Pd-Catalyzed Ligand-Free Synthesis of Arylated Heteroaromatics by Coupling of N-Heteroaromatic Bromides with Iodobenzene Diacetate, Iodosobenzene, or Diphenyliodonium Salts

Article abstract of DOI:10.1021/acs.joc.6b01103

An efficient method for synthesizing arylated heteroaromatics has been reported via Pd-catalyzed ligand-free cross-coupling of N-heteroaromatic bromides with iodine(III) reagents under mild conditions. Iodobenzene diacetate, iodosobenzene, and diphenyliod

Full text of DOI:10.1021/acs.joc.6b01103

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Note
Pd-catalyzed Ligand-Free Synthesis of Arylated heteroaromatics
by Coupling of N-heteroaromatic Bromides with Iodobenzene
diacetate, Iodosobenzen or Diphenyliodonium salts
Xiajun Wang, Yongqin He, Mengdan Ren, Shengkang Liu, He Liu, and Guosheng Huang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01103 • Publication Date (Web): 26 Jul 2016
Downloaded from http://pubs.acs.org on July 27, 2016
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Pd-catalyzed Ligand-Free Synthesis of Arylated heteroaromatics by
Coupling of N-heteroaromatic Bromides with Iodobenzene diacetate,
Iodosobenzene or Diphenyliodonium salts
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Xiajun Wang,a Yongqin He,a Mengdan Ren,a Shengkang Liua, He Liub and Guosheng
Huanga*
a
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, 730000, China.
b Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania
16802, United States.
Abstract: An efficient method for synthesizing arylated heteroaromatics
has been reported via Pdꢀcatalyzed ligandꢀfree crossꢀcoupling of
Nꢀheteroaromatic bromides with iodine (III) reagents under mild
conditions. Iodobenzene diacetate, iodosobenzene and diphenyliodonium
salts act as ideal arylated sources in this reaction, producing bioactive
aromatic substituted pyridines and quinolines in moderate to high yields.
Nitrogenꢀcontaining heteroaromatics are a class of significant
building blocks used in the construction of a wide range of compounds,
including natural products, pharmaceuticals, agrochemicals, ligands, and
advanced materials.1 Amongst them, arylated pyridines and quinolines,
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two important skeleton motifs of heterocycles, are frequently used in the
preparation of diverse medicinal intermediates (Figure 1).2 Examples of
which include an A3 adenosine receptor antagonist,3 a phosophodiesterase
4 (PDE4) inhibitor,4 an antimalarial agent,5 and a strong NorA efflux
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Figure 1. Selected Examples of Arylated Pyridines and Quinolines on Medicine
pump inhibitor.6 Consequently, the synthesis of arylated pyridines and
quinolines have received considerable attention over the past few decades
and significant efforts have been devoted to seeking more efficient
preparation methods. With regard to the arylation of pyridines and
quinolines, one of the most prevalent strategies towards crossꢀcoupling of
heteroaromatic halides with different arylation reagents is done by using
transition metal catalysts.7 Examples include the use of arylmetallic
reagents (Scheme 1, eq 1),8 arylsulfinates (Scheme 1, eq 2),9 even arenes
(Scheme 1, eq 3)10 as arylation reagents
Scheme 1. Arylation of N-heteroaromatics
in this crossꢀcoupling reaction. While prevalent, the requirement of
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unstable arylation reagents and suitable ligands, poor functional group
compatibility, and a somewhat limited substrate scope reduce the
attractiveness of this method.11 Thus, it is meaningful to develop a direct
and efficient arylation approach in the synthesis of this context.
