Mechanistic study of palladium-catalyzed decarboxylative coupling of phenylpropiolic acid and aryl iodide

Article abstract of DOI:10.1002/aoc.2921

The mechanism of decarboxylative coupling of phenylpropiolic acid and methyl 4-iodobenzoate was investigated by gas chromatographic analysis and monitoring the decarboxylation reaction by FT-IR spectroscopy. Among many possible pathways, we found that the

Full text of DOI:10.1002/aoc.2921

Full Paper
Received: 7 February 2012
Revised: 1 August 2012
Accepted: 7 August 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2921
Mechanistic study of palladium-catalyzed
decarboxylative coupling of phenylpropiolic
acid and aryl iodide
a
a
a
b
Ayoung Pyo , Yu Hyun Kim , Kyungho Park , Gwui Cheol Kim ,
a
a
Hyun Chul Choi * and Sunwoo Lee *
The mechanism of decarboxylative coupling of phenylpropiolic acid and methyl 4-iodobenzoate was investigated by gas
chromatographic analysis and monitoring the decarboxylation reaction by FT-IR spectroscopy. Among many possible
pathways, we found that the mechanism involves two possible pathways, namely the decarboxylation of phenylpropiolic
acid and that proceeding through the carboxylated palladium complex. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords: mechanism; decarboxylative coupling; palladium; IR spectroscopy; aryl iodide
Herein, we report a mechanistic study of the decarboxylative
coupling of phenylpropiolic acid using infrared spectroscopy and
Introduction
gas chromatography (GC).
Coupling reactions catalyzed by late transition metals such as Pd, Ni
[
1]
and Cu have been used as powerful tools in organic reactions.
These catalysts showed good abilities in the bond formation of
2
2
Results and Discussion
sp carbon and sp (or sp) carbon. These classical methods consist
of the coupling of aryl halides or pseudohalides and organometal
compounds. Since Kumada first reported the use of a carbon–
There are two possible ways for the decarboxylation of
phenylpropiolic acid to produce the desired coupled product,
as shown in Scheme 1. In one mechanism, the decarboxylation
step proceeds first and then the decarboxylated alkyne reacts
with the palladium complex (path A). (See references suggesting
that the decarboxylation step first took place and then formed
[
2]
magnesium complex as a nucleophilic coupling partner, carbon
nucleophiles having metals such as zinc, tin, boron, copper and
[
3]
[4]
[5]
silane have been developed by Negishi, Stille, Suzuki,
[6]
[7]
Sonogashira and Hiyama, respectively. Although their complexes
have been widely used in organic synthesis, they have some
drawbacks in that they produce equal amounts of metal waste
and some of them are not stable. As one way to address these
problems, the use of transition metal-catalyzed decarboxylative
[14]
the metal complex like as path A. ) Another possible way is
where phenylpropiolic acid reacts with the palladium complex
to produce the phenylpropiolate palladium complex before the
decarboxylation step (path B). (See references suggesting that
the metal carboxylate intermediate was formed first and then
decarboxylation took place.
To investigate the pathway of the decarboxylation step, the
decarboxylative coupling reaction of phenylpropiolic acid and
methyl 4-iodobenzoate was chosen as a model reaction (Scheme 2).
The extent of conversion of methyl 4-iodobenzoate and the
yield of the coupled product were obtained from the calculation
with internal standards in GC. However, detection of the amount
of phenylpropiolic acid using GC failed because it reacted with
DBU (1,8-Diazabicycloundec-7-ene) to form its salt. Our attempts
to use NMR spectroscopy for the mechanistic studies did not give
[
8]
coupling reactions has been studied. There are several advan-
tages to the employment of carboxylic acids as coupling partners.
They are environmentally friendly reagents because they release
carbon dioxide as a byproduct instead of producing metal waste
in the coupling reactions. Moreover, they are readily available and
stable during handling and storage.
[15]
)
In the decarboxylative coupling of aryl carboxylic acids, Myers
reported palladium-catalyzed Heck-type decarboxylative couplings
[9]
in 2002 and Gooßen developed practical methods of aryl–aryl
[
10]
coupling reactions in 2007. We first reported the decarboxylative
[11]
coupling of aryl alkynyl carboxylic acid and aryl halides in 2008.
Alkynyl carboxylic acids were employed as a surrogate of terminal
alkynes and showed good activity in the decarboxylative coupling
reactions in the presence of a palladium catalyst. They provided
an efficient way of synthesizing unsymmetric and symmetric
diaryl alkynes, and reacted with carbon monoxide to produce
*
Correspondence to: Sunwoo Lee, Hyun Chul Choi, Department of Chemistry and In-
stitute of Basic Science, Chonnam National University, 300 Yongbong-dong, Buk-gu,
Gwangju, 500-757, Republic of Korea. E-mail: sunwoo@chonnam.ac.kr(S. Lee);
chc12@chonnam.ac.kr(H. C. Choi)
[
12]
aryl alkynyl ketones in good yields.
Since our first report
on the decarboxylative coupling of alkynyl carboxylic acid, a
[
13]
a Department of Chemistry and Institute of Basic Science, Chonnam National
University, Gwangju, 500-757, Republic of Korea
number of related works have been reported. However, there
has been no mechanistic study of the decarboxylative coupling of
alkynyl carboxylic acids in palladium-catalyzed coupling reactions.
b Jeonnam Nano Bio Research Center, Jeollanam-do, 515-806, Republic of Korea
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

