Copper-catalyzed tandem aerobic oxidative cyclization for the ynthesis of polysubstituted quinolines via C(sp3)/C(sp2)-H bond functionalization

Article abstract of DOI:10.1021/acs.joc.7b01575

One-pot Cu-catalyzed tandem aerobic oxidative cyclization for the synthesis of quinolines from 2-vinylanilines/ 2-arylanilines and 2-methylquinolines via C(sp₃)-H/C(sp₂)- H bond functionalization has been developed. Dioxygen as an ideal oxidant has been employed for this transformation. The substrates bearing various functional groups perform well in this process and generate the desired products in moderate to good yields.

Full text of DOI:10.1021/acs.joc.7b01575

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Article
Copper-catalyzed Tandem Aerobic Oxidative Cyclization for the Synthesis
of Polysubstituted Quinolines via C(sp3)/C(sp2)-H bonds functionalization
Xiaobo Pang, Mingzhong Wu, Jixiang Ni, Fuming Zhang, Jingfeng Lan, Baohua Chen, and Rulong Yan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01575 • Publication Date (Web): 20 Sep 2017
Downloaded from http://pubs.acs.org on September 20, 2017
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Copper-catalyzed Tandem Aerobic Oxidative Cyclization for the
Synthesis of Polysubstituted Quinolines via C(sp3)/C(sp2)-H
bonds functionalization
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Xiaobo Pang, Mingzhong Wu, Jixiang Ni, Fuming Zhang, Jingfeng Lan, Baohua Chen and Rulong
Yan*
State Key Laboratory of Applied Organic Chemistry, Key laboratory of Nonferrous Metal
Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou
University, Lanzhou, Gansu, 730000 (China)
yanrl@lzu.edu.cn
Fax: +86 931 8912596; Tel: +86 931 8912586
Abstract: Oneꢀpot Cuꢀcatalyzed tandem aerobic oxidative cyclization for
the synthesis of quinolines from 2ꢀvinylanilines/2ꢀaryl anilines and
2ꢀmethylquinolines via C(sp3)ꢀH/C(sp2)ꢀH bonds functionalization has
been developed. Dioxygen as an ideal oxidant has been employed for this
transformation. The substrates bearing various functional groups are
performed well in this process and generate the desired products in
moderate to good yields.
Introduction
Transitionꢀmetalꢀcatalyzed tandem aerobic oxidative cyclization has
been emerged as a powerful tool for the synthesis of heterocyclic
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compounds. Among various oxidants, dioxygen as an ideal and potential
oxidant has emitted bright light in transitionꢀmetalꢀcatalyzed tandem
oxidative reaction system. Transitionꢀmetalꢀcatalyzed/dioxygen reaction
system had been heavily investigated in the past years for its great
application prospect in chemical industry.1 For example, the groups of
Glorius,2 Jiao,3 and Jiang4 had reported a series of milestone works about
heterocyclic compounds construction through this reaction system.
Nevertheless, using transitionꢀmetalꢀcatalyzed /dioxygen reaction system
for direct and selective C(sp3)ꢀH bond activation is still challenging due
to low reactivity.5 Thus, the development of novel protocols for the
synthesis of heterocyclic compounds through direct C(sp3)ꢀH bond
activation by transitionꢀmetal catalyzed/dioxygen reaction system is still
highly desirable.
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Heterocyclic compounds, as a crucial class of scaffolds, are widely
applied in organic synthesis, advanced function materials and
pharmaceuticals.6 In the past several decades, continuous efforts had been
devoted to construct polysubstituted heterocyclic compounds.7 In
Particular, quinoline skeletons had been attracted much more attentions
due to their privileged scaffold motifs of physicochemical properties,
biological activities and pharmacological value,8 as shown in Figure 1:
Compound A (18 kDa translocator, TSPO), was a recognized biomarker
of neuroinflammation, with high affinity and human genotype insensity.9
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Compound B and C were potential and selective PI3Kβ/δ dual inhibitors,
as promising target for the treatment of human cancer and a variety of
inflammentry diseases.10 Compound D was an antibiotic with antitumor
activity, which was isolated from streptomyoes lavendulae by Balitz.11
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Figure 1. Several Examples of Bioactive Quinoline Derivatives
Therefore, it was not surprising that many different strategies had been
developed for the synthesis of quinoline skeletons. Classical methods for
the construction of quinolines in organic synthesis had been developed,
such as Skraup, Friendlander, Cambes, Niementowski, Pfitzinger, and
Povarov reactions.12 Recently, Walter's group demonstrated that
2ꢀ(propꢀ1ꢀenꢀ2ꢀyl)anilines underwent a facile conversion to synthesize
quinolines with 3ꢀmethylcyclohexones (Scheme 1, entry a).13 Zeng's
group reported palladiumꢀcatalyzed oxidative cyclization to generate
2ꢀaminoquinolines from 2ꢀvinylanilines and isocyanides (Scheme 1, entry
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b).14 Yu's group developed a novel approach to obtain 2ꢀquinolinones
with 2ꢀvinylanilines and carbon dioxide (Scheme 1, entry c).15
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Scheme 1. Synthesis of Substituted Quinoline
Results and Discussion
Inspired by our previous work,16 herein, we developed oneꢀpot method
for the synthesis of substituted quinolines from substituted
2ꢀvinylanilines/2ꢀaryl anilines and 2ꢀmethylquinolines with dioxygen as
oxidant through Cuꢀcatalyzed cascade oxidative cyclization via
C(sp3)/(sp2)ꢀH bonds functionalization (Scheme 1, entry d). Initial
attempt was started by using 2ꢀ(1ꢀphenylvinyl)aniline 1a and
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Table 1. Optimization of Reaction Conditions a
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Ph
N
Ph
catalyst
solvent
N
N
CH3
NH2
9
3aa
1a
2a
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Entry
1c
2c
3c
4c
Catalyst/equiv
Solvent
CH3NO2
DMSO
DMA
DMF
DMF
NMP
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Yieldb [%]
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CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
CuCl2 (0.1)
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70
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6
trace
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CuBr2 (0.1)
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9
CuI (0.1)
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18d
19e
20
CuCl (0.1)
45
CuBr (0.1)
56
Cu(OAc)2 (0.1)
Cu(OTf)2 (0.1)
CuCl2—2H2O (0.05)
CuCl2—2H2O (0.2)
CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
CuCl2—2H2O (0.1)
ꢀ
40
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69
62
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ꢀ
ꢀ
Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), catalyst (0.03 mmol), solvent (2 mL), O2, 130 C. b Isolated
yields. c TfOH (5 mol%). d Under Air. e Under N2.
a
o
2ꢀmethylquinoline 2a as model substrates and the desired product
4ꢀphenylꢀ2,2'ꢀbiquinoline 3aa was formed in 43% yield in the presence of
10 mol% of CuCl2·2H2O and 5 mol% TfOH (trifluoromethanesulfonic
o
acid) in CH3NO2 at 130 C under O2 (Table 1, entry 1). In order to
improve the yield, different solvents were screened firstly and the product
3aa was obtained in 70% yield when DMF was used (Table 1, entry
4).The yield was slightly improved to 71% when the TfOH was removed
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Table 2. Scope of Substituted 2ꢀVinylanilines a
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a Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), CuCl2·2H2O (0.03 mmol), DMF (2 mL), O2, 130 oC.
