Asymmetric Mukaiyama aldol reaction of silyl enol ethers with aldehydes using a polymer-supported chiral Lewis acid catalyst

Article abstract of DOI:10.1016/j.tet.2005.07.110

Chiral N-sulfonylated α-amino acid monomer (5) derived from (S)-tryptophan was copolymerized with styrene and divinylbenzene under radical polymerization conditions to give a polymer-supported N-sulfonyl-(S)-tryptophan (6). Treatment of the polymer-supported chiral ligand with 3,5- bis(trifluoromethyl)phenyl boron dichloride afforded a polymeric Lewis acid catalyst (16) effective for asymmetric Mukaiyama aldol reaction of silyl enol ethers and aldehydes. Various aldehydes were allowed to react with silyl enol ethers in the presence of the polymeric chiral Lewis acid to give the corresponding aldol adducts in high yield with high levels of enantioselectivity.

Full text of DOI:10.1016/j.tet.2005.07.110

Tetrahedron 61 (2005) 12074–12080
Asymmetric Mukaiyama aldol reaction of silyl enol ethers with
aldehydes using a polymer-supported chiral Lewis acid catalyst
*
Shinichi Itsuno, Shinnosuke Arima and Naoki Haraguchi
Department of Materials Science, Toyohashi University of Technology, Toyohashi, 441-8580 Japan
Received 18 June 2005; revised 27 July 2005; accepted 27 July 2005
Available online 12 October 2005
Abstract—Chiral N-sulfonylated a-amino acid monomer (5) derived from (S)-tryptophan was copolymerized with styrene and
divinylbenzene under radical polymerization conditions to give a polymer-supported N-sulfonyl-(S)-tryptophan (6). Treatment of the
polymer-supported chiral ligand with 3,5-bis(trifluoromethyl)phenyl boron dichloride afforded a polymeric Lewis acid catalyst (16) effective
for asymmetric Mukaiyama aldol reaction of silyl enol ethers and aldehydes. Various aldehydes were allowed to react with silyl enol ethers in
the presence of the polymeric chiral Lewis acid to give the corresponding aldol adducts in high yield with high levels of enantioselectivity.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
quantitative conversion with high enantioselectivity. For
example, the reaction of benzaldehyde with 1-phenyl-1-
(trimethylsilyloxy)ethylene afforded the chiral aldol adduct in
99% yield with 94% ee.12 We have applied the same chiral
oxazaborolidinone catalyst for the preparation of optically
active polymersbymeans ofasymmetricaldol polymerization
method developed by us.14–16 Optically active poly(b-
hydroxycarbonyl)s having high optical purity were first
obtained by this method. On the other hand we have also
developed polymer-supported N-sulfonyl a-amino acids as
chiral ligand of the asymmetric Diels–Alder reaction.17 For
example, polymer-supported oxazaborolidinone prepared
from N-sulfonyl-(S)-valine and borane-dimethyl sulfide
showed excellent activity in Diels–Alder reaction between
cyclopentadiene and methacrolein to give the corresponding
chiral adduct in quantitative yield with up to 95% ee, which
was higher than that obtained from the low-molecular-weight
catalyst in solution system.18 We have now developed
polymer-supported N-sulfonyl-(S)-tryptophan to prepare a
polymeric version of the Yamamoto’s oxazaborolidinone
catalyst. In this paper we discuss the synthesis of a chiral
monomer derived from (S)-tryptophan and its polymerization.
Optimized reaction conditions for asymmetric aldol reaction
between aldehyde and silyl enol ether using this polymeric
catalyst was also discussed.
