Polymer-supported chiral phosphinooxathiane ligands for palladium-catalyzed asymmetric allylations

Article abstract of DOI:10.1016/j.tetasy.2004.11.090

Novel polymer-supported chiral ligands of PS-DES, PS-Et, and TentaGel supporting Pd-phosphinooxathianes were prepared and found to provide high levels of enantioselectivity (up to 99% ee) in palladium-catalyzed asymmetric allylic alkylations and aminations.

Full text of DOI:10.1016/j.tetasy.2004.11.090

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 609–614
Polymer-supported chiral phosphinooxathiane ligands
for palladium-catalyzed asymmetric allylations
Hiroto Nakano,* Kouichi Takahashi, Yuri Suzuki and Reiko Fujita
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Received 25 August 2004; accepted 12 November 2004
Abstract—Novel polymer-supported chiral ligands of PS–DES, PS–Et, and TentaGel supporting Pd-phosphinooxathianes were pre-
pared and found to provide high levels of enantioselectivity (up to 99% ee) in palladium-catalyzed asymmetric allylic alkylations and
aminations.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
particular, only a few successful studies of amination
have been reported.5,6 Furthermore, to the best of our
knowledge, a polymer-supported S–P type ligand has
never been used in this field.
More applications are being found for enantiomerically
pure compounds, for economic, environmental, and
social reasons. Of the various methods used to obtain
single enantiomers, asymmetric catalytic reactions are
amongst the most attractive from the atom-economic
point of view.1 In this field, palladium-catalyzed allylic
substitution reactions are effective tools for constructing
carbon–carbon and carbon–heteroatom bonds, with
several efficient chiral ligands already being explored
for these reactions.2 Recently, we reported that an S–P
type, chiral phosphinooxathiane (POT) ligand 1 is an
effective ligand for such Pd-catalyzed reactions (Scheme
1).3 Nevertheless, despite the huge amount of work on
homogeneous catalysts in this reaction, the use of hetero-
geneous catalysts has not been studied extensively.4 In
Herein, we report the easily prepared novel S–P type
polymer-supported POT ligands 2a–c and apply these
ligands to Pd-catalyzed asymmetric alkylations and amin-
ations (Scheme 1). Excellent enantioselectivity (99% ee)
was observed in the allylic amination.
2. Results and discussion
The polymer-supported chiral ligands 2a–c were easily
synthesized as follows (Scheme 2): Homogeneous POT
ligand 5 was prepared from the condensation reaction
a: R = PS-DES
O
O
b: R = PS-Et-CO
OR
S
c: R = Tenta Gel-MB-CO
S
H
H
Ph2P
Ph2P
1
2a-c
OAc
Nu
Nu = CH(CO2Me)2
NHCH2C6H5
Nu-
*
R
R
R
R
Phthalimide
Scheme 1.
*
Corresponding author. Tel.: +81 22 234 4181; fax: +81 22 275 2013; e-mail: hnakano@tohoku-pharm.ac.jp
0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.11.090

610
H. Nakano et al. / Tetrahedron: Asymmetry 16 (2005) 609–614
CHO
PPh2
3
O
cat. TsOH
benzene
reflux, 2 h
5
+
OH
OH
S
H
Ph2P
H
SH
OH
77%
4
5
3
O
6a: TES-Cl
OR
S
imidazole
H
CH2Cl2, rt, 1 h
Ph2P
6b: Ac2O
6a,b
DMAP,
a: R = TES, 90%
pyridine, rt, 5 h
5
b: R = Ac, 83%
O
2a: PS-DES-Cl
OR
S
imidazole
H
CH2Cl2, rt, 4 h
Ph2P
2b and 2c:
2a-c
PS-Et-COOH or
Tenta Gel-MB-COOH
DIC, CH2Cl2,
a: R = PS-DES, 77%
b: R = PS-Et-CO, 79%
c: R = Tenta Gel-MB-CO, 92%
rt, 48 h
Scheme 2.
of (S)-mercaptoisoborneol 3 with 2-diphenylphosphino-
4-hydroxymethylbenzaldehyde 47 in 77% yield. The ste-
reochemical outcome of 5 was determined using NOE
difference spectra (NOEDS).3 NOE enhancement was
observed between the hydrogens at the 3- and 5-posi-
tions when either the 3- or 5-position was irradiated,
respectively.
