Ferrocenyl-palladium complexes in cross-coupling reactions: A comparative study

Article abstract of DOI:10.1016/j.tet.2005.06.072

Ferrocenecarboxaldehyde hydrazones were converted into palladium complexes on treatment with sodium tetrachloropalladate. The substitution pattern of the ferrocenylhydrazones was found to have a marked influence on the mode the palladium was attached to the organic moiety. The catalytic activity of the new palladium complexes in cross-coupling reactions was examined in detail, and it was compared with conventional catalyst systems.

Full text of DOI:10.1016/j.tet.2005.06.072

Tetrahedron 61 (2005) 9767–9774
Ferrocenyl-palladium complexes in cross-coupling reactions:
a comparative study
*
´
Tibor Zs. Nagy, Antal Csampai and Andras Kotschy
*
´
¨ ¨
´ ´ ´
Department of General and Inorganic Chemistry, Eotvos Lorand University, Pazmany P. s. 1/A, H-1117 Budapest, Hungary
Received 11 March 2005; revised 9 May 2005; accepted 17 June 2005
Available online 21 July 2005
´ ´
Dedicated to Professor Andras Liptak on the occasion of his 70th birthday.
Abstract—Ferrocenecarboxaldehyde hydrazones were converted into palladium complexes on treatment with sodium tetrachloropalladate.
The substitution pattern of the ferrocenylhydrazones was found to have a marked influence on the mode the palladium was attached to the
organic moiety. The catalytic activity of the new palladium complexes in cross-coupling reactions was examined in detail, and it was
compared with conventional catalyst systems.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
unexpected finding provided us an additional opportunity
to establish the influence of the coordination mode of
palladium on its catalytic activity.
The identification of cyclopalladated tri-o-tolylphosphine as
a highly active catalyst in carbon–carbon bond forming
reactions1 has initiated the thorough study of the catalytic
activity of palladacycles. These metallacycles, containing a
carbon–palladium-heteroatom motif and in certain cases
other ancillary ligands, are usually effective catalysts in
cross-coupling reactions and a series of highly active
systems were reported. The selection of ring heteroatoms
includes phosphorous,1–4 oxygen,5 nitrogen,6–9 or sul-
phur,10,11 while additional ligands are mostly phosphanes.12
On the evidence of the accumulated data13,14 a debate
commenced,15 whether the high catalytic activity of such
systems stems from the fact that palladacycles are robust
catalysts, or they are merely a source of low-ligated
palladium complexes.16
Our study was aimed at the synthesis of a series of ferrocene
containing palladacycles, hopefully showing high activity,
and the study of their catalytic behaviour in cross-coupling
reactions. The catalysts were all based on the ferrocenylhy-
drazone framework, and the model reactions of our choice
included the Heck, Suzuki and Sonogashira coupling.
Detailed spectroscopic study of the prepared catalyst
complexes revealed, that in spite of their similar ligand
framework, each ferrocenylhydrazone gave a complex with
a
considerably different coordination mode. This
Keywords: Palladium complexes; Heck coupling; Tetrachloropalladate.
*
Corresponding authors. Tel.: C36 1 372 2910; fax: C36 1 372 2909;
e-mail: kotschy@chem.elte.hu
Scheme 1. The palladation of ferrocenylhydrazones L1–L3 with sodium
tetrachloropalladate.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.072

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T. Zs. Nagy et al. / Tetrahedron 61 (2005) 9767–9774
1
2. Preparation of the ferrocene-based palladium
complexes
In DMSO-d6 C2 gives the H and 13C NMR spectra of L2
referring to dissociation of both Pd–N bonds. In CDCl3 two
isomeric species (in ca. 70 and 30%) were detected, which
may differ in the relative orientation of the two ferrocenyl
groups (N.B. two analogous isomers were identified for the
closely related PdCl2 complex of N,N-dimethyl-ferrocenyl-
hydrazone).20 The presence of Pd–N bonds in both isomers
The studied catalysts were obtained by the treatment of
ferrocenylhydrazone type ligands L1–L3 with Na2PdCl4 in
methanol in the presence of NaOAc at rt (Scheme 1), a
procedure widely applied in the synthesis of carbopalla-
dated complexes.17 Under this condition the chelating
phthalazonyl derivatives L1 and L318 underwent carbopal-
ladation and azapalladation, respectively, affording chloro-
brideged dimers C1* and C3*, while the phenylhydrazone
L219 simply coordinated to PdCl2 to give C2. The dimeric
structure of C1* is stated on the basis of its amide-I IR band
of C2 was supported by H 15N HMBC spectroscopy. The
1
15N signals of N8 shift considerably upfield [234 and
226 ppm for the asymmetric major (A) and 229 ppm for the
symmetric minor (B) component], relative to that measured
for the non-coordinated N8 atom in the free ligand L2
(325 ppm).
