Regio- And Stereoselective Synthesis of Thiazole-Containing Triarylethylenes by Hydroarylation of Alkynes

Article abstract of DOI:10.1021/acs.joc.9b01619

Thiazole-containing π-conjugated moieties are important structural units in the development of new electronic and photochromic materials. We have developed a Pd-catalyzed syn-hydroarylation reaction of diaryl alkynes with thiazoles that provides access to thiazole-containing triarylethylenes. Pd(II) complexes derived from Pd(0) species and carboxylic acids facilitated C-H functionalization of the unsubstituted thiazole with high C5 selectivity. The catalytic system was also compatible with other azoles, such as oxazoles and a pyrazole, allowing the stereoselective syntheses of various trisubstituted olefins.

Full text of DOI:10.1021/acs.joc.9b01619

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Article
Regio- and Stereoselective Synthesis of Thiazole-
Containing Triarylethylenes by Hydroarylation of Alkynes
Woohyeong Lee, Changhoon Shin, Soo Eun Park, and Jung Min Joo
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01619 • Publication Date (Web): 12 Aug 2019
Downloaded from pubs.acs.org on August 13, 2019
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Page 1 of 31
The Journal of Organic Chemistry
Regio- and Stereoselective Synthesis of Thiazole-Containing
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Triarylethylenes by Hydroarylation of Alkynes
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Woohyeong Lee,+ Changhoon Shin,+ Soo Eun Park, Jung Min Joo*
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Department of Chemistry and Chemistry Institute of Functional Materials, Pusan National University,
Busan 46241, Republic of Korea
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RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
ABSTRACT
H
Pd(dba)2
PCy3
Ar
S
H
2
S
+
Ar
Ar
H
N
N
5
RCO2H
Ar
Thiazole-containing π-conjugated moieties are important structural units in the development of new
electronic and photochromic materials. We have developed a Pd-catalyzed syn-hydroarylation reaction of
diaryl alkynes with thiazoles, which provides access to thiazole-containing triarylethylenes. Pd(II)
complexes derived from Pd(0) species and carboxylic acids facilitated C−H functionalization of the
unsubstituted thiazole with high C5 selectivity. The catalytic system was also compatible with other azoles,
such as oxazoles and a pyrazole, allowing the stereoselective syntheses of various trisubstituted olefins.
Introduction
Thiazoles are one of the most important heterocyclic cores found in natural products, pharmaceuticals,
and functional materials.1 Particularly, the presence of the pyridine-like nitrogen atom at the thiazole core
imparts different electronic properties and provides opportunities for hydrogen bonding and metal binding,
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which are otherwise unavailable to its nitrogen-free congener, thiophene. This allows the development of
many thiazole-containing π-conjugated electronic and photochromic materials.2 Therefore, novel methods
allowing facile syntheses of the π-conjugated systems bearing thiazole are crucial for further expansion
of the structural and functional varieties of synthetic materials.
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9
Transition metal-catalyzed C−H bond functionalization of thiazoles with unsaturated hydrocarbons can
offer direct access to thiazole-containing π-conjugated systems.3 Particularly, addition of thiazoles to
alkynes is one of the most straightforward methods for preparing thiazole-containing trisubstituted
ethylene compounds.4 However, attaining a high regioselectivity between the two reactive positions, C2
and C5, of thiazoles, has been quite challenging. For example, Co- and Ni-catalyzed hydroarylation of
alkynes has been applied to the functionalization of the C2 position of thiazole (Figure 1A).5,6 However,
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substituted thiazoles were mainly used, and a single example of unsubstituted thiazole reacting with 4-
octyne resulted in the formation of the corresponding C2-alkenyl thiazole in 23% yield, leaving the
alternative C5-functionalization of thiazoles unexplored.5b In addition, the first row transition metal
catalysts generally gave low yields in the hydroheteroarylation of diaryl alkynes as compared with their
dialkyl counterparts, thereby preventing their broad application to the syntheses of azole-containing π-
conjugated systems.7
(A)
H
2
nPr
S
[Co]
[Co]
5
S
H
nPr
S
+
nPr
nPr
N
N
N
H
23%
(B)
N
[Pd]
S
S
+
N
X
[Pd]
X
(C) This work
S
H
H
O
O
[Pd]
Ar
Ar
R
S
+
Ar
Ar
[Pd]
N
RCO2H
N
Ar
Ar
Figure 1. (A) Hydroarylation of alkynes at the C2-position of thiazole. (B) Pd-catalyzed C−H arylation
at the C5-position of thiazole. (C) Pd-catalyzed hydroarylation of alkynes at the C5-position of thiazole.
In contrast, high C5 selectivity and efficiency have been achieved in Pd-catalyzed C−H arylation of the
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unsubstituted thiazole with aryl halides (Figure 1B).8 Similarly, Pd-catalyzed C−H alkenylation of the
parent thiazole with alkenes as the alkenyl group donors resulted in C5 selectivity, but the scope and
efficiency were limited, indicating the difficulty in the functionalization of the C5 position of thiazoles
compared with other azoles.9,10 Considering the C5 selectivity of thiazoles achieved with Pd(II)
complexes, we envisioned that Pd-catalyzed hydroarylation of alkynes should provide an opportunity for
the stereoselective syntheses of alkenyl thiazoles that are otherwise inaccessible by dehydrogenative
alkenylation with alkenes (Figure 1C).11 Specifically, we hypothesized the involvement of alkenyl Pd(II)
carboxylate complexes resulting from Pd(0) species and carboxylic acids in the C−H functionalization of
heteroarenes.12 Although it has been proposed that low valent Co(0) or Co(I)- and Ni(0)-catalyzed
hydroarylation reactions of alkynes involve oxidative addition of heteroaromatic C−H bonds at the C2
position, Pd(II) carboxylates could selectively functionalize the more nucleophilic C5 position.13 Hiyama
et al. demonstrated the advantage of Pd catalysis in the alkyne functionalization, where alkenyl Pd(II)
carboxylates have been proposed as the key intermediates in the direct C−H activation.14 Although Pd-
catalyzed hydroarylation of diaryl alkynes has been employed for the functionalization of five-membered
heteroarenes, the reaction was largely focused on the electron-rich one-heteroatom-containing
heterocycles, which resulted in modest regio- and stereoselectivity.15 We found that alkenyl Pd(II)
carboxylate complexes were readily formed from Pd(0) species and carboxylic acids with diaryl alkynes,
which allowed the C5-selective alkenylation of thiazoles in a regio- and stereoselective manner.
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Results and Discussion
Simple thiazole 1 and diphenylacetylene were used for the optimization studies, revealing that a
combination of Pd(dba)2, PCy3, and pivalic acid afforded both (E)- and (Z)-isomers (2a and 3a,
respectively) of the corresponding C5-alkenylation products, along with the dialkenylation product 4a
(Table 1). The structure of the major product 2a was analyzed by X-ray crystallography, which revealed
the C5- and syn-selectivity of the hydroarylation (see the Supporting Information).16 It was worth noting
that subjecting the (E)-isomer 2a to the optimized conditions (entry 3) did not promote olefin
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isomerization, indicating that the (Z)-isomer 3a was formed during the Pd-catalyzed process rather than
the isomerization of the (E)-isomer (vide infra). To avoid the formation of the dihydroarylation product
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9
4a, the amount of thiazole was increased to 4.0 equivalents with respect to the alkyne (entries 1-3). Both
pivalic acid and acetic acid gave comparable yields for thiazole (entries 3 and 4), but they affected the
selectivity and efficiency for the substituted thiazoles (see Table 3). However, trifluoroacetic acid was not
effective and the reaction did not proceed in the absence of carboxylic acids (entries 5 and 6). Variation
in the catalytic system by using different Pd precatalysts exhibited consistent C5 selectivity as long as
tricyclohexylphosphine was present (entries 7-9). Phenyl-substituted phosphine ligands gave lower yields
than tricyclohexylphosphine ligands, including the bench-stable form, PCy3H·BF4 (entries 10-12).
However, no reaction took place in the absence of phosphine ligands (entry 13). Decreasing the reaction
temperature slightly reduced the extent of conversion, whereas increasing the reaction temperature
promoted the formation of the (Z)-isomer 3a (entries 14 and 15). Conducting the reaction in various
solvents revealed that the reaction was more selective and efficient in DMA than in 1,4-dioxane and
toluene (entries 16 and 17).
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Table 1. Hydroheteroarylation with thiazolea
Ph
Ph
[Pd]
Ph
S
S
Ph
+
S
Ph
S
+
N
N
Ph
N
Ph
Ph
N
Ph
Ph
1
2a
3a
4a
GC yield (%)
4a PhC≡CPh
Entry
1 (eq.)
