1,1′-Bis(oxazolinyl)ferrocene-based palladium catalysts: Synthesis, X-ray structures and applications in Suzuki and Heck coupling reactions

Article abstract of DOI:10.1016/j.jorganchem.2005.12.018

1,1′-Bis(oxazolinyl)ferrocene-based palladium dichloride complexes 2a and 2b were synthesized. X-ray single-crystal diffraction analyses showed that they are of the N,N′-chelating type, and that the coordination mode of 2a, which has an isopropyl group, is of the cis type, whereas that of 2b, which has a tert-butyl group, is the trans one. These two complexes were employed as catalysts for Suzuki and Heck reactions, and showed high catalytic activities in coupling reactions with various aryl halides and counterparts (phenylboronic acid or n-butyl acrylate). Particularly, the catalyst 2a afforded the coupled product of aryl bromide with phenylboronic acid at room temperature.

Full text of DOI:10.1016/j.jorganchem.2005.12.018

Journal of Organometallic Chemistry 691 (2006) 1347–1355
www.elsevier.com/locate/jorganchem
1,10-Bis(oxazolinyl)ferrocene-based palladium catalysts: Synthesis,
X-ray structures and applications in Suzuki and Heck coupling reactions
*
Sunwoo Lee
Department of Chemistry, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju 500-757, Republic of Korea
Received 31 October 2005; received in revised form 1 December 2005; accepted 7 December 2005
Available online 27 January 2006
Abstract
1,10-Bis(oxazolinyl)ferrocene-based palladium dichloride complexes 2a and 2b were synthesized. X-ray single-crystal diffraction anal-
yses showed that they are of the N,N0-chelating type, and that the coordination mode of 2a, which has an isopropyl group, is of the cis
type, whereas that of 2b, which has a tert-butyl group, is the trans one. These two complexes were employed as catalysts for Suzuki and
Heck reactions, and showed high catalytic activities in coupling reactions with various aryl halides and counterparts (phenylboronic acid
or n-butyl acrylate). Particularly, the catalyst 2a afforded the coupled product of aryl bromide with phenylboronic acid at room
temperature.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Catalyst; Palladium; Ferrocene; Oxazoline; Coordination modes; Suzuki; Heck
1. Introduction
cient catalysis. As one of the methods of overcoming these
problems, nitrogen donor ligands have been employed as
ligands in many transition metal catalyzed transformation
reactions [12]. Nitrogen-based catalysts allow for the gener-
ation of catalytically active complexes which are comple-
mentary to the known phosphine-based systems.
Palladium catalyzed cross-coupling reactions constitute
one of the most useful methods of forming carbon–carbon
bonds and carbon–heteroatom (N, O and S) bonds [1]. Many
different reaction types have been reported, such as Kumada
and co-workers [2], Negish [3], Milstein and Stille [4], Hata-
naka and Hiyama [5], Miyaura and Suzuki [6], Sonogashira
et al. [7], Heck [8] and Hartwig-Buchwald [9] cross-coupling
reactions. They have been widely used for the synthesis of
valuable organic compounds such as pharmaceuticals and
agrochemicals [10]. In most cases, the choice of ligand plays
a major role in the efficiency of the reaction. Recently, a num-
ber of efficient ligands have been reported in order to expand
the scope of the reaction substrates that can be used under
mild conditions [4c,6d,11]. However, these ligands systems,
mostly phosphine derivatives, suffer from drawbacks such
as their high sensitivity to air and moisture and, conse-
quently, inert atmosphere conditions are required for effi-
Our and other research groups have reported that chiral
1,10-bis(oxazolinyl)ferrocene derivatives, which are mainly
based on the phosphine donor group, were synthesized dia-
stereoselectively, and showed high catalytic activities in
palladium catalyzed asymmetric allylic alkylation reactions
[13]. In addition, the palladium complexes of 1,10-bis(oxazo-
linyl)ferrocenes having diphenylphosphinyl groups have
been studied with NMR spectroscopy and X-ray crystal-
lography. They showed N,P-chelating or P,P-chelating
modes depending on their structural features. A couple of
years ago, Ikeda and co-workers reported their NMR stud-
ies of the palladium complexes of 1,10-bis(oxazolinyl)fer-
rocenes, in which they suggested that the 1:2 palladium
complexes of the ligand and palladium was formed [14].
However, we obtained the N,N-chelating type palladium
complexes from the same ligands.
*
Tel.: +82 62 530 3385; fax: +82 62 530 3389.
E-mail address: sunwoo@chonnam.ac.kr.