(1652 cmK1), which is very similar to that (1659 cmK1
)
measured for ligand L1,18 suggesting that the proximal
nitrogen atom (N2) of the phthalazine ring is not
coordinated to the palladium centre. As a consequence of
this, we must assume the stabilization of the palladium by
the formation of a m-chloro-bridged dimmer (C1*). The
presence of the Pd–N2 bond in C3* in the solid state is
clearly reflected in its amide-I frequency (1721 cmK1),
which is significantly higher than that of the free ligand L3
(1652 cmK1).18 In C3* the coordinative saturation of the
palladium centre also requires the formation of the
m-chloro-bridged dimer form. The proposed structures for
C1* and C3* are also supported by other physical
measurements (see later). The solid structure of C2 is
regarded to be analogous to that reported for the closely
Under the same conditions (dissolved in DMSO-d6) C3*
presumably undergoes dissociation to C3 whose strongly
coordinated N2 atom has a significant sp3 character, which
is also reflected by its NMR shift of 154 ppm.21–23 The
strong coordination of the sp2 nitrogen atom (N11) in C1
and C3 is evidenced by its signal (274 and 254 ppm,
respectively), shifted substantially upfield relative to the
free ligands L1 (330 ppm) and L3 (316 ppm). In C3 the H-
20/50 1H NMR signal (5.13 ppm) as well as the C1- and C12
13C NMR signals (158.2 and 149.2 ppm) 0 are downfield
shifted from those of L3 (4.56 ppm for H-2 /50, 143.0 ppm
for C1 and 143.9 ppm for C12)18 providing further evidence
of the presence of the Pd–N2, and Pd–N11 bonds.
In summary, the formed ferrocenylhydrazone complexes
under the conditions, where their catalytic activity is to be
tested, contain the palladium centre in a NPdC attachment
mode in a palladacycle (C1), in a NPdN attachment mode in
a palladacycle (C3), or as part of a loosely coordinated
NPdN complex (C2).
related
PdCl2
complex
of
N,N-dimethyl-
ferrocenylhydrazone.20
The prepared ferrocenylhydrazone-palladium complexes
were also characterized by 1H, 13C and 15N NMR
spectroscopy (Scheme 2). Dissolved in CDCl3 C1* was
transformed into the pentacyclic chelate C10 through the
connection of the phthalazine moiety (N2) and the
palladium centre, as followed by 1H-15N-HMBC spec-
troscopy. The 15N signal of N2 shifts considerably upfield
(245 ppm), relative to that measured for the non-coordi-
nated N2 atom in the free ligand L1 (284 ppm). In DMSO-
d6, representing the more polar conditions of the catalytic
reactions, the weak Pd–N2 bond is cleaved by a
coordinating solvent molecule as reflected by the downfield
shift of the N2 signal to 304 ppm in complex C1. Since we
were unable to grow crystals that were suitable for X-ray
analysis, the relative configuration of the dimeric C1*
structure (meso or racemic) could not be determined so far.
3. Catalysis studies
The first model reaction selected was the Heck coupling of
different aryl halides and methyl acrylate in the presence of
triethylamine as base (Scheme 3). The opening experiments
were aimed at establishing the dependence of the catalytic
activity of C1–C3 on the reaction media. Iodobenzene was
coupled in solvents of different polarity ranging from DCM
to water, to find that polar coordinating solvents such as
DMF or DMA gave the best results under the applied
conditions (Table 1).
Scheme 3. The reactions used to test the catalytic activity of complexes
C1–C3 in Heck couplings.
All conversion measurements presented are an average of at
least three parallel reactions and the determined values are
based on internal standards. The first set of data obtained
after running the reaction for 18 h at 50 8C (Table 1)
revealed that in DMF and DMA both C1 and C2 gave near
Scheme 2. The different coordination modes of complexes C1 and C3.

T. Zs. Nagy et al. / Tetrahedron 61 (2005) 9767–9774
9769
Table 1. The catalytic activity of C1–C3 in the model Heck coupling in various solventsa,b
DCM
THF
MeCN
DMF
H2O
DMA
C1
C2
C3
11.6
16
7.8
11.6
26.6
43.8
16.9
27.3
8.8
17.9
40.9
52.3
35.5
43.8
35.6
55.2
65.8
86.6
99.9
99.9
98.6
99.5
77.6
85.1
2.8
5.1
2.1
13.2
0.7
18.9
99.9
99.9
100
100
94.9
96.5
a Iodobenzene (1 equiv), 1.2 equiv methyl acrylate, 1.4 equiv TEA, 1 ml/mmol solvent, 0.1% C1, 0.1% C2, or 0.2% C3, respectively.
b Normal numbers refer to the conversion values determined by GC analysis of the reaction mixtures after 18 h at 50 8C. Italics refer to the conversion values
obtained after a further 2 h heating at 70 8C.
complete conversion. C3 also gave good results, although, it
was significantly less reactive. Of the other solvents tested
in DCM, THF and MeCN the catalysts showed only
mediocre activity, interestingly C3 being more active than
the other complexes (probably C1* and C2*). Increase of
the temperature to 70 8C for 2 h led to a considerable
improvement of the catalytic activity in all possible cases.
The catalytic activity of C1, C2 and the palladium–
triphenylphosphine system were very similar, showing
only a brief induction period, with Pd(OAc)2 and C2
being the most active under the applied conditions. The
time-conversion curve of C3 is significantly different from
the other catalyst systems, exhibiting a prolonged induction
phase and showing only decreased activity. In the light of
the kinetic studies of Pfaltz and Blackmond on the Heck
coupling reactions using palladacycles24 it is probable, that
the difference in the activity of the examined catalyst
systems originates from the differences in the ease of
formation of the catalytically active species.
