Diastereo- and enantioselective synthesis of anti-1,3-mercapto alcohols from α,β-unsaturated ketones via tandem Michael addition-MPV reduction

Article abstract of DOI:10.1016/j.tetasy.2004.01.020

A new and effective asymmetric synthesis of anti-1,3-mercapto alcohols 3 from α,β-unsaturated ketones 1 utilizing tandem Michael addition-Meerwein-Ponndorf-Verley (MPV) reduction is described. Transformation of the MPV products anti-4 via the Wagner-Meerwein rearrangement was optimized under acidic or basic conditions to afford 1,3-mercapto alcohols anti-3, depending on the substituent R² of 4.

Full text of DOI:10.1016/j.tetasy.2004.01.020

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 895–907
Diastereo- and enantioselective synthesis of anti-1,3-mercapto
alcohols from a,b-unsaturated ketones via tandem Michael
addition–MPV reduction
Minoru Ozeki, Kiyoharu Nishide, Fumiteru Teraoka and Manabu Node*
Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Received 7 January 2004; accepted 16 January 2004
Abstract—A new and effective asymmetric synthesis of anti-1,3-mercapto alcohols 3 from a,b-unsaturated ketones 1 utilizing
tandem Michael addition–Meerwein–Ponndorf–Verley (MPV) reduction is described. Transformation of the MPV products anti-4
via the Wagner–Meerwein rearrangement was optimized under acidic or basic conditions to afford 1,3-mercapto alcohols anti-3,
depending on the substituent R2 of 4.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
new chiral reagent A via a tandem Michael addition–
Meerwein–Ponndorf–Verley (MPV) reduction,2 as
shown in Eq. 1 (Scheme 1). A characteristic of the above
synthetic method was the elimination reaction with a
base producing syn-1,3-mercapto alcohols 3.3 However,
the tandem reaction proceeded in extremely low dia-
stereoselectivity in the case of the substrate 1 having an
alkyl substituent R2. We report herein a new synthetic
method of optically active anti-1,3-mercapto alcohols 3
via the known tandem Michael addition–MPV reduc-
tion using the chiral reagent B, as shown as Eq. 2 in
Scheme 1.
Chiral 1,3-oxathiane derivatives, prepared from opti-
cally active 1,3-mercapto alcohols, have been developed
as chiral auxiliaries for asymmetric synthesis.1 Optically
active 1,3-mercapto alcohols are only available from
natural sources1 with little attention being given on their
asymmetric synthesis. Therefore, asymmetric synthesis
of 1,3-mercapto alcohols still remains as untouched
research region. We have recently reported a new
method for the asymmetric synthesis of 1,3-mercapto
alcohols syn-3 from a,b-unsaturated ketones 1 using the
R2
DBU
R1
Me2AlCl
R1
R2
OH
H
+
OH
SH
S
R2
R1 OH
(1)
(2)
rt, 3 d
BnSH
O
1
1
O
SH
A
92 ~ 99%
R1, R2 = Aryl
56 ~ 63% (100% de)
R1 = Ph, R2 = Alkyl 50 ~ 74% (6 ~ 28% de)
2
(94 ~ 98% ee)
syn-3
Me2AlCl
SH
OH
R2
O
+
OH
SH
S
OH
R2
R1
rt, 1 d
R1
B
anti-3
4
R1 = Aryl, R2 = Alkyl or Aryl
75 ~ 94% (~100% de)
Scheme 1.
* Corresponding author. Tel.: +81-75-595-4639; fax: +81-75-595-4775; e-mail: node@mb.kyoto-phu.ac.jp
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.01.020

896
M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
2. Results and discussion
1
+
The new strategy in Eq. 2 consists of a diastereoselective
construction of two stereogenic centers by the tandem
reaction using B and transformation of the resulting
sulfide 4 into anti-1,3-mercapto alcohols 3 via a
Wagner–Meerwein rearrangement as the key reaction.
As previously reported of the use of the tandem reac-
tion,4 sulfide 4 can be obtained in high yield with short
reaction time when compared to that of the tandem
reaction using A, and furthermore, a different diaste-
reomer anti-3 of 1,3-mercapto alcohol can be obtained.
First, we attempted the tandem reaction of various
kinds of a,b-unsaturated ketones 1 using the chiral
reagent B (1.2 equiv) and dimethylaluminum chloride
(1.2 equiv) in dichloromethane at room temperature.
The results of the tandem reaction are summarized in
Table 1. The reaction of a,b-unsaturated ketones bear-
ing an aromatic group on the b-carbon proceeded in
nearly complete diastereoselectivity and in high yields
(Table 1, entries 1–3). In the cases of a,b-unsaturated
ketones possessing alkyl substituent R1, the tandem
reactions were maintained in high yields but the dia-
stereoselectivities decreased significantly (58–81%)
(Table 1, entries 4–6). However a propyl substituent at
R1 on the b-carbon, gave diastereomeric excesses over
90% de for products 4 (Table 1, entries 7–10). It was
observed that the lowering of diastereoselectivity was
correlated to the decreasing bulkiness of the R1 group at
the b-carbon.
O
O
Me
-
Me
-
R1
10
Al
10
Al
+
H
+
B
H
H
O
O
S
S
Cl
Cl
R1
H
R2
R2
TS-1
TS-2
O
S
O
S
OH
R2
OH
R2
R1
anti-4
R1
syn-4
Scheme 2.
Namely, in the substrates having aromatic substituent
R1, a significant steric repulsion between the aromatic
ring and the C-10 methylene protons on one diastereo-
mer TS-2 of the Michael adduct retarded the rate of the
MPV reaction, whereas the other diastereomer TS-1
without such steric repulsion proceeded smoothly to
give the MPV product anti-4. In the cases of the sub-
strates having an alkyl substituent R1, the above men-
tioned steric repulsion would be smaller than those with
the aromatic groups. Therefore, the MPV reduction
through TS-2 proceeded slowly to give syn-4 and de-
creased the diastereoselectivities. Determination of the
stereochemistry of anti-4 and syn-4 will be discussed in
the Experimental section.
Table 1. Tandem Michael–MPV reaction using B as a chiral reagent
Next, we investigated the transformation of sulfide 4
into anti-1,3-mercapto alcohol 3. Recently, we have
developed a new asymmetric synthesis5 of b-mercapto
esters from a,b-unsaturated esters via a Michael addi-
tion of the chiral thiol B followed by a one-pot degra-
dation of the adducts with boron trifluoride etherate
(BF3ÆOEt2) and odourless 1-dodecanethiol6 (Dod-SH).
This new method of transformation using sulfides 4 was
applied for the 1,3-mercapto alcohols anti-3. As
reported previously,5 the transformation requires three
steps, that is, reduction of the carbonyl group on 4, a
Wagner–Meerwein rearrangement and a thiol exchange
reaction. The ketone anti-4, which was purified by
HPLC, was diastereoselectively reduced with LiAlH4 in
THF at room temperature to give exo-alcohol 5. The
obtained crude diol 5 was then subsequently treated
with BF3ÆOEt2 and Dod-SH in CH2Cl2 at room tem-
perature. The results are summarized in Table 2. By
these transformations, the desired 1,3-mercapto alcohols
anti-3 were obtained in good yields (63–83%) and high
enantiomeric excess (>97% ee) without epimerization
(entries 1–10). However, in the case of R2 ¼ Ph (entry
11), the substrate decomposed during the rearrangement
reaction with BF3ÆOEt2. Besides the expected Wagner–
Meerwein rearrangement, formation of the stable benzyl
cation by elimination of the hydroxyl group probably
occurred under strongly acidic conditions. Therefore, we
examined the reaction under basic conditions using tri-
fluoromethansulfonic anhydride (Tf2O) according to the
B (1.2 equiv)
OH
SH
O
O
Me2AlCl (1.2 equiv)
S
OH
R2
R1
R2
CH2Cl2 rt 24 h
R1
1
4
Entry
1
4
R1
R2
Yield (%)a De (%)
1
2
a
b
c
d
e
f
Ph
Ph
Ph
Me
i-Pr
95
96
92
95
93
92
88
81
81
82
99
99
99
58
81
74
92
95
94
90
3
c-Hex
Et
4
Me
Et
Et
Pr
Pr
Pr
Pr
5
Hex
Oct
Me
Hex
Oct
Ph
6
7
g
h
i
8
9
10
j
a Isolated yields.
The above diastereochemical control can be interpreted
based on dynamic kinetic resolution via a reversible
Michael addition in the tandem reaction, as shown in
Scheme 2.

M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
Table 2. Conversion of sulfides 4 into 1,3-mercapto alcohols anti-3
897
did not proceed under both reaction conditions using
either Et3N or pyridine as the base. The reaction using
Et3N and MsCl instead of Tf2O, afforded the desired
rearrangement product 8m in low yield (entry 3).
Exchange of the protecting group from acetyl (Ac) 6m to
methoxymethyl (MOM) 7m was also not effective (entry
4). In contrast to a small amine like Et3N, the use of
BF3OEt2
LiAlH4
SH OH
OH
anti-4
R1
R2
then Dod-SH
S
OH
R2
R1
anti-3
anti-3
€
5
more bulky amines such as the Hunig base (i-Pr2NEt)
increased the yield from 13% to 41%. However, the use
of even more bulky amines, that is, i-Bu3N was not
effective (entry 6). The optimal result was obtained by
the treatment with Ms2O and i-Pr2NEt, with the desired
rearrangement reaction proceeding successfully in a
short reaction time (entry 7). Under the optimized
reaction conditions, MPV products anti-4j and m were
converted to vinyl sulfides 9j and m in 80–86% overall
yields (three steps).
Entry
4
R1
R2
Yield (%)a Ee (%)b
1
a
k
l
Ph
Ph
Ph
Ph
Ph
Me
Et
Me
Et
74
79
67
78
72
79
68
63
83
63
97
99
99
98
98
98
98
98
98
98
2
3
Pr
4
b
c
i-Pr
c-Hex
Et
5
6
d
e
7
Hex
Oct
Me
Hex
Ph
8
f
Et
Pr
Finally, we turned our attention to the conversion of
vinyl sulfide 9m into 1,3-mercapto alcohol anti-3m by a
thiol exchange reaction using an odourless Dod-SH.
After screening several Lewis acids and protic acids, we
found that the use of n-Bu2BOTf as a Lewis acid, which
is more weak acid than BF3ÆOEt2, was effective in giving
the desired 1,3-mercapto alcohol anti-3m in 68% yield.
Moreover, we studied an alternative conversion of vinyl
sulfides 9j and m by ozonolysis. Namely, vinyl sulfides 9j
and m were converted to thioformate 10j and m by
ozonolysis followed by reductive treatment with PPh3.
9
g
h
m
10
11
Pr
Ph
Decompose
a Isolated yield.
b Enantiomeric excesses were determined by HPLC analysis using
DAICEL CHIRALCEL OB or OD.
reports7 by Martinez et al. (entries 1 and 2 in Table 3).
Unfortunately, the reaction of 6m derived from anti-4m
Table 3. Wagner–Meerwein rearrangement of 6m or 7m to vinyl sulfides 8m or 9m under basic conditions
OH
OX
Reagent, Base
S
OX
S
CH2Cl2
Ph
Ph
Ph
Ph
8m: X = Ac
9m: X = MOM
6m: X = Ac
7m: X = MOM
Entry
Substrate
X
Reagent (equiv)
Base (equiv)
Time
Temperature
Vinyl sulfidea
Yield (%)b
1
2
3
4
5
6
7
6m
6m
6m
7m
7m
7m
7m
Ac
Ac
Ac
Tf2O (1.5)
Tf2O (1.5)
MsCl (10)
MsCl (10)
MsCl (10)
MsCl (10)
Ms2O (10)
Et3N (2)
41 h
24 h
0 ꢁC to rt
0 ꢁC to rt
0 ꢁC
0 ꢁC
0 ꢁC
0 ꢁC
)10 ꢁC
n.r.c
n.r.c
11
Pyridine (neat)
Et3N (20)
Et3N (20)
30 min
30 min
30 min
30 min
15 min
8m
9m
9m
9m
9m
MOM
13
41
n.r.c
MOM
MOM
MOM
i-Pr2NEt (20)
i-Bu3N (20)
i-Pr2NEt (20)
88
a A mixture of E- and Z-isomers.
b Isolated yield.
c No reaction.
1) MOMCl
2) LiAlH4
Ms2O, (i-Pr)2NEt
O
9j,m
(X = MOM)
7j,m
(X = MOM)
S
OH
R
Ph
9j (90%)
9m (88%)
7j (89%)
7m (98%)
anti-4j: R = Pr
anti-4m: R = Ph

