Hydrophobic polymer-supported scandium catalyst for carbon-carbon bond-forming reactions in water

Article abstract of DOI:10.1016/j.tet.2004.06.083

It has been revealed that a hydrophobic polymer-supported scandium(III) catalyst prepared from sulfonated polystyrene resin is an effective catalyst for carbon-carbon bond-forming reactions such as Mukaiyama aldol reactions in water. According to studies

Full text of DOI:10.1016/j.tet.2004.06.083

Tetrahedron 60 (2004) 7673–7678
Hydrophobic polymer-supported scandium catalyst for
carbon–carbon bond-forming reactions in water
*
Shinya Iimura, Kei Manabe and Shu¯ Kobayashi
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received 26 April 2004; revised 24 May 2004; accepted 14 June 2004
Available online 15 July 2004
Abstract—It has been revealed that a hydrophobic polymer-supported scandium(III) catalyst prepared from sulfonated polystyrene resin is
an effective catalyst for carbon–carbon bond-forming reactions such as Mukaiyama aldol reactions in water. According to studies on loading
levels of scandium, hydrophobicity of the catalyst is a key for the efficient catalysis. The scandium catalyst was successfully recovered and
reused. Several ketones instead of aldehydes were also used as substrates in the aldol reactions. Some 1,4-addition reactions also occurred
using the scandium catalyst in water.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Due to the increasing importance of green chemistry in
organic synthesis, development of more efficient and
environmentally friendly processes for chemical trans-
formations is desired.1 One of the ideal methodologies is
the development of organic reactions using highly active,
reusable solid catalysts in water.2,3 Although use of
amphiphilic polymer-supported catalysts has received
much attention, we have recently found that a hydrophobic
polystyrene-supported sulfonic acid (PS-SO3H) is an
effective catalyst for several organic reactions such as
formation of esters, hydrolysis of thioesters, and Mannich-
type reactions in water.4 In addition, as a result of
continuous studies on the loading levels and the structures
of the catalyst, it is suggested that hydrophobicity of the
catalyst is a key for efficient catalysis in water.5 We then
envisaged that hydrophobic polymer-supported Lewis acids
would also work effectively in water. While some solid-
supported Lewis acids which work well in aqueous media
have been reported so far,2 there are still limitations in the
types of reactions and substrates. It is strongly required to
develop more effective, solid-supported Lewis acid
catalysts for organic transformations in water. Here, we
report that a novel hydrophobic polystyrene-supported
scandium(III) is a powerful catalyst for carbon–carbon
bond-forming reactions in pure water.
The aldol-type reactions of silicon enolates with carbonyl
compounds (Mukaiyama aldol reactions) have been recog-
nized as one of the most important tools for carbon–carbon
bond formation that afford synthetically useful b-hydroxy
carbonyl compounds.6 Thus, we performed the reaction of
benzaldehyde with the thioketene silyl acetal (1.5 equiv.)
derived from ethyl 2-methylthiopropionate in water. First,
we tested PS-SO3H, a polymer-supported Brønsted acid
prepared by sulfonation of DVB cross-linked polystyrene
with a loading level of 0.21 mmol/g (Table 1, entry 1). It
was found that the desired product was obtained in a low
yield due to rapid hydrolysis of the silicon enolate. Then, we
tested polymer-supported Lewis acids. Among the Lewis
acids, we focused on scandium(III) because we have already
revealed that it is a water-compatible, strong Lewis acid.7
While several solid-supported scandium(III) catalysts have
been used for aldol reactions in water,2a,i,j wide substrate
generality has not been demonstrated. Moreover, in the
previous example of the same combination of substrates,2a
an excess amount (3.6 equiv.) of the thioketene silyl acetal
was required to obtain the desired adduct in high yield.