In the first coupling experiments iodobenzene was reacted
with methyl acrylate in the presence of the different
palladium complexes C1–C3 (Fig. 1). For the kinetic
study of the Heck coupling catalyst loadings of 10K2
–
2*10K2% were found optimal. For comparison the reaction
was also run in the presence of 10K2% Pd(OAc)2 with and
without 2*10K2% PPh3.
The scope of the use of catalysts C1–C3 in Heck couplings
on a preparative scale is limited to aryl iodides (Table 2).
Using 0.05–0.1% of the catalysts gave appreciable
conversion only with iodobenzene (1a), 4-iodoanisole (1b)
and iodotoluene (1c). The expected cynnamate derivatives
were isolated in good to excellent yields, while less reactive
aryl halides, such as 3-brompyridine (1d) or
4-chlorobenzonitrile (1e) gave no conversion. These results
point out, that our catalysts fall into the same category with
a series of other complexes, which show acceptable
catalytic activity with highly reactive iodoarenes, but are
inefficient when the coupling of bromo-, and chloroaro-
matics are concerned.16
The addition of external ligands, such as triphenyl–
phosphine or tri(tert-butyl)phosphine has a profound effect
on the activity of the catalysts. The coupling of bromo-
benzene and methyl acrylate catalysed by C1, not running in
the absence of external ligands, was also tested in the
Figure 1. Kinetic study of the catalytic activity of C1–C3 in the model
Heck coupling. (a) 10K2% C1; (b) 10K2% C2; (c) 2*10K2% C3; (d) 10K2
Pd(OAc)2 and 2*10K2% PPh3; (e) 10K2% Pd(OAc)2 at 100 8C.
%
Table 2. The catalytic efficiency of complexes C1–C3 in the Heck coupling
of different aryl halides (1a–e) at 0.05% catalyst loadinga,b
ArX
C1
C2
C3
1a
1b
1c
1d
1e
100 (82)
100 (93)
100 (97)
0
100 (51)
100 (99)
100 (95)
0
100 (73)
100 (98)
100 (96)
0
0
0
0
a Numbers refer to conversion values determined by GC, numbers in
parenthesis refer to isolated yields.
Figure 2. Kinetic study of the catalytic activity of C1–C3 in the model
Heck coupling, when the starting material is bromobenzene (a) 0.5%
Pd(OAc)2 and 1% PPh3; (b) 0.5% C1 and 0.5% PPh3; (c) 0.5% C1 and 1%
PPh3; (d) 0.5% C1 and 2% PtBu3.
b Aryl halide (1 equiv), 1.2 equiv methyl acrylate, 1.4 equiv TEA, 1 ml/
mmol DMF, 0.05% C1, 0.05% C2 or 0.1% C3 were heated at 100 8C for
1 h, or until full conversion.

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T. Zs. Nagy et al. / Tetrahedron 61 (2005) 9767–9774
presence of added phosphins. For reference the reaction was
also run in the presence of Pd(OAc)2–2 PPh3. The studied
reactions revealed (Fig. 2) that the addition of PPh3 has a
marked influence on the catalytic activity of C1. Already the
addition of 1 equiv PPh3 to C1 led to some product
formation, and increase of the phosphine–palladium ratio to
2 resulted in a catalytic activity comparable to the
Pd(OAc)2–PPh3 system. The addition of tri(tert-butyl)pho-
sphine, as expected, led to the formation of a highly active
catalyst species, giving nearly full conversion in 5 min.
Tricyclohexylphosphine, although formed an active cata-
lyst, initiated other transformations. The addition of
tetrabutylammonium salts to the reaction mixture, or the
change of base to N-methyl-dicyclohexylamine or sodium
acetate had no significant effect on the catalytic activity of
C1, even when the temperature was raised to 150 8C.
Figure 3. Kinetic study of the catalytic activity of C1–C3 in the model
Suzuki coupling. (a) 0.1% C1; (b) 0.1% C2; (c) 0.2% C3; (d) 0.1% C2 and
0.2% PPh3; (e) 0.1% Pd(OAc)2 and 0.2% PPh3; (f) 0.1% Pd(OAc)2.
We also determined the longevity parameter (TON) for
complexes C1–C3 in the reaction of iodobenzene and
methyl acrylate at 10K3 and 10K4% catalyst loadings. The
determined values, shown in Table 3., correspond to partial
conversions, except for 10K3% C2, where a near complete
conversion was achieved before the catalyst was deacti-
vated. Although, the TON values fall into the same range, a
tendency might be observed, with the loosest bonded
palladium complex (C2) giving the highest number and
the complex where palladium is bound the strongest giving
the lowest TON.
Pd(OAc)2–PPh3 and Pd(OAc)2 catalyst systems were also
examined under the same conditions (0.1% Pd(OAc)2, 0.2%
PPh3) to reveal these catalysts as the most active of the
studied systems. Surprisingly, the addition of triphenyl-
phosphine to the active ferrocene based catalyst, C2, unlike
in the C1 catalysed Heck coupling of bromobenzene (Fig. 2),
led to a marked decrease in the catalytic activity of the system.
