New chiral P-N ligands for the regio- and stereoselective Pd-catalyzed dimerization of styrene

Article abstract of DOI:10.3390/molecules16021804

Two new chiral, enantiomerically pure, hybrid P-N ligands, namely (2R,5S)-2- phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octan-4-one (1) and (2R,5S)-2-phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octane (2), have been synthesized starting from L-proline. The two ligands differ in the presence or not of a carbonyl group in the diazaphosphane ring. Their coordination chemistry towards Pd(II) was studied by reacting them with [Pd(CH₃)Cl(cod)]. A different behaviour was observed: ligand 2 shows the expected bidentate chelating behaviour leading to the mononuclear Pd-complex, while ligand 1 acts as a terdentate ligand giving a dinuclear species. The corresponding cationic derivatives were obtained from the palladium neutral complexes, both as mono- and dinuclear derivatives, and tested as precatalysts for styrene dimerization, yielding E-1,3- diphenyl-1-butene regio- and stereoselectively as the sole product. A detailed analysis of the catalytic behaviour is reported.

Full text of DOI:10.3390/molecules16021804

Molecules 2011, 16, 1804-1824; doi:10.3390/molecules16021804
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
New Chiral P-N Ligands for the Regio- and Stereoselective
Pd-Catalyzed Dimerization of Styrene
Lidia Fanfoni 1, Angelo Meduri 1, Ennio Zangrando 1, Sergio Castillon 2, Fulvia Felluga 1 and
Barbara Milani 1,*
1
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Via Licio Giorgieri 1,
34127 Trieste, Italy; E-Mails: lfanfoni@units.it (L.F.); angelo.meduri@phd.units.it (A.M.);
ezangrando@units.it (E.Z.); ffelluga@units.it (F.F.)
2
Department de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, C. Marcel.lí
Domingo s/n 43007 Tarragona, Spain; E-Mail: sergio.castillon@urv.net (S.C.)
* Author to whom correspondence should be addressed; E-Mail: milaniba@units.it;
Tel.: +39-040-558-3956; Fax: +39-040-558-3903.
Received: 27 December 2010; in revised form: 17 February 2011 / Accepted: 18 February 2011 /
Published: 22 February 2011
Abstract: Two new chiral, enantiomerically pure, hybrid P-N ligands, namely (2R,5S)-2-
phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octan-4-one (1) and (2R,5S)-2-
phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octane (2), have been synthesized
starting from L-proline. The two ligands differ in the presence or not of a carbonyl group in
the diazaphosphane ring. Their coordination chemistry towards Pd(II) was studied by
reacting them with [Pd(CH3)Cl(cod)]. A different behaviour was observed: ligand 2 shows
the expected bidentate chelating behaviour leading to the mononuclear Pd-complex, while
ligand 1 acts as a terdentate ligand giving a dinuclear species. The corresponding cationic
derivatives were obtained from the palladium neutral complexes, both as mono- and
dinuclear derivatives, and tested as precatalysts for styrene dimerization, yielding E-1,3-
diphenyl-1-butene regio- and stereoselectively as the sole product. A detailed analysis of
the catalytic behaviour is reported.
Keywords: hybrid phosphorus-nitrogen ligands; palladium; alkene dimerization

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Molecules 2011, 16
1. Introduction
The concept of hemilability has been coined for ligands possessing a combination of soft and hard
donor atoms and compounds combining phosphorus- and nitrogen-donor atoms represent a
distinguished family of hemilable ligands. In particular, hemilable hybrid P-N multidentate ligands are
able to stabilize metal ions in a variety of oxidation states and geometries. Indeed, the π-acceptor
character of phosphorus atom can stabilize a metal center in a low oxidation state, while the nitrogen
σ-donor ability makes the metal more susceptible to oxidative addition reactions, features that can play
a crucial role in stabilizing intermediate oxidation states and/or geometries during a catalytic cycle [1].
In addition, the possibility of varying the electronic and steric properties of this kind of ligands allows
to obtain potentially multidentate ligands that are able to bind or bridge one or more metal ions
affording homo- or hetero-, bi- or polymetallic complexes [1,2].
Late transition metal complexes with chiral P-N ligands have found, and currently find, wide
application in asymmetric catalysis [3-11]. In the field of ethylene homo- and co-, oligo- and
polymerization Ni(II) complexes with a variety of P-N ligands were preferentially used [12-17].
Palladium complexes containing P-N ligands were applied as precatalysts for CO/alkene
copolymerization; very high CO pressures (up to 320 bar) were required to have catalytic activity
[17-20]. Some Pd(II) complexes with P-N ligands, such as phosphino- phosphinito- and phosphonito-
oxazolines, were applied in the CO/ethylene and CO/methyl acrylate copolymerization in the study of
the stepwise insertion of the monomer on the precatalyst and resulting in the X-ray characterization of
some intermediates [21-23].
Chiral diazaphospholidines, more generally diaminophosphines, constitute a family of ligands in
which two nitrogen atoms are linked to phosphorus in a phosphorus-alkyl or phosphorus-aryl moiety
[24]. Recently, a particular attention has been devoted to diazaphospholidine ligands derived from
proline, which have been successfully used in different catalytic processes such as asymmetric copper-
catalyzed cyclopropanation [4], iridium catalyzed enantio- and regioselective allylic etherification [7],
palladium catalyzed enantioselective allylic amination [1], rhodium-catalyzed asymmetric
hydroformylation [25].
Alkene di- and oligomerization are reactions of high industrial importance for the synthesis of -
olefins. When considering styrene as the substrate, the selective dimerization to E-1,3-diphenyl-1-
butene has been studied using different catalytic systems based on palladium salts modified with
monophosphines [26], or with “phosphine-free” systems in ionic liquids [27], or, more recently, by
applying both ruthenium [28] and iron [29] catalytic systems. The asymmetric codimerization of
styrene with ethylene has been also extensively investigated, using nickel, palladium and cobalt
complexes with chiral mono and bidentate phosphines [30,31].
We have now studied the coordination chemistry towards palladium of a new type of chiral,
enantiomerically pure, diazaphospholidine ligands 1, 2 (Figure 1) derived from proline, together with
the catalytic behavior of the relevant Pd-complexes in styrene dimerization. The main structural
features of these ligands are: a) the pyridine moiety is linked to the nitrogen atom instead of
phosphorus; and b) the electronic properties are modulated for the presence of an amido (compound 1)
or amino group (compound 2).

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Molecules 2011, 16
Figure 1. The ligands studied and their numbering scheme.
3
3
O
N
6
2
2
4'
5'
6'
3' 4'
N
3'
4
4
5'
N
N
N
5
5
N
P
P
6'
1
2
2. Results and Discussion
2.1. Synthesis and Characterization of P-N Ligands 1 and 2
The optically pure ligands 1 and 2 were synthesized from amide (S)-5 and amine (S)-6, respectively,
which in turn were prepared from proline. Thus, proline was initially protected to give the Boc-
derivative 4 [32], which was reacted with 2-aminopyridine using EDC as condensation reagent (EDC
= N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride) to provide the amide [33,34],
which, after Boc removal in acidic medium [35], afforded 5. Reduction of 5 with LiAlH4 provided
derivative 6 (Scheme 1) [36]. Afterwards, the reaction of 5, 6 with PhP(NEt2)2 in toluene at 90 °C
overnight afforded diaminophosphines 1, 2 in 75% and 80% yield, respectively [11]. In agreement
with the literature data [7,37], both ligands were stereoselectively obtained as the single 
diastereoisomer, as determined by an NOE experiment performed upon irradiation of H2, which
resulted in the enhancement of the intensity of the resonance of phenyl protons in the ortho position.
Since the absolute configuration of C2 is known to be S, the stereogenic phosphorus center must have
the R configuration.
Scheme 1. Synthetic pathway for ligands 1 and 2.
i.
N
NH
2
Boc2O
EDC, CH2Cl2
LiAlH4
THF
O
O
OH
N
H
N
H
N
H
3
N
Et3N, CH2Cl2
ii. TFA, CH2Cl2
HN
HN
OH
O
4
Boc
N
N
5
6
toluene, 90 ºC
overnight
toluene, 90 ºC
overnight
PhP(NEt2)2
PhP(NEt2)2
O
N
N
N
P
N
N
N
P
2
1
Ligands 1 and 2 were fully characterized in solution by multinuclear NMR spectroscopy (Table 1)
and circular dicroism.