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.12.018

1348
S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
There have been several reports in which oxazoline-based
nyl)ferrocene (1b) having a t-butyl group on the
ligands were used in palladium catalyzed cross-coupling
reactions [15]. However, to the best of our knowledge,
1,10-bis(oxazolinyl)ferrocenes 1, which have only nitrogen
donor groups, have never been used as ligands in palladium
catalyzed cross-coupling reactions, even though nitrogen
donor ligands are known to be less sensitive to air and
water than phosphine donor ligands. Herein, we report
our findings that the coordination modes of 1,10-bis(oxaz-
olinyl)ferrocene ligands toward palladium are dependent
on the substituted group in the oxazoline ring, and that
these complexes show high catalytic activities in Suzuki
and Heck reactions.
oxazoline ring was reacted with (CH3CN)2PdCl2 in the
same way. The complex 2b was obtained with almost quan-
titative yield and exhibited the same stability. However, in
contrast to 2a, the 1H NMR spectrum of the resulting com-
plex exhibits only one set of signals that are mostly shifted
downfield from the values observed for the free ligand,
indicating that the complex is a C2-symmetric N,N0-type
chelating one. Moreover, this result also implies that the
coordination mode of 2b is different from that of 2a.
In order to define the exact coordination modes of each
complex, the solid state molecular structures of 2a and 2b
were determined by X-ray diffraction, and these are
depicted in Figs. 1 and 2, respectively, together with the
principal bond lengths and bond angles. As elucidated
from the crystallographic data, both two palladium com-
plexes are of the N,N0-chelating type, and 2a has the cis
coordination mode, while 2b has the trans one.
2. Results and discussion
2.1. Synthesis and X-ray crystallography of 1,10-
bis(oxazolinyl)ferrocene palladium dichloride complexes
In the case of the cis palladium complex of the 1,10-
bis(oxazolinyl)ferrocene (2a), only one conformer is able
to be formed. However, in the case of the trans complex,
there are two possible conformers that can be formed,
viz. one in which each substituted group (e.g. tert-butyl)
on the oxazoline ring faces the endo side of the ferrocene
moiety, and the other in which they face the exo side. Of
these two possible conformers, only 2b was obtained,
whereas the other possible conformer 3 was not detected
The coordination modes of 1,10-bis(oxazolinyl)ferroc-
enes toward palladium were examined (Scheme 1). When
1,10-bis(oxazolinyl)ferrocene (1a) bearing an isopropyl
group on the oxazoline ring was treated with 1.0 equivalent
of (CH3CN)2PdCl2 in CH2Cl2 at room temperature, the
palladium dichloride complex 2a was obtained with 86%
yield. The complex is a thermally robust red solid that is
stable in air both in the solid form and in solution. The
1H NMR spectrum of the corresponding metal complex
exhibits two noteworthy features. First, the oxazolinyl pro-
tons and the protons of the cyclopentadienyl rings in ferro-
cene are shifted downfield from the values observed for the
free ligand. Second, the magnetically equivalent protons in
the free ligand, whose equivalence is derived from the cen-
trosymmetry of ferrocene, are transformed into two sets of
non-equivalent signals. These results imply that the palla-
dium and ligand are combined in a 1:1 molar ratio to form
an N,N0-type chelating complex and that their coordina-
tion mode is not C2-symmetry. Next, 1,10-bis(oxazoli-
1
in the H NMR spectrum of the reaction mixture. This
exclusive formation of one conformer of the trans complex
may be due to the existence of two types of steric repulsion.
One type of repulsion between both tert-butyl groups on
the oxazoline rings leads to the trans coordination mode
rather than the cis one, while the other type of repulsion
between the tert-butyl groups and the ferrocene moiety
leads to the exo conformer. This finding suggests that the
geometry and conformation of the palladium complex of
1,10-bis(oxazolinyl)ferrocene is dependent on the size of
the substituted group on the oxazolinyl ring. In contrast
R
N
i-Pr
O
O
(CH3CN)2PdCl2
Fe
Pd
N
O
Cl
Cl
Fe
R
CH2Cl2, rt., 2h
86%
i-Pr
N
N
O
2a
1a : R = i-Pr
1b : R = t-Bu
O
t-Bu
O
Fe
Fe
Pd
Cl
(CH3CN)2PdCl2
CH2Cl2, rt., 2h
98%
N
Cl
N
Pd
t-Bu
t-Bu
O
O
N
Cl
N
Cl
t-Bu
3
2b
Scheme 1. Synthesis of 1,10-bis(oxazolinyl)ferrocene palladium dichlorides, 2a and 2b.