The catalytic efficiency of the polymer-supported ligands
was examined with the Pd-catalyzed asymmetric allylic
alkylation of 1,3-diphenyl-2-propenyl acetate 7 with di-
methyl malonate in the presence of [PdCl(g3-C3H5)]2
and N,O-bis(trimethylsilyl)acetamide (BSA)9 to give
the allylation product 8 (Table 1). First, the catalytic
activities of monomeric chiral ligands 5, 6a, and 6b were
tested as a control experiment. The reaction using ligand
5 with a hydroxy group gave product 8 in 76% yield and
93% enantiomeric excess (entry 1). Ligand 6a with a tri-
ethylsilyloxy group and ligand 6b with an acetoxy group
both afforded product 8 in low chemical yields and mod-
erate enantioselectivities (6a: 45%, 63% ee, 6b: 39%, 68%
ee, entries 2 and 3, respectively).
The resins polystyrene–diethylsilyl (PS–DES), polysty-
rene–ethyl (PS–Et), and polystyrene–poly(ethylenegly-
col–OC2H4–NHCO–C2H5) (TentaGel) were selected.
PS–DES and PS–Et are constituted from styrene and
DVB (divinylbenzene) and have good solvent-swollen
states in dichloromethane. In contrast, TentaGel is a
graft-copolymer of gel-type polystyrene and the catalyst
bound to this support behaves like a homogenous cata-
lyst, rather than a heterogeneous one, in a wide range of
solvents because of the long, flexible poly(ethylenegly-
col) linker. Chiral ligand 5 was linked via ester or ether
bonds to PS–DES–Cl resin, PS–Et–COOH resin, or
TentaGel–COOH resin. The reaction of ligand 5 with
PS–DES–Cl in the presence of imidazole in dichlorome-
thane for 4 h at room temperature gave the desired PS–
DES-supported POT ligand 2a in 77%8 yield. Further-
more, the reactions of 5 with PS–Et–COOH and Tenta-
Gel–COOH in the presence of diisopropylcarbodiimide
(DIC) in dichloromethane for 48 h at room temperature
gave the desired PS–Et- and TentaGel-supported POT
ligands 2b and 2c in 79%8 and 92%8 yields, respectively.
To compare the catalytic efficiency, homogeneous ana-
logues 6a and 6b were also prepared by reacting ligand
5 with TES–Cl and Ac2O, respectively.
With these results in hand, we next investigated the cat-
alytic efficiency of the polymer-supported chiral POT
ligands 2a–c (Table 1). The use of PS–DES-supported
ligand 2a gave a poor chemical yield (39%) and a good
ee (88% ee, entry 4). Decreasing the temperature to 0 °C
improved the enantioselectivity to 96% ee, but gave a
poor chemical yield (22%, entry 5). PS–Et-supported
ligand 2b gave a poor chemical yield (20%) and moder-
ate enantioselectivity (60% ee, entry 6). Furthermore,
TentaGel-supported ligand 2c afforded product 8 in
poor chemical yield (12%) and enantioselectivity (39%
ee, entry 7). This result can be explained based on the
steric interaction of the nucleophile and the bulkier p-
allyl complex, and the influence of the oxygen functional
groups, coordinating to the Pd-moiety in the polymeric
backborne on the chiral ligand 2c. From these results,
PS–DES-supported POT ligand 2a was more effective

H. Nakano et al. / Tetrahedron: Asymmetry 16 (2005) 609–614
Table 1. Asymmetric Pd-catalyzed allylic alkylation of acetate 7
611
Ligand
[PdCl(η3-C3H5)]2
OAc
Ph
MeO2C
CO2Me
Ph
Ph
Ph
CH2(CO2Me)2
base/BSA
CH2Cl2
(R)a-8
7
Entryb
Ligand
Ligand (mol %)
Temp (°C)
Time (h)
Yieldc (%)
Eed (%)
1
2
3
4
5
6
7
5
5
5
5
5
5
5
5
0
0
0
rt
0
0
0
24
24
24
24
24
24
48
76
45
39
39
22
20
12
93
63
68
88
96
60
39
6a
6b
2a
2a
2b
2c
a(R)-Configurations based on the specific rotation with literature data.3
b Molar ratio for entries 1–7: [PdCl(g3-C3H5)]2 (0.025 equiv), dimethyl malonate (3 equiv), N,O-bis-(trimethylsilyl)acetoamide (BSA) (3 equiv),
potassium acetate (0.02 equiv).
