Chiral furanoside phosphite-phosphoroamidites: New ligands for asymmetric catalytic hydroformylation

Article abstract of DOI:10.1016/S0957-4166(01)00489-X

We have designed a new series of phosphite-phosphoroamidites ligands 1-4 based on a furanoside backbone. These ligands were screened in the Rh-catalyzed asymmetric hydroformylation of styrene, inducing high regioselectivities with 2-phenylpropanal and moderate enantioselectivities (up to 65% e.e.). The results showed that the configuration of the stereogenic carbon atom C(3) at the ligand backbone had remarkable effects on the activity and enantioselectivity. Replacing the tert-butyl substituents with methoxy substituents at the para positions of the biphenyl moieties improved the enantioselectivities. We have also studied the solution structures of HRh(PP)(CO)2 complexes.

Full text of DOI:10.1016/S0957-4166(01)00489-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2827–2834
Chiral furanoside phosphite–phosphoroamidites: new ligands for
asymmetric catalytic hydroformylation
Montserrat Die´guez,* 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 8 October 2001; accepted 30 October 2001
Abstract—We have designed a new series of phosphite–phosphoroamidites ligands 1–4 based on a furanoside backbone. These
ligands were screened in the Rh-catalyzed asymmetric hydroformylation of styrene, inducing high regioselectivities with
2-phenylpropanal and moderate enantioselectivities (up to 65% e.e.). The results showed that the configuration of the stereogenic
carbon atom C(3) at the ligand backbone had remarkable effects on the activity and enantioselectivity. Replacing the tert-butyl
substituents with methoxy substituents at the para positions of the biphenyl moieties improved the enantioselectivities. We have
also studied the solution structures of HRh(PP)(CO)2 complexes. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
In the last few years, a group of less electron-rich
phosphorus compounds—phosphoroamidite ligands—
have also demonstrated their potential utility in asym-
metric hydrogenation7 and copper-catalyzed addition
of dialkylzinc to enones.8 The combination of differ-
ent functionalitites in a ligand has already proved
beneficial to the enantiodiscrimination (Achiwa’s
idea).9 In this context, it has been reported how phos-
phine–phosphite ligands used in and hydroformyl-
ation5a hydrogenation10 remarkably improved enan-
tioselectivity with respect to their diphosphine and
diphosphite counterparts.
In the last few years, asymmetric hydroformylation
has attracted much attention as a potential tool for
preparing enantiomerically pure aldehydes, which are
important precursors for synthesizing fine chemicals.1
Since the early seventies, transition metal complexes
based on rhodium and platinum have been used as
catalysts in asymmetric hydroformylation.1 Although
high enantioselectivities have been obtained with Pt/
diphosphine catalysts, they suffer from low chemo-
and regioselectivities.2 In general, Rh/diphosphine cat-
alysts show high catalytic activities and regioselectivi-
ties with branched aldehydes, but the e.e.s do not
exceed 60%.3 In the last decade significant improve-
ments have been made in the rhodium-catalyzed
Following our interest in carbohydrate ligands, and
bearing in mind Achiwa’s idea, we have designed a
new family of chiral bidentate phosphite–phospho-
roamidite ligands 1–4 with xylofuranoside backbone
(Fig. 1). These ligands have the potential advantages
of both types of ligand. We have also investigated
their use in the enantioselective rhodium-catalyzed
asymmetric hydroformylation of styrene. Finally, we
report the solution structures of the species formed
under hydroformylation conditions.
asymmetric
hydroformylation
based
on
new
diphosphite4 and phosphine–phosphite5 ligands.
Recently, a new class of diphosphite ligands, derived
from
D
-(+)-glucose, with sugar furanoside backbones
have demonstrated their potential as catalytic ligands
for asymmetric hydroformylation.4c Carbohydrates are
particularly advantageous because they are inexpen-
sive compounds and their modular nature makes the
systematic introduction of different functionalities
easy.6
To the best of our knowledge, only Agbossou et al.
have reported the application of phosphite–phospho-
roamidite ligands, having ephedrine and pyrrolidine
backbones, in the asymmetric hydroformylation with
modest enantioselectivities.11
* Corresponding author. Fax: +34-977559563; e-mail: dieguez@
quimica.urv.es
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00489-X

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M. Die´guez et al. / Tetrahedron: Asymmetry 12 (2001) 2827–2834
t-Bu
OMe
MeO
t-Bu
t-Bu
t-Bu
t-Bu
O
t-Bu
O
O
O
O
O
O
O
t-Bu
O
O
OMe
O
MeO
P
HN
P
HN
O
t-Bu
P
O
P
O
t-Bu
t-Bu
t-Bu
t-Bu
O
O
2
1
MeO
t-Bu
t-Bu
t-Bu
MeO
t-Bu
O
O
O
O
P
HN
P
HN
t-Bu
t-Bu
O
O
t-Bu
t-Bu
O
O
O
O
O
O
P
MeO
t-Bu
P
O
O
O
O
t-Bu
t-Bu
MeO
4
t-Bu
3
Figure 1.
2. Results and discussion
We also investigated the influence of the stereogenic
carbon atom C(3) by comparing diastereomeric ligands
3 and 4 with ligands 1 and 2, which have the opposite
configuration at C(3) but have the same substituents on
the biphenyl moieties.
2.1. Ligand design
Ligands 1–4 consist of a chiral 1,2-O-protected fura-
noside backbone, which determines their underlying
structure, and one amine group at C(5). Several phos-
phoric acid biphenol esters are attached to this basic
framework (Scheme 1).