Thus, we decided to develop a more effective polymer-
supported scandium. A hydrophobic catalyst, PS-Sc 1, was
readily prepared from hydrophobic PS-SO3H, and ICP
analysis verified that 0.16 mmol/g of Sc was present in the
catalyst. It was exciting to find that the reaction proceeded
smoothly to give the b-hydroxy thioester in excellent yield
when PS-Sc 1 was used as a catalyst (entry 6). Next, we
carried out the reaction with other Lewis acids to compare
the catalytic activities. Sc(O3SOC12H25)3,8 which we
previously developed as a Lewis acid-surfactant-combined
catalyst, gave the aldol product in 75% yield (entry 2). It is
Keywords: Lewis acid; Scandium; Aldol reaction; 1,4-Addition; Water.
*
Corresponding author. Tel.: þ81-3-5841-4790; fax: þ81-3-5684-0634;
e-mail address: skobayas@mol.f.u-tokyo.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.06.083

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S. Iimura et al. / Tetrahedron 60 (2004) 7673–7678
Table 1. Mukaiyama aldol reaction in water with various catalysts
Entry
Catalyst
Loading (mmol/g)a
Yield (%)
1
2
3
4b
5b
6
7
8
9
PS-SO3H
0.21 (S)
—
—
0.64 (Sc)
0.80 (Yb)
0.16 (Sc)
0.67 (Sc)
0.11 (Sc)
0.11 (Sc)
35
75
0
0
0
Sc(O3SOC12H25 3
Sc(OTf)3
PS-Sc
PS-Yb
PS-Sc 1
PS-Sc 1
PS-Sc 2
PS-Sc 3
)
97 (97)c
16c
37c
21c
a
The value is of the element shown in the parenthesis.
Commercially available polymer-supported Lewis acid catalysts.
The catalyst (1 mol%).
b
c
noteworthy that hydrophobic PS-Sc 1 is superior to the
surfactant-type catalyst (Sc(O3SOC12H25)3), which has
been one of the best catalysts for Mukaiyama aldol reactions
in water. Furthermore, only 1 mol% of the catalyst is
enough to complete the reaction (entry 6). On the other
hand, Sc(OTf)3 and commercially available polymer-
supported Lewis acid catalysts (PS-Sc and PS-Yb)9 did
not catalyze the reaction at all in every case (entries 3–5).
While PS-Sc 1 did not seem to swell, these commercially
available polymer-supported Lewis acids swelled signifi-
cantly in water, suggesting that the hydrophobicity of the
polymer-supported catalysts is a key to exhibit high activity
in water. The reaction did not proceed at all in the presence
of the cross-linked polystyrene which is the parent polymer
of PS-Sc 1, revealing the critical role of the scandium. We
also investigated the effects of the loading levels and the
polymer structures on catalytic activity (entry 7–9). It was
revealed that the lower loading PS-Sc 1 (entry 6) gave better
results.
(entry 6). This unique solvent effect might be mainly
attributed to the following two factors: (1) hydrophobic
interactions in water to concentrate the catalyst and the
substrates; (2) hydration of the Sc(III) ion and counteranion
by water molecules lead to dissociation of the catalyst to
form a highly Lewis acidic species.8
We then examined reusability of PS-Sc 1, and it was found
that the catalyst was easily recovered and reused without
any loss of catalytic activity (Eq. 1).
ð1Þ
Next, we examined the effect of solvents in the PS-Sc
1-catalyzed Mukaiyama aldol reaction (Table 2). Interest-
ingly, it turned out that PS-Sc 1 worked well only in water
Various substrates were successfully used in the present
PS-Sc 1-catalyzed Mukaiyama aldol reactions as shown
in Table 3. As for aldehydes, aromatic as well as
a,b-unsaturated, and aliphatic aldehydes worked well to
give the corresponding b-hydroxy thioesters in good to
excellent yields (entries 1–8). While p-chlorobenzaldehyde
is solid (mp 47–50 8C), it also reacted smoothly in water.
