Decarboxylative Hydroamination of 3-Arylpropiolic Acids with N-Heterocycles under Transition-Metal-Free Conditions

Article abstract of DOI:10.1055/s-0033-1338622

A decarboxylative hydroamination cascade reaction of 3-arylpropiolic acids with N-heterocycles under transition-metal-free conditions was developed. 3-Arylpropiolic acids were found to react smoothly with a range of N-heterocycles under the effect of t-BuOK to afford N-vinyl heterocycles in moderate to excellent yields. This reaction represents the first decarboxylative hydroamination of 3-arylpropiolic acids without the aid of a transition-metal catalyst. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1338622

PAPER
▌2057
paper
Decarboxylative Hydroamination of 3-Arylpropiolic Acids with N-Hetero-
cycles under Transition-Metal-Free Conditions
Decarboxylative Hydroamination of 3-Arylpropiolic Acid
Xixian Pan,a Xiaolong Wan,b,c Xin Yu,a Hui Zhang,*a Weiqing Xie*c
a
Department of Chemistry, School of Science & Instrumental Analysis and Research Center, Shanghai University, No. 99, Shangda Road,
Shanghai 200444, P. R. of China
Fax +86(21)66134856; E-mail: yehao7171@shu.edu.cn
b
School of Materials Science and Engineering, Shanghai University, No. 99, Shangda Road, Shanghai 200444, P. R. of China
c
State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: xiewq@mail.sioc.ac.cn
Received: 28.02.2014; Accepted after revision: 25.03.2014
vent of transition-metal catalysts, decarboxylative trans-
Abstract: A decarboxylative hydroamination cascade reaction of
formations of propiolic acid witnessed significant
3-arylpropiolic acids with N-heterocycles under transition-metal-
development not only because of its milder reaction con-
ditions but also because of the diverse range of subsequent
free conditions was developed. 3-Arylpropiolic acids were found to
react smoothly with a range of N-heterocycles under the effect of
t-BuOK to afford N-vinyl heterocycles in moderate to excellent cascade reactions that can involve the transition-metal
catalyst.1,2 Despite these tremendous advances, transition
metals (Pd, Cu or Ag) have, in all cases, been required to
facilitate the decarboxylation and cross-coupling reaction.
However, the use of transition-metal catalysts also has
yields. This reaction represents the first decarboxylative hydroami-
nation of 3-arylpropiolic acids without the aid of a transition-metal
catalyst.
Key words: alkynes, decarboxylation, hydroamination, N-vinyl
heterocycle, potassium tert-butoxide
several disadvantages. High catalyst loading in the decar-
boxylation reaction usually leads to high economic cost,
and further purification procedures are often required to
In recent years, tremendous achievements have been
made by using carboxylic acids as nucleophiles or electro-
philes in C–C bond formation reactions by decarbonyl-
ative or decarboxylative processes.1 Compared with
traditional organometallic reagents, carboxylic acids have
several advantages such as easy availability and stability
to air and moisture. Therefore, transition-metal-catalyzed
cross-coupling through decarboxylative processes involv-
ing carboxylic acids holds an important position in C–C
formation reactions.1 As the equivalent of aryl acetylene
metal species, propiolic acids could participate in various
decarboxylative cross-coupling reactions including sp–
sp3, sp–sp2, and sp–sp C–C and C–heteroatom bond-
formation reactions (Scheme 1).2 In most cases, propiolic
acid is used as an equivalent of alkynyl organometallic
species to participate in various cross-coupling reactions,
and the alkyne moiety remains intact at the end of reac-
tion. Little attention has been paid to decarboxylative cas-
cade reactions involving transformations of the alkyne
functionality.2 To the best of our knowledge, only one ex-
ample has described the decarboxylative hydrosulfination
reaction of 3-arylpropiolic acid with thiol in the presence
of a Cu catalyst.2s
remove metallic contaminants from the product. There-
fore, decarboxylative cross-coupling of propiolic acid
without the need for a transition-metal catalyst remains
highly desirable. In this work, we disclosed the first decar-
boxylative hydroamination of 3-arylpropiolic acids under
transition-metal-free conditions,4 which represents the
first example of decarboxylation hydroamination of 3-ar-
ylpropiolic acid to take place only in the presence of
t-BuOK (Scheme 1).
decarboxylative cross-coupling:
Pd, Cu, or Ag
R
CO2H
cross-couplings
2
1a
(ref. 3)
R = alkyl, aryl, alkynyl, heteroatoms
decarboxylative hydromination:
X
X
X
t-BuOK
N-heterocycle
N
CO2H
X
1
3
(this work)
♦ transition-metal-free
♦ decarboxylative hydramination cascscade reaction
Scheme 1 Decarboxylative cross-coupling and decarboxylative hy-
droamination of 3-arylpropiolic acid
Although it has long been known that decarboxylation of
3-arylpropiolic acid could be effected by heating in ani-
line at high temperature (over 160 °C), its application is
hampered by the harsh reaction conditions.3 With the ad-
This reaction provides a new entry to N-vinyl heterocy-
cles, which are valuable synthetic intermediates.5 For ex-
ample, N-vinylimidazole is a common scaffold found in
various antifungal reagents and exhibits excellent antifun-
gal and antiparasitic activities.5a–c N-Vinylimidazole has
also found wide application in the synthesis of metal com-
SYNTHESIS 2014, 46, 2057–2064
Advanced online publication: 23.04.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338622; Art ID: SS-2014-H0142-OP
© Georg Thieme Verlag Stuttgart · New York

2058
X. Pan et al.
PAPER
plexes, various heterocycles, and poly(N-vinylimid- tion), affording 3a in 99% yield, albeit with poor
azole).5d–h
stereoselectivity (Z/E, 2.7:1). Interestingly, when the re-
action was carried out in the absence of any transition
metal, 3a could also be obtained in 90% yield with almost
the same stereoselectivity (Table 1, entry 7). Omitting the
base from the reaction only resulted in recovery of starting
materials (Table 1, entry 8), and the use of extra pure t-
BuOK also gave a comparable yield (Table 1, entry 9),
which excluded the action of transition-metal impurities
in this reaction.6 We then optimized the reaction under
transitional-metal-free conditions. Interestingly, the use
of other tert-butoxide salts (t-BuONa and t-BuOLi) gave
only negligible amounts of product (Table 1, entries 10
and 11). However, Cs2CO3 was also an effective base,
providing 3a in 80% yield with slightly improved stereo-
selectivity (Z/E, 4:1; Table 1, entry 12). Although excel-
lent regioselectivity (12:1) was obtained by using KOH as
base, the desired product was isolated in only 21% yield
(Table 1, entry 13). The use of stronger bases (LiHMDS,
NaHMDS and KHMDS) gave inferior yields (Table 1, en-
tries 14–16). The yields of this reaction were also strongly
dependant on the amount of t-BuOK employed (Table 1,
entries 17 and 18). The use of either more or less than two
equivalents of t-BuOK resulted in reduced yields. Further-
more, conducting the reaction at either higher or lower
temperature was not beneficial for the reaction, and only
reduced yields were obtained in either case (Table 1, en-
tries 19 and 20).
