Palladium catalyzed Suzuki cross-coupling reactions using N,O-bidentate ligands

Article abstract of DOI:10.1016/j.tet.2005.08.005

Palladium-catalyzed Suzuki cross-coupling reactions employing Schiff-bases as ligands toward a series of substituted arylbromides and boronic acids were pursued. In the presence of N,O-bidentate ligand, 2-[1-(2,4,6-trimethyl- phenylimino)-ethyl]-phenol 5, the catalytic reactions could be carried out efficiently at room temperature with a wide array of arylbromides, even with electronically deactivated arènes. A deprotonated 5, 5′, chelated palladium acetate complex, [5′Pd(II)(OAc)(solv)] 8, was proposed as a precursor of a genuine catalytically active species.

Full text of DOI:10.1016/j.tet.2005.08.005

Tetrahedron 61 (2005) 9484–9489
Palladium catalyzed Suzuki cross-coupling reactions using
N,O-bidentate ligands
*
Yi-Chun Lai, Hsuan-Ying Chen, Wen-Chou Hung, Chu-Chieh Lin and Fung-E Hong
Department of Chemistry, National Chung Hsing University, Taichung 40227, Taiwan
Received 6 June 2005; revised 1 August 2005; accepted 2 August 2005
Abstract—Palladium-catalyzed Suzuki cross-coupling reactions employing Schiff-bases as ligands toward a series of substituted
arylbromides and boronic acids were pursued. In the presence of a N,O-bidentate ligand, 2-[1-(2,4,6-trimethyl-phenylimino)-ethyl]-phenol 5,
the catalytic reactions could be carried out efficiently at room temperature with a wide array of arylbromides, even with electronically
deactivated arenes. A deprotonated 5, 50, chelated palladium acetate complex, [50Pd(II)(OAc)(solv)] 8, was proposed as a precursor of a
genuine catalytically active species.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
some remarkable results of using several new types of N,O-
or N,N-bidentate ligands in palladium-catalyzed Suzuki
coupling reactions. The efficiency of these ligands are
compared and discussed subsequently.
For the past few decades, transition metal-mediated
catalytic cross-coupling reactions are among the most
powerful and convenient tools of modern organic syn-
thesis.1 Recently, the palladium-catalyzed Suzuki reactions,
involving cross-coupling of aryl halides with aryl boronic
acids, have emerged as the most important synthetic
methods for the preparation of biaryl compounds.2–7 As a
result, many efforts have been devoted to the finding of even
more efficient and selective methods in the synthesis of
biaryls. For many years, phosphines have been the most
commonly employed ligands for the reaction. Lately,
N-heterocyclic carbenes (NHC) have been introduced as
potentially effective ligands for Suzuki reactions.8 Never-
theless, these types of ligands are normally either air/
moisture sensitive or expensive, which places significant
limits on their synthetic applications. Besides, these types of
compounds are not ecological friendly. On the contrary,
most of the N,O- or N,N-bidentate ligands are inexpensive,
easy to access and stable.9 Moreover, the process of the
complexation of ligand with palladium is straightforward
and their palladium complexes are found to be quite suitable
for Suzuki cross-coupling reactions. Thereby, the practices
of employing phosphine-free palladium catalysts in Suzuki
cross-coupling reactions are of interest to many.10 To our
knowledge, only few work using Schiff base as ligand in
Suzuki reaction has been reported.11 In this work, we report
2. Results and discussion
Several N,O- or N,N-bidentate ligands, 1–6, were prepared
and screened for the Pd(OAc)2 catalyzed Suzuki cross-
coupling reactions (Fig.1).
Table 1 summarizes the reaction conditions and results of
the Suzuki coupling reactions for 4-bromo-benzaldehyde
and phenylboronic acid. As shown, the best result (90% in
yield) was obtained for employing 5 as the ligand while the
reaction was carried out at 25 8C for 50 min in K3PO4/THF
system (entry 5). Judging from these data alone, 5 is a quite
efficient ligand in this reaction condition. Obviously, the
lower yield obtained by employing 6 as ligand is mainly
due to its more sterically demanding isopropyl groups on
arene (entry 6). It is interesting to see that there is no
catalytic efficiency being observed by using (2,4,6-
trimethyl-phenyl)-(1-pyridin-2-yl-ethylidene)-amine 1 as
ligand at 25 8C in KF/THF system (entry 1). For
comparison, the 1-chelated palladium complex, 1-PdCl2,
was synthesized from the reaction of 1 with another
palladium source, PdCl2. The same results were obtained.
