Suzuki-miyaura cross-coupling reaction catalyzed by 4,4'-tbu2-2,2'- dipyridyl-palladium(II) dichloride complex in aqueous solvent under aerobic condition

Article abstract of DOI:10.14233/ajchem.2014.16166

4 4'-di-tBu-2 2'-dipyridylpalladium(II) dichloride complex [(tBubpy)PdCl2] showed high efficiency for the Suzuki coupling reaction of aryl iodide and bromide with phenylboronic acid in alcohol solvent under aerobic condition. All reactions gave the isolated coupling products in moderate to excellent yields.

Full text of DOI:10.14233/ajchem.2014.16166

Asian Journal of Chemistry; Vol. 26, No. 7 (2014), 2077-2082
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16166
t
Suzuki-Miyaura Cross-Coupling Reaction Catalyzed by 4,4'- Bu
2
-2,2'-dipyridyl-palladium(II)
Dichloride Complex in Aqueous Solvent Under Aerobic Condition
*
I.A. MKHALID and H.F. AL-SHAIKH
Chemistry Department, Faculty of Science, King Abdul Aziz University, P.O. Box 80297, Jeddah 21589, Saudi Arabia
*
Corresponding author: Tel: +966 2 6952293, Fax: +966 2 6952292, E-mail: imkhalid@kau.edu.sa
Received: 8 August 2013;
Accepted: 29 November 2013;
Published online: 22 March 2014;
AJC-14965
t
,4'-di- Bu-2,2'-dipyridylpalladium(II) dichloride complex [( Bubpy)PdCl
t
4
2
] showed high efficiency for the Suzuki coupling reaction of
aryl iodide and bromide with phenylboronic acid in alcohol solvent under aerobic condition. All reactions gave the isolated coupling
products in moderate to excellent yields.
Keywords: Suzuki-Miyaura reaction, Cross-coupling, Bipyridine, Palladium chloride.
has been used as an effective ligand in C-H borylation of arenes
INTRODUCTION
3
and hetero arenes . Interestingly, no report mentioned the
0,31
The discovery of palladium catalyzed organic reactions
has drawn the attention of chemists to use them in formation
t
use of 4,4'-di- Bu-2,2'-bipyridine palladium(II) dichloride
t
complex, [( Bubpy)PdCl
2
], 1, in Suzuki reaction. But there are
1
-3
of C-C bonds . Among them, Suzuki-Miyaura cross-coupling
reaction catalyzed by Pd-complexes is a powerful tool for
examples of 2,2'-bipyridine with palladium, which used as a
ligand in cationic Pd-bipyridine to catalyzed the addition of
phenylboronic acid to β,β-disubstituted enones or as cationic
4
biaryls and heterobiaryl synthesis . This reaction can be the
-8
key step in the synthesis of pharmaceutical mediates or in natural
9
products, ligands, polymer and in advanced materials
4
,4'-bis(bromomethyl)-2,2'-bipyridine with palladium to
-11
.
32,33
catalyzed Suzuki reaction in water . Accordingly, we are
exploring the catalytic effect of 1 on the coupling of aryliodides
or bromides with phenylboronic acid in alcoholic solvent under
atmospheric condition. Preliminary results suggested that 1
can be a good precursor catalyst under atmospheric condition
It is known that the reaction of Suzuki-Miyaura is depen-
1
2-14
dent on the type of ligands . Bulky and electron-rich phos-
phine ligands have been used widely in palladium-catalyzed
Suzuki-Miyaura coupling reactions and excellent results have
1
5-17
been reported . However, most of the phosphines ligands
are sensitive to air and moisture, which causes a limit in their
1
use . Therefore, number of phosphine-free ligands such as
only in a mixing aqueous solvent such as MeOH/H
the presence of stoichiometric amount of K PO ·3H
C. Series of symmetrical and asymmetrical biaryls have been
2
O and in
3
4
2
O at 80
8-20
°
2
1-24
N-heterocyclic carbenes were employed . In addition,
ligands containing donor atoms such as N or O and S become
important in cross-coupling reaction due to their high stability
synthesized according to (Scheme-I).
EXPERIMENTAL
2
5-29
to air, non-toxic and easy to handle . One of the most
t
interesting N-donor ligand is 4,4'-di- Bu-2,2'-bipyridine, which
All reactions were carried out under an air condition. All
compounds were obtained from Aldrich Chemical Company,
X
B(OH)2
t
[
( Bubpy)PdCl ]
2
+
K PO .3H O
3
4
2
MeOH \ Water
o
R1
R2
R1
R
2
t
80 C
2
Scheme-I: [( Bubpy)PdCl ] catalyzed Suzuki-Miyaura cross-coupling reaction

2
078 Mkhalid et al.
Asian J. Chem.
