Regioselective C-H bond cleavage/alkyne insertion under ruthenium catalysis

Article abstract of DOI:10.1021/jo3025237

The ruthenium-catalyzed coupling reactions of benzamides with alkynes in the presence of acetic acid as a promoter smoothly proceeded regio- and stereoselectively through a directed C-H bond cleavage to produce the corresponding ortho-alkenylated products. Phenylpyrazoles and related substrates also underwent a similar coupling to give dialkenylated products selectively. Several competitive experiments were performed to obtain mechanistic insight into both the mono- and dialkenylation reactions.

Full text of DOI:10.1021/jo3025237

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Article
Regioselective C–H Bond Cleavage/
Alkyne Insertion under Ruthenium Catalysis
Yuto Hashimoto, Koji Hirano, Tetsuya Satoh, Fumitoshi Kakiuchi, and Masahiro Miura
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo3025237 • Publication Date (Web): 14 Dec 2012
Downloaded from http://pubs.acs.org on December 17, 2012
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Regioselective C–H Bond Cleavage/Alkyne Insertion
under Ruthenium Catalysis
Yuto Hashimoto,† Koji Hirano,† Tetsuya Satoh,*,†,‡ Fumitoshi Kakiuchi,§ and Masahiro Miura*,†
†Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871,
Japan, ‡JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan, and §Department of
Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku,
Yokohama, Kanagawa 223-8522, Japan
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satoh@chem.eng.osaka-u.ac.jp; miura@chem.eng.osaka-u.ac.jp
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required)
Abstract: The ruthenium-catalyzed coupling reactions of benzamides with alkynes in the presence of
acetic acid as a promoter smoothly proceeded regio- and stereoselectively through a directed C–H bond
cleavage to produce the corresponding ortho-alkenylated products. Phenylpyrazoles and related
substrates also underwent similar coupling to give dialkenylated products selectively. Several
competitive experiments were performed to obtain mechanistic insight into both the mono- and
dialkenylation reactions.
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Introduction
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Since alkenylarene structures can be seen in numerous organic functional materials, methods for their
construction have been widely investigated and developed. The direct alkenylation reactions of arenes
through regioselective C–H bond activation with the aid of directing groups have attracted much
attention as atom- and step-economical methods for their precise syntheses.1 As early examples, we
have demonstrated that 2-phenylphenols, N-sulfonyl-2-phenylanilines, and benzoic acids undergo
oxidative coupling with alkenes in the presence of a Pd or Rh catalyst and an appropriate oxidant to
afford ortho-alkenylated products.2,3 After the discovery, a number of related oxidative alkenylation
reactions of a wide range of aromatic substrates have been reported by us4 and others.5 More recently,
we have succeeded in finding that heteroarene carboxylic acids,6 phenylazoles,7 and benzamides7
undergo similar alkenylation under ruthenium catalysis. The ruthenium-catalyzed reactions seem to be
attractive because of their relatively lower catalyst cost than Pd and Rh. One of such reactions is
depicted in Scheme 1, in which N,N-dimethylbenzamide undergoes the oxidative coupling with butyl
acrylate in the presence of a Ru/Ag catalyst system8 and a copper salt oxidant to form an ortho-
alkenylated product almost quantitatively.8a We next examined the reaction of the amide employing
alkynes in place of alkenes under the same oxidative conditions. As a result, the corresponding
oxidative coupling product could not be obtained at all: instead, C–H bond cleavage and alkyne
insertion took place to give an alkenylarene as a non-oxidative coupling product. It was then confirmed
that this reaction proceeds more efficiently in the absence of any oxidant. Furthermore, the reaction
system was found to be applicable to the alkenylation of phenylazoles. The detailed results obtained
with respect to these coupling reactions are described herein.9 Recently, similar C–H bond
cleavage/alkyne insertion processes using rhodium,10,11 iridium,12 palladium,13 rhenium,14 nickel,15 and
cobalt16 catalysts have been disclosed, but the substrate scope still remains limited.
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SCHEME 1. Ruthenium-Catalyzed Alkenylation of N,N-Dimethylbenzamide
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Results and Discussion
As described above, N,N-dimethylbenzamide (1a) (0.25 mmol) reacted with diphenylacetylene (2a)
(0.5 mmol) in the presence of [Ru(p-cymene)Cl2]2 (0.0125 mmol), AgSbF6 (0.05 mmol), and
Cu(OAc)2•H2O (0.5 mmol) in AmtOH (3 mL) at 100 C under N2 to produce (E)-2-(1,2-
o
diphenylethenyl)-N,N-dimethylbenzamide (3a) in 45% yield (Scheme 1 and entry 1 in Table 1). It was
confirmed that both the ruthenium catalyst and the silver cocatalyst are essential for the present reaction:
without each one of them, 3a could not be obtained at all (entries 2 and 3). While the reaction was
sluggish in DMF (entry 4), the product yield was significantly improved in dioxane and diglyme up to
90% and 88% yields, respectively (entries 5 and 6). At 120 oC, a comparable result was obtained (entry
7). In all cases described above, no oxidative coupling product was detected in spite of the oxidative
conditions using Cu(OAc)2•H2O. However, the reaction efficiency severely decreased without the
copper species (entry 8). Afterward, it was found that it acts as an AcOH source rather than oxidant.
Thus, the reaction was remarkably promoted by addition of AcOH (1 mmol) to afford 3a in 96% yield
(entry 9). Decreasing the amount of AcOH to 0.1 mmol reduced the yield (entry 10). Under conditions
using H2O or KOAc in place of AcOH, 3a was not formed at all (entries 11 and 12). Even with a slight
excess (0.3 mmol) of 2a, the alkenylated product 3a was formed in 82% yield (entry 13).
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TABLE 1. Reaction of N,N-Dimethylbenzamide (1a) with Diphenylacetylene (2a)a
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a Reaction conditions: [1a]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6] = 0.25:0.5:0.0125:0.05 (in mmol), in
solvent (3 mL) at 100 C for 5 h under N2. GC yield based on the amount of 1a used. Value in
parentheses indicates yield after purification. c Without [Ru(p-cymene)Cl2]2. d Without AgSbF6. e At 120
oC. f [2a] = 0.3 mmol.
o
b
Under the conditions employed for entry 9 in Table 1, the reactions of 1a with various alkynes 2a-g
were examined (Table 2). Methyl- (2b) and chloro- (2c) substituted diphenylacetylenes reacted
smoothly to form the corresponding coupling products 3b and 3c, respectively (entries 1 and 2).
