Air-stable Pd(II) catalysts with cryptand-22 ligand for convenient and?efficient Suzuki cross-coupling reactions

Article abstract of DOI:10.1016/j.tet.2008.02.083

Air-stable Pd(II) catalysts with cryptand-22 ligand was easily handled in atm air at room temperature for Suzuki cross-coupling reactions of aryl bromides with arylboronic acids both containing electron-withdrawing and electron-donating groups. Generally, reactions proceeded fast to completion in 2 h to give high product yields. Our Pd(OAc)₂/cryptand-22 catalyst is unique, since the reaction solution remained yellow during reaction period and air-stable without formation of Pd black as usually observed for ordinary simple amine ligands.

Full text of DOI:10.1016/j.tet.2008.02.083

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4268e4274
www.elsevier.com/locate/tet
Air-stable Pd(II) catalysts with cryptand-22 ligand for convenient
and efficient Suzuki cross-coupling reactions
*
Ming-Hui Hsu, Chien-Ming Hsu, Ju-Chun Wang, Chia-Hsing Sun
Department of Chemistry, Soochow University, Taipei, Taiwan, ROC
Received 22 November 2007; received in revised form 22 February 2008; accepted 26 February 2008
Available online 29 February 2008
Abstract
Air-stable Pd(II) catalysts with cryptand-22 ligand was easily handled in atm air at room temperature for Suzuki cross-coupling reactions of
aryl bromides with arylboronic acids both containing electron-withdrawing and electron-donating groups. Generally, reactions proceeded fast to
completion in 2 h to give high product yields. Our Pd(OAc)2/cryptand-22 catalyst is unique, since the reaction solution remained yellow during
reaction period and air-stable without formation of Pd black as usually observed for ordinary simple amine ligands.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Suzuki cross-coupling reactions.12 However, Pd catalysts are
known to aggregate easily and form Pd black, which may
lead to a considerable loss of catalytic activity.13 To overcome
this intrinsic problem of homogeneous Pd catalysis, we ex-
plored a new class of Pd catalyst system based on azacrown
ether. Although it is well-known that the importance of crown
ethers lies in their remarkable ability to complex cations, partic-
ularly those in the alkali and alkaline earth metal families,14
it will be intriguing to investigate the specific binding properties
by these macrocycles, which may help to stabilize Pd catalysts
while retaining its catalytic reactions. To extend the scope of
amines, we plan to evaluate the palladium catalytic systems
composed of a series of commercially available azacrown
ethers as phosphine-free ligands. The flexible macrocyclic
and chelating effect of these N- or O-containing ligands may as-
sist in stabilizing while activating the catalytic species. Herein
we report a new homogeneous palladium catalyst system of
Pd(II)/diazacrown ether that suppresses the Pd black formation
even under 1 atm air. It is air-stable and highly efficient catalyst
system for the Suzuki cross-coupling reaction of aryl halides
and arylboronic acids.
The Suzuki cross-coupling reaction has been proved to be
one of the most widely used synthetic tools in synthesis of biar-
yls,1,2 recurring structural units in many natural products, phar-
maceuticals, and advanced materials3 from aryl halides and
boronic acids. Normally suitable ligand is required to stabilize
palladium catalyst precursor. Palladium complexes with ter-
tiary phosphine ligands4 are traditionally employed to activate
the catalysts in Suzuki cross-coupling reaction with excellent
results. However, phosphine ligands used are sensitive to air
oxidation and therefore require air-free condition to maximize
the catalytic performance, which causes significant inconve-
nience in handling and poses some limitations on synthetic ap-
plications. Therefore, palladium-catalysts with phosphine-free
ligands such as nucleophilic N-heterocyclic carbenes,5 2-aryl-
2-oxazolines,6 diazabutadienes,7 thiourea,8 and N,N-dimethyl-
b-alaninate9 and ligand-free condition such as Pd(OAc)2/
TBAB/PEG-400 system would be desired.10 Amines are gener-
ally used as bases in cross-coupling reactions, which can also
serve to stabilize the reactive palladium intermediates.11 Until
recently, only a few papers have been reported to employ simple
amines (1ꢀ, 2ꢀ, and 3ꢀ) as ligands in palladium-catalyzed
2. Results and discussion
* Corresponding author. Tel.: þ886
2
28819471x6807; fax: þ886
2
As illustrated in Table 1, several commercially available aza-
crown ethers were screened as potential ligands, using a model
28811053.
