Direct arylation of arene and N -heteroarenes with diaryliodonium salts without the use of transition metal catalyst

Article abstract of DOI:10.1021/jo202150t

A novel and simple transition metal-free direct arylation of arene and N-heteroarenes with diaryliodonium salts has been developed. This cross-coupling reaction is promoted only by base and gives the desired products in moderate to good yields.

Full text of DOI:10.1021/jo202150t

Note
pubs.acs.org/joc
Direct Arylation of Arene and N-Heteroarenes with Diaryliodonium
Salts without the Use of Transition Metal Catalyst
Jun Wen, Ruo-Yi Zhang, Shan-Yong Chen, Ji Zhang,* and Xiao-Qi Yu*
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu,
Sichuan 610064, P. R. China
S
* Supporting Information
ABSTRACT: A novel and simple transition metal-free direct
arylation of arene and N-heteroarenes with diaryliodonium salts
has been developed. This cross-coupling reaction is promoted
only by base and gives the desired products in moderate to good
yields.
irect arylation of unreactive C−H bonds has received
conditions, we first studied the cross-coupling reaction between
diphenyliodonium salt and pyrrole, and the results were
summarized in Table 1. Without the use of inorganic base as
additive, only poor yield was obtained (32%, entry 1, Table 1).
Therefore, a range of bases including K3PO4, Na2CO3, K2CO3,
NaHCO3, NaOH, and KOH were screened (entries 2−7, Table
1), and NaOH was found to be the most suitable one to give
the desired product 3a in 78% yield. The use of organic bases
such as tetramethylethylenediamine (TMEDA) and triethyl-
amine led to much decreased yields, and only trace and 47%
yields were obtained, respectively (entries 9 and 10, Table 1).
Investigation of reaction temperature revealed that 80 °C was
the most efficient temperature (entries 6, 11, and 12, Table 1).
The counteranions on diphenyliodonium salts seemed to have
little effect on the reactions, in which almost same yields were
found (entries 6, 13, and 14, Table 1). It was noteworthy that
this reaction has excellent regioselectivity on the active 2-
position of pyrrole. No C-3 arylated or poly-substitution
product, which was commonly found in the literature,6i,8 was
detected. To rule out the effect of the trace amount of
palladium metal contaminants in NaOH, the quantitative
elemental analysis of NaOH was conducted by ICP-AES to give
the Pd concentration of 0.0366 ppm. Under this concentration
of Pd, palladium dichloride was used to catalyze this reaction
without any base, and the yield of 34% was found, which was
almost identical with the yield in entry 1 (Table 1). This result
implicates that the present reaction is not likely to be catalyzed
by trace palladium contaminants. Unfortunately, the attempt to
reduce the amount of pyrrole only led to a harshly decreased
yield (28%, entry 15, Table 1).
D
considerable attention in the field of cross-coupling
reactions in recent years.1 Transition metal complexes,
especially Pd, Rh, and Ru complexes, played a key role in
most of these reactions. Recently, some cheap and environ-
mentally benign metal catalysts such as iron2 and cobalt3 have
also been developed. However, to avoid the drawbacks of metal
usage such as toxicity and heavy transition metal impurities in
final products, the development of transition-metal-free cross-
coupling reactions is of special importance. Very recently,
significant progresses have been made in direct arylation of C−
H bonds in the absence of transition metal catalyst.4 Hayashi,4a
Shi,4b and Lei's groups4c respectively reported the base-
mediated arylation of benzene with aryl halides in the presence
of 1,10-phenanthroline or N,N′-dimethyl-ethylene diamine.
These findings provided a new strategy for direct C−H cross-
coupling reactions in the absence of transition metal catalyst.
