Asymmetric hydroformylation of styrene catalyzed by furanoside phosphine-phosphite-Rh(I) complexes

Article abstract of DOI:10.1016/S0957-4166(02)00030-7

A series of phosphine-phosphite ligands, derived from inexpensive D-(+)-xylose, were tested in the Rh-catalyzed asymmetric hydroformylation of styrene. Systematic variation of the phosphite moiety revealed a remarkable effect on the selectivity of the hyd

Full text of DOI:10.1016/S0957-4166(02)00030-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 3441–3445
Asymmetric hydroformylation of styrene catalyzed by furanoside
phosphine–phosphite–Rh(I) complexes
Oscar Pa`mies, Gemma Net, Aurora Ruiz* and Carmen Claver
Departament de Qu´ımica F´ısica i Inorga`nica, Universitat Rovira i Virgili, Pl. Imperial Ta`rraco 1, 43005 Tarragona, Spain
Received 10 January 2002; accepted 17 January 2002
Abstract—A series of phosphine–phosphite ligands, derived from inexpensive
D-(+)-xylose, were tested in the Rh-catalyzed
asymmetric hydroformylation of styrene. Systematic variation of the phosphite moiety revealed a remarkable effect on the
selectivity of the hydroformylation catalysts. High regioselectivities for 2-phenylpropanal (up to 95%) and moderate enantioselec-
tivity were found under mild reaction conditions (25–40°C, 25 bar of syn gas). The hydroformylation results are explained by the
solution structures of the intermediate species formed under hydroformylation conditions. © 2002 Published by Elsevier Science
Ltd.
1. Introduction
backbone in the asymmetric hydroformylation of
olefins,4c–d we report herein the use of a series of
furanoside phosphine–phosphite ligands derived from
Asymmetric hydroformylation is an attractive route for
synthesising enantiomerically pure aldehydes,1 which
can be used as precursors for the synthesis of high value
compounds such as pharmaceuticals, agrochemicals,
biodegradable polymers and liquid crystals. Rhodium
and platinum/tin catalytic systems modified with phos-
phine ligands have been widely used in asymmetric
hydroformylation.1 However, the enantioselectivity for
rhodium systems2 and the activity and regioselectivity
for platinum/tin systems3 have been highly disappoint-
ing. During the last decade, two new types of ligand—
diphosphite4 and phosphine–phosphite5 ligands—have
emerged as suitable ligands for asymmetric hydro-
formylation, overcoming the limitations of the phos-
phine-based catalytic systems. Most of the research
published to date has been dedicated to diphosphite
ligands.1e Thus, despite the early success of the phos-
phine–phosphite Binaphos ligand in the hydroformyl-
ation of styrene and the fact that Binaphos is the only
ligand with a wide scope in asymmetric hydroformyl-
ation,5 reports on the use of phosphine–phosphite lig-
ands are rare.5,6
inexpensive
D
-(+)-xylose (Fig. 1) in the asymmetric
Rh-catalyzed hydroformylation of styrene.7 We also
discuss the solution structures of the intermediate spe-
cies formed under the hydroformylation conditions.
2. Results and discussion
2.1. Asymmetric hydroformylation of styrene
Phosphine–phosphite ligands 1–4 were tested in the
rhodium-catalyzed asymmetric hydroformylation of
styrene under different reaction conditions. Styrene was
chosen as a substrate because this reaction has been
performed with a wide range of ligands with several
donor groups, enabling direct comparison of the
O
R
R
P O
O
Ph2P
O
O
O
O
O
O
O
=
Encouraged by the success of Binaphos5 and the excel-
lent combination of regio- and enantioselectivities
obtained with diphosphite ligands with furanoside
O
O
R
R
3 Sax
4 Rax
1 R = t-Bu
2 R = H
* Corresponding author. Fax: +34-977559563; e-mail: aruiz@
quimica.urv.es
Figure 1.
0957-4166/01/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0957-4166(02)00030-7

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O. Pa`mies et al. / Tetrahedron: Asymmetry 12 (2001) 3441–3445
efficiency of the different catalytic systems.1 The cata-
lysts were prepared in situ by adding the corresponding
phosphine–phosphite ligand to Rh(acac)(CO)2 as a cat-
alyst precursor, 16 h before the styrene was added. The
conversion and selectivity results are summarized in
Table 1. In all cases hydrogenated or polymerized
products of styrene were not observed.
