Pd-catalysed methoxycarbonylation of vinylarenes using chiral monodentate phosphetanes and phospholane as ligands. Effect of substrate substituents on enantioselectivity

Article abstract of DOI:10.1039/b705230h

Palladium complexes bearing phospholane 1 and phosphetane 2-4 ligands have been synthesised to be used as catalyst precursors in the asymmetric methoxycarbonylation of vinyl arenes. Single crystals of the complex [PdCl ₂(2)₂] II were obtained from a toluene solution and analysed by X-ray crystallography. Using these complexes, excellent regioselectivity (up to 99%) to the branched esters was obtained. Phosphetane ligands provide higher enantioselectivity than the phospholane under the same reaction conditions and an important influence of the substrate was observed. Enantioselectivity up to 50% was obtained using 4-methoxystyrene. The Royal Society of Chemistry.

Full text of DOI:10.1039/b705230h

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PAPER
www.rsc.org/dalton | Dalton Transactions
Pd-catalysed methoxycarbonylation of vinylarenes using chiral monodentate
phosphetanes and phospholane as ligands. Effect of substrate substituents on
enantioselectivity†
a
a
b
a
c
Bianca K. Mu n˜ oz, Cyril Godard, Angela Marinetti, Aurora Ruiz, Jordi Benet-Buchholz and
Carmen Claver*
a
Received 10th April 2007, Accepted 1st August 2007
First published as an Advance Article on the web 14th August 2007
DOI: 10.1039/b705230h
Palladium complexes bearing phospholane 1 and phosphetane 2–4 ligands have been synthesised to be
used as catalyst precursors in the asymmetric methoxycarbonylation of vinyl arenes. Single crystals of
the complex [PdCl
2
(2) ] II were obtained from a toluene solution and analysed by X-ray
2
crystallography. Using these complexes, excellent regioselectivity (up to 99%) to the branched esters was
obtained. Phosphetane ligands provide higher enantioselectivity than the phospholane under the same
reaction conditions and an important influence of the substrate was observed. Enantioselectivity up to
5
0% was obtained using 4-methoxystyrene.
Introduction
use provides high regioselectivity to the branched ester. Cometti
and Chiusoli reported the use of neomenthyldiphenyl phosphine
Palladium carbonylation is an important tool to functionalise
olefins in order to produce valuable compounds and intermediates
in fine chemistry. For instance, linear and branched esters can be
obtained through the palladium-catalysed alkoxycarbonylation of
olefins. The selective synthesis of one isomer is a key point in this
reaction. The linear esters are the desired products to be obtained
from long-chain alkenes. However, high regioselectivity to the
branched product is essential when enantioselectivity is required,
8
(
Fig. 1). Later Nozaki and co-workers used the phospholane
9
ligand (Fig. 1) and recently, the same authors reported on the
application of palladium complexes with binaphthol-derivatives
phosphines (Fig. 1) in the methoxycarbonylation of vinylarenes
achieving 53% of ee with the branched ester as the only reaction
1
10
product. A similar behaviour was observed for related palladium-
catalysed hydroxycarbonylation of styrene, where it was found
that palladium complex containing monodentate ligands produce
excellent regioselectivity to the branched acids but low enantiose-
2
as in the case of functionalised olefins such as vinyl arenes.
Over the past two decades, the asymmetric methoxycarbonyla-
tion of styrene (Scheme 1) has been extensively studied as a route
to obtain 2-arylproprionic acids, the most important class of non-
11a
lectivity (except in one case ), while systems containing bidentate
11b
ligands mainly produce linear acids. The mechanistic aspects of
methoxycarbonylation and hydroxycarbonylation of styrene have
3
steroidal anti-inflammatory drugs.
12–14
been reviewed.
Scheme 1 Pd-catalysed methoxycarbonylation of styrene.
Catalysts containing bidentate diphosphine ligands have been
frequently used for this reaction, but generally afford low regios-
4
electivity to the branched product. However, a few successful
5,6
examples have recently been reported. Monodentate phosphorus
based ligands have recently received more attention due to their
significant potential in various catalytic processes. Interestingly,
Fig. 1 Monodentate phosphines previously used in asymmetric methoxy-
carbonylation of styrene.
