Palladium-Catalyzed Hydrocarboxylation of Alkynes with Formic Acid

Article abstract of DOI:10.1002/anie.201501054

A palladium-catalyzed hydrocarboxylation of alkynes with formic acid has been developed. The method provides acrylic acid and derivatives in good yields with high regioselectivity without the need to handle toxic CO gas. Nontoxic: Acrylic acids are an important chemical feedstock. The title reaction provides acrylic acid and derivatives in good yields with high regioselectivities without the need to handle toxic CO gas.

Full text of DOI:10.1002/anie.201501054

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201501054
German Edition: DOI: 10.1002/ange.201501054
Synthetic Methods
Palladium-Catalyzed Hydrocarboxylation of Alkynes with Formic
Acid**
Jing Hou, Jian-Hua Xie, and Qi-Lin Zhou*
Abstract:
A palladium-catalyzed hydrocarboxylation of
alkynes with formic acid has been developed. The method
provides acrylic acid and derivatives in good yields with high
regioselectivity without the need to handle toxic CO gas.
Scheme 1. Palladium-catalyzed hydrocarboxylation of alkynes with
formic acid.
Acrylic acid, an important commodity chemical, is produced
on a scale of more than 3 million tons per year and is widely
used as a base material for the production of paints, plastics,
superabsorbent polymers, and rubbers.[1] In industry, acrylic
acid is prepared by partial oxidation of propene,[2] which is
refined from petroleum. However, the growing demand for
plastics and superabsorbent polymers, and the diminishing
supply of petroleum have stimulated intense interest in
sustainable processes for the production of acrylic acid.
Catalytic hydrocarboxylation of acetylene with carbon mon-
oxide (CO), a method developed by Reppe and co-workers, is
an atom-economical approach to acrylic acid.[3] However, this
nonpetroleum-based process has a major drawback in that it
uses high-pressure CO gas, which is toxic. In contrast, formic
acid is a nontoxic, renewable liquid and can be produced by
catalytic hydrogenation of CO2[4] and oxidation of biomass.[5]
Formic acid is an ideal replacement for CO gas and has been
used in organic synthesis.[6] For example, formic acid was used
as an in situ source of CO in the hydrocarboxylation and
hydroformylation of olefins.[7] However, the catalytic hydro-
carboxylation of acetylene with formic acid to form acrylic
acids remains unexplored.[8] In 1993, Alper et al. reported that
alkynes can be hydrocarboxylated to form unsaturated
carboxylic acids with formic acid in the presence of a palla-
dium catalyst under 6–8 atm of CO gas. However, CO gas is
essential for this reaction: virtually no reaction occurs in its
absence.[9]
to 350 under mild reaction conditions. We found that this
catalytic system could also be used for efficient hydrocarbox-
ylation of other terminal alkynes, as well as internal alkynes,
thus providing a,b-unsaturated acids in up to 97% yield.
We initially carried out the hydrocarboxylation of acety-
lene (10 atm) with formic acid at 808C in toluene with
Pd(OAc)2 as a catalyst precursor and acetic anhydride (Ac2O)
as a promoter. Screening of various mono- and bidentate
phosphine ligands showed that the nature of the ligand
markedly affected the reaction (Figure 1; see also the
Herein we report that the hydrocarboxylation of acety-
lene with formic acid can be achieved in the presence of
palladium catalysts and a catalytic amount of benzoic
anhydride (Scheme 1). The conversion of acetylene into
acrylic acid occurred with turnover numbers (TONs) of up
Figure 1. Phosphine ligands tested in the hydrocarboxylation of acety-
lene. Numbers within parentheses are TONs.
Supporting Information). Only a few ligands afforded the
desired acrylic acid product, and the biphosphine ligand
Xantphos, which has a large bite angle, gave the best result
(TON = 24; Table 1, entry 2). No reaction occurred in the
absence of an anhydride (compare entries 1 and 2), which is
necessary for the decomposition of formic acid to CO. In
addition to acetic anhydride, trifluoroacetic anhydride
(TFAA) and benzoic anhydride (Bz2O) could also be used,
and Bz2O gave a slightly higher TON than acetic anhydride
(compare entries 2 and 4). The effect of solvent on the
hydrocarboxylation of acetylene was also evaluated: when the
reaction was carried out in either Et2O, DMF, or THF, the
[*] J. Hou, Prof. J.-H. Xie, Prof. Q.-L. Zhou
State Key Laboratory and Institute of Elemento-organic Chemistry
Collaborative Innovation Center of Chemical Science and
Engineering (Tianjin), Nankai University
Tianjin 300071 (China)
E-mail: qlzhou@nankai.edu.cn
Homepage: http://zhou.nankai.edu.cn
[**] We thank the National Natural Science Foundation of China, the
National Basic Research Program of China (2012CB821600), and
the “111” project (B06005) of the Ministry of Education of China for
financial support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201501054.