Unsymmetrical alkylphenylacetylenes, 1-phenylpropyne (2d) and –hexyne (2e), coupled with 1a to
smoothly produce 3d and 3e, respectively (entries 3 and 4). It should be noted that no regio- and
stereoisomers could be detected at all. The reaction of 1-phenyl-2-(trimethylsilyl)acetylene (2f)
proceeded efficiently through C–H bond cleavage/alkyne insertion/desilylation to produce a 1,1-
diarylethene derivative 3f in 63% yield, along with a minor amount of normal product 3f’ (entry 5).
Using a terminal alkyne, triisopropylsilylacetylene (2g), the expected coupling product 3g was obtained,
albeit with a low yield (entry 6). The reaction efficiency was not improved by using various acids in
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place of AcOH (entries 7-9). More sterically hindered alkyne, 1-phenyl-2-(triisopropylsilyl)acetylene,
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did not react with 2a at all.
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TABLE 2. Reaction of N,N-Dimethylbenzamide (1a) with Alkynes 2a
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a
Reaction conditions: [1a]:[2]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] = 0.25:0.5:0.0125:0.05:1 (in
mmol), in dioxane (3 mL) at 100 C for 5 h under N2. A separable byproduct, N,N-dimethyl-2-(1-
o
b
c
phenyl-2-(trimethylsilyl)vinyl)benzamide (3f'), was also formed (17%). CF3CO2H (1 mmol) was
employed in place of AcOH. d 2,6-Me2C6H3CO2H (1 mmol) was employed in place of AcOH. e GC yield.
f 4-MeC6H4SO3H (1 mmol) was employed in place of AcOH.
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Table 3 summarizes the results for the coupling of a number of benzamides 1b-h with 2a. A series of
N,N-disubstituted benzamides having cyclic-, diisopropyl- and diphenylamino groups, 1b-e, reacted
with 2a to form products 3h-k, respectively (entries 1-4). 4-Methyl-, methoxy-, and chlorobenzamides
1f-h also underwent coupling with 2a smoothly to form products 3l-3n in 77-87% yields (entries 5-7).
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TABLE 3. Reaction of Benzamides 1 with Diphenylacetylene (2a)a
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Reaction conditions: [1]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] = 0.25:0.5:0.0125:0.05:1 (in
mmol), in dioxane (3 mL) at 100 oC for 5 h under N2.
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One of possible pathways for the reaction of 1 with 2 is illustrated in Scheme 2. Coordination of an
amide function to Ru center seems to trigger ortho C–H bond cleavage to give a five-membered
ruthenacycle intermediate I accompanied by loss of a proton.17 Then, alkyne insertion into the resulting
Ru-C bond occurs to form a seven-membered species II. Subsequent protonolysis may take place to
produce 3. In cases using unsymmetrical alkynes 2d-g, the regioselectivity of the insertion step from I to
II seems to be governed by steric factors.
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SCHEME 2. Plausible Mechanism for the Reaction of 1 with 2
For providing further mechanistic information, deuterated N,N-dimethylbenzamide (1a-d5) was treated
with 2a under standard reaction conditions (Scheme 3). In the early stage (15 min), deuterium
1
incorporation in the olefinic position of product could not be detected by H NMR. This observation
may exclude the possibility of reaction pathway involving initial oxidative addition of ortho C–H bond,
which leads to deuterium incorporation at the position.16a,d Meanwhile, no significant D–H exchange at
the ortho positions of recovered 1a-d5 as well as at the 6-position of product 3a-d4 was observed. This
result indicates that the amide-directed C–H bond cleavage step to form intermediate I is likely
irreversible.
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SCHEME 3. Reaction of 1a-d5 with 2a in dioxane at 100 oC for 15 mina
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a Reaction conditions: [1a-d5]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] = 0.25:0.5:0.0125:0.05:1
(in mmol).
Next, an intermolecular competition reaction of 1a-d0/1a-d5 with 2a was examined. As shown in
Scheme 4, a considerable primary kinetic isotope effect (KIE) of 2.1 was observed. Two parallel
reactions using 1a-d0 and 1a-d5 were also performed separately and showed a similar KIE value of 2.0
(see the Experimental Section). These facts suggest that the rate-determining step involves C–H(D)
bond cleavage.
SCHEME 4. Competitive Reaction of 1a-d0/1a-d5 in dioxane at 100 oC for 20 mina
a Reaction conditions: [1a-d0]:[1a-d5]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] =
0.125:0.125:0.5:0.0125:0.05:1 (in mmol).
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On the other hand, an intermolecular competition experiment between methyl- (1f) and chloro- (1h)
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2
substituted benzamides was conducted (Scheme 5). Treatment of equimolar amounts of 1f and 1h with
2a under standard conditions for 10 min gave a mixture of 3l and 3n with negligible preference for their
formation (54:46). The observed vanishingly small substituent effect, in combination with the KIE
effect observed, may suggest that the C–H bond cleavage step does not proceed via a simple SEAr
mechanism, but possibly involves an acetate-assisted deprotonation.18
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SCHEME 5. Competitive Reaction of 1f and 1h in dioxane at 100 oC for 10 mina
a Reaction conditions: [1f]:[1h]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] =
0.125:0.125:0.5:0.0125:0.05:1 (in mmol).
Next, the reactions of 1-phenylpyrazoles 4 with 2 were examined by using the same catalyst system.
When 1-phenylpyrazole (4a) (0.25 mmol) was treated with 2a (0.625 mmol) in the presence of [Ru(p-
o
cymene)Cl2]2 (0.0125 mmol), AgSbF6 (0.05 mmol), and AcOH (1 mmol) in dioxane (3 mL) at 100 C
under N2 for 5 h, the coupling reaction took place efficiently in a 1:2 manner to selectively afford
dialkenylated product 5a in 85% yield (entry 1 in Table 4). Substituted diphenylacetylenes 2b, 2c, and
2h also underwent 1:2 coupling to give the corresponding products 5b-d (entries 2-4). The reaction of
unsymmetrical 2d gave 1-[2,6-bis(1-phenylprop-1-en-2-yl)phenyl]pyrazole (5e) in 85% yield (entry 5).