In recent years, hypervalent iodine compounds have received
significant attention owing to their easily available, nonꢀtoxic, highly
stable and lowꢀcost features.12 Although diaryliodonium salt was
extensively studied as an arylation reagent in the past few decades,
iodobenzene diacetate (PIDA), which is widely served as an oxidant or
acetoxylation reagent in organic synthesis,13 was less applied in the
arylation of heterocyclic derivatives. Herein we present a novel
Pdꢀcatalyzed ligandꢀfree method for the synthesis of arylated
Nꢀheteroaromatics by using PIDA and other hypervalent iodine
compounds as arylation reagents. To our best knowledge, this has not
been reported so far.
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We began our investigation with a model reaction using
3ꢀbromopyridine (1a) and PIDA (2a). In the presence of Pd(OAc)2 (10
mol%, 0.02 mmol) as catalyst and Cs2CO3 (2.0 equiv, 0.40 mmol) as base
in N,Nꢀdimethylformamide (DMF) (1 mL) stirring under air at 110 oC for
12 h, the desired product 3ꢀphenylpyridine (3aa) was isolated in 69%
yield (Table 1, entry 1). To standardize the reaction conditions, we
conducted a series of experiments with variation of the reaction
parameters. Palladium and other transition metal catalysts were tested
first, and PdCl2 gave the best result of 78% yield (Table 1, entries 1ꢀ7).
Subsequently, different bases were examined and the results showed that
Cs2CO3 offered higher yield (Table 1, entries 8ꢀ13). Reducing the amount
of Cs2CO3 slightly led to lower yield of 68%, but reactivity was not
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increased when excess Cs2CO3 was applied (Table 1, entries 14 and 15).
Further screening of solvents demonstrated that DMF displayed the best
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Table 1. Optimization of the Reaction Conditionsa
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Base(equiv)
Yieldb (%)
Entry Catalyst(10 mol %)
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMA
NMP
DMSO
xylene
1
Pd(OAc)2
PdCl2
Cs2CO3(2.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
K3PO4(2.0)
K2CO3(2.0)
Na2CO3(2.0)
NaOH(2.0)
tꢀBuOK(2.0)
Et3N(2.0)
69
78
64
69
71
0
2
3
Pd(PPh3)4
Pd(OCOCF3)2
Pd2(dba)3
CuI
4
5
6
7
FeCl3
0
8
PdCl2
64
70
67
50
75
59
68
78
70
74
trace
0
9
PdCl2
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12
13
14
15
16
17
18
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Cs2CO3(1.0)
Cs2CO3(4.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
Cs2CO3(2.0)
PdCl2
PdCl2
PdCl2
PdCl2
19
PdCl2
a
Reaction conditions: 1a (0.20 mmol), 2a (0.40 mmol), catalyst (10
mol%, 0.02 mmol) and base in solvent (1 mL) at 110 oC for 12 h.
b Isolated yields
ability in this transformation (Table 1, entries 16ꢀ19). As a result, we
chose Table 1, entry 2 as the optimized reaction conditions.
With the optimized reaction conditions established, we proceeded to
examine the scope of heteroaryl bromides (Table 2). As expected, we
found that a wide array of heteroaryl bromides bearing different
functional groups (methyl, methoxy, ester) all exhibited good
compatibility in this transformation and the corresponding products
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3aaꢀ3ga were obtained in moderate to high yields under the optimized
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conditions. The heteroaryl bromides containing different electronic effect
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Table 2. Synthesis of Arylated Heteroaromatics from Substituted Heteroaryl
Bromides and PIDAa
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Heteroaryl
bromides
Yieldb
(%)
Heteroaryl
bromides
Products
Yieldb
(%)
Entry
Products
Entry
Br
Br
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2
3
78
41
60
9
72
69
71
N
N
1a
1i
Br
Br
10
11
N
N
1b
1j
Br
N
N
Br
N
1c
1k
Br
Br
Br
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5
50
65
12
13
70
56
N
N
O
1l
1d
Br
O
Br
N
1e
N
1m
Br
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80
14
15
70
62
O
N
Br
1f
N
N
O
1n
Br
O
7
8
43
0
N
N
1g
Br
1o
Br
3oa
N
NO2
1h
a Reaction conditions: heteroaryl halides (0.20 mmol), PIDA (0.40 mmol), PdCl2 (10 mol%, 0.02 mmol) and
Cs2CO3 (0.40 mmol) in DMF (1 mL). The reaction was stirred at 110 oC for 12 h.
