Hydrazone–Cu-Catalyzed Suzuki–Miyaura-Type Reactions of Dibromoalkenes with Arylboronic Acids

Article abstract of DOI:10.1002/ejoc.201700535

We have found that Suzuki–Miyaura-type reactions of dibromoalkenes with arylboronic acids using a hydrazone–Cu catalyst system proceeded smoothly under mild conditions to afford the corresponding internal alkyne derivatives in good yields. Furthermore, we also succeeded in the synthesis of o-allyloxy(ethynyl)benzene derivatives, which are known to be effective precursors of various heterocyclic compounds, through this reaction.

Full text of DOI:10.1002/ejoc.201700535

A Journal of
Accepted Article
Title: Hydrazone-Cu-catalyzed Suzuki-Miyaura-type Reaction of
Dibromoalkene with Arylboronic Acid
Authors: Kohei Watanabe, Takashi Mino, Chikako Hatta, Eri Ishikawa,
Yasushi Yoshida, and Masami Sakamoto
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700535
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10.1002/ejoc.201700535
European Journal of Organic Chemistry
FULL PAPER
Hydrazone-Cu-catalyzed Suzuki-Miyaura-type Reaction of
Dibromoalkene with Arylboronic Acid
Kohei Watanabe,[a] Takashi Mino,*[a],[b] Chikako Hatta,[a] Eri Ishikawa,[a] Yasushi Yoshida,[a],[b] and
Masami Sakamoto[a],[b]
Abstract: We found that
a
Suzuki-Miyaura-type reaction of
As a further protocol for the preparation of internal alkyne
structure, one-pot reaction of Pd-catalyzed Suzuki-Miyaura-type
reaction of dibromoalkenes instead of bromoalkynes followed by
dehydrobromination in the presence of strong base was reported
by the Chelucci group.9 Moreover, Pd-catalyzed cascade
reactions of C-C coupling reaction and dehydrobromination using
dibromoalkenes with various organometalic reagents as coupling
partners were also reported.10 First, the Shen group reported that
Pd-catalyzed Stille coupling reaction of dibromoalkenes with
organostannanes afforded internal alkyne derivatives.10a Second,
the Rao group reported that Pd-catalyzed cascade reaction of
dibromoalkenes with triarylbismuth produced internal alkyne
derivatives.10b Finally, the Schmidt group reported a cascade
reaction for the preparation of internal alkynes from
dibromoalkenes via sequential Pd-catalyzed Suzuki-Miyaura-type
reaction and dehydrobromination.10c These reactions required
precious metal as a catalyst, although these are more efficient
and stronger synthetic strategies for the construction of internal
alkyne structure compared with the reaction using bromoalkyne
as starting material because dibromoalkenes are precursors of
bromoalkynes and easily prepared from readily available
aldehydes via Corey-Fuchs reaction.11 On another front, the Tan
group12a and Mao group12b reported that Cu-catalyzed Suzuki-
Miyaura-type reaction of dibromoalkenes with aryl boronic acids
also afforded the internal alkyne derivatives. However, both
reactions required high temperature exceeding 100 °C and high
loading Cu-catalyst exceeding 10 mol%.
dibromoalkenes with arylboronic acids using a hydrazone-Cu catalyst
system proceeded smoothly under mild conditions to afford the
corresponding internal alkyne derivatives in good yields. Furthermore,
we succeeded in synthesis of o-allyloxyethynylbenzene derivatives,
which are known as effective precursors of various heterocyclic
compounds, via this reaction.
Introduction
Internal alkyne structure is one of the most important compounds
in organic synthetic chemistry because this is a common structure
in useful and versatile synthetic intermediates.1 Recently, various
intramolecular reactions of internal alkyne derivatives were
reported.2 Therefore, development of a synthetic methodology of
internal alkyne derivatives has possibilities to contribute to the
development of organic synthesis, and is strongly desired.
Pd/Cu-catalyzed Sonogashira coupling reaction of arylhalides
with terminal alkynes is a well-known first choice for the
preparation of internal alkyne structures.3 Recently, Sonogashira
coupling reactions using only common metal catalysts such as
Cu-,4 Ni-5 and Fe-catalyst6 instead of precious metal catalyst were
reported. Although these reactions were attractive because
common metals are less toxic and exist abundantly on the earth
compared with precious metal, all reactions required high
temperature except for one.4k Therefore, the preparation of
internal alkyne structures using common metal catalyst remains
challenging.
On the other hand, Pd-catalyzed Suzuki-Miyaura-type reactions
of bromoalkynes with aryl boronic acids for the construction of
internal alkyne structure were reported as an alternative method
of Sonogashira reaction.7 The Wang group7b and Tang group7c
reported that this reaction proceeded even under room
temperature in the presence of Pd-catalyst. In 2011, the Wang
group reported that this reaction using Cu-catalyst proceeded and
gave internal alkyne derivatives.8 However, this reaction also
required reflux conditions.
On the other hand, we previously demonstrated phosphine-free
hydrazone compounds (Figure 1) as effective ligands for Pd-
catalyzed C-C bond formations such as the Suzuki-Miyaura,13
Mizoroki-Heck,14 Sonogashira15 and Hiyama15 cross-coupling
reaction of aryl halides. We also demonstrated that a hydrazone-
Cu-catalyst system was effective for C-C,16 C-O,16 and C-N17
bond formations. Moreover, we recently found that Suzuki-
Miyaura-type reaction of bromoalkynes for internal alkyne
structures proceeded even at room temperature in the presence
of a hydrazone-Cu-catalyst system.18
R1
N
R2
R1
R2
R
N N
N
N
N N
Me
[a]
[b]
Graduate School of Engineering, Chiba University,
1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
E-mail: tmino@faculty.chiba-u.jp
http://chem.tf.chiba-u.jp/gacb06/index.html
Molecular Chirality Research Center, Chiba University,
1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
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. Hydrazones L1 and L2
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700535
European Journal of Organic Chemistry
FULL PAPER
Herein, we describe a hydrazone-Cu-catalyzed Suzuki-Miyaura-
type reaction of dibromoalkenes with arylboronic acids proceeded
smoothly under mild conditions and afforded the corresponding
internal alkyne derivatives.
Table 1. Optimization of reaction conditions
Ligand (5 mol%)
Br
Br
Cu cat. (Cu = 5 mol%)
+
Base (4.0 eq.)
