Nickel-catalyzed oxidative decarboxylative coupling reactions between alkynyl carboxylic acids and arylboronic acids

Article abstract of DOI:10.1016/j.tetlet.2016.09.054

Nickel-catalyzed decarboxylative coupling reactions between aryl alkynyl carboxylic acids and arylboronic acids were developed. When aryl alkynyl carboxylic acids were reacted with arylboronic acids in the presence of NiCl₂(10?mol?%), 2,2′-bipy

Full text of DOI:10.1016/j.tetlet.2016.09.054

Tetrahedron Letters 57 (2016) 4824–4828
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Nickel-catalyzed oxidative decarboxylative coupling reactions
between alkynyl carboxylic acids and arylboronic acids
⇑
Ju-Hyeon Lee, Gabriel Charles Edwin Raja, Yujeong Son, Jisun Jang, Jimin Kim, Sunwoo Lee
Department of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 July 2016
Revised 11 September 2016
Accepted 15 September 2016
Available online 15 September 2016
Nickel-catalyzed decarboxylative coupling reactions between aryl alkynyl carboxylic acids and aryl-
boronic acids were developed. When aryl alkynyl carboxylic acids were reacted with arylboronic acids
in the presence of NiCl2 (10 mol %), 2,20-bipyridine (20 mol %), Na2CO3 (1.0 equiv), and Ag2CO3 (1.0 equiv)
in DMF at 80 °C for 18 h, the corresponding diaryl alkynes products were formed in moderate to good
yields.
Ó 2016 Published by Elsevier Ltd.
Keywords:
Nickel
Decarboxylative coupling
Alkynyl carboxylic acid
Arylboronic acid
Oxidative coupling
Introduction
(Scheme 1a).7 In particular, benzyl bromide and chloride were cou-
pled to give benzyl alkynes in good yields.8 Recently, the coupling
One of the most frequently used methods for the formation of
sp2–sp carbon–carbon bonds is the Sonogashira reaction, which
is a coupling reaction between aryl halides and terminal alkynes
in the presence of Pd/Cu catalysts.1 Since its first report in 1975,
this reaction has been modified, improved, and widely employed
in organic synthesis, especially in the medicinal and material
chemistry fields.2 Notably, it represents a very useful tool for the
synthesis of conjugated polymers bearing an aryl alkyne
backbone.3
Alkynyl carboxylic acid derivatives such as propiolic acid have
received much attention as alkyne sources for the synthesis of aryl
alkyne moieties since their decarboxylative coupling reaction was
reported in 2008.4 Alkynyl carboxylic acids offer several advan-
tages. For example, propiolic acid is easier to handle and store as
an alkyne source compared to acetylene, and less expensive than
other acetylene surrogates such as trimethylsilylacetylene and
bis(tributylstannyl)acetylene.5 In addition, aryl alkynyl carboxylic
acid derivatives are easily prepared and no chromatography purifi-
cation step is required.6
of benzoxazole and indolizine with alkynyl carboxylic acids
through decarboxylation was also reported.9 In addition, the for-
mation of bonds involving heteroatoms such as phosphorus, nitro-
gen, and sulfur has also been reported using decarboxylative
coupling reactions of alkynyl carboxylic acids.10
In most cases of decarboxylative coupling reactions, palladium
or copper were generally employed as major catalysts, although
a few example of nickel catalysts were reported.11 More recently,
we described decarboxylative coupling reactions with organosi-
lanes using a nickel catalyst (Scheme 1b).12 This success prompted
us to develop a nickel-catalyzed decarboxylative coupling using
organoboranes. Although the oxidative decarboxylative coupling
with aryl boronic acids was reported in the presence of a palladium
catalyst or a copper catalyst (Scheme 1c),13 a nickel-based catalytic
system has not been developed so far. Herein, we report a decar-
boxylative coupling reaction between alkynyl carboxylic acids
and organoboranes using a nickel catalyst (Scheme 1d). This
method offers several advantages since nickel is abundant and
much cheaper than palladium,14 and a greater variety of organob-
orane derivatives are commercially available compared to
organosilanes.
In a first Letter, we described the coupling reaction of aryl
halides with alkynyl carboxylic acids in the presence of a palla-
dium catalyst. Aryl iodide, bromide, and chloride were successfully
used as coupling partners in the decarboxylative coupling reaction
In order to find the optimal conditions, phenyl propiolic acid
(1a) and phenylboronic acid (2a) were reacted with Na2CO3 and
Ag2CO3 under a variety of reaction conditions. First, different nickel
sources, ligands, and solvents were tested, and the corresponding
results are summarized in Table 1. Reactions conducted in the
⇑
Corresponding author.
E-mail address: sunwoo@chonnam.ac.kr (S. Lee).
http://dx.doi.org/10.1016/j.tetlet.2016.09.054
0040-4039/Ó 2016 Published by Elsevier Ltd.