A. Pyo et al.
Ar
I
Ar
Ph
Pd
Ar Pd
I
Sample 1
Ar Pd
Ph
Ph
Path A
Sample 2
Sample 3
Sample 4
CO2
O
O
O
Ph
+
DBU
Ph
DBU.H
+
Ph
OH
Path B
2
400
2200
2000
1800
1600
O
-1
Wave number (cm )
Ar Pd
I
Ar Pd
O
Figure 1. IR spectral data of reagents. All samples were dissolved in
diglyme. Sample 1: phenylpropiolic acid (0.3mmol); Sample 2: Sample
Ar
Ar
I
1
+ methyl 4-iodobenzoate (0.3mmol); Sample 3: Sample 2+ Pd(PPh
3 2 2
) Cl
CO2
Pd
(
0.0075 mmol) + dppf (0.015mmol); Sample 4: Sample 3 + DBU (0.3mmol).
Ar Pd
Ph
Ph
ꢁ
1
one at 2225 cm
due to the CꢂC stretch and another at
ꢁ
1
Scheme 1. The proposed mechanism of decarboxylative coupling of
phenylpropiolic acid and aryl iodide by a palladium catalyst.
1711 cm due to the C O stretch of carboxylic acid. When methyl
4-iodobenzoate was added to the solution of phenylpropiolic acid,
ꢁ
1
a new band was observed at 1728 cm due to the C O stretch of
the ester moiety in methyl 4-iodobenzoate. None of the above
bands were changed when palladium and the ligand were added
to the reaction mixture. However, the intensities of the bands from
phenylpropiolic acid were decreased in the presence of DBU,
which might be because phenylpropiolic acid reacted with DBU
to produce its salt in the reaction mixture.
satisfactory results. We therefore turned our attention to the detec-
tion of carbon dioxide, which is released from phenylpropiolic acid
in the decarboxylation step. Infrared spectroscopy is the best in-
strument to detect CO
the best solvent in the decarboxylative coupling reaction, a strong
CO signal is commonly observed in the FT-IR spectrum due to the
high solubility of CO in this solvent. The resulting CO signal in
DMSO is unfavorable for the study of triple-bond formation by
FT-IR. To solve this problem, in this study we used a diglyme
solvent, which did not give rise to a CO2 signal in the FT-IR
spectrum and also gave a good yield of the product. (In the
diglyme solvent, the coupling reaction of phenylpropiolic acid and
methyl 4-iodobenzoate produced the coupled product in 97% yield;
,1 -bis(diphenylphosphino)-ferrocene (dppf) was employed instead
of 1,4-bis(diphenylphosphino)butane (dppb) due to the low
solubility of dppb in diglyme.)
FT-IR was used as a reaction monitor for the decarboxylative
2
in a reaction mixture. Although DMSO is
2
2
2
To understand the decarboxylation step in this coupling
reaction, we monitored the decarboxylation of phenylpropiolic
acid in the absence of palladium and methyl 4-iodobenzoate by
IR spectroscopy. As shown in Fig. 2(a), no change in the signals of
ꢀ
phenylpropiolic acid was found in the absence of DBU at 80 C.
(When we performed TGA measurements on phenylpropiolic acid,
ꢀ
no change in gravity was found up to 140 C.) However, we found
0
ꢁ1
1
that the release of CO (2337 cm ) from phenylpropiolic acid oc-
curred in the presence of DBU at 80 C as shown in Fig. 2(b). These
2
ꢀ
results indicate that thermal decarboxylation does not occur at
ꢀ
[16]
80 C in the absence of a base, and support that path A is possi-
ble in the mechanism of the decarboxylative coupling reaction.
As a model reaction, phenylpropiolic acid (0.3 mmol), methyl
ꢀ
coupling reaction at 80 C. FT-IR spectra were measured at a
ꢁ
1
spectral resolution of 4 cm with a Varian 660-IR spectrometer
equipped with a liquid nitrogen-cooled MCT detector. Temperature-
dependent FT-IR spectra were obtained using a heated
demountable liquid cell accessory (Pike, USA). This accessory
consists of the heated cell, a temperature controller and
windows for IR spectral regions. It is designed for qualitative
and quantitative analysis of liquid sample where it is necessary
to control the temperature of the sample. The temperature
0
4-iodobenzoate (0.3mmol), Pd(PPh ) Cl (0.0075 mmol), 1,1 -bis
3
2
2
(diphenylphosphinoferrocene) (0.015 mmol) and DBU (0.6mmol)
were reacted in diglyme (1.5 ml). The reaction was conducted in
ꢀ
a microreactor at 80 C and monitored by FT-IR and GC. As shown
ꢁ
1
in the IR spectra in Fig. 3(a), a new band appeared at 2337 cm
due to the O C stretch of CO at 1 h, and its intensity increased
2
until the reaction time reached 2 h. When phenylpropiolic acid
ꢀ
ꢀ
range of the accessory is ambient to 200 C. We obtained the
FT-IR spectra data of all of the reagents in diglyme solution, as
shown in Fig. 1. Phenylpropiolic acid showed two sharp peaks:
was reacted with DBU at 80 C for 2 h in diglyme, we found that
[
17]
decarboxylation occurred in 45% yield. (The yield of decarboxyl-
ation was determined from the yield of phenylacetylene after
2
.5 mol% Pd(PPh ) Cl
3
2
2
O
O
O
5.0 mol% dppf
Ph
I
+
Ph
MeO
MeO
HO
DBU (2.0 equiv)
o
Diglyme, 80 C
Scheme 2. Pd-catalyzed decarboxylative coupling of methyl 4-iodobenzoate and phenylpropiolic acid.
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Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2012)