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Molecules 2011, 16
2.2. Study of Palladium Coordination Chemistry
The coordination chemistry of 1 and 2 to palladium was initially studied by in situ NMR
spectroscopy by reacting CD2Cl2 solutions of the ligands with equimolar amounts of [Pd(CH3)Cl(cod)]
1
(cod = 1,5-cyclooctadiene). The reaction progress, monitored by H- and 31P-NMR spectroscopy,
showed an almost instantaneous coordination of the two ligands to the metal centre: no signal of the
free P-N ligand was present after 5 min from the mixing of the two species. On this basis, complexes
1a, 2a were synthesized by reacting the Pd-precursor with the P-N ligand in dichloromethane at room
temperature and isolated as yellow-orange solids upon addition of n-hexane (Scheme 2).
Scheme 2. Schematic representation of the reactivity of ligands 1 (a) and 2 (b) with
[Pd(CH3)Cl(cod)].
CH3
P
CH3
Cl
N'
N
Cl
1
2
Pd
a)
2
+ 2 cod
Pd
Pd
Pd
Cl
N
N'
P
CH3
1a
CH3
Cl
N
P
CH3
Cl
b)
Pd
+ cod
cis/trans-2a
The neutral complexes were fully characterized in CD2Cl2 solution by multinuclear NMR
spectroscopy (Table 1).
Table 1. Selected chemical shift values for the ligands and the relevant palladium complexes.[a]
P-N/
1
31P NMR
CIS[b] (l-c)
CH3 H NMR
JP-CH3 (Hz)
complexes
1
1a
1b
1c
1d
2
106.3
-
-
-
67.0 (M), 75.6 (m)
39.3 (M), 30.7 (m)
2.12 (M), 2.45 (m) 13.0 (M), 11.5 (m)
50.7
55.6
2.38
11.5
50.7
55.6
2.36
2.38
11.5
11.5
50.7
99.7
55.6
-
-
-
2a
2bc
119.9 (m), 133.8 (M)
-20.2 (m), -34.0 (M)
0.69 (M), 1.65 (m)
0.58,d 1.61 (M),
1.71
2.0 (M), 8.5 (m)
8.0 (M), 7.8
120.5 (M), 122.9, 134.2 -20.8 (M), -23.2, -34.5
2c
122.2 (m), 135.5 (M) -22.5 (m), -35.8 (M)
0.58 (M), 1.77 (m)
1.8 (M), 8.6 (m)
[a]Spectra recorded in CD2Cl2 at r.t., values in ppm. M = major species, m = minor species; [b]CIS =
Coordination Induced Shift for 31P in the free ligand (δl) and in the complex (δc); [c]Spectra recorded
in CD2Cl2 at 223 K; [d]The H-31P coupling constant was too small to be measured; the coupling is
1
evident from the 1H,31P-HMBC experiment.

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Molecules 2011, 16
The NMR analysis showed a clear shift of the characteristic signals of the ligand protons with
respect to those of the free P-N, that was diagnostic of the coordination to the palladium centre. In
1
particular, in the H-NMR spectra of both neutral species 1a, 2a the methyl group bound to Pd in the
metal precursor generated two doublets at very different chemical shifts: 2.12 e 2.45 ppm for 1a and
0.69 and 1.65 ppm for 2a (Table 1). These signals indicated for both complexes the presence, in
solution, of two different species in a ratio of 9:1 and 2:1 for 1a and 2a, respectively. This evidence
was confirmed by the 31P-NMR spectra in which two singlets for each complex were recognized.
Interestingly, depending on the nature of the P-N ligand, the 31P-NMR signals of the complexes had an
opposite variation of chemical shift with respect to the same signal in the free ligands: an upfield shift
for 1a (CIS 39.3 and 30.7 ppm) and a downfield shift for 2a (CIS −34.0 and −20.2 ppm) (Table 1).
The comparison of 1H- and 31P-NMR spectra of 1a and 2a suggests that from the reaction of ligands
1 and 2 with [Pd(CH3)Cl(cod)] two different complexes were obtained depending on the nature of the
ligand. In particular, for ligand 2 the data indicated that the isolated species was the expected
mononuclear complex [Pd(CH3)Cl(2)] (2a) [17,38]. It is reasonable to assume that the two species
observed in solution for 2a were the cis and trans isomers differing for the relative position of the Pd-
CH3 fragment with respect to the two halves of the ligand. Conventionally, we labeled trans the isomer
having the Pd-CH3 in trans to the Pd-P bond (Figure 2).
Figure 2. The cis and trans isomers of complex 2a.
N
N
CH3
Cl
Cl
N
N
Pd
Pd
P
P
CH3
N
N
cis-2a
major species
trans-2a
minor species
The downfield shifted 31P signals for complex 2a and the JP-CH3 values suggested that the major
species was the cis isomer. This was in agreement with the complex electronic pattern: chlorido was
trans to the better donor atom (phosphorus), while methyl was trans to the poorer donor (nitrogen)
(Figure 2) [38] and the groups having the highest trans influence were cis to each other. In agreement
with this signal to proton assignment, the doublet of the methyl group in the cis isomer was
remarkably upfield shifted with respect to the same signal in the trans isomer indicating that it fell into
the shielding cone of the phenyl ring bound to phosphorus. The nature of the neutral complex 1a was
elucidated after the characterization of the corresponding cationic derivative.
When the neutral complexes 1a, 2a were reacted with AgPF6 in the presence of acetonitrile, with
the aim to obtain the corresponding monocationic derivatives, no clear product was isolated from the
synthetic mixture. It was possible to obtain the cationic species via halogen abstraction on the neutral
derivatives by using coordinating ligands stronger than acetonitrile like pyridine, 4-methylpyridine and
4-trifluoromethylpyridine (Scheme 3).

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Molecules 2011, 16
Scheme 3. Synthetic pathway for the cationic complexes with ligand 1 (a) and ligand 2 (b).
R
CH3
P
-
2+
2 PF6
CH3
P
R
Cl
N
N
N
N
P
N
N
Pd
a)
Pd
Pd
Pd
P
N
N
AgPF6
N
N
N
Cl
R
CH3
CH3
R = H
R = CH3 1c
1d
1b
1a
R = CF3
R
-
+
PF6
CH3
N
P
N
CH3
N
Pd
Pd
b)
2b
cis/ trans-
N
R = H
P
Cl
2a
AgPF6
2c
R = CH3 cis/trans-
R
cis/trans-
Even though the quality of the crystals was not excellent, an X-ray single crystal diffraction
analysis of complex 1c was of great usefulness to characterize the palladium coordination sphere and
the ligand molecule (Figure 3).
Figure 3. A perspective view of the dinuclear complex 1c.
In fact the structural solution (final R value = 15%) provided evidence for the dinuclear nature of
this complex (Figure 3; Table 1S) having an approximately C2 symmetry with the pseudo twofold axis
passing in between the metals. The two ligand molecules acted as a tridentate unit bridging the Pd ions
in a head-tail arrangement. Each of these chelated one Pd ion with the phosphorus atom and the amidic
nitrogen, that was prone to the coordination due to the cleavage of the P-Namidic bond, and coordinated
the other Pd through the nitrogen atom of the pyridine ring. The metal complex geometry was, as
usual, square planar with no particular distortions and the palladium ions completed the square planar
coordination through the N donor of 4-methylpyridine. The amidic nitrogen was sp2 hybridized as

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Molecules 2011, 16
confirmed by the sum of bond angles around N3 and N7 of ca. 358°. The intermetallic separation was
4.638(4) Å and the mean coordination planes formed a dihedral angle of 71.3(4)°.
It was worth noting the presence of π-stacking interactions, occurring between the pyridine rings
N2/N6 (distance between centroids of 3.67 Å) and also between each picoline ring and the adjacent
phenyl attached to phosphorus (distance of 3.64 and 4.23 Å, respectively for N5 and N1), which
stabilized the overall structure.
A peculiarity of this system was the cleavage of the N-P-N heterocycle and the transmethylation
reaction occurring between the metal center and the phosphorus atom. This reaction might be seen as a
nucleophilic attack of the methyl group, bonded to palladium, at the coordinated phosphine with the
opening of the N-P-N heterocycle and the contemporary coordination of the amidic nitrogen to the
metal centre. Transmethylation reaction was reported to occur on the complex trans-[Pd(CH3)I(PPh3)2]
resulting in the exchange of the methyl group on palladium with one phenyl ring on the phosphorus to
give [Pd(Ph)I(PPh3)(PPh2CH3)] as product [39]. The reaction here observed might be considered as
another example of this type of reactivity, and in this case it occurs on a chiral phosphine.
1
31
All cationic complexes were fully characterized by H- and P-NMR spectroscopy (Table 1). For
complexes 1b-d, both the 31P and the 1H signals were shifted compared to the same signals in the
neutral compound 1a. The signals of the protons of the pyridine-type ligand coordinated to palladium
were also present. It was worth noting that the 31P and the CH3 group signals were not affected by the
nature of the fourth ligand, as well as the value of the P-CH3 coupling constant, the latter being very
similar to the value found for complex 1a (Table 1). On the basis of these NMR data it was reasonable
to assume that all the synthesized complexes containing ligand 1 were dinuclear species with a
geometry analogous to that observed in the solid state for 1c. A dinuclear molecule was also postulated
for the neutral complex 1a. In this case the two species present in solution cannot be the cis and trans
isomers observed for 2a. A reasonable hypothesis for their nature is that they might be the two
different diastereoisomers differing in the absolute configuration of phosphorus.
The 1H-NMR spectrum of 1c at room temperature showed a single broad signal at low field for the
protons in ortho position of 4-picoline, that, in the homonuclear COSY spectrum, was not associated
to any cross peak. As the temperature decreased, it became broader, reaching coalescence at 258 K. A
further decrease of temperature, up to 238 K, resulted in the appearance of four new peaks at 8.63,
8.44, 7.33 and 6.67 ppm, correlated one to each other by a cross peak in the homonuclear COSY
spectrum (Figure 4; Figure 1S). These signals were assigned to the ortho and meta protons of 4-
picoline bound to palladium. In addition to them, even the resonances of the phenyl ring bound to
phosphorus varied with temperature. These NMR data indicated the presence of a dynamic process in
solution, which mainly involved the 4-picoline, that, due to coordination to palladium, had lost its C2
symmetry axis passing through the nitrogen atom and the p-CH3 group. Thus, the two halves of 4-
picoline were no longer equivalent. This suggested that the fluxional process was a hindered rotation
around the Pd-N bond, due to the π-stacking interaction between 4-picoline and the phenyl ring on the
phosphorus atom. Indeed, both for ortho and meta picoline protons, the signal at higher fields could be
attributed to the half of the 4-picoline falling into the shielding cone of the phenyl ring.