898
M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
SH OH
(n-Bu)2BOTf, Dod-SH
68% from 9m
R
Ph
anti-3j,m (99% ee)
84% from 10j
82% from 10m
S
OMOM
Ph
HCl-MeOH
O3, PPh3 (3 equiv)
CH2Cl2 / -78 ˚C to rt
R
OHC-S
R
OMOM
Ph
9j: R = Pr
9m: R = Ph
50% from 9j
58% from 9m
10j,m
Scheme 3. Conversion of vinyl sulfides 9 into 1,3-mercapto alcohols anti-3.
The thioformates 10j and m can be regarded as the
protected compound of 1,3-mercapto alcohols anti-3j
and m on both the hydroxyl and the thiol groups. In-
deed, the thioformates 10j and m were easily deprotected
to give 1,3-mercapto alcohols anti-3j and m by hydro-
lysis with HCl in MeOH. Having these reaction
sequences should prove useful to afford, either the pro-
tected form of 1,3-mercapto alcohols or the free form
1,3-mercapto alcohols directly (Scheme 3).
ian Unity INOVA-400 spectrometer with tetrameth-
ylsilane as an internal standard. 13C NMR spectra were
obtained on a Varian Unity INOVA-400 spectrometer
with CDCl3 as an internal standard. Mass spectra (MS)
were determined on a JEOL JMS-SX 102A QQ or a
JEOL JMS-GC mate mass spectrometer. Specific rota-
tions were recorded on a Horiba SEPA-200 automatic
digital polarimeter. Chiral HPLC analyses were per-
formed with a Shimadzu LC-9A and LC-10A Liquid
Chromatograph series using a Daicel chiral column
(CHIRALCEL OB, OD). Their data were recorded with
Shimadzu C-R6A Chromatopac. Flash column chro-
matography was performed with silica gel 60N (Kanto
Chemical Co., Inc.). Kieselgel 60 F-254 plates (Merck)
were used for thin layer chromatography (TLC). Pre-
parative TLC (PTLC) was done with Kieselgel 60 F-254
plate (0.25 mm, Merck) or silica gel 60 F-254 plate
(0.5 mm, Merk). When necessary, compounds were
further purified by recycled HPLC (JAI LC-908) on a
GPC column (JAIGEL 1H and 2H) after purification on
silica gel. Some diastereomeric mixtures of 4 were sep-
arated by recycled HPLC (JAI LC-908) on SiO2 gel
column (Kusano Si-10) after purification on silica gel.
3. Conclusions
In conclusion, we have developed a diastereo- and
enantioselective synthesis of 1,3-mercapto alcohols from
a,b-unsaturated ketones via a tandem Michael addition–
MPV reduction using chiral reagent B. It was found that
the magnitude of diastereoselectivity in the tandem
reaction depends on the bulkiness of the R1 group rather
than the R2 group, and more bulky R1 group than
Me or Et groups resulted in high diastereoselectivity
(>90%). Transformation of anti-4 to 1,3-mercapto
alcohols anti-3 was effectively achieved via the Wagner–
Meerwein rearrangement and thiol exchange reaction
under the acidic condition using BF3ÆOEt2/Dod-SH
system, except for the substrate with phenyl group at R2.
In the case if R2 is phenyl, the transformation can be
performed by the rearrangement using Ms2O/i-Pr2NEt
followed by the thiol exchange reaction with
n-Bu2BOTf/Dod-SH, or alternatively, by the reductive
ozonolysis of the vinyl sulfide intermediates and sub-
sequent hydrolysis. Consequently, we were able to pro-
vide a new method for preparation of 1,3-mercapto
alcohols anti-3, which was complementary to the pre-
viously reported method.5
4.2. Materials
Toluene, diethyl ether, and tetrahydrofuran were dis-
tilled from sodium benzophenone ketyl, and dichloro-
methane from CaH2, after 10 washing with water to
remove methanol contaminants. Most of the reagents
were obtained from Wako pure Chemical Industries,
Ltd., Nakalai Tesque, Inc., Aldrich Chemical Inc. (S)-
(+)-Camphorsulfonic acid monohydrate were commer-
cially available. Dimethylaluminum chloride (hexane
solution) was purchased from Kanto Chemical Co., Inc.
a,b-Unsaturated ketones (1a, 1b, 1c, 1d, 1g, 1i, 1k, 1m)
are commercially available compounds. Other a,b-
unsaturated ketones are known compound.
4. Experimental
4.1. General
4.3. Synthesis of ())-10-mercaptoisoborneol B
Melting points were taken on a micro hot-stage appa-
ratus (Yanagimoto) and are uncorrected. Infrared (IR)
spectra were recorded on a Shimadzu FTIR-8300 dif-
fraction grating infrared spectrophotometer. H NMR
spectra were obtained on a JEOL JNM-AL300, a Var-
())-10-Mercaptoisoborneol B was prepared by Elielꢀs
procedure1a from (S)-(+)-camphorsulfonic acid mono-
hydrate. The enantiomeric excess of B was determined in
our previous report.4a;b
1

M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
899
4.4. A typical procedure for the tandem Michael–MPV
reaction using B as a chiral reagent
28.3, 27.8, 27.0, 26.9, 26.7, 26.6, 26.4, 20.2, 20.1; IR
(CHCl3): 3649, 2929, 2854, 1735, 1601, 1452 cmꢁ1; MS
(20 eV) m=z: 400 (Mþ, 3), 382 (5), 299 (3), 273 (31), 231
(19), 216 (62), 199 (18), 185 (45), 151 (27), 133 (77), 105
(97), 95 (100), 83 (46), 67 (28), 55 (27); HRMS calcd for
C25H36O2S (Mþ): 400.2434, found 400.2436.
To a dichloromethane solution (20 mL) of ())-10-mer-
captoisoborneol B (100 mg, 0.54 mmol) was added,
dropwise, dimethylaluminum chloride (0.94 M hexane
solution, 0.57 mL, 0.54 mmol) at 0 ꢁC under a nitrogen
atmosphere. After the reaction stirred for 30 min, a
dichloromethane (5 mL) solution of an a,b-unsaturated
ketone 1 (0.45 mmol) was added dropwise at 0 ꢁC, and
the mixture then stirred for 1 day at room temperature.
The reaction mixture was quenched with sat. ammo-
nium chloride aqueous solution. The aqueous layer was
extracted with ethyl acetate. The combined organic layer
was washed with brine, dried over magnesium sulfate,
filtered, and concentrated in vacuo. Purification of the
residue by silica gel column chromatography (hexane/
ethyl acetate ¼ 7:1–10:1) gave products 4 in the yields
shown in Table 1.
4.4.3. (2S,4S)-2-[(1S,4R)-2-Oxobornane-10-sulfenyl]-4-
hexanol anti-4d.
23
D
Colorless oil; ½aꢀ ¼ +69.4 (c 0.95,
1
CHCl3); H NMR (400 MHz, CDCl3): d 3.90–3.99 (m,
1H), 3.08 (ddq, J ¼ 11:0, 6.8, and 4.2 Hz, 1H), 2.71 (d, A
part of AB, JAB ¼ 13:0 Hz, 1H), 2.70–2.65 (br s, 1H),
2.62 (d, B part of AB, JAB ¼ 13:0 Hz, 1H), 2.36 (ddd, A
part of AB, JAB ¼ 18:3 Hz, J ¼ 4:8, 2.4 Hz, 1H), 2.09–
1.94 (m, 3H), 1.88 (d, B part of AB, JAB ¼ 18:3 Hz, 1H),
1.68–1.37 (m, 6H), 1.35 (d, J ¼ 6:8 Hz, 3H), 1.04 (s, 3H),
0.96 (t, J ¼ 7:5 Hz, 3H), 0.90 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 218.1, 70.3, 60.9, 47.9, 43.4 (2),
43.2, 39.7, 30.2, 27.4, 26.8, 26.7, 22.9, 20.11, 20.10, 10.1;
IR (CHCl3): 3695, 3004–2873, 1735, 1446, 1384, 1350,
1110 cmꢁ1; MS (20 eV) m=z: 284 (Mþ, 47), 211 (34), 185
(100), 151 (27), 123 (13), 109 (26); HRMS calcd for
C16H28O2S (Mþ): 284.1810, found 284.1811.
Characterization data for 4a, 4k, 4l, 4m can be referred
to in our previous report.4a;b
Minor diastereomers for 4d, 4e, 4f, 4g, 4h, 4i could not
be separated by HPLC, completely. Characterization
data for minor diastereomers were shown 1H NMR and
MS, mainly.
4.4.4. (2R,4S)-2-[(1S,4R)-2-Oxobornane-10-sulfenyl]-4-
hexanol syn-4d.
1
Colorless oil; H NMR (400 MHz,
CDCl3): d 3.90–3.79 (m, 0.4H), 3.68 (ddt, J ¼ 9:2, 6.2,
and 2.7 Hz, 0.6H), 3.08 (ddq, J ¼ 11:0, 6.8, and 4.2 Hz,
0.4H), 2.94–2.86 (m, 0.6H), 2.87 (d, A part of AB,
JAB ¼ 12:8 Hz, 0.6H), 2.62–2.48 (br s, 0.6), 2.71 (d, A
part of AB, JAB ¼ 13:0 Hz, 0.4H), 2.70–2.65 (br, 0.4H),
2.62 (d, B part of AB, JAB ¼ 13:0 Hz, 0.4H), 2.50 (d, B
part of AB, JAB ¼ 12:8 Hz, 0.6H), 2.37 (ddd, A part of
AB, JAB ¼ 18:4 Hz, J ¼ 4:9, 3.1 Hz, 0.6H) 2.36 (ddd, A
part of AB, JAB ¼ 18:3 Hz, J ¼ 4:8, 2.4 Hz, 0.4H), 2.09–
1.93 (m, 3H), 1.88 (d, B part of AB, JAB ¼ 18:3 Hz,
0.4H), 1.87 (d, B part of AB, J ¼ 18:4 Hz, 0.6H), 1.68–
1.37 (m, 6H), 1.35 (d, J ¼ 6:8 Hz, 1.2H), 1.32 (d,
J ¼ 6:8 Hz, 1.8H), 1.05 (s, 1.8H), 1.04 (s, 1.2H), 0.96 (t,
J ¼ 7:5 Hz, 3H), 0.91 (s, 1.8H), 0.90 (s, 1.2H); MS
(70 eV) m=z: 284 (Mþ, 3), 256 (3), 185 (10), 149 (10), 129
(9), 109 (14), 97 (28), 83 (100), 69 (63), 55 (86); HRMS
calcd for C16H28O2S (Mþ): 284.1810, found 284.1807.
4.4.1.
sulfenyl]-1-phenyl-3-pentanol anti-4b.
(1R,3R)-4-Methyl-1-[(1S,4R)-2-oxobornane-10-
Pale yellow oil;
26
D
½aꢀ ¼ +175.1 (c 1.44, CHCl3); 1H NMR (400 MHz,
CDCl3): d 7.39–7.20 (m, 5H), 4.10 (dd, J ¼ 10:1, 5.1 Hz,
1H), 3.77–3.64 (m, 1H), 2.62 (d, A part of AB,
A part of AB,
JAB ¼ 13:2 Hz, 1H), 2.32 (ddd,
JAB ¼ 18:4 Hz, J ¼ 4:6, 3.3 Hz, 1H), 2.20 (d, B part of
AB, JAB ¼ 13:2 Hz, 1H), 2.20–2.16 (br s, 1H), 2.00–1.80
(m, 4H), 1.83 (d, B part of AB, JAB ¼ 18:4 Hz, 1H),
1.78–1.63 (m, 2H), 1.55–1.47 (m, 1H), 1.36–1.29 (m,
1H), 0.93 (d, J ¼ 6:8 Hz, 3H), 0.91 (d, J ¼ 6:8 Hz, 3H),
0.88 (s, 3H), 0.75 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 218.0, 143.9, 128.4 (2), 127.9 (2), 127.0, 73.8, 60.7,
49.2, 47.8, 43.3, 43.1, 41.3, 33.6, 27.6, 26.8, 26.7, 19.9,
19.8, 18.7, 17.5; IR (CHCl3): 3501, 2964, 2878, 1736,
1599, 1491, 1470, 1452 cmꢁ1; MS (20 eV) m=z: 360 (Mþ,
11), 273 (39), 185 (68), 176 (23), 151 (26), 133 (72), 105
(100), 91 (20), 73 (43), 55 (28); HRMS calcd for
C22H32O2S (Mþ): 360.2123, found 360.2117.
4.4.5. (3S,5S)-3-[(1S,4R)-2-Oxobornane-10-sulfenyl]-5-
undecanol anti-4e.
21
D
Colorless oil; ½aꢀ ¼ +50.6 (c 0.61,
1
CHCl3); H NMR (400 MHz, CDCl3): d 4.00–3.91 (m,
1H), 2.89 (ddt, J ¼ 10:4, 6.4, and 3.7 Hz, 1H), 2.82–2.78
(br s, 1H), 2.68 (d, A part of AB, JAB ¼ 13:0 Hz, 1H),
2.59 (d, B part of AB, JAB ¼ 13:0 Hz, 1H), 2.36 (ddd, A
part of AB, JAB ¼ 18:5 Hz, J ¼ 4:6, 2.2 Hz, 1H), 2.09–
1.97 (m, 3H), 1.88 (d, B part of AB, JAB ¼ 18:5 Hz, 1H),
1.76–1.60 (m, 5H), 1.60–1.36 (m, 5H), 1.36–1.28 (m,
6H), 1.03 (s, 3H), 1.00 (t, J ¼ 7:3 Hz, 3H), 0.89 (s, 3H),
0.88 (br t, J ¼ 7:0 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 218.2, 68.9, 60.9, 47.9, 46.9, 43.3, 43.2, 41.2,
37.6, 31.8, 29.4, 29.2, 27.7, 26.8, 26.6, 25.8, 22.6, 20.14,
20.08, 14.1, 11.3; IR (CHCl3): 3499, 3004, 2963, 2930,
2874, 2856, 1736, 1466, 1454, 1416, 1390, 1375,
1238 cmꢁ1; MS (70 eV) m=z: 354 (Mþ, 9), 336 (1), 225
4.4.2. (1R,3R)-1-Cyclohexyl-3-[(1S,4R)-2-oxobornane-
10-sulfenyl]-3-phenyl-1-propanol anti-4c. Pale yellow oil;
26
D
½aꢀ ¼ +144.9 (c 0.64, CHCl3); 1H NMR (400 MHz,
CDCl3): d 7.39–7.19 (m, 5H), 4.10 (dd, J ¼ 10:3, 5.0 Hz,
1H), 3.75 (ddd, J ¼ 9:3, 5.7, and 3.3 Hz, 1H), 2.62 (d, A
part of AB, JAB ¼ 13:2 Hz, 1H), 2.32 (ddd, A part of
AB, JAB ¼ 18:3 Hz, J ¼ 4:8, 3.5 Hz, 1H), 2.20 (d, B part
of AB, JAB ¼ 13:2 Hz, 1H), 2.03–1.96 (m, 3H), 1.96–1.79
(m, 6H), 1.81 (d, B part of AB, JAB ¼ 18:3 Hz, 1H), 1.54
(ddd, J ¼ 13:6, 9.3, and 5.0 Hz, 1H), 1.38–1.28 (m, 2H),
1.27–1.00 (m, 7H), 0.88 (s, 3H), 0.74 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 218.2, 144.2, 128.6 (2), 128.1 (2),
127.2, 73.5, 61.0, 49.4, 48.0, 44.0, 43.5, 43.3, 41.7, 29.3,