In this case, however, minor amounts (>5%) of isomers were also detected by GC-MS. Meanwhile, 1-
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(4-substituted phenyl)pyrazoles 4b-d reacted with 2a stereoselectively to form 5f-h in good yields
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(entries 6-8).
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TABLE 4. Reaction of 1-Phenylpyrazoles 4 with Alkynes 2a
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a Reaction conditions: [4]:[2]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] = 0.25:0.625:0.0125:0.05:1 (in
mmol), in dioxane (3 mL) at 100 C for 5 h under N2. Minor amounts (>5%) of isomers were also
detected by GCMS.
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b
Under similar conditions, treatment of 2-phenylimidazole (6a) with 2a also resulted in the selective
formation of dialkenylated product 7a in 79% yield (Scheme 6). In contrast, somewhat sterically more
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hindered 1-methyl-2-phenylimidazole (6b) reacted with 2a in a 1:1 manner to produce 7b selectively.4
In this case, dialkenylated product could not be detected at all. Probably the ortho-metalation of 7b
seems to be suppressed due to the steric repulsion between the methyl group on the N1 and the 1,2-
diphenylethenyl group.
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SCHEME 6. Reaction of 2-Phenyimidazoles 6 with 2a in dioxane at 100 oC for 5 ha
HN
N
HN
Ph
N
[Ru(p-cymene)Cl2]2
Ph
Ph
AgSbF6
Ph
Ph
+
AcOH
79%
Ph
2a
6a
7a
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N
N
Me
N
[Ru(p-cymene)Cl2]2
Me
Ph
Ph
AgSbF6
Ph
+
AcOH
65%
Ph
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7b
N
N
N
Me
Ph
N
Me
[Ru]
–H+
[Ru]
[Ru]
Ph
7b
Ph
Ph
H
a Reaction conditions: [6]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] = 0.25:0.625:0.0125:0.05:1
(in mmol). b 2a (0.5 mmol) was employed.
An intermolecular competition reaction of 4a-d0/4a-d5 with 2a was conducted to investigate the
reaction mechanism (Scheme 7). In contrast to the case of 1a-d0/1a-d5 (Scheme 4), no significant KIE
was observed. Two parallel reactions using 4a-d0 and 4a-d5 also showed a small KIE value (see the
Experimental Section).
SCHEME 7. Competitive Reaction of 4a-d0/4a-d5 in dioxane at 100 oC for 20 mina
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a Reaction conditions: [4a-d0]:[4a-d5]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] =
0.125:0.125:0.625:0.0125:0.05:1 (in mmol).
In another competition experiment between methyl- (4b) and chloro- (4d) substituted phenylprazoles
(Scheme 8), the larger difference of reactivities of electron-rich and –poor substrates, compared to that
in benzamides (1f/1h in Scheme 5), was observed. These facts seem to be reasonable if an SEAr-like
mechanism is assumed to be operative at the C–H bond cleavage step. The difference of the C–H bond
cleavage pathways in the reactions of bezamides and phenylpyrazoles may be brought about by the
balance of electron densities of their aromatic rings and C–H acidities.
SCHEME 8. Competitive Reaction of 4b and 4d in dioxane at 100 oC for 20 mina
a Reaction conditions: [4b]:[4d]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] =
0.125:0.125:0.625:0.0125:0.05:1 (in mmol).
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Conclusions
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In summary, we have demonstrated that the ruthenium-catalyzed coupling reactions of benzamides
and phenylazoles with alkynes can be performed efficiently in 1:1 and 1:2 manners, respectively. The
1:1 and 1:2 selectivities may be governed by steric factors. A number of competitive experiments
suggest that the different mechanisms, which possibly involve a rate-determining C–H bond cleavage
and an SEAr like metalation, are operative in these reactions.
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Experimental Section
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General. H and C NMR spectra were recorded at 400 and 100 MHz for CDCl3 solutions. HRMS
data were obtained by EI using a double focusing mass spectrometer, unless noted. GC analysis was
carried out using a silicon OV-17 column (i. d. 2.6 mm x 1.5 m). GC-MS analysis was carried out using
a CBP-1 capillary column (i. d. 0.25 mm x 25 m). The structures of all products listed below were
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unambiguously determined by H and C NMR with the aid of NOE, COSY, HMQC, and HMBC
experiments.
Diarylacetylenes 2b,c,h,19 benzamides 1b-h,11b 1-phenylpyrazoles 4b-d,20 and 1-methyl-2-
phenylimidazole (6b)21 were prepared according to published procedures. Other starting materials and
reagents were commercially available.
General Procedure for Coupling of Benzamides with Alkynes. To a 20 mL two-necked flask with
a reflux condenser, a balloon, and a rubber cup were added benzamide 1 (0.25 mmol), alkyne 2 (0.5
mmol), [Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60
mg), 1,4-diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). Then, the resulting
mixture was stirred under nitrogen at 100 oC for 5 h. After cooling, the reaction mixture was poured into
ethyl acetate (100 mL). The organic layer was washed by water (100 mL, three times), and dried over
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Na2SO4. Product 3 was isolated by column chromatography on silica gel using hexane-ethyl acetate (1:1,
v/v) as eluant.
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Procedure for Reaction of Deuterated Benzamides with Diphenylacetylene. To a 20 mL two-
necked flask with a reflux condenser, a balloon, and a rubber cup were added N,N-dimethylbenzamide-
d5 (1a-d5) (0.25 mmol, 39 mg), diphenylacetylene (2a) (0.5 mmol, 89 mg), [Ru(p-cymeme)Cl2]2 (0.0125
mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60 mg), 1,4-diphenylethane (ca. 30 mg)
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as internal standard, and dioxane (3 mL). The resulting mixture was stirred under N2 at 100 C for 15
min. After cooling, the reaction mixture was poured into water (100 mL), extracted with ethyl acetate
(100 mL), washed with water (100 mL, three times), and dried over Na2SO4. Produced 3a-d4 and
recovered 1a-d5 were isolated by column chromatography on silica gel using hexane-ethyl acetate (1:1)
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as eluant. Recovered 1a-d5 (23.4 mg, 61%): H NMR (400 MHz, CDCl3) δ 2.98 (s, 3H), 3.11 (s, 3H),
7.41 (s, 0.2H). Produced 3a-d4 (16.7 mg, 20%): 1H NMR (400 MHz, CDCl3) δ 2.57 (s, 3H), 2.66 (s, 3H),
6.79 (s, 0.96H), 7.03-7.06 (m, 2H), 7.10-7.16 (m, 5H), 7.22-7.25 (m, 3H).