In addition, it was revealed that silicon enolates derived
from not only a thioester but also an ester and ketones
reacted smoothly to afford the corresponding aldol adducts
in good yields (entries 9–11). It should be noted that highly
water-sensitive silicon enolates were successfully used in
water under these conditions. These results suggest that a
hydrophobic environment created by the catalyst in water
suppresses the hydrolysis of water-sensitive silicon enolates
but accelerates the desired reactions. To the best of our
knowledge, there are no examples of reusable solid
catalysts, which catalyze Mukaiyama aldol reactions in
Table 2. Effect of solvents on PS-Sc 1-catalyzed Mukaiyama aldol reaction
Entry
Solvent
Yield (%)
1
2
3
4
5
6
Neat
10
Trace
9
0
23
97
CH2Cl2
MeOH
THF
THF/H2O (9/1)
H2O

S. Iimura et al. / Tetrahedron 60 (2004) 7673–7678
Table 3. PS-Sc 1-catalyzed Mukaiyama aldol reaction in water
7675
Entry
R1
R2
R3
R4
Yield (%)
1
2
3
4
5
6
7b
8b
9c
10d
11d
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
SEt
SEt
SEt
SEt
SEt
SEt
SEt
SEt
OMe
Ph
97
96
88
91a
95
93
84
78
81
89e
85f
4-MeOC6H4
4-ClC6H4
2-HOC6H4
(E)-PhCHvCH
Ph(CH2)2
n-C5H11
c-C6H11
Ph
Ph
Ph
–(CH2)4–
a
Yield of the cyclized, six-membered lactone which was obtained after purification.
The aldehyde was slowly added to the reaction mixture over 8 h, and then the whole was stirred for 16 h.
b
c
d
e
f
At 0 8C. The sillicon enolate was slowly added to the reaction mixture over 8 h, and then the whole was stirred for 16 h.
The catalyst (2.5 mol%).
syn/anti¼54/46.
syn/anti¼68/32.
water with wide substrate generality. This reaction system
would provide an ideal Mukaiyama aldol reaction with
respect to efficiency and environmental friendliness for
chemical transformations.
and 1,4-adducts could be obtained by simply switching
the reaction systems.13
The wide substrate generality mentioned above encouraged
us to investigate catalytic Mukaiyama aldol reactions of
ketones in water. This type of reactions has not been
reported previously. As results, it was found that the
reaction of an alkynyl ketone with the thioketene silyl acetal
proceeded in good yield using the present catalytic system
(Eq. 2), although the yield was 36% in the case of simple
acetophenone under the same conditions.
ð3Þ
ð4Þ
ð2Þ
Finally, Michael addition of an indole in water using
this catalytic system was carried out (Eq. 5).14 It was
found that the reaction proceeded smoothly in the
presence of only 1 mol% of the catalyst to give the
product in excellent yield.
Furthermore, the reaction of benzalacetone gave the
desired 1,2-adduct (Eq. 3). This result is remarkable, not
only because the aldol reaction with the ketone
proceeded smoothly but also because the 1,2-adduct
was obtained without the 1,4-adduct.10 This regioselec-
tivity is contrary to that of Sc(OTf)3-catalyzed reaction
performed in organic solvents where the corresponding
1,4-adduct was obtained as the sole product.11 On the
other hand, the corresponding 1,4-adduct was obtained
in 47% yield without the 1,2-adduct when phenyl 1-
propenyl ketone was used as a substrate (Eq. 4). While
the yield was still unsatisfactory, this is the first
example of Mukaiyama–Michael reaction12 in water.