Table 1 Optimization of the Decarboxylative Hydroamination of 2-
Phenylpropiolic Acid with Imidazolea
N
N
NH
CO2H
+
N
1a
3a
Entry Metal
Base (equiv)
Solvent
Temp Yield Z/Ed
(°C)
(%)c
1
2
CuIb
CuIb
CuIb
t-BuOK (1.5)
Cs2CO3 (1.5)
t-BuOK (1.5)
t-BuOK (1.5)
Cs2CO3 (1.5)
t-BuOK (2.0)
t-BuOK (2.0)
–
DMF
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
130
100
24
56
73
35
53
99
90
n.r.
89
trace
5
n.d.
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
n.d.
n.d.
3
4
Ag2SO4
n.d.
b
b
5
Ag2SO4
n.d.
2.7:1
2.0:1
6
Ag2SO4
7
–
–
–
–
–
–
–
–
–
–
–
–
–
–
8
9
t-BuOK (2.0)e
t-BuOLi (2.0)
1.6:1
10
11
12
13
14
15
16
17
18
19
20
t-BuONa (2.0) DMSO
n.d.
4:1
After identification of the optimal reaction conditions, the
substrate scope of the reaction was evaluated by using a
range of 3-arylpropiolic acids and N-heterocycles. Phenyl
propiolic acid reacted smoothly with various N-heterocy-
cles to afford the corresponding N-vinyl heterocycles in
moderate to good yields (Table 2, entries 1–10). The ste-
reoselectivity of this reaction depended on the electronic
properties of the N-heterocycle used. A slight excess of
the E-isomer was isolated when heterocycles with one ni-
trogen atom was used, except pyrazole (Table 2, entries
1–3). In contrast, the Z-isomer was found to be the major
product when other N-heterocycles with more than one ni-
trogen atom were used (Table 2, entries 2–8). The effect
of substituents of the 3-arylpropiolic acid on this decar-
boxylative hydroamination process was also evaluated
(Table 2, entries 9–22). 3-Arylpropiolic acids with elec-
tron-rich or electron-deficient substituents could partici-
pate in this cascade reaction with good to excellent yields
(Table 2, entries 9–22). Electron-rich 3-arylpropiolic
acids favored the formation of Z isomers (Table 2, entries
9–16), whereas electron-deficient propiolic acids predom-
inantly afforded the E-isomer (Table 2, entries 17–22). It
is noteworthy that excellent stereoselectivities (E/Z
>12:1) were obtained when 2-halophenylpropiolic acids
reacted with imidazole (Table 2, entries 17–19).
Cs2CO3 (2.0)
KOH (2.0)
DMSO
DMSO
80
21
49
trace
21
32
13
57
64
12:1
1:1.6
LiHMDS (2.0) DMSO
NaHMDS (2.0) DMSO
KHMDS (2.0)
t-BuOK (3.0)
t-BuOK (1.2)
t-BuOK (2.0)
t-BuOK (2.0)
DMSO
DMSO
DMSO
DMSO
DMSO
n.d.
1.4:1
10:1
2:1
4:1
a Reaction conditions: 1a (0.6 mmol), imidazole (0.5 mmol), base,
solvent (2 mL), 24 h.
b Using (±)-N,N′-dimethyl-1,2-cyclohexanediamine (0.1 equiv) as li-
gand.
c Isolated yield.
d Ratio was determined by 1H NMR spectroscopic analysis.
e Using 99.99% t-BuOK as base
In the initial study, we were interested in the decarboxyl-
ative cross-coupling of 2-phenylpropiolic acid (1a) with
imidazole under the effect of copper catalyst to prepare N-
alkynyl imidazole. To our surprise, we only obtained N-
vinyl imidazole 3a instead of the desired N-alkynyl imid-
azole (Table 1, entries 1–3 and the Supporting Informa-
tion). Further screening of the reaction conditions
revealed that Ag2SO4 was the best catalyst for this reac-
tion (Table 1, entries 4–6 and the Supporting Informa-
To gain some insights into the reaction pathway of this de-
carboxylative hydroamination process, several control re-
actions were carried out. In the absence of imidazole,
phenylacetylene was observed by GC to form in 25%
yield when 2-phenylpropiolic acid was subjected to the
Synthesis 2014, 46, 2057–2064
© Georg Thieme Verlag Stuttgart · New York

PAPER
Decarboxylative Hydroamination of 3-Arylpropiolic Acid
2059
standard reaction conditions (Scheme 2, equation 1).7 On In conclusion, decarboxylative hydroamination of 3-aryl-
the other hand, when phenylacetylene reacted with imid- propiolic acids with N-heterocycles has been developed
azole in the presence of 1.1 equivalents of t-BuOK, N- under transition-metal-free conditions. This decarboxyla-
styrylimidazole (3a) could be isolated in 35% yield (Z/E = tive hydroamination process was found to be compatible
1:3; Scheme 2, equation 2).8 The results of these two con- with a range of 3-arylpropiolic acids and N-heterocycles
trol reactions indicate that phenylacetylene might be a re- to produce valuable N-vinyl heterocycles. According to
action intermediate. Based on those observations, we the results of initial mechanistic studies, decarboxylation
propose that this reaction proceeds through decarboxyl- of 3-arylpropiolic acids followed by hydroamination of
ation of 2-phenylpropiolic acid under the effect of the resulting acetylene mediated by t-BuOK is proposed
t-BuOK to afford phenylacetylene, which is captured by for the reaction pathway.
hydroamination with the N-heterocycle to afforded the
corresponding N-vinyl heterocycle.
Table 2 Substrate Scope of the Decarboxylative Hydroamination of 3-Arylpropiolic Acid with N-Heterocyclesa
X
X
X
X
X
N
X
HN
t-BuOK, DMSO
X
+
CO2H
X
R
120 °C
R
1
2
3
Entry
R
Heterocycle (equiv)
3
Yield (%)b
Z/Ec
1
2
H
pyrrole
3b
3c
3d
3e
3f
86
83
91
65
74
75
68
75
86
87
89
91
91
98
62
50
98
98
99
90
96
85
1:2.7
1:1.4
1:1.3
3.7:1
3.8:1.7:2.0:1
1.6:1
6.6:1
1.6:1
2.3:1
1:1.6
2.3:1
1.6:1
10:1
indole
3
pyrazole
4
2-phenylimidazole
4-methylimidazole
benzimidazole
1,2,4-trizole
benzotriazole
imidazole
pyrazole
5
6
3g
3h
3i
7
8
9
2-Me
3-Me
4-Me
3j
10
11
12
13
14
15
16
17
18
19
20
21
22
3k
3l
imidazole
pyrazole
3m
3n
3o
3p
3q
3r
3s
imidazole
pyrazole
3:1
2-MeO
4-MeO
2-Cl
imidazole
imidazole
imidazole
pyrazole
3.8:1
19:1
1:18
E only
1:12
2-Br
4-Br
imidazole
pyrazole
3t
3u
3v
3w
1:3.5
1:1.9
1:1.6
imidazole
pyrazole
a Reaction conditions: 1 (0.6 mmol), 2 (0.5 mmol), base (1.0 mmol), DMSO (2 mL), 120 °C, 24 h.
