Synthesis of Quinolines through Three-Component Cascade Annulation of Aryl Diazonium Salts, Nitriles, and Alkynes

Article abstract of DOI:10.1021/acs.joc.6b02509

An efficient and rapid synthesis of multiply substituted quinolines is described. This method is enabled by a three-component cascade annulation of readily available aryl diazonium salts, nitriles, and alkynes. This reaction is catalyst- and additive-free. Various aryl diazonium salts, nitriles, and alkynes can participate in this transformation, and the yields are up to 83%.

Full text of DOI:10.1021/acs.joc.6b02509

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Note
Synthesis of Quinolines through Three-Component Cascade
Annulation of Aryl Diazonium Salts, Nitriles, and Alkynes
Hao Wang, Qian Xu, Sheng Shen, and Shouyun Yu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02509 • Publication Date (Web): 12 Dec 2016
Downloaded from http://pubs.acs.org on December 13, 2016
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Synthesis of Quinolines through Three-Component Cascade
Annulation of Aryl Diazonium Salts, Nitriles, and Alkynes
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a
a
b
a
Hao Wang, Qian Xu, Sheng Shen,* and Shouyun Yu*
a
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry
and Chemical Engineering, Nanjing University, Nanjing 210023, China.
b
Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower
Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
Eꢀmail: yushouyun@nju.edu.cn (S.Y.); txdqxdl1979@163.com (S.S.)
ABSTRACT: An efficient and rapid synthesis of multiply substituted quinolines is
described. This method is enabled by a threeꢀcomponent cascade annulation of readily
available aryl diazonium salts, nitriles, and alkynes. This reaction is catalystꢀ and
additiveꢀfree. Various aryl diazonium salts, nitriles, and alkynes can participate in this
transformation, and the yields are up to 83%.
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Quinolines represent one of the ubiquitous heterocycles in the natural
alkaloids displaying a wide variety of pharmacological properties, such as
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tumoricidal, angina pectoris, antihypertensive, and antibacterial activities.
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Furthermore, their structures and properties have made them widely applicable
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in the functional materials and asymmetric catalysts. The synthesis of the
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structural core of quinolines has well been established. The most popular
strategy for the construction of quinolone core is based on the condensation of
4, 5
aniline derivatives with various carbonyl compounds, e.g., Combes synthesis,
Conrad-Limpach-Knorr synthesis, and Friedlander synthesis. Recently,
transition-metal-catalyzed couplings have merged as powerful tools for the
4b, 6
efficient and rapid synthesis of quinolines.
Despite these advances, a clean,
efficient, and economic technology is still needed to obtain useful
polyfunctionalized quinolines from readily available starting materials.
Cycloaddition of N-arylnitrilium salts (I) with alkynes can compete with
classical syntheses in the efficacy and rapidity of the quinoline construction
(
Figure 1). Compared to well-established annulation of iminium salts with
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alkynes followed by oxidation to quinolines, annulation of nitrilium salts with
alkynes can give quinolines directly without oxidation. In 1992, Jochims and
co-workers reported that N-arylnitrilium salts (I) could be prepared by
Beckmann rearrangement of the corresponding oximes (II) or abstraction of
8
chloride from the corresponding imidoyl chlorides (III). The preformed
nitrilium salts (I) could undergo polar [4 + 2] cycloaddition with alkynes to give
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substituted quinolines (Figure 1A). Recently, Chen and co-workers found that
N-arylnitrilium salts (I) could be generated in situ by copper-catalyzed aryl
group transfer from diaryliodonium salts (IV) to nitriles, followed by annulation
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with alkynes to give quinolines (Figure 1B).
Encouraged these elegant reports, we sought to make a modified approach for
the synthesis of quinolines via cascade annulation of aryl diazonium salts,
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nitriles, and alkynes. It is known that diazonium salts decompose on warming
2
into aryl cation with the release of N . The inherent electrophilicity of dizonium
salts offers a pathway to introduce cyano group into an aromatic ring to yield
N-arylnitrilium salts (I). As demonstrated by Jochims and Chen, this
N-arylnitrilium salts can undergo [4 + 2] cycloaddition with alkynes to provide
polysubstituted quinolines (Figure 1C). Herein, we would like to report a rapid
and efficient method to synthesize quinolines from three easily accessible
precursors, saying aryl diazonium salts, nitriles, and alkynes. This method
presented here is catalyst and additive-free, economic, and environmentally
benign.
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Figure 1. Syntheses of quinolines by cycloaddition of N-arylnitrilium salts
with alkynes
At the outset of this investigation, we explored the cascade reaction of aryl
diazonium salt 1a and p-methoxyphenylacetylene (2a) using acetonitrile as the
solvent. We were pleased to find that when a mixture of aryl diazonium salt 1a
(
0.3 mmol) and p-methoxyphenylacetylene (2a, 0.6 mmol) in 3 mL of anhydrous
acetonitrile was stirred at room temperature for 30 h, the desired quinoline 3a
was obtained in a 55% isolated yield (Table 1, entry 1). When the reaction
mixture was slightly warned up to 40 ºC, the reaction can go to completion in 6 h
with 82% isolated yield (entry 2). The concentration of the reaction mixture had
significant impact on the chemical yields (entries 3-6). More concentrated or
diluted reaction mixture led to lower isolated yields. Higher temperature could
accelerate the reaction with comparable yields (entries 7-8). The reaction could
finish in one hour at 60 ºC and half an hour at 80 ºC. The dosage of alkyne 2a can
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be reduced to 1.2 and 1.5 equivalents with 79% and 83% isolated yields respectively
at 60 ºC (entries 11-12).