J.-H. Lee et al. / Tetrahedron Letters 57 (2016) 4824–4828
4825
(a)
presence of Ni(acac)2, Ni(OAc)2, and Ni(OH)2 afforded very poor
yields of product 3a (entries 1–3), while Ni(NO3)2 and NiBr2 pro-
vided the desired product in 22% and 28% yields, respectively
(entries 4 and 5). The use of NiCl2 led to an improvement of the
product yield to 51% and a decrease of the yield of by-product 4
to 1% (entry 6), whereas NiF2 gave a very poor yield (entry 7).
The replacement of 2,20-bipyridine (L1) with either 4,40-bis-tert-
butylbipyridine (L2) or 1,10-phenanthroline (L3) did not increase
the product yield (entries 8 and 9). No product was formed in
O
cat. Pd
X
Ar
Ph
Ph
Ar
Ar
R
+
OH
X = I, Br, Cl
(RO)3Si Ar
(b)
O
cat. Ni
R
+
+
OH
(c)
O
cat. Pd or Cu
the reaction with sterically hindered L4 or L-proline (L5) (entries
Ph
Ar
R
(HO)2B Ar
10 and 11). Among the phosphine ligands, only Xantphos (L9) pro-
vided the desired product in 26% yield (entry 15). With respect to
the solvents tested, polar solvents such as DMAc, NMP, and DMSO
provided 3a in 28–45% yields (entries 16–18). However, ethers and
aromatic solvents showed no activity (entries 19–22).
Since the decarboxylative coupling reaction between 1a and 2a
is an oxidative coupling, the oxidant is also an important factor,
thus a number of different reagents were tested. As shown in
OH
This work
(d)
O
Ni
cat.
Ph
Ar
(HO)2B
R
Ar
+
OH
Scheme 1. Transition-metal-catalyzed decarboxylative coupling reactions.
Table 1
Effect of nickel source, ligand, and solvent in the oxidative decarboxylative couplinga
10 mol% Ni
20 mol% Ligand
Ph
(HO)2B
+
O
Ph
3a
Na2CO3 (1.0 equiv)
Ag2CO3 (1.0 equiv)
solvent, 80 oC, 18 h
OH
Ph
Ph
1a
2a
4
Entry
Ni
Ligandc
Solvent
3a yieldb (%)
4 yieldb (%)
1
2
3
4
5
6
7
8
Ni(acac)2
Ni(OAc)2
Ni(OH)2
Ni(NO3)2
NiBr2
NiCl2
NiF2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L6
L7
L8
L9
L1
L1
L1
L1
L1
L1
L1
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAc
NMP
9
8
3
22
28
51
4
30
29
—
—
—
—
—
26
38
28
45
—
5
4
2
5
8
1
2
19
2
1
4
6
12
22
5
2
6
9
10
11
12
13
14
15
16
17
18
19
20
21
22
DMSO
Diglyme
Dioxane
Toluene
Xylene
3
1
5
—
—
NiCl2
NiCl2
NiCl2
NiCl2
—
—
—
a
Reaction condition: 1a (0.3 mmol), 2a (0.3 mmol), Ni (0.03 mmol), ligand (0.06 mmol), Na2CO3 (0.3 mmol), and Ag2CO3 (0.3 mmol) were reacted at 80 °C for 18 h. The
reaction was conducted under air condition.
b
Determined by gas chromatography with internal standard.
Ligand structure
c
t-Bu
t-Bu
N
N
N
N
N
N
N
N
Me
Me
L1
L2
L3
L4
PPh2
PPh2
CO2H
P
Fe
PPh2 PPh2
NH
3
O
PPh2
PPh2
L5
L6
L7
L8
L9