c Isolated yields.
d Determined by HPLC analysis using a DAICEL Chiralcel OD-H.
than the PS–Et- or TentaGel-supported POT ligands 2b
and 2c for this allylic alkylation, and gave a higher
enantioselectivity than ligand 5 and the corresponding
monomeric 6a. Although a clear explanation is not
available as to why ligand 2a gave good enantioselectiv-
ity, it seems to be dependant on the advantageous steric
and electronic interactions of the nucleophile and the p-
allyl complex having the bulky polymeric backbone. In
addition, low chemical yields (entries 4–6) might be ex-
plained by the interfering effects of polymer backbone
on ligands 2a and 2b to the attack of carbon nucleophile.
reaction was carried out in dichloromethane using a cat-
alyst generated by mixing 2.5 mol % [PdCl(g3-C3H5)]2
with 5 mol % chiral ligand 5, 6a, and 6b, respectively,
to give the aminated product 11a. When the reaction
was carried out at 0 °C using chiral ligand 5 and
10 equiv of benzylamine 9 with substrate 7, product
11a was obtained in good chemical yield (94%) and
enantioselectivity (84% ee, entry 1). Furthermore, the
use of ligands 6a and 6b also gave good enantioselectiv-
ities and chemical yields (entry 2: 72%, 83% ee, entry 3:
79%, 87% ee). Next, the catalytic activity of polymer-
supported chiral ligand 2a was examined. The reaction
at room temperature afforded an excellent chemical
yield (99%) and a moderate ee (68%, entry 4). Con-
versely, the reaction at 0 °C under the same conditions
as entries 1 and 2 using monomers 5 and 6a gave a good
chemical yield (90%) and an excellent enantioselectivity
(99% ee, entry 5). However, changing the catalyst
Next, we examined the Pd-catalyzed allylic amination of
acetate 7 with benzylamine 9 acting as the nucleophile
using the PS–DES-supported ligand 2a, which resulted
in an efficient allylic alkylation (Table 2). First, the cat-
alytic activities of the monomeric chiral ligands 5 and 6a
in this reaction were tested as a control experiment. The
Table 2. Asymmetric Pd-catalyzed allylic amination of acetate 7
11a: -NHCH2Ph
Ligand
OAc
Ph
X
[PdCl(η3-C3H5)]2
O
11b:
Ph
Ph
Ph
N
PhCH2NH2
or
potassium phthalimide 10
9
(S)a-11
7
O
CH2Cl2, 24 h
Entryb
Nucleophile
Ligand (mol %)
Nucleophile (equiv to 7)
Temp (°C)
Yieldc (%)
Eed (%)
1
2
9
5 (5)
10
10
10
10
10
10
10
10
3
0
0
94
72
79
99
90
34
62
17
44
35
84
83
87
68
99
79
78
13
88
90
9
6a (5)
6b (5)
2a (5)
2a (5)
2a (2)
2b (5)
2c (5)
2a (5)
2a (5)
3
9
0
4
9
rt
0
5
9
6
9
0
7
9
0
8
9
0
9
10
10
10
rt
0
3
aS-Configurations based on the specific rotation with literature data.3
b Molar ratio for entries 1–10: [PdCl(g3-C3H5)]2 (entries 1–5, 7–10: 0.025 equiv, entry 6: 0.01 equiv).
c Isolated yields.
d Determined by HPLC analysis using a DAICEL Chiralcel OD-H column.

612
H. Nakano et al. / Tetrahedron: Asymmetry 16 (2005) 609–614
loading to 2 mol % led to a substantial decrease in both
chemical yield (34%) and enantioselectivity (79% ee,
entry 6). The catalytic activities of chiral ligands 2b
and 2c were also tested in the reaction under the same
conditions as entry 5. However, satisfying results were
not obtained for chemical yields and enantioselectivities
(entry 7: 62%, 78% ee, entry 8: 17%, 13% ee). Further-
more, the same reaction was examined using potassium
phthalimide 10 as a bulky, reactive nitrogen nucleophile.
