Mesoporous silica nanosphere supported ruthenium catalysts for asymmetric hydrogenation

Article abstract of DOI:10.1002/anie.200705656

(Chemical Equation Presented) Chiral Ruthenium-diphosphine-diamine complexes with a siloxy pendant are grafted onto mesoporous silica nanospheres. The resulting supported ruthenium catalysts are highly active for the asymmetric hydrogenation of aromatic ketones to afford chiral secondary alcohols and racemic aryl aldehydes to give chiral primary alcohols (see scheme). This immobilization strategy should be amenable to the design of similar heterogeneous catalysts.

Full text of DOI:10.1002/anie.200705656

Angewandte
Chemie
DOI: 10.1002/anie.200705656
Supported Catalysts
Mesoporous Silica Nanosphere Supported Ruthenium Catalysts for
Asymmetric Hydrogenation**
David J. Mihalcik and Wenbin Lin*
Asymmetric catalysis is a powerful method for the synthesis
of pharmaceutically important chiral molecules.[1] Numerous
highly selective chiral catalysts have been developed recently,
but their practical applications in industrial processes are
often hindered by their high costs as well as difficulties in
removing trace amounts of toxic metals from the organic
products.[2] Many different approaches have been developed
to immobilize homogeneous asymmetric catalysts in order to
overcome these problems,[3] with the covalent attachment of
chiral catalysts to mesoporous silica materials being one of
the most promising methods for generating heterogenized
asymmetric catalysts.[4] MCM- and SBA-type silicas provide
ideal supports for asymmetric catalyst immobilization owing
to their ordered structures, very high surface areas, and
uniform, large, and tunable pore diameters.[5]
others have shown that base activation of such chiral
ruthenium complexes gives highly active and enantioselective
catalysts for the asymmetric hydrogenation of prochiral
ketones.[9] More recently, chiral RuCl2–diphosphine–diamine
complexes have been shown to be highly active catalysts for
the asymmetric hydrogenation of racemic aldehydes in the
synthesis of chiral primary alcohols via a dynamic kinetic
resolution process.[10] Our immobilization strategy relies on
tethering the chiral ruthenium complexes to MSNs via a
siloxy group installed in the diamine ligand. As shown in
Scheme 1, chiral complexes 1–5, which contain pendant siloxy
Recent elegant studies by Lin et al. and others have shown
that mesoporous silica materials can be obtained as uniform
nanospheres under appropriate synthetic conditions.[6] Mes-
oporous silica nanospheres (MSNs) have further been shown
to be excellent supports for bifunctional catalysts that exhibit
interesting cooperative catalytic activities.[7] Herein we dem-
onstrate the utility of MSNs as supports for ruthenium
catalysts for the asymmetric hydrogenation of aromatic
ketones to afford chiral secondary alcohols and racemic
arylaldehydes to give chiral primary alcohols. We envisage the
generation of highly active heterogeneous catalysts by taking
advantage of both the large channel diameters (> 2 nm) of
MSNs and short diffusion lengths for the organic substrates as
a result of small nanoparticle sizes (< 1 mm). The short
diffusion length is of practical importance owing to the
typically large size (and hence hindered diffusion) of organic
substrates used in asymmetric catalytic processes.
We chose chiral RuCl2–diphosphine–diamine complexes
as model precatalysts to be supported on the MSNs because
these complexes have been shown to be air- and moisture-
stable and can be readily purified by silica-gel chromatog-
raphy.[8] Most importantly, seminal studies by Noyori and
[*] D. J. Mihalcik, Prof. W. Lin
Department of Chemistry, CB#3290
University of North Carolina, Chapel Hill, NC 27599 (USA)
Fax: (+1)919-962-2388
Scheme 1. Synthesis of complexes 1–5 and their immobilization on
MSN-48.
E-mail: wlin@unc.edu
Homepage: http://www.chem.unc.edu/people/faculty/linw/wlin
dex.html
groups, were prepared by heating a mixture of [{RuCl2(p-
cymene)}2] and a chiral diphosphine in 1,2-dichloroethane/
DMF at 808C followed by treatment with siloxy-derivatized
chiral 1,2-cyclohexanediamine (siloxy-DACH). Five chiral
[**] We acknowledge financial support from the NSF (CHE-0512495).
We thank N. A. Zafiropoulos and K. M. L. Taylor for experimental
help and Dr. M. Ogasawara for a gift of tBu-SegPhos. W.L. is a
Camille Dreyfus Teacher-Scholar.
diphosphines,
namely
2,2’-bis(diphenylphosphino)-1,1’-
binaphthyl (binap), 2,2’-bis(diphenylphosphino)-4,4’-bis(tri-
methylsilyl)-1,1’binaphthyl (TMS-binap), [2,2’-bis(di-3,5-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200705656.