b Isolated yield
substituents influenced the yields of the desired products. It is also
observed that strong electronꢀwithdrawing groups showed lower
reactivity compared to electronꢀdonating groups. For example,
5ꢀbromoꢀ2ꢀmethoxypyridine generated the product 3da easily in
moderate yield of 50%, while no reaction occurred when
5ꢀbromoꢀ2ꢀnitropyridine was employed in this reaction. To further extend
the scope of this reaction, we next investigated several other
nitrogenꢀcontaining heterocycles and the expected products 3ia-3ka were
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obtained in good yields. Gratifyingly, disubstituted 3,5ꢀdibromopyridine
participated efficiently as well to give the correspongding product 3la in
70% yield. Notably, 5ꢀ, 6ꢀ or 8ꢀ position bromoꢀsubstituted quinoline
could also undergo the reaction smoothly to give the products 3ma, 3na,
and 3oa in 56%, 70% and 62% yields, respectively.
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Then our attention turned towards expanding the scope of
hypervalent iodine (III) reagents (Table 3). Satisfyingly,
[
bis(trifluoroacetoxy)iodo] benzene was proved to be suitable as an
arylation partner which could deliver the desired products 3aa and 3ia in
72% and 75% yields. Iodosobenzene could also give the corresponding
products 3aa and 3ia in 30% and 25% yields, respectively. Considering
the wide application of quinoline derivatives in pharmaceutical
Table 3. Synthesis of Arylated Heteroaromatics from Substituted Heteroaryl
Bromides and Other Iodine (III) Reagentsa
Heteroaryl
bromides
Iodine (III)
reagents
Yieldb
(%)
Heteroaryl
bromides
Iodine (III)
reagents
Yieldb
(%)
Entry
Products
Entry
Products
OTf
I
I(OCOCF3)2
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2
3
72
30
75
6
7
8
53
31
60
1a
3aa
1i
3ia
2e
2b
F
OTf
I
O
I
1a
1i
3aa
3ia
1i
1i
1i
N
F
F
3p
2c
2f
I(OCOCF3)2
2b
2c
O
I
4
5
25
30
1i
1i
3ia
3ia
9
40
Br
I
2d
a Reaction conditions: heteroaryl bromides (0.20 mmol), iodine(III) reagents (0.40 mmol), PdCl2 (10 mol%, 0.02
mmol) and Cs2CO3 (0.40 mmol) in DMF (1 mL). The reaction was stirred at 110 oC for 12 h.
b Isolated yield
chemistry, further expansion of the scope of diphenyliodonium salts were
investigated, with 3ꢀbromoquinoline selected as the coupling substrate.
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We found that symmetric diphenyliodonium salts with different anion
(Brꢀ, OTfꢀ) were smoothly converted into the corresponding products 3ia
in moderate yields (Table 3, entries 5 and 6). Subsequently, we noticed
that the introduction of an electronꢀdonating/ꢀwithdrawing group on the
diphenyliodonium salts has little impact on the success of this
transformation, albeit with lower yield. Fluorine, methyl and tertꢀbutyl
groups on phenyl rings were well tolerated, affording the arylated
products 3ifꢀ3ih in 31ꢀ60% yields. It is noteworthy that fluorine, methyl
and tertꢀbutyl substituents can be converted into other valuable functional
groups.