The reaction at room temperature gave product 11b in
good enantioselectivity (88% ee), but with a low chemi-
cal yield (44%, entry 9). It seems that the low chemical
yield was given by the steric interaction of both the
bulky nucleophile 10 and the p-allyl complex. Cooling
to 0 °C led to a slight decrease in the chemical yield
(35%) and a slight increase in enantioselectivity (90%
ee, entry 10). From these results, benzylamine 9 is better
than potassium phthalimide 10 as a nucleophile for this
amination. Furthermore, the polymer-supported POT
ligand 2a showed higher asymmetric catalytic activity
than ligand 5 and the corresponding monomeric POT
6a in terms of the chemical yield and enantioselectivity.
For reasons that are unclear, this might be explained
based on the strong nucleophilicity of benzylamine 9
overcoming the steric influence of the bulky polymeric
backbone of the ligand on nucleophile, and the advanta-
geous steric and electronic interactions of nucleophile
and p-allyl complex.
and 67.5 MHz, respectively. The chemical shifts are re-
ported in ppm downfield to TMS (d = 0) for H NMR
1
and relative to the central CDCl3 resonance (d = 77.0)
for 13C NMR. Mass spectra were obtained by EI. The
enantiomeric excesses of the products were determined
by chiral HPLC. Optical rotations were recorded at
the sodium D line with a polarimeter at room tempera-
ture. Commercially available compounds were used
without further purification. Solvents were dried accord-
ing to standard procedures. Chromatography refers to
flash chromatography on silica gel (230–400 mesh), un-
less otherwise noted. PS–DES–Cl,10 was prepared from
the reaction of 1,3-dichloro-5,50-dimethylhydantoin
with diethylsilylbutyl polystyrene (Fluka, 200–400 mesh,
1.5 mmol/g, cross-linked with 1% divinylbenzene), car-
boxyethylpolystylene (Aldrich, 100–200 mesh, 0.8–
1.5 mmol/g, cross-linked with 1% divinylbenzene), and
TentaGel
MB–COOH
(Fluka,
140–170 mm,
0.40 mmol/g) were used. Due to poor resolutions in
the 13C NMR of 2a, 2b, and 2c, those carbon signals
spectrum were not able to be assigned.
4.2. 2-Diphenylphosphino-4-hydroxymethylbenzaldehyde
4
A solution of 2-bromo-4-hydroxymethylbenzaldehyde
(830 mg, 3.86 mmol), diphenylphosphine (0.87 mL,
4.98 mmol), Pd(PPh3)4 (70 mg, 0.06 mmol), and Et3N
(0.69 mL, 4.98 mmol) in toluene (20 mL) was heated
under reflux for 24 h. Then the reaction mixture was
filtered, and the filtrate washed with saturated NH4Cl
solution and brine, dried over anhydrous MgSO4, and
concentrated. The residue was chromatographed on a
column of silica gel with AcOEt–hexane = 1:1 to afford
4 (603 mg, 49%); Yellow solid. Mp 115 °C. IR (KBr)
cmꢀ1 = 699, 1688, 3451. 1H NMR (CDCl3) d: 2.13
(1H, br s), 4.58 (2H, s), 6.91 (1H, dd, J = 1.1, 4.7 Hz),
7.24–7.36 (10H, m), 7.50 (1H, d, J = 6.8 Hz), 7.95 (1H,
dd, J = 3.7, 7.8 Hz), 10.45 (1H, d, J = 5.3 Hz). 13C
NMR (CDCl3) d: 64.42, 126.93, 128.65, 128.75,
128.86, 129.14, 129.43, 130.97, 131.03, 131.63, 133.85,
134.16, 135.84, 135.98, 137.52, 137.73, 141.22, 141.61,
146.80, 191.34. MS m/z: 320 (M+); HRMS: calcd for
C30H33O2PS (M+): 320.0966, found: 320.0955.
Finally, recycling experiments were examined for the
allylic amination with 9 using ligand 2a. After the first
run which gave 90% yield and 99% ee for product 11a,
the mixture was decanted, and the solution of the reac-
tants for the next cycle then added without any further
addition of a Pd source. These cycles were carried out
three times. Consequently, 2a was recycled with 89%
to 59% yields and 99% ee to 79% ee.
