Palladacycle from cyclometalation of the unsubstituted cyclopentadienyl ring in ferrocene: Synthesis, characterization, theoretical studies, and application to suzuki-miyaura reaction

Article abstract of DOI:10.1021/om5008924

The ferrocenylimines of general formula [(η⁵-C₅H₅)Fe(η⁵-C₅H₄)-CH₂N=CH-C(R)=CH-C₆H₅] with R = H (2a) and CH₃ (2b) were conveniently prepared from ferrocenylmethylamine. Reaction of 2a,b with lithium tetrachloropalladate in methanol in the presence of anhydrous sodium acetate resulted in the formation of the di-μ-chloro-bridged heteroannular cyclopalladated complexes 3a,b via the unsubstituted ferrocenyl C-H bond activation of the related ligands. Treatment of 3a,b with triphenylphosphine gave Pd{[(η⁵-C₅H₄)Fe(η⁵-C₅H₄)CH₂N=CH-CH=CH-C₆H₅]}ClPPh₃ (4a) and Pd{[(η⁵-C₅H₄)Fe(η⁵-C₅H₄)-CH₂N=CH-C(CH₃)=CH-C₆H₅]}ClPPh₃ (4b), respectively. The crystal structures of 4a,b confirmed the formation of a carbon-palladium bond by using a carbon atom in the unsubstituted cyclopentadienyl ring. Additionally, theoretical studies using density functional theory calculations were carried out in order to account for the regioselectivity of cyclometalation. As for the catalysts, using 0.1% of palladacycles 4a,b in the presence of K₃PO₄·7H₂O as base exhibited excellent yields in the Suzuki-Miyaura coupling reaction of aryl bromides with phenylboronic acid.

Full text of DOI:10.1021/om5008924

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Article
pubs.acs.org/Organometallics
Palladacycle from Cyclometalation of the Unsubstituted
Cyclopentadienyl Ring in Ferrocene: Synthesis, Characterization,
Theoretical Studies, and Application to Suzuki−Miyaura Reaction
Hengyu Qian,† Zhigang Yin,*,† Tongyan Zhang,† Shihai Yan,‡ Quanling Wang,† and Chunxia Zhang†
†Key Laboratory of Surface & Interface Science of Henan, School of Material & Chemical Engineering, Zhengzhou University of
Light Industry, Zhengzhou 450002, People’s Republic of China
‡College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, People’s Republic of China
S
* Supporting Information
ABSTRACT: The ferrocenylimines of general formula [(η5-C5H5)Fe(η5-C5H4)-CH2NCH-C(R)CH-C6H5] with R = H
(2a) and CH3 (2b) were conveniently prepared from ferrocenylmethylamine. Reaction of 2a,b with lithium tetrachloropalladate
in methanol in the presence of anhydrous sodium acetate resulted in the formation of the di-μ-chloro-bridged heteroannular
cyclopalladated complexes 3a,b via the unsubstituted ferrocenyl C−H bond activation of the related ligands. Treatment of 3a,b
with triphenylphosphine gave Pd{[(η5-C5H4)Fe(η5-C5H4)CH2NCH-CHCH-C6H5]}ClPPh3 (4a) and Pd{[(η5-C5H4)Fe-
(η5-C5H4)-CH2NCH-C(CH3)CH-C6H5]}ClPPh3 (4b), respectively. The crystal structures of 4a,b confirmed the formation
of a carbon−palladium bond by using a carbon atom in the unsubstituted cyclopentadienyl ring. Additionally, theoretical studies
using density functional theory calculations were carried out in order to account for the regioselectivity of cyclometalation. As for
the catalysts, using 0.1% of palladacycles 4a,b in the presence of K3PO4·7H2O as base exhibited excellent yields in the Suzuki−
Miyaura coupling reaction of aryl bromides with phenylboronic acid.
