Synthesis and structural characterization of monophosphine-cyclopalladated ferrocenylpyrimidine complexes and reusable catalytic system for amination of hindered aryl chlorides in peg-400

Article abstract of DOI:10.1021/om801149r

A new ferrocene-based ligand, 4,6-dimethyl-2-pyrimidinylferrocene (1), was conveniently prepared via the coupling reaction of chloromercuriferrocene and 4,6-dimethyl-2-iodopyrimidine, and its mono-phosphine-palladacycle complexes 3-6 were also readily obt

Full text of DOI:10.1021/om801149r

Organometallics 2009, 28, 1909–1916
1909
Synthesis and Structural Characterization of
Monophosphine-Cyclopalladated Ferrocenylpyrimidine Complexes
and Reusable Catalytic System for Amination of Hindered Aryl
Chlorides in PEG-400
Chen Xu,* Zhi-Qiang Wang, Wei-Jun Fu, Xin-Hua Lou, Ying-Fei Li, Fei-Fei Cen,
Hong-Ji Ma, and Bao-Ming Ji*
Colleget of Chemistry and Chemical Engineering, Luoyang Normal UniVersity,
Luoyang, Henan 471022, People’s Republic of China
ReceiVed December 2, 2008
A new ferrocene-based ligand, 4,6-dimethyl-2-pyrimidinylferrocene (1), was conveniently prepared
via the coupling reaction of chloromercuriferrocene and 4,6-dimethyl-2-iodopyrimidine, and its mono-
phosphine-palladacycle complexes 3-6 were also readily obtained from the cyclopalladation reactions
and bridge-splitting reactions. These compound have been fully characterized by 1H NMR, 13C{1H} NMR,
IR, ESI-MS, and elemental analysis. Additionally, their detailed structures have been determined by
X-ray single-crystal diffraction, and many types of intramolecular and intermolecular hydrogen bonds
are found to exist in the crystals of these palladacycles. The catalytic activity of these air- and moisture-
stable palladacycles was evaluated in the Buchwald-Hartwig amination involving a range of sterically
hindered aryl chlorides. 5 and 6 were found to be very efficient for this reaction. Typically, using 1 mol
% of catalyst in the presence of 2 equiv of KtOBu as base in PEG-400 [poly(ethylene glycol-400)] at
120 °C provided coupling products in excellent yields. Moreover, the 6/PEG-400 system could be recycled
and reused three times without any loss of catalytic activity.
palladacycles are one of the most developed and studied classes
of catalyst precursors, primarily due to their easy synthetic
accessibility, structural versatility, extra stability, and high
catalytic activity.5 Since the first report on the use of pallada-
cycles for aminations of aryl chlorides by Beller in 1997,6 a
wide variety of known and new palladacycles have been
successfully used in this reaction. However, only a few
palladacycles have proved to be efficient for the activation of
notoriously unreactive aryl chlorides under relatively mild
reaction conditions.7
In most cases the catalysts employed need to be used in
relatively high loadings, and with poor recovery, which negated
the advantages associated with the use of aryl chlorides. From
an economic and practical point of view, a process featuring
an efficient and recycling catalytic system in combination with
Introduction
Palladium-catalyzed coupling of amines with aryl halides or
sulfonates, commonly dubbed Buchwald-Hartwig amination,
has evolved into a versatile and efficient synthetic transformation
for the preparation of aromatic amines.1 Employing aryl
chlorides for this reaction has been a focus recently because
aryl chlorides are cheaper and more available than their bromide
and iodide counterparts.2 A number of Pd catalyst precursors,
usually simple palladium salts or complexs associated with
appropriate bulky and electron-rich alkylphosphine ligands3 and
sterically hindered N-heterocyclic carbenes (NHCs),4 can medi-
ate the coupling of aryl chlorides with amines. Among them,
* To whom correspondence should be addressed. E-mail: xubohan@
163.com; lyhxxjbm@126.com.
(1) For reviews, see: (a) Schlummer, B.; Scholz, U. AdV. Synth. Catal.
2004, 346, 1599. (b) Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz,
U. AdV. Synth. Catal. 2006, 348, 23. (c) Hartwig, J. F. Synlett 2006, 1283.
(d) Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534.