(Table 1, entry 5). Then different copper salts were also assessed and
CuCl2·2H2O was proved to be the most efficient catalyst for this reaction
(Table 1, entry 7ꢀ13). Finally, the dosage of CuCl2·2H2O, temperature and
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air were also examined, no better result was obtained (Table 1, entry
14ꢀ18). In addition, some control experiments without metal salts and
dioxygen were also performed for this reaction and no desired product
was detected (Table 1, entry 19ꢀ20). Thus the optimized reaction
condition was eatablished with CuCl2·2H2O (0.1 equiv) in DMF at 130oC
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under O2.
Table 3. Scope of Substituted 2ꢀMethylquinolines and 2ꢀMethylpyridines a
a Reaction conditions: 1a (0.3 mmol), 2 (0.6 mmol), CuCl2·2H2O (0.03 mmol), DMF (2 mL), O2, 130 oC.
With the optimized conditions in hand, the scope of
2ꢀvinylanilines/2ꢀaryl anilines and 2ꢀmethylquinoline was evaluated and
the results are shown in Table 2. Most of substrates transformed well in
this reaction system and generated the corresponding quinoline
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derivatives in moderate to good yields. Obviously, in contrast to
substrates with electronꢀdonating groups, electronꢀwithdrawing groups,
such as fluorineꢀ, chlorineꢀ, and bromine, on the benzene ring of substrate
1, produced the target products 3ka-3ra in good yields. Unfortunately, N,
Nꢀdimethylꢀ3ꢀ(1ꢀphenylvinyl)benzeneꢀ1,4ꢀdiamine 1j was failed to give
the desired product 3ja. Meanwhile, to access the scalability of this
protocols, more challenging substrates 1s, 1t, and (E)ꢀ2ꢀstyrylaniline 1u
were also employed for this transformation under the optimized
conditions, the desired products 3sa and 3ta were afforded in 76% and
38% yield respectively, but only trace amount of 3ua was detected.
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Table 4. Scope of Substituted 2ꢀVinylanilines with 2ꢀMethylꢀ1,2,3,4ꢀ
Tetrahydroquinoline a
a Reaction conditions: 1a (0.3 mmol), 4a (0.6 mmol), CuCl2·2H2O (0.03 mmol), DMF (2 mL), O2, 130 oC.
The scope of the substrate investigation was further enlarged to various
substituted 2ꢀmethylquinolines and 2ꢀmethylpyridines. The results are
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Table 5. Scope of Substituted 2ꢀArylanilines with 2ꢀMethylquinolines a
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a Reaction conditions: 1a (0.3 mmol), 2 (0.6 mmol), CuCl2·2H2O (0.03 mmol), DMF (2 mL),
O2, 130 oC.
illustrated in Table 3. 2ꢀMethylquinolines with various substituents at C6,
C7 position (2b-2g) reacted favourably with substrate 1a and generated
the desired substituted quinolines in moderate yields. Interestingly,
2ꢀmethylpyridines 2i and 2j were tolerated with this conditions. Whereas
2ꢀfluoroꢀ6ꢀmethylpyridine 2k failed to give the desired product.
We also evaluated the scope of 2ꢀmethylꢀ1,2,3,4ꢀtetrahydroquinoline
4a with substrate 1 under the optimized conditions (Table 4). The
substrate 4a could also react with substrate 1 and the desired products 3
were isolated in the lower yields. In this process, the substrate 4a was
firstly converted to 2a under the standard reaction conditions, which was
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demonstrated by GCꢀMS (see supporting information, Figure S1).
Based on the success of orthoꢀalkenyl anilines in this reaction and the
similar reactivity in many kinds of C(sp2)ꢀH transformations, we further
investigated the reactions of the substrate 6 and 2 and the desired fused
heterocyclic compounds 5 were isolated in moderate to good yields under
the optimized condtions (Table 5). Above instances demonstrated that this
method had emerged as a powerful tool for the synthesis of fused
heterocyclic compounds.
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Scheme 2. The Scope of 4ꢀMethyl Pyridine, 4ꢀMethyl Quinoline and 2ꢀMethyl Indole
Moreover, the substrates 8a, 8b and 8c were also evaluated under the
optimized reaction conditions and the results were shown in Scheme 2.
Only 3ꢀmethylquinoline reacted with 1a smoothly and generated the
desired product 7aa in 72% yield.
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Scheme 3. Control Experiments
To further gather more information about the reaction mechanism,
several control experiments were performed. First, the reaction of
quinolineꢀ2ꢀcarbaldehyde 9 with 2ꢀ(1ꢀphenylvinyl)aniline 1a was carried
out under the standard conditions (Scheme 3, entry a) and the product 3aa
was obtained in 82% yield. In addition, further investigation was detected
by the GCꢀMS with 1.0 equiv 1a and 2.0 equiv 2a under the standard
conditions for 2 h. The molecular ion peak at m/z = 157 corresponding to
9 was found, and the result are illustrated in Figure S2 of supporting
information. Above results demonstrated that aldehyde should be the
intermediate for this process. Then the radical scavengers of TEMPO
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(2,2,6,6,ꢀtetramethylpiperidylꢀ1ꢀoxyl)
and
BHT
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(2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol) were added to the reaction mixture
respectively, all of the yields were suppressed remarkably (Scheme 3,
entry b). These results demonstrated that the reaction should proceed
through radical pathway. Furthermore, TEMPO was added into the
reaction system of substrate 1a and quinolineꢀ2ꢀcarbaldehyde 9 and the
reaction gave the corresponding product 3aa in 87% yield (Scheme 3,
entry c), which indicated the radical reaction should occur in the process
of oxidation 2ꢀmethylquinoline. When the substrate 1a and
quinolineꢀ2ꢀcarbaldehyde 9 was performed in DMF without catalyst and
dioxygen at 130 oC (Scheme 3, entry d), the 3aa was isolated in 85%
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Scheme 4. Proposed Mechanism
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yield. This result suggested that the desired product 3aa was produced via
6π electrocyclization.