900
M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
(25), 185 (100), 151 (34), 141(22), 123 (21), 113 (54), 81
(50), 69 (49), 55 (98); HRMS calcd for C21H38O2S (Mþ):
354.2592, found 354.2588.
CHCl3); 1H NMR (400 MHz, CDCl3): d 4.17 (ddq,
J ¼ 9:5, 6.2, and 2.4 Hz, 1H), 2.90–2.85 (br s, 1H), 2.93
(ddt, J ¼ 10:3, 6.6, and 3.7 Hz, 1H), 2.69 (d, A part of
AB, JAB ¼ 13:2 Hz, 1H), 2.59 (d, B part of AB,
4.4.6. (3S,5S)-3-[(1S,4R)-2-Oxobornane-10-sulfenyl]-5-
Colorless oil; H NMR (400 MHz,
JAB ¼ 13:2 Hz, 1H), 2.36 (ddd,
A part of AB,
1
undecanol syn-4e.
JAB ¼ 18:5 Hz, J ¼ 4:8, 2.2 Hz, 1H), 2.10–1.94 (m, 3H),
1.88 (d, B part of AB, JAB ¼ 18:5 Hz, 1H), 1.69 (ddd,
J ¼ 14:5, 9.5, and 3.7 Hz, 1H), 1.66–1.34 (m, 7H), 1.21
(d, J ¼ 6:2 Hz, 3H), 1.03 (s, 3H), 0.93 (t, J ¼ 7:3 Hz,
3H), 0.90 (s, 3H); 13C NMR (100 MHz, CDCl3): d 219.3,
66.0, 62.0, 48.9, 46.1, 44.33, 44.25, 44.1, 39.7, 28.7, 27.8,
27.7, 24.5, 21.09, 21.07, 21.0, 15.0; IR (CHCl3): 3666,
3003, 2966, 2930, 2873, 1735, 1466, 1454, 1416, 1391,
1375, 1236 cmꢁ1; MS (20 eV) m=z: 298 (Mþ, 35), 211
(12), 183 (100), 151 (52), 123 (36), 109 (69), 81 (59), 67
(44), 55 (86); HRMS calcd for C17H30O2S (Mþ):
298.1966, found 298.1969.
CDCl3): d 3.80–3.72 (m, 1H), 3.00–2.90 (br s, 1H), 2.83
(d, A part of AB, JAB ¼ 12:7 Hz, 1H), 2.71–2.62 (m, 1H),
2.47 (d, B part of AB, JAB ¼ 12:7 Hz, 1H), 2.37 (ddd, A
part of AB, JAB ¼ 18:4 Hz, J ¼ 4:8, 3.1 Hz, 1H), 2.21–
1.96 (m, 3H), 1.87 (d, B part of AB, JAB ¼ 18:4 Hz, 1H),
1.74–1.56 (m, 4H), 1. 56–1.22 (m, 12H), 1.05 (s, 3H),
1.00 (t, J ¼ 7.3 Hz, 3H), 0.91 (s, 3H), 0.88 (br t,
J ¼ 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 217.6,
71.3, 60.7, 47.9, 47.5, 43.6, 43.1, 41.6, 38.0, 32.0, 29.3,
27.9, 26.9, 26.7, 26.4, 25.5, 22.6, 20.3, 20.2, 14.1, 11.1;
MS (70 eV) m=z: 354 (Mþ, 13), 225 (25), 185 (100), 151
(27), 141 (18), 123 (16), 113 (42), 95 (19), 81 (37), 69 (40),
55 (71); HRMS calcd for C21H38O2S (Mþ): 354.2592,
found 354.2589.
4.4.10. (2S,4R)-4-[(1S,4R)-2-Oxobornane-10-sulfenyl]-2-
heptanol syn-4g.
1
Colorless oil; H NMR (400 MHz,
CDCl3): d 4.04–3.95 (m, 1H), 3.10–2.96 (br s, 1H), 2.83
(d, A part of AB, JAB ¼ 12:7 Hz, 1H), 2.74–2.65 (m, 1H),
2.47 (d, B part of AB, JAB ¼ 12:7 Hz, 1H), 2.37 (ddd, A
part of AB, JAB ¼ 18:4 Hz, J ¼ 4:6, 2.9 Hz, 1H), 2.12–
1.94 (m, 3H), 1.87 (d, B part of AB, JAB ¼ 18:4 Hz, 1H),
1.76–1.62 (m, 2H), 1.60–1.34 (m, 6H), 1.20 (d,
J ¼ 6:2 Hz, 3H), 1.05 (s, 3H), 0.92 (t, J ¼ 7:3 Hz, 3H),
0.91 (s, 3H); 13C NMR (100 MHz, CDCl3): d 217.6, 67.5,
60.7, 47.9, 45.5, 43.8, 43.5, 43.1, 37.6, 26.9, 26.7, 26.1,
23.8, 20.3, 20.2, 19,9, 14.0; MS (70 eV) m=z: 298 (Mþ,
13), 185 (43), 151 (17), 123 (17), 109 (34), 95 (29), 83
(98), 69 (91), 55 (100); HRMS calcd for C17H30O2S
(Mþ): 298.1966, found 298.1971.
4.4.7. (3S,5S)-3-[(1S,4R)-2-Oxobornane-10-sulfenyl]-5-
tridecanol anti-4f.
21
D
Colorless oil; ½aꢀ ¼ +26.4 (c 1.84,
1
CHCl3); H NMR (400 MHz, CDCl3): d 4.00–3.89 (m,
1H), 2.89 (ddt, J ¼ 13:2, 6.2, and 3.5 Hz, 1H), 2.84–2.76
(br, 1H), 2.68 (d, A part of AB, JAB ¼ 13:0 Hz, 1H), 2.59
(d, B part of AB, JAB ¼ 13:0 Hz, 1H), 2.36 (ddd, A part
of AB, JAB ¼ 18:5 Hz, J ¼ 4:8, 2.4 Hz, 1H), 2.09–1.97
(m, 3H), 1.88 (d, B part of AB, JAB ¼ 18:5 Hz, 1H),
1.73–1.36 (m, 10H), 1.34–1.20 (m, 10H), 1.03 (s, 3H),
1.00 (t, J ¼ 7:3 Hz, 3H), 0.89 (s, 3H), 0.88 (br t,
J ¼ 7:0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 218.2,
68.9, 60.9, 47.9, 46.9, 43.3, 43.2, 41.2, 37.6, 31.9, 30.2,
29.6, 29.3, 29.2 (2), 27.6, 26.8, 26.7, 25.8, 22.6, 20.1, 14.1,
11.3; IR (CHCl3): 3665, 3009, 2963, 2930, 2874, 2856,
1739, 1466, 1452, 1417, 1391, 1375, 1236, 1051 cmꢁ1; MS
(70 eV) m=z: 382 (Mþ, 8), 225 (25), 213 (16), 185 (100),
141 (28), 123 (19), 109 (45), 95 (23), 81 (44), 69 (50), 55
(69); HRMS calcd for C23H42O2S (Mþ): 382.2905, found
382.2897.
4.4.11. (4S,6S)-4-[(1S,4R)-2-Oxobornane-10-sulfenyl]-6-
dodecanol anti-4h.
26
D
Colorless oil; ½aꢀ ¼ +48.8 (c 1.07,
1
CHCl3); H NMR (400 MHz, CDCl3): d 4.00–3.88 (m,
1H), 2.93 (ddt, J ¼ 10:1, 6.4, and 3.5 Hz, 1H), 2.86–2.82
(br s, 1H), 2.69 (d, A part of AB, JAB ¼ 13:0 Hz, 1H),
2.58 (d, B part of AB, JAB ¼ 13:0 Hz, 1H), 2.36 (ddd, A
part of AB, JAB ¼ 18:4 Hz, J ¼ 4:8, 2.2 Hz, 1H), 2.09–
1.97 (m, 3H), 1.88 (d, B part of AB, JAB ¼ 18:4 Hz, 1H),
1.71–1.43 (m, 11H), 1.37–1.22 (m, 7H), 1.03 (s, 3H), 0.92
(t, J ¼ 7:3 Hz, 3H), 0.89 (br t, J ¼ 7:1 Hz, 3H), 0.89 (s,
3H); 13C NMR (100 MHz, CDCl3): d 218.2, 68.9, 60.9,
47.9, 45.0, 43.3, 43.1, 41.5, 38.7, 37.6, 31.8, 29.4, 27.5,
26.8, 26.6, 25.8, 22.6, 20.2, 20.1 (2), 14.1, 14.0; IR
(CHCl3): 3690, 2939, 1733, 1458, 1234 cmꢁ1; MS (70 eV)
m=z: 368 (Mþ, 4), 239 (9), 185 (44), 136 (12), 122 (18),
109 (25), 97 (30), 81 (36), 69 (64), 55 (100); HRMS calcd
for C22H40O2S (Mþ): 368.2749, found 368.2745.
4.4.8. (3R,5S)-3-[(1S,4R)-2-Oxobornane-10-sulfenyl]-5-
Colorless oil; H NMR (400 MHz,
1
tridecanol syn-4f.
CDCl3): d 3.81–3.72 (m, 1H), 3.05–2.90 (br s, 1H), 2.83
(d, A part of AB, JAB ¼ 12:8 Hz, 1H), 2.71–2.63 (m, 1H),
2.47 (d, B part of AB, JAB ¼ 12:8 Hz, 1H), 2.37 (ddd, A
part of AB, JAB ¼ 18:4 Hz, J ¼ 4:8, 2.9 Hz, 1H), 2.13–
1.94 (m, 3H), 1.87 (d, B part of AB, JAB ¼ 18:4 Hz, 1H),
1.75–1.56 (m, 4H), 1.56–1.20 (m, 16H), 1.05 (s, 3H), 1.00
(t, J ¼ 7:3 Hz, 3H), 0.91 (s, 3H), 0.90 (br t, J ¼ 7:1 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 217.6, 71.3, 60.7,
47.9, 47.5, 43.5, 43.1, 41.6, 38.0, 31.9, 29.7, 29.6, 29.3,
27.9, 26.9, 26.7, 26.3, 25.5, 22.7, 20.3, 20.2, 14.1, 11.1;
MS (70 eV) m=z: 382 (Mþ, 12), 225 (25), 213 (15), 185
(100), 141 (26), 123 (15), 109 (38), 95 (13), 81 (35), 69
(43), 55 (55); HRMS calcd for C23H42O2S (Mþ):
382.2905, found 382.2908.
4.4.12. (4R,6S)-4-[(1S,4R)-2-Oxobornane-10-sulfenyl]-6-
dodecanol syn-4h.
1
Colorless oil; H NMR (400 MHz,
CDCl3): d 3.80–3.72 (m, 1H), 3.03–2.90 (br s, 1H), 2.83
(d, A part of AB, JAB ¼ 12:7 Hz, 1H), 2.74–2.67 (m, 1H),
2.47 (d, B part of AB, JAB ¼ 12:7 Hz, 1H), 2.37 (ddd, A
part of AB, JAB ¼ 18:4 Hz, J ¼ 4:8, 3.1 Hz, 1H), 2.12–
1.94 (m, 3H), 1.87 (d, B part of AB, JAB ¼ 18:4 Hz, 1H),
1.73–1.25 (m, 18H), 1.05 (s, 3H), 0.92 (t, J ¼ 7:3 Hz,
4.4.9. (2S,4S)-4-[(1S,4R)-2-Oxobornane-10-sulfenyl]-2-
heptanol anti-4g.
24
D
Colorless oil; ½aꢀ ¼ +63.2 (c 0.94,

