Immobilization of chiral phosphine ligands on silica gel by means of the allylsilane method and their use for catalytic asymmetric reactions

Article abstract of DOI:10.1016/j.tetasy.2004.03.044

Three chiral phosphine ligands containing an allylsilyl group at the terminus of the side chain were prepared and immobilized on a silica gel surface by use of the allylsilane modification method. The silica-supported chiral phosphine ligands were used fo

Full text of DOI:10.1016/j.tetasy.2004.03.044

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1771–1777
Immobilization of chiral phosphine ligands on silica gel
by means of the allylsilane method and their use for
catalytic asymmetric reactions
Kazuko Aoki, Toyoshi Shimada and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Received 26 March 2004; accepted 31 March 2004
Available online 6 May 2004
Abstract—Three chiral phosphine ligands containing an allylsilyl group at the terminus of the side chain were prepared and
immobilized on a silica gel surface by use of the allylsilane modification method. The silica-supported chiral phosphine ligands were
used for rhodium-catalyzed hydrogenation and palladium-catalyzed allylic alkylation and showed high enantioselectivity.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
We have recently reported a new method for the mod-
ification of silica gel surfaces by use of organic com-
pounds containing an allylsilane moiety.1 In contrast to
the organosilicon compounds used for the modification,
which are mostly those containing an alkoxy leaving
group (RnSiX4ꢀn: X ¼ OR0),2 the allylsilanes can be
handled under hydrolytic conditions and can be purified
by silica gel chromatography if necessary. Despite such
stability, deallylation of the allylsilane takes place in
refluxing toluene to form the Si–O–Si bond with the
silicon on the silica gel (Scheme 1). Here we report the
application of this allylsilane modification method to
the immobilization of chiral phosphine ligands on silica
gel surfaces and their use for some catalytic asymmetric
reactions. The advantages of immobilized chiral cata-
lysts are well-documented in literatures.3
2.1. Preparation of silica gel-supported chiral phosphine
ligands
As chiral phosphine ligands to be immobilized on silica
gel, we chose ferrocenylbisphosphine [(S)-(R)-bppfa],4
bisphosphine derived from hydroxyproline [(2S,4S)-
capp],5 and phosphinooxazoline [(S)-i-Pr-phox]6
(Scheme 2), in addition to (R)-binap7 whose immobili-
zation has been already reported.1
We designed and prepared some allyl(dimethyl)(prop-
yl)silanes bearing functionalized groups at the terminus
of the propyl group (Scheme 3). They are expected to
connect the chiral phosphine moiety with the allylsilyl
group. The allylsilane containing 3-bromopropyl group
2 was prepared in a high yield by the iridium-catalyzed
hydrosilylation of 2-propenyl bromide with methyl-
dichlorosilane followed by treatment of the resulting
3-bromopropyldimethyl(chloro)silane
allyl Grignard reagent. N-Methyl-3-aminopropyldi-
methyl(allyl)silane 3 was obtained by the amination of
1
with the
Me Me
Me Me
toluene reflux
Si
R
Si
R
Si
O
Si OH
silica gel
H
PPh2
Me
Me2N
Ph2P
Ph2P
O
H
N
Fe
N
Ph2P
N
Scheme 1.
Ph
PPh2
O
(S)-(R)-bppfa
Scheme 2.
(2S,4S)-capp
(S)-i-Pr-phox
* Corresponding author. Fax: +81-75-753-3988; e-mail: thayashi@
kuchem.kyoto-u.ac.jp
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.03.044

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K. Aoki et al. / Tetrahedron: Asymmetry 15 (2004) 1771–1777
Me Me
Si
Me Me
Si
MgBr
Et2O
HSiMe2Cl
Br
Br
Br
Cl
[IrCl(cod)]2
(catalyst)
1 (91%)
2 (96%)
Me Me
Si
Me Me
Si
MeNH2
MeOH
Br
Br
NHMe
NCO
2
3 (88%)
Me Me
Si
Me Me
Si
KNCO, KI
DMF
2
4 (86%)
Scheme 3.
bromide 2 with methylamine in methanol. The substi-
tution of bromide in 2 with potassium isocyanate was
efficiently performed in the presence of potassium iodide
in DMF to give 86% yield of the silylpropyl isocyanate
4. The Grignard reagent generated from bromide 2 was
also used for the introduction of the allylsilyl moiety on
one of the chiral phosphines (vide supra).
nol gave the ferrocenylbisphosphine bearing the allylsil-
yl group (S)-(R)-5, which was purified by silica gel
chromatography (hexane/ethyl acetate ¼ 4/1) keeping
the allylsilane moiety intact. Treatment of the allylsilane
(S)-(R)-5 with an amorphous silica gel in toluene at
reflux for 15 h gave silica-supported chiral phosphine
(silica-bppfa 6), which contains 0.2 mmol/g of the ferr-
ocenylbisphosphine unit. A similar type of supported
bppfa has been previously reported by Thomas and
co-workers8 to be obtained by use of a ferrocenylphos-
phine analogous to 5 but containing a trimethoxysilyl
group in place of the allyldimethylsilyl group.