a
Table 1. Optimization of the Reaction Conditions
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entry
MeCN
3 mL
3 mL
1 mL
2 mL
6 mL
9 mL
2 mL
2 mL
2 mL
2 mL
2 mL
2 mL
temp
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40 ºC
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40 ºC
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80 ºC
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60 ºC
time
30 h
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yield/%
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Reaction conditions: A solution of 1a (0.3 mmol), 2a (0.6 mmol) in anhydrous
b
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acetonitrile was stirred at the indicated temperature. Isolated yields. 1.2 equiv
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of 2a (0.36 mmol) was used. 1.5 equiv of 2a (0.45 mmol) was used. PMP =
para-methoxyphenyl
After the reaction parameter was established, we next explored the scope and
limitation of this reaction (Scheme 1). First, a variety of alkynes reacted with
diazonium salt 1a in acetonitrile. Electron-rich and neutral phenylacetylene
derivatives went through this smoothly with 68-83% yields while
electron-deficient phenylacetylene derivatives were less reactive with 37-54%
yields. Naphthalene- and thiophene-derived terminal alkynes could also
undergo this transformation frequently to provide the quinolines 3k and 3l in 78%
and 77% yields respectively. To our delight, internal aromatic alkynes were also
suitable reaction partners to give the corresponding quinolines 3m-3o in
reasonable isolated yields (53-73%). The reaction with linear aliphatic alkyne
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(
1-octyne) was sluggish and only 33% desired quinolone 3p could be isolated
even through 3.0 equivalents of 1-octyne were employed. However,
ethynylcyclopropane was a good reaction partner and 73% yield of quinoline 3q
could be obtained under optimal conditions. Then, various functionalized aryl
diazonium salts reacted with para-methoxyphenylacetylene (2a) in acetonitrile.
Functional groups, such as ester (3s), ether (3w), trifluoromethyl (3t), ketone
(
3u), and naphthalene (3x), could be tolerated. When meta-methoxyphenyl
diazonium salt was used, two regioisomers 3w and 3w’ were obtained with 81%
combined yield. Annulation of phenyl diazonium salt (1a) and
para-methoxyphenylacetylene (2a) in benzonitrile and pivalonitrile was also
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feasible. The corresponding quinolines 3y and 3z were isolated in 54% and 52%
yields respectively. Finally, multiple functionalized quinolines 3aa-3ac could be
also prepared in acceptable yields by means of this method. In the cases of low
yields, the major by-products were the amides, which were generated from the
hydrolysis of the corresponding nitrilium intermediates.
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Scheme 1. Substrate Scope
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Reaction conditions: A solution of 1 (0.3 mmol), 2 (0.45 mmol) in anhydrous
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nitrile (2 mL) was stirred at 60 ºC for 1 h. 3.0 equiv of 2 was used.
In order to gain insights into the mechanism of this transformation, some
control experiments were carried out (Scheme 2). When 10 equivalents of
distilled water was introduced into the model reaction mixture, no quinoline 3a
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was observed. Instead, the N-phenylacetamide (4) was obtained in a 61% yield
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based on the crude H NMR analysis. Furthermore, when alkyne 2a was removed
from the reaction mixture, the similar result was obtained. These findings
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a, 10
suggests that the nitrilium salt is the key intermediate of this reaction.
Scheme 2. Control Experiments
6a, 7
On the basis of control experiments and the previous reports,
a plausible
mechanism is proposed (Figure 2). Upon heating, the aryl diazonium salt 1a
decomposes into the aryl cation 5 with concomitant releasing of N . Acetonitrile
2
works as a nucleophile to attack the aryl cation 5, resulting in the formation of
nitrilium cation 6. There are two possible pathways to form quinoline 3a. In the
path A, nitrilium cation reacts with alkyne 2a through a concerted Diels-Alder
reaction to give the intermediate 8. After deprotonation, the intermediate 8 can
convert to quinoline 3a. Alternatively, quinoline 3a can be generated in a
stepwise manner (path B). The intermediate 6 is attacked by alkyne 2a to give
the vinyl cation 9 following by Friedel-Crafts-type cyclization to give the desired
quinoline 3a.
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Figure 2. Proposed mechanism
In summary, we have described an efficient and rapid synthesis of multiply
functionalized quinolines from three components, saying aryl diazonium salts,
alkynes, and nitriles. The reaction can finish in one hour at 60 ºC and the yield
was up to 83%. Furthermore, neither catalyst nor additive is necessary. This
economic, and environmentally benign procedure should benefit the future
development of potential industrial processes and makes this protocol
particularly attractive for the chemical community.
Experimental Section
General information. All reagents were used without further purification.
Thin layer chromatography (TLC) was performed on precoated plates (silica gel
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0 F254, Art 5715) and visualized by fluorescence quenching under UV light and
by staining with phosphomolybdic acid or potassium permanganate,
respectively. Column chromatography was performed on Silica Gel 60 (300–400
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Mesh) using a forced flow of 0.5–1.0 bar. H NMR (400 M Hz), C NMR (101 M
19
Hz) and F (376 M Hz) were measured on a 400 M NMR spectrometer.
Chemical shifts are expressed in parts per million (ppm) with respect to the
residual solvent peak. Coupling constants are reported as Hertz (Hz), signal
shapes and splitting patterns are indicated as follows: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet. Infrared (IR) spectra were recorded on an IR
–1
spectrophotometer and are reported as wavenumber (cm ).
11
General Procedure for the preparation of aryl diazonium tetrafluoroborates.