Procedure for Competitive Reaction of 1a-d0 and 1a-d5. To a 20 mL two-necked flask with a reflux
condenser, a balloon, and a rubber cup were added N,N-dimethylbenzamide (1a-d0) (0.125 mmol, 19
mg), N,N-dimethylbenzamide-d5 (1a-d5) (0.125 mmol, 20 mg), diphenylacetylene (2a) (0.5 mmol, 89
mg), [Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60
mg), 1,4-diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). The resulting mixture
o
was stirred under N2 at 100 C for 20 min. After cooling, the reaction mixture was poured into water
(100 mL), extracted with ethyl acetate (100 mL), washed with water (100 mL, three times), and dried
over Na2SO4. The product was isolated by column chromatography on silica gel using hexane-ethyl
acetate (1:1) as eluant (43.9 mg, 53%): 1H NMR (400 MHz, CDCl3) δ 2.56 (s, 3H), 2.66 (s, 3H), 6.79 (s,
1H), 7.03-7.06 (m, 2H), 7.10-7.16 (m, 5H), 7.20-7.25 (m, 3.68H), 7.30-7.34 (m, 0.68H), 7.35-7.41 (m,
1.36H). The kinetic isotope effect was determined by 1H NMR: kH/kD = 0.68/0.32 = 2.1.
Parallel Reactions of 1a-d0 and 1a-d5 (Scheme 9). To a 20 mL two-necked flask were added N,N-
dimethylbenzamide-d0 or -d5 (1a-d0 or 1a-d5) (0.25 mmol), diphenylacetylene (2a) (0.5 mmol, 89 mg),
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[Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60 mg),
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1,4-diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). The resulting mixture was
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stirred under N2 at 100 C for 10 min. GC and GC-MS analyses of the mixture confirmed formation of
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3a-d0 (51%) or 3a-d4 (26%): kH/kD = 2.0.
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SCHEME 9. Parallel Reactions Using 1a-d0 and 1a-d5 in dioxane at 100 oC for 10 mina
a Reaction conditions: [1a-d0 or 1a-d5]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] = 0.25:
0.5:0.0125:0.05:1 (in mmol).
Procedure for Competitive Reaction of 1f and 1h. To a 20 mL two-necked flask with a reflux
condenser, a balloon, and a rubber cup were added N,N,4-trimethylbenzamide (1f) (0.125 mmol, 20 mg),
4-chloro-N,N-dimethylbenzamide (1h) (0.125 mmol, 23 mg), diphenylacetylene (2a) (0.5 mmol, 89 mg),
[Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60 mg),
1,4-diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). The resulting mixture was
o
stirred under N2 at 100 C for 10 min. GC and GC-MS analyses of the mixture confirmed formation of
3l (81%) and 3n (68%).
General Procedure for Coupling of 1-Phenylpyrazoles with Alkynes. To a 20 mL two-necked
flask with a reflux condenser, a balloon, and a rubber cup were added 1-phenylpyrazole 4 (0.25 mmol),
alkyne 2 (0.625 mmol), [Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg),
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AcOH (1 mmol, 60 mg), 1,4-diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). Then,
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the resulting mixture was stirred under nitrogen at 100 C for 5 h. After cooling, the reaction mixture
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was poured into ethyl acetate (100 mL). The organic layer was washed by water (100 mL, three times),
and dried over Na2SO4. Product 5 was isolated by column chromatography on silica gel using hexane-
ethyl acetate (5:1, v/v) as eluant.
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Procedure for Reaction of 4a-d5 with 2a (Scheme 10). To a 20 mL two-necked flask with a reflux
condenser, a balloon, and a rubber cup were added 1-phenylpyrazole-d5 (4a-d5) (0.25 mmol, 37 mg),
diphenylacetylene (2a) (0.625 mmol, 111 mg), [Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6
(0.05 mmol, 17 mg), AcOH (1 mmol, 60 mg), 1,4-diphenylethane (ca. 30 mg) as internal standard, and
o
dioxane (3 mL). The resulting mixture was stirred under N2 at 100 C for 10 min. After cooling, the
reaction mixture was poured into water (100 mL), extracted with ethyl acetate (100 mL), washed with
water (100 mL, three times), and dried over Na2SO4. Produced 5a-d3 and recovered 4a-d5 were isolated
by column chromatography on silica gel using hexane-ethyl acetate (5:1) as eluant. Recovered 4a-d5
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(12.7 mg, 34%): H NMR (400 MHz, CDCl3) δ6.46-6.48 (m, 1H), 7.70 (s, 0.08H), 7.73-7.74 (m, 1H),
1
7.92-7.93 (m, 1H). Produced 5a-d3 (25.3 mg, 20%): H NMR (400 MHz, CDCl3) δ 5.71-5.72 (m, 1H),
6.57 (s, 2H), 6.79-6.80 (m, 1H), 6.87-6.94 (m, 8H), 7.03-7.11 (m, 12H), 7.17-7.18 (m, 1H).
SCHEME 10. Reaction of 4a-d5 with 2a in dioxane at 100 oC for 10 mina
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a Reaction conditions: [4a-d5]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] =
0.25:0.625:0.0125:0.05:1 (in mmol).
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Procedure for Competitive Reaction of 4a-d0 and 4a-d5. To a 20 mL two-necked flask with a reflux
condenser, a balloon, and a rubber cup were added 1-phenylpyrazole (4a-d0) (0.125 mmol, 18 mg), 1-
phenylpyrazole-d5 (4a-d5) (0.125 mmol, 19 mg), diphenylacetylene (2a) (0.625 mmol, 111 mg), [Ru(p-
cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60 mg), 1,4-
diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). The resulting mixture was stirred
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under N2 at 100 C for 20 min. After cooling, the reaction mixture was poured into water (100 mL),
extracted with ethyl acetate (100 mL), washed with water (100 mL, three times), and dried over Na2SO4.