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Based on these experiments, a plausible mechanism is illustrated in
Scheme 4. The 2ꢀmethylquinoline 2a generated to peroxide radical
intermediate A under the optimized conditions firstly. The radical
intermediate A was led to the peroxide radical intermediate B with
dioxygen. Then quinolineꢀ2ꢀcarbaldehyde C, which was produced from
intermediate B, reacted with substrate 1a to generate the imine
intermediate D. Subsequently, D was converted to E via 6π
electrocyclization process. Finally, the product 3aa was achieved from
intermediate E through the oxidation.
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Conclusion
In summary, we have developed a direct method for synthesis
polysubstituted quinoline derivates with 2ꢀvinylanilines and
2ꢀmethylquinolines through C(sp3/sp2)ꢀH bonds activation and tandem
oxidative cyclization. Additionally, 2ꢀmethylꢀ1,2,3,4ꢀtetrahydroquinoline
and 2ꢀaryl anilines also performed well with this reaction system and
generated the desired products in moderate yileds. In the presence of
copperꢀcatalyst and dioxygen reaction system, various functional groups
were tolerated well and gave the corresponding products in moderate to
good yields.
Experimental Section
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General remarks. H NMR and C NMR spectra of materials and
products were respectively recorded on 300MHz and 75MHz (VARIAN
300M), 400MHz and 100MHz (BRUKER 400M or JNMꢀECS 400M) in
CDCl3. All chemical shifts are given as δ value (ppm) with reference to
tetramethylsilane (TMS) as an internal standard. All compounds were
further characterized by HRMS; HRMS was performed on an FTꢀICRMS
mass instrument and measured with electrospray ionization (ESI). Copies
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of their H NMR and C NMR spectra are provided in Supporting
Information. Products were purified by flash chromatography on 200–300
mesh silica gels. All melting points were determined without correction.
Unless otherwise noted, commercially available reagents and solvents
were used without further purification.
General procedure for the synthesis of 2-Vinylanilines and
2-(1H-pyrrol-1-yl)aniline.
1) 1a-1p and 1s were prepared in the method17
Aniline (10 mmol), phenylacetylene (1.0 g, 10 mmol) and
montraorillonite KSF (1.0 g) are introduced in a round bottomed flask
equipped with magnetic stirrer and a reflux condenser. The reaction
mixture is heated at 140°C for 5 h and then cooled to room temperature.
The products was dissolved with dichloromethane and filtered. Then the
solvent were concentrated in vacuo and and the crude was purified by
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column chromatography (silica gel, appropriate mixture of
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petroleum ether /ethyl acetate) to give 1a-1p and 1s.
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2-(1-phenylvinyl)aniline (1a). Yellow solid. H NMR (400 MHz,
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CDCl3, ppm): δ = 7.37ꢀ7.26 (m, 5 H), 7.19ꢀ7.09 (m, 2 H), 6.79ꢀ6.75 (m, 1
H), 6.67ꢀ6.65 (m, 1 H), 5.778ꢀ5.774 (d, J = 1.6 Hz, 1 H), 5.338ꢀ5.335 (d,
13
J = 1.2 Hz, 1 H), 3.51 (br s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ
=147.8, 144.6, 140.3, 131.5, 129.4, 129.2, 128.7, 127.9, 127.3, 118.9,
116.7, 116.2.
2-methyl-6-(1-phenylvinyl)aniline (1b). Colorless oil. 1H NMR (400
MHz, CDCl3, ppm): δ = 7.35ꢀ7.25 (m, 5 H), 7.04 (s, 1 H), 6.98 (s, 1 H),
6.71ꢀ6.69 (m, 1 H), 5.79ꢀ5.78 (m, 1 H), 5.33ꢀ5.32 (m, 1 H), 3.48 (br s, 2
13
H), 2.13 (s, 3 H); C NMR (100 MHz, CDCl3, ppm): δ =148.0, 142.7,
140.4, 130.5, 129.2, 129.1, 128.7, 127.6, 127.2, 122.9, 118.4, 116.7, 18.3.
1
4-methyl-2-(1-phenylvinyl)aniline (1c). Colorless oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.38ꢀ7.26 (m, 5 H), 6.97ꢀ6.92 (m, 2 H),
6.60ꢀ6.58 (d, J = 8.0 Hz, 1 H), 5.765ꢀ5.761 (d, J = 1.6 Hz, 1 H),
5.326ꢀ5.323 (d, J = 1.2 Hz, 1 H), 3.31 (br s, 2 H), 2.25 (s, 3 H); 13C NMR
(100 MHz, CDCl3, ppm): δ = 148.0, 142.1, 140.4, 131.9, 130.0, 129.2,
128.7, 128.12, 128.08, 127.3, 116.6, 116.4, 21.1.
1
2,3-dimethyl-6-(1-phenylvinyl)aniline (1d). Yellow oil. H NMR
(300 MHz, CDCl3, ppm): δ = 7.38ꢀ7.20 (m, 5 H), 6.90ꢀ6.87 (d, J = 9.0 Hz,
1 H), 6.66ꢀ6.63 (d, J = 9.0 Hz, 1 H), 5.79 (d, 1 H), 5.33 (d, 1 H), 3.46 (br
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s, 2 H), 2.30 (s, 3 H), 2.06 (s, 3 H); 13C NMR (75 MHz, CDCl3, ppm): δ =
147.6, 141.9, 139.9, 136.4, 128.4, 127.9, 127.6, 126.6, 125.3, 120.7,
119.8, 115.9, 20.6,13.0.
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2-isopropyl-6-(1-phenylvinyl)aniline (1e). Yellow oil. 1H NMR (300
MHz, CDCl3, ppm): δ = 7.36ꢀ7.26 (m, 5 H), 7.17ꢀ7.14 (m, 1 H),
6.99ꢀ6.96 (m, 1 H), 6.82ꢀ6.77 (m, 1 H), 5.83ꢀ5.81 (t, J = 3.0 Hz, 1 H),
5.35ꢀ5.34 (t, J = 3.0 Hz, 1 H), 3.52 (br s, 2 H), 2.93ꢀ2.79 (m, 1 H),
1.28ꢀ1.27 (d, J = 3.0 Hz, 3 H ), 1.25ꢀ1.24 (d, J = 3.0 Hz, 3 H); 13C NMR
(75 MHz, CDCl3, ppm): δ = 147.6, 140.8, 139.7, 132.6, 128.5, 128.0,
126.5, 124.7, 118.0, 116.1, 27.7, 22.3.
1
4-isopropyl-2-(1-phenylvinyl)aniline (1f). Yellow oil. H NMR
(400 MHz, CDCl3, ppm): δ = 7.39ꢀ7.29 (m, 5 H), 7.04ꢀ7.02 (m, 1 H),
6.98ꢀ6.97 (d, J = 4.0 Hz, 1 H), 6.65ꢀ6.63 (d, J = 8.0 Hz, 1 H), 5.79 (d, 1
H), 5.35 (d, 1 H), 3.35 (br s, 2 H), 2.87ꢀ2.77 (m, 1 H), 1.23ꢀ1.21 (d, J =
8.0 Hz, 6 H); 13C NMR (100 MHz, CDCl3, ppm): δ = 147.6, 141.8, 139.8,
139.0, 128.9, 128.7, 128.2, 127.4, 126.8, 126.7, 116.1, 115.8, 33.3, 24.4.
