74 – 7.68 (m, 2H), 7.57 –
7.50 (m, 3H), 7.46 (dd, J = 8.4, 6.3 Hz, 1H), 3.17 – 3.10 (m,
2H), 1.81 (ddd, J = 12.8, 8.7, 6.7 Hz, 2H), 1.56 – 1.44 (m,
2H), 1.01 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
157.2, 149.4, 148.6, 140.1, 130.6, 129.3, 128.9, 127.7,
126.7, 126.1, 123.6, 118.9, 32.5, 32.4, 23.0, 14.1.
Reaction with isotope labelled 1a-d2 (Scheme 2a): Sol-
id 1a-d2 (0.1 mmol, 1.0 equiv) and tBuONa (10 mg, 0.1
mmol, 1 equiv) were placed in a pre-dried 15 mL sealed
tube. The tube was degassed and purged with argon for
three times.
A standard solution containing 1-(p-
tolyl)ethenone 2c (13 mg, 0.10 mmol, 1 equiv), nickel cata-
lyst 3 (0.8 mg, 2µmol, 2 mol %) in degassed toluene (1.0
mL) was then added and the mixture was stirred at 120 °C
for 4 h. At ambient temperature, EtOAc (5 mL) was added,
and the reaction mixture was washed with brine (5 mL),
dried over sodium sulfate, concentrated under vacuum and
the crude mixture was analyzed by 1H NMR using tetra-
chloroethane as an internal standard.
Reaction with aldol product 6 (Scheme 3b):
1) Anhydrous condition: (E)-3-(2-aminophenyl)-1-
phenylprop-2-en-1-one (6) (112 mg, 0.50 mmol), nickel
catalyst 3 (4 mg, 0.01 mmol, 2 mol %) and tBuONa (48 mg,
0.50 mmol, 1 equiv) were placed in a pre-dried 15 mL
sealed tube. The tube was degassed and purged with argon
for three times. Toluene (2.0 mL) was then added and the
mixture was stirred at 120 °C for 16 h. At ambient temper-
ature, EtOAc (8 mL) was added, and the reaction mixture
was washed with brine (5 mL), dried over sodium sulfate,
concentrated under vacuum and purified by silica gel col-
umn chromatography using 1% ethyl acetate in hexanes
yielded 4aa (15 mg, 15%).
2) In presence of water: (E)-3-(2-aminophenyl)-1-
phenylprop-2-en-1-one (6) (112 mg, 0.50 mmol), nickel
catalyst 3 (4 mg, 0.01 mmol, 2 mol %) and tBuONa (48 mg,
0.50 mmol, 1 equiv) were placed in a pre-dried 15 mL
sealed tube. The tube was degassed and purged with argon
for three times. Toluene (2.0 mL) and H2O (10.8 µl, 0.6
mmol, 1.2 equiv) was then added and the mixture was
stirred at 120 °C for 16 h. At ambient temperature, EtOAc
(8 mL) was added, and the reaction mixture was washed
with brine (5 mL), dried over sodium sulfate, concentrated
under vacuum and purified by silica gel column chroma-
tography using 1% ethyl acetate in hexanes yielded 4aa
(56 mg, 55%).
2,4-Diphenylquinoline (4la):37 The GP 1 was followed
using nickel catalyst
3 (4 mg, 2.0 mol %), 1-(2-
aminophenyl)phenylmethanol 1l (119 mg, 0.6 mmol) and
acetophenone 2a (60 mg, 0.5 mmol). After 24 h, purifica-
tion by column chromatography 1% ethyl acetate in hex-
anes yielded 4la (100 mg, 71%).
