Aryl Chlorides as Coupling Partners in the Palladium-catalyzed Decarboxylative Coupling Reactions of Propiolic Acids

Full text of DOI:10.1002/bkcs.11298

Note
DOI: 10.1002/bkcs.11298
BULLETIN OF THE
J.-H. Lee et al.
KOREAN CHEMICAL SOCIETY
Aryl Chlorides as Coupling Partners in the Palladium-catalyzed
Decarboxylative Coupling Reactions of Propiolic Acids
*
*
Ju-Hyeon Lee, Gabriel Charles Edwin Raja, Jimin Kim, Kye Chun Nam, and Sunwoo Lee
Department of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea.
*E-mail: kcnam@chonnam.ac.kr; sunwoo@chonnam.ac.kr
Received August 17, 2017, Accepted September 15, 2017, Published online October 10, 2017
Keywords: Arylchloride, Decarboxylative coupling, Palladium
Aryl alkynes are very important building blocks, which are
not only used in pharmaceutical and agricultural chemistry,
but also have great relevance for conjugated polymers, as1
well as for the design of electro- and optical materials.
Among the various synthetic methods for the preparation of
aryl alkynes, Sonogashira coupling reactions have been
most widely used. Since Sonogashira first reported that the
palladium-catalyzed coupling reaction of aryl halides and
terminal alkynes afforded aryl alkynes in the presence of a
copper co-catalyst and an amine base, a number of related
works have been reported and some issues have been
chlorides using a ferrocene-based palladacycle and XPhos
in 2013; a modified method using PdCl was reported in
2
2014. However, the former required an additional catalyst
preparation step, and alkyl-substituted propiolic acids were
not successfully used in the latter. The methodology by
Yang and Lim also required a preparation step for the palla-
dium catalyst. Therefore, there is still a need to develop an
easily accessible methodology for the use of aryl chlorides
in decarboxylative coupling reactions. Herein, we report the
decarboxylative coupling reactions of arylpropiolic acids
and aryl chlorides.
2
addressed. Aryl iodides, bromides, and chlorides have been
Phenylpropiolic acid and chlorobenzene were chosen as
the standard substrates, and their reaction under various con-
ditions was investigated. The results are summarized in
Table 1. The reactions utilizing the Buchwald ligands John-
Phos (L1) and RuPhos (L2) afforded the desired product in
57 and 40% yields, respectively (entries 1 and 2). Chelating
ligands such as L3 and L4, which have shown good activi-
ties in decarboxylative coupling reactions of aryl iodides
and bromides, did not give the desired product (entries
3 and 4). When the Josiphos-type ligand L5 was used,
diphenylacetylene was obtained in 82% yield (entry 5).
When we conducted the reaction in the presence of other
palladium sources such as PdCl , Pd(acac) , Pd(PPh ) Cl ,
employed as coupling partners of terminal alkynes. Among
these, aryl iodides are the most reactive substrate, aryl bro-
mides have intermediate reactivity, and aryl chlorides are
relatively inert electrophiles. However, aryl chlorides have
the advantages of being available and inexpensive. There-
fore, several methodologies for Sonogashira coupling reac-
3
tions employing aryl chlorides have been developed.
It is known that the reactivity of aryl chlorides in these
coupling reactions is highly dependent on the nature of the
4
ligand. Decarboxylative coupling reactions have attracted
great attention in the field of organic synthesis because
arylpropiolic acids, which are used as arylalkyne surro-
gates, are readily prepared from the coupling reaction of
2
2
3 2
2
Pd(dba) , and Pd(PPh ) , the desired product was formed in
2
3 4
5
propiolic acid and aryl halides. Transition metals like pal-
moderate to good yields; however, these yields were not
ladium, copper, nickel, and silver have been used as cata-
lysts. Decarboxylative coupling reactions using aryl halides
and pseudohalides have been reported, and oxidative decar-
boxylative coupling reactions using aryl silanes and boronic
higher than those obtained with Pd(OAc) (entries 6–10).