1
4-(tert-butyl)-2-(1-phenylvinyl)aniline (1g). Colorless oil. H
NMR (400 MHz, CDCl3, ppm): δ = 7.37ꢀ7.23 (m, 5 H), 7.18ꢀ7.12 (m, 2
H), 6.59ꢀ6.57 (d, J = 8.0 Hz, 1 H), 5.77 (s, 1 H), 5.33 (s, 1 H), 3.37 (br s,
2 H), 1.28 (s, 9 H); 13C NMR (100 MHz, CDCl3, ppm): δ = 147.6, 141.3,
141.0, 139.6, 128.4, 127.9, 127.5, 126.8, 126.6, 125.5, 115.8, 115.2, 33.8,
31.5.
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4-methoxy-2-(1-phenylvinyl)aniline (1h). Brown oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.37ꢀ7.27 (m, 5 H), 6.77ꢀ6.71 (m, 2 H),
6.63ꢀ6.61 (d, J = 8.0 Hz, 1 H), 5.788ꢀ5.785 (d, J = 1.2 Hz, 1 H),
5.340ꢀ5.337 (d, J = 1.2 Hz, 1 H), 3.73 (s, 3 H), 3.23 (br s, 2 H); 13C NMR
(100 MHz, CDCl3, ppm): δ = 152.4, 147.1, 139.4, 137.6, 128.5, 128.0,
126.6, 116.8, 116.0, 114.6, 55.7.
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3-(1-phenylvinyl)-[1, 1'-biphenyl]-4-amine (1i). Yellow oil. H
NMR (400 MHz, CDCl3, ppm): δ = 7.80ꢀ7.45 (m, 12 H), 6.93ꢀ6.90 (m, 1
H), 6.061ꢀ6.058 (d, J = 1.2 Hz, 1 H), 5647ꢀ5.643 (d, J = 1.6 Hz, 1 H),
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3.78 (br s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ =147.4, 143.9,
141.2, 139.8, 129.6, 129.0, 128.9, 128.5, 127.7, 127.6, 127.0, 126.61,
126.55, 116.5, 116.3.
1
2-fluoro-6-(1-phenylvinyl)aniline (1k). Yellow oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.50ꢀ7.41 (m, 5 H), 7.13ꢀ7.02 (m, 2 H),
6.83ꢀ6.78 (m, 1 H), 5.929ꢀ5.926 (d, J = 1.2 Hz, 1 H), 5.488ꢀ5.485 (d, J =
13
1.2 Hz, 1 H), 3.74 (br s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ =
152.9ꢀ150.6 (J = 230.0 Hz), 146.29ꢀ146.26 (J = 3.0 Hz), 139.4,
132.8ꢀ132.7 (J = 10.0 Hz), 129.33ꢀ129.30 (J = 3.0 Hz ), 128.8, 128.4,
126.8, 126.1ꢀ126.0 (J = 10.0 Hz), 117.6ꢀ117.5 (J = 10.0Hz), 116.6,
114.5ꢀ114.3 (J = 20.0 Hz).
1
4-fluoro-2-(1-phenylvinyl)aniline (1l). Yellow oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.41ꢀ7.33 (m, 5 H), 6.94ꢀ6.88 (m, 2 H),
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6.67ꢀ6.64 (m, 1 H), 5.849ꢀ5.846 (d, J = 1.2 Hz, 1 H), 5.395ꢀ5.392 (d, J =
13
1.2 Hz, 1 H), 3.47 (br s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ =
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157.3ꢀ154.9 (J = 240.0 Hz), 146.4, 140.09ꢀ140.07 (J = 2.0 Hz), 139.1,
128.7, 128.3,126.6, 117.2, 117.0, 116.6, 116.5ꢀ116.4 (J = 10.0 Hz),
115.3ꢀ115.1 (J = 20.0 Hz).
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2-chloro-6-(1-phenylvinyl)aniline (1m). Yellow oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.44ꢀ7.32 (m, 6 H), 7.11ꢀ7.09 (m, 1 H),
6.79ꢀ6.75 (m, 1 H), 5.90 (s, 1 H), 5.43 (s, 1 H), 4.06 (br s, 2 H); 13C NMR
(100 MHz, CDCl3, ppm): δ = 146.7, 140.8, 139.1, 129.3, 128.9, 128.8,
128.42, 128.37, 126.7, 119.5, 118.2, 116.7.
1
4-chloro-2-(1-phenylvinyl)aniline (1n). Yellow oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.32ꢀ7.28 (m, 5 H), 7.10ꢀ7.07 (m, 2 H),
6.59ꢀ6.57 (d, J = 8.0 Hz, 1 H), 5.788ꢀ5.785 (d, J = 1.2 Hz, 1 H),
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5.334ꢀ5.331 (d, J = 1.2 Hz, 1 H), 3.48 (br s, 2 H); C NMR (100 MHz,
CDCl3, ppm): δ = 146.8, 143.3, 139.6, 130.9, 129.3, 129.20, 129.15,
129.0, 127.2, 123.4, 117.4, 117.3.
1
2-bromo-6-(1-phenylvinyl)aniline (1o). Yellow oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.44ꢀ7.42 (m, 1 H), 7.36ꢀ7.32 (m, 5 H),
7.08ꢀ7.06 (m, 1 H), 6.68ꢀ6.64(m, 1 H), 5.84 (d, 1 H), 5.37 (d, 1 H), 4.05
13
(br s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ = 146.8, 141.8, 139.0,
132.1, 130.0, 128.8, 128.5, 128.4, 126.7, 118.8, 116.8, 109.8.
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4-bromo-2-(1-phenylvinyl)aniline (1p). Yellow oil. H NMR (400
MHz, CDCl3, ppm): δ = 7.27ꢀ7.21 (m, 5 H), 7.17ꢀ7.13 (m, 2 H),
6.47ꢀ6.45 (d, J = 8.0 Hz, 1 H), 5.705ꢀ5.703 (d, J = 0.8 Hz, 1 H),
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5.252ꢀ5.250 (d, J = 0.8 Hz, 1 H), 3.45 (br s, 2 H); C NMR (100 MHz,
CDCl3, ppm): δ = 146.7, 143.8, 139.6, 133.7, 132.1, 129.8, 129.4, 129.0,
127.3, 117.8, 117.5, 110.6.