M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
901
3H), 0.90 (s, 3H), 0.88 (br t, J ¼ 7:0 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 217.7, 71.3, 60.7, 47.9, 45.5, 43.5,
43.1, 42.1, 38.0, 37.5, 31.8, 29.4, 26.9, 26.7, 26.2, 25.5,
22.6, 20.3, 20.2, 19.9, 14.1, 14.0; MS (70 eV) m=z: 368
(Mþ, 2), 185 (6), 152 (10), 124 (10), 111 (16), 98 (31), 84
(90), 69 (49), 55 (100); HRMS calcd for C22H40O2S
(Mþ): 368.2749, found 368.2744.
(Mþ, 2), 342 (12), 176 (66), 159 (97), 133 (100), 129 (59),
117 (96), 105 (59), 91 (41), 77 (27), 67 (18), 55 (16);
HRMS calcd for C22H32O2S (Mþ): 360.2123, found
360.2125.
4.4.16. (1R,3R)-3-[(1S,4R)-2-Oxobornane-10-sulfenyl]-1-
22
phenyl-1-hexanol syn-4j. Colorless oil; ½aꢀ ¼ +31.1 (c
D
0.96, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.41–7.32
(m, 4H), 7.29–7.24 (m, 1H), 4.93–4.90 (m, 1H), 3.12 (d,
J ¼ 2:6 Hz, 1H), 2.85 (d, A part of AB, JAB ¼ 12:6 Hz,
1H), 2.69–2.61 (m, 1H), 2.47 (d, B part of AB,
4.4.13. (4S,6S)-4-[(1S,4R)-2-Oxobornane-10-sulfenyl]-6-
25
D
tetradecanol anti-4i. Colorless oil; ½aꢀ ¼ +42.5 (c 2.02,
1
CHCl3); H NMR (400 MHz, CDCl3): d 4.00–3.91 (m,
1H), 2.93 (ddt, J ¼ 10:1, 6.4, and 3.5 Hz, 1H), 2.84–2.78
(br s, 1H), 2.69 (d, A part of AB, JAB ¼ 12:8 Hz, 1H),
2.58 (d, B part of AB, JAB ¼ 12:8 Hz, 1H), 2.36 (ddd, A
part of AB, JAB ¼ 18:4 Hz, J ¼ 4:8, 2.2 Hz, 1H), 2.09
(m, 3H), 1.88 (d, B part of AB, JAB ¼ 18:4 Hz, 1H),
1.70–1.34 (m, 10H), 1.32–1.24 (m, 12H), 1.04 (s, 3H),
0.92 (t, J ¼ 7:1 Hz, 3H), 0.89 (s, 3H), 0.88 (br t,
J ¼ 7:1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 218.1,
68.9, 60.9, 47.9, 44.9, 43.3, 43.1, 41.5, 38.7, 37.6, 31.9,
29.7, 29.5, 29.2, 27.5, 26.8, 26.6, 25.8, 22.6, 20.2, 20.1 (2),
14.1, 14.0; IR (CHCl3): 3510, 2959, 2930, 2874, 3856,
1736, 1466, 1454, 1416, 1391, 1373 cmꢁ1; MS (70 eV)
m=z: 396 (Mþ, 9), 368 (1), 239 (23), 227 (15), 211 (18),
194 (9), 185 (100), 167 (12), 151 (27), 141 (33), 109 (41),
98 (31), 83 (70), 69 (73), 55 (99); HRMS calcd for
C24H44O2S (Mþ): 396.3062, found 396.3058.
JAB ¼ 12:6 Hz, 1H), 2.38 (ddd,
A part of AB,
JAB ¼ 18:3 Hz, J ¼ 4:7, 2.9 Hz, 1H), 2.14–1.88 (m, 5H),
1.88 (d, B part of AB, JAB ¼ 18:3 Hz, 1H), 1.63–1.35 (m,
6H), 1.07 (s, 3H), 0.92 (s, 3H), 0.89 (t, J ¼ 7:2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d 217.7, 144.6, 128.4 (2),
127.5, 125.9 (2), 73.5, 60.7, 47.9, 45.0, 43.9, 43.5, 43.1,
37.4, 26.9, 26.7, 26.2, 20.4, 20.2, 19.9, 13.9; IR (CHCl3):
3421, 3033, 3014, 3004, 2989, 2960, 2933, 2893, 1735,
1602, 1494, 1456, 1415, 1390, 1373, 1317, 1299,
1280 cmꢁ1; MS (70 eV) m=z: 360 (Mþ, 1), 342 (6), 176
(41), 159 (53), 133 (71), 129 (100), 117 (66), 105 (51), 91
(41), 77 (39), 67 (29), 55 (27); HRMS calcd for
C22H32O2S (Mþ): 360.2123, found 360.2119.
4.5. A typical procedure for the conversion of sulfides anti-
4 into 1,3-mercapto alcohols anti-3 under acidic conditions
4.4.14. (4R,6S)-4-[(1S,4R)-2-Oxobornane-10-sulfenyl]-6-
tetradecanol syn-4i. Colorless oil; H NMR (400 MHz,
To
a
suspension of lithium aluminum hydride
1
(0.75 mmol) in tetrahydrofuran (1 mL) was added
dropwise a solution of anti-4 (0.25 mmol) in tetrahy-
drofuran (3 mL) at 0 ꢁC, and the reaction mixture then
stirred for 2 h at room temperature under a nitrogen
atmosphere. The reaction mixture was diluted diethyl
ether, and quenched with sat. sodium sulfate aqueous
solution at 0 ꢁC, and dried over magnesium sulfate, fil-
trated, and concentrated in vacuo to give a crude diol.
To a solution of a crude diol in dichloromethane (3 mL)
was added BF3ÆOEt2 (0.25 mmol), and the resulting
mixture stirred at room temperature under a nitrogen
atmosphere for 2.5 h until all starting material had dis-
appeared on TLC analysis. If any starting material
remained, additional BF3ÆOEt2 (0.05–0.13 mmol) was
added. 1-Dodecanethiol (Dod-SH) (5.0 mmol) was then
added and the resultant mixture stirred for 5.5 h at room
temperature. At this stage, if the reaction has gone to
completion, the additional BF3ÆOEt2 (0.13 mmol) was
added. The reaction mixture was poured into water, and
extracted with ethyl acetate. The combined organic
layers were washed with brine, and dried over magne-
sium sulfate, filtered, and concentrated in vacuo. Puri-
fication of the residue by silica gel column
chromatography (hexane/ethyl acetate ¼ 10:1) gave anti-
3 in the yields shown in Table 2.
CDCl3): d 3.80–3.72 (m, 1H), 3.10–2.92 (br s, 1H), 2.83
(d, A part of AB, JAB ¼ 12:8 Hz, 1H), 2.71 (quintet,
J ¼ 7:1 Hz, 1H), 2.47 (d, B part of AB, JAB ¼ 12:8 Hz,
1H), 1.37 (ddd, A part of AB, JAB ¼ 18:4 Hz, J ¼ 4:8,
2.9 Hz, 1H), 2.12–1.98 (m, 3H), 1.87 (d, B part of AB,
JAB ¼ 18:4 Hz, 1H), 1.72–1.63 (m, 2H), 1.63–1.20 (m,
20H), 1.05 (s, 3H), 0.92 (t, J ¼ 7:1 Hz, 3H), 0.91 (s, 3H),
0.88 (br t, J ¼ 7:1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 217.7, 71.3, 60.7, 47.9, 45.5, 43.5, 43.1, 42.5,
38.0, 37.5, 31.9, 29.7, 29.6, 29.3, 26.9, 26.7, 26.2, 25.5,
22.7, 20.3, 20.2, 19.9, 14.1, 14.0; MS (70 eV) m=z: 396
(Mþ, 12), 239 (25), 227 (15), 185 (100), 151 (25), 141
(31), 123 (15), 109 (37), 81 (39), 69 (49), 55 (63); HRMS
calcd for C24H44O2S (Mþ): 396.3062, found 396.3058.
4.4.15. (1R,3S)-3-[(1S,4R)-2-Oxobornane-10-sulfenyl]-1-
22
phenyl-1-hexanol anti-4j. Colorless oil; ½aꢀ ¼ +53.6 (c
D
1.16, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.40–7.31
(m, 4H), 7.27–7.23 (m, 1H), 5.12 (dt, J ¼ 9:8, 3.5 Hz,
1H), 3.14 (d, J ¼ 4:0 Hz, 1H), 3.00–2.93 (m, 1H), 2.74
(d, A part of AB, JAB ¼ 12:9 Hz, 1H), 2.61 (d, B part of
AB, JAB ¼ 12:9 Hz, 1H), 2.37 (ddd, A part of AB,
JAB ¼ 18:4 Hz, J ¼ 4:9, 2.5 Hz, 1H), 2.09–1.95 (m, 4H),
1.89 (d, B part of AB, JAB ¼ 18:4 Hz, 1H), 1.78–1.36 (m,
7H), 1.05 (s, 3H), 0.91 (s, 3H), 0.91 (t, J ¼ 7:5 Hz, 3H);
13C NMR (100 MHz, CDCl3): d 218.2, 144.9, 128.3 (2),
127.1, 125.6 (2), 71.4, 60.9, 47.9, 45.0, 44.1, 43.4, 43.2,
38.6, 27.6, 26.9, 26.8, 20.2, 20.1, 20.0, 14.0; IR (CHCl3):
3502, 3031, 3022, 3010, 2960, 2933, 2873, 1735, 1602,
1494, 1454, 1415, 1298, 1280 cmꢁ1; MS (70 eV) m=z: 360
4.5.1. (1R,3S)-1-Mercapto-1-phenyl-3-butanol anti-3a.
24
D
1
Colorless oil; ½aꢀ ¼ +121.8 (c 0.59, CHCl3); H NMR
(400 MHz, CDCl3): d 7.36–7.30 (m, 4H), 7.26–7.22 (m,
1H), 4.23 (dt, J ¼ 9:5, 5.7 Hz, 1H), 4.05 (ddq, J ¼ 8:6,
6.1, and 4.0 Hz, 1H), 2.04 (ddd, A part of AB,