Catalytic asymmetric Mukaiyama aldol reactions have
emerged as one of the most important carbon–carbon bond
forming reactions affording synthetically useful optically
active b-hydroxycarbonyl compounds.1–3 Various method-
ologies of the asymmetric Mukaiyama aldol reaction have
been studied, which include chiral Lewis acid promoted
reaction,4 Lewis base mediated reaction,5 and the reaction via
transition metal enolate intermediates.6 These chiral Lewis
acid catalysts include a number of chirally modified boron
complexes that have been prepared and studied as Lewis acid
catalysts for the asymmetric reactions including Mukaiyama
aldol reaction. Chiral N-sulfonyl oxazaborolidinones are
examples that are readily prepared from a-amino acid and
boron compounds. The chiral N-sulfonyl oxazaborolidinones
were originally developed for the catalyst of asymmetric
Diels–Alder reaction by Yamamoto7 and Helmchen.8
Kiyooka indicated the efficiency of the methodology using
oxazaborolidinones as chiral catalyst for the Mukaiyama aldol
reaction.9,10 Corey chose (S)-tryptophan as a chiral a-amino
acid and revealed its effectiveness mainly due to its possibility
of p–p stacking effect based on the indole ring.11 Yamamoto
and Ishihara further improved the efficiency of the (S)-
tryptophan derived N-sulfonyl oxazaborolidinone system by
introducing a new boron substituent of 3,5-bis(trifluoro-
methyl)phenyl group.12,13 By using this catalyst asymmetric
aldol reaction between benzaldehyde and silyl enol ether
smoothly occurred to give the corresponding aldol adduct in
2. Results and discussion
2.1. Chiral monomer synthesis
Keywords: Mukaiyama aldol reaction; N-sulfonyl-(S)-tryptophan; Oxaza-
borolidinone; Chiral Lewis acid; Silyl enol ether.
Yamamoto and Ishihara introduced a new chiral Lewis acid
N-sulfonyloxazaborolidinone 1 using arylboron dichloride
bearing electron-withdrawing substituents as Lewis acid
*
Corresponding author. Tel./fax: C81 532 44 6813;
e-mail: itsuno@tutms.tut.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.110

S. Itsuno et al. / Tetrahedron 61 (2005) 12074–12080
12075
amino acids and used them as polymeric chiral Lewis acid
catalysts of asymmetric reactions including Diels–Alder
reaction,18 we could apply the method to the preparation of
the polymer-supported version of N-sulfonyl-(S)-trypto-
phan. Sodium p-vinylbenzenesulfonate 2 was readily
converted to p-vinylbenzenesulfonylchloride 3, which was
allowed to react with (S)-tryptophan 4 to prepare N-(p-
styrenesulfonyl)-(S)-tryptophan 5 as shown in Scheme 2.19
Because of the instability of the indole ring of (S)-
tryptophan, purification of the chiral monomer required
special care. As soon as the chiral monomer was purified the
monomer should be subjected to the polymerization,
otherwise the monomer was susceptible to decomposition
under air. However, purified chiral monomer 5 could be
stored for long period of time under argon at K20 8C.
Scheme 1. Oxazaborolidinone catalyst derived from N-sulfonyl-(S)-
tryptophan.
2.2. Polymerization
In our previous paper, we have prepared chiral polymer
beads containing N-sulfonylamino acid pendant groups by
means of suspension polymerization method.18 First we
tried the suspension polymerization of N-sulfonyl-(S)-
tryptophan monomer 5 with styrene in the presence of
divinylbenzene as crosslinking agent. However, mainly due
to the low solubility of the chiral monomer in organic
solvent the diluted monomer solution did not form stable
particles in water. Several attempts of suspension polymer-
ization failed to obtain the corresponding polymer beads in
satisfactory yield. Although the monomer showed higher
solubility in THF and DMF, the use of such water miscible
solvents would cause the difficulty in the suspension
polymerization in water. Thus, we changed the polymer-
ization method to solution polymerization. In this case we
could even use the solvents miscible with water. THF was
chosen as the polymerization solvent, because all the
monomers including p-vinylbenzenesulfonyl-(S)-trypto-
phan, styrene and divinylbenzene dissolved well in it. As
soon as the polymerization of the monomers was initiated in
THF the viscosity of the solution increased and finally gel
was formed. As shown in Scheme 3, polymerization
Scheme 2. Preparation of chiral N-sulfonyl-(S)-tryptophan monormer.
components.12 The chiral Lewis acid 1 showed excellent
catalytic activity in an enantioselective Mukaiyama aldol
reaction.12 The chirality of the catalyst is originated from
(S)-tryptophan. The structure of B-substituent in the catalyst
is important to obtain a high enantioselectivity. Introduction
of 3,5-bistrifluoromethylphenyl group generated a highly
enantioselective catalyst 1 (Scheme 1). Since we have
synthesized various types of polymer-supported N-sulfonyl-
Scheme 3. Preparation of polymer-supported chiral N-sulfonyl-(S)-tryptophan.