tested for purity by GC/MS and used without further purifi-
cation. NMR spectra were recorded at ambient temperature
on Bruker Avance 400 and 600. Proton and carbon spectra
(d, JH-H = 8.4 Hz, 2H), 7.62 (d, JH-H = 7.2 Hz, 2H), 7.49 (t, JH-
1
13
3
= 7.2 Hz, 2H), 7.45 (t, JH-H = 7.2 Hz, H). C NMR (CDCl ,
H
150 MHz) δ 147.63, 147.02, 138.74, 129.154, 128.92, 127.81,
+
127.79, 124.12, 117. GC-MS (70 Ev) m/z (relt.): 179 M
were referenced to external SiMe
4
via residual protons in the
+
N), 153 [M-CN] (C12
deuterated solvents or solvent resonance respectively. Elemental
analyses were carried out by Perkin-Elmer 2400 series-II
elemental analyzer in the Department of Chemistry at King
Abdul Aziz University. GC-MS analyses were performed on
a Shamadzu Series II gas chromatograph equipped with a 5971
mass selective detector. A fused silica capillary column (10 m
or 12 m cross-linked 5 % phenylmethylsilicone) was used and
the oven temperature was ramped from 50 to 280 °C at a
(C13
H
9
H
9
). Anal. calcd. for C13
H
9
N: C
87.12; H 5.06; N 7.82. Found: C 86.97; H 5.03; N 7.88. m.p.
(86-88 °C), lit. m.p. (83-85 °C).
4-Cyano-4'-methoxy biphenyl : (62.6 mg, 0.30 mmol,
39
1
98 %), H NMR (CDCl
3
, 600 MHz) δ 7.68-7.71 (m, 2H), 7.63-
7.66 (m, 2H), 7.53-7.56 (m, 2H), 6.99-7.02 (m, 2H), 3.86 (s,
13
3H, OCH
132.76, 132.58, 128.37, 127.11, 119.12, 114.60 (CN), 110.07,
55.41. GC-MS (70 Ev) m/z (relt.): 209 (C14 11NO), 195 [M-
11NO: C 80.36; H 5.30; N
3 3
). C NMR (CDCl , 150 MHz) δ 160.17, 145.22,
rate of 20 °C/min. UHP grade helium was used as the carrier
t
gas. All complexes [( Bupby)PdCl
H
+
2
], [(MeObpy)PdCl
2
],
N] (C14H11O). Anal. calcd. for C14H
[
(bpy)PdCl
2
], [(Mebpy)PdCl
prepared according to literatures
2
] and [PdCl (PhCN) ] were
2
2
6.69. Found: C 80.14; H 5.28; N 6.77. m.p. (102-103 °C), (lit.
101-102 °C).
3
4-36
.
38
1
Typical procedure for Suzuki reaction of aryl iodo or
bromides with arylboronic acids:All reactions were perfor-
med under aerobic conditions. To a mixture of the appropriate
aryl bromide/iodiede (1 equiv.), phenylboronic acid or 4-
4-Acetyl biphenyl : (74 mg, 0.38 mmol, 99 %), H NMR
(CDCl , 400 MHz) δ 8 (d, JH-H = 8.4 Hz, 2H), 7.69 (d, JH-H
8.4 Hz, 2H), 7.62-7.64 (m, 2H), 7.46-7.49 (m, 2H), 7.39-7.42
3
=
13
(m, 1H), 2.64 (s, 3H, CH
196.50 (CO), 146, 140.08, 136.06, 129.15, 129.11, 128.43,
127.47, 127,43, 26.86, (CH ). GC-MS (70 Ev) m/z (relt.): 196
3 3
). C NMR (CDCl , 150 MHz) δ
methoxyphenyl boronic acid (50 mg, 0.41 mmol), K PO
3
4 2
·3H O
(
(
[
3 equiv. 320 mg, 1.20 mmol) in the presence of 1 or 2 mol %
3
-
3
-3
2 mg, 4.50 × 10 mmol or 4 mg, 8.98 × 10 mmol) of complex
+
+
M (C14
H
12O), 182 [M-CH
12O: C 85.68; H 6.16. Found: C 85.55; H 6.13. m.p. (119-
120 °C).
4-Phenyl benzaldehyde : (60 mg, 0.33 mmol, 98 %),
H NMR (CDCl , 600 MHz) δ 10.06 (s, 1H, CHO), 7.95-7.97
(m, 2H), 7.75-7.78 (m, 2H), 7.63-7.65 (m, 2H), 7.47-7.50 (m,
2
] (C13H10O). Anal. calcd. for
t
( Bubpy)PdCl
2
] and methanol/water (20/4 mL) was added.