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xylylphosphino)-1,1’-binaphthyl (Xyl-binap), (4,4’-bi-1,3-ben-
zodioxole)-5,5’-diylbis(diphenylphosphine) (SegPhos), and
(7,7’-tert-butyl-4,4’-bi-1,3-benzodioxole)-5,5’-diylbis(diphe-
nylphosphine) (tBu-SegPhos), were used.[11] All chiral com-
plexes 1–5 are diamagnetic and stable to both air and
moisture. They are readily purified by silica gel chromatog-
raphy and were characterized by 1H and 31P{1H} NMR
spectroscopy as well as ESI mass spectrometry.
Precatalysts 1–5 display a characteristic pair of doublets in
the range d = 37–49 ppm in their 31P{1H} NMR spectra due to
the unsymmetrical nature of the monosubstituted diamine.
Their ESI mass spectra show the presence of peaks corre-
sponding to the loss of a chloride ligand from the molecular
ion, thus confirming the nature of ruthenium(II) precatalysts
1–5.
Mesoporous silica nanospheres with three-dimensional
channels (MSN-48) were prepared according to a literature
procedure by hydrolysis and condensation of tetraethoxysi-
lane in a water/ethanol solution of cetyltrimethylammonium
bromide and ammonia.[12] The particles were isolated by
centrifugation and calcined at 6008C to remove the surfactant
template. The spherical morphology of MSN-48 is clearly
visible in the SEM image (Figure 1a). The diameters of MSN-
48 particles are tunable from 75 nm to 1 mm, depending on the
reagent concentrations used. The TEM image shows striation
across the nanosphere, thereby indicating the regularity of the
pores (the ordered channels) over the whole particle (Fig-
ure 1b). The ruthenium complexes 1–5 were grafted onto
MSN-48 by refluxing in toluene for 24 h. Nitrogen adsorption
isotherms indicated that the calcined MSN-48 has a Barrett–
Joyner–Halenda (BJH) surface area of 1737 m2 gÀ1 and a pore
diameter of 2.2 nm (Figure 1c). The solid 1’ obtained upon
grafting 1 has a BJH surface area of 1131 m2 gÀ1 and a pore
diameter of 1.7 nm. The reduced surface area and pore
diameter of 1’ suggests attachment of the ruthenium complex
1 to the surface of MSN-48 via the siloxy linkage. Consistent
with this, the pore volume decreases from 1.07 cm3 gÀ1 for
MSN-48 to 0.61 cm3 gÀ1 for 1’.
The ruthenium precatalyst loadings on MSN-48 were
estimated by thermogravimetric analysis (TGA), which gives
the percent weight loss due to the organic moieties, and the
ruthenium content was determined by direct current plasma
(DCP) spectroscopy. The MSN-supported materials 1’–5’
prepared in this fashion have a consistent ruthenium(II)
precatalyst loading of 5–7 wt% as determined by TGA and
DCP.
Upon activation with base co-catalysts, complexes 1–5
were shown to be highly active for the homogeneous
asymmetric hydrogenation of aromatic ketones, with enan-
tiomeric excesses of up to 94% ee (Table 1). Control experi-
ments with [Ru(binap)(1,2-cyclohexanediamine)Cl2] (6) indi-
cated that the propyl(triethoxy)silane pendant in 1 enhances
the enantioselectivity significantly. It is well known that
RuCl2–diphosphine–diamine homogeneous catalysts with two
primary amine groups (such as 1,2-diphenylethylenediamine
and 1,1-bis(4-methoxyphenyl)-3-methyl-1,2-butanediamine)
provide a significant enhancement of enantioselectivity
compared with either bulky substituents on the 4,4’-positions
of the binaphthyl framework or bulkier 3,5-dimethylphenyl
Figure 1. a) Representative SEM image of the MSN-48 showing that
the particles range from 300 nm to 1 mm in diameter in this batch.
b) TEM image of an MSN-48 particle showing the striations across the
nanospheres that correspond to the ordered channels. c) Nitrogen
adsorption isotherms for the calcined MSN-48 and the MSN-48
sample (1’) grafted with precatalyst 1. d) Pore-size distribution for the
calcined MSN-48 and 1’.
groups on the phosphino moieties.[8,9] Such a beneficial
substituent effect is absent in complexes 1–5 with an alkylated
1,2-cyclohexanediamine ligand. Thus, the ruthenium(II) com-
plex with a binap ligand (1) gives higher ee values than those
with TMS-binap (2) or Xyl-binap (3), whereas the tBu groups
on the 7,7’-position of SegPhos (in 5) significantly enhance the
enantioselectivity, presumably as a result of the difference in
dihedral angles between the binaphthyl system and the
SegPhos system.
