Chiral Rh phosphine-phosphite catalysts immobilized on ionic resins for the enantioselective hydrogenation of olefins in water

Article abstract of DOI:10.1039/c5gc00485c

The asymmetric hydrogenation of prochiral enamides with Rh complexes bearing chiral phosphine-phosphite ligands (P-OP) supported on sulphonated polystyrene resins has been studied. The complexes have been supported by simple treatment of preformed [Rh(dio

Full text of DOI:10.1039/c5gc00485c

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ARTICLE
Chiral Rh phosphine-phosphite catalysts immobilized
on ionic resins for the enantioselective hydrogenation
of olefins in water
P. Kleman,a P. Barbarob * and A. Pizzanoa *
The asymmetric hydrogenation of prochiral enamides with Rh complexes bearing chiral
phosphineꢀphosphite ligands (PꢀOP) supported on sulphonated polystyrene resins has been
studied. The complexes have been supported by simple treatment of preformed
[Rh(diolefin)(PꢀOP)](BF4) with the Li salt of resin. In MeOH, high enantioselectivities were
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observed in the hydrogenation of methyl
αꢀNꢀacetamido acrylate (4a), while they decreased for
less reactive methyl ꢀacetamido cinnamate (4b). Moreover, a significant Rh leaching was
αꢀN
observed in these reactions. In contrast, a low Rh leaching was observed in reactions
performed in water. Catalyst optimization enabled by the highly modular structure of PꢀOP
ligands, led to efficient catalysts for the hydrogenation of 4a and 4b in water, with
enantioselectivities over 95 % ee and S/C values up to 2300 and 500, respectively. To
investigate the synthetic potential of the present catalytic system, the hydrogenation of a set of
β
ꢀaryl αꢀdehydroaminoacids (4cꢀ4j) in water has also been studied. For these reactions good
catalytic activity and high enantioselectivity (87ꢀ97 % ee) were also observed. In the case of
brominated substrates 4i and 4j an unexpected debromination reaction in water has been
observed. This phenomenon seems associated to the use of the supported catalyst and water
and could be minimized by the use of catalyst formed from 3f. In addition, gelꢀphase 31P{1H}
NMR studies performed with a representative supported complex show an analogous reactivity
to that displayed by its soluble tetrafluoroborate counterpart. Finally, a selective deuterium
labelling of product has been observed in hydrogenations of 4a and 4b in D2O, similar to that
observed in the homogeneous hydrogenation of these enamides with water soluble catalysts.
as water is a cheap, nonꢀtoxic and nonꢀflammable solvent.5
Moreover, the generally low solubility of hydrogenated
Introduction
Rhodium catalyzed enantioselective hydrogenation of olefins is
a highly practical and versatile tool for the synthesis of chiral
compounds.1 Due to the broad scope and outstanding
performance the corresponding catalysts have reached, a
plethora of optically active compounds have efficiently been
prepared by this hydrogenation.2 This transformation has
frequently been included in multiꢀstep synthesis by the fineꢀ
chemical and pharmaceutical industries.3 This widespread use
therefore raises the interest in environmentally related and
practical aspects of this transformation, often relegated by other
fundamental aspects. In connection with this, it should be
recalled the challenge that the mentioned industrial sectors face
to decrease the environmental impact of their production.4
Hydrogenations of this kind are usually run with homogeneous
catalysts in methylene chloride or methanol solutions, while the
catalyst separation step is frequently done in a less polar
organic solvent. Accordingly, the development of catalytic
systems operating in water constitutes a highly interesting goal
products in water, may also enable an straightforward product
separation.6
The attainment of efficient asymmetric olefin hydrogenations in
water is, however, a rather challenging goal and only very rare
cases of highly enantioselective reactions in neat water have
been described in the literature.7 This fact is in clear contrast
with the outstanding results these hydrogenations have often
shown in conventional organic solvents. However, the use of
water as a reaction medium may introduce deep changes in the
catalytic system. Hydrophobic effects and hydrogen bonding
interaction with the substrate and catalytic intermediates caused
by water,8, 9 as well as the low solubility of hydrogen in this
solvent may have an important influence in the reaction.
Moreover, reaction of water with catalytic intermediates (e.g.
by coordination or by protonation/deprotonation steps),10 may
provide alternative reaction pathways to the catalytic cycle
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operating in organic solvents,11 with a potential erosion of not been substantiated yet. Interestingly, a study about the
enantioselectivity. application of water soluble Ir catalysts supported on exchange
Extensive research pursuing efficient hydrogenation reactions resins in the nonꢀasymmetric hydrogenation of Nꢀheterocyclic
in water following different approaches has been described in substrates in water has recently been reported.22
the literature.12 Among them, those based on water soluble In this contribution we present a study on the immobilization of
catalysts, either by ligand modification with suitable functional cationic rhodium complexes based on chiral phosphineꢀ
polar groups13 or by attaching them to a water soluble carrier,14 phosphite ligands23 on an ion exchange resin. Enabled by a high
have been covered thoroughly. However, these catalysts swelling of the resin in water, the corresponding catalysts show
generally display a worse performance than the parent non good catalyst activity in this medium, while
waterꢀsoluble ones in organic solvents.15 Moreover, a perusal of enantioselective catalyst, efficient for both solutions of
the literature depicts a rather narrow scope of waterꢀsoluble slurries of in water, was found by a modular approach.
catalysts. Thus, high enantioselectivities have been achieved in Finally, complementary information obtained by gelꢀphase
the reduction of water soluble substrates like methyl
31P{1H} NMR about the reactivity of supported complexes
acetamido acrylate ( ꢀacetamido cinnamic under hydrogenation conditions is also presented.
, 99 % ee)7c or
acid (
, 94 % ee),7a while lower values have been reported for
less soluble substrates.15, 16 For instance, in the hydrogenation
of prototypical methyl ꢀacetamido cinnamate ( , Ar = Ph),
a
highly
A
and
C
αꢀNꢀ
A
αꢀN
B
Results and discussion
α
ꢀ
N
C
the highest value obtained in neat water is 88 % ee,16c while 89
% ee has been reported for a CH2Cl2/H2O (1:1) system.16a In
contrast, addition of surfactants allow the reaction to occur in
micelles, which may produce a dramatic increase in catalyst
activity and enantioselectivity, even in the case of low soluble
olefins.17 For instance, the Group of Oehme has reported
enantioselectivities up to 97 % ee in the hydrogenation of
Preparation of supported catalysts
Rhodium catalysts based on phosphineꢀphosphite ligands have
become an important class of catalysts for the asymmetric
hydrogenation of olefins. Thus, these catalysts have provided
excellent results in the reduction of diverse type of substrates
like unsaturated phosphonates, enamides of enolꢀesters.24
Considering this synthetic utility, the development of supported
versions of rhodium phosphineꢀphosphite catalysts appears to
be a particularly interesting goal. Towards this, a simple
approach that does not require a further ligand modification is
highly desirable. In this respect, nonꢀcovalent immobilization
on an ionic resin is ideal as it can directly be performed with
the homogeneous catalyst precursor by a simple anion
exchange.20 It should also be stressed that this approach is
limited to solvents that produce a good swelling of the resin,
typically alcohols and water. Thus, by stirring a solution of
methyl
α
ꢀ
N
ꢀacetamido cinnamate derivatives C 17c
.