The GP 2 was followed using nickel catalyst 3 (4 mg, 2.0
mol %), 1-(2-aminophenyl)phenylmethanol 1l (119 mg,
0.6 mmol) and 1-phenylethanol 5a (61 mg, 0.5 mmol). Af-
ter 24 h, purification by column chromatography using 1%
ethyl acetate in hexanes yielded 4la (65 mg, 46%) as a
ASSOCIATED CONTENT
1
solid (M.p.: 111-112 °C). H NMR (400 MHz, CDCl3) δ 8.27
ACS Paragon Plus Environment

Page 9 of 10
The Journal of Organic Chemistry
4462. (d) Mukherjee, A.; Nerush, A.; Leitus, G.; Shimon, L. J.; Ben
Supporting Information
David, Y.; Espinosa Jalapa, N. A.; Milstein, D. J. Am. Chem. Soc.
2016, 138, 4298. (e) Mastalir, M.; Glatz, M.; Pittenauer, E.;
Allmaier, G.; Kirchner, K. J. Am. Chem. Soc. 2016, 138, 15543. (f)
Elangovan, S.; Neumann, J.; Sortais, J. B.; Junge, K.; Darcel, C.; Bel-
ler, M. Nat. Commun. 2016, 7, 12641. (g) Pena-Lopez, M.; Piehl, P.;
Elangovan, S.; Neumann, H.; Beller, M. Angew. Chem. Int. Ed. 2016,
55, 14967.
(10) (a) Guđmundsson, A.; Gustafson, K. P. J.; Mai, B. K.; Yang,
B.; Himo, F.; Bäckvall, J.-E. ACS Catal. 2017, 12. (b) Di Gregorio, G.;
Mari, M.; Bartoccini, F.; Piersanti, G. J. Org. Chem. 2017, 82, 8769.
(c) Brown, T. J.; Cumbes, M.; Diorazio, L. J.; Clarkson, G. J.; Wills, M.
J. Org. Chem. 2017, 82, 10489. (d) Yan, T.; Feringa, B. L.; Barta, K.
ACS Catal. 2015, 6, 381. (e) Yan, T.; Feringa, B. L.; Barta, K. Nat.
Commun. 2014, 5, 5602.
(11) (a) Daw, P.; Ben-David, Y.; Milstein, D. ACS Catal. 2017, 7,
7456. (b) Zhang, G.; Yin, Z.; Zheng, S. Org. Lett. 2016, 18, 300. (c)
Mastalir, M.; Tomsu, G.; Pittenauer, E.; Allmaier, G.; Kirchner, K.
Org. Lett. 2016, 18, 3462. (d) Deibl, N.; Kempe, R. J. Am. Chem. Soc.
2016, 138, 10786. (e) Rosler, S.; Ertl, M.; Irrgang, T.; Kempe, R.
Angew. Chem. Int. Ed. 2015, 54, 15046. (f) Zhang, G.; Vasudevan, K.
V.; Scott, B. L.; Hanson, S. K. J. Am. Chem. Soc. 2013, 135, 8668. (g)
Moselage, M.; Li, J.; Ackermann, L. ACS Catal. 2016, 6, 498.
(12) (a) Vellakkaran, M.; Singh, K.; Banerjee, D. ACS Catal. 2017,
7, 8152. (b) Parua, S.; Das, S.; Sikari, R.; Sinha, S.; Paul, N. D. J. Org.
Chem. 2017, 82, 7165. (c) Chakraborty, S.; Piszel, P. E.; Brennessel,
W. W.; Jones, W. D. Organometallics 2015, 34, 5203. (d) Weiss, C.
J.; Das, P.; Miller, D. L.; Helm, M. L.; Appel, A. M. ACS Catal. 2014, 4,
2951.
(13) Srimani, D.; Ben-David, Y.; Milstein, D. Chem. Commun.
2013, 49, 6632.
(14) (a) Cho, C. S.; Kim, B. T.; Kim, T. J.; Shim, S. C. Chem. Com-
mun. 2001, 2576. (b) Cho, C. S.; Kim, B. T.; Choi, H. J.; Kim, T. J.;
Shim, S. C. Tetrahedron 2003, 59, 7997.
(15) Martínez, R.; Brand, G. J.; Ramón, D. J.; Yus, M. Tetrahedron
Lett. 2005, 46, 3683.
