C1-symmetric diphosphite ligands derived from carbohydrates: Influence of structural modifications on the rhodium-catalyzed asymmetric hydroformylation of styrene

Article abstract of DOI:10.1002/ejoc.200801093

New 3,5-diphosphite-substituted xylofuranoside (1b, 25a,b, and 26a,b) and glucofuranoside (3a, 7a, 8a,b) ligands with C₁ symmetry have been prepared and used in the Rh-catalyzed asymmetric hydroformylation of styrene. The main structural features of these ligands are a) the presence of a 6-O-isopropyl group in ligands with a gluco configuration, b) the absence of 1,2-O-isopropylidene, a common group in many ligands with a furanoside skeleton, c) the presence of an alkyl chain bound to the 2-OH, and d) modification of the diol in the phosphite moiety. Modification of the carbohydrate backbone and diphosphite bridge affects the activity and selectivity of the reaction. Catalytic systems with ligands 1b and 8b were not active at 40 °C, although the formation of the expected hydride species [RhH(CO)₂(1b)] was demonstrated by NMR spectroscopy. The highest enantioselectivity (83%) was obtained with the catalytic system Rh/8a. The complex [RhH(CO)₂(8a)] was characterized by NMR spectroscopy using high-pressure techniques and was shown to exist in solution as two isomers in equilibrium; the two isomers adopt an equatorial-equatorial (eq-eq) configuration. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Full text of DOI:10.1002/ejoc.200801093

FULL PAPER
DOI: 10.1002/ejoc.200801093
C1-Symmetric Diphosphite Ligands Derived from Carbohydrates: Influence of
Structural Modifications on the Rhodium-Catalyzed Asymmetric
Hydroformylation of Styrene
Aitor Gual,[a] Cyril Godard,[a] Carmen Claver,*[a] and Sergio Castillón*[b]
Keywords: Phosphorus / Carbohydrates / Asymmetric catalysis / Hydroformylation / Styrene
New 3,5-diphosphite-substituted xylofuranoside (1b, 25a,b,
and 26a,b) and glucofuranoside (3a, 7a, 8a,b) ligands with C1
symmetry have been prepared and used in the Rh-catalyzed
asymmetric hydroformylation of styrene. The main structural
features of these ligands are a) the presence of a 6-O-isopro-
ity of the reaction. Catalytic systems with ligands 1b and 8b
were not active at 40 °C, although the formation of the ex-
pected hydride species [RhH(CO)2(1b)] was demonstrated by
NMR spectroscopy. The highest enantioselectivity (83%) was
obtained with the catalytic system Rh/8a. The complex
pyl group in ligands with a gluco configuration, b) the ab- [RhH(CO)2(8a)] was characterized by NMR spectroscopy
sence of 1,2-O-isopropylidene, a common group in many li-
gands with a furanoside skeleton, c) the presence of an alkyl
chain bound to the 2-OH, and d) modification of the diol in
the phosphite moiety. Modification of the carbohydrate back-
bone and diphosphite bridge affects the activity and selectiv-
using high-pressure techniques and was shown to exist in
solution as two isomers in equilibrium; the two isomers adopt
an equatorial–equatorial (eq–eq) configuration.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
of branched aldehydes with enantioselectivities of up to
53% for the S product through the use of a catalytic system
containing ligand 1.[5a] Later, the ligand structure was
modified to provide insights into the effect of different moi-
eties in these ligands on the activity and/or selectivity of the
catalytic system. The use of ligand 2 afforded 53% ee of the
R product, which demonstrates that the configuration of
the catalytic product is determined by the configuration at
Introduction
Owing to their structural properties, carbohydrates have
been extensively used as starting materials for the synthesis
of enantiomerically pure compounds. The presence of hy-
droxy groups facilitates the synthesis of oxygenated phos-
phorus functions and over the past decade, intensive work
has been carried out by our group to develop ligands de-
rived from carbohydrates and to analyze their behavior in
asymmetric catalysis.[1] Most carbohydrates possess C1 sym-
metry and as such the potential for the synthesis of ligand
derivatives is very large. Furthermore, the successful use of
C1-symmetric diphosphite ligands has been reported in sev-
eral asymmetric processes such as Pd-catalyzed allylic alky-
lation[2] and Rh-catalyzed hydrogenation.[3] Recently, the
ability of these ligands to stabilize palladium nanoparticles
was also demonstrated[4] and successfully applied in allylic
alkylation.[4a,4b] Rhodium complexes containing C1-sym-
metric diphosphites with a furanoside backbone 1–6 (Fig-
ure 1) behave as active catalysts in the asymmetric hydrofor-
mylation of vinylarenes.[5–7] In 1995, van Leeuwen and co-
workers achieved excellent regioselectivity in the formation
the C-3 stereocenter.[5b] The introduction of
a new
stereocenter at the C-5 position revealed that the value of
the enantiomeric excess of the product is the result of a
cooperative effect between the C-3 and C-5 stereocen-
ters.[5c,5d] Within these ligand series, the highest selectivity
in the asymmetric hydroformylation of vinylarenes was
achieved by using the Rh/3 system; the branched aldehydes
were formed with regioselectivities of up to 98% and ees of
up to 93%.[5c,5d] In these studies the nature of the group
contained within the phosphite moiety was also investigated
and found to play an important role in the activity and
enantioselectivity of the catalysts in this reaction.[5] Thus,
the introduction of bulky substituents at the ortho position
and electron-donating groups at the para position was
found to be the most appropriate combination in terms of
activity and selectivity.
[a] Departament de Quι´mica Fι´sica i Química Inorgànica, Facultat
de Química, Universitat Rovira i Virgili,
c/ Marcel.li Domingo s/n 43007 Tarragona, Spain
Fax: +34-977559563
Owing to the interesting results obtained by modifying
ligands 1 and 2 at C-5, we decided to explore other modifi-
cations. We report herein the synthesis of new C1-symmetric
diphosphite ligands (7 and 8, Scheme 1) with a glucofur-
anoside backbone and their use in the rhodium-catalyzed
hydroformylation of styrene. The main structural features
E-mail: carmen.claver@urv.cat
[b] Departament de Química Analítica i Química Orgànica, Facul-
tat de Química, Universitat Rovira i Virgili,
c/ Marcel.li Domingo s/n 43007 Tarragona, Spain
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2009, 1191–1201
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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A. Gual, C. Godard, C. Claver, S. Castillón
FULL PAPER
Figure 1. Reported diphosphites with a furanoside carbohydrate backbone.
of these new ligands with regard to compound 3 are the 1,2-O-isopropylidene groups, which can be carried out by
following: a) a higher substitution at the 6-position of the controlled hydrolysis and reduction of the acetal function,
sugar to increase the steric hindrance in the proximity of respectively.
the coordinating phosphorus atom, b) the absence of a 1,2-
The diol 10 was synthesized in a straightforward manner
O-isopropylidene ring to increase the conformational free- by selective reductive opening of the 5,6-O-isopropylidene
dom, and c) a new diol skeleton in the diphosphite moiety group of 12 by reaction with BF3·Et2O with triethylsilane
(see diol b in Scheme 5), which will provide a different envi- as the hydride source (Scheme 2).[8]
ronment around the rhodium center.
Scheme 2. Synthesis of the diol backbone 10.
To explore new routes to the introduction of bulky sub-
stituents at the C-6 position, compound 12 was treated with
N-bromosuccinimide (NBS)/PPh3 to obtain the 6-bromo
derivative 13, which was isolated in 78% yield
(Scheme 3).[9,10] This reaction involves the migration of the
5,6-O-isopropylidene group to the 3,5-position with entry
of the bromine at the C-6 position.
Scheme 1. Retrosynthetic strategies for the synthesis of 3, 7, and 8.
Results and Discussion
Synthesis of Diphosphite Ligands with a Carbohydrate
Backbone
The general synthetic strategies used to obtain ligands 3,
7, and 8 from the commercially available compound 12 are
shown in Scheme 1. Ligand 7 was prepared from diol 10,
which in turn can be easily prepared from 12. The synthesis
of ligand 8 from 12 requires the removal of the 5,6- and Scheme 3. Synthesis of diol backbone 9.
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Diphosphite Ligands Derived from Carbohydrates
Various substitution reactions of the bromide in 13 were
Finally, the diols 9–11, 15, 23, and 24 were treated with
attempted, but all were unsuccessful because in all cases the phosphorochloridites derived from the bis-phenols a and b
major product was the elimination product. However, the (Scheme 5), which had previously been synthesized in situ
reaction of 13 with LiAlH4 afforded 14; selective hydrolysis by standard procedures, to yield the corresponding diphos-
of the 3,5-O-isopropylidene acetal afforded 9, thus complet- phite ligands 1a,b, 3a, 7a, 8a,b, 25a,b, and 26a,b in moder-
ing a new and shorter synthetic route to the diol 9, which ate-to-good yields (20–70%).[13] All these ligands were char-
is the precursor of the diphosphite 3. The overall yield of acterized by NMR spectroscopy and elemental analysis (see
the last three steps was 68% (Scheme 3).
Exptl. Sect. for spectroscopic details). Ligands 8a,b, 25a,b,
The diols 11, 23, and 24 (Scheme 4), were synthesized and 26a,b, which contain an alkyl chain, were recently used
from compounds 9 and 15, which were prepared for com- to stabilize ruthenium nanoparticles and used as catalysts
parative purposes with the corresponding ligands.[5] Ini- in arene hydrogenation.[14]
tially, the 3,5-hydroxy groups in compounds 15 and 9 were
protected as benzyl ether groups by reaction with BnBr to
give compounds 16 and 17 in 85 and 60% yields, respec-
tively.[11] Treatment of 16 and 17 with Et3SiH/BF3·Et2O af-
forded the alcohols 18 and 19 in high yields (86 and 70%,
respectively).[12] However, the replacement of BF3·Et2O by
trimethylsilyl triflate resulted in the formation of the 2-O-
isopropyl derivatives (10–20%) as byproducts. The p-meth-
oxybenzyl ether derivatives of 9 and 15 were also prepared
in order to have alternative deprotection procedures.[11]
However, when these compounds were treated with Et3SiH/
BF3·Et2O deprotection of the pMeO-benzyl ether groups
occurred.