2.2. Synthesis of the chiral phosphite–phosphoroamidite
ligands
The new ligands 1–4 were synthesized very efficiently in
one step from the corresponding amino alcohols 5a12
and 5b,13 which were easily prepared on a large scale
We investigated how the different groups attached to
the para positions of the bisphenol moieties affected
enantioselectivity using ligands 1 and 2, which have the
same configuration at C(3).
from inexpensive
D
-(+)-xylose (Scheme 1). Reacting
aminoalcohols 5 with 2 equiv. of the desired in situ
formed phosphorochloridite 6 (either 3,3%-di-tert-butyl-
R'
R
H2N
O
OH
c)
O
O
1, 2
+
PCl
O
O
a)
5a
R'
R
6a R = R' = t-Bu
R = t-Bu; R' = OMe
D-(+)-xylose
6b
b)
H2N
O
c)
+
6
3, 4
O
O
OH
5b
Scheme 1. Synthesis of ligands 1–4. (a) Ref. 12; (b) Ref. 13; (c) Py, toluene, 100°C.

M. Die´guez et al. / Tetrahedron: Asymmetry 12 (2001) 2827–2834
2829
5,5%-di-methoxy-1,1%-biphenyl-2,2%-diyl phosphorochlo-
ridite or 3,3%,5,5%-tetra-tert-butyl-1,1%-biphenyl-2,2%-diyl
phosphorochloridite) in the presence of pyridine pro-
duced ligands 1–4 in good overall yield.
Varying the ligand-to-rhodium ratio showed that these
catalyst systems are highly stable under hydroformyla-
tion conditions and no excess of ligand is needed (entry
4). This is an important advantage over the most
successful catalysts based on diphosphites4a,b and phos-
phine–phosphite,5 which need larger excesses of ligand.
All of the ligands were stable during purification on
neutral alumina under an atmosphere of argon and
they were isolated as solids. They were stable at room
temperature and are fairly robust towards hydrolysis.
The 1H and 13C NMR spectra agree with those
expected for these C1 ligands (see Section 4).
When ligand 2 with methoxy groups instead of tert-
butyl groups in the para positions of the biphenyl
moieties was used, the activity and enantioselectivity
was higher than with the catalyst system Rh/1 (entry 1
versus 5). These results are in line with the beneficial
para methoxy effect observed in enantioselectivity using
diphosphite ligands.4a,c,14
2.3. Asymmetric hydroformylation of styrene
The phosphite–phosphoroamidite ligands 1–4 were then
tested in the rhodium-catalyzed asymmetric hydro-
formylation of styrene under different reaction condi-
tions. The catalysts were prepared in situ by adding 1
equiv. of the corresponding phosphite–phosphoroamid-
ite ligand to Rh(acac)(CO)2 as a catalyst precursor,
since other precursors were reported to be less enan-
tioselective.5a The styrene hydroformylation results are
given in Table 1. Hydrogenated or polymerized prod-
ucts of styrene were not observed.
Ligands 3 and 4, whose configuration at C(3) is oppo-
site to those of ligands 1 and 2, followed the same trend
as catalyst precursors Rh/1 and Rh/2 but activities were
higher and the product enantiomeric excesses were
smaller (entries 6 and 7). A monodentate coordination
of the ligand may explain their higher activities15 but
this can be excluded from the spectroscopic data
obtained under hydroformylation conditions (vide
infra). A more plausible explanation is that the confor-
mation adopted by ligands 3 and 4 probably causes less
steric hindrance at the rhodium complexes than the
[HRh(CO)2 (ligands 1 or 2)], and therefore, they are
more reactive and less enantioselective. Moreover,
unlike when related diphosphite ligands are used,14b the
sense of the asymmetric induction is not controlled by
the absolute configuration of stereogenic carbon atom
C(3). Therefore, irrespective of the configuration of
C(3) of the ligand, the absolute configuration of the
major enantiomer of the product aldehyde is always S.
The effects of different reaction parameters were inves-
tigated for the catalytic precursor containing ligand 1.
After identical catalyst preparation, hydroformylation
experiments were carried out under different partial
pressures of CO and H2 (entries 1–3). Higher partial
pressures of H2 clearly led to higher initial turnover
frequencies. Moreover, comparing entries 1–3 shows
that regio- and enantioselectivity were not affected by
varying the partial pressure of H2.
Table 1. Asymmetric hydroformylation of styrene catalyzed by Rh(acac)(CO)2/phosphite–phosphoroamidite 1–4a
CHO
CHO
Rh(acac)(CO)2 / 1-4
+
*
CO / H2
Entry
Ligand
TOFb
Convc (%)
2-PPd (%)
E.e.e (%)
1
1
1
1
1
2
3
4
1
2
30
21
15
31
35
51
52
4
68
46
35
69
83
100
100
10
97
97
97
97
96
96
96
97
97
35 (S)
36 (S)
35 (S)
36 (S)
55 (S)
15 (S)
19 (S)
45 (S)
65 (S)
2f
3g
4h
5
6
7
8i
9i
5
12
a Reaction conditions: T=40°C, P=10 bar, styrene (13 mmol), Rh(acac)(CO)2 (0.0135 mmol), ligand/Rh=1.1, toluene (15 mL), PCO/PH2=0.5.
b TOF in mol styrene×mol Rh−1×h−1 determined after 1 h reaction time by GC.
c % Conversion of styrene after 24 h.
d Regioselectivity in 2-phenylpropanal.
e % E.e. measured by GC.
f PCO/PH2=1.
g PCO/PH2=2.
h Ligand/Rh=2.
i T=20°C.

