Palladium-Catalyzed Decarboxylative Homodimerization of Propiolic Acids: Synthesis of 1,3-Enynes

Article abstract of DOI:10.1002/bkcs.12221

The 1,3-enyne product was obtained as a result of a decarboxylative homodimerization reaction when a variety aryl propiolic acids were reacted in the presence of Pd(TFA)2/i-PrPPh2 and K₂CO₃. It was found that aryl propiolic acids bearing an electrondonating substituent provided the desired product; however, aryl propiolic acids an bearing electron-withdrawing substituent did not give the desired product.

Full text of DOI:10.1002/bkcs.12221

Communication
DOI: 10.1002/bkcs.12221
BULLETIN OF THE
E. Seo et al.
KOREAN CHEMICAL SOCIETY
Palladium-Catalyzed Decarboxylative Homodimerization of Propiolic
Acids: Synthesis of 1,3-Enynes
*
*
Eunkyeong Seo, Jonghoon Oh, and Sunwoo Lee
Department of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea.
*E-mail: jnoh@chonnam.ac.kr; sunwoo@chonnam.ac.kr
Received December 19, 2020, Accepted January 3, 2021, Published online January 20, 2021
The 1,3-enyne product was obtained as a result of a decarboxylative homodimerization reaction when a
variety aryl propiolic acids were reacted in the presence of Pd(TFA)2/i-PrPPh2 and K2CO3. It was found
that aryl propiolic acids bearing an electrondonating substituent provided the desired product; however,
aryl propiolic acids an bearing electron-withdrawing substituent did not give the desired product.
Keywords: Homocoupling, Dimerization, Decarboxylation, Propiolic acid, Palladium
Conjugated 1,3-enynes are one of the most important build-
ing blocks in organic synthesis used for preparing biologi-
cally active molecules and conjugated functional materials.1
Given their prominence, a variety of synthetic methods
have been developed toward the synthesis of conjugated
1,3-enynes. For example, the cross-coupling reaction of ter-
minal alkynes with vinyl halides or pseudohalides,2 dehy-
dration of propargyl alcohols,3 and Wittig reaction of
conjugated alkynals4 are well established and widely used.
However, they have some drawbacks, such as a high cata-
lyst loading, harsh reaction conditions, and the requirement
of a multistep process for the preparation of their
corresponding starting materials.
system can be used to provide the desired gem-1,3-enyne
product in a moderate to good yield. One year later, we
also found that using PdI2 as the catalyst showed a good
selectivity and activity toward the formation of gem-
1,3-enynes.11
While studying the Pd-catalyzed decarboxylative addition
reaction of propiolic acids, we found that the decarboxylative
homodimerized product, which is a 1,3-enyne, was formed
Table 1. Optimization of the palladium catalyst and ligand used
in the homodimerization of phenylpropiolic acid.a
To address these issues, the transition metal-catalyzed
dimerization of two terminal alkynes has received consider-
able attention in the organic chemistry community.5 Not
only second-row transition metals6 but also first-row transi-
tion metals7 have been employed in the dimerization of two
terminal alkynes. These dimerization methods are straight-
forward and atom-economic. In addition, numerous studies
have reported employing a terminal alkyne and alkene
toward the formation of 1,3-enynes. However, aryl-
substituted terminal alkynes are mostly prepared using a
multistep reaction between an aryl halide and a protected
terminal alkyne. However, this has resulted in the limited
substrate scope of the reaction.
Compared to aryl-substituted terminal alkynes, aryl
propiolic acid derivatives are readily prepared via a one-
step coupling reaction between an aryl halide and propiolic
acid without the need for column chromatography as a
purification step.8 A variety of decarboxylative coupling
reactions using not only aryl propiolic acid derivatives9 but
also cinnamic acid derivatives10 have been reported by our
group and other researchers.
Entry
Pd
L
Yield (%)b
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(acac)2
PdI2
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
dppe
dppb
PPh3
EtPPh2
CyPPh2
Cy2PPh
i-PrPPh2
Trace
Trace
Trace
Trace
Trace
PdCl2
Pd(MeCN)2Cl2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
30 (E/Z = 10:1)
Trace
Trace
9
12 (E/Z = 2:1)
30 (E/Z = 8:1)
36 (E/Z = 9:1)
39 (E/Z = 10:1)
