Palladium-Catalyzed Allylic C-H Oxidative Annulation for Assembly of Functionalized 2-Substituted Quinoline Derivatives

Article abstract of DOI:10.1021/acs.joc.6b01909

An efficient and practical palladium-catalyzed aerobic oxidative approach to afford functionalized 2-substituted quinolines in moderate to good yields from readily available allylbenzenes with aniline is developed. The present annulation process has high functional-group tolerance and high atom economy, making it a valuable and practical method in synthetic and medicinal chemistry. Moreover, this transformation is supposed to proceed through oxidation of allylic C-H functionalization to form C-C and C-N bonds in one pot.

Full text of DOI:10.1021/acs.joc.6b01909

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Article
Palladium-Catalyzed Allylic C-H Oxidative Annulation for
Assembly of Functionalized 2-Substituted Quinoline Derivatives
Chunsheng Li, Jianxiao Li, Yanni An, Jianwen Peng, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01909 • Publication Date (Web): 28 Oct 2016
Downloaded from http://pubs.acs.org on October 28, 2016
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PalladiumꢀCatalyzed Allylic CꢀH Oxidative Annulation for
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Assembly of Functionalized 2ꢀSubstituted Quinoline Derivatives
Chunsheng Li, Jianxiao Li, Yanni An, Jianwen Peng, Wanqing Wu* and Huanfeng Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical
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Engineering, South China University of Technology, Guangzhou 510640, P. R. China
Fax: (+86) 20ꢀ8711ꢀ2906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
Abstract: An efficient and practical palladiumꢀcatalyzed aerobic oxidative approach
to afford functionalized 2ꢀsubstituted quinolines in moderate to good yields from
readily available allylbenzenes with aniline is developed. The present annulation
process has high functionalꢀgroup tolerance and high atom economy, making a
valuable and practical method in synthetic and medicinal chemistry. Moreover, this
transformation is supposed to proceed through oxidative of allylic C–H
functionalization to form C–C and C–N bonds in one pot.
INTRODUCTION
Transitionꢀmetalꢀcatalyzed oxidative functionalization of allylic CꢀH bond has been
an essential strategy for the direct transformation of nonsubstituted simple alkenes
into complex molecules in a concise manner.1 In addition, the practical utility of direct
allylic CꢀH activation and subsequent installation of functionality into hydrocarbon
frameworks is highly desirable from atomꢀeconomic and environmental perspectives.
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Among them, metal complexes of copper,2 iron,3 ruthenium4 and other metals5 have
been defined as markedly efficient catalysts for allylic CꢀH bond activation. Recently,
elegant works have also been reported on Pdꢀcatalyzed oxidation of allylic C–H bonds
into more synthetically useful C–C,6 C–N,7 C–O,8 C–F9 and C–Si10 bonds (Scheme
1a). Our group has also reported a facile synthesis of (E)ꢀalkenyl aldehydes via
palladiumꢀcatalyzed aerobic oxidative allylic C–H oxygenation (Scheme 1b).11 Next,
a significant advance in double allylic C–H oxygenation reaction for the expedient
and selective synthesis of a broad range of linear aryl α, βꢀunsaturated esters with
alcohol as nucleophile was documented in 2015 (Scheme 1c).12
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Quinolines and their derivatives are important substructures in a large number of
natural or designed products due to their wide spectrum of biological activities.13
2ꢀArylquinoline skeletons, for instance, are associated with a wide range of biological
properties, such as Pꢀselectin antagonism, antimalarial, and antitumor activties.14 As a
consequence of their proven potential bioactivity, a great deal of advanced methods
for the synthesis of substituted quinolines have been wellꢀdeveloped over these years.
Generically, two distinctive methods are employed: (i) the traditional metalꢀfree,
including Skraup, Friedländer, and Doebner ꢀ Miller reactions, cascade condensation
/cyclization reactions;15 (ii) the transitionꢀmetal catalyzed crossꢀcoupling reactions
from readily available materials like alkenes or alkynes.16 Despite the significant
progress that has been achieved along this line, most of these elegant developments
suffer from certain limitations such as troublesome operation, harsh reaction
conditions, or low yields, prohibiting their wider applications in organic synthesis.
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Therefore, the development of novel and expeditious approaches for the preparation
of a diverse range of substituted quinolines, based on the idea of high efficiency and
atomꢀeconomy, remain an active research area. On the basis of these precedents, we
envision that the allylꢀPd intermediate could be captured by water (H2O),11 which
would undergo the subsequent cascade condensation/oxidative cyclization to generate
2ꢀarylquinolines in the presence of aniline.15h Moreover, the use of molecular oxygen
as a terminal oxidant realized the goal of high atom economy and green chemisty.17, 18
Herein we would like to report a strategically distinct approach to synthesize
2ꢀarylquinolines through palladiumꢀcatalyzed aerobic oxidative allylic C–H
functionalization of terminal olefins (Scheme 1d).
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Scheme 1. Pdꢀcatalyzed oxidative functionalization of allylic C–H bonds
RESULTS AND DISCUSSION
Table 1. Optimization of the reaction conditionsa
Entry
Catalyst
ꢀ
Additive
AcOH
AcOH
AcOH
AcOH
Solvent
DMSO
DMSO
DMSO
DMSO
Yield (%)b
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Pd(OAc)2
PdCl2
8
Pd(TFA)2
trace
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Pd(CH3CN)2Cl2
AcOH
AcOH
AcOH
AcOH
AcOH
H2SO4
CF3SO3H
BF3ꢁEt2O
ZnCl2
DMSO
7
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Toluene
DMF
7
trace
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8
Dioxane
DMA
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16c
17d
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
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trace
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86
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FeCl2
TsOH
TsOH
TsOH
a
Unless otherwise noted, all reactions were performed with 1a (0.25 mmol), 2a (0.5 mmol), Pd
catalyst (10 mol %), additive (20 mol %) and H2O (0.25 mL) in the indicated solvent (1.0 mL)
under 1 atm oxygen at 110 C for 24 h. b Determined by GC using dodecane as the internal
o
standard. c The reaction was performed at 100 oC. d The reaction was performed at 120 oC
.
The investigation was initiated by using the reaction of aniline (1a) with
allylbenzene (2a) as a model system to screen the optimal conditions. As shown in
Table 1, the reaction did not proceed without palladium catalyst (Table 1, entry 1).
Initially, different palladium species such as Pd(OAc)2, PdCl2, Pd(TFA)2 and
Pd(CH3CN)2Cl2 were tested (entries 2ꢀ5), and Pd(OAc)2 proved to be more efficient in
this reaction. Subsequently, we also closely examined the solvent effects, and it
appears that DMSO was the most suitable solvent for this reaction (entry 2 vs entries
6ꢀ9). Finally, several additives were screened, such as H2SO4, CF3SO3H, BF3ꢁEt2O,
ZnCl2, FeCl2 and TsOH, and TsOH was found to be the best one (entries 10ꢀ15).
Furthermore, the lower or the higher temperature was disfavored the reaction, and 3a
was obtained in 67% and 45% yields, respectively (entries 16 and 17). Thus, the
optimized reaction conditions are as the following: 10 mol % Pd(OAc)2 and 20 mol %
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TsOH in 1 mL DMSO at 110 oC for 24 h.
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Scheme 2. Substrate scope of various anilinesa
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a Reactions were performed with 1 (0.25 mmol), 2a (0.5 mmol), Pd(OAc)2 (10 mol %), TsOH (20
mol %), H2O (0.25 mL) and DMSO (1 mL) under 1 atm oxygen at 110 oC for 24 h. Yields referred
to isolated yield.