b Isolated yield.
c Ratio was determined by 1H NMR spectroscopic analysis.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2057–2064

2060
X. Pan et al.
PAPER
control reaction:
t-BuOK (2.2 equiv), DMSO
(1)
(2)
CO2H
120 °C, 8 h
1a
25% by GC
N
t-BuOK (1.1 equiv), DMSO
N
N
Ph
+
HN
120 °C, 12 h
3a
35%, Z/E 1:3
reaction pathway:
t-BuOK
t-BuOK
N
N
CO2H
Ph
N
3a
HN
CO2
1a
Scheme 2 Control reaction and proposed mechanism
Unless otherwise noted, all commercially available reagents were
obtained from commercial suppliers and used without further puri-
fication. Solvents were purified by standard methods and stored
over molecular sieves. All reactions were performed using oven-
dried glassware under a nitrogen atmosphere. Organic solutions
were concentrated with a Büchi rotary evaporator. Column chroma-
tography was carried out over silica gel (40–60 μm, 230–400 mesh,
Silicycle P60) and TLC was performed using Merck 60 F254 pre-
coated silica gel plates. 1H and 13C NMR spectra were recorded with
a Mercury spectrometer in CDCl3/DMSO-d6 using TMS as internal
reference with chemical shift values being reported in ppm. Chem-
ical shifts for 1H NMR spectra are reported in ppm relative to TMS.
The following abbreviations are used to indicate multiplicities:
s = singlet, d = doublet, t = triplet, dd = doublet of doublets,
dq = doublet of quartets, m = multiplet. All coupling constants (J)
are reported in hertz (Hz). Mass spectra were recorded with a Shi-
madzu LCMS-2010EV mass spectrometer (ESI). High-resolution
mass spectra were recorded with an Ion Spec 4.7 Tesla FTMS mass
spectrometer (MALDI) or a Bruker APEXIII 7.0 TESLA FTMS
(ESI).
(E)-1-Styryl-1H-imidazole [(E)-3a]
Yield: 26 mg (30%); pale-yellow solid; mp 83–85 °C.
IR (acetone): 3107, 2923, 1659, 1487, 939, 755, 732, 668, 655 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.77 (s, 1 H), 7.43–7.29 (m, 7 H),
7.16 (s, 1 H), 6.76 (d, J = 14.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 136.4, 134.4, 130.5, 128.9, 128.1,
126.2, 122.7, 118.9, 116.3.
MS (ESI): m/z = 171.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C11H11N2: 171.0917; found:
171.0919.
(Z)-1-Styryl-1H-pyrrole [(Z)-3b]
Yield: 20 mg (23%); colorless oil.
IR (acetone): 2923, 1714, 668 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.29–7.16 (m, 5 H), 6.70 (d,
J = 11.5 Hz, 1 H), 6.63 (t, J = 2.5 Hz, 2 H), 6.13 (t, J = 2.5 Hz, 2 H),
6.08 (d, J = 11.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 135.2, 128.92, 128.87, 128.6,
Decarboxylative Hydroamination; General Procedure
3-Arylpropiolic acid 1 (0.5 mmol, 1.2 equiv), heterocycle 2 (0.6
mmol, 1.0 equiv), and t-BuOK (10.0 mmol, 2.0 equiv) were added
to a dried test tube. The tube was sealed with a septum and purged
with N2 three times. DMSO (2 mL) was added by using a syringe at
r.t. under N2 atmosphere. The resulting mixture was heated to
120 °C and stirred for 24 h. After cooling to r.t., H2O was added to
the reaction mixture, and the aqueous layer was extracted three
times with EtOAc. The organic layers were combined, dried over
Na2SO4, and concentrated in vacuo. The residue was purified by
column chromatography (petroleum ether–EtOAc) to provide the
desired product 3.
128.5, 127.7, 126.5, 121.0, 118.4, 109.6.
MS (ESI): m/z = 170.2 [M + H]+.
(E)-1-Styryl-1H-pyrrole [(E)-3b]
Yield: 54 mg (63%); brown solid; mp 96–98 °C.
IR (acetone): 1659, 1483, 939, 726 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.41 (d, J = 7.5 Hz, 2 H), 7.38 (t,
J1 = 2.0 Hz, J2 = 5.5 Hz, 2 H), 7.33 (d, J = 15.0 Hz, 1 H), 7.28–7.25
(m, 1 H), 7. 02 (t, J = 2.0 Hz, 2 H), 6. 63 (d, J = 14.5 Hz, 1 H), 6.32
(t, J = 2.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 135.7, 128.8, 127.03, 126.95,
125.8, 119.1, 114.3, 110.5.
MS (ESI): m/z = 170.1 [M + H]+.
(Z)-1-Styryl-1H-imidazole [(Z)-3a]
Yield: 51 mg (60%); pale-yellow liquid.
IR (acetone): 3109, 3055, 1658, 1492, 1447, 1073, 696 cm–1.
HRMS (EI): m/z [M – H]+ calcd for C11H10N2: 168.0808; found:
1H NMR (500 MHz, CDCl3): δ = 7.47 (s, 1 H), 7.31–7.27 (m, 3 H),
7.12–7.10 (m, 2 H), 7.04 (s, 1 H), 6.86 (s, 1 H), 6.74 (d, J = 9.5 Hz,
1 H), 6.36 (d, J = 9.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 137.0, 133.7, 129.6, 128.8, 128.5,
128.3, 123.36, 123.38, 118.5.
MS (ESI): m/z = 171.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C11H11N2: 171.0917; found:
168.0815.
(Z)-1-Styryl-1H-indole [(Z)-3c]
Yield: 38 mg (35%); pale-white solid; mp 77–79 °C.
IR (acetone): 3054, 1647, 1460, 742 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.64 (d, J = 7.5 Hz,1 H), 7.39 (d,
J = 8.0 Hz,1 H), 7.28–7.17 (m, 7 H), 7.04 (d, J = 3.0 Hz, 1 H), 6.98
(d, J = 9.5 Hz, 1 H), 6.51 (d, J = 3.5 Hz, 1 H), 6.30 (d, J = 9.0 Hz,
1 H).
171.0921.
Synthesis 2014, 46, 2057–2064
© Georg Thieme Verlag Stuttgart · New York

PAPER
Decarboxylative Hydroamination of 3-Arylpropiolic Acid
2061
13C NMR (125 MHz, CDCl3): δ = 135.9, 135.0, 128.7, 128.6, 128.4,
127.5, 127.1, 123.3, 122.4, 120.9, 120.7, 119.6, 110.1, 103.9.