Diaryliodonium salts were used widely in organic synthesis
because of their low toxicity, stability, high reactivity, and
availability. They have been utilized in direct electrophilic
arylation of various nucleophiles and transition-metal-mediated
cross-coupling reactions.5 In recent years, significant progresses
have been made in transition-metal-catalyzed direct arylation of
C−H bonds with diaryliodonium salts.6 However, seeking
relative arylation in the absence of transition metal still remains
a challenge. In 2010, Kita and co-workers reported direct
arylation of electron-rich aromatic compounds with diary-
liodonium salts in the absence of transition metal catalyst.7
More recently, Ackermann and co-workers found that indoles
could be directly arylated with diaryliodonium salts under
metal-free conditions.8 Nevertheless, in these reports, only
some special substrates such as methoxybenzenes and indole
derivatives can provide the cross-coupling products in good
yields. Herein, we wish to report a novel transition metal-free
direct arylation of arene and N-heteroarenes with diary-
liodonium salts.
The substrate scope was subsequently investigated under the
optimized conditions. First, various substituted diaryliodonium
salts were prepared and used for the direct coupling toward
pyrrole. The results listed in Table 2 indicate that diary-
liodonium salts with electron-withdrawing substituents can give
Diaryliodonium salts could be simply prepared by oxidation
Received: October 20, 2011
Published: December 2, 2011
of arenes and aryl iodides.9 To optimize the reaction
© 2011 American Chemical Society
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a
Table 1. C-2 Arylation of Pyrrole with Diphenyliodonium Salt
b
entry
base
X
temp (°C)
yield of 3a (%)
1
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
BF4
80
80
80
80
80
80
80
80
80
80
60
100
80
80
80
32
61
2
K3PO4
Na2CO3
K2CO3
NaHCO3
NaOH
KOH
3
75
4
71
5
60
6
78
7
63
8
t-BuOK
TMEDA
Et3N
68
9
trace
47
10
11
12
13
14
NaOH
NaOH
NaOH
NaOH
NaOH
55
68
78
Br
77
c
15
OTf
28
a
b
c
Reaction conditions: [Ph2I]X (0.2 mmol), 1a (1 mL), base (1.5 equiv), 10 h, under air. Isolated yields. 1a (5 equiv).
a
Table 2. Base-Mediated Arylation of Pyrrole with Diaryliodonium Salts
b
entry
R
X
product
yield (%)
1
H (2a)
OTf
Br
3a
3b
3c
3d
3e
3f
78
91
65
93
71
50
84
76
83
73
73
12
2
4-Cl (2b)
3
4-Br (2c)
Br
4
4-F (2d)
Br
5
4-Me (2e)
OTf
Br
6
4-CH(CH3)2 (2f)
3-NO2 (2g)
7
Br
3g
3h
3i
8
3-COOEt (2h)
2-Me-5-NO2 (2i)
3,4-diMe (2j)
2,4-diMe (2k)
2,4,6-triMe (2l)
Br
9
Br
10
11
12
OTf
OTf
OTf
3j
3k
3l
a
b
Reaction conditions: 2 (0.2 mmol), 1a (1 mL), NaOH (1.5 equiv), 80 °C, 10 h, under air. Isolated yields.
Scheme 1. Intramolecular Competition Experiment
relative products with better yields. Excellent yields of 91 and
93% were achieved for the reactions involving chloro- and
fluoro-groups, respectively (entries 2 and 4, Table 2). The
electron-withdrawing nitro-group also benefits the reaction
(84% yield, entry 7, Table 2), and even the ortho-methyl group
with steric hindrance would not affect the result (entry 9, Table
2). Some alkyl-substitued diaryliodonium salts also gave good
results, and only 2,4,6-trimethyl diphenyliodonium triflate 2l
gave a dramatically decreased yield (entry 12, Table 2). In
addition, intramolecular competition experiments with iodo-
nium salts bearing two different aryl substituents (2m and 2n)
were carried out. As shown in Scheme 1, the cross-coupling
products 3a and 3m were obtained in 33 and 13% yields,
respectively (eq 1, Scheme 1). Moreover, the more electron-
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withdrawing chloro-group showed higher selectivity (eq 2,
Scheme 1). These results suggest that the less electron-rich
group is favored as arylating agent.
Different arenes, including substituted pyrroles, pyridine,
pyrazine, and benzene, were then applied to the coupling
reaction. As shown in Table 3, substituted pyrroles could be 2-
desired product with moderate yield of 50% (entry 9, Table 3).