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Molecules 2011, 16
1
Figure 4. H-NMR spectra of 1c, in CD2Cl2: variation with temperature (the ortho and
meta protons of 4-picoline are evidenced).
Analogous spectra variations with temperature were observed for the cationic derivatives 1b and 1d
indicating that the same fluxional process occurred regardless to the nature of the pyridine ligand
(Figures 2S-5S). As expected, complexes 1b-d were optically active and their CD spectra (Figure 6S)
showed the same Cotton effect, allowing to assign to all of them the same absolute configuration.
Complexes 2b-c were also characterized in CD2Cl2 solution by multinuclear NMR spectroscopy. In
analogy with the neutral compound 2a, even for the monocationic derivative 2c the number of signals
1
and their integration in the H-NMR spectrum indicated the presence of two species in solution that
were recognized as the cis and trans isomers. For complex 2c this was also confirmed by the two
1
signals in the 31P-NMR spectrum. For complex 2b in the H-NMR spectrum recorded at room
temperature the doublets of the Pd-CH3 fragment had chemical shifts values very close to those of the
neutral compound 2a, while all the other signals, including those of pyridine, were quite broad. In the
31P-NMR spectrum at room temperature two broad peaks were present too (Figure 7S). Upon
decreasing temperature remarkable variations were observed and the decoalescence was reached at 223
1
K. In particular, in the H-NMR spectrum three new signals at 8.86, 6.88 and 6.67 ppm appeared
(Figure 8S) and they were assigned to the pyridine ring of the P-N ligand; as well as three new
doublets at 1.71, 1.61 and 0.58 ppm assigned to the Pd-CH3 fragment (Figure 9S). Even in the
corresponding 31P-NMR spectrum three singlets were observed, which correlated to the doublets of the
1
Pd-CH3 group in the H,31P-HMBC spectrum (Figure 10S). On the basis of these NMR data we
speculate that 2b is a mixture of three species which might be assigned as the cis and trans isomers of
[Pd(CH3)(py)(2)][PF6] and the neutral derivative [Pd(CH3)Cl(2')(py)] having coordinated to Pd the
pyridine in place of the nitrogen of the pyridine ring of the P-N ligand that acted as a monodentate
molecule 2'.
2.3. Catalytic Activity of Cationic Complexes 1b-d, 2b-c
The cationic complexes 1b-d were tested as precatalysts for CO/styrene copolymerization under
standard conditions: T = 303 K, 1 atm of CO, [styrene]/[Pd] = 6,800, an excess of 1,4-benzoquinone

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Molecules 2011, 16
(BQ) with respect to palladium ([BQ]/[Pd] = 40), 24 h, in 2,2,2-trifluoroethanol (TFE). No polymer
was isolated at the end of the catalytic runs. After drying the reaction mixture an oil was obtained that
was characterized as E-1,3-diphenyl-1-butene (Scheme 4). Despite the optical activity of the
complexes, the product was obtained as a racemic mixture.
Scheme 4. Styrene dimerization reaction.
cat
2
Carbon monoxide was not required for the reaction. The effect of some parameters was studied by
using complex 1c as precatalyst. Increasing the temperature from 303 to 343 K resulted in a
remarkable increase of catalytic activity and at 343 K the induction time, observed at 303 and 323 K,
was no longer observed (Figure 5, Table 2S). At 343 K 20% conversion was reached after 7 h of
reaction and it increased up to 25% after 24 h, indicating catalyst deactivation due to decomposition to
palladium black.
Figure 5. Styrene dimerization: effect of temperature. Precatalyst: 1c.a
100
90
303 K
80
70
60
50
40
30
20
10
0
323 K
343 K
0
100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500
time (min)
a
Reaction conditions: nPd = 1.27 × 10−5 mol, [BQ]/[Pd] = 40, [styrene]/[Pd] = 6,800, styrene
V = 10 mL, TFE V = 20 mL. Conversion determined by HRGC analysis.
A small enhancement in the conversion, up to 32%, was realized by decreasing the styrene to
palladium ratio to 3,400 (Figure 11S). By performing the catalytic reactions at T = 343 K and with
[styrene]/[Pd] = 3,400 the effect of the nature of the P-N and of the pyridine-type ligand was
investigated (Figure 6).

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Molecules 2011, 16
Figure 6. Styrene dimerization: effect of the precatalyst.a
100
90
80
70
60
50
40
30
20
10
0
1b
1c
1d
2c
0
100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500
time (min)
a Reaction conditions: see Figure 5; [styrene]/[Pd] = 3,400, T = 343 K.
All tested precatalysts generated an active species for styrene dimerization; the maximum
conversion reached was 49% with precatalyst 1b. In all cases the reaction was regiospecific and
stereospecific in leading to the E-1,3-diphenyl-1-butene as the sole product. The catalytic activity was
affected by the nature of the P-N ligand, being all complexes with ligand 1 more active than the
complex with ligand 2. For complexes with ligand 1 the nature of the pyridine-type ligand remarkably
affected catalyst activity and stability. Within the first two hours of reaction the trend of the activity
might be related to the Lewis basicity of the pyridine-type ligand: it increased on decreasing the Lewis
basicity of the ligand, being complex 1d with the 4-CF3-pyridine the most active and 1c with the 4-
CH3-pyridine the least active among the three (Figure 6). On prolonging the reaction time, catalyst
stability became predominant and, while catalysts generated by complexes 1d and 1c deactivated after
4 h, catalyst obtained from 1b was active for at least 8 h.
In palladium catalyzed oligo- and polymerization reactions the catalyst stability is related to the
presence of 1,4-benzoquinone, thus its effect was investigated in this reaction, too (Figure 7, Table
3S). Varying the [BQ]/[Pd] ratio from 0 to 80 resulted in a remarkable increase of the reaction rate,
while only a slight effect on catalyst lifetime was observed. This was particularly evident from the
values of conversion, measured after 2 h, for the reaction carried out with no addition of BQ and that
with [BQ]/[Pd] = 20, of 3.1 and 22.2, respectively. A similar trend was recently observed for the Pd-
catalyzed CO/styrene oligomerization reaction: no product was isolated when benzoquinone was not
added to the reaction mixture, while a productivity of 185 g PK/g Pd (g PK/g Pd = grams of oligomer
per gram of palladium) was obtained performing the oligomerization at [BQ]/[Pd] = 40; however the
lack of CO uptake data did not allow to assign this effect to an increase of catalyst lifetime or catalyst
activity [40].