Scheme 5. Synthesis of diphosphite ligands.
Rh-Catalyzed Asymmetric Hydroformylation of Styrene
Catalytic systems containing the synthesized chiral di-
phosphites were used in the rhodium-catalyzed asymmetric
hydroformylation of styrene (Scheme 6).
Scheme 4. Synthesis of the diol backbones 11, 23, and 24.
Scheme 6. Rhodium-catalyzed asymmetric hydroformylation of
styrene.
The catalytic systems were formed in situ by the addition
Compounds 18 and 19 were treated with NaH and of 1.1 equiv. of the diphosphite ligand (L = 1a,b, 3a, 7a,
nBuBr, n-C14H29Br, or n-C16H33Br to give compounds 20– 8a,b, 25a,b, and 26a,b) to toluene solution of
a
22 in high yields (90, 77, and 70%, respectively). The benzyl [Rh(acac)(CO)2] (acac = acetylacetonate). The substrate
groups were removed by hydrogenolysis using Pd/C as cata- was then added and the solution was introduced into an
lyst under 1 atm of H2 to afford the diols 23, 24, and 11 in autoclave. Finally, the autoclave was pressurized with
high yields (93, 99, and 86%, respectively; Scheme 4).
25 bar of CO/H2 (ratio 1:1) and heated at 40 °C for 15 h.
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A. Gual, C. Godard, C. Claver, S. Castillón
FULL PAPER
Total chemoselectivity to aldehydes was achieved in all the ee increased to 75% (Entry 2, Table 2). The effect of the
cases. The results are summarized in Tables 1, 2, and 3. diphosphite bridge in 8a,b (Entries 2–4) is similar to that
Table 1 summarizes the results obtained for the rhodium- described for ligands 1a,b (Entries 1 and 2, Table 1). Again,
catalyzed hydroformylation of styrene using the xylofur- a temperature of 80 °C was required to obtain significant
anoside-derived ligands 1a,b, 25a,b, and 26a,b. When the conversions with 8b, but the selectivity suggests the pres-
reaction was performed in the presence of ligand 1a, the ence of the unmodified [RhH(CO)4] active species under
conversion was measured as 41% with a regioselectivity of these conditions (Entry 4, Table 2).[15] As previously ob-
96% for the formation of the branched product and an ee served, the ee values obtained with the ligands with the glu-
of 50% (Entry 1, Table 1). This result is in agreement with cofuranoside backbone (7a and 8a; up to 75%) were higher
that previously reported for this system.[5a]
than those obtained with ligands with a xylofuranoside
backbone (1a, 25a, and 26a; up to 61%).[5c,5d]
Table 1. Rhodium-catalyzed hydroformylation of styrene using di-
phosphites 1a,b, 25a,b, and 26a,b.[a,b]
Table 2. Rhodium-catalyzed hydroformylation of styrene using di-
Entry
Ligand % Conversion % Regioselectivity[c] % ee (config.)
phosphites 7a, 8a, and 8b.[a,b]
Entry
Ligand
% Conversion % Regioselectivity[c] % ee (config.)
1
2
1a
1b
1b
41
0
0
56
11
30
23
33
96
–
–
58
97
96
96
94
50 (S)
–
–
27 (S)
61 (S)
60 (S)
60 (S)
61 (S)
1
2
7a
8a
8b
8b
48
50
0
97
97
–
68 (S)
75 (S)
–
3[d]
4[e]
5
1b
3
25a
25b
26a
26b
4[d]
97
54
–
6
7
8
[a] Substrate/Rh ratio: 1000, styrene: 13 mmol, Rh/L = 1:1.1,
[Rh(acac)(CO)2]: 0.0135 mmol, P = 25 bar, PCO/H2 = 1, toluene:
15 mL, t = 15 h, T = 40 °C. [b] The conversion of styrene and the
regioselectivity and enantiomeric excess were determined by GC.
[c] 2-Phenylpropanal. [d] T = 80 °C.
[a] Substrate/Rh ratio: 1000, styrene: 13 mmol, Rh/L = 1:1.1,
[Rh(acac)(CO)2]: 0.0135 mmol, P = 25 bar, PCO/H2 = 1, toluene =
15 mL, t = 15 h, T = 40 °C. [b] The conversion of styrene and the
regioselectivity and enantiomeric excess were determined by GC.
[c] 2-Phenylpropanal. [d] Incubation: 16 h at 40 °C. [e] T = 80 °C.
The reaction conditions were optimized with catalytic
systems containing ligands 7a and 8a and the results are
presented in Table 3. Interestingly, when the total pressure
was decreased from 25 to 10 bar, an increase in the activity
of the catalytic system was observed without affecting the
regio- or enantioselectivity of the reaction (Entries 1 and 2).
Furthermore, lowering the CO/H2 ratio also increased the
conversion (83%), but the regio- and enantioselectivity re-
mained unchanged (Entry 3). These results can be attrib-
uted to the presence of inactive carbonyl dinuclear or clus-
ter species at high CO pressure.[16] When the temperature
was decreased to 20 °C, the enantiomeric excess increased
to 73% (Entry 4). However, no noticeable effect on the ee
value was observed when the ligand/rhodium ratio was in-
creased from 1.1 to 2 (Entry 5). The catalytic system con-
taining ligand 8a provided low conversions under these con-
ditions and the enantioselectivity slightly increased to 79%.
Surprisingly, by using the catalytic system containing li-
gand 1b, in which the bis-phenyl moiety was modified, no
conversion was observed at 40 °C (Entry 2). An incubation
period to promote the formation of the active species[5a,5b]
did not promote activity (Entry 3). It was found that a tem-
perature of 80 °C (Entry 4) is required to obtain significant
conversion (56%), although the regio- and enantio-
selectivity decrease (58 and 27%, respectively), which sug-
gests the formation of the [RhH(CO)4] species. Further in-
vestigations into this system were performed in situ by using
high-pressure NMR techniques and will be presented later
in this article. When ligands 25a,b and 26a,b were used (En-
tries 5–8), the resulting catalytic systems were moderately
active, achieving conversions of up to 33%. All these sys-
tems yielded the branched product with high regioselectiv-
ity (up to 97%) and moderate enantioselectivity (up to
61%). These results indicate that the use of ligands contain-
ing a monocyclic backbone provide higher ees than the bi-
cyclic ligand 1a. However, slightly lower conversions were
obtained and no effect was observed on the regioselectivity
of the reaction.
Table 3. Rhodium-catalyzed hydroformylation of styrene using di-
phosphites 7a and 8a.[a,b]
Entry
L
P
[bar]
PCO/H2 T[a]
[°C] Conv.
%
% Regioselectivity[c] % ee (config.)
Previously we have shown that the introduction of a
stereogenic center at C-5 (glucofuranoside derivatives) im-
proves the catalytic results.[5c,5d] Therefore, we considered it
of interest to synthesize ligands 3a, 7a, and 8a,b containing
substituents at the C-5 position.
The Rh/7a catalytic system, in which the ligand is a bicy-
clic structure with an O-CH(CH3)2 substituent at the C-6
position, afforded 48% conversion, 97% regioselectivity,
and 68% enantiomeric excess (Entry 1, Table 2). The cata-
lytic system containing the monocyclic ligand 8a provided
1
2
3
7a 25
7a 10
7a 10
7a 10
7a 10
8a 10
8a 10
1
1
40
40
40
20
20
20
20
48
66
83
78
38
10
29
97
97
97
99
96
97
98
68 (S)
67 (S)
67 (S)
73 (S)
76 (S)
79 (S)
83 (S)
0.5
0.5
0.5
0.5
0.5
4[d]
5[d,e]
6[d,e]
7[d]
[a] Substrate/Rh ratio: 1000, styrene: 13 mmol, Rh/L = 1:1.1,
[Rh(acac)(CO)2]: 0.0135 mmol, toluene: 15 mL. [b] The conversion
of styrene and the regioselectivity and enantiomeric excess were
determined by GC. [c] 2-Phenylpropanal. [d] t = 48 h, incubation:
a similar conversion and regioselectivity as ligand 7a, but 16 h at 40 °C. [e] Rh/L = 1:2.0.
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Diphosphite Ligands Derived from Carbohydrates
By using a lower ligand/metal ratio (Entry 7), the activity broad multiplet assigned to [RhH(CO)2(8a)].[5c,5d] A broad
was found to increase (29%) without affecting the regio- hydride signal (∆ω½ Յ 90 Hz) was detected in the corre-
(98%) and enantioselectivity (83%).
sponding 1H NMR spectrum. Broadening of the signals
The enantiomeric excesses obtained with ligands 7a and was observed when the temperature was decreased to
8a in the rhodium-catalyzed hydroformylation of styrene 233 K. Signals of the [RhH(CO)2(8a)] complex were found
were both rather high (76 and 83%, respectively) although to sharpen at 184 K with the detection of two second-order
they do not exceed that previously reported for ligand signals in the 31P{1H} NMR spectrum (Figure 3, d). In the
3a.[5c,5d]
corresponding 1H NMR spectrum, two broad hydride
peaks were detected.
High-Pressure NMR Study
To gain information about the effect of modifications to
the phosphite moieties as well as the sugar backbone, high-
pressure NMR experiments of the systems containing 1b
and 8a were performed.
