A simple catalyst system for the palladium-catalyzed coupling of aryl halides with terminal alkynes

Article abstract of DOI:10.1016/j.tet.2005.07.099

A convenient catalyst system consisting of Pd(OAc)₂, PPh ₃, K₃PO₄ and DMSO was found to be effective for the coupling reaction of aryl halides with terminal alkynes as well as the deacetonative coupling reaction using a 4-aryl-2-methylbut-3-yn-2-ol as a terminal alkyne precursor. An iminophosphine as a ligand worked more effectively for some combination of substrates than triphenylphosphine.

Full text of DOI:10.1016/j.tet.2005.07.099

Tetrahedron 61 (2005) 9878–9885
A simple catalyst system for the palladium-catalyzed coupling of
aryl halides with terminal alkynes
a,
b
*
Takaaki Kitabata, Hidehito Otsuka and Teruhisa Tsuchimoto
a
b
Eiji Shirakawa,
a
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Graduate School of Materials Science, Japan Advanced Institute of Science and Technology, Asahidai, Nomi, Ishikawa 923-1292, Japan
b
Received 28 April 2005; accepted 27 July 2005
2 3 3 4
Abstract—A convenient catalyst system consisting of Pd(OAc) , PPh , K PO and DMSO was found to be effective for the coupling
reaction of aryl halides with terminal alkynes as well as the deacetonative coupling reaction using a 4-aryl-2-methylbut-3-yn-2-ol as a
terminal alkyne precursor. An iminophosphine as a ligand worked more effectively for some combination of substrates than
triphenylphosphine.
q 2005 Elsevier Ltd. All rights reserved.
1
0
1
. Introduction
even at room temperature. Numerous studies on copper-
free protocols have followed it, the protocols being called as
to the copper-free Sonogashira coupling but not as to the
Heck and/or Cassar coupling.
The palladium-catalyzed alkynylation of aryl and alkenyl
halides using terminal alkynes has become one of the most
convenient methods to prepare arylalkynes and conjugated
1
,2
enynes,
products, pharmaceuticals and molecular organic
which are important precursors for natural
4
The copper-free protocols thus far reported should be
classified into two groups on the basis of reagents used. The
first group, which includes the original methods developed
by Heck or Cassar, utilizes a simple system consisting of an
easily available palladium precursor, a conventional
phosphine ligand such as triphenylphosphine, a simple
base and a usual solvent. The second group uses expensive
and/or elaborated compounds, for example, (1) stoichio-
metric amount of activators such as silver(I) oxide and
3
5
materials. The two earliest studies in this field were
6
7
reported independently by the Heck’s Group and Cassar in
975. Heck and co-workers used a Pd(OAc) –PPh complex
as a catalyst and triethylamine or piperidine as a base and a
solvent, which are based on the Mizoroki–Heck reaction,
namely the palladium-catalyzed arylation or alkenylation of
alkenes. On the other hand, a palladium catalyst coordinated
by PPh in combination with sodium methoxide as a base
3
and DMF as a solvent was disclosed in the Cassar’s report.
The both methods generally require high temperature (up to
1
2
3
1
1
ammonium salts, (2) a special medium such as ionic
liquids, (3) expensive, difficult to handle ligands such
1
2
1
as tri(t-butyl)phosphine, or (4) special catalysts such as
3
1
4
palladacycles. Most of the methods in the second group
achieve higher efficiency and/or wider scope but require one
or more compounds that have low accessibility and/or
difficulty in handling. Some protocols seem to spoil the
1
00 8C). Later but in the same year, Sonogashira and
Hagihara reported that addition of a catalytic amount of CuI
greatly accelerates the reaction to enable the alkynylation at
room temperature. Thereafter the Sonogashira–Hagihara
8
coupling, alternatively called simply as to the Sonogashira
coupling, had expelled all other protocols from the field of
the palladium-catalyzed coupling of aryl or alkenyl halides
with terminal alkynes. However, copper-free protocols have
recently emerged as matches for the Sonogashira coupling
reaction. In 1993, Alami and Linstrumelle found that cyclic
9
amines such as pyrrolidine and piperidine as a base and a
solvent enhanced the reaction rate to promote the coupling
(
1)
Keywords: Alkynes; Aryl halides; Coupling reactions; Palladium and
compounds.