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Molecules 2011, 16
Figure 7. Styrene dimerization: effect of [BQ]/[Pd]. Precatalyst: 1b.a
100
90
80
70
60
50
40
30
20
10
0
BQ/Pd = 80
BQ/Pd = 40
BQ/Pd = 20
BQ/Pd = 0
0
100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500
time (min)
a Reaction conditions: see Figure 5; [styrene]/[Pd] = 3,400, T = 343 K.
These trends differed from the effect that benzoquinone typically shows in CO/alkene co- and ter-
polymerization reactions. For the latter reactions a linear relationship between [BQ]/[Pd] ratio and
catalyst lifetime was observed together with no effect on the reaction rate [19,41]. The role played by
benzoquinone in the copolymerization reactions is well understood and it consists in the oxidation of
Pd(0) to Pd(II) with the concomitant formation of hydroquinone [42-45]. The Pd species resulting
from this reaction was a Pd-alkoxy derivative and the corresponding carbo-alkoxy group was found as
one end group of the polymeric chains. In the currently investigated reaction, as well as in the
CO/styrene oligomerization, no alkoxy (or carbo-alkoxy) group was incorporated into the reaction
product. In addition, in styrene dimerization benzoquinone affected catalyst activity rather than
catalyst lifetime, thus indicating that it increased the number of active sites. The available experimental
data do not allow to make any speculation on the specific activation reaction involving benzoquinone.
Complex 1b was tested as precatalyst for styrene/ethylene codimerization under mild reaction
conditions (1.5 bar of ethylene, T = 343 K, [styrene]/[Pd] = 3,400, [BQ]/[Pd] = 40). No codimer was
formed, being E-1,3-phenyl-1-butene the unique reaction product detected, thus indicating the
selective reactivity of this complex toward the vinyl arene with respect to the aliphatic alkene.
Despite the fact that the collected experimental data are very preliminary, the following hypothesis
for the mechanism of the dimerization reaction is proposed (Scheme 5). The trend of activity with
respect to the nature of the pyridine-type ligand indicated that the dissociation of this ligand was
required for the catalysis and it might be followed by the cleavage of the Pd-N bond of the pyridine
ring of the P-N ligand creating, in this way, a mononuclear intermediate 7 with two cis coordination
sites available for the catalysis (Scheme 5). The nature of the catalytic product indicated that the
catalyst was a Pd-hydride species, that might be formed by the reaction of 7 with trifluoroethanol
and/or water (present in traces in the solvent). This reaction might involve benzoquinone and a
rearrangement of the ligand: the amidic nitrogen might undergo an electrophilic attack with the
cleavage of the related Pd-N bond followed by the coordination of the pyridine ring of the P-N ligand

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Molecules 2011, 16
yielding a Pd-H monocationic species, where styrene coordination and insertion took place leading to
the Pd-alkyl intermediate. On the latter the second molecule of the vinyl arene coordinated and
inserted followed by -hydrogen elimination, which led to E-1,3-phenyl-1-butene and to the Pd-H that
might reenter the catalytic cycle or decompose to Pd metal (Scheme 5). Both styrene migratory
insertions were regiospecific and occurred with secondary regiochemistry.
Scheme 5. Proposed catalytic cycle.
CH3
-
2+
2 PF6
R
P
N
N
N
N
P
Pd
Pd
N
N
R
R
CH3
-
N
CH3
P
-
+
PF6
N
2
N
Pd
7
TFE, H2O,
BQ
-
N
+
CH3
PF6
Ph
P
H
H
C
N
Pd
CH3
C
H
Ph
Ph
-
-
N
+
N
+
CH3
PF6
CH3
PF6
P
H
P
N
N
Pd
Pd
Ph
Ph
CH
CH2
Ph
CH
CH3
Ph
-
N
+
CH3
PF6
P
N
Pd
Ph
HC
CH3
Ph

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Molecules 2011, 16
3. Experimental
3.1. General
13
1H- and C-NMR spectra were run on a JEOL EX 400 Spectrometer at 400 MHz and on a Varian
500 spectrometer at 500 MHz for proton and at 100.1 and 125.68 MHz for carbon, respectively, by
using deuterochloroform and deuterodichloromethane as the solvents and referenced to the solvent
residual peak to TMS (CDCl3 at 7.26 ppm, CD2Cl2 at 5.32 ppm for proton; CDCl3 at 77.0 ppm and
CD2Cl2 at 54.00 ppm for carbon), at 25 °C where not differently indicated. 31P-NMR spectra were
recorded at 202.32 MHz on a Varian 500 spectrometer and automatically referenced to H3PO4.
NOESY experiments were performed according to the automatic parameters of the software with a
mixing time of 500 ms. Optical rotations and CD spectra were determined at 25 °C. TLC were
performed on silica gel, using light petroleum - ethyl acetate or dichloromethane - methanol mixtures
as the eluent. Flash chromatography was run on silica gel, 230–400 mesh using mixtures of light
petroleum 40–70 °C or chloroform and ethyl acetate as the eluent. HRGC analysis were run on a SE 30
capillary column (30 m × 0.32 mm) carrier gas He 50 KPa, split 1:60. The chiral P-N ligands and the
related complexes were synthesized under argon atmosphere with Schlenk technique and using freshly
distilled and degassed solvents.
3.2. Synthesis of P-N Ligands
(S)-(-)-N-(pyridine-2-yl)pyrrolidine-2-carboxamide ((S)-5). Compound (S)-4 (1.000 g, 4.65 mmol) was
dissolved in dichloromethane (20 mL). The solution was cooled to 0 °C, and EDC (0.908 g,
4.74 mmol) was added. The solution was stirred at 0 °C for 0.5 h and then 2-aminopyridine (0.439 g,
4.65 mmol) was added in one portion. The mixture was left at room temperature and followed by TLC
(EtOAc/CH3OH/NH3 8:2:0.1). After removal of the solvent under reduced pressure, the residue was
purified by column chromatography on silica gel (petroleum ether/ethyl acetate 3:7, petroleum
ether/ethyl acetate 4:6, then petroleum ether/ethyl acetate/ammonia 4:6:0.2) to give Boc-(S)-5 as a
white solid. [α]D –71 (c 0.25, CH3OH); 1H-NMR (400 MHz, CDCl3): δ 1.26–1.42 (bs, 9H, t-Bu), 1.69
(bs, 1H), 1.91 (m, 2H), 2.24 (bs, 1H), 3.53 (bs, 2H), 4.32 (bs, 1H, CHCO), 7.01 (bs, 1H), 7.68 (bs,
13
1H), 8.21 (d, J = 8.0 Hz, 1H), 8.28 (dm, 1H), 9.22 (bs, 1H, NH); C-NMR (100.1 MHz, CDCl3): δ
21.4, 24.8, 28.3, 47.2, 62.3, 80.96, 113.8, 119.78, 138.22, 148.0, 151.8, 155.2, 172.0; ESI-MS: 292
(M+H+), 314 (M+Na+).
Boc-(S)-5 (1.508 g, 5.17 mmol) was dissolved in a trifluoroacetic acid solution (15 mL, 40% in
CH2Cl2) at 0 °C and the solution was stirred for 2 h at room temperature. Then the trifluoroacetic acid
was neutralized by addition of Et3N (15 mL, 0.10 mmol) at 0 °C. The solution was washed with water,
dried over anhydrous Na2SO4, and concentrated under reduced pressure obtaining (S)-5 as a yellow oil
in 90% yield. [α]D –56.4 (c 0.5, CH3OH); IR (neat) max: 3276, 2969, 2870, 1692, 1589, 1574, 1510,
1434, 1299, 1148, 1095, 779 cm−1; 1H-NMR (400 MHz, CDCl3): δ 1.69 (m, 2H), 1.97 (m, 1H), 2.16
(m, 1H), 2.54 (bs, 1H, NH-amine), 3.00 (m, 2H), 3.84 (dd, J = 4.0, 5.2 Hz, 1H, CHCO), 6.97 (ddd,
J = 0.8, 2.4, 4.8 Hz, 1H), 7.64 (td, J = 2.0, 8.0 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.24 (dm, J = 4.8 Hz,