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Based on the observations above, we proposed a plausible
mechanism for this reaction in Scheme 2. Step i: oxidative addition of
3ꢀbromopyridine (1a) to Pd(0) to form the arylꢀPd(II)ꢀBr species A.14a,14b
Step ii: PIDA degrades to iodobenzene with the aid of base in DMF under
o
110 C.12d Step iii: iodobenzene, which is obtained from step ii, reacts
with arylꢀPd(II)ꢀBr species A, affording intermediate B.14c,14d Step iv:
reductive elimination of B would produce the product 3aa and regenerate
the Pd(0) species for next catalytic cycle.14e
Scheme 2. Possible Mechanism
Br
Pd
(II)
I
I(OAc)2
N
Br
DMF
A
Cs2CO3
N
1a
oxidative
addition
Pd(0)
Pd
(II)
B
N
reductive
elimination
N
3aa
In summary, we have developed a novel and convenient protocol for
the synthesis of arylated nitrogenꢀcontaining heteroaromatics using
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heteroaryl bromides, hypervalent iodine(III) reagents and a Pdꢀbased
catalyst. This method shows good functional compatibility. It uses
iodine(III) compounds as a promising direct arylation reagent and
generates the corresponding products in moderate to high yields.
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Experimental Section
General Remarks: Reagents and solvents were purchased commercially
and used without further purification. Silica gel (200ꢀ300 mesh) was used
for column chromatography. 1H NMR spectra were recorded on 400MHz
or 300MHz in CDCl3; 13C NMR spectra were recorded on 101 MHz or 75
MHz in CDCl3 using tetramethylsilane (TMS) as internal standard. The
highꢀresolution mass spectra (HRMS) was recorded on an FTꢀICR mass
spectrometer using electrospray ionization (ESI). All melting points were
determined without correction.
General Procedure for the Synthesis of 3 (3aa as an example).
3ꢀbromopyridine (1a) (31.6 mg, 0.20 mmol), PIDA (2a) (128.8 mg, 0.40
mmol), PdCl2 (3.5 mg, 0.02 mmol), Cs2CO3 (130.3 mg, 0.40 mmol) were
added to a test tube. Then 1 mL DMF was added using a syringe. The
o
reaction was stirred at 110 C for 12 h under air atmosphere. After
completion of the reaction (monitored by TLC), the test tube was allowed
to cool to room temperature. After that, the solution was diluted with
ethyl acetate (10 mL), washed with brine (5 mL) and dried over Na2SO4.
Then the solvent was evaporated in vacuo, the residues were purified by
column chromatography on silica gel (petroleum ether/EtOAc = 8:1) to
give the desired product 3aa.
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Analytical Data for Products.
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3ꢀPhenylpyridine (3aa).8b Yellow oil (24 mg, 78%). 1H NMR (300 MHz,
CDCl3) δ 8.86 (d, J = 2.2 Hz, 1H), 8.60 (dd, J = 4.8, 1.6 Hz, 1H), 7.88 (dt,
J = 8.8, 3.2 Hz, 1H), 7.62ꢀ7.55 (m, 2H), 7.52ꢀ7.34 (m, 4H). 13C NMR (75
MHz, CDCl3) δ 148.4, 148.2, 137.7, 136.6, 134.4, 129.0, 128.1, 127.1,
123.5. HRMS(ESI)m/z calcd for C11H9N [M+H]+ 156.0808, found
156.0806 .
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1
2ꢀMethylꢀ3ꢀphenylpyridine (3ba).15 Yellow oil (14 mg, 41%). H NMR
(400 MHz, CDCl3) δ 8.50 (dd, J = 4.8, 1.5 Hz, 1H), 7.51 (dd, J = 7.6, 1.5
Hz, 1H), 7.45ꢀ7.42 (m, 2H), 7.40ꢀ7.34 (m, 1H), 7.34ꢀ7.29 (m, 2H), 7.17
(dd, J = 7.6, 4.9 Hz, 1H), 2.51 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
155.8, 147.8, 139.9, 137.1, 136.9, 128.9, 128.3, 127.4, 120.9, 23.3.
HRMS(ESI)m/z calcd for C12H11N [M+H]+ 170.0964, found 170.0966 .