Next, the substrate scope of various anilines 1 with allylbenzene (2a) were
performed under the optimized condition, and the representative results are
summarized in Scheme 2. Gratifyingly, both electronꢀdeficient and electronꢀrich
aniline components delivered the corresponding products in moderate to good yields.
Delightfully,
a
series of paraꢀsubstituted anilines, including some with
electronꢀdonating groups (Me, iPr, tBu, Ph, OMe and OPh) and some with
electronꢀwithdrawing groups (F, Cl, Br, CF3 and CN), were converted into the
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corresponding 2ꢀsubsitituted quinolines in moderate to excellent yields (3aꢀ3m).
Furthermore, various orthoꢀsubstituted anilines could transfer to the corresponding
products 3nꢀ3q in moderate yields under the optimized condition. As expected, this
transformation could be successfully extended to some disubstituted anilines,
furnishing the corresponding quinoline derivatives 3rꢀ3u in 57%ꢀ69% yields. These
results showed that this new transformation was tolerant toward electronic and steric
effects of the aromatic ring. In addition, when 3ꢀmethylaniline (1v) was employed
under the optimized conditions, two regioisomeric products 3v and 3v’ were obtained
with poor selectivity (6:1 d.r.), and the 8ꢀsubstituted regioisomer 3v was the major
product. Notably, naphthalenꢀ2ꢀamine (1w) was also suitable for the current procedure
to furnish the corresponding product 3w in 67% yield. Disappointingly, only trace
desired product was observed by GCꢀMS when pyridinꢀ4ꢀamine (1x) was employed
in this reaction. Despite the significance of this currently catalytic system, as the
byproducts of this transformation, a small amount of cinnamaldehyde derivatives
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were observed by GCꢀMS analysis when the reaction was finished.
Scheme 3. Substrate scope of various allylbenzenesa
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a Reactions were performed with 1a (0.25 mmol), 2 (0.5 mmol), Pd(OAc)2 (10 mol %), TsOH (20
mol %), H2O (0.25 mL) and DMSO (1 mL) under 1 atm oxygen at 110 oC for 24 h. Yields referred
to isolated yield.
To expand the scope of this method, we subsequently investigated a variety of
allylbenzenes, and the results are presented in Scheme 3. Generally, almost all of the
allylbenzenes used in this study were successfully coupled under our optimized
conditions (4aꢀ4p). Moreover, allylbenzenes bearing electronꢀdonating groups (Me,
iPr, tBu and OMe) at the para, meta and ortho positions of the phenyl ring could react
smoothly and afford the corresponding products 4aꢀ4i in moderate yields ranging
from 54% to 69%. Similarly, allylbenzenes possessing electronꢀwithdrawing groups
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are also good coupling partners (4jꢀ4m). Notably, this transformation was compatible
with the Clꢀsubstituted aryl ring, which might allow for further synthetic
transformations by transitionꢀmetalꢀcatalyzed coupling. Pleasingly, as for the
sterically hindered (2ꢀmethylallyl)benzene (2o), the reaction also furnished the
corresponding products 4o in 64% yield. Significantly, when 2ꢀallylthiophene was
employed as substrate, the desired product 4p was isolated in 50% yield.
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Unfortunately,
functionalized
allylbenzene
derivatives,
such
as
1ꢀallylꢀ2,3,4,5,6ꢀpentafluorobenzene (2q) and 2ꢀallylꢀ1Hꢀindole (2r), failed to afford
the desired products. Finally, longꢀchain alkenes, such as 1ꢀoctene (2s), were also
investigated, but no desired product was obtained under the optimal conditions.
Scheme 4. Synthesis of 2ꢀsubtituted quinoline derivatives from transꢀβꢀmethylstyrene
with 1aa
a Reactions were performed with 1a (0.25 mmol), 2 (0.5 mmol), Pd(OAc)2 (10 mol %), TsOH (20
mol %), H2O (0.25 mL) and DMSO (1 mL) under 1 atm oxygen at 110 oC for 24 h. Yields referred
to isolated yield.
Remarkably, as shown in Scheme 4, when transꢀβꢀmethylstyrenes were used as
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the substrates, the desired 2ꢀsubtituted quinoline derivatives were obtained, which was
in good agreement with the result obtained when the corresponding reactions were
performed with allylbenzenes (3a, 4fꢀ4h). However, when we subjected
propꢀ1ꢀenꢀ2ꢀylbenzene to the standard reaction conditions, only a trace amount of the
desired product 5b was detected by GCꢀMS.
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Scheme 5. Control Experiments
CHO
standard conditions
89%
(1)
(2)
6
2a
CHO
NH2
standard conditions
79%
N
Ph
3a
6
1a
1a
Pd(OAc)2 (10 mol %)
TsOH (20 mol %)
NH2
(3)
Super dry DMSO, O2 balloon
trace
N
Ph
3a
2a
Several control experiments were carried out to get further insights into this
unique transformation (Scheme 5). Under the standard conditions, the control
experiment without aniline was performed, and cinnamaldehyde 6 was observed in
89% GC yield (Eq. 1).11 Furthermore, when 6 was reacted with aniline (1a) under the
standard conditions, product 3a was detected in 79% GC yield (Eq. 2).15 These
observations indicated that the reaction might proceed via cinnamaldehyde 6 as the
key intermediate. Finally, when super dry DMSO was used as solvent, only a trace
amount of the desired product 3a was detected by GCꢀMS (Eq. 3). We reasoned that
water played a vital role and was indispensable for the present method.
Scheme 6. Proposed Mechanism
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Based on the current results and previous literature, a plausible mechanism was
proposed which is shown in Scheme 6. First, the corresponding πꢀallylpalladium
species intermediate I is formed through the coordination of the allylic CꢀH bond of
the olefin to palladium.19, 20 Then, nucleophilic attack by H2O subsequently occurs to
afford the cinnamic alcohol intermediate II. Oxidation of II by O2 affords the
cinnamaldehyde 6.11 Then, the next step was a traditional condensation leading to the
formation of an imine,21a followed by a conjugate addition of a second molecule of
imine in the presence of TsOH. Therefore, the labile diazetidinium cation
intermediates 8 was formated. Then following by the irreversible cyclization and
elimination of 7, 2ꢀphenylꢀ1,2ꢀdihydroquinolin 10 was generated with the subsquent
oxidation to afford the desire product.21b Finally, Pd(0) is oxidized to regenerate the
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active species Pd(II) by dioxygen.12
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In conclusion, we report the Pd(II)/TsOH/O2ꢀcatalyzed oxidative/cyclization of
simple alkenes with water and simple amines to afford 2ꢀarylꢀsubstitutedꢀquinolines
in moderate to good yields. More importantly, this method provides a new tool for the
construction of biologically important 2ꢀarylꢀsubstitutedꢀquinoline derivatives from
inexpensive starting materials with broad substrate scope and excellent functional
group compatibility.
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Experimental Section
General method. Melting points were measured using a melting point instrument and
1
are uncorrected. H and 13C NMR spectra were recorded on a 400 MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.24 and 77.0 ppm,
respectively, and chloroform was used as a solvent with TMS as the internal standard.
IR spectra were obtained with an infrared spectrometer on either potassium bromide
pellets or liquid films between two potassium bromide pellets. GC−MS data were
obtained using electron ionization. HRMS was carried out on a highꢀresolution mass
spectrometer (LCMSꢀITꢀTOF). TLC was performed using commercially available
100−400 mesh silica gel plates (GF254). Unless otherwise noted, purchased chemicals
were used without further purification.