*
Corresponding author; e-mail: shirakawa@kuchem.kyoto-u.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.099

E. Shirakawa et al. / Tetrahedron 61 (2005) 9878–9885
9879
a
Table 1. Palladium-catalyzed coupling of 4-bromoacetophenone or 4-bromoanisole with phenylacetylene
b
c
Entry
Aryl bromide
Solvent
Base
2a/1
Conv. (%)
Yield (%)
d
1
1a
DMF
DMF
DMF
NaOMe
NaOMe
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.2
1.2
O99
O99
O99
O99
87
35
43
83
89
63
56
92
96
81
51
59
87
78
2
3
4
5
6
7
8
9
K
K
K
K
3
3
3
3
PO
PO
PO
PO
4
4
4
4
DMSO
1,4-Dioxane
Toluene
DMSO
Piperidine
DMSO
DMSO
Piperidine
DMSO
DMSO
80
Et
—
3
N
O99
O99
O99
79
67
O99
O99
1b
K
Et
—
3
PO
N
4
10
11
12
13
3
1a
1b
K
K
3
PO
PO
4
3
4
a
The reaction was carried out in a solvent (1.6 mL) at 80 8C for 24 h using 4-bromoacetophenone or 4-bromoanisole (0.80 mmol), phenylacetylene (1.2 mmol)
and a base (0.96 mmol) in the presence of Pd(OAc) (8.0 mmol) and PPh (32 mmol).
Determined by the yield of the recovered aryl bromide.
Isolated yield based on the aryl bromide.
2
3
b
c
d
2 3 2 3 2 3
A combination of PdCl (PPh ) (8.0 mmol) and PPh (16 mmol) was used instead of Pd(OAc) –PPh .
merit to omit the copper catalyst. Consequently, the
simplest methods to couple aryl and alkenyl halides with
terminal alkynes thus far available should be the following
three procedures: (1) the Heck’s method with an amine as a
2. Results and discussion
We first examined the effect of bases and solvents in the
coupling of 4-bromoacetophenone (1a) with phenylacetyl-
ene (2a) using a catalyst (1 mol%) consisting of a
1
5
base and a solvent, (2) its descendant using a cyclic amine
as a base and a solvent reported by Alami and Linstru-
palladium precursor and PPh (4 equiv to Pd) at 80 8C for
3
7
4 h (Eq. 1). Under the Cassar’s conditions, which employ
1
0,16
2
PdCl (PPh ) –PPh (1/2) as a catalyst, NaOMe as a base,
melle,
inorganic base.
and (3) the Cassar’s method featuring an
1
7,18
All of these do not require any
2
3 2
3
and DMF as a solvent, the reaction of 1a with 2a (1:1.5)
afforded only 35% yield of 4-acetylphenyl(phenyl)acetylene
commercially unavailable reagents except for the substrates
themselves. The Cassar’s method is hardly explored in
contrast that the amine-based methods seem to have
become mature. Here, we report a convenient system,
based on the Cassar’s original report, for the coupling
reaction of aryl or alkenyl halides with terminal alkynes,
consisting solely of commercially available and easy to
handle materials.
(
2)
a
Table 2. Coupling of aryl halides with phenylacetylene
b
Entry
1
Aryl halide 1
Pd (mol%)
3
Product 3
Yield (%)
94
3
c
2
3
93
3
d
3
4
5
1
1
1
81
80
89
3
e
3
f
3
g
6
3
84
3
3
h
b
c
7
3
3
80
89
8
3
e
a
The reaction was carried out in DMSO (1.6 mL) at 80 8C for 24 h using an aryl halide (0.80 mmol), phenylacetylene (1.2 mmol), K
3 4
PO (0.96 mmol),
Pd(OAc) and PPh (4.0 equiv to Pd).
2
Isolated yield based on the aryl halide.
The reaction was carried out at 60 8C.
3
b
c

9880
E. Shirakawa et al. / Tetrahedron 61 (2005) 9878–9885
(3a) with a complete consumption of 1a (entry 1 of Table 1).