1
2ꢀMethylꢀ5ꢀphenylpyridine (3ca).15 Yellow oil (20 mg, 60%). H NMR
(400 MHz, CDCl3) δ 8.74 (d, J = 2.0 Hz, 1H), 7.77 (dd, J = 8.0, 4.0Hz,
1H), 7.59ꢀ7.54 (m, 2H), 7.48ꢀ7.44 (m, 2H), 7.40ꢀ7.36 (m, 1H), 7.22 (d, J
= 8.1 Hz, 1H), 2.61 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 157.2, 147.5,
137.9, 134.7, 133.7, 129.0, 127.8, 126.9, 123.1, 24.0. HRMS(ESI)m/z
calcd for C12H11N [M+H]+ 170.0964, found 170.0966 .
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2ꢀMethoxyꢀ5ꢀphenylpyridine (3da).8b Yellow oil (18 mg, 50%). 1H NMR
(300 MHz, CDCl3) δ 8.39 (dd, J = 2.5, 0.7 Hz, 1H), 7.79 (dd, J = 8.6, 2.6
Hz, 1H), 7.56ꢀ7.49 (m, 2H), 7.48ꢀ7.41 (m, 2H), 7.39ꢀ7.31 (m, 1H), 6.82
(dd, J = 8.6, 0.7 Hz, 1H), 3.98 (s, 3H). 13C NMR (75 MHz, CDCl3) δ
163.5, 144.9, 137.8, 137.4, 130.0, 128.9, 127.3, 126.6, 110.8, 53.5.
HRMS(ESI)m/z calcd for C12H11NO [M+H]+ 186.0914, found 186.0915
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3ꢀMethoxyꢀ5ꢀphenylpyridine (3ea).16 Yellow oil (24 mg, 65%). 1H NMR
(400 MHz, CDCl3) δ 8.47 (s, 1H), 8.31 (s, 1H), 7.59 (d, J = 7.4 Hz, 2H),
13
7.48 (t, J = 7.4 Hz, 2H), 7.43ꢀ7.38 (m, 2H), 3.93 (s, 3H). C NMR (101
MHz, CDCl3) δ 140.7, 137.6, 136.0, 129.0, 128.2, 127.2, 119.1, 55.6,
29.7. HRMS(ESI)m/z calcd for C12H11NO [M+H]+ 186.0914, found
186.0915
2ꢀMethoxyꢀ6ꢀphenylpyridine (3fa).17 White solid (30 mg, 80%), m. p.
103ꢀ115 oC. 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.4 Hz, 1H), 7.68
(t, J = 7.7 Hz, 1H), 7.60 (d, J = 8.1, 2H), 7.44 (t, J = 7.6 Hz, 2H),
7.37ꢀ7.33 (m, 1H), 6.75 (d, J = 8.1 Hz, 1H), 4.03 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 163.3, 153.3, 141.2, 139.2, 128.7, 127.2, 127.1, 113.6,
110.8, 53.2. HRMS(ESI)m/z calcd for C12H11NO [M+H]+ 186.0914,
found 186.0915 .
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Methylꢀ5ꢀphenylpicolinate (3ga).18 Yellow oil (18 mg, 43%). H NMR
(400 MHz, CDCl3) δ 9.20 (s, 1H), 9.01 (s, 1H), 8.50 (t, J = 2.0 Hz, 1H),
7.66ꢀ7.59 (m, 2H), 7.51 (t, J = 7.4 Hz, 2H), 7.44 (t, J = 7.3 Hz, 1H), 3.99
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 165.8, 151.8, 149.4, 135.2, 129.2,
128.6, 127.2, 52.5. HRMS(ESI)m/z calcd for C13H11NO2 [M+H]+
214.0863, found 214.0861.