General procedure for synthesis of quinoline derivatives: amine (0.25 mmol),
allylbenzene derivatives (0.50 mmol), Pd(OAc)2 (10 mol %), TsOH (20 mol %) and
water (0.25 mL) were added to DMSO (1 mL) under 1 atm oxygen. The mixture was
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stirred under 1 atm oxygen at 110 C for the desired reaction time. After that, water
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was added and extracted with ethyl acetate twice. The combined organic phase was
dried over MgSO4 and concentrated. The residue was eventually purified by flash
column chromatography on a silica gel (hexane/ethyl acetate) to afford the product.
Compounds 3cꢀ3d, 3g, 3k, 3m, 3q, 3s, 4c, 4d, 4i and 5a are all new compounds.
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o
2ꢀPhenylquinoline (3a)16a: Yield: 86% (44.3 mg) as yellow solid; mp = 86 ꢀ 87 C; Rf = 0.69
(10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.8 Hz, 2H), 8.17 (d, J =
7.2 Hz, 2H), 7.88 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.73 (t, J = 7.2 Hz, 1H), 7.53 (t, J
= 6.8 Hz, 3H), 7.49 ꢀ 7.43 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 157.3, 148.1, 139.5, 136.9,
129.8, 129.6, 129.4, 128.9, 127.6, 127.5, 127.2, 126.4, 119.1 ppm; νmax(KBr)/cmꢀ1 3450, 2923,
1625, 1603, 1021, 830, 799, 688; MS (EI) m/z 51, 76, 88, 102, 113, 128, 151, 164, 176, 205, 206;
HRMSꢀESI (m/z): calcd for C15H12N, [M+H]+: 206.0964, found 206.0969.
6ꢀMethylꢀ2ꢀphenylquinoline (3b)16f: Yield: 65% (35.6 mg) as yellow solid; mp = 91 ꢀ 92 oC; Rf =
0.59 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.46 ꢀ 7.91 (m, 4H), 7.83 (d, J =
8.0 Hz, 1H), 7.62 ꢀ 7.48 (m, 4H), 7.51 ꢀ 7.40 (m, 1H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
156.5, 146.8, 139.7, 136.2, 136.2, 132.2, 129.3, 129.2, 128.8, 127.5, 127.2, 126.3, 119.0, 21.5 ppm;
νmax(KBr)/cmꢀ1 3448, 2920, 1628, 1504, 1448, 1271, 965, 840; MS (EI) m/z 219, 204, 189, 165,
140, 115, 108, 95, 89 , 63; HRMSꢀESI (m/z): calcd for C16H14N, [M+H]+: 220.1121, found
220.1125.
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6ꢀ(isoꢀPropyl)ꢀ2ꢀphenylquinoline (3c): Yield: 60% (37.4 mg) as yellow solid; mp = 96 ꢀ 97 C;
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Rf = 0.52 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.17 (dd, J = 16.0, 8.0Hz,
4H), 7.85 (d, J = 8.0 Hz, 1H), 7.67 ꢀ 7.63 (m, 2H), 7.53 (t, J = 8.0 Hz, 2H), 7.47 (d, J = 8.0 Hz,
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1H), 3.11 (dt, J = 13.2, 6.4 Hz, 1H), 1.37 (d, J = 4.0 Hz, 6H); 13C NMR (100MHz, CDCl3) δ 156.6,
147.1, 146.8, 139.5, 136.8 129.8, 129.3, 129.1, 127.6, 127.3, 123.6, 119.0, 34.1, 23.9 ppm;
νmax(KBr)/cmꢀ1 3727, 3059, 2958, 2349, 1592, 1458, 1306, 1025, 885; MS (EI) m/z 248, 232, 204,
176, 154, 127, 108, 77; HRMSꢀESI (m/z): calcd for C18H18N, [M+H]+: 248.1434, found 248.1435.
6ꢀ(tertꢀButyl)ꢀ2ꢀphenylquinoline (3d): Yield: 58% (38.1 mg) as yellow solid; mp = 103 ꢀ 104 oC;
Rf = 0.62 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.17 (dd, J = 18.0, 8.0 Hz,
4H), 7.86 ꢀ 7.82 (m, 2H), 7.74 (s, 1H), 7.52 (t, J = 6.4 Hz, 2H), 7.46 (d, J = 8.0 Hz, 1H), 1.44 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 156.7, 149.3, 146.5, 137.0, 129.3, 129.0, 128.8, 128.1, 127.9,
127.6, 126.9, 122.5, 119.0, 34.9, 31.2 ppm; νmax(KBr)/cmꢀ1 3428, 3061, 2960, 2865, 1597, 1456,
889, 796, 692; MS (EI) m/z 261, 246, 230, 218, 206, 168, 152, 128, 108, 95; HRMSꢀESI (m/z):
calcd for C19H20N, [M+H]+: 262.1590, found 262.1595.
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2,6ꢀDiphenylquinoline (3e): Yield: 71% (50.1 mg) as yellow solid; mp = 196 ꢀ 197 oC; Rf = 0.54
(10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.0 Hz, 2H), 8.18 (d, J =
8.0 Hz, 2H), 8.00 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.55 ꢀ
7.48 (m, 5H), 7.40 (t, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 157.3, 147.6, 140.4, 139.6,
139.1, 137.0, 130.1, 129.4, 129.4, 128.9, 128.9, 127.7, 127.6, 127.4, 127.4, 125.2, 119.4 ppm;
νmax(KBr)/cmꢀ1 3052, 2955, 1600, 1455, 1069, 957, 765, 696; MS (EI) m/z 281, 280, 278, 226,
139, 126, 113, 100, 76, 51; HRMSꢀESI (m/z): calcd for C21H16N, [M+H]+: 282.1277, found
282.1277.
6ꢀMethoxyꢀ2ꢀphenylquinoline (3f)16a: Yield: 73% (42.3 mg) as yellow solid; mp = 128 ꢀ 129 oC;
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Rf = 0.42 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 1H),
8.11 (d, J = 9.2 Hz, 1H.), 7.86 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 6.0 Hz, 2H), 7.49 ꢀ 7.40 (m, 2H),
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7.12 (s, 1H), 3.97 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.7, 155.1, 144.4, 139.8, 135.5, 131.2,
128.9, 128.8, 128.2, 127.3, 122.3, 119.3, 105.0, 55.6 ppm; νmax(KBr)/cmꢀ1 3060, 2921, 2851, 1595,
1494, 832, 758, 694; MS (EI) m/z 235, 220, 204, 192, 176, 165, 139, 117, 95, 88; HRMSꢀESI
(m/z): calcd for C16H14NO, [M+H]+: 236.1070, found 236.1074.
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6ꢀPhenoxyꢀ2ꢀphenylquinoline (3g): Yield: 61% (45.5 mg) as yellow solid; mp = 196 ꢀ 197 oC; Rf
= 0.50 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.17 (dd, J = 16.0, 8.0 Hz, 3H),
8.07 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 6.4 Hz, 3H), 7.49 ꢀ 7.35 (m, 3H),
7.20 ꢀ 7.10 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 156.7, 156.1, 155.6, 144.9, 139.5, 136.0,
131.5, 129.9, 129.3, 128.9, 127.9, 127.5, 123.9, 123.4, 119.6, 119.5, 112.6 ppm; νmax(KBr)/cmꢀ1
3441, 2922, 2852, 1632, 1486, 1229, 755, 694; MS (EI) m/z 297, 268, 243, 220, 203, 191, 165,
148, 115, 77; HRMSꢀESI (m/z): calcd for C21H16NO, [M+H]+: 298.1226, found 298.1227.