[Pd]
L
Acid
Solvent
2a
60
69
84
84
1
3a
5
4
2
3
3
0
6
2
5
4
2
1
0
1
7
0
0
1
2
3
4
5
2.0
3.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(PCy3)3
Pd2(dba)3
Pd(OAc)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
−
PivOH
PivOH
PivOH
AcOH
TFA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
15
11
8
2
2
2
5
3
0
0
8
48
94
0
6
−
0
7
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
76
75
76
73
51
18
0
76
67
69
38
8b
9
PCy3
PCy3
9
1
8
1
10
11
12
13
14c
15d
16
17
PCy3H·BF4
PCyPh2
PPh3
6
6
2
0
0
10
8
35
71
89
5
−
PCy3
PCy3
PCy3
1
1,4-dioxane
toluene
8
4
12
24
PCy3
a
Reaction conditions: thiazole (as indicated), diphenylacetylene (0.50 mmol), Pd(dba)2 (0.025 mmol),
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b
ligand (0.10 mmol), carboxylic acid (0.15 mmol), solvent (0.50 M), 14 h, Temperature: 130 °C.
Pd2(dba)3 (0.0125 mmol) was employed. c Temperature: 110 °C. d Temperature: 150 °C.
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9
The Pd-catalyzed hydroarylation of symmetrical alkynes generated a variety of thiazole-containing
triarylethylene compounds (Table 2).17 Both electron-donating and electron-withdrawing substituents on
diaryl alkynes were used under the optimal reaction conditions to examine the substrate scope.
Furthermore, the reaction showed tolerance toward substituents at different positions: p-, m-, and o-
methoxy and fluoro derivatives in the aryl ring afforded the corresponding products in good yields (2g–
2i and 2j–2l). Naphthalene as well as heterocyclic thiophene-substituted alkynes could also successfully
couple with thiazole (2m–2o). However, hydroarylation of unsymmetrical diaryl alkynes gave an
inseparable mixture of regioisomers (2p–2s). The ratio between the two regioisomeres indicated that both
electronic and steric effects affected the regioselectivity, but to a larger extent by steric effects than
electronic effects. In addition, no products were obtained with alkynes having alkyl groups, presumably
because β-H elimination of the hydropalladation intermediate took place and the resulting allyl Pd(II)
intermediates were not suitable for allylation of thiazole.14d
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Table 2. Substrate Scope of Alkynesa
1
2
Pd(dba)2, PCy3
3
4
5
6
7
8
(CH3)3CCO2H
Ar
S
S
+
Ar
Ar'
S
H
N
N
N
DMA, 130 o
C
Ar
2a-2o
1
Me
Ar = Ar'
Me
S
S
N
N
9
Me
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11
12
13
14
15
16
17
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22
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Me
2c (66%)
2a (83%)
2b (77%)
CO2Et
CF3
S
S
tBu
OMe
F
S
N
N
N
CO2Et
2e (92%)
CF3
tBu
2d (69%)
2f (63%)
OMe
MeO
S
S
S
N
N
N
MeO
OMe
MeO
2h (90%)
2g (88%)
2i (38%)
F
F
S
S
S
N
N
N
F
F
F
2j (67%)
2k (69%)
2l (67%)
S
S
S
S
S
N
N
N
S
S
2n (51%)
2o (47%)
2m (70%)
Ar
Ar'
Ar  Ar'
C6H5
C6H5
(o-MeO)C6H4 2p (82%, 2.45:1)
(p-MeO)C6H4 2q (83%, 1.58:1)
2r (98%, 1.71:1)
(p-EtO2C)C6H4 (p-MeO)C6H4 2s (91%, 1.91:1)
Ar'
+
Ar
S
N
S
(p-EtO2C)C6H4 C6H4
N
Ar
Ar'
a
Reaction conditions: thiazole (2.0 mmol), alkyne (0.50 mmol), Pd(dba)2 (0.025 mmol), PCy3 (0.10
mmol), pivalic acid (0.15 mmol), DMA (0.50 M), 14 h, Temperature: 130 °C.
The Pd-catalyzed system involving Pd(dba)2, PCy3, and carboxylic acids was also compatible for
substituted thiazoles and other azole compounds (Table 3). Either diphenylacetylene or 1,2-bis(4-
methoxyphenyl)ethyne was selected as the alkyne partner for easy isolation. When the C2 position of
thiazoles was substituted, the formation of the (Z)-isomers was noticeable. To avoid the isomerization,
the reaction temperature was decreased and the amount of the solvent was reduced (5a–c). In addition, 4-
phenyl thiazoles were transformed into the corresponding hydroheteroarylation products (5d–f). In these
reactions, the corresponding benzannulation products involving C−H functionalization of the C4-phenyl
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ring were not observed, favoring the mechanism based on hydropalladation of alkynes with carboxylic
acid over carbometallation of alkynes with thiazole.18 Generally, the addition of acetic acid afforded
higher selectivity than pivalic acid for C4-substituted thiazoles, in which both C2 and C5 positions were
available (5d and 5g). The presence of an ester group at the C4 position reduced the extent of conversion,
giving 5g in 27% yield (see the Supporting Information for the determination of regiochemistry). However,
the impact of the ester substitution was alleviated upon blocking the C2 position, affording 5h in 82%
yield. When the C5 position of thiazoles was blocked, hydroarylation occurred at the C2 position (5i and
4a). Furthermore, the Pd(0) catalytic system was useful for the hydroarylation of oxazoles and
benzoxazole (6a–e). There are a couple of examples of hydroarylation of alkynes with (benz)oxazoles
using Co and Rh catalysts, but the scope of (benz)oxazoles is still underexplored.5a,19 When 4-phenyl
oxazole was tested, the preference to the C5 position was observed (6a), representing a rare example of
the hydroarylation of alkynes through the C5 position of oxazole. However, in contrast to the phenyl-
substituted oxazole, ethyl oxazole-4-carboxylate was converted to the corresponding C2-functionalized
product 6b in good yield, consistent with the selectivity of aryl Pd(II) complexes in the C–H arylation of
oxazole-4-carboxylates.20 Oxazoles substituted at C2 and C4 positions underwent alkenylation at the only
available site (6c and 6d). Although the reaction was not compatible with benzothiazole and
benzimidazole (not shown), benzoxazole and caffeine underwent the alkenylation, giving 6e and 7,
respectively. The scope of azoles could be further extended to the functionalization of 4-nitropyrazole (8).
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Table 3. Substrate Scope of Azolesa
1
2
3
4
5
6
7
8
9
Pd(dba)2, PCy3
R
het
(CH3)3CCO2H
het
H
+
R
R
DMA, 130 o
C
R = H or OMe
R
O
iBu
Ph
OMe
OMe
OMe
OMe
S
S
OMe
Ph
S
S
S
Me
N
N
N
N
N
Ph
5d (61%)c
Ph
OMe
5b (75%, E/Z>15:1)b
OMe
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
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42
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60
OMe
5a (82%, E/Z=12:1)b
5c (93%, E/Z=12:1)b
5e (73%)
Ph
Ph
Me
Me
OMe
OMe
S
S
S
Me
S
Ph
S
N
N
N
N
N
Ph
EtO
O
EtO
O
OMe
5g (27%)c
OMe
5h (82%, E/Z=6:1)
OMe
5i (55%)
5f (70%)
4a (72%)
Ph
Ph
OMe
OMe
OMe
O
O
N
O
O
O
N
N
EtO
N
N
Ph
Ph
O
EtO
O
OMe
OMe
6b (81%)c
OMe
OMe
6d (86%)
6a (61%)c
6c (83%)c
6e (81%)
O
NO2
Me
N
Me
O
N
N
N
Me
N
N
Me
7 (69%)
8 (58%)
a Reaction conditions: azole (1.0 mmol), alkyne (0.50 mmol), Pd(dba)2 (0.025 mmol), PCy3 (0.10 mmol),
pivalic acid (0.15 mmol), DMA (0.50 M), 14 h, Temperature: 130 °C. b Azole (2.0 mmol) was used in
DMA (0.75 M) at 110 °C. c Azole (2.0 mmol) and acetic acid (0.15 mmol) were used.
The success with the PCy3 ligand prompted us to compare the PCy3-dependent catalytic system with
Pd(PEt3)4, which was reported to afford the corresponding syn-hydropalladation product.12 Stoichiometric
amounts of Pd(PCy3)2, acetic acid, and diphenylacetylene produced the corresponding alkenyl Pd(II)
carboxylate complex 9 (Figure 2A).16 It was remarkable that the sterically bulky PCy3 ligand, often having
distinct catalytic activities compared with PEt3, allowed the facile syn-hydropalladation of
diphenylacetylene and isolation of complex 9.14b,c Furthermore, the addition of four equivalents of
thiazole to the isolated complex 9 led to the formation of the corresponding alkenylation products, 2a and
3a, supporting the involvement of these species in the C−H functionalization of thiazole. Similar to the
isomerization of triethylphosphine-ligated alkenyl Pd(II) complexes, the formation of the other
stereoisomer 3a is attributed to the isomerization of the pre-formed syn-hydropalladation product 9,
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presumably via zwitterionic Pd carbene species.12,21 In addition, deuterium labeling experiments were
carried out with deuterated solvent DMF, more readily available than deuterated DMA, AcOD and C5-
deuterated thiazole (Figure 2B). Although the use of deuterated species increased the formation of the
corresponding (Z)-isomer, it was found that the incorporation of deuterium took place only when AcOD
and the deuterated thiazole were employed. Additionally, the kinetic isotope effects indicated that the
cleavage of the heterocyclic C–H bond was a rate-determining step (Figure 2C).