Solvent (0.25 M)
60 °C, Ar, 18 h
(HO)2B
O
O
3aa
Yield
3aa (%)[a]
1a
2a
Results and Discussion
of
Initially, we explored the optimizing reaction conditions for the
Cu-catalyzed Suzuki-Miyaura-type reaction using 4-(2,2-
diboromovinyl)-1-methoxybenzene (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 EtOH as solvent at 60 °C gave the
corresponding internal alkyne product of 1-methoxy-4-(p-
tolylethynyl)benzene (3aa) in a 90% yield (Entry 1). We tested
various bishydrazone ligands L1b-e (Entries 2-5). The reaction
using a phenyl-methyl-type bishydrazone ligand L1b afforded the
corresponding product 3aa in 60% yield with recovery of starting
material 1a (Entry 2). When we used bishydrazone ligands L1c-e
bearing 5-7 member rings, the desired product 3aa was obtained
in 92%, 83% and 58% yields, respectively (Entries 3-5). In
particular, bishydrazone ligand L1c with 5 member rings is the
most effective for this reaction (Entry 3). We also tested pyridine-
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, phosphine ligand such as PPh3 was
not effective for this reaction (Entry 8). Next, we investigated the
effect of the Cu-catalyst (Entries 3 and 9-13). We found that CuBr,
CuCl, CuBr2 and Cu(OAc)2 were also effective for this reaction
and led to good yields of product, respectively (Entries 9-12). On
the other hand, the reaction using Cu2O afforded the
corresponding product in low yield (Entry 13). Various bases were
tested (Entries 3 and 14-20). While K3PO4 was effective for this
reaction (Entry 3), the reaction using Na3PO4 afforded only a trace
amount of product with recovery of 1a (Entry 14). Other potassium
salts such as KOAc, KF and K2CO3 were not effective for this
reaction (Entries 15-17). The reactions in the presence of Cs2CO3
or Ca(OH)2 afforded only a trace amount of the corresponding
product (Entries 18 and 19). Amine base such as Et3N was also
not effective for this reaction (Entry 20). Next, the effects of
solvent were investigated (Entries 3 and 21-29). First, we tried to
use various protic solvents (Entries 3 and 21-23). We found that
EtOH was the most suitable for this reaction (Entry 3). We also
tested aprotic solvents (Entries 24-29). Although the reaction in
MeCN afforded the corresponding product in relatively good yield
(Entry 24), the reaction using other solvents gave low yields or a
trace amount of product (Entries 25-29).
Entry
Ligand
Catalyst
Base
Solvent
1
L1a
L1b
L1c
L1d
L1e
L2a
L2b
CuI
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Na3PO4
KOAc
KF
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
iPrOH
nPrOH
MeCN
DMSO
NMP
90
2
CuI
60
CuI
CuI
92
3
4
83
CuI
58
5
6
CuI
73
7
CuI
84
CuI
17
8
PPh3 (10 mol%)
L1c
9
CuBr
CuCl
CuBr2
Cu(OAc)2
Cu2O
CuI
80
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
L1c
85
L1c
82
L1c
79
L1c
26
L1c
trace
trace
12
L1c
CuI
L1c
CuI
L1c
CuI
K2CO3
Cs2CO3
Ca(OH)2
Et3N
26
L1c
CuI
trace
trace
trace
39
L1c
CuI
L1c
CuI
L1c
CuI
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
L1c
CuI
37
L1c
CuI
46
L1c
CuI
73
L1c
CuI
33
L1c
CuI
24
L1c
CuI
DMF
trace
trace
6
L1c
CuI
THF
L1c
CuI
Toluene
[a] Isolated yield.
coupling products in moderate yields (Entries 4 and 5). The
reactions using electron-poor dibromoalkenes 1f and 1g led to
moderate yields of coupling products (Entries 6 and 7). The
reaction of 2-(2,2-dibromovinyl)naphthalene (1h) with p-
tolylboronic acid (2a) proceeded and afforded (p-
tolylethynyl)naphthalene (3ha) in 81% yield (Entry 8). 1-(2,2-
Dibromovinyl)-2-(methoxymethoxy)benzene (1i) was allowed to
react with p-tolylboronic acid (2a) to produce internal alkyne
derivative 3ia in 73% yield (Entry 9). When we tested 3- and 2-
substituted arylboronic acids 2c and 2d, both reactions also
proceeded (Entries 10 and 11). Phenylboronic acid (2e), which
has no substituent, was also tolerated in this reaction (Entry 12).
The reaction using arylboronic acids 2f and 2g with halogen
atoms such as chloro and bromo gave the corresponding
products in moderate yields. (Entries 13 and 14). In the case of
using electron-deficient arylboronic acid 2h, we obtained the
desired product in 44% yield (Entry 15). 2-Thienylboronic acid (2i)
Optimizing reaction conditions in hand (Table 1, Entry 3), we tried
to investigate the scope and limitation of this reaction by using
various dibromoalkenes 1 and arylboronic acids 2 (Table 2). We
found that 3- and 2-substituted (2,2-dibromovinyl)benzenes 1b
and 1c were also tolerated and afforded the corresponding
products in 77% and 66% yield, respectively (Entries 2 and 3).
The reactions using electron-rich dibromoalkenes 1d and 1e
bearing
a
methyl group and tert-butyl group with 4-
methoxyphenylboronic acid (2b) also proceeded and gave the
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10.1002/ejoc.201700535
European Journal of Organic Chemistry
FULL PAPER
was
also
tolerated
and
gave
2-((p-
yields, respectively (Entries 2-4). Furthermore, cinnamyloxy
compound 4e and prenyloxy compound 4f were also tolerated in
this reaction and afforded the corresponding products 5e and 5f
in good yields (Entries 5 and 6). The reaction of allyloxy
compound 4a with phenylboronic acid (2e) also proceeded (Entry
7). From these results, this reaction has potential to become a
more efficient protocol for o-allyloxyethynylbenzene derivatives
than Cu-catalyzed Suzuki-Miyaura-type reaction of o-
allyloxy(bromoethynyl)benzenes.
methoxyphenyl)ethynyl)thiophene (3ai) (Entry 16). In the case of
the reaction of 1-(2,2-dibromovinyl)-4-methoxybenzene (1a) with
2-hydroxyphenylboronic acid (2j), the internal alkyne product of
2-((4-methoxyphenyl)ethynyl)phenol
was
10%
not
yield
detected.
of 2-(4-
Alternatively,
we
obtained
methoxyphenyl)benzofuran,19 which was formed by annulation of
internal alkyne product in the presence of a large amount of base
(Entry
17).