2
The alternative solvents tested, DMF (dimethylformamide),
NMP (N Methyl-2-pyrrolidone), xylene, and toluene,
resulted in less product formation than DMSO (Dimethyl
sulfoxide) (entries 11–14). When the reactions were con-
ducted with K CO and Na CO , the yields of the products
6
acids have also been developed. Furthermore, multicompo-
nent reactions using propiolic acid derivatives were devel-
2
3
2
3
7
oped to provide useful heterocyclic skeletons.
were 52 and 17%, respectively (entries 15 and 16). The
organic bases DBU (1,8-Diazabicyclo(5.4.0)undec-7-ene)
and DBN (1,5-Diazabicyclo(4.3.0)non-5-ene) afforded the
desired products in 63 and 45% yield, respectively (entries
17 and 18). The reaction yield using the optimized condi-
tions was 47% at 3 h, and the reaction was not completed
Very recently, we developed palladium-catalyzed decar-
boxylative coupling reactions with aryl tosylates, which are
known as the least reactive electrophiles in coupling reac-
tions. This success prompted us to develop decarboxylative
coupling reactions using aryl chloride. Aryl chlorides have
previously been used in decarboxylative coupling reactions
ꢀ
after 6 h. When the reaction was conducted at 100 C, the
8
by several groups, independently. The first report by the
yield of the product decreased to 35%.
Li group described only three examples. The group of
Yang & Wu reported the use of a broad range of aryl
Next, we evaluated a variety of aryl chlorides under the
optimized conditions. The results are summarized in
Bull. Korean Chem. Soc. 2017, Vol. 38, 1368–1371
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a
Table 1. The optimization of decarboxylative coupling with chlorobenzene.
b
Entry
Pd source
Pd(OAc)
Pd(OAc)2
Ligand
Base
Cs CO
Cs CO3
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
2
L1
L2
L3
L4
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
2
3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
57
40
0
2
Pd(OAc)
Pd(OAc)
2
2
Cs
Cs
2
2
CO
CO
3
3
0
Pd(OAc)2
PdCl
Pd(acac)
Cs CO3
82
72
68
57
47
69
45
44
Trace
Trace
52
17
63
45
47
62
35
2
2
Cs
Cs
2
2
CO
CO
3
3
2
Pd(PPh ) Cl
Cs CO3
2
3
2
2
Pd(dba)
3
Pd(PPh )
2
Cs
Cs
2
2
CO
CO
3
3
10
11
12
13
14
15
16
17
18
19
20
21
a
4
Pd(OAc)2
Cs CO3
2
Pd(OAc)
Pd(OAc)
2
2
Cs
Cs
2
2
CO
CO
3
3
NMP
Xylene
Toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Pd(OAc)2
Cs CO3
2
Pd(OAc)
Pd(OAc)
2
2
K
2
CO
3
Na
2
CO
3
Pd(OAc)2
DBU
DBN
Pd(OAc)
Pd(OAc)
2
2
c
d
e
Cs
2 3
CO
Pd(OAc)2
Pd(OAc)
Cs CO3
2
2
2 3
Cs CO
Reaction conditions: PhCl (0.3 mmol), phenylpropiolic acid (0.3 mmol), Pd (0.0045 mmol), ligand (0.009 mmol), and base (0.36 mmol) were
ꢀ
reacted at 130 C for 12 h.
Determined by gas chromatography with an internal standard.
Reaction time = 3 h.
Reaction time = 6 h.
Reaction temperature = 100 C
b
c
d
e
ꢀ
t
t
P Bu
P Bu
iPrO
2
2
PCy
O Pr
2
C
y
2P
Fe
i
O
PPh2 PPh2
PPh2
PPh2
L1
L2
L3
L4
L5
Table 2. Diphenylacetylene was successfully isolated in
3% yield (entry 1). Chlorotoluenes and chloroanisoles
gave the desired coupled products; however, their ortho-
and meta-substituted isomers showed lower yields than the
A variety of substituted propiolic acids were used in reac-
8
tions with chlorobenzene (Table 3). Ortho-, meta-, and
para- tolylpropiolic acids afforded the corresponding diaryl
alkynes in 66, 74, and 87% yields, respectively (entries
1
–3). We did not find any steric effect from the substituents
para-substituted
isomers
(entries
2–7).
