Synthesis of o-Allyloxy(ethynyl)benzene Derivatives by Cu-Catalyzed Suzuki–Miyaura-Type Reaction and Their Transformations into Heterocyclic Compounds

Article abstract of DOI:10.1002/ejoc.201700217

We have found that Suzuki–Miyaura-type reactions of o-allyloxy(bromoethynyl)benzenes with arylboronic acids using a hydrazone/Cu catalyst system proceeded smoothly in iPrOH under mild conditions to afford the corresponding o-allyloxy(arylethynyl)benzene derivatives in good yields without decomposition of the allyloxy group. We have further demonstrated that annulation and enyne metathesis of the o-allyloxy(arylethynyl)benzene derivatives using transition-metal catalysts led to various heterocyclic compounds.

Full text of DOI:10.1002/ejoc.201700217

A Journal of
Accepted Article
Title: Synthesis of o-Allyloxyethynylbenzene Derivatives via
Cu-Catalyzed Suzuki-Miyaura-Type Reaction and Their
Transformations for Heterocyclic Compounds
Authors: Kohei Watanabe, Takashi Mino, Eri Ishikawa, Miyu Okano,
Tatsuya Ikematsu, Yasushi Yoshida, Masami Sakamoto,
Kazuki Sato, and Kazuhiro Yoshida
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700217
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700217
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
Synthesis of o-Allyloxyethynylbenzene Derivatives via Cu-
Catalyzed Suzuki-Miyaura-Type Reaction and Their
Transformations for Heterocyclic Compounds
Kohei Watanabe,[a] Prof. Dr. Takashi Mino, * [a], [b] Eri Ishikawa,[a] Miyu Okano,[a] Tatsuya Ikematsu,[a]
Prof. Dr. Yasushi Yoshida,[a],[b] Prof. Dr. Masami Sakamoto,[a],[b] Kazuki Sato[c] and Prof. Dr. Kazuhiro
Yoshida[b],[c]
Abstract: We found that a Suzuki-Miyaura-type reaction of o-(bromoethynyl)allyloxybenzene with arylboronic acid using a
hydrazone-Cu catalyst system proceeded smoothly in i-PrOH under mild conditions to afford the corresponding o-
allyloxyethynylbenzene derivatives in good yields without decomposition of the allyloxy group. We further demonstrate that three
types of transformations using transition metal catalysts to o-allyloxyethynylbenzene derivatives lead to various respective
heterocyclic compounds.
terminal alkyne using a Pd/Cu (copper) catalyst system is the
first choice for the synthesis of internal alkyne derivatives.[10]
Introduction
However, the Pd element is known as a highly toxic precious
metal. Moreover, using a Pd catalyst triggers not only the
formation of an internal alkyne structure, but also the
decomposition of the allyloxy group via construction of a π-allyl-
palladium complex. Therefore, an alternative protocol for
internal alkyne using a cheaper metal catalyst instead of the
expensive Pd catalyst was necessary for the preparation of an
The Internal alkyne structure is an important synthetic
precursors for various natural products and pharmaceutical
products,[1] and various intermolecular annulations of internal
alkynes using its unique reactivity have been reported.[2] On the
other hand, effective intramolecular annulations of internal
alkyne have also been reported.[3] In particular, o-
allyloxyethynylbenzene has an interesting reactivity that leads
to important heterocyclic compounds such as benzofuran and
benzopyran. For example, Cacchi’s group,[4] Monteiro’s group[5],
Liang’s group[6] and our group[7] reported annulation of o-
allyloxyethynylbenzene afforded 3-allyl-2-arylbenzofuran by
using a palladium (Pd) catalyst. On the other hand, Tanaka’s
group reported that 3-benzyl-2-vinylbenzofuran was delivered
internal-alkyne-bearing
allyloxy
group
such
as
o-
allyloxyethynylbenzene. Recently, common metals such as
Cu,[11] nickel (Ni)-,[12] and iron (Fe)-catalyzed[13] Sonogashira
type coupling reactions were reported. However, all reactions
required harsh conditions except for one example.[11k] Given this
situation, protocols for internal alkyne derivatives using a
common-metal catalyst remained challenging. On the other
hand, Cu-catalyzed Sonogashira type reactions of terminal
alkynes with arylboronic acids instead of aryl halides have also
been reported.[14] Although some reactions proceeded in
relatively mild conditions to afford the corresponding internal
alkynes, these reactions required a large amount of amine
bases, such as pyridine or lutidine. On another front, Suzuki-
Miyaura-type reactions of arylboronic acid with bromoalkynes
were reported as another synthetic protocol for internal alkyne
derivatives.[15] In this reaction, the Pd catalyst worked well and
promoted the reaction under mild conditions.[15c] Furthermore,
Wang’s group reported a Cu-catalyzed Suzuki-Miyaura-type
reaction of bromoalkyne with aryl boronic acid for an internal
alkyne derivative.[16] Although this reaction has the potential to
from o-allyloxyethynylbenzene by using
a rhodium (Rh)
catalyst.[8] In addition, Lovely’s group reported that
a
benzopyran derivative could be obtained by Pauson-Khand
reaction of o-allyloxyethynylbenzene using Co2(CO)3.[9] As
demonstrated by three reports, synthetic methodology of o-
allyloxyethynylbenzene is very important for the synthesis of
various heterocyclic compounds.
Generally, a Sonogashira coupling reaction of aryl halide with
[a]
Kohei Watanabe, Prof. Dr. Takashi Mino, Eri Ishikawa, Miyu Okano,
Tatsuya Ikematsu, Prof. Dr.Yasushi Yoshida, Prof. Dr. Masami
Sakamoto
Department of Applied Chemistry and Biotechnology, Graduate
School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku,
Chiba 263-8522, (Japan)
become
an
effective
synthetic
method
for
o-
allyloxyethynylbenzene, it also requires a reflux condition.
We previously demonstrated easily prepared and air-stable
hydrazone compounds (Figure 1) as effective ligands for Pd-
catalyzed C-C bond formations such as the Suzuki-Miyaura,[17]
Mizoroki-Heck,[18] and Sonogashira[19] cross-coupling reactions
of aryl halides. We also demonstrated that a hydrazone-Cu
catalyst system was effective for C-C,[20] C-O,[20] and C-N[21]
bond formations.
E-mail: tmino@faculty.chiba-u.jp
http://chem.tf.chiba-u.jp/gacb06/index.html
[b]
[c]
Prof. Dr. Takahsi Mino, Prof. Dr. Yasushi Yoshida, Prof. Dr. Masami
Sakamoto, Prof. Dr. Kazuhiro Yoshida
Molecular Chirality Research Center, Chiba University,
1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, (Japan)
Kazuki Sato, Prof. Dr. Kazuhiro Yoshida
Department of Chemistry, Graduate School of Science, Chiba
University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, (Japan)
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
R1
N
R2
R1
R2
R
desired product than using L1b (Entry 9). Next, we investigated
the effect of the Cu catalyst (Entries 2 and 10-13) and found
that only CuI was effective for this coupling reaction. Various
bases were tested (Entries 2 and 14-18). While K3PO4 was
effective for this reaction (Entry 2), the reaction using Na3PO4,
which was effective base in the Wang’s report,[16] afforded a low
N
N N
N
N N
Me
L1
L2
a: R1 = 2-Pyridyl, R2 = Me
b: R1 = Ph, R2 = Me
c: R1, R2 = -(CH2)4-
d: R1, R2 = -(CH2)5-
e: R1, R2 = -(CH2)6-
a: R = 2-Pyridyl
b: R = Ph
Figure 1. Hydrazone ligands.
Table 1. Optimization of reaction conditions.
Herein, we describe
a
Cu-catalyzed Suzuki-Miyaura-type
(HO)2B
reaction of o-allyloxy(bromoethynyl)benzene derivatives 1,
which were easily prepared from readily accessible
salicylaldehyde through three step reactions[22] (Scheme 1),
with arylboronic acid using a hydrazone ligand under a mild
2a
Ligand (5 mol%)
Cu cat. (Cu = 5 mol%)
+
Br
Base (2.0 eq.)
O
Solvent (0.25 M)
40 °C, Ar, 6 h
condition,
that
affords
the
corresponding
o-
O
3aa
allyloxyethynylbenzene derivatives without decomposition of
the allyloxy group. Moreover, we demonstrate three types of
transformations using transition metal catalysts to o-
allyloxyethynylbenzene derivatives 3 for access to various
heterocyclic compounds.
1a
Entry
1
Ligand
L1a
Cu cat.
Base
Solvent
Yield (%)[a]
CuI
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Na3PO4
KOAc
KF
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
MeOH
EtOH
25
88
73
77
68
46
80
72
82
9
2
L1b
L1c
CuI
CuI
Br
3
CHO
OH
CHO
O
R1
R1
R1
4
L1d
L1e
CuI
R2
O
R2
5
CuI
1
Scheme 1. Preparation of 1
6
L2a
CuI
7
L2b
CuI
[b]
8
PPh3
CuI
Results and discussion
9
8-Quinolinol
L1b
CuI
Initially, we started to explore the optimizing reaction conditions
for the Cu-catalyzed Suzuki-Miyaura-type reaction using o-
(bromoethynyl)cinnamyloxybenzene (1a) and p-tolylboronic
acid (2a) as model substrates (Table 1). Using 5 mol% of CuI
and bishydrazone L1a as a ligand, we found that the reaction
with K3PO4 as a base in i-PrOH as a solvent gave the
corresponding product such as 1-cinnamyloxy-2-(p-tolylethynyl)
benzene (3aa) in a 25% yield with recovery of starting material
1a (Entry 1). We tested various bishydrazone ligands L1b-e
(Entries 2-5). Using a phenyl-methyl type bishydrazone ligand
L1b led to consumption of starting material 1a completely
without decomposition of the allyloxy group and afforded the
corresponding product 3aa in an 88% yield (Entry 2). When we
used bishydrazone ligands L1c-e bearing 5-7 member rings,
the desired product 3aa was obtained in 73%, 77% and 68%
yields, respectively (Entries 3-5). We also tested pyridine-
methyl type monohydrazone ligands L2a and L2b (Entries 6
and 7). While the reaction using the pyridine-methyl type
bishydrazone ligand L2a afforded a moderate yield of the
corresponding product 3aa (Entry 6), the reaction using L2b
afforded a good yield of 3aa (Entry 7). On the other hand, a
phosphine ligand such as PPh3 was not suitable for this
reaction when compared with L1b (Entry 8). Furthermore, the
reaction using 8-quinolinol, which was the effective ligand in
Wang’s report,[16] also resulted in a slightly lower yield of the
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
CuBr
CuBr2
Cu2O
Cu(OAc)2
CuI
L1b
17
N.D.
