Access to α,β-unsaturated carboxylic acids through water-soluble palladium catalyzed hydroxycarbonylation of alkynes using water as the solvent

Article abstract of DOI:10.1039/d1cy00699a

A sulfoxantphos modified palladium-catalyzed synthesis of α,β-unsaturated carboxylic acids from alkynes with CO and H₂O was described. The atom-economic hydroxycarbonylation of various symmetrical and unsymmetrical alkynes can be achieved with chemo-, stereo-, and regioselectivity, affording the corresponding carboxylic acids in good to excellent yields. Using water as the reaction solvent, the water-soluble palladium catalyst was easily separated from the product and could be reused for 5 cycles.

Full text of DOI:10.1039/d1cy00699a

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Access to α,β-unsaturated carboxylic acids
through water-soluble palladium catalyzed
hydroxycarbonylation of alkynes using water as
the solvent†
Cite this: Catal. Sci. Technol., 2021,
11, 4708
Received 19th April 2021,
Accepted 9th June 2021
Jinhe Lv,‡a Lingbo Zong,‡a Jinrong Zhang,a Jiaxin Song,a Jinyu Zhao,a Kai Zhang,a
DOI: 10.1039/d1cy00699a
Ziqin Zhou,a Mingjie Gao,b Congxia Xie,
a Xiaofei Jia
a and Xinyi Renc
*
*
rsc.li/catalysis
A sulfoxantphos modified palladium-catalyzed synthesis of α,β-
unsaturated carboxylic acids from alkynes with CO and H2O was
described. The atom-economic hydroxycarbonylation of various
symmetrical and unsymmetrical alkynes can be achieved with
An alternative green route is the direct synthesis of α,β-
unsaturated carboxylic acids by hydroxycarbonylation of alkynes
with carbon monoxide and H2O. Since Walter Reppe reported
the Ni(CO)4-catalyzed the carbonylation of acetylene, CO and
H2O to form acrylic acid in 1939,6 a lot of palladium catalysts
have been developed for the synthesis of valuable carboxylic
acids.7 Compared with the well-studied palladium catalyzed
hydroxycarbonylation of alkenes,8 the investigation about
hydroxycarbonylation of alkynes with CO and H2O has attracted
relatively less attention in the past few decades.9 The acids
chemo-,
stereo-,
and
regioselectivity,
affording
the
corresponding carboxylic acids in good to excellent yields. Using
water as the reaction solvent, the water-soluble palladium
catalyst was easily separated from the product and could be
reused for 5 cycles.
α,β-Unsaturated carboxylic acids and their derivatives have
wide industrial applications as versatile intermediates for
synthesis of adhesives, and coatings, and polymers.1 The
oxidation reaction is an important method for the synthesis
of α,β-unsaturated carboxylic acids, but the methods are
often plagued by the prefunctionalization, limited functional
group tolerance, low selectivity and dangers of oxidants
(Scheme 1a).2 The hydrocarboxylation of alkynes with
abundant and inexpensive CO2 has been developed for
(Brønsted/Lewis)
are
often
used
to
promote
hydroxycarbonylation in these systems (Scheme 1d). The system
of Pd(OAc)2/2-PyPPh2/CF3SO3H, first invented by Drent and
coworkers,10a was introduced by Wang for hydroxycarbonylation
of acetylene in acetone.10b In 2019, Liu's group developed a
Lewis
acidic
phosphonium
of terminal
for
Pd-catalyzed
alkynes with
hydroxycarbonylation
1-methylpyrrolidin-2-one (NMP) or [Bmim]NTf2 as the solvent.11
Although a variety of catalysts have been successfully
developed for synthesis of α,β-unsaturated carboxylic acids
accessing α,β-unsaturated carboxylic acids. However,
a
stoichiometric amount of an organometallic reagent3 (ZnEt2,
AlEt3, HSi(OEt)3 and EtMgBr) or metal4 (Mn and Zn) is
required as reducing agents for the regeneration of
catalytically active species (path Scheme 1b). Another route
for the hydrocarboxylation of alkynes is the use of a nontoxic
and renewable formic acid along with a catalytic amount of
acid anhydride as an additive (Scheme 1c).5
a Shandong Key Laboratory of Biochemical Analysis, College of Chemistry and
Molecular Engineering, Qingdao University of Science and Technology, Qingdao
266042, P. R. China. E-mail: xiecongxia@126.com, jiaxiaofei139@163.com
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032,
P. R. China
c Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of
Chemistry and Molecular Engineering, East China Normal University, Shanghai
200241, P. R. China
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1cy00699a
‡ Jinhe Lv and Lingbo Zong contributed equally.