E-mail address: chsun@mail.scu.edu.tw (C.-H. Sun).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.083

M.-H. Hsu et al. / Tetrahedron 64 (2008) 4268e4274
4269
Table 1
Screening of ligandsa
tightly as to deactivate the catalyst. This is due to the intrinsic
flexibility of macrocyclic ring containing four peripheral oxy-
gen atoms assisting as required to protect the palladium atom
from aggregation into Pd black. Cryptand-22 is thus the supe-
rior ancillary ligand for palladium-catalyzed cross-coupling
reactions as compared to simple amines.
Br
2 mole% Pd(OAc)2
2 mole% L
K3PO4 / EtOH
RT , 2h
+
H3CO
(HO)2B
H3CO
Base was required for Suzuki cross-coupling reaction
of aryl halides and arylboronic acids, since very low yields
were obtained in the absence of base (Table 2). Among the ba-
ses screened for their influence on the yields of reaction, use of
K3PO4 (93%) with mild basicity resulted in the best conver-
sions to the product and was used in all subsequent reactions.
A significant cation effect was observed when carbonates
(85% for K2CO3 vs 10% for Na2CO3) and hydroxides (92%
for KOH vs 86% for NaOH) were used as bases. Although
KOH worked as well, it was not chosen owing to its strong ba-
sicity. In many cases, Cs2CO3 and KF, usually the best choice
of bases, proved to be less effective, leading to only 63 and
64% isolated yields, respectively.
Entry
L
Isolated
yield (%)
Pd black
formation
1
2
3
4
Aza-12-crown-4 ether
Aza-15-crown-5 ether
Aza-18-crown-6 ether
1,4,10-Trioxa-7,13-diaza-
cyclopentadecane
Cryptand-22
90
88
91
86
ꢁ
ꢁ
þ
ꢁ
5
6
93
91
ꢁ
þ
4,7,13,16,21,24-Hexaoxa-1,10-
diazabicyclo[8.8.8]-hexacosane
(2,2,2,-Kryptafix)
Aniline
7
90
88
89
67
70
0
þ
þ
þ
þ
þ
ꢁ
8
Diisopropylamine
Dicyclohexylamine
Triethylamine
9
10
11
12
a
Table 2
Base effecta
Pyridine
2,2-Bipyridine
Br
)
2 mole% Pd(OAc 2
Reaction conditions: 1.0 mmol of aryl bromide, 1.5 mol of boronic acid,
2 mole% Cryptand-22
+
2.0 mmol of K3PO4, 5.0 mL of EtOH.
Base / EtOH
RT , 2h
H3CO
(HO)2B
H3CO
cross-coupling reaction of 4-bromoanisole and phenylboronic
acid in the presence of 2 mol % of Pd(OAc)2, 4 mol % of ligand
(entries 1e3) or 2 mol % of ligand (entries 4 and 5), and
2.0 equiv of K3PO4 in EtOH in atmospheric air at room temper-
ature for 2 h. Generally, high yields were obtained for the
aerobic coupling reactions. Notably, the catalytic reactions pro-
ceeded very fast in the yellow solution containing active palla-
dium species, which was stable (entries 1, 2, 4, 5) without
formation of Pd black, while Pd black formed significantly
within 5 min when simple amines, such as triethylamine, dicy-
clohexylamine, diisopropylamine, aniline, and pyridine (entries
7e11), were used as ligands. Pd black also formed in 30 min
when cryptand-22 and 4,7,13,16,21,24-hexaoxa-1,10-diazabi-
cyclo-[8.8.8]-hexacosane (2,2,2,-Kryptafix) were used as li-
gands (entries 2 and 6). It indicates that azacrown ethers with
smaller ring system of 12 or 15 atoms (entries 1 and 2) can
stabilize palladium catalyst better than larger ring system of
18 atoms containing only one nitrogen atom (entry 3) or two ni-
trogen atoms of 3ꢀ amine (entry 6). Both bidentate diazacrown
ethers, i.e., 1,4,10-trioxa-7,13-diaza-cyclopentadecane (entry
4) and cryptand-22 (entry 5) with either 15 or 18 atoms on
the ring were also capable of stabilizing the palladium catalyst
through loosely chelating effect. The trend in stabilizing ability
on palladium catalyst in situ reflects a trade-off between ring
size and coordinating ability. Based on the highest yields and
the best air-stability, Pd(OAc)2/cryptand-22 catalyst is unique,
since the yellow reaction solution of which remained yellow
for at least two weeks. And even on the top of silica-gel column
after being chromatographed, the yellow band was air-stable
without formation of Pd black. Cryptand-22, a bidentate ligand,
is capable of chelating palladium atom adequately, yet not too
Entry
Base
Yieldb (%)
1
2
3
4
5
6
7
8
9
a
No base
Na2CO3
K2CO3
Cs2CO3
K3PO4
K2HPO4
KF
5
10
85
63
91/18c
6.5
64
KOH
NaOH
92
86
Reaction conditions: 1.0 mmol of aryl bromide, 1.5 mmol of boronic acid,
2.0 mmol of base, 5.0 mL of EtOH.
b
Isolated yield.