The hydridorhodium diphosphite complexes [RhH-
(CO)2(L)] (L = bidentate ligand) are often observed as rest-
ing states in the hydroformylation reaction. Two isomeric
tbpy structures can be formed with the coordinated biden-
tate ligand (Figure 2).[14] The complexes with an eq–eq
(equatorial–equatorial) configuration are expected to exhi-
bit JP-H Ͻ 10 Hz and JP-P ≈ 250 Hz couplings, whereas for
the eq–ax (equatorial–axial) configuration, JP-H ≈ 180–
200 Hz and JP-P ≈ 70 Hz couplings are usually ob-
served.[5,15,17–19]
Figure 3. Simulated 31P{1H} NMR spectra corresponding to two
isomers (traces a and b) of the complex [RhH(CO)2(8a)] with 8a
in an eq–eq configuration; c) overlay of simulated spectra a + b; d)
recorded 31P{1H} NMR spectra of the complex [RhH(CO)2(8a)]
formed from the precursor [Rh(acac)(CO)2] in the presence of li-
gand 8a under hydroformylation conditions (incubation: t = 16 h,
T = 40 °C, P = 10 bar, PCO/H2 = 0.5) in [D8]toluene. The spectrum
was recorded at 184 K.
Figure 2. Equatorial–equatorial (eq–eq) and equatorial–axial (eq–
ax) [RhH(CO)2L] species.
One equivalent of the diphosphite ligand (1b or 8a) was
added to a 2 m solution of [Rh(acac)(CO)2] in [D8]toluene
in a 10 mm NMR tube at room temperature. In both cases,
a rapid change of color was observed at this stage. The
NMR tube was pressurized with syngas, shaken for 16 h at
40 °C, placed in the spectrometer, and the NMR spectra
were recorded at various temperatures. Under these condi-
tions, signals corresponding to the rhodium hydride species
[RhH(CO)2(L)] (L = 1b and 8a) were readily detected. The
general mechanism for the formation of these species is
shown in Scheme 7.
To determine the identity of these two species, the
31P{1H} NMR spectra were simulated by using the gNMR
V4.0 software. The results of these simulations indicate that
the spectrum obtained experimentally (Figure 3, trace d)
corresponds to the sum of the signals (Figure 3, trace c)
arising from two distinct species that exhibit coupling con-
stants JRh-P between 250 and 231 Hz and JP-P between 247
and 227 Hz, which is in agreement with eq–eq structures
for both species. The simulated spectra corresponding to
each species separately are shown in parts a and b of Fig-
ure 3. It was therefore concluded that two isomeric com-
plexes of formula [(eq–eq)-RhH(CO)2(8a)] coexist in solu-
tion.
Interestingly, in a previous report on the bicyclic diphos-
phite system Rh/3a, only one species containing the ligand
coordinated in an eq–eq fashion was detected.[5c,5d] The
flexibility induced by the monocyclic structure of ligand 8a
could explain the formation of two species that differ by
spatial arrangement of the ring or by the relative position of
Scheme 7. Formation of [RhH(CO)2(L)] from [Rh(acac)(CO)2] and
diphosphites (L = 1b, 8a).
The 31P{1H} NMR spectra of the solution containing the alkyl chain pointing towards/away from the phosphite
[Rh(acac)(CO)2]/8a under 10 bar of syngas at room tem- moieties. The formation of two diastereoisomeric species
perature showed four doublets exhibiting a characteristic can, however, not be discarded (Figure 4). The spectral fea-
1JRh-P ≈ 300 Hz and JP-P ≈ 100 Hz, which were readily at- tures of the complex [RhH(CO)2(8a)] at temperatures be-
tributed to the [Rh(acac)(CO)(8a)] complex, together with a tween 184 and 298 K are summarized in Table 4.
2
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A. Gual, C. Godard, C. Claver, S. Castillón
FULL PAPER
phite bridge (ligands 1b, 8b, 25b, and 26b) led to a decrease
or a lack of activity, depending on the substituents in the
backbone. In spite of this lack of activity, the intermediate
[RhH(CO)2(L)] (L = 1b) was observed by high-pressure
NMR techniques, which demonstrates that the formation
of this species is not a limiting step of the reaction. Enantio-
selectivities of up to 83% ee were obtained for ligand 8a.
The high-pressure NMR study provided a possible explana-
tion for the lower ee value obtained with ligand 8a when
compared with that obtained with ligand 3a. Two eq–eq
[RhH(CO)2L] isomers where detected for the ligand 8a,
whereas in the case of ligand 3a only one species was
formed.[5c,5d]
Figure 4. Schematic representation of two possible diastereoiso-
meric species of formula [RhH(CO)2(8a)] detected by high-pressure
NMR spectroscopy.
1
Table 4. Selected H and 31P{1H} NMR spectroscopic data for the
[RhH(CO)2(8a)] complex.[a,b]
T [K]
δ(P1)
δ(P1)
JRh-P1
JRh-P2
JP1-P2
δ(H) [ppm]
[ppm]
[ppm]
[Hz]
[Hz]
[Hz]
298
233
193
153.3(m)
broad
160.3
157.1
160.3
153.3(m)
broad
151.0
148.0
150.9
–
–
241
231
241
234
–
–
229
225
229
224
–
–
235
228
235
229
–9.8
–9.8
–9.8
–9.8
–9.7
–9.9
Experimental Section
184
General Methods: All syntheses were performed by using standard
Schlenk techniques under N2. Solvents were purified by standard
procedures. All other reagents were used as received. Elemental
analyses were performed with a Carlo–Erba EA-1108 instrument.
Optical rotations were measured at room temperature in a 10-cm
157.2
148.0
[a] Rh/L ratio 1:1.1, solvent: [D8]toluene, P = 10 bar, PCO/H2 = 0.5,
incubation: 16 h at 40 °C. [b] 31P and 1H NMR spectra recorded
using a 10-mm high-pressure NMR tube.
1
cell. H, 13C{1H}, and 31P{1H} NMR spectra were recorded with
In the 31P{1H} NMR spectrum of [RhH(CO)2(1b)] under
25 bar of syngas at room temperature, two broad doublets
arising from Rh–P coupling (1JRh-P = 232.08 Hz and
1JRh-P = 233.90 Hz) were observed without discernible 2JP-P
a Varian Gemini 400 MHz spectrometer. Chemical shifts are rela-
tive to SiMe4 (1H and 13C) as the internal standard or H3PO4 (31P)
as the external standard. All NMR spectral assignments were de-
termined by COSY and HSQC spectra. Hydroformylation reac-
tions were carried out in a 100 mL Berghof stainless steel autoclave.
Gas chromatographic analyses were preformed with a Hewlett–
Packard HP 5890A instrument (split/splitless injector, J&W Scien-
tific, HP-5, 25 m column, internal diameter 0.25 mm, film thickness
0.33 mm, carrier gas 150 kPa He, FID detector) equipped with a
Hewlett–Packard HP3396 series II integrator. The enantiomeric ex-
cesses of the hydroformylation reaction were measured after oxi-
dation of the aldehydes to the corresponding carboxylic acids with
a Hewlett–Packard HP 5890A gas chromatograph (split/splitless
injector, J&W Scientific, FS-Cyclodex β-I/P 50 m column, internal
diameter 0.2 mm, film thickness 0.33 mm, carrier gas 100 kPa He,
FID detector). Absolute configurations was determined by com-
paring retention times with optically pure (S)-(+)-2-phenylpropi-
onic and (R)-(–)-2-phenylpropionic acids.
1
coupling. The hydride signal was observed in the H NMR
spectrum as a broad multiplet (∆ω½ Յ 36 Hz). Broad sig-
nals were again observed when 1H and 31P{1H} NMR spec-
tra were recorded at lower temperatures. In previous work
on the system containing diphosphite ligand 1a, only one
31P doublet resonance was reported for the corresponding
1
complex with a JRh-P coupling constant close to 236 Hz
2
and without a discernible JP-P coupling constant. An eq–
eq configuration was then assigned to this complex.[5a] It
was therefore concluded that, although no conversion was
observed with this system (see Table 1, Entries 3 and 4), the
hydride species was formed under these conditions. Thus,
as modification of the phosphite moiety does not affect the
formation of the hydride complex, the cause of the inac-
tivity of this system must be arise at a later stage of the
catalytic cycle. The steric bulk of this moiety could hinder
Synthesis of the Ligands
6-O-Isopropyl-1,2-O-isopropylidene-α-
D-glucofuranoside (10): Et3-
SiH (4.26 mL, 26.7 mmol) and BF3·Et2O (1.51 mL, 11.9 mmol)
the coordination of the substrate, thus hampering the reac- were added to a solution of 12 (1.76 g, 6.63 mmol) in CH2Cl2
(250 mL) cooled to –10 °C. The reaction mixture was stirred at
–10 °C for 2 h and then quenched by careful addition to saturated
NaHCO3/H2O (50 mL). The aqueous layer was extracted with
CH2Cl2 (3ϫ50 mL) and the combined organic phases were washed
with brine and dried with MgSO4. Purification by flash chromatog-
raphy (EtOAc, Rf = 0.42) gave compound 10 as a colorless oil
(748 mg, 43%). [α]2D5 = –1.13 (c = 1.0, CH2Cl2). 1H NMR
(400 MHz, CDCl3): δ = 1.19 {d, J = 5.6 Hz, 6 H, [OCH(CH3)2]},
1.32 [s, 3 H, O2C(CH3)2], 1.49 [s, 3 H, O2C(CH3)2], 3.54 (dd, J =
10, 5.6 Hz, 1 H, 6-H), 3.67 [m, 1 H, OCH(CH3)2], 3.74 (dd, J =
10, 3.2 Hz, 1 H, 6Ј-H), 4.08 (dd, J = 5.8, 2.7 Hz, 1 H, 4-H), 4.15
(m, 1 H, 5-H), 4.35 (br., 1 H, 3-H), 4.55 (d, J = 3.2 Hz, 1 H, 2-H),
5.97 (d, J = 3.6 Hz, 1 H, 1-H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 22.1 [OCH(CH3)2], 26.3 [O2C(CH3)2], 26.9 [O2C-
(CH3)2], 68.9 (C-6), 69.7 (C-5), 72.7 [OCH(CH3)2], 76.0 (C-4), 80.2
(C-3), 85.2 (C-2), 105.0 (C-1), 111.7 [O2C(CH3)2] ppm. C12H22O6
tion. At a higher temperature (80 °C) the results obtained
support the formation of the unmodified rhodium hydride
carbonyl system, which would explain why the reaction
showed no enantioselectivity.