The reaction pathway of the decarboxylative coupling
(
a)
(b)
8
0°C, 0h
8
8
0°C, 0h
0°C, 1.0h
8
0°C, 1.0h
80°C, 2.0h
8
0°C, 2.0h
80°C, 3.0h
80°C, 3.0h
2400
2200
2000
1800
1600
2400
2200
2000
1800
1600
-1
Wave number (cm-1)
Wave number (cm )
ꢁ1
Figure 2. IR spectral data of phenylpropiolic acid in the absence of DBU (a) and in the presence of DBU (b). (We found a peak at 1619 cm when DBU
was dissolved in diglyme, and a peak at 1649 cm when phenylpropiolic acid and DBU were dissolved in diglyme.)
ꢁ1
Figure 3. (a) IR spectra of the decarboxylative coupling of phenylpropiolic acid and methyl 4-iodobenzoate. (b) Yield of methyl 4-(phenylethynyl)benzene
ꢀ
from the coupling of phenylpropiolic acid and methyl-4-iodobenzoate at 80 C.
treatment of the reaction mixture with acid.) These results support
the reaction mechanism involving path B, because the release of
DBU were then added to the reaction mixture and the coupling
reaction was conducted at various temperatures. The results are
shown in Table 1.
CO still occurred after 1 h. In addition, yields of decarboxylative
2
coupled product at 1 h and 2 h were higher than the yield of decar-
boxylation, as shown in Fig. 3(b). (The peak of the triple bond of
the product appeared at 2217 cm ; however, we could not find
its peak owing to its very low intensity.)
As expected, the coupling reaction in experiment 1 did not
produce the desired product at low temperature (entries 1 and 2).
The decarboxylative coupling of phenylpropiolic acid required a
ꢁ
1
ꢀ
high temperature (80 C) (entry 3). We found that phenylacetylene
To investigate the mechanism in detail, we carried out the
following control experiments. (1) The decarboxylative coupling
reaction of phenylpropiolic acid was conducted at various
temperatures. (2) The coupling reaction of phenylacetylene, which
is a fragment of the decarboxylated product of phenylpropiolic
acid, was conducted at various temperatures. (3) The decarbox-
ylation of phenylpropiolic acid was first conducted in the
coupled with aryl iodide at low temperature from experiment 2
(entries 4–6). In the case of experiment 3, the yields of the
ꢀ
ꢀ
product are reasonable at 25 C and 40 C, because the yield of
decarboxylation is 45% and the yields of coupling reaction from
phenylacetylene are 57% and 73%, respectively. The results from
experiment 3 suggest that path A might be a possible pathway
in the decarboxylative coupling reaction. Based on these results,
we propose that the decarboxylative coupling reaction proceeds
ꢀ
presence of DBU at 80 C; methyl 4-iodobenzoate, catalyst, and
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