Scheme 1 Synthesis of α,β-unsaturated carboxylic acids.
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from alkynes, the catalyst recycling, required additives and
organic reaction solvent still affect the green conversion of
alkynes. Using water as a green reaction solvent offers many
advantages, such as being abundant, inexpensive, nontoxic
A Pd–H intermediate was widely
accepted as the catalytic active species in Pd-catalyzed
hydroxycarbonylation.7b The sulfoxantphos ligand containing
The reaction didn't proceed at all in the absence of L2 (entry 1).
A considerable enhancement of the yield towards the 2a was
observed by employing a 1 : 1 molar ratio of Pd(OAc)2/L2 (entry
2). Further increasing the ligand/metal ratio to 2 and 3 resulted
in a 99% yield, respectively (entries 3 and 4). As expected, the
pressure of CO also played an important role in the
hydroxycarbonylation. Surprisingly, 90% of the desired product
was isolated when the reaction was performed under a pressure
of 1 bar (entry 5). It should be noted that a relatively high
pressure of CO (10 bar) was necessary for the
hydroxycarbonylation of alkynes as reported in the
literature.10b,11 In this catalytic system, increasing the CO
pressure to 10 bar led to a decreased yield (86%, entry 7). In
addition, either decreasing the reaction temperature from 100 to
90 °C or increasing the temperature to 110 °C led to a decline in
yield of 2a (entries 8 and 9). The amount of H2O was also found
to be crucial for hydroxycarbonylation of 1,2-diphenylethyne.
Increasing the amount of H2O from 1 to 2 and 3 mL significantly
reduced the yield of the reaction to 89 and 42% (entries 10 and
11), respectively. Meanwhile, palladium black was observed in
the reaction solution. We reasoned that the increase of water led
to a decrease in the concentration of the ligand coordinated with
Pd, which resulted in catalyst deactivation. When xantphos (L1)
and L3 were used as ligands, 92% and 93% yields of 2a were
obtained, respectively (entries 12 and 14). Although higher yields
(96% and 97%) were observed in the presence of p-TsOH (entries
and nonflammable.12
a diphosphine fragment and
a –SO3H group not only
promotes the formation and stability of active Pd–H
species,13 but also makes Pd in the aqueous phase owing to
the water solubility of the ligand to reduce the loss of Pd,
thereby facilitating the separation of the product, catalyst
recovery and recycling. Herein, we reported a sulfoxantphos
modified palladium catalyst for hydroxycarbonylation of
alkynes to afford α,β-unsaturated carboxylic acids with high
selectivities and good recyclability. Importantly, the water
was used as both a reactant and solvent, and no additives
were required in the catalytic system (Scheme 1e).
The palladium-catalyzed hydroxycarbonylation of alkynes was
first studied with water-soluble sulfoxantphos L2 as the ligand
and 1,2-diphenylethyne as the model substrate. The catalyst was
prepared in situ by mixing Pd(OAc)2 with ligand L2 in water. The
effects of various parameters such as the Pd/L2 ratio, pressure of
CO, reaction temperature and amount of H2O were investigated,
and the results are summarized in Table 1. The molar ratio of
Pd(OAc)2/L2 exhibited a significant effect on the catalytic activity.