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2-(1-phenylvinyl)naphthalen-1-amine (1s). Brown solid. H NMR
(400 MHz, CDCl3, ppm): δ = 7.87ꢀ7.85 (d, J = 8.0 Hz, 2 H), 7.52ꢀ7.25 (m,
10 H), 6.02ꢀ5.98 (d, J = 14.0 Hz, 1 H), 5.51ꢀ5.48 (d, J = 14.0 Hz, 1 H),
13
4.08 (br s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ = 147.4, 140.0,
139.1, 134.0, 128.9, 128.6, 128.5, 128.2, 126.9, 125.8, 125.2, 123.7,
121.7, 121.2, 118.3, 116.7.
2) Substrates 1q-1r were prepared in the method18
To a solution of methyltriphenylphosphonium bromide (4.64 g, 13 mmol),
tBuONa (2.50 g, 26 mmol) in THF (100 mL) was added, then the
resulting reaction mixture was stirred at room temperature for 5 min.
Afterwards (2ꢀaminophenyl)(phenyl)methanone (10 mmol) was added
and the reaction solution was stirred at 65 oC overnight. Then the solvent
was removed under reduced pressure and the residue was purified by
silica gel flash chromatography (eluent: petroleum ether /ethyl acetate =
20 / 1) to afford the materials 1q-1r.
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4-bromo-2-(1-(2-fluorophenyl)vinyl)aniline (1q).Yellow oil. H
NMR (400 MHz, CDCl3, ppm): δ = 7.29ꢀ7.04 (m, 6 H), 6.56ꢀ6.54 (d, J =
8.0 Hz, 1 H), 5.85 (d, 1 H), 5.59 (d, 1 H), 3.66 (br s, 2 H); 13C NMR (100
MHz, CDCl3, ppm): δ = 162.1ꢀ159.7 (J = 240.0 Hz), 143.4, 141.1, 133.1,
132.0, 130.94, 130.91, 130.3, 124.91ꢀ124.88 (J = 3.0 Hz), 122.2, 117.8,
117.0ꢀ116.7 (J = 30.0 Hz), 110.5.
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4-chloro-2-(1-(2-chlorophenyl)vinyl)aniline (1r). Orange oil. H
NMR (400 MHz, CDCl3, ppm): δ = 7.38ꢀ7.25(m, 4 H), 7.04ꢀ7.01 (m, 1
H), 6.90ꢀ6.89 (d, J = 4.0 Hz, 1 H), 6.62ꢀ6.59 (d, J = 12.0 Hz, 1 H), 5.69
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(d, 1 H), 5.62 (d, 1 H), 3.85 (br s, 2 H); C NMR (100 MHz, CDCl3,
ppm): δ = 144.4, 142.3, 140.3, 131.0, 130.2, 129.34, 129.25, 128.4, 128.2,
127.1, 122.8, 121.3, 117.1.
3) 1t were prepared in the method19
To a stirred solution of Ph3PMeBr (1.5 equiv., 12.2 mmol) in Dry THF
(15 mL) was added KOtBu (1.5equiv. 12.2 mmol) in portions under
nitrogen. After the mixture was stirred at room temperature for 0.5 h, a
solution of corresponding benzophenone (1 equiv. 8.14 mmol) in THF
(15 mL) was added dropwise. The reaction mixture was then stirred at
room temperature under nitrogen overnight. The reaction mixture was
quenched with water and extracted with ethyl acetate (50 mL ×2). The
combined organic layers was washed with saturated NaHCO3 (50 mL)
and brine (50 mL), dried over anhydrous Na2SO4, and concentrated on
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rotary evaporator under vacuum and purified by column chromatography
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(silica gel, appropriate mixture of petroleum ether /ethyl acetate) to afford
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1t.
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2-(prop-1-en-2-yl)aniline (1t). Colorless oil. H NMR (400 MHz,
CDCl3, ppm): δ = 7.08ꢀ7.03 (m, 2 H), 6.75ꢀ6.69 (m, 2 H), 5.29 (d, 1 H),
5.06 (d, 1 H), 3.83 (br s, 2 H), 2.07 (d, 3 H); 13C NMR (100 MHz, CDCl3,
ppm): δ = 144.1, 143.4, 129.9, 128.9, 128.5, 118.8, 116.2, 116.0, 24.6.
4) 1u were prepared in the method20
The general procedure was followed 2ꢀbromoaniline (2.0 mmol, 1.0
equiv.), transꢀ2ꢀphenylꢀvinylboronic acid (3.0 mmol, 1.5 equiv.), 10
mmol % of Pd(PPh3) (0.2 mmol) and 4 equiv. of K2CO3 (8.0 mmol)
4
were added to a mixed solvent of toluene, EtOH and H2O (5/2/1, 4 mL).
The reaction mixtrure was poured into water and extracted with diethyl
ether for several times. The combined organic layers were dried over
Na2SO4. Filtered and concentrated. The residue was purified by column
chromatography (petroleum ether /ethyl acetate) to afford the products
1u.
1
(E)-2-styrylaniline (1u). white solid. H NMR (400 MHz, CDCl3,
ppm): δ = 7.56ꢀ7.54 (m, 2 H), 7.46ꢀ7.44 (m, 1 H), 7.42ꢀ7.38 (m, 2 H),
7.32ꢀ7.28 (m, 1 H), 7.22ꢀ7.18 (d, J = 16.0 Hz, 1 H), 7.17ꢀ7.13 (m, 1 H),
7.05ꢀ7.01 (d, J = 16.0 Hz, 1 H), 6.88ꢀ6.84 (m, 1 H), 6.75ꢀ6.73 (m, 1 H),
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3.77 (br s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ =143.8, 137.5,
130.2, 128.62 128.60, 127.5, 127.1, 126.4, 124.1, 123.8, 119.1, 116.2.
5) 4a-4f were prepared in the method21
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Compound 4a was purchased from commercial sources and used as
received. Compounds 4bꢀ4f were prepared in the following method. A
screwꢀcap vial containing a stirring bar, was added 2ꢀiodoanilines (2.0
mmol), CuI (10 mol %), DMEDA (N,N'ꢀDimethylꢀ1,2ꢀethanediamine, 20
mol %), K3PO4 (2.2 equiv), pyrrole (1.2 equiv), and toluene (2.0 mL).
o
The mixture was stirred at 110 C for 24 h under argon. The reaction
mixture was diluted with ethyl acetate (50 mL) after cooling to room
temperature. The mixture was filtered through a plug of silica gel and
additional ethyl acetate was used to elute the silica gel. The filtrate was
concentrated and the resulting residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate) to provide
2ꢀ(1Hꢀpyrrolꢀ1ꢀyl)aniline.