Fe(η5-C5H4)CH2NCH-C4H3S]ClPPh3} in the Mizoroki−
INTRODUCTION
■
Heck reaction has been described.5b,e,f Although pioneering
Recent studies of the fundamental chemistry of organo-
strides have been made, the development of heteroannular
palladium compounds have generated new impetus for the
cyclopalladation of ferrocene compounds and their applications
construction of novel palladacycles and their potential
applications in organic synthesis,1 new molecular materials,2
in cross-coupling reactions still remain a major challenge,
and medical and biological chemistry.3 In particular, ferrocenyl
probably because of the inherent difficulty in the course of
cyclometalation.
derivatives have been cyclopalladated at the substituted
cyclopentadienyl ring since the 1960s,4 where the Pd−C
In light of this and the potential application of heteroannular
cyclopalladated complexes in organic synthesis, the ligands (η5-
bond was stabilized by the intramolecular coordination of
C5H5)Fe(η5-C5H4)-CH2NCH-C(R)CH-C6H5 [R = H
donor atoms (N, P, O, or S). Moreover, palladation at the
unsubstituted cyclopentadienyl ring gave heteroannular cyclo-
palladated derivatives, in which the carbon nitrogen double
bond was not coplanar with the substituted cyclopentadienyl
ring and might direct the palladium atom toward the lower
one.5 Only scattered attention had been paid to the study of
their properties. In 2005, Moyano et al. reported the first
heteroannular palladacycle that promoted the aza-Claisen
rearrangement with excellent enantioselectivity.5d Meanwhile,
the application of heteroannular palladacycle {Pd[(η5-C5H4)-
(2a), CH3 (2b)] are described in this paper. In compounds
2a,b, the −NCH− moiety was not coplanar with the
substituted cyclopentadienyl ring. This might provide three
different activations of the σ C−H bond in cyclometalation.
The activation of the σ C−H bond of the substituted C5H4 ring
would result in the formation of ortho-palladated derivatives
Received: September 3, 2014
Published: October 15, 2014
© 2014 American Chemical Society
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(Figure 1 A), while palladation of the C5H5 ring would produce
the unexpected heteroannular palladacycles (Figure 1 B).
substituted cyclopentadienyl ring. Notably, from their 13C
NMR spectra there exists some evidence for the formation of
heteroannular complexes. For example, one signal for the
carbon atoms in the unsubstituted cyclopentadienyl ring
appears at 68.8 and 67.3 ppm for ligands 2a and 2b, while
five carbon signals corresponding to the unsubstituted
cyclopentadienyl ring are found in complexes 4a,b, among
which a new quarternary C-signal for the metalated carbon
atom resonates at 81.7 and 82.7 ppm, respectively.
For the palladium complexes 4a and 4b, the 31P NMR signal
appears at 34.1 ppm (4a) and 35.3 ppm (4b), which is in
accordance with those reported for the trans disposition of the
phosphorus ligand and the nitrogen atom.8
Figure 1. Schematic view of three different types of palladacycles.
Moreover, the palladacycles with a σ Pd−Csp2,phenyl bond due to
the “endo effect” in cyclometalation (Figure 1 C) could not be
ruled out.6 Our experimental results showed that only the
heteroannular palladacycles were obtained (Figure 1 B). in
order to explain these results, a theoretical investigation on
these palladium(II) complexes is presented. The detailed
results are discussed below.
Molecular Structures of Palladium Complexes 4a,b.