Scheme 4 summarizes the connection of the allylsilane
moiety with the three types of chiral phosphines shown
above. It has been reported that the substitution of the
acetoxy group in bppfOAc4 with nucleophiles including
amino groups takes place with retention of configura-
tion at the ferrocenylmethyl position.4 The nucleophilic
substitution of (S)-(R)-bppfOAc with N-methyl-3-
aminopropyldimethyl(allyl)silane 3 in refluxing metha-
For connection of the pyrrolidinobisphosphine with the
allylsilane moiety, isocyanate 4 was conveniently used.
Thus, the reaction of (2S,4S)-ppm5;9 with a slight excess
H
H
Me
Me
Si
NHMe
H
Me
AcO
Ph2P
Ph2P
Si
N
O
Me Me
3
silica gel
Si
Si
Me Me
N
Fe
Fe
Me Ph2P
Me Me
Fe
Me Ph2P
toluene reflux
MeOH
Ph2P
Ph2P
(S)-(R)-bppfOAc
(S)-(R)-5 (78%)
silica-bppfa 6 (0.2 mmol/g)
PPh2
PPh2
PPh2
Si
Me Me
CH2Cl2
NCO
Me Me
H
N
Me Me
Si
H
4
silica gel
Si
Si
O
N
N
H
N
N
toluene reflux
PPh2
O
PPh2
PPh2
O
silica-ppm 8 (0.5 mmol/g)
(2S,4S)-ppm
(2S,4S)-7 (87%)
Me Me
Si
Br
Cl
O
Br
MgBr
Si
Me Me
10 (99%)
1) (S)-valinol, Et3N, DMAP
2) TsCl, Et3N
O
N
O
PdCl2(dppf) (4 mol%)
Et2O
N
9 (53%)
Si
Me Me
11 (40%)
1) sec-BuLi/TMEDA
2) ClPPh2
silica gel
O
O
Si
Si
Me Me
toluene reflux
Ph2P
N
O
Ph2P
silica-phox 12 (0.3 mmol/g)
N
Scheme 4.

K. Aoki et al. / Tetrahedron: Asymmetry 15 (2004) 1771–1777
1773
of isocyanate 4 in dichloromethane at room temperature
gave, after purification by silica gel chromatography
(hexane/ethyl acetate ¼ 4/1), 87% yield of the pyrrol-
idinobisphosphine (2S,4S)-7, which possesses the allyl-
silyl group at the terminus of urea side chain. In a
similar manner to the immobilization of 5, allylsilane 7
was treated with silica gel in refluxing toluene to give
silica-ppm 8 (0.5 mmol/g loading). The immobilization
of pyrrolidinobisphosphine has been also reported by
Pugin10 using triethoxysilyl group for the connection
with silica gel.
is an R isomer of 93% ee, was obtained from the liquid
phase in 97% isolated yield. The enantioselectivity is not
lower than that reported with the silica-supported ppm
ligand reported by Pugin.10 The second run using the
recovered silica catalyst was not as effective as the first
run. The yield was lower even after a prolonged reaction
time, although the enantioselectivity was kept high
(entry 1). Addition of [Rh(cod)(MeCN)2]BF4 (0.5
mol %) at the second run recovered the catalytic activity
of the silica-rhodium catalyst without loss of the
enantioselectivity (entry 2).
There have been no examples of solid support of phos-
phinooxazoline ligands represented by (S)-i-Pr-phox.6
The key compound 11, which is the phosphinooxazoline
bearing allylsilyl group was prepared by way of the
palladium-catalyzed Grignard cross-coupling of 3-(all-
yldimethylsilyl)propylmagnesium bromide. Thus, (S)-4-
oxazolylbromobenzene derived from amide 9 was sub-
jected to the cross-coupling in the presence of 4 mol % of
PdCl2(dppf)11 to give a quantitative yield of the allyl-
silane 10. Lithiation of 10 with sec-butyllithium and
TMEDA in THF followed by addition of chlorodiphen-
ylphosphine gave allylsilane-linked (S)-i-Pr-phox 11.
Silica gel-supported phosphinooxazoline (silica-phox
12) (0.5 mmol/g loading) was obtained by the reaction
with silica gel in a similar manner.