902
M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
JAB ¼ 14:1 Hz, J ¼ 8:6, 5.7 Hz, 1H), 1.93 (ddd, B part of
AB, JAB ¼ 14:1 Hz, J ¼ 9:5, 4.0 Hz, 1H), 1.93 (d,
J ¼ 5:7 Hz, 1H), 1.57 (br s, 1H), 1.25 (d, J ¼ 6:2 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 145.0, 128.7 (2),
127.2, 126.7 (2), 65.8, 48.3, 40.8, 23.8; IR (CHCl3): 3610,
3008, 2970, 2931, 1600, 1492, 1454, 1377, 1126 cmꢁ1; MS
(70 eV) m=z: 182 (Mþ, 10), 164 (21), 148 (14), 123 (10),
105 (100), 91 (14), 77 (20); HRMS calcd for C10H14OS
(Mþ): 182.0765, found 182.0773. [97% ee, chiral HPLC
analysis; DAICEL CHIRALCEL OD (25 · 0.46); elu-
ent: hexane/isopropanol ¼ 10/1; flow rate: 1.0 mL/min;
Temp.: 26 ꢁC; detector: 254 nm, ()): 9.6 min, (+):
11.5 min].
83 (100), 69 (76), 55 (46); HRMS calcd for C6H14OS
(Mþ): 134.0765, found 134.0770.
4.5.5. (3S,5S)-3-Mercapto-5-undecanol anti-3e. Colorless
26
D
1
oil; ½aꢀ ¼ +28.8 (c 1.44, CHCl3); H NMR (400 MHz,
CDCl3): d 3.99–3.89 (m, 1H), 3.05–2.97 (m, 1H), 1.77–
1.63 (m, 3H), 1.62–1.42 (m, 5H), 1.42–1.22 (m, 7H), 1.34
(d, J ¼ 7:3 Hz, 1H), 1.02 (t, J ¼ 7:3 Hz, 3H), 0.90 (br t,
J ¼ 7:0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 69.4,
45.6, 39.5, 38.0, 32.9, 31.8, 29.3, 25.6, 22.6, 14.1, 11.5; IR
(CHCl3): 3620, 3007, 2963, 2932, 2874, 2858, 1460,
1379 cmꢁ1; MS (20 eV) m=z: 204 (Mþ, 10), 186 (42), 170
(28), 157 (73), 141 (35), 129 (65), 115 (82), 97 (100), 88
(96), 75 (88), 55 (54); HRMS calcd for C11H24OS (Mþ):
204.1548, found 204.1552.
4.5.2. (1R,3R)-1-Mercapto-4-methyl-1-phenyl-3-pentanol
24
D
1
anti-3b. Colorless oil; ½aꢀ ¼ +125.5 (c 1.49, CHCl3); H
NMR (400 MHz, CDCl3): d 7.38–7.29 (m, 5H), 4.28 (dt,
J ¼ 9:0, 5.9 Hz, 1H), 3.73 (dt, J ¼ 7:5, 5.3 Hz, 1H),
2.02–1.92 (m, 2H), 1.89 (d, J ¼ 5:9 Hz, 1H), 1.70 (septet
d, J ¼ 6:9, 5.3 Hz, 1H), 1.65–1.50 (br s, 1H), 0.94 (d,
J ¼ 6:9 Hz, 6H); 13C NMR (100 MHz, CDCl3): d 145.5,
128.7 (2), 127.2, 126.8 (2), 74.2, 43.6, 41.2, 33.9, 18.9,
17.5; IR (CHCl3): 3622, 3065, 2964, 2912, 2897, 2876,
1601, 1493, 1468, 1452, 1389, 1369 cmꢁ1; MS (20 eV)
m=z: 210 (Mþ, 5), 192 (12), 176 (7), 158 (7), 133 (71), 105
(100), 91 (24), 73 (33), 55 (26); HRMS calcd for
C12H18OS (Mþ): 210.1078, found 210.1076. [99% ee,
chiral HPLC analysis; DAICEL CHIRALCEL OD
(25 · 0.46); eluent: hexane/isopropanol ¼ 9/1; flow rate:
0.2 mL/min; Temp.: 27 ꢁC; detector: 254 nm, ()):
27.9 min, (+): 35.0 min].
4.5.6. (3S,5S)-3-Mercapto-5-tridecanol anti-3f. Colorless
26
D
1
oil; ½aꢀ ¼ +27.8 (c 1.06, CHCl3); H NMR (400 MHz,
CDCl3): d 3.98–3.89 (m, 1H), 3.04–2.94 (m, 1H), 1.73–
1.64 (m, 3H), 1.62–1.41 (m, 5H), 1.36–1.24 (m, 11H),
1.34 (d, J ¼ 7:3 Hz, 1H), 1.02 (t, J ¼ 7:3 Hz, 3H), 0.89
(br t, J ¼ 7:1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d
69.4, 45.6, 39.5, 38.0, 32.9, 31.8, 29.6, 29.5, 29.2, 25.7,
22.6, 14.1, 11.5; IR (CHCl3): 3690, 2961, 2930, 2856,
1458, 1437 cmꢁ1; MS (20 eV) m=z: 232 (Mþ, 10), 214
(17), 198 (8), 185 (28), 167 (22), 157 (28), 167 (22), 157
(28), 141 (38), 129 (8), 115 (33), 98 (90), 83 (100), 69 (53),
58 (62); HRMS calcd for C13H28OS (Mþ): 232.1861,
found 232.1857.
4.5.7. (2S,4S)-4-Mercapto-2-heptanol anti-3g. Colorless
24
D
1
oil; ½aꢀ ¼ +32.6 (c 1.25, CHCl3); H NMR (400 MHz,
4.5.3. (1R,3R)-1-Cyclohexyl-3-mercapto-3-phenyl-1-pro-
panol anti-3c.
CDCl3): d 4.15 (ddq, J ¼ 9:5, 6.4, and 2.9 Hz, 1H), 3.09–
2.99 (m, 1H), 1.76 (ddd, J ¼ 14:3, 9.5, and 3.5 Hz, 1H),
1.65–1.40 (m, 6H), 1.37 (d, J ¼ 7:1 Hz, 1H), 1.23 (d,
J ¼ 5:5 Hz, 3H), 0.92 (t, J ¼ 7:1 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 65.5, 47.7, 42.0, 37.5, 24.1, 20.1,
13.7; IR (CHCl3): 3647, 2999, 2930, 1456 cmꢁ1; MS
(20 eV) m=z: 148 (Mþ, 10), 146 (50), 130 (13), 114 (37),
97 (100), 83 (63), 71 (27), 55 (65); HRMS calcd for
C7H16OS (Mþ): 148.0922, found 148.0916.
26
D
Colorless oil; ½aꢀ ¼ +128.3 (c 0.44,
1
CHCl3); H NMR (400 MHz, CDCl3): d 7.37–7.21 (m,
5H), 4.29 (dt, J ¼ 9:0, 6.0 Hz, 1H), 3.75–3.68 (br m, 1H),
2.05–1.90 (m, 2H), 1.88 (d, J ¼ 6:0 Hz, 1H), 1.86–1.63
(m, 5H), 1.60–1.56 (br s, 1H), 1.42–1.31 (m, 1H), 1.30–
0.98 (m, 5H); 13C NMR (100 MHz, CDCl3): d 145.6,
128.7 (2), 127.1, 126.8 (2), 73.7, 44.0, 43.7, 41.2, 29.1,
27.9, 26.4, 26.2, 26.1; IR (CHCl3): 3601, 3007, 2930,
2855, 1495, 1450, 1387, 1238, 1223 cmꢁ1; MS (20 eV)
m=z: 250 (Mþ, 2), 232 (15), 216 (12), 198 (23), 169 (7),
155 (12), 133 (86), 105 (93), 95 (70), 77 (56), 55 (100);
HRMS calcd for C15H22OS (Mþ): 250.1391, found
250.1386. [99% ee, chiral HPLC analysis; DAICEL
CHIRALCEL OD (25 · 0.46); eluent: hexane/isopropa-
nol ¼ 50/1; flow rate: 0.5 mL/min; Temp.: 26 ꢁC; detec-
tor: 254 nm, ()): 13.7 min, (+): 17.3 min].
4.5.8. (4S,6S)-4-Mercapto-6-dodecanol anti-3h. Colorless
23
D
1
oil; ½aꢀ ¼ +26.7 (c 0.60, CHCl3); H NMR (400 MHz,
CDCl3): d 3.99–3.90 (m, 1H), 3.12 (m, 1H), 1.73 (ddd,
J ¼ 14:3, 9.9, and 3.3 Hz, 1H), 1.68–1.40 (m, 9H), 1.40–
1.28 (m, 7H), 1.36 (d, J ¼ 7:3 Hz, 1H), 0.92 (t,
J ¼ 7:1 Hz, 3H), 0.90 (br t, J ¼ 7:1 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 69.4, 46.0, 42.2, 38.0, 31.9, 29.6,
29.2, 25.7, 22.7, 20.2, 14.1, 13.8; IR (CHCl3): 3630, 2958,
2931, 2858, 1458, 1379 cmꢁ1; MS (20 eV) m=z: 218 (Mþ,
10), 200 (37), 184 (20), 167 (25), 157 (79), 141 (35), 129
(83), 113 (63), 102 (69), 97 (100), 89 (87), 81 (50), 69 (59),
55 (67); HRMS calcd for C12H26OS (Mþ): 218.1704,
found 218.1707.
4.5.4. (2S,4S)-2-Mercapto-4-hexanol anti-3d. Colorless
24
D
1
oil; ½aꢀ ¼ +63.3 (c 0.26, CHCl3); H NMR (400 MHz,
CDCl3): d 3.80–3.78 (m, 1H), 3.27–3.16 (m, 1H), 1.70
(ddd, J ¼ 14:3, 9.9, and, 3.8 Hz, 1H), 1.67–1.63 (br m,
1H), 1.56–1.45 (m, 3H), 1.49 (d, J ¼ 6:8 Hz, 1H), 1.38
(d, J ¼ 6:8 Hz, 3H), 0.96 (t, J ¼ 7:5 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 71.0, 47.3, 32.5, 30.6, 26.8, 9.9; IR
(CHCl3): 3620, 2968, 2926, 2878, 1456, 1377 cmꢁ1; MS
(20 eV) m=z: 134 (Mþ, 12), 132 (32), 116 (65), 100 (68),
4.5.9. (1R,3S)-1-Mercapto-1-phenyl-3-pentanol anti-3k.
Colorless oil; ½aꢀ ¼ +120.9 (c 0.88, CHCl3); H NMR
23
D
1