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Molecules 2011, 16
1H), 10.17 (bs, 1H, NH-amide); 13C-NMR (100.1 MHz, CDCl3): δ 26.3, 30.9, 47.4, 61.0, 113.6, 119.7,
138.3, 148.0, 151.2, 174.4; ESI-MS: 192 (M+H+), 214 (M+Na+).
(S)-(+)-N-(pyrrolidin-2-yl-methyl)pyridin-2-amine ((S)-6). To a cooled (-10 °C) and stirred solution of
the amide (S)-5 (0.304 g, 1.05 mmol) in dry THF (42 mL) LiAlH4 (0.470 g, 12.4 mmol) was added
portionwise, and the mixture was stirred at r.t. until almost all starting material was consumed. The
mixture was concentrated and the residue diluted with CH2C12. The reaction was quenched by the
careful addition of 2 M NaOH by using an ice-bath. Stirring was continued to obtain a clear organic
layer and the white residue was filtered off. The two-phase mixture was separated and the aqueous
layer was extracted with CH2Cl2. The combined organic phases were dried over anhydrous Na2SO4,
and evaporated. The product (S)-6 was obtained as a yellow oil in 90% yield and used without further
purifications. [α]D +28.9 (c 0.35, CH3OH); IR (neat) max: 3287, 2961, 2870, 1606, 1518, 1488, 1291,
771, 736 cm−1. 1H-NMR (400 MHz, CDCl3): δ 1.47 (m, 1H), 1.75 (m, 2H), 1.89 (m, 1H), 2.52 (bs, 1H,
NH-prolinic amine), 2.93 (td, J = 0.8, 6.4 Hz, 1H ), 3.14 (m, 1H), 3.39 (m, 2H), 4.94 (bs, 1H, NH-
amine), 6.4 (dt, J = 0.8, 8.4 Hz, 1H), 6.53 (ddd, J = 0.8, 2.0, 5.2 Hz, 1H), 7.36 (ddd, J = 0.4, 1.6,
6.8 Hz, 1H), 8.04 (dm, J = 5.6 Hz, 1H); 13C-NMR (100.1 MHz, CDCl3): δ 25.5, 29.0, 46.2, 58.3,
107.9, 112.8, 137.3, 147.7, 158.8; ESI-MS: 178 (M+H+).
General procedure for preparation of P-N ligands 1 and 2
Amide (S)-5 or amine (S)-6 (1.05 mmol) was weighted in a Schlenk and azeotropically dried three
times with distilled and degassed toluene. 5 mL of toluene were then added, and
bis(diethylamino)phenylphosphine (244 μL, 0.94 mmol) was added dropwise under Ar at 0 °C. The
reaction mixture was heated to 90 °C and stirred overnight. After cooling, the solution was evaporated
in vacuo. Compound 1 was washed 7 times with distilled and degassed n-pentane, giving a white solid.
Compound 2 was used as a crude reaction product (viscous orange oil) without further purifications.
(2R,5S)-(-)-2-phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octan-4-one (1). [α]D −128.9 (c
1
0.35, CH3OH); H-NMR (500 MHz, CD2Cl2): δ 1.72 (m, 1H, CH2, H4), 1.87 (m, 1H, CH2, H4), 2.18
(m, 1H, CH2, H3), 2.24 (m, 1H, CH2, H3), 3.39 (m, 1H, CH2, H5), 3.46 (m, 1H, CH2, H5), 4.16 (dd,
J = 3.0, 9 Hz, 1H, CH, H2), 7.04 (dd, J = 2.0, 5.5 Hz, 1H, H4’), 7.35 (m, 3H, Ph), 7.57 (m, 2H, Ph),
7.73 (td, J = 1.5, 8.0 Hz, 1H, H5’), 8.25 (dm, J = 4.0 Hz, 1H, CH, H3’), 8.33 (dm, J = 8.5 Hz, 1H, CH,
H6’); 13C-NMR (100.1 MHz, CDCl3): δ 26.5 (C4), 30.9 (C3), 55.4 (C5), 68.3 (C2), 114.4 (C6’), 120.1
(C4’), 128.6 (CPh-P), 129.8 (Ph), 130.0 (Ph), 138.3 (C5’), 147.7 (C3’), 152.4 (C2’), 178.1 (CO); 31P-
NMR (202.32 MHz, CD2Cl2): δ 106.29; ESI-MS: 298.1 (M+H+), 320.1 (M+Na+).
(2R,5S)-(-)-2-phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octane (2). [α]D −170.6 (c 0.485,
CH3OH); 1H-NMR (500 MHz, CD2Cl2): δ 1.78 (m, 2H, CH2, H4 and 1H, CH2, H3), 2.07 (m, 1H, CH2,
H3), 3.08 (m, 1H, CH2, H6), 3.31 (m, 1H, CH2, H5), 3.37 (m, 1H, CH2, H5), 3.55 (m, 1H, CH2, H6),
4.00 (q, J = 2.0, 18.5 Hz, 1H, CH, H2), 6.61 (d, J = 8.0 Hz, 1H, H5’), 6.64 (ddd, J = 1.0, 2.0, 5.0 Hz,
13
1H, H3’), 7.30 (m, 3H, Ph), 7.47 (m, 2H, Ph and 1H, H4’), 8.10 (dm, J = 4.5 Hz, 1H, H6’); C-NMR
(100.1 MHz, CD2Cl2): δ 26.1 (C4), 31.3 (C3), 52.2 (C6), 52.6 (C5), 64.8 (C2), 108.5 (C5’), 113.7 (C3’),

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Molecules 2011, 16
128.5 (Ph), 129.2 (Ph), 129.9 (CPh-P), 137.9 (C4’), 148.7 (C6’); 31P-NMR (202.32 MHz, CD2Cl2): δ
99.71; ESI-MS: 284.1 (M+H+).
3.3. Synthesis of Pd Complexes
All complexes were prepared starting from [Pd(CH3)Cl(cod)], following the procedure reported in
the literature. Briefly, ligand 1 or 2 (1.50 mmol) was added to a solution of [Pd(CH3)Cl(cod)] (332 mg,
1.25 mmol) in freshly distilled dichloromethane (5 mL) and stirred at room temperature. After 1.5 h
the reaction mixture was concentrated and the product precipitated as a yellow - orange solid upon
addition of n-hexane.
1
[Pd(CH3-1)Cl]2 (1a): yield 70%; [α]D −7.6 (c 0.29, CH3OH); IR (nujol) max: 1693 cm−1; H-NMR
(500 MHz, CD2Cl2): δ 1.94–2.11 (m, 2H, CH2, H4 and 1H, CH2, H3 ), 2.12 (d, J = 13.0 Hz, 3H, CH3-
P), 2.45 (d, J = 11.5 Hz, 3H, CH3-P minor isomer), 2.61 (m, 1H, CH2, H3), 3.29 (m, J = 7.5 Hz, 1H,
CH2, H5), 3.39 (m, 1H, CH2, H5), 3.81 (m, 1H, CH, H2), 6.91 (t, J = 6.0 Hz, 1H, H5’), 7.55 (tm, J = 2.5,
7 Hz, 2H, m-H-Ph), 7.59 (m, 1H, p-H-Ph), 7.68 (td, J = 1.5, 8.0 Hz, 1H, H4’), 7.79 (d, J = 8.5 Hz, 1H,
13
H3’), 7.96 (m, J = 2.5 Hz, 1H, H6’), 8.06 (dd, J = 5.5, 7.5 Hz, 2H, o-H-Ph ); C-NMR (125 MHz,
CD2Cl2): δ 15.3 (d, J = 182.5 Hz, CH3-P), 25.4 (d, J = 48.5 Hz, C4), 29.7 (d, J = 38.5 Hz, C3), 49.6
(C5), 65.0 (C2), 115.2 (C3’), 117.9 (C5’), 128.8 (p-Ph), 129.6 (d, J = 47.5 Hz, o-Ph), 132.3 (d,
J = 51 Hz, m-Ph), 133.0 (Ph-P), 140.5 (C4’), 144.7 (C6’), 170.3 (CO); 31P-NMR (202.32 MHz,
CD2Cl2): δ 67.05 (minor isomer), 75.57 (major isomer). Isomeric ratio 9:1.
[Pd(CH3)Cl(2)] (2a): yield 66%; [α]D −20.4 (c 0.12, CH3OH); 1H-NMR (500 MHz, CD2Cl2): δ 0.69
(d, J = 2.0 Hz, 3H, CH3-Pd, cis isomer), 1.57 (m, 1H, H3, cis isomer), 1.65 (d, J = 8.8 Hz, 3H, CH3-Pd,
trans isomer), 1.94 (m, 2H, H4, cis isomer), 2.18 (m, 1H, H3, cis isomer), 2.64–3.00 (m, aliphatic
proton of the trans isomer), 3.29 (m, 1H, H6 cis isomer), 3.49 (m, 1H, H5, cis isomer), 3.70 (m, 1H, H6
and 1H, H5, cis isomer), 3.86 (m, aliphatic protons, trans isomer), 4.06 (m, 1H, H2 cis and aliphatic
protons of the trans isomer), 6.67 (d, J = 8.5 Hz, 1H, H3’), 6.85 (d, J = 8.0 Hz, 1H, H3’, trans isomer),
6.95 (m, 1H, H5’ of both cis and trans isomers), 7.07 (t, J = 7.5 Hz, Ph, trans isomer), 7.46 (m, 3H,
aromatic protons of both cis and trans isomers), 7.73 (m, 2H, Ph and 1H, H4’, cis isomer and Ph H4’,
trans isomer), 8.98 (m, 1H, H6’); 13C-NMR (125 MHz, CD2Cl2): δ 0.69 (d, J = 2.0 Hz, 3H, CH3-Pd, cis
isomer), 18.5 (CH3-Pd, trans isomer), 26.2 (C4, cis isomer), 32.8 (C3, cis isomer), 51.6 (C6, cis
isomer), 52.2 (C5, cis isomer), 65.9 (C2, cis isomer), 109.6 (C3’, cis isomer), 110.4 (C3’, trans isomer),
116.5 (C5’, cis isomer), 123.4 (C5’, trans isomer), 127.0 (aromatic carbon, trans isomer), 128.6
(aromatic carbon, cis isomer), 130.2 (aromatic carbon, cis isomer), 131.5 (aromatic carbon, trans
isomer), 137.7 (aromatic carbon, cis isomer), 139.9 (C4’, cis isomer and C4’, trans isomer), 148.7 (C6’,
cis isomer); 31P-NMR (202.32 MHz, CD2Cl2): δ 119.9 (cis isomer), 133.7 (trans isomer); Ratio
cis/trans = 2:1.