Structures
A
-
C
An appealing approach to perform these reactions in water is
the immobilization of homogeneous catalysts on a hydrophilic
support. Moreover, the heterogeneous nature of the system
should enable a simple product isolation, with potential
advantages over procedures based on biphasic systems or
surfactants. However, immobilized catalysts have mostly been
studied in conventional organic solvents,18 while the
information about their performance in water is very limited.19
A remarkable study in this context, reported by Sheldon and
coworkers, describes high activities and enantioselectivities up
complex [Rh(diolefin)(PꢀOP)](BF4) (diolefin = COD, NBD; Pꢀ
23c, 24aꢀb
OP = 1a
ꢀ
g
)
over a sulfonated gelꢀtype resin (Dowex
50WX2ꢀ100, 2% crossꢀlinked, 4.8 mequiv./g exchange
capacity) as its lithium salt (herein abbreviated as Liꢀresin,
Scheme 1) the corresponding supported catalyst precursor was
to 96 % ee in the hydrogenation in water of
A using a Rh
phosphoramidite catalyst immobilized on different supports.19g
Particularly good results were obtained with diverse inorganic
supports (TOF up to 750 hꢀ1 and 96 % ee), while the
performance decreased for catalysts supported on NaꢀNafion
(TOF up to 270 hꢀ1 and 92 % ee), which was attributed to a
poor swelling of the resin in water. In this regard,
immobilization on ion exchange resins is an approach of great
interest due to the high swelling in water of these materials.20
Diverse precedents of Rh catalysts with chiral Pꢀligands
immobilized onto exchange resins, as well as their successful
application to the asymmetric hydrogenation of olefins in
MeOH can be found in the literature.21 However, the relevance
of such supported catalysts for reactions performed in water has
Scheme 1 Preparation of immobilized complexes.
2 | J. Name., 2012, 00, 1-3
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prepared [diolefin = COD, PꢀOP = 1d
(
2d); NBD, PꢀOP = 1a showed full conversion, but rather low enantioselectivity (43 %
3g), 1h 3h)]. It is ee, entry 2). Moreover, this catalyst provided high conversion
(
3a), 1b 3b), 1c 3c), 1e 3e), 1f 3f), 1g
(
(
(
(
(
(
worth noting that the incorporation of the Rh complex into the (84 %) but an even lower enantioselectivity in a reaction
resin was moderate to high and ranged from 61 to 87 % (see performed at S/C = 600 (entry 3). Remarkably, no catalytic
experimental). This accounts for values between 1.6 and 2.2 % activity of the supernatant solution was observed when it was
of the sulphonic groups of the resin bound to [Rh(diolefin)(Pꢀ transferred to another reactor under hydrogen.26 It should be
OP)]+ cations.
noticed, in addition, that a significant Rh leaching has been
observed in reactions performed in MeOH (see supporting
information for details). Thus, for reactions using 2d, 15 and 18
Hydrogenations in methanol
In the initial stage of the study, we examined the performance % were observed in the hydrogenations of 4a (entry 7, Table 1)
of representative catalyst precursors in the prototypical and 4b (entry 2, Table 2), respectively. Moreover, in reactions
hydrogenation of methyl
αꢀNꢀacetamido acrylate (4a, Scheme with 3a a moderate leaching was also observed. Thus, in the
2) in methanol under standard conditions (4 bar of H2, room hydrogenation of 4a (entry 1, Table 1) and 4b (entry 1, Table
temperature). Thus, we observed full conversion and an 2), Rh leaching values of 12 and 9 % were observed,
excellent enantioselectivity using complex 3a (99 % ee; entry 1, respectively. These values are higher than those reported for
Table 1). This catalyst showed lower activity, while supported catalysts based on diphosphine and diphosphinite
maintaining constantly high enantioselectivity upon recycling, ligands21 and may be connected to some degradation of the
as 87 % (99 % ee) and 78 % (99 % ee) conversions were phosphite fragment in methanol under hydrogenation
obtained in the second and third cycles, respectively (entries 2, conditions.
3). Moreover, the same catalyst exhibited good activity
although somewhat lower enantioselectivity at a lower catalyst
loading (entry 4).
Table 1 Hydrogenation of 4a in MeOH with supported catalystsa
Entry
Cat.
S/C
80
Timeb
2 (1st cycle)
2 (2nd cycle)
3 (3rd cycle)
14
% conv
95
% ee (Conf)
99 (R)
99 (R)
99 (R)
94 (R)
35 (R)
48 (R)
80 (R)
73 (R)
60 (R)
66 (R)
83 (R)
1
2
3a
80
87
3
80
78
4
5
6
7
8
9
3a
3b
3c
2d
320
70
70
60
60
60
600
100
>99
43
97
>99
>99
>99
>99
>99
2
2
2 (1st cycle)
2 (2nd cycle)
2 (3rd cycle)
16
10
2d
3g
11c
14
a Reactions were performed using the proper amounts of 4a and resin
supported complex under 4 bar H2 at room temperature in MeOH (3 mL),
unless otherwise stated. Conversion was determined by 1H NMR.
Enantiomeric excess analyzed by chiral GC or HPLC. Product configuration
was assigned by comparison with literature data. b Reaction time in hours. In
recycling experiments, the number of the cycle is stated in brackets. c
Reaction performed in 1 mL of MeOH.
Scheme 2 Hydrogenation of enamides.
For comparison, we tested catalyst precursors bearing PEt2 (3b
)
Table 2 Hydrogenation of 4b in MeOH with supported catalystsa
and PCy2 3c) groups, although they were significantly less
(
enantioselective than 3a (entries 5, 6). On the other hand,
binaphthyl based complex 2d provided 80 % ee and a good
activity (entry 7). Upon recycling, activity was maintained
while a severe drop on enantioselectivity was observed in the
second and third cycles (entries 8, 9). This catalyst provided
full conversion and a significant decrease on enantioselectivity
at a lower catalyst loading (66 % ee, S/C = 600, entry 10).