24
5
L1b
L1b
L1b
L1b
CuI
3
L1b
CuI
6
L1b
CuI
Cs2CO3
Et3N
8
L1b
CuI
22
9
L1b
CuI
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
L1b
CuI
42
81
78
39
22
5
L1b
CuI
n-PrOH
n-BuOH
i-BuOH
THF
L1b
CuI
L1b
CuI
L1b
CuI
L1b
CuI
DMF
L1b
CuI
MeCN
Toluene
i-PrOH
17
12
83[c]
L1b
CuI
L1b
CuI
[a] Isolated yield. [b] 10 mol% of PPh3 was added. [c] This reaction was carried
out at room temperature using 10 mol% of CuI and L1b for 24 h.
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
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2b-e with 1a produced high yields of the corresponding
coupling products (Entries 12-15). Moreover, alkenylboronic
acids 2f and 2g were also tolerated in this reaction and afforded
corresponding products 3af and 3ag, respectively (Entries 16
and 17).
yield of the corresponding product with recovery of 1a because
the Na3PO4 had poor dissolubility in i-PrOH and could not
supply anion as a base (Entry 14). Other potassium salts such
as KOAc and KF were not effective for this reaction (Entries 15
and 16). The reaction in the presence of Cs2CO3 afforded an
8% yield of the corresponding product (Entry 17). The reaction
using an amine base such as Et3N led to a low yield (Entry 18).
Next, the effects of solvent were investigated (Entries 2 and 19-
27). Firstly, we tried to use various protic solvents (Entries 2
and 19-23). The yield of product was improved as the carbon
chain of protic solvents became longer until n-PrOH (Entries 2
and 19-21). We found EtOH was not suitable for the Cu-
catalyzed Suzuki-Miyaura-type reaction under these mild
conditions (Entry 20). Moreover, using a branch-type protic
solvent such as i-PrOH improved the yield of product 3aa (Entry
2). However, the reaction using i-BuOH afforded a low yield of
the product (Entry 23). We also tested aprotic solvents (Entries
24-27), which proved ineffective for this reaction. Surprisingly,
we found that this reaction proceeded at room temperature,
although with a long reaction time, and 10 mol% of CuI and L1b
were required (Entry 28).
Table 2. Scope of coupling reaction.
L1b (5 mol%)
CuI (5 mol%)
Br
Ar
3
6
2
1
4
5
Ar
+
(HO)2B
R1
R1
K3PO4 (2.0 eq.)
i-PrOH (0.25 M)
40 °C, Ar, 6 h
O
R2
O
R2
1
2
3
Yield (%)[a]
Entry
R1
R2 (1)
Ar (2)
(3)
1
H
Ph (1a)
Ph (1b)
Ph (1c)
Ph (1d)
Ph (1e)
Ph (1f)
H (1g)
H (1h)
H (1h)
H (1i)
4-MeC6H4 (2a)
Ph (2b)
88 (3aa)
76[b] (3bb)
62[b] (3cb)
83[b] (3db)
83[b] (3eb)
48[b] (3fb)
77 (3gb)
82 (3hb)
86 (3hc)
50[b] (3ib)
57[b] (3jb)
81 (3ab)
86 (3ac)
81 (3ad)
71 (3ae)
72 (3af)
2
4-Me
Ph (2b)
3
4-OMe
5-OMe
4-Cl
Ph (2b)
4
Ph (2b)
5
Ph (2b)
6
3,4-(CH=CH)2
In this stage, we created a reaction using Pd(OAc)2 as a Pd
catalyst in stead of CuI (Scheme 2).
Ph (2b)
7
H
Ph (2b)
8
4-Me
4-Me
4-OMe
4-Cl
H
L1b (5 mol%)
9
4-OMeC6H4 (2c)
Ph (2b)
Pd(OAc)2 (5 mol%)
4: 7%
1a + 2a
K3PO4 (2.0 eq.)
10
11
12
13
14
15
16
17
i-PrOH (0.25 M)
40 °C, Ar, 6 h
O
O
Ph (2b)
H (1j)
3aa: Trace
5: 10%
Ph (2b)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Scheme 2. Pd-catalyzed Suzuki-Miyaura-type reaction.
As we predicted, using a Pd catalyst caused not only a Suzuki-
Miyaura reaction to form the target product 3aa, but also
decomposition of 3aa to form π-allyl-palladium intermediate
followed by allylic arylation[23] with p-tolylboronic acids 2a to
afford the 1,3-diarylpropene 4. After decomposition of the
allyloxy group, annulation of o-ethynylphenoxide[24] occurred to
afford 2-arylbenzofuran 5. Eventually, we could not obtain target
product 3aa and achieved only a trace amount when using the
Pd catalyst. As this result shows, using the Cu catalyst was
important for the preparation of o-allyloxyethynylbenzene
derivative.
H
4-OMeC6H4 (2c)
4-ClC6H4 (2d)
4-CF3C6H4 (2e)
(E)-CH=CH-Ph (2f)
(E)-CH=CH-n-Hex (2g)
H
H
H
H
90 (3ag)
[a] Isolated yield. [b] This reaction was carried out for 18 h.
Next, we investigated the generality of this reaction by using
bromoalkynes 6 having a non-allyloxy group (Table 3). We
found that (bromoethynyl)benzene (6a) and various
bromoalkynes 6b-h were tolerated in this reaction (Entries 1-8).
Furthermore, the reactions using various boronic acids 2b-e
proceeded smoothly to produce good yields of the
corresponding products (Entry 9-12). In particular, when using
With the optimized reaction conditions in hand (Table 1, Entry
2), we investigated about scope and limitation of this reaction
using various o-allyloxy(bromoethynyl)benzenes
1
with
arylboronic acids 2 (Table 2). Bromoalkynes 1b-d having methyl
or methoxy groups were also tolerated in this reaction (Entries
2-4). Moreover, the reaction using bromoalkyne 1e with chloro
group also proceeded (Entry 5). In the case of using
bromoalkyne 1f, the coupling product was obtained in moderate
yield (Entry 6). Furthermore, we tested using allyloxy
compounds 1g-j instead of cinnamyloxy compounds (Entries 7-
11). As a result, allyloxybenzenes 1g-j also reacted with
arylboronic acid 2b to give the corresponding coupling
products. Coupling reactions using various arylboronic acids
p-methoxyphenylboronic acid (2c),
a 97% yield of the
corresponding product 7bc was obtained (Entry 10). p-
Chlorophenylboronic acid (2d) was also tolerated in this
reaction and gave the corresponding product 7bd in 73% (Entry
11). The reaction of p-(trifluromethyl)phenylboronic acid (2e)
with 6b was carried out for 18 h and afforded 7be in 84% yield
(Entry 12). We found that 2- and 3-substituted arylboronic acids
2h and 2i were also tolerated in this reaction (Entries 13 and
14). Even in this reaction case, the coupling reaction proceeded
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
derivatives effectively.[7] Here, we tried to use some of newly
prepared o-allyloxyethynylbenzene derivatives 3 by a Cu-
catalyzed Suzuki-Miyaura-type reaction (Table 4).
at room temperature in the presence of 10 mol% of CuI and
L1a (Entry 2). These results indicate that this reaction is an
effective
synthetic
method
for
not
only
an
o-
allyloxyethynylbenzene derivative, but also an internal alkyne
structure.
As a result, we achieved the corresponding 3-allylbenzofuran
derivatives
8cb,
8eb,
8af
and
8ag
from
o-
allyloxyethynylbenzenes 3cb, 3eb, 3af and 3ag in high yields,
respectively, by using a hydrazone-Pd catalyst system.
On the other hand, a gold (Au) catalyst was known to cause
annulation via coordination of a cationic Au atom to triple
bond.[25] When we use the Au catalyst to o-
cinnamyloxyethynylbenzene derivative 3aa, we found that
branch-type 3-allylbenzofuran 9aa could be obtained in a 37%
yield (Scheme 3).
Table 3. Scope of coupling reaction.
L1b (5 mol%)
Ar
Br
CuI (5 mol%)
2
Ar
1
3
4
+
(HO)2B
K3PO4 (2.0 eq.)
i-PrOH (0.25 M)
40 °C, Ar, 6 h
R
R
6
5
6
2
7
Entry
1
R (6)
Ar (2)
Yield (%)[a] (7)
71 (7aa)
81, 82[b] (7ba)
85 (7ca)
87 (7da)
90 (7ea)
84 (7fa)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
Ph (2b)
H (6a)
2
4-OMe (6b)
3-OMe (6c)
2-OMe (6d)
4-tBu (6e)
AuClPPh3 (10 mol%)
AgSbF6 (10 mol%)
Ph
3
Toluene(0.25 M)
25 °C, Ar, 24 h
O
4
O
Ph
3aa
9aa : 37%
5
Scheme 3. Au-catalyzed annulation.