6ꢀFluoroꢀ2ꢀphenylquinoline (3h)16d:Yield: 49% (27.5 mg) as yellow solid; mp = 106 ꢀ 107 oC; Rf
= 0.61 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.15 ꢀ 8.14 (m, 4H), 7.88 (d, J
= 8.0 Hz, 2H), 7.54 ꢀ 7.42 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 160.4( d, J =246.0 Hz), 156.7 (
d, J =3.0 Hz), 145.4, 139.4, 136.2 (d, J = 5.3 Hz), 132.2 (d, J = 9.0 Hz), 129.4, 128.9, 127.7 ( d, J
=10.0 Hz), 127.5, 119.9, 119.7, 110.5 (d, J =21.0 Hz) ppm; νmax(KBr)/cmꢀ1 3063, 2970, 1552,
1499, 1235, 870, 692; MS (EI) m/z 223, 204, 194, 175, 169, 146, 126, 101, 88, 75; HRMSꢀESI
(m/z): calcd for C15H11NF, [M+H]+: 224.0870, found 224.0871.
6ꢀChloroꢀ2ꢀphenylquinoline (3i)16d: Yield: 58% (34.8 mg) as yellow solid; mp = 108 ꢀ 109 oC; Rf
= 0.52 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.14 (t, J = 6.0 Hz, 4H), 7.90
(d, J = 8.0 Hz, 1H), 7.81 (s, 1H), 7.66 (d, J =9.0 Hz, 1H), 7.55 ꢀ 7.48 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 157.6, 146.6, 139.1, 135.9, 131.9, 131.3, 130.6, 129.6, 128.9, 127.7, 127.6, 126.2,
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119.8 ppm; νmax(KBr)/cmꢀ1 3450, 2922, 2852, 1636, 1547, 879, 785, 694; MS (EI) m/z 239, 204,
176, 151, 119, 102, 88, 74; HRMSꢀESI (m/z): calcd for C15H11ClN, [M+H]+: 240.0575, found
240.0575.
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6ꢀBromoꢀ2ꢀphenylquinoline (3j)16a: Yield: 62% (44.0 mg) as yellow solid; mp = 123 ꢀ 124 oC; Rf
= 0.63 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.14 (t, J = 8.0 Hz, 3H), 8.05
(d, J = 8.0 Hz, 1H), 7.98 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 12.0 Hz, 1H), 7.50 (dt, J =
13.2, 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 157.7, 146.8, 139.1, 135.8, 133.2, 131.4, 129.7,
129.5, 128.9, 128.3, 127.6, 120.1, 119.8 ppm; νmax(KBr)/cmꢀ1 3433, 2922, 2854, 1594, 1483, 830,
694; MS (EI) m/z 283, 204, 176, 164, 151, 127, 102, 88, 75, 51; HRMSꢀESI (m/z): calcd for
C15H11BrN, [M+H]+: 284.0069, found 284.0066.
2ꢀPhenylꢀ6ꢀ(trifluoromethoxy)quinoline (3k): Yield: 76% (55.1 mg) as yellow solid; mp = 123 ꢀ
124 oC; Rf = 0.59 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.0 Hz,
2H), 8.16 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 8.0 Hz, 1H), 7.65 (s, 1H), 7.59 ꢀ 7.48 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ 157.9, 146.8 (q, J = 4.0 Hz), 139.1, 136.6, 131.9, 129.7 (q, J = 241.2
Hz), 128.9, 127.6, 127.2, 123.8, 121.9, 119.9, 119.3, 117.5 ppm; νmax(KBr)/cmꢀ1 3444, 2924, 1605,
1255, 1164, 839, 754, 697; MS (EI) m/z 289, 207, 204, 191, 165, 139, 115, 89, 69; HRMSꢀESI
(m/z): calcd for C16H11F3NO, [M+H]+: 290.0787, found 290.0792.
2ꢀPhenylꢀ6ꢀ(trifluoromethyl)quinoline (3l)16d: Yield: 77% (52.7 mg) as yellow solid; mp = 132 ꢀ
133 oC; Rf = 0.63 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 8.0 Hz,
2H), 8.18 (d, J = 8.0 Hz, 2H), 8.12 (s, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.52
(dq, J = 14.4, 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.3, 149.2, 138.9, 137.6 , 130.8,
130.0 (q, J = 265.1 Hz), 128.9, 128.2, 127.9, 127.7, 126.09, 125.4 (q, J = 4.0 Hz), 122.8, 120.1
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ppm; νmax(KBr)/cmꢀ1 3449, 2922, 1636, 1162, 1119, 836, 758, 692; MS (EI) m/z 273, 252, 204,
169, 151, 136, 126, 102, 88, 75; HRMSꢀESI (m/z): calcd for C16H11F3N, [M+H]+: 274.0838, found
274.0834.
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2ꢀPhenylquinolineꢀ6ꢀcarbonitrile (3m): Yield: 72% (41.2 mg) as yellow solid; mp = 137 ꢀ 138
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oC; Rf = 0.26 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 14.4, 8.4
Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.57 ꢀ 7.51 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 160.0, 149.2, 138.5, 137.1, 133.7, 131.1, 130.5, 130.4, 129.1, 127.8, 126.5, 120.5,
118.6, 109.8 ppm; νmax(KBr)/cmꢀ1 3438, 2924, 2853, 1627, 1595, 1458, 833, 751, 694; MS (EI)
m/z 230, 201, 175, 164, 153, 126, 114, 101, 88, 75; HRMSꢀESI (m/z): calcd for C16H10N2,
[M+H]+:231.0917, found 231.0914.
8ꢀMethylꢀ2ꢀphenylquinoline (3n)16a: Yield: 63% (34.6 mg) as yellow oil; Rf = 0.78 (10:1
hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 8.0 Hz, 2H), 8.18 (d, J = 8.0 Hz,
1H), 7.90 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.58 ꢀ 7.51 (m, 3H), 7.45 ꢀ 7.39 (m, 2H),
2.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 155.6, 147.2, 139.9, 137.7, 136.7, 129.7, 129.2, 128.8,
127.5, 127.1, 126.0, 125.4, 118.2, 17.9 ppm; νmax(KBr)/cmꢀ1 3448, 2920, 1628, 1504, 965, 840,
756, 690; MS (EI) m/z 219, 204, 191, 165, 141, 109, 95, 89, 63; HRMSꢀESI (m/z): calcd for
C16H14N, [M+H]+: 220.1121, found 220.1118.
8ꢀMethoxyꢀ2ꢀphenylquinoline (3o)15d: Yield: 59% (34.8 mg) as yellow oil; Rf = 0.32 (10:1
hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J =4.0 Hz, 3H), 7.94(d, J =8.0 Hz,
1H), 7.54 (t, J = 8.0 Hz, 2H), 7.45 (dd, J = 15.2, 8.0 Hz, 3H), 7.11 (d, J = 4.0 Hz, 1H), 4.14 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 156.4, 155.6, 140.1, 139.7, 136.8, 129.1, 128.8, 128.3, 127.7,
126.5, 119.5, 119.4, 108.2, 56.2 ppm; νmax(KBr)/cmꢀ1 3474, 2921, 2852, 1465, 1257, 840, 761, 704;
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MS (EI) m/z 235, 204, 191, 176, 163, 128, 117, 102, 88, 76; HRMSꢀESI (m/z): calcd for
C16H14NO, [M+H]+: 236.1070, found 236.1070.