These results seem to indicate that a slight degradation of the
catalyst generated from 2d in methanol occurs leading to a
species featured by a less effective asymmetric transfer.
Finally, good activity and a moderate enantioselectivity was
obtained with ethane bridged complex 3g (83 % ee, entry 11).
After initial experiments, we turned our attention to the
Entry
Cat.
3a
2d
2d
3e
S/C
70
60
600
50
Timeb
14
14
16
14
% conv
40
>99
84
% ee (Conf)
94 (R)
43 (R)
33 (R)
84 (R)
1
2
3
4
>99
a Reactions were performed using the proper amounts of 4b and resin
supported complex under 4 bar H2 at room temperature in MeOH (1 mL).
Conversion was determined by 1H NMR. Enantiomeric excess analyzed by
chiral GC or HPLC. Product configuration was assigned by comparison with
literature data. b Reaction time in hours.
Study of the model hydrogenation of 4a in water
The practical application of the present supported catalysts in
methanol is strongly limited by the high Rh leaching observed
and prompted us to find a more robust catalytic system. In this
context, the study by Sheldon and coworkers highlighted above
also reported a high metal leaching in hydrogenations of 4a in
methanol with a Rhꢀphosphoramidite catalyst supported on
Nafion. Moreover, this catalyst provided a significantly lower
hydrogenation of methyl
αꢀacetamido cinnamate (4b) as a
representative substrate for the synthesis of important
β
ꢀarylꢀ
αꢀ
aminoacid derivatives.25 Initially, low conversion (40 %) and
good enantioselectivity (94 % ee, entry 1, Table 2) was
obtained with complex 3a. In contrast, catalyst precursor 2d
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leaching and a better enantioselectivity in water.19g Following respectively (entries 16ꢀ17). It is also interesting to note that 3e
this precedent, we examined the behavior of catalysts displayed a significantly better performance in water than in
precursors
2ꢀ3 in water. Initially, hydrogenation of water MeOH (entry 4, Table 2). On the other hand, complex 3f,
soluble 4a with catalyst precursor 2d at S/C = 60 showed full characterized by a H8ꢀbinaphthyl fragment, also exhibited a
conversion and 84 % ee (entry 1, Table 3). It is worth noting high reactivity and was able to complete a reaction at S/C =
that this catalyst exhibited a good performance on recycling as 1500. However, enantioselectivity for this reaction (88 % ee,
complete reactions and constant enantioselectivities were entry 18) was slightly lower than that provided by 3e. Finally,
obtained in the second and third cycles (entries 2ꢀ3). These complex 3g, possessing an ethane bridged ligand, also provided
observations contrast with the decrease in enantioselectivity full conversion and a good enantioselectivity (89 % ee, entry
observed in recycling experiments in MeOH and therefore 19). It did not improve, however, the value provided by the
suggest a higher stability in water of catalyst generated from corresponding benzene bridged complex 3a
.
2d. Moreover, this catalyst exhibited enough activity to finish
in 24 h a reaction prepared at S/C = 600, with a moderate
enantioselectivity (84 % ee, entry 4). Moreover, the reaction
was also completed at S/C = 1800, but a significant decrease in
enantioselectivity was observed (77 % ee; entry 5). These
results clearly show a better performance of 2d in water than in
MeOH. On the other hand, 3a showed an outstanding
enantioselectivity in the hydrogenation of 4a. Thus, for a
reaction prepared at S/C = 160, 91 % conversion and 99 % ee
were obtained (entry 6). A good indication of the beneficial
effect of supporting the catalyst is demonstrated by the
relatively poor performance of [Rh(NBD)(1a)](BF4) in the
hydrogenation of 4a (S/C = 100, 4 bar H2, room temperature),
which after 24 h showed 90 % conversion and 65 % ee. In
addition, a satisfactory behavior upon recycling was observed
for 3a, affording high conversion and enantioselectivity (91ꢀ96
% ee, entries 7ꢀ9). Interestingly, a lower enantioselectivity was
observed in the first cycle. This phenomenon has already been
reported and appears to be related to a lower enantioselectivity
in the initial step of the reaction or during the activation
process.21a Moreover, a reaction prepared at S/C = 2300 showed
80 % conversion and 99 % ee after 24 h, while full conversion
and 99 % ee was observed after 72 h (entry 10). On the other
hand, as observed in MeOH reactions, the substitution of the
PPh2 group by a PCy2 fragment has a detrimental effect. Thus,
catalyst precursor 3c provided 88 % conversion and a low
enantioselectivity (47 % ee, entry 11), well below results
Table 3 Hydrogenations of 4a in water with complexes
2
and 3a
Entry
1
2
3
4
5
6
7
8
Cat.
2d
S/C
60
60
Time[b]
% conv
>99
>99
>99
>99
>99
91
>99
>99
>99
80
% ee (Conf)
84 (R)
83 (R)
83 (R)
84 (R)
77 (R)
99 (R)
91 (R)
95 (R)
96 (R)
99 (R)
99 (R)
47 (R)
97 (R)
96 (R)
93 (R)
89 (R)
94 (R)
95 (R)
88 (R)
89 (R)
2 (1st cycle)
2 (2nd cycle)
60
2 (3rd cycle)
2d
2d
3a
3a
600
1800
160
80
16
24
2
2 (1st cycle)
3 (2nd cycle)
9
10
4 (3rd cycle)
3a
2300
24
72
2.5
>99
88
11
12[c]
13[c]
14[c]
15
3c
3e
3e
3e
3e
70
100
500
1500
50
50
50
1500
70
24
24
24
>99
>99
>99
98
>99
>99
>99
>99
2 (1st cycle)
2 (2nd cycle)
2 (3rd cycle)
19
16
17
18[c]
19[c]
3f
3g
24
a Reactions were performed at room temperature in water (3 mL) using
the resin supported catalyst and the proper amount of 4a under 4 bar H2
unless otherwise stated. Conversion was determined by 1H NMR.
Enantiomeric excess analyzed by chiral GC or HPLC. b Reaction time
in hours. In recycling experiments, the number of the cycle is stated in
brackets. c Reaction performed in 1 mL of water.