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M. Die´guez et al. / Tetrahedron: Asymmetry 12 (2001) 2827–2834
Lowering the temperature to 20°C resulted in increased
enantioselectivity (up to 65%) with good regioselectivity
for 2-phenylpropanal (up to 97%) (entries 8 and 9).
These results represent a remarkable improvement with
respect to the best enantioselectivities (19% e.e.)
reported by Agbossou et al. using phosphite–phospho-
roamidite ligands in the Rh-catalyzed hydroformylation
of styrene.11b
H
H
P
P
OC
P
Rh
CO
Rh
CO
CO
ee
P
ea
Scheme 3. Equilibrium between equatorial–equatorial (ee)
and equatorial–axial (ea) species.
2.4. Characterization of HRh(PP)(CO)2 complexes
Table 3. Selected HP-IR data (cm−1) for complexes 7–10
Hydridorhodium phosphite–phosphoroamidite dicar-
bonyl complexes denoted as HRh(PP)(CO)2 7–10,
which are known to be responsible for the catalytic
activity, have been prepared to elucidate the solution
structures of these catalysts.1 The complexes were pre-
pared in situ under hydroformylation conditions (10
bar, 40°C) by adding 1 equiv. of phosphite–phop-
shoroamidite ligand 1–4 to the catalyst precursor
Rh(acac)(CO)2 (Scheme 2). NMR spectroscopy under
atmospheric conditions showed no detectable decompo-
sition of the complexes. Table 2 shows the selected data
for complexes 7–10.
Complex
w1 (ee)
w2 (ea)
w3 (ee)
w4 (ea)
7
8
9
10
2078 (s)
2076 (s)
2077 (s)
2076 (s)
2056 (w)
2055 (w)
2057 (w)
2056 (w)
2024 (s)
2022 (s)
2021 (s)
2023 (s)
2001 (w)
1999 (w)
2001 (w)
2000 (w)
bonyl species with ee coordinating ligands14a,17b and
second, a fast equilibrium mixture of bis-equatorially
and equatorial–axial (ea) species, which gives averaged
signals in the NMR spectra (Scheme 3).18 Evidence for
the latter should be supplied by the HP-IR spectra
because of the faster time-scale and lower detection
limit of this technique compared to the NMR.18 If an
equilibrium between two isomers occurs, two sets of
carbonyl frequencies originating from the two isomers
should be observed. In general, the carbonyl bands of
the ea isomer are found at lower wavenumbers than
those of the ee isomer.17b The infra red spectra of
complexes 7–10 showed four carbonyl absorption
bands in the 2100–1900 cm−1 region, which can be
attributed to a mixture of ee and ea isomers (Table
3).17a The relative intensities of the absorption bands
obtained from the HP-IR indicate that the propor-
tion of ea species are rather lower than the ee species,
which is in agreement with the observed phosphorous-
hydride coupling constants. The large values of the
phosphorous–phosphorous coupling constants for
HRh(PP)(CO)2 complexes are further evidence of the
dominant role of the ee species in the mentioned
equilibrium.4c
At room temperature, the 31P{1H} NMR spectra of
complexes 7, 9 and 10 showed the expected eight-line
spectrum due to the two non-equivalent coordinated
phosphorus atoms and a rhodium atom (ABX system).
The 31P{1H} NMR spectrum of complex 8, showed a
doublet at 164.7 ppm due to the 31P–103Rh coupling.
The fact that there is a doublet, not the expected
eight-line spectra, was caused by the coincidental
isochronicity of the two phosphorus atoms in fluxional
behavior. This was confirmed by measuring the low-
temperature 31P {1H} NMR spectrum.16
1
For all complexes, the H NMR spectra in the hydride
region revealed a double triplet, due to the coupling
with rhodium and the two phosphorus atoms. The fact
that there was a double triplet instead of the expected
double double doublet was caused by the coincidence
of the phosphorus-hydride coupling constants. The val-
ues of the phosphorus-hydride coupling constants are
relatively large for a pure bis-equatorial (ee) coordina-
tion.17 There are two explanations for this; first, the
formation of a distorted TBP hydridorhodium dicar-
3. Conclusions
A series of new phosphite–phosphoroamidite ligands
with a furanoside backbone have been easily synthe-
CO/H2
Rh(acac)(CO)2
HRh(PP)(CO)2
+
P-P
sized in a few steps from commercial
D
-(+)-xylose.
These ligands were employed in the asymmetric Rh-cat-
alyzed hydroformylation of styrene. The results show
that the type of substituents at the para positions in the
1-4
7-10
Scheme 2. Synthesis of HRh(PP)(CO)2 complexes 7–10.
1
Table 2. Selected H and 31P NMR data for HRh(PP)(CO)2 complexes 7–10a
Complex
PP
l P1
l P2
1JRh–P1
1JRh-P2
2JP1-P2
l H
2JH-P
2JH-P
1JH-Rh
7
8
9
10
1
2
3
4
161.2
164.7
162.6
166.2
164.3
164.7
166.2
168.9
234.3
229.2
234.8
239.1
224.3
229.2
232.1
228.3
271.0
–
278.5
271.8
−10.52 (dt)
−10.30 (dt)
−10.67 (dt)
−10.34 (dt)
10.5
8.1
9.8
8.8
10.5
8.1
9.8
8.8
3.3
3.3
3.2
3.6
a Prepared in toluene-d8. NMR spectra recorded under atmospheric conditions at room temperature. l in ppm. Coupling constants in Hz.