There is not detectable catalytic ability being observed for
1-PdCl2 in Suzuki–Miyaura coupling reaction. By contrast,
in similar catalytic reactions a wide range of activities
(from 0 to 99%) were reported for employing various
Keywords: Suzuki reaction; Palladium complex; Schiff-base; Bidentate
ligand.
*
Corresponding author. Fax: C886 4 22862547;
e-mail: fehong@dragon.nchu.edu.tw
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.005

Y.-C. Lai et al. / Tetrahedron 61 (2005) 9484–9489
9485
Figure 1. Some selected N,N- and N,O-bidentate ligands 1–6.
Table 1. Suzuki coupling reactions of 4-bromo-benzaldehyde with phenylboronic acid employing ligands 1–6
Entrya
Ligand
Base
Solvent
Time (min)
Conv. (%)b
Yield (%)c
K3PO4
K3PO4
KF
Toluene
THF
Toluene
THF
50
50
50
50
NR
NR
NR
NR
NR
NR
NR
NR
1
1
KF
K3PO4
K3PO4
KF
Toluene
THF
Toluene
THF
50
50
20
50
57
73
20
86
50
65
13
85
2
3
4
5
2
3
4
5
KF
K3PO4
K3PO4
KF
Toluene
THF
Toluene
THF
50
50
190
50
68
63
16
46
68
61
6
KF
45
K3PO4
K3PO4
KF
Toluene
THF
Toluene
THF
20
20
20
350
33
0
17
87
25
0
17
86
KF
K3PO4
K3PO4
KF
Toluene
THF
Toluene
THF
90
60
20
50
80
92
22
90
77
90
10
81
KF
K3PO4
K3PO4
Toluene
THF
50
50
50
150
50
44
65
77
85
72
39
63
—
81
70
d
6
6
KF
KF
Toluene
THF
a Reaction conditions: 1.0 equiv of ArBr, 1.5 equiv of Ar0B(OH)2.
b NMR yield.
c Isolated yield.
d Not isolated.
diazabutadienes at reaction temperature around 80 8C.12
Lower efficiency were observed for reactions employing 2,
3 or 4 as ligand than that of 5. In summary, the catalytic
efficiencies of these types of ligands are in the sequence of
imine–phenolOketimineOimine–pyridine. It implies that
the catalytic efficiency is better while the ligand–metal
bonding mode is a grouping of chelated oxide- and imine–
palladium bonds.
in Table 2. Here, two bromobenzaldehydes having electron-
donating substituents, –OMe and –Me were used as the
bromide sources. As expected, low conversion rates were
observed for all the L/Pd(OAc)2 combinations.
Table 3 summarizes the results of the palladium-catalyzed
Suzuki reactions for various substituted arylbromides and
phenylboronic acids by employing 5 as ligand. Excellent
yields were obtained for the reactions of arylbromides with
electron-withdrawing groups at 25 8C for 50–120 min
(entries 1, 2, 7, and 8). On the contrary, rather low yield
was observed for arylbromide with electron-donating group
at that temperature (entry 6). Yields might be improved
while the reaction temperature was raised to 100 8C for
In palladium-catalyzed cross-coupling reactions, it is
generally accepted that better conversions are assured for
aryl halides with electron-withdrawing rather than donating
substituent.13 The Suzuki coupling reactions were carried
out and the reaction conditions and results were summarized

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Y.-C. Lai et al. / Tetrahedron 61 (2005) 9484–9489
Table 2. Suzuki coupling reactions of 4-bromo-benzene derivatives with phenylboronic acid employing ligands 1–6
Entrya
Ligand
R
Base
Solvent
Time (min)
Conv. (%)b
Yield (%)c
d
1
2
3
4
5
6
7
8
9
2
20
50
50
50
1210
20
50
120
50
13
13
7
22
50
11
20
23
24
—
11
CH3
KF
THF
d
3
4
OCH3
K3PO4
Toluene
—
d
—
48
CH3
KF
THF
d
—
d
—
5
6
CH3
KF
KF
THF
20
17
OCH3
Toluene
a Reaction conditions: 1.0 equiv of ArBr, 1.5 equiv of Ar0B(OH)2.
b NMR yield.
c Isolated yield.
d Not isolated.