14
C H
The reaction mixture was heated to 80 °C with vigorous stirring
for 2, 4 or 16 h. Then, the mixture was cooled to room
temperature and extracted with diethyl ether (3 × 30 mL) and
washed with 5 mL of EtOAc. The organic layer was dried
4
0
1
3
1
3
over MgSO
4
and concentrated under reduced pressure. The
crude product was purified by flash column chromatography
2H), 7.41-7.44 (m, 1H). C NMR (CDCl , 150 MHz) δ 192.03
(CO), 147.22, 139.70, 135.14, 130.30, 129.02, 128.48, 127.70,
3
+
on silica gel. The yields were based on aryl halide.
127.37. GC-MS (70 Ev) m/z (relt.): 182 M (C13
H
10O), 153
10O: C 85.69; H 5.53.
Found C 85.57; H 5.50. m.p. (85-86 °C).
4-(4'-Methoxyphenyl)benzaldehyde : (60 mg, 0.28
3
7
+
4
-Methoxyl-biphenyl : (73.1 mg, 0.40 mmol, 98 %),
H NMR (CDCl , 600 MHz) δ 7.80 (d, JH-H = 8.4 Hz, 2H),
.51-7.54 (m, 2H), 7.42-7.39 (m, 2H), 7.28-7.32 (m, 1H), 6.96-
9
[M-CHO] (C12H ).Anal. calcd. for C13H
1
3
4
1
7
6
1
3
1
.99 (m, 2H), 3.85 (s, 3H,OCH
3
). C NMR (CDCl , 150 MHz)
3
mmol, 98 %), H NMR (CDCl
7.00-7.02 (m, 2H), 7.92-7.94 (m, 2H), 7.2 (d, JH-H = 7.8 Hz,
3
, 600 MHz) δ 10.03 (s, 1H),
δ 159.10, 140.80, 133.72, 128.71, 128.14, 126.72, 126.64,
+
14.14, 55.33. GC-MS (70 Ev) m/z (relt.): 184 M (C13
13
1
1
6
8
H12O),
2H), 7.58-7.61 (m, 2H), 3.87 (s, 3H, OCH
150 MHz) δ 191.97 (CO), 160.08, 146.79, 134.63, 132.04,
130.34, 128.51, 127.06, 114.45, 55.40 (OCH ). GC-MS (70
3 3
). C NMR (CDCl ,
+
9
69 [M-Me] (C12H O).Anal. calcd. for C13H12O: C, 84.75; H,
.57. Found: C 84.55; H 6.55. m.p. (85-86 °C), (lit. 84.0-
5.0 °C).
3
+
+
ev) m/z (relt.): 212 M (C14
Anal. calcd. for C14 : C 79.22; H 5.70. Found: C 79.07; H
5.66. m.p. (103-104 °C).
4-Trifluoromethyl biphenyl : (73.6 mg, 0.33 mmol,
12 2 3 9
H O ), 181 [M-OCH ] (C13H O).
3
7
1
-Nitro-biphenyl : (67.3 mg, 0.34 mmol, 90 %), H NMR
4
12 2
H O
3
(CDCl , 600 MHz) δ 7.73 (d, JH-H = 8 Hz, 2H), 7.69 (d, JH-H
=
4
2
8
2
Hz, 2H), 7.59 (d, JH-H = 7.2 Hz, 2H), 7.49 (t, JH-H = 7.2 Hz,
13
1
H), 7.43 (t, JH-H = 7.2 Hz, 1H). C NMR (CDCl , 150 MHz)
3
99 %), H NMR (CDCl
(m, 2H), 7.45-7.49 (m, 2H), 7.39-7.42 (m, 2H). C NMR
(CDCl , 150 MHz) δ 144.95, 139.99, 129.67, 129.45, 129.22,
128.39, 127.63, 127.49. GC-MS (70 ev) m/z (relt.): 222 M
3
, 400 MHz) δ 7.69 (s, 3H), 7.59-7.61
13
δ 145.65, 139.14, 132.60, 130.08, 129.10, 128.65, 127.73,
+
1
27.22. GC-MS (70 Ev) m/z (relt.): 199 M (C12
H
9
NO
: C 72.35; H
.55; N 7.03. Found: C 72.13; H 4.51; N 7.12. m.p. (112-113
2
), 183
3
+
+
[
9 9 2
M-O] (C12H NO). Anal. calcd. for C12H NO
+
4
(C13
H F
9 3
), 201 [M-H
2 7 3 9 3
F] (C13H F ).Anal. calcd. for C13H F C
°
C), (lit. 115-116 °C).
-Nitro-4'-methoxy biphenyl : (60 mg, 0.26 mmol,
70.27; H 4.08. Found: C 70.12; H 4.03. m.p. (69-70 °C).