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Molecules 2011, 16
3.4. Synthesis of the Cationic Complexes 1b-d, 2b-c
All complexes were obtained starting from the corresponding neutral derivatives upon addition of
AgPF6 in a mixture of CH2Cl2 and pyridine or pyridine derivative. In particular, the neutral complex 1a
(0.22 mmol) was dissolved in the minimal amount of CH2Cl2 under argon and kept in the dark. A
solution of AgPF6 in CH2Cl2 (0.0615 g, 0.24 mmol) was added, and then dropwise the pyridine
derivative leading to the precipitation of AgCl. After 1.5 h, the solution was filtered over Celite and
concentrated to minimal volume in vacuo. Upon addition of diethyl ether the product precipitated as a
white solid.
[Pd(CH3-1)(Py)]2[PF6]2 (1b): yield 80%, [α] +90.9 (c = 0.11 in CH3OH); IR (nujol) max: 1706, 842,
557 cm−1; 1H-NMR (500 MHz, CD2Cl2, 233 K): δ 2.09 (m, 2H, CH2, H5), 2.32 (m, 1H, CH2, H3), 2.38
(d, J = 11.5 Hz, 3H, CH3-P), 2.92 (m, 1H, CH2, H3 and 1H, CH2, H4), 3.21 (m, 1H, CH2, H4), 5.03 (m,
J = 4.5, 11.0 Hz, 1H, CH, H2), 6.72 (t, J = 6.0 Hz, 1H, H5’), 6.87 (t, J = 6.5 Hz, 1H, m-Py), 7.33 (m,
5H, Ph and 1H, m-Py), 7.56 (m, 1H, H6’ and 1H, p-Py), 7.62 (d, J = 8.0 Hz, 1H, H3’), 7.81 (t,
J = 7.5 Hz, 1H, H4’), 8.66 (d, J = 5.5 Hz, 1H, o-Py), 8.85 (d, J = 5.5 Hz, 1H, o-Py); 31P-NMR (202.32
MHz, CD2Cl2 298 K): δ 50.73.
1
[Pd(CH3-1)(4-CH3Py)]2[PF6]2 (1c): yield 85%, IR (nujol) max: 1711, 842, 557 cm−1; H-NMR
(500 MHz, CD2Cl2, 238 K): δ 2.09 (m, 2H, CH2, H5), 2.20 (s, 3H, CH3-Py), 2.29 (m, 1H, CH2, H3),
2.35 (d, J = 11.5 Hz, 3H, CH3-P), 2.89 (m, 1H, CH2, H4), 2.93 (m, 1H, CH2, H3), 3.20 (m, 1H, CH2,
H4), 5.00 (m, 1H, CH, H2), 6.67 (bs, 1H, m-4-CH3Py), 6.71 (t, J = 5.5 Hz, 1H, H5’), 7.17 (bs, 1H, m-4-
CH3Py), 7.34 (m, 5H, aromatic proton), 7.53 (m, 1H, H6’), 7.60 (d, J = 8.0 Hz, 1H, H3’), 7.80 (dt,
J =1.5, 7.5 Hz, 1H, H4’), 8.44 (bs, 1H, o-4-CH3Py), 8.63 (bs, 1H, o-4-CH3Py); 31P-NMR (202.32 MHz,
CD2Cl2 298 K): δ 50.73.
[Pd(CH3-1)(4-CF3Py)]2[PF6]2 (1d): yield 75%, [α] +120.5 (c = 0.22 in CH3OH); 1H-NMR (500 MHz,
CD2Cl2, 233 K): δ 2.13 (m, 2H, CH2, H5), 2.36 (m, 1H, CH2, H3), 2.40 (d, J = 11.5 Hz, 3H, CH3-P),
2.95 (m, 1H, CH2, H4 and 1H, CH2, H3), 3.22 (m, 1H, CH2, H4), 5.06 (m, 1H, CH, H2), 6.77 (t,
J = 6.0 Hz, 1H, H5’), 7.08 (bs, 1H, m-4-CF3Py), 7.22 (bs, 1H, m-4-CF3Py), 7.31 (m, 3H, aromatic
protons), 7.40 (m, 2H, aromatic protons) 7.66 (m, 1H, H6’ and 1H, H3’), 7.85 (t, J = 6.5 Hz, 1H, H4’),
8.97 (d, J = 6.0 Hz, 1H, o-4-CF3Py), 9.18 (d, J = 6.0 Hz, 1H, o-4-CF3Py); 31P -NMR (202.32 MHz,
CD2Cl2 298 K): δ 50.73.
The synthesis of complexes 2b-c was performed following a procedure analogous to that of 1b-d,
with the unique difference that AgPF6 was dissolved in pyridine (or in 4-picoline) and the solution was
added to the reaction mixture.
1
[Pd(2)(CH3)(Py)][PF6] (2b): IR (nujol) max: 838, 555 cm−1; H-NMR (500 MHz, CD2Cl2, 223 K): δ
0.58 (3H, CH3-Pd), 1.57 (b, H3), 1.61 (3H, J = 8.0 Hz, CH3-Pd, M isomer), 1.71 (3H, J = 7.8 Hz, CH3-
Pd), 2.02 (b, H3), 2.52 (b, H4), 2.77 (b, H3), 3.23 (t, J = 10.3 Hz, H6), 3.33 (m, H6), 3.45 (b), 3.64 (m,
H5 H6), 3.84 (b, H5), 3.94 (b, H6), 4.01 (b, H2), 4.09 (b, H2), 6.67 (d, H3'), 6.88 (d, H3', M isomer), 6.96

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Molecules 2011, 16
(b, H5'), 7.05 (b, aromatic protons of phenyl ring), 7.40-7.44 (b, aromatic protons of phenyl ring and
pyridine), 7.54 (b, aromatic protons of phenyl ring and pyridine), 7.72 (b, H4'), 7.78 (b, H4', M isomer),
31
7.84 (b, aromatic protons), 7.89 (b, aromatic protons), 8.60 (b, aromatic protons), 8.86 (b, H6'); P-
NMR (202.32 MHz, CD2Cl2, 223 K): δ 120.5, 122.9, 134.2.
1
[Pd(2)(CH3)(4-CH3Py)][PF6] (2c): yield% [α]D −12.3 (c 0.105, CH3OH); H-NMR (500 MHz,
CD2Cl2): δ 0.58 (d, J = 1.8 Hz, 3H, CH3-Pd, cis isomer), 1.05 (t, aliphatic protons, trans isomer), 1.37
(t, aliphatic protons, trans isomer), 1.70 (m, 1H, H3, cis isomer), 1.77 (d, J = 8.6 Hz, 3H, CH3-Pd,
trans isomer), 2.07 (m, 2H, H4, cis isomer), 2.28 (m, 1H, H3, cis isomer), 2.32 (s, 3H, CH3-Py, trans
isomer), 2.41 (s, 3H, CH3-Py, cis isomer), 2.77 (m, aliphatic proton, trans isomer), 3.07 (m, 1H, H4 cis
isomer), 3.38 (m, 1H, H6, cis isomer), 3.59 (m, 1H, H5, cis isomer), 3.67 (m, 1H, H5, cis isomer), 3.77
(m, 1H, H6, cis isomer), 4.15 (m, 1H, H2, cis isomer), 6.86 (m, 2H, p-Ph, cis and trans isomer), 7.05
(m, 2H, Ph, trans isomer), 7.14 (d, 2H, m-CH3-Py, trans isomer), 7.24 (d, 2H, m-CH3-Py, cis isomer),
7.31 (d, aromatic protons), 7.40 (m, 1H, Ph, trans isomer), 7.54 (m, aromatic protons and o-Ph, cis
isomer), 7.74 (m, m-Ph, cis isomer), 7.83 (t, m-Ph, cis isomer), 7.88 (m, Ph, trans isomer), 8.05 (d, 2H,
o-CH3-Py, trans isomer), 8.44 (d, 2H, o-CH3-Py, cis isomer), 8.50 (b, 2H, aromatic protons of cis and
trans isomer); 31P-NMR (202.32 MHz, CD2Cl2): δ 122.2 (trans isomer), 135.5 (cis isomer). Ratio
cis/trans 2:1.
3.5. Dimerization Reaction
All catalytic experiments were carried out in a three-necked, thermostated, 75 mL glass reactor
equipped with a magnetic stirrer and connected to a temperature controller. After establishment of the
reaction temperature, the precatalyst, 1,4-benzoquinone, styrene and TFE were placed inside. The
system was stirred at the same temperature for 24 h. At the end of the reaction time the two layers
formed were separated (dimer being the lower density phase), the Pd(0) residue was filtered over
Celite and washed with dichloromethane. The product was dried under vacuo. IR (neat) max: 3081,
3059, 3025, 2964, 2928, 2870, 1945, 1873, 1806, 1599, 1492, 1450, 965 cm−1; 1H-NMR (400 MHz,
CDCl3):  1.47 (d, 3H, J = 7.0 Hz, CH3CH), 3.65 (m, 1H, CH3CH), 6.42 (m, 2H, J = 5.2, 16.2 Hz,
HC=CH trans), 7.19-7.48 (m, 10H, Ph); 13C-NMR (125 MHz, CDCl3):  21.2, 42.5, 126.1, 126.2,
127.0, 127.3, 128.5, 135.1, 137.5, 145.6.
3.6. Codimerization Reaction
A 50 mL Büchi Tinyclave glass reactor was used for this reaction. The Tinyclave was charged with
1,4-benzoquinone, 1b (1.3·× 10−5 mol), styrene (10 mL), TFE (20 mL), connected to the ethylene tank
and pressurized at the desired pressure. The reactor was placed in an oil bath and warmed up to 343 K.
The mixture was stirred for 24 h. The reactor was vented, the solution was filtered over Celite to
remove palladium black and evaporated under vacuum obtaining a yellow oil.