7
in the palladium-catalysed methoxycarbonylation of styrene, their
Phosphetane ligands have only recently been introduced in
15
homogeneous catalysis. Their restricted conformational free-
dom, due to the presence of a four-membered ring, is expected
a
Departament de Qu ´ı mica F ´ı sica i Inorg a` nica, Universitat Rovira i Virgili,
Marcel.li Domingo s/n, 43007, Tarragona, Spain. E-mail: carmen.claver@
urv.net; Fax: +34 977 559563; Tel: +34 977 559575
16
to enhance the chiral induction during the catalytic processes.
b
Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse,
These highly hindered, chiral phosphines have been reported in
asymmetric hydrogenation reactions catalysed by rhodium and
9
1198, Gif-sur-Yvette, France
c
Institute of Chemical Research of Catalonia (ICIQ), 43007, Tarragona,
Spain
17
ruthenium complexes. Phosphetane based palladium catalysts
were also used in processes such as olefin hydrosilylation and allylic
†
CCDC reference number 647859. For crystallographic data in CIF or
18
other electronic format see DOI: 10.1039/b705230h
nucleophilic substitutions.
5
524 | Dalton Trans., 2007, 5524–5530
This journal is © The Royal Society of Chemistry 2007

Concerning phospholane ligands, their use in asymmetric
catalysis has been reported for several transition metal catalysed
Synthesis of palladium complexes [PdCl
2
(1)
2
] I and [PdCl
2
(2)
2
] II
19
A solution of corresponding ligand (0.94 mmol) in dichloro-
methane (7 mL) was added to a solution of [PdCl (PhCN)
processes such as hydrogenation, allylic alkylation, hydroacy-
20
2
2
]
lation or hydrovinylation. The success of these ligands has
been attributed to the rigid chiral environment at the 2,5-
(
179.6 mg; 0.47 mmol) in dichloromethane (3 mL). The resulting
21
yellow solution was stirred for 1 h and concentrated under vacuum.
Addition of diethyl ether yielded the precipitation of a pale-yellow
solid, which was filtered and washed with diethyl ether before
positions of the five membered ring. Their use in Rh-catalysed
hydroformylation of olefins is more recent and showed to induce
22
good enantioselectivity. Phospholane ligands have also been
used in the Pd-catalysed copolymerisation of a-olefins and carbon
monoxide and led to the production of isotactic materials with
being dried under vacuum.
I: Yield: 220.6 mg (84%). H NMR (d in CDCl
1
3
): d 0.84 (m, 4H),
23a
d 0.99 (br, 2H), d 1.59 (br m, 2H), d 1.67 (b, 1H), d 1.73 (d, 3H,
ee’s higher than 90%. Copolymerisation reactions of CO using
phospholanes have been extended to produce polymers with
amides, carbamate, hydroxyl and carboxylate olefins, as well as
J
1
HH = 7 Hz), d 1.78 (d, 3H, JHH = 7 Hz), d 1.88 (m, 1H), d 2.07 (m,
H), d 2.13 (br m, 2H), d 2.37 (br m, 2H), d 3.02 (m, 1H), d 3.09
23b–23e
(m, 1H), d 3.59 (b, 2H), d 7.15 (b, 2H), d 7.27 (d, JHH = 7 Hz, 2H),
d 7.41 (t, JHH = 7 Hz, 2H), d 7.44 (b, 1H), d 7.79 (m, 2H); C{ H}
d in CDCl
): d 14.8 (s), d 15.4 (s), d 21.1 (t, JPC = 5 Hz), d 22.3
vinyl epoxides and fluoroalkenes.
1
3
1
We recently reported preliminary results concerning the use
of palladium systems bearing chiral phosphetane ligands in the
(
3
24
(t, JPC = 7 Hz), d 31.8 (t, JPC = 12 Hz), d 32.7 (t, JPC = 12 Hz),
asymmetric methoxycarbonylation of styrene. Here, we report
further investigations into these catalytic systems. The ligands
used for this study are shown in Fig. 2. The synthesis of a series of
Pd complexes, their characterisation and their application in the
asymmetric methoxycarbonylation of vinyl arenes are described.
d 33.05 (d, JPC = 30 Hz), d 34.2 (s), d 34.8 (s), d 35.75 (d, JPC
=
3
0 Hz), d 128.05 (s), d 128.1 (s), d 128.15 (s), d 130.4 (s), d 132.4
3
1
1
(
s), d 134.05 (t, JPC = 6 Hz) P{ H} (d in CDCl
3
): 53.1 ppm (v. br,
cis-complex) 44.3 ppm (s, trans-complex).