As Pd(OAc) , a more easily available precursor than
participated in the coupling reaction (entries 1–3). In
addition to diarylacetylenes, alkyl(aryl)acetylenes were
obtained from aliphatic alkynes (entries 4–6). In the
2
PdCl (PPh ) , in combination with PPh (4 equiv to Pd)
2
3 2
3
scored a comparable yield (entry 2), we used Pd(OAc)2–
PPh as a catalyst thereafter. The change of the base from
coupling of 1-octyne, use of increased amounts of K
and the alkyne was much more effective than that of an
increased amount of the palladium catalyst. The Pd–PPh
3 4
PO
3
1
NaOMe to K PO raised the yield to 83% (entry 3). Then
9
3
4
3
2
0
we compared DMF with other solvents to find that DMSO
was rather superior to DMF, and much more effective than
,4-dioxane and toluene (entries 4–6). Use of triethylamine
instead of K PO in DMSO, which recalls the Heck’s
catalyst is applicable also to the coupling of 2-methylbut-3-
yn-2-ol, whose coupling products are known to undergo
2
1
1
deacetonation to give terminal alkynes (entry 7).
4-Bromo(trifluoromethyl)benzene also coupled with
-methylbut-3-yn-2-ol, where a lower reaction temperature
was found to be more suitable (entry 8).
3
4
6
2
method, also was found to be effective (entry 7), and
piperidine as a solvent and a base, the system of Alami and
1
0
Linstrumelle, was even more efficient (entry 8). However,
with these organic bases, an electron-rich aryl halide,
4
-bromoanisole (1b), coupled sluggishly with 2a to give
only!60% yield of 3b after 24 h, whereas K PO worked
3
4
well also with 1b (entries 9–11). The coupling of 1a or 1b
with a decreased amount of 2a resulted in a slightly lower
yield (entries 12 and 13).
(
3)
The protocol can be applied to various combinations of
substrates, though some reactions required 3 or 5 mol% of
the catalyst for completion within 24 h. Phenylacetylene
coupled with phenyl bromides having an electron-with-
drawing or -donating group other than acetyl or methoxy at
the para position in high yields (Eq. 2 and entries 1–4 of
Table 2). The reaction is applicable also to heteroaryl
bromides in addition to an aryl iodide and a triflate (entries
As we have described thus far, a palladium complex
coordinated by triphenylphosphine, one of the most
common phosphine ligands, conveniently catalyzes the
coupling of various combinations of aryl halides with
alkynes. However, sometimes the yields are not sufficient.
For such cases, a palladium complex having N-(2-
5–8), where a lower temperature raised the yield in the
reaction of an active electrophile such as 4-iodoanisole.
2
2
diphenylphosphinobenzylidene)-2-phenylethylamine (IP)
as a ligand was found to be more effective. IP can be easily
Next, we examined the scope on terminal alkynes in the
coupling with 4-bromoanisole (1b) (Eq. 3 and Table 3).
Phenylacetylenes substituted by an electron-withdrawing or
prepared by condensation of 2-(diphenylphosphino)benz-
aldehyde with 2-phenylethylamine, both of which are
commercially available. The results using Pd(OAc) and
2
2
3
-
donating group as well as a heteroarylacetylene also
IP in
a
1:2 ratio compared with those with
a
Table 3. Coupling of aryl bromides with terminal alkynes
b
Entry
1
Alkyne 2
Pd (mol%)
3
Product 3
Yield (%)
82
3
i
2
3
3
3
1
3
71
72
58
84
86
3
j
3
4
3
k
3
l
l
c
5
3
6
7
3
m
5
5
76
77
3
n
o
d
8
3
a
The reaction was carried out in DMSO (1.6 mL) at 80 8C for 24 h using an aryl bromide (0.80 mmol), a terminal alkyne (1.2 mmol), K
Pd(OAc) and PPh (4.0 equiv to Pd).
Isolated yield based on the aryl bromide.
PO (1.6 mmol) and 1-octyne (1.6 mmol) were used.
-Bromo(trifluoromethyl)benzene was used instead of 4-bromoanisole. Reaction temperatureZ70 8C.
3 4
PO (0.96 mmol),
2
3
b
c
d
K
4
3
4

E. Shirakawa et al. / Tetrahedron 61 (2005) 9878–9885
9881
effectively proceeded with phenyl bromide in addition to
that having an electron-withdrawing group, whereas the
coupling reaction with 4-bromoanisole resulted in a low
yield, which was recovered in some extent by using an
excess amount of K PO .