Conclusions
A new series of diphosphite ligands 1b, 7a, 8a,b, 25a,b,
and 26a,b with C1 symmetry have been prepared by mod-
ifying the 1,2-O-isopropylidenefuranoside backbone, the
substituent at C-6, and the diphosphite moiety. We have
developed new synthetic routes to these ligands and also a
shorter route to the reference ligand 3a. These new diphos-
phite ligands were used in the Rh-catalyzed asymmetric hy-
droformylation of styrene. The introduction of a new phos- (262.30): calcd. C 54.95, H 8.45; found C 54.59, H 8.70.
1196 Eur. J. Org. Chem. 2009, 1191–1201
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Diphosphite Ligands Derived from Carbohydrates
6-Bromo-6-deoxy-1,2:3,5-di-O-isopropylidene-α- -glucofuranoside
D
3,5-Di-O-benzyl-1,2-isopropylidene-α-D-xylofuranoside (16): Com-
(13): Compounds 12 (5 g, 19.2 mmol), Ph3P (8.31g, 31.7 mmol),
and N-bromosuccinimide (5.13g, 28.8 mmol) were dissolved in tol-
uene (50 mL). The resulting solution was heated at 90 °C for 2 h,
then cooled, washed with 5% NaHCO3/H2O, and dried (MgSO4).
Purification by flash chromatography (EtOAc/hexane = 1:16, Rf =
0.25) gave 13 as a colorless oil (4.84 g, 78%). [α]2D5 = +31.82 (c =
pound 16 was synthesized according to the general procedure de-
scribed above. The product was isolated as a colorless oil in 85%
yield (1.26g) after purification using the eluent system EtOAc/hex-
ane = 1:8 (Rf = 0.34). [α]2D5 = –4.45 (c = 1.0, CH2Cl2). H NMR
1
(400 MHz, CDCl3): δ = 1.33 [s, 3 H, O2C(CH3)2], 1.50 [s, 3 H,
O2C(CH3)2], 3.77 (m, 2 H, 5,5Ј-H), 3.99 (d, J = 3.2 Hz, 1 H, 3-H),
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.32 {s, 3 H, 4.41 (dt, J = 6.8, 2.8 Hz, 1 H, 4-H), 4.52 (m, 2 H, OCH2Ph), 4.62
[O2C(CH3)2]}, 1.36 [s, 3 H, O2C(CH3)2], 1.37 [s, 3 H, O2C(CH3)2],
1.48 [s, 3 H, O2C(CH3)2], 3.43 (dd, J = 11.2, 7.6 Hz, 1 H, 6-H),
3.60 (dd, J = 11.0, 3.4 Hz, 1 H, 6Ј-H), 3.73 (td, J = 7.2, 3.2 Hz, 1
H, 5-H), 4.22 (d, J = 4.4 Hz, 1 H, 3-H), 4.31 (dd, J = 7.2, 4.0 Hz,
1 H, 4-H), 4.58 (d, J = 3.6 Hz, 1 H, 2-H), 5.98 (d, J = 3.6 Hz, 1
(m, 3 H, 2-H, OCH2Ph), 5.95 (d, J = 3.6 Hz, 1 H, 1-H), 7.32 (m,
10 H, Ph) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 26.5
[O2C(CH3)2], 27.0 [O2C(CH3)2], 67.7 (C-5), 72.2 (OCH2Ph), 73.7
(OCH2Ph), 79.4 (C-4), 81.9 (C-3), 82.6 (C-2), 105.3 (C-1), 111.9
[O2C(CH3)2], 127.8–128.6 (aromatic), 137.7 (aromatic), 138.2 (aro-
H, 1-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 23.9 [O2C- matic) ppm. C22H26O5 (370.44): calcd. C 71.33, H 7.07; found C
(CH3)2], 24.0 [O2C(CH3)2], 26.6 [O2C(CH3)2], 27.3 [O2C(CH3)2], 70.98, H 7.25.
33.1 (C-6), 72.0 (C-5), 75.2 (C-3), 81.7 (C-4), 84.0 (C-2), 101.5
[O2C(CH3)2], 106.5 (C-1), 112.5 [O2C(CH3)2] ppm. C12H19BrO5
(323.18): calcd. C 44.60, H 5.93; found C 44.28, H 6.12.
3,5-Di-O-benzyl-6-deoxy-1,2-isopropylidene-α-D-glucofuranoside
(17): Compound 17 was synthesized according to the general pro-
cedure described above. The product was isolated as a colorless oil
in 60% yield (923 mg, 2.4 mmol) after purification using the eluent
system EtOAc/hexane = 1:8 (Rf = 0.30). [α]2D5 = –26.83 (c = 1.0,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.35 [s, 3 H, O2C-
(CH3)2], 1.41 (d, J = 6.0 Hz, 3 H, 6-H), 1.53 [s, 3 H, O2C(CH3)2],
4.02 (m, 1 H, 5-H), 4.10 (dd, J = 9.0, 3.0 Hz, 1 H, 3-H), 4.15 (d, J
= 2.8 Hz, 1 H, 4-H), 4.48 (m, 2 H, OCH2Ph), 4.66 (br., 3 H, 2-H,
OCH2Ph), 5.95 (d, J = 3.6 Hz, 1 H, 1-H), 7.30 (m, 10 H, Ph) ppm.
13C NMR (100.6 MHz, CDCl3): δ = 17.4 (C-6), 26.4 [O2C(CH3)2],
26.9 [O2C(CH3)2], 70.9 (C-5), 72.1 (OCH2Ph), 72.2 (OCH2Ph), 81.6
(C-4), 82.3 (C-2), 83.4 (C-3), 105.0 (C-1), 111.7 [O2C(CH3)2],
127.6–128.5 (10 aromatic), 137.8 (aromatic), 138.7 (aromatic) ppm.
C23H28O5 (384.47): calcd. C 71.85, H 7.34; found C 71.58, H 7.47.
6-Deoxy-1,2:3,5-di-O-isopropylidene-α-D-glucofuranoside (14): Li-
AlH4 (275mg, 7.0 mmol) was added to a solution of 13 (900 mg,
2.7 mmol) in THF (30 mL). The mixture was stirred overnight at
room temperature. The reaction was quenched by careful addition
of EtOAc and 2.5  NaOH (5 mL). The precipitate formed was
removed by filtration. The aqueous layer was extracted with
CH2Cl2 (3ϫ50 mL) and the combined organic phases were washed
with brine and dried with MgSO4. Purification by flash chromatog-
raphy (EtOAc/hexane = 1:14, Rf = 0.25) gave 14 as a colorless oil
(581 mg, 88%). [α]2D5 = +34.43 (c = 1.0, CH2Cl2). 1H NMR
(400 MHz, CDCl3): δ = 1.28 [s, 3 H, O2C(CH3)2], 1.30 [s, 6 H,
O2C(CH3)2], 1.31 (d, J = 4.0 Hz, 3 H, 6-H), 1.46 [s, 3 H, O2C-
(CH3)2], 3.61 (m, 1 H, 5-H), 4.18 (dd, J = 7.2, 3.6 Hz, 1 H, 3-H),
4.17 (d, J = 3.6 Hz, 1 H, 4-H), 4.55 (d, J = 4.0 Hz, 1 H, 2-H), 5.96
(d, J = 3.6 Hz, 1 H, 1-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ
= 19.7 (C-6), 24.2 [O2C(CH3)2], 24.3 [O2C(CH3)2], 26.7 [O2C-
(CH3)2], 27.3 [O2C(CH3)2], 68.0 (C-5), 74.9 (C-3), 84.3 (C-4), 85.0
(C-2), 100.7 [O2C(CH3)2], 106.4 (C-1), 112.2 [O2C(CH3)2] ppm.
C12H20O5 (244.28): calcd. C 59.00, H 8.25; found C 58.76, H 8.50.
General Procedure for the Deprotection/Reduction of 1,2-O-Isopro-
pylidenefuranosides: Et3SiH (1.5 mL, 9.2 mmol) and BF3·Et2O
(1.2 mL, 9.4 mmol) were added to a solution of the starting mate-
rial 16 or 17 (2.0 mmol) in CH2Cl2 (15 mL) cooled to 0 °C. The
reaction mixture was stirred at room temperature for 2 h. The reac-
tion was quenched by careful addition of saturated NaHCO3/H2O
(15 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted
with CH2Cl2 (3ϫ50 mL) and the combined organic phases were
washed with brine and dried with MgSO4. Purification by flash
chromatography gave the corresponding alcohols 18 and 19.