Table 3. Suzuki coupling reactions of substituted arylbromides and phenylboronic acids employing ligand 5
Entrya
R
Base/solvent
Time (min)
Conv. (%)b
Yield (%)c
R0
1d
2d
3e
CHO
COCH3
CH3
H
H
H
H
H
H
NO2
NO2
NO2
NO2
H
KF/THF
KF/THF
KF/THF
KF/EtOH
KF/CH3CN
KF/THF
KF/THF
KF/THF
KF/EtOH
KF/CH3CN
KF/EtOH
50
50
90
92
23
77
34
10
82
71
87
40
10
81
90
20
68
30
120
120
240
720
120
120
120
360
1440
4e
CH3
5e
MeO
MeO
CHO
COCH3
CH3
6d
7d
8d
9e
—
f
75
70
83
33
10e
11e
MeO
CHO
f
—
a Reaction conditions: 1.0 equiv of ArBr, 1.5 equiv of Ar0B(OH)2.
b NMR yield.
c Isolated yield.
d The reaction was conducted at 25 8C.
e At 100 8C.
Not isolated.
f
arylbromides with electron-donating group (entries 3, 5, and
10). Recently, a reductive process of Pd(II) to Pd(0) through
the b-H elimination of the coordinated alkoxide ligand was
proposed by Nolan et al.8a Nevertheless, there was no
formation of acetaldehyde being observed by 1H NMR
while the reaction was performed in ethanol, Pd(OAc)2, and
5 at 100 8C for 24 h (entries 4 and 9). Even though the b-H
elimination process did not take place in this case, it indeed
increases the solubility of the reactants and eventually speed
up the reaction (entry 3 vs 4). Accidentally, the 5/Pd(OAc)2
catalytic system worked for aryl chlorides. About 10%
conversion was observed for the reaction of 4-chlorobenz-
aldehyde with phenylboronic acid at 100 8C for 24 h
employing 5/Pd(OAc)2 as catalyst.
Table 4. Crystal data of 7
Formula
Fw
C34H36N2O2Pd
611.05
Monoclinic
P2(1)
15.987(3)
20.699(3)
8.9941(15)
95.428(3)
2963.1(8)
4
1.370
0.71073
0.658
Crystal system
Space group
˚
a (A)
˚
b (A)
˚
c (A)
b (8)
3
˚
V (A )
Z
Density (calcd) (Mg/m3)
˚
l (Mo Ka) (A)
Absorption coefficient (mmK1
F(000)
)
1264
Crystal size
2q Range (8)
0.60!0.35!0.21 mm3
2.35–26.038
16,492
Reflections collected
Independent reflections
Data/restraints/parameters
R1 for significant reflectionsa
A bis-50-chelated palladium complex, 7, was obtained
while in an attempt to isolate the active species in the
reaction. The orange crystals of 7 were grown in toluene at
room temperature, then suitable crystals were sampled and
subjected for X-ray crystal structural determination
(Table 4). The ORTEP drawing of 7 are depicted in
Figure 2. The bond angles for O(1)–Pd(1)–N(1),
5790 [R(int)Z0.0753]
5790/0/355
0.0578
0.1484
0.962
wR2 for significant reflectionsb
GoFc
a R1ZjS(jFojKjFcj)/jSFok.
1
b
2
2 2
2 2
⁄
2
wR2Z{S[w(FoKFc) ]/S[w(Fo) ]} ; wZ0.0993 for 7.
1
c GoFZ[Sw(Fo2KFc2)2/(NrflnsKNparams)] .