1
II: Yield: 244 mg (75%). H NMR (d in d
2
-dichloromethane):
) d 0.97
), d 1.31 (t,
), d 1.54 (s, CH ), d
), d 1.84 (m, CH), d 2.0 (m, CH),
d 0.82 (d, JHH = 7 Hz, CH
3
), d 0.89 (d, JHH = 7 Hz, CH
), d 0.98 (d, JHH = 7 Hz, CH ), d 1.30 (s, CH
PH = 7 Hz, CH), d 1.38 (t, JPH = 9 Hz, CH
.59 (m, CH ), d 1.75 (m, 2 CH
3
(
J
1
s, CH
3
3
3
3
3
2
2
1
3
1
d 2.13 (m, CH), d 2.66 (d, JHP = 13 Hz, CH
dichloromethane): d 17.5 (s, CH ), d 21.9 (s, CH
d 23.7 (s, CH ), d 23.8 (s, CH
), d 24.8 (t, JPC = 6 Hz, CH
t, CH ), d 27.2 (s, CH
), d 30.9 (s, CH), d 33.7 (t, JPC = 6 Hz, CH),
d 34.8 (s, CH ), d 36.2 (s, CH ), d 40.7 (s, C), d 42.9 (s, CH), d 45.9
s, CH), d 49.4 (broad, CH
); P{ H} (d in d
203 K): d 61.1 (s, br), d 59.9 (s).
2
). C{ H} (d in d
), d 22.5 (s, CH
), d 25.6
2
-
),
3
3
3
3
3
2
(
3
3
Fig. 2 Ligands used in this study.
2
2
3
1
1
(
3
2
-dichloromethane,
Experimental
General methods
X-Ray data collection and structure determination of [PdCl
2
(2)
2
] II
All palladium complexes were synthesised using standard Sch-
lenck techniques under a nitrogen atmosphere. Diethyl ether,
toluene and THF were distilled over sodium–benzophenone
Crystals of trans-[PdCl (2) ] suitable for X-ray analysis were
2
2
◦
obtained from a toluene solution at 0 C. Data were collected
and dichloromethane was distilled over P
2
O
5
. All solvents were
at 100(2) K. The complex crystallizes in a trigonal space group
3
˚
˚
deoxygenated before use. The phospholane 1 and the phosphetane
with a = 13.3102(7) A, c = 19.1593(19) and V = 2939.5(4) A .
The crystal structure was solved and refined using the SHELXTL
package. Structure solutions were obtained in the space groups
18b,25–27
ligands 2–4,
PdCl (3) ] III and [PdCl
to previously reported methods. PdCl
and the palladium complexes [PdCl
2
(NCPh)
were synthesised according
was purchased from
2
],
18a,28
[
2
2
2
(4) ] IV
2
2
P3
2
and P3 21. Since the heavy atom position corresponds to
2
Johnson Matthey Inc. and used without further purification.
All other reagents, except vinylnaphthalene that was purified by
flash chromatography (silica, hexane), were used as received from
commercial suppliers. Deuterated solvents used for routine NMR
the higher symmetry space group, it is difficult to distinguish
between twinning and disorder of the light atoms. Applying a
matrix for twinning by merohedry (0 1 0 1 0 0 0 0 −1, BASF
0.5) in the space group P3 the R1 value could be lowered from
2
1
13
1
measurements were dried over molecular sieves. H, C{ H}
9.18% to 6.88%. Nevertheless the atom positions were showing a
strong correlation and negative atomic displacement parameters.
A structure solution obtained in the higher symmetric space group
3
1
1
and P{ H} spectra were recorded on a Varian Mercury 400
spectrometer (400.14, 100.63 and 161.98 MHz, respectively).
Chemical shifts were referenced to either TMS as an internal
P3 21 could be refined, applying restraints on some carbon–
2
1
13
1
standard ( H and C{ H} NMR spectra) or 85% H
3
PO
4
as an
carbon distances, restraints on the atoms with the strongest
anisotropic displacement parameters and a disorder model. In
this case, the structure refined to a R1-value of 7.45% and
no negative atomic displacement parameters were observed. In
the disordered model, two structures can be observed with the
menthyl rests on similar positions but showing slightly different
conformations. For the description of the molecule the higher
3
1
1
external standard ( P{ H} NMR spectra). Gas chromatography
analyses were performed using a Hewlett-Packard 5890 series
II chromatograph with flame ionisation detector and Ultra-2
(
5% diphenylsilicone–95% dimethylsilicone) (25 m × 0.2 mm
Ø) capillary column. Enantiomeric excesses were determined
by High Performance Liquid Chromatography analysis (Daicel
CHIRACEL OJ, hexane–2-propanol = 95 : 5, 1.5 ml min ).
