Application of tripodal linker units to immobilized rhodium complex catalysts for asymmetric hydrogenation

Article abstract of DOI:10.1246/cl.2011.212

The tripodal linker unit with one bromopropyl group and three anchoring silicon atoms was used to immobilize a chiral phosphinerhodium complex catalyst on an ordered mesoporous silica support. The rhodium and phosphorus leaching levels into the reaction solution after asymmetric hydrogenation were lower for this catalyst than for immobilized catalysts prepared using conventional triethoxysilane.

Full text of DOI:10.1246/cl.2011.212

doi:10.1246/cl.2011.212
212
Published on the web January 26, 2011
Application of Tripodal Linker Units to Immobilized Rhodium Complex Catalysts
for Asymmetric Hydrogenation
Norihisa Fukaya,*1 Shun-ya Onozawa,1 Masae Ueda,1 Takayuki Miyaji,2 Yukio Takagi,2
Toshiyasu Sakakura,1 and Hiroyuki Yasuda*1
1National Institute of Advanced Industrial Science and Technology (AIST),
Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565
2N.E. CHEMCAT Corporation, 678 Ipponmatsu, Numazu, Shizuoka 410-0314
(Received December 10, 2010; CL-101046; E-mail: h.yasuda@aist.go.jp, n.fukaya@aist.go.jp)
The tripodal linker unit with one bromopropyl group and
The tripodal linker unit containing three isopropoxysilyl
moieties 1b was prepared in a one-pot process via the iridium-
catalyzed hydrosilylation of triallyl(3-bromopropyl)silane with
dimethylchlorosilane, followed by treatment of the resulting
tris(dimethylchlorosilyl) compound with triethylamine in isopro-
pyl alcohol, as described previously.6 The attachment of a chiral
phosphine ligand to the linker unit was conducted as follows: 1b
was first converted to isocyanate 2 by reaction with potassium
isocyanate in the presence of potassium iodide (Scheme 2). Then,
the reaction of 2 with (2S,4S)-4-(diphenylphosphino)-2-[(diphen-
ylphosphino)methyl]pyrrolidine yielded the tripodal chiral phos-
phine ligand 3.13 The grafting reaction of 3 onto the ordered
mesoporous silica (TMPS-4)8 was carried out in heptane under
reflux for 24 h, giving the chiral pyrrolidinobisphosphine ligand-
modified silica 4.9 To compare the effects of the linker structure
on the catalytic performance, chiral ligand-modified silica 5 was
prepared using conventional triethoxysilane according to report-
ed procedures (Scheme 3).9c The organic contents in 4 and 5,
determined by elemental analysis of carbon, were 0.30 and
0.33 mmol g¹1, respectively, indicating that the tripodal linker
secured surface loading levels that were comparable to those
reached using a conventional trialkoxy linker.
three anchoring silicon atoms was used to immobilize a chiral
phosphine-rhodium complex catalyst on an ordered mesoporous
silica support. The rhodium and phosphorus leaching levels into
the reaction solution after asymmetric hydrogenation were lower
for this catalyst than for immobilized catalysts prepared using
conventional triethoxysilane.
The immobilization of molecular catalysts via linkers, such
as the trimethylene chain, on insoluble solid supports, such as
silica, is a promising strategy for simplifying the separation of
catalysts from reagents and products, as well as for facilitating
catalyst recycling.1 Immobilized molecular catalysts may be
adapted to continuous flow processes. However, poor stability is
a major drawback to immobilized metal complex catalysts.2 The
elimination of metal fragments from anchored ligands and the
cleavage of the bond between a ligand and the support permit
leaching of the metal and/or ligand into the reaction solution.
Strong ·-donating3 or chelating ligands4 are occasionally
effective for overcoming the former problem, whereas few
attempts have been made to fortify ligand support bonds against
leaching.5
Recently, we developed a novel tripodal linker unit
possessing three leaving allylsilyl or isopropoxysilyl groups
(Scheme 1).6 This linker unit binds tightly to the surface of
a silica support via three independent siloxane bridges. The
tripodal linker unit additionally contains a bromopropyl moiety
to which various organic functional molecules, including
auxiliary ligands for metal complexes, may be attached. This
linker unit thus prevents grafted organic functional moieties
from leaving the support. Here, we report application of the
tripodal linker unit to the grafting of a chiral phosphine ligand
onto mesoporous silica supports, and we describe the use of
tethered rhodium complex catalysts for the asymmetric hydro-
genation of cinnamic acid derivatives. The advantages of
immobilized chiral catalysts have been well-documented in the
literature.7
The X-ray diffraction (XRD) pattern of the chiral ligand-
modified silica 4 was similar to that of the parent mesoporous
silica (Figure 1).8 Three peaks were assigned to a 2D hexagonal
structure, indicating that grafting of the pyrrolidinobisphosphine
Me Me
Si
iPrO
Me Me
Si
iPrO
KI, KNCO
NCO
Si
Br
Si
DMF
3
3
1b
PPh2
2
PPh2
O
HN
Me
Si
Me
PPh2
NH
N
Si
iPrO
3
CH2Cl2
PPh2
PPh2
3
O
Me Me
Si
O
2
SiO2
NH
N
Si
SiO
heptane
PPh2
3
4
Me Me
Me Me
Scheme 2. Synthesis and grafting of the tripodal chiral phosphine
ligand onto the silica surface.
Si
Me Me
LG
Si
Me Me
O
SiO2
Si
Si
Me
Br
Br
O
O
Si
Si
Me Me
LG
PPh2
PPh2
O
Me
O
O
O
O
2
SiO2
Si
LG
H
Si
NH
N
Si
LG
SiO
NH
N
(EtO)3Si
heptane
PPh2
1a: LG = CH2CH=CH2
1b: LG = OCH(CH3)2
PPh2
5
Scheme 1. Tripodal linker units and their grafting onto silica
surfaces.
Scheme 3. Grafting of the chiral phosphine ligand containing
triethoxysilyl groups onto the silica surface.
Chem. Lett. 2011, 40, 212-214
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

