Synthesis of aryl alkynyl carboxylic acids and aryl alkynes from propiolic acid and aryl halides by site selective coupling and decarboxylation

Article abstract of DOI:10.1016/j.tetlet.2011.11.117

The coupling of propiolic acid with aryl iodides afforded the aryl alkynyl carboxylic acids and aryl alkynes in generally good yields. Aryl alkynyl carboxylic acids were obtained when the reaction was performed in the presence of Pd(PPh₃)₂Cl₂ (2.5 mol %), dppb (5.0 mol %) and DBU (5 equiv) at 50°C. For the synthesis of the terminal aryl alkynes, the reaction was conducted in the presence of Pd(PPh₃) ₂Cl₂ (2.5 mol %), dppb (5.0 mol %), DBU (5.0 equiv), and Cu(acac)₂ (10 mol %) at 25°C for 5 h, and further reacted at 60°C for 6 h.

Full text of DOI:10.1016/j.tetlet.2011.11.117

Tetrahedron Letters 53 (2012) 733–737
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of aryl alkynyl carboxylic acids and aryl alkynes from propiolic
acid and aryl halides by site selective coupling and decarboxylation
⇑
Kyungho Park, Thiruvengadam Palani, Ayoung Pyo, Sunwoo Lee
Department of Chemistry and Institute of Basic Science, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The coupling of propiolic acid with aryl iodides afforded the aryl alkynyl carboxylic acids and aryl alkynes
in generally good yields. Aryl alkynyl carboxylic acids were obtained when the reaction was performed in
the presence of Pd(PPh3)2Cl2 (2.5 mol %), dppb (5.0 mol %) and DBU (5 equiv) at 50 °C. For the synthesis of
the terminal aryl alkynes, the reaction was conducted in the presence of Pd(PPh3)2Cl2 (2.5 mol %), dppb
(5.0 mol %), DBU (5.0 equiv), and Cu(acac)2 (10 mol %) at 25 °C for 5 h, and further reacted at 60 °C for 6 h.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 28 October 2011
Revised 20 November 2011
Accepted 24 November 2011
Available online 8 December 2011
Keywords:
Alkynyl carboxylic acid
Terminal alkyne
Palladium
Copper
Decarboxylation
In 1966, Nilsson reported the first decarboxylative Ullmann
coupling reaction.1 However, it was not practical because it gave
a low yield, had limited scope and required a large amount of
Cu2O and high temperature. Therefore, it garnered little attention
in organic synthesis for 35 years until Myers reported the palla-
dium-catalyzed decarboxylative Heck-type reaction in 2002.2 Four
years later, Gooben developed a practical and efficient large scale
synthesis of biaryls by using decarboxylative coupling.3 Carboxylic
acids have several advantages as surrogates of organometallic
nucleophiles. They are stable, easy to make and store, and readily
available. In addition, they produce environmentally benign carbon
dioxide as a byproduct in the decarboxylative coupling reaction
instead of producing metal waste. A variety of decarboxylative
coupling reactions of carboxylic acids have been developed over
the past few decades.4 Recently, we first reported the decarboxyla-
tive coupling of alkynyl carboxylic acids and aryl halides using a
palladium catalyst, which provides an efficient method for the syn-
thesis of unsymmetrical and symmetrical diaryl alkynes.5 Aryl al-
kynes are important building blocks in the preparation of
pharmaceutical6 and conjugated functional materials.7 Classically,
the Sonogashira reaction, which is the coupling of aryl halides
and terminal alkynes by palladium and copper catalysts in the
presence of an amine base, has been widely used for the prepara-
tion of aryl alkynes.8 The employment of alkynyl carboxylic acids
as an alternative to terminal alkynes provides a very useful tool
in the handling of alkynes with a low boiling point and might pre-
vent the dimerization of the terminal alkynes which are byprod-
ucts in the Sonogashira reaction.