Based on the report by Roy’s group,[25b] the Au-catalyst
coordinated to triple bond to cause an annulation reaction,
followed by the Claisen rearrangement affording the branch-
type 3-allylbenzofuran in this reaction.
Furthermore, in the case of enyne metathesis[26] of o-
allyloxyethynylbenzene derivatives 3gb, 3ib and 3jb using the
Grubbs 2nd catalyst, the corresponding benzopyran derivatives
10gb, 10ib and 10jb were produced in high yields, respectively
6
4-Cl (6f)
7
4-CF3 (6g)
91 (7ga)
76 (7ha)
75 (7bb)
97 (7bc)
73 (7bd)
84[c] (7be)
91 (7bh)
85 (7bi)
3,4-(CH=CH)2 (6h)
4-OMe (6b)
4-OMe (6b)
4-OMe (6b)
4-OMe (6b)
4-OMe (6b)
4-OMe (6b)
8
9
10
11
12
13
14
4-OMeC6H4 (2c)
4-ClC6H4 (2d)
4-CF3C6H4 (2e)
3-MeC6H4 (2h)
2-MeC6H4 (2i)
(Table
5,
Entries
1-3).
Unfortunately,
the
o-
cinnamyloxyethynybenzene derivative 3ab was not tolerated in
this metathesis reaction (Entry 4).
Table 5. Enyne metathesis.
Ph
Ph
Grubbs 2nd-generation
(5 mol%)
R2
[a] Isolated yield. [b] This reaction was carried out at room temperature using
10 mol% of CuI and L1b for 24 h. [c] This reaction was carried out for 18 h.
R1
R1
Toluene (0.02 M)
40 °C, C2H4, 5 h
O
R2
O
Next, we demonstrated the various reactions of o-
allyloxyethynylbenzene using transition metal catalysts for
access to various heterocyclic compounds such as benzofuran
and benzopyran derivatives. As described in our introduction,
3
10
Entry
R1
R2 (3)
Yield (%)[a] (10)
95 (10gb)
96 (10ib)
87 (10jb)
N.R.
1
2
3
4
H
H (3gb)
OMe
Cl
H (3ib)
we
already
reported
that
annulation
of
an
o-
H (3jb)
allyloxyethynylbenzene derivative in the presence of an L1a-Pd
H
Ph (3ab)
catalyst system afforded linear-type 3-allylbenzofuran
[a] Isolated yield.
Table 4. Pd-catalyzed annulation.
These results, we could demonstrate three types of
transformations using o-allyloxyethynylbenzene derivatives 3
for access to various heterocyclic compounds.
Ph
R2
L1a (10 mol%)
Pd2(dba)3 (5 mol%)
R1
R1
Et3N (2.0 eq.)
R2
Dioxane/H2O (3/1) (0.25 M)
O
Ph
O
50 °C, Ar, 1 h
3
8
Conclusions
Entry
R1
OMe
Cl
R2 (3)
Yield (%)[a] (8)
86 (8cb)
1
2
3
4
Ph (3cb)
Ph (3eb)
We found that a Cu-catalyzed Suzuki-Miyaura-type reaction of
bromoalkyne with arylboronic acid using hydrazone L1b as a
ligand proceeded smoothly in i-PrOH under mild conditions to
afford the corresponding o-allyloxyethynylbenzene derivatives 3
88 (8eb)
(E)-CH=CH-Ph (3af)
(E)-CH=CH-nHex (3ag)
H
92 (8af)
H
88 (8ag)
[a] Isolated yield.
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
in good yields without decomposition of the allyloxy group. This
reaction proceeded at room temperature in spite of using only a
common-metal catalyst such as CuI without any amine base.
Furthermore, we demonstrated three types of transformations
using transition metal catalysts to o-allyloxyethynylbenzene
derivatives for access to various heterocyclic compounds.
153.7, 153.6, 136.6, 132.3, 131.6, 128.5, 128.3, 128.2, 127.7, 126.5,
124.7, 123.4, 117.7, 115.8, 115.1, 114.2, 93.6, 85.8, 70.4, 55.7 ppm; EI-
MS m/z (rel intensity) 340 (M+, 23); HRMS (ESI-orbitrap): calcd for
C24H20O2+H [M+H]+: 341.1536; found: 341.1531.
2-Cinnamyloxy-4-methoxy-1-(phenylethynyl)benzene[7] (3db) (Table
2, Entry 4). Compound 3db was obtained from 1-(bromoethynyl)-2-
cinnamyloxy-4-methoxybenzene (1d) (85.5 mg) and phenylboronic acid
(2b) (61.0 mg) according to the general procedure (18 h) in 83% yield
(70.9 mg, 0.208 mmol) as a cream solid: m.p. 85-86 °C; 1H NMR (300
MHz, CDCl3): δ = 7.56-7.53 (m, 2H), 7.46-7.23 (m, 9H), 6.86 (d, J = 16.0
Hz, 1H), 6.52-6.41 (m, 3H), 4.79 (dd, J = 5.2, 1.1 Hz, 2H), 3.82 ppm (s,
3H); 13C NMR (75 MHz, CDCl3): δ = 161.0, 160.2, 136.5, 134.1, 132.4,
131.4, 128.6, 128.2, 127.77, 127.74, 126.5, 124.1, 123.9, 105.6, 105.3,
100.1, 92.2, 85.9, 69.1, 55.4 ppm; EI-MS m/z (rel intensity) 340 (M+, 21).
Experimental Section
General procedure for Cu-catalyzed Suzuki-Miyaura coupling
reaction of bromoalkynes with arylboronic acids for internal alkyne
3 and 7 (Tables 2 and 3)
A mixture of bromoalkyne derivative 1 or 6 (0.25 mmol), arylboronic
acids 2 (0.50 mmol), K3PO4 (0.50 mmol), CuI (12.5 μmol, 5 mol %) and
ligand L1b (12.5 μmol, 5 mol %) in i-PrOH (1.0 mL) at 40 °C under an Ar
atmosphere was stirred for 6 h. After the reaction, the reaction was
quenched with distilled water. The solution was extracted with ethyl
acetate, washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by silica gel
4-Chloro-1-cinnamyloxy-2-(phenylethynyl)benzene (3eb) (Table 2,
Entry 5). Compound 3eb was obtained from 2-(bromoethynyl)-4-chloro-
1-cinnamyloxybenzene (1e) (86.8 mg) and phenylboronic acid (2b)
(61.4 mg) according to the general procedure (18 h) in 83% yield (71.1
mg, 0.206 mmol) as a white solid: m.p. 95-96 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.57-7.55 (m, 2H), 7.49 (d, J = 2.6 Hz, 1H), 7.40-7.21 (m.
9H), 6.88-6.80 (m, 2H), 6.42 (dt, J = 16.0, 5.3 Hz, 1H), 4.78 ppm (dd, J
= 5.3, 1.2 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ = 157.7, 136.3, 132.8,
132.7, 131.7, 129.3, 128.6, 128.4, 128.3, 127.9, 126.5, 125.6, 123.8,
123.1, 114.8, 113.8, 94.7, 84.5, 69.5 ppm; EI-MS m/z (rel intensity) 344
(M+, 7); HRMS (ESI-orbitrap): calcd for C23H17ClO+H [M+H]+: 345.1041,
found: 345.1039.
chromatography (hexane, hexane/ethyl acetate (v/v
= 100-4/1) or
hexane/toluene (v/v = 10-2/1)) to afford the corresponding internal
alkyne products 3 or 7.
1-Cinnamyloxy-2-(p-tolylethynyl)benzene[7] (3aa) (Table 1, Entry 2).
Compound
3aa
was
obtained
from
1-(bromoethynyl)-2-
cinnamyloxybenzene (1a) (78.3 mg) and p-tolylboronic acid (2a) (68.0
mg) according to the general procedure in 88% yield (71.4 mg, 0.220
mmol) as a white solid: m.p. 86-87 °C; 1H NMR (300 MHz, CDCl3): δ =
7.51 (dd, J = 13.0, 7.3 Hz, 1H), 7.46 (d, J = 7.9 Hz. 2H), 7.39 (d, J = 7.0
Hz, 2H), 7.25-7.34 (m, 4H), 7.14 (d, J = 7.9 Hz, 2H), 6.93-6.98 (m, 2H),
6.86 (d, J = 16.0 Hz, 1H), 6.46 (dt, J = 16.0, 5.2 Hz, 1H), 4.81 (dd, J =
5.2, 1.5 Hz, 2H), 2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ =
159.0, 138.2, 136.6, 133.4, 132.2, 131.5, 129.4, 129.0, 128.5, 127.7,
126.5, 124.4, 120.8, 120.5, 113.3, 112.6, 93.8, 85.1, 69.1, 21.5 ppm; EI-
MS m/z (rel intensity) 324 (M+, 17).