Table 1 Optimization of the reaction conditions for palladium-catalyzed hydroxycarbonylation of 1,2-diphenylethynea
Entry
Catalyst
L
CO (bar)
T (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
—
—
3
3
3
3
1
5
10
3
3
3
3
3
3
3
3
3
3
100
100
100
100
100
100
100
90
110
100
100
100
100
100
100
100
100
0
95
99
99
90
99
86
87
91
89
42
92
96
93
97
15
87
1 : 1
1 : 2
1 : 3
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L1
L1
L3
L3
L4
L2
9
10c
11d
12
13e
14
15e
16f
17g
a
b
c
d
e
Reaction conditions: 1a (0.5 mmol), Pd(OAc)2 (2 mol%), H2O (1 mL) for 24 h. Isolated yield. H2O (2 mL). H2O (3 mL). p-CH3C6H4SO3H
(p-TsOH, 0.04 mmol). f p-TsOH (0.06 mmol). g Pd(PPh3)4 (2 mol%).
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Table 2 Palladium-catalyzed hydroxycarbonylation of alkynes with CO and H2Oa
Entry
1
Substrate
Product
Yieldb (%)
99
1a
2a
2b
2c
2
3
4
51
86
98
1b
1c
1d
2d
5
86
1e
2e
6
7
83
91
2f
1f
1g
1h
2g
2h
8
78
71
92
9
1i
2i
10
1j
2j
11
12
13
14
95
1k
2k
2l
93
(α/β = 6.7 : 1)
1l
72
(α/β = 1.5 : 1)
1m
1n
2m
2n
61
(α/β = 1.7 : 1)
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Table 2 (continued)
Entry
15
Substrate
Product
Yieldb (%)
83
(α/β = 2 : 1)
1o
2o
16
17
18
73
(α/β = 4 : 1)
1p
2p
64
(α/β = 1.1 : 7)
1q
2q
50
1r
2r
a
Reaction conditions: alkyne (0.5 mmol), Pd(OAc)2 (2 mol%), L2 (4 mol%), H2O (1 mL), 100 °C, 24 h. The ratio of regioisomers was
determined on the basis of 1H NMR analysis. No E isomer was detected. b Isolated yield.
13 and 15), it was still lower than that using L2 (entry 3). As
anticipated, the efficiency of hydroxycarbonylation strongly
depends on ligand species. The application of monophosphine
ligand TPPTS (L4) provided the product 2a in a lower yield (entry
16). Further studies revealed that the Pd(0) catalyst was effective
for the hydroxycarbonylation of 1,2-diphenylethyne (87% yield,
entry 17).
Under optimal reaction conditions, we set out to explore
the scope of Pd-catalyzed hydroxycarbonylation of alkynes
(Table 2). For various symmetrical aromatic alkynes, the
corresponding α,β-unsaturated diarylcarboxylic acids were
obtained in good to excellent yields (51–99%) with cis
configuration. Both electron-rich and electron-poor
diarylacetylenes performed well in this catalytic system.
Methyl, methoxy, and even formyl substituents on the
aromatic ring were well-tolerated. 1,2-Di-o-tolylethyne 1b was
used affording the product in 51% yield, probably due to
steric hindrance. The aromatic heterocyclic 1,2-di(thiophen-3-
yl)ethyne 1g was tolerant, giving the desired product 2g in
excellent yield of 91%. In addition to diaryl alkynes, different
dialkyl substituted alkynes worked well, producing the
corresponding hydroxycarbonylation products 2h and 2i in
good yields (78% and 71%).
afforded the corresponding α-arylated alkenyl carboxylic
acids 2j–2l as the major product in excellent yields (92–95%).
No β-regioisomer was detected in the reaction with 1j and 1k
as substrates. The challenging asymmetric diarylalkyne
substrates were investigated, which was rarely studied in
previous reports.3c Diarylalkynes 1m–1o bearing electron-rich
meta-methyl, ortho-methyl and para-methoxy regioselectively
were used affording 2m–2o in good yields, in which the
α-carboxylated product was the major isomer. It was found
that the ratio of the two regioisomers (α/β) increased along
with the increase of the electron donating abilities of the
substituents. When 1-(phenylethynyl)naphthalene 1p was
used, although the naphthyl moieties showed a higher steric
hindrance than the phenyl group, the –COOH group was
mainly added to the carbon atom linked to the naphthalene
ring. Alkyne 1q containing an electron-withdrawing CHO
group was used to produce 2q in 64% yield (α/β = 1/1.7).