3
4
(
4)
(
5)
Scheme 1. Palladium–IP-catalyzed coupling of organic halides with
3
terminal alkynes. The results using PPh (4.0 equiv to Pd) instead of IP are
shown in parenthesis.
triphenylphosphine are summarized in Scheme 1. The yield
in the coupling of an aliphatic alkyne drastically increased
without use of increased amounts of some of the reagents,
though the effect of IP was not so drastic in the reaction of
phenylacetylene. A sterically hindered aryl bromide,
Besides the above two-pot reaction consisting of the
coupling using 2-methylbut-3-yn-2-ol and the deacetonative
coupling, the one-pot version through a coupling-deaceto-
2-methylbut-3-yn-2-ol and an alkenyl bromide also received
the benefit of the iminophosphine ligand.
2
5,26
nation-coupling sequence also was found to be possible.
2
-Methylbut-3-yn-2-ol can be regarded as a masked
Symmetrical diarylacetylenes were obtained by treatment of
an aryl bromide and 2-methylbut-3-yn-2-ol (2:1.1) with a
catalytic amount of Pd(OAc) –PPh (1/4) and K PO at
acetylene, one of whose acetylenic protons is protected
with a hydroxy(dimethyl)methyl group. The protecting
group can be removed as acetone by treatment of a base
2
3
3
4
80 8C for 48 h (Eq. 6). Although the propargyl alcohol
2
1
such as KOH or NaOH. We expected that K PO , the base
3
4
coupled twice with 4-(trifluoromethyl)phenyl bromide
eliminating acetone in a good yield, the reaction of
used in our coupling reaction, also would mediate the
deacetonation, and found that arylpropargyl alcohol 3n
underwent deacetonation by treatment of 0.2 or 1.2 equiv of
4
4
-bromoanisole gave the desired diarylacetylene only in
2% yield, which was accompanied by formation of a
1
K PO in DMSO at 80 8C for 24 h, giving 4-methoxy-
3
4
considerable amount (ca. 20% estimated by H NMR) of
1-(4-methoxylphenyl)-2-phenylethyne. The phenyl group of
phenylacetylene in 80% or 96% yield, respectively (Eq. 4).
However, any examination aiming the K PO -mediated
3
4
the unsymmetrical diarylacetylene must be derived from
triphenylphosphine, where the 4-methoxyphenyl group in
exchange for the phenyl group should be transferred from
the bromine to the phosphorous atom of the phosphine
deacetonation in the presence of a palladium catalyst failed.
Thus, the coupling-deacetonation sequence using
2
phenyl or 4-(trifluoromethyl)phenyl bromide afforded only
-methylbut-3-yn-2-ol in combination with 4-methoxy-
2
7
through the palladium. Unsymmetrical diarylacetylenes
can be prepared in moderate yields with a similar procedure,
where a second aryl bromide as well as two-thirds amount of
K PO were added after 24 h interval (Eq. 7). The order of
2
4
a trace amount of the corresponding terminal alkyne,
probably because most of them were consumed through the
influence of the palladium catalyst. In sharp contrast, in the
presence of an aryl bromide, the deacetonation proceeded
successfully, being accompanied by the coupling reaction to
give diarylacetylenes (Eq. 5). The deacetonative coupling
3
4
adding aryl bromides did not affect so significantly the
yields of 1-(4-methoxyphenyl)-2-[4-(trifluoromethyl)-
phenyl]ethyne (3j).

9882
E. Shirakawa et al. / Tetrahedron 61 (2005) 9878–9885
3
.2. Palladium-catalyzed coupling of aryl halides with
terminal alkynes. A general procedure (Tables 2 and 3,
and Scheme 1)
(6)
A solution of an aryl halide (0.80 mmol), an alkyne
(1.2 mmol), Pd(OAc) , a ligand (PPh : 4.0 equiv to Pd, or
IP: 2.0 equiv to Pd), and K PO (204 mg, 0.96 mmol) in
2 3
3
4
DMSO (1.6 mL) was degassed by four freeze-thaw cycles.
After stirring at 80 8C for 24 h, water (30 mL) was added
and the resulting mixture was extracted with diethyl ether
(20 mL!3). The combined organic layer was washed with
brine (30 mL), and dried over anhydrous magnesium
sulfate. Evaporation of the solvent followed by purification
with PTLC, column chromatography, or gel permeation
ð7Þ chromatography gave the corresponding arylalkyne.