Although a higher efficiency of this reaction would be desirable,
this might be a promising method for the coupling of
unactivated arenes.
Diaryliodonium salts are known to be able to transform into
aryl radicals via decomposition.10 To get further insight into
our reaction, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
was added to the base-mediated reaction between pyrrole and
diphenyliodonium triflate as a radical scavenger (Scheme 2).
Table 3. Base-Mediated Arylation of Arene Derivatives with
a
Diaryliodonium Salts
Scheme 2. Radical Trapping Experiments
Only trace product was found in the reaction using 1 equiv of
TEMPO, and a considerable amount of byproduct 2,2,6,6-
tetramethyl-1-phenylpiperidine was detected. These results
indicate that radical intermediates were involved in such
reaction. Kita et al have proposed a cationic radical species via
single-electron-transfer (SET) pathway for the TMSOTf-
promoted direct arylation of electron-rich aromatic compounds
with diaryliodonium salts.7 However, in our reaction system, no
homocoupling product of pyrrole was detected, while biphenyl
was observed as byproduct. Besides, as shown in Scheme 2, an
efficient phenyl radical trapping agent 1,1-diphenylethylene was
also added to a reaction (Scheme 2), and the product was
obtained in only 19% yield. This result was consistent with the
aryl radical mechanism.4b
In conclusion, we report here a novel and simple cross-
coupling between an inert aromatic C−H and diaryliodonium
salts in the absence of any added transition metal catalyst. This
direct arylation was promoted only by inorganic base. Some N-
heteroarenes were arylated smoothly to provide target products
in moderate to good yields. Benzene was also found to be
suitable for the coupling. Mechanistic studies suggest that this
reaction is possibly a phenyl radical pathway by decomposition
of the diaryliodonium salts.
a
Reaction conditions: 2 (0.2 mmol), 1 (1 mL), NaOH (1.5 equiv), 80
b
c
d
°C, 10 h, under air. Isolated yields. Reaction under 130 °C. t-
BuONa (1.5 equiv) instead of NaOH, 110 °C. NaHCO3 (1.5 equiv)
instead of NaOH, with TMEDA (3 equiv).
e
arylated smoothly with high regioselectivity (entries 1−3, Table
3). When one of the α-positions of pyrrole was occupied, a
higher reaction temperature was needed. However, if both α,α-
occupied pyrrole were employed, only trace 3-phenyl product
was detected (entry 4, Table 3), indicating that the coupling
has excellent regioselectivity toward the active 2-position of
pyrrole. For pyridine, after preliminary optimization of reaction
conditions, we used t-BuONa instead of NaOH as a base, and
the mixed ortho, meta, and para coupling products were
obtained in a total yield of 58% with the amount ratio of 5:3.7:1
(entry 5, Table 3). Meanwhile, pyrazine could also give phenyl
product with good yield (entry 6, Table 3). Benzene seemed to
be unreactive for this coupling, and diphenyl ether was found as
main byproduct. After optimization of reaction conditions, it
was found that the formation of diphenyl ether could be
inhibited by addition of TMEDA (entries 7−9, Table 3). In the
presence of NaHCO3 instead of NaOH, the coupling between
benzene and di-m-nitrophenyliodonium bromide 2g gave the
EXPERIMENTAL SECTION
■
General Information. All reagents were purchased from
commercial suppliers and used without further purification.
Diaryliodonium salts were prepared according to the literature
procedure.9 1H NMR and 13C NMR spectra were measured on
a NMR spectrometer (400 MHz or 100 MHz, respectively)
with CDCl3 as solvent and recorded in ppm relative to internal
tetramethylsilane standard. Mass spectroscopy data of the
products were collected on GCMS-EI or ESI mass
spectrometers; ICP-AES data of the NaOH was collected on
an ICP-AES.
General Procedure for the Arylation of Pyrrole. A
reflux tube equipped with a magnetic stir bar charged with
diaryliodonium salts 0.2 mmol (2, 1.0 equiv), NaOH (1.5
equiv), pyrrole (1 mL), and the reaction vessel was placed in an
80 °C oil bath. After stirring at this temperature for 10 h, the
mixture was distilled in vacuo to recover the redundant pyrrole.