S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
1349
complex of ligand-to-metal [14]. The different results
between our complexes and theirs might be the nature of
the solvent used. When the coordinating solvent-like
CH3CN was used, 1:2 complex is formed, while non-coor-
dinating solvent-like CH2Cl2 gave 1:1 complex. This ratio-
nalization is supported by the following experiment. When
the complexation reaction between 1b and (CH3CN)2PdCl2
1
performed in CD3CN, the H NMR spectrum showed the
same pattern as that reported by Ikeda and co-workers,
suggesting 1:2 complex was formed. Moreover, their com-
plexation behavior was independent of the substituted
group on the oxazolinyl ring. It is well known that the
coordination mode (cis or trans) of a chelating ligand is
dependent on the donor atom-metal-donor atom bite
angle, which is derived from the length and flexibility of
the ligand backbone [16]. The general feature of chelating
ligands is their cis-coordination. Of course, there have been
several reports of trans-chelating ligands in palladium com-
plexes; for example, phosphine ligands based on the xan-
thene framework [17] or on the ferrocene unit [18],
nitrogen ligands such as bis-pyridine [19] and carbene type
ligands such as bis-imidazolylidene [20].
Fig. 1. X-ray structure of 2a with 50% probability. Selected bond
distances (A): Pd(1)–N(101) = 2.055(6), Pd(1)–N(102) = 2.041(7), Pd(1)–
Cl(1) = 2.322(2), Pd(1)–Cl(2) = 2.309(2). Selected bond angles (ꢁ):
N(101)–Pd(1)–N(102) = 88.5(3), N(102)–Pd(1)-Cl(2) = 179.4(2), N(101)–
Pd(1)–Cl(2) = 90.91(19), N(102)–Pd(1)–Cl(1) = 88.01(2), N(101)–Pd(1)–
Cl(1) = 176.51(19), Cl(1)–Pd(1)–Cl(2) = 92.43(7).
˚
2.2. Suzuki cross-coupling reactions
The complexes prepared in this work were employed as
catalysts for Suzuki and Heck reactions. These reactions
were used as a standard test reaction to probe the reactivity
of these new palladium complexes. First, the catalysts 2a
and 2b were applied to the Suzuki cross-coupling reaction
with phenylboronic acid and 4-bromo-tert-butylbenzene.
Table 1 summarizes the results obtained from the screening
of a variety of bases and solvents for model substrates that
undergo C–C coupling reactions. Several trends are readily
apparent. The catalyst 2a with its cis-chelating mode
showed a faster cross-coupling reaction rate than the
trans-chelating catalyst 2b (entries 1 and 13). As shown
in Fig. 3, the catalyst 2a afforded the coupled product in
70% yield within 30 min and almost quantitative yield in
2 h. However, the complex 2b showed only 50% yield even
after 2 h, and required a longer reaction time to produce a
yield of more than 90% of the coupled product. Various
less expensive bases were examined for their effect on the
reaction efficiency in the toluene solvent. K2CO3 was the
most effective (entry 1) and K3PO4 showed comparable
results (entry 2). KF displayed moderate efficiency, gener-
ating the coupled product in 65% yield (entry 3). Sodium
bases such as Na2CO3 and Na3PO4 showed low activities
(entries 4 and 5). Interestingly, although they are com-
monly used and effective bases for Pd/phosphine Suzuki-
type reactions [6d,21], Cs2CO3 and CsF proved to fairly
ineffective in the present system (entries 6 and 7). Among
the tested solvents, the non-polar solvent toluene was
found to be the most productive, whereas polar aprotic sol-
vents, such as DMF, NMP, THF and dioxane, and polar
protic solvents, such as i-PrOH, afforded low coupled
product yields (entries 8–12). A similar beneficial effect of
Fig. 2. X-ray structure of 2b with 50% probability. Selected bond
˚
distances (A): Pd(2)–N(3) = 1.993(12), Pd(2)–N(4) = 1.997(10), Pd(2)–
Cl(3) = 2.331(4), Pd(2)–Cl(4) = 2.317(3). Selected bond angles (ꢁ): N(3)–
Pd(2)–N(4) = 1165.9(5),
N(3)–Pd(2)–Cl(4) = 93.6(3),
N(4)–Pd(2)–
Cl(4) = 87.8(3), N(3)–Pd(2)–Cl(3) = 88.1(4), N(4)–Pd(2)–Cl(3) = 93.7(3),
Cl(4)–Pd(2)–Cl(3) = 166.62(15).
1
to our results, based on their H NMR experimental data,
Ikeda and co-workers suggested that the palladium com-
plexes of 1,10-bis(oxazolinyl)ferrocenes did form a 1:2

1350
S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
Table 1
Optimization of conditions for Suzuki coupling of 4-bromo-tert-butylbenzene and phenylboronic acida
cat. Pd complex
tBu
tBu
Br
(HO)2B
+
Base, Solvent
25 ~ 110 oC
Entry
Pd (mol%)
Catalyst
Solvent
Base
Temperature (ꢁC)
Time (h)
Yieldb (%)
1
2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
4.2 · 10ꢀ3
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2a
2a
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
K2CO3
K3PO4
KF
Na2CO3
Na3PO4
Cs2CO3
CsF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
60
60
60
60
60
60
60
60
60
60
60
60
60
25
110
2
2
2
2
2
98
94
65
18
27
10
5
40
10
62
14
57
94
92
82
3
4
5
6
2
2
7
8
12
12
12
12
12
10
24
24
9
NMP
THF
10
11
12
13
14
15c
a
Dioxane
i-PrOH
Toluene
Toluene
Toluene
Reaction conditions: 1.0 mmol aryl halide, 1.1 mmol PhB(OH)2, 1.5 mmol base, 2.0 ml solvent.