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S. Itsuno et al. / Tetrahedron 61 (2005) 12074–12080
Table 1. Asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone catalyzed by oxazaborolidinone catalyst
Entry
Lewis acid catalyst
Silyl enol ether
–OSiR3
ee (%)b
–OH
ee (%)b
Yield (%)a
Yield (%)a
1
15
1
1
1
1
13b
13a
13b
13b
13c
18
91
95
69
69
—
93
92
65
16
76
4
4
30
29
—
68
87
42
88
2c
3
4d
5
a Isolated yield.
b Determined chiral HPLC.
c Data from Ref. 12.
d Reaction was performed at room temperature.
ligand to form oxazaborolidinone 1, which was an efficient
chiral Lewis acid catalyst of the aldol reaction to afford
optically active b-hydroxyketone in quantitative conversion
at K78 8C.12,13 We surveyed the effect of several silyl
substituents on the silyl enol ether. From the results obtained
in Table 1, we chose triethylsilyl enol ether as a substrate of
the asymmetric aldol reaction. In order to keep high
enantioselectivity the reaction should be performed at
lower temperature (K78 8C). The absolute configuration
of the aldol adducts indicated in Table 1 was uniformly R
(Scheme 4).
Scheme 4. Asymmetric aldol reaction using polymer-supported chiral
oxazaborolidinone.
occurred to give the corresponding crosslinked polymer 6.
The obtained gel was crushed in methanol and washed on a
glass filter to give the powdered polymer-supported
N-sulfonyl-(S)-tryptophan. The degree of crosslinking and
the chiral ligand loading were controlled by the change of
the monomers composition. Crosslinking agents (10, 11)
other than divinylbenzene could be used in this polymer-
ization. Acrylonitrile 8 instead of styrene as achiral
monomer was also used to give the crosslinked chiral
polymer 6j. All these polymers were gel-like materials,
which were insoluble in organic solvents but swellable in
THF, DMF, and propionitrile. Polymerization without
crosslinking agent afforded the linear chiral polymer that
was soluble in THF.
2.3.1. Asymmetric aldol reaction using polymeric
oxazaborolidinone. Since the B-aryloxazaborolidine
could not be prepared from arylboronic acid,20,21 the
oxazaborolidinones were prepared from arylboron
dichlorides. We have prepared the polymeric oxaza-
borolidinone 16 from the chiral polymer 6 possessing
N-sulfonyl-(S)-tryptophan moiety and arylboron dichloride
15 in dichloromethane according to the method reported by
Ishihara.12 (Scheme 5) Our initial studies using the
polymeric oxazaborolidinone were conducted with benzal-
dehyde and enol silane 13b derived from acetophenone at
K78 8C in propionitrile as a solvent in the presence of 16 as
a catalyst. The asymmetric aldol reaction smoothly occurred
in the presence of the polymeric catalyst 16 to give the
corresponding (R)-b-hydroxyketone in high yield with a
high level of enantioselectivity. Table 2 shows the effect of
catalyst loading and crosslinking degree on the asymmetric
aldol reaction. Lightly crosslinked polymer 6b having 5%
catalyst loading showed the best result. The enantio-
selectivity obtained was almost same as that from
2.3. Asymmetric aldol reaction
Mukaiyama aldol reaction between benzaldehyde and silyl
enol ether proceeded smoothly in the presence of boron
dichloride 15 to give the corresponding aldol adduct in high
yield as shown in Table 1, run 1. The chloride was easily
substituted with N-(p-toluenesulfonyl)-(S)-tryptophan chiral
Scheme 5. Preparation of polymer-supported chiral oxazaborolidinone catalyst.