MS (ESI): m/z = 220.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C16H14N+: 220.1121; found:
1H NMR (500 MHz, CDCl3): δ = 7.68 (d, J = 6.5 Hz, 2 H), 7.50–
7.47 (m, 3 H), 7.41 (s, 2 H), 7.49–7.36 (m, 5 H), 7.24 (s, 1 H), 6.79
(d, J = 14.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 129.6, 129.3, 129.2, 128.9, 128.8,
128.7, 128.6, 124.4, 125.1, 126.3, 123.7, 120.2, 117.7.
220.1122.
MS (ESI): m/z = 247.2 [M + H]+.
(E)-1-Styryl-1H-indole [(E)-3c]
Yield: 66 mg (60%); white solid; mp 120–122 °C.
IR (acetone): 1649, 1459, 933, 718, 694 cm–1.
+
HRMS (ESI): m/z [M + H]+ calcd for C17H15N2 : 247.1230; found:
247.1222.
1H NMR (500 MHz, DMSO-d6): δ = 8.11 (d, J = 15.0 Hz, 1 H),
7.96–7.95 (m, 2 H), 7.64–7.60 (m, 3 H), 7.37 (t, J = 7.5 Hz, 2 H),
7.27–7.21 (m, 2 H), 7.13 (t, J = 7.5 Hz, 1 H), 6.96 (d, J = 15.0 Hz,
1 H), 6.72 (d, J = 3.0 Hz, 1 H).
4-Methyl-1-styryl-1H-imidazole and 5-Methyl-1-styryl-1H-im-
idazole (3f)
Obtained as a mixture of four stereoisomers 0.7:1.4:1.1:1.0.
Yield: 68 mg (74%); pale-yellow liquid.
1H NMR (500 MHz, CDCl3): δ = 7.79 (s, 0.62 H), 7.63 (s, 1 H),
7.43–7.24 (m, 19 H), 7.18 (s, 0.36 H), 7.16–7.14 (m, 2 H), 7.00 (s,
1.35 H), 6.98–6.96 (m, 1.81 H), 6.84 (d, J = 8.0 Hz, 1.50 H), 6.77
(d, J = 14.5 Hz, 0.72 H), 6.67 (d, J = 2.5 Hz, 1 H), 6.64 (d,
J = 8.0 Hz, 1 H), 6.58–6.56 (m, 2 H), 6.51 (d, J = 9.5 Hz, 1 H), 6.26
(d, J = 9.0 Hz, 1 H), 2.29 (d, J = 1.0 Hz, 2.16 H), 2.27 (s, 4.26 H),
2.18 (s, 3.24 H), 2.13 (d, J = 1.0 Hz, 3 H).
13C NMR (125 MHz, DMSO-d6): δ = 136.7, 135.9, 129.1, 128.8,
127.0, 126.3, 124.8, 124.3, 123.0, 121.23, 121.20, 113.7, 111.0,
105.7.
MS (ESI): m/z = 220.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C16H14N+: 220.1121; found:
220.1125.
13C NMR (100 MHz, CDCl3): δ = 139.4, 136.7, 136.2, 136.1, 134.4,
128.96, 128.92, 128.9, 128.8, 128.7, 128.54, 128.47, 128.4, 128.3,
128.0, 126.4, 126.2, 126.1, 122.5, 122.2, 120.5, 118.5, 115.1, 112.8,
13.5, 13.3, 9.6, 9.2.
(Z)-1-Styryl-1H-pyrazole [(Z)-3d]
Yield: 34 mg (40%); pale-yellow oil.
IR (acetone): 2925, 1654, 1400, 752, 696 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.60 (d, J = 1.5 Hz, 1 H), 7.34–
7.27 (m, 4 H), 7.22 (d, J = 1.5 Hz, 1 H), 7.20 (s, 1 H), 7.03 (d,
J = 10.0 Hz, 1 H), 6.27 (d, J = 9.5 Hz, 1 H), 6.21 (t, J = 1.5 Hz,
1 H).
MS (ESI): m/z = 185.3 [M + H]+.
+
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
185.1071.
13C NMR (125 MHz, CDCl3): δ = 140.3, 134.4, 129.5, 128.7, 128.6,
127.9, 127.0, 119.0, 106.6.
(Z)-1-Styryl-1H-benzo[d]imidazole [(Z)-3g]
Yield: 50 mg (45%); pale-yellow solid; mp 115–116 °C.
MS (ESI): m/z = 171.0 [M + H]+.
IR (acetone): 1484, 764, 696 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C11H10N2Na: 193.0742;
found: 193.0737.
1H NMR (500 MHz, CDCl3): δ = 7.83–7.81 (m, 2 H), 7.37–7.30 (m,
3 H), 7.24 (t, J = 3.0 Hz, 3 H), 7.10–7.08 (m, 2 H), 6.87 (d,
J = 9.5 Hz, 1 H), 6.59 (d, J = 8.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 143.2, 142.0, 133.6, 133.0, 128.8,
128.48, 128.46, 125.4, 123.6, 122.8, 120.40, 120.31, 110.3.
(E)-1-Styryl-1H-pyrazole [(E)-3d]
Yield: 44 mg (51%); pale-yellow oil.
IR (acetone): 1896, 1392, 745, 692 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.69–7.68 (m, 1 H), 7.53 (d,
J = 14.5 Hz, 1 H), 7.45 (s, 1 H), 7.44 (s, 1 H), 7.37 (t, J = 7.5 Hz,
2 H), 7.29–7.26 (m, 1 H), 7.07 (d, J = 14.5 Hz, 1 H), 6.41 (t,
J = 2.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 141.1, 135.0, 128.8, 127.9, 127.6,
126.4, 126.2, 117.0, 107.3.
MS (ESI): m/z = 221.1 [M + H]+.
+
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2 : 221.1073; found:
221.1076.
(E)-1-Styryl-1H-benzo[d]imidazole [(E)-3g]
Yield: 32 mg (29%); pale-yellow solid; mp 85–87 °C.
IR (acetone): 1488, 1458, 741 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.27 (s, 1 H), 7.87 (d, J = 7.5 Hz,
1 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.55 (d, J = 14.5 Hz, 1 H), 7.50 (d,
J = 7.5 Hz, 2 H), 7.44–7.34 (m, 5 H), 7.01 (d, J = 14.5 Hz, 1 H).
MS (ESI): m/z = 171.0 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C11H10N2Na: 193.0742;
found: 193.0738.
13C NMR (125 MHz, CDCl3): δ = 140.8, 134.6, 129.0, 128.5, 128.2,
126.2, 124.0, 123.7, 123.2, 121.3, 120.8, 120.2, 110.4.
MS (ESI): m/z = 221.1 [M + H]+.
(Z)-2-Phenyl-1-styryl-1H-imidazole [(Z)-3e]
Yield: 63 mg (51%); pale-yellow liquid.
IR (acetone): 3058, 2924, 1468, 772, 694 cm–1.
+
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2 : 221.1073; found:
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 6.8 Hz, 2 H), 7.43–
7.37 (m, 3 H), 7.28–7.26 (m, 3 H), 7.16–7.13 (m, 3 H), 6.86 (s,
1 H), 6.71 (d, J = 9.2 Hz, 1 H), 6.42 (d, J = 8.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 133.3, 129.2, 128.82, 128.76,
128.6, 128.5, 128.43, 124.40, 125.2, 123.8, 120.9.