¨
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10.1021/om801149r CCC: $40.75
2009 American Chemical Society
Publication on Web 02/17/2009

1910 Organometallics, Vol. 28, No. 6, 2009
Scheme 1. Synthesis of Monophosphine-Cyclopalladated Ferrocenylpyrimidine Complexes
Xu et al.
an inexpensive solvent would be highly desirable. PEGs have
clear advantages as solvents in organic synthesis because they
are cheap, steady, readily available, and nontoxic.8 Recently,
liquid PEGs have been adopted as a new approach for catalyst
recycling, in a broad range of catalytic organic reactions.9 To
the best of our knowledge, there are no reports concerning a
reusable catalytic system for amination of aryl chlorides in liquid
PEGs.
We have also found biaryl phosphane-cyclopalladated fer-
rocenylimine complexes are very efficient for the amination of
aryl chlorides in water.10 These precatalysts combine the stability
induced by the presence of a palladacycle framework with the
high activity commonly associated with phosphine ligands and
were far more active than the corresponding dimeric pallada-
cycles.7a-c,11 In view of these findings and our continuous
interest in the cyclopalladation of ferrocene compounds with
nitrogen-containing substituents as well as applications in
coupling reactions, we present the first synthesis of monophos-
phine-cyclopalladated ferrocenylpyrimidine complexes 3-6 and
report their catalytic activity in Buchwald-Hartwig amination.
Here, we expected to employ the monophosphine-palladacycles
to effect amination on a recyclable basis. In particular we report
that 6, in combination with PEG-400 as the solvent, is an
extremely effective and reusable system for the coupling of
sterically hindered aryl chlorides with amines.
and easy availability by a direct mercuration of ferrocene.12 The
coupling reaction of chloromercuriferrocene and 4,6-dimethyl-
2-iodopyrimidine readily afforded ferrocenylpyrimidine 1. The
following cyclopalladation reaction was carried out with 1 and
1.1 equiv of Li2PdCl4 and NaOAc in methanol at room
temperature for 24 h. The formed red solids of 2 (yield: 88%)
were collected by filtration, were washed several times with
methanol, and can be assigned as a dimeric complex of
palladium.13 Because of its poor solubility in all common
organic solvents, it was directly subjected to bridge-splitting
reactions with a monophosphine ligands to produce the mono-
phosphine-palladacycle complexes 3-6. So 2 was characterized
only by IR. All the new palladacycles are air- and moisture-
stable both in the solid state and in solution. They are very
soluble in chloroform, dichloromethane, and acetone, but
insoluble in petroleum ether and n-hexane.
Complexes 1 and 3-6 were fully characterized by elemental
1
analysis, IR, H NMR, 13C{1H} NMR, and ESI-MS. The IR
spectra of 2-6 showed a strong absorption peak at ca.
1514-1502 cm-1 assigned to the CdN stretching of the
pyrimidine ring, which was shifted to lower wavenumber at
about ca. 50 cm-1 by comparison with free ligand 1 due to
1
intramolecular coordination of nitrogen to palladium. The H
NMR spectra of complexes 1 and 3-5 are consistent with the
proposed structures; 3 and 5 exhibit similar peaks for the Cp
ring with the proton ratio of 1:1:1:5, while 4 exhibits the
corresponding peaks with the proton ratio of 1:2:5, clearly
showing that they are ortho-cyclopalladated products. In contrast
Results and Discussion
Synthesis and Characterization of Compounds 1-6. The
synthetic route of 1 and monophosphine-palladacycle complexes
3-6 is demonstrated in Scheme 1. The organomercury com-
pounds have a number of notable advantages over other
organometallic compounds commonly used in cross-coupling
reactions, including higher selectivity of reactions, extra stability,
1
to those of 3-5, the H NMR spectrum of 6 exhibits more si-
gnals than expected, suggesting the existence of isomers in
solution. A similar phenomenon was also found in the 1H NMR
spectra of cyclopalladated complexes.10,11c,d,14 In the mass
spectra of palladacycles 3-6, the most intense peak was
attributed to [M - Cl]+. In order to further investigate the
(8) (a) Andrade, C. K. Z.; Alves, L. M. Curr. Org. Chem. 2005, 9, 195.
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Zhu, Y.; Wu, Y. J. Aust. J. Chem. 2007, 60, 190.
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Org. Lett. 2002, 4, 4399. (b) Li, J. H.; Zhu, Q. M.; Liang, Y.; Yang, D. J.
Org. Chem. 2005, 70, 5347. (c) Li, J. H.; Liu, W. J.; Xie, Y. X. J. Org.
Chem. 2005, 70, 5409. (d) Wang, L.; Zhang, Y.; Liu, L.; Wang, Y. J. Org.