Hydrogenations of β-aryl-dehydroaminoacids in water
The satisfactory results obtained with 4a committed us to study
the more challenging hydrogenation of 4b in water. This
reaction is hampered by the low solubility of this compound in
water (7.3 × 10ꢀ3 mol/L at 25 ºC),27 as substrate amounts
typically used in the present hydrogenations (0.06ꢀ0.3 mol/L,
for S/C = 100ꢀ500) are well above this solubility value. As an
alternative to the substrate slurry, we have initially tested a
mixture of water and environmentally friendly 2ꢀMeꢀthf (9:1
v/v, reaction conditions A), which is able to dissolve the
required amount of 4b. Hydrogenation of the resulting solution
with catalyst precursor 2d provided full conversion for a
reaction performed at S/C = 120 with 88 % ee (entry 1, Table
4). On the other hand, precatalyst 3a showed a very slow
reaction under these conditions, with a conversion lower than
10 % in 14 h (entry 2). In contrast, 3e provided full conversion
and a remarkable 96 % ee (entry 3). Moreover, an increase in
reaction temperature up to 40 ºC only caused a small decrease
on enantioselectivity (94 % ee, entry 4).
provided by 3a
.
Following the dissimilar performance of 2d and 3a, we
rationalized that the use of a phosphite fragment with
intermediate steric properties could provide a better catalyst.
Complex 3e, characterized by a binaphthyl fragment with
methyl substituents at positions 3 and 3’, was accordingly
prepared and tested. We were delighted to observe that the
corresponding catalyst showed both good activity and
enantioselectivity. Thus, it finished in 24 h a reaction prepared
at S/C = 100 with 97 % ee (entry 12). Moreover, this catalyst
exhibited enough activity to complete reactions prepared at S/C
ratios of 500 and 1500 with 96 and 93 % ee (entries 13, 14),
respectively. Most remarkably, very low Rh leaching (lower
than 0.8 %) was observed in both reactions. In addition, this
catalyst maintained a good performance upon recycling. Thus,
full conversion was obtained in three cycles while the
enantioselectivity observed in the first cycle (89 % ee, entry 15)
improved up to 94 and 95 % ee in the second and third cycles,
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As an additional approach to facilitate the hydrogenation of 4b enantioselectivity was observed (92 % ee, entry 3). In contrast,
in water, we have considered the addition of a surfactant to catalysts formed from 2d and 3e were more active and finished
disperse the substrate in the reaction media. In order not to the reaction in 14 h at room temperature under 4 bar H2 (entries
interfere in the electrostatic catalyst immobilization, a polar 4, 5). Worth of noting, 3e provided
a
remarkable
surfactant instead of an ionic one was preferred. Thus, a set of enantioselectivity of 97 % ee. Also pertinent to note, an
reactions were prepared by adding TritonꢀX100 to the reaction increase in reaction temperature up to 40 ºC had a negligible
medium (reaction conditions B).28 Initially, a reaction under effect on enantioselectivity (entry 6). Under these conditions,
these conditions using catalyst precursor 3a and 10 % mol of complex 3f also provided a high catalyst activity and a good
surfactant relative to substrate, showed a very slow reaction and enantioselectivity (91 % ee, entry 7), while 3h offered high
a low conversion was observed after a prolonged reaction time conversion (90 %) and an outstanding enantioselectivity (97 %
(30 %, entry 5). Alternatively, the use of complex 3e under ee, entry 8).
these reaction conditions, led to complete conversion and a high Among these catalysts, 3e displayed a suitable performance.
enantioselectivity (96 % ee, entry 6). Moreover, a similar Initially, a reaction prepared at room temperature and S/C ratio
performance was observed at a S/C ratio of 200 (97 % ee, entry of 500 showed high enantioselectivity (97 % ee), although the
7). In addition, a decrease by half of the amount of surfactant conversion was only moderate (75 %, entry 9). However,
did not affect catalyst performance appreciably (entry 8). raising the reaction temperature to 40 ºC significantly increased
Moreover, an increase in temperature up to 40 ºC only produces conversion to 93 %, without an important effect on
a small decrease in enantioselectivity (95 % ee, entry 9). A enantioselectivity (entry 10). Finally, full conversion and a
further reduction of the amount of surfactant to 2.5 mol % and remarkable enantioselectivity of 95 % ee were obtained at 50
of the catalyst loading (S/C = 500) also showed full conversion, ºC (entry 11).
while enantioselectivity was reduced slightly (93 % ee, entry To the best of our knowledge, the results presented in Table 5
10).
provide the highest enantioselectivities to date in the
hydrogenation of 4b in neat water. Most interestingly, aside
from the practical advantages associated to catalyst
heterogenization, the support also has a remarkable effect on
catalyst performance. Thus, the hydrogenation of 4b in H2O
using [Rh(NBD)(1e)](BF4) (S/C = 200, 4 bar H2, 40 ºC)
showed 40 % conversion and 32 % ee after 24 h. These values
indicate both lower catalyst activity and enantioselectivity than
Table 4 Hydrogenation of 4b with complexes
2
and
3
performed in
H2O/2ꢀMeꢀthf or in H2O/TritonꢀX100a
Entry
1
2
Cond.b
A
A
A
A
B (10 %)
B (10 %)
B (10 %)
B (5 %)
B (5 %)
B (2.5 %)
Cat.
2d
3a
3e
3e
3a
3e
3e
3e
3e
3e
S/C
120
160
100
100
160
100
200
200
200
500
Time
14
14
18
18
40
18
18
18
18
24
% conv
>99
10
>99
>99
30
>99
>99
>99
>99
>99
% ee (Conf)
88 (R)
n.d.
3
96 (R)
94 (R)
88 (R)
96 (R)
97 (R)
96 (R)
95 (R)
93 (R)
4c
5
provided by corresponding supported catalyst 3e
.
6
7
Table 5 Hydrogenation of 4b with complexes and
2
3
in neat watera
8
9c
10c
Entry
1
Cat.
3a
3a
3a
2d
3e
3e
3f
3h
3e
3e
3e
S/C
160
160
160
120
100
100
100
130
500
500
500
Time
14
24
24
14
14
24
24
24
24
24
24
% conv
8
44
>99
>99
>99
>99
>99
90
% ee
98 (R)
98 (R)
92 (R)
89 (R)
97 (R)
96 (R)
91 (R)
97 (R)
97 (R)
96 (R)
95 (R)
2b
a Reactions were performed at room temperature using the resin supported
catalyst and the proper amount of 4b in the corresponding solvent (2 mL)
under 4 bar H2 unless otherwise stated. Conversion was determined by 1H
NMR. Enantiomeric excess analyzed by chiral GC or HPLC. b Conditions A:
reactions performed in H2O/2ꢀMeꢀthf (9:1 v/v); conditions B: TritonꢀX100
added, % mol relative to substrate in brackets. c Reaction at 40 ºC.