MS (ESI): m/z = 247.2 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C17H15N2 : 247.1230; found:
221.1079.
(Z)-1-Styryl-1H-1,2,4-triazole [(Z)-3h]
Yield: 51 mg (59%); pale-yellow liquid.
IR (acetone): 3084, 3056, 1657, 1501, 1131, 696, 672 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.98 (s, 1 H), 7.90 (s, 1 H), 7.31–
7.26 (m, 3 H), 7.11–7.10 (dd, J1 = 7.5 Hz, J2 = 2.0 Hz, 2 H), 6.91
(d, J = 10.0 Hz, 1 H), 6.52 (d, J = 9.5 Hz, 1 H).
+
247.1237.
13C NMR (125 MHz, CDCl3): δ = 151.7, 143.2, 133.1, 129.0, 128.6,
128.3, 124.4, 123.2.
MS (ESI): m/z = 172.1 [M + H]+.
(E)-2-Phenyl-1-styryl-1H-imidazole [(E)-3e]
Yield: 17 mg (14%); pale-yellow liquid.
IR (acetone): 2924, 1469, 695 cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2057–2064

2062
X. Pan et al.
PAPER
+
HRMS (ESI): m/z [M + H]+ calcd for C10H10N3 : 172.0869; found:
172.0866.
1H NMR (400 MHz, CDCl3): δ = 7.67 (d, J = 2.0 Hz, 3.2 H), 7.54
(s, 1 H), 7.47–7.45 (m, 1.7 H), 7.40 (s, 0.6 H), 7.36 (s, 1.2 H), 7.27–
7.13 (m, 12 H), 7.04 (d, J = 2.4 Hz, 1 H), 6.40 (s, 1.6 H), 6.19 (d,
J = 9.6 Hz, 1 H), 6.12 (s, 1 H), 2.41 (s, 5.10 H), 2.22 (s, 3.06 H).
13C NMR (100 MHz, CDCl3): δ = 141.1, 140.0, 136.0, 134.2, 134.0,
130.5, 130.3, 128.8, 128.7, 128.1, 128.0, 127.6, 127.1, 126.3, 126.1,
125.1, 115.5, 115.0, 20.0, 19.7.
(E)-1-Styryl-1H-1,2,4-triazole [(E)-3h]
Yield: 8 mg (9%); pale-yellow oil.
IR (acetone): 2925, 1661, 1506, 1275, 1001, 748, 672 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.32 (s, 1 H), 8.05 (s, 1 H), 7.52
(d, J = 14.5 Hz, 1 H), 7.46 (d, J = 9.0 Hz, 2 H), 7.39 (t, J = 7.5 Hz,
2 H), 7.33 (tt, J1 = 9.0 Hz, J2 = 2.5 Hz, 1 H), 7.28 (d, J = 13.0 Hz,
1 H).
MS (ESI): m/z = 185.4 [M + H]+.
+
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
185.1070.
13C NMR (125 MHz, CDCl3): δ = 152.4, 142.2, 133.8, 129.0, 128.6,
126.6, 121.9, 121.4.
MS (ESI): m/z = 172.0 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C10H10N3 : 172.0869; found:
172.0872.
1-(3-Methylstyryl)-1H-imidazole (3l)
Yield: 82 mg (89%); pale-yellow liquid; Z/E = 2.3:1.
IR (acetone): 2913, 1655, 1392, 748 cm–1.
+
1H NMR (300 MHz, CDCl3): δ = 7.73 (s, 0.4 H), 7.46 (s, 0.88 H),
7.32 (d, J = 14.7 Hz, 0.44 H), 7.25–7.01 (m, 5.8 H), 6.88 (d,
J = 16.8 Hz, 2.8 H), 6.72–6.67 (m, 1.5 H), 6.31 (d, J = 9.0 Hz, 1 H),
2.35 (s, 1.33 H), 2.26 (s, 3.18 H).
13C NMR (100 MHz, CDCl3): δ = 138.8, 138.6, 137.4, 136.7, 134.3,
133.6, 130.3, 129.40, 129.36, 129.33, 129.20, 129.0, 128.8, 127.1,
125.6, 124.0, 123.6, 122.5, 122.2, 119.7, 118.9, 116.6, 21.6, 21.5.
1-Styryl-1H-benzo[d][1,2,3]triazole (3i)
Yield: 83 mg (75%); pale-yellow oil; Z/E = 1.6:1.
IR (acetone): 2923, 1655, 1488, 1455, 1052, 743 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.12 (d, J = 8.4 Hz, 1.55 H), 8.06
(d, J = 8.0 Hz, 1 H), 7.95 (d, J = 14.8 Hz, 1.60 H), 7.77 (d,
J = 8.4 Hz, 1.60 H), 7.61–7.55 (m, 5 H), 7.48 (d, J = 14.8 Hz,
2.20 H), 7.42 (t, J = 7.6 Hz, 4 H), 7.35 (d, J = 7.6 Hz, 1.60 H),
7.32–7.28 (m, 3 H), 7.19–7.13 (m, 3 H), 6.99 (d, J = 7.2 Hz,
2.77 H), 6.78 (d, J = 8.8 Hz, 1 H).
MS (ESI): m/z = 185.4 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
+
185.1070.
13C NMR (100 MHz, CDCl3): δ = 134.4, 129.0, 128.8, 128.7,
128.53, 128.48, 128.3, 127.7, 127.6, 126.6, 124.6, 124.1, 121.8,
121.2, 121.1, 120.5, 119.9, 110.9, 110.0.
(Z)-1-(3-Methylstyryl)-1H-pyrazole (3m)
Yield: 84 mg (91%); pale-yellow liquid; Z/E = 1.7:1.
IR (acetone): 2920, 1660, 1392, 751 cm–1.
MS (ESI): m/z = 222.0 [M + H]+.
1H NMR (400 MHz, CDCl3): δ = 7.66 (s, 1 H), 7.59 (s, 1 H), 7.51
(d, J = 14.8 Hz, 0.59 H), 7.31 (d, J = 2.0 Hz, 1 H), 7.25–7.17 (m,
3.2 H), 7.09–6.99 (m, 5.2 H), 6.39 (s, 0.54 H), 6.23 (d, J = 9.6 Hz,
1 H), 6.19 (s, 1 H), 2.37 (s, 2 H), 2.3 (s, 3.17 H).
13C NMR (100 MHz, CDCl3): δ = 141.0, 140.2, 138.4, 138.2, 135.0,
134.3, 129.5, 129.3, 128.7, 128.6, 128.5, 128.4, 127.9, 126.9, 126.3,
125.6, 123.3, 119.1, 117.0, 21.4, 21.3.
+
HRMS (ESI): m/z [M + H]+ calcd for C14H12N3 : 222.1026; found:
222.1025.
(Z)-1-(2-Methylstyryl)-1H-imidazole [(Z)-3j]
Yield: 55 mg (60%); pale-yellow liquid.