46 (E/Z = 12:1)
10
11
12
13
a Reaction conditions: 1a (0.3 mmol), Pd (0.03 mmol), ligand
(0.03 mmol), Cs2CO3 (0.3 mmol), DMSO (1.2 mL), 120ꢀC, 12 h.
b Yields and stereoselectivity were determined by 1H NMR.
Recently, we reported the decarboxylative addition of
propiolic acid to a terminal alkyne to synthesize gem-
1,3-enynes. In 2019, we reported that a Ni/Cu dual catalytic
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Table 2. Optimization of the base and solvent used in the
homodimerization of phenylpropiolic acid.a
Entry
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
K2CO3
Na2CO3
K3PO4
DBU
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Diglyme
DMF
62 (E/Z = 20:1)
57 (E/Z = 12:1)
55 (E/Z = 12:1)
42 (E/Z = 9:1)
Trace
Et3N
Pyridine
TMEDA
DBN
K2CO3
K2CO3
K2CO3
Trace
Trace
Trace
9
10
11
32 (E/Z = 5:1)
49 (E/Z = 14:1)
Trace
o-Xylene
a Reaction condition: 1a (0.3 mmol), Pd(TFA)2 (0.03 mmol), i-PrPPh2
(0.03 mmol), base (0.3 mmol), solvent (1.2 mL), 120ꢀC, 12 h.
b Yields and stereoselectivity were determined by 1H NMR.
when the aryl propiolic acid was reacted without any termi-
nal alkyne partner in the presence of a Pd catalyst and weak
base. This result motivated us to develop the selective
decarboxylative homodimerization of propiolic acids using a
Pd catalyst. Herein, we report the (E)-selective synthesis of
1,3-enynes from aryl propiolic acids.
Phenylpropiolic acid was chosen as a model substrate. Ini-
tially, the palladium source was evaluated in the presence of
Cs2CO3 as the base and dimethyl sulfoxide (DMSO) as the
solvent (Table 1).
A variety of palladium(II) complexes were investigated
in the reaction; however, only Pd(TFA)2 afforded the
desired homodimerized enyne product with a 30% yield.
The ratio of (E)- and (Z)-2a was 10:1. A variety of chelat-
ing phosphine ligands, such as dppe and dppb, were then
investigated in the reaction using Pd(TFA)2 as the palla-
dium source. However, no product was formed. Several
monophosphine ligands were studied. PPh3 gave the
desired product in 12% yield with a low stereoselectivity.
The reactions using EtPPh2, CyPPh2, and Cy2PPh provided
the desired product in 30, 36, and 39% yield, respectively.
The reaction using i-PrPPh2 exhibited the highest yield and
the best stereoselectivity.
Scheme 1. Decarboxylative homodimerization of aryl propiolic
acids (reaction condition: 1 (1.0 mmol), Pd(TFA)2 (0.1 mmol),
i-PrPPh2 (0.1 mmol), K2CO3 (1.0 mmol), DMSO (1.2 mL),
120ꢀC, 12 h. Stereoselectivity was determined by 1H NMR).
the product was formed with a 62% yield and exhibited the
highest stereoselectivity. The reactions using Na2CO3 and
K3PO4 did not exhibit any improvement with respect to the
yield and stereoselectivity compared to that using K2CO3
(entries 1–3). When DBU was employed, the yield of prod-
uct was not satisfactory (entry 4). The desired product was
not observed when organic bases were employed in the
reaction (entries 5–8). The reactions carried out in other
solvents such as diglyme, DMF, and o-xylene showed infe-
rior yields compared to that of DMSO (entries 9–11).
Based on these results, the optimized reaction conditions
were: an environment with arylpropiolic acid (1.0 equiv),
Pd(TFA)2 (10 mol %), i-PrPPh2 (10 mol %), K2CO3 (1.0
equiv), DMSO at 120ꢀC for 12 h.
With the optimized reaction condition known, a variety
of substituted aryl propiolic acids were evaluated in the
decarboxylative homodimerization reaction. When ortho-,
Subsequently, we investigated a variety of bases and sol-
vents in the presence of Pd(TFA)2/i-PrPPh2 (Table 2).
When the standard reaction was carried out using K2CO3,
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the desired homodimerized products in moderate to good
yield. In all cases, the (E)-isomer was the major product of
the reaction. However, arylpropiolic acids bearing electron-
withdrawing groups did not give the desired product.
Acknowledgments. This research was supported by the
National Research Foundation of Korea (NRF) grant
funded
by
the
Korea
government
(NRF-
2017R1A2B2002929). The spectral data were obtained
from the Gwangju center of Korea Basic Science Institute.
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In summary, we have developed a decarboxylative
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