213
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
(A)
SiO2
0
100
50
-50
-100
ppm
SiO2
(B)
4
TMPS-4
9
1
2
3
4
5
6
7
8
10
2
θ
/degree
Figure 1. XRD patterns of 4 and the mesoporous silica support
(TMPS-4).
0
-50
-100
100
(C)
50
ppm
1000
900
800
700
600
500
400
300
CH3
CH3
SiO CH
ppm
50
0
100
200
(D)
150
200
4
TMPS-4
100
0
0
0.2
0.4
0.6
0.8
1
p/p0
Figure 2. Nitrogen adsorption/desorption isotherms of 4 and the
mesoporous silica support (TMPS-4).
ppm
0
-50
100
50
Figure 3. (A) 29Si CP/MAS spectrum of 4; (B) 29Si CP/MAS
spectrum of 5; (C) 13C CP/MAS spectrum of 4; and (D) 31P CP/
MAS spectrum of 4.
unit via the tripodal linker unit preserved the mesoporous
structure. The nitrogen adsorption/desorption isotherm of 4
showed a type IV sorption curve typical of mesoporous
structures (Figure 2). Grafting of the tripodal chiral phosphine
Figure 3C shows the 13C CP/MAS spectrum of the modified
silica 4. The peaks at ¹3, 5-60, 125-140, and 157 ppm were
assigned, respectively, to the methyl groups on silicon, the
methylene and methyne carbons of the tripodal linker and the
chiral pyrrolidinobisphosphine unit, the aromatic carbons on the
phosphorus, and the ureidic carbonyl carbon, by comparison with
the chemical shifts in the 13C NMR spectrum of 3 in CD2Cl2. The
13C CP/MAS spectrum revealed peaks that could be assigned to
an isopropoxy group, the methyl peaks of which overlapped with
the methylene peaks of the linker. This suggested that the
isopropoxysilyl groups of 3 remained partially unreacted in 4.
However, the presence of the isopropoxide species on silica
(iPrO-Si) formed by the reaction of the eliminated isopropyl
alcohol and the surface silanol group could not be excluded.
Thus, the chiral ligand-modified silica 4 may unfortunately
contain bipodally and/or monopodally anchored species in
addition to tripodal species. However, 4 showed apparent
advantages in terms of reduced leaching during catalysis relative
to 5 (vide infra). In the 31P CP/MAS spectra of 4, two peaks
corresponding to the diphenylphosphino groups were observed at
¹21 and ¹7 ppm (Figure 3D). A minor peak observed at 36 ppm
was probably due to the oxidized diphenylphosphino species.
¹1
ligand reduced the pore volume from 1.46 to 1.18 cm3 g and
narrowed the average pore size from 3.8 to 3.3 nm. However, 4
maintained a high surface area (868 m2 g¹1).
The chiral ligand-modified silicas 4 and 5 were further
characterized by 29Si, 13C, and 31P CP/MAS NMR spectroscopy.
The 29Si CP/MAS spectrum of 4 exhibited two peaks at 2 and
17 ppm, which corresponded to a single tetraalkyl-coordinated
silicon center and three trialkylmonooxygen-coordinated silicon
centers in 4, in addition to the broad peaks around ¹100 ppm
due to Q3 and Q4 silicon in silica (Figure 3A).10 Both peaks at 2
and 17 ppm had shoulders around 6 and 15 ppm, which were
probably due to species containing unreacted isopropoxysilyl
groups. This was further confirmed by 13C CP/MAS of 4 (vide
infra).
Figure 3B shows the 29Si CP/MAS spectrum of the modi-
fied silica 5. Although condensation of conventional trialkoxy-
silanes with surface silanol groups in principle permits linkage
through three siloxane bridges, the sole peak (¹51 ppm)
observed in the organosilane region was assigned to T1 silicon.11
This indicated that the chiral phosphine in 5 was predominantly
bound to the silica surface via a single Si-O-Si bond.
Chem. Lett. 2011, 40, 212-214
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