Although the origin of this unique regioselectivity is not
clear at this stage, these results suggest that both 1,2-
ð5Þ
In summary, we have developed a novel hydrophobic

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S. Iimura et al. / Tetrahedron 60 (2004) 7673–7678
polystyrene-supported scandium catalyst for carbon–
carbon bond-forming reactions in water. This work will
not only expand our concept related to hydrophobic
Brønsted acid catalysts but also provide new possibilities
for organic reactions in water. Detailed mechanistic studies of
the unique regioselective reaction in Mukaiyama–Michael
reaction in water and application of the concept of
hydrophobic polymer-supported catalysts to other Lewis
acid catalysis are now in progress.
changing the loading of the starting PS-SO3H
(1.55 mmol/g). PS-Sc 2 was also similarly prepared
from ALPS-SO3H (0.37 mmol/g). PS-Sc 3 was also
similarly prepared from PS-spacer-SO3H (0.57 mmol/g).
3.4. A typical experimental procedure for PS-Sc-
catalyzed Mukaiyama aldol reactions in water (Table 1,
entry 6)
Benzaldehyde (26.5 mg, 0.25 mmol) and the thioketene
silyl acetal (76.4 mg, 0.374 mmol) derived from ethyl
2-methylthiopropionate were successively added to a
mixture of PS-Sc (0.16 mmol/g, 38.8 mg, 0.0064 mmol) in
degassed water (1.5 mL) at 30 8C. The reaction mixture was
stirred for 12 h at the same temperature. The polymer was
filtered and washed with water and ethyl acetate. After
extraction with ethyl acetate, the organic layer was dried
over anhydrous Na2SO4, and evaporated. The mixture was
purified by preparative TLC on silica gel to give the desired
product (57.8 mg, 97%).
3. Experimental
3.1. General
Melting points were uncorrected. Infrared (IR) spectra were
recorded on a JASCO FT/IR-610 spectrometer. Nuclear
magnetic resonance (NMR) spectra were recorded on a
JEOL JNM-LA300 or JNM-LA400 spectrometer in CDCl3
unless otherwise noted. Tetramethylsilane (d¼0) was used
as an internal standard for 1H NMR and CDCl3 (d¼77.0) for
13C NMR. Mass spectra (MS) were measured with a JEOL
JMS-MS700V or Burker BIO TOF-II spectrometer. Column
chromatography was conducted on Silica gel 60 (Merck)
and preparative thin-layer chromatography (TLC) was
carried out using Wakogel B-5F. Distilled water was used as
a solvent for aqueous reactions. Polystyrene resin (1% DVB
cross-linked) was purchased from Advanced ChemTech Co.,
Inc. All other reagents were purified based on standard
procedures unless otherwise noted. Starting materials are
commercially available or were synthesized by the reported
procedure. The structures of the known compounds were
confirmed by comparison with published data.
3.4.1. Ethyl 3-hydroxy-2,2-dimethyl-3-phenylthiopropio-
nate.15 Colorless oil; 1H NMR (CDCl3) d 1.12 (3H, s), 1.22
(3H, s), 1.26 (3H, t, J¼7.4 Hz), 2.89 (2H, q, J¼7.4 Hz), 2.96
(1H, br s), 4.94 (1H, s), 7.27–7.35 (5H, m); 13C NMR
(CDCl3) d 14.4, 19.0, 23.3, 23.7, 54.3, 78.9, 127.78, 127.80,
139.9, 208.0.
3.4.2. S-Ethyl 3-hydroxy-3-(4-methoxyphenyl)-2,2-
1
dimethylpropanethioate. Colorless oil; H NMR (CDCl3)
d 1.09 (3H, s), 1.20 (3H, s), 1.25 (3H, t, J¼7.4 Hz), 2.88
(2H, q, J¼7.4 Hz), 2.94 (1H, br d, J¼3.7 Hz), 3.79 (3H, s),
6.81–6.88 (2H, m), 7.20–7.25 (2H, m); 13C NMR (CDCl3)
d 14.4, 18.9, 23.3, 23.6, 54.5, 55.2, 78.5, 113.1, 128.8,
132.0, 159.1, 208.0; IR (neat) 3502, 2974, 1670, 1512, 1248,
1038, 945 cm21; MS (ESI-TOF) m/z 291 (MþþNa). Anal.