Chem. 2006, 71, 1284. (e) Zhou, H. F.; Fan, Q. H.; Tang, W. J.; Xu, L. J.;
He, Y. M.; Deng, G. J.; Zhao, L. W.; Gu, L. Q.; Chan, A. S. C. AdV. Synth.
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Monophosphine-Cyclopalladated Ferrocenylpyrimidine Complexes
Organometallics, Vol. 28, No. 6, 2009 1911
Figure 3. 3D framework of 3 formed by hydrogen bonds and π-π
stacking interactions. The intramolecular hydrogen bonds and non-
hydrogen-bonding H atoms are omitted for clarity.
Figure 1. 2D layer structure of compound 1 formed by C-H · · · π
and π-π stacking interactions.
Figure 4. Molecular structure of 4 · CH2Cl2 showing the intramo-
lecular C-H · · · Cl and C-H · · · Pd hydrogen bonds. CH2Cl2 and
non-hydrogen-bonding H atoms are omitted for clarity.
Figure 2. Molecular structure of 3 showing the intramolecular
C-H · · · Cl and C-H · · · Pd hydrogen bonds. Non-hydrogen-bond-
ing H atoms are omitted for clarity.
(the interplane distances are about 3.441 and 3.678 Å),16 which
are attributed to the construction of the 2D layer structure of 1
(Figure 1).
structures of these compounds, their detailed structures have
been determined by X-ray single-crystal diffraction.
The single-crystal X-ray analysis indicates that the palladacycles
3-6 are trans complexes in the solid state. The Pd atom in each
complex is in a slightly distorted square-planar environment bonded
to the phosphorus atom, the chloride atom, the pyrimidinyl nitrogen
atom, and the carbon atom of the ferrocenyl moiety. The Pd-N
[2.164(3)-2.240(3) Å] and Pd-P [2.2382(7)-2.2763(11) Å] bond
lengths of the four complexes are similar to those of the related
Molecular Structures of Complexes 1 and 3-6. All the
crystals were obtained by recrystallization from CH2Cl2-
petroleum ether solution at room temperature. The molecules
are shown in Figures 1-7 (displacement ellipsoids are drawn
at the 50% probability level). Selected bond lengths and bond
angles are listed in Table 1. The crystal structure of 1 reveals
two molecules in the asymmetric unit with somewhat different
geometry. The pyrimidine ring and the Cp ring are ap-
proximately coplanar with a dihedral angel of 3.0°. In the crystal
of 1, there are three different C-H · · · π interactions15 and two
different π-π stacking interactions between the pyrimidine rings
(15) Nishio, M. CrystEngComm 2004, 6, 130.
(16) (a) Janiak, C. Dalton Trans. 2000, 3885. (b) Malathy Sony, S. M.;
Ponnuswamy, M. N. Cryst. Growth Des. 2006, 6, 736.

1912 Organometallics, Vol. 28, No. 6, 2009
Xu et al.
plexs (the interplane distances are about 3.428 Å). Finally, these
2D layers are further interlinked into a 3D framework by strong
intermolecular π-π stacking interactions (Figure 3).
Like 3, 4 · CH2Cl2 also has a 1D chain structure; the chlorine
atom not only forms a hydrogen bond with the adjacent C-H
group of Cp ring but also forms a hydrogen bond with the
adjacent C-H group of CH2Cl2. In addition, there are two
different C-H · · · Cl (CH2Cl2) hydrogen bonds and strong
intermolecular π-π stacking interactions between the pyrimi-
dine rings (the interplane distances are about 3.498 Å), which
are attributed to the 2D lamellar structure of complex 4 · CH2Cl2
(Figure 5). It can be seen from Figure 6 that complex 5 exists
as a dimer in the crystal due to intermolecular C-H · · · Cl
hydrogen bonds between the chlorine atom and the adjacent
C-H group of the pyrimidine ring (the distance is 2.755 Å).
Complex 6 like 5 has similar types of C-H · · · Cl hydrogen
bonds, which are attributed to the 1D chain structure of complex
6 (Figure 7).