The catalysts C1–C3 were also tested in the Suzuki
coupling of other substrates (Table 4). Comparison of the
conversion data observed after running the reactions for 4 h
are in good agreement with the kinetic measurements.
Table 3. The turnover numbers determined for complexes C1–C3 in the
model Heck coupling at 10K3 and 10K4% catalyst loadingsa,b
C1
C2
C3
TON
62,000 (48,000) 92,500 (96,000) 23,000 (35,000)
Table 4. The catalytic efficiency of complexes C1–C3 in the Suzuki
coupling of different aryl halides (1b–i) at 0.5% catalyst loadinga,b
a Regular numbers refer to values determined at 10K3, and italic numbers to
values determined at 10K4% catalyst loading.
ArX
C1
C2
C3
b Iodobenzene (1 mmol), 1.2 mmol methyl acrylate, 1.4 mmol TEA, 1 ml
DMF, and 10K3 or 10K4% of the appropriate catalyst (C1–C3) were
heated at 100 8C for a period of time (maximum 72 h), after which no
significant conversion was observed.
1b
1c
1d
1e
1f
1g
1h
1i
75 (97)
89 (71)
96 (95)
0
92 (67)
21
14
96
99
98
0
99
33
40
0
80
90
71
0
90
15
12
0
In the next set of experiments we studied the efficiency of
our catalysts C1–C3 in the Suzuki coupling of different aryl
halides (1b–i) and phenylboronic acid (4) (Scheme 4). The
reaction of 2-fluoro–bromobenzene (1f) and 4, in the
presence of potassium carbonate in DMF, was used to
establish the kinetic profile of the transformations (Fig. 3).
0
a Numbers refer to conversion values determined by GC after 4 h, numbers
in parenthesis refer to isolated yields after full conversion.
b Aryl halide (1 equiv), 1.5 equiv phenylboronic acid, 2 equiv K2CO3, 8 ml/
mmol DMF, 0.5% C1, 0.5% C2, or 1% C3, respectively, were heated at
100 8C.
In each case, where appreciable conversion was observed
(1b–d,f–h) C2 gave the best results and C3 the lowest
conversion values. In case of C1 the processes were
repeated on a preparative scale too, and the products of
the couplings were isolated where the conversion values
were satisfactory giving the expected biaryls in good to
excellent yield. Unlike in the Heck coupling, in these
reactions we observed some conversion for bromoaromatics
too, although, our catalysts are of limited synthetic value in
this respect.
Scheme 4. The reactions used to test the catalytic activity of complexes
C1–C3 in Suzuki couplings.
The ligands C1 and C2, when added in 0.1 mol%, both
showed a similar activity, giving acceptable conversions in
about 3 h. C2 was again slightly superior to C1 (cf. Fig. 1),
suggesting that the ease of palladium’s release from the
starting complex might have a major influence on the
catalyst’s activity. C3, alike in the Heck coupling, showed a
prolonged induction period and decreased catalytic activity
compared to the other complexes. For comparison the
Finally, we also tested the activity of our catalysts in the
Sonogashira coupling of different aryl halides (1a–d,e,g,j)
and 2-methyl-3-butyn-2-ol (6) (Scheme 5). As it is well

T. Zs. Nagy et al. / Tetrahedron 61 (2005) 9767–9774
9771
Table 5. The catalytic efficiency of complexes C1–C3 in the Sonogashira
coupling of different aryl halides (1a–d,e,g,j) at 2% catalyst loadinga,b
ArX
C1
C2
C3
1a
1b
1c
1d
1e
1g
1j
99 (56)
44 (25)
65 (46)
100 (89)
0
99
99
99
99
0
65
26
36
99
0
Scheme 5. The reaction used to test the catalytic activity of complexes C1–
C3 in Sonogashira coupling.
20
100 (51)
30
80
30
65
known, the Sonogashira coupling is more sensitive to the
nature and amount of the catalyst used, and we had to
increase the loading of C1–C3 a further order of magnitude
to obtain reasonable conversions.
a Numbers refer to conversion values determined by GC after 4 h, numbers
in parenthesis refer to isolated yields.
b Aryl halide (1 equiv), 1.2 equiv 2-methyl-3-butyn-2-ol, 2 equiv diisopro-
pylamine, 5 ml/mmol DMF, 2% C1–C3, respectively, and 4% PPh3 were
heated at 100 8C.
Iodobenzene (1a) and 6 were reacted in the presence of
copper iodide and diisopropylamine in DMF. Addition of
the catalysts C1–C3 and Pd(OAc)2 in 2 mol% to the
reaction mixture led to no appreciable conversion and it was
only after the addition of 4 mol% triphenylphosphine to the
mixture that the Sonogashira coupling commenced. Com-
parison of the activity of C1–C3 and Pd(OAc)2 in the
presence of 2 equiv of trihenylphosphine (relative to
palladium), shows a picture that is analogous to the previous
cases (Fig. 4).