39
4-Trifluoromethyl-4'-methoxy biphenyl : (60.4 mg,
3
7
4
1
8 %), H NMR (CDCl
1
0.24 mmol, 99 %), H NMR (CDCl
9
8
3
1
3
, 600 MHz) δ 7.00-7.03 (m, 2H), 8.26-
.28 (m, 2H), 7.70-7.78 (m,, 2H), 7.58-7.60 (m, 2H), 3.87 (s,
3
, 400 MHz) δ 7.64-7.67
(m, 4H), 7.53-7.56 (m, 2H), 7.99-.027 (m, 2H), 3.86 (s, 3H,
13
13
H). C NMR (CDCl , 150 MHz) δ 160.41, 147.21, 146.50,
3
31.06, 128.58, 127.08, 124.15, 114.59, 55.43. GC-MS (70
OCH ). C NMR (CDCl
3
3
, 150 MHz) δ 158.82, 143.27, 131.17,
). GC-
127.32, 125.84, 124.65, 124.63, 113.40, 54.36 (OCH
+
MS (70 ev) m/z (relt.): 252 M (C14 O), 237 [M-Me]
3
+
+
+
Ev) m/z (relt.): 229 M (C13
H
11NO
3
), 198 [M-OMe]
: C 68.11; H 4.84; N
.11. Found: C 67.97; H 4.83; N 6.20. m.p. (107-108 °C).
H
11
F
3
(C
13
H
8
NO). Anal. calcd. for C13
H11NO
3
(C13
H
8
F
3
11 3
O). Anal. calcd. for C14H F O: C 66.66; H 4.40.
6
Found: C 66.44, H 4.39. m.p. (121-122 °C) (lit. 124-125°C).
3,5-bis(Trifluoromethyl)biphenyl: (70.5 mg, 0.24 mmol,
38
1
4
-Cyano biphenyl : (67.3 mg, 0.38 mmol, 99 %), H
1
99 %), H NMR (CDCl
NMR (CDCl , 600 MHz) δ 8.30 (d, JH-H = 8.4 Hz, 2H), 7.74
3
3
, 400 MHz) δ 8.01 (s, 2H), 7.85 (s,

t
2
Vol. 26, No. 7 (2014) Suzuki-Miyaura Cross-Coupling Reaction Catalyzed by 4,4'- Bu -2,2'-dipyridyl-palladium(II) Dichloride Complex 2079
3
8
1
1
H), 7.60-7.62 (m, 2H), 7.50-7.53 (m, 2H), 7.45-7.48 (m, 1H).
3-Methyl biphenyl : 30.6 mg, 0.18 mmol, 41 %), H
NMR (CDCl , 400 MHz) δ 7.57-7.60 (m, 2H), 7.41-7.45 (m,
2H), 7.35-7.37 (m, 1H), 7.32-7.35 (m, 1H), 7.17-7.20 (m, 1H),
13
C NMR (CDCl , 150 MHz) δ 137.20, 136.60, 131.80, 129.0,
3
3
1
2
27.50, 127.42, 127.40, 121.00. GC-MS (70 ev) m/z (relt.):
+
+
), 271 [Me-M] (C14
90 M (C14
8
H F
6
H
8
5
F ). Anal. calcd. for
7.13 (t, JH-H = 6.6 Hz, 1H), 6.88-6.91 (dd, JH-H = 8.4, 8.4 Hz,
1
3
C
14
H
8
F
6
: C 57.94; H 2.78. Found: C 57.77; H 2.74.
1H), 3.87 (s, 3H, CH
3 3
). C NMR (CDCl , 150 MHz) δ 143.1,
43
4
-Phenyl benzoic acid : (74.7 mg, 0.38 mmol, 99 %),
H NMR (CDCl , 400 MHz) δ 8.18 (d, JH-H = 8.4 Hz, 2H),
.70 (d, JH-H = 8.4Hz, 2H), 7.63-7.65 (m, 2H), 7.47 (t, JH-H
141.2 141.40, 136.56, 129, 127.90, 127.12, 119.70, 113.40,
+
1
3
112.90, 21.20 (CH
3
). GC-MS (70 ev) m/z (relt.): 168 M
+
7
7
=
(C13
H
12), 153 [M-CH ] (C13H12). Anal. calcd. for C13H12: C
3
13
.6 Hz, 2H), 7.40-7.43 (m, 1H), 1.74 (s, 1H, OH). C NMR
, 150 MHz) δ 170.74 (CO), 146.45, 139.85, 130.73,
28.96, 128.29, 127.85, 127.32, 127.18. GC-MS (70 ev) m/z
92.81; H 7.19. Found: C 92.66; H 7.16.
(
CDCl
3
1
RESULTS AND DISCUSSION
+
+
(relt.): 198 M (C13
Calcd. for C13H10O2: C 78.77; H 5.09. Found: C 78.56; H
10 2
H O ), 169 [M-COH] (C12H9O). Anal.
t
Effect of solvents on the [( Bubpy)PdCl
2
] catalyzed
5
.01. m.p. (25-26°C).