−
1
symmetry structure solution in P3
2
21 was selected. The hydrogen
This journal is © The Royal Society of Chemistry 2007
Dalton Trans., 2007, 5524–5530 | 5525

atoms were included as fixed contributions in the final stages of
least-squared refinement, while anisotropic temperature factors
were used for all other atoms.
Catalysis
High-pressure experiments were carried out in a Berghof auto-
clave, and the reaction mixtures were magnetically stirred and
electrically heated. In a typical experiment, a solution of the
palladium precursor (0.015 mmol), p-TsOH (0.15 mmol) and
styrene (3 mmol) in 5 mL of THF–MeOH mixture (1 : 1)
were introduced into the evacuated autoclave. Carbon monoxide
was introduced and the system was then heated. When thermal
equilibrium was reached, stirring was initiated. After reaction, the
autoclave was cooled to room temperature and depressurised. The
product was filtered in a short column of Celite and solvent was
removed under vacuum. The pure ester was isolated by column
chromatography on silica gel using hexane–ethyl acetate (9 : 1)
as the eluent. Conversions, chemo-, regio- and enantioselectivities
were determined by GC and HPLC analyses.
31
1
Fig. 4 Ratio of the P{ H} peak intensities as a function of the
temperature and nature of the solvent for complex [PdCl (2) ].
2
2
techniques, these two resonances were found to exchange in all
solvents. These results suggested the presence of two isomers
that could correspond to the cis and trans configuration of the
ligands or to two rotamers of II. In the C{ H} spectrum of
II, the major isomer exhibited 3 resonances with pseudo triplet
multiplicity that indicated a trans configuration of the phosphorus
ligands, generating the second order pattern. However, the low
intensity of the signals arising from the minor isomer did not
allow to distinguish between the two possible types of isomerism.
Results and discussion
13
1
Synthesis of complexes [PdCl
2
(1)
2
] I and [PdCl
2
(2)
2
] II
The palladium complexes were obtained by reaction of
[
PdCl (NCPh) ] with 2 equivalents of the appropriate ligand in
2
2
dichloromethane. The products were precipitated by addition of
3
1
1
diethyl ether and obtained in high yields. In the P{ H} NMR
spectra of a solution containing the complex II, a single broad
resonance at d ∼ 61 was observed at 295 K. However, at 203 K,
two singlet resonances were detected at d 61.1 (major) and d 59.9
The cis/trans isomerisation of PdCl
2
2
(L) complexes is known to
2
9
occur in an intermolecular manner while in the case of two
rotamers, the interchange mechanism is expected to occur in
an intramolecular way. In order to clearly identify the minor
isomer, P{ H}spectra of II were recorded in the presence of
1 equivalent of free ligand 2. In these experiments, the lineshape
of the resonances was found to be unaffected, indicating that
no change in the rate of interchange between the two species
was apparent. These results suggested that the interchange was
occuring via an intramolecular process and that the two signals
3
1
1
(
minor) with distinct intensities (Fig. 3). The ratio of the peak
intensities was found to vary with temperature and slightly with
the nature of the solvent, as shown in Fig. 4.
corresponded to two rotameric forms of trans-[PdCl
2
(2) ] (Fig. 5).
2
Fig. 5 Rotamers of complex II.
3
1
1
Fig. 3 Selected region of the P{ H} NMR spectrum of [PdCl
-toluene at (a) 295 K and (b) 203 K.
2
2
(2) ] II in
d
8
When the X-ray diffraction of single crystals of II was per-
formed, the rotamer (B), containing both menthyl groups situated
on the same side of the plane defined by the Pd, Cl and P atoms was
identified. A selected molecular structure for one of the disorder
models of complex II is shown in Fig. 6. The coordination sphere
around the palladium atom was found to correspond to a slightly
For all solvents used, an identical trend was observed with an
increase of the amount of the minor species when the temperature
is increased from 193 to 253 K and in solvents of lower polarity.