3. Conclusion
In summary, we have easily prepared in two steps a
novel class of polymer-supported chiral POT ligands
2a–2c for heterogeneous asymmetric allylic substitution
reactions. In particular, the PS–DES-based POT ligand
2a exhibited excellent activity and enantioselectivity for
Pd-catalyzed allylic amination. We found that polymer-
supported POT is better than the monomeric POT for
giving excellent enantioselectivity. This is the first
reported use of a polymer-supported S–P type chiral
ligand in a catalytic asymmetric reaction. Studies to
optimize the reaction conditions for continuous process-
ing, recycling, and application to other asymmetric reac-
tions are in progress.
4.3. (1R,3R,5R,8S)-11,11-Dimethyl-5-(2-diphenyl-
phosphino-4-hydroxymethyl)-phenyl-4-oxo-6-thiatricyclo
undecane 5
A solution of (1S)-(ꢀ)-10-mercaptoisoborneol 3 (99 mg,
0.53 mmol),
2-diphenylphosphino-4-hydroxymethyl-
benzaldehyde 4 (170 mg, 0.53 mmol), and p-TsOHÆH2O
(9 mg, 0.05 mmol) in benzene (20 mL) was heated under
reflux for 2 h. Then the solvent was evaporated under re-
duced pressure. The residue was chromatographed on a
column of silica gel with AcOEt–hexane = 1:1 to afford
23
D
4. Experimental
4.1. General
5 (200 mg, 77%); White solid. Mp 65 °C. ½aꢁ ¼ ꢀ63:8
(c 2.13, CHCl3). IR (KBr) cmꢀ1 = 694, 746, 1722,
1
2952, 3401. H NMR (CDCl3) d: 0.87–0.93 (4H, m),
0.98–1.04 (1H, m), 1.42–1.49 (4H, m), 1.60 (1H, dd,
J = 7.9, 13.5 Hz), 1.64–1.72 (2H, m), 1.84–1.90 (2H,
m), 2.70 (1H, d, J = 14.1 Hz), 3.18 (1H, d,
J = 14.4 Hz), 3.57 (1H, dd, J = 3.1, 7.9 Hz), 4.45 (2H,
Melting points are uncorrected. IR spectra were re-
corded as KBr pellets (solids) or thin films (liquids).
1
The H and 13C NMR spectra were recorded at 270

H. Nakano et al. / Tetrahedron: Asymmetry 16 (2005) 609–614
613
s), 6.37 (1H, d, J = 7.8 Hz), 6.89 (1H, dd, J = 1.6,
4.3 Hz), 7.26–7.32 (10H, m), 7.37 (1H, dd, J = 1.7,
8.1 Hz), 7.71 (1H, dd, J = 4.1, 8.1 Hz). 13C NMR
(CDCl3) d: 20.45, 23.39, 27.25, 29.95, 34.29, 37.85,
41.81, 45.53, 46.74, 64.83, 80.94, 85.62, 127.68, 128.25,
128.38, 128.45, 128.56, 128.71, 131.98, 133.54, 133.91,
134.19, 134.34, 136.35, 136.45, 136.90, 141.06, 141.07,
143.40, 143.64. 31P NMR (CD3COCD3) d: ꢀ17.63 (s).
MS m/z: 488 (M+); HRMS: calcd for C30H33O2PS
(M+): 488.1939, found: 488.1929.
128.49, 128.54, 128.62, 128.78, 128.88, 131.98, 132.12,
132.74, 133.43, 133.72, 133.84, 134.12, 134.43, 136.18,
143.72, 144.67, 17.60. MS m/z: 530 (M+); HRMS: calcd
for C32H35O2PS (M+): 530.2045, found: 530.2072.
4.6. PS–DES-supported ligand 2a
A mixture of 5 (103 mg, 0.21 mmol), chlorodiethylsilyl
polystyrene (PS–DES–Cl, 100 mg, 0.14 mmol), and
imidazole (33 mg, 0.49 mmol) in CH2Cl2 (1 mL) was
stirred at rt for 4 h. The reaction mixture was filtered
and the polymer washed with CHCl3, MeOH, acetone,
and ether. The polymer was dried under reduced pres-
sure to give 2a (130 mg, 77%, 43% conversion,
0.47 mmol/g of ligand in polymer). 31P NMR
(CD3COCD3) d: ꢀ17.64 (s).