-(4'-Methoxyphenyl)benzoate: (74.1 mg, 0.31 mmol,
Suzuki-Miyaura reaction: In initial investigation, we exami-
ned the coupling reaction of the model substrate 4-iodoanisole
(1 equiv.) with phenylboronic acid (1 equiv.) using 1 (1 mol
4
1
9 %), H NMR (CDCl
9
6
3
3
, 400 MHz) δ 8.12 (d, JH-H = 8.4, 2H),
.65 (d, JH-H = 8.4, 2H), 7.58-7.60 (m, 2H), 6.99-7.02 (m, 2H),
2 3
%) as a catalyst and K CO (3 equiv.) as a base with different
1
3
.87 (s, 3H, OCH ), 1.44 (s, 3H, CH
3
3
). C NMR (CDCl , 150
3
solvents at 80 ºC for 16 h as shown in Table-1. For instance,
the polar solvents gave the coupling product good to excellent
yield; this may be due to the high complex solubility. The
biphenyl product obtained in methanol resulted in excellent
yield (98 %) (Table-1, Entry-1) and a nearly quantitative
conversion was obtained from the reactions in ethanol (92 %)
(Table-1, Entry- 2). In contrast, when DMF was used as solvent,
low yield of the biaryl product were obtained, 46 %, (Table-1,
Entry-3). Whereas the nonpolar solvent toluene gave a poor
yield (42 %) (Table-1, Entry-4), but 1,4-dioxane and water
showed no activity for the reaction (Table-1, Entries-5, 6).
Therefore methanol was chosen for further study because it
was readily available, low cost and had a higher efficiency.
MHz) δ 167 (CO), 160.90, 140.91, 130.22, 129.40, 128.90,
28. 47, 127.30, 114.60, 56.00 (OCH ), 50.40 (C OOCH ).
1
3
3
+
+
GC-MS (70 ev) m/z (relt.) 242 M (C15
).Anal. calcd. For C14 : C 73.67; H 5.30. Found:
C 73.54; H 5.22. m.p. (253-255 °C).
-Hydroxy-4-(4'-methoxyphenyl)benzaldehyde: (57.8
14 3
H O ), 227 [M-Me]
(C
H
14 11
O
3
12 3
H O
2
1
mg, 0.25 mmol, 79 %), H NMR (CDCl , 600 MHz) δ 10.96
(s, 1H, CHO), 9.96 (s, 1H, OH), 7.72 (d, JH-H = 8.4 Hz, 1H),
3
6
2
.98-7 (m, 2H), 7.71-7.73 (m, 1H), 7.70 (d, JH-H = 2.4 Hz,
13
3
H), 7.47-7.49 (m, 2H), 3.86 (s, 3H). C NMR (CDCl , 150
MHz) δ 196.75 (CO), 160.50, 159.16, 135.46, 133.04, 131.89,
31.35, 127.66, 120.67, 118.04, 114.38, 55.38 (OCH ). GC-
1
3
+
+
12 3
MS (70 ev) m/z (relt.): 228 M (C14H O ), 211 [M-OH]
TABLE-1
EFFECT OF SOLVENTS ON THE [(Bubpy)PdCl ]
CATALYZED SUZUKI–MIYAURA REACTION
(
C
14
H
11
O
2
).Anal. calcd. for C14
H
12
O
3
: C 73.67; H 5.30. Found:
t
2
a
C 73.55; H 5.24. m.p. (114-115 °C).
l44
1
-Methoxy bipheny : (52.3 mg, 0.28 mmol, 70 %), H
2
I
B(OH)2
NMR (CDCl
3
, 400 MHz) δ 7.55-7.58 (m, 2H), 7.43-7.46 (m,
[(tBubpy)PdCl2]
2
1
1
1
H) 7.37-7.35 (m, 3H), 7.05-7.08 (m, 1H), 7.032-7.01 (m,
H), 3.85 (s, 3H, OCH
+
H3CO
1
). C NMR (CDCl
3
K CO \ Solvent
2
3
, 150 MHz) δ
3
3
o
8
0 C
60.29, 143.06, 141.70, 130.06, 129, 127.40, 127.30, 121.10,
+
OCH3
14.60, 112.98, 55.80. GC-MS (70 ev) m/z (relt.): 184 M
H
b
Yield (%)
Entry
Solvent
Methanol
Ethanol
DMF
Time (h)
16
+
12O), 169 [M-Me] (C12
(C
13
9
H ). Anal. calcd. for C13H12O: C
1
2
3
4
5
6
97
92
46
42
0
8
4.75; H 6.57. Found: C 84.57; H 6.55.