(16) Vander Mierde, H.; Van Der Voort, P.; De Vos, D.; Verpoort,
F. Eur. J. Org. Chem. 2008, 1625.
(17) Motokura, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Tetrahe-
dron Lett. 2004, 45, 6029.
(18) (a) Pan, B.; Liu, B.; Yue, E.; Liu, Q.; Yang, X.; Wang, Z.; Sun,
W.-H. ACS Catal. 2016, 6, 1247. (b) Xie, F.; Zhang, M.; Chen, M.; Lv,
W.; Jiang, H. ChemCatChem 2015, 7, 349.
(19) (a) Wang, R.; Fan, H.; Zhao, W.; Li, F. Org. Lett. 2016, 18,
3558. (b) Taguchi, K.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett.
2005, 46, 4539.
(20) (a) Chen, B. W. J.; Chng, L. L.; Yang, J.; Wei, Y. F.; Yang, J. H.;
Ying, J. Y. ChemCatChem 2013, 5, 277. (b) Cho, C. S.; Ren, W. X. J.
Organomet. Chem. 2007, 692, 4182.
1
2
3
4
5
6
7
8
The Supporting Information is available free of charge on the
ACS Publications website at DOI: Copies of 1H and 13C NMR
spectra for all compounds (PDF).
AUTHOR INFORMATION
Corresponding Author
* Email: sds@iiserkol.ac.in
9
Notes
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 authors declare no competing financial interest.
ACKNOWLEDGMENT
Generous support by the CSIR [Fellowship to DM and SD],
SERB, DST, India [ECR/2016/000225 to SDS] and IISER Kol-
kata for infrastructure is gratefully acknowledged.
REFERENCES
(1) Jones, G. In Comprehensive Heterocyclic Chemistry II; Rees, C.
W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996, p 167.
(2) Michael, J. P. Nat. Prod. Rep. 2008, 25, 166.
(3) (a) Bax, B. D.; Chan, P. F.; Eggleston, D. S.; Fosberry, A.; Gen-
try, D. R.; Gorrec, F.; Giordano, I.; Hann, M. M.; Hennessy, A.; Hibbs,
M.; Huang, J.; Jones, E.; Jones, J.; Brown, K. K.; Lewis, C. J.; May, E.
W.; Saunders, M. R.; Singh, O.; Spitzfaden, C. E.; Shen, C.; Shillings,
A.; Theobald, A. J.; Wohlkonig, A.; Pearson, N. D.; Gwynn, M. N.
Nature 2010, 466, 935. (b) Lilienkampf, A.; Mao, J.; Wan, B.; Wang,
Y.; Franzblau, S. G.; Kozikowski, A. P. J. Med. Chem. 2009, 52, 2109.
(c) Chen, S.; Chen, R.; He, M.; Pang, R.; Tan, Z.; Yang, M. Bioorg.
Med. Chem. 2009, 17, 1948. (d) Stauffer, F.; Maira, S. M.; Furet, P.;
Garcia-Echeverria, C. Bioorg. Med. Chem. Lett. 2008, 18, 1027. (e)
Gakhar, G.; Ohira, T.; Shi, A. B.; Hua, D. H.; Nguyen, T. A. Drug Dev.
Res. 2008, 69, 526.
(4) Jenekhe, S. A.; Lu, L. D.; Alam, M. M. Macromolecules 2001,
34, 7315.
(5) (a) Kouznetsov, V.; Mendez, L.; Gomez, C. Curr. Org. Chem.
2005, 9, 141. (b) Marco-Contelles, J.; Perez-Mayoral, E.; Samadi,
A.; Carreiras Mdo, C.; Soriano, E. Chem. Rev. 2009, 109, 2652.
(6) (a) Friedlaender, P. Ber. Dtsch. Chem. Ges. 1882, 15, 2572.
(b) Doebner, O.; v. Miller, W. Ber. Dtsch. Chem. Ges. 1881, 14, 2812.
(c) Gould, R. G.; Jacobs, W. A. J. Am. Chem. Soc. 1939, 61, 2890. (d)
Böttinger, C. Ber. Dtsch. Chem. Ges. 1880, 13, 2165.