214
H
2 (1 bar)
Table 2. Catalyst recycling experiments for the asymmetric hydro-
genation using the rhodium complex catalyst prepared from 4a
[Rh(cod)(CH3CN)2]BF4 (1.5 mol%)
H
Ph
H
NHCOMe
COOH
Ph
H
4 or 5 (3.0 mol% Ligand)
NHCOMe
COOH
Run
Yield/%b,c
ee/%b
MeOH, r.t., 2 h
H
1st
2nd
3rd
98
99
98
95
95
96
Scheme 4. Asymmetric hydrogenation of ACA.
aACA: 0.5 mmol, catalyst: 1.5 mol % on Rh, H2: 1 bar,
Table 1. Results of the asymmetric hydrogenation of ACA using
the rhodium complex catalysts prepared from 4 and 5a
b
methanol: 7 mL, room temperature, 2 h. Determined by HPLC
c
using a Chiralpack AD-H column. Sum of enantiomers.
Leaching of Leaching of
Ligand Yield/%b,c ee/%b
¹1
¹1
Rh/mg L
P/mg L
This research was financially supported by Development of
Microspace and Nanospace Reaction Environment Technology
for Functional Materials Project of NEDO, Japan. We thank Dr.
Toshikazu Takahashi for helpful discussion on CP/MAS spec-
troscopy.
4
5
98d
98
95
94
12
24
0.9
3.9
aACA: 0.5 mmol, catalyst: 1.5 mol % on Rh, H2: 1 bar, methanol:
7 mL, room temperature, 2 h. bDetermined by HPLC using a
Chiralpack AD-H column. cSum of enantiomers. dIsolated yield
was 96% after silica gel chromatography (ethyl acetate as eluent).
References and Notes
1
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The catalytic performance of the chiral ligand-modified
silica 4 was probed in the rhodium-catalyzed asymmetric
hydrogenation of (Z)-¡-(acetamido)cinnamic acid (ACA) in
methanol under a hydrogen pressure of 1 bar at room temper-
ature (Scheme 4). In the presence of a catalyst prepared by
mixing [Rh(cod)(CH3CN)2]BF4 with two equivalents of 4 (Rh:
1.5 mol %), the reaction was completed within 2 h to quantita-
tively yield N-acetylphenylalanine in 95% ee (Table 1). The
enantioselectivity was comparable to that reported for the
homogenously catalyzed reaction.12 Although the catalytic
activity and enantioselectivity of 4 were similar to those of the
catalyst prepared from 5, obvious differences in the leaching of
metal and ligand were observed. After the reaction, the catalyst
was separated by filtration, and the extent of rhodium and
phosphorus leaching into the reaction solution was determined
by ICP-AES. The leaching levels of the catalyst prepared from 4
2
3
a) D. J. Cole-Hamilton, Science 2003, 299, 1702. b) W. Keim, Green
Chem. 2003, 5, 105.
For example: a) K. Hara, R. Akiyama, S. Takakusagi, K. Uosaki, T.
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4
¹1
¹1
5
6
E. A. Smith, W. Chen, Langmuir 2008, 24, 12405.
N. Fukaya, S. Onozawa, M. Ueda, K. Saitou, Y. Takagi, T. Sakakura,
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(12 mg L for Rh and 0.9 mg L for P) were lower than those
¹1
of the catalyst prepared from 5 (24 mg L
for Rh and
¹1
3.9 mg L for P). The tripodal linker in 4 cannot inhibit the
leaching of rhodium and phosphorus via de-coordination of
rhodium and/or decomposition of the chiral phosphine part
(e.g., cleavage of the NH-C(O)-N bond) during the asymmetric
hydrogenation. However, firm immobilization utilizing the
tripodal linker most likely effectively prevented the chiral
phosphine-rhodium complex from leaving the silica support via
cleavage of the Si-O-Si linkage.
The recyclability of the rhodium catalyst from 4 was
assessed by hydrogenating ACA, removing the reaction super-
natant via centrifugation and decantation, and recharging the
reaction tube with ACA and a solvent. The recovered rhodium
catalyst exhibited similar performances in the second and third
runs as in the first run (Table 2).
In summary, we successfully used the tripodal linker unit
to immobilize the chiral pyrrolidinobisphosphine ligand onto
ordered mesoporous silica. The rhodium complex catalyst
prepared from the silica-immobilized tripodal chiral phosphine
ligand showed activity and enantioselectivity that were com-
parable to their homogeneous counterparts during asymmetric
hydrogenation. Additionally, the catalyst containing the tripodal
linker showed lower leaching levels of rhodium and phospho-
rus than the catalyst attached via a conventional trialkoxy
linker.
7
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8
9
Ordered mesoporous silica with a 2D hexagonal structure (TMPS-4)
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¹1
pore volume, and average pore size were 1039 m2 g¹1, 1.46 cm3 g
,
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Behringer, J. Blümel, J. Liq. Chromatogr. Relat. Technol. 1996, 19,
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Chem. Lett. 2011, 40, 212-214
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/