The phosphinooxazoline ligand (S)-i-Pr-phox is known
to be one of the most enantioselective ligands for the
palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-
propenyl acetate 15 with a malonate anion (Scheme 6).6
The palladium catalyst coordinated with the silica-phox
12 showed high catalytic activity and enantioselectivity
for the asymmetric allylic alkylation (Table 2). Thus, the
reaction of 15 with a sodium salt of dimethyl malonate,
generated from dimethyl malonate and sodium hydride
in THF, was completed within 6 h at 20 °C in the pres-
ence of 5 mol % of the palladium catalyst prepared by
mixing [PdCl(p-C3H5)]2 with silica-phox 12. After cen-
trifuging and the removal of the solution phase with
syringe, the recovered silica-phox 12/palladium catalyst
was used directly for the next run. From the solution
phase, a quantitative yield of (S)-dimethyl 1,3-diphenyl-
2-propenylmalonate 16 was obtained in 81% ee.
Although the recovered silica-phox 12/palladium cata-
lyst was less active than the original catalyst, it gave (S)-
16 of the same or even higher enantiomeric purity at the
second or third run.
2.2. Catalytic asymmetric reactions using silica-supported
chiral phosphine ligands
Rhodium-catalyzed asymmetric hydrogenation of
methyl (Z)-a-(acetamido)cinnamate 13 was examined by
use of silica-ppm 8 (Scheme 5, Table 1). A mixture of
rhodium catalyst precursor [Rh(cod)(MeCN)2]BF4
(1 mol %), silica-ppm 8, and 13 was stirred in methanol
under 2 atm of hydrogen pressure for 10 h. The silica-
rhodium catalyst was separated by decantation and the
hydrogenation product N-acetylphenylalanine 14, which
To summarize, we have successfully applied our allyl-
silane modification method to the preparation of some
silica-supported chiral phosphine ligands and used them
as chiral ligands for rhodium-catalyzed asymmetric
hydrogenation and palladium-catalyzed asymmetric
NaCH(COOMe)2
H2 (2 atm)
[Rh(cod)(MeCN)2]BF4 (1 mol%)
[PdCl(π-C3H5)]2 (5 mol% Pd)
L* (10 mol%)
Ph
Ph
Ph
Ph
Ph
NHCOMe
COOMe
Ph
NHCOMe
COOMe
L* (1.2 mol%)
THF, 20 °C
OAc
CH(COOMe)2
MeOH
13
14
15
16
Scheme 5.
Scheme 6.
Table 1. Rhodium-catalyzed asymmetric hydrogenation of methyl (Z)-a-(acetamido)cinnamate 13 with silica-ppm 8a
Entry
1
Ligand
Run
Time (h)
Yieldb (%)
Ee (%)c (config)
Silica-ppm 8
First
Second
First
Secondd
Firste
10
60
10
15
10
97
91
98
97
91
93 (R)
91 (R)
93 (R)
90 (R)
94 (R)
2
Silica-ppm 8
3
(2S,4S)-capp
a The hydrogenation was carried out with 13 (0.70 mmol), [Rh(cod)(MeCN)2]BF4 (7.1 mmol), and silica-ppm 8 or (2S,4S)-capp (8.4 lmol) in 7.0 mL
of methanol under 2 atm hydrogen. The catalyst recovered by decantation was used for the second run.
b Isolated yield by silica gel chromatography.
c Determined by HPLC with a chiral stationary phase column.
d [Rh(cod)(MeCN)2]BF4 (3.6 mmol) was added at the second run.
e Homogeneous reaction.

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K. Aoki et al. / Tetrahedron: Asymmetry 15 (2004) 1771–1777
Table 2. Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 15 with dimethyl malonate in the presence of silica-
phox 12a
Entry
1
Ligand
Run
Time (h)
Conversionb (%)
Ee (%)c (config)
Silica-phox 12
First
6
34
34
6
100
100
100
100
81 (S)
82 (S)
90 (S)
98 (S)
Second
Third
Firstd
2
(S)-i-Pr-phox
a The allylic alkylation was carried out with 15 (0.20 mmol), dimethyl sodiomalonate (0.60 mmol), [PdCl(p-C3H5)]2 (10 mmol Pd), and silica-phox 13
or (S)-i-Pr-phox (20 mmol) in 2.0 mL of THF at 20 °C. The catalyst recovered by centrifuging was used for the next run.
b Determined by 1H NMR spectra of the reaction mixture.
c Determined by HPLC with a chiral stationary phase column.
d Homogeneous reaction.
allylic alkylation. We are now in a position to immo-
bilize various types of organic molecules on the silica
support.
distilled under reduced pressure to give 2.3 g (91% yield)
of chloro(3-bromopropyl)dimethylsilane. 1H NMR
(CDCl3) d 0.44 (s, 6H), 0.96 (m, 2H), 1.97 (m, 2H), 3.43
(t, J ¼ 6:9 Hz, 2H); 13C NMR (CDCl3) d 1.47, 17.97,
26.86, 35.27; 29Si NMR (CDCl3) d 30.38. Anal. Calcd
for C5H12BrClSi: C, 27.86; H, 5.61. Found: C, 27.65; H,
5.48.