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CH3
O
O
(A)
(B)
S
Cy3P
O
Pd(PCy3)2
+
+
2a (29%)
+
H3C
OH
Pd
N
PCy3
benzene
DMA
130 o
3a (42%)
25 o
C
C
9
H/D
Pd(dba)2, PCy3
iBu
S
iBu
Ar
Ar 5b
S
5
Ar
Ar
H/D
N
N
50 mol% AcOH/D
130 o
C
Ar = p-MeOC6H4
D-incorporation
in the E isomer
C5
AcOH/D Solvent
Yield
H
H
D
AcOH
AcOD
AcOH
DMF-d6 85% (E/Z = 1.3:1)
0%
32%
35%
DMA
DMA
79% (E/Z = 6:1)
77% (E/Z = 3:1)
Pd(dba)2, PCy3
AcOH
(C)
iBu
S
5b
Ar
Ar
H/D
kH/kD = 2.63
N
DMA, 130 o
C
Ar = p-MeOC6H4
Figure 2. (A) Synthesis of the alkenyl Pd(II) carboxylate complex 9. (B) Deuterium labeling
experiments. (C) Kinetic isotope effects.
Based on these results, we propose the following catalytic cycle: the alkenyl Pd(II) acetate 9 derived
from syn-hydropalladation enables rate-limiting concerted metalation-deprotonation of thiazole followed
by reductive elimination to afford the hydroarylation product 2a and regenerate the Pd(0) catalyst (Figure
3). The deuterium labeling can be explained by hydropalladation of AcOD, which was originally added
or in situ generated by concerted metalation-deprotonation of the C5-deuterated thiazole.
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Figure 3. Proposed mechanism
Conclusion
In conclusion, we have developed a hydroarylation reaction of diaryl alkynes with thiazoles. Selective
C5-alkenylation of thiazoles was achieved by the reaction of alkenyl Pd(II) carboxylate complexes
derived from syn-hydropalladation of alkynes with Pd(0) species and carboxylic acids. In addition to the
functionalization of the C5 position of thiazole, the Pd-catalyzed system could be generally applied to the
functionalization of oxazole, benzoxazole, and pyrazole. Complementary to C2-functionalization of low
valent Co- and Ni-catalyzed hydroarylation of alkynes, this method based on the intermediacy of Pd(II)
complexes enabled high site-selectivity for the C5 position of thiazole and high efficiency for the
hydroarylation of diaryl alkynes. This method provided easy access to azole-containing triarylethylene
systems, which can facilitate the development of new five-membered-heterocycle-based materials beyond
the conventional thiophene derivatives.
Experimental Section
NMR spectra were recorded in CDCl3 at 300 K on a 300 MHz Fourier transform NMR spectrometer.
Proton chemical shifts are expressed in parts per million (ppm, δ scale) and are referenced to residual
protium in the NMR solvent (CDCl3, δ 7.26). Carbon chemical shifts are expressed in parts per million
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The Journal of Organic Chemistry
(ppm, δ scale) and are referenced to the carbon resonance of the NMR solvent (CDCl3, δ 77.16). Crude
yields were determined by GC analysis using triphenylethylene as an internal standard, which was added
to reaction mixtures after cooling to 25 °C. High-resolution mass spectra (HRMS) were acquired on high-
resolution mass spectrometers: Q-TOF (ionization mode: ESI).
1
2
3
4
5
6
7
8
9
General Procedure for Hydroarylation of Azoles. To an 8 mL-glass vial equipped with a magnetic stir
bar, a thiazole substrate (as indicated), an alkyne substrate (0.50 mmol), pivalic acid (15 mg, 0.15 mmol)
[or acetic acid (9.0 mg, 0.15 mmol) as indicated], N,N-dimethylacetamide (1.0 mL, 0.50 M), Pd(dba)2 (14
mg, 0.025 mmol) and PCy3 (29 mg, 0.10 mmol) were sequentially added in an argon-purged glove box.
The reaction mixture was stirred in a preheated reaction block at 130 °C for 14 h. After cooled to 25 °C,
the solution was purified by flash column chromatography to afford the desired product.
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60
S
N
(E)-5-(1,2-diphenylvinyl)thiazole (2a). Following the general procedure, the reaction was set up with
thiazole (172 mg, 2.0 mmol) and diphenylacetylene (91 mg, 0.50 mmol). Purification by flash column
chromatography (hexanes/EtOAc = 14:1) provided 2a as a pale yellow solid (105 mg, 80% yield). Crystals
suitable for X-ray crystallography were obtained from vapor diffusion of hexanes into a saturated
chloroform solution of 2a at 25 °C. mp 86-88 ℃; IR (film) 3055, 3021, 1596, 1488, 1443, 865 cm-1; 1H
NMR (300 MHz, CDCl3)  8.69 (s, 1H), 7.49 (s, 1H), 7.43-7.38 (m, 3H), 7.33-7.27 (m, 2H), 7.15-7.10
(m, 3H), 7.02 (s, 1H), 7.00-6.95 (m, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 152.0, 141.6, 138.6, 136.0,
133.2, 129.6, 129.5, 129.0, 128.2, 128.1, 127.4; HRMS (ESI) calcd for C17H14NS [M+H]+ 264.0841,
found 264.0832.
S
N
(Z)-5-(1,2-diphenylvinyl)thiazole (3a). Following the general procedure, the reaction was set up with
thiazole (172 mg, 2.0 mmol) and diphenylacetylene (91 mg, 0.50 mmol). Purification by flash column
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chromatography (hexanes/EtOAc = 14:1) provided 3a as a pale yellow solid. mp 95-97 °C; IR (film)
3054, 3022, 1596, 1490, 1444, 866 cm-1; 1H NMR (300 MHz, CDCl3)  8.84 (s, 1H), 7.69 (s, 1H), 7.48-
1
2
3
4
5
6
13
7.31 (m, 5H), 7.31-7.21 (m, 3H), 7.21-7.12 (m, 2H), 7.08 (s, 1H); C{1H} NMR (75 MHz, CDCl3)
7
8
 154.0, 144.0, 142.5, 136.6, 132.5, 131.7, 129.4, 128.5, 128.5, 128.3, 127.8, 127.5; HRMS (ESI) calcd
9
for C17H14NS [M+H]+ 264.0841, found 264.0844.
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50
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59
60
S
N
2,5-bis((E)-1,2-diphenylvinyl)thiazole (4a). Following the general procedure, the reaction was set up
with 2a (263 mg, 1.0 mmol) and diphenylacetylene (91 mg, 0.50 mmol). Purification by flash column
chromatography (hexanes/EtOAc = 40:1) provided 4a as a pale yellow solid (159 mg, 72% yield). mp
158-160 °C; IR (film) 3054, 3022, 1595, 1494, 1443, 755 cm-1; 1H NMR (300 MHz, CDCl3)  7.77 (s,
1H), 7.49-7.44 (m, 3H), 7.42-7.35 (m, 6H), 7.33-7.27 (m, 2H), 7.17-7.13 (m, 3H), 7.12-7.08 (m, 3H),
7.07-7.03 (m, 2H), 6.95-6.90 (m, 2H), 6.90 (s, 1H); C{1H} NMR (75 MHz, CDCl3)  170.3, 143.6,
13
142.4, 138.5, 136.3, 135.8, 134.8, 133.9, 130.4, 130.3, 130.1, 129.8, 129.6, 129.3, 129.1, 128.9, 128.7,
128.3, 128.2, 128.1, 127.3; HRMS (ESI) calcd for C31H24NS [M+H]+ 442.1624, found 442.1615.
Me
S
N
Me
(E)-5-(1,2-di-p-tolylvinyl)thiazole (2b). Following the general procedure, the reaction was set up with
thiazole (172 mg, 2.0 mmol) and 1,2-di-p-tolylethyne (103 mg, 0.50 mmol). Purification by flash column
chromatography (hexanes/EtOAc = 9:1) provided 2b as a yellow solid (112 mg, 77% yield). mp 64-66
°C; IR (film) 3020, 2918, 2858, 1603, 1492, 867 cm-1; 1H NMR (300 MHz, CDCl3)  8.66 (s, 1H), 7.49
(s, 1H), 7.24-7.14 (m, 4H), 7.00-6.93 (m, 3H), 6.92-6.87 (m, 2H), 2.41 (s, 3H), 2.26 (s, 3H); C{1H}
13
NMR (75 MHz, CDCl3)  151.6, 143.6, 141.3, 137.9, 137.2, 135.8, 133.3, 132.3, 129.8, 129.5, 129.3,
128.9, 21.4, 21.2; HRMS (ESI) calcd for C19H18NS [M+H]+ 292.1154, found 292.1154.