4826
J.-H. Lee et al. / Tetrahedron Letters 57 (2016) 4824–4828
Table 2
Effect of base, oxidant, and temperature in the oxidative decarboxylative couplinga
Ph
Ph
10 mol% NiCl2
L1
(HO)2B
O
20 mol%
3a
4
Ph
+
Base (1.0 equiv)
Oxidant (1.0 equiv)
OH
Ph
1a
2a
DMF, Temp, 18 h
Entry
Ratio (1a/2a)
Base
Oxidant
Temp
3a yieldb (%)
4 yieldb (%)
1
2
3
4
5
6
7
8
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:2
1:2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
Cs2CO3
CsF
Ag2O
80
80
80
80
80
80
80
80
80
80
80
80
80
110
60
80
110
45
6
24
24
5
38
17
18
15
2
8
AgOAc
Cu(OAc)2
Cu(OTf)2
O2
24
22
7
1
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
14
10
5
2
1
—
36
5
21
3
9
KF
NaOH
KOH
10
11
12
13
14
15
16
17
—
KOtBu
NaOtBu
Na2CO3
Na2CO3
Na2CO3
Na2CO3
11
19
42
16
86
75
5
8
a
Reaction condition: 1a (0.3 mmol), 2a (0.3 mmol), NiCl2 (0.03 mmol), L1 (0.06 mmol), base (0.3 mmol), and oxidant (0.3 mmol) were reacted in DMF at 80 °C for 18 h. The
reaction was conducted under air condition.
b
Determined by gas chromatography with internal standard.
Table 3
Nickel-catalyzed oxidative decarboxylative coupling reaction with alkynyl carboxylic acids and arylboronic acidsa
10 mol% NiCl2
L1
20 mol%
O
Ar1
Ar2
Ar1
(HO)2B Ar2
+
Na2CO3 (1.0 equiv)
Ag2CO3 (1.0 equiv)
DMF, 80 oC, 18 h
OH
1
3
2
Entry
Ar1
Ar2
Product
3b
Yieldb (%)
1
2
3
4
5
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-EtC6H4
34
95
82
94
71
3c
3d
3e
4-MeCOC6H4
3f
6
7
8
9
2-MeC6H4
2-MeC6H4
3-MeC6H4
3-MeC6H4
3g
3h
3i
58
52
41
34
O2N
NC
O2N
3j
NC
MeO
10
3-MeC6H4
3k
55
MeO
OMe