The product was isolated by column chromatography on silica gel using hexane-ethyl acetate (5:1) as
eluant (40 mg, 32%): 1H NMR (400 MHz, CDCl3) δ 5.71-5.72 (m, 1H), 6.58 (s, 2H), 6.79-6.80 (m, 1H),
6.88-6.94 (m, 8H), 7.06-7.11 (m, 12H), 7.18-7.19 (m, 1H), 7.43 (m, 1.54H). The kinetic isotope effect
was determined by 1H NMR: kH/kD = 0.51/0.49 = 1.04.
Parallel Reactions of 4a-d0 and 4a-d5 (Scheme 11). To a 20 mL two-necked flask were added 1-
phenylpyrazole-d0 or -d5 (4a-d0 or 4a-d5) (0.25 mmol), diphenylacetylene (2a) (0.625 mmol, 111 mg),
[Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60 mg),
1,4-diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). The resulting mixture was
stirred under N2 at 100 oC for 10 min. GC and GC-MS analyses of the mixture confirmed conversion of
4a-d0 (58%) or 4a-d5 (52%): kH/kD = 1.1.
SCHEME 11. Parallel Reactions Using 4a-d0 and 4a-d5 in dioxane at 100 oC for 10 mina
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a Reaction conditions: [4a-d0 or 4a-d5]:[2a]:[{Ru(p-cymene)Cl2}2]:[AgSbF6]:[AcOH] = 0.25:
0.625:0.0125:0.05:1 (in mmol).
Procedure for Competitive Reaction of 4b and 4d. To a 20 mL two-necked flask with a reflux
condenser, a balloon, and a rubber cup were added 1-(4-methylphenyl)pyrazole (4b) (0.125 mmol, 20
mg), 1-(4-chlorophenyl)pyrazole (4d) (0.125 mmol, 22 mg), diphenylacetylene (2a) (0.625 mmol, 111
mg), [Ru(p-cymeme)Cl2]2 (0.0125 mmol, 7.6 mg), AgSbF6 (0.05 mmol, 17 mg), AcOH (1 mmol, 60
mg), 1,4-diphenylethane (ca. 30 mg) as internal standard, and dioxane (3 mL). The resulting mixture
o
was stirred under N2 at 100 C for 20 min. A mixture of 5f and 5h was obtained by column
1
chromatography on silica gel using hexane-ethyl acetate (5:1) as eluant (61 mg). H-NMR analysis of
the mixture confirmed the ratio of 5f and 5h (64:36).
(E)-2-(1,2-Diphenylethenyl)-N,N-dimethylbenzamide (3a):9 oil, 66 mg (81%); 1H NMR (400 MHz,
CDCl3) δ 2.56 (s, 3H), 2.66 (s, 3H), 6.79 (s, 1H), 7.03-7.06 (m, 2H), 7.10-7.16 (m, 5H), 7.20-7.25 (m,
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13
4H), 7.30-7.41 (m, 3H); C NMR (100 MHz, CDCl3) δ 34.2, 38.6, 126.9, 127.0, 127.4, 127.5, 127.9,
128.0, 128.8, 129.5, 130.38, 130.40, 130.8, 136.3, 137.2, 139.5, 141.5, 141.8, 170.7;ꢀ HRMS m/z calcd
for C23H21NO (M+) 327.1623, found 327.1622.
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(E)-2-[1,2-Bis(4-methylphenyl)ethenyl]-N,N-dimethylbenzamide (3b): oil, 57 mg (65%);1H NMR
(400 MHz, CDCl3) δ 2.27 (s, 3H), 2.33 (s, 3H), 2.61 (s, 3H), 2.68 (s, 3H), 6.71 (s, 1H), 6.92-6.95 (m,
4H), 7.04 (s, 4H), 7.21-7.22 (m, 1H), 7.29-7.35 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 21.2, 21.3, 34.3,
38.7, 127.1, 127.3, 128.6, 128.7, 128.8, 129.3, 130.2, 130.3, 130.4, 134.5, 136.2, 136.6, 136.7, 137.0,
140.5, 142.1, 170.8; HRMS m/z calcd for C25H25NO (M+) 355.1936, found 355.1935.
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(E)-2-[1,2-Bis(4-chlorophenyl)ethenyl]-N,N-dimethylbenzamide (3c):9 oil, 73 mg (73%); 1H NMR
(400 MHz, CDCl3) δ 2.59 (s, 3H), 2.68 (s, 3H), 6.76 (s, 1H), 6.96 (d, J = 8.2 Hz, 2H), 7.07 (d, J = 7.5
Hz, 2H) , 7.11 (d, J = 7.2 Hz, 2H), 7.20-7.23 (m, 3H), 7.32-7.38 (m, 3H); 13C NMR (100 MHz, CDCl3)
δ 34.3, 38.8, 127.1, 127.9, 128.3, 128.4, 129.0, 129.9, 130.4, 130.7, 131.8, 132.8, 133.5, 135.3, 136.2,
137.7, 141.1, 141.2, 170.4;ꢀ HRMS m/z calcd for C23H19Cl2NO (M+) 395.0844, found 395.0845.
1
(E)-2-(1-Methyl-2-phenylethenyl)-N,N-dimethylbenzamide (3d):9 oil, 51 mg (77%); H NMR (400
MHz, CDCl3) δ 2.23 (s, 3H), 2.82 (s, 3H), 3.06 (s, 3H), 6.57 (s, 1H), 7.23-7.26 (m, 1H), 7.31-7.41 (m,
8H); 13C NMR (100 MHz, CDCl3) δ 19.1, 34.8, 38.6, 126.7, 127.1, 127.3, 128.0, 128.2, 128.95, 128.97,
130.2, 135.1, 136.9, 137.8, 142.6, 171.6;ꢀ HRMS m/z calcd for C18H19NO (M+) 265.1467, found
265.1470.