⁄
2

Y.-C. Lai et al. / Tetrahedron 61 (2005) 9484–9489
9487
efficiency is further improved by adding in additional
amount of Pd(OAc)2. By that, presumably more species 8
was formed via equilibrium. Nonetheless, the proposed
complex 8 is still regarded as a precursor of the genuine
catalytically active species, which might be a Pd(0)
complex.
3. Conclusion
We have demonstrated the exceptional catalytic reactivity
of a N,O-bidentate ligand, 2-[1-(2,4,6-trimethyl-phenyl-
imino)-ethyl]-phenol 5, in the palladium-catalyzed Suzuki
cross-coupling reaction. These types of ligands are
attractive alternatives to the conventional phosphine
ligands. A deprotonated 5, 50, chelated palladium acetate
complex, [50Pd(II)(OAc)(solv)] 8, was proposed as a
precursor of a genuine catalytically active species and
which has been proposed from the ligand exchange reaction
of 7 with Pd(OAc)2.
Figure 2. ORTEP drawing of 7 with the numbering. Some carbon and
˚
hydrogen atoms are omitted for clarity. Selected bond lengths (A) and
4. Experimental
4.1. General
angles (8): Pd(1)–O(1) 1.974(11); Pd(1)–O(2) 1.989(10); Pd(1)–N(1)
1.980(14); Pd(1)–N(2) 2.051(15); O(1)–C(8) 1.32(2); O(1)–C(25)
1.29(2); N(1)–C(2) 1.19(2); N(1)–C(9) 1.54(2); N(2)–C(26) 1.38(2);
N(2)–C(19) 1.39(2); O(1)–Pd(1)–N(1) 88.1(5); O(1)–Pd(1)–O(2)
179.0(8); N(1)–Pd(1)–O(2) 92.6(6); O(1)–Pd(1)–N(2) 89.8(5); N(1)–
Pd(1)–N(2) 177.8(7); O(2)–Pd(1)–N(2) 89.5(6); C(8)–O(1)–Pd(1)
121.3(11); O(25)–O(2)–Pd(1) 120.3(10).
All manipulations were carried out under a dry nitrogen
atmosphere. All solvents including deuterated solvents were
purified before use. 1H and 13C NMR spectra were recorded
1
on a Varian Mercury-400 (400 MHz for H and 100 MHz
for 13C) spectrometer with chemical shifts given in ppm
from the internal TMS or center line of CHCl3. Mass spectra
were recorded on JOEL JMS-SX/SX 102A GC/MS/MS
spectrometer. Microanalyses were performed using a
Heraeus CHN-O-RAPID instrument.
N(1)–Pd(1)–O(2), O(1)–Pd(1)–N(2) and O(2)–Pd(1)–N(2)
are 88.1(5)8, 92.6(6)8, 89.8(5)8 and 89.5(6)8, respectively.
Obviously, the Pd(II) metal center is a typical square planar
environment with d8 electron configuration. The bond
lengths of Pd(1)–O(1), Pd(1)–O(2), Pd(1)–N(1) and
Pd(1)–N(2) are 1.974(11), 1.989(10), 1.980(14), and
2.051(15), respectively. Interestingly, two oxides and two
nitrogen atoms are trans to each other. This arrangement is
believed due to the steric demand from two tri-methyl-
phenyl rings rather than the reflection of the electronic
effect.
4.1.1. Synthesis of (2,4,6-trimethyl-phenyl)-(1-pyridin-2-
yl-ethylidene)-amine 1. 2-Acetylpyridine (12 mmol,
1.4 mL), 2,4,6-trimethylaniline (10 mmol, 1.4 mL), and
benzenesulfonic acid (0.30 mL) were placed in a 100 mL
round flask and was refluxed in absolute toluene (10 mL) for
36 h. After being cooled to room temperature, the orange
extraction was dried over MgSO4 and filtered. Removal of
the solvent in vacuum afforded 1 as the desired light yellow
oily product. Yield: 2.2 g (90%). 1H NMR (CDCl3, d/ppm):
7.38–8.68 (m, 4H, Py), 6.88 (s, 2H, Ph), 2.88 (s, 3H,
MeCN); 1.99 (s, 6H, Ph-o-Me), 2.18 (s, 3H, Ph-p-Me);
Elemental Anal. Calcd for C16H18N2: C, 80.63; H, 7.6; N,
11.75%. Found: C, 80.79; H, 7.61; N, 11.87%.