The appropriate aniline (10 mmol) was dissolved in a mixture of 3.4 mL of
hydrofluoroboric acid (50%) and 4 mL of distilled water. The reaction mixture was
cooled down to 0°C using an iceꢀwater bath, and then sodium nitrite (NaNO2)
solution (0.69 g in 1.5 mL) was added drop wise. The resulting reaction mixture was
stirred for 40 min at 0ꢀ5 °C and the obtained precipitate was collected by filtration,
dried and reꢀdissolved in a minimum amount of acetone. Diethyl ether was added
until precipitation of diazonium tetrafluoroborate, which is filtered, washed several
times with small portions of diethyl ether and dried under vacuum.
General procedure for synthesis of quinolones. A 10 mL round bottom flask
equipped with a rubber septum and magnetic stir bar was charged with aryl diazonium
salt 1a (0.3 mmol, 1.0 equiv). Then pꢀMeO phenylacetylene 2a (0.45 mmol, 1.5 equiv)
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and CH
3
CN (2.0 mL) were added with a syringe. The mixture was placed in an oil
bath preheated to 60 °C. After the reaction was complete (as judged by TLC analysis),
the mixture was poured into a separatory funnel containing 20 mL of H O and 20 mL
2
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of Et O. The layers were separated and the aqueous layer was extracted with Et O (2
2
2
×
20 mL). The combined organic layers were dried over Na
2
SO
4
and concentrated
under reduced pressure after filtration. The crude product was purified by flash
chromatography on silica gel to afford the desired product 3a.
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4
-(4-methoxyphenyl)-2-methylquinoline (3a):
Purification by chromatography
1
(petroleum ether/EtOAc = 10:1) afforded 3a as a white solid (62.1 mg, 83%); H
3
NMR (400 MHz, CDCl ) δ 8.08 (d, J = 8.4 Hz, 1H), 7.90 (dd, J = 8.4, 0.8 Hz, 1H),
7.67 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.45ꢀ7.41 (m, 3H), 7.21 (s, 1H), 7.05 (d, J = 8.7
13
Hz, 2H), 3.89 (s, 3H), 2.76 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 159.8, 158.5,
148.5, 148.3, 130.8, 130.4, 129.3, 129.0, 125.7, 125.6, 125.3, 122.2, 114.0, 55.4, 25.4.
-(3-methoxyphenyl)-2-methylquinoline (3b): Purification by chromatography
(petroleum ether/EtOAc = 10:1) afforded 3b as a yellow solid (55.6 mg, 74%). Mp
4
ꢀ1
–1 1
7
2ꢀ73 ºC. IR (film, cm ): 1581; 1464; 1038; 887; 766 cm . H NMR (400 MHz,
CDCl ) δ 8.09 (d, J = 8.3 Hz, 1H), 7.88 (dd, J = 8.4, 0.8 Hz, 1H), 7.68 (ddd, J = 8.3,
.9, 1.3 Hz, 1H), 7.44ꢀ7.40 (m, 2H), 7.23 (s, 1H), 7.07 (d, J = 7.7 Hz, 1H), 7.03ꢀ7.00
3
6
1
3
(m, 2H), 3.85 (s, 3H), 2.77 (s, 3H). C NMR (101 MHz, CDCl ) δ 159.6, 158.5,
3
1
48.41, 148.35, 139.5, 129.6, 129.4, 129.0, 125.8, 125.7, 125.1, 122.1, 121.9, 115.1,
+
113.8, 55.4, 25.4. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C17
H
15NO:
2
50.1226; found: 250.1226.
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-(2-methoxyphenyl)-2-methylquinoline (3c): Purification by chromatography
(petroleum ether/EtOAc = 10:1) afforded 3c as a yellow solid (59.3 mg, 79%). Mp
ꢀ1
–1 1
1
05ꢀ106 ºC. IR (film, cm ): 1592; 1487; 1023; 873; 763 cm . H NMR (400 MHz,
10
11
12
13
14
15
16
17
18
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CDCl ) δ 8.07 (d, J = 8.4 Hz, 1H), 7.64 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.55ꢀ7.53 (m,
3
1
H), 7.45 (td, J = 8.3, 1.7 Hz, 1H), 7.38ꢀ7.34 (m, 1H), 7.24 (dd, J = 7.5, 1.8 Hz, 1H),
.22 (s, 1H), 7.08 (dt, J = 8.3, 4.1 Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H), 3.69 (s, 3H), 2.76
7
1
3
(
s, 3H). C NMR (101 MHz, CDCl
3
) δ 158.5, 156.8, 148.0, 146.0, 131.2, 129.9,
1
29.1, 128.8, 127.0, 126.1, 125.8, 125.4, 123.0, 120.7, 111.1, 55.5, 25.4. HRMS
+
(
DARTꢀFTICI Positive) ([M+H] ) Calcd for C H NO: 250.1226; found: 250.1225.
17 15
12
4
-(4-fluorophenyl)-2-methylquinoline (3d):
Purification by chromatography
1
(petroleum ether/EtOAc = 10:1) afforded 3d as a yellow solid (54.3 mg, 76%). H
3
NMR (400 MHz, CDCl ) δ 8.09 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.68
19
(ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 7.47ꢀ7.41 (m, 3H), 7.23ꢀ7.18 (m, 3H), 2.77 (s, 3H). F
13
NMR (377 MHz, CDCl ) δ ꢀ113.40. C NMR (101 MHz, CDCl ) δ 162.7 (d, J =
3
3
248.0 Hz), 158.5, 148.4, 147.5, 134.1, 134.1, 131.2 (d, J = 8.2 Hz), 129.3 (d, J = 30.9
Hz), 125.9, 125.36, 125.1, 122.3, 115.6 (d, J = 21.6 Hz), 25.3.