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Molecules 2011, 16
4. Conclusions
In this work we report the synthesis of two new, chiral, enantiomerically pure, hybrid P-N ligands,
together with the study of their coordination chemistry towards palladium and the catalytic behavior of
the synthesized complexes in styrene dimerization reactions. Starting from the same Pd precursor,
complexes of different nature were obtained depending on the nature of the ligand. In particular, ligand
1 having an amidic nitrogen led to a Pd-dinuclear species with the concomitant transfer of the methyl
group from the metal centre to the phosphorus atom, while ligand 2 gave the expected mononuclear
derivative. This different behavior might be related to the different nature of the nitrogen atom
deriving from 2-aminopyridine: in ligand 1 this nitrogen atom is sp2 hybridized enforcing a planar,
more strained, conformation of the N-P-N heterocycle, while in ligand 2 this nitrogen atom is sp3
hybridized and thus the related heterocycle should result more flexible and, as a consequence, more
stable than in ligand 1.
The monocationic palladium complexes were found to generate catalysts with modest activity for
styrene dimerization reaction leading, regio- and stereospecifically, to E-1,3-phenyl-1-butene. Despite
the optical activity of the precatalysts no asymmetric induction was observed, and the product was
obtained as a racemic mixture. It was noted that 1,4-benzoquinone plays a fundamental role for the
catalytic reaction, being involved in catalyst activation. Further investigations are required to clarify
these specific reactions.
Supplementary Materials
Supplementary materials can be accessed at http://www.mdpi.com/1420-3049/16/2/1804/s1.
Acknowledgments
This work was supported by MIUR (PRIN N° 207HMTJWP_002), by Regione Friuli Venezia
Giulia and by DGYCIT-Spain CTQ2008-01569/BQU. Fondazione CRTrieste is also gratefully
acknowledged for the generous donation to the Dipartimento di Scienze Chimiche e Farmaceutiche of
a Varian 500 MHz spectrometer. Fondazione Benefica “Kathleen Foreman Casali” is gratefully
acknowledged for the generous donation of the Büchi Tinyclave glass reactor.
References and Notes
1. Espinet, P.; Soulantica, K. Phosphine-pyridyl and related ligands in synthesis and catalysis.
Coord. Chem. Rev. 1999, 193-195, 499-556.
2. Maggini, S. Classification of P,N-binucleating ligands for hetero- and homobimetallic complexes.
Coord. Chem. Rev. 2009, 253, 1793-1832.
3. Schoenleber, M.; Hilgraf, R.; Pfaltz, A. Chiral Bis(N-arylamino)phosphine-oxazolines: Synthesis
and Application in Asymmetric Catalysis. Adv. Synth. Catal. 2008, 350, 2033-2038.
4. Mothes, E.; Sentets, S.; Luquin, M.A.; Mathieu, M.; Lugan, N.; Lavigne, G. New insight into the
reactivity of pyridine-functionalized phosphine complexes of ruthenium(II) with respect to olefin
metathesis and transfer hydrogenation. Organometallics 2008, 27, 1197-1206.

1822
Molecules 2011, 16
5. Roseblade, S.J.; Pfaltz, A. Iridium-Catalyzed Asymmetric Hydrogenation of Olefins. Acc. Chem.
Res. 2007, 40, 1402-1411.
6. Cipot, J.; McDonald, R.; Ferguson, M.J.; Schatte, G.; Stradiotto, G. Cationic and formally
zwitterionic rhodium(I) and iridium(I) derivatives of a P,N-substituted indene: A comparative
synthetic, structural and catalytic investigation. Organometallics 2007, 26, 594-608.
7. Kimura, M.; Uozomi, Y. Development of New P-Chiral Phosphorodiamidite Ligands Having a
Pyrrolo[1,2-c]diazaphosphol-1-one Unit and Their Application to Regio- and Enantioselective
Iridium-Catalyzed Allylic Etherification. J. Org. Chem. 2007, 72, 707-714.
8. Arrayas, R.G.; Adrio, J.; Carrettero, J.C. Recent applications of chiral ferrocene ligands in
asymmetric catalysis. Angew. Chem. Int. Ed. 2006, 45, 7674-7715.
9. Giuri, P.J.; Saunders, C.P. The development of bidentate P,N ligands for asymmetric catalysis.
Adv. Synth. Catal. 2004, 346, 497-537.
10. Franciò, G.; Drommi, D.; Graiff, C.; Faraone, F.; Tiripicchio, A. Synthesis of phosphonito,N and
phosphito,N ligands based on quinolines and (R)-binaphthol or substituted biphenol and their
rhodium(I), palladium(II) and platinum(II) complexes. Inorg. Chim. Acta 2002, 338, 59-69.
11. Brumel, J.M.; Legrand, O.; Reymond, S.; Buono, G. First Iminodiazaphospholidines with a
Stereogenic Phosphorous Center. Application to Asymmetric Copper-Catalyzed
Cyclopropanation. J. Am. Chem. Soc. 1999, 121, 5807-5808.
12. Bluhm, M.E.; Folli, C.; Walter, O.; Doering, M. Nitrogen- and phosphorus-coordinated nickel(II)
complexes as catalysts for the oligomerization of ethylene. J. Mol. Cat. A Chem. 2005, 229,
177-181.
13. Cheng, H.-P.; Liu, Y.-H.; Peng, S.-M.; Liu, S.-T. New bulky phosphino-pyridine ligands.
Palladium and nickel complexes for the catalytic polymerization and oligomerization of ethylene.
Organometallics 2003, 22, 4893-4899.
14. Sun, W.-H.; Li, Z.; Hu, H.; Wu, B.; Yang, H.; Zhu, N.; Leng, X.; Wang, H. Synthesis and
characterization of novel nickel(II) complexes bearing N,P ligands and their catalytic activity in
ethylene oligomerization. New J. Chem. 2002, 26, 1474-1478.
15. Daugulis, O.; Brookhart, M. Polymerization of ethylene with cationic palladium and nickel
catalysts containing bulky nonenolizable imine-phosphine ligands. Organometallics 2002, 21,
5926-5934.
16. Keim, W.; Killat, S.; Nobile, C.F.; Suranna, G.P.; Englert, U.; Wang, R.; Mecking, S.; Schroeder,
D.L. Synthesis, characterization and catalytic activity of Pd(II) and Ni(II) complexes with new
cyclic alpha-diphenylphosphino-ketoimines. Crystal structure of 2,6-diisopropyl-N-(2-
diphenylphosphino-cyclopropylidene)aniline and of 2,6-diisopropyl-N-(2-diphenylphosphino-
cyclohexylidene)aniline. J. Organomet. Chem. 2002, 662, 150-171.
17. Sirbu, D.; Consiglio, G.; Gischig, S. Palladium and nickel complexes of (P,N)-ligands based on
quinolines: Catalytic activity for polymerization and oligomerization. J. Organomet. Chem. 2006,
691, 1143-1150.
18. Aeby, A.; Consiglio, G. P^N versus N^N ligands for the palladium-catalyzed alternating
copolymerization of styrene and carbon monoxide. Inorg. Chim. Acta 1999, 296, 45-51.
19. Gsponer, A.; Schmid, T.M.; Consiglio, G. Ligand-dependent diastereoselectivity in the
palladium-catalyzed copolymerization of styrene with carbon monoxide. Helv. Chim. Acta 2001,
84, 2986-2995.