M. Die´guez et al. / Tetrahedron: Asymmetry 12 (2001) 2827–2834
2831
biphenyl moieties and the configuration of the stereo-
genic center at C(3) of the ligand backbone had
remarkable effects on the activity and enantioselectivity
of the hydroformylation reaction. The enantiomeric
excess for these diasteroisomeric ligands was higher for
ligand 3, which had para-methoxy substituents in the
biphenyl moieties and (S)-configuration at C(3).
Although the enantioselectivities achieved with these
ligands are similar to those of related diphosphite lig-
ands, their behavior is different. Therefore, unlike the
results with related diphosphite ligands, the sense of the
asymmetric induction is not controlled by the absolute
configuration of the stereogenic carbon atom C(3).
Absolute configuration was determined by comparing
the retention times with enantiomerically pure (S)-(+)-
2-phenylpropionic and (R)-(−)-2-phenylpropionic acids.
Optical rotations were measured at 20°C on a Perkin–
Elmer 241 MC Polarimeter. The specific rotations are
given in deg cm3 g−1 dm−1 units.
4.2. 3,5-Bis[(3,3%,5,5%-tetra-t-butyl-1,1%-biphenyl-2,2%-
diyl)phosphite]-5-amine-5-deoxy-1,2-O-isopropylidene-a-
D
-xylofuranose 1
In situ formed phosphorochloridite 6a (2.2 mmol) was
dissolved in toluene (5 mL) to which pyridine (0.36 mL,
4.6 mmol) was added. 5-Amine-5-deoxy-1,2-O-iso-
We have characterized the rhodium complexes formed
under hydroformylation conditions by the NMR tech-
nique and in situ IR spectroscopy. Our results show
that the most stable bis-equatorial diastereomers of
hydridorhodium dicarbonyl complexes 7–10 are in
equilibrium with equatorial–axial species. Based on the
encouraging results obtained by using these new types
of furanoside ligands, further research into more active
and stereoselective catalysts is now in progress, exploit-
ing the advantage that these sugar ligands can be so
easily modified.
propylidene-a- -xylofuranose 5a (0.19 g, 1 mmol) was
D
azeotropically dried with toluene (3×1 mL) and dis-
solved in toluene (10 mL), to which pyridine (0.18 mL,
2.3 mmol) was added. The diol solution was transferred
slowly over 30 min to the solution of phosphorochlo-
ridite 6a at room temperature. The reaction mixture
was stirred under reflux overnight and the pyridine salts
were removed by filtration. Evaporation of the solvent
gave a white foam which was purified by flash chro-
matography (eluent: toluene/NEt3 100/1, Rf 0.9) to
produce a white powder (0.86 g, 81%). Anal. calcd for
C64H93NO8P2: C, 72.08; H, 8.79; N, 1.31. Found: C,
72.02; H, 8.43; N, 1.52%. [h]2D0=−11.2 (c 1.0, CH2Cl2).
4. Experimental
1
31P{1H} NMR: l 144.8 (b), 145.1 (s). H NMR: l 1.18
(s, 3H, CH3), 1.34 (s, 9H, CH3, t-Bu), 1.36 (s, 9H, CH3,
t-Bu), 1.37 (s, 9H, CH3, t-Bu), 1.39 (s, 9H, CH3, t-Bu),
1.42 (s, 3H, CH3), 1.46 (s, 18H, CH3, t-Bu), 1.47 (s, 9H,
CH3, t-Bu), 1.48 (s, 9H, CH3, t-Bu), 2.87 (m, 1H, H-5),
3.05 (m, 1H, H-5%), 3.42 (dt, 1H, NH, JH-P=31.2 Hz,
J=7.2 Hz), 4.21 (m, 1H, H-4), 4.35 (b, 1H, H-2), 4.60
(dd, 1H, H-3, 3J3-P=9.2 Hz, 3J3-4=2.8 Hz), 5.63 (d, 1H,
H-1, 3J1-2=3.2 Hz), 7.2–7.5 (m, 8H, CHꢀ). 13C NMR: l
26.5 (CH3), 26.8 (CH3), 31.2 (CH3, t-Bu), 31.4 (CH3,
t-Bu), 31.7 (CH3, t-Bu), 34.4 (C, t-Bu), 34.9 (C, t-Bu),
35.5 (C, t-Bu), 35.6 (C, t-Bu), 35.7 (C, t-Bu), 39.2 (d,
C-5, J5-P=6.4 Hz), 76.8 (d, C-3, J3-P=3.4 Hz), 80.8 (m,
C-4), 84.5 (C-2), 105.0 (C-1), 111.9 (CMe2), 124.2
(CHꢀ), 124.3 (CHꢀ), 124.6 (CHꢀ), 126.5 (CHꢀ), 126.6
(CHꢀ), 126.8 (CHꢀ), 126.9 (CHꢀ), 132.6 (C), 132.7 (C),
133.2 (C), 139.8 (C), 140.3 (C), 140.4 (C), 145.8 (C),
146.2 (C), 146.9 (C), 147.2 (C).