(E)-2-(1-Butyl-2-phenylethenyl)-N,N-dimethylbenzamide (3e):9 oil, 53 mg (68%); 1H NMR (400
MHz, CDCl3) δ 0.80 (t, J = 7.2 Hz, 3H), 1.22-1.34 (m, 4H), 2.57 (t, J = 6.9 Hz, 2H), 2.85 (s, 3H), 3.05
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(s, 3H), 6.48 (s, 1H), 7.23-7.40 (m, 9H); C NMR (100 MHz, CDCl3) δ 13.8, 22.7, 30.9, 31.3, 34.8,
38.9, 126.6, 126.9, 127.2, 128.2, 128.7, 128.8, 129.1, 129.8, 135.4, 137.8, 141.3, 143.3, 171.5;ꢀ HRMS
m/z calcd for C21H25NO (M+) 307.1936, found 307.1935.
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(E)-2-(1-Phenylethenyl)-N,N-dimethylbenzamide (3f):9 oil, 40 mg (63%); H NMR (400 MHz,
CDCl3) δ 2.80 (s, 3H), 3.17 (s, 3H), 7.10 (s, 2H), 7.24-7.41 (m, 6H),7.47-7.49 (m, 2H),7.69 (d, J = 7.8
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Hz, 1H); C NMR (100 MHz, CDCl3) δ 34.8, 38.6, 125.1, 125.5, 126.6, 126.7, 127.7, 128.0, 128.7,
129.1, 131.2, 134.0, 135.9, 137.0, 171.1;ꢀ HRMS m/z calcd for C17H17NO (M+) 251.1310, found
251.1315.
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2-[1-Phenyl-2-(trimethylsilyl)ethenyl]-N,N-dimethylbenzamide (3f’):9 oil, 14 mg (17%); 1H NMR
(400 MHz, CDCl3) δ -0.04 (s, 9H, major), 0.11 (s, 9H, minor), 2.87 (s, 3H, major), 2.88 (s, 3H, minor),
3.16 (s, 3H, major), 3.17 (s, 3H, minor), 6.76-6.78 (m, 1H, minor), 6.91-6.96 (m, 2H, minor), 7.10-7.11
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(m, 2H), 7.16 (s, 1H, major), 7.18-7.23 (m, 2H), 7.27-7.37 (m, 6H), 7.38-7.42 (m, 1H); C NMR (100
MHz, CDCl3) δ -1.6, 0.7, 34.65, 34.70, 38.4, 38.5, 125.8, 125.9, 126.1, 127.0, 127.4, 127.8, 127.9, 128.0,
128.3, 128.5, 129.2, 129.6, 136.32, 136.34, 141.8, 147.0, 148.7, 170.8;ꢀ HRMS m/z calcd for
C20H25NOSi (M+) 323.1705, found 323.1709.
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(E)-2-[2-(Triisopropylsilyl)ethenyl]-N,N-dimethylbenzamide (3g):9 oil, 16 mg (19%); H NMR
(400 MHz, CDCl3) δ 1.07 (d, J = 6.8 Hz, 18H), 1.12-1.20 (m, 3H), 2.76 (s, 3H), 3.11 (s, 3H), 6.39 (d, J
= 19.5 Hz, 1H), 6.95 (d, J = 19.5 Hz, 1H), 7.22-7.38 (m, 3H), 7.59 (d, J = 7.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 10.9, 18.6, 34.6, 38.4, 125.4, 126.2, 127.7, 128.0, 128.9, 135.5, 135.6, 142.4, 171.2;ꢀ
HRMS m/z calcd for C20H33NOSi (M+) 331.2331, found 331.2333.
{2-[(1E)-1,2-Diphenylethenyl]phenyl}-1-pyrrolidinylmethanone (3h):9 oil, 70 mg (79%); 1H NMR
(400 MHz, CDCl3) δ 1.52-1.64 (m, 4H), 2.97-3.15 (m, 4H), 6.81 (s, 1H), 7.02-7.04 (m, 2H), 7.10-7.11
(m, 3H), 7.14-7.25 (m, 6H), 7.29-7.38 (m, 2H) 7.42 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
24.2, 25.6, 45.0, 48.1, 126.78, 126.82, 127.3, 127.5, 127.9, 128.0, 128.9, 129.4, 130.48, 130.50, 130.7,
137.2, 137.3, 139.5, 141.6, 141.7, 169.0;ꢀ HRMS m/z calcd for C25H23NO (M+) 353.1780, found
353.1775.
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{2-[(1E)-1,2-Diphenylethenyl]phenyl}-1-piperidinylmethanone (3i):9 oil, 51 mg (56%); H NMR
(400 MHz, CDCl3) δ 1.37-1.59 (m, 6H), 2.74-2.81 (m, 1H), 2.95-3.01 (m, 1H), 3.18-3.21 (m, 1H), 3.68-
3.71 (m, 1H), 6.80 (s, 1H), 7.02-7.05 (m, 2H), 7.08-7.17 (m, 5H), 7.22-7.26 (m, 4H), 7.28-7.39 (m, 3H);
13C NMR (100 MHz, CDCl3) δ 24.4, 25.2, 26.0, 41.9, 47.9, 126.8, 126.9, 127.39, 127.43, 127.9, 128.2,
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128.6, 129.5, 130.4, 130.5, 130.9, 136.4, 137.2, 139.8, 141.2, 141.6, 169.3;ꢀ HRMS m/z calcd for
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C26H25NO (M+) 367.1936, found 367.1935.
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(E)-2-(1,2-Diphenylethenyl)-N,N-diisopropylbenzamide (3j): mp 170-171 C, 69 mg (72%); H
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NMR (400 MHz, CDCl3) δ 1.05 (d, J = 6.8 Hz, 3H), 1.11-1.16 (m, 6H), 1.51 (d, J = 6.8 Hz, 3H), 3.30-
9
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3.37 (m, 1H), 3.90-3.96 (m, 1H), 6.89 (s, 1H), 7.02-7.13 (m, 6H), 7.19-7.30 (m, 8H); C NMR (100
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MHz, CDCl3) δ 20.1, 20.5, 20.6, 20.9, 45.7, 50.8, 126.3, 126.7 127.2, 127.4, 127.85, 127.90, 128.4,
129.5, 130.5, 130.7, 130.9, 137.2, 138.3, 140.6, 140.7, 140.9, 170.4; HRMS m/z calcd for C27H29NO
(M+) 383.2249, found 383.2248.