A. Pyo et al.
a
Table 1. Control experiments of the coupling reactions
b
Entry
Experiment
Condition
Yield (%)
ꢀ
1
2
3
4
5
6
7
8
9
(1)
(1)
(1)
(2)
(2)
(2)
(3)
(3)
(3)
25 C, 12 h
—
Trace
98
ꢀ
40 C, 8 h
ꢀ
80 C, 4 h
ꢀ
25 C, 12 h
57
ꢀ
40 C, 8 h
73
ꢀ
80 C, 4 h
98
ꢀ
25 C, 12 h
24
ꢀ
40 C, 8 h
29
ꢀ
80 C, 4 h
95
a
2 2 6 4 3 2 2
Reaction conditions: PhCCCO H or PhCCH (0.6 mmol), 4-MeO CC H I (0.6 mmol), DBU (1.2 mmol), diglyme (2.0 ml). Catalyst: Pd(PPh ) Cl
(
0.015 mmol), dppf (0.03 mmol).
b
Determined by GC with internal standard.
through both paths A and B. If the reaction proceeds through only
path A, the yield of the coupling product is similar to that of
decarboxylation. We found that the presented mechanism is
consistent with the copper-catalytic system.aoc2921-bib-0006
To clarify this proposed mechanism, we monitored the IR spectra
B – decarboxylative coupling through the carboxylated palladium
complex – is the predominant pathway.
6d
Acknowledgments
of the reaction of Pd(PPh
propiolate at 80 C. Neither reaction showed any CO
However, the reaction of Pd(PPh ) Cl
3 2 2
3
)
2
Cl
2
and phenylpropiolic acid or sodium
peak.
and sodium propiolate
in the presence of 4-iodobenzoate showed a CO peak in IR
spectroscopy. These results suggest that the oxidative adduct
This research was supported by the Basic Science Research Pro-
gram through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology
(2012R1A1B3000871).
ꢀ
2
2
(
(
ArPdI(PPh
When PhPd(I)(PPh )
3
)
2
) is a reactive species for the decarboxylation.
was reacted with phenylpropiolic acid in
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