M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
903
(400 MHz, CDCl3): d 7.36–7.29 (m, 4H), 7.25–7.21 (m,
1H), 4.28 (dt, J ¼ 8:8, 6.0 Hz, 1H), 3.83 (tt, J ¼ 7:5,
4.9 Hz, 1H), 1.99 (m, 2H), 1.91 (d, J ¼ 6:0 Hz, 1H), 1.59
(br s, 1H), 1.58–1.44 (m, 2H), 0.97 (t, J ¼ 7:4 Hz, 3H);
13C NMR (100 MHz, CDCl3): d 145.2, 128.7 (2), 127.2,
126.7 (2), 70.9, 46.2, 40.9, 30.5, 9.8; IR (CHCl3): 3616,
2968, 2935, 2879, 1600, 1492, 1454 cmꢁ1; MS (70 eV)
m=z: 196 (Mþ, 4), 178 (16), 162 (8), 136 (22), 123 (13),
105 (100), 91 (14), 77 (13), 59 (38); HRMS calcd for
C11H16OS (Mþ): 196.0922, found 196.0915. [99% ee,
chiral HPLC analysis; DAICEL CHIRALCEL OB
(25 · 0.46); eluent: hexane/isopropanol ¼ 100/1; flow
rate: 0.5 mL/min; Temp.: 25 ꢁC; detector: 254 nm, ()):
35.5 min, (+): 39.6 min].
part of AB, JAB ¼ 14:5 Hz, J ¼ 8:1, 4.8 Hz, 1H), 1.85–
1.72 (m, 2H), 1.47 (d, J ¼ 7:0 Hz, 3H), 0.98 (t,
J ¼ 7:3 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 191.4,
166.1, 137.2, 133.1, 132.7, 130.6 (2), 129.6 (2), 128.5 (2),
128.2 (2), 127.1, 73.7, 40.2, 36.4, 27.2, 21.9, 9.3; IR
(CHCl3): 2970–2927, 1712, 1658, 1600, 1581, 1450 cmꢁ1
;
MS (20 eV) m=z: 342 (Mþ, 0.5), 220 (24), 204 (18), 187
(29), 115 (31), 105 (100), 77 (8); HRMS calcd for
C20H22O3S (Mþ): 342.1280, found 342.1290. [99% ee,
chiral HPLC analysis; DAICEL CHIRALCEL OD
(25 · 0.46); eluent: hexane/isopropanol ¼ 50/1; flow rate:
0.5 mL/min; Temp.: 28 ꢁC; detector: 254 nm, (+):
11.8 min, ()): 14.9 min].
4.6.1.2. (3S,5S)-3-Benzoylthioundec-5-yl benzoate 11e.
25
97% yield. Colorless oil; ½aꢀ ¼ +38.3 (c 1.08, CHCl3);
D
1H NMR (400 MHz, CDCl3): d 8.06–8.01 (m, 2H), 7.91–
7.86 (m, 2H), 7.54–7.50 (m, 2H), 7.45–7.37 (m, 4H),
5.34–5.25 (m, 1H), 3.83 (ddt, J ¼ 9:0, 7.5, and 5.3 Hz,
1H), 2.15 (ddd, A part of AB, JAB ¼ 14:5 Hz, J ¼ 8:6,
5.3 Hz, 1H), 2.01 (ddd, B part of AB, JAB ¼ 14:5 Hz,
J ¼ 9:0, 4.2 Hz, 1H), 1.91–1.65 (m, 4H), 1.45–1.20 (m,
8H), 1.03 (t, J ¼ 7:1 Hz, 3H), 0.88–0.82 (br t,
J ¼ 7:1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 191.4,
166.1, 137.3, 133.1, 132.7, 130.7, 129.6 (2), 128.4 (2),
128.2 (2), 127.2 (2), 72.8, 42.7, 38.5, 34.5, 31.7, 29.2,
28.4, 25.1, 22.5, 14.1, 11.2; IR (CHCl3): 2961, 2932,
2860, 1711, 1659, 1601, 1581, 1450, 1276 cmꢁ1; MS
(20 eV) m=z: 412 (Mþ, 0.4), 290 (19), 274 (6), 257 (11),
206 (4), 185 (31), 169 (6), 152 (43), 122 (26), 105 (100), 82
(10), 68 (7), 55 (2); HRMS calcd for C25H32O3S (Mþ):
412.2072, found 412.2076. [99% ee, chiral HPLC anal-
ysis; DAICEL CHIRALCEL OD (25 · 0.46); eluent:
hexane/isopropanol ¼ 200/1; flow rate: 0.5 mL/min;
Temp.: 28 ꢁC; detector: 254 nm, (+): 11.6 min, ()):
14.5 min].
4.5.10. (1R,3S)-1-Mercapto-1-phenyl-3-hexanol anti-3l.
Colorless oil; ½aꢀ ¼ +105.8 (c 0.76, CHCl3); H NMR
23
D
1
(400 MHz, CDCl3): d 7.36–7.29 (m, 4H), 7.26–7.21 (m,
1H), 4.27 (dt, J ¼ 8:1, 6.0 Hz, 1H), 3.90 (quintet,
J ¼ 5:9 Hz, 1H), 2.02–1.94 (m, 2H), 1.90 (d, J ¼ 6:0 Hz,
1H), 1.56 (br s, 1H), 1.52–1.31 (m, 4H), 0.94 (t,
J ¼ 7:0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 145.3,
128.7 (2), 127.2, 126.7 (2), 69.4, 46.7, 40.9, 39.9, 18.7,
14.0; IR (CHCl3): 3618, 3064–2873, 1600, 1492, 1465,
1454, 1434, 1380 cmꢁ1; MS (20 eV) m=z: 210 (Mþ, 9), 192
(19), 176 (27), 159 (24), 133 (39), 123 (16), 105 (100), 91
(12); HRMS calcd for C12H18OS (Mþ): 210.1078, found
210.1077. [99% ee, chiral HPLC analysis; DAICEL
CHIRALCEL OB (25 · 0.46); eluent: hexane/isopropa-
nol ¼ 50/1; flow rate: 0.5 mL/min; Temp.: 27 ꢁC; detec-
tor: 254 nm, ()): 21.4 min, (+): 25.6 min].
4.6. Determination of the enantiomeric excess of 1,3-
mercapto alcohols 3d, 3e, 3f, 3g, 3h
4.6.1.3. (3S,5S)-3-Benzoylthiotridec-5-yl benzoate 11f.
The enantiomeric excesses of 3d, 3e, 3f, 3g, 3h were
determined by chiral HPLC analyses of their S-, O-
benzoylated compounds 11d, 11e, 11f, 11g, 11h,
respectively.
26
94% yield. Colorless oil; ½aꢀ ¼ +34.7 (c 0.91, CHCl3);
D
1H NMR (400 MHz, CDCl3): d 8.08–8.00 (m, 2H), 7.91–
7.86 (m, 2H), 7.58–7.50 (m, 2H), 7.45–7.37 (m, 4H),
5.34–5.25 (m, 1H), 3.82 (ddt, J ¼ 8:9, 7.3, and 5.3 Hz,
1H), 2.15 (ddd, A part of AB, JAB ¼ 14:5 Hz, J ¼ 8:6,
5.3 Hz, 1H), 2.01 (ddd, B part of AB, JAB ¼ 14:5 Hz,
J ¼ 8:9, 4.0 Hz, 1H), 1.89–1.65 (m, 4H), 1.35–1.18 (m,
12H), 1.03 (t, J ¼ 7:3 Hz, 3H), 0.86 (br t, J ¼ 7:1 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 191.4, 166.1, 137.3,
133.1, 132.7, 130.7, 129.6 (2), 128.4 (2), 128.2 (2), 127.2
(2), 72.7, 42.7, 38,5, 34.5, 31.8, 29.5 (2), 29.4, 29.2, 28.4,
25.1, 22.6, 14.1; IR (CHCl3): 2957, 2928, 2856, 1711,
1659, 1601, 1581, 1450, 1315, 1277 cmꢁ1; MS (20 eV)
m=z: 440 (Mþ, 0.4), 318 (16), 302 (5), 285 (12), 213 (29),
197 (7), 180 (36), 157 (5), 122 (13), 105 (100), 82 (20), 68
(12), 57 (3); HRMS calcd for C27H36OS (Mþ): 440.2385,
found 440.2390. [99% ee, chiral HPLC analysis; DAI-
CEL CHIRALCEL OD (25 · 0.46); eluent: hexane/iso-
propanol ¼ 200/1; flow rate: 0.5 mL/min; Temp.: 28 ꢁC;
detector: 254 nm, (+): 12.6 min, ()): 14.8 min].
4.6.1. General procedure for benzoylation of 1,3-mercapto
alcohols. To a pyridine solution (3 mL) of anti-3
(0.70 mmol) was added benzoic anhydride (4.2 mmol)
and 4-dimethylaminopyridine (0.04 mmol), and the
reaction mixture was stirred at room temperature under
a nitrogen atmosphere for 2 h. The reaction mixture was
quenched with a sat. sodium hydrogen carbonate
aqueous solution, and the aqueous layer was extracted
with hexane. The organic layer was dried over sodium
sulfate, and concentrated in vacuo to give crude mate-
rial. Purification of the crude material by silica gel col-
umn chromatography (hexane/ethyl acetate ¼ 20:1) gave
benzoylated compounds 11.
4.6.1.1. (2S,4S)-2-Benzoylthiohex-4-yl benzoate 11d.
22
92% yield. Colorless oil; ½aꢀ ¼ +66.8 (c 1.14, CHCl3);
D
1H NMR (400 MHz, CDCl3): d 8.07–8.02 (m, 2H), 7.90–
7.86 (m, 2H), 7.58–7.50 (m, 2H), 7.43–7.36 (m, 4H),
5.30–5.21 (m, 1H), 3.95–3.84 (m, 1H), 2.11 (ddd, A part
of AB, JAB ¼ 14:5 Hz, J ¼ 7:9, 6.0 Hz, 1H), 2.06 (ddd, B
4.6.1.4. (2S,4S)-4-Benzoylthiohept-2-yl benzoate 11g.
26
D
96% yield. Colorless oil; ½aꢀ ¼ +74.3 (c 0.54, CHCl3);
1H NMR (400 MHz, CDCl3): d 8.06–8.02 (m, 2H), 7.91–
7.87 (m, 2H), 7.57–7.50 (m, 2H), 7.44–7.37 (m, 4H),

904
M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
5.34–5.28 (m, 1H), 3.96–3.88 (m, 1H), 2.21 (ddd, A part
of AB, JAB ¼ 14:5 Hz, J ¼ 8:8, 5.2 Hz, 1H), 1.96 (ddd, B
part of AB, JAB ¼ 14:5 Hz, J ¼ 9:0, 4.2 Hz, 1H), 1.79–
1.70 (m, 2H), 1.58–1.44 (m, 2H), 1.41 (d, J ¼ 6:2 Hz,
3H), 0.94 (t, J ¼ 7:3 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 191.4, 166.1, 137.2, 133.1, 132.7, 130.7, 129.5
(2), 128.5 (2), 128.2 (2), 127.2 (2), 69.4, 41.1, 40.9, 37.5,
20.4, 20.0, 13.8; IR (CHCl3): 3065, 2961, 2934, 2874,
1713, 1659, 1601, 1582, 1450, 1281 cmꢁ1; MS (70 eV)
m=z: 356 (Mþ, 0.6), 251 (2), 234 (20), 218 (9), 192 (16),
129 (30), 105 (100), 96 (10), 55 (4); HRMS calcd for
C21H24O3S (Mþ): 356.1446, found 356.1438. [99% ee,
chiral HPLC analysis; DAICEL CHIRALCEL OD
(25 · 0.46); eluent: hexane/isopropanol ¼ 50/1; flow rate:
0.1 mL/min; Temp.: 26 ꢁC; detector: 254 nm, (+):
48.0 min, ()): 50.9 min].
chromatography (hexane/ethyl acetate ¼ 15:1) gave 7 in
the yields shown in Table 3.
4.7.1.1. (1R,3S)-1-Methoxymethoxy-3-[(1S,2R,4R)-2-
hydroxybornane-10-sulfenyl]-1-phenylhexane 7j. Color-
26
D
less oil; ½aꢀ ¼ +71.6 (c 1.01, CHCl3); 1H NMR
(400 MHz, CDCl3): d 7.36–7.25 (m, 5H), 4.96 (dd,
J ¼ 9:9, 3.3 Hz, 1H), 4.55 (d,
A part of AB,
JAB ¼ 6:6 Hz, 1H), 4.52 (d, B part of AB, JAB ¼ 6:6 Hz,
1H), 3.95–3.92 (br m, 1H), 3.39 (s, 3H), 2.92–2.84 (m,
1H), 2.84 (d, J ¼ 2:9 Hz, 1H), 2.69 (d, A part of AB,
JAB ¼ 10:4 Hz, 1H), 2.54 (d,
B
part of AB,
JAB ¼ 10:4 Hz, 1H), 2.07 (ddd, J ¼ 14:8, 9.9, and 3.8 Hz,
1H), 1.83–1.42 (m, 10 H), 1.28–1.21 (m, 1H), 1.07 (s,
3H), 1.06–1.02 (m, 1H), 0.93 (t, J ¼ 7:3 Hz, 3H), 0.84 (s,
3H); 13C NMR (100 MHz, CDCl3): d 142.3, 128.5 (2),
127.6, 126.6 (2), 94.8, 76.7, 76.4, 56.0, 51.9, 47.6, 45.1,
43.3, 43.2, 39.0, 38.1, 31.0, 29.3, 27.2, 20.7, 20.0, 19.9
14.0; IR (CHCl3):3519, 3006, 2989, 2956, 2881, 1602,
1492, 1465, 1454, 1388, 1369, 1309, 1284, 1199, 1095,
1033, 914 cmꢁ1; MS (20 eV) m=z:406 (Mþ, 3), 343 (51),
326 (20), 223 (29), 158 (43), 129 (100), 105 (48), 91 (21),
77 (6); HRMS calcd for C24H38O3S (Mþ):406.2542,
found 406.2549.
4.6.1.5. (4S,6S)-4-Benzoylthiododec-6-yl benzoate 11h.
24
96% yield. Colorless oil; ½aꢀ ¼ +32.7 (c 0.61, CHCl3);
D
1H NMR (400 MHz, CDCl3): d 8.05–8.00 (m, 2H), 7.90–
7.85 (m, 2H), 7.56–7.49 (m, 2H), 7.44–7.36 (m, 4H),
5.33–5.25 (m, 1H), 3.92–3.82 (m, 1H), 2.14 (ddd, A part
of AB, JAB ¼ 14:4 Hz, J ¼ 8:6, 5.1 Hz, 1H), 2.00 (ddd, B
part of AB, JAB ¼ 14:4 Hz, J ¼ 9:0, 4.0 Hz, 1H), 1.80–
1.60 (m, 4H), 1.62–1.22 (m, 10H), 0.91 (t, J ¼ 7:3 Hz,
3H), 0.85 (br t, J ¼ 7:0 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 191.4, 166.1, 137.3, 133.1, 132.7, 130.7, 129.6
(2), 128.4 (2), 128.2 (2), 127.2 (2), 72.7, 41.0, 39.0, 37.6,
34.5, 31.7, 29.2, 25.1, 22.5, 20.0, 14.1, 13.8; IR
(CHCl3):2959, 2931, 2872, 2860, 1711, 1659, 1601, 1581,
1450, 1466, 1379, 1362, 1315, 1277, 1176, 1115 cmꢁ1; MS
(20 eV) m=z: 426 (Mþ, 0.4), 304 (13), 288 (5), 271 (10),
262 (8), 199 (31), 166 (30), 129 (8), 105 (100), 96 (13), 82
(10), 67 (7), 55 (3); HRMS calcd for C26H34O3S (Mþ):
426.2229, found 426.2236. [99% ee, chiral HPLC anal-
ysis; DAICEL CHIRALCEL OD (25 · 0.46); eluent:
hexane/isopropanol ¼ 200/1; flow rate: 0.5 mL/min;
Temp.: 27 ꢁC; detector: 254 nm, (+): 12.0 min, ()):
13.8 min].
4.7.1.2. (1R,3R)-1-Methoxymethoxy-3-[(1S,2R,4R)-2-
hydroxybornane-10-sulfenyl]-1,3-diphenylpropane
7m.
23
D
1
Colorless oil; ½aꢀ ¼ +128.3 (c 1.26, CHCl3); H NMR
(400 MHz, CDCl3): d 7.37–7.22 (m, 10H), 4.84 (dd,
J ¼ 8:9, 4.8 Hz, 1H), 4.55 (d,
A part of AB,
JAB ¼ 6:6 Hz, 1H), 4.52 (d, B part of AB, JAB ¼ 6:6 Hz,
1H), 3.92 (dd, J ¼ 9:5, 5.5 Hz, 1H), 3.86–3.83 (br m,
1H), 3.39 (s, 3H), 2.56 (d, A part of AB, JAB ¼ 10:8 Hz,
1H), 2.51 (d, J ¼ 2:9 Hz, 1H), 2.36 (ddd, A part of AB,
JAB ¼ 14:3 Hz, J ¼ 8:9, 5.5 Hz, 1H), 2.23 (d, B part of
AB, JAB ¼ 10:8 Hz, 1H), 2.14 (ddd, B part of AB,
JAB ¼ 14:3 Hz, J ¼ 9:5, 4.8 Hz, 1H), 1.77–1.56 (m, 4H),
1.33–1.26 (m, 1H), 1.15–1.08 (m, 1H), 1.02–0.95 (m,
1H), 0.97 (s, 3H), 0.68 (s, 3H); IR (CHCl3): 3529, 3028,
3012, 2954, 2823, 1600, 1492, 1454, 1369 cmꢁ1; MS
(70 eV) m=z: 440 (Mþ, 1), 422 (2), 360 (14), 275 (8), 222
(21), 192 (49), 165 (13), 134 (73), 105 (100), 91 (39), 77
(41); HRMS calcd for C27H36O3S (Mþ): 440.2385, found
440.2382.
4.7. A typical procedure for conversion of sulfides anti-4
into vinyl sulfides 9 through a Wagner–Meerwein rear-
rangement under basic conditions
To a solution of anti-4 (1.4 mmol) in tetrahydrofuran
(5 mL) was added N,N-diisopropylethylamine (41 mmol)
and chloromethyl methyl ether (14 mmol). The reaction
mixture was refluxed for 5 h under a nitrogen atmo-
sphere. The mixture was poured into water, and neu-
tralized with 1 M HCl, and extracted with ethyl acetate.
The combined organic layer was washed with brine, and
dried over magnesium sulfate, filtered, and concentrated
in vacuo to give a crude material. Subsequently, to a
suspension of lithium aluminum hydride (1.0 mmol) in
tetrahydrofuran (2 mL) was added dropwise a solution
of the above crude material in tetrahydrofuran (6 mL) at
0 ꢁC, and the reaction mixture stirred for 2 h at room
temperature under a nitrogen atmosphere. The reaction
mixture was diluted diethyl ether, and quenched with
sat. sodium sulfate aqueous solution at 0 ꢁC, and then
dried over magnesium sulfate, and filtrated, concen-
trated in vacuo to give a crude diol derivative. Purifi-
cation of the residue by silica gel column
To a solution of 7 (0.4 mmol) and N,N-diisopropyleth-
ylamine (10.6 mmol) in dichloromethane (3 mL) was
added
a
solution of methanesulfonic anhydride
(3.5 mmol) in dichloromethane (2 mL) at )10 ꢁC. The
reaction mixture was stirred for 15 min at )10 ꢁC. It was
then poured into water, and neutralized with 1 M HCl,
and extracted with ethyl acetate. The combined organic
layers were washed with brine, and dried over magne-
sium sulfate, filtered, and concentrated in vacuo. Puri-
fication of the residue by silica gel column
chromatography (hexane/ethyl acetate ¼ 100:1) gave
9j,m in the yields shown in Table 3.
4.7.2.1. (1R,4S)-3-[(1R,3S)-1-Methoxymethoxy-1-phe-
nylhexylsulfanylmethylene]-2,2-dimethyl-bicyclo[2.2.1]-
1
heptane 9j. Colorless oil; H NMR (300 MHz, CDCl3) d
7.36–7.23 (m, 5H), 5.60 (s, 0.09H), 5.39 (s, 0.91H), 4.93
(dd, J ¼ 9:6, 3.9 Hz, 1H), 4.55 (d, A part of AB,