3
16
45
1
-Methoxyl biphenyl : (21.0 mg, 0.11 mmol, 28 %), H
16
Toluene
16
NMR (CDCl , 400 MHz) δ 7.65 (d, JH-H = 7.2 Hz, 2H), 7.48 (t,
3
1,4-Dioxane
Water
16
JH-H = 7.8 Hz, 2H), 7.42-7.39 (m, 2H), 7.23 (d, JH-H = 7.8 Hz,
16
0
1
H), 7.18 (s, 1H), 6.95 (d, JH-H = 8.4 Hz, 1H), 3.92 (s, 3H,
a
Conditions: Phenylboronic acid 1 equiv (50.0 mg, 0.41 mmol), 4-
iodoanisole 1 equiv (96.0 mg, 0.41 mmol), K CO 3 equiv (171 mg,
13
3 3
OCH ). C NMR (CDCl , 150 MHz) δ 160.50, 143.16, 141.40,
2
3
t
1.24 mmol), Catalyst ( BubpyPdCl ) 1 mol % (2.00 mg, 4.50 × 10
-3
1
34.17, 129.00, 128.40, 127.30, 126.80, 114.54, 112.90, 55.70
+
2
b
mmol), 80 ºC, Isolated yields
(
OCH
3
). GC-MS (70 ev) m/z (relt.): 184 M (C13H12O), 169
+
M-Me] (C12
[
H
9
). Anal. calcd. for C13
H12O: C 84.75; H 6.57.
Effect of Pd-complex containing substituted 2,2'-dipyridyl
ligands on Suzuki-Miyaura reaction: From Table-1, we
observe that MeOH is the best solvent for the coupling reaction.
Therefore, we used the same previous model with MeOH as a
solvent to explore the catalytic effect of series of palladium
complexes containing substituted 2,2'-dipyridyl derivatives
Found: C 84.66; H 6.53.
2
3
8
1
-Methyl biphenyl : (38.3 mg, 0.23 mmol, 51 %), H
NMR (CDCl
3
, 400 MHz) δ 7.56-7.59 (m, 2H), 7.44-7.41 (m,
4
3
1
H) 7.31-7.35 (m, 2H), 7.16 (d, JH-H = 7.6 Hz, 1H), 2.39 (s,
13
3 3
H, CH ). C NMR (CDCl , 150 MHz) δ 142.2, 142.1, 137.30,
36.60, 129.70, 129.00, 127.40, 127.30, 126.00, 136.70, 20.2
+
). GC-MS (70 ev) m/z (relt.): 168 M (C13
such as 4,4'-MeO
complex, [(MeObpy)PdCl
dichloride complex [(bpy)PdCl
2
-2,2'-dipyridyl-palladium(II) dichloride
] (2), 2,2'-dipyridyl-palladium(II)
] (3) and 4,4'-Me -2,2'-
(CH
CH
3
H12), 153 [M-
12: C 92.81; H 7.19. Found:
+
3
] (C13H12).Anal. calcd. for C13
H
2
C 92.79; H 7.14.
2
2

2
080 Mkhalid et al.
Asian J. Chem.
dipyridyl-palladium(II) dichloride complex [(Mebpy)PdCl
(
2
]
TABLE-3
EFFECT OF BASES ON THE [(Bubpy)PdCl ]
CATALYSED SUZUKI–MIYAURA REACTION
t
4), on the coupling of 4-iodoanisole with phenylboronic acid
2
a
2 3
in the presence of 1 mol % of catalyst and K CO as a base
I
B(OH)2
with MeOH as a solvent at 80 °C, Table-2.
Under the optimized conditions shown in Table-2, the
t
[( Bubpy)PdCl2]
+
OCH3
Base / MeOH
0 o
best results were obtained when complex 1 containing 4,4'-
t
8
C
Bu
2
-2,2'-dipyridyl was used as the ligand for the reaction; the
OCH3
b
Yield (%)
isolated yield of biaryl product was 97 % (Table-2, Entry-1).
Complex 2 containing 4,4'-MeO -2,2'-dipyridyl as ligand also
Entry
Base
K PO .3H O
Time (h)
2
1
2
3
4
5
6
7
8
9
3
4
2
2
98
97
95
94
76
81
81
74
54
gave good yield of biaryl product, 90 %, (Table-2, Entry-2).
However, our results showed a significant decrease in isolated
yield when complex 3 containing 2,2'-dipyridyl was used as a
ligand and the coupling product was 86 % (Table-2, Entry-3).
K
2
CO
3
16
16
16
16
16
16
16
16
2
Na CO3
KOH
NaOH
C(CH ) OK
3
3
Complex 4 containing 4,4'-Me
activity for the reaction, the yield of biaryl product was only
6 % (Table-2, Entry-4). Nevertheless, when PdCl (PhCN)
2
-2,2'-dipyridyl also showed less
CH COONa
3
Piperidine
6
2
2
Et N
3
a
was applied as the catalysts, the coupling reaction gave mode-
rate yield 85 % (Table-2, Entry-5). Interestingly, when we
carried out the Suzuki-Miyaura reaction in air under ligand-
free, only 72 % of the biaryl product was isolated (Table-2,
Entry-6). These results indicate that electron-rich bulky ligands
such as complex, 1, shows high efficiency in the coupling
reaction.