2-Cinnamyloxy-1-(phenylethynyl)naphthalene[7] (3fb) (Table 2, Entry
6). Compound 3fb was obtained from 1-(bromoethynyl)-2-
cinnamyloxynaphthalene (1f) (90.5 mg) and phenylboronic acid (2b)
(61.0 mg) according to the general procedure (18 h) in 48% yield (43.5
mg, 0.121 mmol) as a white solid: m.p. 105-106 °C; 1H NMR (300 MHz,
CDCl3): δ = 8.38 (d, J = 8.4 Hz, 1H), 7.80 (dd, J = 9.2, 3.2 Hz, 2H), 7.68
(dd, J = 3.7, 2.1 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.43-7.22 (m, 10H),
6.89 (d, J = 15.9 Hz, 1H), 6.50 (dd, J = 15.9, 5.3 Hz, 1H), 4.97 ppm (dd,
J = 5.3, 1.1 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ = 158.1, 136.5,
134.4, 132.5, 131.6, 130.0, 128.8, 128.6, 128.3, 128.13, 128.07, 127.8,
127.3, 126.6, 125.4, 124.5, 124.4, 123.8, 114.9, 107.5, 99.1, 84.0, 70.2
ppm; EI-MS m/z (rel intensity) 360 (M+, 51).
1-Cinnamyloxy-4-methyl-2-(phenylethynyl)benzene (3bb) (Table 2,
Entry 2). Compound 3bb was obtained from 2-(bromoethynyl)-1-
cinnamyloxy-4-methylbenzene (1b) (81.8 mg) and phenylboronic acid
(2b) (61.0 mg) according to the general procedure (18 h) in 76% yield
(61.7 mg, 0.190 mmol) as a white solid: m.p. 79-81 °C; 1H NMR (300
MHz, CD2Cl2): δ = 7.48-7.43 (m, 2H), 7.34-7.13 (m, 9H), 7.03 (dd, J =
8.4, 1.9 Hz, 1H), 6.81-6.73 (m, 2H), 6.39 (dt, J = 16.0, 5.3 Hz, 1H), 4.70
(dd, J = 5.3, 1.6 Hz, 2H), 2.20 ppm (s, 3H); 13C NMR (75 MHz, CD2Cl2):
δ = 157.5, 137.0, 134.1, 132.6, 131.8, 130.76, 130.72, 129.0, 128.8,
128.5, 128.2, 126.9, 125.0, 124.0, 113.2, 113.0, 93.4, 86.5, 69.7, 20.4
ppm; EI-MS m/z (rel intensity) 324 (M+, 14); HRMS (ESI-orbitrap): calcd
for C24H20O+Na [M+Na]+: 347.1406, found: 347.1399.
1-Allyloxy-2-(phenylethynyl)benzene[7] (3gb) (Table 2, Entry 7).
Compound 3gb was obtained from 1-allyloxy-2-(bromoethynyl)benzene
(1g) (58.6 mg) and phenylboronic acid (2b) (61.2 mg) according to the
general procedure in 77% yield (45.1 mg, 0.193 mmol) as a yellow oil:
1H NMR (300 MHz, CDCl3): δ = 7.56-7.53 (m, 2H), 7.50 (dd, J = 7.5, 1.6
Hz, 1H), 7.37-7.30 (m, 3H), 7.26 (d, J = 8.4 Hz, 1H), 6.94 (td, J = 7.5,
0.8 Hz, 1H), 6.89 (d, J = 8.4 Hz. 1H), 6.10 (dquin, J = 17.2, 4.8 Hz, 1H),
5.55 (dq, J = 17.2, 1.6 Hz, 1H), 5.31 (dq, J = 10.6, 1.6 Hz, 1H), 4.64
ppm (dt, J = 4.8, 1.6 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ = 158.9,
133.3, 132.9, 131.5, 129.5, 128.2, 128.0, 123.6, 120.7, 117.1, 113.0,
112.3, 93.4, 85.7, 69.1 ppm; EI-MS m/z (rel intensity) 234 (M+, 100).
1-Cinnamyloxy-4-methoxy-2-(phenylethynyl)benzene (3cb) (Table 2,
Entry 3). Compound (3cb) was obtained from 2-(bromoethynyl)-1-
cinnamyloxy-4-methoxybenzene (1c) (86.0 mg) and phenylboronic acid
(2b) (61.3 mg) according to the general procedure (18 h) in 62% yield
(52.7 mg, 0.155 mmol) as a cream solid: m.p. 64-66 °C; 1H NMR (300
MHz, CDCl3): δ = 7.59-7.55 (m, 2H), 7.40-7.24 (m, 8H), 7.06 (d, J = 2.9
Hz, 1H), 6.92-6.79 (m, 3H), 6.45 (dt, J = 15.9, 5.4 Hz, 1H), 4.76 (dd, J =
5.4, 1.4 Hz, 2H), 3.79 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ =
1-Allyloxy-4-methyl-2-(phenylethynyl)benzene (3hb) (Table 2, Entry
8). Compound 3hb was obtained from 1-allyloxy-2-(bromoethynyl)-4-
methylbenzene (1h) (62.8 mg) and phenylboronic acid (2b) (61.4 mg)
according to the general procedure in 82% yield (50.6 mg, 0.204 mmol)
as a yellow oil: 1H NMR (300 MHz, CDCl3): δ = 7.55-7.52 (m, 2H), 7.37-
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
7.29 (m, 4H), 7.06 (dd, J = 8.3, 1.7 Hz, 1H), 6.79 (d, J = 8.3 Hz. 1H),
6.09 (dquin, J = 17.2, 4.8 Hz, 1H), 5.52 (dq, J = 17.2, 1.7 Hz, 1H), 5.29
(dq, J = 10.5, 1.6 Hz, 1H), 4.61 (dt, J = 4.8, 1.6 Hz, 2H), 2.27 ppm (s,
3H); 13C NMR (75 MHz, CDCl3): δ = 157.0, 133.7, 133.2, 131.5, 130.1,
130.0, 128.2, 127.9, 123.7, 117.0, 112.8, 112.6, 93.1, 85.9, 69.4, 20.2
ppm; EI-MS m/z (rel intensity) 248 (M+, 100); HRMS (ESI-orbitrap):
calcd for C19H16O+Na [M+Na]+: 271.1093, found: 271.1093.
113.2, 112.7, 93.6, 85.8, 69.2 ppm; EI-MS m/z (rel intensity) 310 (M+,
13).
1-Cinnamyloxy-2-((p-methoxyphenyl)ethynyl)benzene[7] (3ac) (Table
2, Entry 13). Compound 3ac was obtained from 1-(bromoethynyl)-2-
cinnamyloxybenzene (1a) (77.9 mg) and p-methoxyphenylboronic acid
(2c) (76.0 mg) according to the general procedure in 86% yield (73.0
mg, 0.214 mmol) as a cream solid: m.p. 84-85 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.50 (d, J = 8.5 Hz, 3H), 7.39 (d, J = 7.1 Hz, 2H), 7.34-7.24
(m, 4H), 6.97-6.92 (m, 2H), 6.87-6.82 (m, 3H), 6.45 (dt, J = 16.0, 5.2 Hz,
1H), 4.80 (dd, J = 5.2, 1.4 Hz, 2H), 3.81 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): δ = 159.5, 158.9, 136.6, 133.3, 133.0, 132.3, 129.3, 128.5,
127.7, 126.5, 124.4, 120.8, 115.8, 113.9, 113.5, 112.7, 93.6, 84.4, 69.2,
55.3 ppm; EI-MS m/z (rel intensity) 340 (M+, 27).
1-Allyloxy-2-((p-methoxyphenyl)ethynyl)-4-methylbenzene
(Table 2, Entry 9). Compound 3hc was obtained from 1-allyloxy-2-
(bromoethynyl)-4-methylbenzene (1h) (62.5 mg) and 4-
(3hc)
methoxyphenylboronic acid (2c) (75.7 mg) according to the general
procedure in 86% yield (59.7 mg, 0.214 mmol) as a cream solid: m.p.
36-37 °C; 1H NMR (300 MHz, CDCl3): δ = 7.48 (dt, J = 8.7, 2.7 Hz, 2H),
7.30 (d, J = 2.0 Hz, 1H), 7.04 (dd, J = 7.0, 2.2 Hz, 1H), 6.87 (dt, J = 8.7,
2,7 Hz, 2H), 6.78 (d, J = 8.4 Hz, 1H), 6.09 (dquin, J = 17.2, 4.8 Hz, 1H),
5.52 (dq, J = 17.2, 1.6 Hz, 1H), 5.29 (dd, J = 10.6, 1.6 Hz, 1H), 4.61 (dt,
J = 4.9, 1.6 Hz, 2H), 3.82 (s, 3H), 2.27 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): δ = 159.4, 156.9, 133.6, 133.3, 133.0, 130.1, 129.8, 117.0,
115.9, 113.9, 113.2, 112.7, 93.2, 84.5, 69.5, 55.3, 20.2 ppm; EI-MS m/z
(rel intensity) 278 (M+, 100); HRMS (ESI-orbitrap): calcd for
C19H18O2+Na [M+Na]+: 301.1199, found: 301.1196.
1-((p-Chlorophenyl)ethynyl)-2-cinnamyloxybenzene (3ad) (Table 2,
Entry 14). Compound 3ad was obtained from 1-(bromoethynyl)-2-
cinnamyloxybenzene (1a) (77.8 mg) and p-chlorophenylboronic acid
(2d) (78.5 mg) according to the general procedure in 81% yield (69.9
mg, 0.203 mmol) as a white solid: m.p. 98-99 °C; 1H NMR (300 MHz,
CD2Cl2): δ = 7.43-7.38 (m, 3H), 7.34-7.31 (m, 2H), 7.27-7.14 (m, 6H),
6.89 (td, J = 8.1, 0.9 Hz, 2H), 6.76 (d, J = 16.0 Hz, 1H), 6.39 (dt, J =
16.0, 5.3 Hz, 1H), 4.72 ppm (dd, J = 5.3, 1.5 Hz, 2H); 13C NMR (75
MHz, CD2Cl2): δ = 161.6, 138.9, 136.4, 135.7, 135.1, 134.8, 132.4,
131.06, 130.98, 130.3, 128.9, 126.7, 124.5, 123.2, 114.98, 114.96, 94.6,
89.3, 71.5 ppm; EI-MS m/z (rel intensity) 344 (M+, 8); HRMS (ESI-
orbitrap): calcd for C23H17OCl+H [M+H]+: 345.1041, found: 345.1041.