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2,8ꢀDiphenylquinoline (3p)16e: Yield: 69% (34.8 mg) as yellow oil; Rf = 0.74 (10:1 hexanes/ethyl
acetate); 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.0 Hz, 1H), 8.15 (d, J = 4.0 Hz, 2H), 7.93 (d,
J = 8.0 Hz, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.79 (t, J = 8.0 Hz, 2H), 7.58 ꢀ 7.54 (m, 3H), 7.50 ꢀ 7.38
(m, 4H); 13C NMR (100 MHz, CDCl3) δ 156.0, 145.6, 140.8, 139.6, 139.5, 137.1, 131.2, 130.4,
129.3, 128.8, 127.7, 127.4, 127.2, 126.2, 118.1 ppm; νmax(KBr)/cmꢀ1 3052, 2955, 1600, 1455,
1069, 957, 765, 696; MS (EI) m/z 281, 280, 278, 226, 139, 126, 113, 100, 76, 51; HRMSꢀESI
(m/z): calcd for C21H16N, [M+H]+: 282.1277, found 282.1272.
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2ꢀPhenylꢀ8ꢀ(trifluoromethoxy)quinoline (3q): Yield: 71% (51.5 mg) as yellow oil; Rf = 0.57
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(10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.18 (dd, J = 19.2, 8.0 Hz, 4H), 7.92
(d, J = 8.0 Hz, 1H), 7.65 (s, 1H), 7.59 ꢀ 7.48 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 157.9, 146.8,
146.5, 139.2, 136.6, 131.9, 129.7 (q, J = 220.1 Hz), 128.9, 127.6, 127.2, 123.7, 121.9, 119.9,
119.3, 117.5 ppm; νmax(KBr)/cmꢀ1 3444, 2924, 1605, 1255, 1164, 839, 754, 697; MS (EI) m/z 289,
268, 203, 202, 191, 176, 139, 115, 88, 63; HRMSꢀESI (m/z): calcd for C16H11F3NO, [M+H]+:
290.0787, found 290.0786.
6,7ꢀDimethylꢀ2ꢀphenylquinoline (3r)16a: Yield: 65% (38.0 mg) as yellow solid; mp = 109 ꢀ 110
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oC; Rf = 0.68 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 18.4 Hz,
8.0 Hz, 3H), 7.99 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.56 (dd, J = 14.4, 8.0 Hz, 3H), 7.47 (t, J = 8.0
Hz, 1H), 2.52 (s, 3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.5, 147.4, 139.9, 136.3,
135.8, 129.1, 128.8 , 127.5, 126.7, 125.8, 118.2, 20.5, 20.4 ppm; νmax(KBr)/cmꢀ1 3457, 2972, 2932,
1632, 1447, 872, 756, 690; MS (EI) m/z 233, 218, 204, 189, 154, 128, 115, 108, 95, 77;
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HRMSꢀESI (m/z): calcd for C17H16N, [M+H]+: 234.1277, found 234.1280.
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6,7ꢀDifluoroꢀ2ꢀphenylquinoline (3s): Yield: 69% (41.8 mg) as yellow solid; mp = 94 ꢀ 95 oC; Rf
= 0.63 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.0 Hz, 3H), 7.92 ꢀ
7.75 (m, 2H), 7.52 ꢀ 7.34 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 157.7 (d, J = 3.0 Hz), 152.5 (dd,
J = 253.1, 15.1 Hz), 148.8 (d, J = 16.1 Hz), 145.5 (d, J = 10.0 Hz), 139.0, 135.9 (dd, J = 5.1, 1.6
Hz), 129.7, 128.9, 127.5, 123.9 (d, J = 8.3 Hz), 119.1 (d, J = 2.2 Hz), 115.9 (d, J = 16.0 Hz), 112.6
(dd, J = 17.6, 1.5 Hz) ppm; νmax(KBr)/cmꢀ1 3445, 2924, 1636, 1501, 1297, 882, 754, 696; MS (EI)
m/z 241, 222, 212, 193, 164, 144, 120, 110, 87, 75; HRMSꢀESI (m/z): calcd for C15H10F2N,
[M+H]+: 242.0776, found 242.0775.
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5,7ꢀDimethylꢀ2ꢀphenylquinoline (3t)15f: Yield: 61% (35.6 mg) as yellow oil; Rf = 0.29 (10:1
hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 8.0 Hz, 1H), 8.20 (d, J = 8.0 Hz,
2H), 7.88 ꢀ 7.83 (m, 2H), 7.56 (t, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.23 (s, 1H), 2.69 (s,
3H), 2.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.8, 148.8, 139.7, 139.6, 133.9, 133.0, 129.2,
128.8, 127.5, 126.9, 124.6, 117.7, 21.8, 18.5 ppm; νmax(KBr)/cmꢀ1 3701, 2922, 1727, 1497, 1459,
1030, 786, 698; MS (EI) m/z 233, 218, 204, 189, 154, 115, 108, 95, 77; HRMSꢀESI (m/z): calcd
for C17H16N, [M+H]+: 234.1277, found 234.1274.
6ꢀPhenylꢀ[1,3]dioxolo[4,5ꢀg]quinoline (3u)16d: Yield: 57% (35.6 mg) as yellow solid; mp = 110 ꢀ
111 oC; Rf = 0.38 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.0 Hz,
2H), 8.02 (d, J = 12.0 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.52 ꢀ 7.41 (m, 2H), 7.06 (s, 1H), 6.10 (s,
2H); 13C NMR (100 MHz, CDCl3) δ 155.3, 150.9, 147.8, 146.5, 139.6, 135.6, 128.9, 128.8, 127.3,
124.2, 117.3, 106.1, 102.6, 101.7 ppm; νmax(KBr)/cmꢀ1 3459, 2921, 1644, 1467, 920, 859, 748, 696;
MS (EI) m/z 249, 234, 207, 190, 163, 139, 124, 95, 81; HRMSꢀESI (m/z): calcd for C16H12NO2 ,
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[M+H]+:250.0863, found 250.0866.
7ꢀMethylꢀ2ꢀphenylquinoline (3v) : 5ꢀMethylꢀ2ꢀphenylquinoline (3v′)= 6:1 : Yield: 60% (33 mg)
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as yellow solid; mp= 95 ꢀ 96 C; Rf = 0.56 (10:1 hexanes/ethyl acetate); H NMR (400 MHz,
CDCl3) δ 8.36 (d, J = 8.8 Hz, 0.2H), 8.15 (d, J = 8.0 Hz, 3H), 8.03 (d, J = 8.4 Hz, 0.17H), 7.96 (s,
1H), 7.87 (d, J = 8.8 Hz, 0.22H), 7.79 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.63 ꢀ 7.57 (m,
0.29H), 7.51 (d, J =8.0 Hz, 2H), 7.45 (d, J = 4.0Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 2.69 (s, 0.5H),
2.57 (s, 3H);13C NMR (100 MHz, CDCl3) δ 157.3, 148.6, 139.9, 139.8, 136.4, 134.4, 133.2, 129.4,
129.3, 129.2, 128.9, 128.8, 128.8, 128.6, 128.1, 127.6, 127.1, 126.8, 125.3, 118.2, 21.9, 18.6 ppm;
νmax(KBr)/cmꢀ1 3045, 2921, 2854, 1600, 1489, 835, 767, 693; MS (EI) m/z 219, 204, 189, 165,
147, 115, 108, 95, 89, 63; HRMSꢀESI (m/z): calcd for C16H14N, [M+H]+: 220.1121, found
220.1124.