4.1. General comments
All syntheses were performed using standard Schlenk
techniques under argon atmosphere. Solvents were
purified by standard procedures. All syntheses were
performed using standard Schlenk techniques under
argon atmosphere. Solvents were purified by standard
procedures. Compounds and 5b12 and 5b13 phospho-
rochloridites 619 were prepared by previously described
methods. All other reagents were used as commercially
available. Elemental analyses were performed on a
Carlo Erba EA-1108 instrument. 1H, 13C{1H} and
31P{1H} NMR spectra were recorded on a Varian
Gemini 400 MHz spectrometer. Chemical shifts are
relative to SiMe4 (1H and 13C) as internal standard or
H3PO4 (31P) as external standard. All the NMR spectra
were recorded using CDCl3 as solvent except in the case
of HPNMR were toluene-d8 were used. All assignments
in NMR spectra were determined by COSY and HET-
COR 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 oxidation of the
aldehydes to the corresponding carboxylic acids on a
Hewlett–Packard HP 5890A gas chromatograph (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).
4.3. 3,5-Bis[(3,3%-bis-t-butyl-5,5%-bis-methoxy-1,1%-
biphenyl-2,2%-diyl)phosphite]-5-amine-5-deoxy-1,2-O-iso-
propylidene-˜-D-xylofuranose 2
Treatment of in situ formed phosphorochloridite 6b
(2.2 mmol) and 5a (0.19 g, 1 mmol) as described for
compound 1 afforded phosphite–phosphoroamidite 2,
which was purified by flash chromatography (eluent:
toluene/NEt3 100/1, Rf 0.9) to produce a white powder
(0.68 g, 71%). Anal. calcd for C52H69NO12P2: C, 64.92;
H, 7.23; N, 1.46. Found: C, 64.99; H, 7.30; N, 1.50%.
[h]2D0=−91.1 (c 1.0, CH2Cl2). 31P{1H} NMR: l 144.0
1
(s), 145.9 (s). H NMR: l 1.22 (s, 3H, CH3), 1.30 (s,
9H, CH3, t-Bu), 1.37 (s, 3H, CH3), 1.39 (s, 9H, CH3,
t-Bu), 1.41 (s, 9H, CH3, t-Bu), 1.44 (s, 9H, CH3, t-Bu),

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M. Die´guez et al. / Tetrahedron: Asymmetry 12 (2001) 2827–2834
2.63 (m, 1H, H-5), 2.97 (m, 1H, H-5%), 3.43 (dt, 1H,
NH, JH-P=36.4 Hz, J=7.6 Hz), 3.76 (s, 3H, OMe),
3.80 (s, 3H, OMe), 3.81 (s, 3H, OMe), 3.83 (s, 3H,
OMe), 4.28 (m, 1H, H-4), 4.47 (b, 1H, H-2), 4.60
143.5 (s), 149.3 (s). 1H NMR: l 1.29 (s, 3H, CH3),
1.31 (s, 9H, CH3, t-Bu), 1.38 (s, 9H, CH3, t-Bu), 1.40
(s, 3H, CH3), 1.44 (s, 9H, CH3, t-Bu), 1.46 (s, 9H,
CH3, t-Bu), 2.68 (m, 1H, H-5), 3.27 (m, 1H, H-5%),
3.35 (m, 1H, NH), 3.78 (s, 3H, OMe), 3.81 (s, 3H,
OMe), 3.82 (s, 3H, OMe), 3.85 (s, 3H, OMe), 4.12
(m, 1H, H-4), 4.32 (m, 2H, H-2, H-3), 5.64 (d, 1H,
3
3
(dd, 1H, H-3, J3-P=10.4 Hz, J3-4=2.8 Hz), 5.72 (d,
3
1H, H-1, J1-2=3.6 Hz), 6.66 (m, 2H, CHꢀ), 6.72 (m,
2H, CHꢀ), 6.90 (m, 2H, CHꢀ), 6.96 (m, 2H, CHꢀ).
13C NMR: l 26.0 (CH3), 26.5 (CH3), 30.5 (CH3, t-
Bu), 30.9 (CH3, t-Bu), 31.2 (CH3, t-Bu), 35.0 (C, t-
Bu), 35.2 (C, t-Bu), 35.4 (C, t-Bu), 38.5 (m, C-5),
55.3 (OMe), 55.4 (OMe), 55.5 (OMe), 55.6 (OMe),
76.1 (d, C-3, J3-P=6.1 Hz), 80.2 (m, C-4), 84.0 (C-2),
105.0 (C-1), 111.8 (CMe2), 112.4 (CHꢀ), 112.9 (CHꢀ),
113.2 (CHꢀ), 113.9 (CHꢀ), 114.0 (CHꢀ), 114.3 (CHꢀ),
133.1 (C), 133.9 (C), 141.8 (C), 142.2 (C), 142.3 (C),
142.5 (C), 154.8 (C), 155.2 (C), 155.5 (C), 156.0 (C).