6-Deoxy-1,2-O-isopropylidene-α-D-glucofuranoside (9): Compound
14 (1.0 g, 4.1 mmol) was dissolved in AcOH/H2O (65%, 5 mL) and
the mixture was stirred at 40 °C for 10 h. After cooling to room
temperature, the solution was co-evaporated with EtOH and tolu-
ene at reduced pressure and the residue was purified by flash
chromatography (EtOAc/hexane = 1:1, Rf = 0.1) to afford 9 as a
colorless oil (829 mg, 99% yield). [α]2D5 = –10.43 (c = 1.0, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 1.31 [s, 3 H, O2C(CH3)2], 1.37
(d, J = 6.0 Hz, 3 H, 6-H), 1.48 [s, 3 H, O2C(CH3)2], 3.93 (m, 1 H,
5-H), 4.31 (m, 1 H, 3-H), 4.36 (d, J = 2.0 Hz, 1 H, 4-H), 4.52 (d,
J = 3.6 Hz, 1 H, 2-H), 5.97 (d, J = 3.6 Hz, 1 H, 1-H) ppm. 13C
NMR (100.6 MHz, CDCl3): δ = 18.7 (C-6), 26.3 [O2C(CH3)2], 26.9
[O2C(CH3)2], 67.4 (C-5), 75.6 (C-3), 82.0 (C-4), 85.4 (C-2), 105.0
(C-1), 111.9 [O2C(CH3)2] ppm. C9H16O5 (204.22): calcd. C 52.90,
H 7.90; found C 52.70, H 8.02.
1,4-Anhydro-3,5-di-O-benzyl-D-xylitol (18): Compound 18 was syn-
thesized according to the general procedure described above. The
product was isolated as a white solid in 86% yield (541 mg,
1.72 mmol) after purification using the eluent system EtOAc/hex-
1
ane = 1:4 (Rf = 0.30). [α]2D5 = –11.09 (c = 1.0, CH2Cl2). H NMR
(400 MHz, CDCl3): δ = 3.74 (m, 3 H, 1Ј-H, 5,5Ј-H), 3.94 (d, J =
4.0 Hz, 1 H, 2-H), 4.19 (dd, J = 9.6, 4.4 Hz, 1 H, 1-H), 4.32 (m, 1
H, 4-H), 4.37 (m, 1 H, 3-H), 4.55 (m, 2 H, OCH2Ph), 4.64 (m, 2
H, OCH2Ph), 7.30 (m, 10 H, Ph) ppm. 13C NMR (100.6 MHz,
CDCl3):
δ = 69.0 (C-5), 72.8 (C-1), 74.0 (OCH2Ph), 74.1
(OCH2Ph), 75.6 (C-3), 79.7 (C-4), 84.8 (C-2), 129.0–128.0 (aro-
matic), 138.1 (aromatic), 138.5 (aromatic) ppm. C19H22O4 (314.38):
calcd. C 72.59, H 7.05; found C 72.42, H 7.40.
General Procedure for the Benzylation of 9 and 15: NaH (653 mg,
16.0 mmol) was added to a solution of diol 9 or 15 (4.0 mmol) in
THF (30 mL) at room temperature and the reaction was main-
tained for 1 h. Afterwards, benzyl bromide (1.94 mL, 16 mmol) was
added and the reaction mixture was stirred overnight at room tem-
perature. The reaction was quenched by careful addition of H2O.
The aqueous layer was extracted with CH2Cl2 (3ϫ50 mL) and the
combined organic phases were washed with brine and dried with
MgSO4. Purification by flash chromatography gave the correspond-
ing benzylated products 16 and 17.
1,4-Anhydro-3,5-di-O-benzyl-6-deoxy-D-glucitol (19): Compound 19
was synthesized according to the general procedure described
above. The product was isolated as a white solid in 70% yield
(460 mg, 1.40 mmol) after purification using the eluent system
EtOAc/hexane = 1:3 (Rf = 0.20). [α]2D5 = –19.04 (c = 1.0, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 1.62 (d, J = 4.8 Hz, 3 H, 6-H),
3.95 (m, 1 H, 5-H), 4.19 (m, 2 H, 1,1Ј-H), 4.34 (dd, J = 6.6, 3.9 Hz,
1 H, 4-H), 4.48 (d, J = 3.6 Hz, 1 H, 3-H), 4.63 (m, 2 H, OCH2Ph),
4.75 (m, 1 H, 2-H), 4.85 (m, 2 H, OCH2Ph), 7.54 (m, 10 H,
Eur. J. Org. Chem. 2009, 1191–1201
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1197

A. Gual, C. Godard, C. Claver, S. Castillón
Ph) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 17.4 (C-6), 70.9 (C- (100.6 MHz, CDCl3): δ = 14.7 [O(CH2)15CH3], 17.8 (C-6), 23.2
FULL PAPER
5), 72.1 (OCH2Ph), 72.9 (OCH2Ph), 73.9 (C-1), 74.3 (C-3), 83.3
(C-4), 83.8 (C-2), 127.5–128.5 (aromatic), 138.2 (aromatic), 138.7
(aromatic) ppm. C20H28O4 (332.43): calcd. C 73.15, H 7.37; found
C 72.89, H 7.70.
[O(CH2)15CH3], 26.6 [O(CH2)15CH3], 30.2–29.9 [11ϫCH2,
O(CH2)15CH3], 32.4 [O(CH2)15CH3], 70.1 (C-5), 71.1 {[O(CH2)15-
CH3]}, 72.4 (C-1), 72.5 (OCH2Ph), 73.0 (OCH2Ph), 81.7 (C-3), 82.9
(C-4), 84.3 (C-2), 128.8–127.8 (aromatic), 138.6 (aromatic), 139.3
(aromatic) ppm. C37H60O4 (568.87): calcd. C 78.12, H 10.63; found
C 77.88, H 10.50.
General Procedure for the Etherification of 1,4-Anhydro-3,5-di-O-
benzylalditols: NaH (320 mg, 8.0 mmol) was added to a solution of
starting material 18 or 19 (2.0 mmol) in THF (15 mL) at room
temperature. The reaction mixture was stirred at room temperature
for 1 h and then the corresponding alkyl bromide (2.2 mmol) was
added together with catalytic quantities of 18-crown-6 ether. The
reaction mixture was stirred overnight at room temperature and
then quenched by the careful addition of H2O. The aqueous layer
was extracted with CH2Cl2 (3ϫ50 mL) and the combined organic
phases were washed with brine and dried with MgSO4. Purification
by flash chromatography gave the corresponding products 20, 21,
and 22.
General Procedure for Removing Benzyl Groups from the 1,4-Anhy-
dro-3,5-di-O-benzyl-2-alkylalditols: A catalytic amount of Pd/C
(0.5 mmol) was added to a solution of 20, 21, or 22 (5 mmol) in
THF (15 mL). The reaction mixture was stirred for 12 h over 1 bar
H2 pressure. The H2 pressure was then purged. The mixture was
filtered though Celite to obtain the corresponding diols 23, 24, and
11.
1,4-Anhydro-2-O-butyl-D-xylitol (23): Compound 23 was synthe-
sized according to the general procedure described above. The
product was isolated as a white solid in 93% yield (885 mg,
1
4.65 mmol). [α]2D5 = –8.74 (c = 1.0, CH2Cl2). H NMR (400 MHz,
1,4-Anhydro-2-O-butyl-3,5-di-O-benzyl-D-xylitol (20): Compound
CDCl3): δ = 0.89 [t, J = 6.0 Hz, 3 H, O(CH2)3CH3], 1.40 [m, 2 H,
O(CH2)3CH3], 1.55 [m, 2 H, O(CH2)3CH3], 3.48 [m, 2 H, O(CH2)3-
CH3], 3.79 (dd, J = 10.0, 2.4 Hz, 1 H, 1Ј-H), 3.88 (dd, J = 4.4,
2.0 Hz, 1 H, 2-H), 3.95 (d, J = 2.8 Hz, 1 H, 4-H), 4.00 (m, 1 H, 5Ј-
H), 4.05 (m, 1 H, 5-H), 4.19 (dd, J = 10, 2.4 Hz, 1 H, 1-H), 4.29
(m, 1 H, 3-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 13.1
[O(CH2)3CH3], 19.4 [O(CH2)3CH3], 32.0 [O(CH2)3CH3], 60.5 (C-
5), 70.5 [O(CH2)3CH3], 72.3 (C-1), 77.7 (C-3), 79.4 (C-4), 86.3 (C-
2) ppm. C9H18O4 (190.24): calcd. C 56.82, H 9.54; found C 56.57,
H 9.80.
20 was synthesized according to the general procedure described
above. The product was isolated as a colorless syrup in 90% yield
(667 mg, 1.80 mmol) after purification using the eluent system
EtOAc/hexane = 1:8 (Rf = 0.30). [α]2D5 = –2.55 (c = 1.0, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 0.98 [t, J = 7.2 Hz, 3 H, O(CH2)3-
CH3], 1.40 [m, 2 H, O(CH2)3CH3], 1.58 [m, 2 H, O(CH2)3CH3],
3.43 [t, J = 6.6 Hz, 2 H, O(CH2)3CH3], 3.81 (m, 3 H, 1Ј-H, 5,5Ј-
H), 4.01 (m, 2 H, 2-H, 3-H), 4.23 (m, 2 H, 1-H, 4-H), 4.57 (m, 2
H, OCH2Ph), 4.67 (m, 1 H, OCH2Ph), 7.35 (m, 10 H, Ph) ppm.
13C NMR (100.6 MHz, CDCl3): δ = 13.1 [O(CH2)3CH3], 19.4
[O(CH2)3CH3], 32.0 [O(CH2)3CH3], 68.7 (C-5), 69.6 [O(CH2)3-
CH3], 71.9 (C-1), 74.0 (OCH2Ph), 74.1 (OCH2Ph), 75.6 (C-3), 79.7
(C-4), 82.9 (C-2), 128.7–127.8 (aromatic), 138.1 (aromatic), 138.5
(aromatic) ppm. C23H30O4 (370.48): calcd. C 74.56, H 8.16; found
C 74.31, H 8.35.