3b,c
4
5
6b
7b
8b
9d
75
93
>99
10b, d
11d, e
Considering the high water content of the swelled resin, results
obtained in the hydrogenation of 4b with catalyst precursor 3e
under conditions A and B, indicate that the supported catalyst is
able to provide good catalyst activity and enantioselectivity for
this substrate in an essentially aqueous reaction medium.
Accordingly, we rationalized that if the substrate has some
solubility in water, an effective hydrogenation of this substrate
could then be effected in neat water. Thus, we next explored the
hydrogenation of a slurry of 4b.6 Initially, complex 3a only
provided low conversion at room temperature (8 %), although
the corresponding catalyst afforded very high enantioselectivity
(98 % ee, entry 1, Table 5). In order to increase conversion, a
reaction at 40 ºC was also explored. This provided a moderate
conversion (44 %, entry 2) and a high enantioselectivity (98 %
ee). An alternative experiment prepared at 40 ºC under 20 bar
H2 showed a reaction completed, although a decrease on
a Reactions were performed at room temperature using the resin supported
catalyst and a slurry of 4b in water (1 mL) under 4 bar H2 unless otherwise
stated. Conversion was determined by 1H NMR. Enantiomeric excess
analyzed by chiral GC or HPLC. b Reaction at 40 ºC. c Reaction at 20 bar H2. d
Slurry in 6 mL of water. e Reaction at 50 ºC.
An analysis of the Rh leaching in hydrogenations of 4b in water
with complex 3e indicates generally low values. Thus, for type
A reaction conditions, Rh concentration was lower than 0.2
ppm, which corresponds to a leaching lower than 0.9 % (entry
3, Table 4). This value was however increased up to 2.4 % in
the reaction performed at 40 ºC (entry 4). On the other hand,
the use of 10 % mol surfactant in conditions of type B also
showed values lower than 0.9 % for reactions performed at
room temperature (entries 6, 7). In contrast, the metal leaching
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significantly increased up to 2.0 % for the reaction heated at 40 In contrast with the previous reactions,
p
ꢀBr substrate 4i
ºC (entry 9). Most remarkably, reactions performed in neat showed a different reactivity than previous enamides. Thus, a
water at 40 ºC exhibited a very low metal leaching. Thus, lower hydrogenation performed under our standard conditions
values than 0.5 % were observed for reactions performed at S/C afforded a product mixture (80 % conv.) composed by desired
ratios of 100 and 500 (entries 6, 10, Table 5). Likewise, the Rh product 5i and debrominated product 5b in a 50:50 ratio (entry
leaching also kept lower than 0.5 % for the reaction performed 10). On the other hand, the
at 50 ºC (entry 11). reaction towards the desired hydrogenated product 5j, although
It is also worth to comment that a comparison of results of it also showed an appreciable formation of 5b in the reaction.
hydrogenations of 4a and 4b indicates that both the nature of Thus, the 5j 5b ratio was 80:20 (75 % conversion, entry 11).
mꢀBr substrate 4j showed a cleaner
:
phosphine and phosphite fragments have a strong impact on the Pursuing more selective reactions with Br substituted
catalytic hydrogenation. On one hand, catalysts bearing a PPh2 substrates, complex 3f was also tested. The corresponding
fragment provided better results than those bearing catalyst afforded higher conversion and selectivity, providing
dialkylphosphino groups. On the other, substitution of the 80 % of 5i and 85 % of 5j, respectively, in the corresponding
phosphite biphenyl fragment is required for the attainment of products. Moreover, enantioselectivities were only slightly
high enantioselectivity. Moreover, the size of these substituents lower than those provided by 3e and values of 85 and 84 % ee,
also has an impact on catalyst activity. Thus, tꢀBu substituted were obtained for 5i and 5j, respectively (entries 12, 13).
3a provided the best enantioselectivities, but it displayed a
lower catalyst activity. In contrast, less sterically hindered 2d
and 3f provided higher catalyst activity but lower
enantioselectivities. Among them, complex 3e which possess
phosphite steric properties between the two prior limiting cases,
compromises both suitable catalyst activity and good
enantioselectivity.
Having achieved good results in the hydrogenation of
representative substrate 4b in water, we investigated the
asymmetric hydrogenation of related substrates 4cꢀ4j.
However, to broaden the scope of the present catalytic system
is not trivial, as the introduction of aryl substituents further
reduces substrate solubility in water, ranging between 1.4 × 10ꢀ3 Figure 1 Photographs of vials corresponding to hydrogenations of diverse
mol/L (4j) and 3.9 × 10ꢀ3 mol/L (4g) at 25 ºC.27 Initially,
hydrogenation of the pꢀMe enamide 4c using precatalyst 3e at
substrates 4 performed with complex 3e (4 bar H2, 40 °C, 24 h). (a): 4d (S/C =
250; 40 % conv.); (b): 4d (S/C = 100; > 99 % conv.); (c): 4e (S/C = 250; > 99 %
conv.); (d): 4b (S/C = 100; > 99 % conv.); (e): 4a (S/C = 100; > 99 % conv.).
40 ºC provided full conversion and 94 % ee (entry 1, Table 6),
although the catalyst was not reactive enough to complete a
reaction at S/C = 250 (entry 2). On the other hand, the
In order to provide additional information about the unexpected
debromination of 4i some additional experiments were also
performed. We first examined the behavior of 4i under standard
homogeneous hydrogenation conditions. Thus, complete
conversion of 4i into 5i (99 % ee, S/C = 100, 24 h) was
corresponding
with 96 % ee (entry 3). In addition, the
m
ꢀMe substrate 4d produced a complete reaction
ꢀMeO substrate 4e
p
provided full conversion and 95 % ee (entry 4). An increase to
S/C = 250 also showed a complete reaction, while the
enantioselectivity decreased down to 90 % ee (entry 5). On the
observed in
a
reaction performed with unsupported
[Rh(NBD)(1e)](BF4) in CH2Cl2. Moreover, formation of 5a
was not observed in the hydrogenation of 4i in MeOH using
complex 3e (>99 % conversion, 59 % ee, 14 h). It seems
therefore that the interplay of water and the supported catalyst
is required for debromination. Moreover, we have observed that
5i can undergo the debromination reaction under hydrogenation
conditions. Thus, when a solution of 5i was exposed to 4 bar H2
in the presence of 3e, a mixture of 5a and 5i in 15:85 ratio was
observed after 14 h at 40 ºC. As expected, this reaction was not
observed when 3e was substituted by the complexꢀfree Liꢀresin.