S. Itsuno et al. / Tetrahedron 61 (2005) 12074–12080
12077
Table 2. Asymmetric aldol reaction of 12 and 13b using polymer-supported oxazaborolidinone catalyst in propionitrile at K78 8C for 24 h
Entry
Polymer
Catalyst loading
(%)
Crosslinking agent
Degree of cross-
linking (%)
14
Yield (%)a
ee (%)b
1
6a
6b
6b
6b
6c
6d
6e
6f
5
5
5
5
5
5
5
10
20
5
5
5
—
9
9
9
9
9
9
9
9
0
1
1
1
99
90
99
99
99
99
89
83
73
98
98
99
89
91
91
90
90
88
83
80
75
76
83
71
2c
3
4d
5
6
7
8
9
10
11
12
2
2.5
4.5
2
2
1
6g
6h
6i
10
11
9
1
1
6j
a Isolated yield.
b Determined by chiral HPLC.
c After 3 h.
d Recycled polymer-supported N-sulfonyl-(S)-tryptophan was used.
the low-molecular-weight catalyst 1 in homogeneous
solution system. Higher crosslinking and catalyst loading
decreased both reactivity and enantioselectivity to some
extent. After the reaction completed the polymeric catalyst
could be readily removed by simple filtration. The
polymeric catalyst prepared from the recycled polymer
was shown to keep its activity (entry 4) in a second cycle.
Polymers crosslinked with 10 and 11 were also effective for
the same reaction (entries 10 and 11). Somewhat lower
enantioselectivities were obtained with these polymeric
catalysts compared to the corresponding divinylbenzene
crosslinked polymers.
Not only benzaldehyde, also other several aldehydes reacted
with the silyl enol ether in the presence of chiral
oxazaborolidinone 1 to give the corresponding aldol
products in high enantioselectivity (Scheme 6). Table 3
shows the results of the asymmetric aldol reactions with 8.
As shown in Table 4 the polymeric oxazaborolidinone 16
was also effective in forming the same product in the same
level of the enantioselectivity. The amount of the polymeric
catalyst used had no effect on the enantioselectivity of the
aldol product (entry 2). Aliphatic aldehydes showed high
enantioselectivity (95% ee) using both 1 and 16.
Table 4. Asymmetric aldol reaction of aldehyde and silyl enol ether 13b
with polymer-supported oxazaborolidinone catalyst 16 derived from 6b
Entry
Aldehyde
Aldol product
Yield (%)a
ee (%)b
1
2c
3
4
5
6
7
8
9
12
12
14
14
99
99
81
74
71
69
72
47
72
91
91
71
83
91
75
95
72
70
17a
17b
17c
17d
17e
17f
17g
18a
18b
18c
18d
18e
18f
18g
a Isolated yield.
b Determined by chiral HPLC.
c Compound 16 (20 mol%) was used.
Scheme 6. Asymmetric aldol reaction of various aldehyde with silyl enol
ether.
2.4. Some other asymmetric reactions using the
polymeric oxazaborolidinone catalyst
Table 3. Asymmetric aldol reaction of aldehyde and silyl enol ether 13b
with oxazaborolidinone catalyst 1
Chiral oxazaborolidinones are known to be an efficient
Lewis acid catalyst for various kinds of carbon–carbon bond
forming reactions. Since we succeeded in maintaining the
catalytic activities of chiral oxazaborolidinone on the
crosslinked polymer, the polymer-supported oxazaborolidi-
none would be applicable to these reactions. The polymeric
catalyst 16 was used for reactions including Mannich type
reaction of imine with silyl enol ether and allylation of
aldehyde. Scheme 7 revealed that the silyl enol ether 13b
reacted with aldimine 19 to yield the b-aminoketone 20 in
high yield with enantioselectivity of 56%. The same catalyst
Entry
Aldehyde
Aldol product
Yield (%)a
ee (%)b
1
2
3
4
5
6
7
8
12
14
99
97
93
99
99
98
98
99
92
82
82
93
81
95
80
80
17a
17b
17c
17d
17e
17f
17g
18a
18b
18c
18d
18e
18f
18g
a Isolated yield.
b Determined by chiral HPLC.