Optimization of the Buchwald-Hartwig Amination Condi-
tions. Our initial exploration of reaction conditions focused on
the coupling of 2-chloroanisole with 2,5-dimethylaniline in PEG-
400 at 120 °C for 12 h. After screening a variety of bases (e.g.,
Na2CO3, K2CO3, Cs2CO3, NaOH, KOH, K3PO4, NEt3, NatOBu,
and KtOBu) (some of the data are shown in Table 2, entries
1-9), KtOBu was found to give the best result (98%, entry 9),
and NatOBu and K3PO4 displayed moderate efficiency, produc-
ing the products in 80 and 65% yields, respectively. Further-
more, the activities of several related catalytic systems in the
same model reaction were investigated. The dimeric complex
2, PPh3-palladacycle complex 3, and PCy3-palladacycle complex
4 were almost inactive under the same reaction conditions
(entries 10-12). The similar complex 5, without a N, N-
dimethylamino group in comparison with complex 6, generated
the product in moderate yield under the same conditions (73%,
entry 13). A significant increase in activity was observed with
the 2/DCPAB system (70%, entry 14), and it was more active
than the commonly used Pd(II) precursors Pd(OAc)2 in com-
bination with DCPAB (58%, entry 15). Although the complex
6 loadings could be decreased to 0.5%, only moderate yields
were obtained (58%, entry 16). Finally, we investigated room-
temperature amination of 2-chloroanisole; the results indicated
that these palladacycles were almost inactive. A possible reason
was that the lower temperature did not favor the cleavage of
stable palladacycles [Pd(II)] to form catalytically active Pd(0)
species.11d The reaction time was not further optimized.
Figure 5. 2D lamellar structure of 4 · CH2Cl2 formed by hydrogen
bonds and π-π stacking interactions. The intramolecular hydrogen
bonds and non-hydrogen-bonding H atoms are omitted for clarity.
cyclopalladated ferrocene derivatives,11c,d,13,17while the above
bond lengths in complex 4 · CH2Cl2 are longer than those of
complexes 3, 5, and 6 possibly due to the steric bulk of the
PCy3 ligand.
The most striking common features of the structures of
palladacycles 3-6 are intramolecular C-H · · · Cl and C-H · · · Pd
hydrogen bonds (Figures 2, 4, 6, and 7). Although these
interactions have been extensively studied,18 there were few
reports concerning organopalladium complexes.19 It is worthy
of notice that intramolecular C(Cp)-H · · · Pd hydrogen bonds
are present in the crystal of 4 · CH2Cl2; in addition, hydrogen
bonds between the nitrogen atom of the phosphine ligand and
the adjacent C-H group of the Cp ring are also present in the
crystal of 6, which makes a contribution to the stability of the
molecule.
In complex 3, the chlorine atom forms an intermolecular
C-H · · · Cl hydrogen bond with the adjacent C-H group of the
Cp ring, which gives rise to a 1D chain. Interestingly, the
uncoordinated pyrimidinyl nitrogen atom also forms an inter-
molecular C-H · · · N hydrogen bond with the adjacent C-H
group of the benzene ring, which is not found in the complexes
3, 5, and 6, giving the 2D layer structure of complex 3.
Furthermore, there are strong intermolecular π-π stacking
interactions between the pyrimidine rings of the nearest com-
Precatalyst 6 in the Buchwald-Hartwig Amination. A
variety of electronically and structurally diverse aryl chlorides
could be coupled efficiently with various amines by using 1
mol % of complex 6 under the optimized reaction conditions
(KtOBu, PEG-400, 120 °C) (Table 3). The desired products of
2-chloroanisole were obtained in excellent yields (95-97%)
with N-methylaniline and very sterically hindered 2,6-dimethyl-
aniline (entries 1 and 2). Even the electron-rich 2-chloroanisole
also afforded the desired products in excellent yields with
arylamines (89-98%, entries 3-6). We then studied the reaction
of very sterically hindered 2-chloro-m-xylene with various
amines. In contrast to 2-chloroanisole, the yields of 2-chloro-
m-xylene in this system decreased slightly but still were very
high (92-94%, entries 7-9). Similar to the results of the
arylamines, the reactions of 2-chloroanisole and 2-chloro-m-
xylene with primary aliphatic amines provided high isolated
yields (88-95%, entries 10-14). This is mainly because the
sterically hindered aryl chlorides prevent the formation of
disubstituted aliphatic amines. Finally, the coupling of hindered
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W.; Sun, J. J. Am. Chem. Soc. 2001, 123, 6508. (c) Moyano, A.; Rosol,
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Y. J. Tetrahedron 2007, 63, 5529.
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J. Chem. 1999, 145. (b) Brammer, L.; Bruton, E. A.; Sherwood, P. Cryst.