It is worth noting that along with the debromination we have
observed a significant Li leaching of the resin, while Rh
leaching remained lower than 0.5 %. Thus, for hydrogenations
of 4i and 4j (0.06 mmol of substrate in 1 mL of water) using
complex 3e (entries 10, 12) values of [Li] = 3.9 × 10ꢀ3 M (22 %
Li leaching) and [Li] = 3.6 × 10ꢀ3 M (20 % Li leaching) were
other hand the
mꢀMeO enamide 4f also yielded a complete
reaction and 97 % ee under our standard conditions (entry 6). In
contrast to the above results, dimethoxy substrate 4g was less
reactive and only 60 % conversion was observed, although it
provided a high enantioselectivity (96 % ee, entry 7). However,
an increase in reaction temperature up to 50 ºC yielded full
conversion without erosion on enantioselectivity (97 % ee,
entry 8). Moreover, pꢀF substrate 4h also provided good results,
with full conversion and 96 % ee under our standard conditions
(entry 9). It is also pertinent to comment on the visual changes
produced by the reaction. Thus, hydrogenations providing low
conversion clearly show the presence of remaining solid
substrate (Figure 1a). In reactions with high conversion,
disappearance of suspended solid is observed and product
5 can
generate a new oily phase over the aqueous one (Figures 1bꢀ
1c), or apparently be dissolved in the aquatic phase (Figures 1dꢀ
1e).
obtained, respectively. As a reference value, [Li] = 1.1 × 10ꢀ3
M
6 | J. Name., 2012, 00, 1-3
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(6 % Li leaching) was observed after the hydrogenation of 4b Finally we attempted to perform catalyst recycling in water
under identical reaction conditions. In contrast, in the with complex 3e. At this regard it should be recalled that due to
hydrogenation of 4i with 3e in MeOH, a negligible Li leaching their low solubility, solid substrates 4bꢀ4j cannot be transferred
was observed (0.1 %). We speculated that this leaching could as water solutions at the required concentration for the
be favored by the formation of HBr under hydrogenation hydrogenations. Moreover, the present hydrogenation catalysts
30
conditions,29,
which should result in the generation of 5b are very reactive towards oxygen, therefore recycling
from 5i (or of 4b from 4i).31 Thus, the presence of acid in the operations should be made under an inert atmosphere or
solution may produce some Li/H exchange in the resin, due to preferably under hydrogen. Upon these considerations we
the low selectivity coefficient of Li cation on polystyrene devised a simple procedure to add solid substrates to the reactor
sulphonated resin.32 According to this, treatment of Liꢀresin inside a piece of teflon tubing (see supporting information). To
(5.0 mg) with solutions of HBr (1.0 mL) at 40 ºC for 24 h test this procedure, we examined a hydrogenation of 4f. Results
showed a higher Li concentration when the concentration of obtained indicated full conversion and 97 % ee in the first and
acid was raised. Thus, when the latter grew from 0.006 M to second cycles (entries 22, 23), while unfortunately, a rapid
0.058 M, an increase in [Li] from 2.2 × 10ꢀ3 M to 7.3 × 10ꢀ3
was observed.
M
degradation in catalyst performance was observed in the third
and fourth cycles (entries 24, 25). It is worth noting that Rh
Besides these experiments, due to the high enantioselectivitity concentration in solution kept lower than 0.2 ppm (Rh leaching
displayed in the hydrogenation of 4b, we were also interested in lower than 2 %) in all cycles. We therefore speculated that the
examining the performance of complex 3h in the hydrogenation loss of catalyst performance observed may be associated to the
of substrates 4c
conditions were
ꢀ
4j. Then, a set of reactions under standard introduction of oxygen traces upon recycling. Therefore, an
prepared (entries 14ꢀ21). The improved reactor design is required to implement an efficient
enantioselectivities observed were generally high, between 94 catalyst recycling of the present catalysts in water.
and 98 % ee, with the exception of dimethoxy substituted
Mechanistic studies
substrate 4g, for which a very low conversion and a value of 86
%
ee was obtained (entry 18). Despite the high In order to provide additional information, we have monitored
enantioselectivities, the catalytic activity shown by complex 3h by gel phase 31P{1H} NMR the progress of a selected
was however lower than that provided by 3e
.
hydrogenation.33 Initially, we observed that complex 3g
provided a spectrum of satisfactory quality in CD3OD. In this
spectrum the typical pattern for a phosphineꢀphosphite ligand
coordinated to a rhodium atom is observed (Figure 2a). The
phosphite group appears as a doublet of doublet centered at
Table 6 Hydrogenation reactions of 4c
ꢀ
4f in watera
Entry
1
2
3
4
Subs.
4c
4c
4d
4e
4e
4f
4g
4g
4h
4i
4j
4i
4j
4c
4d
4e
4f
4g
4h
4i
Cat.
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3f
S/C
100
250
100
100
250
100
100
100
100
100
100
100
100
130
130
130
130
130
130
130
130
50
Time (h)[b]
% conv
>99
40
>99
>99
>99
>99
60
>99
>99
80
75
85
95
50
90
55
65
15
80
25
% ee
94
94
96
95
90
97
96
97
96
87
88
85
84
96
95
96
96
86
94
98
94
97
97
86
n.d.
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
2
123.6 ppm (1JRhP = 259 Hz, JPP = 69 Hz), while for the
phosphine, the corresponding signal appears as a doublet of
doublet centered at 7.4 ppm (1JRhP = 147 Hz). It is worth noting
that a spectrum of the methanol supernatant only showed low
intense singlets assigned to phosphorus impurities after
standing 3 days at room temperature, indicating the stability of
the catalyst precursor under these conditions. As expected,
these data closely match the data for corresponding soluble
5
6
7
8[c]
9
10[d]
11[e]
12[f]
13[g]
14
3f
[Rh(NBD)(1g)](BF4) in CD3OD [δPO = 123.1 (dd,
J(P, Rh) =
3h
3h
3h
3h
3h
3h
3h
3h
3e
257 Hz,
Hz].
J(P, P) = 68 Hz, PO), δPC = 8.7 (dd, J(P, Rh) = 147
15
16
17
18
19
20
21
24
24
24
24
24
When the sample of 3g was pressurized with 4 bar of H2, fast
reaction was detected and immediate disappearance of 3g was
observed along with the formation of new species 6g (Scheme
3). The latter is characterized in the 31P{1H} NMR by two
multiplets centred at 127.7 and 33.0 ppm (Figure 2b),
corresponding to phosphite and phosphine groups, respectively
(Figure 2c). Remarkably, no signals were detected in the
hydride region of the 1H NMR experiment. By comparison with
4j
4f
50
22[h]
23[h]
24[h]
25[h]
12 (1st cycle)
12 (2nd cycle)
12 (3rd cycle)
12 (4th cycle)
>99
>99
60
50
50
50
5
a Reactions were performed at 40 ºC using the resin supported catalyst and a
slurry of substrate in water (1 mL) under 4 bar H2 unless otherwise stated.