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S. Itsuno et al. / Tetrahedron 61 (2005) 12074–12080
F254) were used for thin layer chromatography. Silica gel
(Wakogel C-200) was used for column chromatography.
Optical rotations were taken on a JASCO DIP-140 digital
polarimeter using a 10 cm thermostated microcell.
4.1.1. Preparation of silyl enol ethers 13. Silyl enol ethers
13 were prepared by quenching the corresponding lithium
enolates, derived from ketones, with lithium N,N-diiso-
propylamine (LDA) in THF, with chlorosilane.14,22
Scheme 7. Asymmetric Mannich reaction.
was also active in the asymmetric allylation reactions.
Especially methallyltrimethylsilane 21 (RZSiMe3) reacted
with benzaldehyde to give the optically active homoallyl
alcohol 22 in quantitative yield with 73% ee (Scheme 8).
4.1.2. Preparation of N-(p-vinylbenzenesulfonyl)-(S)-
tryptophan 5. p-Vinylbenzenesulfonyl chloride was
prepared by the reported procedure.23 To a suspension of
(S)-tryptophan (1.52 g, 8.0 mmol) in water (30 mL) and
THF (5 mL) was added triethylamine (1.9 mL, 19.2 mmol).
The resulting clear solution was stirred at 0 8C and a THF
(3 mL) solution of p-vinylbenzenesulfonyl chloride (1.94 g,
9.6 mmol) was added to the mixture. The resulting mixture
was then stirred at room temperature for 3 h. The solution
was cooled to 0 8C and acidified with 2 M HCl to pH 2. The
aqueous layer was extracted with ethyl acetate (20 mL!3).
The combined organic layer was dried over MgSO4 and
evaporated to give the crude product, which was purified by
silica gel column chromatography (hexane/ethyl acetate,
1:1). Yield 87% (2.58 g). Mp 67–68 8C. 1H NMR
(300 MHz, CDCl3): d 3.05–3.28 (m, 2H), 4.23 (m, 1H),
5.37 (d, JZ11 Hz, 1H), 5.50 (d, JZ8 Hz, 1H), 5.77 (d, JZ
17 Hz, 1H), 6.60 (dd, JZ11, 17 Hz, 1H), 6.90–7.55 (m,
10H). 13C NMR (75 MHz, CDCl3): d 175.9, 141.9, 137.9,
136.3, 135.6, 127.2, 126.6, 124.3, 122.2, 119.8, 117.6,
111.7, 108.6, 56.2, 28.9. IR (KBr) 3400, 1730, 1430, 1330,
1150, 1090 cmK1. [a]D23 C38 (c 1.0, ethanol). Anal. Calcd
for C19H18N2O4S: C, 61.61; H, 4.90; N, 7.56. Found: C,
61.58; H, 4.92; N, 7.55%.
Scheme 8. Asymmetric allylation of benzaldehyde.
3. Conclusion
The chiral monomer of N-sulfonylated (S)-tryptophan was
prepared and polymerized with styrene and crosslinking
agent such as divinylbenzene to give polymeric chiral
ligand 6. The reaction of the obtained polymer 6 and 3,5-
bis(trifluoromethyl)phenylboron dichloride 15 gave poly-
meric chiral oxazaborolidionone 16. We have found that 16
worked well as a catalyst in the asymmetric Mukaiyama
aldol reaction of aldehyde and silyl enol ether. High level of
enantioselectivity was obtained using the polymeric chiral
catalyst. Other than the Mukaiyama aldol reaction Mannich
type reaction and allylation reaction were asymmetrically
catalyzed by the same polymeric catalyst.
4.1.3. Preparation of polymer-immobilized N-(p-vinyl-
benzenesulfonyl)-(S)-tryptophan 6. A 20 mL glass
ampoule equipped with a magnetic stirring bar was charged
with THF (5 mL), 5 (0.749 g, 2.02 mmol), styrene (3.98 g,
38.2 mmol), 2,20-azobis(isobutyronitrile) (AIBN) (60 mg).