3
H-1, J1-2=3.6 Hz), 6.75 (m, 2H, CHꢀ), 6.79 (m, 2H,
CHꢀ), 6.93 (m, 2H, CHꢀ), 7.00 (m, 2H, CHꢀ). 13C
NMR: l 26.2 (CH3), 26.8 (CH3), 30.4 (CH3, t-Bu),
30.7 (CH3, t-Bu), 31.2 (CH3, t-Bu), 35.2 (C, t-Bu),
35.4 (C, t-Bu), 35.5 (C, t-Bu), 35.6 (C, t-Bu), 40.2
(m, C-5), 55.4 (OMe), 55.5 (OMe), 55.6 (OMe), 74.2
(m, C-3), 78.3 (C-2), 80.0 (m, C-4), 103.2 (C-1), 112.1
(CMe2), 113.1 (CHꢀ), 113.2 (CHꢀ), 113.6 (CHꢀ),
113.9 (CHꢀ), 114.0 (CHꢀ), 114.2 (CHꢀ), 133.4 (C),
133.6 (C), 141.9 (C), 142.0 (C), 142.2 (C), 142.3 (C),
155.2 (C), 155.4 (C), 155.5 (C).
4.4. 3,5-Bis[(3,3%,5,5%-tetra-t-butyl-1,1%-biphenyl-2,2%-
diyl)phosphite]-5-amine-5-deoxy-1,2-O-isopropylidene-a-
4.6. Hydroformylation experiments
D
-ribofuranose 3
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 phosphite–phospho-
roamidite (0.015 mmol) in toluene (10 mL). After
pressurizing to the desired pressure with syn gas and
heating the autoclave to the reaction temperature, the
reaction mixture was stirred for 16 h to form the
active catalyst. The autoclave was depressurized and a
solution of styrene (13 mmol) in toluene (5 mL) was
brought into the autoclave and pressurized again.
During the reaction several samples were taken from
the autoclave. After the desired reaction time, the
autoclave was cooled to room temperature and
depressurized. The reaction mixture was analyzed by
gas chromatography.
Treatment of in situ formed phosphorochloridite 6a
(2.2 mmol) and 5b (0.19 g, 1 mmol) as described for
compound 1 afforded phosphite–phosphoroamidite 3,
which was purified by flash chromatography (eluent:
toluene/NEt3 100/1, Rf 0.9) to produce a white pow-
der (0.84 g, 79%). Anal. calcd for C64H93NO8P2: C,
72.08; H, 8.79; N, 1.31. Found: C, 72.12; H, 8.83; N,
1.42%. [h]2D0=−26.7 (c 0.3, CH2Cl2). 31P{1H} NMR: l
143.2 (s), 150.2 (s). 1H NMR: l 1.29 (s, 3H, CH3),
1.34 (s, 9H, CH3, t-Bu), 1.36 (s, 27H, CH3, t-Bu),
1.42 (s, 9H, CH3, t-Bu), 1.44 (s, 9H, CH3, t-Bu), 1.47
(s, 18H, CH3, t-Bu), 1.52 (s, 3H, CH3), 2.90 (m, 1H,
H-5), 3.30 (m, 2H, NH, H-5%), 4.06 (m, 1H, H-4),
4.17 (m, 1H, H-3), 4.21 (m, 1H, H-2), 5.55 (d, 1H,
H-1, 3J1-2=3.2 Hz), 7.1–7.5 (m, 8H, CH=). 13C
NMR: l 26.7 (CH3), 26.9 (CH3), 31.3 (d, CH3, t-Bu,
J
C-P=1.5 Hz), 31.4 (d, CH3, t-Bu, JC-P=3.0 Hz), 31.5
(d, CH3, t-Bu, JC-P=3.0 Hz), 31.6 (d, CH3, t-Bu,
C-P=1.5 Hz), 31.7 (CH3, t-Bu), 31.8 (CH3, t-Bu),
4.7. High-pressure IR experiments
J
These experiments were performed in an SS 316 50
mL autoclave equipped with IRTRAN windows
(ZnS, transparent up to 70 cm−1, 10 mm i.d. optical
path length 0.4 mm), a mechanical stirrer, a tempera-
ture controller, and a pressure device. In a typical
experiment a degassed solution of Rh(acac)(CO)2
(0.013 mmol) and phosphite–phosphoroamidite (0.015
mmol) in methyltetrahydrofuran (15 mL) was intro-
duced into the high-pressure IR autoclave. The auto-
clave was purged twice with CO and pressurized to
10 bar of CO/H2 and heated to 40°C.
34.8 (C, t-Bu), 34.9 (C, t-Bu), 35.5 (C, t-Bu), 41.8 (d,
C-5, J5-P=22.4 Hz), 74.5 (d, C-3, J3-P=5.3 Hz), 78.9
(d, C-2, J2-P=2.3 Hz), 79.4 (t, C-4, J4-P=3.8 Hz),
103.5 (C-1), 113.5 (CMe2), 124.1 (CHꢀ), 124.3 (CHꢀ),
124.5 (CHꢀ), 126.4 (CHꢀ), 126.7 (CHꢀ), 126.9 (CHꢀ),
128.4 (CHꢀ), 129.3 (CHꢀ), 132.8 (C), 133.2 (C), 140.2
(C), 140.3 (C), 140.4 (C), 140.5 (C), 145.9 (C), 146.0
(C), 146.8 (C), 146.9 (C).