Conversion was determined by 1H NMR. Enantiomeric excess analyzed by
chiral GC or HPLC. b In recycling experiments, the number of the cycle in
brackets. c Reaction at 50 ºC. d Mixture of 5i:5a products in a 50:50 ratio
obtained. e Mixture of 5j:5a products in a 80:20 ratio obtained. f Mixture of
5i:5a products in a 80:20 ratio obtained. g Mixture of 5j:5a products in 85:15
ratio obtained. hSlurry in 6 mL of water.
the
spectrum
obtained
after
hydrogenation
of
[Rh(NBD)(1f)](BF4) in CD3OD, 6g can be assigned to the
supported methanol solvate. As a next step we investigated the
formation of complexes of enamides
4. Thus, addition of 3
equivalents of 4b to 6g showed a mixture of the latter and new
species 8g in ca. 3:1 ratio.34 A further addition of 4b up to 12
equivalents increased the amount of 8g and a 0.7:1 6g:8g ratio
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was then observed (Figure 2d). Complex 8g is characterized by The NMR study described above indicates a close similarity
a doublet of doublet in the coordinated phosphine region between the homogeneous and the resin immobilized catalytic
centered at 0.3 ppm (1JRhP = 152 Hz, 2JPP = 70 Hz), while in the hydrogenation systems. It should be recalled, in connection
phosphite region signals corresponding to 6g and 8g overlap in with this, that a product labelling at position
α in the
a broad doublet of doublet centred at 128.2 ppm (1JRhP = 246 hydrogenation of 4a and 4b in D2O using water soluble
2
10d
Hz, JPP = 70 Hz). Data for 8g are in good accord with those of complexes has been described in the literature.10b,
This
soluble enamide adducts prepared in our laboratory.23c For selective labeling has been proposed to result from an exchange
further comparison, a sample of [Rh(CD3OD)2(1g)](BF4) was between the hydridoꢀalkyl intermediate and D2O, leading to the
treated with 20 equivalents of 4b. This showed a mixture of the corresponding Rh deuteride (Scheme 4).
deuteromethanol adduct and [Rh(4b)(1g)](BF4) in a 1:3 ratio.
O
S
O
S
H2
The latter species was characterized by phosphine and
+
[Rh(CD3OD)2(1g)]+
-O
-O
1g
[Rh(NBD)( )]
2
phosphite signals at
δ
= 0.8 (1JRhP = 151 Hz, JPP = 70 Hz) and
CD3OD
O
O
2
= 128.4 (1JRhP = 243 Hz, JPP = 70 Hz), respectively (Figure
3g
6g
δ
2f). Thus, an analogous behavior is observed for the
immobilized and the homogeneous systems. On the other hand,
an addition of 3 equiv of 4a to 6g showed nearly full
displacement of CD3OD by the enamide. A subsequent increase
of the amount of 4a up to 12 equiv showed full conversion into
the corresponding enamide adduct 7g. This compound show
rather similar data to 8g. Thus, 7g is characterized by two
4
(excess)
NBD
O
S
O
S
H2
or
-
+ O
1g +-O
[Rh(4)(1g)]
[Rh(CD3OD)2( )]
5a
5b
-
O
O
6g
4
4a 7g 4b 8g
( ), )
=
(
Scheme 3
doublet of doublet centered at
Hz) and a broad doublet of doublet at
2JPP roughly ranging 230 and 70 Hz, respectively. Moreover,
δ
= 2.3 (1JRhP = 152 Hz, 2JPP = 70
1
δ
= 127.5 with JRhP and
With the intention to investigate if such effect operates in the
present system, we have prepared some hydrogenations of 4b in
D2O. Thus, the reaction with complex 2d exhibited a deuterium
exposing the latter sample to 4 bar H2 only showed the presence
of the supported deuteromethanol adduct 6g
, while no
labelling of 67 % in position
was observed in position . On the other hand, the reaction
performed with complex 3e showed 40 % D in the position
while no labelling was observed in position (entry 3). Finally,
a smaller labelling (5 %) was observed in the reaction
performed with complex 3a (entry 2). Likewise, in
hydrogenations of 4a, a low labelling (4 %, entry 4) was
observed in the reaction using 3a, while the corresponding
hydrogenation using 2d as catalyst precursor showed a
significantly higher value of deuterium incorporation in
α (entry 1, Table 7), while 9 % D
intermediates in the catalytic cycle were observed. In
connection with this, Reek and coworkers reported a similar
observation in studies with Rh complexes bearing Indolphos
ligands, which possess similar electronic properties to PꢀOP.35
As a final remark, the high coordinating ability of NBD in the
present system should be stressed. Thus, addition of an excess
β
α,
β
of NBD (12 equivalents) to the 6g
regenerated 3g (Figure 2e). A similar observation was observed
in the case of 8g
:8g mixture cleanly
.
position
α
(75 %, entry 5).
+
+
Me
Me
O
O
β
+
α
NH
CO2Me
NH
D2O
P
S
P
P
P
R
P
P
Rh
+
Rh
Rh
D
S
S
NHAc
S
-HDO
CO2Me
CO2Me
D
H
5a
R = H ( -d),
R
R
Ph (5b-d)
R = H, Ar
Scheme 4 Proposed formation of deuterated 5a-d and 5b-d.
These results outline a similar behavior to that reported for
water soluble catalysts. Moreover, in good accord with the
proposed labelling mechanism involving exchange between the
alkylꢀhydride intermediate and water (i.e. after the generation
of the stereogenic center), the enantioselectivities obtained in
these reactions are very close to those obtained in H2O. Finally,
a dependence of labelling with the steric properties of the
ligand, being the labelling higher with less sterically
encumbered ligands has been observed. At this regard, a slower
Figure 2 Gel-phase 31P{1H} NMR spectra in CD3OD of the following samples: (a)
complex 3g; (b) after pressurizing with 4 bar H2; (c) 0.5 h later; (d) after addition
of 12 equivalents of 4b; (e) after addition of 12 equivalents of NBD; (f) 31P{1H}
NMR spectrum of sample obtained after hydrogenation of [Rh(NBD)(1g)](BF4) in
reaction with D2O due to steric hindrance caused by the tꢀBu
CD3OD followed by addition of 20 equivalents of 4b
.
substituents may tentatively be proposed to explain the results.