From the experiments above, it was observed that the
regioselectivity mainly depends on the electronic nature of
the aromatic ring, and CO insertion took place
predominantly onto the electron-rich substituted side of the
triple bond. The regioselectivity is similar to Helaja's work on
electronic regioselectivity of diarylalkynes in the cobalt-
mediated Pauson–Khand reaction.14 However, when the
terminal alkyne ethynylbenzene 1r was investigated,
carboxylic acid 2r was obtained in 50% yield along with the
The present catalytic reaction was further successfully
extended to a variety of unsymmetrical disubstituted alkynes.
In the case of the aryl alkyl alkynes, the hydrocarboxylation
Scheme 2 Large-scale transformation.
Scheme 3 Isotope-labeling studies of hydrocarboxylation.
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alkyne into the Pd–H bond should afford alkenyl–Pd
intermediate B. In this step, the stability of intermediate B
probably
determines
the
regioselectivity
of
the
hydrocarboxylation product. The acylpalladium intermediate
C could be formed by CO insertion into the Pd–C bond. The
σ-bond metathesis of intermediate D could deliver the
product along with regeneration of the Pd(II)–H species.
The reusability of the Pd/L2 catalyst was investigated in
hydroxycarbonylation of alkynes. After completion of the
reaction, the mixture was extracted with ethyl acetate to
remove the hydroxycarbonylation product 2a, while the
catalyst in the aqueous phase was used to test the next run.
As shown in Fig. 1, the catalyst can be reused for 5 cycles,
highlighting its good reusability. Meanwhile, the Pd and P
leaching in the combined organic phase were determined to
be 0.01 and 12 ppm by ICP-OES analysis, respectively.
Scheme 4 Plausible reaction mechanism.
Conclusions
In conclusion, we have developed a reusable and water-
soluble palladium-catalyzed hydroxycarbonylation of alkynes
with CO and H2O. Under mild pressure of CO, various kinds
of alkynes were successfully transformed into α,β-unsaturated
carboxylic acids with good yields and regioselectivity in water
reaction medium. Further experiments, especially for
improving catalyst stability and exploring the wide substrates,
as well as mechanistic investigations, are currently ongoing
in our laboratories.
Fig.
1 Recycling tests of Pd/L2 in hydrocarboxylation of
1,2-diphenylethyne with CO and H2O. Reaction conditions: 1a (1.0
mmol), Pd(OAc)2 (2 mol%), L2 (7 mol%), CO (3 bar), H2O (2 mL), 100 °C
for 24 h.
Author contributions
XJ designed the research and wrote the initial draft; CX
directed the research and revised the manuscript; JL and LZ
conducted the research and investigation process; JZ, JS and
JZ analyzed the study data; KZ, ZZ and MG verified the
reproducibility of experiments. All authors have given
approval to the final version of the manuscript.
recovered substrate. The less electron-richness properties of
1r probably leads to low reactivity, while the linear selectivity
of hydroxycarbonylation may be due to the minimal steric
hindrance of the –H group. In addition, a 97% yield was also
obtained in a gram-scale reaction, which indicated the
excellent scalability of the reaction (Scheme 2).
Conflicts of interest
A
deuterium labelling experiment was performed to
There are no conflicts to declare.
understand the mechanism. When D2O (>99% D) was used
instead of H2O under the optimal reaction conditions, the
reaction afforded a deuterated product 2a-D in 22% isolated
yield with excellent deuterium incorporation (Scheme 3). We
reasoned that the hydrolysis rate of the acylpalladium species
may be reduced in the presence of D2O.15 Additionally, the
catalytically active hydride complex had been detected in this
reaction system. A singlet line at −14.51 ppm was observed in
the 1H NMR spectra of the mixture of Pd(OAc)2 and L2 in
D2O/H2O under CO, corresponding to the signal of H bonded
to Pd (Fig. S1†).
Acknowledgements
We acknowledge financial support from the National Natural
Science Foundation of China (No. 21703116, 51702180) and the
Open Fund of the Department of Chemistry of Qingdao
University of Science and Technology (QUSTHX201932,
QUSTHX202010).
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