Rather low efficiency was observed by employing 7 as the
catalyst in Suzuki reaction than that of using the mixed
5/Pd(OAc)2 in situ. Apparently, 7 is not the genuine
catalytically active species. It might be, at most, a precursor
of a more reactive compound. Nevertheless, the catalytic
process could be greatly improved while 1 equiv of
Pd(OAc)2 was added to 7. It is believed that certain amount
of 8, 50Pd(OAc)(solv), was formed through the process of
disproportionation and most of the catalytic reactivity was
caused by this newly formed complex (Scheme 1). The
4.1.2. Synthesis of 4-(1-penyl-ethylamino)-pent-3-en-2-
one 2. DL-a-Methyl benzylamine (0.1 mol, 12.1 g),
Scheme 1. The formation of a proposed catalyst precursor 8.

9488
Y.-C. Lai et al. / Tetrahedron 61 (2005) 9484–9489
2,4-pentanedione (0.1 mol, 10.0 g), and benzenesulfonic
acid (0.30 mL) were placed in a 100 mL round flask and was
refluxed in absolute toluene (10 mL) for 24 h. Removal of
the solvent in vacuum afforded mixture. The resulting
mixture was extracted by water and toluene. The organic
extraction was recrystallized from hexane at 0 8C to afford a
yellow solid 2 as the desired product. Yield: 18.29 g (90%).
1H NMR (CDCl3, d/ppm): 11.24 (s, 1H, COH), 7.20–7.32
(m, 5H, Ph), 4.99 (s, 1H, CCHC), 4.66, 2.26 (m, 2H, PhCH),
2.04 (s, 1H, H(CO)C), 1.78 (s, 1H, NCHCH); 13C NMR
(CDCl3, d/ppm): 18.8 (PhCC), 125.2, 126.9, 128.1, 143.9
(Ph), 24.4 (NCCH3), 28.5 (O]CCH3), 32.7 (PhC), 95.5
(NC]CH), 162.3 (NC]C), 194.9 (O]CCH3); MS (FAB,
m/z): 203 (MC).
1H, OH), 7.61–7.65 (m, 1H, Ph), 7.33–7.42 (m, 1H, Ph);
7.01–7.05 (m, 1H, Ph), 6.85–6.89 (m, 3H, Ph), 2.30 (s, 3H,
C]NCH3), 2.16 (s, 6H, o-PhCH3), 2.03 (s, 3H, p-PhCH3);
13C NMR (CDCl3, d/ppm): 171.90 (C]N), 162.33, 142.42,
133.67, 132.85, 128.75, 128.63, 127.35, 119.18, 118.15,
117.84 (Ph), 20.64 (C]NCH3), 17.98 (o-PhCH3), 16.71
(p-PhCH3); MS (EI, m/z): 253 (MC); Elemental Anal. Calcd
for C17H19NO: C, 80.60; H, 7.56; N, 5.53%. Found: C,
80.84; H, 7.64; N, 5.90%.
4.1.6. Synthesis of 2-[1-(2,6-diisopropyl-phenylimino)-
ethyl]-phenol 6. 2-Hydroxyacetophenone (50 mmol,
6.0 mL), 2,6-diisopropylaniline (50 mmol, 9.4 mL), and
benzenesulfonic acid (0.30 mL) were placed in a 100 mL
round flask and was refluxed in 1-butanol (50 mL) for 48 h.