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Table 1: Optimization of reaction conditions for hydrocarboxylation of
acetylene.[a]
Entry [Pd]
Xantphos/[Pd] Anhydride Solvent TON[b]
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
2
2
2
2
2
2
2
2
2
2
2
2
5
–
toluene
0
Ac2O
TFAA
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
toluene 24
toluene 14
toluene 27
Et2O
DMF
THF
HCO2H 10
CH3CN
THF
THF
THF
THF
THF
37
43
46
Figure 3. The effect of the initial pressure of acetylene on the hydro-
carboxylation reaction. Reaction conditions: [Pd2(dba)3]·CHCl3
(2.5 mmol), Xantphos (50 mmol), benzoic anhydride (0.1 mmol),
HCO2H (1.5 mmol), in THF (3 mL) at 1008C for 12 h.
9
Pd(OAc)2
7
37
58
85
101
140
10
11
12
13
14
[Pd(acac)2]
[PdCl2(PhCN)2]
[Pd2(dba)3]·CHCl3
[Pd2(dba)3]·CHCl3
[Pd2(dba)3]·CHCl3
A plot of TON versus formic acid concentration clearly
indicated that the optimal concentration was approximately
1 mmolmLÀ1 (Figure 4). Finally, from a plot of TON against
the reaction time, we observed that TON increased with
increasing reaction time, thus reaching a plateau of 350 after
12 h (Figure 5).
10
[a] Reaction conditions: initial pressure P(C2H2)=10 atm (12 mmol),
[Pd] (5 mmol), anhydride (0.1 mmol), HCO2H (1.5 mmol), solvent
(3 mL). [b] Yield was determined by GC analysis using n-hexadecane as
an internal standard. DMF=N,N-dimethylformamide, THF=tetrahy-
drofuran.
Encouraged by the results obtained with acetylene, we
investigated the hydrocarboxylation of other alkynes with
TON was higher than that in toluene (entries 5–7). However,
reactions in pure formic acid and in CH3CN had lower TONs
(entries 8 and 9). Various palladium catalyst precursors were
compared, and [Pd2(dba)3]·CHCl3 was found to be the best,
thus giving a TON of 85 (entries 10–12). Increasing the ratio
of the ligand to palladium from 2 to 5 and 10 markedly
improved the TON of the reaction, to 101 and 140 (entries 13
and 14), respectively.
We also studied the effects of reaction temperature,
acetylene pressure, formic acid concentration, and reaction
time on the TON. A plot of TON versus reaction temperature
showed that 1008C was optimal (Figure 2). The pressure of
acetylene strongly affected the TON, which increased with
increasing acetylene pressure up to 15 atm and then reached
a plateau (Figure 3).
Figure 4. The effect of the concentration of formic acid on the hydro-
carboxylation reaction. Reaction conditions: [Pd2(dba)3]·CHCl3
(2.5 mmol), Xantphos (50 mmol), benzoic anhydride (0.1 mmol), acety-
lene (initial pressure 15 atm, ca. 18 mmol), in THF (3 mL) at 1008C
for 12 h.
Figure 2. The effect of reaction temperature on the hydrocarboxylation
of acetylene. Reaction conditions: [Pd2(dba)3]·CHCl3 (2.5 mmol), Xant-
phos (50 mmol), benzoic anhydride (0.1 mmol), HCO2H (1.5 mmol),
acetylene (initial pressure 10 atm, ca.12 mmol), in THF (3 mL) for
12 h.
Figure 5. The effect of reaction time on the hydrocarboxylation reac-
tion. Reaction conditions: [Pd2(dba)3]·CHCl3 (2.5 mmol), Xantphos
(50 mmol), benzoic anhydride (0.1 mmol), HCO2H (3 mmol), acetylene
(initial pressure 15 atm, ca.18 mmol), in THF (3 mL) at 1008C.
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Table 2: Catalytic hydrocarboxylation of terminal and internal alkynes
with formic acid.[a]
Entry
1
R1
R2
2/3
Yield [%][b]
1
2
3
4
5
6
1b
1c
1d
1e
1 f
1g
1h
1i
C6H5
H
H
H
H
H
H
H
H
C6H5
Me
nPr
Me
93:7
96:4
95:5
98:2
98:2
93:7
100:0
10:90
–
76
84
82
56
84
71
70
62
97
87
64
61
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-MeOC6H4
4-ClC6H4
nBu
tBu
C6H5
C6H5
nPr
7[c]
8[c]
9
Scheme 2. Proposed mechanism.