4.5. 3,5-Bis[(3,3%-bis-t-butyl-5,5%-bis-methoxy-1,1%-
biphenyl-2,2%-diyl)phosphite]-5-amine-5-deoxy-1,2-O-iso-
propylidene-a-
D
-ribofuranose 4
4.8. In situ HP-NMR hydroformylation experiments
Treatment of in situ formed phosphorochloridite 6b
(2.2 mmol) and 5b (0.19 g, 1 mmol) as described for
compound 1 afforded phosphite–phosphoroamidite 4,
which was purified by flash chromatography (eluent:
toluene/NEt3 100/1, Rf 0.9) to produce a white pow-
der (0.69 g, 73%). Anal. calcd for C52H69NO12P2: C,
64.92; H, 7.23; N, 1.46. Found: C, 65.01; H, 7.27; N,
1.51%. [h]2D0=−40.2 (c 0.3, CH2Cl2). 31P{1H} NMR: l
In a typical experiment, a sapphire tube (ƒ=10 mm)
was filled under argon with
a
solution of
Rh(acac)(CO)2 (0.030 mmol) and ligand (molar ratio
PP/Rh=1.1) in toluene-d8 (1.5 mL). The HP-NMR
tube was purged twice with CO and pressurized to
the appropriate pressure of CO/H2. After a reaction
time of 16 h shaking at the desired temperature, the
solution was analyzed.

M. Die´guez et al. / Tetrahedron: Asymmetry 12 (2001) 2827–2834
2833
4.8.1. [HRh(CO)21] 7. 31P{1H} NMR: l 161.2 (dd, 1P,
Acknowledgements
2
1
1JP-Rh=234.3 Hz, JP-P=271.0 Hz), 164.3 (dd, 1P, JP-
2
1
Rh=224.3 Hz, JP-P=271.0 Hz). H NMR: l −10.52
1
2
(dt, 1H, JRh-H=3.3 Hz, JP-H=10.5 Hz), 0.81 (s, 3H,
CH3), 1.03 (s, 9H, CH3, t-Bu), 1.04 (s, 9H, CH3, t-Bu),
1.05 (s, 9H, CH3, t-Bu), 1.14 (s, 9H, CH3, t-Bu), 1.24
(s, 3H, CH3), 1.37 (s, 9H, CH3, t-Bu), 1.47 (s, 9H, CH3,
t-Bu), 1.51 (s, 9H, CH3, t-Bu), 1.53 (s, 9H, CH3, t-Bu),
2.52 (m, 2H, H-5, H-5%), 3.58 (m, 1H, H-4), 3.67 (m,
We thank the Spanish Ministerio de Educacio´n y Cul-
tura and the Generalitat de Catalunya (CIRIT) for
their financial support (PB97-0407-CO5-01).
References
3
1H, NH), 4.19 (d, 1H, H-2, J2-1=3.2 Hz), 4.86 (m, 1H,
3
H-3), 5.28 (d, 1H, H-1, J1-2=3.2 Hz), 6.8–7.5 (m, 8H,
1. (a) Beller, M.; Cornils, B.; Frohning, C. D.; Kohlpainter,
V. W. J. Mol. Catal. 1995, 104, 17; (b) Agboussou, F.;
Carpentier, J.-F.; Mortreux, A. Chem. Rev. 1995, 95,
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CHꢀ). 13C NMR: l 26.1 (CH3), 26.9 (CH3), 31.3 (CH3,
t-Bu), 31.4 (CH3, t-Bu), 31.5 (CH3, t-Bu), 31.6 (CH3,
t-Bu), 31.7 (CH3, t-Bu), 32.6 (CH3, t-Bu), 33.4 (CH3,
t-Bu), 34.5 (C, t-Bu), 34.6 (C, t-Bu), 34.7 (C, t-Bu),
35.7 (C, t-Bu), 38.7 (m, C-5), 77.2 (m, C-3), 82.1 (m,
C-4), 84.5 (C-2), 105.0 (C-1), 111.8 (CMe2), 124.1
(CHꢀ), 124.3 (CHꢀ), 125.5 (CHꢀ), 126.1 (CHꢀ), 126.4
(CHꢀ), 126.7 (CHꢀ), 127.6 (CHꢀ), 128.2 (CHꢀ), 133.4
(C), 133.5 (C), 133.7 (C), 140.2 (C), 140.6 (C), 146.2
(C), 146.3 (C), 146.6 (C), 146.9 (C).
3. Die´guez, M.; Pereira, M. M.; Masdeu-Bulto´, A. M.;
Claver, C.; Bayo´n, J. C. J. Mol. Catal. A: Chemical 1999,
143, 111 and references cited therein.
4.8.2. [HRh(CO)22] 8. 31P{1H} NMR: l 164.7 (d, 2P,
1JP-Rh=229.2 Hz). 1H NMR: l −10.30 (dt, 1H, 1JRh-H
=
2
3.3 Hz, JP-H=8.1 Hz), 0.98 (s, 3H, CH3), 1.44 (s, 3H,
CH3), 1.52 (s, 9H, CH3, t-Bu), 1.61 (s, 9H, CH3, t-Bu),
1.66 (s, 1H, CH3, t-Bu), 2.08 (m, 2H, H-5, H-5%), 3.28
(s, 3H, OMe), 3.30 (s, 3H, OMe), 3.33 (s, 3H, OMe),
3.42 (s, 3H, OMe), 3.84 (m, 1H, NH), 4.50 (d, 1H, H-2,
3J2-1=3.6 Hz), 4.53 (m, 1H, H-4), 5.08 (m, 1H, H-3),
4. (a) Babin, J. E.; Whiteker, G. T. Union Carbide Chem.
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P. C. J.; van Leeuwen, P. W. N. M.; Vogt, D.