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Me
1
2
3
4
5
6
7
8
S
N
Me
(E)-5-(1,2-di-m-tolylvinyl)thiazole (2c). Following the general procedure, the reaction was set up with
thiazole (172 mg, 2.0 mmol) and 1,2-di-m-tolylethyne (103 mg, 0.50 mmol). Purification by flash column
chromatography (hexanes/EtOAc = 10:1) provided 2c as a yellow oil (96 mg, 66% yield). IR (film) 3015,
2919, 2854, 1598, 1486, 869 cm-1; 1H NMR (300 MHz, CDCl3)  8.67 (s, 1H), 7.49 (s, 1H), 7.30 (d, J =
7.4 Hz, 1H), 7.20 (d, J = 7.2 Hz, 1H), 7.14-7.05 (m, 2H), 7.01 (d, J = 7.5 Hz, 1H), 6.97-6.91 (m, 2H),
6.84 (s, 1H), 6.74 (d, J = 7.2 Hz, 1H), 2.35 (s, 3H), 2.19 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3)  151.8,
143.4, 141.6, 138.8, 138.7, 137.6, 136.1, 133.2, 130.7, 130.1, 129.5, 129.0, 128.3, 128.0, 126.7, 126.5,
21.5, 21.4; HRMS (ESI) calcd for C19H18NS [M+H]+ 292.1154, found 292.1155.
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58
59
60
tBu
S
N
tBu
(E)-5-(1,2-bis(4-(tert-butyl)phenyl)vinyl)thiazole (2d). Following the general procedure, the reaction
was set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(4-(tert-butyl)phenyl)ethyne (145 mg, 0.50
mmol). Purification by flash column chromatography (hexanes/EtOAc = 8:1) provided 2d as a yellow oil
(129 mg, 69% yield). IR (film) 2956, 2924, 2863, 1604, 1461, 867 cm-1; 1H NMR (300 MHz, CDCl3) 
8.65 (s, 1H), 7.46 (s, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.3 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 6.96
(s, 1H), 6.92 (d, J = 8.4 Hz, 2H), 1.38 (s, 9H), 1.25 (s, 9H); C{1H} NMR (75 MHz, CDCl3)  151.6,
13
151.3, 150.6, 143.8, 141.5, 135.9, 133.4, 132.4, 129.4, 129.3, 129.2, 126.1, 125.2, 34.8, 34.7, 31.5, 31.3;
HRMS (ESI) calcd for C25H30NS [M+H]+ 376.2093, found 376.2093.
CO2Et
S
N
CO2Et
(E)-diethyl 4,4'-(1-(thiazol-5-yl)ethene-1,2-diyl)dibenzoate (2e). Following the general procedure, the
reaction was set up with thiazole (172 mg, 2.0 mmol) and diethyl 4,4'-(ethyne-1,2-diyl)dibenzoate (161
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mg, 0.50 mmol). Purification by flash column chromatography (hexanes/EtOAc = 2:1) provided 2e as a
yellow oil (188 mg, 92% yield). IR (film) 3078, 2979, 2920, 1712, 1603, 868 cm-1; 1H NMR (300 MHz,
CDCl3)  8.72 (s, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.49 (s, 1H), 7.35 (d, J = 8.3 Hz,
2H), 7.07 (s, 1H), 7.00 (d, J = 8.3 Hz, 2H), 4.40 (q, J = 7.1 Hz, 2H), 4.31 (q, J = 7.1 Hz, 2H), 1.41 (t, J =
1
2
3
4
5
6
7
8
9
13
7.1 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H); C{1H} NMR (75 MHz, CDCl3)  166.2, 152.8, 142.8, 142.3,
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141.9, 140.0, 134.5, 130.7, 130.4, 129.8, 129.5, 129.4, 129.24, 129.16, 61.3, 61.1, 14.42, 14.37; HRMS
(ESI) calcd for C23H22NO4S [M+H]+ 408.1264, found 408.1266.
CF3
S
N
CF3
(E)-5-(1,2-bis(4-(trifluoromethyl)phenyl)vinyl)thiazole (2f). Following the general procedure, the
reaction was set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(4-(trifluoromethyl)phenyl)ethyne (157
mg, 0.50 mmol). Purification by flash column chromatography (hexanes/EtOAc = 9:1) provided 2f as a
1
yellow solid (126 mg, 63% yield). mp 65-67 ℃; IR (film) 3070, 2929, 1613, 1317, 1105, 868 cm-1; H
NMR (300 MHz, CDCl3)  8.75 (s, 1H), 7.69 (d, J = 8.0 Hz , 2H), 7.50 (s, 1H), 7.43 (d, J = 3.4 Hz, 2H),
7.40 (d, J = 3.8 Hz, 2H), 7.09 (s, 1H), 7.06 (d, J = 8.4 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3)  152.9,
142.5, 141.9, 139.0, 134.2, 131.0 (q, J = 32.9 Hz), 130.2, 129.7, 129.1 (q, J = 30.0 Hz), 128.9, 126.3 (q,
J = 3.7 Hz), 124.0 (q, J = 272.1 Hz), 125.3 (q, J = 3.7 Hz); HRMS (ESI) calcd for C19H12F6NS [M+H]+
400.0589, found 400.0589.
OMe
S
N
OMe
(E)-5-(1,2-bis(4-methoxyphenyl)vinyl)thiazole (2g). Following the general procedure, the reaction
was set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(4-methoxyphenyl)ethyne (119 mg, 0.50 mmol).
Purification by flash column chromatography (hexanes/EtOAc = 6:1) provided 2g as a colorless oil (143
mg, 88% yield). IR (film) 2999, 2930, 2834, 1602, 1509, 867 cm-1; 1H NMR (300 MHz, CDCl3)  8.64
(s, 1H), 7.49 (s, 1H), 7.22 (d, J = 8.5 Hz, 2H), 6.96-6.92 (m, 5H), 6.68 (d, J = 8.6 Hz, 2H), 3.87 (s, 3H),
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3.75 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3)  159.5, 158.9, 151.5, 141.0, 131.1, 131.0, 130.9, 130.8,
1
2
3
129.0, 128.9, 114.6, 113.8, 113.7, 55.3, 55.2; HRMS (ESI) calcd for C19H18NO2S [M+H]+ 324.1053,
4
5
6
found 324.1052.
7
OMe
8
9
S
N
10
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12
13
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59
60
MeO
(E)-5-(1,2-bis(3-methoxyphenyl)vinyl)thiazole (2h). Following the general procedure, the reaction
was set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(3-methoxyphenyl)ethyne (119 mg, 0.50 mmol).
Purification by flash column chromatography (hexanes/EtOAc = 4:1) provided 2h as a colorless oil (146
mg, 90% yield). IR (film) 2999, 2923, 2833, 1595, 1486, 868 cm-1; 1H NMR (300 MHz, CDCl3)  8.68
(s, 1H), 7.52 (s, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.08 (t, J = 7.9 Hz, 1H), 6.98 (s, 1H), 6.95-6.88 (m, 2H),
6.84 (s, 1H), 6.71-6.65 (m, 2H), 6.51 (s, 1H), 3.76 (s, 3H), 3.53 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3)
 160.2, 159.1, 151.9, 141.6, 140.0, 137.1, 133.2, 130.2, 129.2, 129.0, 122.5, 121.9, 114.8, 114.2, 114.0,
113.6, 55.2, 54.8; HRMS (ESI) calcd for C19H18NO2S [M+H]+ 324.1053, found 324.1054.
MeO
S
N
MeO
(E)-5-(1,2-bis(2-methoxyphenyl)vinyl)thiazole (2i). Following the general procedure, the reaction was
set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(2-methoxyphenyl)ethyne (119 mg, 0.50 mmol).
Purification by flash column chromatography (hexanes/EtOAc = 4:1) provided 2i as a brown oil (61 mg,
38% yield). IR (film) 3000, 2927, 2834, 1594, 1490, 868 cm-1; H NMR (300 MHz, CDCl3)  8.63 (s,
1
1H), 7.50 (s, 1H), 7.41-7.29 (m, 2H), 7.16-7.05 (m, 2H), 6.98-6.89 (m, 2H), 6.83 (d, J = 8.2 Hz, 1H), 6.74
(d, J = 7.6 Hz, 1H), 6.58 (t, J = 7.5 Hz, 1H), 3.86 (s, 3H), 3.66 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3)
 157.6, 157.4, 151.3, 143.1, 140.1, 131.2, 129.8, 129.7, 129.2, 128.7, 128.0, 125.6, 125.3, 121.2, 120.1,
111.5, 110.4, 55.66, 55.65; HRMS (ESI) calcd for C19H18NO2S [M+H]+ 324.1053, found 324.1048.
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F
S
1
N
2
3
4
F
5
6
7
8
(E)-5-(1,2-bis(4-fluorophenyl)vinyl)thiazole (2j). Following the general procedure, the reaction was
set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(4-fluorophenyl)ethyne (107 mg, 0.50 mmol).