4.4. (1R,3R,5R,8S)-11,11-Dimethyl-5-(2-diphenylphosph-
ino-4-triethylsilyloxy-methyl)phenyl-4-oxo-6-thiatricyclo
undecane 6a
To a solution of 5 (65 mg, 0.13 mmol) and imidazole
(18 mg, 0.27 mmol) in CH2Cl2 (5 mL) was added TES–
Cl (0.05 mL, 0.27 mmol) at rt. The reaction mixture
was stirred at rt for 1 h. Then the reaction mixture
was quenched with H2O, extracted twice with ether,
dried over anhydrous MgSO4, and concentrated. The
residue was chromatographed on a column of silica gel
4.7. PS–Et-supported ligand 2b
A mixture of 5 (112 mg, 0.23 mmol), carboxyethylpoly-
styrene (PS–Et–COOH, 100 mg, 0.12 mmol), and diiso-
propylcarbodiimide (DIC, 0.04 mL, 0.23 mmol) in
CH2Cl2 (2 mL) was stirred at rt for 48 h. The reaction
mixture was filtered and the polymer washed with
CHCl3, MeOH, acetone, and ether. The polymer was
dried under reduced pressure to give 2b (124 mg, 79%,
43% conversion, 0.40 mmol/g of ligand in polymer).
31P NMR (CD3COCD3) d: ꢀ18.05 (s).
with AcOEt–hexane = 1:10 to afford 6a (72 mg, 90%);
21
Colorless oil. ½aꢁ ¼ ꢀ84:8 (c 1.05, CHCl3). IR (film)
D
cmꢀ1 = 759, 1216, 3019. 1H NMR (CDCl3) d: 0.48
(6H, q, J = 8.0 Hz), 0.84 (9H, t, J = 7.9 Hz), 0.91 (3H,
s), 0.94–1.05 (2H, m), 1.43–1.56 (4H, m), 1.59–1.69
(3H, m), 1.84–1.89 (1H, m), 2.70 (1H, d, J = 14.2 Hz),
3.19 (1H, d, J = 14.2 Hz), 3.59 (1H, dd, J = 2.9,
7.8 Hz), 4.56 (2H, s), 6.38 (1H, d, J = 7.7 Hz), 6.94
(1H, d, J = 3.0 Hz), 7.26–7.32 (11H, m), 7.67 (1H, dd,
J = 4.3, 7.9 Hz). 13C NMR (CDCl3) d: 4.42, 5.39, 5.81,
6.59, 6.74, 7.29, 20.47, 23.41, 27.28, 29.98, 34.33,
37.88, 41.84, 45.58, 46.78, 65.00, 81.00, 85.65, 127.28,
127.44, 127.75, 128.36, 128.43, 128.51, 128.64, 131.35,
132.05, 134.56, 133.74, 133.86, 134.19, 136.43, 136.78,
141.27, 142.86, 143.63. MS m/z: 602 (M+); HRMS: calcd
for C36H47O2PSSi (M+): 602.2803, found: 602.2789.
4.8. TentaGel-supported ligand 2c
A mixture of 5 (30 mg, 0.06 mmol), TentaGel MB–
COOH (100 mg, 0.04 mmol), and DIC (0.01 mL,
0.8 mmol) in CH2Cl2 (2 mL) was stirred at rt for 48 h.
The reaction mixture was filtered and the polymer
washed with CHCl3, MeOH, acetone, and ether. The
polymer was dried under reduced pressure to give 2c
(107 mg, 92%, 36% conversion, 0.13 mmol/g of ligand
in polymer). 31P NMR (CD3COCD3) d: ꢀ17.93 (s).