J.-H. Lee et al. / Tetrahedron Letters 57 (2016) 4824–4828
4827
Table 3 (continued)
Entry
Ar1
Ar2
Product
Yieldb (%)
Me
11
12
13
3-MeC6H4
3l
63
31
54
O
MeO
4-MeC6H4
4-MeC6H4
3m
3n
O
Me
O
14
15
4-MeC6H4
4-EtC6H4
3o
3p
41
58
NC
NC
Me
16
4-EtC6H4
3q
3r
56
45
O
MeO
17
18
4-MeCOC6H4
MeO
OMe
4-MeCOC6H4
4-MeCOC6H4
3s
3t
32
38
NC
MeO
19
O
a
Reaction condition: 1 (2.0 mmol), 2 (4.0 mmol), NiCl2 (0.2 mmol), 2,20-bipyridine (0.4 mmol), Na2CO3 (2.0 mmol), and Ag2CO3 (2.0 mmol) react in DMF at 80 °C for 18 h.
The reaction was conducted under air condition.
b
Isolated yield.
Table 2, Ag2O afforded 45% yield (entry 1), however, other oxidants
including copper and oxygen showed lower activities (entries 2–5).
Next, other bases were employed in place of Na2CO3. The use of
K2CO3, Cs2CO3, CsF, and KF did not improve the yield of compound
3a (entries 6–9), while strong bases led to poor yields (entries 10–
13). No improvement was observed at high temperature (entry 14),
and when the reaction temperature decreased to 60 °C, the yield
dropped to 16% (entry 15). Finally, when the amount of 2a was
increased to 2.0 equiv, the desired product was obtained in 86%
yield (entry 16). However, when the reaction was carried out at
high temperature, no further improvement was observed (entry
17).
Based on these results, the optimal conditions can be summa-
rized as follows: alkynyl carboxylic acid (1.0 equiv), arylboronic
acid (2.0 equiv), NiCl2 (10 mol %), 2,20-bipyridine (20 mol %), Na2-
CO3 (1.0 equiv), and Ag2CO3 (1.0 equiv) were reacted in DMF at
80 °C for 18 h. To evaluate this optimized protocol, a variety of
arylboronic acids were employed in the decarboxylative coupling
reaction with phenyl propiolic acid. The corresponding results
are summarized in Table 3. Alkyl substituted phenylboronic acids
afforded coupling products in good yields (entries 1–4), with the
exception of 2-methylphenylboronic acid that gave a low yield
due to steric hindrance. The reaction between phenyl propiolic acid
and 4-acetylphenylboronic acid gave the desired product in 71%
yield (entry 5). 4-Nitro or 4-cyano substituted phenyl propiolic
acids reacted with 2- or 3-methyl phenyl boronic acids affording
3g, 3h, 3i, and 3j in 58%, 52%, 41%, and 34% yield, respectively
(entries 6–9). 3,4,5-Trimethoxy and 4-acetyl substituted phenyl
propiolic acids reacted with 3-methyl phenylboronic acid to pro-
vide 3k and 3l in 55% and 63% yield, respectively (entries 10 and
11). 4-Alkyl substituted phenyl propiolic acids produced the
desired products in moderate yields (entries 12–16). The reaction
of 4-methoxycarbonylphenylboronic acid led to moderate yields
of products (entries 17–19). Unfortunately, when octynoic acid
was reacted with phenylboronic acid under this optimized condi-
tion, no desired coupled product was formed.
In order to investigate the reactivity of the nickel catalyst in this
coupling reaction, diphenylacetylene was employed as a starting
material in place of phenylpropiolic acid. When diphenylacetylene
was reacted under the optimized conditions, it did not undergo
further reaction with phenylboronic acid. Based on this result, it
was found that the coupled product was stable under these reac-
tion conditions even when two equivalents of arylboronic acid
were employed.
To study the reaction mechanism, a model reaction was con-
ducted under the optimized conditions in the presence of TEMPO
(1 equiv), which is known to be a radical scavenger. Since the yield
of the resulting product did not change, a possible radical pathway
could be ruled out. Based on these results and a previous Letter,13a
oxidant
(HO)2B Ar
Ni (II)
Ph
Ni(0)
Base
+
Ar
X
Ni Ar
I
Ph
Ni Ar
II
O
Ph
Base
CO2
HO
+
Base = Na2CO3, NaHCO3, Ag2CO3
Scheme 2. Proposed mechanism.

4828
J.-H. Lee et al. / Tetrahedron Letters 57 (2016) 4824–4828
Chinchilla, R.; Nájera, C. Chem. Soc. Rev. 2011, 40, 5084–5121; (d) Bakherad,
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we proposed the reaction pathway shown in Scheme 2. The
arylboronic acid reacts with nickel(II) to give aryl nickel complex
I, which then reacts with the decarboxylated alkyne to provide
aryl alkynyl nickel complex II. The subsequent reductive
elimination affords the desired coupled product and nickel(0). In
this catalytic cycle, Ag2CO3 acts as an oxidant for the oxidation of
nickel(0) to nickel(II).
In summary, we developed a nickel-catalyzed oxidative decar-
boxylative coupling reaction between alkynyl carboxylic acids
and aryl boronic acids. Under the optimized conditions, the reac-
tion was carried out in the presence of NiCl2 (10 mol %), 2,20-bipyr-
idine (20 mol %), Na2CO3 (1.0 equiv), and Ag2CO3 (1.0 equiv) in
DMF at 80 °C for 18 h. A variety of aryl boronic acids bearing differ-
ent groups reacted with aryl alkynyl carboxylic acids to give the
desired diaryl alkynes in good yields. Mechanistic studies revealed
that this nickel-based catalytic cycle involved an ionic rather than
a radical process.
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This research was supported by a National Research Foundation
of Korea (NRF) grant provided by the Korean government (MSIP)
(NRF-2012M3A7B4049655, NRF-2015R1A4A1041036). Spectral
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