Suitable crystals of palladium complexes 4a,b were obtained
from dichloromethane/methanol. The structures, as shown in
Figures 2 and 3, indicate that the unsubstituted cyclo-
RESULTS AND DISCUSSION
■
The Ligands. The required ligands 2a,b were prepared by
the condensation of ferrocenylmethylamine and cinnamalde-
hyde or α-methyl cinnamaldehyde in 75.8% and 72.3% yields,
and the carbon nitrogen double bond in the IR spectra displays
an intense band at 1625 cm−1 for 2a and 1630 cm−1 for 2b,
1
respectively, as shown in Scheme 1. The H NMR spectra of
Scheme 1. Synthesis of the Heteroannular Palladacycles 4a,b
Figure 2. Molecule drawing for 4a. All H atoms have been omitted for
clarity. Selected bond lengths (Å) and angles (deg): Pd1−C19,
2.030(4); Pd1−N1, 2.130(4); Pd1−P1, 2.2392(15); Pd1−Cl1,
2.4089(12); N1−C30, 1.274(6); C19−Pd1−N1, 88.27(16); C19−
Pd1−P1, 90.00(14); N1−Pd1−Cl1, 91.07(10); P1−Pd1−Cl1,
91.05(5).
2a,b exhibit peaks for the ferrocene moiety with a proton ratio
of 2:2:5 in the range 4.20−4.39 ppm, showing that they are
monosubstituted ferrocene derivatives.
Synthesis and Characterization of Palladacycles 4a,b.
With the expected ligands in hand, the corresponding
palladation was carried out following the procedure4e that
afforded the dimeric cyclopalladated complex. Due to its poor
solubility in all common organic solvents, it was subjected to a
bridge-splitting reaction with PPh3 in dichloromethane for 2 h.
The unexpected heteroannular palladacycles 4a,b with σ Pd−
Csp2,ferrocene bond by using a carbon atom in the remote
unsubstituted cyclopentadienyl ring were obtained in 68.2%
and 65.8% yields. In their IR spectra, the CN absorptions are
shifted to lower wave numbers by 14−17 cm−1 (1611 cm−1 for
4a and 1613 cm−1 for 4b), when compared with the
corresponding starting ligands, indicating the existence of
N→Pd coordination. In addition, the two absorption bands at
around 1100 and 1000 cm−1, a feature of the monosubstituted
ferrocene derivatives,7 are not detected in complexes 4a,b,
indicating the disappearance of the unsubstituted cyclo-
pentadienyl ring in this molecule. Moreover, in comparison
pentadienyl ring is palladated, forming an unexpected metal-
lacycle, and the remaining coordination sites are occupied by a
chloride, the imine nitrogen, and the phosphorus atom of the
PPh3, showing the tetracoordinate palladium(II) complexes.
The Pd(II) center in each complex is in a slightly distorted
square-planar environment, with the largest deviation from the
mean plane being −0.1002 Å at N(1) for 4a and 0.0918 Å at
C(19) for 4b, and the dihedral angles between the planes
C(19)Pd(1)N(1) and P(1)Pd(1)Cl(1) are 7.1° and 8.0° for 4a
and 4b, respectively. Due to the existence of intramolecular
N→Pd coordination,9 the plane bearing the −NC−CC−
group is twisted from its attached phenyl ring with a dihedral
angle of 7.0° in 4a and 9.7° in 4b. The N(1)−Pd(1)−P(1)
angles are 173.6° and 178.9°, in agreement with a trans
arrangement between the PPh3 and the imine nitrogen, as
indicated by the 31P NMR feature of complexes 4a and 4b. The
Pd−N bond length (2.130(4) Å for 4a; 2.138(4) Å for 4b) is
appreciably longer than that reported for the endo-type
cyclopalladated ferrocenylimines, but the Pd(1)−C(19) bond
length (2.030(4) Å for 4a; 1.997(6) Å for 4b) falls comfortably
within the range found for these palladium(II) complexes.10
1
with the H NMR spectra of the corresponding ligands 2a,b,
the resonance of the unsubstituted cyclopentadienyl ring in the
upfield region (around 3−5 ppm) in complexes 4a,b is absent,
indicating that palladation occurs on the remote, non-
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Table 1. Comparison of the Calculated (Lower Row) Bond
Distances (Å) and Bond Angles (deg) around the Pd Atoms
with Those Obtained by X-ray Diffraction (Upper Row)
4a
4b
Pd1−C19
2.030(4)
2.0257
1.997(6)
2.034
Pd1−N1
2.130(4)
2.1921
2.138(4)
2.2160
Pd1−P1
2.2392(15)
2.3550
2.2576(17)
2.3526
Pd1−Cl1
2.4089(12)
2.4887
2.4176(19)
2.4963
C19−Pd1−N1
C19−Pd1−P1
N1−Pd1−Cl1
P1−Pd1−Cl1
88.27(16)
89.47
90.04(19)
90.37
90.00(14)
91.57
88.86(16)
91.62
91.07(10)
86.10
84.82(12)
85.10
Figure 3. Molecule drawing for 4b. All H atoms and the methanol
molecule have been omitted for clarity. Selected bond lengths (Å) and
angles (deg): Pd1−C19, 1.997(6); Pd1−N1, 2.138(4); Pd1−P1,
2.2576(17); Pd1−Cl1, 2.4176(19); N1−C30, 1.255(7); C19−Pd1−
N1, 90.40(19); C19−Pd1−P1, 88.86(16); N1−Pd1−Cl1, 84.82(12);
P1−Pd1−Cl1, 95.82(6).