The ampoule was sealed after three freeze-thaw cycles
under liquid nitrogen. Copolymerization was carried out at
70 8C for 24 h. The ampoule was opened and the resulting
mixture was poured into methanol and the formed
precipitate was filtered, washed with methanol and dried
to give the corresponding polymer 6a as a white powder
(4.17 g, 88%). MnZ28,000, Mw/MnZ2.27. 1H NMR
(300 MHz, CDCl3): d 1.2–2.2 (polymer main chain CH,
CH2), 3.2 (br s, tryptophan CH2), 4.2 (br s, tryptophan CH),
6.3–7.6 (aromatic protons). IR (KBr) 3627, 3427, 3025,
2920, 1731, 1600, 1490, 1450, 1330, 1156, 1090. Anal.
Calcd for (C8H8)0.95(C19H18N2O4S)0.05: C, 87.43; H, 7.29;
N, 1.19. Found: C, 87.50; H, 7.25; N, 1.22%.
4. Experimental
4.1. General
Unless otherwise noted, all reactions were performed in
oven-dried glassware, under an atmosphere of argon. H
1
NMR (300 MHz) spectra were recorded on Varian Mercury
300 spectrometer using tetramethylsilane as an internal
standard, and J values are recorded in Hz. IR spectra were
recorded with a JEOL JIR-7000 FT-IR spectrometer and are
reported in reciprocal centimeter (cmK1). Elemental
analyses were performed at the Microanalytical Center of
Kyoto University. HPLC analyses were performed with a
JASCO HPLC system composed of 3-line degasser DG-
980-50, HPLC pump PV 980, column oven CO-965,
equipped with a chiral column (Chiralcel OD-H, Daicel)
using hexane/2-propanol as an eluent. A UV detector
(JASCO UV-975) was used for the peak detection. GC
analyses of reaction conversion were performed with a
Shimadzu Capillary Gas Chromatograph 14A equipped
with a capillary column (Astec Chiraldex G-TA, 30 m!
0.25 mm). Precoated silica gel plates (Merck 5554, 60
Crosslinked polymers 6b–6j were prepared from 5, achiral
monomer, and crosslinking agent by the same procedure
described for the solution polymerization. After the
polymerization was completed gel was treated with
methanol. The methanol suspension of the gel was then
washed with methanol on a glass filter. The obtained
polymer was dried in vacuo.

S. Itsuno et al. / Tetrahedron 61 (2005) 12074–12080
12079
4.2. General procedure for the Mukaiyama aldol
reaction catalyzed by 16
HPLC analysis using Chiralcel OD column (hexane/
2-propanol, 20:1), flow rateZ0.4 mL/min, column
temperature; 30 8C, tSZ47.8 min (S), tRZ56.5 min (R).
A suspension of 3,5-bis(trifluoromethyl)boronic acid (5.8 g,
22.4 mmol) in benzene was heated for 12 h at reflux with
removal of water using CaH2 in a Soxhlet thimble. The
resulting solution was cooled to room temperature and
concentrated in vacuo to give trimeric anhydride as a white
solid. A solution of boron trichloride (45 mL, 45 mmol) in
heptane was added to the above solid and heated at reflux for
6 h. After the solvent was removed the product 15 was
isolated as a colorless oil by distillation under reduced
pressure.12
4.2.5. 3-Hydroxy-1-phenylheptan-1-one 18e. The enantio-
meric excess was determined by chiral HPLC analysis using
Chiralcel OD column (hexane/2-propanol, 20:1), flow
rateZ0.2 mL/min, column temperature; 30 8C, tSZ
32.7 min (S), tRZ36.8 min (R).
4.2.6. 3-Hydroxy-3-naphthalen-1-yl-1-phenylpropan-1-
one 18f. The enantiomeric excess was determined by chiral
HPLC analysis using Chiralcel OD column (hexane/
2-propanol, 20:1), flow rateZ0.4 mL/min, column
temperature; 30 8C, tSZ52.2 min (S), tRZ71.8 min (R).