(E)-2-(1,2-Diphenylethenyl)-N,N-diphenylbenzamide (3k):9 mp161-162 oC, 53 mg (47%); 1H NMR
(400 MHz, CDCl3) δ 6.59-6.61 (m, 2H), 6.79-6.88 (m, 6H), 7.10-7.23 (m, 15H), 7.32 (dt, J = 1.0, 7.6 Hz,
13
1H), 7.61 (dd, J = 1.2, 7.7 Hz, 1H); C NMR (100 MHz, CDCl3) δ 127.1, 127.4, 127.6, 128.0
(overlapped), 128.1, 128.8 (overlapped), 129.2, 129.6 (overlapped), 130.1, 130.4, 130.99,
131.04(overlapped), 136.5, 137.2, 139.4, 140.6, 141.2, 143.2, 171.1;ꢀ HRMS m/z calcd for C33H25NO
(M+) 451.1936, found 451.1938.
1
(E)-2-(1,2-Diphenylethenyl)-N,N-dimethyl-4-methylbenzamide (3l): oil, 66 mg (77%); H NMR
(400 MHz, CDCl3) δ 2.37 (s, 3H), 2.56 (s, 3H), 2.64 (s, 3H), 6.77 (s, 1H), 7.03-7.09 (m, 2H), 7.10-7.16
(m, 7H), 7.20-7.24 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 21.2, 34.2, 38.7, 126.8, 127.0, 127.4, 127.9,
128.0, 128.1, 129.5, 130.4, 130.5, 131.0, 133.5, 137.2, 138.7, 139.5, 141.7, 141.8, 170.9; HRMS m/z
calcd for C24H23NO (M+) 341.1780, found 341.1775.
o
(E)-2-(1,2-Diphenylethenyl)-N,N-dimethyl-4-methoxybenzamide (3m): mp 111-112 C, 75 mg
(84%); 1H NMR (400 MHz, CDCl3) δ 2.57 (s, 3H), 2.63 (s, 3H), 3.83 (s, 3H), 6.80 (s, 1H), 6.85 (dd, J =
2.5, 8.3 Hz, 1H), 6.94 (d, J = 2.6 Hz, 1H), 7.04-7.06 (m, 2H), 7.11-7.16 (m, 6H), 7.21-7.23 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 34.3, 38.8, 55.4, 112.7, 115.9, 126.9, 127.4, 127.9, 128.0, 128.5, 128.9,
129.5, 130.4, 130.7, 137.1, 139.2, 141.6, 143.6, 159.7, 170.7; HRMS m/z calcd for C24H23NO2 (M+)
357.1729, found 357.1727.
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(E)-2-(1,2-Diphenylethenyl)-N,N-dimethyl-4-chlorobenzamide (3n): mp 110-111 oC, 79 mg (87%);
1H NMR (400 MHz, CDCl3) δ 2.54 (s, 3H), 2.64 (s, 3H), 6.80 (s, 1H), 7.02-7.05 (m, 2H), 7.11-7.16 (m,
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6
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6H), 7.24-7.26 (m, 3H), 7.31 (dd, J = 2.0, 8.2 Hz, 1H), 7.42 (d, J = 1.9 Hz, 1H); C NMR (100 MHz,
7
8
9
CDCl3) δ 34.3, 38.6, 127.2, 127.5, 127.7, 128.0, 128.2, 128.4, 129.5, 130.3, 130.4, 131.7, 134.6, 134.7,
136.7, 138.8, 140.3, 143.7, 169.7; HRMS m/z calcd for C23H20ClNO (M+) 361.1233, found 361.1238.
1-[2,6-Bis[(1E)-1,2-diphenylethenyl]phenyl]pyrazole (5a):9 oil, 106 mg (85%);1H NMR (400 MHz,
CDCl3) δ 5.71-5.72 (m, 1H), 6.57 (s, 2H), 6.80 (d, J = 2.2, 1H), 6.87-6.94 (m, 8H), 7.04-7.11 (m, 12H),
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7.18-7.19 (m, 1H), 7.42-7.43 (m, 3H); C NMR (100 MHz, CDCl3) δ 105.7, 126.7, 126.9, 127.78,
127.81, 128.5, 129.3, 129.4, 130.5, 130.7, 131.6, 137.1, 137.4, 139.2, 139.3, 139.7, 143.1;ꢀ HRMS m/z
calcd for C37H28N2 (M+) 500.2252, found 500.2249.
1-[2,6-Bis[(1E)-1,2-bis(4-methylphenyl)ethenyl]phenyl]pyrazole (5b): oil, 116 mg (83%);1H NMR
(400 MHz, CDCl3) δ 2.22 (s, 6H), 2.25 (s, 6H), 5.73-5.74 (m, 1H), 6.47 (s, 2H), 6.78-6.89 (m, 17H),
13
7.19 (d, J = 1.7 Hz, 1H), 7.35-7.38 (m, 3H); C NMR (100 MHz, CDCl3) δ 21.1, 21.2, 105.5, 128.3,
128.49, 128.53, 129.1, 129.2, 130.1, 130.2, 131.7, 134.4, 136.3, 136.4, 136.6, 137.3, 138.7, 139.0,
143.4;ꢀ HRMS m/z calcd for C41H36N2 (M+) 556.2878, found 556.2877.
1-[2,6-Bis[(1E)-1,2-bis(4-chlorophenyl)ethenyl]phenyl]pyrazole (5c): oil, 122 mg (77%);1H NMR
(400 MHz, CDCl3) δ 5.75-5.76 (m, 1H), 6.56 (s, 2H), 6.72-6.75 (m, 4H), 6.78 (d, J = 2.4 Hz, 1H), 6.85-
13
6.87 (m, 4H), 6.99-7.08 (m, 8H), 7.12 (d, J = 1.8 Hz, 1H), 7.44-7.50 (m, 3H); C NMR (100 MHz,
CDCl3) δ 106.1, 128.1, 128.2, 128.9, 130.0, 130.5 (overlapped), 130.9, 131.6, 132.8, 133.0, 135.0, 137.0,
137.2, 139.3, 139.4, 142.5;ꢀ HRMS m/z calcd for C37H24Cl4N2 (M+) 636.0694, found 636.0693.