1,4-Anhydro-2-O-tetradecyl-D-xylitol (24): Compound 24 was syn-
thesized according to the general procedure described above. The
product was isolated as a white solid in 99% yield (1.64 g,
1
4.95 mmol). [α]2D5 = –2.07 (c = 1.0, CH2Cl2). H NMR (400 MHz,
CDCl3): δ = 0.89 [t, J = 6.0 Hz, 3 H, O(CH2)13CH3], 1.25 [s, 22 H,
O(CH2)13CH3], 1.58 [m, 2 H, O(CH2)13CH3], 3.48 [m, 2 H,
O(CH2)13CH3], 3.79 (dd, J = 9.2, 2.0 Hz, 1 H, 1Ј-H), 3.90 (m, 1 H,
2-H), 3.98 (m, 1 H, 4-H), 4.02 (m, 1 H, 5-H), 4.10 (m, 1 H, 5Ј-H),
4.20 (dd, J = 10.0, 4.8 Hz, 1 H, 1-H), 4.31 (m, 1 H, 3-H) ppm. 13C
1,4-Anhydro-3,5-di-O-benzyl-2-O-tetradecyl-D-xylitol (21): Com-
pound 21 was synthesized according to the general procedure de-
scribed above. The product was isolated as a colorless syrup in 77%
yield (812 mg, 1.54 mmol) after purification using the eluent system
EtOAc/hexane = 1:8 (Rf = 0.37). [α]2D5 = –0.94 (c = 1.0, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 0.91 [t, J = 9.2 Hz, 3 H, O(CH2)13-
CH3], 1.29 [s, 22 H, O(CH2)13CH3], 1.54 [m, 2 H, O(CH2)13CH3],
3.43 [t, J = 6.6 Hz, 2 H, O(CH2)13CH3], 3.80 (m, 3 H, 1Ј-H, 5,5Ј-
H), 4.01 (m, 2 H, 2-H, 3-H), 4.23 (m, 2 H, 1-H, 4-H), 4.59 (m, 2
H, OCH2Ph), 4.69 (m, 2 H, OCH2Ph), 7.37 (m, 10 H, Ph) ppm.
13C NMR (100.6 MHz, CDCl3): δ = 14.3 [O(CH2)13CH3], 22.9
[O(CH2)13CH3],26.3[O(CH2)13CH3],30.0–29.6[9ϫCH2,O(CH2)13-
CH3], 32.1 [O(CH2)13CH3], 68.7 (C-5), 69.9 [O(CH2)13CH3], 71.9
(C-1), 74.0 (OCH2Ph), 74.1 (OCH2Ph), 79.7 (C-3), 82.2 (C-4), 82.9
(C-2), 128.6–127.8 (aromatic), 138.2 (aromatic), 138.5 (aro-
matic) ppm. C33H50O4 (510.75): calcd. C 77.60, H 9.81; found C
77.2, H 10.9.
NMR (100.6 MHz, CDCl3):
δ = 14.7 [O(CH2)13CH3], 23.2
[O(CH2)13CH3],26.6[O(CH2)13CH3],30.3–29.9[9ϫCH2,O(CH2)13-
CH3], 32.5 [O(CH2)13CH3], 62.3 (C-5), 70.5 [O(CH2)13CH3], 72.3
(C-1), 77.7 (C-3), 79.4 (C-4), 86.2 (C-2) ppm. C19H38O4 (330.50):
calcd. C 69.05, H 11.59; found C 68.78, H 11.78.
1,4-Anhydro-2-O-hexadecyl-D-glucitol (11): Compound 11 was syn-
thesized according to the general procedure described above. The
product was isolated as a white powder in 86% yield (1.60 g,
4.30 mmol). [α]2D5 = –16.59 (c = 1.0, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ = 0.88 [t, J = 6.8 Hz, 3 H, O(CH2)15CH3], 1.26 [s, 26 H,
O(CH2)15CH3] 1.39 (d, J = 6.4 Hz, 3 H, 6-H), 1.55 [m, 2 H,
O(CH2)15CH3], 3.48 [m, 2 H, O(CH2)15CH3], 3.75 (dd, J = 3.8 Hz,
1 H, 4-H), 3.82 (dd, J = 9.4, 1.4 Hz, 1 H, 1Ј-H), 3.89 (d, J = 4.4 Hz,
1 H, 2-H), 4.23 (dd, J = 9.6, 4 Hz, 1 H, 1-H), 4.28 (dd, J = 7.0,
4.2 Hz, 1 H, 5-H), 4.33 (d, J = 2.4 Hz, 1 H, 3-H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 14.7 [O(CH2)15CH3], 18.3 (C-6), 22.3
[O(CH2)15CH3], 26.0 [O(CH2)15CH3], 30.2–29.7 [11ϫCH2,
O(CH2)15CH3], 31.8, 67.8 (C-5), 69.7 [O(CH2)15CH3], 71.9 (C-1),
75.1 (C-3), 82.3 (C-4), 85.1 (C-2) ppm. C22H44O4 (372.58): calcd.
C 70.92, H 11.90; found C 70.65, H 12.03.
1,4-Anhydro-3,5-di-O-benzyl-2-O-hexadecyl-D-glucitol (22): Com-
pound 22 was synthesized according to the general procedure de-
scribed above. The product was isolated as a colorless syrup in 79%
yield (797 mg, 1.40 mmol) after purification using the eluent system
EtOAc/hexane = 1:14 (Rf = 0.40). [α]2D5 = –12.79 (c = 1.0, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 0.89 [t, J = 6.8 Hz, 3 H,
O(CH2)15CH3], 1.27 [s, 26 H, O(CH2)15CH3], 1.36 (d, J = 6.0 Hz,
3 H, 6-H), 1.52 [m, 2 H, O(CH2)15CH3], 3.36 [m, 2 H, O(CH2)15- General Procedure for the Synthesis of the Diphosphite Ligands: A
CH3], 3.75 (dd, J = 10, 1.6 Hz, 1 H, 5-H), 3.82 (dd, J = 8.6, 3.4 Hz, solution of the diol 9, 10, 11, 15, 23, or 24 (1.0 mmol), previously
1 H, 1Ј-H), 3.93 (m, 2 H, 2-H, 1-H), 4.07 (d, J = 3.6 Hz, 1 H, 3-
azeotropically dried with toluene (3ϫ1 mL), in dry and degassed
H), 4.13 (dd, J = 9.8, 4.6 Hz, 1 H, 4-H), 4.42 (m, 2 H, OCH2Ph), toluene (10 mL) and cooled to 0 °C, was slowly added to a solution
4.60 (m, 2 H, OCH2Ph), 7.30 (m, 10 H, Ph) ppm. 13C NMR of phosphorochloridites a or b (2.1 mmol), synthesized in situ by
1198
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 1191–1201

Diphosphite Ligands Derived from Carbohydrates
standard procedures, in dry and degassed pyridine (1.5 mL). The
mixture was allowed to warm to room temperature and stirred
overnight. The mixture was then filtered to eliminate the pyridine
salts and the filtrate was concentrated to dryness. The white foam
obtained was purified by flash chromatographic techniques over
nitrogen.
30.9 Hz) ppm. C56H76O14P2 (1035.14): calcd. C 64.98, H 7.40;
found C 64.76, H 7.59.
1,4-Anhydro-3,5-bis-O-[(3,3Ј-di-tert-butyl-5,5Ј-dimethoxy-1,1Ј-bi-
phenyl-2,2Ј-diyldioxy)phosphanyl]-2-O-butyl-D-xylitol (25a): Com-
pound 25a was synthesized according to the general procedure de-
scribed above. The product was isolated as a white solid in 71%
yield (684 mg, 0.71 mmol) after purification by flash column
chromatography (toluene/THF = 98:2, Rf = 0.35). [α]2D5 = –3.30 (c
= 1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 0.81 [t, J =
6.4 Hz, 3 H, O(CH2)3CH3], 1.40 [m, 40 H, oC(CH3)3, O(CH2)3-
CH3], 3.14 [m, 2 H, O(CH2)3CH3], 3.60 (m, 2 H, 1Ј-H, 4-H), 3.80
(2ϫs, 12 H, pOCH3), 3.90 (dd, J = 9.6, 4.4 Hz, 1 H, 1-H), 4.00
(m, 2 H, 5,5Ј-H), 4.08 (m, 1 H, 2-H), 4.70 (dd, J = 8.0, 2.0 Hz, 1
H, 3-H), 6.97–6.67 (m, 8 H, aromatic) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 14.3 [O(CH2)3CH3], 19.3 [O(CH2)3CH3], 31.2
[oC(CH3)3], 31.9 [O(CH2)3CH3], 35.6 [oC(CH3)3], 55.8 (pOCH3),
62.8 (C-5), 69.6 [O(CH2)3CH3], 71.9 (C-1), 76.5 (C-3), 79.4 (C-4),
84.2 (C-2), 156.0–113.0 (aromatic) ppm. 31P NMR (161.97 MHz,
CDCl3): δ = 136.3 (s), 143.2 (s) ppm. C53H72O12P2 (963.08): calcd.
C 66.10, H 7.54; found C 65.90, H 7.67.