Since we first reported the decarboxylative coupling of alkynyl
carboxylic acids, a variety of such reactions involving alkynyl car-
boxylic acids have been reported by many research groups.9 How-
ever, the number of commercially available alkynyl carboxylic
acids is limited. There are several methods of preparing alkynyl
carboxylic acids (Scheme 1). For example, the carboxylation of a
terminal alkyne using a copper10 or silver11 catalyst in the presence
of a strong base, and the oxidation of aldehydes12 or alcohols.13
However, these methods have some drawbacks. In the former case,
the requirement of a strong base affords low functional group tol-
erance. In the latter case, the preparation of the corresponding
alcohols and aldehydes needs a multistep process. In the case of
aryl alkynyl carboxylic acids, the most popular way is the carbon-
ylation of terminal aryl alkynes synthesized using the Sonogashira
coupling reaction of aryl halides and alkynes.14 However, this re-
quires an expensive protected alkyne source such as trimethylsilyl-
acetylene and 2-methylbut-3-yn-2-ol for the preparation of the
terminal aryl alkynes. The direct coupling of aryl halides with pro-
piolates or propiolic acid has been reported. However, it is known
to produce low yields in the Sonogashira coupling of terminal
alkynes bearing electron withdrawing groups such as esters,15
although the employment of the diarylidodium salt has been re-
ported to increase the yield of the products.16 Nonetheless, an
additional step is needed to convert the coupled products into car-
boxylic acids.17 In the case of the direct coupling reactions with
propiolic acid, examples of the successful isolation of the product
are rare. To the best of our knowledge, only phenyl iodide led to
the successful isolation of its product, phenyl propiolic acid, in
⇑
Corresponding author. Tel.: +82 62 530 3385.
E-mail address: sunwoo@chonnam.ac.kr (S. Lee).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.117

734
K. Park et al. / Tetrahedron Letters 53 (2012) 733–737
(c)
H
PG
Ar
Ar
H
Ar
Ar
PG
previous works / Multistep
deprotection
cat. Pd
PG : SiR3, CMe2OH
(a)
carboxylation
Ar
X
(d)
CO2H
oxidation
Y
H
CO2R
cat. Pd
CO2R
deprotection
(b)
Ar
Y : CH2OH, CHO
cat. Pd
Ar
CO2H
Ar
I
+
H
CO2H
3
this work / One-Pot
Ar
H
2
1
cat. Pd / Cu
4
Scheme 1. The synthesis of aryl alkynyl carboxylic acids and aryl alkynes.
the palladium-catalyzed coupling reaction with propiolic acid.18
Considering the increasing attention being given to the decarboxy-
lative coupling reaction with aryl alkynyl carboxylic acids, a simple
and general preparation method is required for the expansion of
these coupling reactions. In addition, propiolic acid might be em-
ployed as the alkyne source in the generation of terminal aryl
alkynes from one-pot sequential reactions consisting of the Sono-
gashira and decarboxylation reactions. Herein, we report a practi-
cal synthesis of aryl alkynyl carboxylic acids and aryl acetylenes
from the coupling of propiolic acid and aryl iodides.
For the one-pot synthesis of terminal aryl alkynes from the cou-
pling of propiolic acid and aryl halides, it is necessary for the Sono-
gashira coupling and decarboxylation reactions to proceed in a
stepwise manner. It was found that the Sonogashira coupling of
propiolic acid is faster than the decarboxylative coupling reactions,
and the selective coupling reaction of aryl iodide and propiolic acid
was optimized in our previous report. Therefore, we first investi-
in 24% and 48% yields, respectively (entries 2 and 3). Copper(II)
complexes such as CuCl2, CuBr2, and Cu(OAc)2 gave very low yields
of the product (entries 4, 5 and 6). Interestingly, when Cu(acac)2
was used as a catalyst, the desired product 4a was obtained in an
83% yield (entry 7). No homocoupled product, 1,4-diphenylbuta-
1,3-diyne, was found.19 As Kolarovic reported, we also found that
ˇ
the decaroboxylative reaction occurred in the absence of DBU or
copper,20 however, both cases afforded lower yields than that in
the presence of both.
With the success of the decarboxylation of phenyl propiolic
acid, we next investigated the coupling reaction of phenyl iodide
and propiolic acid in the absence or presence of the copper catalyst.
The results are summarized in Table 2.