This ratio could not be measured at higher temperatures due to
the broadness of these resonances above 253 K. Using EXSY
◦
distorted square-planar geometry, with a value of 177.91(6) for
5
526 | Dalton Trans., 2007, 5524–5530
This journal is © The Royal Society of Chemistry 2007

When the reaction was carried out under 35 bar of CO and
in the presence of a 10-fold excess of para-toluensulfonic acid
(
entry 1), the conversion was measured to be 22% and moderate
chemo- and regioselectivity to the branched product (70 and
5% respectively, entry 1) were obtained. When hydrochloric acid
7
was used as the acid source (entry 2), the conversion increased
to 40%. Furthermore, both chemo- and regioselectivity to the
branched ester were improved to 95% and 90%, respectively.
When greater ratios of acid to Pd were used (entry 3 and 4), the
conversions were found to increase up to 91%. However, a slight
decrease in chemoselectivity was observed. The regioselectivity to
the branched esters was measured to be up to 95% under these
highly acidic conditions.
When the CO pressure was decreased to 20 bar (entry 5),
the conversion decreased to 55%, together with the chemo- and
regioselectivities (83 and 90%, respectively). However, when the
CO pressure was increased to 50 bar (entry 6), the conversion
was found to be 97% and the chemo- and regioselectivies were
significantly improved to 95 and 96%, respectively. Such an effect
Fig. 6 Molecular structure of the palladium complex II showing one of
the selected disorder models. Hydrogen atoms have been omitted for the
sake of clarity.
31
was previously reported for this reaction. When a mixture of
toluene and methanol (1 : 1) was used as solvent (entry 7), only
the chemoselectivity (78%) was found to significantly vary when
compared to the results obtained in THF : MeOH mixture under
the same conditions (entry 3). The by-products detected are shown
in Fig. 7.
◦
the Cl(1)–Pd–Cl(2) angle and 174.92(6) for P(1)–Pd–P(2). The
˚
Pd–Cl bond lengths were measured to be ca. 2.3 A while the Pd–
P bonds were ca. 2.33 A. These values are very similar to those
previously reported for the related complex trans-[PdCl
The two groups are related via a C symmetry axis passing through
˚
18a
2
(3)
2
].
2
the Pd center and perpendicular to both Cl(1)–Pd–Cl(2) and
P(1)–Pd–P(2) axis. This arrangement was also observed for trans-
[PdCl
2
(3) ] that was previously reported.
2
Catalytic results
Asymmetric methoxycarbonylation of styrene using the
phospholane complex [PdCl
2
(1) ] I as precursor
2
Although this work has focused on the use of the phosphetanes
in Pd-catalysed asymmetric methoxycarbonylation, phospholane
ligand 1 was first probed due to its structural relationship with
phosphetanes and the successful use of this type of ligands in other
Fig. 7 By-products observed in the methoxycarbonylation reaction under
acidic conditions.
22,23
asymmetric carbonylation reactions.
PdCl (1) ] I, containing the five-membered ring phospholane
was first used as a catalyst precursor for the asymmetric
The palladium complex
[
2
2
The major by-product observed was (2-methyl)benzylmethyl-
ether (M) formed by etherification of the substrate. Etherification
products are normally formed by the acid-catalysed addition of
1
methoxycarbonylation of styrene. The catalytic reactions were
◦
32
carried out over a period of 24 h at 90 C. The presence of acid
MeOH to styrene. The formation of the hydrogenation products
is required in order to form in situ the active species involved in
the catalytic reaction. The results obtained using this system are
summarised in Table 1.
(H) as traces can be explained by the presence of dihydrogen in the
media via the water gas shift reaction. The presence of water is
explained by the use of p-toluenesulfonic acid as a monohydrate.
30
33
a
Table 1 Methoxycarbonylation of styrene using complex I as precursor
+
Entry
Pd/H
Solvent
Acid
P
CO/bar
C (%)
(b + l) (%)
H (%)
M (%)
b : l
ee (%)
1
2
3
4
5
6
7
1/10
1/10
1/100
1/200
1/100
1/100
1/100
THF : MeOH
THF : MeOH
THF : MeOH
THF : MeOH
THF : MeOH
THF : MeOH
Toluene : MeOH
p-TsOH
HCl
HCl
HCl
HCl
HCl
HCl
35
35
35
35
20
50
35
22
40
81
91
55
97
77
70
95
93
89
83
95
78
0
0
0
0
0
0
<1
30
5
7
11
17
5
75:25
90:10
92:8
95:5
90:10
96:4
11 (S)
4 (S)
3 (S)
0
4 (S)
0
21
95:5
2 (S)
a
◦
Reaction conditions: 0.5 mol% Pd (0.015 mmol), Pd/acid = 1/10, 24 h, MeOH : THF (1 : 1), 90 C; (C = conversion; b = branched ester; l = linear
ester; H = hydrogenation product (ethylbenzene); M = etherification product (2-methyl)benzylmethyl ether).