M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
905
JAB ¼ 6:7 Hz, 1H), 4.54 (d, B part of AB, JAB ¼ 6:7 Hz,
1H), 3.36 (s, 3H), 3.15 (br, 1H), 2.40–2.80 (m, 1H), 2.07–
1.98 (m, 1H), 1.92 (br d, J ¼ 2:4 Hz, 1H), 1.80–1.35 (m,
8H), 1.28–1.13 (m, 3H), 1.03 (s, 3H), 1.01 (s, 3H), 0.93–
0.88 (m, 3H); IR (CHCl3): 2958, 2893, 2871, 1602, 1492,
1456, 1382, 1361, 1097, 1033 cmꢁ1; MS (70 eV) m=z: 388
(Mþ, 52), 343 (14), 223 (42), 136 (77), 117 (43), 105
(100), 91 (68), 77 (23), 55 (32); HRMS calcd for
C24H36O2S (Mþ): 388.2436, found 388.2430.
4.8.2. (1R,3R)-S-(3-Methoxymethoxy-1,3-diphenylpropyl)
23
thioformate 10m. Colorless oil; ½aꢀ ¼ +219.0 (c 0.32,
D
CHCl3); 1H NMR (400 MHz, CDCl3): d 10.10 (d,
J ¼ 0:8 Hz, 1H), 7.37–7.23 (m, 10H), 4.95 (dd, J ¼ 9:6,
6.0 Hz, 1H), 4.62 (dd, J ¼ 8:8, 4.9 Hz, 1H), 4.49 (s, 2H),
3.31 (s, 3H), 2.49 (dddd, A part of AB, JAB ¼ 14:5 Hz,
J ¼ 8:8, 6.0, and 0.8 Hz, 1H), 2.28 (ddd, B part of AB,
JAB ¼ 14:5 Hz, J ¼ 9:5, 4.9 Hz, 1H); IR (CHCl3): 3004,
2950, 2827, 1670, 1600, 1492, 1454, 1346 cmꢁ1; MS
(20 eV) m=z: 316 (Mþ, 0.2), 271 (11), 225 (28), 209 (19),
193 (28), 151 (100), 105 (86), 77 (8); HRMS calcd for
C18H20O3S (Mþ): 316.1133, found 316.1112.
4.7.2.2. (1R,4S)-3-[(1R,3R)-3-Methoxymethoxy-1,3-
diphenylpropylsulfanylmethylene]-2,2-dimethyl-bicy-
clo[2.2.1]heptane 9m. Colorless oil; 1H NMR (300 MHz,
CDCl3): d 7.36–7.17 (m, 10.0H), 5.42 (s, 0.1H), 5.21 (s,
0.9H), 4.78–4.66 (m, 1.0H), 4.54–4.48 (m, 2.0H), 3.87
(dd, J ¼ 8:2, 6.9 Hz, 0.9H), 3.75 (dd, J ¼ 8:2, 6.9 Hz,
0.1H), 3.34 (s, 2.7H), 3.33 (s, 0.3H), 3.01 (d, J ¼ 3:4 Hz,
0.9H), 2.56–2.12 (m, 2.2H), 1.85–1.80 (m, 0.9H), 1.62–
1.45 (m, 3.0H), 1.35–1.26 (m, 1.0H), 1.18–0.76 (m,
2.0H), 0.93 (s, 2.7H), 0.88 (s, 2.7H), 0.79 (s, 0.3H), 0.77
(s, 0.3H); IR (CHCl3): 3028, 2954, 2889, 2823, 1600,
1492, 1454, 1380, 1361 cmꢁ1; MS (70 eV) m=z: 422 (Mþ,
32), 360 (25), 345 (11), 212 (38), 193 (35), 151 (100), 134
(42), 121 (54), 105 (83), 91 (54), 77 (35); HRMS calcd for
C27H34O2S (Mþ): 422.2279, found 422.2281.
4.9. A typical procedure for hydrolysis of thioformate 10
to 1,3-mercapto alcohols anti-3
A solution of 10 (0.21 mmol) in methanol (5 mL) was
adjusted to pH 1 with concd HCl, and stirred at 55 ꢁC
overnight. The mixture was neutralized with sat. sodium
hydrogen carbonate aqueous solution and the solvent
removed in vacuo. Water was added to this residue, and
extracted with ethyl acetate. The combined organic layer
was washed with brine, dried over magnesium sulfate,
filtered, and concentrated in vacuo. Purification of the
residue by silica gel column chromatography (hexane/
ethyl acetate ¼ 7:1) gave anti-3 in the yields shown in
Scheme 3.
4.8. A typical procedure for conversion of vinyl sulfides 9
into thioformate 10 by ozonolysis
A solution of 9 (0.04 mmol) in dichloromethane (15 mL)
was bubbled through with ozone until the solution was
changed blue at )78 ꢁC. The reaction mixture was then
stirred at )78 ꢁC for 30 min. After 30 min, ozone was
displaced with oxygen, followed by nitrogen. The reac-
tion mixture was added dropwise to a solution of tri-
phenylphosphine (0.13 mmol) in dichloromethane
(1 mL) at )78 ꢁC, with the resulting mixture then stirred
for 1 h at )78 ꢁC. After 1 h, the reaction mixture was
allowed to warm to room temperature, and stirred
overnight. The reaction mixture was concentrated in
vacuo to give a crude material. The crude material was
purified by preparative TLC (hexane/ethyl acetate ¼ 5:1)
to give 10 in the yields shown in Scheme 1.
4.9.1. (1R,3S)-3-Mercapto-1-phenyl-1-hexanol anti-3j.
Colorless oil; ½aꢀ ¼ +45.2 (c 1.53, CHCl3); H NMR
23
D
1
(400 MHz, CDCl3): d 7.39–7.25 (m, 5H), 5.06 (dd,
J ¼ 10:1, 2.9 Hz, 1H), 3.15–3.06 (m, 1H), 2.13 (br s, 1H),
2.09 (ddd, A part of AB, JAB ¼ 14:3 Hz, J ¼ 10:1,
3.5 Hz, 1H), 1.69–1.38 (m, 4H), 1.67 (ddd, B part of AB,
JAB ¼ 14:3 Hz, J ¼ 10:7, 2.9 Hz, 1H), 1.43 (d,
J ¼ 7:7 Hz, 1H), 0.91 (t, J ¼ 7:1 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 144.8, 128.5 (2), 127.5, 125.6 (2),
71.8, 48.3, 41.9, 37.6, 20.1, 13.7; IR (CHCl3): 3600, 3008,
2960, 2933, 2910, 2873, 1602, 1492, 1465, 1456, 1436,
1309, 1280, 1002 cmꢁ1; MS (70 eV) m=z: 210 (Mþ, 6), 208
(10), 192 (48), 176 (21), 159 (100), 145 (26), 129 (36), 117
(85), 105 (71), 91 (20), 55 (9); HRMS calcd for C12H18OS
(Mþ): 210.1078, found 210.1076. [99% ee, chiral HPLC
analysis; DAICEL CHIRALCEL OD (25 · 0.46); elu-
ent: hexane/isopropanol ¼ 50/1; flow rate: 1.0 mL/min;
Temp.: 26 ꢁC; detector: 254 nm, (+): 16.1 min, ()):
18.8 min].
4.8.1. (1R,3S)-S-(3-Methoxymethoxy-1-phenylhexyl) thio-
21
formate 10j. Colorless oil; ½aꢀ ¼ +77.5 (c 1.14, CHCl3);
D
1H NMR (400 MHz, CDCl3): d 10.18 (s, 1H), 7.36–7.25
(m, 5H), 4.71 (dd, J ¼ 10:3, 2.9 Hz, 1H), 4.51 (d, A part
of AB, JAB ¼ 3:4 Hz, 1H), 4.50 (d, B part of AB,
JAB ¼ 3:4 Hz, 1H), 4.02 (dddd, J ¼ 10:6, 7.3, 5.8, and
3.6 Hz, 1H), 3.32 (s, 3H), 2.16 (dddd, A part of AB,
JAB ¼ 14:9 Hz, J ¼ 10:3, 3.6, and 1.1 Hz, 1H), 1.81 (ddd,
B part of AB, JAB ¼ 14:9 Hz, J ¼ 10:6, 2.9 Hz, 1H),
1.71–1.58 (m, 2H), 1.50–1.36 (m, 2H), 0.92 (t,
J ¼ 7:3 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 187.9,
141.7, 128.5 (2), 127.8, 126.6 (2), 94.6, 75.7, 56.1, 43.0,
39.8, 38.4, 19.8, 13.8; IR (CHCl3): 3009, 2960, 2933,
2893, 2875, 2844, 2827, 1666, 1602, 1492, 1465, 1456,
1348, 1149, 1095, 1033, 1024, 916 cmꢁ1; MS FAB(+)
m=z: 305 (Mþ+Na, 36); HRMS calcd for C15H22O3SNa
(Mþ+Na): 305.1187, found 305.1191.
4.9.2. (1R,3R)-3-Mercapto-1,3-diphenyl-1-propanol anti-
3m.
25
D
1
Colorless oil; ½aꢀ ¼ +105.7 (c 0.77, CHCl3); H
NMR (400 MHz, CDCl3): d 7.38–7.21 (m, 10H), 4.90–
4.86 (br m, 1H), 4.18 (ddd, J ¼ 9:4, 6.1, and 5.8 Hz, 1H),
2.40 (ddd, A part of AB, JAB ¼ 14:2 Hz, J ¼ 8:8, 5.8 Hz,
1H), 2.21 (ddd, B part of AB, JAB ¼ 14:2 Hz, J ¼ 9:4,
4.7 Hz, 1H), 2.03 (br s, 1H), 1.97 (d, J ¼ 6:1 Hz, 1H);
13C NMR (100 MHz, CDCl3): d 144.7, 143.9, 128.8 (2),
128.6 (2), 127.9, 127.3, 126.8 (2), 125.9 (2), 72.2, 48.3,
40.6; IR (CHCl3): 3602, 3064, 3035, 3006, 1602, 1494,
1454, 1053 cmꢁ1; MS (70 eV) m=z: 244 (Mþ, 2), 226 (15),
210 (69), 122 (27), 105 (96), 104 (100), 91 (16), 51 (29);