The residue was cooled to room temperature, diluted with 20
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mL of ethyl acetate, and washed with brine (15 mL) and water
(15 mL), and then the organic layer was dried over Na2SO4.
After being concentrated in vacuo, the crude product was
purified by column chromatography. The identity and purity of
the known product was confirmed by 1H NMR, 13C NMR, and
GC-MS.
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a white solid (yield 65%): 1H NMR (400 MHz, CDCl3) δ 8.44
(s, 1H), 7.49−7.52 (d, 2H, J = 8.4 Hz), 7.34−7.37 (d, 2H, J =
8.4 Hz), 6.85 (s, 1H), 6.51 (s, 1H), 6.30−6.28 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 156.3, 149.8, 138.3, 136.9, 131.9,
128.5, 123.4, 122.4, 120.3; MS (EI) m/z (%) 223 (M+, 98), 221
(100), 142 (12), 115 (46).
2-(4-Fluorophenyl)-1H-pyrrole (3d, known compound, see
ref 2b) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a white solid (yield 93%): 1H NMR (400 MHz, CDCl3) δ 8.35
(s, 1H), 7.40−7.38 (m, 2H), 7.06−7.20 (t, 2H, J = 8.8 Hz),
6.82 (s, 1H), 6.45 (s, 1H), 6.29−6.28 (d, 1H, J = 2.8 Hz); 13C
NMR (100 MHz, CDCl3) δ 162.7, 160.3, 131.3, 129.2, 129.1,
125.6, 125.5, 118.9, 115.9, 115.7, 110.2, 105.9; MS (EI) m/z
(%) 161 (M+, 100), 133 (54).
2-(p-Tolyl)-1H-pyrrole (3e, known compound, see ref 2b)
was obtained following the general procedure, after purification
by flash chromatography (n-hexane/EtOAc 4:1), as a white
solid (yield 71%): 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H),
7.39−7.42 (d, 2H, J = 8 Hz), 7.19−7.22 (d, 2H, J = 8 Hz),
6.86−6.87 (d, 1H, J = 1.2 Hz), 6.50−6.52 (m, 1H), 6.31−6.34
(m, 1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 135.9,
132.3, 130.1, 129.6, 123.9, 118.5, 110.0, 105.4, 21.2; MS (EI)
m/z (%) 157 (M+, 100), 128 (11).
2-(4-Isopropylphenyl)-1H-pyrrole (3f, known compound,
see ref 2b) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a white solid (yield 50%): 1H NMR (400 MHz, CDCl3) δ 8.30
(s, 1H), 7.31−7.34 (d, 2H, J = 8 Hz), 7.14−7.17 (d, 2H, J = 8.4
Hz), 6.75−6.76 (d, 1H, J = 1.6 Hz), 6.39−6.41 (m, 1H), 6.20−
6.22 (d, 1H, J = 3.2 Hz), 2.79−2.87 (m, 1H), 1.17−1.20 (d, 6H,
J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 147.0, 132.3,
130.5, 127.0, 124.0, 118.4, 110.0, 105.5, 33.8, 24.0; MS (EI) m/
z (%) 185 (M+, 66), 170 (100).
2-(3-Nitrophenyl)-1H-pyrrole (3g, known compound, see
ref 2b) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a yellow solid (yield 84%): 1H NMR (400 MHz, CDCl3) δ 8.71
(s, 1H), 8.28 (s, 1H), 8.01−7.99 (m, 1H), 7.78−7.76 (m, 1H),
7.52−7.48 (m, 1H), 6.94 (s, 1H), 6.65 (s, 1H), 6.34−6.33 (d,
1H, J = 2.8 Hz); 13C NMR (100 MHz, CDCl3) δ 148.8, 134.4,
129.8, 129.6, 129.5, 120.6, 120.4, 118.0, 110.7, 108.0; MS (EI)
m/z (%) 188 (M+, 100), 142 (44), 115 (48).