The
reaction
of
1-(2,2-dibromovinyl)-2-
(methoxymethoxy)benzene (1i) with 2-bromophenylboronic acid
(2k) gave bromoalkyne derivative 1i’ in 63% yield without coupling
reaction (Entry 18).
Table 3. Preparation of o-allyloxyethynylbenzene derivatives
Ar
(HO)2B
2
L1c (5 mol%)
CuI (5 mol%)
Table 2. Scope and limitation
+
Ar
Br
Br
R3
K3PO4 (4.0 eq.)
EtOH (0.25 M)
60 °C, Ar, 18 h
L1c (5 mol%)
CuI (5 mol%)
Ar
R1
Br
Br
R2
R3
O
Ar
R1
+
(HO)2B
R
K3PO4 (4.0 eq.)
EtOH (0.25 M)
60 °C, Ar, 18 h
5
R2
R
O
4
1
2
3
Entry
Ar (2)
R1
H
R2
H
R3 (4)
Yield of (5) (%)[a]
75 (5a)
Entry
R (1)
Ar (2)
Yield of 3 (%)[a]
1
2
3
4
5
6
7
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
Ph (2e)
H (4a)
H (4b)
H (4c)
H (4d)
H (4e)
Me (4f)
H (4a)
1
4-OMe (1a)
3-OMe (1b)
2-OMe (1c)
4-Me (1d)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
4-MeOC6H4 (2b)
4-MeOC6H4 (2b)
4-MeOC6H4 (2b)
4-MeOC6H4 (2b)
4-MeC6H4 (2a)
4-MeC6H4 (2a)
3-MeC6H4 (2c)
2-MeC6H4 (2d)
Ph (2e)
92 (3aa)
77 (3ba)
66 (3ca)
54 (3db)
64 (3eb)
59 (3fb)
65 (3gb)
81 (3ha)
73 (3ia)
88 (3ac)
64 (3ad)
60 (3ae)
65 (3af)
54 (3ag)
44 (3ah)
27 (3ai)
N.D.[c]
4-Cl
4-Me
4-OMe
H
H
83 (5b)
2
H
74 (5c)
3
H
78 (5d)
4
Ph
Me
H
80 (5e)
4-tBu (1e)
5
H
86 (5f)
6
4-Cl (1f)
H
75 (5g)
4-CF3 (1g)
7
[a] Isolated yield.
8
3,4-(CH)2- (1h)
2-OMOM (1i)
4-OMe (1a)
4-OMe (1a)
4-OMe (1a)
4-OMe (1a)
4-OMe (1a)
4-OMe (1a)
4-OMe (1a)
4-OMe (1a)
2-OMOM (1i)
On the other hand, we previously reported that Pd-catalyzed
Heck-type reaction of allylic aryl ether with aryl halides afforded
cinnamyl aryl ether product.14b For the preparation of various o-
cinnamyloxyethynylbenzene derivatives, we tried a Heck-type
reaction of o-allyloxy(phenylethynyl)benzene (5g) with p-
iodetoluene using a L1c-Pd(OAc)2 catalyst system (Scheme 1).
9
10
11
12
13
14
15
16
17[b]
18
4-ClC6H4 (2f)
4-BrC6H4 (2g)
4-CF3C6H4 (2h)
2-Thiophen (2i)
2-HOC6H4 (2j)
2-BrC6H4 (2k)
L1c (10 mol%)
I
Pd(OAc)2 (10 mol%)
+
K3PO4 (3.0 eq.)
N.D.[d]
DMF (0.25 M)
70 °C, Ar, 18 h
O
O
5g
(3.0 eq.)
6
[a] Isolated yield. [b] This reaction was carried out at 80 °C. [c] 2-(4-
Methoxyphenyl)benzofuran was obtained in 10% yield instead of internal
alkyne derivative. [d] 1-(Bromoethynyl)-2-(methoxymethoxy)benzene 1i’
was obtained in 63% instead of internal alkyne derivative.
23%
Scheme 1. Heck-type reaction of o-allyloxyethynylbenzene (5g)
As a result, we succeeded in installing an aryl group at the end
of an allyloxy moiety by Pd-catalyzed Heck-type reaction and in
obtaining o-cinnamyloxyethynylbenzene derivative 6.