Upon activation with KOtBu, the MSN-48-immobilized
ruthenium complexes 1’–5’ are also very active catalysts for
the asymmetric hydrogenation of aromatic ketones. As shown
in Table 1, no decreases of catalytic activities were observed
for the immobilized catalysts, although 1’–5’ exhibit lower
enantioselectivities than their parent homogeneous catalysts.
The highest ee value of 82% was obtained for the hydro-
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Table 1: Enantioselectivities [% ee] for the asymmetric hydrogenation of
aromatic ketones with complexes 1–5 and their heterogeneous coun-
terparts supported on MSN-48 (1’–5’).[a]
Table 2: Enantioselectivities [% ee] for th asymmetric hydrogenation of
aryl aldehydes with complexes 1–3 and their heterogeneous counterparts
supported on MSN-48 (1’–3’).[a]
Homogeneous catalyst
Ar
R
Homogeneous
Heterogeneous
Ar
1
2
3
4
5
6
1
2
3
1’
2’
3’
Ph
82
94
83
83
71
80
89
77(86)
80(83)
80(97)
64(84)
64(86)
47(80)
76
79
78
90
76
86
68
84
67(95)
79(97)
61(96)
67(95)
56(95)
70(96)
74(93)
80
92
82
81(94)
76
62(93)
73(94)
72(94)
62(94)
61(91)
63(95)
78(94)
Ph
Ph
Ph
Me
iPr
nBu
Me
Me
Me
42
35
40
47
53
44
70
97
80
69
76
72
72
99
92
74
83
72
52
52
55
52
63
68
76
97
84
78
78
83
86
86
49
83
88
86
1-naphthyl
2-naphthyl
4-MeC6H4
4-ClC6H4
4-MeOC6H4
4-tBuC6H4
4-ClC6H4
4-MeOC6H4
2-Naphthyl
85
77
[a] All reactions were carried out under a hydrogen pressure of 700 psi in
the presence of ruthenium precatalyst and KOtBu in 2-propanol at room
temperature for 24 h. All the reactions were run with a 0.1 mol% catalyst
loading and were judged to be complete by HPLC and 1H NMR
spectroscopy. The ee values were determined by HPLC on a Chiralcel AD
column.
MSN-supported catalyst (mol% loading)
Ar
1’(0.8)
2’(0.7)
3’(1.0)
4’(1.1)
5’(0.9)
Ph
61(94)
67(96)
68
47
57
71
76(87)
82
66
72
59
52
66
60
62
49
53
58(97)
76
58(97)
60
51
53
73
72
69
61
57
56(97)
49
1-naphthyl
2-naphthyl
4-MeC6H4
4-ClC6H4
4-MeOC6H4
4-tBuC6H4
68
77
64(48)
69
that obtained with the soluble RuCl2–diphosphine–1,2-cyclo-
hexanediamine complexes examined by Zhou et al.,[10]
thereby suggesting the positive influence of the propyl(trie-
thoxy)silane pendant on the enantioselectivity of the dynamic
kinetic resolution process. It is of interest to note that there is
significant enantioselectivity enhancement with either bulky
substituents on the 4,4’-positions of the binaphthyl framework
(for 2) or bulkier 3,5-dimethylphenyl groups on the phosphi-
no moieties (for 3).
69(94)
[a] All reactions were carried out under a hydrogen pressure of 700 psi in
the presence of ruthenium precatalyst and KOtBu in 2-propanol at room
temperature for 24 h. All the homogeneous reactions were run with a
1 mol% catalyst loading. Conversions (%) and ee values (%) were
determined by GC on a Supelco b-Dex 120 column for all of the
secondary alcohols. [b] The catalyst loading for 1’–5’ was estimated
based on the ruthenium content determined by DCP. [c] All the reactions
went to completion except those where percent conversions are shown in
parentheses.
The MSN-48-supported ruthenium complexes 1’–3’ are
also highly active catalysts for the asymmetric hydrogenation
of racemic a-branched aryl aldehydes (Table 2). Interestingly,
unlike the asymmetric hydrogenation of aromatic ketones,
the immobilized catalysts 1’–3’ gave higher enantioselectivity
for most of the aryl aldehydes examined (with as much as a
24% increase of the ee value for the hydrogenation of a-2-
naphthylpropionaldehyde using 1 vs. 1’). The highest ee value
obtained for the heterogeneously catalyzed reaction is 97%
for 3-methyl-2-phenylbutanal with 2’. The different effects of
immobilization on the enantioselectivity of two asymmetric
hydrogenation reactions highlight the subtlety of catalyst
immobilization and the need to examine other reaction types
and immobilization strategies.