K3PO4 (0.5 mmol).
c
Notably, solvents were found to have profound effect on
palladium catalytic activity (Table 3). Attempts on optimiza-
tion with respect to solvent showed that the reaction proceeded
best in EtOH (93%), and other protic solvents such as MeOH
(77%) and 1-PrOH (87%) produced lower yields than EtOH
with the lowest yield for sterically bulky 2-PrOH (34%). All
other aprotic nonpolar or polar solvents such as toluene, ace-
tone, dioxane, THF, and DMF proved to be ineffective with
no more than 1.3% yields. The optimized conditions thus in-
clude EtOH solvent, K3PO4 base, cryptand-22, and Pd(OAc)2
catalyst.
The catalytic activities were found not too sensitive to
the change in ratios of ligand/Pd (Table 4). Without ligand,
cross-coupling reaction gave low yield of 58%. No effect
was observed on the reaction yields (91e93%) with ligand/
Pd ratios in 0.5e2. The reaction yields started to drop to

4270
M.-H. Hsu et al. / Tetrahedron 64 (2008) 4268e4274
Table 3
Solvent effecta
reverse electronic effect was observed, where electron-donat-
ing arylboronic acid gave higher yields (43%) than that of
electron-withdrawing arylboronic acid (30%) (entry 13 vs en-
try 10), but both produced lower yield than unsubstituted aryl-
boronic acid (68%) (entry 9). In a typical reaction mechanism
proposed for Suzuki coupling reaction, arylboronic acid reacts
with base to produce borate, an arylboronic acidebase adduct,
followed by transmetallation step where aryl group is trans-
ferred to palladium. Presumably, a compromise is required
on the electronic properties of the acidity of arylboronic acid
to form borate species and basicity of which for aryl transme-
tallation to palladium center. Either electron-withdrawing
or electron-donating groups inhibit one of the above two steps.
Under the same reaction conditions, similar results were ob-
tained when Na2PdCl4 was utilized as Pd source instead of
Pd(OAc)2 (Table 6 entries 1e8). When complex 1 was used
as Pd source, the reaction yields were 90e95% (Table 6
entries 9e11), and no Pd black was observed. (Cryptand-
22)PdCl2, complex 1 a yellow solid, which is stable in the
air, was prepared from Pd(OAc)2 and cryptand-22 in ethanol
Br
2 mole% Pd(OAc)2
2 mole% Cryptand-22
+
Base / EtOH
RT , 2h
H3CO
(HO)2B
H3CO
Entry
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
9
a
Toluene
Acetone
Dioxane
DMF
1.2
0.7
1
0.6
1.3
77
THF
MeOH
EtOH
91
87
1-PrOH
2-PrOH
34
Reaction conditions: 1.0 mmol of aryl bromide, 1.5 mmol of boronic acid,
2.0 mmol of K3PO4, 5.0 mL of solvent.
b
Isolated yield.
1
and its structure was fully characterized by H, 13C NMR, el-
82% at ratio of 4, and further down to 77% at even higher ratio
of 8. The low sensitivity of catalytic activity to the variation of
ligand/Pd reflects a weaker binding power of cryptand-22 than
ordinary tertiary phosphines. For homogeneous catalytic reac-
tions, it may partly account for the higher catalytic activity of
the former than the latter at room temperature. As illustrated in
Table 5, the palladium-catalyzed Suzuki coupling reaction
with diazacrown ether as ancillary ligand proved exceptionally
active. This reaction can tolerate a variety of functionalities
including NO2, CHO, and CN. Generally, the electronic prop-
erties of aryl bromides did not influence significantly the ease
of the coupling reactions, and reactions proceeded very fast
and resulted in high yields in 2 h for both electron-deficient
and electron-rich aryl bromides. When reaction time was
shortened to 15 min, electron-deficient aryl bromide was
found consumed faster than electron-rich aryl bromides (entry
1 vs entry 9). Notably, in contrast to aryl bromides, electronic
effect was more pronounced when substituted arylboronic acid
was allowed to react with p-bromoanisole in 15 min, and
emental analyses, and X-ray crystallography (shown in Fig. 1).