Purification by flash column chromatography (hexanes/EtOAc = 8:1) provided 2j as a white solid (100
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44
45
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48
49
50
51
52
53
54
55
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58
59
60
1
mg, 67% yield). mp 81-83 ℃; IR (film) 2921, 2851, 1598, 1506, 1226, 827 cm-1; H NMR (300 MHz,
CDCl3)  8.69 (s, 1H), 7.49 (s, 1H), 7.27-7.23 (m, 2H), 7.10 (t, J = 8.5 Hz, 2H), 6.99-6.91 (m, 3H), 6.84
(t, J = 8.7 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3)  162.7 (d, J = 248.3 Hz), 162.0 (d, J = 248.9 Hz),
152.1, 142.8, 141.7, 134.3 (d, J = 3.6 Hz), 132.1 (d, J = 3.7 Hz), 131.6 (d, J = 8.1 Hz), 131.2 (d, J = 8.0
Hz), 128.7, 116.4 (d, J = 21.5 Hz), 115.3 (d, J = 21.5 Hz); HRMS (ESI) calcd for C17H12F2NS [M+H]+
300.0653, found 300.0651.
F
S
N
F
(E)-5-(1,2-bis(3-fluorophenyl)vinyl)thiazole (2k). Following the general procedure, the reaction was
set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(3-fluorophenyl)ethyne (107 mg, 0.50 mmol).
Purification by flash column chromatography (hexanes/EtOAc = 5:1) provided 2k as a yellow oil (103
mg, 69% yield). IR (film) 3066, 2953, 2852, 1605, 1579, 1255, 871 cm-1; 1H NMR (300 MHz, CDCl3) 
8.72 (s, 1H), 7.51 (s, 1H), 7.40 (q, J = 7.2 Hz, 1H), 7.17-7.05 (m, 3H), 7.04-6.95 (m, 2H), 6.89-6.76 (m,
2H), 6.63 (d, J = 10.5 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3)  163.2 (d, J = 247.9 Hz), 162.5 (d, J =
245.4 Hz), 152.5, 142.1, 142.0, 140.3 (d, J = 7.7 Hz), 137.8 (d, J = 8.0 Hz), 133.2, 130.9 (d, J = 8.3 Hz),
129.7 (d, J = 8.5 Hz), 128.7 (d, J = 2.8 Hz), 125.44 (d, J = 3.6 Hz), 125.39 (d, J = 3.3 Hz), 116.6 (d, J =
21.8 Hz), 115.9 (d, J = 22.5 Hz), 115.7 (d, J = 20.9 Hz), 114.7 (d, J = 21.4 Hz); HRMS (ESI) calcd for
C17H12F2NS [M+H]+ 300.0653, found 300.0653.
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F
1
2
3
4
5
6
7
S
N
F
(E)-5-(1,2-bis(2-fluorophenyl)vinyl)thiazole (2l). Following the general procedure, the reaction was
set up with thiazole (172 mg, 2.0 mmol) and 1,2-bis(2-fluorophenyl)ethyne (107 mg, 0.50 mmol).
Purification by flash column chromatography (hexanes/EtOAc = 7:1) provided 2l as a yellow solid (101
mg, 67% yield). mp 98-100 ℃; IR (film) 3062, 2924, 2852, 1603, 1489, 1222, 869 cm-1; 1H NMR (300
MHz, CDCl3)  8.69 (s, 1H), 7.49 (s, 1H), 7.37 (q, J = 6.8 Hz, 1H), 7.26-7.20 (m, 2H), 7.12 (q, J = 8.2
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Hz, 3H), 6.99 (t, J = 9.3 Hz, 1H), 6.78-6.71 (m, 2H); C{1H} NMR (75 MHz, CDCl3)  160.8 (d, J =
13
249.4 Hz), 160.3 (d, J = 248.5 Hz), 152.4, 141.7, 141.6, 131.6 (d, J = 3.2 Hz), 130.7 (d, J = 8.0 Hz), 129.5
(d, J = 8.5 Hz), 129.3 (d, J = 2.5 Hz), 128.8, 125.8 (d, J = 16.1 Hz), 124.8 (d, J = 3.7 Hz), 123.9 (d, J =
12.4 Hz), 123.7 (d, J = 3.6 Hz), 123.5 (d, J = 5.3 Hz), 116.5 (d, J = 21.5 Hz), 115.5 (d, J = 22.2 Hz);
HRMS (ESI) calcd for C17H12F2NS [M+H]+ 300.0653, found 300.0645.
S
N
(E)-5-(1,2-di(naphthalen-2-yl)vinyl)thiazole (2m). Following the general procedure, the reaction was
set up with thiazole (172 mg, 2.0 mmol) and diethyl 1,2-di(naphthalen-2-yl)ethyne (161 mg, 0.50 mmol).
Purification by flash column chromatography (hexanes/EtOAc = 2:1) provided 2m as a yellow solid (128
mg, 70% yield). mp 59-61 °C; IR (film) 3051, 2921, 2851, 1593, 1460, 811 cm-1; 1H NMR (300 MHz,
CDCl3)  8.72 (s, 1H), 7.92-7.86 (m, 3H), 7.78 (d, J = 7.7 Hz, 1H), 7.66-7.57 (m, 4H), 7.53 (t, J = 7.0 Hz,
2H), 7.44-7.35 (m, 4H), 7.28 (s, 1H), 6.98 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3)  152.2,
143.4, 141.8, 136.3, 133.8, 133.7, 133.33, 133.31, 133.2, 132.6, 130.1, 129.8, 129.1, 128.9, 128.3, 128.2,
128.0, 127.8, 127.6, 126.71, 126.65, 126.5, 126.4, 126.3; HRMS (ESI) calcd for C25H18NS [M+H]+
364.1154, found 364.1154.
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S
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(E)-5-(1,2-di(thiophen-2-yl)vinyl)thiazole (2n). Following the general procedure, the reaction was set
up with thiazole (172 mg, 2.0 mmol) and 1,2-di(thiophen-2-yl)ethyne (95 mg, 0.50 mmol). Purification
by flash column chromatography (hexanes/EtOAc = 4:1) provided 2n as a brown oil (70 mg, 51% yield).
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IR (film) 3072, 2999, 2920, 2851, 1594, 1489, 855 cm-1; H NMR (300 MHz, CDCl3)  8.66 (s, 1H),
7.59-7.53 (m, 2H), 7.33 (s, 1H), 7.21-7.16 (m, 2H), 7.10 (d, J = 3.4 Hz, 1H), 7.05 (d, J = 3.1 Hz, 1H),
6.93 (t, J = 4.3 Hz, 1H); C{1H} NMR (75 MHz, CDCl3)  151.7, 142.4, 141.4, 139.5, 137.4, 130.5,
13
129.0, 128.5, 128.1, 128.0, 126.5, 126.1, 122.9; HRMS (ESI) calcd for C13H10NS3 [M+H]+ 275.9970,
found 275.9966.
S
S
N
S
(E)-5-(1,2-di(thiophen-3-yl)vinyl)thiazole (2o). Following the general procedure, the reaction was set
up with thiazole (172 mg, 2.0 mmol) and 1,2-di(thiophen-3-yl)ethyne (95 mg, 0.50 mmol). Purification
by flash column chromatography (hexanes/EtOAc = 4:1) provided 2o as a brown solid (65 mg, 47%
yield). mp 76-79 ℃; IR (film) 2982, 2921, 2849, 1596, 1490, 871 cm-1; H NMR (300 MHz, CDCl3) 
1
8.66 (s, 1H), 7.53 (s, 1H), 7.47-7.43 (m, 1H), 7.29-7.26 (m, 1H), 7.12-7.09 (m, 1H), 7.04 (s, 1H), 7.03-
7.01 (m, 1H), 6.96-6.93 (m, 1H), 6.54 (d, J = 5.0 Hz, 1H); C{1H} NMR (75 MHz, CDCl3)  151.7,
13
142.5, 141.2, 138.6, 137.8, 128.6, 127.8, 126.7, 125.4, 125.2, 124.7, 124.5; HRMS (ESI) calcd for
C13H10NS3 [M+H]+ 275.9970, found 275.9966.
O
OMe
S
Me
N
OMe
(E)-1-(5-(1,2-bis(4-methoxyphenyl)vinyl)thiazol-2-yl)ethenone (5a). Following the general
procedure, the reaction was set up with 1-(thiazol-2-yl)ethanone (260 mg, 2.0 mmol), 1,2-bis(4-
methoxyphenyl)ethyne (119 mg, 0.50 mmol) and N,N-dimethylacetamide (0.7 mL, 0.75 M). The reaction
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The Journal of Organic Chemistry
mixture was stirred at 110 ℃. Purification by flash column chromatography (hexanes/EtOAc = 7:1)
provided 5a as a yellow oil (150 mg, 82% yield). The isolated 1H NMR of the 5a showed the formation
of Z-alkenylation product (E/Z = 12:1). IR (film) 2955, 2930, 2836, 1679, 1603, 1510 cm-1; 1H NMR (300
MHz, CDCl3)  7.57 (s, 1H), 7.20 (d, J = 8.2 Hz, 2H), 7.08 (s, 1H), 6.98-6.94 (m, 4H), 6.69 (d, J = 8.5
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Hz, 2H), 3.87 (s, 3H), 3.76 (s, 3H), 2.67 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3)  191.8, 164.1, 159.6,
159.3, 151.9, 141.8, 131.3, 131.2, 130.9, 130.44, 130.41, 128.5, 114.8, 113.8, 55.4, 55.3, 25.7; HRMS
(ESI) calcd for C21H20NO3S [M+H]+ 366.1164, found 366.1159.