In summary, we have prepared chiral RuCl2–diphosphine–
diamine complexes with a siloxy functionality which can be
readily attached to a silica surface. We have successfully
immobilized these ruthenium complexes on mesoporous
silica nanospheres with three-dimensional channels, and
have demonstrated for the first time the utility of MSNs as
supports for ruthenium catalysts in the asymmetric hydro-
genation of aromatic ketones to afford chiral secondary
alcohols and racemic aryl aldehydes to give chiral primary
alcohols. The generality of this catalyst immobilization
strategy should allow the design of many highly active and
enantioselective heterogeneous asymmetric catalysts.
genation of 2-acetonaphthone using 2’ as catalyst. A similar
drop in enantioselectivities has been observed for many
asymmetric catalysts immobilized on bulk mesoporous sili-
cas.[13]
These highly active MSN-48-supported catalysts were
readily recovered by centrifugation and were shown to be
reusable for the asymmetric hydrogenation of aromatic
ketones. For example, for the hydrogenation of acetophe-
none, 1’ was recovered and reused at least five times, with
conversions of > 99%, > 99%, 89%, > 99%, and 65% and ee
values of 61%, 58%, 70%, 68%, and 65% for the five
consecutive runs. DCP measurements indicated that less than
4% of the ruthenium species leached from the MSN-
supported catalyst during each catalytic cycle.
Intrigued by recent elegant work concerning homoge-
neous asymmetric hydrogenation of racemic a-branched aryl
aldehydes by RuCl2–diphosphine–diamine complexes for the
synthesis of chiral primary alcohols,[10] we have also examined
the utility of MSN-48-immobilized ruthenium complexes in
such a dynamic kinetic resolution process (Table 2). At a
0.1 mol% catalyst loading, homogeneous catalysts 1–3 all
gave complete conversion of aryl aldehydes to their hydro-
genated products, with ee values as high as 99% (for 3-
methyl-2-phenylbutanal, which has an iPr group at the a-
position). This level of enantioselectivity is slightly superior to
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Experimental Section
Typical procedure: 1: A solution of (R)-binap (25 mg, 40.1 mmol) and
[{Ru(p-cymene)Cl2}2] (12.5 mg, 20 mmol) in dichloromethane (2 mL)
and DMF (0.5 mL) was heated at 508C under argon for 24 h and then
cooled to room temperature. (R,R)-Siloxy-DACH (12.8 mL,
40.1 mmol) was added and the mixture was heated at 508C for
another 24 h. The solvents were removed under reduced pressure to
yield a dark red solid, which was purified by silica gel column
chromatography with hexanes/ethyl acetate (2:1, v/v) as eluent.
Typical procedure: 3’: A mixture of 3 (11 mg, 8.9 mmol) and MSN-
48 (110 mg) in toluene (3 mL) was heated to reflux under argon for
24 h. After cooling to room temperature, the mixture was washed
with toluene (3 ” 10 mL) and dichloromethane (2 ” 10 mL). The
resulting MSN-48 material was dried under reduced pressure for
18 h. TGA and DCP indicated the ruthenium precatalyst loading to
be in the 5–7 wt% range.
Asymmetric Hydrogenation: The precatalyst (0.5 mmol) and
KOtBu (5 mmol) were added to a one-dram vial containing 50 mmol
of aromatic ketone and a stir bar inside a drybox. 2-Propanol (1 mL)
was added under argon and the vial was capped with a septum
punched with a needle. The reaction vessel was quickly transferred to
a stainless-steel autoclave and sealed. After purging six times with H2,
the final H2 pressure was adjusted to 700 psi. The autoclave was
depressurized after 24 h and the reaction mixture extracted with
diethyl ether. The ether layer was collected and passed through a
small silica gel column. The resulting solution was concentrated and
an aliquot was analyzed by GC to determine conversion and ee values.
The asymmetric hydrogenation of racemic aryl aldehydes was carried
out in a similar manner except the ee values were determined by
HPLC and the conversions were determined by HPLC and 1H NMR
spectroscopy.
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Received: December 11, 2007
Revised: February 20, 2008
Published online: July 9, 2008
Keywords: asymmetric catalysis · heterogeneous catalysis ·
.
hydrogenation · mesoporous materials · ruthenium
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