IR (acetone): 2923, 1662, 1490, 1074, 742, 656 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.38 (s, 1 H), 7.21 (d, J = 3.6 Hz,
2 H), 7.14–7.10 (m, 1 H), 7.06 (d, J = 7.6 Hz, 1 H), 6.91 (s, 1 H),
6.82 (d, J = 10.0 Hz, 1 H), 6.68 (s, 1 H), 6.28 (d, J = 9.6 Hz, 1 H),
2.21 (s, 3 H).
MS (ESI): m/z = 185.3 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
+
185.1070.
13C NMR (100 MHz, CDCl3): δ = 137.2, 136.2, 133.6, 130.4, 129.4,
128.5, 128.2, 126.2, 123.0, 118.9, 118.3, 19.7.
(Z)-1-(4-Methylstyryl)-1H-imidazole [(Z)-3n]
Yield: 76 mg (83%); pale-yellow liquid.
MS (ESI): m/z = 185.3 [M + H]+.
IR (acetone): 2922, 1694, 1654, 1510, 1491, 1073, 656 cm–1.
+
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
185.1067.
1H NMR (500 MHz, CDCl3): δ = 7.49 (s, 1 H), 7.10 (d, J = 8.5 Hz,
2 H), 7.06 (s, 1 H), 6.99 (d, J = 8.5 Hz, 2 H), 6.90 (s, 1 H), 6.70 (d,
J = 9.5 Hz, 1 H), 6.35 (d, J = 9.5 Hz, 1 H), 2.33 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 138.4, 130.7, 129.5, 129.43,
129.40, 128.5, 123.9, 121.8, 118.6, 21.3.
(E)-1-(2-Methylstyryl)-1H-imidazole [(E)-3j]
Yield: 24 mg (26%); pale-yellow liquid.
IR (acetone): 2923, 1655, 1496, 1485, 1079, 750.
MS (ESI): m/z = 185.1 [M + H]+.
1H NMR (400 MHz, CDCl3): δ = 7.76 (s, 1 H), 7.43–7.42 (m, 1 H),
7.28 (s, 1 H), 7.21 (d, J = 3.2 Hz, 3.4 H), 7.17 (d, J = 13.2 Hz,
1.6 H), 6.93 (d, J = 14.4 Hz, 1 H), 2.39 (s, 3 H).
+
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
185.1070.
13C NMR (100 MHz, CDCl3): δ = 135.8, 133.4, 130.6, 130.4, 128.6,
128.1, 126.4, 125.3, 123.6, 117.1, 116.3, 19.9.
(E)-1-(4-Methylstyryl)-1H-imidazole [(E)-3n]
Yield: 7 mg (8%); pale-yellow oil.
MS (ESI): m/z = 185.4 [M + H]+.
IR (acetone): 2921, 1494, 1082, 1026 cm–1.
+
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
185.1067.
1H NMR (500 MHz, CDCl3): δ = 7.77 (s, 1 H), 7.33–7.31 (m, 3 H),
7.20–7.16 (m, 3 H), 6.74 (d, J = 14.5 Hz, 1 H), 2.38 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 138.4, 131.5, 129.6, 129.5, 128.4,
126.1, 124.1, 121.9, 119.1, 21.2.
MS (ESI): m/z = 185.1 [M + H]+.
1-(2-Methylstyryl)-1H-pyrazole (3k)
Yield: 80 mg (87%); orange liquid; Z/E = 1:1.6.
IR (acetone): 2923, 1655, 1392, 748 cm–1.
+
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
185.1068.
Synthesis 2014, 46, 2057–2064
© Georg Thieme Verlag Stuttgart · New York

PAPER
Decarboxylative Hydroamination of 3-Arylpropiolic Acid
2063
+
(Z)-1-(4-Methylstyryl)-1H-pyrazole [(Z)-3o]
Yield: 68 mg (74%); pale-yellow liquid.
HRMS (ESI): m/z [M + H]+ calcd for C11H10ClN2 : 205.0527;
found: 205.0528.
IR (acetone): 2922, 1655, 1516, 1440, 1392, 752 cm–1.
(E)-1-(2-Chlorostyryl)-1H-pyrazole (3s)
1H NMR (500 MHz, CDCl3): δ = 7.60 (d, J = 1.0 Hz, 1 H), 7.34 (d,
J = 2.5 Hz, 1 H), 7.13–7.07 (m, 4 H), 6.97 (d, J = 9.5 Hz, 1 H), 6.24
(d, J = 10.0 Hz, 1 H), 6.21 (t, J = 2.0 Hz, 1 H), 2.33 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 140.2, 137.8, 131.4, 129.5, 129.3,
128.6, 126.5, 119.5, 106.5, 21.3.
Yield: 100 mg (98%); pale-yellow liquid; E-isomer only.
IR (acetone): 2924, 1655, 1392, 747 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.75 (d, J = 2.5 Hz, 1 H), 7.70 (s,
1 H), 7.51–7.57 (m, 2 H), 7.41 (d, J = 8.0 Hz, 1 H), 7.37 (d,
J = 15.0 Hz, 1 H), 7.28–7.20 (m, 2 H), 6.43 (s, 1 H).
13C NMR (125 MHz, CDCl3): δ = 141.5, 133.3, 130.0, 128.6, 128.5,
127.9, 127.0, 126.2, 113.2, 107.6.
MS (ESI): m/z = 185.3 [M + H]+.
+
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
185.1070.
MS (ESI): m/z = 205.9 [M + H]+.
+
(E)-1-(4-Methylstyryl)-1H-pyrazole [(E)-3o]
Yield: 22 mg (24%); pale-yellow oil.
HRMS (ESI): m/z [M + H]+ calcd for C11H10ClN2 : 205.0527;
found: 205.0527.
IR (acetone): 2922, 1658, 1392, 751 cm–1.
1-(2-Bromostyryl)-1H-imidazole (3t)
1H NMR (500 MHz, CDCl3): δ = 7.67–7.66 (m, 2 H), 7.49 (d,
J = 14.5 Hz,1 H), 7.33 (d, J = 8.5 Hz, 2 H), 7.17 (d, J1 = 2.5 Hz,
2 H), 7.03 (d, J = 14.0 Hz, 1 H), 6.40 (t, J = 2.0 Hz, 1 H), 2.37 (s, 3
H).
13C NMR (125 MHz, CDCl3): δ = 140.9, 137.5, 132.1, 129.5, 127.8,
126.1, 125.7, 117.0, 107.1, 21.2.
MS (ESI): m/z = 185.3 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2 : 185.1073; found:
Yield: 123 mg (99%); pale-yellow liquid; Z/E = 1:12.
IR (acetone): 2923, 1657, 1467, 1087, 749 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.78 (s, 1 H), 7.61 (d, J = 8.5 Hz,
1 H), 7.51 (d, J = 8.0 Hz, 1 H), 7.34–7.26 (m, 3 H), 7.18–7.15 (m,
2 H), 7.08 (d, J = 14.0 Hz, 1 H), 6.87 (d, J = 9.5 Hz, 0.08 H), 6.74
(d, J = 9.0 Hz, 0.08 H).