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N
OMe
(E)-5-(1,2-bis(4-methoxyphenyl)vinyl)-2-isobutylthiazole (5b). Following the general procedure, the
reaction was set up with 2-isobutylthiazole (291 mg, 2.0 mmol), 1,2-bis(4-methoxyphenyl)ethyne (119
mg, 0.50 mmol) and N,N-dimethylacetamide (0.7 mL, 0.75 M). The reaction mixture was stirred at 110
℃. Purification by flash column chromatography (hexanes/EtOAc = 10:1) provided 5b as a green oil (143
mg, 75% yield). IR (film) 3000, 2954, 2868, 2834, 1602, 1507 cm-1; 1H NMR (300 MHz, CDCl3)  7.21
(d, J = 8.8 Hz, 2H), 7.19 (s, 1H), 6.95-6.89 (m, 4H), 6.82 (s, 1H), 6.67 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H),
13
3.74 (s, 3H), 2.82 (d, J = 7.2 Hz, 2H), 2.18-2.02 (m, 1H), 1.00 (d, J = 6.6 Hz, 6H); C{1H} NMR (75
MHz, CDCl3)  169.0, 159.3, 158.6, 143.0, 139.9, 131.4, 131.0, 130.7, 129.2, 128.0, 114.4, 113.6, 55.3,
55.2, 42.7, 29.9, 22.4; HRMS (ESI) calcd for C23H26NO2S [M+H]+ 380.1684, found 380.1684.
Ph
OMe
S
N
OMe
(E)-5-(1,2-bis(4-methoxyphenyl)vinyl)-2-phenylthiazole (5c). Following the general procedure, the
reaction was set up with 2-phenylthiazole22 (322 mg, 2.0 mmol), 1,2-bis(4-methoxyphenyl)ethyne (119
mg, 0.50 mmol) and N,N-dimethylacetamide (0.7 mL, 0.75 M). The reaction mixture was stirred at 110
℃. Purification by flash column chromatography (hexanes/EtOAc = 22:1) provided 5c as a yellow solid
1
(186 mg, 93% yield). The isolated H NMR of the 5c showed the formation of Z-alkenylation product
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(E/Z = 12:1). mp 45-48 °C; IR (film) 3000, 2921, 2851, 1601, 1507, 1452 cm-1; H NMR (300 MHz,
1
1
2
3
CDCl3)  7.97-7.88 (m, 2H), 7.45-7.37 (m, 4H), 7.23 (s, 1H), 7.04-6.83 (m, 6H), 6.68 (d, J = 8.8 Hz, 2H),
4
5
6
7
8
9
3.86 (s, 3H), 3.74 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3)  166.3, 159.5, 158.8, 144.0, 141.5, 133.9,
131.3, 131.1, 131.0, 130.0, 129.2, 129.1, 128.6, 126.5, 114.6, 113.7, 55.4, 55.3; HRMS (ESI) calcd for
C25H22NO2S [M+H]+ 400.1371, found 400.1372.
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(E)-5-(1,2-diphenylvinyl)-4-phenylthiazole (5d).
4-Phenylthiazole was prepared by Suzuki reaction.23 To a 40 mL-glass vial equipped with a magnetic stir
bar were sequentially added 4-bromothiazole (492 mg, 3.0 mmol), phenylboronic acid (549 mg, 4.5
mmol), K2CO3 (829 mg, 6.0 mmol), 1,4-dioxane (3.0 mL), H2O (1.0 mL) and Pd(PPh3)4 (231 mg, 0.065
mmol). The reaction mixture was purged with argon through a Teflon-lined cap. Then, the cap was
replaced with a new Teflon-lined solid cap. The reaction vial was heated at 100 °C for 18 h. After cooling
to 25 °C, the reaction mixture was treated with water (15 mL) and EtOAc (15 mL) and transferred to a
125 mL-separatory funnel. The organic layer was collected and the aqueous layer was extracted with
EtOAc (15 mL × 2). The combined organic layers were washed with brine (20 mL), dried over sodium
sulfate and filtered. The residue was then purified by flash column chromatography (hexanes/EtOAc =
1
10:1) to afford 4-phenylthiazole as a white solid (300 mg, 62% yield). H NMR was matched with the
reported data.8i 1H NMR (300 MHz, CDCl3) δ 8.90 (s, 1H), 7.94 (d, J = 6.6 Hz, 2H), 7.55 (s, 1H), 7.48-
7.42 (m, 2H), 7.39-7.33 (m, 1H).
Following the general procedure, the reaction was set up with 4-phenylthiazole (322 mg, 2.0 mmol),
diphenylacetylene (91 mg, 0.50 mmol) and acetic acid (9 mg, 0.15 mmol). Purification by flash column
chromatography (hexanes/EtOAc = 20:1) provided 5d as a yellow solid (104 mg, 61% yield). mp 118-
120 °C; IR (film) 3054, 3022, 1598, 1477, 1443, 767 cm-1; 1H NMR (300 MHz, CDCl3)  8.78 (s, 1H),
7.77 (d, J = 7.1 Hz, 2H), 7.36-7.18 (m, 8H), 7.18-7.09 (m, 3H), 7.08-6.98 (m, 2H), 6.85 (s, 1H); 13C{1H}
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The Journal of Organic Chemistry
NMR (75 MHz, CDCl3)  152.1, 151.3, 139.0, 136.6, 136.4, 134.9, 133.4, 132.5, 129.9, 129.5, 128.9,
128.5, 128.3, 128.2, 128.1, 127.9, 127.5; HRMS (ESI) calcd for C23H18NS [M+H]+ 340.1160, found
340.1156.
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(E)-5-(1,2-diphenylvinyl)-2,4-diphenylthiazole (5e). Following the general procedure, the reaction
was set up with 2,4-diphenylthiazole24 (237 mg, 1.0 mmol) and diphenylacetylene (91 mg, 0.50 mmol).
Purification by flash column chromatography (Et2O/EtOAc = 10:1) provided 5e as a white solid (152 mg,
1
73% yield). mp 124-126 °C; IR (film) 3054, 3022, 1597, 1478, 1441, 857 cm-1; H NMR (300 MHz,
CDCl3)  8.06-7.97 (m, 2H), 7.91-7.82 (m, 2H), 7.48-7.42 (m, 3H), 7.35-7.23 (m, 8H), 7.19-7.14 (m, 3H),
13
7.10-7.03 (m, 2H), 6.92 (s, 1H); C{1H} NMR (75 MHz, CDCl3)  165.6, 152.4, 139.2, 136.8, 136.6,
135.3, 133.7, 133.0, 132.8, 130.1, 130.0, 129.5, 129.03, 128.96, 128.5, 128.3, 128.2, 128.1, 127.8, 127.4,
126.5; HRMS (ESI) calcd for C29H22NS [M+H]+ 416.1473, found 416.1466.
Me
S
N
Ph
(E)-5-(1,2-diphenylvinyl)-2-methyl-4-phenylthiazole (5f). Following the general procedure, the
reaction was set up with 2-methyl-4-phenylthiazole (175 mg, 1.0 mmol) and diphenylacetylene (91 mg,
0.50 mmol). Purification by flash column chromatography (hexanes/DCM = 5:1) provided 5f as a white
solid (123 mg, 70% yield). mp 114-116 °C; IR (film) 2920, 2847, 1736, 1650, 1598, 1491, 768 cm-1; 1H
NMR (300 MHz, CDCl3)  7.78-7.66 (m, 2H), 7.26-7.10 (m, 10H), 7.02-6.96 (m, 2H), 6.79 (s, 1H), 2.72
(s, 3H); 13C{1H} NMR (75 MHz, CDCl3)  164.2, 151.1, 139.3, 136.6, 136.1, 135.2, 132.9, 132.8, 129.9,
129.4, 128.9, 128.5, 128.3, 128.1, 128.0, 127.7, 127.3, 19.4; HRMS (ESI) calcd for C24H20NS [M+H]+
354.1311, found 354.1309.