4.5. (1R,3R,5R,8S)-5-(4-Acetoxymethyl-2-diphenyl-
phosphino)phenyl-11,11-dimethyl-4-oxo-6-thiatricyclo
undecane 6b
4.9. General procedure for the Pd-catalyzed allylic
alkylation using polymer-supported ligand
To a solution of 5 (50 mg, 0.10 mmol) and Et3N
(0.03 mL, 0.20 mmol) in CH2Cl2 (5 mL) was added
Ac2O (0.01 mL, 0.15 mmol) at rt. The reaction mixture
was stirred for 5 h at rt. The mixture was quenched with
H2O and extracted twice with CHCl3. The combined or-
ganic layers were washed with brine, dried over anhy-
drous MgSO4, and concentrated. The residue was
chromatographed on a column of silica gel with
A mixture of polymer-supported ligand (0.01 mmol,
5 mol %),
[PdCl(g3-C3H5)]2
(2 mg,
0.005 mmol,
2.5 mol %), 1,3-diphenyl-2-propenyl acetate 7 (50 mg,
0.2 mmol), and KOAc (0.4 mg, 0.004 mmol, 2 mol %)
in CH2Cl2 (1 mL) was stirred for 1 h at rt under argon.
To this mixture at the desired reaction temperature was
added dimethyl malonate (0.07 mL, 0.59 mmol) and
N,O-bis(trimethylsilyl)acetamide (0.15 mL, 0.59 mmol).
After 24 h, the reaction mixture was quenched with sat-
urated NH4Cl solution and filtered. The filtrate was ex-
tracted twice with ether. The combined organic layers
were washed with brine, dried over anhydrous MgSO4,
and concentrated. The residue was purified by prepara-
tive TLC (hexane–AcOEt = 2:1) to afford 8.
AcOEt–hexane = 1:10 to afford 6b (45 mg, 83%); Color-
20
less oil. ½aꢁ ¼ ꢀ73:0 (c 1.00, CHCl3). IR (film)
D
1
cmꢀ1 = 756, 1216, 1249, 1733, 3021. H NMR (CDCl3)
d: 0.86–0.88 (1H, m), 0.92 (3H, s), 0.95–1.06 (1H, m),
1.42 (1H, s), 1.45 (3H, s), 1.59–1.72 (3H, m), 1.83–1.89
(1H, m), 1.97 (3H, s), 2.71 (1H, d, J = 14.2 Hz), 3.18
(1H, d, J = 14.2 Hz), 3.55 (1H, dd, J = 3.0, 8.0 Hz),
4.93 (2H, s), 6.34 (1H, d, J = 7.3 Hz), 6.84 (1H, dd,
J = 1.5, 4.3 Hz), 7.27–7.37 (10H, m), 7.47–7.57 (1H,
m), 7.71 (1H, dd, J = 4.2, 8.0 Hz). 13C NMR (CDCl3)
d: 20.42, 23.36, 27.23, 29.69, 29.95, 34.29, 37.23, 41.83,
45.54, 46.74, 65.59, 81.35, 85.38, 127.67, 128.39,
4.10. General procedure for the Pd-catalyzed allylic
amination using polymer-supported ligand
A mixture of polymer-supported ligand (0.01 mmol,
[PdCl(g3-C3H5)]2
5 mol %),
(2 mg,
0.005 mmol,

614
H. Nakano et al. / Tetrahedron: Asymmetry 16 (2005) 609–614
Y.; Fujita, R.; Hongo, H. Tetrahedron: Asymmetry 2003,
14, 2361.
2.5 mol %), and 7 (50 mg, 0.2 mmol) in CH2Cl2 (1 mL)
was stirred for 1 h at rt under argon. To this mixture
at the desired reaction temperature was added benzyl-
amine 9 (0.22 mL, 1.98 mmol) or potassium phthalimide
10 (110 mg, 0.60 mmol). After 24 h, the reaction mixture
was quenched with saturated NH4Cl solution and fil-
tered. The filtrate was extracted twice with ether. The
combined organic layers were washed with brine, dried
over anhydrous MgSO4, and concentrated. The residue
was purified by preparative TLC (hexane–AcOEt = 2:1)
to afford 11.
4. For recent reviews on heterogeneous asymmetric catalysis,
see: (a) Chiral Catalyst Immobilization and Recycling; De
Vos, D. E., Vankelecom, I. F. J., Jacobs, P. A., Eds.;
Wiley-VCH: Weinheim, 2000; (b) Fan, Q.-H.; Li, Y.-M.;
Chan, A. S. C. Chem. Rev. 2002, 102, 3365; (c) Aoki, K.;
Shimada, T.; Hayashi, T. Tetrahedron: Asymmetry 2004,
15, 1771.