Growth Des. 2001, 1, 277. (c) Braga, D.; Grepioni, F.; Tedesco, E.; Biradha,
K.; Desiraju, G. R. Organometallics 1997, 16, 1846.
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Chem. Soc. 2004, 126, 1184. (b) Troitskaya, L. L.; Starikova, Z. A.;
Demeshchik, T. V.; Ovseenko, S. T.; Vorontsov, E. V.; Sokolov, V. I. J.
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Monophosphine-Cyclopalladated Ferrocenylpyrimidine Complexes
Organometallics, Vol. 28, No. 6, 2009 1913
Figure 6. Dimeric structure of 5 showing the hydrogen bonds. Non-hydrogen-bonding H atoms are omitted for clarity.
Figure 7. One-dimensional chain structure of 6 showing the hydrogen bonds. Non-hydrogen-bonding H atoms are omitted for clarity.
Table 1. Selected Bond Lengths (Å) and Angles (deg) for Complexes 1 and 3-6
4 · CH2Cl2
1
3 (X ) C(9))
(X ) C(1))
5 (X ) C(10))
6 (X ) C(9))
N(1)-C(11)
1.337(3)
1.347(3)
1.366(3)
1.354(3)
2.2006(18)
2.2382(7)
2.3995(7)
1.989(2)
169.37(5)
162.95(6)
80.98(7)
93.62.(6)
98.09(5)
1.357(6)
1.355(6)
2.256(3)
1.362(4)
1.342(4)
2.164(3)
2.2529(8)
2.3951(9)
1.997(3)
174.76(7)
162.27(9)
80.23(11)
94.59(12)
93.63(7)
91.57(3)
1.361(4)
1.352(4)
2.240(3)
2.2602(8)
2.4122(9)
1.970(3)
162.08(7)
166.04(8)
80.38(11)
94.60(8)
99.32(8)
89.66(3)
N(1)-C(12)
Pd(1)-N(1)
Pd(1)-P(1)
2.2763(11)
2.4154(13)
1.989(4)
163.77(10)
162.64(12)
80.38(15)
96.15(12)
96.68(10)
91.19(4)
Pd(1)-Cl(1)
Pd(1)-X
N(1)-Pd(1)-P(1)
X-Pd(1)-Cl(1)
X-Pd(1)-N(1)
X-Pd(1)-P(1)
N(1)-Pd(1)-Cl(1)
P(1)-Pd(1)-Cl(1)
89.74(2)
arylamines with 2-chloro-m-xylene gave the desired products
in excellent yields (92-95%, entries 15-17), which shows that
the steric hindrances of arylamines have no deleterious effect
on these reactions.
Reusable System for the Buchwald-Hartwig Amination. To
check the reusability of the solvent PEG-400 as well as the
catalyst, the coupling reaction of 2-chloroanisole with 2,5-
dimethylaniline was first examined in the presence of 1 mol %
of 6. After initial experimentation, the reaction mixture was
extracted with dry diethyl ether, and the PEG and catalyst were
solidified and subjected to a second run of the amination by
charging with the same substrates (2-chloroanisole, 2,5-dim-
ethylaniline, and KtOBu). The results of this experiment and
two subsequent experiments were consistent in yields (98%,
92%, and 86%, respectively, entry 1 in Table 4). For the same
reaction in the presence of Pd(OAc)2/DCPAB (1/2), however,
the activity of the system was decreased sharply in the second
run (entry 2), and the catalyst system could not be reused. The
amination of 2-chloroanisole and 2-chloro-m-xylene with 2,5-
dimethylaniline or morpholine could also be recycled and reused
three times without any loss of activity in the presence of 5 or
6 (1 mol %) (entries 3-5).

1914 Organometallics, Vol. 28, No. 6, 2009
Xu et al.
Table 2. Optimization of Reaction Conditions for the Coupling of
2-Chloroanisole with 2,5-Dimethylanilinea
romethane, then the combined organic layers were washed with
water, dried over MgSO4, and filtered, and the solvent was removed
on a rotary evaporator. The product was separated by passing
through a short silica gel column with CH2Cl2/petroleum ether
solution (1:2) as eluent. The second band was collected and afforded
the red solid 1, yield 52%. Mp: 168-169 °C. 1H NMR (400 MHz,
CDCl3): δ 6.76 (s, 1H, Ar-H), 5.15 (s, 2H, C5H4), 4.41 (s, 2H,
C5H4), 4.06 (s, 5H, C5H5), 2.46 (s, 6H, CH3). 13C{1H} NMR (100
MHz, CDCl3): δ 132.1, 128.5, 116.4, 82.7, 77.1, 70.4, 69.5, 69.2,
24.1. IR (KBr, cm-1): 3434, 1633, 1587, 1557, 1499, 1435, 1342,
1103, 1032, 1001. Anal. Calcd for C16H16FeN2: C, 65.78; H, 5.52;
N, 9.59. Found: C, 65.92; H, 5.33; N 9.72. MS-ESI+: m/z 293.1
([M + H]+).