Compound 15 (32 mg, 0.11 mmol) prepared above was
treated with polymer-supported N-sulfonyl-(S)-tryptophan
6b (0.24 g, 0.1 mmol) suspended in dichloromethane
(4 mL) at room temperature. After being stirred for 1 h,
the reaction mixture was concentrated in vacuo to give the
polymer-supported oxazaborolidinone 16. A suspension of
16 in propionitrile (4 mL) was cooled to K78 8C. After
benzaldehyde (106 mg, 1 mmol) was added to the mixture,
1-phenyl-1-(triethylsilyloxy)ethylene (281 mg, 1.2 mmol)
in propionitrile (1 mL) was subsequently added dropwise.
The reaction mixture was stirred at K78 8C for 24 h and
then quenched by addition of saturated aqueous NaHCO3.
The polymeric catalyst was removed by filtration and the
filtrate was extracted with ether. The combined organic
phases were dried over MgSO4 and evaporated. The residue
was dissolved in THF (2 mL) and 1 M aqueous HCl (2 mL),
and the resulting solution was allowed stand for 30 min.
Saturated NaHCO3 was added and the mixture was
extracted with ether. The combined organic phases were
dried over MgSO4 and evaporated to an oily residue. Silica
gel chromatography (hexanes/ethyl acetate, 4:1) afforded
224 mg (99% yield) of the aldol product 14. 1H NMR and IR
spectroscopic data are in agreement with those reported in
the literature.24 The enantioselectivity was determined by
chiral HPLC analysis using Chiralcel OD column (hexane/
2-propanol, 20:1), flow rateZ0.4 mL/min, column
temperature; 30 8C, tSZ42.3 min (S), tRZ47.0 min (R).
4.2.7. 3-Furan-2-yl-3-hydroxy-1-phenylpropan-1-one
18g. The enantiomeric excess was determined by chiral
HPLC analysis using Chiralcel OD column (hexane/
2-propanol, 20:1), flow rateZ0.4 mL/min, column
temperature; 30 8C, tSZ48.4 min (S), tRZ54.3 min (R).
4.3. Asymmetric Mannich reaction using polymer-
supported oxazaborolidinone
Suspension of 16 (0.1 mmol, 10 mol%) prepared from 6b
(5% loading, 1% crosslinking) in THF (4 mL) was cooled to
K78 8C. After N-benzilidenebenzenamine (181 mg,
1 mmol) was added to the mixture, 1-phenyl-1-(triethyl-
silyloxy)ethylene (281 mg, 1.2 mmol) in propionitrile
(1 mL) was subsequently added dropwise. The reaction
mixture was stirred at K78 8C for 24 h and then quenched
by addition of saturated aqueous NaHCO3. The polymeric
catalyst was removed by filtration and the filtrate was
extracted with ether. The combined organic phases were
dried over MgSO4 and evaporated. The combined organic
phases were dried over MgSO4 and evaporated to an oily
residue. Silica gel chromatography (hexanes/ethyl acetate,
1:1) afforded 280 mg (93% yield) of b-amino ketone 20. 1H
NMR (300 MHz, CDCl3): d 3.47 (m, 2H), 5.02 (m, 1H),
6.50–7.90 (m, 15H). The enantiomeric excess (56% ee) was
determined by chiral HPLC analysis using Chiralcel OD
column (hexane/2-propanol, 3:1), flow rateZ0.2 mL/min,
column temperature; 30 8C, tSZ23.8 min (S), tRZ29.1 min
(R).
4.2.1. 3-Hydroxy-1-phenyl-3-(4-methoxyphenyl)-pro-
pan-1-one 18a. The enantiomeric excess was determined
by chiral HPLC analysis using Chiralcel OD column
(hexane/2-propanol, 20:1), flow rateZ0.4 mL/min, column
temperature; 30 8C, tSZ42.3 min (S), tRZ47.0 min (R).