Ethyl 3-(1H-pyrrol-2-yl)benzoate (3h, unknown com-
pound) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a colorless oil (yield 76%): 1H NMR (400 MHz, CDCl3) δ 8.72
(s, 1H), 8.13 (s, 1H), 7.87−7.84 (d, 1H, J = 7.6 Hz), 7.68−7.66
(d, 1H, J = 8 Hz), 7.43−7.38 (m, 1H), 6.88 (s, 1H), 6.59 (s,
1H), 6.31−6.30 (d, 1H, J = 2.4 Hz), 4.42−4.36 (q, 2H), 1.42−
1.38 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 166.7,
133.0, 131.1, 131.0, 128.9, 128.2, 127.0, 124.5, 119.5, 110.3,
106.7, 61.2, 14.4. HRMS (ESI) Calcd for: C13H12NO2,
214.0868. Found: 214.0884.
2-(2-Methyl-5-nitrophenyl)-1H-pyrrole (3i, unknown com-
pound) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a yellow solid (yield 83%): 1H NMR (400 MHz, CDCl3) δ 8.51
(s, 1H), 8.19−8.18 (d, 2H, J = 2 Hz), 7.99−7.96 (m, 1H),
7.39−7.37 (d, 1H, J = 8.4 Hz), 6.95 (s, 1H), 6.45, (s, 1H),
6.37−6.35 (m, 1H), 2.56 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 146.4, 142.6, 134.0, 132.0, 128.8, 122.2, 121.0, 119.5,
General Procedure for the Arylation of Pyridine and
Pyrazine. A reflux tube equipped with a magnetic stir bar
charged with diaryliodonium salts 0.2 mmol (2, 1.0 equiv), t-
BuONa (1.5 equiv), pyridine or pyrazine (1 mL), and the
reaction vessel was placed in a 110 °C oil bath. After stirring at
this temperature for 10 h, the mixture was distilled in vacuo to
recover the redundant pyridine or pyrazine. The residue was
cooled to room temperature, diluted with 20 mL of ethyl
acetate, and washed with brine (15 mL) and water (15 mL),
and then the organic layer was dried over Na2SO4. After being
concentrated in vacuo, the crude product was purified by
column chromatography. The identity and purity of the known
1
product was confirmed by H NMR, 13C NMR, and GC-MS.
General Procedure for the Arylation of Benzene. A
reflux tube equipped with a magnetic stir bar charged with
diaryliodonium salts 0.2 mmol (2, 1.0 equiv), NaHCO3 (1.5
equiv), TMEDA (3 equiv), benzene (1 mL), and the reaction
vessel was placed in an 80 °C oil bath. After stirring at this
temperature for 10 h, the mixture was distilled in vacuo to
recover the redundant benzene. The residue was cooled to
room temperature, diluted with 20 mL of ethyl acetate, and
washed with brine (15 mL) and water (15 mL), and then the
organic layer was dried over Na2SO4. After being concentrated
in vacuo, the crude product was purified by column
chromatography. The identity and purity of the known product
1
was confirmed by H NMR, 13C NMR, and GC-MS.
Investigation of Radical Scavenger Effect. Following
the general procedure using diphenyliodonium salt (0.2 mmol),
2,2,6,6-tetramethyl-1-piperridinyloxy (free radical, TEMPO, 50
mol % and 100 mol %, respectively), NaOH (1.5 equiv), and
pyrrole (1 mL) at 80 °C for 10 h, decreased yields of 17 and
less than 3% were obtained, respectively.
Following the general procedure using diphenyliodonium salt
(0.2 mmol), 1,1-diphenylethylene (1 equiv), NaOH (1.5
equiv), and pyrrole (1 mL) at 80 °C for 10 h, the product
was detected in 19% yield.
2-Phenyl-1H-pyrrole (3a, known compound, see ref 2b) was
obtained following the general procedure, after purification by
flash chromatography (n-hexane/EtOAc 4:1), as a white solid
1
(yield 78%): H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H),
7.45−7.47 (m, 2H), 7.34−7.39 (m, 2H), 7.18−7.23 (m, 1H),
6.85−6.88 (d, 1H, J = 8 Hz), 6.51−6.54 (m, 1H), 6.29−6.32 (d,
1H, J = 8 Hz); 13C NMR (100 MHz, CDCl3) δ 132.8, 132.1,
128.9, 126.2,123.9, 118.9, 110.1, 105.9; MS (EI) m/z (%) 143
(M+, 100), 115 (45).