In our previous study, phenyl propiolic acid was converted into
methyl phenyl propiolate for the determination of the yield, be-
cause it was unstable in the acidic workup process. We found that
the treatment with cold 1 N HCl(aq) was an important factor to ob-
tain the desired product without any decomposition in the workup
procedure. Based on this technical method, we investigated the
effect of the temperature, time, and amount of base on the synthe-
sis of phenyl propiolic acid. When the reaction time reached 5 h,
the yield of phenyl propiolic acid was maximized at 87% (entry
2). When the reaction time exceeded 5 h, the yield of phenyl pro-
piolic acid slowly decreased, however the yield of phenyl acetylene
did not increase (entry 3). The continuation of the reaction at 80 °C
accelerated the decomposition of phenyl propiolic acid without
increasing the yield of phenyl acetylene (entry 4). By increasing
the amount of DBU to 5 equiv, the yield of phenyl propiolic acid
was increased to 92% (entry 6). Coupling at room temperature
did not show the complete conversion of phenyl iodide and pro-
duced a 63% yield of phenylpropiolic acid (entry 7). Next, the opti-
mized conditions for the decarboxylation of phenyl propiolic acid
were combined with the reaction conditions for the coupling reac-
tion of phenyl iodide and propiolic acid. When the reaction was
carried out in the presence of Cu(acac)2 at 50 °C, the double cou-
pled product, diphenyl acetylene (5a) was formed as the major
product. When the reaction temperature was decreased to 25 °C,
phenyl propiolic acid was formed in an 85% yield with a trace
amount of phenylacetylene (entry 9). In the presence of 10 mol %
Cu(acac)2, the reaction at 25 °C for 5 h and additional reaction at
60 °C for 6 h afforded phenyl acetylene in an 80% yield (entry
10), From these results, we made the following conclusions: (1)
At 25 °C, the selective coupling of phenyl iodide and propiolic acid
occurred to produce phenyl propiolic acid, but it required a long
reaction time. However, the reaction rate was accelerated in the
presence of Cu(acac)2. (2) At 50 °C, only the Sonogashira coupling
ˇ
gated the decarboxylation of phenyl propiolic acid. Kolarovic re-
ported that CuCl acted as a catalyst for the decarboxylation of 2-
alkynoic acids. Considering the one-pot reaction conditions for
the synthesis of phenyl acetylene (4a), a variety of copper sources
were screened in the presence of DBU, because DBU is used as a
base for the preparation of phenyl propiolic acid (3a). The results
are summarized in Table 1.
When CuCl, which showed good results in the decarboxylation
ˇ
by Kolarovic, was employed, phenyl acetylene was formed in a 43%
yield (entry 1). CuBr and CuI produced the decarboxylated product
Table 1
Screening of copper sources for decarboxylationa
10 mol% Cu
O
Ph
H
Ph
DBU (1.0 equiv.)
4a
OH
3a
DMSO, 60 o
C
Entry
Cu
Yieldb (%)
1
2
3
4
5
6
7
CuCl
CuBr
CuI
CuCl2
CuBr2
Cu(OAc)2
Cu(acac)2
43
24
48
3
4
17
83
a
Reaction Conditions: 3a (1.0 mmol), Cu (0.1 mmol), DBU (1.0 mmol), and DMSO
(3.0 mL) at 60 °C for 6 h.
b
Yield was determined by GC after the treatment with aqueous NH4Cl.

K. Park et al. / Tetrahedron Letters 53 (2012) 733–737
735
Table 2
The synthesis of phenyl propiolic acid and phenyl acetylenea
O
Ph
Pd(PPh3)2Cl2 2.5 mol%
OH
3a
4a
O
dppb 5.0 mol%
+
Ph
I
H
Ph
Ph
H
Additive
OH
DBU, DMSO, Temp
1a
2
Ph
5a
Entry
Additive
Temp (°C)
Time (h)
DBU (equiv)
Convb (%)
Yieldc (%)
3a
4a
5a
1
2
3
4
5
6
7
—
—
—
—
—
—
—
50
3
5
2
2
2
2
3
5
5
5
5
5
92
95
95
96
95
96
72
90
95
90
86
87
62
43
85
92
63
—
6
6
5
4
2
2
2
—
—
—
—
—
—
—
40
—
—
12
12?6
5
5
12
3
5
50?80
50
50
25
50
8c
9c
10c
Cu(acac)2
Cu(acac)2
Cu(acac)2
10
Trace
80
25
25?60
85
Trace
5?6
a
b
c
Reaction conditions: 1a (1.0 mmol), 2 (1.0 mmol), Pd(PPh3)2Cl2 (0.025 mmol), dppb (0.05 mmol), DBU and DMSO (3.0 mL).