Calcd for C14H20O3S: C, 62.66; H, 7.51. Found: C, 62.40;
H, 7.50.
3.2. Preparation of polymer-supported sulfonic acid
catalysts
Various types of polystyrene-supported sulfonic acid
catalysts (PS-SO3H, ALPS-SO3H, PS-spacer-SO3H) were
prepared according to the our previous report.5a
3.4.3. S-Ethyl 3-(4-chlorophenyl)-3-hydroxy-2,2-di-
1
methylpropanethioate. Colorless oil; H NMR (CDCl3) d
1.11 (3H, s), 1.19 (3H, s), 1.25 (3H, t, J¼7.4 Hz), 2.88 (2H,
q, J¼7.4 Hz), 3.10 (1H, br s), 4.90 (1H, s), 7.20–7.31 (4H,
m); 13C NMR (CDCl3) d 14.4, 19.1, 23.3, 23.4, 54.2, 78.2,
127.9, 129.1, 133.5, 138.4, 207.9.
3.3. Preparation of polymer-supported scandium
catalyst
To a suspension of hydrophobic polystyrene-supported
sulfonic acid (PS-SO3H 1, 0.20 mmol/g, 2.00 g,
0.41 mmol) in THF/H2O (3/1, 25 mL) was slowly
added 1 N aq. NaOH (2.0 mL, 2.00 mmol) at rt, and
stirred for 24 h at the temperature. The resin was
collected on a glass filter, rinsed with water, water/
THF, THF, and dichloromethane, and dried in vacuo to
give the sodium salt of PS-SO3H. Scandium triflate was
immobilized into the resin in the following step.
Sc(OTf)3 (536 mg, 1.01 mmol) was added to a suspen-
sion of PS-SO3Na (1.82 g, ca. 0.37 mmol) in THF
(35 mL) at rt. After being stirred for 72 h at the same
temperature, the resin was collected on a glass filter,
rinsed with water, water/THF, THF, and dichloro-
methane, and dried in vacuo to give the hydrophobic
polymer-supported scandium catalysts (PS-Sc). From a
result of ICP analysis (found: Sc, 0.74%; Na, 0.01%), the
scandium content was estimated as 0.16 mmol/g. PS-Sc 1
with another loading level was similarly prepared by
3.4.4. 4-Hydroxy-3,3-dimethyl-2-chromanone.16 Color-
less needles. Mp 101.6–101.9 8C; 1H NMR (CDCl3) d
1.19 (3H, s), 1.39 (3H, s), 2.16 (1H, br s), 4.49 (1H, s), 7.06
(5H, d, J¼7.7 Hz), 7.14–7.20 (1H, m), 7.31–7.39 (2H, m);
13C NMR (CDCl3) d 19.7, 22.5, 43.5, 74.0, 116.6, 124.4,
124.7, 127.9, 130.2, 150.5, 172.7.
3.4.5. (E)-S-Ethyl 3-hydroxy-2,2-dimethyl-5-phenylpent-
4-enethioate. Colorless oil; 1H NMR (CDCl3) d 1.26 (3H, t,
J¼7.5 Hz), 1.27 (3H, s), 1.30 (3H, s), 2.72 (1H, d, J¼
5.4 Hz), 2.88 (2H, q, J¼7.4 Hz), 4.38–4.43 (1H, m), 6.19
(1H, dd, J¼15.9, 7.1 Hz), 6.63 (1H, d, J¼15.8 Hz), 7.22–
7.39 (5H, m); 13C NMR (CDCl3) d 14.5, 20.2, 23.2, 54.0,
78.1, 126.6, 127.3, 127.8, 128.6, 132.9, 136.6, 207.4; IR
(neat) 3485, 2972, 2931, 1668, 1462, 945 cm21; MS (FAB)