3. Experimental
3.1. General
3.4. Preparation of 2-propenyl(3-bromopropyl)dimethyl-
silane 2
All moisture sensitive manipulations were carried out
under a nitrogen atmosphere. Nitrogen gas was dried by
passage through P2O5. NMR spectra were recorded on
1
To a solution of chloro(3-bromopropyl)dimethylsilane 1
(8.6 g, 40.0 mmol) in Et2O (100 mL) was added allyl-
magnesium bromide in Et2O (1 M, 50.0 mL, 50.0 mmol)
at 0 °C, and the reaction mixture was stirred at room
temperature for 11 h. The mixture was quenched with
saturated ammonium chloride solution and extracted
with Et2O. The organic layer was washed with saturated
sodium bicarbonate solution and brine. After drying
over MgSO4, the solvent was removed in vacuo and the
residue was chromatographed on silica gel (hexane/ethyl
acetate ¼ 4/1) to give 8.40 g (96% yield) of 2-propenyl(3-
bromopropyl)dimethylsilane 2. 1H NMR (CDCl3) d
0.01 (s, 6H), 0.64 (m, 2H), 1.53 (ddd, J ¼ 8:2, 1.3,
1.1 Hz, 2H), 1.85 (m, 2H), 3.38 (t, J ¼ 7:2 Hz, 2H), 4.84
(ddt, J ¼ 10:2, 2.1, 1.0 Hz, 1H), 4.85 (ddt, J ¼ 16:9, 2.0,
1.5 Hz, 1H), 5.77 (ddt, J ¼ 16:9, 10.2, 8.2 Hz, 1H); 13C
NMR (CDCl3) d )3.89, 14.17, 23.04, 27.94, 35.85,
113.19, 134.21; 29Si NMR (CDCl3) d 1.49. Anal. Calcd
for C8H17BrSi: C, 43.44; H, 7.75. Found: C, 43.73; H,
7.74.
a JEOL JNM LA500 spectrometer (500 MHz for H,
125 MHz for 13C, 100 MHz for 29Si, and 200 MHz for
31P). Chemical shifts are reported in d ppm referenced to
1
an internal SiMe4 standard for H and 29Si NMR, and
chloroform-d (d 77.0) for 13C NMR and external 85%
H3PO4 standard for 31P NMR.
3.2. Materials
Silica gel (Davisil), with a particle diameter range of
100–200 mesh and a surface area of 480 m2/g, was pur-
chased from Aldrich. It was refluxed with concd HCl for
6 h, filtered, washed with water, and dried at 140 °C for
17 h under vacuum at 10ꢀ5 mmHg. (S)-(R)-bppfa,4
(2S,4S)-capp,5 [IrCl(cod)]2,12 (S)-1-[(R)-10,2-bis(diph-
enylphosphino)ferrocenyl]-ethyl
bppfOAc],4
enylphosphino)-methyl]pyrrolidine
acetate
(2S,4S)-4-(diphenylphosphino)-2-[(diph-
[(S)-(R)-
((2S,4S)-ppm),9
PdCl2(dppf),11 methyl (Z)-a-(acetamido)cinnamate 13,13
[Rh(cod)(CH3CN)2]BF4,14 ( )-1,3-diphenyl-2-propenyl
16
acetate 15,15 [PdCl(p-C3H5)]2 were prepared according
to the reported procedures. 4-Brombenzoyl chloride was
prepared from 4-bromobenzoic acid and thionyl chlo-
ride. (S)-(+)-2-Amino-3-methyl-1-butanol (S-valinol)
was prepared by reduction of (S)-valine with LiAlH4.
3.5. Preparation of 2-propenyl(3-methylaminopropyl)di-
methylsilane 3
Prepared from 2-propenyl(3-bromopropyl)dimethylsi-
lane 2 according to the procedure for amination of 3-
chloropropyl group.18 2-Propenyl(3-bromopropyl)di-
methylsilane (664 mg, 3.0 mmol) was stirred in a meth-
anol solution of methylamine at 80 °C for 12 h. After
removal of the solvent under reduced pressure, the res-
idue was extracted with Et2O. After drying over MgSO4,
organic solvent was removed in vacuo to give 569 mg
(88% yield) of 2-propenyl(3-methylaminopropyl)di-
3.3. Preparation of 2-chloro(3-bromopropyl)dimethyl-
silane 1
This compound was prepared according to the reported
procedures.10;17 To a mixture of [IrCl(cod)]2 (0.8 mg,
0.001 mmol Ir), allyl bromide (1.0 mL, 11.6 mmol), and
1,5-cyclooctadiene (5 lL, 0.04 mmol) was added chlo-
rodimethylsilane (1.5 mL, 13.5 mmol) at 35 °C, and the
mixture was stirred at 40 °C for 17 h. The mixture was
1
methylsilane 3. H NMR (CDCl3) d )0.01 (s, 6H), 0.52
(m, 2H), 1.17 (br s, 1H), 1.48 (m, 2H), 1.52 (ddd,
J ¼ 8:2, 1.3, 1.0 Hz, 2H), 2.43 (s, 3H), 2.56 (t,

K. Aoki et al. / Tetrahedron: Asymmetry 15 (2004) 1771–1777
1775
J ¼ 7:2 Hz, 2H), 4.82 (ddt, J ¼ 10:0, 2.2, 0.9 Hz, 1H),
4.84 (ddt, J ¼ 17:4, 2.2, 1.4 Hz, 1H), 5.78 (ddt, J ¼ 17:0,
10.2, 8.1 Hz, 1H); 13C NMR (CDCl3) d )4.75, 11.44,
22.33, 23.24, 35.38, 54.61, 111.95, 133.76; 29Si NMR
(CDCl3) d )0.21. Anal. Calcd for C9 H21NSi: C, 63.08;
H, 12.35; N, 8.17. Found: C, 62.90; H, 12.55; N, 8.07.