Conversion of 1a and determined by GC.
0.1 mmol of Cu(acac)2 was used.
Table 3
The synthesis of alkynyl carboxylic acids and terminal alkynes from aryl iodidesa
O
50 oC, 5 h
Method A
Ar
Ar
O
OH
Ar I +
H
3
4
OH
1
2
25 oC, 5 h and 60 oC, 6 h
Method B
cat. Pd /dppb, DBU, DMSO
H
Entry
ArI
Method
Product
Yieldb (%)
O
1
2
1a
1b
1c
A
B
A
B
A
B
3a
4a
3b
4b
3c
4c
92
79
I
OH
H
O
Me
3
4
5
6
72
63
67
66
Me
I
OH
Me
H
O
MeO
I
MeO
OH
MeO
H
O
I
I
7
8
9
1d
A
B
A
3d
4d
3e
56
48
48
OH
Me
Me
H
Me
O
1e
OH
OMe
OMe
(continued on next page)

736
K. Park et al. / Tetrahedron Letters 53 (2012) 733–737
Table 3 (continued)
Entry
ArI
Method
B
Product
Yieldb (%)
42
H
10
4e
OMe
O
F
I
F
11
12
13
14
15
1f
A
B
A
B
A
3f
23
15
55
21
45
OH
4f
F
H
O
Cl
I
Cl
1g
1h
3g
4g
3h
OH
Cl
H
O
O
O
I
Me
Me
O
OH
H
16
17
18
B
A
B
4h
3i
30
62
42
Me
O
O
O
I
1i
1j
MeO
MeO
O
OH
H
4i
MeO
O
I
19
A
B
3j
4j
77
71
OH
H
20
a
Reaction conditions: Method A : ArI (2.0 mmol), propiolic acid (2.0 mmol), Pd(PPh3)2Cl2 (0.05 mmol), dppb (0.1 mmol), and DBU (10.0 mmol) were reacted in DMSO at
50 °C for 5 h; Method B : ArI (2.0 mmol), propiolic acid (2.0 mmol), Pd(PPh3)2Cl2 (0.05 mmol), dppb (0.1 mmol), Cu(acac)2 (0.2 mmol), and DBU (10.0 mmol) were reacted at
25 °C for 5 h, and further reacted at 60 °C for 6 h.
b
Isolated yields and characterized by 1H NMR, 13C NMR see Ref. 21.
occurred in the absence of the copper catalyst, however, both the
Sonogashira and decarboxylative couplings occurred to produce di-
phenyl acetylene in the presence of the copper catalyst. (3) a high
temperature (60 °C) was needed for the decarboxylation reaction
even in the presence of the copper catalyst.
groups were generally lower than those from aryl iodides bearing
electron neutral and donating groups. 1-Iodonaphthalene provided
the corresponding alkynyl carboxylic acid in a 77% yield and the ter-
minal alkyne in a 71% yield (entries 19 and 20).
In conclusion, we developed practical and complementary
cross-coupling methods for the synthesis of aryl alkynyl carboxylic
acids or aryl alkynes from aryl iodides and propiolic acid. In the
case of aryl alkynyl carboxylic acids, the site selective coupling
reaction of propiolic acid and aryl iodides afforded the desired
products, and they were easily isolated with high purity and yields
by simple chromatography. In the case of aryl alkynes, the addition
of 10 mol % Cu(acac)2 to the palladium-catalyzed reaction mixture
and the control of the reaction temperature allowed the desired
products to be obtained in high yields. This method does not re-
quire an isolation step and does not produce toxic by-products.
To the best of our knowledge, there have been no reports on the
isolation of aryl alkynyl carboxylic acids from the coupling reaction
of aryl iodides and propiolic acid, except for one example involving
phenyl iodide. Therefore, this is the first general method for the
preparation of both aryl alkynyl carboxylic acids and aryl alkynes
from the coupling of aryl iodides and propiolic acid.
Using the optimized conditions, we expanded the scope of aryl
iodides for the synthesis of aryl alkynyl carboxylic acids and aryl-
alkynes (Table 3). For the aryl alkynyl carboxylic acids, we employed
the following conditions: aryl iodide (1.0 equiv), propiolic acid
(1.1 equiv), Pd(PPh3)2Cl2 (2.5 mol %), dppb (5.0 mol %), DBU
(5.0 equiv), and DMSO were reacted at 50 °C for 5 h (Method A).