entry
catalyst (mol %)
6 (1)
6 (1)
6 (1)
6 (1)
base
yield (%)b
1
2
3
4
Na2CO3
K2CO3
Cs2CO3
NaOH
KOH
25
42
58
28
5
6 (1)
57
6
7
6 (1)
6 (1)
K3PO4
NEt3
65
21
General Procedure for the Synthesis of the Cyclopalladated
Ferrocenylpyrimidine Monophosphine Complexes 3-6. A mixture
of 1 (1 mmol), Li2PdCl4 (1.1 mmol), and NaOAc (1 mmol) in 20
mL of dry methanol was stirred for 24 h at room temperature. The
red solids of 2 (yield: 88%) were collected by filtration and washed
several times with methanol. Without further purification, complex
2 was treated with monophosphine ligands (1.1 mmol) in dry
CH2Cl2 at room temperation for 1 h. The product was separated
by passing through a short silica gel column with CH2Cl2 as eluent.
The first band was collected and afforded the corresponding
monophosphine-cyclopalladated ferrocenylpyrimidine complexes.
[PdCl{[(η5-C5H5)]Fe[(η5-C5H3)-N2C4H-2CH3]}(PPh3)] (3): red
8
9
6 (1)
6 (1)
2 (1)
3 (1)
4(1)
5 (1)
NatOBu
KtOBu
KtOBu
KtOBu
KtOBu
KtOBu
KtOBu
KtOBu
KtOBu
80
98
trace
trace
16
73
70
58
56
10
11
12
13
14
15
16
2/DCPAB (0.5/2)
Pd(OAc)2/DCPAB (1/2)
6 (0.5)
a Reaction conditions: 2-chloroanisole (1 mmol), 2,5-dimethylaniline
(1.2 mmol), base (2.0 mmol), PEG-400 (4 g), T ) 120 °C, 12 h.
b Isolated yields (average of two experiments).
1
solid, yield 89%, mp 180-181 °C. H NMR (400 MHz, CDCl3):
Conclusions
δ 7.80-7.75 (m, 6H, Ph-H), 7.36-7.19 (m, 9H, Ph-H), 6.65 (s,
1H, Ar-H), 4.79 (bs, 1H, C5H3), 4.00 (bs, 1H, C5H3), 3.75 (s, 5H,
C5H5), 3.45 (bs, 1H, C5H3), 2.94 (s, 3H, -CH3), 2.40(s, 3H, -CH3).
13C{1H} NMR (100 MHz, CDCl3): δ 174.4, 169.9, 167.4, 134.7,
132.3, 131.8, 130.3, 128.1, 117.1, 86.8, 77.3, 76.9, 76.7, 76.4, 70.5,
68.8, 65.6, 26.3, 23.9. IR (KBr, cm-1): 3433, 1628, 1592, 1538,
1502, 1479, 1434, 1346, 1097. Anal. Calcd for C34H30ClFeN2PPd:
C, 58.73; H, 4.35; N, 4.03. Found: C, 58.98; H, 4.21; N 3.87. MS-
ESI+: m/z 659.0 ([M - Cl]+).
A series of monophosphine-cyclopalladated ferrocenylpyri-
midine complexes 3-6 have been easily synthesized. These
complexes are thermally stable and are not sensitive to air and
moisture. Single-crystal X-ray analysis confirms that there are
many types of intramolecular and intermolecular hydrogen
bonds in the crystals of 3-6. Their catalytic activity was
evaluated in the Buchwald-Hartwig amination of a range of
sterically hindered aryl chlorides. A highly efficient and reusable
catalytic system for this reaction has been developed. Currently,
further efforts to extend the applications involving this type of
palladacycle in other palladium-catalyzed reactions are underway
in our laboratory.