13C NMR (100 MHz, CDCl3): δ = 137.0, 134.4, 133.5, 130.3, 129.7,
128.0, 126.7, 124.6, 124.1, 118.8, 116.8.
+
185.1070.
MS (ESI): m/z = 249.1 [M]+.
+
(E)-1-(2-Methoxystyryl)-1H-imidazole (3p)
Yield: 62 mg (62%); pale-yellow oil; Z/E = 3.8:1.
HRMS (ESI): m/z [M + H]+ calcd for C11H10BrN2 : 249.0022;
found: 249.0027.
IR (acetone): 3002, 2836, 1657, 1491, 1248, 1024, 754 cm–1.
1-(2-Bromostyryl)-1H-pyrazole (3u)
1H NMR (500 MHz, CDCl3): δ = 7.76 (s, 0.23 H), 7.47 (s, 1 H),
7.30–7.26 (m, 2 H), 6.99 (s, 1 H), 6.91–6.84 (m, 3 H), 7.78 (d,
J = 9.5 Hz, 1 H), 6.40 (d, J = 9.0 Hz, 1 H), 3.91 (s, 0.72 H), 3.79 (s,
3.37 H).
13C NMR (125 MHz, CDCl3): δ = 156.9, 137.0, 136.4, 130.1, 129.7,
129.4, 129.08, 129.06, 127.5, 123.6, 123.2, 122.6, 120.9, 120.7,
118.5, 117.5, 116.3, 115.0, 111.0, 110.8, 55.5, 55.4.
Yield: 113 mg (90%); pale-yellow liquid; Z/E = 1:3.5.
IR (acetone): 3067, 1655, 1520, 1439, 1391, 746 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 2.4 Hz, 1 H), 7.66 (s,
1 H), 7.61–7.49 (m, 2.72 H), 7.43 (d, J = 14.4 Hz, 1 H), 7.31 (d,
J = 14.4 Hz, 1 H), 7.28–7.07 (m, 4 H), 6.38 (s, 1 H), 6.18 (d,
J = 10.0 Hz, 0.33 H), 6.14 (s, 0.28 H).
13C NMR (100 MHz, CDCl3): δ = 141.7, 140.6, 135.2, 133.4, 133.1,
130.6, 129.6, 128.7, 128.4, 128.2, 127.9, 127.7, 126.5, 124.1, 116.5,
115.8, 107.8, 107.2.
MS (ESI): m/z = 201.4 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2O+: 201.1022; found:
201.1020.
MS (ESI): m/z = 249.1 [M]+.
+
(E)-1-(3-Methoxystyryl)-1H-imidazole (3q)
Yield: 50 mg (50%); pale-yellow liquid; Z/E = 19:1.
HRMS (ESI): m/z [M + H]+ calcd for C11H10BrN2 : 249.0022;
found: 249.0034.
IR (acetone): 3001, 2837, 1607, 1512, 1491, 1254, 1179, 1029 cm–1.
1-(4-Bromostyryl)-1H-imidazole (3v)
1H NMR (500 MHz, CDCl3): δ = 7.52 (s, 1 H), 7.09 (s, 1 H), 7.00
(d, J = 8.5 Hz, 2 H), 6.90 (s, 1 H), 6.80 (d, J = 8.5 Hz, 2 H), 6.65 (d,
J = 9.5 Hz, 1 H), 6.33 (d, J = 9.5 Hz, 1 H), 3.84 (s, 0.16 H), 3.80 (s,
3.18 H).
13C NMR (125 MHz, CDCl3): δ = 159.6, 136.9, 130.0, 129.4, 128.6,
125.8, 124.5, 120.8, 118.6, 114.2, 114.1, 55.2.
Yield: 120 mg (96%); pale-yellow liquid; Z/E = 1:1.9.
IR (acetone): 3122, 2923, 1660, 1487, 1294, 1072, 767 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.76 (s, 2 H), 7.51–7.47 (m,
4.63 H), 7.42 (d, J = 9.0 Hz, 2 H), 7.34 (d, J = 15.0 Hz, 2 H), 7.28–
7.27 (m, 6.25 H), 7.16 (s, 1 H), 7.06 (s, 1 H), 6.97 (d, J = 8.5 Hz,
2 H), 6.85 (s, 1 H), 6.77 (d, J = 9.0 Hz, 1 H), 6.68 (d, J = 14.5 Hz,
1.85 H), 6.29 (d, J = 9.5 Hz, 1 H).
MS (ESI): m/z = 201.3 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N2O+: 201.1022; found:
201.1020.
13C NMR (100 MHz, CDCl3): δ = 137.5, 136.9, 132.7, 132.2, 132.1,
131.9, 130.1, 129.4, 128.8, 127.8, 123.9, 122.8, 122.7, 122.4, 122.3,
119.6, 119.0, 116.9.
1-(2-Chlorostyryl)-1H-imidazole (3r)
Yield: 100 mg (98%); pale-yellow liquid; Z/E = 1:18.
IR (acetone): 3110, 3073, 1656, 1494, 1294, 1025, 749 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.78 (s, 1 H), 7.53 (d, J = 1.5 Hz,
1 H), 7.42 (d, J = 7.5 Hz, 1 H), 7.33–7.23 (m, 4 H), 7.17 (s, 1 H),
7.10 (d, J = 15.0 Hz, 1 H), 6.88 (d, J = 9.5 Hz, 0.06 H).
MS (ESI): m/z = 249.1 [M]+.
+
HRMS (ESI): m/z [M + H]+ calcd for C11H10BrN2 : 249.0022;
found: 249.0019.
1-(4-Bromostyryl)-1H-pyrazole (3w)
Yield: 106 mg (85%); pale-yellow foam; Z/E = 1:1.6.
13C NMR (125 MHz, CDCl3): δ = 136.6, 133.3, 132.7, 130.7, 130.0,
IR (acetone): 3116, 1487, 1391, 933, 753 cm–1.
129.1, 127.2, 126.3, 124.6, 116.3, 115.1.
MS (ESI): m/z = 205.4 [M + H]+.
1H NMR (400 MHz, CDCl3): δ = 7.69 (s, 1 H), 7.66 (d, J = 2.4 Hz,
1 H), 7.62 (d, J = 1.2 Hz, 0.61 H), 7.52 (s, 0.5 H), 7.48 (d,
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2057–2064

2064
X. Pan et al.
PAPER
J = 8.8 Hz, 2.59 H), 7.44 (d, J = 7.6 Hz, 1.28 H), 7.32 (d,
J = 2.4 Hz, 0.66 H), 7.29 (d, J = 8.4 Hz, 2.28 H), 7.08 (d,
J = 8.4 Hz, 1.26 H), 7.02 (d, J = 9.6 Hz, 0.6 H), 7.01 (d,
J = 14.8 Hz, 1 H), 6.42 (t, J = 2.0 Hz, 1 H), 6.25 (t, J = 2.0 Hz,
0.62 H), 6.18 (d, J = 10.0 Hz, 0.63 H).
13C NMR (100 MHz, CDCl3): δ = 141.5, 140.8, 134.2, 133.4,
132.14, 132.12, 132.09, 132.06, 131.92, 131.90, 130.58, 130.56,
129.7, 128.4, 127.85, 127.83, 127.81, 127.78, 127.76, 127.50,
127.0, 122.0, 121.4, 118.2, 115.9, 107.7, 107.1.