The similarity of the catalytic behaviour of complexes C1
and C2 in cross-coupling reactions, as well as the
resemblance of their activity to palladium acetate suggests,
that the active species in these catalytic systems are
probably of alike nature. The minor differences might
arise from the difference in the way the catalytically active
species is formed from the starting complex, and the
presence of different loosely coordinating ferrocenylhydra-
zone moieties in the reaction mixture. In case of complex
C3 we observed a decreased activity in all cases, which
might be attributed to the strong coordination of the
phtalazolyl moiety to the palladium, hindering the for-
mation of the catalytically active species and leading to an
elongated induction period and different kinetic
characteristics.
In summary, three palladium complexes were prepared
containing similar ferrocenylhydrazone-based ligands in
different coordination modes: one a palladacycle, the other a
palladium-imine and the third a palladium-amide connec-
tion. The catalytic activity of the complexes was compared
with the palladium acetate–triphenylphosphine system in
cross-coupling reactions. On the basis of the accumulated
data it is proposed, that the catalytically active species is of
similar nature in most cases, and the differences in the
behaviour of the examined complexes originate in the mode
and kinetics of the formation of the active species. The
weaker the attachment of the palladium to the ligand, the
higher the observed activity of the catalyst system. The
results suggest that the principal role of the organic
backbone (ligand) is to make the palladium available for
activation in the reaction media. Although, the described
complexes are not highly active, the authors hope that the
presented data contributes to the better understanding of
catalytic processes and thereby helps in the future to design
highly active catalyst systems.
Figure 4. Kinetic study of the catalytic activity of C1–C3 and Pd(OAc)2 in
the model Sonogashira coupling. (a) 2% Pd(OAc)2 and 4% PPh3; (b) 2% C1
and 4% PPh3; (c) 2% C2 and 4% PPh3; (d) 2% C3 and 4% PPh3 (e) 2%
Pd(OAc)2.
C1, C2 and Pd(OAc)2 show a similar activity, with
Pd(OAc)2 being slightly more efficient than the ferrocene
containing catalysts. The activity of C3, as in all other cases,
is inferior to the other systems. Of C1 and C2 the latter has a
longer lifetime, reaching near complete conversion (just as
Pd(OAc)2), while C1 is deactivated at ca. 80% conversion.
The catalysts C1–C3 were also tested in the Sonogashira
coupling of other substrates (1a–d,e,g,j; Table 4). Com-
parison of the conversion data observed after running the
reactions for 4 h are in good agreement with the kinetic
measurements. All aryl iodides and the reactive bromopyr-
idine gave near complete conversion with C2, while of the
other complexes C1 gave the higher conversion values. The
catalysts were also active with bromobenzene (1j), while the
less reactive bromoanisole (1g) was only partially converted
and 4-chlorobenzonitrile (1e) remained intact. These results
are comparable with our recent observations using the
Pd/C–PPh3 catalyst system25 (Table 5).
4. Experimental
4.1. General
Melting points (uncorrected) were determined on a Boetius
1
hotplate. The H, 13C and 15N NMR spectra were recorded
in 5 mm tubes at rt on a Bruker DRX-500 spectrometer at
500 MHz (1H), 125 MHz (13C) and 50 MHz (15N) (for C1–
C3) or on a Bruker DRX-250 spectrometer (3a–c, 5b–h) at
250 MHz (1H), 62.5 MHz (13C) with the deuterium signal of

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T. Zs. Nagy et al. / Tetrahedron 61 (2005) 9767–9774
1
the solvent as the lock. In H and 13C measurements the
residual peaks of the solvent were used as reference, while
in the 15N measurements the scale was adjusted to the
reference signal of liquid NH3 (dZ0 ppm). The exact
assignment of the 1H, 13C and 15N signals for C1–C3 were
based on 2D-COSY, 2D-HSQC and 2D-HMBC measure-
ments. The IR spectra were obtained on a Bruker IFS-55
FTIR spectrometer. Gas chromatography was carried out on
a Hewlett-Packard 5790A instrument. Silica gel (0.04–
0.063 mm) was used for flash column chromatography.
6.81 (1H, t, JZ8.1 Hz, H4), 4.61 (2H, br s, H20/50), 4.31
(2H, br s, H30/40), 4.15 (5H, s, Cp ring), 3.16 (3H, s, H10);
dC (DMSO-d6) 148.5 (C1), 133.4 (C9), 129.8 (C3/5), 120.1
(C4), 1150.4 (C2/6), 83.6 (C10), 69.8 (Cp ring), 69.6 (C30/40),
67.2 (C2 /50), 33.6 (C10) (the spectra are identical with
those measured for ligand L2): dH (CDCl3) 8.26, 7.59 (2!s,
H9, A), 8.16 (s, H9, B), 7.5–7.0 (overlap0ping m’s, H2-6 A
and B), 4.6–4.5 (overlapping m’s, H20-5 , A), 4.46 (t, JZ
1.8 Hz, H20/50, B), 4.23 (t, JZ1.8 Hz, H30/40, B), 4.31 and
4.20 (2!s, Cp rings, A), 4.23 (s, Cp ring, B), 3.57 and 3.19
(2!s, H10, A), 3.13 (s, H10, B); dN (CDCl3) 234 and 226
(N8, A), 229 (N8, B), 130 and 127 (N7, A), 125 (N7, B). For
comparison the 15N NMR data of L2: dN (CDCl3) 325 (N8),
129 (N7). Anal. Calcd for C36H36Cl2Fe2N4Pd (814.00) C
53.12, H 4.46, N 6.88; Found C 53.05, H 4.55, N 6.81%.