2-(4-Chlorophenyl)-1H-pyrrole (3b, unknown compound)
was obtained following the general procedure, after purification
by flash chromatography (n-hexane/EtOAc 4:1), as a white
solid (yield 91%): 1H NMR (400 MHz, CDCl3) δ 8.28 (s, 1H),
7.29−7.26 (d, 2H, J = 8.4 Hz), 7.24−7.21 (d, 2H, J = 8.4 Hz),
6.75 (s, 1H), 6.42 (s, 1H), 6.22−6.20 (d, 1H, J = 2.8 Hz); 13C
NMR (100 MHz, CDCl3) δ 131.7, 131.3, 131.0, 129.1, 125.0,
119.3, 110.3, 106.4; MS (EI) m/z (%) 179 (M+, 35), 177
(100), 142 (9), 115 (43). HRMS (ESI) Calcd for: C10H9ClN,
178.0424. Found: 178.0421.
2-(4-Bromophenyl)-1H-pyrrole (3c, known compound, see
ref 2b) was obtained following the general procedure, after
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110.5, 109.9, 21.7. HRMS (ESI) Calcd for: C11H9N2O2,
201.0664. Found: 201.0675.
(yield 71%): 1H NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 8.63
(s, 1H), 8.50 (s, 1H), 8.03−8.01 (d, 2H, J = 7.6 Hz), 7.54−7.45
(m, 3H); 13C NMR (100 MHz, CDCl3) δ 152.9, 144.2, 142.9,
142.2, 136.4, 129.9, 129.1, 127.0; MS (EI) m/z (%) 156 (M+,
100), 129 (11), 103 (59), 76 (12).
1,1′-Biphenyl (4h, known compound, see ref 4b) was
obtained following the general procedure, after purification by
flash chromatography (n-hexane), as a white solid (yield 31%):
1H NMR (400 MHz, CDCl3) δ 7.58−7.61 (d, 4H, J = 8 Hz),
7.41−7.46 (m, 4H), 7.32−7.36 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 141.3, 128.8, 127.3, 127.2; MS (EI) m/z (%) 154
(M+, 100), 76 (10).
2-(3,4-Dimethylphenyl)-1H-pyrrole (3j, unknown com-
pound) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
1
a pale pink solid (yield 73%): H NMR (400 MHz, CDCl3) δ
8.36 (s, 1H), 7.23−7.18 (m, 2H), 7.12−7.10 (d, 1H, J = 8 Hz),
6.81 (s, 1H), 6.46, (s, 1H), 6.28−6.27 (d, 1H, J = 2.8 Hz), 2.28
(s, 3H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.0,
134.6, 132.4, 130.5, 130.1, 125.4, 121.4, 118.3, 109.9, 105.3,
19.9, 19.4; MS (EI) m/z (%) 171 (M+, 100), 156 (29), 143
(17), 128 (24). HRMS (ESI) Calcd for: C12H14N, 172.1126.
Found: 172.1129.
4-Fluoro-1,1′-biphenyl (4i, known compound, see ref 4b)
was obtained following the general procedure, after purification
by flash chromatography (n-hexane), as a white solid (yield
2-(2,4-Dimethylphenyl)-1H-pyrrole (3k, known com-
pound, see ref 11) was obtained following the general
procedure, after purification by flash chromatography (n-
1
21%): H NMR (400 MHz, CDCl3) δ 7.56−7.52 (m, 4H),
1
hexane/EtOAc 4:1), as a colorless oil (yield 73%): H NMR
7.45−7.41 (m, 2H), 7.36−7.32 (m, 1H), 7.14−7.12 (d, 2H, J =
8.8 Hz); 13C NMR (100 MHz, CDCl3) δ 162.3, 140.3, 133.1,
128.8, 128.7, 128.6, 127.2, 127.0, 115.7, 115.5; MS (EI) m/z
(%) 171 (M+, 100).
