2
424
P. R. Boruah et al. / Tetrahedron Letters 55 (2014) 2423–2425
They believed that the promoting effect in the presence of Na
could be due to the in situ formation of a water soluble ate complex
Na PdCl (SO which catalyzed the Suzuki–Miyaura reactions. In
BMIM][OH], the reaction of 4-bromotoluene and phenyl boronic
acid afforded only <10% products (Table 1, entry 4). The same reac-
tion when carried out in the presence of LiCl, the yields were
improved (55% yields in 6 h, Table 1, entry 5). Better results were
2 4
SO
N
N
[
OH]
[OH]
N
N
4 2
)
2
2
[
[
BMIM][OH]
[EMIM][OH]
N
N
N
obtained when [C
for Suzuki coupling reactions. The reaction of phenyl boronic acid
with 4-bromotoluene in [C -DABCO][acetate] in the presence of
2 mol % PdCl at 110 °C afforded 80% yields of the desired product
Table 1, entry 6). In the presence of 20% 5 M LiCl aqueous solution
1.8 mL ionic liquid and 0.4 mL LiCl solution), 86% yields were
4
-DABCO] based basic ionic liquids were used
[
N(CN)2]
[
CH COO]
N
9
3
C H
4 9
C H
4
4
[
C -DABCO][Acetate]
4
[C -DABCO][dca]
4
2
(
(
Figure 1. Basic ionic liquids used for this study.
observed in 3 h (Table 1, entry 7). When the same reaction was car-
ried out in [C -DABCO][N(CN) ] in identical reaction conditions,
0% yields of the desired product were obtained in 3 h (Table 1,
entry 9). From these initial experiments, [C -DABCO][N(CN)
was found to be the best basic ionic liquid for Suzuki cross coupling
reactions with LiCl acting as a promoter.
Different electron rich and electron deficient aryl halides and
boronic acid derivatives were used to construct biaryls in a base-
free and ligand-free environment (Table 2). Under this reaction
condition, various aryl bromides bearing electron-withdrawing
groups such as nitro, nitrile and aldehyde moieties, and electron-
releasing groups such as methyl and methoxy moieties react with
aryl boronic acids to afford biaryls in high yields along with trace
amount of homocoupling products of aryl boronic acids (2–5%).
The coupling of 4-bromotoluene with phenyl boronic acid afforded
ionic liquid without the use of base to compare the results with basic
ionic liquids.
4
2
9
The reaction of phenyl boronic acid with 4-bromotoluene cata-
4
2
]
lyzed by 2 mol % PdCl
imidazolium tetrafluoroborate, [BMIM][BF
2
in neutral ionic liquid 1-butyl-3-methyl
] at room temperature
4
did not proceed at all (Table 1, entry 1). Even when the tempera-
ture was raised to 110 °C, no product formation was detected.
The result was as expected because there was no base used in
the reaction. Welton et al. carried out the reaction of 4-bromotol-
uene and phenyl boronic acid in [BMIM][BF
4
] using Pd(PPh
3 2
) as
3
catalyst and Na CO as base. This condition afforded 4-methylbi-
2 3
phenyl in 30% yields after 6 h. But, they observed catalyst decom-
position under this reaction condition which was evidenced by the
formation of black precipitate. The reaction of phenyl boronic acid
and 4-bromotoluene when carried out in basic ionic liquid [EMI-
M][OH] at 110 °C, only trace amount of product formation was ob-
served (Table 1, entry 2). In the presence of 5 M LiCl (1.6 mL of
ionic liquid and 0.4 mL of 5 M LiCl solution in water), the yields in-
creased and 70% yields were obtained after 6 h (Table 1, entry 3).
No further progress was observed after 6 h. Lithium chloride, a
salting-out agent, was found to accelerate Diels–Alder reaction.