4.2. Preparation of complexes C1*, C2 and C3*
A mixture of the corresponding hydrazone (1 mmol),
Na2PdCl4 (0.294 g, 1 mmol) and NaOAc*3H2O (0.136 g,
1 mmol) was dissolved in dry methanol (20 mL). The deep
red solution was stirred at rt for 1 day. The resulted
precipitate was filtered off and the solution was evaporated
to dryness. Complex C2 was purified by washing the
precipitate with cold methanol. For the isolation of C1* the
precipitate was subjected to column chromatography on
Silica using chloroform as eluent. The second deep orange
band was collected and after the evaporation of the
chloroform the oily residue was crystallized with cold
methanol. The first orange band consists of the unchanged
hydrazone L1. For the isolation of C3* the residue, obtained
by the evaporation of the volatiles from the reaction
mixture, was purified by chromatography on Silica using
chloroform as eluent. The first deep red band was collected
and after the evaporation of the chloroformic solution the
oily residue was crystallized with cold methanol–diethy-
lether (3–3 mL).
4.2.3. Description of C3*. Deep red powder; 0.140 g
(27%); mp: 190–194 8C (decomp.); nmax 1721, 1642, 1571,
1506 cmK1; dH (DMSO-d6) 9.42 (1H, s, H3), 8.18 (1H, d,
JZ7.8 Hz, H5), 8.15 (1H, d, JZ7.8 Hz, H8), 7.87 (1H, t,
JZ7.8 Hz, H7), 7.80 (1H0, t, JZ7.8 Hz, H6), 7.62 (1H, 0s,
H12), 5.13 (2H, br s, H2 /H50), 4.55 (2H, br s, H30/H4 ),
4.20 (5H, s, Cp ring); dC (DMSO-d6) 158.2 (C11), 157.1
(C4), 149.2 (C12), 134.5 (C7), 132.2 (C6), 0128.0 (C5),
127.6 (C8),125.7 (C8a), 125.5, (C4a), 75.8 (C1 ), 72.9 (C30/
C40), 72.2 (C20/C50), 70.2 (Cp ring); dN (DMSO-d6) 254
(N11), 243 (N10), 154 (N2), 134 (N3) (the spectra for C3);
for comparison the 15N NMR data of L3: dN (DMSO-d6)
316 (N11), 261 (N2), 175 (N3), 138 (N10). Anal. Calcd for
C19H15ClFeN4PdO (515.37) C 44.28, H 2.93, N 10.87;
Found C 44.35, H 3.00, N 10.82%.
4.3. General conditions for cross-coupling reactions
4.2.1. Description of C1*. Deep red powder; 0.189 g
(35%); mp: 213–216 8C (decomp.); IR nmax 1652, 1578,
1540 cmK1; the NMR spectra for C10: dH (CDCl3) 8.42 (1H,
d, JZ7.8 Hz, H5), 7.96 (1H, s, H12) 7.97 (1H, d, JZ7.8 Hz,
H8), 7.88 (1H, t, JZ70.8 Hz, H7), 7.84 (1H, t, JZ7.8 Hz,
H6), 5.30 (1H, br s, H3 ), 4.38 (2H, br s, H40 and H50), 4.34
(5H, s, Cp ring), 4.03 (3H, s, H9), 3.57 (3H, s, H13); dC
(CDCl3) 168.4 (C12), 157.8 (C4), 150.2 (C1), 133.6 (C7),
129.0 (C4a), 129.7 (C6), 128.3 (C5), 1026.6, (C8a) 126.4
(C8), 100.5 (C20), 86.5 (C10), 74.3 (C3 ), 71.8 (Cp ring),
69.0 (C40), 67.0 (C50), 46.5 (C9), 41.0 (C13); dN (CDCl3)
254 (N11), 245 (N2), 178 (N3), 126 (N10); the NMR spectra
for C1: dH (DMSO-d6) 8.38 (1H, s, H12), 8.27 (1H, d, JZ
7.8 Hz, H5), 8.12 (1H, d, JZ7.8 Hz, H8), 7.98 (1H, t, JZ
7.80Hz, H7), 7.85 (1H, 0t, JZ7.8 Hz, H6), 5.13 (1H, br s,
H3 ), 4.43 (1H, br s, H4 ), 4.41 (1H, br s, H50), 4.18 (5H, s,
Cp ring), 3.69 (3H, s, H9), 3.20 (3H, s, H13); dC (DMSO-d6)
172.8 (C12), 159.0 (C4), 145.5 (C1), 133.8 (C7), 132.5
(C6), 129.02 (C4a), 1207.3 (C5), 127.0, (C8a) 126.5 (C8),
108.5 (C2 ), 83.6 (C1 ), 75.6 (C30), 70.9 (Cp ring), 70.0
(C40), 68.6 (C50), 40.5 (C13), 39.6 (C9); dN (DMSO-d6) 304
(N2), 274 (N11), 182 (N3), 127 (N10). Anal. Calcd for
C21H19ClFeN4PdO (541.40) C 46.59, H 3.54, N 10.35;
Found C 46.50, H 3.60, N 10.38%.