3. Conclusion
In conclusion, we have demonstrated that air-stable Pd(II)
catalysts with cryptand-22 as ligand were very efficient and
conveniently handled in the air at room temperature. Gener-
ally, Suzuki cross-coupling reactions of aryl bromides with
arylboronic acids both containing electron-withdrawing and
electron-donating groups proceeded fast in 2 h to give high
yields. Our in situ catalytic system of Pd(II)/cryptand-22 cata-
lyst is unique, since the reaction solution remained yellow and
air-stable for at least one month without formation of Pd black
as usually observed for ordinary simple amine ligands in sev-
eral minutes. The utilization of cryptand-22 as the ancillary li-
gand proved to be effective in stabilizing the reactive
palladium intermediates. The isolation of complex 1 may
help to understand the reaction mechanism. The reaction pro-
ceeded equally well as in situ catalytic system when carried
out in the presence of well-defined complex 1. Studies to
delineate the origin of its air-stability and to explore catalyst
utility for other reactions are currently in progress.
Table 4
Effect of ratios of ligand to Pda
Br
)
X mole% Pd(OAc 2
Y mole% Cryptand-22
+
Base / EtOH
RT , 2h
4. Experimental
H3CO
(HO)2B
4.1. General remarks
H3CO
Entry
X
Y
Yieldb (%)
1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were
recorded on a Bruker AVA-300 spectrometer with TMS as
internal standard. All reagents were used directly as obtained
commercially. All products are known.
1
2
3
4
5
6
a
2
2
2
2
2
2
0
1
58
93
91
92
82
77
2
4
8
16
4.1.1. Typical experimental procedure for the palladium-
catalyzed Suzuki cross-coupling reaction
Under an atmosphere of air, a mixture of aryl bromide
(1 mmol), arylboronic acid (1.5 mmol), Pd(II) catalyst
Reaction conditions: 1.0 mmol of aryl bromide, 1.5 mmol of boronic acid,
2.0 mmol of K3PO4, 5.0 mL of EtOH.
b
Isolated yield.

M.-H. Hsu et al. / Tetrahedron 64 (2008) 4268e4274
4271
Table 5
Pd(OAc)2/cryptand-22-catalyzed cross-coupling of aryl bromides with various arylboronic acidsa
N
H
O
O
O
O
Br
Y
X
H
N
+
Pd(OAc)2,RT , 2 h, Air
K3PO4, EtOH
X
(HO)2B
Y
Entry
1
Aryl bromide
Boronic Acid
Product
Timeb (h)
2/0.25
Yieldc (%)
95/75
NC
Br
Br
Br
B(OH)2
NC
O2N
NO2
2
3
2
2
90
92
NC
B(OH)2
B(OH)2
CH3
NC
O2N
O2N
H3C
4
2
83
O2N
Br
B(OH)2
B(OH)2
B(OH)2
O2N
O2N
O2N
5
6
2
2
90
86
Br
Br
HOC
HOC
HOC
HOC
7
2
90
B(OH)2
B(OH)2
B(OH)2
Br
Br
8
2
93
H3C
H3C
9
2/0.25
93/68
85/30
84
H3CO
H3CO
H3CO
H3CO
Br
H3CO
10
11
12
2/0.25
Br
Br
Br
NC
B(OH)2
B(OH)2
B(OH)2
H3CO
CN
2
2
F3C
H3CO
H3CO
CF3
89
13
2/0.25
92/43
H3CO
Br
H3CO
B(OH)2
H3CO
OCH3
a
Reaction conditions: 1.0 mmol of aryl bromide, 1.5 mmol of arylboronic acid, 2.0 mmol of K3PO4, 2 mol % of Pd(OAc)2, 2 mol % of cryptand-22, 5.0 ml of
EtOH.
b
Time not optimized.
Isolated yield.
c
(2 mol %), ligand (2 mol % or as indicated), base (2 mmol),
and solvent (5 mL) were added to a 25 mL round-bottom flask
and stirred at room temperature for 2 h. After ordinary workup
and being evaporated by rotary evaporator, the residue was pu-
rified by column chromatography to give the required biphenyl
derivative (hexane/ethyl acetate).