Conditions: Phenylboronic acid 1 equiv (50.0 mg, 0.41 mmol), 4-
t
Iodoanisole 1 equiv (96.0 mg, 0.41 mmol), Bases 3 equiv., [( Bubpy)
b
PdCl ] complex 1 mol % (2.00 mg, 4.50 × 10 mmol), 80 ºC. Isolated
-3
2
yield
t
( Bubpy)PdCl
[
2
] catalyzed Suzuki-Miyaura reaction of
arylhalides with arylboronic acids under aerobic condition:
From the optimized conditions, we observed that the coupling
reaction was proceeding smoothly in the presence of MeOH
as a solvent and 1 mol % of 1 as a catalyst with 3 equiv. of
TABLE-2
EFFECT OF Pd-COMPLEX CONTAINING SUBSTITUTED 2,2’-
DIPYRIDYL LIGANDS ON SUZUKI–MIYAURA REACTION
3 4 2
K PO ·3H O as a base.As a result, we conducted our optimized
condition with series of substituted arylhalides in the presence
of phenylboronic acid or 4-methoxyphenylbo-ronic acid as
sources of nucleophile. The results are summarized in Table-4.
Aryl iodides easily underwent the reaction to give the
desired products over than 97 % as a product (Table-4, Entries
1-5) and also with 2 mol % of the catalyst, the coupling of
iodoaniline with phenylboronic acid reached completion within
4 h (Entry-5). However, the reaction of 1-iodo-3,5-bis(trifluo-
romethyl)benzene with 4-methoxyphenylboronic acid resulted
in lower yields compared with other aryl iodides, giving only
I
B(OH)2
Pd-complex
+
OCH3
K2CO3 / MeOH
0 o
8
C
OCH3
b
Time (h) Yield (%)
Entry
Pd-Catalyst
t
[( Bubpy)PdCl ]
No.
1
1
2
3
4
5
6
16
16
16
16
16
16
97
90
86
66
85
72
2
[(MeObpy)PdCl2]
2
[(bpy)PdCl2]
3
[(Mebpy)PdCl2]
4
PdCl (PhCN)
2
5
2
94 % (Table-4, Entry-6). Low catalyst loading (0.1 mol %)
PdCl2
6
a
was also examined for electronically donating substrates but
low yield were observed after 12 h (Table-4, Entry-7). Good
to excellent yields were obtained in the coupling of aryl bromides
with phenylboronic acid or 4-methoxyphenylboronic acid and
were also efficiently carried out with 1-2 mol % loading of
the catalyst. The coupling reactions of electron-withdrawing
substituents such as 4-bromobenzoate, 4-bromobenzaldehyde,
1-bromo-4-tri-flouromethylbenzene, 4-bromoacetophenone,
4-bromonitryl-benzene and 4-bromonitrobenzene gave
excellent yields of functionalized biphenyls with a 1-2 mol %
of the catalyst within 2 h (Table-4, Entries 8-20). Again, with
low catalyst loading (0.1 mol %), the coupling of 4-bromo-
nitrobenzene with phenylboronic acid gave only 86 % of the
desired products after 16 h. But with 1 mol % of catalyst, the
yield reached 90 % after 2 h, Table-4, (Table-4, Enteries-21
and 19). Unexpectedly, the coupling of 4-bromoanisole with
phenylboronic acid could only achieve a comparable result
after we extended the reaction time to 16 h (Table-4, Entry-
20).
Conditions: Phenylboronic acid 1 equiv (50.0 mg, 0.41 mmol), 4-
Iodoanisole 1 equiv (96.0 mg, 0.41 mmol), K CO 3 equiv (171 mg,
2
3
b
.24 mmol), Pd-complexes 1 mol %, 80 ºC, Isolated yields
1
t
Effect of bases on the [( Bubpy)PdCl
2
] catalyzed Suzuki-
Miyaura reaction: With the preliminary results in mind, we
carried out our studies to determine how bases influenced the
coupling reaction. We studied the activities of series bases for
3 4 2
the coupling. Of the bases tested, only K PO ·3H O resulted
in high coupling yield after 2 h and the corresponding coupling
product was obtained in 98 % yield (Table-3, Entry-1) and
K
2
CO
Entry-2). Other bases, including C(CH
provided the product in moderate yield 81 % (Table-3, Entries-
, 7). Notably, NaOH, which is usually an effective base for
3
gave slightly less yields 97 % but after 16 h, (Table-3,
3
)
3
OK, CH COONa,
3
6
Suzuki cross-couplings reaction, proved to be less active giving
only 76 % (Table-3, Entry-5) and also piperidine was found
3
equally effective (Table-3, Entry-8). However, when Et N was
used for the reaction, under these conditions, poor yield was
obtained (Table-3, Entry-9). The results are summarized in
Table-3.