91.05(5)
93.46
95.82(6)
93.25
Moreover, the values of the torsion angles Cphenyl−CC−
C(30) and CC−C(30)−N(1) [179.85° and 177.61° in
model B, 179.47° and 176.99° in model E] compare well to the
observed values for the corresponding ligands [179.74° and
179.75° in model A, 179.16° and 179.89° in model D], so the
imine moiety was coplanar with the phenyl ring in models A
and D. Additionally, the C(29)−N(1)−C(30) angles obtained
for the optimized geometries were 117.5° [model A] and
117.7° [model D], respectively. Therefore, this conformation
for these ligands might direct the donor atom toward the lower,
nonsubstituted cyclopentadienyl ring.
Further, it is well known that cyclometalation of the
nitrogen-donor ligands proceeds in two steps:4e,11 (1) the
coordination of the nitrogen atom to the metal; (2) the
electrophilic attack of metal at the carbon atom. Once the
donor atom is coordinated to the metal, the C−H bond
susceptible to the metalation must be in close proximity to the
metal and adopt a suitable position to form the corresponding
metallacycles. On this basis, the geometries of model complexes
{Pd[(η5-C5H5)Fe(η5-C5H4)-CH2-NCH-C(R)CH-C6H5]-
Cl3}− (where nitrogen is coordinated to palladium through its
lone pair exclusively; R = H, model E and R = CH3, model J)
were undertaken using the B3LYP methods. For the optimized
geometry, the electron density on C(19) in the unsubstituted
cyclopentadienyl ring is higher than on C(28) in the substituted
cyclopentadienyl ring and C(38 or 39) in the phenyl ring
(Table 2). In addition, the distances between the palladium and
the carbon atoms (C19, C28, C38, or C39), being inclined to
undergo metalation, are 3.428, 3.863, and 5.291 Å in model C
and 3.418, 3.847, and 6.280 Å in model F, respectively. For this
The two cyclopentadienyl rings are nearly eclipsed with a
dihedral angle of 2.4° and 3.7° for 4a and 4b, respectively.
Computational Studies on the Regioselectivity of
Cyclopalladation. In an effort to explain the unexpected
formation of palladium(II) complexes (4a and 4b), molecular
geometries were calculated for the ligands and the palladium
complexes. The detailed results are shown in Figure 4.
As shown in Table 1, the predicted geometries for models B
and E from density functional theory (DFT) calculations are in
good agreement with the X-ray experimental parameters.
Table 2. Partial Mulliken Charges and the Distances between
Palladium and the Carbon Atoms Involved in
Cyclometalation
a
b
atom
C19
C28
C38 /C39
a
a
−0.141 /−
b
a
−0.118 /−
b
Mulliken charge −0.153 /−
b
0.158
0.130
0.114
a
b
a
b
a
b
distance (Å)
3.428 /3.418
3.863 /3.847
5.291 /6.280
Figure 4. Optimized structures of models A−F. The hydrogen atoms
have been omitted. Models A and D: ligand; models B and E: the
heteroannular palladacycle; models C and F: the intermediate.
a
b
The atom number is listed in model C. The atom number is listed in
model F.