[PdCl{[(η5-C5H5)]Fe[(η5-C5H3)-N2C4H-2CH3]}(PCy3)] (4): red
1
solid, yield 86%, mp 172-173 °C. H NMR (400 MHz, CDCl3):
δ 6.60 (s, 1H, Ar-H), 4.84 (s, 1H, C5H3), 4.28 (s, 2H, C5H4), 4.06
(s, 5H, C5H5), 2.88 (s, 3H, -CH3), 2.50 (m, 3H, PCy3), 2.37 (s,
3H, -CH3), 2.16 (bs, 4H, PCy3), 1.98 (bs, 4H, PCy3), 1.80 (bs,
4H, PCy3), 1.72-1.23 (m, 18H, PCy3). 13C{1H} NMR (100 MHz,
CDCl3): δ 174.2, 130.9, 128.8, 117.0, 101.1, 87.2, 77.3, 77.0, 76.7,
75.8, 70.5, 69.5, 68.9, 66.3, 65.5, 35.5, 35.3, 31.9, 30.6, 30.4, 29.7,
27.7, 26.5, 23.8, 22.7. IR (KBr, cm-1): 3431, 2926, 1633, 1589,
1539, 1506, 1445, 1384, 1120. Anal. Calcd for C34H48ClFeN2PPd:
C, 57.24; H, 6.78; N, 3.93. Found: C, 57.46; H, 6.53; N 3.72. MS-
ESI+: m/z 677.1 ([M - Cl]+).
Experimental Section
General Procedures. All reactions were carried out under a dry
nitrogen atmosphere using standard Schlenk techniques. Solvents
were dried and freshly distilled prior to use. All other chemicals
were commercially available expect for chloromercuriferrocene20
and 4,6-dimethyl-2-iodopyrimidine,21 which were prepared accord-
ing to the published procedures. Melting points were measured using
a WC-1 microscopic apparatus and were uncorrected. Elemental
analyses were determined with a Carlo Erba 1160 elemental
analyzer. IR spectra were collected on a Bruker VECTOR22
[PdCl{[(η5-C5H5)]Fe[(η5-C5H3)-N2C4H-2CH3]}(DCPB)] (5):
red solid, yield 85%, mp 182-183 °C. 1H NMR (400 MHz, CDCl3):
δ 7.39 (s, 2H, Ph-H), 7.30 (s, 6H, Ph-H), 7.09 (bs, 1H, Ph-H),
6.60 (s, 1H, Ar-H), 4.82 (s, 1H, C5H3), 4.02 (s, 1H, C5H3), 3.77
(s, 5H, C5H5), 3.04 (s, 1H, C5H3), 2.93 (s, 3H, -CH3), 2.41 (s, 3H,
-CH3), 1.69-1.22 (m, 22H, PCy3). 13C{1H} NMR (100 MHz,
CDCl3): δ 174.6, 169.2, 166.9, 145.6, 142.1, 139.2, 138.9, 131.8,
129.2, 127.7, 127.4, 127.2, 125.4, 116.7, 86.6, 77.3, 77.0, 76.7,
74.2, 70.3, 69.4, 68.6, 66.6, 32.2, 29.7, 27.8, 26.8, 26.4, 26.0, 25.4,
23.8. IR (KBr, cm-1): 3444, 2924, 1633, 1589, 1537, 1504, 1444,
1384, 1105, 1032, 1000. Anal. Calcd for C40H46ClFeN2PPd: C,
61.32; H, 5.92; N, 3.58. Found: C, 61.13; H, 5.73; N 3.72. MS-
ESI+: m/z 747.2 ([M - Cl]+).
1
spectrophotometer in KBr pellets. H and 13C{1H} NMR spectra
were recorded on a Bruker DPX-400 spectrometer in CDCl3 with
TMS as an internal standard. Mass spectra were measured on a
LC-MSD-Trap-XCT instrument.
Synthesis of 4,6-Dimethyl-2-pyrimidinylferrocene (1). In a
flask equipped with a reflux condenser and gas inlet chloromer-
curiferrocene (1 mmol), 4,6-dimethyl-2-iodopyrimidine (1.1 mmol),
NaI (2 mmol), Pd(PPh3)4 (0.05 mmol), 18 mL of absolute THF,
and 12 mL of absolute Me2CO were placed under a N2 atmosphere.