J¼4.5 Hz, 2H), 7.48 (t, J¼7.5 Hz, 2H), 7.42e7.49 (m, 1H);
13C NMR (75 MHz, CDCl3): d 145.6, 139.1, 132.5, 129.0,
128.6, 127.7, 127.2, 118.9, 110.8.
4.1.2.2. Entry 2: 4-cyano-30-nitrobiphenyl.16 Slightly yellow
solid, mp 172e173 ꢀC; 1H NMR (300 MHz, CDCl3):
d 8.46 (dd, J¼1.8, 1.8 Hz, 1H), 8.28 (ddd, J¼8.4, 0.9,
1.2 Hz, 1H), 7.92 (ddd, J¼7.8, 0.9, 0.9 Hz, 1H), 7.80 (d,
J¼8.1 Hz, CDCl3), 7.74 (d, J¼8.4 Hz, 2H), 7.68 (dd,
J¼8.1, 7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 148.7,
142.9, 140.7, 133.0, 132.9, 1320.2, 127.8, 123.3, 122.1,
118.4, 112.3.
4.1.2. Analytical data for biphenyl derivatives (Table 5)
4.1.2.1. Entry 1: 4-phenylbenzonitrile.15,17 Slightly yellow
1
solid, mp 140e142 ꢀC; H NMR (300 MHz, CDCl3): d 7.73
(d, J¼8.5 Hz, 2H), 7.68 (d, J¼8.5 Hz, 2H), 7.59 (t,

4272
M.-H. Hsu et al. / Tetrahedron 64 (2008) 4268e4274
Table 6
Na2PdCl4/cryptand-22-catalyzed cross-coupling of aryl bromides with various arylboronic acidsa
N
H
O
O
O
O
Br
Y
X
H
N
+
Na2PdCl4,RT , 2 h, Air
K3PO4, EtOH
X
(HO)2B
Y
Entry
Aryl bromide
Boronic Acid
B(OH)2
Product
Timeb (h)
Yieldc (%)
1
2
3
4
5
6
7
8
2
2
2
2
2
2
2
2
97
91
89
95
93
94
91
93
NC
Br
Br
Br
Br
Br
Br
Br
Br
NC
O2N
O2N
HOC
H3C
B(OH)2
B(OH)2
HOC
H3C
B(OH)2
H3CO
H3CO
H3CO
H3CO
B(OH)2
H3CO
NC
B(OH)2
B(OH)2
B(OH)2
H3CO
CN
H3CO
H3CO
H3CO
OCH3
9
2
2
95d
90d
NC
Br
Br
B(OH)2
NC
10
HOC
B(OH)2
HOC
11
2
95d
H3CO
Br
B(OH)2
H3CO
a
Reaction conditions: 1.0 mmol of aryl bromide, 1.5 mmol of arylboronic acid, 2.0 mmol of K3PO4, 2 mol % of Na2PdCl4, 2 mol % of cryptand-22, 5.0 ml of
EtOH.
b
c
d
Time not optimized.
Isolated yield.
(Cryptand-22)PdCl2 is used.
4.1.2.3. Entry 3: 4-nitrobiphenyl.17e19 White solid, mp 114e
1
115.5 ꢀC; H NMR (300 MHz, CDCl3): d 8.30 (d, J¼8.4 Hz,
2H), 7.74 (d, J¼8.7 Hz, 2H), 7.62 (dd, J¼8.1, 1.5 Hz, 2H),
7.53e7.41 (m, 3H); 13C NMR (75 MHz, CDCl3): d 147.6,
147.0, 138.7, 129.1, 128.9, 127.8, 127.4, 124.1.
4.1.2.4. Entry 4: 20-methyl-4-nitrobiphenyl.16 White solid, mp
100e102 ꢀC; 1H NMR (300 MHz, CDCl3): d 8.27 (d,
J¼8.7 Hz, 2H), 7.84 (d, J¼8.1 Hz, 2H), 7.31e7.20 (m, 4H),
2.28 (s, 3H); 13C NMR (75 MHz, CDCl3): d 148.8, 146.8,
139.6, 135.0, 130.7, 130.1, 129.4, 128.4, 126.1, 123.4, 20.3.
4.1.2.5. Entry 5: 3-nitrobiphenyl.16 White solid, mp 55e
57 ꢀC; 1H NMR (300 MHz, CDCl3): d 8.45 (dd, J¼2.1,
1.8 Hz, 1H), 7.19 (dd, J¼8.1, 2.1 Hz, 1H), 7.91 (d,
J¼7.5 Hz, 1H), 7.61 (dd, J¼8.1, 8.4 Hz, 3H), 7.52e7.42 (m,
3H); 13C NMR (75 MHz, CDCl3): d 148.7, 142.9, 138.6,
133.0, 129.7, 129.1, 128.5, 127.1, 122.02, 121.95.