m/z 265 (Mþþ1). Anal. Calcd for C15H20O2S: C, 68.14; H,
7.62. Found: C, 68.13; H, 7.63.

S. Iimura et al. / Tetrahedron 60 (2004) 7673–7678
7677
3.4.6. S-Ethyl 3-hydroxy-2,2-dimethyl-5-phenylpentane-
1
thioate. Colorless oil; H NMR (CDCl3) d 1.22 (3H, s),
56.1, 77.8, 126.9, 127.3, 127.4, 143.4, 210.9; IR (neat) 3481,
2976, 2933, 1641, 1450, 1375, 962, 704 cm21; MS (FAB)
m/z 253 (Mþþ1). Anal. Calcd for C14H20O2S: C, 66.63; H,
7.99. Found: C, 66.65; H, 7.97.
1.225 (3H, s), 1.231 (3H, t, J¼7.5 Hz), 1.56–1.67 (1H, m),
1.73–1.81 (1H, m), 2.50 (1H, d, J¼6.6 Hz), 2.59–2.68 (1H,
m), 2.85 (2H, q, J¼7.4 Hz), 2.90–2.98 (1H, m), 3.67 (1H,
ddd, J¼10.6, 6.7, 2.0 Hz), 7.16–7.30 (5H, m); 13C NMR
(CDCl3) d 14.5, 20.9, 22.7, 23.1, 32.9, 33.7, 54.1, 76.6,
125.9, 128.4, 128.5, 142.0, 207.8; IR (neat) 3492, 2974,
1672, 1456, 1076, 937 cm21; MS (FAB) m/z 267 (Mþþ1).
Anal. Calcd for C15H22O2S: C, 67.63; H, 8.32. Found: C,
67.37; H, 8.27.
3.4.13. S-Ethyl 3-hydroxy-2,2,3-trimethyl-5-phenylpent-
4-ynethioate. Colorless oil; 1H NMR (CDCl3) d1.24 (3H, t,
J¼7.4 Hz), 1.39 (3H, s), 1.51 (3H, s), 1.53 (3H, s), 2.79–2.97
(2H, m), 4.50 (1H, br s), 7.25–7.43 (5H, m); 13C NMR (CDCl3)
d 14.3, 20.9, 22.1, 23.5, 24.8, 56.2, 72.9, 83.9, 91.2, 122.7,
128.2, 128.3, 131.7, 209.8; IR (neat) 3469, 2978, 2933, 1645,
1387, 960 cm21; MS (FAB) m/z 277 (Mþþ1). Anal. Calcd for
C16H20O2S: C, 69.53; H, 7.29. Found: C, 69.27; H, 7.44.
3.4.7. S-Ethyl 3-hydroxy-2,2-dimethyloctanethioate.
1
Colorless oil; H NMR (CDCl3) d 0.89 (3H, t, J¼6.8 Hz),
1.21–1.35 (15H, m), 1.40–1.47 (1H, m), 1.54–1.63 (1H,
m), 2.27 (1H, d, J¼6.6 Hz), 2.86 (2H, q, J¼7.5 Hz), 3.62–
3.68 (1H, m); 13C NMR (CDCl3) d 14.1, 14.5, 20.9, 22.5,
22.6, 23.1, 26.4, 31.7, 31.8, 54.2, 77.2, 207.8; IR (neat)
3477, 2929, 1672, 1464, 939 cm21; MS (FAB) m/z 233
(Mþþ1). Anal. Calcd for C12H24O2S: C, 62.02; H, 10.41.
Found: C, 61.75; H, 10.26.