Finally, two conceivable mechanisms of a Suzuki-Miyaura-type
coupling reaction were illustrated in Scheme 2. As the first
reaction mechanism (Cycle 1), the catalytic cycle that was
initiated after dehydrobromination from dibromoalkene 1 by base
afforded bromoalkyne 1’. Next, oxidative addition of Cu(I) catalyst
to bromoalkyne 1’ occurred and formed alkynyl-bromo-Cu(III)
Next, we aimed to prepare o-allyloxyethynylbenzene derivatives
which are known as useful precursors for the various oxygen-
containing heterocyclic compounds.20 Recently, we reported
effective preparation of o-allyloxyethynylbenzene derivatives via
Cu-catalyzed
Suzuki-Miyaura-type
reaction
of
o-
allyloxy(bromoethynyl)benzenes.18 In this stage, we tried to apply
1-allyloxy-2-(2,2-dibromovinyl)benzene derivatives 4 as a starting
material to this reaction for the preparation of o-
allyloxyethynylbenzene derivatives (5) (Table 3). We found that
the reaction of 1-allyloxy-(2,2-dibromovinyl)benzene (4a) with p-
tolylboronic acid (2a) also proceeded under the optimized
reaction conditions (Table 1, Entry 3) and provided 1-allyloxy-2-
(p-tolylethynyl)benzene (5a) in 75% yield (Entry 1). Next, we
tested dibromovinylbenzenes 4b, 4c and 4d bearing various
substituents and obtained 5b, 5c and 5d in 83%, 74% and 78%
complex A. On the other hand, arylboronic acid
2 was
transformed into complex 2’ by base. Next, complex 2’ underwent
transmetalation with Cu(III) complex A to generate alkynyl-aryl-
Cu(III) complex B followed by reductive elimination of Cu(III)
complex B; this afforded the corresponding internal alkyne
derivative and regenerated Cu(I), and the catalytic cycle was
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10.1002/ejoc.201700535
European Journal of Organic Chemistry
FULL PAPER
Ar2
Ar2
Br
-HBr
Ar1
Base
Ar1
3
3'
Cu(III)Ar2
Br
Cu(III)Ar2
Ar1
Ar1
B
D
Br-B(OH)2
Base
Br-B(OH)2
Base
Cu(I)
Cycle 2
Cycle 1
Ar2B(OH)2
Base
Ar2B(OH)2
Base
2’
2’
Cu(III)Br
Br
Cu(III)Br
Base
Base
Ar1
Ar1
Ar2B(OH)2
Ar2B(OH)2
A
C
2
2
Br
Br
Br
Base
-HBr
Ar1
Ar1
1'
1
Scheme 2. Plausible reaction mechanism
General procedure for Cu-catalyzed Suzuki-Miyaura-type
coupling reaction of dibromoalkenes with arylboronic acids
(Tables 2 and 3)
completed. This catalytic cycle was supported by the result of the
reaction affording bromoalkyne intermediate 1i’ (Table 2, Entry
18). As a second conceivable reaction mechanism (Cycle 2), the
catalytic cycle was initiated by oxidative addition of Cu(I) to
dibromoalkene 1 directly to afford alkenyl-bromo-Cu(III) complex
C, followed by transmetalation with complex 2’ forming alkenyl-
aryl-Cu(III) D. Next, reductive elimination of Cu(III) complex D
A mixture of (2,2-dibromovinyl)bromoalkene derivatives 1 or 4
(0.25 mmol), arylboronic acids 2 (0.50 mmol), K3PO4 (1.0 mmol),
CuI (12.5 μmol, 5 mol %) and ligand L1c (12.5 μmol, 5 mol %) in
EtOH (1.0 mL) at 60 °C under an Ar atmosphere was stirred. After
18 h, 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, hexane/ethyl
acetate (v/v = 250-40/1) or hexane/diethylether (v/v = 40/1)) to
afford the corresponding internal alkyne products 3 or 5.
produced
internal
alkene
intermediate
3’.
Finally,
dehydrobromination of intermediate occurred by base to afford
the corresponding internal alkyne 3. This catalytic cycle was also
supported by the result of the reaction using 2-
hydroxyphenylboronic acid (2j) (Table 2, Entry 17). In this reaction,
we observed ion peak at m/z = 304, which was derived from
internal alkene intermediate 3ik’ of 2-(1-bromo-2-(4-
methoxyphenyl)vinyl)phenol, on GC-MS analysis. Therefore, it is
conceivable that two catalytic cycles competed with each other in
this reaction.
1-Methoxy-4-(p-tolylethynyl)benzene (3aa)18 (Table 1, Entry 3).
Compound 3aa was obtained from 1-(2,2-dibromovinyl)-4-
methoxybenzene (1a) (72.5 mg) and p-tolylboronic acid (2a) (68.0
mg) according to the general procedure in 92% yield (50.8 mg,
0.229 mmol) as a white solid: m.p. 125-126 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.46 (dt, J = 8.9, 2.8 Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H),
7.14 (d, J = 7.9 Hz, 2H), 6.87 (dt, J = 8.9, 2.8 Hz, 2H), 3.82 (s,
3H), 2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.4,
138.0, 132.9, 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).
Conclusions
In summary, we found that hydrazone-Cu-catalyzed Suzuki-
Miyaura-type reaction of (2,2-dibromovinyl)benzene derivatives 1
with arylboronic acids 2 proceeded smoothly at 60 °C using 5
mol% of Cu-catalyst and afforded the corresponding internal
alkyne products 3 in good yields. Furthermore, we demonstrated
that this reaction has potential to become an efficient protocol for
the preparation of o-allyloxyethynylbenzene derivatives 5, which
are known as useful precursors for various heterocyclic
compounds.
1-Methoxy-3-(p-tolylethynyl)benzene (3ba)18 (Table 2, Entry 2).
Compound 3ba was obtained from 1-(2,2-dibromovinyl)-3-
methoxybenzene (1b) (72.7 mg) and p-tolylboronic acid (2a) (68.0
mg) according to the general procedure in 77% yield (42.9 mg,
0.193 mmol) as a white solid: m.p. 63-64 °C; 1H NMR (300 MHz,
CDCl3): δ = 7.43 (d, J = 8.1 Hz, 2H), 7.24 (t, J = 7.7 Hz, 1H), 7.14
(t, J = 7.9 Hz, 3H), 7.06-7.05 (m, 1H), 6.90-6.86 (m, 1H), 3.81 (s,
3H), 2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.3,
138.4, 131.5, 129.3, 129.1, 124.4, 124.1, 120.0, 116.2, 114.8,
89.4, 88.6, 55.2, 21.5 ppm; EI-MS m/z (rel intensity) 222 (M+, 100).
Experimental Section
General: Melting points were measured with a melting point
1
instru-ment. H and13C NMR spectra were recorded with a 300
MHz NMR spectrometers. Chemical shifts are given in ppm
downfield from TMS with chloroform as an internal standard.
HRMS(ESI or APCI) data were recorded with an Orbitrap mass
spectro-meter. Unless otherwise noted, all reagents were used
without fur-ther purification.
1-Methoxy-2-(p-tolylethynyl)benzene (3ca)18 (Table 2, Entry 3).
Compound 3ca was obtained from 1-(2,2-dibromovinyl)-2-
methoxybenzene (1c) (72.1 mg) and p-tolylboronic acid (2a) (68.5
mg) according to the general procedure in 66% yield (36.2 mg,
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10.1002/ejoc.201700535
European Journal of Organic Chemistry
FULL PAPER
1
0.163 mmol) as a colorless oil; H NMR (300 MHz, CDCl3): δ =
2.38 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 138.4, 133.0,
132.7, 131.5, 131.2, 129.1, 128.4, 127.9, 127.7 (2C), 126.53,
126.47, 120.7, 120.1, 89.9, 89.1, 21.5 ppm; EI-MS m/z (rel
7.51-7.45 (m, 3H), 7.33-7.27 (m, 1H), 7.15 (d, J = 7.9 Hz, 2H),
6.97-6.89 (m, 2H), 3.92 (s, 3H), 2.36 ppm (s, 3H); 13C NMR (75
MHz, CDCl3): δ = 159.8, 133.5, 131.5, 138.2, 129.5, 129.0, 120.43, intensity) 242 (M+, 100).