Figure 1. ORTEP drawing of complex 1. Thermal ellipsoids shown at 30%
probability level. Hydrogens are omitted for clarity.

M.-H. Hsu et al. / Tetrahedron 64 (2008) 4268e4274
4273
4.1.2.6. Entry 6: 4-biphenylaldehyde.15,17 White solid, mp
59e60 ꢀC; 1H NMR (300 MHz, CDCl3): d 10.05 (s, 1H),
7.95 (d, J¼8.1 Hz, 2H), 7.75 (d, J¼8.1 Hz, 2H), 7.65e7.62
(m, 2H), 7.50e9.39 (m, 3H); 13C NMR (75 MHz, CDCl3):
d 147.6, 147.0, 138.7, 129.1, 128.9, 127.8, 127.4, 124.1.
reaction mixture was filtered, the yellow precipitate was then
dissolved and filtered through a filter paper by DCM. The sol-
vent was removed under reduced pressure. The resulting solid
was collected and recrystallized from dichloromethane/diethyl
ether to give complex 1 as a yellow-orange solid (1.17 g, yield:
70%). Mp 196e198 ꢀC; 1H NMR (300 MHz, CDCl3): d 6.94e
6.92 (m, 2H), 2.82e2.79 (m, 4H), 2.48e2.36 (m, 4H), 1.91e
1.66 (m, 30H), 1.29e1.17 (m, 12H); 13C NMR (75 MHz,
CDCl3): d 68.3, 66.1, 52.0. Anal. Calcd for C12H26N2O4Pd:
C, 32.78; H, 5.96; N, 6.37. Found: C, 32.40; H, 6.33; N, 6.34.
4.1.2.7. Entry 7: 3-biphenylaldehyde.16 1H NMR (300 MHz,
CDCl3): d 10.08 (s, 1H), 8.10 (s, 1H), 8.49 (dd, J¼7.5,
1.8 Hz, 2H), 7.64e7.58 (m, 3H), 7.50e7.37 (m, 3H); 13C
NMR (75 MHz, CDCl3): d 192.3, 142.1, 139.6, 133.0, 129.4,
128.9, 128.7, 128.1, 127.9, 127.1.
4.1.4. Crystal structure data experimental
4.1.2.8. Entry 8: 4-methylbiphenyl.15,18 White solid, mp 44e
46 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.50 (d, J¼7.5 Hz,
2H), 7.43 (d, J¼8.1 Hz, 2H), 7.35 (dd, J¼7.5, 7.8 Hz, 2H),
7.25 (dd, J¼7.5, 7.5 Hz, 1H) 7.18 (d, J¼8.1 Hz, 2H), 2.40
(s, 3H); 13C NMR (75 MHz, CDCl3): d 141.1, 138.3, 137.0,
129.4, 128.7, 127.0, 126.9, 21.1.
Structure of complex 1, (cryptand-22)PdCl2, has been unam-
biguously identified by X-ray crystallography. Crystals suitable
for X-ray structure analysis were grown from DCM/ether. Ayel-
low crystal with dimensions of 0.5ꢂ0.5ꢂ0.04 mm was mounted
on a glass fiber on a Siemens P4 diffractometer equipped with
monochromated Mo Ka radiation. Intensity data were collected
and reduced by using well-established software package
XSCANS.22 The structure was solved by direct method and
was refined using SHELXTL.23 All non-hydrogen atoms were
located from difference maps and refined anisotropically.
H-atoms attached on the two N-atoms were found from differ-
ence maps and isotropically refined as normal atoms. The rest
of the H-atoms were placed at idealized positions. The final re-
siduals of the refinement were R1¼0.0431, wR2¼0.0969, and
S¼1.041. Crystal data in CIF format can be found in the supple-
mentary data.
4.1.2.9. Entry 9: 4-methoxybiphenyl.17,19 White solid, mp 82e
84 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.54 (dd, J¼7.2,
6.9 Hz, 4H), 7.38 (dd, J¼7.5, 7.5 Hz, 2H), 7.30 (dd, J¼7.2,
7.2 Hz, 1H), 6.97 (d, J¼6.9 Hz, 2H), 3.85 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 159.1, 140.8, 133.7, 128.7, 128.1,
126.7, 126.6, 114.1, 55.3.