1-Allyloxy-4-methoxy-2-(phenylethynyl)benzene (3ib) (Table 2, Entry
10). Compound 3ib was obtained from 1-allyloxy-2-(bromoethynyl)-4-
methoxybenzene (1i) (58.6 mg) and phenylboronic acid (2b) (60.8 mg)
according to the general procedure (18 h) in 50% yield (32.8 mg, 0.124
mmol) as a yellow oil: 1H NMR (300 MHz, CD2Cl2): δ = 7.46-7.42 (m,
2H), 7.31-7.23 (m, 3H), 6.95 (t, J = 2.0 Hz, 1H), 6.79-6.73 (m, 2H), 6.02
(dquin, J = 17.2, 5.0 Hz, 1H), 5.41 (dq, J = 17.2, 1.6 Hz, 1H), 5.20 (dd, J
1-Cinnamyloxy-2-((p-(trifluoromethyl)phenyl)ethynyl)benzene (3ae)
(Table 2, Entry 15). Compound 3ae was obtained from 1-
(bromoethynyl)-2-cinnamyloxybenzene (1a) (77.6 mg) and p-
(trifluoromethyl)phenylboronic acid (2e) (95.1 mg) according to the
general procedure in 71% yield (66.9 mg, 0.177 mmol) as a white solid:
m.p. 114-116 °C; 1H NMR (300 MHz, CDCl3): δ = 7.65 (d, J = 8.2 Hz,
2H), 7.57 (d, J = 8.4 Hz, 2H), 7.52 (dd, J = 7.9, 1.5 Hz, 1H), 7.39-7.25
(m, 6H), 6.97 (dd, J = 8.7, 6.9 Hz, 2H), 6.84 (d, J = 16.0 Hz, 1H), 6.45
(dt, J = 16.0, 5.3 Hz, 1H), 4.81 ppm (dd, J = 5.3, 1.5 Hz, 2H); 13C NMR
(75 MHz, CDCl3): δ = 159.3, 136.4, 133.6, 132.6, 131.8, 130.3, 129.7 (q,
J = 32.6 Hz), 128.6, 127.9, 127.5 (q, J = 1.5 Hz), 126.5, 125.2 (q, J =
3.9 Hz), 124.1, 124.0 (q, J = 272.0 Hz), 120.9, 112.6, 112.4, 92.2, 88.4,
69.2 ppm; EI-MS m/z (rel intensity) 378 (M+, 8); HRMS (ESI-orbitrap):
calcd for C24H17OF3+H [M+H]+: 379.1304, found: 379.1309.
= 12.1, 1.6 Hz, 1H), 4.49 (dt, J = 5.0, 1.6 Hz, 2H), 3.68 ppm (s, 3H); 13
C
NMR (75 MHz, CD2Cl2): δ = 153.94, 153.86, 133.9, 131.8, 128.8, 128.7,
123.8, 118.1, 117.2, 116.0, 114.7, 114.0, 93.6, 86.2, 70.6, 56.1 ppm; EI-
MS m/z (rel intensity) 264 (M+, 100); HRMS (ESI-orbitrap): calcd for
C18H16O2+Na [M+Na]+: 287.1043, found: 287.1036.
1-Allyloxy-4-chloro-2-(phenylethynyl)benzene (3jb) (Table 2, Entry
11). Compound 3jb was obtained from 1-allyloxy-2-(bromoethynyl)-4-
chlorobenzene (1j) (67.7 mg) and phenylboronic acid (2b) (61.4 mg)
according to the general procedure (18 h) in 57% yield (38.4 mg, 0.143
mmol) as a white solid: m.p. 36-38 °C; 1H NMR (300 MHz, CDCl3): δ =
7.55-7.51 (m, 2H), 7.47 (d, J = 2.6 Hz, 1H), 7.38-7.32 (m, 3H), 7.22 (dd,
J = 8.9, 2.6 Hz, 1H), 6.81 (d, J = 8.9 Hz, 1H), 6.07 (dquin, J = 17.2, 4.8
Hz, 1H), 5.52 (dq, J = 17.2, 1.7 Hz, 1H), 5.32 (dq, J = 10.6, 1.7 Hz, 1H),
4.61 (dt, J = 4.8, 1.6 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ = 157.7,
132.8, 132.6, 131.6, 129.3, 128.4, 128.3, 125.5, 123.1, 117.4, 114.7,
113.6, 94.6, 84.4, 69.6 ppm; EI-MS m/z (rel intensity) 268 (M+, 100);
HRMS (ESI-orbitrap): calcd for C17H13ClO+H [M+H]+: 269.0728, found:
269.0730.
1-Cinnamyloxy-2-((E)-styrylethynyl)benzene (3af) (Table 2, Entry 16).
Compound
3af
was
obtained
from
1-(bromoethynyl)-2-
cinnamyloxybenzene (1a) (78.0 mg) and (E)-styrylboronic acid (2f) (74.4
mg) according to the general procedure in 72% yield (60.3 mg, 0.179
mmol) as a white solid: m.p. 97-98 °C; 1H NMR (300 MHz, CDCl3): δ =
7.45-7.39 (m, 5H), 7.36-7.23 (m, 7H), 7.06 (d, J = 16.2 Hz, 1H), 6.97-
6.91 (m, 2H), 6.84 (d, J = 16.0 Hz, 1H), 6.46 (dt, J = 16.2, 5.5 Hz, 2H),
4.81 ppm (dd, J = 5.3, 1.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ =
159.0, 145.0, 136.5, 136.4, 133.4, 132.6, 129.6, 128.7, 128.6, 127.8,
126.6, 128.5, 126.3, 124.3, 120.8, 113.3, 112.6, 108.5, 93.1, 88.2, 69.2
ppm; EI-MS m/z (rel intensity) 336 (M+, 7); HRMS (ESI-orbitrap): calcd
for C25H20O+Na [M+Na]+: 359.1406, found: 359.1407.
1-Cinnamyloxy-2-(phenylethynyl)benzene[7] (3ab) (Table 2, Entry 12).
Compound
3ab
was
obtained
from
1-(bromoethynyl)-2-
cinnamyloxybenzene (1a) (78.6 mg) and phenylboronic acid (2b) (61.2
mg) according to the general procedure in 81% yield (62.7 mg, 0.202
1
mmol) as a white solid: m.p. 100-102 °C; H NMR (300 MHz, CDCl3): δ
= 7.59-7.50 (m, 3H), 7.41-7.22 (m, 9H), 6.98-6.93 (m, 2H), 6.86 (d, J =
16.0 Hz, 1H), 6.46 (dt, J = 16.0, 5.3 Hz, 1H), 4.81 ppm (dd, J = 5.3, 1.6
Hz, 2H); 13C NMR (75 MHz, CDCl3): δ = 159.1, 136.5, 133.4, 132.3,
131.6, 129.6, 128.6, 128.3, 128.1, 127.8, 126.5, 124.3, 123.6, 120.8,
1-Cinnamyloxy-2-((E)-dec-3-en-1-yn-1-yl)benzene (3ag) (Table 2,
Entry 17). Compound 3ag was obtained from 1-(bromoethynyl)-2-
cinnamyloxybenzene (1a) (78.2 mg) and (E)-oct-1-en-1-ylboronic acid
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
(2g) (78.2 mg) according to the general procedure in 90% yield (77.8
mg, 0.226 mmol) as a white solid: m.p. 44-46 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.43-7.21 (m, 7H), 6.93-6.88 (m, 2H), 6.81 (d, J = 16.0 Hz,
1H), 6.43 (dt, J = 16.0, 5.3 Hz, 1H), 6.27 (dt, J = 15.9, 7.1 Hz, 1H), 5.76
(d, J = 15.9 Hz, 1H), 4.78 (dd, J = 5.3, 1.4 Hz, 2H), 2.16 (q, J = 7.1 Hz,
2H), 1.43-1.25 (m, 8H), 0.88 ppm (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz,
CDCl3): δ = 158.9, 145.0, 136.6, 133.3, 132.4, 129.2, 128.5, 127.8,
126.5, 124.4, 120.8, 113.5, 112.5, 109.8, 92.7, 84.1, 69.2, 33.2, 31.7,
28.8, 28.7, 22.6, 14.1 ppm; EI-MS m/z (rel intensity) 344 (M+, 3); HRMS
(ESI-orbitrap): calcd for C25H28O+Na [M+Na]+: 367.2032, found:
367.2027.
13C NMR (75 MHz, CDCl3): δ = 151.3, 138.1, 131.4, 131.2, 129.1,
125.3, 120.40, 120.38, 88.85, 88.81, 34.8, 31.2, 21.5 ppm; EI-MS m/z
(rel intensity) 248 (M+, 68).
1-Chloro-4-(p-tolylethynyl)benzene[32] (7fa) (Table 3, Entry 6).
Compound 7fa was obtained from 1-(bromoethynyl)-4-chlorobenzene
(6f) (53.5 mg) and p-tolylboronic acid (2a) (68.0 mg) according to the
general procedure in 84% yield (47.6 mg, 0.211 mmol) as a white solid:
m.p. 148-150 °C; 1H NMR (300 MHz, CDCl3): δ = 7.47-7.40 (m, 4H),
7.31 (dt, J = 8.6, 2.3 Hz, 2H), 7.16 (d, J = 7.9 Hz, 2H), 2.37 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): δ = 138.7, 134.0, 132.7, 131.5, 129.1,
128.6, 122.0, 119.8, 90.5, 87.6, 21.5 ppm; EI-MS m/z (rel intensity) 226
(M+, 100).