120.38, 112.5, 110.6, 93.6, 84.9, 55.8, 21.5 ppm; EI-MS m/z (rel
intensity) 222 (M+, 100).
1-(Methoxymethoxy)-2-(p-tolylethynyl)benzene (3ia) (Table 2,
Entry 9). Compound 3ia was obtained from 1-(2,2-dibromovinyl)-
1-Methoxy-4-(p-tolylethynyl)benzene (3db)18 (Table 2, Entry 4). 2-(methoxymethoxy)benzene (1i) (80.0 mg) and p-tolylboronic
Compound 3db was obtained from 1-(2,2-dibromovinyl)-4-
methylbenzene (1d) (6 .2 mg) and p-methoxyphenylboronic acid
(2b) (75.7 mg) according to the general procedure in 54% yield
(28.9 mg, 0.130 mmol) as a white solid; m.p. 125-126 °C; 1H NMR
(300 MHz, CDCl3): δ = 7.46 (dt, J = 8.8, 2.8 Hz, 2H), 7.41 (d, J =
8.1 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 6.87 (dt, J = 8.8, 2.7 Hz, 2H),
3.83 (s, 3H), 2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ =
159.4, 138.0, 132.9, 131.3, 129.1, 120.4, 115.5, 113.9, 88.6, 88.2,
55.3, 21.5 ppm; EI-MS m/z (rel intensity) 222 (M+, 100).
acid (2a) (68.4 mg) according to the general procedure in 73%
yield (46.2 mg, 0.183 mmol) as a colorless oil; 1H NMR (300 MHz,
CDCl3): δ = 7.50 (dd, J = 7.7, 1.7 Hz, 1H), 7.44 (d, J = 8.1 Hz, 2H),
7.30-7.24 (m, 1H), 7.16-7.12 (m, 3H), 6.99 (td, J = 7.5, 1.1 Hz,
1H), 5.28 (s, 2H), 3.55 (s, 3H), 2.36 ppm (s, 3H); 13C NMR (75
MHz, CDCl3): δ = 157.6, 138.2, 133.4, 131.4, 129.4, 129.0, 121.9,
120.4, 115.4, 114.1, 95.1, 93.4, 85.0, 56.3, 21.5 ppm; EI-MS m/z
(rel intensity) 252 (M+, 33); HRMS (ESI-orbitrap) calcd for
C17H16O2+Na [M+Na]+: 275.1043, found: 275.1033.
1-((4-tert-Butylphenyl)ethynyl)-4-methoxybenzene
(3eb)21
1-Methoxy-4-(m-tolylethynyl)benzene (3ac)18 (Table 2, Entry
10). Compound 3ac was obtained from 1-(2,2-dibromovinyl)-4-
methoxybenzene (1a) (72.0 mg) and m-tolylboronic acid (2c)
(68.0 mg) according to the general procedure in 88% yield (48.5
mg, 0.218 mmol) as a colorless oil; 1H NMR (300 MHz, CDCl3): δ
= 7.46 (dt, J = 8.9, 2.8 Hz, 2H), 7.33 (d, J = 11.4 Hz, 2H), 7.22 (t,
J = 8.1 Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 6.87 (dt, J = 8.9, 2.8 Hz,
2H), 3.82 (s, 3H), 2.35 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,
(Table 2, Entry 5). Compound 3eb was obtained from 1-(tert-
butyl)-4-(2,2-dibromovinyl)benzene (1e) (79.3 mg) and p-
methoxyphenylboronic acid (2b) (75.8 mg) according to the
general procedure in 64% yield (42.1 mg, 0.159 mmol) as a white
solid; m.p. 121-122 °C; 1H NMR (300 MHz, CDCl3): δ = 7.48-7.43
(m, 4H), 7.35 (dt, J = 8.5, 1.9 Hz, 2H), 6.86 (dt, J = 8.8, 2.7 Hz,
2H), 3.81 (s, 3H), 1.32 ppm (s, 9H); 13C NMR (75 MHz, CDCl3): δ
= 159.4, 151.1, 133.0, 131.1, 125.3, 120.5, 115.6, 113.9, 88.6,
88.1, 55.2, 34.7, 31.2 ppm; EI-MS m/z (rel intensity) 264 (M+, 100). 113.9, 89.0, 88.2, 55.3, 21.2 ppm; EI-MS m/z (rel intensity) 222
(M+, 100).
1-((4-Chlorophenyl)ethynyl)-4-methoxybenzene
(Table 2, Entry 6). Compound 3fb was obtained from 1-chloro-4-
(2,2-dibromovinyl)benzene (1f) (73.9 mg) and p-
methoxyphenylboronic acid (2b) (76.5 mg) according to the
general procedure in 59% yield (35.8 mg, 0.148 mmol) as a white
solid; m.p. 121-122 °C; 1H NMR (300 MHz, CDCl3): δ = 7.44 (tt, J
= 8.8, 2.1 Hz, 4H), 7.30 (dt, J = 8.7, 2.0 Hz, 2H), 6.88 (dt, J = 8.9,
2.1 Hz, 2H), 3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ =
159.8, 133.8, 133.1, 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).
(3fb)12a
1-Methoxy-4-(o-tolylethynyl)benzene (3ad)18 (Table 2, Entry
11). Compound 3ad was obtained from 1-(2,2-dibromovinyl)-4-
methoxybenzene (1a) (72.1 mg) and o-tolylboronic acid (2d) (68.4
mg) according to the general procedure in 64% yield (35.1 mg,
0.158 mmol) as a white solid; m.p. 77-78 °C 1H NMR (300 MHz,
CDCl3): δ = 7.47 (d, J = 8.9 Hz, 3H), 7.23-7.16 (m, 3H), 6.88 (d, J
= 8.9 Hz, 2H), 2.51 (s, 3H), 3.83 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, 20.8 ppm; EI-MS m/z (rel intensity)
222 (M+, 100).