of the biphenyl moiety in ligand 1, leads to slightly
higher activity and lower regio- and enantioselectivity
than the catalyst system Rh/1 (entry 4 versus 6). This
behaviour is similar to that observed for diphosphite
ligands for which the presence of bulky substituents in
the ortho positions of the biphenyl moieties are crucial
to obtain good regio- and enantioselectivities.4
The effects of different reaction parameters (i.e. CO/H2
pressure ratio, ligand-to-rhodium ratio and tempera-
ture) were investigated for the catalytic precursor con-
taining ligand 1. After identical catalyst preparation,
hydroformylation experiments were carried out under
different CO and H2 partial pressures (entries 1, 3 and
4). The results clearly show that higher partial pressures
of H2 lead to higher initial turnover frequencies. More-
over, comparison of entries 1, 3 and 4 shows that both
the regio- and enantioselectivity are hardly affected by
varying the partial H2 pressure.
The use of ligand 3, containing enantiopure (S)-binaph-
thyl moiety, showed better activity and similar enan-
tioselectivity than the catalyst precursor containing
ligand 1 (entry 7). However, the regioselectivity is simi-
lar to that observed for the Rh/2 catalyst system (entry
6 versus 7).
The catalyst precursor containing ligand 4, with an
enantiopure (R)-binaphthyl moiety, induced much
higher reaction rate and a lower enantioselectivity than
3 (entry 7 versus 8). Monodentate coordination of the
ligand could explain its higher activity and lower enan-
tioselectivity but this can be excluded from the spectro-
scopic data obtained under hydroformylation
conditions (vide infra). A more plausible explanation is
that the conformation adopted by ligand 4 probably
causes less steric hindrance at the rhodium complexes
than the HRh(CO)2(3) and, therefore, it is more reac-
tive and less enantioselective.
Varying the ligand-to-rhodium ratio shows that these
catalyst systems are highly stable under hydroformyl-
ation conditions and no excess of ligand is needed
(entry 2). This is an important advantage over the rest
of the phosphine–phosphite ligands, for which a greater
excess of ligand is needed.5,6 However, at higher ligand-
to-rhodium ratios, the turnover frequencies are slightly
lower (entries 1 versus 2). This is probably due to
competition between the active species HRh(CO)2(1)
and other less active species that have more than one
ligand coordinated to the rhodium centre.
2.2. Characterization of HRh(PP)(CO)2 complexes
In order to obtain information about the HRh(PP)-
(CO)2 species, which are known to be responsible for
the catalytic activity, we studied by HP NMR spec-
troscopy the solution structures of hydridorhodium
dicarbonyl catalysts (HRh(PP)(CO)2, PP=phosphine–
phosphite ligand). They were prepared in situ under
hydroformylation conditions by adding 1.1 equivalent
of phosphine–phosphite ligand to the catalyst precursor
Lowering the temperature of the reaction to room
temperature resulted in an increase in enantioselectivity
(up to 49%) (entry 5).
The use of ligand 2, which results from removing the
bulky tert-butyl groups at the ortho and para positions
Table 1. Asymmetric hydroformylation of styrene catalysed by Rh(acac)(CO)2/phosphine–phosphite 1–4a
CHO
3-PP
% Conv.d
Rh(acac)(CO)2
CHO
*
+
1-4
2-PP
b
Entry
Ligand
CO/H2
T (°C)
TOFc
% 2-PPe
%eef
1
2g
3
4
5
6
7
8
1
1
1
1
1
2
3
4
1
1
2
0.5
0.5
0.5
0.5
0.5
40
40
40
40
25
40
40
40
54
49
28
67
9
75
87
164
23
19
15
32
58h
36
41
81
94
94
94
94
95
89
90
91
35 (S)
33 (S)
36 (S)
35 (S)
49 (S)
7 (S)
38 (S)
20 (S)
a Reaction conditions: P=25 bar, styrene (13 mmol), Rh(acac)(CO)2 (0.013 mmol), ligand/Rh=1.1, toluene (15 mL).
b pCO/pH2 ratio.
c TOF in mol styrene×mol Rh−1×h−1 determined after 1 h reaction time by GC.
d % Conversion of styrene after 5 h.
e Regioselectivity in 2-phenylpropanal.
f % Enantiomeric excess measured by GC.
g Ligand/Rh=2.
h Conversion after 72 h.

O. Pa`mies et al. / Tetrahedron: Asymmetry 12 (2001) 3441–3445
3443
O
P O
O
O
O
Ph2P
CO
CO
CO / H2
O
HRh(PP)(CO)2
+
Rh
O
O
5
6
7
PP = 1
PP = 3
PP = 4
Scheme 1. Preparation of complexes 5–7.