Removal of the solvent in vacuum afforded 6. The organic
extraction was recrystallized from hexane at 0 8C to afford
4.1.3. Synthesis of 4-pentafluorophenylamino-pent-3-en-
2-one 3. Pentafluoroaniline (0.02 mol, 3.6 g), 2,4-pentane-
dione (0.02 mol, 2.0 g), and benzenesulfonic acid (0.30 mL)
were placed in a 100 mL round flask and was refluxed in
absolute toluene (10 mL) for 24 h. Removal of the solvent in
vacuum yielded mixture. The resulting mixture was
extracted by water and toluene. The organic extraction
was recrystallized from hexane at 0 8C to gave a desired
yellow solid 3. Yield: 3.88 g (25%). 1H NMR (CDCl3,
d/ppm): 2.15 (s, 1H, H3C(CO)CH), 5.340 (s, 1H,
H3C(CO)CH), 1.86 (s, 1H, NCHCH(CO)); 13C NMR
(CDCl3, d/ppm): 136.4–144.8 (Ph), 18.6 (NCCH3), 29.1
(O]CCH3), 99.5 (NC]CH), 159.7 (NC]C) 197.9
(O]CCH3); Elemental Anal. Calcd for C11H8NOF5: C,
49.82; H, 3.04; N, 5.28%. Found: C, 49.55; H, 3.12; N,
4.98%.
1
a yellow solid 6. Yield: 4.43 g (32%). H NMR (CDCl3,
d/ppm): 7.65 (d, JZ4 Hz, 1H, Ph), 7.39 (t, JZ3 Hz, 1H,
Ph), 7.19 (d, 1H, Ph), 7.07 (d, JZ4 Hz, 1H, Ph), 6.93 (t, JZ
2 Hz, 1H, Ph), 2.75–2.81 (m, 2H, CH(CH3)2), 2.20 (s, 3H,
C]NCH3), 1.13 (d, 6H, CH(CH3)2); 13C NMR (CDCl3,
d/ppm): 172.22 (C]N), 162.42, 142.15, 138.14, 133.17,
128.93, 125.23, 123.27, 119.08, 118.36, 118.04 (Ph), 28.36
(C]NCH3), 23.62 (CH(CH3)2), 22.78 (CH(CH3)2), 17.60
(CH(CH3)2); MS (EI, m/z): 295 (MC); Elemental Anal.
Calcd for C20H25NO: C, 81.31; H, 8.53; N, 4.74%. Found:
C, 81.48; H, 8.47; N, 4.64%.
4.1.7. Synthesis of Pd(C17H18NO)2 7. 2-[1-(2,4,6-Tri-
methyl-phenylimino)-ethyl]-phenol (2.0 mmol, 0.506 g)
and palladium acetate (1.0 mmol, 0.224 g) were placed in
a 100 mL round bottle, and removal of air in vacuum for 1 h.
The mixture was then allowed to react in absolute THF
(10 mL) at room temperature for 1 h. Removal of the
solvent in vacuum afforded 7 as a brown solid product.
4.1.4. Synthesis of 2-((2-methoxyphenyl)amino)-4-((2-
methoxyphenyl)imino)-2-pentene 4. 2-Methoxyaniline
(12.30 g, 100 mmol), 2,4-pentanedione (5.00 g, 50 mmol),
and benzenesulfonic acid (0.30 mL) were placed in a
100 mL round flask and was refluxed in absolute toluene
(30 mL) for 24 h. After being cooled to room temperature,
volatile materials were removed under vacuum to give
brown oil. Diethyl ether (100 mL) were then added and the
resulting precipitate was extracted by CH2Cl2 (30 mL). The
orange extraction was dried over MgSO4, and filtered.
Removal of the solvent in vacuum afforded a light yellow
1
Yield: 0.604 g (96%). H NMR (CDCl3, d/ppm): 7.37 (q,
JZ2 Hz, 1H, Ph), 7.06 (m, JZ8 Hz, 1H, Ph), 6.98 (s, 2H,
Ph), 6.49 (m, JZ8 Hz, 1H, Ph), 6.32 (d, JZ2 Hz, 1H, Ph),
2.33 (s, 3H, p-PhCH3), 2.32 (s, 6H, o-PhCH3), 2.03 (s, 3H,
C]NCH3); MS (EI, m/z): 610 (MC).