3.2.1. 1-(4-Methoxyphenyl)-2-(3-thienyl)ethyne (3k). A
pale yellow powder; mp 63–65 8C; H NMR (500 MHz,
1
CDCl ) d 3.82 (s, 3H), 6.84–6.90 (m, 2H), 7.18 (dd, JZ5.0,
3
1
.1 Hz, 1H), 7.28 (dd, JZ5.0, 3.1 Hz, 1H), 7.42–7.47 (m,
H), 7.48 (dd, JZ3.1, 1.1 Hz, 1H); C NMR (125 MHz,
13
2
CDCl ) d 55.3, 83.1, 88.8, 114.0, 115.3, 122.6, 125.2, 128.0,
3
In conclusion, we have disclosed a simple catalyst system,
consisting merely of commercially available, relatively
inexpensive materials, for the palladium-catalyzed coupling
reaction of aryl halides with terminal alkynes. The protocol is
not only as simple as the Casser’s original method but also
shows much wider scope than that, where electron-rich and
1
4
29.9, 133.0, 160.0. Anal. Calcd for C H OS: C, 72.87; H,
13 10
.70. Found: C, 73.14; H, 4.87.
Other coupling products are the compounds already
reported in literature. Their spectroscopic data are as
follows.
-
poorarylelectrophileshavinga bromide, iodideortriflateasa
13b
.2.2. 1-(4-Acetylphenyl)-2-phenylethyne (3a). A white
leaving group coupled with various aryl and aliphatic terminal
alkynes. Another feature of this protocol is the simple catalyst
system applicable also to the deacetonative coupling reaction
of a-dimethyl-g-arylpropargyl alcohols with aryl halides.
Symmetrical and unsymmetrical diarylacetylenes can be
obtained by simple one-pot procedures from aryl bromides
and 2-methylbut-3-yn-2-ol without adding other reagents. We
also described efficiency of IP, prepared from commercially
available reagents in one step, in the present coupling reaction.
3
powder; H NMR (300 MHz, CDCl ) d 2.62 (s, 3H), 7.35–
7
7
1
3
.41 (m, 3H), 7.52–7.58 (m, 2H), 7.59–7.65 (m, 2H), 7.92–
.98 (m, 2H).
2
9
3
white powder; H NMR (500 MHz, CDCl ) d 3.83 (s,
.2.3. 1-(4-Methoxyphenyl)-2-phenylethyne (3b).
A
1
3
3
4
H), 6.85–6.91 (m, 2H), 7.28–7.37 (m, 3H), 7.44–7.53 (m,
H).
3
.2.4. 1-Phenyl-2-[4-(trifluoromethyl)phenyl]ethyne
3
0
1
(3c). A white powder; H NMR (300 MHz, CDCl ) d
3
7
.35–7.41 (m, 3H,), 7.52–7.58 (m, 2H), 7.60–7.64 (m, 4H).
3. Experimental
1
1c
3
.2.5. Ethyl 4-(phenylethynyl)benzoate (3d).
A pale
) d 1.41 (t, JZ
.2 Hz, 3H), 4.39 (q, JZ7.2 Hz, 2H), 7.34–7.40 (m, 3H),
7.52–7.62 (m, 4H), 8.00–8.06 (d, JZ8.4, 2 H).
1
3
.1. General
yellow powder; H NMR (300 MHz, CDCl
3
7
All manipulations of oxygen- and moisture-sensitive
materials were conducted with a standard Schlenk technique
under a nitrogen atmosphere. Nuclear magnetic resonance
3
3.2.6. Diphenylethyne (3e). A white powder; H NMR
1
1
1
spectra were taken on a Varian Gemini 2000 ( H, 300 MHz)
or a JEOL JNM LA-500 ( H, 500 MHz; C, 125 MHz)
(500 MHz, CDCl
3
) d 7.31–7.37 (m, 6H), 7.52–7.56 (m, 4H).
1
13
1
13
31
3.2.7. 1-(4-Methylphenyl)-2-phenylethyne (3f). A pale
spectrometer using tetramethylsilane ( H and C) as an
internal standard. Preparative recycling gel permeation
chromatography was performed with JAI LC-908 equipped
with JAIGEL-1H and -2H using chloroform as an eluent.