(400 MHz, CDCl3) δ 8.21 (s, 1H), 7.24−7.22 (d, 1H, J = 7.6
Hz), 7.07 (s, 1H), 7.04−7.01 (d, 1H, J = 7.6 Hz), 6.84−6.83 (d,
1H, J = 2 Hz), 6.30−6.29 (d, 2H, J = 2 Hz), 2.41 (s, 3H), 2.33
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 136.5, 135.0, 131.8,
131.4, 130.1, 128.0, 126.7, 117.6, 109.1, 108.4, 21.1, 21.0; MS
(EI) m/z (%) 171 (M+, 100), 156 (27), 143 (17), 128 (22).
1-Methyl-2-phenyl-1H-pyrrole (4b, known compound, see
ref 2b) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 10:1),
3-Nitro-1,1′-biphenyl (4j, known compound, see ref 2a) was
obtained following the general procedure, after purification by
flash chromatography n-hexane/EtOAc 10:1), as a yellow solid
1
(yield 50%): H NMR (400 MHz, CDCl3) δ 8.45−8.47 (m,
1H), 8.23−8.26 (d, 1H, J = 8.4 Hz), 7,91−7.93 (d, 1H, J = 8
Hz), 7.61−7.65 (m, 3H), 7.41−7.51 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 149.0, 143.0, 138.8, 133.2, 129.8, 128.7, 127.3,
122.2, 122.1; MS (EI) m/z (%) 199 (M+, 100), 152 (89), 76
(9).
1
as a colorless oil (yield 69%): H NMR (400 MHz, CDCl3) δ
7.40 (m, 4H), 7.29−7.31 (m, 1H), 6.70−6.72 (m, 1H), 6.20−
6.23 (m, 2H), 3.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
134.6, 133.4, 128.7, 128.4, 126.7, 123.6, 108.7, 107.8, 35.1; MS
(EI) m/z (%) 157 (M+, 100), 115 (19).
2-Methyl-5-phenyl-1H-pyrrole (4c, known compound, see
ref 2b) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a white solid (yield 67%): 1H NMR (400 MHz, CDCl3) δ 8.11
(s, 1H), 7.40−7.43 (d, 2H, J = 7.6 Hz), 7.30−7.35 (m, 2H),
7.13−7.17 (m, 1H), 6.38−6.41 (m, 1H), 5.94 (s, 1H), 2.32 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 133.0, 130.8, 129.1,
128.8, 125.7, 123.4, 108.0, 106.2, 13.2; MS (EI) m/z (%) 157
(M+, 100), 128 (6).
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Optimization of reaction conditions, reaction mechanism, H
and 13C NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: xqyu@scu.edu.cn (X.-Q.Y.); ji_zhang@163.com
(J.Z.).
■
3,5-Dimethyl-2-phenyl-1H-pyrrole (4d, known compound,
see ref 2b) was obtained following the general procedure, after
purification by flash chromatography (n-hexane/EtOAc 4:1), as
a red solid (yield 53%): 1H NMR (400 MHz, CDCl3) δ 7.81 (s,
1H), 7.36−7.39 (m, 4H), 7.19−7.21 (m, 1H), 5.82 (s, 1H),
2.29 (s, 3H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
133.9, 128.6, 127.5, 126.7, 125.9, 125.5, 116.5, 110.3, 13.0, 12.5;
MS (EI) m/z (%) 170 (M+, 100), 156 (10), 128 (7).
2-Phenylpyridine (4f, known compound, see ref 12) and 3-
phenylpyridine (4f′, known compound, see ref 12) were
obtained following the general procedure, after purification by
flash chromatography (n-hexane/EtOAc 10:1), both as white
ACKNOWLEDGMENTS
■
This work was financially supported by the National Science
Foundation of China (No. 20725206, 20732004, and
21021001), Program for Changjiang Scholars and Innovative
Research Team in University, the Key Project of Chinese
Ministry of Education in China, and Scientific Fund of Sichuan
Province for Outstanding Young Scientists. We also thank the
Sichuan University Analytical and Testing Center for NMR
spectroscopic analysis.
1
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■
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