4.4. Asymmetric allylation of benzaldehyde using
polymer-supported oxazaborolidinone
4.2.2. 3-Hydroxy-1-phenyl-3-(4-bromophenyl)-propan-
1-one 18b. The enantiomeric excess was determined by
chiral HPLC analysis using Chiralcel OD column (hexane/
2-propanol, 20:1), flow rateZ0.4 mL/min, column
temperature; 30 8C, tSZ49.4 min (S), tRZ56.2 min (R).
Suspension of 16 (0.1 mmol, 10 mol%) prepared from 6b
(5% loading, 1% crosslinking) in propionitrile (4 mL) was
cooled to K78 8C. After benzaldehyde (106 mg, 1 mmol) in
propionitrile (1 mL) was added to the mixture, trimethyl-2-
methallylsilane (153 mg, 1.2 mmol) was subsequently
added dropwise. The reaction mixture was stirred at
K78 8C for 24 h and then quenched by addition of saturated
aqueous NaHCO3. The polymeric catalyst was removed by
filtration and the filtrate was extracted with ether. The
combined organic phases were dried over MgSO4 and
evaporated. The combined organic phases were dried over
MgSO4 and evaporated to an oily residue. Silica gel
chromatography (hexanes/ethyl acetate, 1:1) afforded
161 mg (99% yield) of homoallylalcohol 22. 1H NMR
4.2.3. 3-Hydroxy-1-phenyl-3-(4-trifluoromethylphenyl)-
propan-1-one 18c. The enantiomeric excess was
determined by chiral HPLC analysis using Chiralcel OD
column (hexane/2-propanol, 20:1), flow rateZ0.4 mL/min,
column temperature; 30 8C, tSZ49.4 min (S), tRZ56.2 min
(R).
4.2.4. 3-Hydroxy-1-phenyl-3-(4-nitrophenyl)-propan-1-
one 18d. The enantiomeric excess was determined by chiral

12080
S. Itsuno et al. / Tetrahedron 61 (2005) 12074–12080
9. Kiyooka, S.; Kaneko, Y.; Komura, M.; Matsuo, H.; Nakano,
M. J. Org. Chem. 1991, 56, 2276.
(300 MHz, CDCl3): d 1.78 (s, 3H), 2.28–2.48 (m, 2H), 4.80
(m, 1H), 4.83 (br, 1H), 4.91 (br, 1H), 7.20–7.40 (m, 5H).
The enantiomeric excess (73% ee) was determined by chiral
HPLC analysis using Chiralcel OD column (hexane/
2-propanol, 20:1), flow rateZ0.4 mL/min, column
temperature; 30 8C, tSZ19.9 min (S), tRZ21.9 min (R).
10. Kiyooka, S. J. Synth. Org. Chem. Jpn. 1997, 55, 313.
11. Corey, E. J.; Cywin, C. L.; Roper, T. D. Tetrahedron Lett.
1992, 33, 6907.
12. Ishihara, K.; Kondo, S.; Yamamoto, H. J. Org. Chem. 2000,
65, 9125.
13. Ishihara, K.; Kondo, S.; Yamamoto, H. Synlett 1999, 1283.
14. Itsuno, S.; Komura, K. Tetrahedron 2002, 58, 8273.
15. Itsuno, S.; Watanabe, H. Polym. Bull. 2003, 51, 183.
16. Itsuno, S. Prog. Polym. Sci. 2005, 30, 540.
Acknowledgements
This work was partially supported by a Grant-in-Aid for
Scientific Research from Ministry of Education, Science,
Sports and Culture of Japan.
17. Kamahori, K.; Tada, S.; Ito, K.; Itsuno, S. Tetrahedron:
Asymmetry 1995, 6, 2547.
18. Kamahori, K.; Ito, K.; Itsuno, S. J. Org. Chem. 1996, 61, 8321.
19. Preparation of some other N-sulfonyl derivatives of (R)-
tryptophan were reported. See: Tamura, Y.; Watanabe, F.;
Nakatani, T.; Yasui, K.; Fuji, M.; Komurasaki, T.; Tsuzuki, H.;
Maekawa, R.; Yoshioka, T.; Kawada, K.; Sugita, K.; Ohtani,
M. J. Med. Chem. 1998, 41, 640.
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