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2ꢀPhenylbenzo[g]quinoline (3w)15g: Yield: 67% (41.8 mg) as yellow solid; mp = 195 ꢀ 196 oC; Rf
= 0.58 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 9.00 (d, J = 8.0 Hz, 1H), 8.63
(d, J = 8.0 Hz, 1H), 8.22 (d, J = 4.0 Hz, 2H), 8.09 (d, J = 8.0 Hz, 1H), 8.01 (t, J = 8.0 Hz, 2H),
7.94 (d, J = 8.0 Hz, 1H), 7.67 (dt, J = 22.0, 7.2 Hz, 2H), 7.54 (t, J = 6.0 Hz, 2H), 7.47 (t, J = 8.0
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 156.9, 148.2, 139.4, 131.7, 131.6, 131.0, 129.6, 129.3,
128.9, 128.7, 128.6, 127.5, 127.2, 127.1, 124.2, 122.6, 118.8 ppm; νmax(KBr)/cmꢀ1 3366, 2922,
1567, 1457, 1269, 833, 751, 694; MS (EI) m/z 255, 226, 207, 177, 151, 127, 113, 100, 75;
HRMSꢀESI (m/z): calcd for C19H14N , [M+H]+: 256.1121, found 256.1123.
2ꢀ(pꢀTolyl)quinoline (4a)15e: Yield: 61% (33.6 mg) as yellow solid; mp = 81 ꢀ 82 C; Rf = 0.55
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(10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.19 (t, J = 8.0 Hz, 2H), 8.07 (d, J =
4.0 Hz, 2H), 7.84 (dd, J = 19.2, 8.0 Hz, 2H), 7.72 (t, J = 8.0 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.33
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(d, J = 8.0 Hz, 2H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.3, 148.2, 139.5, 136.9, 129.6,
129.6, 129.3, 128.5, 127.5, 127.4, 127.1, 126.1, 118.9, 21.3 ppm; νmax(KBr)/cmꢀ1 2922, 2853, 1600,
1033, 813, 748, 615; MS (EI) m/z 219, 204, 189, 176, 165, 139, 128, 95, 83, 75, 63; HRMSꢀESI
(m/z): calcd for C16H14N, [M+H]+: 220.1121, found 220.1123.
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2ꢀ(mꢀTolyl)quinoline (4b)15e: Yield: 58% (31.9 mg) as yellow oil; Rf = 0.66 (10:1 hexanes/ethyl
acetate); 1H NMR (400 MHz, CDCl3) δ 8.24 (t, J = 10.0 Hz, 2H), 8.04 (s, 1H), 7.96 (d, J = 4.0 Hz,
1H), 7.88 (dd, J = 18.2, 8.0 Hz, 2H), 7.76 (t, J = 8.0 Hz, 1H), 7.56 (t, J = 6.0 Hz, 1H), 7.45 (t, J =
8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 2.51 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.6, 148.2,
139.6, 138.5, 136.8, 130.2, 129.8, 129.7, 128.7, 128.3, 127.5, 127.2, 126.3, 124.7, 119.2, 21.6
ppm; νmax(KBr)/cmꢀ1 3700, 3058, 2924, 1728, 1028, 831, 786, 704; MS (EI) m/z 219, 204, 189,
165, 128, 108, 95, 83, 63; HRMSꢀESI (m/z): calcd for C16H14N, [M+H]+: 220.1121, found
220.1122.
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2ꢀ(4ꢀ(isoꢀPropyl)phenyl)quinoline (4c): Yield: 69% (41.1 mg) as yellow solid; mp = 84 ꢀ 85 C;
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Rf = 0.66 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.18 (t, J = 6.0 Hz, 2H),
8.09 (d, J = 8.0 Hz, 2H), 7.83 (dd, J = 18.2, 8.0 Hz, 2H), 7.71 (t, J = 8.0 Hz, 1H), 7.51 (t, J = 6.0
Hz, 1H), 7.39 (d, J = 4.0 Hz, 2H), 2.99 (dt, J = 14.4, 7.2 Hz, 1H), 1.31 (d, J = 4.0 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ 157.5, 150.4, 148.3, 137.3, 136.7, 129.6, 129.6, 127.6, 127.4, 127.1,
126.9, 126.1, 118.9, 34.0, 23.9 ppm; νmax(KBr)/cmꢀ1 3055, 2959, 2924, 1601, 1058, 820, 756, 616;
MS (EI) m/z 247, 232, 217, 204, 176, 151, 128, 115, 101, 77; HRMSꢀESI (m/z): calcd for
C18H18N, [M+H]+: 248.1434, found 248.1440.
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2ꢀ(4ꢀ(tertꢀButyl)phenyl)quinoline (4d): Yield: 64% (41.9 mg) as yellow solid; mp = 84 ꢀ 85 C;
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Rf = 0.72 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.19 (t, J = 8.0 Hz, 2H),
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8.09 (d, J = 8.0 Hz, 2H), 7.83 (dd, J = 19.2, 8.0 Hz, 2H), 7.71 (t, J = 8.0 Hz,1H), 7.59 ꢀ 7.47 (m,
3H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 157.4, 152.6, 148.3, 136.9, 136.7, 129.7, 129.6,
127.4, 127.3, 127.1, 126.1, 125.8, 118.9, 34.8, 31.3 ppm; νmax(KBr)/cmꢀ1 3453, 2959, 1549, 1269,
1019, 821, 755, 569; MS (EI) m/z 261, 246, 230, 217, 204, 191, 176, 128, 108, 101, 77;
HRMSꢀESI (m/z): calcd for C19H20N, [M+H]+: 262.1590, found 262.1590.
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2ꢀ(3,5ꢀDimethylphenyl)quinoline (4e)15e: Yield: 54% (31.6 mg) as yellow oil; Rf = 0.59 (10:1
hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.0 Hz, 2H), 7.84 (dd, J = 16.0,
8.0 Hz, 2H), 7.80 ꢀ 7.69 (m, 3H), 7.52 (t, J = 8.0 Hz, 1H), 7.11 (s, 1H), 2.44 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 157.8, 148.1, 139.5, 138.4, 136.8, 131.1, 129.7, 129.6, 127.4, 127.2, 126.2,
125.5, 119.3, 21.5 ppm; νmax(KBr)/cmꢀ1 3697, 2922, 1596, 1503, 1266, 1024, 824, 754; MS (EI)
m/z 233, 217, 189, 167, 115, 108, 102, 77; HRMSꢀESI (m/z): calcd for C17H16N, [M+H]+:
234.1277, found 234.1280.
2ꢀ(4ꢀMethoxyphenyl)quinoline (4f)16a: Yield: 55% (31.6 mg) as yellow solid; mp = 113 ꢀ 114 oC;
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Rf = 0.40 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.19 (t, J = 8.0 Hz, 4H),
7.91 ꢀ 7.79 (m, 2H), 7.74 (t, J = 8.0 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 2H),
3.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.9, 156.9, 148.2, 136.8, 132.1, 129.7, 129.4, 128.9,
127.4, 126.9, 125.9, 118.6, 114.3, 55.4 ppm; νmax(KBr)/cmꢀ1 3686 ,2921, 1711, 1246, 1028, 820,
787, 727; MS (EI) m/z 235, 220, 204, 192, 165, 128, 117, 96, 88, 75; HRMSꢀESI (m/z): calcd for
C16H14NO, [M+H]+:236.1070, found 236.1074.