3.4.14. S-Ethyl 2,2,3-trimethyl-5-oxo-5-phenylpentane-
1
thioate. Colorless oil; H NMR (CDCl3) d 0.92 (3H, d,
J¼6.3 Hz), 1.18–1.27 (9H, m), 2.62–2.75 (2H, m), 2.87
(2H, q, J¼7.4 Hz), 3.02 (1H, br d, J¼14.6 Hz), 7.42–7.59
(3H, m), 7.91–7.98 (2H, m); 13C NMR (CDCl3) d 14.6,
14.9, 21.2, 23.1, 23.5, 36.8, 41.4, 52.7, 128.2, 128.6, 133.0,
137.1, 199.5, 206.8; IR (neat) 2972, 1680, 1450, 1292,
957 cm21; MS (FAB) m/z 279 (Mþþ1). Anal. Calcd for
C16H22O2S: C, 69.02; H, 7.96. Found: C, 68.93; H, 8.13.
3.4.8. S-Ethyl 3-cyclohexyl-3-hydroxy-2,2-dimethyl-
1
propanethioate. Colorless oil; H NMR (CDCl3) d 1.11–
1.71 (20H, m), 2.84 (2H, d, J¼7.3 Hz), 2.85 (1H, br s), 3.40
(1H, br s); 13C NMR (CDCl3) d 14.3, 22.7, 23.0, 24.1, 26.2,
26.3, 26.7, 27.4, 32.1, 40.4, 53.2, 82.6, 208.6; IR (neat)
3465, 2933, 2852, 1674, 1450, 943 cm21; MS (FAB) m/z
245 (Mþþ1). Anal. Calcd for C13H24O2S: C, 63.89; H, 9.90.
Found: C, 63.70; H, 9.99.
3.4.15. (E)-S-Ethyl 3-hydroxy-2,2,3-trimethyl-5-phenyl-
1
pent-4-enethioate. Pale yellow oil; H NMR (CDCl3) d
1.18 (3H, t, J¼7.3 Hz), 1.34 (9H, s), 2.73–2.88 (2H, m),
4.09 (1H, br s), 6.29 (1H, d, J¼15.9 Hz), 6.66 (1H, d, J¼
15.9 Hz), 7.18–7.39 (5H, m); 13C NMR (CDCl3) d 14.2,
21.4, 23.4, 23.7, 56.1, 76.4, 126.5, 127.4, 128.5, 129.4,
132.4, 137.1, 210.1; IR (neat) 3486, 2973, 1642, 961 cm21
;
3.4.9. Methyl 3-hydroxy-2,2-dimethyl-3-phenylpropano-
1
MS (FAB) m/z 279 (Mþþ1). Anal. Calcd for C16H22O2S: C,
ate.17 Colorless oil; H NMR (CDCl3) d 1.11 (3H, s), 1.15
69.02; H, 7.96. Found: C, 69.09; H, 8.12.
(3H, s), 3.05 (1H, br s), 3.73 (3H, s), 4.90 (1H, s), 7.27–7.35
(5H, m); 13C NMR (CDCl3) d 19.1, 23.1, 47.8, 52.2, 78.8,
127.4, 127.7, 127.8, 140.0, 178.3.
3.4.16. S-Ethyl 2,2-dimethyl-5-oxo-3-phenylhexanethio-
1
ate. Colorless oil; H NMR (CDCl3) d 1.07 (3H, s), 1.19
(3H, s), 1.23 (3H, t, J¼7.3 Hz), 1.98 (3H, s), 2.68 (1H, dd,
J¼16.3, 3.6 Hz), 2.84 (2H, q, J¼7.3 Hz), 3.01 (1H, dd,
J¼16.3, 11.2 Hz), 3.64 (1H, dd, J¼11.2, 3.6 Hz), 7.17–7.29
(5H, m); 13C NMR (CDCl3) d 14.5, 20.5, 23.3, 25.6, 30.2,
44.8, 48.2, 52.7, 127.0, 128.0, 129.6, 139.2, 206.6, 206.8; IR
(neat) 2972, 1718, 1668, 1456, 1360, 958 cm21; MS (FAB)