(907 mg, 2.0 mmol) in 15 mL of dichloromethane was
added 2-propenyl(3-isocyanatopropyl)dimethylsilane 4
(513 mg, 2.8 mmol), and the mixture was stirred at room
temperature for 14 h. After removal of the solvent, the
residue was purified by silica gel chromatography (hex-
ane/ethyl acetate ¼ 4/1) to give 1.1 g (87% yield) of the
20
D
1
title compound 7. ½aꢁ ¼ ꢀ13 (c 1.00, chloroform); H
NMR (CDCl3) d )0.03 (s, 6H), 0.43 (m, 2H), 1.37 (m,
2H), 1.49 (ddd, J ¼ 8:1, 1.1, 1.0 Hz, 2H), 1.89 (m, 1H),
2.16 (ddd, J ¼ 13:5, 10.2, 2.2 Hz, 1H), 2.31 (m, 1H), 2.83
(m, 1H), 3.00 (dt, J ¼ 13:5, 3.2 Hz, 1H), 3.06 (m, 2H),
3.20 (q, J ¼ 9:6 Hz, 1H), 3.57 (br t, J ¼ 8:3 Hz, 1H),
3.88–3.94 (m, 2H), 4.77–4.83 (m, 2H), 5.74 (ddt,
J ¼ 16:9, 10.1, 8.2 Hz, 1H), 7.26–7.41 (m, 16H), 7.43–
7.47 (m, 2H), 7.54–7.57 (m, 2H); 13C NMR (CDCl3) d
)3.92, 11.86, 22.98, 24.69, 34.95 (d, JC–P ¼ 13:4 Hz),
35.44 (d, JC–P ¼ 9:3 Hz), 37.19 (dd, JC–P ¼ 16:5, 7.8 Hz),
43.65, 50.44 (d, JC–P ¼ 27:9 Hz), 56.02 (dd, JC–P ¼ 20:6,
6.8 Hz), 112.75, 128.17 (d, JC–P ¼ 6:8 Hz), 128.23, 128.39
(d, JC–P ¼ 7:8 Hz), 128.42, 128.47, 128.48, 128.55,
128.85, 132.57 (d, JC–P ¼ 19:0 Hz), 132.89 (d,
JC–P ¼ 19:1 Hz), 132.94 (d, JC–P ¼ 19:6 Hz), 133.12 (d,
JC–P ¼ 19:0 Hz), 134.57, 136.71 (d, JC–P ¼ 12:4 Hz),
137.07 (d, JC–P ¼ 12:9 Hz), 137.67 (d, JC–P ¼ 12:9 Hz),
138.98 (d, JC–P ¼ 12:4 Hz), 156.31; 29Si NMR (CDCl3) d
1.67; 31P NMR (CDCl3) d )8.06, )22.17. Anal. Calcd
for C38H46N2OP2Si: C, 71.67; H, 7.28; N, 4.40. Found:
C, 71.39; H, 7.31; N, 4.48.
3.6. Preparation of 2-propenyl(3-isocyanatopropyl)-
dimethylsilane 4
A mixture of 2-propenyl(3-bromopropyl)dimethylsilane
2 (1.1 g, 5.0 mmol) and potassium iodide (125 mg,
0.8 mmol) in 5 mL of DMF was heated at 100 °C for
0.5 h, followed by addition of potassium isocyanate
(650 mg, 8.0 mmol). The mixture was heated at 100 °C
for 0.5 h. After filtration of potassium chloride precipi-
tates, the reaction mixture was distilled under vacuum to
give 0.79 g (86% yield) of 2-propenyl(3-isocyanatoprop-
1
yl)dimethylsilane 4. H NMR (CDCl3) d 0.02 (s, 6H),
0.57 (m, 2H), 1.54 (ddd, J ¼ 8:1, 1.2, 1.0 Hz, 2H), 1.62
(m, 2H), 3.26 (t, J ¼ 6:8 Hz, 2H), 4.84 (ddt, J ¼ 10:2,
2.2, 0.9 Hz, 1H), 4.89 (ddt, J ¼ 16:9, 2.1, 1.4 Hz, 1H),
5.77 (ddt, J ¼ 16:9, 10.3, 8.1 Hz, 1H); 13C NMR
(CDCl3) d )3.70, 12.20, 23.28, 26.67, 46.27, 113.39,
122.14, 134.50; 29Si NMR (CDCl3) d 1.71. Anal. Calcd
for C9H17ONSi: C, 58.97; H, 9.35; N, 7.64. Found: C,
58.68; H, 9.48; N, 7.58.