1
3
4-(4-chlorophenyl)-2-methylquinoline (3e):
Purification by chromatography
1
(
petroleum ether/EtOAc = 10:1) afforded 3e as a yellow solid (56.7 mg, 75%). H
NMR (400 MHz, CDCl ) δ 8.09 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.3 Hz, 1H),
3
13
7
.70ꢀ7.66 (m, 1H), 7.49ꢀ7.40 (m, 5H), 7.19 (s, 1H), 2.77 (s, 3H). C NMR (101 MHz,
CDCl
3
) δ 158.5, 148.3, 147.3, 136.5, 134.6, 130.8, 129.5, 129.1, 128.8, 126.0, 125.3,
1
24.8, 122.2, 25.3.
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2
-methyl-4-(4-(trifluoromethyl)phenyl)quinolone
(3f):
Purification
by
chromatography (petroleum ether/EtOAc = 10:1) afforded 3f as a yellow solid (38.4
1
mg, 45%). H NMR (400 MHz, CDCl
3
) δ 8.11 (d, J = 8.4 Hz, 1H), 7.80ꢀ7.69 (m, 4H),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
19
7
.61 (d, J = 7.7 Hz, 2H), 7.41ꢀ7.43 (m, 1H), 7.22 (s, 1H), 2.79 (s, 3H). F NMR (377
13
3 3
MHz, CDCl ) δ ꢀ62.57. C NMR (101 MHz, CDCl ) δ 158.5, 148.4, 147.0, 141.8,
1
1
4
30.6 (q, J = 32.6 Hz), 129.9, 129.6, 129.2, 128.2, 126.2, 125.5 (q, J = 3.6 Hz), 124.6,
24.1 (q, J = 272.3 Hz), 122.2, 25.3.
12
-(2-methylquinolin-4-yl)benzonitrile (3g):
Purification by chromatography
1
(
petroleum ether/EtOAc = 10:1) afforded 3g as a yellow solid (27.0 mg, 37%). H
3
NMR (400 MHz, CDCl ) δ 8.11 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 8.3 Hz, 2H),
7.74ꢀ7.70 (m, 2H), 7.62 (d, J = 8.3 Hz, 2H), 7.49ꢀ7.45 (m, 1H), 7.22 (s, 1H), 2.79 (s,
13
3
H). C NMR (101 MHz, CDCl
3
) δ 158.6, 148.4, 146.4, 142.9, 132.4, 130.3, 129.8,
129.3, 126.4, 124.8, 124.3, 122.1, 118.5, 112.4, 25.4.
12
2
-methyl-4-phenylquinoline (3h):
Purification by chromatography (petroleum
1
ether/EtOAc = 10:1) afforded 3h as a yellow solid (52.6 mg, 80%). H NMR (400
MHz, CDCl
7.51ꢀ7.45 (m, 5H), 7.42ꢀ7.38 (m, 1H), 7.21 (s, 1H), 2.76 (s, 3H). C NMR (101 MHz,
CDCl ) δ 158.5, 148.6, 148.4, 138.2, 129.5, 129.3, 129.0, 128.5, 128.3, 125.8, 125.7,
3
) δ 8.09 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.69ꢀ7.64 (m, 1H),
1
3
3
125.1, 122.2, 25.4.
Methyl 4-(2-methylquinolin-4-yl)benzoate (3i): Purification by chromatography
(petroleum ether/EtOAc = 10:1) afforded 3i as a yellow solid (44.6 mg, 54%). Mp
ꢀ1
–1 1
1
10ꢀ111 ºC. IR (film, cm ): 1700; 1432; 1019; 858; 758 cm . H NMR (400 MHz,
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CDCl
3
) δ 8.19 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 8.3 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H),
7
1
1
1
.70 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.44 (ddd, J = 8.2, 7.0,
1
3
3
.1 Hz, 1H), 7.23 (s, 1H), 3.98 (s, 3H), 2.79 (s, 3H). C NMR (101 MHz, CDCl ) δ
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
66.7, 158.5, 148.4, 147.4, 142.8, 130.1, 129.8, 129.6, 129.5, 129.2, 126.1, 125.2,
+
24.6, 122.1, 52.3, 25.4. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for
C
18
H
15NO
2
: 278.1176; found: 278.1173.
(3-(2-methylquinolin-4-yl)phenyl)carbamate
chromatography (petroleum ether/EtOAc = 10:1) afforded 3j as a white solid (64.9
Allyl
(3j):
Purification
by
ꢀ1
–1 1
mg, 68%). Mp 166ꢀ167 ºC. IR (film, cm ): 1717; 1432; 1104; 858; 775 cm . H
NMR (400 MHz, CDCl ) δ 8.07 (d, J = 8.2 Hz, 1H), 7.84 (dd, J = 8.4, 0.8 Hz, 1H),
7.65 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 7.55ꢀ7.51 (m, 3H), 7.42ꢀ7.37 (m, 2H), 7.19 (s,
H), 7.15 (d, J = 7.5 Hz, 1H), 5.94 (ddt, J = 17.0, 10.5, 5.7 Hz, 1H), 5.33 (dq, J = 17.2,
3
1
1.5 Hz, 1H), 5.23 (dd, J = 10.4, 1.3 Hz, 1H), 4.66 (d, J = 5.7 Hz, 2H), 2.74 (s, 3H).
13
C NMR (101 MHz, CDCl ) δ 158.5, 153.5, 148.3, 148.2, 139.0, 138.4, 132.4, 129.4,
3
129.2, 128.9, 125.8, 125.6, 125.0, 124.6, 122.2, 119.7, 118.6, 118.2, 65.9, 25.2.
+
HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C20
18 2 2
H N O : 319.1441; found:
319.1441.