1-Methoxy-4-((4-(trifluoromethyl)phenyl)ethynyl)benzene
(3gb)11a (Table 2, Entry 7). Compound 3gb was obtained from 1-
(2,2-dibromovinyl)-4-(trifluoromethyl)benzene (1g) (81.8 mg) and
p-methoxyphenylboronic acid (2b) (76.1 mg) according to the
general procedure in 65% yield (44.5 mg, 0.161 mmol) as a yellow
1-Methoxy-4-(phenylethynyl)benzene (3ae)18 (Table 2, Entry
12). Compound 3ae was obtained from 1-(2,2-dibromovinyl)-4-
methoxybenzene (1a) (72.7 mg) and phenylboronic acid (2e)
(60.7 mg) according to the general procedure in 60% yield (31.1
1
1
solid; m.p. 112-114 °C; H NMR (300 MHz, CDCl3): δ = 7.59 (s,
mg, 0.150 mmol) as a yellow solid; m.p. 56-57 °C H NMR (300
4H), 7.49 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 3.84 ppm
(s, 3H); 13C NMR (75 MHz, CDCl3): δ = 160.0, 133.2, 131.6, 129.5
(q, J = 32.5 Hz), 127.4 (d, J = 1.1 Hz), 125.2 (q, J =3.9 Hz), 124.0
(d, J = 272.1 Hz), 114,6, 114.1, 91.9, 86.8, 55.3 ppm; EI-MS m/z
(rel intensity) 276 (M+, 100).
MHz, CDCl3): δ = 7.53-7.45 (m, 4H), 7.36-7.31 (m, 3H), 6.90-6.86
(m, 2H), 3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.6,
133.0, 131.4, 128.3, 127.9, 123.6, 115.3, 114.0, 89.3, 88.0, 55.3
ppm; EI-MS m/z (rel intensity) 208 (M+, 100).
1-((4-Chlorophenyl)ethynyl)-4-methoxybenzene (3af)18 (Table
2, Entry 13). Compound 3af was obtained from 1-(2,2-
dibromovinyl)-4-methoxybenzene (1a) (72.1 mg) and 4-
chlorophenylboronic acid (2f) (78.6 mg) according to the general
procedure in 65% yield (38.9 mg, 0.161 mmol) as a yellow solid;
2-(p-Tolylethynyl)naphthalene (3ha)18 (Table 2, Entry 8).
Compound
3ha
was
obtained
from
2-(2,2-
dibromovinyl)naphthalene (1h) (77.0 mg) and p-tolylboronic acid
(2a) (68.5 mg) according to the general procedure in 81% yield
(48.8 mg, 0.201 mmol) as a white solid; m.p. 137-139 °C; 1H NMR
(300 MHz, CDCl3): δ = 8.04 (s, 1H), 7.83-7.79 (m, 3H), 7.57 (dd,
J = 8.5, 1.6 Hz, 1H), 7.50-7.46 (m, 4H), 7.17 (d, J = 7.9 Hz, 2H),
1
m.p.121-123 °C; H NMR (300 MHz, CDCl3): δ = 7.48-7.42 (m,
4H), 7.31 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.83 ppm
(s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.7, 133.8, 133.0, 132.6,
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10.1002/ejoc.201700535
European Journal of Organic Chemistry
FULL PAPER
128.6, 122.1, 114.9, 114.0, 90.3, 87.0, 55.3 ppm; EI-MS m/z (rel
intensity) 242 (M+, 100).
1-Allyloxy-2-(p-tolylethynyl)benzene (5a) (Table 3, Entry 1).
Compound
5a
was
obtained
from
1-allyloxy-2-(2,2-
dibromovinyl)benzene (4a) (79.1 mg) and p-tolylboronic acid (2a)
(67.8 mg) according to the general procedure in 75% yield (46.9
mg, 0.189 mmol) as a colorless oil; 1H NMR (300 MHz, CDCl3): δ
= 7.49 (dd, J = 7.5, 1.7 Hz, 1H) 7.44 (d, J = 8.1 Hz, 2H), 7.29-7.23
(m, 1H), 7.15 (d, J = 7.9 Hz, 2H), 6.96-6.87 (m, 2H), 6.16-6.04 (m,
1H), 5.54 (dq, J = 17.3, 1.6 Hz, 1H), 5.30 (dq, J =10.6, 1.6 Hz,
1H), 4.64 (dt, J = 4.8, 1.6 Hz, 2H), 2.36 ppm (s, 3H); 13C NMR (75
MHz, CDCl3): δ = 159.0, 138.1, 133.3, 133.0, 131.4, 129.4, 129.0,
120.7, 120.6, 117.1, 113.3, 112.5, 93.7, 85.1, 69.2, 21.5 ppm; EI-
MS m/z (rel intensity) 248 (M+, 100); HRMS (APCI-orbitrap) calcd
for C18H16O+H [M+H]+: 249.1274, found: 249.1263.
1-((4-Bromophenyl)ethynyl)-4-methoxybenzene
(3ag)12a
(Table 2, Entry 14). Compound 3ag was obtained from 1-(2,2-
dibromovinyl)-4-methoxybenzene (1a) (72.5 mg) and 4-
bromophenylboronic acid (2g) (100.9 mg) according to the
general procedure in 54% yield (38.8 mg, 0.135 mmol) as a white
solid; m.p.150-151 °C; 1H NMR (300 MHz, CDCl3): δ = 7.48-7.45
(m, 4H), 7.36 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.9 Hz, 2H), 3.83
ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.7, 133.0, 132.8,
131.5, 122.5, 122.0, 114.9, 114.0, 90.5, 87.0, 55.3 ppm; EI-MS
m/z (rel intensity) 286 (M+, 100).
1-Allyloxy-4-chloro-2-(p-tolylethynyl)benzene (5b) (Table 3,
Entry 2). Compound 5b was obtained from 1-allyloxy-4-chloro-2-
(2,2-dibromovinyl)benzene (4b) (88.0 mg) and p-tolylboronic acid
(2a) (68.4 mg) according to the general procedure in 83% yield
(59.2 mg, 0.210 mmol) as a yellow solid; m.p. 36-37 °C; 1H NMR
(300 MHz, CDCl3): δ = 7.46-7.42 (m, 3H), 7.23-7.15 (m, 3H), 6.81
(d, J = 8.9 Hz, 1H), 6.14-6.01 (m, 1H), 5.53 (dd, J = 17.2, 1.6 Hz,
1H), 5.32 (dd, J = 10.6, 1.4 Hz, 1H), 4.61 (dt, J = 4.8, 1.5 Hz, 2H),
2.37 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 158.6, 138.6,
132.7, 132.6, 131.5, 129.09, 129.06, 125.4, 120.0, 117.4, 114.9,
113.6, 94.8, 83.8, 69.6, 21.5 ppm; EI-MS m/z (rel intensity) 282
(M+, 100); HRMS (APCI-orbitrap) calcd for C18H15OCl+H [M+H]+:
283.0884, found: 283.0879.