Yields determined by GC.
10.0 mmol scale of aryl halide used.
b
c
coupling reactions for aryl bromides bearing thermally
unstable moiety.
100
80
60
40
20
0
The Suzuki cross-coupling of activated and deactivated
aryl bromides or aryl chloride with phenylboronic acid
were carried out in the presence of 0.5 mol% of catalyst
2a to give the cross-coupled products (Table 2). Bromoben-
zene reacted with phenylboronic acid in 2 h to give biphe-
nyl in 98% isolated yield (entry 1). The activated substrates
reacted with phenylboronic acid to give the corresponding
cross-coupled products in generally good isolated yield
(entries 2 and 9–12). Some of the deactivated substrates
required an elevated temperature to give the products in
high yield (entries 5 and 7). The sterically hindered 2-
bromotoluene resulted in high yields. However, the very
sterically congested and deactivated substrate, bromome-
sitylene, reacted with phenylboronic acid to give the
cross-coupled product in only modest yield (entries 14
and 15). The use of 2-bromo and 3-bromo pyridines, which
have the potential to bind to palladium through the nitro-
gen atom, gave 46% and 89% yields, respectively (entries 16
and 17). More vigorous conditions were required to effect
the Suzuki cross-coupling of aryl chlorides (entries 18
and 19).
2a
2b
0
20
40
60
80
100
120
Reaction Time (min)
Fig. 3. Reaction profile for the Suzuki cross-coupling reaction of 4-
bromo-tert-butylbenzene and phenylboronic acid using catalyst 2a (m)
and 2b (s) at 60 ꢁC.
non-polar solvents on coupling reactions was also observed
for phosphine-based systems [6d]. For room temperature
couplings, the reaction required a 1.0 mol% catalytic load-
ing of the complex 2a (entry 14). The reaction needed an
elevated temperature and long reaction time for a high
turnover number (TON = 19,524) to be obtained for the
complex 2a (entry 15). To the best of our knowledge, there
have been only a few reports of N-coordinated palladium
complex mediated Suzuki cross-coupling reactions of aryl
bromides at room temperature [22]. This result implies that
complex 2a can be employed as a catalyst in Suzuki cross-
2.3. Heck cross-coupling reactions
Afterwards, the Heck reactions of 4-bromotoluene and
n-butyl acrylate were carried out with various bases and
solvents. The use of a phosphate base generally leads to
higher yields for the coupling reactions, and in this case
K3PO4 gave the product in 94% yield (entries 1 and 2). Car-

S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
1351
Table 2
Suzuki cross-coupling reactions by catalyst 2aa
Ar
0.5mol% 2a
B(OH)2
+
Ar
X
K2CO3, toluene
X = Br, Cl
Temperature (ꢁC) Timeb (h) Yieldc (%) Entry ArBr
Entry ArBr
Temperature (ꢁC) Timeb (h) Yieldc (%)
1
60
2
98
11
Br
60
2
99
Br
MeO
O
2
60
60
2
2
99
96
12
13
Br
60
60
2
2
98
92
Br
Br
Br
Me
O2N
O
3
Br
Me
Me
Me
Me
4
5
60
90
3
2
64
90
14
15
Me
60
90
3
2
40
68
Br
Me2N
Me
6
7
60
90
3
2
60
86
16
17
60
60
2
2
46
89
Br
Br
MeO
N
N
Br
8
60
2
91
MeO
Br
9
60
60
2
2
99
98
18
19
80
4
6
26
45
Br
Cl
Ph
Me
O
10
Br
110
a
b
c
Reaction conditions: 1.0 equiv of aryl halide, 1.1 equiv of phenylboronic acid, 0.5 mol% 2a, 1.5 equiv of K2CO3, toluene (0.1 M).
Reaction times were not optimized.