2
-methyl-4-(naphthalen-1-yl)quinolone (3k): Purification by chromatography
(petroleum ether/EtOAc = 10:1) afforded 3k as a white solid (63.0 mg, 78%). Mp
ꢀ1
–1 1
1
64ꢀ165 ºC. IR (film, cm ): 1597; 1505; 1020; 764; 739 cm . H NMR (400 MHz,
CDCl ) δ 8.13 (d, J = 8.4 Hz, 1H), 7.94 (dd, J = 11.0, 8.4 Hz, 2H), 7.67ꢀ7.63 (m, 1H),
.58ꢀ7.54 (m, 1H), 7.49ꢀ7.42 (m, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.31ꢀ7.24 (m, 3H),
3
7
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5
5
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5
5
5
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6
1
3
2
1
1
3
.80 (s, 3H). C NMR (101 MHz, CDCl ) δ 158.6, 148.1, 147.5, 135.8, 133.5, 131.97,
29.5, 128.9, 128.7, 128.3, 127.3, 126.5, 126.4, 126.22, 126.16, 126.0, 125.8, 125.3,
+
23.4, 25.5. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C20
H15N: 270.1277;
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
found: 270.1277.
-methyl-4-(thiophen-3-yl)quinolone (3l): Purification by chromatography (petroleum
ether/EtOAc = 10:1) afforded 3l as a yellow solid (52.2 mg, 77%). Mp 101ꢀ102 ºC. IR
2
ꢀ1
–1 1
(
film, cm ): 1596; 1414; 1022; 796; 760 cm . H NMR (400 MHz, CDCl
3
) δ 8.08 (d,
J = 8.4 Hz, 1H), 8.00 (d, J = 8.3 Hz, 1H), 7.69ꢀ7.65 (m, 1H), 7.47ꢀ7.41 (m, 3H), 7.30
13
(
dd, J = 3.5, 2.9 Hz, 1H), 7.25 (s, 1H), 2.75 (s, 3H). C NMR (101 MHz, CDCl ) δ
3
1
58.6, 148.4, 143.2, 138.6, 129.4, 129.1, 128.9, 126.2, 125.9, 125.5, 125.1, 124.8,
+
122.0, 25.3. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C14
found: 226.0684.
H11NS: 226.0685;
1
4
2-methyl-3,4-diphenylquinoline (3m): Purification by chromatography (petroleum
1
ether/EtOAc = 10:1) afforded 3m as a yellow solid (46.8 mg, 53%). H NMR (400
MHz, CDCl
3
) δ 8.12 (d, J = 8.4 Hz, 1H), 7.70ꢀ7.66 (m, 1H), 7.50 (d, J = 7.7 Hz, 1H),
13
7
.38 (t, J = 7.6 Hz, 1H), 7.26ꢀ7.14 (m, 6H), 7.10ꢀ7.05 (m, 4H), 2.55 (s, 3H). C NMR
(101 MHz, CDCl
3
) δ 157.9, 147.1, 146.6, 138.7, 136.8, 134.1, 130.13, 130.07, 129.1,
1
28.7, 127.9, 127.7, 127.2, 126.9, 126.6, 126.3, 125.9, 25.47.
1
5
2,3-dimethyl-4-phenylquinoline (3n): Purification by chromatography (petroleum
1
ether/EtOAc = 10:1) afforded 3n as a yellow solid (50.9 mg, 73%). H NMR (400
MHz, CDCl
3
) δ 8.04 (d, J = 8.4 Hz, 1H), 7.59 (dt, J = 8.4, 4.1 Hz, 1H), 7.53ꢀ7.44 (m,
13
3
H), 7.31 (d, J = 3.7 Hz, 2H), 7.24ꢀ7.22 (m, 2H), 2.75 (s, 3H), 2.17 (s, 3H). C NMR
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(
101 MHz, CDCl
3
) δ 158.9, 146.3, 146.1, 137.7, 129.4, 128.5, 128.5, 128.2, 127.7,
1
27.5, 126.9, 126.1, 125.5, 24.6, 17.0.
-methyl-4-phenyl-3-(trimethylsilyl)quinolone (3o): Purification by chromatography
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
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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
(
petroleum ether/EtOAc = 10:1) afforded 3o as a white solid (53.7 mg, 61%). Mp
ꢀ1
–1 1
7
7ꢀ78 ºC. IR (film, cm ): 1562; 1480; 1019; 761; 701 cm . H NMR (400 MHz,
CDCl
3
) δ 7.97 (d, J = 8.4 Hz, 1H), 7.59 (ddd, J = 8.3, 5.5, 2.7 Hz, 1H), 7.44ꢀ7.42 (m,
13
3
3
H), 7.29ꢀ7.22 (m, 4H), 2.89 (s, 3H), 0.00 (s, 9H). C NMR (101 MHz, CDCl ) δ
1
60.4, 154.0, 145.0, 137.9, 128.3, 128.2, 127.6, 126.2, 126.02, 125.99, 124.4, 124.0,
+
1
23.4, 26.6, 0.0. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C H NSi:
19 21
2
92.1516; found: 292.1515.
1
6
4-hexyl-2-methylquinoline (3p):
Purification by chromatography (petroleum
1
ether/EtOAc = 10:1) afforded 3p as a white solid (18.1 mg, 27%). H NMR (400
MHz, CDCl
3
) δ 8.01 (dd, J = 19.8, 8.2 Hz, 2H), 7.68ꢀ7.63 (m, 1H), 7.51ꢀ7.47 (m, 1H),
7
.13 (s, 1H), 3.03ꢀ3.00 (m, 2H), 2.71 (s, 3H), 1.74 (dt, J = 15.5, 7.6 Hz, 2H), 1.43 (dd,
13
J = 14.8, 6.9 Hz, 2H), 1.37ꢀ1.32 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H). C NMR (101
MHz, CDCl ) δ 158.6, 148.8, 148.0, 129.3, 129.0, 125.9, 125.4, 123.4, 121.6, 32.2,
31.7, 30.1, 29.4, 25.3, 22.6, 14.1.