1-Methoxy-4-((4-(trifluoromethyl)phenyl)ethynyl)benzene
(3ah)18 (Table 2, Entry 15). Compound 3ah was obtained from 1-
(2,2-dibromovinyl)-4-(trifluoromethyl)benzene (1a) (72.5 mg) and
4-(trifluoromethyl)phenylboronic acid (2h) (95.2 mg) according to
the general procedure in 44% yield (30.3 mg, 0.110 mmol) as a
white solid; m.p. 86-88 °C; 1H NMR (300 MHz, CDCl3): δ = 7.59
(s, 4H), 7.48 (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 = 32.6 Hz), 127.5 (q, J = 1.1 Hz), 125.2
(q, J = 3.7 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).
2-((4-Methoxyphenyl)ethynyl)thiophene (3ai)10b (Table 2, Entry
16). Compound 3ai was obtained from 1-(2,2-dibromovinyl)-4-
methoxybenzene (1a) (72.7 mg) and 3-thiophenylboronic acid (2i)
(64.4 mg) according to the general procedure in 27% yield (14.5
mg, 0.0678 mmol) as a yellow solid; m.p.53-55 °C; 1H NMR (300
MHz, CDCl3): δ = 7.49-7.44 (m, 3H), 7.30-7.28 (m, 1H), 7.18 (dd,
J = 5.0, 1.1 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 3.82 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): δ = 159.5, 132.9, 129.8, 128.0, 125.2,
122.5, 115.2, 113.9, 88.7, 83.1, 55.3 ppm; EI-MS m/z (rel
intensity) 214 (M+, 100).
1-Allyloxy-4-methyl-2-(p-tolylethynyl)benzene (5c) (Table 3,
Entry 3). Compound 5c was obtained from 1-allyloxy-2-(2,2-
dibromovinyl)-4-methylbenzene (4c) (82.5 mg) and p-tolylboronic
acid (2a) (67.8 mg) according to the general procedure in 74%
yield (48.8 mg, 0.186 mmol) as a colorless oil; 1H NMR (300 MHz,
CDCl3): δ = 7.43 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 1.7 Hz, 1H), 7.14
(d, J = 7.9 Hz, 2H), 7.05 (dd, J = 8.4, 16.0 Hz, 1H), 6.63 (d, J =
8.4 Hz, 1H), 6.15-6.03 (m, 1H), 5.52 (dd, J = 17.2, 1.6 Hz, 1H),
5.29 (dd, J = 10.6, 1.5 Hz, 1H), 4.61-4.59 (m, 2H), 2.35 (s, 3H),
2.27 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 156.9, 138.0,
133.7, 133.2, 131.4, 130.0, 129.9, 129.0, 120.6, 117.0, 113.0,
112.6, 93.4, 85.2, 69.4, 21.5, 20.3 ppm; EI-MS m/z (rel intensity)
262 (M+, 100); HRMS (APCI-orbitrap) calcd for C19H18O+H
[M+H]+: 263.1430, found: 263.1424.
2-(4-Methoxyphenyl)benzofuran19 (Table 2, Entry 17). 2-(4-
Methoxyphenyl)benzofuran
was
obtained
from
1-(2,2-
dibromovinyl)-4-methoxybenzene (1a) (72.2 mg) and 2-
hydroxyphenylboronic acid (2j) (69.4 mg) according to the general
procedure in 10% yield (14.5 mg, 0.0254 mmol) as a white solid;
m.p.150-151 °C; 1H NMR (300 MHz, CDCl3): δ = 7.80 (dt, J = 8.9,
2.8 Hz, 2H), 7.57-7.49 (m, 2H), 7.18-7.18 (m, 2H), 6.98 (dt, J =
8.8, 2.9 Hz, 2H), 6.89 (s, 1H), 3.86 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): δ = 159.9, 156.0, 154.6, 129.4, 126.4, 123.7, 123.3, 122.8,
120.5, 114.2, 111.0, 99.6, 55.4 ppm; EI-MS m/z (rel intensity) 224
(M+, 100).
1-Allyloxy-4-methoxy-2-(p-tolylethynyl)benzene (5d) (Table 3,
Entry 4). Compound 5d was obtained from 1-allyloxy-2-(2,2-
dibromovinyl)-4-methoxybenzene (4d) (86.0 mg) and p-
tolylboronic acid (2a) (68.5 mg) according to the general
procedure in 78% yield (54.2 mg, 0.195 mmol) as a white solid;
m.p. 74-75 °C; 1H NMR (300 MHz, CDCl3): δ = 7.44 (d, J = 8.1 Hz,
2H), 7.15 (d, J = 7.9 Hz, 2H), 7.03 (dd, J = 2.4, 1.0 Hz, 1H), 6.86-
6.79 (m, 2H), 6.15-6.03 (m, 1H), 5.51 (dq, J = 17.3, 1.7 Hz, 1H),
5.28 (dq, J = 10.6, 1.5 Hz, 1H), 4.59 (dt, J = 4.9, 1.6 Hz, 2H), 3.78
(s, 3H), 2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 153.53,
153.46, 138.3, 133.4, 131.5, 129.0, 120.4, 117.6, 117.1, 115.5,
114.7, 114.2, 93.7, 85.0, 70.4, 55.7, 21.5 ppm; EI-MS m/z (rel
intensity) 278 (M+, 100); HRMS (APCI-orbitrap) calcd for
C19H18O2+H [M+H]+: 279.1380, found: 279.1370.
1-(Bromoethynyl)-2-(methoxymethoxy)benzene (1i’)22 (Table
2, Entry 18). Compound 1i’ was obtained from 1-(2,2-
dibromovinyl)-4-(methoxymethoxy)benzene (1i) (79.6 mg) and 2-
bromophenylboronic acid (2k) (100.8 mg) according to the
general procedure in 63% yield (37.8 mg, 0.158 mmol) as a yellow
oil; 1H NMR (300 MHz, CDCl3): δ = 7.42 (dd, J = 7.6, 1.7 Hz, 1H),
7.28 (dt, J = 8.5, 1.7 Hz, 1H), 7.11 (d, J = 7.5 Hz, 1H), 6.95 (td, J
= 7.6, 1.1 Hz, 1H), 5.24 (s, 2H), 3.52 ppm (s, 3H); 13C NMR (75
MHz, CDCl3): δ = 158.4, 133.9, 130.0, 121.7, 115.1, 113.1, 94.9,
76.4, 56.3, 52.9 ppm; EI-MS m/z (rel intensity) 240 (M+, 10).