3.7. Preparation of (S)-N-methyl–N-[3-((2-propenyl)di-
methylsilyl)propyl]-1-[(R)-10,2-bis(diphenylphosphino)ferro-
cenyl]ethylamine 5
3.9. Preparation of (S)-4-[4-(isopropyl)oxazol-2-yl]-1-
bromobenzene 9
Prepared from (S)-1-[(R)-10,2-bis(diphenylphosphino)-
ferrocenyl]ethyl acetate ((S)-(R)-bppfOAc) according
to the procedure for amination of ferrocenylethyl
To a solution of (S)-(+)-2-amino-3-methyl-1-butanol
(3.0 g, 30 mmol), triethylamine (4.0 g, 40 mmol), and 4-
dimethylaminopyridine (122 mg, 1.0 mmol) in dichlo-
romethane (30 mL) was added 4-brombenzoyl chloride
(4.4 g, 20.0 mmol) at 0 °C, and the reaction mixture was
stirred for 12 h at room temperature. The reaction
mixture was quenched with saturated aqueous sodium
bicarbonate, extracted with dichloromethane, and
combined organic layer was dried over anhydrous
magnesium sulfate, and concentrated under reduced
pressure. The residue was chromatographed on silica gel
(hexane/ethyl acetate ¼ 1/1) to give 3.2 g (57% yield) of
acetate.5
A
mixture of (S)-1-[(R)-10,2-bis(diphenyl-
phosphino)ferrocenyl]ethyl acetate [(S)-(R)-bppfOAc]
(314 mg, 0.50 mmol) and 2-propenyl(3-methylamino-
propyl)dimethylsilane 3 (857 mg, 5.0 mmol) in 1 mL of
methanol was refluxed for 19 h. After removal of the
solvent, the residue was purified by silica gel chroma-
tography (hexane/ethyl acetate ¼ 4/1) to give 290 mg
20
(78% yield) of the title compound 5. ½aꢁ ¼ þ297 (c 0.51,
D
chloroform); 1H NMR (CDCl3) d )0.13 (s, 6H), 0.19 (m,
2H), 0.83 (m, 2H), 1.17 (d, J ¼ 6:8 Hz, 3H), 1.40 (d,
J ¼ 8:2 Hz, 2H), 1.65 (s, 3H), 2.14 (m, 1H), 2.32 (m, 1H),
3.49 (s, 1H), 3.65 (s, 1H), 3.94 (s, 1H), 4.08 (dt, J ¼ 11:0,
1.0 Hz, 2H), 4.18 (m, 1H), 4.38 (d, J ¼ 10:0 Hz, 2H),
4.78–4.82 (m, 2H), 5.72 (ddt, J ¼ 18:8, 10.8, 8.2 Hz, 1H),
7.06–7.10 (m, 2H), 7.14–7.16 (m, 3H), 7.22–7.31 (m,
13H), 7.50 (td, J ¼ 7:6, 1.9 Hz, 2H); 29Si NMR (CDCl3)
d 1.50; 31P NMR (CDCl3) d )16.76, )22.92. Anal. Calcd
for C45H51NP2SiFe: C, 71.89; H, 6.84; N, 1.86. Found: C,
71.82; H, 6.77; N, 1.67.