-cyclopropyl-2-methylquinoline (3q): Purification by chromatography (petroleum
3
12
4
1
ether/EtOAc = 10:1) afforded 3q as a yellow oil (40.1 mg, 73%). H NMR (400 MHz,
CDCl ) δ 8.25 (d, J = 8.2 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.68ꢀ7.64 (m, 1H), 7.50 (t,
3
J = 7.3 Hz, 1H), 6.92 (s, 1H), 2.68 (s, 3H), 2.40ꢀ2.33 (m, 1H), 1.14ꢀ1.11 (m, 2H),
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2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
5
5
6
1
3
0
1
6
.84ꢀ0.80 (m, 2H). C NMR (101 MHz, CDCl
3
) δ 158.8, 149.4, 147.7, 129.1, 127.0,
25.4, 123.8, 118.0, 25.4, 12.0, 7.6.
-(tert-butyl)-4-(4-methoxyphenyl)-2-methylquinoline
(3r):
Purification
by
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
chromatography (petroleum ether/EtOAc = 10:1) afforded 3r as a brown solid (68.8
ꢀ1
–1 1
mg, 75%). IR (film, cm ): 1608; 1461; 1032; 831; 768 cm . H NMR (400 MHz,
CDCl ) δ 8.02 (d, J = 8.8 Hz, 1H), 7.87 (s, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.46 (d, J =
.4 Hz, 2H), 7.18 (s, 1H), 7.06 (d, J = 8.4 Hz, 2H), 3.99 (m, 3H), 2.74 (s, 3H), 1.34 (s,
3
8
9
1
13
3
H). C NMR (101 MHz, CDCl ) δ 159.7, 157.7, 148.3, 148.1, 146.9, 130.73, 130.67,
28.5, 128.1, 124.7, 122.2, 120.6, 114.0, 55.4, 35.0, 31.2, 25.2. HRMS (DARTꢀFTICI
+
Positive) ([M+H] ) Calcd for C21
H
23NO: 306.1852; found: 306.1852.
Methyl 4-(4-methoxyphenyl)-2-methylquinoline-6-carboxylate (3s): Purification by
chromatography (petroleum ether/EtOAc = 10:1) afforded 3s as a white solid (64.5
ꢀ1
–1 1
mg, 70%). Mp 89ꢀ90 ºC. IR (film, cm ): 1716; 1464; 1026; 855; 760 cm . H NMR
(
400 MHz, CDCl ) δ 8.66 (d, J = 1.7 Hz, 1H), 8.26 (dd, J = 8.8, 1.8 Hz, 1H), 8.09 (d,
3
J = 8.8 Hz, 1H), 7.45ꢀ7.43 (m, 2H), 7.27 (s, 1H), 7.08 (d, J = 8.6 Hz, 2H), 3.92 (s, 3H),
13
3
.91 (s, 3H), 2.78 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 166.9, 161.0, 160.1, 150.4,
149.6, 130.8, 129.7, 129.3, 129.0, 128.8, 127.3, 124.5, 122.9, 114.3, 55.4, 52.3, 25.5.
+
HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C19
3
H17NO : 308.1281; found:
308.1280.
4
-(4-methoxyphenyl)-2-methyl-6-(trifluoromethyl)quinolone (3t): Purification by
chromatography (petroleum ether/EtOAc = 10:1) afforded 3t as a yellow solid (32.3
ꢀ1
–1 1
mg, 34%). Mp 61ꢀ62 ºC. IR (film, cm ): 1609; 1468; 1031; 832; 780 cm . H NMR
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(
400 MHz, CDCl
3
) δ 8.22 (s, 1H), 8.17 (d, J = 8.8 Hz, 1H), 7.85 (dd, J = 8.8, 1.8 Hz,
1
H), 7.43 (d, J = 8.7 Hz, 2H), 7.31 (s, 1H), 7.09 (d, J = 8.7 Hz, 2H), 3.92 (s, 3H), 2.80
19
13
3 3
(s, 3H). F NMR (377 MHz, CDCl ) δ ꢀ62.04. C NMR (101 MHz, CDCl ) δ 160.9,
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
1
60.2, 149.5, 149.2, 130.7, 130.2, 129.4, 127.5 (q, J = 32.4 Hz), 125.0 (q, J = 3.0 Hz),
24.5, 124.2 (q, J = 272.3 Hz) , 123.8 (q, J = 4.5 Hz), 123.3, 114.4, 55.4, 25.5. HRMS
+
(DARTꢀFTICI Positive) ([M+H] ) Calcd for C18
H
14
F
3
NO: 318.1100; found:
3
1
18.1099.
-(4-(4-methoxyphenyl)-2-methylquinolin-6-yl)ethan-1-one (3u): Purification by
chromatography (petroleum ether/EtOAc = 10:1) afforded 3u as a white solid (69.5
ꢀ1
–1 1
mg, 80%). Mp 109ꢀ110 ºC. IR (film, cm ): 1675; 1454; 1270; 1021; 880 cm . H
NMR (400 MHz, CDCl ) δ 8.55 (d, J = 1.8 Hz, 1H), 8.22 (dd, J = 8.8, 1.9 Hz, 1H),
.09 (d, J = 8.8 Hz, 1H), 7.46ꢀ7.44 (m, 2H), 7.28 (s, 1H), 7.09ꢀ7.07 (m, 2H), 3.91 (s,
3
8
13
3H), 2.78 (s, 3H), 2.60 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 197.6, 161.1, 160.2,
1
50.5, 149.7, 134.1, 130.8, 129.6, 129.5, 128.0, 127.6, 124.5, 122.9, 114.3, 55.4, 26.7,
+
25.6. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C19
2
H17NO : 292.1332;
found: 292.1331.