1
1-[2,6-Bis[(1E)-1,2-bis(4-methoxyphenyl)ethenyl]phenyl]pyrazole (5d): oil, 135 mg (87%); H
NMR (400 MHz, CDCl3) δ 3.72 (s, 6H), 3.74 (s, 6H), 5.73-5.74 (m, 1H), 6.44 (s, 2H), 6.59-6.63 (m,
8H), 6.80-6.82 (m, 5H), 6.88-6.90 (m, 4H), 7.18 (d, J = 1.3 Hz, 1H), 7.37-7.40 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 55.1 (overlapped), 105.5, 113.20, 113.23, 128.3, 129.4, 130.0, 130.3, 130.4, 130.5,
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131.6, 132.1, 137.3, 137.6, 139.0, 143.4, 158.2, 158.3;ꢀ HRMS m/z calcd for C41H36N2O4 (M+)
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2
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620.2675, found 620.2681.
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5
6
o
1-[2,6-Bis[(1E)-1-methyl-2-phenylethenyl]phenyl]pyrazole (5e): mp 78-80 C, 80 mg (85%); 1H
7
8
9
NMR (400 MHz, CDCl3) δ 1.70 (s, 6H), 6.36-6.37 (m, 1H), 6.46 (s, 2H), 7.19-7.23 (m, 6H), 7.30,-7.34
(m, 4H), 7.38-7.45 (m, 3H), 7.55 (d, J = 2.1 Hz, 1H), 7.66-7.67 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
18.2, 106.4, 126.5, 128.1, 128.3, 128.7, 128.8, 128.9, 129.9, 132.3, 137.0, 137.7, 139.7, 143.5;ꢀ HRMS
m/z calcd for C27H25N2 (M+H+) 377.2012, found 377.2019.
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o
1-[2,6-Bis[(1E)-1,2-diphenylethenyl]-4-methylphenyl]pyrazole (5f): mp 171-172 C, 112 mg
(87%);1H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 5.69-5.70 (m, 1H), 6.56 (s, 2H), 6.77 (d, J = 2.2 Hz,
1H), 6.88-6.93 (m, 8H), 7.05-7.08 (m, 12H), 7.16 (d, J = 1.7 Hz, 1H), 7.23 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 21.2, 105.5, 126.6, 126.8, 127.75, 127.77, 129.2, 129.4, 130.4, 131.0, 131.7, 135.0, 137.1,
138.3, 139.0, 139.3, 139.8, 142.8;ꢀ HRMS m/z calcd for C38H30N2 (M+) 514.2409, found 514.2411.
o
1-[2,6-Bis[(1E)-1,2-diphenylethenyl]-4-methoxyphenyl]pyrazole (5g): mp 160-161 C, 118 mg
(89%);1H NMR (400 MHz, CDCl3) δ 3.85 (s, 3H), 5.67-5.68 (m, 1H), 6.59 (s, 2H), 6.71 (d, J = 2.1 Hz,
1H), 6.87-6.95 (m, 10H), 7.03-7.10 (m, 12H), 7.15 (d, J = 1.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
55.6, 105.4, 115.5, 126.7, 126.9, 127.77, 127.80, 129.3 (overlapped), 130.6, 130.8, 131.9, 137.0, 138.9,
139.1, 139.8, 144.4, 158.8;ꢀ HRMS m/z calcd for C38H30N2O (M+) 530.2358, found 530.2357.
o
1-[2,6-Bis[(1E)-1,2-diphenylethenyl]-4-chlorophenyl]pyrazole (5h): mp 146-147 C, 112 mg
(84%);1H NMR (400 MHz, CDCl3) δ 5.71-5.72 (m, 1H), 6.58 (s, 2H), 6.77 (d, J = 2.4 Hz, 1H), 6.86-
6.93 (m, 8H), 7.06-7.12 (m, 12H), 7.17 (d, J = 1.8 Hz, 1H), 7.43 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
106.0, 127.0, 127.2, 127.8, 127.9, 129.3 (overlapped), 130.1, 131.4, 131.6, 134.1, 136.0, 136.6, 138.57,
138.59, 139.5, 144.7;ꢀ HRMS m/z calcd for C37H27ClN2 (M+) 534.1863, found 534.1864.
2-[2,6-Bis[(1E)-1,2-diphenylethenyl]phenyl]-1H-imidazole (7a): oil, 98 mg (79%); 1H NMR (400
MHz, CDCl3) δ 6.33 (s, 1H), 6.63 (s, 2H), 6.70 (s, 1H), 6.80-6.82(m, 4H), 6.95-6.97 (m, 4H), 7.03-7.07
(m, 12H), 7.45-7.46 (m, 3H), 7.73 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 115.2, 126.7, 126.8, 127.8,
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128.2, 128.9, 129.3, 129.4, 129.7, 130.1, 130.5, 137.2, 140.1, 142.2, 144.1, 146.4;ꢀ HRMS m/z calcd
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for C37H28N2 (M+) 500.2252, found 500.2249.
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5
6
1
(E)-2-[(1,2-Diphenylethenyl)phenyl]-1-methyl-1H-imidazole (7b):9 oil, 55 mg (65%); H NMR
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8
(400 MHz, CDCl3) δ 3.10 (s, 3H), 6.55 (s, 1H), 6.69 (s, 1H), 6.83-6.86 (m, 2H), 6.87-6.88(m, 1H), 6.97-
9
13
7.00 (m, 2H), 7.05-7.09 (m, 6H), 7.30-7.32 (m, 1H), 7.36-7.39 (m,1H), 7.44-7.50 (m, 2H); C NMR
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(100 MHz, CDCl3) δ 33.0, 120.0, 126.7, 126.8, 127.3, 127.80, 127.84, 128.2, 129.1, 129.26, 129.31,
130.2, 130.45, 130.53, 131.2, 137.2, 140.0, 142.1, 145.7, 147.1;ꢀ HRMS m/z calcd for C24H20N2 (M+)
336.1626, found 336.1628.
Acknowledgment. This work was partly supported by Grants-in-Aid from MEXT and JSPS, Japan.
Supporting Information Available: Copies of 1H- and 13C-NMR spectra of products. This material is
available free of charge via the Internet at http://pubs.acs.org.
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(a) Ueyama, T.; Mochida, S.; Fukutani, T.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2011, 13,
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