1
Isolated yields of compounds are an average of at least two runs. All compounds are characterized by comparison of H and 13C NMR spectra with
authentic samples or literature data.
bonate bases, such as K2CO3, Na2CO3 and Cs2CO3, gave
the products in modest to low yields (entries 3–5). Organic
bases such as Et3N showed low activity (entry 7). N-Meth-
ylpyrrolidione (NMP), which is a cyclic amide solvent, was
the best solvent in this system. Other non-cyclic amide sol-
vents such as DMF and DMA led to the coupled product
being generated in moderate yield. The catalysts 2a and 2b
showed similar product yields of 94% and 90%, respectively
(entries 1 and 12) at a concentration of 0.1 mol%, and their
turnover number were 4650 and 4500, respectively, when

1352
S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
Table 3
Optimization of conditions for Heck reaction of 4-bromo-toluene and n-butyl acrylatea
O
cat. Pd complex
Base, Solvent
O
n-Bu
+
Me
Br
O
n-Bu
O
Me
Entry
Pd (mol%)
Catalyst
Solvent
Base
Temperature (ꢁC)
Time (h)
Yieldb (%)
1
2
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
NMP
NMP
NMP
NMP
NMP
NMP
NMP
DMF
DMA
NMP
NMP
NMP
NMP
K3PO4
Na3PO4
K2CO3
Na2CO3
Cs2CO3
NaOAc
Et3N
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
140
140
140
140
140
140
80
140
140
140
140
140
140
3
3
3
3
3
3
12
6
6
8
94
80
65
70
24
50
3
59
53
93
8
3
4
5
6
7
8
9
0.1
10
11
12
13
a
0.02
0.002
0.1
12
3
12
90
90
0.02
Reaction conditions: 1.0 mmol aryl halide, 1.5 mmol n-butyl acrylate, 2.0 mmol base, 2.5 ml solvent.
Yields determined by GC.
b
they were used at a concentration of 0.02 mol% (entries 10
4. Experimental
and 13). At a concentration of 0.002 mol%, the catalyst 2a
led to the coupled product being generated in only 8% yield
(entry 11). In contrast to these results, Ueda and co-work-
ers reported that trans-chelating complexes exhibited
higher catalytic activities in Heck reactions for aryl iodides
than cis-chelating complexes [19c]. However, their trans-
chelating complex produced the coupled product of aryl
bromide in very low yield (1–4%) (see Table 3).
A wide range of electronically and structurally diverse
aryl bromides can be cross-coupled efficiently with n-butyl
acrylate under these optimized conditions. The results are
summarized in Table 4. It is noteworthy that the use of
deactivated, electron-rich aryl bromides as well as acti-
vated, electron-poor ones also resulted in high yields.
4.1. General procedures
The reagents and solvents were obtained from commer-
cial sources and were generally used without further purifi-
cation. 1,10-Bis(oxazolinyl)-ferrocenes (1) were prepared
according to the procedures described in the literature
[13a]. Naphthalene was used as a standard in the quantita-
tive GC experiments using response factors determined
from isolated products. All NMR spectra were recorded
in CDCl3 with a Bruker AM 300 spectrometer. Chemical
1
shifts are given in d ppm downfield from Me4Si (d 0, H)
or CDCl3 (d 77, 13C) as an internal standard. Elemental
analyses were performed by the Center for Biofunctional
Molecules, Pohang University of Science and Technology.
3. Conclusion
4.2. Synthesis of [1,10-bis{(S)-4-isopropyloxazolin-2-
yl}ferrocene]palladium(II) dichloride (2a)
In summary, the 1,10-bis(oxazolinyl)ferrocene palladium
dichloride complexes 2a and 2b were synthesized with 86%
and 98% yields, respectively. Their N,N0-type chelating
modes were determined by X-ray single-crystal diffraction.
It was found that the complex 2a operates in the cis mode,
and complex 2b in the trans mode. Moreover, the com-
pound 1b afforded only one of two possible trans-chelating
palladium complexes. Complexes 2a and 2b were employed
as catalysts in Suzuki and Heck reactions, and showed high
catalytic activities. The catalyst 2a showed a faster reaction
rate than the catalyst 2b in Suzuki reactions, however, their
reactivities were not significantly different in Heck reac-
tions. In particular, the catalyst 2a afforded the coupled
product of an aryl bromide with phenylboronic acid at
room temperature. Based on these results, further investi-
gations into the use of chiral catalysts in asymmetric reac-
tions are under way.
A solution of 1a (172 mg, 0.42 mmol) and (CH3CN)2-
PdCl2 (109 mg, 0.42 mmol) in CH2Cl2 (6 mL) was stirred
at room temperature for 2 h, and then the volatiles were
removed in vacuo. The residue was washed with hexane
and dried in vacuo, giving 2a as a red solid (212 mg,
0.36 mmol, yield 86%), which was recrystallized from
CH2Cl2 and hexane at ꢀ18 ꢁC to produce red crystals of
1
2a. H NMR (CDCl3): d 6.74 (m, 1H), 6.88 (m, 1H), 4.68
(m, 1H), 4.64 (m, 1H), 4.61 (m, 1H), 4.53 (t, J = 1.2 Hz,
1H), 4.49 (m, 2H), 4.48 (m, 1H), 4.31 (m, 1H), 4.20–4.05
(m, 4H), 2.95 (m, 1H), 2.41 (m, 1H), 1.83 (d, J = 6.9 Hz,
3H), 0.90 (d, J = 6.9 Hz, 6H), 0.69 (d, J = 6.9 Hz, 3H).