5. Reviews on allylic amination: (a) Johannsen, M.; Jorgen-
sen, K. A. Chem. Rev. 1998, 98, 1689; (b) Heumann, A. In
Transition Metals for Organic Synthesis; Beller, M., Bolm,
C., Eds.; Wiley-VCH: Weinheim, 1998; p 251.
4.11. Recycling experiments with polymer-supported
POT ligand 2a
6. For some recent successful publications on polymer-
supported chiral ligands in Pd-catalyzed allylic alkylation
and amination: (a) Greenfield, S. J.; Agarkov, A.; Gil-
bertson, S. R. Org. Lett. 2003, 5, 3069; (b) Agarkov, A.;
Uffman, E. W.; Gilbertson, S. R. Org. Lett. 2003, 5, 2091;
(c) Uozumi, Y.; Tanaka, H.; Shibatomi, K. Org. Lett.
2004, 6, 281; (d) Song, C. E.; Yang, J. W.; Roh, E. J.; Lee,
S.-g.; Ahn, J. H.; Han, H. Angew. Chem., Int. Ed. 2002, 41,
4691; (e) Trost, B. M.; Pan, Z.; Zambrano, J.; Kujat, C.
Angew. Chem., Int. Ed. 2002, 41, 3852; (f) Uozumi, Y.;
Shibatomi, K. J. Am. Chem. Soc. 2001, 123, 2919; (g)
Hallman, K.; Moberg, C. Tetrahedron: Asymmetry 2001,
12, 1475; (h) Glos, M.; Reiser, O. Org. Lett. 2000, 2, 2045;
(i) Hallman, K.; Macedo, E.; Nordstrom, K.; Moberg, C.
Tetrahedron: Asymmetry 1999, 10, 4037; (j) Uozumi, Y.;
Danjo, H.; Hayashi, T. Tetrahedron Lett. 1998, 39, 8303;
(k) Gamez, P.; Dunjic, B.; Fache, F.; Lemaire, M.
Tetrahedron: Asymmetry 1995, 6, 1109.
After reaction, the mixture was decanted off by using a
cannula, and the solution of the reactants added to the
polymer-supported 2a for the next cycles. This proce-
dure was recycled three times.
References
1. (a) Comprehensive Asymmetric Catalysis; Jacobsen, E.
N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
1999; Vols. I–III; (b) Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; Wiley-VCH: New York, 2000.
2. For a recent review on asymmetric allylic substitution, see:
(a) Hayashi, T. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; VCH: Weinheim, 1993; p 325; (b) Trost, B. M.; van
Vranken, D. L. Chem. Rev. 1996, 96, 395; (c) Helmchen,
G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336; (d) Seebach,
D.; Beck, A. K.; Heckel, A. Angew. Chem., Int. Ed. 2001,
40, 92; (e) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003,
103, 2921.
3. (a) Nakano, H.; Okuyama, Y.; Hongo, H. Tetrahedron
Lett. 2000, 41, 4615; (b) Nakano, H.; Okuyama, Y.;
Yanagida, M.; Hongo, H. J. Org. Chem. 2001, 66, 620; (c)
Nakano, H.; Suzuki, Y.; Kabuto, C.; Fujita, R.; Hongo,
H. J. Org. Chem. 2002, 67, 5011; (d) Nakano, H.;
Yokoyama, J.; Fujita, R.; Hongo, H. Tetrahedron Lett.
2002, 43, 7761; (e) Nakano, H.; Yokoyama, J.; Okuyama,
7. Dufresne, C.; Leblanc, Y.; Lau, C. K.; Li, C.-Si.; Roy, P.
Patent, WO 02/102813 A1.
8. The conversions and loading efficiencies of 2a–c were
calculated from the difference of the weights of the resins
(PS–DES–Cl, PS–Et–COOH, and TentaGel–COOH)
before the reactions, and those weights of the reactant
resins after the reactions. The chemical yields of 2a–c were
calculated based on the theoretical yields.
9. Trost, B. M.; Murphy, D. J. Organometallics 1985, 4,
1143.
10. Hu, Y.; Porco, J. A., Jr.; Labadie, J. W.; Gooding, O. W.;
Trost, B. M. J. Org. Chem. 1998, 63, 4518.