This journal is © The Royal Society of Chemistry 2007
Dalton Trans., 2007, 5524–5530 | 5527

Transfer hydrogenation could also explain the detection of the
was induced by this system (ee = 0%). Changing the acid used
from p-TsOH to HCl (entry 5) did not yield an increase of the ee
value. When HCl was used, the conversion was found to decrease
to 58%, which is in contrast with the results observed using the
Pd complex containing the phospholane 1 as ligand (Table 1). The
effect of the polarity of the co-solvent was also probed by replacing
THF by the less polar toluene. Under these conditions and using
34
hydrogenation product. Under these conditions, the ee values
obtained were all found to be low (up to 11%, entry 1). It should
be noted that Nozaki et al. reported an ee value of 2.4% using
◦
this ligand in the presence of Pd-clay at 125 C and 45 atm
9
of CO.
In summary, using the palladium complex I as a catalyst
precursor, high regioselectivity to the branched ester was obtained.
However, this system was found to induce low enantioselectivity
during the reaction. In the following section, the results obtained
using systems bearing phosphetanes 2–4 are described.
[PdCl
increased to 97%. However, no significant variations in chemo-,
regio- and enantioselectivity could be observed. When [PdCl (4a)
2
(2)
2
] as the catalyst precursor (entry 6), the conversion was
2
2
]
was used as catalyst precursor (entry 7), lower conversion (26%)
was obtained but a significant increase of the ee value (29%) was
observed. This latter result could be explained by the greater steric
hindrance induced by the presence of a dioxolane group in ligand
Asymmetric methoxycarbonylation of styrene using the
phosphetane complexes II–IV as precursors
4. Using this system, high chemoselectivity and regioselectivity
The optimisation of the reaction conditions for the methoxycar-
bonylation of styrene using phosphetane-containing systems was
to the desired ester was again achieved (94 and 97% (b : l =
32.3), respectively). When the complex [PdCl (4b) ], containing
2
2
previously reported by our group using PdCl
2
, ligand 3 and p-
the ligand 4b with the configuration P(R)C(R)(S,S), very similar
results to those obtained with [PdCl (4a) ] were obtained in terms
24
TsOH. The results obtained for the palladium-catalysed asym-
metric methoxycarbonylation of styrene using isolated complexes
bearing phosphetanes 2, 3 and 4 under the previously optimised
conditions are summarised in Table 2. These ligands structurally
differ by the nature of the substituents of the phosphetane ring:
hydrogen, benzyl and dioxolane group, respectively (Fig. 2). First,
using the isolated palladium complex bearing ligand 3, 99% con-
version was obtained and high values for chemoselectivity (>99%)
and regioselectivity to the branched ester (99%) were achieved
2
2
of conversion, chemo- and regioselectivity (entry 8). However,
the enantioselectivity was found to decrease from 29 to 4%,
when compared to entry 7. These results indicate that the
enantioselectivity induced by the phosphetane ligand 4 arises from
the combination of the spatial arrangements of all the substituents
of these ligands.
Under these conditions, these Pd systems containing
phosphetane ligands hence afford very high chemo- and regiose-
lectivity to the branched ester for this reaction, independently of
the nature of the substituents of the phosphetane ring. However,
the catalytic activity and enantioselectivity were found to greatly
depend on the nature of this substituent, with conversions
measured from 26 to 99% and ee from 0, where only protons
were in the 4-position of the four membered ring of the ligand, to
29% when ligand 4a was used.
(
entry 1). However, the enantioselectivity of the reaction under
these conditions was found to be 6%. When the concentration of
PdCl (3) ] III was reduced to 0.25 mol% (entry 2), the conversion
[
2
2
slightly decreased to 90% whereas high values for the chemo- and
regioselectivities were measured (98% and 96%, respectively). Very
low enantiomeric excess was again measured. When the reaction
was repeated in the presence of an excess of ligand 3 (entry 3), the
catalytic results were found to be similar.