4.2. Exchanging procedure for the Suzuki coupling of
aryl bromide
1
solid 4 as the targeted product. Yield: 3.88 g (25%). H
NMR (CDCl3, d/ppm): 12.20 (1H, s, NH), 6.99 (4H, d, JZ
7.2 Hz, MeOArH), 6.86–6.88 (4H, m, ArH), 4.92 (1H, s,
b-CH), 3.77 (6H, s, CH3O), 1.98 (6H, s, a-CH3) ppm; 13C
NMR (CDCl3, d/ppm): 160.21 (C]N), 151.51 (MeOCCN),
135.61 (MeOCCN), 123.84, 123.29, 120.74, 111.68 (Ph),
98.16 (b-C), 55.98 (CH3O), 21.39 (C]CHC); Elemental
Anal. Calcd for C19H22N2O2: C, 73.52; H, 7.14; N, 9.03%.
Found: C, 72.66; H, 7.58; N, 8.40%.
An oven-dried flask was evacuated and charged with
complex 7 (3.05 mg, 0.5 mmol%), Pd(OAc)2 (1.10 mg,
0.5 mmol%), the boronic acid (0.183 g, 1.0 mmol),
4-bromo-benzaldehyde (0.185 g, 1.0 mmol), KF (0.116 g,
2.0 mmol). Toluene (1 mL) was added and the mixture was
stirred. After 50 min, 37% conversion was observed. Then,
the conversion reached 81% after 7 days in reaction.
4.1.5. Synthesis of 2-[1-(2,4,6-trimethyl-phenylimino)-
ethyl]-phenol 5. 2-Hydroxyacetophenone (50 mmol,
6.0 mL), 2,4,6-trimethylaniline (50 mmol, 7.0 mL), and
benzenesulfonic acid (0.30 mL) were placed in a 100 mL
round flask and was refluxed in 1-butanol (50 mL) for 48 h.
Removal of the solvent in vacuum afforded mixture. The
mixture was purified by column chromatography (silica gel,
ethyl acetate/hexaneZ1:23). The organic extraction was
recrystallized from hexane at 0 8C to gave a yellow solid 5.
4.3. X-ray crystallographic studies
Suitable crystals of 7 were sealed in thin-walled glass
capillaries under nitrogen atmosphere and mounted on a
Bruker AXS SMART 1000 diffractometer. Intensity data
were collected in 1350 frames with increasing (width of 0.38
per frame). The absorption correction was based on the
symmetry equivalent reflections using SADABS program.
The space group determination was based on a check of
the Laue symmetry and systematic absences, and was
1
Yield: 4.05 g (32%). H NMR (CDCl3, d/ppm): 14.90 (s,

Y.-C. Lai et al. / Tetrahedron 61 (2005) 9484–9489
9489
Commun. 2002, 616–617. (d) McLachlan, F.; Mathews, C. J.;
Smith, P. J.; Welton, T. Organometallics 2003, 22,
5350–5357.
confirmed using the structure solution. The structure was
solved by direct methods using a SHELXTL package. All
non-H atoms were located from successive Fourier maps
and hydrogen atoms were refined using a riding model.
Anisotropic thermal parameters were used for all non-H
atoms, and fixed isotropic parameters were used for H
atoms.
5. Selected works for the Suzuki reaction carried out with ligand
free system: (a) Deng, Y.; Gong, L.; Mi, A.; Liu, H.; Jiang, Y.
Synthesis 2003, 337–339. (b) Li, C. J. Angew. Chem., Int. Ed.
2003, 42, 4856–4858. (c) Campi, E. M.; Jackson, W. R.;
Marcuccio, S. M.; Naeslund, C. G. M. Chem. Commun. 1994,
2395–2396. (d) Badone, D.; Baroni, M.; Cardamone, R.;
Ielmini, A.; Guzzi, U. J. Org. Chem. 1997, 62, 7170–7173.
(e) Bussolari, J. C.; Rehborn, D. C. Org. Lett. 1999, 1,
965–967. (f) Zim, D.; Monteiro, A. L.; Dupont, J. Tetrahedron
Lett. 2000, 41, 8199–8202. (g) Kabalka, G. W.; Namboodiri,
V.; Wang, L. Chem. Commun. 2001, 775–776. (h) Sakurai, H.;
Tsukuda, T.; Hirao, T. J. Org. Chem. 2002, 67, 2721–2722.
(i) Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68,
4302–4314.