2ꢀ(3ꢀMethoxyphenyl)quinoline (4g)15e: Yield: 63% (37.2 mg) as yellow oil; Rf = 0.28 (10:1
hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 18.4, 8.0 Hz, 2H), 7.96 ꢀ 7.78
(m, 3H), 7.69 (t, J = 8.0 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.12 (t, J = 8.0
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Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.3, 157.1,
148.3, 135.1, 131.5, 130.4, 129.8, 129.6, 129.3, 127.4, 127.1, 126.2, 123.5, 121.3, 111.5, 55.7 ppm;
νmax(KBr)/cmꢀ1 3413, 2925, 1596, 1249, 965, 831, 754, 692; MS (EI) m/z 235, 206, 190, 176, 139,
130, 102, 95, 89, 63; HRMSꢀESI (m/z): calcd for C16H14NO, [M+H]+:236.1070, found 236.1073.
2ꢀ(3,4ꢀDimethoxyphenyl)quinoline (4h)16c: Yield: 61% (40.6 mg) as yellow solid; mp = 121 ꢀ
122 oC; Rf = 0.37 ( 10:1 hexanes : ethyl acetate);Rf = 0.69 (10:1 hexanes/ethyl acetate); 1H NMR
(400 MHz, CDCl3) δ 8.16 (d, J = 8.0 Hz, 2H), 7.88 (s, 1H), 7.81 (dd, J = 16.0, 8.0 Hz, 2H), 7.75 ꢀ
7.57 (m, 2H), 7.49 (t, J = 8.0 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 4.04 (s, 3H), 3.95 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 156.8, 150.4, 149.4, 148.2, 136.6, 132.5, 129.6, 129.5, 127.5, 126.9,
126.0, 120.3, 118.6, 111.1, 110.5, 56.0, 56.0 ppm; νmax(KBr)/cmꢀ1 2922, 2851, 1628, 1503, 1025,
816, 727, 622; MS (EI) m/z 265, 250, 219, 207, 191, 178, 167, 124, 102, 89, 76; HRMSꢀESI (m/z):
calcd for C17H16NO2, [M+H]+: 266.1176, found 266.1180.
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2ꢀ(3,4,5ꢀTrimethoxyphenyl)quinoline (4i): Yield: 55% (40.2 mg) as yellow solid; mp = 141 ꢀ
142oC; Rf = 0.16 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.24 ꢀ 8.13 (m, 2H),
7.83 (d, J = 8.0 Hz, 2H), 7.73 (t, J = 8.0 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.41 (s, 2H), 4.01 (s,
6H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.9, 153.6, 148.1, 139.5, 136.8, 135.3, 129.7,
129.6, 127.5, 127.1, 126.3, 118.9, 104.9, 60.9, 56.3 ppm; νmax(KBr)/cmꢀ1 2929, 1591, 1497, 1419,
1126, 1105, 822, 782; MS (EI) m/z 295, 280, 249, 222, 219, 166, 140, 132, 89, 83; HRMSꢀESI
(m/z): calcd for C18H18NO3, [M+H]+: 296.1281, found 296.1285.
2ꢀ(4ꢀFuorophenyl)quinoline (4j)15e: Yield: 51% (28.6 mg) as yellow solid; mp = 99 ꢀ 100 oC; Rf
= 0.52 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.18 (dd, J = 16.0, 7.2 Hz, 4H),
7.81 (d, J = 8.0 Hz, 2H), 7.72 (s, 1H), 7.52 (s, 1H), 7.20 (t, J = 8.0 Hz, 2H); 13C NMR (100 MHz,
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CDCl3) δ 163.9 (d, J = 248 Hz), 156.2, 148.2, 136.9, 135.8, (d, J = 3.0 Hz), 129.8, 129.7, 129.4 (d,
J = 9.0 Hz), 127.4, 127.1, 126.4, 118.6, 115.8 (d, J = 22.0 Hz) ppm; νmax(KBr)/cmꢀ1 3701, 2922,
2854, 1592, 1459, 828, 786, 698; MS (EI) m/z 223, 202, 175, 169, 128, 111, 101, 75, 74;
HRMSꢀESI (m/z): calcd for C15H11FN, [M+H]+: 224.0870, found 224.0872.
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2ꢀ(3ꢀChlorophenyl)quinoline (4k)16d: Yield: 74% (44.4 mg) as yellow solid; mp = 91 ꢀ 92 oC; Rf
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= 0.31 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.22 ꢀ 8.12 (m, 3H), 7.98 (s,
1H), 7.76 (dd, J = 8.0, 5.6 Hz, 2H), 7.70 (t, J = 8.0 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.40 (d, J
=4.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 155.7, 148.2, 141.4, 137.0, 134.9, 130.1, 129.9,
129.8, 129.3, 127.7, 127.5, 127.4, 126.7, 125.6, 118.6 ppm; νmax(KBr)/cmꢀ1 3450, 2923, 1597,
1432, 876, 827, 749, 692; MS (EI) m/z 239, 204, 176, 151, 128, 119, 102, 88, 75; HRMSꢀESI
(m/z): calcd for C15H11ClN, [M+H]+: 240.0575, found 240.0578.
2ꢀ(4ꢀ(Trifluoromethyl)phenyl)quinoline (4l)16a: Yield: 48% (34.2 mg) as yellow solid; mp = 131
ꢀ 132 oC; Rf = 0.62 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.27 (t, J = 8.0 Hz,
3H), 8.19 (d, J = 8.0 Hz, 1H), 7.87 (dd, J = 12.0, 9.2 Hz, 2H), 7.76 (t, J = 10.0 Hz, 3H), 7.56 (t, J
= 6.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 155.7, 148.3, 142.9, 137.2, 131.3, 130.9 (q, J =
245.2 Hz), 130.0, 129.9, 127.9, 127.5, 127.5, 126.9, 125.8 (q, J = 3.7 Hz), 125.6, 118.8 ppm;
νmax(KBr)/cmꢀ1 2921, 1600, 1330, 1072, 851, 759, 675; MS (EI) m/z 273, 252, 204, 194, 176, 169,
151, 126, 101, 75; HRMSꢀESI (m/z): calcd for C16H11F3N, [M+H]+: 274.0838, found 274.0842.
3ꢀ(Quinolinꢀ2ꢀyl)benzonitrile (4m)16g: Yield: 54% (31.2 mg) as yellow solid; mp = 99 ꢀ 101 oC;
Rf = 0.23 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.41 (d, J =8.0
Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 8.18 (t, J = 10.0 Hz, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.76 (dd, J =
16.8, 8.0 Hz, 2H), 7.63 (t, J = 7.6 Hz, 2H), 7.58 (t, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3)
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δ 154.6, 148.3, 140.8, 137.4, 132.5, 131.6, 131.3, 130.1, 129.8, 129.6, 127.6, 127.5, 118.8, 118.3,
113.1 ppm; MS (EI) m/z 230, 201, 175, 151, 128, 115, 101, 88, 75; HRMSꢀESI (m/z): calcd for
C16H10N2, [M+H]+: 231.0917, found 231.0915.
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2ꢀ(4ꢀNitrophenyl)quinoline (4n)16a: Yield: 58% (26.8 mg) as yellow solid; mp = 130 ꢀ 131 oC; Rf
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= 0.27 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.32 (s, 4H), 8.26 (d, J = 8.0
Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.86 (dd, J = 13.6, 8.4 Hz, 2H), 7.76 (t, J = 8.0 Hz, 1H), 7.57 (t,
J = 6.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 154.5, 148.3, 148.3, 145.4, 137.3, 130.2, 129.9,
128.3, 127.6, 127.3, 123.9, 118.7 ppm; νmax(KBr)/cmꢀ1 3450, 2922, 2228, 1635, 1268, 797, 755,
690; MS (EI) m/z 250, 220, 204, 192, 176, 151, 128, 101, 88, 75; HRMSꢀESI (m/z): calcd for
C15H11N2O2, [M+H]+: 251.0815, found 251.0811.