When the palladium precursor [PdCl
2
(2) ] II was used (entry 4),
2
Asymmetric methoxycarbonylation of vinyl arenes using
the conversion decreased to 82% although the chemoselectivity
to esters was still very high (95%) and the regioselectivity to
the branched product was 92% (b : l = 11.5). In these reac-
tions, the by-product was identified by GC-MS analysis as (2-
methyl)benzylmethyl ether, corresponding to the acid-catalysed
etherification products of styrene. However, no enantioselectivity
[
PdCl
2
(2) ] II as precursor
2
In order to probe the effect of the nature of the substrate on the
activity of these systems, the methoxycarbonylation reactions of
4-methoxystyrene, 4-methylstyrene, styrene, 4-fluorostyrene and
2-vinylnaphthalene were completed using [PdCl (2) ] II as the
2
2
catalyst precursor. Catalytic reactions were performed at milder
◦
conditions, 60 C under 35 bar of CO, using a 10-fold excess of
Table 2 Asymmetric methoxycarbonylation of styrene catalyzed by
a
palladium-phosphetane complexes
p-TsOH. The results obtained for these reactions are described in
Table 3.
Under these conditions, the methoxycarbonylation of styrene
Entry Catalyst
C (%)
(b + l) (%) M (%)
b : l
ee (%)
(
entry 3) was found to exhibit a conversion of 63%, a chemoselec-
1
2
3
4
5
6
7
8
[PdCl
[PdCl
[PdCl
[PdCl
[PdCl
[PdCl
[PdCl
[PdCl
2
2
2
2
2
2
2
2
(3)
(3)
(3)
(2)
(2)
(2)
2
2
2
2
2
2
]
]
]
]
]
]
99
90
92
82
58
97
26
27
>99
98
99
95
98
99
94
92
<1
2
1
5
2
1
6
8
99:1
96:4
99:1
92:8
98:2
95:5
97:3
89:11
6 (R)
2 (R)
6 (R)
0
0
0
b
tivity quasi-total to the esters (98%), a regioselectivity of 94% to
the branched product with 3% ee. When the reaction was carried
out using 4-methoxystyrene as substrate (Table 4, entry 1), the
conversion was found to be 71%, the chemoselectivity to the esters
21% with a high regioselectivity to the branched product (94%).
However, the most striking result achieved for this reaction is the
ee value of 50%, which is in contrast with the value obtained
when styrene was the substrate (3%). When the substrate was 4-
methylstyrene (entry 2), a conversion of 33% was achieved with
b,c
d
e
(4a)
2
]
]
29 (R)
4 (S)
(4b)
2
a
Reaction conditions: 0.5 mol% Pd (0.015 mmol), Pd/p-TsOH = 1/10,
◦
b
c
2
4 h, THF : MeOH (1 : 1), PCO 35 bar, T = 70 C. 0.25 mol% Pd. Excess
d e
of ligand (1 equiv.). HCl instead of p-TsOH. Toluene : MeOH (1 : 1)
as mixture of solvents. (H = hydrogenation product (ethylbenzene); M =
etherification product (2-methyl)benzylmethyl-ether).
5
8% of the products being the desired esters. The regioselectivity
was again greatly in favour of the branched ester (92%), and the
5
528 | Dalton Trans., 2007, 5524–5530
This journal is © The Royal Society of Chemistry 2007

a
Table 3 Asymmetric methoxycarbonylation of olefins catalyzed by II–p-TsOH system
Entry
R
C (%)
(b + l) (%)
H (%)
M (%)
b : l
ee (%)
1
2
3
4
5
OMe
Me
H
F
71
33
63
11
36
21
58
98
75
84
0
3
0
9
5
79
39
2
16
11
94 : 6
92 : 8
94 : 6
96 : 4
93 : 7
50 (S)
25 (S)
3 (S)
2 (R)
8 (R)
Naphthalene
a
Reaction conditions: 0.5 mol% Pd (0.015 mmol), Pd/p-TsOH=1 : 10, 24 h, THF: MeOH (1 : 1), 60 ◦C, PCO 35 bar. H = hydrogenation product
ethylbenzene); M = etherification product (2-methyl)benzylmethyl ether).
(
ee value obtained was intermediate between those of styrene and
-methoxystyrene (25%). When the substituent in the para position
contains electron-withdrawing substituents (entries 4 and 5), the
hydrogenation process becomes more substantial.