5. Supplementary information available
Crystallographic data for the structural analysis have been
deposited with the Cambridge Crystallographic Data
Center, CCDC no. 253791 for compound 7. Copies of this
information may be obtained free of charge from the
Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(fax: C44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk
or www: http://www.ccdc.cam.ac.uk).
6. Suzuki reaction carried out by microwave technique:
(a) Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68,
888–892. (b) Gong, Y. Org. Lett. 2002, 4, 3803–3805.
(c) Basu, B.; Das, P.; Bhuiyan, M. M. H.; Jha, S. Tetrahedron
Lett. 2003, 44, 3817–3820.
Acknowledgements
We are grateful to the National Science Council of the ROC.
(Grant NSC 93-2113-M-005-020) for financially supporting
this research.
7. Applications of Suzuki reaction: (a) Tomioka, H.; Itoh, T.;
Hirai, K. J. Am. Chem. Soc. 2004, 126, 1130–1140. (b) Miura,
Y.; Oka, H.; Momoki, M. Synthesis 1995, 1419–1422.
(c) Meier, P.; Legraverant, S.; Muller, S.; Schaub, J. Synthesis
2003, 551–554. (d) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D.
Angew. Chem., Int. Ed. 2005, 44, 2–49.
8. (a) Navarro, O.; Kelly, R. A., III; Nolan, S. P. J. Am. Chem.
Soc. 2003, 125, 16194–16195. (b) Viciu, M. S.; Kelly, R. A.,
III; Stevens, E. D.; Naud, F.; Studer, M.; Nolan, S. P. Org. Lett.
2003, 5, 1479–1482. (c) Yin, J.; Rainka, M. P.; Zhang, X. X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162–1163.
(d) Stambuli, J. P.; Kuwano, R.; Hartwig, J. F. Angew. Chem.,
Int. Ed. 2002, 41, 4746–4748.
References and notes
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A., Stang, P. J., Eds. 2nd ed.; Wiley-VCH: Weinheim, 2004.
(b) Transition Metals for Organic Synthesis; Beller, M., Bolm,
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Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev.
2002, 102, 1359–1470.
9. (a) Weng, Z.; Teo, S.; Koh, L. L.; Hor, T. S. A. Organo-
metallics 2004, 23, 3603–3609. (b) Li, J. H.; Liu, W. J.; Xie,
Y. X. J. Org. Chem. 2005, 70, 5409–5412. (c) Domin, D.;
2. Reviews: (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457–2483. (b) Suzuki, A. J. Organomet. Chem. 1999, 576,
147–168.
˝
Benito-Garagorri, D.; Mereiter, K.; Frohlich, J.; Kirchner, K.
Organometallics 2005, 24, 3957–3965. (d) Mino, T.; Shirae,
Y.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2005, 70,
2191–2194. (e) Najera, C.; Gil-Molto, J.; Karlstrom, S.;
Falvello, L. R. Org. Lett. 2003, 5, 1451–1454. (f) Mazet, C.;
Gade, L. H. Organometallics 2001, 20, 4144–4146.
3. Suzuki reaction employs various metal complexes as
precatalysts: (a) Kabalka, G. W.; Wang, L.; Pagni, R. M.;
Hair, C. M.; Namboodiri, V. Synthesis 2003, 217–222.
(b) Zim, D.; Monteiro, A. L. Tetrahedron Lett. 2002, 43,
4009–4011. (c) Shintou, T.; Kikuchi, W.; Mukaiyama, T.
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Han, H.; Ko, S.; Chang, S. J. Am. Chem. Soc. 2004, 126,
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´
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´ ´
11. Gonzalez-Arellano, C.; Corma, A.; Iglesias, M.; Sanchez, F.
Adv. Synth. Catal. 2004, 346, 1758–1764.
12. Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3,
1077–1080.
4. Suzuki reaction carried out in ionic liquid: (a) McNulty, J.;
Capretta, A.; Wilson, J.; Dyck, J.; Adjabeng, G.; Robertson, A.
Chem. Commun. 2002, 1986–1987. (b) Mathews, C. J.; Smith,
P. J.; Welton, T. Chem. Commun. 2000, 1249–1250.
(c) Rajagopal, R.; Jarikote, D. V.; Srinivasan, K. V. Chem.
13. Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J. Org.
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