ACCEPTED MANUSCRIPT
2
Catalysis Communications
MeOH (1:1), H O-EtOH (1:1), H O-EG (1:1)] and an aliquot of
3. Result and discussion
2
2
0
.01 M solution of palladium complexes PdCl (L) or Pd[(L) ]Cl
2 2 4 2
Initially, to test the activity of PdCl -aminopyridines, the
2
in MeOH (0.001-0.2 mol%) under air atmosphere. The reaction
mixture was placed in a preheated oil bath: at 100 °C for MeOH-
H O, at 110 °C for EtOH-H O, at 140 °C for H O and at 160 °C
for EG-H O; and stirred under reflux for the given time. After
this time, the mixture was cooled, acidified by 5 M HCl (in the
model reactions of 3-iodobenzoic acid, 4-bromoaniline, 2-
bromoaniline and 4-bromoanisole with 3(4)-methoxy-, 4-chloro-
and 4-methylphenylboronic acids were studied under air
atmosphere. Water, aqueous ethanol and ethylene glycol (EG)
were used as solvents and K CO as a base (Table 1) for these
2
2
2
2
2
3
case of acids) and diluted with 10 mL of H O and 10 mL of Et O
2
2
25
reactions, based on our previous results. These results indicate
that aminopyridine complexes, PdCl (L) and [Pd(L) ]Cl , are
(or EtOAc). The organic phase was separated, and the aqueous
2
2
4
2
layer was extracted with Et O EtOAc) (2 x 10 mL). The
2
very effective and high-turnover catalysts for Suzuki-Miyaura
reaction in aqueous media. In the reaction of water-soluble aryl
iodides catalyst amount can be reduced up to 0.001 mol% level
without noticeable activity decrease. For instance, 3-iodobenzoic
acid reacted with 4-methoxyphenylboronic acids (entry 3) for 5
min with turnover numbers (TON) up to 100000 and turnover
frequencies (TOF) up to 1200000 h ., The yield of cross-
coupling product did not exceed 65 % in the absence of ligands
and the reaction could not go to completion (entry 8). It was
combined organic layers were washed with H O (10 mL), brine
2
(
10 mL), and dried over Na SO . The pure products were
2 4
obtained by a simple filtration of ether solution through silica gel
pad and evaporation of a solvent.
-
1
Scheme 2. Cross-coupling of aryl halides with arylboronic acids catalyzed by PdCl -aminopyridine complexes.
2
surprising that in the presence of 0.1 mol% of complex
PdCl (L3) even such electron-rich aryl bromide as 4-
yield (entry 11). Then, we examined the effect of bases on the
reaction of 4-bromoaniline and 4-methoxyphenylboronic acid in
the presence of 0.1 mol% of PdCl (L1) in ethanol-water mixture
2
2
bromoanisole interacted in water without organic co-solvent at
2
2
o
o
1
00 C for less than 10 minutes, also indicating on high activity
(1:1) at 85 C. The use of Na CO , K CO , and K PO as bases
2 3 2 3 3 4
of new catalysts. The product was obtained with quantitative
Table 1. Screening of the aminopyridine ligands on Suzuki-Miyaura reactions.
a
Entry
Pd-L
Pd, mol%
Time, min
Yield, %
o
3
4
-IC
6
H
4
COOH (1 mmol), 4-MeOC
6
H
4
B(OH)
2
(1.2 mmol), K
2
CO
3
2
(2.5 mmol), H O, 100 C
1
2
3
PdCl
PdCl
PdCl
2
2
2
(L1)
(L2)
(L4)
2
2
2
0.02
10
10
5
99
99
0.02
0.001
100
o
-BrC
6
H
4
NH
2
(1 mmol), 4-MeOC
6
H
4
B(OH)
2
(1.2 mmol), K
2
CO
3
(1.5 mmol), H
2
O-EtOH, 85 C
4
5
6
7
PdCl
2
(L1)
2
0.1
10
10
10
2
99
94
91
99
Pd[(L1)
Pd[(L2)
4
]Cl
2
2
0.2
4
]Cl
0.02
PdCl
2
(L4)
2
0.05
o
2
4
-BrC
6
6
H
4
4
NH
2
(1 mmol), 4-ClC
6
H
4
B(OH)
2
(1.2 mmol), K
2
CO
3
(1.5 mmol), H
2
O-EG, 110 C
8
9
PdCl
2
2
0.1
0.1
0.1
15
15
65
96
94
PdCl
(L3)
2
1
0
Pd[(L3)
4
]Cl
2
15
o
-BrC
H
OMe (1 mmol), 4-MeC
6
H
4
B(OH)
2
(1.2 mmol), K
2
CO
3
(1.5 mmol), H
2
O, 100 C
1
a
1
PdCl (L3)
2
2
0.1
10
100
NMR yield.
resulted in quantitative yield of the coupling product (Table 2,
entries 4-6). KF and KOH provided the cross-coupling product in
good yields (entries 2, 3). It was not surprising that the cross-
coupling reaction proceeded in low yield with NaOAc, a fairly
weak base relative to Na CO K CO or K PO . The effect of
the Suzuki–Miyaura reaction using PdCl -aminopyridines as
2
catalysts and K CO as a base in water and aqueous alcoholic
2
3
solvents at reflux temperatures (Table 4). Reactions of water-
soluble and water-insoluble aryl iodides and bromides proceeded
in water without organic co-solvent in the presence of 0.02-0.1
mol% of palladium giving cross-coupling products with high
yields for 5-10 min (entries 1, 8 and 14). Reactions of arylboronic
acids which are unstable to protodeboration were carried out in
aqueous methanol (1:1). In this solvent 4-iodobenzoic acid, 2-
and 4-iodoanilines reacted easily with 2-furyl- and 2-
thienylboronic acids in 89-92% yields for 10 min at 0.01 mol%
loading of palladium, corresponding to 8900-9200 TON and
2
3,
2
3
3
4
solvent in the model reaction of 2-bromoaniline and 4-
methylphenylboronic acid in the presence of 0.1 mol% of
complexes PdCl (L3) and [Pd(L3) ]Cl using K CO as a base
2
2
4
2
2
3
under reflux was examined. As expected, the high or good yields
of product were obtained in protic solvents: in water, aqueous
ethanol, ethylene glycol and isopropanol (Table 3, entries 1-5). In
nonpolar aprotic solvents such as toluene, which is commonly
used in Suzuki-Miyaura coupling, the reaction proceeded in low
yield (entry 7).
-
1
53400-55200 h TOF (entries 2, 6, and 7). Aryl(heteroaryl)
bromides with electron-withdrawing groups gave also the
coupling products in high yields at low catalyst loading for 10-20
We next estimated the scope and limitations of substrates for