1
5-methyl-2-(1H-pyrrol-1-yl)aniline (4b). White solid. H NMR (400
MHz, CDCl3, ppm): δ = 7.03ꢀ7.01 (d, J = 8.0 Hz, 1 H), 6.80ꢀ6.79 (m, 2
H), 6.60ꢀ6.56 (m, 2 H), 6.32ꢀ6.31 (m, 2 H), 3.62 (br, 2 H), 2.30 (s, 3 H);
13C NMR (100 MHz, CDCl3, ppm): δ = 141.9, 138.6, 127.0, 125.2, 121.9,
119.2, 116.6, 109.2, 21.2.
1
4-methoxy-2-(1H-pyrrol-1-yl)aniline (4c). White solid. H NMR (400
MHz, CDCl3, ppm): δ = 6.85ꢀ6.84 (m, 2 H), 6.79ꢀ6.73 (m, 3 H),
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6.34ꢀ6.33 (m, 2 H), 3.74 (s, 3 H), 3.44 (br, 2 H); C NMR (100 MHz,
CDCl3, ppm): δ = 152.5, 135.5, 128.1, 121.7, 117.3, 114.8, 112.5, 109.5,
55.9.
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4-fluoro-2-(1H-pyrrol-1-yl)aniline (4d). White solid. H NMR (400
MHz, CDCl3, ppm): δ = 6.91ꢀ6.87 (m, 2 H), 6.83ꢀ6.82 (d, J = 2.0 Hz, 2
H), 6.74ꢀ6.70 (m, 1 H), 6.35ꢀ6.34 (m, 2 H), 3.59 (br, 2 H); 13C NMR (100
MHz, CDCl3, ppm): δ = 156.7ꢀ154.3 (d, J = 236.3 Hz, 1 C),
138.1ꢀ138.1(d, J = 2.4 Hz, 1 C), 127.7ꢀ127.6 (d, J = 9.5 Hz, 1 C), 121.5,
116.7ꢀ116.7 (d, J = 8.2 Hz, 1 C), 115.3ꢀ115.0 (d, J = 21.9 Hz, 1 C),
114.1ꢀ113.8 (d, J = 23.6 Hz, 1 C), 109.8.
1
5-chloro-2-(1H-pyrrol-1-yl)aniline (4e). White solid. H NMR (400
MHz, CDCl3, ppm): δ = 7.06ꢀ7.04 (d, J = 8.4 Hz, 1 H), 6.79ꢀ7.77 (m, 3
H), 6.75ꢀ6.72 (m, 1 H), 6.34ꢀ6.33 (m, 2 H), 3.77 (br, 2 H); 13C NMR (100
MHz, CDCl3, ppm): δ = 143.2, 134.0, 128.2, 125.9, 121.6, 118.2, 115.6,
109.8.
1
4-chloro-2-fluoro-6-(1H-pyrrol-1-yl)aniline (4f).White solid. H NMR
(400 MHz, CDCl3, ppm): δ = 7.05ꢀ7.02 (m, 1 H), 6.99ꢀ6.98 (m, 1 H),
13
6.83ꢀ6.82 (m, 2 H), 6.36ꢀ6.35 (m, 2 H), 3.80 (br, 2 H); C NMR (100
MHz, CDCl3, ppm): δ = 152.5ꢀ150.1 (d, J = 241.2 Hz, 1 C), 130.0ꢀ129.8
(d, J = 13.9 Hz, 1 C), 129.0ꢀ128.9 (d, J = 6.2 Hz, 1 C), 124.5,
122.4ꢀ122.4 (d, J = 3.3 Hz, 1 C), 121.3, 115.0ꢀ114.8 (d, J = 22.2 Hz, 1 C),
110.2.
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General procedure for synthesis of Substituted Quinolines:
2ꢀVinylanilines 1 (0.3 mmol) and 2ꢀmethylquinoline 2 (0.6 mmol)
were mixed in 2mL of DMF and this mixture was carried out in the
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presence of 10 mol% CuCl2·2H2O and O2. After being stirred at 130 C
for 32 h, the reaction mixture was cooled to room temperature and
evaporated in vacuum. Then the crude product was purified by column
chromatography, eluting with appropriate eluent to afford the desired
quinolines 3.
4-phenyl-2,2'-biquinoline (3aa). Yellow solid (44.8 mg, 71% yield);
melting point: 191ꢀ194 oC; 1H NMR (400 MHz, CDCl3) δ 8.89ꢀ8.87 (d, J
= 8.0 Hz, 1 H), 8.81 (s, 1 H), 8.33ꢀ8.28 (m, 2 H), 8.20ꢀ8.18 (d, J = 8.0 Hz,
1 H), 7.97ꢀ7.95 (m, 1 H), 7.87ꢀ7.85 (d, J = 8.0 Hz, 1 H), 7.75ꢀ7.71 (m, 2
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H), 7.64ꢀ7.62 (m, 2 H), 7.58ꢀ7.49 (m, 5 H); CNMR (100 MHz, CDCl3)
δ 156.3, 155.7, 149.2, 148.5, 148.0, 138.6, 136.7, 130.4, 130.0, 129.7,
129.5, 129.4, 128.53, 128.48, 128.3, 127.7, 127.02, 126.98, 126.94, 125.9,
119.7, 119.5; HRMS(ESI)m/z calcd for C24H17N2 [M+H]+ 333.1386,
found 333.1377.
8-methyl-4-phenyl-2,2'-biquinoline (3ba). White solid (50.2 mg, 66%
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yield); melting point: 172ꢀ176 C; H NMR (400 MHz, CDCl3) δ
9.01ꢀ9.00 (d, J = 8.0 Hz, 1 H), 8.86 (s, 1 H), 8.34ꢀ8.32 (d, J = 8.0 Hz, 1
H), 8.23ꢀ8.21 (d, J = 8.0 Hz, 1 H), 7.90ꢀ7.88 (d, J = 8.0 Hz, 1 H),
7.83ꢀ7.81 (d, J = 8.0 Hz, 1 H), 7.77ꢀ7.73 (m, 1 H), 7.66ꢀ7.64 (m, 3 H),
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7.62ꢀ7.53 (m, 4 H), 7.44ꢀ7.41 (m, 1 H), 3.05 (s, 3 H); 13CNMR (100 MHz,
CDCl3) δ 156.6, 154.0, 149.3, 147.9, 147.3, 139.0, 138.1, 136.5, 129.9,
129.8, 129.7, 129.5, 129.4, 128.43, 128.39, 128.1, 127.6, 126.9, 126.8,
126.6, 123.8, 119.5, 119.1, 18.4; HRMS(ESI)m/z calcd for C25H19N2
[M+H]+ 347.1543, found 347.1535.