1-Cinnamyloxy-2-(p-tolylethynyl)benzene (5e) (Table 3, Entry
5). Compound 5e was obtained from 1-cinnamyloxy-2-(2,2-
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10.1002/ejoc.201700535
European Journal of Organic Chemistry
FULL PAPER
dibromovinyl)benzene (4e) (98.4 mg) and p-tolylboronic acid (2a)
128.1, 126.4, 123.6, 123.2, 120.8, 112.6, 113.1, 93.6, 85.8, 69.3,
(68.4 mg) according to the general procedure in 80% yield (64.8
mg, 0.200 mmol) as a white solid; m.p. 76-78 °C; H NMR (300
21.2 ppm; EI-MS m/z (rel intensity) 324 (M+, 4).
1
MHz, CDCl3): δ = 7.51 (dd, J = 7.9, 1.5 Hz, 1H), 7.46 (d, J = 8.1
Hz, 2H), 7.41-7.22 (m, 6H), 7.14 (d, J = 7.9 Hz, 2H), 6.97-6.93 (m,
2H), 6.86 (d, J = 16.0 Hz, 1H), 6.46 (dt, J = 16.0, 5.2 Hz, 1H), 4.81
(dd, J = 5.3 1.5 Hz, 2H), 2.36 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): δ = 159.0, 138.2, 136.6, 133.4, 132.3, 131.5, 129.4, 129.0,
128.5, 127.7, 126.5, 124.4, 120.8, 120.5, 113.4, 112.7, 93.8, 85.1,
69.2, 21.5 ppm; EI-MS m/z (rel intensity) 324 (M+, 18); HRMS
(APCI-orbitrap) calcd for C24H20O+H [M+H]+: 325.1587, found:
325.1574.
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 a Leading Research Promotion Program “Soft Molecular
Activation” of Chiba University for financial support.
1-((3-Methylbut-2-en-1-yl)oxy)-2-(p-tolylethynyl)benzene (5f)
(Table 3, Entry 6). Compound 5f was obtained from 1-(2,2-
dibromovinyl)-2-((3-Methylbut-2-en-1-yl)oxy)benzene (4f) (86.3
mg) and p-tolylboronic acid (2a) (67.7 mg) according to the
general procedure in 86% yield (59.4 mg, 0.215 mmol) as a
Keywords: copper • coupling reaction • alkyne • dibromoalkene
1
colorless oil; H NMR (300 MHz, CDCl3): δ = 7.49-7.42 (m, 3H),
[1]
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7.29-7.23 (m, 1H), 7.14 (d, J = 8.1 Hz, 2H), 6.95-6.88 (m, 2H),
5.56-5.52 (m, 1H), 4.64 (d, J = 6.4 Hz, 2H), 2.36 (s, 3H), 1.79 (s,
3H), 1.75 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 159.3,
138.0, 137.3, 133.4, 131.5, 129.3, 129.0, 120.7, 120.5, 120.0,
113.4, 112.7, 93.5, 85.3, 65.9, 25.8, 21.5, 18.3 ppm; EI-MS m/z
(rel intensity) 276 (M+, 8); HRMS (ESI-orbitrap) calcd for
C20H20O+H [M+H]+: 277.1587, found: 277.1587.
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1-Allyloxy-2-(phenylethynyl)benzene (5g)18 (Table 3, Entry 7).
Compound
5g
was
obtained
from
1-allyloxy-2-(2,2-
dibromovinyl)benzene (4a) (79.1 mg) and phenylboronic acid (2e)
(61.4 mg) according to the general procedure in 75% yield (45.4
mg, 0.194 mmol) as a colorless oil; 1H NMR (300 MHz, CDCl3): δ
= 7.56-7.49 (m, 3H), 7.38-7.28 (m, 4H), 6.97-6.88 (m, 2H), 6.15-
6.04 (m, 1H), 5.55 (dq, J = 17.3, 1.7 Hz, 1H), 5.31 (dq, J = 10.6,
1.6 Hz, 1H), 4.64 ppm (dt, J = 4.8, 1.5 Hz, 2H); 13C NMR (75 MHz,
CDCl3): δ = 159.0, 133.4, 133.0, 131.5, 129.6, 128.2, 128.0, 123.6,
120.7, 117.1, 113.0, 112.4, 93.5, 85.7, 69.2 ppm; EI-MS m/z (rel
intensity) 234 (M+, 62).
Heck-type reaction of o-allyloxyethynylbenzene (Scheme 1)
A mixture of 1-allyloxy-2-(phenylethynyl)benzene 5g (70.7 mg,
0.30 mmol), p-iodetoluene (21.8 mg, 0.10 mmol), K3PO4 (63.6 mg,
0.30 mmol), Pd(OAc)2 (10.0 μmol, 2.97 mg) and ligand L1c (10.0
μmol, 1.92 mg) in DMF (0.4 mL) at 70 °C under an Ar atmosphere
was stirred for 18 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/toluene (v/v
= 10/1) afford (E)-1-
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European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Cross-Coupling
Ar
Ligand (5 mol%)
CuI (5 mol%)
Ar
(HO)2B
+
Kohei Watanabe, Takashi Mino,*
Chikako Hatta, Eri Ishikawa, Yasushi
Yoshida, and Masami Sakamoto
N N
N N
K3PO4 (4.0 eq.)
EtOH (0.25 M)
60 °C, Ar, 18 h
Br
R
R
Ligand
Br
Page No. – Page No.
We found that hydrazone-Cu-catalyzed Suzuki-Miyaura-type reaction of (2,2-
dibromovinyl)benzene derivatives with arylboronic acids proceeded smoothly at
60 °C using 5 mol% of Cu-catalyst and afforded the corresponding internal alkyne
products in good yields.
Hydrazone-Cu-catalyzed Suzuki-
Miyaura-type Reaction of
Dibromoalkene with Arylboronic Acid
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