4-(4-methoxyphenyl)-2-methyl-6-phenylquinoline
(3v):
Purification
by
chromatography (petroleum ether/EtOAc = 10:1) afforded 3v as a brown oil (33.7 mg,
ꢀ1
–1 1
35%). IR (film, cm ): 1604; 1487; 1245; 1028; 833 cm . H NMR (400 MHz, CDCl )
3
δ 8.14 (d, J = 8.7 Hz, 1H), 8.09 (d, J = 2.0 Hz, 1H), 7.95 (dd, J = 8.7, 2.1 Hz, 1H),
7.62ꢀ7.60 (m, 2H), 7.49ꢀ7.41 (m, 2H), 7.43 (t, J = 7.5 Hz, 2H), 7.35ꢀ7.32 (m, 1H),
13
7
.23 (s, 1H), 7.06 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H), 2.78 (s, 3H). C NMR (101 MHz,
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1
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
5
6
CDCl
3
) δ 159.8, 158.5, 148.5, 147.9, 140.8, 138.4, 130.8, 130.4, 129.5, 128.9, 128.9,
1
27.5, 127.4, 125.4, 123.6, 122.6, 114.1, 55.4, 25.4. HRMS (DARTꢀFTICI Positive)
+
([M+H] ) Calcd for C23
H19NO: 326.1539; found: 326.1538.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7
-methoxy-4-(4-methoxyphenyl)-2-methylquinoline
-methoxy-4-(4-methoxyphenyl)-2-methylquinoline
(3w);
7
(3w’):
Purification
by
chromatography (petroleum ether/EtOAc = 10:1) afforded as a white solid 3w (44.4
ꢀ1
mg, 52%), 3w’ (20.0mg, 24%). 3w: Mp 96ꢀ97 ºC. IR (film, cm ): 1584; 1463; 1029;
–1
1
8
3
3
3
78; 834 cm . H NMR (400 MHz, CDCl ) δ 7.78 (d, J = 9.2 Hz, 1H), 7.44ꢀ7.40 (m,
H), 7.08 (dd, J = 9.2, 2.6 Hz, 1H), 7.08 (s, 1H), 7.03 (d, J = 8.7 Hz, 2H), 3.95 (s, 3H),
13
.89 (s, 3H), 2.73 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 160.5, 159.8, 158.8, 150.3,
148.2, 130.7, 130.6, 126.8, 120.2, 120.1, 118.5, 114.0, 107.2, 55.5, 55.4, 25.3. HRMS
+
(DART Positive) ([M+H] ) Calcd for C18
2
H17NO : 280.1332; found: 280.1331. 3w’:
–
1
1
Mp 71ꢀ72 ºC. 1607; 1465; 1032; 872; 833 cm . H NMR (400 MHz, CDCl
3
) δ 7.70
(dd, J = 8.5, 0.9 Hz, 1H), 7.58 (t, J = 8.1 Hz, 1H), 7.25 (d, J = 8.8 Hz, 2H), 7.06 (s,
1H), 6.94ꢀ6.91 (m, 2H), 6.78 (d, J = 7.7 Hz, 1H), 3.88 (s, 3H), 3.55 (s, 3H), 2.72 (s,
13
3
H). C NMR (101 MHz, CDCl
3
) δ 158.7, 158.1, 156.5, 150.0, 147.8, 135.1, 129.5,
129.4, 124.3, 121.6, 117.3, 112.4, 105.6, 55.4, 55.3, 24.9. HRMS (DARTꢀFTICI
+
Positive) ([M+H] ) Calcd for C18
H
17NO
2
: 280.1332; found: 280.1331.
(3x): Purification
chromatography (petroleum ether/EtOAc = 10:1) afforded 3x as a white solid (51.8
4-(4-methoxyphenyl)-2-methylbenzo[h]quinoline
by
ꢀ1
–1 1
mg, 58%). Mp 111ꢀ112 ºC. IR (film, cm ): 1589; 1497; 1033; 837; 777 cm . H
NMR (400 MHz, CDCl
3
) δ 9.40 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 7.1 Hz, 1H), 7.78 (d,
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J = 9.1 Hz, 1H), 7.72ꢀ7.62 (m, 3H), 7.42 (d, J = 8.7 Hz, 2H), 7.29 (s, 1H), 7.03 (d, J =
1
3
8
1
1
3
.7 Hz, 2H), 3.86 (s, 3H), 2.83 (s, 3H). C NMR (101 MHz, CDCl ) δ 159.7, 157.1,
48.1, 146.5, 133.5, 131.6, 130.9, 128.0, 127.5, 126.8, 126.4, 124.9, 123.1, 122.7,
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
+
22.5, 114.0, 55.4, 25.4. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for
C
21
H
17NO: 300.1383; found: 300.1382.
1
7
4
-(4-methoxyphenyl)-2-phenylquinoline (3y):
Purification by chromatography
1
(petroleum ether/EtOAc = 10:1) afforded 3y as a white solid (50.3 mg, 54%). H
NMR (400 MHz, CDCl
3
) δ 8.23 (d, J = 8.0 Hz, 1H), 8.20ꢀ8.18 (m, 2H), 7.95 (dd, J =
8
7
.4, 0.8 Hz, 1H), 7.79 (s, 1H), 7.72 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.54ꢀ7.44 (m, 6H),
13
3
.08 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H). C NMR (101 MHz, CDCl ) δ 159.9, 157.0,
148.9, 139.8, 130.9, 130.7, 130.2, 129.5, 129.3, 128.9, 127.6, 126.3, 126.0, 125.7,
19.4, 114.1, 55.5.