OMe
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N
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(E)-ethyl 5-(1,2-bis(4-methoxyphenyl)vinyl)thiazole-4-carboxylate (5g). Following the general
procedure, the reaction was set up with ethyl thiazole-4-carboxylate (321 mg, 2.0 mmol), 1,2-bis(4-
methoxyphenyl)ethyne (119 mg, 0.50 mmol) and acetic acid (9 mg, 0.15 mmol). Purification by flash
column chromatography (hexanes/EtOAc = 3:1) provided 5g as a yellow oil (53 mg, 27% yield). IR (film)
2955, 2933, 2836, 1719, 1603, 1509 cm-1; 1H NMR (300 MHz, CDCl3)  8.67 (s, 1H), 7.18 (d, J = 8.7
Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 6.83 (s, 1H), 6.81 (d, J = 5.8 Hz, 2H), 6.71 (d, J = 8.8 Hz, 2H), 4.21 (q,
J = 7.1 Hz, 2H), 3.81 (s, 3H), 3.77 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) 
162.4, 159.3, 159.2, 151.1, 149.4, 142.4, 133.0, 131.8, 131.1, 131.0, 128.8, 128.6, 114.0, 113.7, 61.4,
55.31, 55.29, 14.3; HRMS (ESI) calcd for C22H22NO4S [M+H]+ 396.1270, found 396.1268.
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(E)-ethyl 5-(1,2-bis(4-methoxyphenyl)vinyl)-2-phenylthiazole-4-carboxylate (5h). Following the
general procedure, the reaction was set up ethyl 2-phenylthiazole-4-carboxylate25 (194 mg, 1.0 mmol)
and 1,2-bis(4-methoxyphenyl)ethyne (119 mg, 0.50 mmol). Purification by flash column chromatography
(hexanes/EtOAc = 4:1) provided 5h as a yellow solid (194 mg, 82% yield). The isolated 1H NMR of the
5h showed the formation of Z-alkenylation product (E/Z = 6:1). mp 70-72 °C; IR (film) 3052, 2933, 1718,
1509, 1247, 829 cm-1; 1H NMR (300 MHz, CDCl3)  8.00-7.89 (m, 2H), 7.45-7.40 (m, 3H), 7.22 (d, J =
8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 6.85 (s, 1H), 6.83 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 4.16
(q, J = 7.1 Hz, 2H), 3.82 (s, 3H), 3.78 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3)
 165.6, 162.9, 159.2, 159.0, 148.3, 142.8, 132.9, 132.4, 131.6, 131.01, 131.00, 130.4, 129.0, 128.9, 128.8,
126.7, 113.9, 113.6, 61.3, 55.20, 55.16, 14.2; HRMS (ESI) calcd for C28H26NO4S [M+H]+ 472.1577,
found 472.1578.
Me
OMe
N
S
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OMe
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(E)-2-(1,2-bis(4-methoxyphenyl)vinyl)-4,5-dimethylthiazole (5i). Following the general procedure,
the reaction was set up with 4,5-dimethylthiazole (231 mg, 2.0 mmol) and 1,2-bis(4-
methoxyphenyl)ethyne (119 mg, 0.50 mmol). Purification by flash column chromatography
(hexanes/EtOAc = 21:1) provided 5i as a yellow oil (97 mg, 55% yield). IR (film) 2998, 2952, 2919,
2834, 1600, 1507 cm-1; 1H NMR (300 MHz, CDCl3)  7.60 (s, 1H), 7.28-7.21 (m, 2H), 7.03-6.90 (m, 4H),
6.66 (d, J = 7.7 Hz, 2H), 3.85 (s, 3H), 3.73 (s, 3H), 2.36 (s, 3H), 2.28 (s, 3H); 13C{1H} NMR (75 MHz,
CDCl3)  167.8, 159.6, 159.0, 149.3, 132.1, 131.5, 131.4, 129.0, 127.7, 127.3, 114.5, 113.7, 55.4, 55.3,
15.1, 11.6; HRMS (ESI) calcd for C21H22NO2S [M+H]+ 352.1371, found 352.1366.
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(E)-5-(1,2-bis(4-methoxyphenyl)vinyl)-4-phenyloxazole (6a). Following the general procedure, the
reaction was set up with 4-phenyloxazole (290 mg, 2.0 mmol), 1,2-bis(4-methoxyphenyl)ethyne (119 mg,
1
0.50 mmol) and acetic acid (9.0 mg, 0.15 mmol). The H NMR of the reaction mixture showed the
formation of the corresponding C5- and C2-alkenylation products (C5:C2 = 10:1). Purification by flash
column chromatography (hexanes/EtOAc = 9:1) provided the C5 isomer, 6a, as a yellow oil (117 mg,
61% yield). IR (film) 3001, 2955, 2931, 2835, 1603, 1509 cm-1; 1H NMR (300 MHz, CDCl3)   s,
1H), - m, 2H), - m, 3H), 7.14 (d, J = 8.7 Hz, 2H),   s, 1H), 7.00 (d, J = 4.7 Hz,
2H), 6.74 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.9 Hz, 2H), 3.77 (s, 3H), 3.76 (s, 3H); 13C NMR (75 MHz,
CDCl3)  159.4, 159.1, 149.6, 148.2, 135.9, 132.1, 131.23, 131.16, 131.0, 128.9, 128.7, 128.1, 127.8,
127.5, 127.4, 114.2, 113.7, 55.4, 55.3; HRMS (ESI) calcd for C22H22NO5 [M+H]+ 384.1600, found
384.1590.
(E)-2-(1,2-bis(4-methoxyphenyl)vinyl)-4-phenyloxazole (the C2 isomer). 1H NMR (300 MHz, CDCl3)
 7.86 (s, 1H), 7.76 (d, J = 7.1 Hz, 2H), 7.73 (s, 1H), 7.44-7.35 (m, 2H), 7.35-7.27 (m, 3H), 7.07 (d, J =
8.6 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.77 (s, 3H).
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EtO
O
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(E)-ethyl 2-(1,2-bis(4-methoxyphenyl)vinyl)oxazole-4-carboxylate (6b). Following the general
procedure, the reaction was set up with ethyl oxazole-4-carboxylate (294 mg, 2.0 mmol) 1,2-bis(4-
methoxyphenyl)ethyne (119 mg, 0.50 mmol) and acetic acid (9.0 mg, 0.15 mmol). The 1H NMR of the
reaction mixture showed the formation of the corresponding C2- and C5-alkenylation products (C2/C5 =
8:1).Purification by flash column chromatography (hexanes/EtOAc = 9:1) provided the C2 isomer, 6b, as
a yellow solid (154 mg, 81% yield). mp 124-125 °C; IR (film) 2957, 2933, 2836, 1716, 1602, 1509 cm-1;
1H NMR (300 MHz, CDCl3)   s, 1H), 7.80 (s, 1H), 7.25 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 8.5 Hz,
2H), 6.96 (d, J = 8.3 Hz, 2H), 6.71 (d, J = 8.5 Hz, 2H), 4.40 (q, J = 7.0 Hz, 2H), 3.87 (s, 3H), 3.76 (s, 3H),
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1.39 (t, J = 7.0 Hz, 3H); C{1H} NMR (75 MHz, CDCl3)  164.9, 161.7, 159.9, 159.6, 143.6, 134.9,
134.5, 132.0, 131.3, 127.9, 127.6, 125.4, 114.6, 113.8, 61.4, 55.40, 55.35, 14.5; HRMS (ESI) calcd for
C22H22NO5 [M+H]+ 380.1498, found 380.1493.
1
(E)-ethyl 5-(1,2-bis(4-methoxyphenyl)vinyl)oxazole-4-carboxylate (the C5 isoemr). H NMR (300
MHz, CDCl3)  7.75 (s, 1H), 7.42 (s, 1H), 7.17 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.6 Hz, 2H), 6.88 (d, J =
8.8 Hz, 2H), 6.71 (d, J = 8.8 Hz, 2H), 4.25 (q, J = 7.1 Hz, 2H), 3.83 (s, 3H), 3.77 (s, 3H), 1.27 (t, J = 7.1
Hz, 3H).
Ph
OMe
O
N
Ph
OMe
(E)-5-(1,2-bis(4-methoxyphenyl)vinyl)-2,4-diphenyloxazole (6c). Following the general procedure,
the reaction was set up with 2,4-diphenyloxazole (443 mg, 2.0 mmol), 1,2-bis(4-methoxyphenyl)ethyne
(119 mg, 0.50 mmol) and acetic acid (9.0 mg, 0.15 mmol). Purification by flash column chromatography
(hexanes/EtOAc = 15:1) provided 6c as a yellow solid (190 mg, 83% yield). mp 63-66 °C; IR (film) 3053,
2986, 1604, 1553, 1510, 1263 cm-1; 1H NMR (300 MHz, CDCl3)  - m, 2H), - m, 5H),
- m, 4H), 7.12 (d, J = 3.9 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 6.71 (d, J = 4.9 Hz, 2H), 6.69 (d, J
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= 4.8 Hz, 2H), 3.77 (s, 3H), 3.76 (s, 3H); 13C NMR (75 MHz, CDCl3)  159.8, 159.4, 159.0, 147.9, 138.2,
132.6, 131.5, 131.2, 130.4, 130.1, 129.2, 128.8, 128.6, 128.2, 127.9, 127.6, 127.4, 126.6, 114.1, 113.7,
55.4, 55.3; HRMS (ESI) calcd for C22H22NO5 [M+H]+ 460.1913, found 460.1909.