8 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5GC00485C
Table 7 Hydrogenation of 4aꢀ
4b performed in D2Oa
and Mass Spectrometry Services of Universidad de Sevilla
(CITIUS) for the analytical and mass spectrometry
determinations, respectively.
Entry
1
2
Subst.
Cat.
S/C
120
160
100
500
500
% conv
95
40
>99
80
>99
% eeb
% D (α)
67
5
40
4
75
4b
4b
4b
4a
4a
2d
3a
3e
3a
2d
85 (83)
97 (98)
96 (97)
99 (99)
83 (84)
Notes and references
3
4c
5c
a
Instituto de Investigaciones Químicas (IIQ) and Centro de Innovación
en Química Avanzada (ORFEOꢀCINQA), CSIC and Universidad de
Sevilla, Américo Vespucio 49, 41092 Sevilla, Spain.
b Istituto di Chimica dei Composti Organometallici (ICCOMꢀCNR), Area
di Ricerca CNR di Firenze, via Madonna del Piano 10, 50019 Sesto
Fiorentino (FI), Italy.
a Conditions: reactions performed at 40 ºC in D2O for 24 h unless otherwise
stated. Conversion was determined by 1H NMR. Enantiomeric excess
analyzed by chiral GC or HPLC. b Enantioselectivity of the corresponding
reaction in H2O in brackets. c Reaction performed at room temperature.
Electronic Supplementary Information (ESI) available: [Synthesis and
characterization of ligands and Rh complexes, representative procedures
for asymmetric hydrogenation, NMR spectra and chromatograms]. See
DOI: 10.1039/b000000x/
Conclusions
In this contribution we present a convenient immobilization of
rhodium phosphineꢀphosphite catalysts on an ionic resin. The
procedure is simple, as it does not require chemical
modification of the readily accessible cationic rhodium
complexes, and provides the supported complexes in moderate
to high yield. The corresponding catalysts show a good
performance in the hydrogenation of 4a in MeOH, with
enantioselectivities up to 99 % ee. On the other hand, no
catalyst was found to provide both high activity and
enantioselectivity in the hydrogenation of 4b in MeOH.
Moreover, a high metal leaching was observed in these
1
(
a
) W. Tang and X. Zhang, Chem. Rev., 2003, 103, 3029; (
b
) J.ꢀH.
) D.
Xie, S.ꢀF. Zhu and Q.ꢀL. Zhou, Chem. Rev., 2010, 111, 1713; (
c
J. Ager, A. H. M. de Vries and J. G. de Vries, Chem. Soc. Rev., 2012,
41, 3340.
2
For some recent examples, see: (
Zhang, Y. Horiuchi, M. Sugiya, K. Yoshida, A. Yanagisawa and I. D.
Gridnev, J. Am. Chem. Soc., 2012, 134, 1754; ( ) G. Liu, X. Liu, Z.
Cai, G. Jiao, G. Xu and W. Tang, Angew. Chem. Int. Ed., 2013, 52
4235; ( ) K. Dong, Y. Li, Z. Wang and K. Ding, Angew. Chem. Int.
Ed., 2013, 52, 14191; ( ) W. Chen, F. Spindler, B. Pugin and U.
Nettekoven, Angew. Chem. Int. Ed., 2013, 52, 8652; ( ) J. Jiang, Y.
Wang and X. Zhang, ACS Catal., 2014, , 1570.
) H.ꢀU. Blaser, B. Pugin and F. Spindler, J. Mol. Catal. A Chem.
2005, 231, 1; ( ) N. B. Johnson, I. C. Lennon, P. H. Moran and J. A.
Ramsden, Acc. Chem. Res., 2007, 40, 1291; ( ) C. S. Shultz and S.
) P. Etayo and A.
a) T. Imamoto, K. Tamura, Z.
b
,
reactions. In contrast,
a suitable catalyst (3e) for the
c
hydrogenation of 4b in water, providing good activity and an
enantioselectivity up to 97 % ee, was found following a rational
approach. For this substrate, extensively studied in the
literature, this is the highest value obtained in neat water. This
catalyst has a broader scope and provides both good activity
and enantioselectivity, between 87 and 97 % ee, in the
d
e
4
3
4
5
(a
,
b
c
hydrogenation of several
βꢀaryl dehydroaminoacids (4cꢀ4j).
W. Krska, Acc. Chem. Res., 2007, 40, 1320; (
d
Thus, besides to the general advantage on an easier catalyst
separation provided by immobilization, the high swelling of the
resin supporting the catalyst, enables to perform efficient
hydrogenations in water in the present case. Moreover, the
hydrophilic support significantly enhances the performance of
the catalyst in comparison with that observed by the
corresponding tetrafluoroborates in water. On the other hand, in
the hydrogenation of brominated substrates 4i and 4j an
unexpected formation of debrominated 5b was observed as a
side reaction. This phenomenon seems associated with the use
of both water and the Liꢀresin. In addition, NMR studies show a
similar behavior of the supported catalysts to the homogeneous
one. Likewise, a similar deuterium labelling than reported in
the literature for homogeneous hydrogenation of 4a in water,
has also been observed in the present system.
VidalꢀFerran, Chem. Soc. Rev., 2013, 42, 728.
(
a
) R. A. Sheldon, Green Chem., 2005,
Chem. Commun., 2008, 3352; ( ) B. H. Lipshutz, N. A. Isley, J. C.
Fennewald and E. D. Slack, Angew. Chem. Int. Ed., 2013, 52, 10952;
7, 267; (b) R. A. Sheldon,
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Acknowledgements
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The research leading to these results has received funding from
the European Community's Seventh Framework Programme
through the Marie Curie Initial Training Network NANOꢀ
HOST (grant agreement n° 215193), Junta de Andalucía
(2009/FQMꢀ4832) and CSIC (Grant 201480E031). We thank
Carmen MorenoꢀMarrodán and Francesca Liguori for technical
assistance. We also gratefully acknowledge the Microanalysis
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Green Chemistry
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DOI: 10.1039/C5GC00485C
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Green Chemistry
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DOI: 10.1039/C5GC00485C
Chiral Rh phosphine-phosphite catalysts immobilized on ionic resins for the enantioselective
hydrogenation of olefins in water
P. Kleman,a P. Barbarob * and A. Pizzanoa *
Rh phosphine-phosphite chiral catalysts immobilized on ion exchange resins provides highly
enantioselective hydrogenation of enamides in water.