The reaction mixture was then placed in an oil bath and heated at
70 °C for 4 h, cooled, and quenched with water. The organic layer
was separated and the aqueous layer was extracted with dichlo-
[PdCl{[(η5-C5H5)]Fe[(η5-C5H3)-N2C4H-2CH3]}(DCPAB)] (6): red
solid, yield 78%, mp 211-213 °C. The 1H NMR (400 MHz, CDCl3)
spectrum of complex 6 is more complicated than expected. It was
difficult to identify the signals of different isomers, and the ratio
of the isomers could not be calculated consequently. The main peaks
are given as follows: δ 7.43 (bs, 2H, Ph-H), 7.28-7.20 (s, 6H,
Ph-H), 6.60 (s, 1H, Ar-H), 4.80 (s, 1H, C5H3), 3.99 (s, 1H, C5H3),
(20) Rausch, M.; Vogel, M.; Rosenberg, H. J. Org. Chem. 1957, 22,
900.
(21) Kosolapoff, G. M.; Roy, C. H. J. Org. Chem. 1961, 26, 1895.

Monophosphine-Cyclopalladated Ferrocenylpyrimidine Complexes
Organometallics, Vol. 28, No. 6, 2009 1915
Table 3. Cross-Coupling of Various Amines with Hindered Aryl Chlorides Catalyzed by 6a
a Reaction conditions: aryl chloride (1 mmol), amine (1.2 mmol), KtOBu (2.0 mmol), 6 (1 mol %), PEG-400 (4 g), T ) 120 °C, 12 h. bIsolated
yields (average of two experiments).
Table 4. Recovery and Reuse of the System for the Coupling of Various Amines with Aryl Chloridesa
a
b
Reaction conditions: aryl chloride (1 mmol), amine (1.2 mmol), KtOBu (2.0 mmol), PEG-400 (4 g), T ) 120 °C, 12 h. Isolated yields.

1916 Organometallics, Vol. 28, No. 6, 2009
Xu et al.
3.78 (s, 5H, C5H5), 2.98 (s, 1H, C5H3), 2.93 (s, 3H, -CH3), 2.92
(s, 3H, -CH3), 2.45 (s, 6H, -NMe2), 1.64-1.17 (m, 22H, PCy3).
13C{1H} NMR (100 MHz, CDCl3): δ 174.6, 169.0, 168.5, 166.9,
152.1, 144.6, 138.4, 133.8, 129.1, 128.5, 121.9, 116.6, 77.3, 77.7,
70.1, 68.5, 67.9, 44.2, 30.7, 27.1, 26.7, 26.5, 25.4, 23.8. IR (KBr,
cm-1): 3453, 2922, 1633, 1590, 1537, 1503, 1428, 1384, 1103,
1032, 999. Anal. Calcd for C42H51ClFeN3PPd: C, 61.03; H, 6.22;
N, 5.08. Found: C, 61.22; H, 6.41; N 4.95. MS-ESI+: m/z 790.1
([M - Cl]+).
General Procedure for the Buchwald-Hartwig Amination.
In a Schlenk tube, a mixture of the prescribed amount of catalyst,
aryl chloride (1.0 mmol), amine (1.2 mmol), and the selected base
(2.0 mmol) in PEG-400 (4 g) was evacuated and charged with
nitrogen. The reaction mixture was then placed in an oil bath and
heated at 120 °C for 12 h. After being cooled, the mixture was
extracted with dry diethyl ether and evaporated, and the residue
was isolated by flash chromatography on silica gel (dichlo-
romethane/petroleum ether) to afford the desired coupled products.
X-ray Diffraction Studies. Crystallographic data for 1 and 3-6
were collected on a Bruker SMART APEX-II CCD diffractometer
with Mo KR radiation (λ ) 0.071073 Å). The data were corrected
for Lorentz-polarization factors as well as for absorption. Structures
were solved by direct methods and refined by full-matrix least-
squares methods on F2 with the SHELX-97 program.22 All non-
hydrogen atoms were refined anisotropically, while hydrogen atoms
were placed in geometrically calculated positions. CCDC reference
numbers are 668048, 669736, 600773, 602222, and 602221 for
complexes1 and 3-6, respectively.
Acknowledgment. We are grateful to the National
Natural Science Foundation of China (No. 20872057) and
the Natural Science Foundation of Henan Province, China
(No. 082300420040) for financial support of this work.
Supporting Information Available: This material is available
free of charge via the Internet at http://pubs.acs.org.
After extracting with diethyl ether, the mixture of catalyst and
PEG-400 was solidified (cooled and then evaporated in vacuo) and
subjected to a second run of the amination by charging with the
same substrates (aryl chloride, amine, and KtOBu).
OM801149R
(22) Sheldrick, G. M. SHELXL-97, Program for refinement of crystal
structure; University of Go¨ttingen: Germany, 1997.