4.1.2.10. Entry 10: 4-cyano-40-methoxybiphenyl.18,20 White
1
solid, mp 178e180 ꢀC; H NMR (300 MHz, CDCl3): d 7.7e
7.62 (m, 2H), 7.55e7.52 (m, 2H), 7.02 (t, 2H), 6.9 (t, 2H),
3.86 (s, 3H); 13C NMR (75 MHz, CDCl3): d 160.2, 145.2,
132.5, 131.5, 128.3, 127.1, 119.1, 114.5, 110.1, 55.42.
5. Supplementary data
Crystallographic data for the structure of complex 1 has
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 665828.
Copies of the data can be obtained, free of charge, on applica-
tion to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[fax:þ44(0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk.
4.1.2.11. Entry 11: 4-trifluoromethyl-40-methoxybiphenyl.17,18
1
White solid, mp 122e124 ꢀC; H NMR (300 MHz, CDCl3):
d 7.67e7.64 (m, 4H), 7.55e7.50 (d, J¼8.7 Hz, 2H), 7.0e
6.97 (d, J¼8.6 Hz, 2H), 3.85 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 159.8, 144.3, 132.2, 128.4, 126.8, 126.2, 125.6,
122.6, 114.4, 55.37.
Acknowledgements
4.1.2.12. Entry 12: 4-tert-butyl-40-methoxybiphenyl.21 White
1
solid, mp 127e128 ꢀC; H NMR (300 MHz, CDCl3): d 7.54
We thank Soochow University for support of this work.
References and notes
(d, J¼8.9 Hz, 2H), 7.49 (d, J¼8.7 Hz, 2H), 7.43 (d,
J¼8.7 Hz, 2H), 6.98 (d, J¼8.9 Hz, 2H), 3.85 (s, 3H), 1.37
(s, 9H); 13C NMR (75 MHz, CDCl3): d 158.9, 149.6, 137.9,
133.6, 128.0, 126.3, 125.6, 114.1, 55.3, 34.5, 31.4.
1. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b) Suzuki, A.
Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang, P. J.,
Eds.; Wiley-VCH: Weinheim, 1998; pp 49e97 and references therein;
(c) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369;
(d) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int. Ed.
1998, 37, 481; (e) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10;
(f) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 36, 3437.
2. (a) Stanforth, S. P. Tetrahedron 1998, 54, 263; (b) Suzuki, A. J. Organo-
met. Chem. 1999, 576, 147; (c) Kotha, S.; Lahiri, K.; Kashinath, D. Tetra-
hedron 2002, 58, 9633.
4.1.2.13. Entry 13: 4,40-dimethoxybiphenyl.15,18 White solid,
1
mp 180e182 ꢀC; H NMR (300 MHz, CDCl3): d 7.49e7.46
(d, J¼9.3 Hz, 4H), 6.97e6.94 (d, J¼8.7 Hz, 4H), 3.84 (s,
6H); 13C NMR (75 MHz, CDCl3): d 158.7, 133.5, 127.7,
114.1, 55.4.
4.1.3. Synthesis of (cryptand-22)PdCl2
3. (a) Smith, G. B.; Dezeny, G. C.; Hughes, D. L.; King, A. O.; Verhoeven,
T. R. J. Org. Chem. 1994, 59, 8151; (b) Nicolaou, K. C.; Boddy, C. N. C.;
Brase, S.; Winssinger, N. Angew. Chem., Int. Ed. 1999, 38, 2096.
4. (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513; (b)
Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387; (c) Littke,
Cryptand-22 (118.1 mg, 0.45 mmol) was added into a solu-
tion of Na2PdCl4 (117.7 mg, 0.4 mmol) in ethanol (30 mL) at
room temperature. The mixture was stirred at room temperature
for 2.5 h, during which a yellow precipitate appeared. After the

4274
M.-H. Hsu et al. / Tetrahedron 64 (2008) 4268e4274
A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020; (d) Zapf, A.;
Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed. 2000, 39, 4153; (e)
11. Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J. Am. Chem. Soc.
2003, 125, 13978.
Wolfe, J. P.; Buchwald, S. L. Angew. Chem., Int. Ed. 1999, 38, 2413;
(f) Wolfe, J. P.; Singer, R. A.; Yang, B.; Buchwald, S. L. J. Am. Chem.