1
Table 2. Selected H and 31P NMR data for HRh(PP)(CO)2 complexes 5–7a
Complex
lP1
lP2
1JRh–P1
1JRh–P2
2JP1–P2
lH
2JH–P1
2JH–P2
1JH–Rh
5
6
7
8.25
7.87
7.32
158.2
169.3
174.1
115
112
109
225
221
217
11
38
42
−9.61 (ddd)
−9.53 (ddd)
−9.42 (ddd)
75.9
74.4
78.2
32.7
57.4
68.1
8.4
9.1
9.3
a Prepared in toluene-d8. l in ppm. Coupling constants in Hz. P1=phosphine phosphorus. P2=phosphite phosphorus.
Similar behavior has been observed for complexes 6
Rh(acac)(CO)2 (Scheme 1). No HRh(CO)2(2) com-
plexes were prepared because the expected formation of
mixtures of diastereoisomeric complexes made this
unattractive for an in situ NMR study.4b,8 The spectro-
scopic data are summarized in Table 2.
2
and 7. Interestingly, the coupling constants, JH–P2 for
these complexes were higher than those of complex 5,
which indicates that the relative amount of
diastereoisomer containing the phosphite in the axial
position is higher for these complexes than for complex
5.
The 31P{1H} NMR spectrum of HRh(CO)2(1), 5
showed two double doublets at 8.25 and 158.2 ppm,
which we attributed to the phosphine (P1) and phos-
1
3. Conclusions
phite (P2) phosphorus, respectively. The H NMR spec-
trum of 5 revealed a double double doublet in the
hydride region, due to the coupling with rhodium and
the two non-equivalent phosphorus atoms. The magni-
A series of phosphine–phosphite ligands 1–4, derived
from inexpensive
D
-(+)-xylose, were screened in the
1
Rh-catalyzed asymmetric hydroformylation of styrene.
Good regioselectivities in 2-phenylpropanal (up to 95%)
and moderate enantioselectivities (up to 49%) were
obtained. The results show that bulky substituents in
the ortho positions of the biphenyl moiety have a
positive effect on the regio- and enantioselectivity of the
reaction. The enantioselectivity and activity were also
affected by the configuration of the binaphthyl at the
phosphite moiety. We used HP NMR to characterise
the rhodium complexes formed under CO/H2. The
results indicate that HRh(PP)(CO)2 complexes exist in
two diastereoisomeric equatorial-axial forms in fast
exchange. In the most stable diastereoisomer, the phos-
phine occupies an axial position, while the phosphite,
the best p-acceptor, occupies an equatorial position.
These results contrast with the coordination mode
found for HRh(Binaphos)(CO)2 in which the phosphine
occupies an equatorial position and the phosphite moi-
ety is in the axial position, and this could explain why
the enantioselectivities obtained with these catalysts are
moderate.
tude of the JH–Rh is typical of an equatorial-axial (ea)
coordination for the phosphine–phosphite moieties (i.e.
1JH–Rh with the phosphorus atom trans to the hydride is
1
around 9 Hz, whereas JH–Rh with a carbonyl group
trans to the hydride is less than 4 Hz).6c Small cis
phosphorus–hydride coupling constants (typically
between 1 and 10 Hz) are reported in HRh(PP)(CO)2
complexes with diequatorially (ee) coordinating diphos-
phine and diphosphite ligands.1e,4b,4d In contrast, rela-
tively large phosphorus–hydride coupling constants
(between 150 and 180 Hz for phosphites1e,4b and
between 90 and 110 Hz for phosphines9) are reported
when phosphorus is located trans to the hydride atom.
2
2
The intermediate values for the JH–P1 and JH–P2 indi-
cate a rapid equilibrium between two equatorial-axial
(ea) diastereoisomers, which are in fast exchange on the
NMR time-scale (Scheme 2). Taking into account the
2
typical values of JH–P for phosphine and phosphite in
an equatorial and axial position, it seems clear that the
diastereoisomer with the phosphine in an axial position
and the phosphite in an equatorial position is much
more stable under hydroformylation conditions. This
contrasts with the coordination mode found for HRh(-
Binaphos)(CO)2 in which the phosphine occupies an
equatorial position and the phosphite moiety the axial
position,5a which may explain why the enantioselectivi-
ties obtained with these catalysts were only moderate.
H
H
OC
P2
OC
P1
Rh CO
P1
Rh CO
P2
Scheme 2. Equatorial-axial phosphorus exchange.