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6-methyl-4-phenyl-2,2'-biquinoline (3ca). White solid (39.1 mg, 47%
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yield); melting point: 179ꢀ182 C; H NMR(400 MHz, CDCl3) δ
8.90ꢀ8.87 (d, J = 8.0 Hz, 1 H), 8.78 (s, 1 H), 8.35ꢀ8.33 (d, J = 8.0 Hz, 1
H), 8.22ꢀ8.19 (m, 2 H), 7.90ꢀ7.88 (d, J = 8.0 Hz, 1 H), 7.77ꢀ7.73 (m, 2 H),
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7.67ꢀ7.54 (m, 7 H), 2.51 (s, 3 H); CNMR (100 MHz, CDCl3) δ 156.4,
154.9, 148.4, 147.9, 147.1, 138.8, 137.0, 136.6, 131.6, 130.1, 129.9,
129.7, 129.5, 128.5, 128.4, 128.2, 127.6, 127.0, 126.8, 124.6, 119.7,
119.4, 21.9; HRMS(ESI)m/z calcd for C25H19N2 [M+H]+ 347.1543,
found 347.1537.
7,8-dimethyl-4-phenyl-2,2'-biquinoline (3da). White solid (59.8 mg,
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83% yield); melting point: 232ꢀ234 oC; H NMR(400 MHz, CDCl3) δ
8.97ꢀ8.95 (d, J = 8.0 Hz, 1 H), 8.74 (s, 1 H), 8.31ꢀ8.29 (d, J = 8.0 Hz, 1
H), 8.18ꢀ8.16 (d, J = 8.0 Hz, 1 H), 7.86ꢀ7.84 (d, J = 8.0 Hz, 1 H),
7.73ꢀ7.68 (m, 2 H), 7.62ꢀ7.60 (m, 2 H), 7.56ꢀ7.49 (m, 4 H), 7.33ꢀ7.31 (d,
J = 8.0 Hz, 1 H), 2.96 (s, 3 H), 2.54 (s, 3 H); 13CNMR (100 MHz, CDCl3)
δ 156.9, 154.0, 149.2, 147.9, 147.2, 139.1, 137.0, 136.5, 135.3, 129.9,
129.8, 129.7, 129.4, 128.42, 128.37, 128.1, 127.6, 126.7, 125.3, 122.7,
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119.6, 118.2, 20.6, 13.7; HRMS(ESI)m/z calcd for C26H21N2 [M+H]+
361.1699, found 361.1689.
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8-isopropyl-4-phenyl-2,2'-biquinoline (3ea). White solid (77.8 mg, 80%
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yield); melting point: 184ꢀ188 C; H NMR(400 MHz, CDCl3) δ
8.96ꢀ8.93 (d, J = 8.6 Hz, 1 H), 8.81 (s, 1 H), 8.33ꢀ8.30 (d, J = 8.6 Hz, 1
H), 8.19ꢀ8.17 (d, J = 8.0 Hz, 1 H), 7.88ꢀ7.86 (d, J = 8.0 Hz, 1 H),
7.80ꢀ7.69 (m, 2 H), 7.66ꢀ7.45 (m, 8 H), 4.68ꢀ4.58 (m, 1 H), 1.54ꢀ1.51 (d,
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J = 4.0 Hz, 6 H); CNMR (100 MHz, CDCl3) δ 156.7, 153.8, 149.4,
148.0, 147.9, 146.1, 139.1, 136.5, 129.9, 129.7, 129.4, 128.41, 128.39,
128.1, 127.6, 127.0, 126.9, 126.8, 125.2, 123.5, 119.5, 119.0, 28.1, 23.6;
HRMS(ESI)m/z calcd for C27H23N2 [M+H]+ 375.1856, found 375.1848.
6-isopropyl-4-phenyl-2,2'-biquinoline (3fa). Yellow solid (45.6 mg,
61% yield); melting point: 130ꢀ133 oC; H NMR(300 MHz, CDCl3) δ
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8.88ꢀ8.85 (d, J = 8.4 Hz, 1 H), 8.76 (s, 1 H), 8.33ꢀ8.30 (d, J = 8.4 Hz, 1
H), 8.25ꢀ8.17 (m, 2 H), 7.88ꢀ7.85 (d, J = 8.0 Hz, 1 H), 7.76ꢀ7.64 (m, 5 H),
7.60ꢀ7.52 (m, 4 H), 3.09ꢀ3.00 (m, 1 H), 1.31ꢀ1.29 (d, J = 7.0 Hz, 6 H);
13CNMR (75 MHz, CDCl3) δ 156.5, 155.0, 148.7, 147.9, 147.8, 147.4,
138.8, 136.6, 130.3, 129.9, 129.7, 129.5, 128.9, 128.5, 128.4, 128.2,
127.6, 126.9, 126.8, 122.1, 119.7, 119.4, 34.4, 23.9; HRMS(ESI)m/z
calcd for C27H23N2 [M+H]+ 375.1856, found 375.1844.
6-(tert-butyl)-4-phenyl-2,2'-biquinoline (3ga). White solid (27.0 mg,
41% yield); melting point: 151ꢀ155 oC; H NMR(400 MHz, CDCl3) δ
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8.88ꢀ8.86 (d, J = 8.0 Hz, 1 H), 8.77 (s, 1 H), 8.33ꢀ8.31 (d, J = 8.0 Hz, 1
H), 8.24ꢀ8.17 (m, 2 H), 7.933ꢀ7.927 (d, J = 2.0 Hz, 1 H), 7.87ꢀ7.85 (m, 2
H), 7.73ꢀ7.70 (m, 1 H), 7.67ꢀ7.65 (m, 2 H), 7.60ꢀ7.52 (m, 4 H), 1.37 (s, 9
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H); CNMR (100 MHz, CDCl3) δ 156.5, 155.2, 149.9, 149.0, 147.9,
147.0, 138.7, 136.6, 129.89, 129.85, 129.7, 129.5, 128.5, 128.4, 128.2,
127.6, 126.8, 126.5, 120.8, 119.7, 119.5, 35.2, 31.2; HRMS(ESI)m/z
calcd for C28H25N2 [M+H]+ 389.2012, found 389.2000.