For the synthesis of the terminal aryl alkynes, the reaction was con-
ducted in the presence of Pd(PPh3)2Cl2 (2.5 mol %), dppb (5.0 mol %),
DBU (5.0 equiv) and Cu(acac)2 (10 mol %) at 25 °C for 5 h, and further
reacted at 60 °C for 5 h (Method B). As expected, phenyl iodide affor-
ded phenyl propiolic acid and phenyl acetylene in 92 % and 79 %
yields, respectively (entries 1 and 2). Aryl iodides bearing electron
donating groups such as methyl and methoxy at the para position
produced the desired products in good yields, however, ortho substi-
tuted aryl iodides gave lower yields than the para substituted ones
due to their steric effects (entries 3–10). Fluoro and chloro substi-
tuted aryl iodides afforded the corresponding alkynyl carboxylic
acids in 23% and 55% yields (entries 11 and 13), and their terminal
alkynes were formed in 15% and 21% yields, respectively (entries
12 and 14). Aryl iodides bearing ketone and ester groups provided
the desired products in moderate yields (entries 15–18). We found
that the yields from aryl iodides bearing electron withdrawing
Acknowledgment
This work was supported by National Research Foundation of
Korea Grant funded by the Korean Government (2009-0072357).

K. Park et al. / Tetrahedron Letters 53 (2012) 733–737
737
under vacuum, and the resulting crude product was purified by flash
chromatography on silica gel to give 3a (208.6 mg, 96% yield). The
spectroscopic data of 3a–j are as follows.
References and notes
1. Nilsson, M. Acta Chem. Scand. 1966, 20, 423–426.
2. Myers, A. G.; Tanaka, D.; Mannion, M. R. J. Am. Chem. Soc. 2002, 124, 11250–
11251.
Compound 3a: 1H NMR (300 MHz, DMSO d6) d 7.64–7.46 (m, 5H); 13C NMR
(75 MHz, DMSO-d6) d 154.3, 132.6, 130.9, 129.1, 119.0, 84.4, 81.7;
Compound 3b: 1H NMR (300 MHz, acetone d6) d 7.96 (d, J = 7.8 Hz, 2H), 7.73 (d,
J = 8.3 Hz, 2H), 2.82 (s, 3H); 13C NMR (75 MHz, acetone d6) d 154.6, 142.3,
133.6, 130.4, 117.4, 86.4, 81.4, 21. 6;
3. Gooben, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662–664.
4. (a) Gooben, L. J.; Rodríguez, N.; Gooben, K. Angew. Chem., Int. Ed. 2008, 47, 3100–
3120; (b) Gooben, L. J.; Knauber, T. J. Org. Chem. 2008, 73, 8631–8634; (c) Fu, Z.;
Huang, S.; Su, W.; Hong, M. Org. Lett. 2010, 12, 4992–4995; (d) Shang, R.; Yang,
Z.; Zhang, S.; Liu, L. J. Am. Chem. Soc. 2010, 132, 14391–14393; (e) Rodríguez, N.;
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Fu, Y.; Liu, L. Angew. Chem., Int. Ed. 2011, 50, 4470–4474; (g) Chou, C.-M.;
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2008, 10, 945–948; (b) Moon, J.; Jang, M.; Lee, S. J. Org. Chem. 2009, 74, 1403–
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2010, 75, 6244–6251; (d) Park, K.; Bae, G.; Park, A.; Kim, Y.; Choe, J.; Song, K. H.;
Lee, S. Tetrahedron Lett. 2011, 52, 576–580; (e) Lee, H. J.; Park, K.; Bae, G.; Choe,
J.; Song, K. H.; Lee, S. Tetrahedron Lett. 2011, 52, 5064–5067.