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O. Pa`mies et al. / Tetrahedron: Asymmetry 12 (2001) 3441–3445
4. Experimental
(m, 1H, H-5), 3.01 (m, 1H, H-5%), 3.25 (m, 1H, H-4),
3
4.09 (d, 1H, H-2, J2-1=3.3 Hz), 5.16 (dd, 1H, H-3,
3
3
All experiments were carried out under an argon atmo-
sphere. All solvents were dried using standard methods
and distilled prior to use. Compounds 1–4 were pre-
pared as previously described.7 1H and 31P{1H} NMR
spectra were recorded on a Varian Gemini 300 MHz
spectrometer. Chemical shifts are relative to SiMe4 (1H)
as internal standard or H3PO4 (31P) as external stan-
dard. All assignments in NMR spectra were determined
by COSY spectra. Gas chromatographic analyses were
run on a Hewlett–Packard HP 5890A instrument (split/
splitless injector, J&W Scientific, Ultra-2 25 m column,
internal diameter 0.2 mm, film thickness 0.33 mm,
carrier gas: 150 kPa He, F.I.D. detector) equipped with
a Hewlett–Packard HP 3396 series II integrator.
Hydroformylation reactions were carried out in a
home-made 100 mL stainless steel autoclave. Enan-
tiomeric excesses were measured after the aldehydes
had been oxidised to their corresponding carboxylic
acids with a Hewlett–Packard HP 5890A gas chro-
matograph (split/splitless injector, J&W Scientific, FS-
Cyclodex b-I/P 50 m column, internal diameter 0.2 mm,
film thickness 0.33 mm, carrier gas: 100 kPa He, F.I.D.
detector). The absolute configuration was determined
by comparing the retention times with enantiomerically
pure (S)-(+)-2-phenylpropionic and (R)-(−)-2-phenyl-
propionic acids.
3J3-4=2.1 Hz, J3-P=13.5 Hz), 5.44 (d, 1H, H-1, J1-2
=
3.3 Hz), 6.8–7.6 (m, 14H, CHꢀ).
4.2.2. [HRh(CO)2(3)], 6. 31P NMR, l: 7.87 (dd, 1P, P1,
1JP1–Rh=112 Hz, 2JP–P=38 Hz), 169.3 (dd, 1P, JP2–
1
2
1
Rh=221 Hz, JP–P=38 Hz). H NMR, l: −9.53 (ddd,
2
2
1
1H, JP1–H=74.4 Hz, JP2–H=57.4 Hz, JRh–H=9.1 Hz),
1.09 (s, 3H, CH3), 1.53 (s, 3H, CH3), 3.11 (m, 2H, H-5,
H-5%), 3.78 (m, 1H, H-4), 4.28 (m, 1H, H-2), 5.24 (m,
3
1H, H-3), 5.39 (d, 1H, H-1, J1-2=3.6 Hz), 6.8–8.0 (m,
22H, CHꢀ).
4.2.3. [HRh(CO)2(4)], 7. 31P NMR, l: 7.32 (dd, 1P, P1,
1JP1–Rh=109 Hz, 2JP–P=42 Hz), 174.1 (dd, 1P, JP2–
1
2
1
Rh=217 Hz, JP–P=42 Hz). H NMR, l: −9.42 (ddd,
2
2
1
1H, JP1–H=78.2 Hz, JP2–H=68.1 Hz, JRh–H=9.3 Hz),
1.11 (s, 3H, CH3), 1.47 (s, 3H, CH3), 3.03 (m, 2H, H-5,
H-5%), 3.89 (m, 1H, H-4), 4.32 (m, 1H, H-2), 5.21 (m,
3
1H, H-3), 5.43 (d, 1H, H-1, J1-2=3.6 Hz), 6.8–8.0 (m,
22H, CHꢀ).
Acknowledgements
We thank the Spanish Ministerio de Educacio´n, Cul-
tura y Deporte and the Generalitat de Catalunya
(CIRIT) for financial support (PB97-0407-CO5-01) and
for awarding a research grant (to O.P.). We thank
Professor P. W. N. M. van Leeuwen for his suggestions
and comments.
4.1. Hydroformylation of styrene
In a typical experiment, the autoclave was purged three
times with CO. The solution was formed from
Rh(acac)(CO)2 (0.013 mmol) and the phosphine–phos-
phite (0.014 mmol) in toluene (10 mL). When the
autoclave was pressurized with syn gas and heated to
the reaction temperature, the reaction mixture was
stirred for 16 h to form the active catalyst. The auto-
clave was depressurized and a solution of styrene (13
mmol) in toluene (5 mL) was placed in the autoclave
and pressurized again. During the reaction, several
samples were taken out of the autoclave. After the
desired reaction time, the autoclave was cooled to room
temperature and depressurized. The reaction mixture
was analyzed by gas chromatography.
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