Organometallics 1997, 16, 2929; (c) Die´guez, M.; Pa`mies,
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5. (a) Nozaki, K.; Sakai, N.; Nanno, T.; Higashijima, T.;
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7. (a) van den Berg, M.; Minnaard, A. J.; Schudde, E. P.;
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9. Inoguhi, K.; Sakuraba, S.; Achiwa. K. Synlett 1992, 169.
Achiwa’s idea is that two different donor sites can a priori
match the intermediates better and so influence their
reactivity and enantioselectivity positively.
10. Pa`mies, O.; Die´guez, M.; Net, G.; Ruiz, A.; Claver, C.
Chem. Commun. 2000, 2383.
11. (a) Lot, O.; Suisse, I.; Mortreux, A.; Agbossou, F. J.
Mol. Catal. 2000, 164, 125; (b) Naili, S.; Suisse, I.;
Mortreux, A.; Agbossou-Niedercorn, F.; Nowogrocki, G.
J. Organomet. Chem. 2001, 628, 114.
3
5.61 (d, 1H, H-1, J1-2=3.6 Hz), 6.66 (m, 4H, CHꢀ),
7.10 (m, 4H, CHꢀ). 13C NMR: l 26.1 (CH3), 26.8
(CH3), 31.4 (CH3, t-Bu), 32.6 (CH3, t-Bu), 33.2 (CH3,
t-Bu), 35.6 (C, t-Bu), 35.7 (C, t-Bu), 36.2 (C, t-Bu),
36.3 (C, t-Bu), 38.9 (m, C-5), 54.9 (OMe), 55.0 (OMe),
77.4 (m, C-3), 82.2 (m, C-4), 84.5 (C-2), 105.0 (C-1),
111.8 (CMe2), 113.2 (CHꢀ), 113.6 (CHꢀ), 114.4 (CHꢀ),
114.5 (CHꢀ), 114.7 (CHꢀ), 114.8 (CHꢀ), 115.7 (CHꢀ),
115.9 (CHꢀ), 134.1 (C), 134.3 (C), 142.4 (C), 142.5 (C),
142.6 (C), 156.0 (C), 156.4 (C), 156.7 (C).
4.8.3. [HRh(CO)23] 9. 31P{1H} NMR: l 162.6 (dd, 1P,
2
1
1JP-Rh=234.8 Hz, JP-P=278.5 Hz), 166.2 (dd, 1P, JP-
2
1
Rh=232.1 Hz, JP-P=278.5 Hz). H NMR: l −10.67
1
2
(dt, 1H, JRh-H=3.2 Hz, JP-H=9.8 Hz), 1.01 (s, 3H,
CH3), 1.04 (s, 9H, CH3, t-Bu), 1.05 (s, 9H, CH3, t-Bu),
1.15 (s, 9H, CH3, t-Bu), 1.21 (s, 3H, CH3), 1.25 (s, 9H,
CH3, t-Bu), 1.52 (s, 9H, CH3, t-Bu), 1.55 (s, 18H, CH3,
t-Bu), 1.57 (s, 9H, CH3, t-Bu), 2.71 (m, 2H, H-5, H-5%),
3.29 (m, 1H, NH), 3.34 (m, 1H, H-4), 4.10 (m, 1H,
3
H-2), 4.24 (m, 1H, H-3), 5.21 (d, 1H, H-1, J1-2=3.6
Hz), 6.8–7.5 (m, 8H, CHꢀ).
4.8.4. [HRh(CO)24] 10. 31P{1H} NMR: l 166.2 (dd, 1P,
2
1
1JP-Rh=239.1 Hz, JP-P=271.8 Hz), 168.9 (dd, 1P, JP-
2
1
Rh=228.3 Hz, JP-P=271.8 Hz). H NMR: l −10.34
1
2
(dt, 1H, JRh-H=3.6 Hz, JP-H=8.8 Hz), 0.99 (s, 3H,
CH3), 1.32 (s, 3H, CH3), 1.44 (s, 9H, CH3, t-Bu), 1.47
(s, 9H, CH3, t-Bu), 1.52 (s, 9H, CH3, t-Bu), 1.56 (s, 9H,
CH3, t-Bu), 2.19 (m, 2H, H-5, H-5%), 3.30 (s, 3H, OMe),
3.31 (s, 3H, OMe), 3.33 (s, 6H, OMe), 3.52 (m, 1H,
NH), 3.98 (m, 1H, H-4), 4.26 (m, 1H, H-2), 4.98 (m,
12. Ewing, D. F.; Goethals, G.; Mackenzie, G.; Martin, P.;
Ronco, G.; Vanbaelinghem, L.; Villa, P. J. Carbohydr.
Chem. 1999, 18, 441.
3
1H, H-3), 5.47 (d, 1H, H-1, J1-2=3.6 Hz), 6.5–7.5 (m,
8H, CHꢀ).

2834
M. Die´guez et al. / Tetrahedron: Asymmetry 12 (2001) 2827–2834
13. Ewing, D. F.; Goethals, G.; Mackenzie, G.; Martin, P.;
Ronco, G.; Vanbaelinghem, L.; Villa, P. Carbohydr. Res.
1999, 321, 190.
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Klootwijk, A.; Kamer, P. C. J.; van Leeuwen, P. W. N.
M. Tetrahedron: Asymmetry 1995, 6, 719; (b) Pa`mies, O.;
Net, G.; Ruiz, A.; Claver, C. Tetrahedron: Asymmetry
2000, 11, 1097.
when the temperature was lowered to −80°C.
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16. Broad signals were observed when the temperature was
lowered. We were not able to resolve these signals, nor