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Compound 3c: 1H NMR (300 MHz, acetone d6) d 7.48 (d, J = 7.8 Hz, 2H), 6.88 (d,
J = 7.8 Hz, 2H), 3.84 (s, 3H); 13C NMR (75 MHz, acetone d6) d 161.8, 154.1,
134.7, 114.5, 111.1, 86.0, 80.3, 55.0;
Compound 3d: 1H NMR (300 MHz, CD3OD) d 8.76 (d, J = 7.8 Hz, 1H), 8.60 (t,
J = 8.3 Hz, J = 7.5 Hz, 1H), 8.52–8.44 (m, 2H), 3.67 (s, 3H); 13C NMR (75 MHz,
CD3OD) d 153.1, 140.9, 132.2, 129.8, 128.9, 125.0, 118.3, 83.7, 83.5, 18.7;
Compound 3e: 1H NMR (300 MHz, acetone d6) d 8.80 (d, J = 7.8 Hz, 1H), 8.74 (d,
J = 7.8 Hz, 1H), 8.35 (d, J = 7.8 Hz, 1H), 8.26 (t, J = 7.8 Hz, 1H), 5.16 (s, 3H); 13C
NMR (75 MHz, acetone d6) d 162.4, 154.8, 135.3, 133.4, 121.4, 112.1, 109.3,
85.5, 83.5, 56.2;
Compound 3f: 1H NMR (300 MHz, acetone d6) d 7.50 (d, J = 8.3 Hz, 1H), 7.35 (t,
J = 7.8 Hz, 1H), 6.97–6.90 (m, 2H), 3.92 (s, 3H), 3.35 (s, 1H); 13C NMR (75 MHz,
acetone d6) d 166.4, 163.1, 154.7, 136.3, 117.2, 84.8, 81.8;
Compound 3g: 1H NMR (300 MHz, acetone d6) d 7.66 (d, J = 7.8 Hz, 2H), 7.53 (d,
J = 7.8 Hz, 2H); 13C NMR (75 MHz, acetone d6) d 154.1, 137.0, 134.9, 129.8,
119.0, 84.1, 82.4;
Compound 3h: 1H NMR (300 MHz, acetone d6) d 8.05 (d, J = 8.3 Hz, 2H), 7.76 (d,
J = 7.8 Hz, 2H), 2.62 (s, 3H); 13C NMR (75 MHz, acetone d6) d 197.4, 154.4,
139.1, 133.7, 129.3, 124.7, 84.3, 83.9, 26.8;
Compound 3i: 1H NMR (300 MHz, acetone d6) d 8.00 (d, J = 8.3 Hz, 2H), 7.77 (d,
J = 7.8 Hz, 2H), 3.87 (s, 3H); 13C NMR (75 MHz, acetone d6) d 165.4, 154.0,
132.9, 131.2, 129.5, 123.6, 83.8, 82.9, 52.5;
Compound 3j: 1H NMR (300 MHz, acetone d6) d 8.15 (d, J = 7.8 Hz, 1H), 7.84 (d,
J = 8.3 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.71 (d, J = 8.3 Hz, 1H), 7.48 (t, J = 7.8 Hz,
1H), 7.40 (t, J = 7.8 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H); 13C NMR (75 MHz, acetone
d6) d 154.8, 134.1, 133.8, 133.7, 132.1, 129.4, 128.5, 127.7, 126.0, 125.9, 117.6,
86.5, 84.3.
Method B; Pd(PPh3)2Cl2 (35.1 mg, 0.05 mmol), 1,4-bis(diphenylphosphino)
butane (42.6 mg, 0.1 mmol), Cu(acac)2 (52.4 mg, 0.2 mmol), aryl halides
(2.0 mmol), and DBU (1.52 g, 10.0 mmol) were combined with DMSO
9. (a) Vouutchkova, A.; Coplin, A.; Leadbeater, N. E.; Crabtree, R. H. Chem.
Commun. 2008, 6312–6314; (b) Kim, H.; Lee, P. H. Adv. Synth. Catal. 2009, 351,
(4.0 mL), in
a small round-bottomed flask. Propiolic acid (1a) (140.0 mg,
ˇ
2827–2832; (c) Kolarovic, A.; Fáberová, Z. J. Org. Chem. 2009, 74, 7199; (d)
2.0 mmol) was dropped at 0–5 °C, and the flask was sealed with a septum. The
resulting mixture was stirred at 25 °C for 5 h. Then the reaction temperature
was increased to 60 °C, and the mixture was stirred for 6 h. The reaction was
poured into Ethyl acetate and washed with water saturated by NH4Cl. The
organic layer dried over MgSO4, and filtered. The solvent was removed under
vacuum, and the resulting crude product was purified by flash chromatography
on silica gel to give 4a (230.9 mg, 79% yield). The spectroscopic data of 4a-j are
as follows.