Unless otherwise noted, reagents were commercially
available and used without further purification. Anhydrous
DMF, DMA, and DMSO were purchased from Aldrich
Chemical Co. and Kanto Chemicals and used as received.
Toluene and 1,4-dioxane were distilled from sodium/
1
yellow powder; H NMR (300 MHz, CDCl ) d 2.37 (s, 3H),
3
7.13–7.19 (m, 2H), 7.30–7.39 (m, 3H), 7.40–7.46 (m, 2H),
7.50–7.56 (m, 2H).
3
2
3.2.8. 1-Phenyl-2-(2-pyridyl)ethyne (3g). A colorless oil;
1
H NMR (300 MHz, CDCl ) d 7.22–7.28 (m, 1H), 7.34–
3
7.40 (m, 3H), 7.51–7.56 (m, 1H), 7.58–7.64 (m, 2H), 7.65–
7.73 (m, 1H), 8.61–8.65 (m, 1H).
2
8
benzophenone ketyl. 3-Ethynylthiophene and N-(2-di-
phenylphosphinobenzylidene)-2-phenylethylamine (IP)
were prepared according to the literature methods.
2
2a
33
3.2.9. 1-Phenyl-2-(3-thienyl)ethyne (3h). A pale yellow
1
powder; H NMR (300 MHz, CDCl ) d 7.20 (dd, JZ4.8,
3

E. Shirakawa et al. / Tetrahedron 61 (2005) 9878–9885
9883
1.2 Hz, 1H), 7.30 (dd, JZ4.8, 2.7 Hz, 1H), 7.32–7.39 (m,
3H), 7.49–7.55 (m, 3H).
resulting mixture was extracted with diethyl ether (20 mL!
3). The combined organic layer was washed with brine
(
30 mL), and dried over anhydrous magnesium sulfate.
2
.2.10. Bis(4-methoxyphenyl)ethyne (3i). A yellow
6
3
powder; H NMR (300 MHz, CDCl ) d 3.83 (s, 6H),
6
Evaporation of the solvent followed by purification with
PTLC (hexane/EtOAcZ3:1 for 3b, 2:1 for 3i, 4:1 for 3j)
gave 3b, 3i or 3j.
1
3
.84–6.90 (m, 4H), 7.42–7.48 (m, 4H).
3.2.11. 1-(4-Methoxyphenyl)-2-[4-(trifluoromethyl)-
phenyl]ethyne (3j).
3.5. One-pot synthesis of symmetrical diarylacetylenes
from an aryl bromide and 2-methylbut-3-yn-2-ol (Eq. 6)
3
1
1
A white powder; H NMR
(
300 MHz, CDCl ) d 3.84 (s, 3H), 6.87–6.93 (m, 2H),
3
7
.46–7.52 (m, 2H), 7.57–7.62 (m, 4H).
A solution of an aryl bromide (0.80 mmol), 2-methylbut-3-
yn-2-ol (37 mg, 0.44 mmol), Pd(OAc) (4.5 mg, 20 mmol),
2
3
4
.2.12. 1-(4-Methoxyphenyl)-1-octyne (3l). A pale
3
PPh (21 mg, 80 mmol), and K PO (309 mg, 1.46 mmol) in
3
3
4
1
brown oil; H NMR (300 MHz, CDCl ) d 0.90 (t, JZ
DMSO (0.80 mL) was degassed by four freeze-thaw cycles.
After stirring at 80 8C for 48 h, water (30 mL) was added
and the resulting mixture was extracted with diethyl ether
(20 mL!3). The combined organic layer was washed with
brine (30 mL), and dried over anhydrous magnesium
sulfate. Evaporation of the solvent followed by purification
with column chromatography (hexane for 3r, hexane/
EtOAcZ10:1 for 3i) gave 3r or 3i.
3
7
1
6
.0 Hz, 3H), 1.25–1.39 (m, 4H), 1.40–1.51 (m, 2H), 1.53–
.66 (m, 2H), 2.38 (t, JZ7.2 Hz, 2H), 3.79 (s, 3H), 6.79–
.82 (m, 2H), 7.28–7.35 (m, 2H).