4-tert-
of the phenyl ring of the arylpropiolic acids. Alkoxy-
substituted propiolic acids showed good yields of the
expected products (entries 4 and 5). Thiophenyl-, biphenyl-,
and naphthyl-substituted propiolic acids gave the corre-
sponding alkynes in 42, 65, and 68% yields, respectively
Butylchlorobenzene provided the desired product in 84%
yield (entry 8). 4-Fluorochlorobenzene showed a yield of
83% (entry 9). Aryl chlorides having ester and ketone
groups afforded the desired products in 63 and 48% yields,
respectively (entries 10 and 11). 1-Chloronaphthalene and
(
entries 6–8). The alkyl-substituted propiolic acids, butynoic
2-chlorothiophene exhibited good yields of their corre-
acid, pentynoic acid, and octynoic acid, afforded the corre-
sponding alkylated alkynes in 64, 94, and 58% yields,
respectively (entries 9–11).
sponding products (entries 12 and 13); however, the yield
from 3-chloropyridine was somewhat lower (entry 14).
Bull. Korean Chem. Soc. 2017, Vol. 38, 1368–1371
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KOREAN CHEMICAL SOCIETY
Table 2. Decarboxylative coupling reaction of aryl chlorides and
phenylpropiolic acid.
Table 3. Decarboxylative coupling reaction of chlorobenzene and
substituted propiolic acids.
a
a
b
Entry
1
Aryl chloride
Product
Yield (%)
83
Yield
(%)
b
Entry Arylpropiolic acid
1
Product
66
74
2
3
31
41
2
3
4
5
87
72
67
4
5
74
33
6
34
6
7
8
42
65
68
7
8
9
65
84
83
63
9
64
94
58
1
1
1
0
1
2
1
0
48
87
11
a
Reaction condition: PhCl (1.0 mmol), arylpropiolic acid (1.0 mmol),
Pd(OAc)
2
(0.015 mmol), L5 (0.03 mmol), and Cs
2
CO
3
(1.2 mmol)
ꢀ
were reacted in DMSO at 130 C for 12 h.
Isolated yield.
b
1
1
3
4
75
40
Experimental
Alkynyl carboxylic acid (1.0 mmol), aryl chloride
a
b
Reaction conditions: ArCl (1.0 mmol), phenylpropiolic acid
(
(
1.0 mmol), Pd(OAc)2 (3.4 mg, 0.015 mmol), L5
(
(
1.0 mmol), Pd(OAc)
1.2 mmol) were reacted in DMSO at 130 C for 12 h.
2
(0.015 mmol), L5 (0.03 mmol), and Cs
2
CO
3
17.5 mg, 0.03 mmol), Cs CO (391 mg, 2.4 mmol), and
2
3
ꢀ
DMSO (5.0 mL) were added to the reaction vial. The mix-
Isolated yield.
ꢀ
ture was stirred at 130 C for 12 h, after which the mixture
was extracted with Et O and the organic layer was dried
2
In conclusion, we developed decarboxylative coupling
reactions with propiolic acids and aryl chlorides. The opti-
over magnesium sulfate. Evaporation of the solvent under
reduced pressure provided the crude product, which was
purified by column chromatography on silica gel.
mized conditions (Pd(OAc) [1.5 mol%], L5 [3.0 mol%],
2
and Cs CO [1.2 equiv]) were determined and subsequently
2
3
used in the reaction of propiolic acid derivatives and aryl
chlorides. The reactions were conducted in DMSO at
ꢀ
1
30 C for 12 h. A variety of aryl chlorides and propiolic
acid derivatives afforded the desired products in moderate
to good yields. The substituents of the aryl chlorides were
found to have a steric effect on the reactions; however, no
such effect was found for the propiolic acids.
Acknowledgments. This research was supported by the
National Research Foundation of Korea (NRF) grant
funded by the Korea government (MSIP) (NRF-
2
017R1D1A3B03035736, NRF-2015R1A4A1041036).
Bull. Korean Chem. Soc. 2017, Vol. 38, 1368–1371
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Bull. Korean Chem. Soc. 2017, Vol. 38, 1368–1371
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