13C NMR (CDCl3): d 171.8, 170.08, 99.86, 86.54, 74.00,
72.92, 72.75, 72.57, 71.83, 71.51, 70.19, 69.36, 68.58,
68.25, 31.96, 29.45, 22.37, 19.59, 18.23, 15.03. Anal. found:

S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
1353
Table 4
Heck cross-coupling reactions by catalyst 2aa
O
0.1mol% 2a
O
Bu
+
O
Br
Bu
R
R
O
K3PO4, NMP
140oC
Entry
ArBr
Yieldb (%)
97
Entry
ArBr
Yieldb (%)
96
Br
1
5
Br
MeO
O
2
3
98
6
95
Br
Br
Me
O2N
O
94
85
7
8
88
92
Br
Br
Br
Me
Me
Ph
Me
4
Br
MeO
a
Reaction conditions: 1.0 equiv of aryl halide, 1.5 equiv of butyl acrylate, 2.0 equiv of K3PO4, 0.1 mol% 2a, NMP(0.2 M) at 140 ꢁC for 3 h.
b
1
Isolated yields of compounds are an average of at least two runs. All compounds are characterized by comparison of H and 13C NMR spectra with
authentic samples or literature data.
C, 45.00; H, 4.72; N, 4.60. Calc. for C22H28Cl2FeN2O2Pd:
C, 45.12; H, 4.82; N, 4.78%.
oil bath at the appropriate temperature until the starting
material was consumed, as determined by GC and TLC.
The reaction mixture was poured into 20 mL of saturated
aqueous ammonium chloride and extracted (3 · 20 mL)
with Et2O. The combined ether extracts were washed with
brine (60 mL), dried over MgSO4, and filtered. The solvent
was removed under vacuum, and the resulting crude prod-
uct was purified by flash chromatography on silica gel. The
product was eluted with 5% ethyl acetate in hexanes.
4.3. Synthesis of [1,10-bis{(S)-4-tert-butyloxazolin-2-
yl}ferrocene]palladium(II) dichloride (2b)
A solution of 1b (149 mg, 0.341 mmol) and (CH3CN)2-
PdCl2 (88 mg, 0.34 mmol) in CH2Cl2 (6 mL) was stirred
at room temperature for 2 h, and then the volatiles were
removed in vacuo. The residue was washed with n-hexane
and dried in vacuo, giving 2b as a dark red solid (204 mg,
0.333 mmol, yield 98%), which was recrystallized from
CH2Cl2 and hexane at ꢀ18 ꢁC to produce dark red crystals
of 2b. 1H NMR (CDCl3): d 6.95 (t, J = 1.4 Hz, 2H), 4.87 (t,
J = 1.4 Hz, 2H), 4.69 (t, J = 1.3 Hz, 2H), 4.44 (m, 4H),
4.21 (m, 4H), 1.14 (s, 18H). 13C NMR (CDCl3): d 171.78,
80.39, 74.02, 72.38, 70.85, 70.23, 69.67, 34.42, 26.43. Anal.
found: C, 46.61; H, 4.94; N, 4.99. Calc. for C24H32Cl2Fe-
N2O2Pd: C, 46.97; H, 5.26; N, 4.56%.
4.5. Heck cross-coupling reactions
The aryl bromide (2.0 mmol), n-butyl acrylate (3.0 mmol)
and the catalyst 2a or 2b (0.002 mmol, 0.1 mol%) were com-
bined with K3PO4 (4.0 mmol) in a small round-bottom
flask. NMP was added and the flask was sealed with a sep-
tum. The flask was maintained in an oil bath at 140 ꢁC until
the starting material was consumed, as determined by GC
and TLC. The reaction mixture was poured into 20 mL of
saturated aqueous ammonium chloride and extracted
(3 · 20 mL) with Et2O. The combined ether extracts were
washed with brine (60 mL), dried over MgSO4, and filtered.
The solvent was removed under vacuum, and the resulting
crude product was purified by flash chromatography on
silica gel. The product was eluted with 5% ethyl acetate in
hexanes.
4.4. Suzuki cross-coupling reactions
The aryl halide (2.0 mmol), phenylboronic acid
(2.2 mmol), and the catalyst 2a or 2b (0.01 mmol,
0.5 mol%) were combined with K2CO3 (3.0 mmol) in a
small round-bottom flask. Toluene was added and the flask
was sealed with a septum. The flask was maintained in an

1354
S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
4.6. X-ray crystallographic study of 2a and 2b
References
[1] For leading references, see: E. Negishi, Handbook of Organopalla-
dium Chemistry for Organic Synthesis, Wiley, New York, 2002.