J. Am. Chem. Soc. 2008, 130, 8118. (l) Moon, J.; Jeong, M.;
Nam, H.; Ju, J.; Moon, J. H.; Jung, H. M.; Lee, S. Org. Lett.
2008, 10, 945. (m) Zhao, D.; Gao, C.; Su, X.; He, Y.; You,
J.; Xue, Y. Chem. Commun. 2010, 46, 9049. (n) Qu, X.; Li,
T.; Sun, P.; Zhu, Y.; Yang, H.; Mao, J. Org. Biomol. Chem.
2011, 9, 6938. (o) Feng, C.; Loh, T.-P. Chem. Commun.
2010, 46, 4779. For sp–sp bond formation, see: (p) Yu, M.;
Pan, D.; Jia, W.; Chen, W.; Jiao, N. Tetrahedron Lett. 2010,
51, 1287. (q) Park, J.; Park, E.; Kim, A.; Park, S.-A.; Lee, Y.;
Chi, K.-W.; Jung, Y. H.; Kim, I. S. J. Org. Chem. 2011, 76,
2214. (r) Kim, Y.; Park, A.; Park, K.; Lee, S. Tetrahedron
Lett. 2011, 52, 1766. For sp–heteroatom bond formation,
see: (s) Ranjit, R.; Duan, Z.; Zhang, P. X.; Liu, X. Org. Lett.
2010, 12, 4134. (t) Jia, W.; Jiao, N. Org. Lett. 2010, 12,
2000. (u) Hu, J.; Zhao, N.; Yang, B.; Wang, G.; Guo, L. N.;
Liang, Y. M.; Yang, S. D. Chem. Eur. J. 2011, 17, 5516.
(v) Priebbenow, D. L.; Becker, P.; Bolm, C. Org. Lett. 2013,
15, 6155.
MS (ESI): m/z = 249.1 [M]+.
+
HRMS (ESI): m/z [M + H]+ calcd for C11H10BrN2 : 249.0022;
found: 249.0022.
Acknowledgment
We are grateful for financial support from the National Natural Sci-
ence Foundation of China (grant No. 21202187, 21372239).
(3) (a) Reychler, A. Bull. Soc. Chim. Fr. 1897, 515.
(b) Gattermann, L. Justus Liebigs Ann. Chem. 1906, 347,
353.
Supporting Information for this article is available online at
(4) For recent developments in cross-coupling reactions under
transition-metal-free conditions, see: (a) Shirakawa, E.;
Watabe, R.; Murakami, T.; Hayashi, T. Chem. Commun.
2013, 49, 5219. (b) Shirakawa, E.; Hayashi, Y.; Itoh, K.;
Watabe, R.; Uchiyama, N.; Konagaya, W.; Masui, S.;
Hayashi, T. Angew. Chem. Int. Ed. 2012, 51, 218.
(5) (a) Ross, W. J.; Jamieson, W. B.; McCowen, M. C. J. Med.
Chem. 1973, 16, 347. (b) Hamada, Y.; Shinomoto, S.;
Yamada, I.; Koike, H. EP 162359, 1985, Chem. Abstr. 1986,
104, 168465v. (c) Cockerrill, A. F.; Rackham, D. M.;
Franklin, N. C.; Norman, C. J. Chem. Soc., Perkin Trans. 2
1973, 509. (d) Gist-Brocades, N. V. NL 8005204, 1982,
Chem. Abstr. 1982, 100, 492276. (e) Kurdaziel, K.;
Glowiak, T. J. Coord. Chem. 2002, 55, 327. (f) Mano, N.;
Kim, Y.; Zhang, H. H.; Heller, A. J. Am. Chem. Soc. 2002,
124, 6480. (g) Branowska, D. Synthesis 2003, 2096.
(h) Beghdadi, S.; Miladi, I. A.; Addis, D.; Romdhane, H. B.;
Bernard, J.; Drockenmuller, E. Polym. Chem. 2012, 3, 1680.
(6) Extra-pure t-BuOK (sublimed grade, 99.99% trace metals
basis) was purchased from Sigma–Aldrich.
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
References
(1) For selected reviews, see: (a) Gooβen, L. J.; Rodríguez, N.;
Gooβen, K. Angew. Chem. Int. Ed. 2008, 47, 3100.
(b) Baudoin, O. Angew. Chem. Int. Ed. 2007, 46, 1373.
(c) You, S.-L.; Dai, L.-X. Angew. Chem. Int. Ed. 2006, 45,
5246. (d) Tunge, J.; Burger, A. E. Eur. J. Org. Chem. 2005,
1715.
(2) For sp–sp3 bond formation, see: (a) Rayabarapu, D. K.;
Tung, J. A. J. Am. Chem. Soc. 2005, 127, 13510. (b) Zhang,
W.-W.; Zhang, X.-G.; Li, J.-H. J. Org. Chem. 2010, 75,
5259. (c) Torregrosa, R. R.; Ariyarathna, P. Y.;
Chattopadhyay, K.; Tunge, J. A. J. Am. Chem. Soc. 2010,
132, 9280. (d) Choe, J.; Yang, J.; Park, K.; Palani, T.; Lee,
S. Tetrahedron Lett. 2012, 53, 6908. For sp–sp2 bond
formation, see: (e) Moon, J.; Jang, M.; Lee, S. J. Org. Chem.
2009, 74, 1403. (f) Wang, Z. Y.; Ding, Q. P.; He, X. D.; Wu,
J. Tetrahedron 2009, 65, 4635. (g) Wang, Z. Y.; Ding, Q. P.;
He, X. D.; Wu, J. Org. Biomol. Chem. 2009, 7, 863.
(h) Gooβen, L. J.; Zimmermann, B.; Knauber, T. Angew.
Chem. Int. Ed. 2008, 47, 7103. (i) Gooβen, L.; Rudolphi, J.
F.; Oppel, C.; Rodríguez, N. Angew. Chem. Int. Ed. 2008,
47, 3043. (j) Gooβen, L. J.; Rodríguez, N.; Linder, C. J. Am.
Chem. Soc. 2008, 130, 15248. (k) Wang, C.; Tunge, J. A.
(7) Phenylacetylene was found to be labile in the presence of
t-BuOK because no phenylacetylene was detected by GC
under the same reaction conditions after 24 h.
(8) No product was isolated when t-BuOK (2.2 equiv) was used,
probably due to the instability of phenylacetylene in the
presence of excess t-BuOK.
Synthesis 2014, 46, 2057–2064
© Georg Thieme Verlag Stuttgart · New York