1-Methyl-4-(phenylethynyl)benzene[27] (7aa) (Table 3, Entry 1).
Compound 7aa was obtained from (bromoethynyl)benzene (6a) (45.1
mg) and p-tolylboronic acid (2a) (68.0 mg) according to the general
procedure in 71% yield (34.1 mg, 0.178 mmol) as a white solid: m.p. 69-
71 °C; 1H NMR (300 MHz, CDCl3): δ = 7.54-7.46 (m, 2H), 7.43 (d, J =
8.0 Hz, 2H), 7.38-7.31 (m, 3H), 7.15 (d, J = 7.8 Hz, 2H), 2.36 ppm (s,
3H); 13C NMR (75 MHz, CDCl3): δ = 138.4, 131.51, 131.46, 129.1,
128.3, 128.1, 123.4, 120.1, 89.5, 88.7, 21.5 ppm; EI-MS m/z (rel
intensity) 192 (M+, 100).
1-(p-Tolylethynyl)-4-(trifluoromethyl)benzene[33] (7ga) (Table 3, Entry
7). Compound 7ga was obtained from 1-(bromoethynyl)-4-
(trifluoromethyl)benzene (6g) (61.9 mg) and p-tolylboronic acid (2a)
(67.7 mg) according to the general procedure in 91% yield (58.9 mg,
0.227 mmol) as a white solid: m.p. 125-127 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.60 (t, J = 9.0 Hz, 4H), 7.44 (d, J = 8.1 Hz, 2H), 7.17 (d, J =
7.9 Hz, 2H), 2.38 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ = 139.1,
131.7, 131.6, 129.2 (q, J = 32.6 Hz), 129.2, 127.3, 125.2 (q, J = 3.7 Hz),
124.7 (q, J = 272.0 Hz), 119.4, 92.0, 87.4, 21.5 ppm; EI-MS m/z (rel
intensity) 260 (M+, 100).
1-Methoxy-4-(p-tolylethynyl)benzene[28] (7ba) (Table 3, Entry 2).
Compound 7ba was obtained from 1-(bromoethynyl)-4-methoxybenzene
(6b) (52.6 mg) and p-tolylboronic acid (2a) (68.0 mg) according to the
general procedure in 81% yield (45.0 mg, 0.203 mmol) as a white solid:
m.p. 126-128 °C; 1H NMR (300 MHz, CDCl3): δ = 7.46 (dt, J = 8.9, 2.6
Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 6.87 (dt, J =
8.9, 2.6 Hz, 2H), 3.82 (s, 3H), 2.36 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): δ = 159.4, 138.0, 133.0, 131.3, 129.1, 120.5, 115.6, 113.9, 88.6,
88.2, 55.3, 21.5 ppm; EI-MS m/z (rel intensity) 222 (M+, 100).
2-(p-Tolylethynyl)naphthalene[34] (7ha) (Table 3, Entry 8). Compound
7ha was obtained from 2-(bromoethynyl)naphthalene (6h) (57.7 mg)
and p-tolylboronic acid (2a) (68.0 mg) according to the general
procedure in 76% yield (46.2 mg, 0.191 mmol) as a white solid: m.p.
145-147 °C; 1H NMR (300 MHz, CDCl3): δ = 8.04 (s, 1H), 7.82-7.78 (m,
3H), 7.59-7.46 (m, 5H), 7.17 (d, J = 7.8 Hz, 2H), 2.37 ppm (s, 3H); 13C
NMR (75 MHz, CDCl3): δ = 138.4, 133.0, 132.7, 131.5, 131.3, 129.1,
128.4, 127.9, 127.7 × 2, 126.5, 126.5, 120.8, 120.2, 90.0, 89.1, 21.5
ppm; EI-MS m/z (rel intensity) 242 (M+, 71).
1-Methoxy-3-(p-tolylethynyl)benzene[29] (7ca) (Table 3, Entry 3).
Compound 7ca was obtained from 1-(bromoethynyl)-3-methoxybenzene
(6c) (52.5 mg) and p-tolylboronic acid (2a) (67.7 mg) according to the
general procedure in 85% yield (47.4 mg, 0.213 mmol) as a brown solid:
m.p. 38-40 °C; 1H NMR (300 MHz, CDCl3): δ = 7.43 (d, J = 8.1 Hz, 2H),
7.25 (t, J = 8.1 Hz, 1H), 7.17-7.04 (m, 3H), 7.05 (dd, J = 2.6, 1.4 Hz,
1H), 6.88 (ddd, J = 8.3, 2.6, 0.9 Hz, 1H), 3.82 (s, 3H), 2.36 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): δ = 159.3, 138.4, 131.5, 129.4, 129.1,
124.4, 124.1, 120.0, 116.2, 114.8, 89.4, 88.6, 55.3, 21.5 ppm; EI-MS
m/z (rel intensity) 222 (M+, 100).
1-Methoxy-4-(phenylethynyl)benzene[35] (7bb) (Table 3, Entry 9).
Compound
7bb
was
obtained
from
1-(bromoethynyl)-4-
methoxybenzene (6b) (52.8 mg) and phenylboronic acid (2b) (61.1 mg)
according to the general procedure in 75% yield (39.1 mg, 0.188 mmol)
as a white solid: m.p. 58-60 °C; 1H NMR (300 MHz, CDCl3): δ = 7.53-
7.45 (m, 4H), 7.37-7.30 (m, 3H), 6.87 (dt, J = 8.9, 2.1 Hz, 2H), 3.83 ppm
(s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.6, 133.0, 131.4, 128.3,
127.9, 123.5, 115.3, 114.0, 89.3, 88.0, 55.3 ppm; EI-MS m/z (rel
intensity) 208 (M+, 100).
1-Methoxy-2-(p-tolylethynyl)benzene[30] (7da) (Table 3, Entry 4).
Compound 7da was obtained from 1-(bromoethynyl)-2-methoxybenzene
(6d) (52.9 mg) and p-tolylboronic acid (2a) (68.0 mg) according to the
general procedure in 87% yield (48.5 mg, 0.218 mmol) as a yellow oil:
1H NMR (300 MHz, CDCl3): δ = 7.51-7.44 (m, 3H) 7.32-7.25 (m, 1H),
7.14 (d, J = 7.8 Hz, 2H), 6.96-6.88 (m, 2H), 3.91 (s, 3H), 2.36 ppm (s,
3H); 13C NMR (75 MHz, CDCl3): δ = 159.8, 138.2, 133.51, 133.47,
131.5, 129.5, 129.0, 120.4, 112.6, 110.6, 93.6, 85.0, 55.8, 21.5 ppm; EI-
MS m/z (rel intensity) 222 (M+, 100).
1,2-Bis(p-methoxyphenyl)acetylene[28] (7bc) (Table 3, Entry 10).
Compound 7bc was obtained from 1-(bromoethynyl)-4-methoxybenzene
(6b) (52.8 mg) and p-methoxyphenylboronic acid (2c) (75.8 mg)
according to the general procedure in 97% yield (57.4 mg, 0.241 mmol)
as a yellow solid: m.p. 142-144 °C; 1H NMR (300 MHz, CDCl3): δ = 7.45
(dt, J = 8.9, 2.7 Hz, 4H), 6.86 (dt, J = 8.9, 2.7 Hz, 4H), 3.82 ppm (s, 6H);
13C NMR (75 MHz, CDCl3): δ = 159.3, 132.8, 115.7, 113.9, 87.9, 55.3
ppm; EI-MS m/z (rel intensity) 238 (M+, 100).
1-(tert-Butyl)-4-(p-tolylethynyl)benzene[31] (7ea) (Table 3, Entry 5).
Compound 7ea was obtained from 1-(bromoethynyl)-4-(tert-
butyl)benzene (6e) (59.5 mg) and p-tolylboronic acid (2a) (68.5 mg)
according to the general procedure in 90% yield (55.8 mg, 0.225 mmol)
as a white solid: m.p. 116-118 °C; 1H NMR (300 MHz, CDCl3): δ = 7.47-
7.34 (m, 6H), 7.14 (d, J = 8.3 Hz, 2H), 2.36 (s, 3H), 1.32 ppm (s, 9H);
1-Chloro-4-((p-methoxyphenyl)ethynyl)benzene[36] (7bd) (Table 3,
Entry 11). Compound 7bd was obtained from 1-(bromoethynyl)-4-
methoxybenzene (6b) (53.2 mg) and p-chlorophenylboronic acid (2d)
(78.2 mg) according to the general procedure in 73% yield (44.3 mg,
0.183 mmol) as a white solid: m.p. 85-87 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.48-7.42 (m, 4H), 7.30 (dt, J = 8.5, 2.3 Hz, 2H), 6.88 (dt, J
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
= 8.8, 2.7 Hz, 2H), 3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ =
159.8, 133.8, 133.0, 132.6, 128.6, 122.1, 115.0, 114.0, 90.3, 87.0, 55.3
ppm; EI-MS m/z (rel intensity) 242 (M+, 100).
2-(p-Tolyl)benzofuran[38] (5) Yellow solid: m.p. 125-127 °C; 1H NMR
(300 MHz, CDCl3): δ = 7.77 (d, J = 8.4 Hz, 2H), 7.59-7.56 (m, 1H), 7.51
(dt, J = 6.8, 1.3 Hz, 1H), 7.30-7.19 (m, 4H), 6.97 (d, J = 0.7 Hz, 1H),
2.40 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 156.1, 154.7, 138.6,
129.5, 129.3, 127.7, 124.9, 124.0, 122.8, 120.7, 111.1, 100.5, 21.4 ppm;
EI-MS m/z (rel intensity) 208 (M+, 100).