4
of the phenyl ring of the substrate was a fluoro group (entry 4), the
conversion of the reaction decreased considerably to 11% although
the regioselectivity of these reactions was still superior to 90% and
the chemoselectivity was increased to 75% when compared with
the result obtained with 4-methoxystyrene but still lower than in
the case of styrene (98%). The ee was found to be close to 0%, like
in the case of styrene. When 2-vinylnaphthalene was used as the
substrate (entry 5), the conversion was measured to be 36%, the
chemoselectivity was 84% to the esters with a regioselectivity of
In terms of regioselectivity, the values obtained for these
substrates were all superior to 90% to the branched product and
no significant variations were observed as a function of the nature
of the substrate.
In contrast, the values of enantioselectivity for these reactions
were found to vary greatly depending on the substrate used,
with an increase of ee when an electron donor group is in
para position of the vinyl unit. The ee values obtained for the
methoxycarbonylation of styrene and 4-fluorostyrene under these
conditions were close to 0%. However, an enantiomeric excess of
25% was obtained with 4-methylstyrene as the substrate and 50%
when 4-methoxystyrene was used. The effect of the group in the
para position of the phenyl ring is therefore significant for the
methoxycarbonylation reaction. However, such an effect has not
been reported so far for this reaction, although Nozaki and co-
workers reported that for the Pd-catalysed methoxycarbonylation
of vinylarenes using systems bearing alkylarylphosphines, the
highest ee value (53%) was obtained when the substrate was
9
3% to the branched product. The ee value in this case was found
to be 8% to the (R) enantiomer.
In terms of conversion, the results obtained were shown to vary
considerably depending on the substituent attached to the phenyl
ring of the substrate. The highest conversion was obtained when
the electron donor group—OMe is present in the 4-position of
the substrate (71%), while the lowest value was observed when the
electron-withdrawing group—F is present in this position (11%).
When a hydrogen atom was in this position, an intermediate value
was measured (63%). The result obtained with 2-vinylnaphthalene
was 36%, thus lower than in the latter case. It was therefore
concluded that the presence of a donor group on the phenyl
ring of the substrates increases the reactivity of the substrate to
different processes in competition with carbonylation reactions.
The conversion observed when 4-methylstyrene is the substrate
10
2-methoxy-6-vinylnaphthalene. It should also noted that an
increase in ee was previously observed for other carbonylation
reactions such as hydroformylation of vinyl arenes when the results
37
obtained with 4-methoxystyrene and styrene were compared. In
the case of 2-vinylnaphthalene, 8% ee was found for the other
enantiomer, namely the (R) enantiomer.
3
5
(
33%) is in agreement with results previously observed by Seayad
36
and Inoue, who reported an important decrease of the catalytic
activity for 4-alkylstyrene (alkyl = Me, Bu, Bu) when compared
Conclusions
t
i
to the results obtained with styrene.
Palladium complexes PdCl
2
(L)
2
bearing phospholane and
In terms of chemoselectivity, the lowest values were obtained
when electron-donating groups were present in the 4-position,
with 4-methoxystyrene (21%) and 4-methylstyrene (58%) while the
highest value was obtained when styrene was the substrate (98%).
In the case of 4-methoxystyrene, the only reaction by-product
was identified as the etherification product (79%). This can be
explained by the enhanced reactivity to acid-catalysed addition
of methanol due to the presence of a donor group. Indeed, when
the electronegativity of the substituent increases, the electronic
density of the vinyl moiety of the substrate decreases, and the
nucleophilic attack of methanol is therefore disfavoured. In this
case, the Pd-catalysed methoxycarbonylation reaction takes place
much faster than the etherification process, thus improving the
chemoselectivity of the reaction. However, when the substrate
phosphetane ligands were synthesised, characterised and used as
catalyst precursors for the methoxycarbonylation of vinyl arenes.
The bis-phosphetane complex [PdCl
2
(2) ] II crystallised in the
2
trans configuration and was characterised by X-ray crystallogra-
phy. This species was found to exist as a mixture of rotamers in so-
lution. In the methoxycarbonylation of styrene, both phospholane
and phosphetane systems afforded excellent regioselectivity to the
branched ester, although only the phosphetane systems provided
moderate enantioselectivities (up to 29%). However, when other
vinyl arenes were used as substrates, the enantioselectivity of the
reaction was found to greatly vary depending on the nature of
the substituent in the 4-position of the phenyl ring. The ee values
were found to vary from 3% in the case of styrene up to 50% for
4-methoxystyrene, under identical conditions.
This journal is © The Royal Society of Chemistry 2007
Dalton Trans., 2007, 5524–5530 | 5529

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