3
.2.13. 1-(4-Methoxyphenyl)-3,3-dimethyl-1-butyne
3m). A pale yellow powder; H NMR (300 MHz,
3
5
1
(
CDCl ) d 1.30 (s, 9H), 3.79 (s, 3H), 6.77–6.83 (m, 2H),
3
7
.29–7.35 (m, 2H).
1
3f
3
white powder; H NMR (500 MHz, CDCl ) d 7.62–7.67
.5.1. Bis[4-(trifluoromethyl)phenyl]ethyne (3r).
A
1
3.2.14. 4-(4-Methoxyphenyl)-2-methylbut-3-yn-2-ol
3n). A pale yellow powder; H NMR (500 MHz,
3
3
4
1
(
CDCl ) d 1.61 (s, 6H), 1.99 (s, 1H), 3.81 (s, 3H), 6.81–
(m, 8H).
3
6
.86 (m, 2H), 7.32–7.37 (m, 2H).
3
.6. One-pot synthesis of an unsymmetrical diaryl-
acetylene from two different aryl bromides and
-methylbut-3-yn-2-ol
3
2
1
.2.15. 4-[4-(Trifluoromethyl)phenyl]-2-methylbut-3-yn-
2
3
-ol (3o). A brown powder; H NMR (500 MHz, CDCl ) d
6
1
3
.63 (s, 6H), 2.03 (s, 1H), 7.49–7.59 (m, 4H).
A solution of an aryl bromide (0.40 mmol), 2-methylbut-3-
yn-2-ol (50 mg, 0.60 mmol), Pd(OAc) (4.5 mg, 20 mmol),
PPh (21 mg, 80 mmol), and K PO (102 mg, 0.48 mmol) in
3
DMSO (0.80 mL) was degassed by four freeze-thaw cycles.
After stirring at 80 8C for 24 h, another aryl bromide
2
3
.2.16. 1-Phenyl-2-(2-tolyl)ethyne (3p). A brown oil; H
1
1
3
NMR (300 MHz, CDCl ) d 2.52 (s, 3H), 7.13–7.21 (m, 1H),
7
3
4
3
.22–7.25 (m, 2H), 7.30–7.40 (m, 3H), 7.47–7.58 (m, 3H).
(
0.48 mmol) and K PO (123 mg, 0.58 mmol) were added.
3 4
3
7
3
brown oil; H NMR (300 MHz, CDCl ) d 1.79 (s, 3H), 1.89
(
.2.17. 3,4-Dimethyl-1-phenylpent-3-en-1-yne (3q).
A
After the reaction mixture was stirred at 80 8C for 24 h,
water (30 mL) was added and the resulting mixture was
extracted with diethyl ether (20 mL!3). The combined
organic layer was washed with brine (30 mL), and dried
over anhydrous magnesium sulfate. Evaporation of the
solvent followed by purification with column chromato-
graphy (hexane/EtOAcZ5:1) gave 3j.
1
3
s, 3H), 2.02 (s, 3H), 7.22–7.34 (m, 3H), 7.39–7.45 (m, 2H).
3
3
.3. Deacetonation of 4-(4-methoxyphenyl)-2-methylbut-
-yn-2-ol (Eq. 4)
A solution of 4-(4-methoxyphenyl)-2-methylbut-3-yn-2-ol
(
3n, 76.6 mg, 0.403 mmol) and K PO (102 or 16.3 mg,
3 4
0
.48 or 0.077 mmol) in DMSO (0.80 mL) was degassed by
Acknowledgements
four freeze-thaw cycles. After stirring at 80 8C for 24 h,
water (30 mL) was added and the resulting mixture was
extracted with diethyl ether (20 mL!3). The combined
organic layer was washed with brine (30 mL), and dried
over anhydrous magnesium sulfate. Evaporation of the
solvent followed by purification with PTLC (hexane/
EtOAcZ4:1) gave 4-methoxyphenylethyne.
We thank Professor Tamio Hayashi (Kyoto University) for
helpful discussions. This work was supported in part by
Daicel Chemical Industries, Ltd.
3.4. Deacetonative coupling of 4-(4-methoxyphenyl)-2-
methylbut-3-yn-2-ol with terminal alkynes (Eq. 5)
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4
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9884
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2
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E. Shirakawa et al. / Tetrahedron 61 (2005) 9878–9885
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