3ꢀMethylꢀ2ꢀphenylquinoline (4o)16c: Yield: 64% (35.2 mg) as yellow oil; Rf = 0.52 (10:1
hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 7.99 (s, 1H), 7.76
(d, J = 8.0 Hz, 1H), 7.64 (t, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.53 ꢀ 7.30 (m, 5H), 2.44 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 160.6, 146.7, 140.9, 136.7, 129.3, 129.2, 128.9, 128.6, 128.3,
128.2, 127.6, 126.7, 126.4, 20.6 ppm; νmax(KBr)/cmꢀ1 3456, 2923, 1626, 1488, 1268, 1007, 758,
703; MS (EI) m/z 219, 189, 140, 115, 108, 95, 83; HRMSꢀESI (m/z): calcd for C16H14N, [M+H]+:
220.1121, found 220.1125.
2ꢀ(Thiophenꢀ2ꢀyl)quinoline (4p)16a: Yield: 50% (26.8 mg) as yellow solid; mp = 130 ꢀ 131 oC; Rf
= 0.52 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.13 (t, J = 11.2 Hz, 2H), 7.74
(dt, J = 15.2, 9.0 Hz, 4H), 7.55 ꢀ 7.41 (m, 2H), 7.17 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 152.3,
148.0, 136.7, 129.9, 129.3, 129.2, 128.7, 128.1, 127.5, 127.2, 126.2, 125.9, 117.8 ppm;
νmax(KBr)/cmꢀ1 3697, 2922, 1593, 1268, 1026, 825, 755, 714; MS (EI) m/z 211, 185, 178, 167, 151,
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139, 128, 105, 83, 75; HRMSꢀESI (m/z): calcd for C13H10NS, [M+H]+: 212.0528, found 212.0524.
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2ꢀPhenylquinoline (3a)16a: Yield: 65% (33.5 mg) as yellow solid; mp = 86 ꢀ 87 C; Rf = 0.69
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(10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.20 (dd, J = 23.2 Hz, 8.0 Hz, 4H),
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7.85 (dd, J = 20.0, 8.0 Hz, 2H), 7.73 (t, J = 8.0 Hz, 1H), 7.50 (dt, J = 25.2, 7.2 Hz, 4H); 13C NMR
(100 MHz, CDCl3) δ 157.3, 148.1, 139.5, 136.9, 129.8, 129.6, 129.4, 128.9, 127.6, 127.5, 127.2,
126.4, 119.0 ppm; νmax(KBr)/cmꢀ1 3450, 2923, 1625, 1603, 1021, 830, 799, 688; MS (EI) m/z 206,
205, 176, 164, 151, 128, 113, 102, 88, 76, 51; HRMSꢀESI (m/z): calcd for C15H12N, [M+H]+:
206.0964, found 206.0969.
2ꢀ(4ꢀMethoxyphenyl)quinoline (4f)16a: Yield: 61% (35.9 mg) as yellow solid; mp = 113 ꢀ 114 oC;
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Rf = 0.40 (10:1 hexanes/ethyl acetate); H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.0 Hz, 4H),
7.87 ꢀ 7.81 (m, 2H), 7.74 (t, J = 6.0 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 2H),
3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.9, 156.9, 148.3, 136.7, 132.2, 129.6, 129.5, 128.9,
127.4, 126.9, 125.9, 118.6, 114.3, 55.4 ppm; νmax(KBr)/cmꢀ1 3686, 2921, 1711, 1246, 1028, 820,
787, 727; MS (EI) m/z 235, 220, 204, 192, 165, 128, 117, 96, 88, 75; HRMSꢀESI (m/z): calcd for
C16H14NO, [M+H]+: 236.1070, found 236.1074.
2ꢀ(3ꢀMethoxyphenyl)quinoline (4g)15e: Yield: 67% (39.6 mg) as yellow oil; Rf = 0.28 (10:1
hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 16.8, 8.0 Hz, 2H), 7.95 ꢀ 7.78
(m, 3H), 7.70 (t, J = 8.0 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.41 (t, J = 6.0 Hz, 1H), 7.13 (t, J = 6.0
Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.3, 157.1,
148.3, 135.1, 131.5, 130.3, 129.8, 129.2, 127.4, 127.1, 126.2, 123.5, 121.3, 111.5, 55.7 ppm;
νmax(KBr)/cmꢀ1 3413, 2925, 1596, 1249, 965, 831, 754, 692; MS (EI) m/z 235, 206, 190, 176, 139,
130, 102, 95, 89, 63; HRMSꢀESI (m/z): calcd for C16H14NO, [M+H]+: 236.1070, found 236.1073.
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2ꢀ(3,4ꢀDimethoxyphenyl)quinoline (4h)16c: Yield: 66% (43.9 mg) as yellow solid; mp = 103 ꢀ
104 oC; Rf = 0.37 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.0 Hz,
2H), 7.89 ꢀ 7.80 (m, 3H), 7.74 ꢀ 7.66 (m, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 8.0 Hz, 1H),
4.06 (s, 3H), 3.96 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.8, 150.5, 149.5, 148.0, 136.8, 132.3,
129.7, 129.4, 127.5, 126.9, 126.1, 120.4, 118.7, 111.1, 110.6, 56.1, 56.0 ppm; νmax(KBr)/cmꢀ1 3413,
2925, 1596, 1249, 965, 831, 754, 692; MS (EI) m/z 265, 250, 219, 207, 191, 178, 167, 124, 102,
89, 76; HRMSꢀESI (m/z): calcd for C17H16NO2, [M+H]+: 266.1176, found 266.1180.
2ꢀ(4ꢀEthoxyꢀ3ꢀmethoxyphenyl)quinoline (5a): Yield: 71% (49.7 mg) as yellow solid; mp = 108 ꢀ
109 oC; Rf = 0.17 (10:1 hexanes/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 8.0 Hz,
1H), 8.08 (d, J = 12.0 Hz,1H), 7.88 (s, 1H), 7.75 (dd, J = 12.0, 8.0 Hz, 2H), 7.68 (t, J = 6.0 Hz,
1H), 4.12 (dd, J = 13.2, 6.4 Hz, 2H), 4.00 (s, 3H), 1.47 (t, J =8.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 156.8, 149.8, 149.7, 148.2, 136.6, 132.4, 129.6, 129.5, 127.5, 126.9, 125.9, 120.3, 118.6,
112.4, 110.7, 64.4, 56.1, 14.8 ppm; νmax(KBr)/cmꢀ1 3058, 2979, 1597, 1505, 1464, 1036, 817, 756;
MS (EI) m/z 279, 264, 235, 222, 191, 178, 167, 152, 128, 113, 89; HRMSꢀESI (m/z): calcd for
C18H18NO2 [M+H]+: 280.1332, found 280.1338.
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Acknowledgments
The authors thank the National Program on Key Research Project (2016YFA0602900), the
National Natural Science Foundation of China (21490572, 21502055 and 21420102003), and the
Fundamental Research Funds for the Central Universities (2015ZY001) for financial support.
Supporting Information
1
Copies of H and 13C NMR spectra data for all compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
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