(S)-N-(1-hydroxymethyl-2-methylpropyl)-40-bromophen-
20
yl-2-carboxylamide. ½aꢁ ¼ ꢀ29 (c 0.56, chloroform);
D
1H NMR (CDCl3) d 1.02 (d, J ¼ 6:9 Hz, 3H), 1.04 (d,
J ¼ 6:9 Hz, 3H), 2.02 (m, 1H), 2.31 (t, J ¼ 5:4 Hz, 1H),
3.80–3.82 (m, 2H), 3.94 (m, 1H), 6.28 (br d, J ¼ 7:5 Hz,
1H), 7.58 (d, J ¼ 8:6 Hz, 2H), 7.65 (d, J ¼ 8:6 Hz, 2H);
13C NMR (CDCl3) d 19.03, 19.59, 29.26, 57.48, 63.86,
126.27, 128.54, 131.86, 133.38, 167.26. A solution of the
amide thus obtained (4.72 g, 16.5 mmol), p-toluene-
sulfonyl chloride (3.50 g, 18.2 mmol), and triethylamine
(8.35 g, 82.5 mmol) in dichloromethane (110 mL) was
refluxed for 17 h. Then 1.0 mL of water was added and
heating continued for an additional 1 h. The organic
layer was washed with water and dried over anhydrous
magnesium sulfate, and concentrated under reduced
pressure. The residue was chromatographed on silica gel
3.8. Preparation of (2S,4S)-N-[3-((2-propenyl)dimethyl-
silyl)propyl]-aminocarbonyl-4-(diphenylphosphino)-2-
[(diphenylphosphino)methyl]pyrrolidine 7
To a solution of (2S,4S)-4-(diphenylphosphino)-2-
[(diphenylphosphino)methyl]pyrrolidine [(2S,4S)-ppm]
(hexane/ethyl acetate ¼ 2/1) to give 4.1 g (93% yield) of
20
the title compound 9. ½aꢁ ¼ ꢀ60 (c 0.50, chloroform);
D

1776
K. Aoki et al. / Tetrahedron: Asymmetry 15 (2004) 1771–1777
1H NMR (CDCl3) d 0.92 (d, J ¼ 6:8 Hz, 3H), 1.03 (d,
J ¼ 6:7 Hz, 3H), 1.85 (m, 1H), 4.06–4.15 (m, 2H), 4.41
(dd, J ¼ 9:3, 8.0 Hz, 1H), 7.54 (ddd, J ¼ 8:7, 2.3, 1.9 Hz,
2H), 7.81 (ddd, J ¼ 8:7, 2.3, 1.9 Hz, 2H); 13C NMR
(CDCl3) d 18.10, 18.91, 32.81, 70.31, 72.72, 125.80,
126.90, 129.79, 131.52, 162.56. Anal. Calcd for
C12H14BrNO: C, 53.75; H, 5.26; N, 5.22. Found: C,
53.64; H, 5.25; N, 5.25.
compound 11. Unreacted 10 (116 mg, 0.4 mmol) was
recovered by silica gel chromatography. 1H NMR
(CDCl3) d )0.09 (s, 6H), 0.37 (m, 2H), 0.70 (d,
J ¼ 6:9 Hz, 3H), 0.80 (d, J ¼ 6:8 Hz, 3H), 1.39 (m, 2H),
1.44 (d, J ¼ 8:2 Hz, 2H), 1.47–1.52 (m, 1H), 2.44 (t,
J ¼ 7:5 Hz, 2H), 3.80–3.87 (m, 1H), 4.10–4.14 (m, 2H),
4.77–4.86 (m, 2H), 5.67–5.81 (m, 1H), 6.63 (dd, J ¼ 4:3,
1.5 Hz, 1H), 7.13 (dd, J ¼ 8:5, 1.3 Hz, 1H), 7.28–7.33
(m, 10H), 7.81 (dd, J ¼ 8:0, 4.0 Hz, 1H); 31P NMR
(CDCl3) d )4.71.
3.10. Preparation of 4-[3-((2-propenyl)dimethylsilyl)prop-
yl]-(S)-1-[4-(isopropyl)oxazol-2-yl]benzene 10
3.12. Loading of phosphine ligands on silica gel
A solution of 3-[(2-propenyl)dimethylsilyl]-propylmag-
nesium bromide was prepared in the usual manner from
547 mg (22.5 mmol) of magnesium and 1.6 g (7.5 mmol)
The loading was carried out according to the reported
procedures.1 A typical procedure is given for the prep-
aration of silica-ppm 8: To a suspension of dry silica gel
(280 mg) in 7.0 mL of toluene was added 7 (900 mg,
1.4 mmol), and the mixture was refluxed for 15 h. The
ppm-modified silica gel was filtered and dried at 120 °C
under reduced pressure (0.2 mmHg) for 15 h. Elemental
analysis: Found: C, 15.86; H, 1.74; N, 1.04. From the
filtrates and extracts 832 mg (1.3 mmol) of 7 was
recovered.