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arrangement it shows that the C−H bond in the unsubstituted
cyclopentadienyl ring is extremely close to the palladium and
has the proper orientation to be suitable for activation. These
findings may be responsible for the formation of the
heteroannular palladium(II) complex via an unexpected
cyclometalation at the unsubstituted cyclopentadienyl ring.
Catalytic Studies for the Suzuki−Miyaura Reaction.
The Suzuki−Miyaura cross-coupling reaction of aryl halides
and aryl boronic acids is one of the most versatile and powerful
synthetic tools for carbon−carbon bond formation.12 Some
palladium complexes were developed and displayed good
efficiency in this kind of reaction.13 Despite the progress in this
field, the search for novel palladium complexes remains a major
challenge in the development of high catalytic activity with wide
substrate tolerance. Thus, we wonder whether the present
novel heteroannular palladium complexes 4a and 4b can
proceed in carbon−carbon bond forming reactions. Initially, the
Suzuki−Miyaura coupling between bromobenzene and phenyl-
boronic acid in the presence of palladacycle 4a was selected as
the model reaction to examine the catalytic efficiency, and the
results are outlined in Table 3. After optimization of the
Table 4. Suzuki Coupling of Aryl Halides with
Phenylboronic Acid
a
Aryl Bromide + PhB(OH)2 → Ar-Ph
b
yield (%)
entry
aryl bromide
bromobenzene
catalyst 4a
catalyst 4b
1
91.5
86.3
80.2
36.4
89.6
94.6
93.6
85.2
83.4
35.2
88.5
95.8
2
4-bromoethylbenzene
2-bromotoluene
3
4
1-bromo-2,4-dimethoxybenzene
4-bromofluorobenzene
4-bromobenzotrifluoride
4-bromobenzotrifluoride
1-bromo-4-nitrobenzene
1-bromo-4-nitrobenzene
chlorobenzene
5
6
c
c
7
92.3
91.2
8
96.8
97.2
c
c
9
94.5
93.4
10
11
12
13
14
7.2
8.3
d
d
chlorobenzene
21.8
19.4
1-chloro-4-nitrobenzene
1-chloro-4-nitrobenzene
1-chloro-4-nitrobenzene
17.5
18.4
d
d
40.3
39.8
e
e
60.4
58.2
a
Reaction conditions: ArBr (1 mmol), PhB(OH)2 (1.2 mmol), catalyst
(0.5 mol %), base (1 mmol), solvent (5 mL), reaction time (2 h).
b
c
d
Table 3. Effect of Base and Solvent on the Suzuki−Miyaura
Isolated yield (average of two runs). Catalyst: 0.1 mol %. Catalyst:
a
e
2 mol %. Catalyst: 2 mol %; reaction time: 10 h.
Reaction of Bromobenzene with Phenylboronic Acid
b
entry
base
solvent/temp
yield (%)
4, entry 10). Finally, the coupling of the activated chloride (1-
chloro-4-nitrobenzene) with phenylboronic acid afforded a
moderate yield (Table 4, entries 12 and 13). On increasing the
catalyst loading to 2 mol % and prolonging the reaction time to
10 h, the yield of the biaryl could reach 60.4% and 58.2%
(Table 4, entry 14), respectively.