Ranjit, S.; Duan, Z.; Zhang, P.; Liu, X. Org. Lett. 2010, 12, 4134–4136; (e) Jia, W.;
Jiao, N. Org. Lett. 2010, 12, 2000–2003; (f) Zhang, W.-W.; Zhang, X.-G.; Li, J.-H. J.
Org. Chem. 2010, 75, 5259–5264; (g) Yu, M.; Pan, D.; Jia, W.; Chen, W.; Jiao, N.
Teterahedron Lett. 2010, 51, 1287; (h) Feng, C.; Loh, T.-P. Chem. Commun. 2010,
46, 4779–4781; (i) Zhao, D.; Gao, C.; Su, X.; He, You J.; Xue, Y. Chem. Commun.
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2010, 46, 9049–9051; (j) Kolarovic, A.; Schnürch, M.; Mihovilovic, M. D. J. Org.
Chem. 2011, 76, 2613–2618; (k) Park, J.; Park, E.; Kim, A.; Park, S.-A.; Lee, Y.; Chi,
K.-W.; Jung, Y. H.; Kim, I. S. J. Org. Chem. 2011, 76, 2214–2219.
10. (a) Gooben, L. J.; Rodriguez, N.; Manjolinho, F.; Lange, P. P. Adv. Synth. Catal.
2010, 352, 2913–2917; (b) Dingyi, Y.; Yugen, Z. Green Chem. 2011, 13, 1275–
1279.
11. (a) Saravanakumar, R.; Varghese, B.; Sankararaman, S. Cryst. Eng. Comm. 2009,
11, 337–346; (b) Zhang, X.; Zhang, W.-Z.; Ren, X.; Zhang, L.-L.; Lu, X.-B. Org.
Lett. 2011, 13, 2402–2405.
12. (a) Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51, 567–569; (b) Webb, K. S.;
Ruszkay, S. J. Tetrahedron 1988, 54, 401–410.
13. Zhao, M.; Li, J.; Mano, E.; Song, Z.; Tschaen, D. M.; Grabowski, E. J. J.; Reider, P. J.
J. Org. Chem. 1999, 64, 2564–2566.
Compound 4a: 1H NMR (300 MHz, CDCl3) d 7.49–7.46 (m, 2H), 7.31–7.27 (m,
3H) 3.05 (s, 1H); 13C NMR (75 MHz, CDCl3) 132.1, 128.7, 128.2, 122.1, 83.6,
77.2;
Compound 4b: 1H NMR (300 MHz, CDCl3) d 7.40 (d, J = 7.8 Hz, 2H), 7.13 (d,
J = 7.8 Hz, 2H),3.04 (s, 1H), 2.36 (s, 3H); 13C NMR (75 MHz, CDCl3) d 138.9,
132.0, 129.1, 119.0, 83.8, 76.4, 21.5;
Compound 4c: 1H NMR (300 MHz, CDCl3) d 7.47 (d, J = 7.8 Hz, 2H), 6.87 (d,
J = 7.8 Hz, 2H), 3.84 (s, 3H), 3.05 (s, 1H); 13C NMR (75 MHz, CDCl3) d 159.9,
133.5, 114.1, 113.9, 83.6, 75.7, 55.6;
Compound 4d: 1H NMR (300 MHz, CDCl3) d 7.48 (d, J = 7.9 Hz, 1H), 7.16–7.27
(m, 3H), 3.29 (s, 1H), 2.47 (s, 3H); 13C NMR (75 MHz, CDCl3) d 140.4, 132.2,
129.4, 128.4, 125.5, 122.5, 80.4, 79.9, 18.6;
14. Dingyi, Y.; Yugen, Z. Geen Chem. 2011, 13, 1275–1279.
15. (a) Yoneda, N.; Matsuoka, S.; Miyaura, N.; Fukuhara, T.; Suzuki, A. Bull. Chem.
Soc. Jpn. 1990, 63, 2124–2126; (b) Sakamoto, T.; Shiga, F.; Yasuhara, A.;
Uchiyama, D.; Kondo, Y.; Yamanaka, H. Synthesis 1992, 746–748; (c) Kundu, N.