In addition, reactions of donating aryl bromides bearing
a functional group such as hydroxyl or amino groups afforded

t
2
Vol. 26, No. 7 (2014) Suzuki-Miyaura Cross-Coupling Reaction Catalyzed by 4,4'- Bu -2,2'-dipyridyl-palladium(II) Dichloride Complex 2081
the coupling products in moderate to poor yields. For example,
the reaction of 4-bromophenol with phenylboronic acid and
Conclusion
In summary, a stable and efficient complex was applied
for high yield Suzuki-Miyaura cross-coupling reaction of
t
aryliodide and bromide with phenylboronic acid. 4,4'- Bu
4
-methoxyphenylboronic acid gave only 77 and 87 % respec-
tively after we extended the time of the reaction with increasing
the concentration of the catalyst (Table-4, Entries 22 and 23).
But with the reaction of 4-bromaniline and 4-methoxyphenyl-
boronic acid the conversion was only 36 % (Table-4, Entry-
2
-
2
,2'-dipyridyl ligand showed high efficiency for the coupling
and it was an attractive alternative to the phosphine ligands.
The catalytic system showed high efficiency for the coupling
of activated and deactivated para-aryl iodides and bromide
with phenylboronic acid or methoxphenylboronic acid in
aqueous solvent under aerobic conditions. But our condition
is not suitable for arylchloride and also shows less reactivity
for steric aryl halide.
2
4). Furthermore, the reactions of 2-bromobenzaldehyde
proceeded slower than 4-bromobenzal-dehyde and the reaction
gave only 60 % of coupling product over a period of 4 h (Table-
4
, Entry-25) indicating that the steric hindrance plays some
roles in the coupling reaction. The hindered substrates, 2- and
-bromo anisole and also 2- and 3-bromotoluene, showed a
3
ACKNOWLEDGEMENTS
poor reactivity (Table-4, Entry 26-29) explaining that our
optimized condition is not suitable for the steric hindrance
substituted aryl halide. In addition, no product was observed
in the coupling of 4-chlorobenzaldehyde with phenylboronic
acid within 16 h (Table-4, Entry-30).
This paper was funded by the Deanship of Scientific
Research (DSR), KingAbdulaziz University, Jeddah, Kingdom
ofSaudiArabiaundergrantnumber(130/144).Theauthors, therefore,
acknowledged with thanks DSR for technical and financial support.
TABLE-4
( Bubpy)PdCl ] CATALYSED SUZUKI–MIYAURA REACTION OF ARYLHALIDES WITH ARYLBORONIC ACIDS
t
[
2
X
B(OH)2
t
[
( Bubpy)PdCl ]
2
+
K PO .3H O
3
4
2
R1
R2
MeOH \ Water
o
R1
R2
8
0 C
2
R
1
b
Entry
R
X
I
Pd (mol %)
Time (h)
Yield
%
1
2
3
4
5
6
7
8
9
4-MeO
4-COOH
4-MeO
3,5-CF3
4-NH2
3,5-CF3
4-MeO
4-NH2
4-COOMe
4-CF3
MeO
H
1
1
2
2
100
99
I
I
H
1
2
98
d
97
I
H
1
2
I
H
2
4
99
d
94
I
OMe
H
1
2
I
0.1
2
16
4
93
e
99
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
2-Br
3-Br
3-Br
2-Br
Cl
H
MeO
H
1
2
99
99
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
e
99
4-CF3
OMe
H
1
2
4-COMe
4-CN
1
2
99
98
99
98
98
91
98
90
96
86
H
1
2
4-CN
H
2
2
4-CN
MeO
MeO
H
1
2
4-CHO
4-CHO
4-NO2
4-NO2
4-OMe
4-NO2
4-OH
1
2
1
2
MeO
H
1
2
1
2
H
1
16
16
4
H
0.1
2
c,e
H
77
c,e
4-OH
MeO
MeO
H
2
4
87
e
4-NH2
2-CHO
4-OMe
4-OMe
4-CH3
2
2
36
e
1
4
60
d
H
2
4
69
d
H
2
4
28
d
H
1
4
51
d
4-CH3
H
1
4
41
4-CHO
H
2
16
0
a
t
Conditions: Phenylboronic acid or methoxyphenylboronic acid 1 equiv (50.0 mg, 0.41 mmol; 0.0032 mmol), aryl halides 1 equiv., [( Bubpy)PdCl ]
2
-3
-3
complex 1 or 2 mol % (2.00 mg, 4.50 × 10 mmol or 4.00 mg, 8.98 × 10 mmol), K PO .3H O 3 equiv., 80 ºC Isolated yields Phenylboronic
b
c
3
4
2
d
acid 1.2 equiv (60.0 mg, 0.49 mmol) Oil Yield of biphenyl determined by GC
e

2
082 Mkhalid et al.
Asian J. Chem.
2
5. C. Nájera, J. Gil-Moltó, S. Karlström and L.R. Falvello, Org. Lett., 5,
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