6-methoxy-4-phenyl-2,2'-biquinoline (3ha). White solid (35.5mg, 49%
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yield); melting point: 147ꢀ151 C; H NMR(400 MHz, CDCl3) δ
8.85ꢀ8.83 (d, J = 8.4 Hz, 1 H), 8.75 (s, 1 H), 8.32ꢀ8.30 (d, J = 8.0 Hz, 1
H), 8.21ꢀ8.16 (m, 2 H), 7.87ꢀ7.85 (d, J = 8.0 Hz, 1 H), 7.75ꢀ7.63 (m, 3 H),
7.60ꢀ7.49 (m, 4 H), 7.44ꢀ7.40 (m, 1 H), 7.25ꢀ7.24 (d, J = 3.8 Hz, 1 H),
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3.81 (s, 3 H); CNMR (100 MHz, CDCl3) δ 158.4, 156.4, 153.6, 148.0,
147.8, 144.6, 138.8, 136.6, 131.8, 129.8, 129.5, 129.4, 128.6, 128.33,
128.25, 128.0, 127.6, 126.7, 121.8, 120.0, 119.3, 103.9, 55.5;
HRMS(ESI)m/z calcd for C25H19N2O [M+H]+ 363.1492, found 363.1500
4,6-diphenyl-2,2'-biquinoline (3ia). Yellow solid (35.4 mg, 51% yield);
melting point: 223ꢀ226 oC; H NMR(400 MHz, CDCl3) δ 8.91ꢀ8.89 (d, J
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= 8.0 Hz, 1 H), 8.83 (s, 1 H), 8.37ꢀ8.33 (m, 2 H), 8.21ꢀ8.15 (m, 2 H),
8.04ꢀ8.01 (m, 1 H), 7.89ꢀ7.87 (d, J = 8.0 Hz, 1 H), 7.74ꢀ7.72 (m, 1 H),
7.69ꢀ7.65 (m, 4 H), 7.61ꢀ7.51 (m, 4 H), 7.47ꢀ7.43 (m, 2 H), 7.38ꢀ7.35 (m,
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1H); CNMR (100 MHz, CDCl3) δ 156.2, 155.6, 149.3, 148.0, 147.9,
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140.6, 139.7, 138.5, 136.7, 130.8, 130.0, 129.7, 129.5, 129.1, 128.9,
128.6, 128.5, 128.4, 127.7, 127.5, 127.2, 126.9, 123.6, 120.1, 119.5;
HRMS(ESI)m/z calcd for C30H21N2 [M+H]+ 409.1699, found 409.1690.
8-fluoro-4-phenyl-2,2'-biquinoline (3ka). White solid (51.1 mg, 73%
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yield); melting point: 256ꢀ258 C; H NMR(400 MHz, CDCl3) δ
8.96ꢀ8.94 (d, J = 8.0 Hz, 1 H), 8.88 (s, 1 H), 8.35ꢀ8.33 (d, J = 8.0 Hz, 1
H), 8.19ꢀ8.17 (d, J = 8.0 Hz, 1 H), 7.89ꢀ7.88 (d, J = 7.2 Hz, 1 H),
7.76ꢀ7.72 (m, 2 H), 7.63ꢀ7.61 (m, 2 h), 7.60ꢀ7.53 (m, 4 H), 7.46ꢀ7.43 (m,
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2 H); CNMR (100 MHz, CDCl3) δ 158.7 (J = 250.0 Hz), 155.8, 155.7,
149.1 (J = 3.0 Hz), 147.9, 138.9 (J = 10.0 Hz), 138.3, 136.8, 129.9,
129.64, 129.57, 128.8, 128.6, 128.5, 127.7, 127.1, 126.5 (J = 10.0 Hz),
121.6 (J = 5.0 Hz), 120.5, 119.6, 113.5 (J = 20.0 Hz); HRMS(ESI)m/z
calcd for C24H16FN2 [M+H]+ 351.1292, found 351.1285.
6-fluoro-4-phenyl-2,2'-biquinoline (3la). White solid (45.9 mg, 69%
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yield); melting point: 198ꢀ201 C; H NMR(400 MHz, CDCl3) δ
8.86ꢀ8.83 (m, 2 H), 8.34ꢀ8.27 (m, 2 H), 8.19ꢀ8.17 (d, J = 8.0 Hz, 1 H),
7.89ꢀ7.87 (d, J = 8.0 Hz, 1 H), 7.76ꢀ7.72 (m, 1 H), 7.63ꢀ7.50 (m, 8 H);
13CNMR (100 MHz, CDCl3) δ 161.1 (J = 250.0 Hz), 156.0, 155.2, 148.7
(J = 10.0 Hz), 147.9, 145.6, 138.1, 136.8, 132.8 (J = 10.0 Hz), 129.9,
129.6, 129.5, 128.7, 128.6, 128.5, 127.9 (J = 10.0 Hz), 127.7, 127.0,
120.2, 119.6 (J = 20.0 Hz), 119.3, 109.3 (J = 20.0 Hz); HRMS(ESI)m/z
calcd for C24H16FN2 [M+H]+ 351.1292, found 351.1287.
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8-chloro-4-phenyl-2,2'-biquinoline (3ma). White solid (60.0 mg, 78%
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yield); melting point: 152ꢀ156 C; H NMR(400 MHz, CDCl3) δ
9.06ꢀ9.03 (m, 1 H), 8.90ꢀ8.89 (d, J = 4.0 Hz, 1 H), 8.37ꢀ8.34 (m, 1 H),
8.19ꢀ8.17 (d, J = 8.0 Hz, 1 H), 7.90ꢀ7.86 (m, 3 H), 7.76ꢀ7.71 (m, 1 H),
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7.62ꢀ7.51 (m, 6 H), 7.45ꢀ7.39 (m, 1 H); CNMR (100 MHz, CDCl3) δ
155.9, 155.8, 149.7, 147.9, 144.6, 138.3, 136.8, 134.6, 129.9, 129.7,
129.54, 129.5, 128.64, 128.6, 128.51, 128.5, 127.7, 127.1, 126.6, 125.0,
120.2, 119.8; HRMS(ESI)m/z calcd for C24H16ClN2 [M+H]+ 367.0997,
found 367.0995.
6-chloro-4-phenyl-2,2'-biquinoline (3na). White solid (35.5 mg, 57%
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yield); melting point: 147ꢀ150 C; H NMR(400 MHz, CDCl3) δ
8.86ꢀ8.83 (m, 2 H), 8.35ꢀ8.33 (d, J = 8.0 Hz, 1 H), 8.24ꢀ8.17 (m, 2 H),
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(100 MHz, CDCl3) δ 156.0, 155.8, 148.4, 147.9, 146.9, 137.9, 136.8,
132.9, 131.9, 130.3, 130.0, 129.61, 129.6, 128.7, 128.6, 128.5, 127.7,
127.6, 127.1, 124.7, 120.4, 119.3; HRMS(ESI)m/z calcd for C24H16ClN2
[M+H]+ 367.0997, found 367.0992.
8-bromo-4-phenyl-2,2'-biquinoline (3oa). Yellow solid (51.1 mg, 89%
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yield); melting point: 188ꢀ193 C; H NMR(400 MHz, CDCl3) δ
9.08ꢀ9.05 (m, 1 H), 8.89 (s, 1 H), 8.37ꢀ8.34 (m, 1 H), 8.19ꢀ8.17 (d, J =
8.0 Hz, 1 H), 8.11ꢀ8.08 (m, 1 H), 7.93ꢀ7.88 (m, 2 H), 7.76ꢀ7.71 (m, 1 H),
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