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3ꢀPhenylquinoline (3ia).9 Yellow oil (29 mg, 72%). H NMR (300 MHz,
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CDCl3) δ 9.19 (d, J = 2.2 Hz, 1H), 8.30 (d, J = 2.2 Hz, 1H), 8.15 (d, J =
8.4 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.76ꢀ7.68 (m, 3H), 7.61ꢀ7.39 (m,
4H). 13C NMR (75 MHz, CDCl3) δ 149.9, 147.3, 137.8, 133.8, 133.2,
129.4, 129.2, 129.1, 128.1, 128.0, 127.4, 127.0. HRMS(ESI)m/z calcd
for C15H11N [M+H]+ 206.0964, found 206.0966.
4ꢀPhenylisoquinoline (3ja).9 Yellow oil (28 mg, 69%). H NMR (300
1
MHz, CDCl3) δ 9.27 (s, 1H), 8.50 (s, 1H), 8.09ꢀ8.00 (m, 1H), 7.92 (d, J =
8.1 Hz, 1H), 7.73ꢀ7.59 (m, 2H), 7.58ꢀ7.43 (m, 5H). 13C NMR (101 MHz,
MHz, CDCl3) δ 151.9, 142.7, 136.9, 134.2, 133.3, 130.5, 130.1, 128.6,
127.9, 127.8, 127.1, 124.8. HRMS(ESI)m/z calcd for C15H11N [M+H]+
206.0964, found 206.0966.
5ꢀPhenylpyrimidine (3ka).9 Yellow oil (22 mg, 71%). H NMR (300
1
MHz, CDCl3) δ 9.22 (s, 1H), 8.97 (s, 2H), 7.64ꢀ7.43 (m, 5H). 13C NMR
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(75 MHz, CDCl3) δ 157.4, 154.9, 134.3, 134.2, 129.4, 129.0, 127.0.
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HRMS(ESI)m/z calcd for C10H8N2 [M+H]+ 157.0760, found 157.0763.
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3,5ꢀDiphenylpyridine (3la).19 White solid (33 mg, 70%), m. p. 115ꢀ132
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oC. H NMR (400 MHz, CDCl3) δ 8.83 (s, 2H), 8.05 (t, J = 2.1 Hz, 1H),
7.66ꢀ7.64 (m, 4H), 7.53ꢀ7.47 (m, 4H), 7.45ꢀ7.40 (m, 2H). 13C NMR (101
MHz, CDCl3) δ 147.0, 137.8, 132.9, 129.1, 128.2, 127.3.
HRMS(ESI)m/z calcd for C17H13N [M+H]+ 232.1121, found 232.1122 .
5ꢀPhenylquinoline (3ma).8d White solid (23 mg, 56%), m. p. 74ꢀ78 oC. 1H
NMR (400MHz, CDCl3) δ 8.96ꢀ8.90 (m, 1H), 8.26ꢀ8.21 (m, 1H), 8.13 (d,
J = 8.5 Hz, 1H), 8.13 (d, J = 8.5 Hz, 1H), 7.54ꢀ7.42 (m, 6H), 7.35 (dd, J =
13
8.6, 4.2 Hz, 1H). C NMR (101 MHz, CDCl3) δ 150.2, 148.5, 140.5,
139.4, 134.3, 130.0, 128.9, 128.9, 128.4, 127.6, 127.2, 126.7, 121.0.
HRMS(ESI)m/z calcd for C15H11N [M+H]+ 206.0964, found 206.0966.
6ꢀPhenylquinoline (3na).8d White solid (28 mg, 70%), m. p. 99ꢀ112 C.
o
1H NMR (300 MHz, CDCl3) δ 8.92 (d, J = 2.8 Hz, 1H), 8.25ꢀ8.14 (m,
2H), 7.99 (d, J = 7.8 Hz, 2H), 7.72 (d, J = 7.3 Hz, 2H), 7.50 (t, J = 7.4 Hz,
2H), 7.44ꢀ7.38 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 150.3, 147.6, 140.3,
139.3, 136.2, 129.9, 129.2, 128.9, 128.5, 127.7, 127.4, 125.5, 121.4.