G.; Dasgupta, S. K. J. Chem. Soc., Perkin Trans. 1 1993, 2657–2663.
16. Radhakrishnan, U.; Stang, P. J. Org. Lett. 2001, 3, 859–860.
17. Lee, A. S.-Y.; Hu, Y.-J.; Chu, S.-F. Tetrahedron 2001, 57, 2121–2126.
18. Suzuka, T.; Okada, Y.; Ooshiro, K.; Uozumi, Y. Tetrahedron 2010, 66, 1064–1069.
19. When K2CO3 was employed as a base instead of DBU, the decarboxylative
homocoupled product, 1,4-diphenylbuta-1,3-diyne, was obtained in 21% yield.
See: Kim, Y.; Park, A.; Park, K.; Lee, S. Tetrahedron Lett. 2011, 52, 1766–1769.
20. We found that no decarboxylation of phenyl propiolic acid took place without
DBU.
Compound 4e: 1H NMR (300 MHz, CDCl3) d 7.50 (d, J = 8.3 Hz, 1H), 7.35 (t,
J = 7.8 Hz, 1H), 6.97–6.90 (m, 2H), 3.92 (s, 3H), 3.35 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 160.5, 134.0, 130.2, 120.3, 111.1, 110.5, 81.0, 80.0, 55.7;
Compound 4f: 1H NMR (300 MHz, CDCl3) d 7.40 (d, J = 7.8 Hz, 2H), 7.13 (d,
J = 7.8 Hz, 2H), 3.04 (s, 1H); 13C NMR (75 MHz, CDCl3) d 163.09, 154.0, 138.9 ,
115.8, 83.7, 81.4;
Compound 4g: 1H NMR (300 MHz, CDCl3) d 7.41 (d, J = 7.8 Hz, 2H), 7.29 (d,
J = 7.8 Hz, 2H), 3.10 (s, 1H); 13C NMR (75 MHz, CDCl3) d 134.9, 133.3, 128.6,
120.6, 82.5, 78.2;
Compound 4h: 1H NMR (300 MHz, CDCl3) d 7.91 (d, J = 7.8 Hz, 2H), 7.57 (d,
J = 7.8 Hz, 2H), 3.26 (s, 1H), 2.61 (s, 3H); 13C NMR (75 MHz, CDCl3) d 197.2,
136.7, 132.2, 128.1, 126.9, 82.7, 80.3, 26.6;
21. Typical experimental procedure: Method A; Pd(PPh3)2Cl2 (35.1 mg, 0.05 mmol),
1,4-bis(diphenylphosphino)butane (42.6 mg, 0.1 mmol), aryl halides
(2.0 mmol), and DBU (1.52 g, 10.0 mmol) were combined with DMSO
Compound 4i: 1H NMR (300 MHz, CDCl3) d 7.97 (d, J = 7.8 Hz, 2H), 7.52 (d,
J = 7.8 Hz, 2H), 3.89 (s, 3H), 3.23 (s, 1H); 13C NMR (75 MHz, CDCl3) d 166.3,
132.0, 130.0, 129.4, 126.6, 82.70, 80.0, 52.2;
(4.0 mL), in
a small round-bottomed flask. Propiolic acid (1a) (140.0 mg,
Compound 4j: 1H NMR (300 MHz, CDCl3) d 8.15 (d, J = 8.3 Hz, 1H), 8.52 (d,
J = 7.8 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.70 (t, J = 7.8 Hz,
1H), 7.62 (t, J = 7.8 Hz, 1H), 7.51(t, J = 7.8 Hz, 1H) 36.59 (s, 1H); 13C NMR
(75 MHz, CDCl3) d 133.5, 133.0, 131.2, 129.2, 128.2, 126.9, 126.4, 126.0, 125.0,
119.7, 82.0, 81.7.
2.0 mmol) was added, and the flask was sealed with a septum. The resulting
mixture was placed in an oil bath at 50 °C for 5 h. The reaction was poured into
Ethyl acetate and extracted with water saturated by NaHCO3. The aqueous
layer was acidified to pH 2.0 by cold 1 N HCl(aq) and extracted with CH2Cl2.
The organic layer dried over MgSO4, and filtered. The solvent was removed