A mixture of the aryl halide, coupling partner, catalyst, base,
internal standard and co-catalyst (where applicable) were
taken up in the appropriate solvent in a vial. After flushing
with argon and sealing, the vial was placed in a temperated
oil bath and the contents were stirred. Samples were taken
by a Hamilton syringe and were diluted by DCM before
analysis. The work-up of the reactions included the addition
of aqueous ammonium chloride, separation, extraction with
DCM, drying of the combined organic phases and
purification by column chromatography after evaporation
of the solvent under reduced pressure.
4.3.1. Component ratios for the coupling reactions and
the characterization of isolated products.
4.3.1.1. Heck coupling. Aryl halide (1a–e) (1 equiv),
1.2 equiv methyl acrylate (2) and 1.4 equiv triethylamine
were stirred under argon in 1 mL solvent/1 mmol aryl halide
at 70–100 8C.
4.3.1.2. Suzuki coupling. Aryl halide(1b–i) (1 equiv),
1.5 equiv phenylboronic acid (4), and 2 equiv of K2CO3, in
8 mL DMF/1 mmol aryl halide were stirred under argon at
100 8C.
4.2.2. Description of C2. Deep red powder; 0.338 g (83%);
mp: 178–184 8C (decomp.); IR nmax 1597, 1495, 1107 and
476 cmK1; (for comparision the IR for L2: 1590, 1500,
1112 and 488 cmK1); dH (DMSO-d6) 7.44 (1H, s, H9), 7.29
(2H, d, JZ8.1 Hz, H2/6), 7.24 (2H, t, JZ8.1 Hz, H3/5),
4.3.1.3. Sonogashira coupling. Iodobenzene (1a)
(1 equiv), 1.2 equiv 2-methylbut-3-yn-2-ol (6) and 2 equiv
of diisopropylamine were stirred under argon in 5 mL DMF/
1 mmol iodobenzene at 100 8C.

T. Zs. Nagy et al. / Tetrahedron 61 (2005) 9767–9774
9773
4.3.1.4. Methyl cinnamate (3a).26 Starting from 1a
(302 mg, 1.48 mmol) we obtained 197 mg (82%) 3a. dH
(CDCl3) 7.43 (1H, d, JZ16.1 Hz), 7.20–7.15 (2H, m), 7.07–
7.01 (3H, m), 6.17 (1H, d, JZ16.1 Hz), 3.48 (3H, s); dC
(CDCl3) 166.4, 144.0, 133.7, 129.6, 128.2, 127.4, 117.2,
50.8 ppm.
4.3.1.13. 4-(40-Methoxyphenyl)-2-methylbut-3-yn-2-ol
(7b).35 Starting from 1b (108 mg, 0.46 mmol) we obtained
23 mg (25%) 7b. dH (CDCl3) 7.29–7.24 (2H, m), 6.77–6.71
(2H, m), 3.71 (3H, s), 2.19 (1H, s), 1.52 (6H, s); dC (CDCl3)
159.47, 133.01, 114.79, 113.82, 92.4, 81.93, 65.57, 55.21,
31.53 ppm.
4.3.1.5. Methyl 40-methoxy-cinnamate (3b).27 Starting
from 1b (346 mg, 1.48 mmol) we obtained 263 mg (93%)
3b. dH (CDCl3) 7.56 (1H, d, JZ16.0 Hz), 7.40 (2H, d, JZ
8.8 Hz), 6.83 (2H, d, JZ8.8 Hz) 6.21 (1H, d, JZ16.0 Hz),
3.76 (3H, s) ppm.
4.3.1.14. 2-Methyl-4-(30-methylphenyl)-3-butyn-2-ol
(7c).25 Starting from 1c (100 mg, 0.46 mmol) we obtained
37 mg (46%) 7c. dH (CDCl3) 7.18–7 (4H, m), 2.42 (1H, br
s), 2.31 (3H, s), 1.6 (6H, s) ppm.
4.3.1.15. 2-Methyl-4-(30-pyridyl)-3-butyn-2-ol (7d).25
Starting from 1d (73 mg, 0.46 mmol) we obtained 66 mg
(89%) 7d. dH (CDCl3) 8.74 (1H, br s), 8.47 (1H, br s), 7.65
(1H, d, JZ7.9 Hz), 7.26–7.12 (1H, m), 5.14 (1H, br s), 2.29
(6H, s); dC (CDCl3) 151.64, 147.66, 138.75, 123.23, 120.5,
98.53, 78.02, 64.68, 31.23 ppm.
4.3.1.6. Methyl 30-methyl-cinnamate (3c).28 Starting
from 1c (323 mg, 1.48 mmol) we obtained 252 mg (97%)
3c. dH (CDCl3) 7.54 (1H, d, JZ16.1 Hz), 7.42–7. 00 (4H,
overlapping m’s), 6.30 (1H, d, JZ16.1 Hz), 3.67 (3H, s),
2.22 (3H, s) ppm.