2-(tert-butyl)-4-(4-methoxyphenyl)quinoline (3z): Purification by chromatography
petroleum ether/EtOAc = 10:1) afforded 3z as a yellow oil (45.4 mg, 52%). IR (film,
1
(
ꢀ1
–1 1
cm ): 1609; 1496; 1245; 1033; 832 cm . H NMR (400 MHz, CDCl
3
) δ 8.11 (d, J =
8
.4 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.67ꢀ7.63 (m, 1H), 7.46ꢀ7.39 (m, 4H), 7.05 (d, J
1
3
= 8.6 Hz, 2H), 3.88 (s, 3H), 1.49 (s, 9H). C NMR (101 MHz, CDCl
3
) δ 168.8, 159.7,
1
48.1, 147.9, 131.2, 130.9, 129.8, 128.9, 125.6, 125.5, 125.3, 118.5, 114.0, 55.4, 38.2,
+
30.2. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C H NO: 292.1696;
20
21
found: 292.1695.
Methyl 4-(4-(methoxycarbonyl)phenyl)-2-methylquinoline-6-carboxylate
(3aa):
Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3aa as a
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5
5
5
5
5
5
5
5
5
6
ꢀ
1
white solid (35.5 mg, 35%). Mp 188ꢀ189 ºC. IR (film, cm ): 1715; 1563; 1277; 1103;
–
1 1
8
1
2
57 cm . H NMR (400 MHz, CDCl
3
) δ 8.52 (d, J = 1.5 Hz, 1H), 8.29 (dd, J = 8.8,
.7 Hz, 1H), 8.23 (d, J = 8.2 Hz, 2H), 8.13 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 8.2 Hz,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
H), 7.31 (s, 1H), 4.00 (s, 3H), 3.91 (s, 3H), 2.81 (s, 3H). C NMR (101 MHz, CDCl )
3
δ 166.7, 161.0, 150.3, 148.7, 142.0, 130.5, 130.0, 129.6, 129.5, 129.2, 128.4, 127.6,
+
1
23.9, 122.9, 52.37, 52.36, 25.6. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for
C
20
H
17NO
4
: 336.1230; found: 336.1231.
Methyl
4-(3-(((allyloxy)carbonyl)amino)phenyl)-2-methylquinoline-6-carboxylate
(
3ab): Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3ab
ꢀ1
as a white solid (52.5 mg, 47%). Mp 83ꢀ84 ºC. IR (film, cm ): 1721; 1593; 1278;
–1 1
1050; 845 cm . H NMR (400 MHz, CDCl
.8, 1.9 Hz, 1H), 8.10 (d, J = 8.8 Hz, 1H), 7.59 (s, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.47
(t, J = 7.8 Hz, 1H), 7.29 (s, 1H), 7.20ꢀ7.17 (m, 1H), 7.06 (s, 1H), 5.96 (ddt, J = 16.1,
0.5, 5.7 Hz, 1H), 5.36 (ddd, J = 17.2, 2.9, 1.4 Hz, 1H), 5.26 (dd, J = 10.4, 1.2 Hz,
3
) δ 8.60 (d, J = 1.7 Hz, 1H), 8.26 (dd, J =
8
1
1
3
3
1H), 4.68 (d, J = 5.7 Hz, 2H), 3.91 (s, 3H), 2.78 (s, 3H). C NMR (101 MHz, CDCl )
δ 166.9, 161.0, 153.2, 150.3, 149.4, 138.40, 138.38, 132.3, 129.5, 129.4, 129.0, 128.9,
127.39, 124.7, 124.3, 123.0, 119.5, 118.9, 118.5, 66.0, 52.3, 25.6. HRMS
+
(
DARTꢀFTICI Positive) ([M+H] ) Calcd for C22
H
20
N
2
O
4
: 377.1496; found: 377.1496.
(3ac): Purification by
chromatography (petroleum ether/EtOAc = 10:1) afforded 3ac as a white solid (41.1
1-(4-cyclopropyl-2-methylquinolin-6-yl)ethan-1-one
ꢀ1
–1 1
mg, 61%). Mp 88ꢀ89 ºC. IR (film, cm ): 1670; 1596; 1257; 1063; 831 cm . H NMR
(400 MHz, CDCl
3
) δ 8.92 (d, J = 1.8 Hz, 1H), 8.21 (dd, J = 8.8, 1.9 Hz, 1H), 8.05 (d,
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J = 8.8 Hz, 1H), 6.97 (s, 1H), 2.75 (s, 3H), 2.71 (s, 3H), 2.48 (ddd, J = 13.7, 8.3, 5.4
13
Hz, 1H), 1.23 (ddd, J = 8.4, 6.3, 4.5 Hz, 2H), 0.91ꢀ0.87 (m, 2H). C NMR (101 MHz,
CDCl
3
) δ 197.8, 161.5, 151.3, 149.8, 133.8, 129.6, 127.6, 126.3, 125.7, 118.58, 26.8,
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
+
2
2
5.6, 11.9, 8.3. HRMS (DARTꢀFTICI Positive) ([M+H] ) Calcd for C H NO:
15
15
26.1226; found: 226.1226.
Acknowledgments
Financial support from the National Natural Science Foundation of China (21472084
and 81421091), and the State Key Laboratory of Bioorganic Chemistry, Shanghai
Institute of Organic Chemistry, CAS is acknowledged.
Supporting Information
The Supporting Information is available free of charge on the ACS Publication
website at DOI:
1
13
19
Characterization of products (copies of H, C, and F NMR spectra)
References
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