of 2-propenyl(3-bromopropyl)dimethylsilane
2.5 mL of diethyl ether. To a suspension of (S)-4-[4-
(isopropyl)oxazol-2-yl]-1-bromobenzene (804 mg,
2
in
9
3.0 mmol) and PdCl2(dppf) (66.0 mg, 0.12 mmol) in
40 mL of diethyl ether was added the Grignard solution,
and the mixture was refluxed for 12 h. The reaction
mixture was quenched with saturated aqueous ammo-
nium chloride, extracted with diethyl ether, and com-
bined organic layer was dried over anhydrous
magnesium sulfate, and concentrated under reduced
pressure. The residue was chromatographed on silica gel
3.13. Rhodium-catalyzed heterogeneous asymmetric
hydrogenation of a dehydroamino acid using silica-ppm 8
(hexane/ethyl acetate ¼ 7/1) to give 980 mg (99% yield)
20
of the title compound 10. ½aꢁ ¼ ꢀ43 (c 0.51, chloro-
D
form); 1H NMR (CDCl3) d )0.03 (s, 6H), 0.55 (m, 2H),
0.92 (d, J ¼ 6:7 Hz, 3H), 1.03 (d, J ¼ 6:7 Hz, 3H), 1.50
(ddd, J ¼ 8:2, 1.3, 1.2 Hz, 2H), 1.62 (m, 2H), 1.86 (m,
1H), 2.65 (t, J ¼ 7:6 Hz, 2H), 4.07–4.14 (m, 2H), 4.39
(td, J ¼ 7:5, 1.1 Hz, 1H), 4.80 (ddt, J ¼ 10:2, 2.3, 0.9 Hz,
1H), 4.82 (ddt, J ¼ 16:9, 2.2, 1.5 Hz, 1H), 5.75 (ddt,
J ¼ 16:9, 10.2, 8.2 Hz, 1H), 7.20 (d, J ¼ 8:4 Hz, 2H),
7.86 (d, J ¼ 8:3 Hz, 2H); 13C NMR (CDCl3) d )3.70,
14.86, 18.25, 19.10, 23.36, 25.92, 33.18, 40.05, 70.13,
72.93, 112.97, 125.87, 128.54, 128.56, 134.95, 146.12,
163.60; 29Si NMR (CDCl3) d )0.76. Anal. Calcd for
C20H31NOSi: C, 72.89; H, 9.48; N, 4.25. Found: C,
72.62; H, 9.48; N, 4.02.
A typical procedure is given for the reaction of methyl
(Z)-a-(acetamido)cinnamate 13 using silica-ppm 8 as
ligand (Scheme 5, Table 1, entry 1): A mixture of silica-
ppm 8 (16.8 mg, 8.4 lmol ppm), [Rh(cod)(CH3CN)2]BF4
(2.4 mg, 7.1 lmol), and methyl (Z)-a-(acetamido)cinna-
mate 13 (212.0 mg, 0.70 mmol) in MeOH (7.0 mL) was
stirred at room temperature for 10 h under 2 atm of
hydrogen pressure. After releasing hydrogen gas, silica-
ppm 8 was recovered by decantation and used directly
for the second run. After evaporation of the solvent, the
residue was chromatographed on silica gel (diethyl
ether) to give 14 (207.3 mg, 97% yield). The enantio-
meric purity was determined to be 93.3% ee by HPLC
analysis with a chiral stationary phase column, Daicel
Chiralcel OD-H (hexane/2-propanol ¼ 9/1).
3.11. Preparation of 4-[3-((2-propenyl)dimethylsilyl)prop-
yl]-(S)-1-[4-(isopropyl)oxazol-2-yl]-2-(diphenylphosph-
ino)benzene 11
3.14. Palladium-catalyzed heterogeneous asymmetric
allylic alkylation of (%)-1,3-diphenyl-2-propenyl acetate
15 using silica-phox 12
To a mixture of 4-[3-((2-propenyl)dimethylsilyl)propyl]-
(S)-1-[4-(isopropyl)oxazol-2-yl]benzene 10 (247 mg,
0.8 mmol) and TMEDA (221 mg, 1.9 mmol) in THF
(150 mL) was added dropwise sec-butyllithium (1.5 mL,
1.5 mmol) in hexane at )96 °C. After the mixture was
stirred for 2 h at )96 °C, chlorodiphenylphosphine
(353 mg, 1.6 mmol) was added at this temperature. The
reaction mixture was stirred for 2 h at )96 °C and then
for 11 h at room temperature. The reaction mixture was
quenched with saturated aqueous ammonium chloride,
extracted with diethyl ether. The reaction was quenched
by adding 5.0 g of dry silica gel via syringe and evapo-
ration of the solvent under reduced pressure. The resi-
due was chromatographed on silica gel (hexane/ethyl
acetate ¼ 4/1) to give 154 mg (40% yield) of the title
A typical procedure is given for the reaction of ( )-1,3-
diphenyl-2-propenyl acetate 15 with dimethyl malonate
using silica-phox 12 as ligand (Scheme 6, Table 2, entry
1): To a mixture of silica-phox 12 (67 mg, 20 lmol phox),
[PdCl(p-C3H5)]2 (1.8 mg, 10 lmol Pd), and ( )-1,3-di-
phenyl-2-propenyl acetate 15 (50.5 mg, 0.20 mmol) in
1.0 mL of THF was added a solution of dimethyl mal-
onate (79.5 mg, 0.60 mmol) and sodium hydride
(14.4 mg, 0.60 mmol) in THF (1.0 mL). The reaction
mixture was stirred at 20 °C for 6 h. After centrifuging
and the removal of the solution phase with syringe, the
recovered silica-phox 12 was used directly for the next
run. The separated solution phase was washed with

K. Aoki et al. / Tetrahedron: Asymmetry 15 (2004) 1771–1777
1777
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Acknowledgements
This work was supported in part by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan.
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