9
0% yields in 3 h (Table 2, entry 1). With 4-methoxybromoben-
zene, 3-methoxybromobenzene, and 4-nitro bromo benzene, poor
yields (only 40–50% yields after 6 h) were obtained (Table 2,
entries 2, 3, and 7). Regarding boronic acids, better results were ob-
tained with electron rich boronic acids as compared to the results
with unsubstituted boronic acids (compare entries 1 and 5,
Table 2). The reaction of bromobenzene with 4-methoxy boronic
acid afforded 98% yields (Table 2, entry 4). Identical results were
obtained when 4-bromotoluene was reacted with 4-methoxy
boronic acid (99% yields, Table 2, entry 5). Our results were well
Kumar co-workers showed dramatic acceleration of Diels–Alder
reaction rate in the presence of 5 M LiCl solution.8 The effect of
salts on kinetics of Diels–Alder reactions has been discussed in
terms of several parameters like hydrophobic packing, solvent
pressure, hydrogen bonding, hydrophobic hydration etc. To the
best of our knowledge, no such observations are reported in
literature for Suzuki–Miyaura cross coupling reactions. Bora and
1
0
supported by literature report. Sajiki et al. carried out Suzuki
couplings of aryl halides with electron-rich boronic acids such as
2
-, 3-, or 4-methoxy phenyl boronic acids in the presence of 10%
Pd-C and Na
2
CO
3
in 50% EtOH in water. They observed that the
co-workers recently reported the accelerating effect of Na
Suzuki reactions performed in water.9 The reaction of 4-nitro
bromobenzene with phenyl boronic acid in the presence of PdCl
and Na SO afforded 90% yields in 5 h whereas the same reaction
2 4
SO in
2
2
4
Table 2
a
without Na
2
SO
4
gave very poor yields, that is, 20% yields in 10 h.
Effect of substituent on Suzuki–Miyaura reactions
Br
B(OH)
2
[
C
4
-DABCO][dca]
, 110 °C R1
M LiCl, PdCl
2
R2
2
5
R1
Entry
R
Table 1
a
Effect of basic ionic liquids and 5 M LiCl on Suzuki couplings
R1
R2
Time (h)
Yieldsb (%)
Br
B(OH)
2
2
PdCl , solvent
1
2
3
4
5
6
7
8
9
4-Me
4-OMe
3-OMe
H
4-Me
4-CN
H
H
H
3
6
6
3
3
6
6
6
6
6
90
40
45
98
99
110 °C
Entry
Solvent
Time (h)
Yieldsb (%)
4-OMe
4-OMe
1
2
3
4
5
6
7
8
9
[BMIM][BF
[EMIM][OH]
4
]
6
6
6
6
6
6
3
6
3
—
c
<10
70
<10
55
80
86
85
90
H
H
H
H
H
80
c
[EMIM][OH] + 5 M LiCl
[BMIM][OH]
[BMIM][OH] + 5 M LiCl
-DABCO][Ac]
-DABCO][Ac] + 5 M LiCl
-DABCO][dca]
4-NO
2
50
c
4-CHO
3-CHO
2-CHO
85
70
50
[C
[C
[C
[C
4
4
4
4
10
a
Reaction conditions: Aryl halide (1 mmol), arylboronic acid (1.2 mmol), PdCl
2 mol %), ionic liquid (1.6 mL, 7.4 mmol), 5 M LiCl aqueous solution (0.4 mL),
10 °C.
2
(
1
-DABCO][dca] + 5 M LiCl
a
b
Reaction conditions: 4-Bromotoluene (1 mmol), phenylboronic acid (1.2 mmol),
PdCl (2 mol %), ionic liquid (1.6 mL, 7.4 mmol), 5 M LiCl aqueous solution (0.4 mL),
10 °C.
Isolated yields.
c
2
Due to solubility problems of the solid bromo compounds (entries 6–8) in ionic
liquids, 1 mL isopropanol was added to 1 mL ionic liquid/aq. LiCl system (0.8 mL
ionic liquid, 0.2 mL 5 M LiCl solution).
1
b
Isolated yields.