1
K3PO4·7H2O
K3PO4·7H2O
K3PO4·7H2O
K3PO4·7H2O
K3PO4·7H2O
Cs2CO3
tetrahydrofuran/66 °C
dioxane/100 °C
methanol/65 °C
toluene/110 °C
toluene/110 °C
toluene/110 °C
toluene/110 °C
toluene/110 °C
toluene/110 °C
toluene/110 °C
toluene/110 °C
43.8
70.2
55.2
91.5
2
3
4
c
5
92.8
6
82.5
55.4
32.5
75.2
71.8
36.5
7
K2CO3
CONCLUSION
■
8
KF·2H2O
KOH
In summary, reaction of Schiff bases derived from ferroce-
nylmethylamine with Li2PdCl4 led to the formation of the
unexpected heteroannular palladium complexes 4a and 4b,
resulting from cyclometalation of the unsubstituted cyclo-
pentadienyl ring. Single-crystal X-ray analysis confirmed that
the carbon−palladium bond was formed by using a carbon
atom in the unsubstituted ferrocene ring. Theoretical studies
based on DFT show a reasonable agreement with these
observation. In addition, these palladacycles exhibit high activity
for the Suzuki−Miyaura reaction of aryl bromides with
phenylboronic acid, giving the biaryl products in high yields.
This protocol provides a promising method for the formation
of heteroannular cyclometalated complexes. Further studies are
in progress centered on the mechanism of cyclometalation and
their applications in organic synthesis.
9
10
11
NaOH
Et3N
a
Reaction conditions: PhBr (1 mmol), PhB(OH)2 (1.2 mmol),
catalyst 4a (0.5 mol %), base (1 mmol), solvent (5 mL), reaction time
(2 h). Isolated yields (average of two runs). Reaction time: 4 h.
b
c
reaction conditions with bromobenzene, it was found that
K3PO4·7H2O and toluene were the most appropriate base and
solvent, and the reaction was stopped after 2 h instead of 4 h.
To gain insight into the broad functional group tolerance of
this system, a representative range of aryl bromides and
chlorides were tested in the presence of palladacycles 4a and
4b. An electron-deficient aryl bromide bearing an electron-
withdrawing −CF3 or −NO2 group reacted with phenylboronic
acid with the reduction of catalyst loading to 0.1% and yielded
the corresponding products almost quantitatively for both
palladium complexes 4a and 4b (Table 4, entries 6−9). In the
case of 4-bromoethylbenzene, the electron-rich counterparts
could couple with phenylboronic acid in excellent yield (Table
4, entry 2). In addition, reaction of 2-bromotoluene with
phenylboronic acid gave the corresponding product in 80.2%
and 83.4% yields for palladacycles 4a and 4b. A comparatively
lower yield was obtained employing 1-bromo-2,4-dimethox-
ybenzene instead of 2-bromotoluene as the substrate (Table 4,
entries 3 and 4). This result suggested a strong steric effect of
the substituted group of the phenyl ring on the catalytic activity
in this reaction. When chlorobenzene was used as the coupling
partner, only a trace amount of the biaryl was obtained (Table
EXPERIMENTAL SECTION
■
General Procedures. Melting points were measured on an
microscopic apparatus and were uncorrected. IR spectra were obtained
as KBr disks on a spectrophotometer. Elemental analyses were carried
out with a microanalyzer. NMR spectra were recorded on a DPX 400
spectrometer in CDCl3. Chemical shifts were cited relative to SiMe4.
Solvents were dried and distilled under nitrogen prior to use.
Synthesis of Ligands 2a,b. A mixture of ferrocenylmethylamine
(903 mg, 4.2 mmol), the corresponding aldehyde (4 mmol)
[cinnamaldehyde (528 mg) or α-methylcinnamaldehyde (584 mg)],
and 10 mL of methanol was stirred for 2 h at room temperature. The
mixture was concentrated to dryness and purified by chromatography
on a silica gel plate (petroleum/CH2Cl2 = 10:1).
(η5-C5H5)Fe(η5-C5H4)-CH2-NCH-CHCH-C6H5 (2a): orange oil
(997 mg, 75.8%). IR (KBr pellet): 3084, 2915, 1649, 1625, 1601, 1429,
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dx.doi.org/10.1021/om5008924 | Organometallics 2014, 33, 6241−6246