[2] (a) K. Tamao, K. Sumitani, M. Kumada, J. Am. Chem. Soc. 94
(1972) 4374;
(b) A.F. Littke, G.C. Fu, Angew. Chem. Int., Ed. 41 (2002) 4176;
(c) N.T.S. Phan, D.H. Brown, P. Styring, Green Chem. 6 (2004) 526.
[3] (a) E. Negishi, Acc. Chem. Res. 15 (1982) 340;
(b) E. Negishi, L. Anastasia, Chem. Rev. 103 (2003) 1979.
[4] (a) D. Milstein, J.K. Stille, J. Am. Chem. Soc. 100 (1978) 3636;
(b) J.K. Stille, Angew. Chem. Int., Ed. 25 (1986) 508;
(c) A.F. Littke, G.C. Fu, Angew. Chem. Int., Ed. 38 (1999) 2411;
(d) J.C. Garcia-Martinez, R. Lezutekong, R.M. Crooks, J. Am.
Chem. Soc. 127 (2005) 5097.
[5] (a) Y. Hatanaka, T. Hiyama, J. Org. Chem. 53 (1988) 918;
(b) Y. Hatanaka, T. Hiyama, Pure Appl. Chem. 66 (1994) 1471;
(c) P. DeShong, C.J. Handy, M.E. Mowery, Pure Appl. Chem. 9
(2000) 1655;
(d) P. Pierrat, P. Gros, Y. Fort, Org. Lett. 7 (2005) 697.
[6] (a) N. Miyaura, A. Suzuki, Chem. Rev. 95 (1995) 2457;
(b) A. Suzuki, J. Organomet. Chem. 576 (1999) 147;
(c) J.P. Wolfe, R.A. Singer, B.H. Yang, S.L. Buchwald, J. Am.
Chem. Soc. 121 (1999) 9550;
Suitable crystals of the complexes 2a and 2b were
obtained by layering concentrated solutions of the com-
pounds in dichloromethane with n-hexane and allowing
slow diffusion at ꢀ18 ꢁC. The crystals were sealed in capil-
laries before collecting the intensity data with an Enraf-
Nonius CAD4 difractometer using monochromated Mo
˚
Ka (k = 0.71013 A) radiation. The raw data collected were
processed to produce conventional intensity data using the
program, SAINT. The intensity data were corrected for
Lorentz and polarization effects. The structures were
solved by a combination of the Patterson and difference
Fourier methods provided by the program package,
SHELXTL. All of the non-hydrogen atoms were refined
anisotropically. The hydrogen atom positions were calcu-
lated and included in the final cycle of refinement.
4.6.1. Crystal data for 2a
Empirical formula = C46H58Cl8Fe2N4O4Pd2, formula
(d) A.F. Littke, C. Dai, G.C. Fu, J. Am. Chem. Soc. 122 (2000) 4020;
(e) O. Navarro, Y. Oonishi, R.A. Kelly, E.D. Stevens, O. Briel, S.P.
Nolan, J. Organomet. Chem. 689 (2004) 3722.
weight = 1339.06, red crystals, 0.1 · 0.3 · 0.3 mm3, ortho-
rhombic, P212121, a = 14.664(2), b = 18.691(4), c =
3
˚
˚
[7] (a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 16
(1975) 4467;
(b) K. Sonogashira, J. Organomet. Chem. 653 (2002) 46.
[8] (a) R.F. Heck, Palladium Reagents in Organic Synthesis, Academic
Press, London, 1990;
26.825(7) A, V = 5455.0(17) A , Z = 4, density = 1.630
Mg/m3, absorption coefficient = 1.606 mmꢀ1, T = 188(2)
K, 10,281 unique reflections measured, R(F) for all data =
0.0549, Rw(F) for all data = 0.1303, goodness-of-fit = 1.096.
(b) I.P. Beletskaya, A.V. Cheprakov, Chem. Rev. 100 (2000) 3009;
(c) A.F. Littke, G.C. Fu, J. Am. Chem. Soc. 123 (2001) 6989.
[9] (a) J.F. Hartwig, Angew. Chem. Int., Ed. 37 (1998) 2046;
(b) S.L. Buchwald, Acc. Chem. Res. 31 (1998) 805;
(c) B. Schlummer, U. Scholz, Adv. Synth. Catal. 346 (2004) 1599.
[10] M. Beller, C. Bolm, Transition Metals for Organic Synthesis, Wiely-
VCH, Weinheim, 2004.