4.3.1.7. 4-Methoxybiphenyl (5b).29 Starting from 1b
(61 mg, 0.26 mmol) we obtained 46 mg (97%) 5b. dH
(CDCl3) 7.44 (2H, d, JZ7.7 Hz), 7.41 (2H, d, JZ8.6 Hz),
7.30 (1H, t, JZ7.7 Hz), 7.18 (1H, t, JZ7.7 Hz), 6.86 (2H, d,
JZ8.2 Hz), 3.71 (3H, s); dC (CDCl3) 159.1, 140.7, 133.7,
128.7, 128.1, 126.7, 126.6, 114.2, 55.2 ppm.
Acknowledgements
Financial support of the Hungarian Research Fund (OTKA
F047125) is gratefully acknowledged.
4.3.1.8. 3-Methylbiphenyl (5c).30 Starting from 1c
(57 mg, 0.26 mmol) we obtained 31 mg (71%) 3c. dH
(CDCl3) 7.56 (2H, d, JZ7.5 Hz), 7.44–7.26 (6H, overlap-
ping m’s), 7.12 (1H, d, JZ7.0 Hz), 2.38 (3H, s); dC (CDCl3)
141.3, 141.2, 138.2, 128.71, 128.65, 127.95, 127.92, 127.20,
127.13, 124.2, 21.5 ppm.
References and notes
1. Herrmann, W. A.; Brossmer, C.; Ofele, K.; Reisinger, C. P.;
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int. Ed.
Engl. 1995, 34, 1844.
2. Shaw, B. L.; Perera, S. D.; Staley, E. A. Chem. Commun. 1998,
1361.
4.3.1.9. 3-Phenylpyridine (5d).31 Starting from 1d
(41 mg, 0.26 mmol) we obtained 38 mg (95%) 3d. dH
(CDCl3) 8.85 (1H, dd, JZ1.6 Hz), 8.59 (1H, dd, JZ4.7,
1.2 Hz), 7.86 (1H, d, JZ6.3 Hz), 7.58 (2H, d, JZ7.6 Hz),
7.48 (2H, t, JZ7.6 Hz), 7.42 (1H, t, JZ7.6 Hz), 7.35 (1H,
dd, JZ6.3, 4.7 Hz), 3.71 (3H, s); dC (CDCl3) 148.4, 148.3,
137.7, 126.5, 134.3, 129.0, 128.0, 127.1, 123.5 ppm.
3. Bedford, R. B.; Hazlewood, S. L.; Limmert, M. E.; Albisson,
D. A.; Draper, S. M.; Scully, P. N.; Coles, S. J.; Hursthouse,
M. B. Chem. Eur. J. 2003, 9, 3216.
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1999, 40, 7379.
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2001, 622, 89.
4.3.1.10. 2-Fluorobiphenyl (5f).32 Starting from 1f
(58 mg, 0.26 mmol) we obtained 30 mg (67%) 3f. dH
(CDCl3) 7.54 (2H, d, JZ7.8 Hz), 7.45–7.40 (3H, overlap-
ping m’s), 7.36 (1H, t, JZ7.8 Hz), 7.29–7.13 (3H,
overlapping m’s); dC (CDCl3) 158.7 (d, JZ227.7 Hz),
134.8, 129.7 (d, JZ3.3 Hz), 128.1, 128.0, 127.9, 127.4,
126.6, 123.3 (d, JZ3.7 Hz) 115.0 (d, JZ22.5 Hz) ppm.
6. Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H. U.
Angew. Chem., Int. Ed. 2002, 41, 3668.
7. Bedford, R. B.; Cazin, C. S. J.; Coles, S. J.; Gelbrich, T.;
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Trans. 2003, 3350.
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67, 5588.
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(44 mg, 0.26 mmol) we obtained 35 mg (81%) 5h. dH
(CDCl3) 7.49 (2H, d, JZ7.7 Hz), 7.41 (2H, d, JZ8.2 Hz),
7.36 (1H, t, JZ7.7 Hz), 7.23 (1H, t, JZ7.7 Hz), 7.16 (2H, d,
JZ8.2 Hz) 2.31 (3H, s); dC (CDCl3) 141.1, 138.3, 137.0,
129.5, 128.73, 128.68, 126.97, 126.95, 21.5 ppm.
9. Iyer, S.; Jayanthi, A. Tetrahedron Lett. 2001, 42, 7877.
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Ebeling, G.; Burrow, R. A. Organometallics 2001, 20, 171.
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4.3.1.12. 2-Methyl-4-phenylbut-3-yn-2-ol (7a).34 Start-
ing from 1a (94 mg, 0.462 mmol) we obtained 41 mg
(56%) 11. dH (CDCl3) 7.44–7.40 (2H, m), 7.31–7.27
(3H, m), 2.15 (1H, d), 1.62 (6H, s); dC (CDCl3) 131.6,
128.2 (two coalesced lines), 122.6, 93.7, 82.1, 65.6,
31.5 ppm.
14. Bedford, R. B. Chem. Commun. 2003, 1787.
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