(7) (a) González Miera, G.; Martínez-Castro, E.; Martín-Matute,
B. Organometallics 2017, DOI: 10.1021/acs.organomet.7b00220.
(b) Zell, T.; Milstein, D. Acc. Chem. Res. 2015, 48, 1979. (c) Yang,
Q.; Wang, Q.; Yu, Z. Chem. Soc. Rev. 2015, 44, 2305. (d) Nan-
dakumar, A.; Midya, S. P.; Landge, V. G.; Balaraman, E. Angew.
Chem. Int. Ed. 2015, 54, 11022. (e) Gunanathan, C.; Milstein, D.
Science 2013, 341, 1229712. (f) Watson, A. J.; Williams, J. M. Sci-
ence 2010, 329, 635. (g) Gunanathan, C.; Ben-David, Y.; Milstein,
D. Science 2007, 317, 790.
(8) Selected examples: (a) Dobereiner, G. E.; Crabtree, R. H.
Chem. Rev. 2010, 110, 681. (b) Kawahara, R.; Fujita, K.; Yamagu-
chi, R. J. Am. Chem. Soc. 2010, 132, 15108. (c) Zhang, M.; Imm, S.;
Bahn, S.; Neumann, H.; Beller, M. Angew. Chem. Int. Ed. 2011, 50,
11197. (d) Akhtar, W. M.; Cheong, C. B.; Frost, J. R.; Christensen, K.
E.; Stevenson, N. G.; Donohoe, T. J. J. Am. Chem. Soc. 2017, 139,
2577. (e) Maji, M.; Chakrabarti, K.; Paul, B.; Roy, B. C.; Kundu, S.
Adv. Syn. Catal. 2017, DOI: 10.1002/adsc.201701117. (f)
Chakrabarti, K.; Maji, M.; Panja, D.; Paul, B.; Shee, S.; Das, G. K.;
Kundu, S. Org. Lett. 2017, 19, 4750.
(21) (a) Zhang, G.; Wu, J.; Zeng, H.; Zhang, S.; Yin, Z.; Zheng, S.
Org. Lett. 2017, 19, 1080. (b) Wang, Q.; Wang, M.; Li, H. J.; Zhu, S.;
Liu, Y.; Wu, Y. C. Synthesis-Stuttgart 2016, 48, 3985. (c) Xi, L. Y.;
Zhang, R. Y.; Zhang, L.; Chen, S. Y.; Yu, X. Q. Org. Biomol. Chem.
2015, 13, 3924. (d) Elangovan, S.; Sortais, J. B.; Beller, M.; Darcel,
C. Angew. Chem. Int. Ed. 2015, 54, 14483. (e) Cho, C. S.; Ren, W. X.;
Yoon, N. S. J. Mol. Catal. 2009, 299, 117. (f) Cho, C. S.; Ren, W. X.;
Shim, S. C. Tetrahedron Lett. 2006, 47, 6781.
(22) Parua, S.; Sikari, R.; Sinha, S.; Das, S.; Chakraborty, G.; Paul,
N. D. Org. Biomol. Chem. 2018, 16, 274.
(23) (a) Jäger, E. G. Z. Anorg. Allg. Chem. 1969, 364, 177. (b)
Goedken, V. L.; Weiss, M. C.; Place, D.; Dabrowiak, J. 1980, 20, 115.
(24) Niewahner, J. H.; Walters, K. A.; Wagner, A. J. Chem. Educ.
2007, 84, 477.
(25) (a) Kusumoto, S.; Akiyama, M.; Nozaki, K. J. Am. Chem. Soc.
2013, 135, 18726. (b) Song, H.; Kang, B.; Hong, S. H. ACS Catal.
2014, 4, 2889.
(26) Ding, M.; Liu, D.; He, P. Faming Zhuanli Shenqing
CN102408409A, 2012.
(9) (a) Fu, S.; Shao, Z.; Wang, Y.; Liu, Q. J. Am. Chem. Soc. 2017,
139, 11941. (b) Espinosa-Jalapa, N. A.; Kumar, A.; Leitus, G.;
Diskin-Posner, Y.; Milstein, D. J. Am. Chem. Soc. 2017, 139, 11722.