1823
Molecules 2011, 16
20. Braunstein, P.; Fryzuk, M.D.; Le Dall, M.; Naud, F.; Rettig, S.J.; Speiser, F. Synthesis and
structure of Pd(II) complexes containing chelating (phosphinomethyl)oxazoline P,N-type ligands.
copolymerisation of ethylene/CO. J. Chem. Soc., Dalton Trans. 2000, 1067-1074.
21. Agostinho, M.; Braunstein, P. Palladium(II) complexes with the new P,N-type ligand (2-
oxazoline-2-ylmethyl)di-isopropylphosphine as intermediates in CO/ethylene or CO/methyl
acrylate insertion. C.R. Chim. 2007, 10, 666-676.
22. Agostinho, M.; Braunstein, P.; Welter, R. Phosphinito- and phosphonito-oxazoline Pd(ii)
complexes as CO/ethylene insertion intermediates: Synthesis and structural characterization.
Dalton Trans. 2007, 759-770.
23. Agostinho, M.; Braunstein, P. Structurally characterized intermediates in the stepwise insertion of
CO-ethylene or CO-methyl acrylate into the metal-carbon bond of Pd(II) complexes stabilized by
(phosphinomethyl)oxazoline ligands. Chem. Commun. 2007, 58-60.
24. Buono, G.; Toselli, N.; Martin, D. Chiral Diazaphospholidine Ligands in Phosphorus Ligands in
Asymmetric Catalysis; Börner, A., Ed.; Wiley-VCH: Weinheim, Germany, 2008; pp. 529-546.
25. Breeden, S.; Cole-Hamilton, D.J.; Foster, D.F.; Schwarz, G.J.; Will, M. Rhodium-mediated
asymmetric hydroformylation with a novel bis(diazaphospholidine) ligand. Angew. Chem. Int. Ed.
2000, 39, 4106-4108.
26. Myagmarsuren, G.; Tkack, V.S.; Shmidt, F.K.; Mohamad, M.; Suslov, D.S. Selective
dimerization of styrene ot 1,3-diphenyl-1-butene with bis(beta-diketonato)palladium/boron
trifloride etherate catalyst system. J. Mol. Cat. A Chem. 2005, 235, 154-160.
27. Peng, J.; Li, J.; Qiu, H.; Jiang, J.; Jiang, K.; Mao, J.; Lai, G. Dimerization of styrene to 1,3-
diphenyl-1-butene catalyzed by palladium-Lewis acid in ionic liquid. J. Mol. Cat. A Chem. 2006,
255, 16-18.
28. Lee, D.W.; Yi, C.S. Chain-Selective and Regioselective Ethylene and Styrene Dimerization
Reactions Catalyzed by a Well-Defined Cationic Ruthenium Hydride Complex: New Insights on
the Styrene Dimerization Mechanism. Organometallics 2010, 29, 3413-3417.
29. Cabrero-Antonino, J.R.; Leyva-Perez, A.; Corma, A. Iron-Catalysed Regio- and Stereoselective
Head-to-Tail Dimerisation of Styrenes. Adv. Synth. Catal. 2010, 352, 1571-1576.
30. Vogt, D. Cobalt-Catalyzed Asymmetric Hydrovinylation. Angew. Chem. Int. Ed. 2010, 49,
7166-7168.
31. RajanBabu, T.V. Asymmetric Hydrovinylation Reaction. Chem. Rev. 2003, 103, 2845-2860.
32. Pettit, G.R.; Singh, S.B.; Herald, D.L.; Lloyd-Williams, P.; Kantoci, D.; Burkett, D.D.; Barkoczy,
J.; Hogan, F.; Wardlaw, T.R. The Dolastatins. 17. Synthesis of Dolaproine and Related
Diasteroisomers. J. Org. Chem. 1994, 59, 6287-6295.
33. Xu, X.-Y.; Tang, Z.; Wang, Y.-Z.; Luo, S.-W.; Cun, L.-F.; Gong, L.-Z. Asymmetric
Organocatalytic Direct Aldol Reactions of Ketones with alpha-Keto acids and Their Application
to the Synthesis of 2-Hydroxy-gamma-butyrolactones. J. Org. Chem. 2007, 72, 9905-9913.
34. Luo, S.; Xu, H.; Li, J.; Zhang, L.; Mi, X.; Zheng, X.; Cheng, J.-P. Facile evolution of asymmetric
organocatalysts in water assisted by surfactant Brønsted acids. Tetrahedron 2007, 63,
11307-11314.
35. Bartoli, G.; Bosco, M.; Dalpozzo, R.; Giuliani, A.; Marcantoni, E.; Mercozzi, T.; Sambri, L.;
Torregiani, E. An Efficient Procedure for the Preparation of (E)-alpha-Alkylidene Cycloalkanones

1824
Molecules 2011, 16
Mediated by CeCl3*7H2O-NaI System. Novel Methodology for the Synthesis of (S)-(-)-Pulegone.
J. Org. Chem. 2002, 67, 9111-9114.
36. Torisawa, Y.; Hashimoto, A.; Okouchi, M.; Limori, T.; Nagasawa, M.; Hino, T.; Nakagawa, M.
Manzamine C Congeners with Modified Azacyclic Rings: Synthesis and Biological Evaluation.
Bioorg. Med. Chem. Lett. 1996, 6, 2565-2570.
37. Legrand, O.; Brumel, J.M.; Constantieux, T.; Buono, G. Totally Stereoselective P-O to P-C
Migration Rearrangement: Application to the Synthesis of New Chiral o-Hydroxyaryl Phosphine
Oxides. Chem. Eur. J. 1998, 4, 1061-1067.
38. del Campo, O.; Carbayo, A.; Cuevas, J.V.; García-Herbosa, G.; Muñoz, A. Isomeric Preference in
Complexes of Palladium(II) with Chelating P,N-Donor Ligands. Eur. J. Inorg. Chem. 2009,
2254-2260.
39. Morita, D.K.; Stille, J.K.; Norton, J.R. Methyl/Phenyl Exchange between Palladium and a
Phosphine Ligand. Consequences for Catalytic Coupling Reactions. J. Am. Chem. Soc. 1995, 117,
8576-8581.
40. D'Amora, A.; Fanfoni, L.; Cozzula, D.; Guidolin, N.; Zangrando, E.; Felluga, F.; Gladiali, S.;
Benedetti, F.; Milani, B. Addressing the Poly- to Oligo-ketone selectivity in styrene
Carbonylation Catalyzed by Palladium/bpy Complexes. Effect of the 6-Alkyl Substitution.
Organometallics 2010, 29, 4472-4485.
41. Durand, J.; Scarel, A.; Milani, B.; Seraglia, R.; Gladiali, S.; Carfagna, C.; Binotti, B. Palladium-
Promoted Carbon Monoxide/Ethylene/Styrene Terpolymerization Reaction: Throwing Light on
the Different Reactivity of the Two Alkenes. Helv. Chim. Acta 2006, 89, 1752-1771.
42. Drent, E.; Budzelaar, P.H.M. Palladium catalyzed alternating copolymerization of alkenes and
carbon monoxide. Chem. Rev. 1996, 96, 663-681.
43. Milani, B.; Anzilutti, A.; Vicentini, L.; Sessanta o Santi, A.; Zangrando, E.; Geremia, S.;
Mestroni, G. Bis-chelated palladium(II) complexes with nitrogen-donor chelating ligands are
efficient catalyst precursors for the CO/styrene copolymerization reaction. Organometallics 1997,
16, 5064-5075.
44. Scarel, A.; Durand, J.; Franchi, D.; Zangrando, E.; Mestroni, G.; Carfagna, C.; Mosca, L.;
Seraglia, R.; Consiglio, G.; Milani, B., Mono- and dinuclear bioxazoline-palladium complexes for
the stereocontrolled synthesis of CO/styrene polyketones. Chem. Eur. J. 2005, 11, 6014-6023.
45. Axet, M.R.; Amoroso, F.; Bottari, G.; D'Amora, A.; Zangrando, E.; Faraone, F.; Drommi, D.;
Saporita, M.; Carfagna, C.; Natanti, P.; Seraglia, R.; Milani, B. Application of chiral amine-imine
ligands in palladium-catalyzed polyketones synthesis: Effect of ligand backbone on the polymer
stereochemistry. Organometallics 2009, 28, 4464-4474.
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