HRMS(ESI)m/z calcd for C15H11N [M+H]+ 206.0964, found 206.0966.
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8ꢀPhenylquinoline (3oa).8d Yellow oil (25 mg, 62%). 1H NMR (400 MHz,
CDCl3) δ 8.95 (dd, J = 4.1, 1.7 Hz, 1H), 8.20 (dd, J = 8.1, 3.7, 1H), 7.82
(dd, J = 8.1, 1.2 Hz, 1H), 7.75ꢀ7.67 (m, 3H), 7.60 (t , J = 7.9, 1H), 7.49 (t,
J = 7.5 Hz, 2H), 7.44ꢀ7.37 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 150.2,
146.1, 140.9, 139.5, 136.2, 130.6, 130.3, 128.7, 128.0, 127.5, 127.3,
126.2, 120.9. HRMS(ESI)m/z calcd for C15H11N [M+H]+ 206.0964,
found 206.0966.
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3ꢀ(4ꢀFlourophenyl)quinoline (3if).8g Yellow solid (14 mg, 31%), m. p.
83ꢀ89 oC. 1H NMR (300 MHz, CDCl3) δ 9.14 (d, J = 2.3 Hz, 1H), 8.25 (d,
J = 2.3 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H),
7.77ꢀ7.63 (m, 3H), 7.62ꢀ7.54 (m, 1H), 7.27ꢀ7.16 (m, 2H). 13C NMR (75
MHz, CDCl3) δ 162.9 (d, J = 246.7 Hz), 149.7, 147.3, 134.0, 133.1, 132.9,
129.5, 129.2, 129.1, 129.0, 127.9, 127.1, 116.1 (d, J = 21.7 Hz).
HRMS(ESI)m/z calcd for C15H10FN [M+H]+ 224.0870, found 224.0873.
o
3ꢀ(pꢀTolyl)quinoline (3ig).8g Yellow solid (26 mg, 60%), m. p. 82ꢀ84 C.
1H NMR (400 MHz, CDCl3) δ 9.17 (d, J = 2.3 Hz, 1H), 8.24 (d, J = 2.1
Hz, 1H), 8.13 (d, J = 8.5 Hz, 1H), 7.83 (d, J = 8.2 Hz, 1H), 7.70ꢀ7.66 (m,
1H), 7.59 (d, J = 8.1 Hz, 2H), 7.56ꢀ7.51 (m, 1H), 7.30 (d, J = 7.9 Hz, 2H),
2.41 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 149.9, 147.2, 138.0, 134.9,
133.7, 132.7, 129.8, 129.2, 129.1, 128.0, 127.9, 127.2, 126.8, 21.1.
HRMS(ESI)m/z calcd for C16H13N [M+H]+ 220.1121, found 220.1120.
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3ꢀ((4ꢀtertꢀButyl)phenyl)quinoline (3ih).11g Yellow oil (21 mg, 40%). H
NMR (400 MHz, CDCl3) δ 9.20 (s, 1H), 8.29 (d, J = 2.1 Hz, 1H), 8.14 (d,
J = 8.4 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.74ꢀ7.65 (m, 3H), 7.59ꢀ7.55
(m, 3H), 1.39 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 151.3, 150.0, 147.2,
134.9, 133.7, 132.9, 129.2, 128.1, 127.9, 127.1, 126.9, 126.2, 34.7, 31.3.
HRMS(ESI)m/z calcd for C19H19N [M+H]+ 262.1590, found 262.1591.
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Supporting Information
NMR spectra of all compounds. The materials is available free of charge
on the ACS Publications website.
Corresponding Authors:
*Fax: +86 931 8912596. Tel: +86 931 8912586. Eꢀmail: hgs@lzu.edu.cn
(G.H.).
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