(c) Bauer, J. O.; Chakraborty, S.; Milstein, D. ACS Catal. 2017, 7,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 10
(27) Muchowski, J. M.; Maddox, M. L. Can. J. Chem. 2004, 82,
461.
(28) Chen, X.; Qiu, S.; Wang, S.; Wang, H.; Zhai, H. Org. Biomol.
(37) Martinez, R.; Ramon, D. J.; Yus, M. J. Org. Chem. 2008, 73,
9778.
(38) Chen, B. W. J.; Chng, L. L.; Yang, J.; Wei, Y.; Yang, J.; Ying, J. Y.
ChemCatChem 2013, 5, 277.
(39) Liang, Y.-F.; Zhou, X.-F.; Tang, S.-Y.; Huang, Y.-B.; Feng, Y.-
S.; Xu, H.-J. RSC Adv. 2013, 3, 7739.
(40) Liu, Q.; Xing, R.-G.; Li, Y.-N.; Han, Y.-F.; Wei, X.; Li, J.; Zhou,
B. Synthesis 2011, 2066.
(41) Zheng, Z.; Deng, G.; Liang, Y. RSC Adv. 2016, 6, 103478.
(42) Liu, F.; Yu, L.; Lv, S.; Yao, J.; Liu, J.; Jia, X. Adv. Syn. Catal.
2016, 358, 459.
1
2
3
4
5
6
7
8
Chem. 2017, 15, 6349.
(29) Li, B.; Wang, G.; Song, Y.; Wu, S.; Fan, X.; Shi, X.; Yu, H.; Lv, L.
Faming Zhuanli Shenqing CN104650038A, 2015.
(30) (a) Jiang, L.; Xu, R.; Kang, Z.; Feng, Y.; Sun, F.; Hu, W. J. Org.
Chem. 2014, 79, 8440. (b) Zhao, Y.; Huang, B.; Yang, C.; Chen, Q.;
Xia, W. Org. Lett. 2016, 18, 5572.
(31) Li, X.; Li, H.; Song, W.; Tseng, P. S.; Liu, L.; Guzei, I. A.; Tang,
W. Angew. Chem. Int. Ed. 2015, 54, 12905.
(32) Dogan, I. S.; Sarac, S.; Sari, S.; Kart, D.; Essiz Gokhan, S.;
Vural, I.; Dalkara, S. Eur. J. Med. Chem. 2017, 130, 124.
(33) Otani, T.; Onishi, M.; Seino, T.; Furukawa, N.; Saito, T. RSC
Adv. 2014, 4, 53669.
(34) Yuan, J.-W.; Yang, L.-R.; Mao, P.; Qu, L.-B. Org. Chem. Front.
2017, 4, 545.
9
(43) Li, B.; Guo, C.; Fan, X.; Zhang, J.; Zhang, X. Tetrahedron Lett.
2014, 55, 5944.
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
(44) Zemtsova, M. N.; Kulemina, S. V.; Rybakov, V. B.; Klimo-
chkin, Y. N. Rus. J. Org. Chem. 2015, 51, 636.
(45) Liu, W.; Yang, X.; Zhou, Z.-Z.; Li, C.-J. Chem 2017, 2, 688.
(46) Korivi, R. P.; Cheng, C. H. J. Org. Chem. 2006, 71, 7079.
(47) Zhu, J.; Hu, W.; Sun, S.; Yu, J.-T.; Cheng, J. Adv. Syn. Catal.
2017, 359, 3725.
(35) Li, H.-J.; Wang, C.-C.; Zhu, S.; Dai, C.-Y.; Wu, Y.-C. Adv. Syn.
Catal. 2015, 357, 583.
(36) Hu, B.; Li, Y.; Dong, W.; Xie, X.; Wan, J.; Zhang, Z. RSC Adv.
2016, 6, 48315.
ACS Paragon Plus Environment