3,5-Bis-O-(4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]-
dioxaphosphocin-2-yl)-1,2-O-isopropylidene-α-D-xylofuranoside
(1b): Compound 1b was synthesized according to the general pro-
cedure described above. The product was isolated as a white solid in
65% yield (603 mg, 0.65 mmol) after purification by flash column
chromatography (toluene, Rf = 0.60). [α]2D5 = –2.08 (c = 1.0,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.50 [s, 3 H, O2C-
(CH3)2], 1.58 [4ϫs, 36 H, oC(CH3)3], 1.73 [s, 3 H, O2C(CH3)2],
2.45 (2 ϫ s, 12 H, pCH3), 3.53 (dd, J = 12.8, 5.6 Hz, 2 H,
PhCH2Ph), 4.53 (m, 2 H, PhCH2Ph), 5.04 (m, 3 H, 4-H, 5,5Ј-H),
5.63 (d, J = 2.4 Hz, 1 H, 2-H), 5.79 (d, J = 6.0 Hz, 1 H, 3-H), 6.31
(d, J = 3.6 Hz, 1 H, 1-H), 7.41–7.16 (m, 8 H, aromatic) ppm. 13C
NMR (100.6 MHz, CDCl3): δ = 21.4 (pCH3), 26.6 [O2C(CH3)2],
27.0 [O2C(CH3)2], 31.1 [oC(CH3)3], 34.9 (PhCH2Ph), 61.6 (C-5),
77.3 (C-3), 80.4 (C-4), 84.3 (C-2), 105.3 (C-1), 112.3 [O2C(CH3)2],
146.0–125.4 (aromatic) ppm. 31P NMR (161.97 MHz, CDCl3): δ =
129.2 (s), 132.1 (s) ppm. C54H72O9P2 (927.09): calcd. C 69.96, H
7.83; found C 69.67, H 8.01.
1,4-Anhydro-3,5-bis-O-(4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo-
[d,g][1,3,2]dioxaphosphocin-2-yl)-2-O-butyl-D-xylitol (25b): Com-
pound 25b was synthesized according to the general procedure de-
scribed above. The product was isolated as a white solid in 55%
yield (510 mg, 0.55 mmol) after purification by flash column
chromatography (toluene, Rf = 0.60). [α]2D5 = –2.15 (c = 1.0,
3,5-Bis-O-[(3,3Ј-di-tert-butyl-5,5Ј-dimethoxy-1,1Ј-biphenyl-2,2Ј-diyl-
dioxy)phosphanyl]-6-deoxy-1,2-O-isopropylidene-α-D-glucofurano-
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ = 1.03 [t, J = 10.0 Hz, 3
side (3a): Compound 3a was synthesized according to the general
procedure described above. The product was isolated as a white
solid in 50% yield (489 mg, 0.5 mmol) after purification by flash
H, O(CH2)3CH3], 1.41 [m, 2 H, O(CH2)3CH3], 1.55 [s, 36 H,
oC(CH3)3], 1.71 [m, 2 H, O(CH2)3CH3], 2.45 (2ϫs, 12 H, pCH3),
3.54 (dd, J = 11.2, 5.6 Hz, 2 H, PhCH2Ph), 3.77 [m, 1 H, O(CH2)3-
CH3], 3.87 [m, 1 H, O(CH2)3CH3], 4.12 (d, J = 13.2 Hz, 1 H, 1Ј-
H), 4.50 (m, 2 H, PhCH2Ph), 4.57 (dd, J = 13.2, 5.6 Hz, 1 H, 1-
H), 4.77 (m, 1-H, 4-H), 4.90 (m, 1 H, 5Ј-H), 5.00 (d, J = 5.2 Hz, 1
H, 2-H), 5.08 (m, 1 H, 5-H), 5.75 (dd, J = 8.4, 4.4 Hz, 1 H, 3-H),
7.21–7.17 (m, 8 H, aromatic) ppm. 13C NMR (100.6 MHz, CDCl3):
δ = 14.2 [O(CH2)3CH3], 19.5 [O(CH2)3CH3], 21.3 (pCH3), 31.3
[oC(CH3)3], 32.1 [O(CH2)3CH3], 34.9 (PhCH2Ph), 62.5 (C-5), 69.9
[O(CH2)3CH3], 72.3 (C-1), 77.4 (C-3), 80.3 (C-4), 84.3 (C-2), 142.3–
125.5 (aromatic) ppm. 31P NMR (161.97 MHz, CDCl3): δ = 129.3
(s), 131.6 (s) ppm. C55H76O8P2 (927.13): calcd. C 71.25, H 8.26;
found C 70.95, H 8.40.
column chromatography (toluene/THF = 99:1, Rf = 0.25). [α]2D5
=
1
+110.12 (c = 1.0, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 1.13
[s, 3 H, O2C(CH3)2], 1.30 (d, J = 6.4 Hz, 3 H, 6-H), 1.47–1.42 [s,
39 H, oC(CH3)3, O2C(CH3)2], 3.83–3.80 (s, 12 H, pOCH3), 3.97 (d,
J = 3.6 Hz, 1 H, 2-H), 4.05 (dd, J = 8.2, 2.6 Hz, 1 H, 4-H), 4.73
(m, 1 H, 5-H), 4.82 (d, J = 2.8 Hz, 1 H, 3-H), 5.59 (d, J = 3.2 Hz, 1
H, 1-H), 6.99–6.70 (m, 8 H, aromatic) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 20.1 (C-6), 26.0 [O2C(CH3)2], 26.7 [O2C(CH3)2], 31.3–
29.7 [oC(CH3)3], 35.6–35.4 [oC(CH3)3], 55.8 (pOCH3), 68.9 (C-5),
76.3 (C-3), 83.2 (C-4), 84.2 (C-2), 104.9 (C-1), 111.7 [O2C(CH3)2],
156.3–113.2 (aromatic) ppm. 31P NMR (161.97 MHz, CDCl3): δ =
144.8 (s, J = 43.9 Hz, 2 P) ppm. 31P NMR (161.97 MHz, [D8]tolu-
ene): δ = 144.8 (d, J = 35.3 Hz), 145.3 (d, J = 35.3 Hz) ppm.
C53H70O13P2 (977.06): calcd. C 65.15, H 7.22; found C 64.95, H
7.45.
1,4-Anhydro-3,5-bis-O-[(3,3Ј-di-tert-butyl-5,5Ј-dimethoxy-1,1Ј-bi-
phenyl-2,2Ј-diyldioxy)phosphanyl]-2-O-tetradecylxylitol (26a): Com-
pound 26a was synthesized according to the general procedure de-
scribed above. The product was isolated as a white solid in 27%
yield (298 mg, 0.27 mmol) after purification by flash column
chromatography (toluene/THF = 98:2, Rf = 0.35). [α]2D5 = –0.60 (c
= 1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 0.81 [t, J =
6.4 Hz, 3 H, O(CH2)13CH3], 1.40 [m, 60 H, oC(CH3)3, O(CH2)
13CH3], 3.14 [m, 2 H, O(CH2)13CH3], 3.60 (m, 2 H, 1Ј-H, 4-H),
3.82–3.80 (s, 12 H, pOCH3), 3.92 (dd, J = 10.0, 4.4 Hz, 1 H, 1-H),
4.01 (m, 2 H, 5,5Ј-H), 4.09 (m, 1 H, 2-H), 4.71 (dd, J = 8.8, 3.2 Hz,
1 H, 3-H), 6.97–6.67 (m, 8 H, aromatic) ppm. 13C NMR
3,5-Bis-O-[(3,3Ј-di-tert-butyl-5,5Ј-dimethoxy-1,1Ј-biphenyl-2,2Ј-diyl-
dioxy)phosphanyl]-6-O-isopropyl-1,2-O-isopropylidene-α-D-glucofur-
anoside (7a): Compound 7a was synthesized according to the gene-
ral procedure described above. The product was isolated as a white
solid in 54% yield (559 mg, 0.54 mmol) after purification by flash
column chromatography (toluene/THF = 95:5, Rf = 0.35). [α]2D5
=
1
+129.49 (c = 1.0, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 1.14
[dd, J = 6.4 Hz, 6 H, OCH(CH3)2], 1.20 [s, 3 H, O2C(CH3)2], 1.50
[4ϫs, 39 H, O2C(CH3)2, oC(CH3)3], 3.54 [m, 1 H, OCH(CH3)2],
3.80 (dd, J = 11.0, 5.4 Hz, 1 H, 6-H), 3.85–3.89 (s, 14 H, 2-H, 6-
H, pOCH3), 4.41 (d, J = 6.4 Hz, 1 H, 4-H), 4.71 (m, 1 H, 5-H),
4.89 (d, J = 4.4 Hz, 1 H, 3-H), 5.67 (d, J = 3.6 Hz, 1 H, 1-H), 7.30–
6.70 (m, 8 H, aromatic) ppm. 13C NMR (100.6 MHz, CDCl3): δ =
22.1 [2ϫC, OCH(CH3)2], 26.1 [O2C(CH3)2], 26.8 [O2C(CH3)2],
31.2 [oC(CH3)3], 35.6 [oC(CH3)3], 55.8 (pOCH3), 68.0 (C-6), 72.2
[OCH(CH3)2], 72.4 (C-5), 76.7 (C-3), 79.2 (C-4), 83.8 (C-2), 105.0
(C-1), 111.8 [O2C(CH3)2], 156.0–112.7 (aromatic) ppm. 31P NMR
(161.97 MHz, CDCl3): δ = 144.5 (d, J = 30.9 Hz), 145.8 (d, J =
(100.6 MHz, CDCl3): δ = 14.3 [O(CH2)13CH3], 26.2 [O(CH2)13
-
CH3], 29.2 [O(CH2)13CH3], 29.8 [O(CH2)13CH3], 31.2 [oC(CH3)3],
32.1 [O(CH2)13CH3], 35.6 [oC(CH3)3], 55.8 (pOCH3), 62.8 (C-5),
70.0 [O(CH2)13CH3], 71.9 (C-1), 76.5 (C-3), 79.3 (C-4), 84.2 (C-2),
156.0–113.0 (aromatic) ppm. 31P NMR (161.97 MHz, CDCl3): δ =
136.3 (s), 143.2 (s) ppm. C63H92O12P2 (1103.34): calcd. C 68.58, H
8.40; found C 68.27, H 8.57.