m/z 279 (Mþþ1). Anal. Calcd for C16H22O2S: C, 69.02; H,
7.96. Found: C, 68.73; H, 7.96.
3.4.10. 3-Hydroxy-2-methyl-1,3-diphenylpropan-1-
1
one.18 Colorless oil; (syn/anti¼54/46): H NMR (CDCl3)
d 1.06 (1.38H, d, J¼7.1 Hz), 1.19 (1.62H, d, J¼7.1 Hz),
3.03 (0.46H, br s), 3.64–3.75 (1.08H, m), 3.83 (0.46H,
quint, J¼7.3 Hz), 4.99 (0.46H, br d, J¼8.1 Hz), 5.23
(0.54H, br d, J¼3.1 Hz), 7.23–7.62 (8H, m), 7.90–7.99
(2H, m); 13C NMR (CDCl3) d 11.2, 15.7, 47.1, 48.0, 73.1,
76.8, 126.0, 126.7, 127.3, 127.9, 128.2, 128.45, 128.48,
128.54, 128.6, 128.8, 128.9, 133.3, 133.6, 135.7, 136.8,
141.8, 142.2, 204.9, 205.7.
3.4.17. 4-(1-Methyl-1H-indol-3-yl)butan-2-one. Colorless
oil; 1H NMR (CDCl3) d 2.12 (3H, s), 2.82 (2H, t, J¼7.3 Hz),
3.03 (2H, t, J¼7.3 Hz) 3.71 (3H, s), 6.83 (1H, s), 7.07–7.12
(1H, m), 7.19–7.28 (2H, m), 7.6 (1H, d, J¼8.1 Hz); 13C
NMR (CDCl3) d 19.2, 30.0, 32.5, 44.3, 109.2, 113.6, 118.69,
118.73, 121.6, 126.3, 127.5, 137.0, 208.7; IR (neat) 3055,
2925, 1714, 1475, 1159, 741 cm21; MS (FAB) m/z 202
(Mþþ1). Anal. Calcd for C13H15NO: C, 77.58; H, 7.51; N,
6.96. Found: C, 77.54; H, 7.72; N, 6.96.
3.4.11. 2-(Hydroxy(phenyl)methyl)cyclohexanone.18
1
Colorless crystals; (syn/anti¼68/32): H NMR (CDCl3) d
1.23–1.38 (0.32H, m), 1.43–1.89 (4.68H, m), 2.01–2.14
(1H, m), 2.31–2.68 (3H, m), 3.02 (0.68H, br s), 3.98
(0.32H, br s), 4.78 (0.32H, d, J¼8.8 Hz), 5.39 (0.68H, m),
7.21–7.38 (5H, m); 13C NMR (CDCl3) d 24.7, 24.9,
26.0, 27.8, 28.0, 30.9, 42.7, 57.2, 57.5, 70.6, 74.8, 125.8,
126.98, 127.03, 127.9, 128.2, 128.4, 141.0, 141.5, 214.8,
215.6.
Acknowledgements
3.4.12. S-Ethyl 3-hydroxy-2,2-dimethyl-3-phenylbutane-
thioate. Colorless oil; 1H NMR (CDCl3) d 1.19 (3H, s), 1.22
(3H, s), 1.22 (3H, t, J¼7.3 Hz), 1.61 (3H, s), 2.84 (2H, q,
J¼7.3 Hz), 4.57 (1H, br s), 7.19–7.35 (3H, m), 7.42–7.47
(2H, m); 13C NMR (CDCl3) d 14.2, 21.8, 21.9, 23.5, 25.0,
This work was partially supported by CREST, SORST, and
ERATO, Japan Science and Technology Corporation (JST),
and a Grant-in-Aid for Scientific Research from Japan
Society of the Promotion of Science.

7678
S. Iimura et al. / Tetrahedron 60 (2004) 7673–7678
2003, 1, 2416. (b) Iimura, S.; Manabe, K.; Kobayashi, S.
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