Soc. 1999, 121, 9550; (g) Yin, J.; Rainka, M. P.; Zhang, X.; Buchwald,
S. L. J. Am. Chem. Soc. 2002, 124, 1162; (h) Shae, B. L.; Perera, S. D.
Chem. Commun. 1998, 1863; (i) Feuerstein, M.; Laurenti, D.; Bougeant,
C.; Doucet, H.; Santelli, M. Chem. Commun. 2001, 325; (j) Feuerstein,
M.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2001, 42, 6667; (k)
Shaughnessy, K. H.; Booth, R. S. Org. Lett. 2001, 3, 2757; (l) Nishimura,
M.; Ueda, M.; Miyaura, N. Tetrahedron 2002, 58, 5779.
12. (a) Tao, B.; Boykin, D. W. Tetrahedron Lett. 2003, 44, 7993; (b) Li, J.-H.;
Liu, W.-J. Org. Lett. 2004, 6, 2809.
13. (a) van Leeuwen, P. W. N. M. Appl. Catal., A 2001, 212, 61; (b) Parshall,
G. D.; Ittel, S. D. Homogeneous Catalysis; John Wiley and Sons: New
York, NY, 1992; p 168; (c) Iwasawa, T.; Tokunaga, M.; Obora, T.; Tsuji,
Y. J. Am. Chem. Soc. 2004, 126, 6554.
14. (a) Gokel, G. W. Crown Ethers and Cryptands; Royal Society of Chemis-
try: Letchworth, UK, 1991; (b) Gokel, G. W. Crown Ethers and Cryptands.
In Large Ring Molecules; Semlyen, J. A., Ed.; John Wiley: New York, NY,
1996; pp 263e307; (c) Inoue, Y.; Gokel, G. W. Cation Binding by Macro-
cycles; Marcel Dekker: New York, NY, 1990; (d) Comprehensive Supra-
molecular Chemistry; Gokel, G. W., Ed.; Elsevier Science: Oxford,
1996; Vol. 1.
5. (a) Gstottmayr, C. W. K.; Bohm, V. P. W.; Herdtweck, E.; Grosche, M.;
¨
¨
Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1363; (b) Altenhoff,
G.; Goddard, R.; Lehmann, C. W.; Glorius, F. Angew. Chem., Int. Ed.
2003, 42, 3690; (c) Navarro, O.; Kelly, R. A., III; Nolan, S. P. J. Am.
Chem. Soc. 2003, 125, 16194; (d) Bohm, V. P. W.; Gstottmayr,
15. Kingston, J. V.; Verkade, J. G. J. Org. Chem. 2007, 72, 2816.
16. Tao, B.; Boykin, D. W. J. Org. Chem. 2004, 69, 4330.
17. Li, S.; Lin, Y.; Cao, J.; Zhang, S. J. Org. Chem. 2007, 72, 4067.
18. Liu, L.; Zhang, Y.; Xin, B. J. Org. Chem. 2006, 71, 3994.
19. Molander, G. A.; Biolatto, B. Org. Lett. 2002, 4, 1867.
20. Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302.
21. Cho, C.-H.; Yun, H. S.; Park, K. J. Org. Chem. 2003, 68, 3017.
22. XSCANS, Release 2.21; Siemens Energy and Automation: Madison, WI,
1995.
¨
¨
C. W. K.; Weskamp, T.; Herrmann, W. A. J. Organomet. Chem. 2000,
595, 186; (e) Andrus, M. B.; Song, C. Org. Lett. 2001, 3, 3761; (f)
Zhao, Y. H.; Zhou, Y. Y.; Ma, D. D.; Liu, J. P.; Li, L.; Zhang, T. Y.; Zhang,
H. B. Org. Biomol. Chem. 2003, 1, 1643.
6. Tao, B.; Boykin, D. W. Tetrahedron Lett. 2002, 43, 4955.
7. Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3, 1077.
8. (a) Dai, M.; Liang, B.; Wang, C.; Chen, J.; Yang, Z. Org. Lett. 2004, 6, 221;
(b) Dai, M.; Liang, B.; Wang, C.; Chen, J.; Yang, Z. Org. Lett. 2004, 6, 1577.
9. Cui, X.; Qin, T.; Wang, R.; Liu, L.; Guo, Q.-X. Synthesis 2007, 393.
10. Liu, W.-J.; Xie, Y.-X.; Liang, Y.; Li, J.-H. Synthesis 2006, 860.
23. SHELXTL, Version 5.10; Bruker Analytical X-ray Instruments:
Karlsruche, Germany, 1997.