1,4-Anhydro-3,5-bis-O-(4,8-di-tert-butyl-2,10-dimethyl-12H-di-
benzo[d,g][1,3,2]dioxaphosphocin-2-yl)-2-O-tetradecyl-
D
-xylitol
Eur. J. Org. Chem. 2009, 1191–1201
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1199

A. Gual, C. Godard, C. Claver, S. Castillón
FULL PAPER
(26b): Compound 26b was synthesized according to the general
procedure described above. The product was isolated as a white
solid in 50% yield (534 mg, 0.50 mmol) after purification by flash
column chromatography (toluene, Rf = 0.60). [α]2D5 = –0.82 (c = 1.0,
131.9 (s), 133.5 (s) ppm. C68H102O8P2 (1109.48): calcd. C 73.61, H
9.27; found C 73.31, H 9.42.
In Situ High-Pressure NMR Experiments: In a typical experiment,
a sapphire tube (ø = 10 mm) was filled under argon with a solution
of [Rh(acac)(CO)2] (2.10–2 m) and the ligand (molar ratio L/Rh
= 1.1) in [D8]toluene (2 mL). The solution was analyzed and then
the high-pressure NMR tube was purged three times with CO and
pressurized to the appropriate pressure of CO/H2. After the reac-
tion, during which the solution was shaken at 40 °C, the solution
was analyzed.
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ = 0.90 [t, J = 10.0 Hz, 3
H, O(CH2)13CH3], 1.28 [m, 22 H, O(CH2)13CH3], 1.43 [s, 36 H,
oC(CH3)3], 1.61 [m, 2 H, O(CH2)13CH3], 2.31 (2ϫs, 12 H, pCH3),
3.40 (dd, J = 12.8, 8.4 Hz, 2 H, PhCH2Ph), 3.64 [m, 1 H, O(CH2)13-
CH3], 3.70 [m, 1 H, O(CH2)13CH3], 3.99 (d, J = 10.0 Hz, 1 H, 1Ј-
H), 4.36 (m, 2 H, PhCH2Ph), 4.42 (dd, J = 9.6, 4.4 Hz, 1 H, 1-H),
4.63 (m, 1 H, 4-H), 4.78 (m, 1 H, 5Ј-H), 4.86 (d, J = 4.0 Hz, 1 H,
2-H), 4.94 (m, 1 H, 5-H), 5.60 (dd, J = 6.0, 3.2 Hz, 1 H, 3-H),
7.14–7.01 (m, 8 H, aromatic) ppm. 13C NMR (100.6 MHz, CDCl3):
δ = 14.6 [O(CH2)13CH3], 21.5 (pCH3), 23.1 [O(CH2)13CH3], 26.6
[O(CH2)13CH3], 29.9 [O(CH2)13CH3], 30.1 [oC(CH3)3], 31.4
[O(CH2)13CH3], 35.2 (PhCH2Ph), 62.7 (C-5), 70.5 [O(CH2)13CH3],
72.5 (C-1), 77.4 (C-3), 80.5 (C-4), 84.5 (C-2), 136.6–127.2 (aro-
matic) ppm. 31P NMR (161.97 MHz, CDCl3): δ = 129.7 (s), 132.1
(s) ppm. C65H96O8P2 (1067.40): calcd. C 73.14, H 9.07; found C
73.00, H 9.24.
Hydroformylation Experiments: In a typical experiment, the auto-
clave was purged three times with CO. The solution was formed
from [Rh(acac)(CO)2] (0.013 mmol), diphosphite (0.015 mmol),
and styrene (13 mmol) in toluene (15 mL). The autoclave was pres-
surized to the desired pressure of CO/H2. After the desired reaction
time, the autoclave was cooled to room temperature and depressur-
ized. The reaction mixture was analyzed by gas chromatography.
The aldehydes obtained from the hydroformylation were oxidized
to carboxylic acids to determine the enantiomeric excesses.
Supporting Information (see also the footnote on the first page of
this article): 1H, 13C, and 31P NMR spectra of the new ligands, and
1H and 31P NMR spectra of complexes Rh/1b and Rh/8a recorded
under reaction conditions.
1,4-Anhydro-3,5-bis-O-[(3,3Ј-di-tert-butyl-5,5Ј-dimethoxy-1,1Ј-bi-
phenyl-2,2Ј-diyldioxy)phosphanyl]-6-deoxy-2-O-hexadecyl-D-glucitol
(8a): Compound 8a was synthesized according to the general pro-
cedure described above. The product was isolated as a white solid
in 50% yield (573 mg, 0.5 mmol) after purification by flash column
chromatography (toluene/THF = 99:1, Rf = 0.25). [α]2D5 = –0.34 (c
= 1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 0.89 [t, J =
6.4 Hz, 3 H, O(CH2)15CH3], 1.27 [s, 26 H, O(CH2)15CH3], 1.33 (d,
J = 6.4 Hz, 3 H, 6-H), 1.46 [m, 36 H, oC(CH3)3], 1.40 [m, 2 H,
O(CH2)15CH3], 3.23 [m, 1 H, O(CH2)15CH3], 3.35 [m, 1 H, O(CH2)15-
CH3], 3.60 (m, 1 H, 1Ј-H), 3.65 (m, 1 H, 4-H), 3.82–3.80 (s, 13 H,
1-H, pOCH3), 3.87 (dd, J = 8.0, 2.8 Hz, 1 H, 2-H), 4.72 (m, 1 H,
5-H), 4.82 (dd, J = 7.0, 2.6 Hz, 1 H, 3-H), 6.97–6.70 (m, 8 H,
aromatic) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 14.3 [O(CH2)15-
CH3], 20.3 (C-6), 23.3 [O(CH2)15CH3], 26.7 [O(CH2)15CH3], 29.9
[O(CH2)15CH3], 30.4 [O(CH2)15CH3], 31.7 [oC(CH3)3], 32.5
[O(CH2)15CH3], 35.9 [oC(CH3)3], 56.1 (pOCH3), 69.7 (C-5), 70.5
[O(CH2)15CH3], 72.6 (C-1), 76.0 (C-3), 84.0 (C-4), 84.5 (C-2),
156.3–113.2 (aromatic) ppm. 31P NMR (161.97 MHz, CDCl3): δ =
144.0 (d, J = 43.9 Hz), 146.5 (d, J = 43.7 Hz) ppm. C66H98O12P2
(1105.42): calcd. C 69.21, H 8.62; found C 69.02, H 8.79.
Acknowledgments
We are grateful to the Spanish Ministerio de Educacion y Ciencia
(MEC) (CTQ2007-62288/BQU, CTQ2005-03124, Consolider In-
genio 2010, CSD2006-0003 and a Juan de la Cierva fellowship to
C.G.) and the Generalitat de Catalunya (2005SGR007777 and a
Distinction for Research Promotion, 2003, to C. C.) for financial
support. We are grateful to MEC for awarding a research grant to
A. G. (FPU program/AP2005-1263).
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1,4-Anhydro-3,5-bis-O-(4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo-
[d,g][1,3,2]dioxaphosphocin-2-yl)-6-deoxy-2-O-hexadecyl-D-glucitol
(8b): Compound 8b was synthesized according to the general pro-
cedure described above. The product was isolated as a white solid in
51% yield (566 mg, 0.51 mmol) after purification by flash column
chromatography (toluene, Rf = 0.64). [α]2D5 = –20.04 (c = 1.0,
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ = 0.91 [t, J = 6.8 Hz, 3
H, O(CH2)15CH3], 1.27 [s, 26 H, O(CH2)15CH3], 1.44 [s, 36 H,
oC(CH3)3], 1.60 [m, 2 H, O(CH2)15CH3], 1.88 (d, J = 6.4 Hz, 3 H,
6-H), 2.30 (s, 12 H, pCH3), 3.50 (dd, J1 = J2 = 12 Hz, 2 H,
PhCH2Ph), 3.65 [m, 1 H, O(CH2)15CH3], 3.75 [m, 1 H, O(CH2)15-
CH3], 3.99 (d, J = 9.6 Hz, 1 H, 1Ј-H), 4.36 (ddd, J = 17.9, 12.7,
2.7 Hz, 2 H, PhCH2Ph), 4.45 (dd, J = 9.8, 4.6 Hz, 1 H, 1-H), 4.62
(dd, J1 = J2 = 3.6 Hz, 1 H, 4-H), 4.92 (d, J = 3.6 Hz, 1 H, 2-
H), 5.55 (m, 1 H, 3-H), 5.58 (m, 1 H, 5-H), 7.00–7.30 (m, 8 H,
aromatic) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 14.0 [O(CH2)15-
CH3], 19.3 (C-6), 20.9 (pCH3), 21.4 [O(CH2)15CH3], 22.6 [O(CH2)15-
CH3], 26.2 [O(CH2)15CH3], 29.3 [O(CH2)15CH3], 29.5 [O(CH2)15-
CH3], 30.7 [oC(CH3)3], 31.8 [O(CH2)15CH3], 34.6 (PhCH2Ph), 70.0
[O(CH2)15CH3], 71.9 (C-5), 72.2 (C-1), 78.0 (C-3), 83.8 (C-2, C-4),
142.1–125.1 (aromatic) ppm. 31P NMR (161.97 MHz, CDCl3): δ =
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Received: November 5, 2008
Published Online: January 28, 2009
Eur. J. Org. Chem. 2009, 1191–1201
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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