1-Methoxy-4-((p-(trifluoromethyl)phenyl)ethynyl)benzene[37] (7be)
(Table 3, Entry 12). Compound 7be was obtained from 1-
(bromoethynyl)-4-methoxybenzene
(6b)
(52.9
mg)
and
p-
(trifluoromethyl)phenylboronic acid (2e) (94.6 mg) according to the
general procedure (18 h) in 84% yield (57.9 mg, 0.210 mmol) as a
yellow solid: m.p. 85-87 °C; 1H NMR (300 MHz, CDCl3): δ = 7.59 (t, J =
9.2 Hz, 4H), 7.49 (dt, J = 8.9, 2.7 Hz, 2H), 6.89 (dt, J = 8.9, 2.7 Hz, 2H),
3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 160.0, 133.2, 131.6,
129.5 (q, J = 32.7 Hz), 127.5 (q, J = 1.5 Hz), 125.2 (q, J = 3.9 Hz), 124.0
(q, J = 272.0 Hz), 114.6, 114.1, 91.9, 86.8, 55.3 ppm; EI-MS m/z (rel
intensity) 276 (M+, 100).
General
procedure
for
Pd-catalyzed
annulation
of
o-
allyloxyethynylbenzene 3 (Table 4)
A mixture of o-allyloxyethynylbenzene 3 (0.25 mmol), Et3N (0.5 mmol),
Pd2dba3 (12.5 μmol, 5 mol %) and ligand L1a (25.0 μmol, 10 mol %) in
1,4-dioxane/H2O (3/1) (1.0 mL) at 50 °C under an Ar atmosphere was
stirred for 1 h. After the reaction, the reaction was quenched with
distilled water. The solution was extracted with ethyl acetate, washed
with brine, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by silica gel chromatography
(hexane) to afford the corresponding benzofuran product 8.
1-Methoxy-4-(m-tolylethynyl)benzene[28] (7bh) (Table 3, Entry 13).
Compound
7bh
was
obtained
from
1-(bromoethynyl)-4-
methoxybenzene (6b) (53.3 mg) and m-tolylboronic acid (2h) (67.9 mg)
according to the general procedure in 91% yield (50.3 mg, 0.227 mmol)
as a yellow oil; 1H NMR (300 MHz, CDCl3): δ = 7.46 (dt, J = 8.9, 2.7 Hz,
2H), 7.32 (d, J = 11.2 Hz, 2H), 7.22 (t, J = 7.2 Hz, 1H), 7.12 (d, J = 7.6
Hz, 1H), 6.87 (dt, J = 8.9, 2.7 Hz, 2H), 3.81 (s, 3H), 2.34 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): δ = 159.5, 137.9, 133.0, 132.0, 128.8,
128.5, 128.2, 123.3, 115.4, 113.9, 89.0, 88.2, 55.3, 21.2 ppm; EI-MS
m/z (rel intensity) 222 (M+, 100).
3-Cinnamyl-5-methoxy-2-phenylbenzofuran (8cb) (Table 4, Entry 1).
Compound 8cb was obtained from 1-cinnamyloxy-4-methoxy-2-
(phenylethynyl)benzene 3cb (85.2 mg) according to the general
procedure in 86% yield (73.6 mg, 0.216 mmol) as a white solid: m.p. 94-
95 °C; 1H NMR (300 MHz, CDCl3): δ = 7.70 (d, J = 7.4 Hz, 2H), 7.41-
7.11 (m, 9H), 6.93 (d, J = 2.4 Hz, 1H), 6.83 (dd, J = 8.6, 2.5 Hz, 1H),
6.42-6.41 (m, 2H), 3.75 (s, 3H), 3.72-3.71 ppm (m, 2H); 13C NMR (75
MHz, CDCl3): δ = 155.8, 152.6, 149.0, 137.2, 131.0, 130.93, 130.91,
128.7, 128.5, 128.3, 127.2, 127.1, 126.9, 126.1, 113.2, 113.0, 111.5,
102.3, 55.9, 27.7 ppm; EI-MS m/z (rel intensity) 340 (M+, 100); HRMS
(ESI-orbitrap): calcd for C24H20O2+H [M+H]+: 341.1536; found:
341.1535.
1-Methoxy-4-(o-tolylethynyl)benzene[28] (7bi) (Table 3, Entry 14).
Compound 7bi was obtained from 1-(bromoethynyl)-4-methoxybenzene
(6b) (52.6 mg) and o-tolylboronic acid (2i) (67.8 mg) according to the
general procedure in 85% yield (47.3 mg, 0.213 mmol) as a yellow solid:
m.p. 76-78 °C; 1H NMR (300 MHz, CDCl3): δ = 7.47 (dt, J = 8.9, 2.7 Hz,
3H), 7.24-7.14 (m, 3H), 6.88 (dt, J = 8.9, 2.7 Hz, 2H), 3.82 (s, 3H), 2.50
ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.5, 139.9, 132.9, 131.6,
129.4, 127.9, 125.5, 123.3, 115.6, 114.0, 93.3, 87.0, 55.3, 20.7 ppm; EI-
MS m/z (rel intensity) 222 (M+, 90).
5-Chloro-3-cinnamyl-2-phenylbenzofuran (8eb) (Table 4, Entry 2).
Compound 8eb was obtained from 4-chloro-1-cinnamyloxy-2-
(phenylethynyl)benzene 3eb (86.7 mg) according to the general
procedure in 88% yield (75.8 mg, 0.220 mmol) as a white solid: m.p.
115-116 °C; 1H NMR (300 MHz, CDCl3): δ = 7.78 (d, J = 7.2 Hz, 2H),
7.52-7.18 (m, 11H), 6.47-6.46 (m, 2H), 3.78-3.77 ppm (m, 2H); 13C NMR
(75 MHz, CDCl3): δ = 153.2, 152.4, 137.0, 131.8, 131.3, 130.4, 128.8,
128.7, 128.5, 128.2, 127.3, 127.0, 126.6, 126.2, 124.6, 119.3, 112.8,
112.1, 27.5 ppm; EI-MS m/z (rel intensity) 344 (M+, 100); HRMS (ESI-
orbitrap): calcd for C23H17OCl [M]+: 344.0962; found: 344.0974.
Procedure for Pd-catalyzed Suzuki-Miyaura-type reaction of o-
cinnamyloxybromoalkyne (1a) with p-tolylboronic acid (2a)
(Scheme 2)
A mixture of 1-(bromoethynyl)-2-cinnamyloxybenzene (1a) (0.25 mmol,
78.3 mg), p-tolylboronic acid (2) (0.50 mmol, 67.4 mg), K3PO4 (0.5
mmol, 0.1057 g), Pd(OAc)2 (12.5 μmol, 5 mol %, 2.81 mg) and ligand
L1b (12.5 μmol, 5 mol %, 3.34 mg) in i-PrOH (1.0 mL) at 40 °C under an
Ar atmosphere was stirred for 6 h. After the reaction, the reaction was
quenched with distilled water. The solution was extracted with ethyl
acetate, washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by silica gel
chromatography (hexane) to afford 1-cinnamyl-4-methylbenzene (4) (3.6
mg, 0.017 mmol) in 7% and 2-(p-tolyl)benzofuran (5) (5.2 mg, 0.025
mmol) in 10%.
1-Cinnamyl-4-methylbenzene[23c] (4) Yellow oil: 1H NMR (300 MHz,
CDCl3): δ = 7.34 (tt, J = 9.9, 0.9 Hz, 2H), 7.28 (tt, J = 7.7, 1.5 Hz, 2H),
7.22-7.10 (m, 5H), 6.45 (d, J = 15.9 Hz, 1H), 6.34 (dt, J = 15.9 and 6.4
Hz, 1H), 3.51 (d, J = 6.4 Hz, 2H), 2.33 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): δ = 137.5, 137.0, 135.7, 130.8, 129.5, 129.1, 128.53, 128.46,
127.0, 126.1, 38.9, 21.0 ppm; EI-MS m/z (rel intensity) 208 (M+, 100).
3-Cinnamyl-2-((E)-styryl)benzofuran (8af) (Table 4, Entry 3).
Compound
8af
was
obtained
from
1-cinnamyloxy-2-((E)-
styrylethynyl)benzene 3af (84.1 mg) according to the general procedure
in 92% yield (77.7 mg, 0.231 mmol) as a yellow solid: m.p. 90-91 °C; 1H
NMR (300 MHz, CDCl3): δ = 7.55-7.51 (m, 3H), 7.47 (d, J = 8.1 Hz, 1H),
7.39-7.16 (m, 11H), 7.11 (d, J = 16.1 Hz, 1H), 6.53 (d, J = 15.8 Hz, 1H),
6.38 (dt, J = 15.8, 6.0 Hz, 1H), 3.71 ppm (dd, J = 6.0, 1.0 Hz, 2H); 13C
NMR (75 MHz, CDCl3): δ = 154.3, 150.9, 137.1, 136.8, 131.2, 129.8,
129.5, 128.7, 128.5, 128.0, 127.3, 127.2, 126.6, 126.1, 124.8, 122.5,
119.7, 115.6, 114.3, 110.8, 27.2 ppm; EI-MS m/z (rel intensity) 336 (M+,
78); HRMS (ESI-orbitrap): calcd for C25H20O-H [M-H]-: 335.1430; found:
335.1429.
3-Cinnamyl-2-((E)-oct-1-en-1-yl)benzofuran (8ag) (Table 4, Entry 4).