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EtO
O
OMe
(E)-ethyl 5-(1,2-bis(4-methoxyphenyl)vinyl)-2-phenyloxazole-4-carboxylate (6d). Following the
general procedure, the reaction was set up with ethyl 2-phenyloxazole-4-carboxylate21 (217 mg, 1.0
mmol), and 1,2-bis(4-methoxyphenyl)ethyne (119 mg, 0.50 mmol). Purification by flash column
chromatography (hexanes/EtOAc = 2:1) provided 6d as a yellow solid (195 mg, 86% yield). mp 137-139
°C; IR (film) 3052, 2933, 1719, 1508, 1246, 828 cm-1; 1H NMR (300 MHz, CDCl3)  - m, 2H),
7.46-7.41 (m, 3H), 7.38 (s, 1H), 7.23 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.6 Hz,
2H), 6.72 (d, J = 8.8 Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H), 3.78 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H);
13C{1H} NMR (75 MHz, CDCl3)  162.3, 159.5, 159.4, 159.2, 156.8, 134.6, 131.4, 131.0, 130.8, 129.3,
128.7, 128.4, 126.8, 126.5, 125.8, 114.1, 113.6, 61.2, 55.3, 55.2, 14.2; HRMS (ESI) calcd for C28H26NO5
[M+H]+ 456.1805, found 456.1810.
O
N
(E)-2-(1,2-diphenylvinyl)benzo[d]oxazole (6e). Following the general procedure, the reaction was set
up with benzoxazole (119 mg, 1.0 mmol) and diphenylacetylene (91 mg, 0.50 mmol). Purification by
flash column chromatography (hexanes/EtOAc = 9:1) provided 6e as a white solid (121 mg, 81% yield).
1H NMR was matched with the reported data.20 1H NMR (300 MHz, CDCl3)  7.98 (s, 1H), 7.77-7.69 (m,
1H), 7.56-7.51 (m, 1H), 7.48-7.44 (m, 3H), 7.43-7.37 (m, 3H), 7.34-7.29 (m, 2H), 7.21-7.19 (m, 2H),
7.14-7.10 (m, 2H).
O
Me
Me
O
N
N
N
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Me
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(E)-8-(1,2-diphenylvinyl)-1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione (7).26 Following the general
procedure, the reaction was set up with 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione (caffeine, 194 mg,
1.0 mmol) and diphenylacetylene (91 mg, 0.50 mmol). Purification by flash column chromatography
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8
(hexanes/EtOAc = 6:1) provided 7 as a white solid (129 mg, 69% yield). H NMR (300 MHz, CDCl3)
9
7.35-7.33 (m, 4H), 7.26-7.09 (m, 7H), 3.65 (s, 3H), 3.47 (s, 3H), 3.41 (s, 3H).
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NO2
N
N
Me
(E)-5-(1,2-diphenylvinyl)-1-methyl-4-nitro-1H-pyrazole (8). Following the general procedure, the
reaction was set up with 1-methyl-4-nitro-1H-pyrazole27 (127 mg, 1.0 mmol) and diphenylacetylene (91
mg, 0.50 mmol). Purification by flash column chromatography (hexanes/EtOAc = 9:1) provided 8 as a
yellow solid (88 mg, 58% yield). mp 108-109 °C; IR (film) 3124, 3054, 3023, 2949, 1543, 1498 cm-1; 1H
NMR (300 MHz, CDCl3)  8.14 (s, 1H), 7.28-7.20 (m, 10H), 6.83 (s, 1H), 3.79 (s, 3H); 13C{1H} NMR
(75 MHz, CDCl3)  143.1, 136.34, 136.27, 135.9, 134.9, 129.7, 129.4, 128.9, 128.59, 128.57, 128.4,
127.5, 38.0; HRMS (ESI) calcd for C18H16N3O2 [M+H]+ 306.1243, found 306.1235.
CH3
Cy3P
O
Pd
O
PCy3
Synthesis and Characterization of Alkenyl Pd(II) Complex 9
To an 8 mL-glass vial equipped with a magnetic stir bar, diphenylacetylene (182 mg, 1.0 mmol),
Pd(PCy3)2 (178 mg, 1.0 mmol) and benzene (2.2 mL, 0.45 M) were added. After 30 minutes of stirring at
25 °C, acetic acid (57 μL, 1.0 mmol) was injected. The reaction mixture was stirred at 25 °C for 11 h, and
a white solid precipitated. The solution was filtered and the filtrate was washed with pentane three times
to afford 9 as a white solid (570 mg, 63% yield). Crystals suitable for X-ray crystallography were obtained
1
from vapor diffusion of hexanes into a saturated benzene solution of 9 at −20 °C. H NMR (300 MHz,
CDCl3) δ 7.96 (d, J = 6.7 Hz, 2H), 7.14-7.03 (m, 5H), 7.01-6.93 (m, 3H), 6.13 (s, 1H), 2.10-1.98 (m,
12H), 1.84 (s, 3H), 1.83-1.59 (m, 30H), 1.34-1.02 (m, 24H); 13C{1H} NMR (75 MHz, CDCl3) δ 175.4,
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151.8, 146.0, 138.7, 131.0, 128.54, 128.46, 127.7, 127.5, 126.1, 124.6, 33.2 (t, J = 8.1 Hz), 29.9, 29.1,
28.3 (t, J = 4.8 Hz), 28.1 (t, J = 5.2 Hz), 26.7, 25.3.
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Hydroarylation Using Alkenyl Pd(II) Complex 9. To an 8 mL-glass vial equipped with a magnetic stir
bar, thiazole (17 mg, 0.2 mmol), complex 9 (45 mg, 0.05 mmol), and N,N-dimethylacetamide (0.50 mL,
0.10 M) were sequentially added in an argon-purged glove box. The reaction mixture was stirred at 130 ℃
for 14 h and cooled to 25 ℃. The GC analysis of the reaction mixture showed the formation of 2a and 3a
in 29% and 42% yields, respectively.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
NMR spectra and X-ray data (PDF)
Crystallographic data for 2a (CIF)
Crystallographic data for 9 (CIF)
AUTHOR INFORMATION
Corresponding Author
* E-mail: jmjoo@pusan.ac.kr
ORCID
Jung Min Joo: 0000-0003-1645-3322
Author Contributions
+ These authors contributed equally to this work.
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Acknowledgments. This research was supported by the Basic Science Research Program through the
National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning
(NRF-2016R1D1A1B03930762 and NRF-2019R1A2C1007852). We thank Prof. Ok-Sang Jung at Pusan
National University for assistance with analysis of x-ray structures and for helpful discussions.
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9
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(9) For regioselective C5-alkenylation of unsubstituted two-heteroatom-containing azoles using alkenes,
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Q.; Shi, Z.-J., Diversified Syntheses of Multifunctionalized Thiazole Derivatives via Regioselective and
Programmed C−H Activation. Chem. Commun. 2015, 51, 4599−4602. (b) Achar, T. K.; Biswas, J. P.;
Porey, S.; Pal, T.; Ramakrishna, K.; Maiti, S.; Maiti, D., Palladium-Catalyzed Template Directed C-5
Selective Olefination of Thiazoles. J. Org. Chem. 2019, 84, 8315−8321. (c) Kim, H. T.; Ha, H.; Kang,
G.; Kim, O. S.; Ryu, H.; Biswas, A. K.; Lim, S. M.; Baik, M.-H.; Joo, J. M., Ligand-Controlled
Regiodivergent C−H Alkenylation of Pyrazoles and its Application to the Synthesis of Indazoles. Angew.
Chem. Int. Ed. 2017, 56, 16262−16266. (d) Kim, H.; Hwang, Y. J.; Han, I.; Joo, J. M., Regioselective
C−H Alkenylation of Imidazoles and its Application to the Synthesis of Unsymmetrically Substituted
Benzimidazoles. Chem. Commun. 2018, 54, 6879−6882.
(10) For C5-alkenylation of substituted thiazoles, see: (a) Miyasaka, M.; Hirano, K.; Satoh, T.; Miura,
M., Palladium-Catalyzed Direct Oxidative Alkenylation Of Azoles. J. Org. Chem. 2010, 75, 5421−5424.
(b) Li, Z.; Ma, L.; Tang, C.; Xu, J.; Wu, X.; Yao, H., Palladium(II)-Catalyzed Oxidative Heck Coupling
Of Thiazole-4-Carboxylates. Tetrahedron Lett. 2011, 52, 5643−5647.
(11) We proposed hydropalladation of alkynes in the C−H functionalization of nitropyrazoles with
terminal alkynes. Ha, H.; Shin, C.; Bae, S.; Joo, J. M., Divergent Palladium-Catalyzed Cross-Coupling of
Nitropyrazoles with Terminal Alkynes. Eur. J. Org. Chem. 2018, 2018, 2645−2650.
(12) Shen, R.; Chen, T.; Zhao, Y.; Qiu, R.; Zhou, Y.; Yin, S.; Wang, X.; Goto, M.; Han, L.-B., Facile
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