4.6.2. Crystal data for 2b
Empirical formula = C51H74Cl10Fe2N4O6Pd2, formula
weight = 1518.14, dark red crystals, 0.20 · 0.20 · 0.05 mm3,
orthorhombic, P212121, a = 10.4354(2), b = 12.7792(2),
3
˚
˚
c = 45.4510(4) A, V = 6061.17(16) A , Z = 8, density =
3.327 Mg/m3, absorption coefficient = 3.087 mmꢀ1, T =
188(2) K, 24,888 unique reflections measured, R(F) for all
data = 0.0970, Rw(F) for all data = 0.1844, goodness-
of-fit = 1.244.
[11] (a) J.P. Stambuli, S.R. Stauffer, K.H. Shaughnessy, J.F. Hartwig, J.
Am. Chem. Soc. 123 (2001) 2677;
(b) J.F. Hartwig, M. Kawatsura, S.I. Hauck, K.H. Shaughnessy,
L.M. Alcazar-Roman, J. Org. Chem. 64 (1999) 5575.
[12] (a) A. Togni, L.M. Venanzi, Angew. Chem. Int., Ed. 33 (1994) 497;
(b) B. Milani, A. Marson, A. Scarel, G. Mestroni, J.M. Ernsting, C.J.
Elsevier, Organometallics 23 (2004) 1974;
(c) S. Iyer, G.M. Kulkarni, C. Ramesh, Tetrahedron 60 (2004) 2163.
[13] (a) J. Park, S. Lee, K.H. Ahn, C.-W. Cho, Tetrahedron Lett. 36
(1995) 7263;
Acknowledgement
This work was financially supported by research fund of
Chonnam National University in 2004.
(b) J. Park, S. Lee, K.H. Ahn, C.-W. Cho, Tetrahedron Lett. 37
(1996) 6137;
(c) K.H. Ahn, C.-W. Cho, J. Park, S. Lee, Tetrahedron: Asymmetry
8 (1997) 1179;
Appendix A. Supplementary material
(d) S. Lee, J.H. Koh, J. Park, J. Organomet. Chem. 637–639 (2001) 99;
(e) W. Zhang, Y. Adachi, T. Hirao, I. Ikeda, Tetrahedron: Asymmetry
7 (1995) 1235;
The crystallographic data used for the structural analy-
sis were deposited with the Cambridge Crystallographic
Data Centre, CCDC no 287803 for compound 2a and no
287804 for 2b. Copies of this information may be obtained
free of charge from The Director, CCDC, 12 Union Road,
Cambridge CB2 1EX, UK (Fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk or www.ccdc.cam.ac.uk/data_re-
quest/cif). Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/
j.jorganchem.2005.12.018.
(f) W. Zhang, T. Hirao, I. Ikeda, Tetrahedron Lett. 37 (1996) 4545.
[14] Y. Imai, W. Zhang, T. Kida, Y. Nakatsuji, I. Ikeda, Chem. Lett.
(1999) 243.
[15] (a) C. Mazet, L.H. Gade, Organometallics 20 (2001) 4144;
(b) C. Mazet, L.H. Gade, Eur. J. Inorg. Chem. (2003) 1161;
(c) R.A. Gossage, H.A. Jenkins, P.N. Yadav, Tetrahedron Lett. 45
(2004) 7689.
[16] (a) P.W.N.M. van Leeuwen, P.C.J. Kamer, J.N.H. Reek, Pure Appl.
Chem. 8 (1999) 1443;
(b) P.W.N.M. van Leeuwen, P.C.J. Kamer, J.N.H. Reek, Chem.
Rev. 8 (1999) 1443, and references cited therein.

S. Lee / Journal of Organometallic Chemistry 691 (2006) 1347–1355
1355
[17] J. Yin, S.L. Buchwald, J. Am. Chem. Soc. 124 (2002) 6034.
[18] M. Sawamura, H. Hamashima, M. Sugawara, R. Kuwano, Y. Ito,
Organometallics 14 (1995) 4549.
[20] D.S. Clyne, J. Jin, E. Genest, J.c. Galluci, T.V. RajanBabu, Org.
Lett. 2 (2000) 1125.
[21] W. Shen, Teterahedron Lett. 38 (1997) 5575.
´
´
[19] (a) E. Bosch, C.L. Barnes, Inorg. Chem. 40 (2001) 3097;
(b) Y.-Z. Hu, C. Chamchoumis, J.S. Grebowicz, R.P. Thummel,
Inorg. Chem. 41 (2002) 2296;
[22] (a) C. Najera, J. Gil-Molto, S. Karlstromo¨, Adv. Synth. Catal. 346
(2004) 1798;
(b) Z. Weng, S. Teo, L.L. Koh, T.S.A. Hor, Organometallics 23
(2004) 3603;
(c) B. Tao, D.W. Boykin, J. Org. Chem. 69 (2004) 4330.
(c) T. Kawano, T. Shinomaru, I. Ueda, Org. Lett.
2545.
4 (2002)