1j
1k
1l
10[d]
11[c]
12[c]
63:37
–
0:100
acid to produce the mixed anhydride HCO2COR’, which
decomposes to CO in situ.[11] Coordination of CO to the
1m
tBu
À
palladium atom of B and subsequent insertion into the Pd C
bond form the intermediate C. Reductive coupling of C gives
the anhydride D, which decomposes to the acrylic acid
product and CO, and regenerates the palladium catalyst.[12]
In conclusion, we have developed a palladium-catalyzed
hydrocarboxylation reaction of alkynes with formic acid. The
reaction provides a new approach to acrylic acids, an
important chemical feedstock, in high yields with high
regioselectivities. Further studies to determine the mecha-
nism and enhance the catalytic activity are in progress in our
laboratory.
[a] Reaction conditions: alkyne (0.5 mmol), Pd(OAc)2 (0.5 mol%),
Xantphos (1 mol%), HCO2H (0.75 mmol), Ac2O (20 mol%), toluene
(3 mL), 808C, 12 h. [b] Yield of the isolated product. Selectivity
determined by NMR spectroscopy. [c] 5 mol% Pd(OAc)2, 10 mol%
Xantphos. [d] 24 h.
formic acid (Table 2). Reaction of phenylacetylene (1b) with
formic acid proceeded smoothly in toluene at 808C in the
presence of 0.5 mol% Pd(OAc)2, 1 mol% Xantphos, and
20 mol% Ac2O to give the phenylacrylic acids 2b and 3b in
a combined 76% yield (entry 1). The reaction was highly
regioselective, the major product being a-phenylacrylic acid
(2b, 93%), thus arising from the addition of the carboxyl Experimental Section
Hydrocarboxylation of acetylene: In a glove box, a glass vessel was
group to the substituted side of the triple bond. Other
monosubstituted aryl acetylenes also underwent hydrocar-
boxylation, thus mainly producing a-substituted acrylic acids
in good yields (entries 2–6). Compared with aromatic acety-
lenes, aliphatic acetylenes were less reactive and required
higher catalyst loading (5 mol%, entries 7 and 8). The
hydrocarboxylation of 1-hexyne exclusively provided a-n-
butyl acrylic acid (2h; entry 7), whereas sterically hindered
tert-butylacetylene gave b-tert-butylacrylic acid (3i) as the
major product (entry 8). Acetylenes with sterically bulky
substituents, such as 1e which has a 2-methylphenyl group,
and 1i which has a tert-butyl group, afforded relatively low
product yields (entries 4 and 8). In addition to terminal
alkynes, disubstituted alkynes also underwent hydrocarbox-
ylation reactions with formic acid in good to excellent yields
(61–97%; entries 9–12). Again, the aromatic acetylenes were
more reactive and gave higher yields (entries 9 and 10) than
the aliphatic acetylenes, which required higher catalyst
loading (5 mol%; entries 11 and 12). Very high regioselectiv-
ity was obtained in the hydrocarboxylation of an internal
acetylene with a tert-butylgroup (2/3 = 0:100; entry 12).
Although the exact mechanism of the reaction is unclear,
we propose the mechanism illustrated in Scheme 2. Acetylene
is activated by the formation of a palladium complex, which
reacts with formic acid to generate the intermediate B.[9b,10] At
the same time, the anhydride R’CO2COR’ reacts with formic
charged with the catalyst [Pd2(dba)3]·CHCl3 (2.6 mg, 2.5 mmol) and
Xantphos (29 mg, 50 mmol). The vessel was placed into an autoclave
and was purged three times with argon. A solution of HCO2H
(138 mg, 3 mmol) and Bz2O (22.6 mg, 0.1 mmol) in dry THF (3 mL)
was added through the injection port. The autoclave was flushed with
acetylene three times before it was charged with acetylene to 15 atm.
The reaction mixture was stirred at 1008C. After 12 h, the autoclave
was cooled to room temperature, and the pressure was released. n-
Hexadecane was added as an internal standard, and an aliquot of the
mixture was taken and filtered through a short silica column, and the
filtrate was submitted to analysis of the yield of acrylic acid by GC.
Keywords: alkynes · carboxylic acids · palladium · P ligands ·
synthetic methods
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[12] To prove the involvement of CO in the mechanism, we carried
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benzoic anhydride [conditions: P(CO) = 1 atm, P(C2H2) =
15 atm (18 mmol), [Pd2(dba)3]·CHCl3 (5 mmol), Xantphos
(50 mmol), HCO2H (2.5 mmol), THF (3 mL)]. The desired
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Received: February 3, 2015
Published online: && &&, &&&&
4
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Synthetic Methods
J. Hou, J.-H. Xie,
Q.-L. Zhou*
&&&& — &&&&
Palladium-Catalyzed Hydrocarboxylation
of Alkynes with Formic Acid
Nontoxic: Acrylic acids are an important
chemical feedstock. The title reaction
provides acrylic acid and derivatives in
good yields with high regioselectivities
without the need to handle toxic CO gas.
Angew. Chem. Int. Ed. 2015, 54, 1 – 5
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!