Compound 8ag was obtained from 1-cinnamyloxy-2-((E)-dec-3-en-1-yn-
1-yl)benzene 3ag (84.4 mg) according to the general procedure in 88%
yield (76.0 mg, 0.221 mmol) as a white solid: m.p. 36-38 °C; 1H NMR
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
(300 MHz, CDCl3): δ = 7.48 (d, J = 7.3 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H),
7.33-7.12 (m, 7H), 6.54-6.43 (m, 3H), 6.38- 6.29 (m, 1H), 3.60 (dd, J =
6.0, 1.1 Hz, 2H), 2.26 (q, J = 14.0, 6.8 Hz, 2H), 1.55-1.25 (m, 8H), 0.89
ppm (t, J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 154.0, 150.9,
137.3, 133.4, 130.8, 129.8, 128.5, 127.6, 127.1, 126.1, 124.1, 122.3,
119.4, 116.5, 112.8, 110.6, 33.3, 31.7, 29.1, 28.9, 26.9, 22.6, 14.1 ppm;
EI-MS m/z (rel intensity) 344 (M+, 76); HRMS (ESI-orbitrap): calcd for
C25H28O-H [M-H]-: 343.2056; found: 343.2051.
procedure in 96% yield (24.1 mg, 0.096 mmol) as a colorless oil; 1H
NMR (500 MHz, CDCl3): δ = 7.43-7.41 (m, 2H), 7.30-7.23 (m, 3H), 6.78
(d, J = 8.7 Hz, 1H), 6.62 (dd, J = 8.7, 3.0 Hz, 1H), 6.40 (d, J = 3.0 Hz,
1H), 5.90 (t, J = 3.9 Hz, 1H), 5.66 (d, J = 1.5 Hz, 1H), 4.80 (d, J = 3.9
Hz, 2H), 3.37 (d, J = 1.5 Hz, 1H), 3.53 ppm (s, 3H); 13C NMR (125 MHz,
CDCl3): δ = 153.8, 148.1, 146.4, 139.3, 136.8, 128.4, 127.9, 126.6,
123.7, 122.1, 116.4, 115.8, 114.2, 111.4, 65.2, 55.4 ppm; EI-MS m/z (rel
intensity) 264 (M+, 100); HRMS (ESI- orbtirap): calcd for C18H16O2+Na
[M+Na]+: 287.1043; found: 287.1043.
Au-catalyzed
annulation
of
1-cinnamyloxy-2-((p-
tolyl)ethynyl)benzene (3aa) for synthesis of 3-(1-phenylallyl)-2-(p-
6-Chloro-4-(1-phenylvinyl)-2H-benzopyran (10jb) (Table 5, Entry 3).
tolyl)benzofuran (9aa) (Scheme 3)
Compound
10jb
was
obtained
from
1-allyloxy-4-chloro-2-
A mixture of 1-cinnamyloxy-2-((p-tolyl)ethynyl)benzene (3aa) (32.3 mg,
0.10 mmol), AuClPPh3 (5.00 mg, 10.0 μmol, 10 mol %) and AgSbF6
(3.56 mg, 10.0 μmol, 10 mol %) in toluene (1.0 mL) at 25 °C under an Ar
atmosphere was stirred for 24 h. After the reaction, the reaction was
quenched with distilled water. The solution was extracted with ethyl
acetate, washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by silica gel
chromatography (hexane/ethyl acetate = (v/v = 250/1)) to afford 3-(1-
phenylallyl)-2-(p-tolyl)benzofuran (9aa) in 37% yield (12.0 mg, 0.0370
mmol) as a yellow oil; 1H NMR (300 MHz, CDCl3): δ = 7.61 (d, J = 8.1
Hz, 2H), 7.50 (d, J = 8.1 Hz, 1H), 7.35-7.19 (m, 9H), 7.07 (td, J = 7.6,
0.9 Hz, 1H), 6.53-6.42 (m, 1H), 5.30 (dt, J = 10.1, 1.5 Hz, 1H), 5.20 (d, J
= 6.5 Hz, 1H), 5.13 (dt, J = 17.1, 1.5 Hz, 1H), 2.41 ppm (s, 3H); 13C
NMR (75 MHz, CDCl3): δ = 154.3, 152.3, 141.6, 138.7, 138.5, 129.4,
129.9, 128.4, 128.2, 127.9, 127.7, 126.5, 123.9, 122.2, 121.6, 117.1,
115.8, 111.1, 45.3, 21.4 ppm; EI-MS m/z (rel intensity) 324 (M+, 100);
HRMS (ESI-orbitrap): calcd for C24H20O+H [M+H]+: 325.1587; found:
325.1587.
(phenylethynyl)benzene (3jb) (26.8 mg) according to the general
1
procedure in 87% yield (23.3 mg, 0.087 mmol) as a yellow oil; H NMR
(500 MHz, CDCl3): δ = 7.42-7.40 (m, 2H), 7.32-7.27 (m, 3H), 7.00 (dd, J
= 8.6, 2.5 Hz, 1H), 6.80 (d, J = 2.5 Hz, 1H), 6.76 (d, J = 8.5 Hz, 1H),
5.86 (t, J = 3.8 Hz, 1H), 5.70 (d, J = 1.4 Hz, 1H), 5.35 (d, J = 1.4 Hz,
1H), 4.86 ppm (d, J = 3.8 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ =
152.8, 145.7, 138.7, 135.9, 128.7, 128.5, 128.1, 126.5, 126.0, 125.7,
124.4, 122.3, 117.3, 116.1, 65.4 ppm; EI-MS m/z (rel intensity) 268 (M+,
100); HRMS (APCI-orbitrap): calcd for C17H13OCl+H [M+H]+: 269.0728;
found: 269.0716.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research (C)
(No. 26410109) from Japan Society for the Promotion of Science
(JSPS). We thank the Tonen General Sekiyu Research and
Development Encouragement Foundation and the COE Program in
Chiba University for financial support.
General
procedure
for
enyne
metathesis
of
o-
allyloxyethynylbenzene 3 using Grubbs 2nd catalyst (Table 5)
Keywords: copper • coupling reaction • alkyne • allyl •
To a solution of o-allyloxyethynylbenzene derivatives 3 (0.10 mmol) in
toluene (5 mL) was added Grubbs 2nd-generation catalyst (5.0 μmol,
5.0 mol%) under nitrogen. The reaction container was filled with
ethylene gas (1 atm) in three cycles. The reaction mixture was heated to
40 °C and stirred for 5 h. After cooling to room temperature, the mixture
was concentrated under reduced pressure and purified by silica-gel
column chromatography (hexane/ethyl acetate = (v/v = 7/3)) to afford
the corresponding benzopyran product 10.
heterocycle
[1]
[2]
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4-(1-Phenylvinyl)-2H-benzopyran (10gb) (Table 5, Entry 1).
Compound
10gb
was
obtained
from
1-allyloxy-2-
(phenylethynyl)benzene (3gb) (23.0 mg) according to the general
procedure in 95% yield (21.8 mg, 0.095 mmol) as a colorless oil; 1H
NMR 500 MHz, CDCl3): δ = 7.44-7.42 (m, 2H), 7.30-7.23 (m, 3H), 7.05
(td, J = 8.0, 1.5 Hz, 1H), 6.82 (ddd, J = 7.6, 6.7, 1.5 Hz, 2H), 6.70 (td, J
= 7.5, 1.2 Hz, 1H), 5.85 (t, J = 3.8 Hz, 1H), 5.68 (d, J = 1.5 Hz, 1H), 5.37
(d, J = 1.5 Hz, 1H), 4.87 ppm (d, J = 3.8 Hz, 2H); 13C NMR (75 MHz,
CDCl3): δ = 154.2, 146.4, 139.2, 136.7, 129.0, 128.4, 127.9, 126.5,
126.1, 123.0, 121.3, 121.2, 116.0, 115.6, 65.3 ppm; EI-MS m/z (rel
intensity) 234 (M+, 100); HRMS (ESI-orbitrap): calcd for C17H14O+Na
[M+Na]+: 257.0937; found: 257.0937.
6-Methoxy-4-(1-phenylvinyl)-2H-benzopyran (10ib) (Table 5, Entry 2).
Compound 10ib was obtained from 1-allyloxy-4-methoxy-2-
(phenylethynyl)benzene (3ib) (25.2 mg) according to the general
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
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10.1002/ejoc.201700217
European Journal of Organic Chemistry
FULL PAPER
Cross-coupling
Kohei Watanabe. Prof. Dr. Takashi
We found that Suzuki-Miyaura-type
reaction of o-allyloxy(bromoethynyl)-
benzene with arylboronic acid using a
Mino,* Eri Ishikawa, Miyu Okano,
Tatsuya Ikematsu, Prof. Dr. Yasushi
Yoshida, Prof. Dr. Masami Sakamoto,
Kazuki Sato and Prof. Dr. Kazuhiro
Yoshida
Ar B(OH)2
Cu catalyst
Ar
Br
Mild
condition!
hydrazone-Cu
proceeded smoothly in i-PrOH under
mild conditions to afford the
corresponding o-allyloxyethynyl-
catalyst
system
O
R
O
R
Pd
Au
Grubbs
Page No. – Page No.
benzene derivatives. We further
demonstrate that three types of
transformation using transition metal
catalysts to o-allyloxyethynylbenzene
derivatives lead to various respective
heterocyclic compounds.
R
R
Ar
Synthesis
of
o-Allyloxyethynyl-
benzene Derivatives via Cu-Catalyzed
Suzuki-Miyaura-Type Reaction and
Ar
Ar
O
O
O
Their
Transformations
for
Various heterocyclic compounds
from one starting material
Heterocyclic Compounds
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