906
M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
HRMS calcd for C15H16OS (Mþ): 244.0922, found
244.0924. [99% ee, chiral HPLC analysis; DAICEL
CHIRALCEL OD (25 · 0.46); eluent: hexane/isopropa-
nol ¼ 50/1; flow rate: 1.0 mL/min; Temp.: 25 ꢁC; detec-
tor: 254 nm, ()): 32.4 min, (+):37.8 min].
from syn-4j by the same method were identical to 12j
and 13j, respectively. Consequently, the absolute con-
figuration of the minor isomer syn-4j was determined.
4.12.1. A typical procedure for conversion into homoal-
lylic alcohol 12j and allylic alcohol 13j from 4j.
To a
4.10. A procedure for the conversion of vinyl sulfide 9m
into 1,3-mercapto alcohol anti-3m using an n-Bu2BOTf/
Dod-SH system
solution of anti- (or syn-) 4j (0.44 mmol) in methanol
(10 mL) was added sodium periodate (0.67 mmol), and
stirred at room temperature overnight. The reaction
mixture was filtered, and the solvent removed in vacuo.
The residue was added water, and extracted with ethyl
acetate. The combined organic layers were washed with
brine, dried over magnesium sulfate, filtered, and con-
centrated in vacuo. Purification of the residue by silica
gel column chromatography (hexane/ethyl acetate ¼ 1:1)
gave a sulfoxide (quantitative yield). Subsequently, to a
solution of this sulfoxide (0.44 mmol) in toluene (20 mL)
was added calcium carbonate (1.09 mmol), and refluxed
overnight. The reaction mixture was filtered, and the
solvent removed in vacuo to give a crude product. The
crude product was then purified with silica gel column
chromatography (hexane/ethyl acetate ¼ 8:1) to give a
mixture of 12j and 13j (70–82%, 12j:13j@1:1). The mix-
ture of 12j and 13j was separated into each compound
by HPLC.
To a solution of 9m (13 mg, 0.03 mmol) and Dod-SH
(71 lL, 0.30 mmol) in dichloromethane (1 mL) was
added dropwise dibutylboron triflate (1.0 M dichloro-
methane, 30 lL, 0.03 mmol) at )30 ꢁC. The reaction
mixture was stirred at )30 ꢁC for 1.5 h under a nitrogen
atmosphere. After 1.5 h, the reaction mixture was
allowed to warm to room temperature, and stirred at
room temperature for 3.5 h. The reaction mixture was
poured into water and then extracted with ethyl acetate.
The combined organic layer was washed with brine,
dried over magnesium sulfate, filtered, and concentrated
in vacuo. Purification of the residue by preparative TLC
(hexane/ethyl acetate ¼ 5:1) gave the title compound
(anti-3m) (5 mg, 68%).
4.11. Determination of the absolute configuration of major
isomer anti-4
4.12.1.1. (3E,1R)-1-Phenylhex-3-en-1-ol 12j. Colorless
22
D
1
oil; ½aꢀ ¼ +66.5 (c 0.74, CHCl3); H NMR (400 MHz,
Previously, we determined the absolute configuration of
the major isomer by the following procedure. A com-
pound anti-4a was converted into crystalline sulfone by
oxidation using Oxoneꢂ. The absolute configuration of
this sulfone was determined by X-ray crystallographic
analysis.4a;b
CDCl3): d 7.37–7.26 (m, 5H), 5.67–5.59 (m, 1H), 5.44–
5.36 (m, 1H), 4.68 (br dd, J ¼ 7:0, 5.4 Hz, 1H), 2.51–
2.35 (m, 2H), 2.08 (br, 1H), 2.04 (quintet, J ¼ 7:5 Hz,
2H), 0.98 (t, J ¼ 7:5 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 144.0, 136.7, 128.3 (2), 127.3, 125.8 (2), 124.4,
73.4, 42.8, 25.6, 13.7; IR (CHCl3): 3602, 3006, 2966,
2933, 2873, 2850, 1602, 1494, 1454, 1436, 1382,
1315 cmꢁ1; MS FAB(+) m=z: 199 (Mþ+Na, 27); HRMS
calcd for C12H16ONa (Mþ+Na): 199.1099, found
199.1102.
4.12. Determination of the absolute configuration of minor
isomer syn-4
Each of the diastereomers anti-4j and syn-4j were sepa-
rated by HPLC. Absolute configuration of the minor
isomer was determined by the following sequence
(Scheme 4). Compound anti-4j was oxidized to the
sulfoxide, and the sulfoxide subsequently converted into
the homoallylic alcohol 12j (known compound8) and
allylic alcohol 13j. Compounds 12j0 and 13j0 obtained
4.12.1.2. (3E,1R)-1-Phenylhex-3-en-1-ol 12j0. Color-
25
D
less oil; ½aꢀ ¼ +65.9 (c 0.36, CHCl3); 1H NMR
(400 MHz, CDCl3): d 7.37–7.24 (m, 5H), 5.69–5.59 (m,
1H), 5.45–5.36 (m, 1H), 4.68 (ddd, J ¼ 8:0, 4.6, and
2.2 Hz, 1H), 2.51–2.36 (m, 2H), 2.07 (br, 1H), 2.04
(quintet, J ¼ 7:5 Hz, 2H), 0.98 (t, J ¼ 7:5 Hz, 3H); 13C
NMR (100 MHz, CDCl3): d 144.0, 136.8, 128.3 (2),
OH
Ph
12j; [α]D22 = +66.5
12j'; [α]D25 = +65.9
1) NaIO4
MeOH, rt
1) NaIO4
MeOH, rt
O
O
S
S
OH
OH
+
2) CaCO3
toluene, reflux
82%
2) CaCO3
toluene, reflux
78%
OH
Ph
Ph
Ph
13j; [α]D25 = -33.7
13j'; [α]D24 = -33.6
anti-4j
syn-4j
(12 : 13 ≅ 1 : 1)
Scheme 4.

M. Ozeki et al. / Tetrahedron: Asymmetry 15 (2004) 895–907
907
Eliel, E. L. J. Am. Chem. Soc. 1984, 106, 2943–2948; (d)
Eliel, E. L.; Lynch, J. E.; Kume, F.; Frye, S. V. Org. Syn.
1987, 65, 215–223; (e) Utimoto, K.; Nakamura, A.;
Matsubara, S. J. Am. Chem. Soc. 1990, 112, 8189–8190;
(f) Utimoto, K.; Kodama, T.; Matsubara, S. Synlett 1995,
501–502; (g) Nakano, H.; Okuyama, Y.; Hongo, H.
Tetrahedron Lett. 2000, 41, 4615–4618; (h) Matsubara, S.;
Kasuga, Y.; Yasui, T.; Yoshioka, M.; Yamin, B.; Utimoto,
K.; Oshima, K. Chirality 2003, 15, 38–40; (i) Aggarwal, V.
K.; Ford, J. G.; Fonquerna, S.; Adams, H.; Jones, R. V. H.;
Fieldhouse, R. J. Am. Chem. Soc. 1998, 120, 8328–8339; (j)
Aggarwal, V. K.; Lattanzi, A.; Fuentes, D. Chem. Commun.
2002, 2534–2535, also see references cited therein.
2. Shiraki, H.; Nishide, K.; Node, M. Tetrahedron Lett. 2000,
41, 3437–3441.
127.4, 125.8 (2), 124.4, 73.4, 42.8, 25.6, 13.7; IR
(CHCl3): 3600, 3006, 2966, 2933, 2873, 2850, 1602, 1494,
1454, 1434, 1382, 1315 cmꢁ1; MS FAB(+) m=z: 199
(Mþ+Na, 21); HRMS calcd for C12H16ONa (Mþ+Na):
199.1099, found 199.1103.
4.12.1.3. (2E,1R)-1-Phenylhex-2-en-1-ol 13j. Colorless
25
D
1
oil; ½aꢀ ¼ )33.7 (c 0.84, CHCl3); H NMR (400 MHz,
CDCl3): d 7.39–7.25 (m, 5H), 5.76 (dt, J ¼ 15:2, 6.4 Hz,
1H), 5.66 (ddt, J ¼ 15:2, 6.6, and 1.1 Hz, 1H), 5.16 (d,
J ¼ 6:6 Hz, 1H), 2.03 (br q, J ¼ 7:2 Hz, 2H), 1.91 (br,
1H), 1.42 (sextet, J ¼ 7:5 Hz, 2H), 0.90 (t, J ¼ 7:5 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 143.4, 132.6, 132.4,
128.4 (2), 127.5, 126.1 (2), 75.2, 34.2, 22.2, 13.7; IR
(CHCl3): 3600, 3006, 2962, 2931, 2873, 1666, 1602, 1492,
1454, 1379, 968 cmꢁ1; MS (20 eV) m=z: 176 (Mþ, 23), 158
(42), 133 (86), 129 (100), 105 (26), 91 (11), 55 (16); HRMS
calcd for C12H16O (Mþ): 176.1201, found 176.1204.
3. The stereochemistry of 3 should be corrected with syn-3 on
the description in the communication (Ref. 2).
4. (a) Nishide, K.; Shigeta, Y.; Obata, K.; Node, M. J. Am.
Chem. Soc. 1996, 118, 13103–13104; (b) Node, M.; Nishide,
K.; Shigeta, Y.; Shiraki, H.; Obata, K. J. Am. Chem. Soc.
2000, 122, 1927–1936; (c) Nishide, K.; Ozeki, M.; Kunish-
ige, H.; Shigeta, Y.; Patra, P. K.; Hagimoto, Y.; Node, M.
Angew. Chem., Int. Ed. 2003, 42, 4515–4517.
5. Nishide, K.; Ohsugi, S.; Shiraki, H.; Tamakita, H.; Node,
M. Org. Lett. 2001, 3, 3121–3124.
6. Node, M.; Kumar, K.; Nishide, K.; Ohsugi, S.; Miyamoto,
T. Tetrahedron Lett. 2001, 42, 9207–9210.
7. (a) Garcia Martinez, A.; Teso Vilar, E.; Osio Barcina, J.;
Rodriguez Herrero, M. E.; de la Moya Cerero, S.; Hanack,
M.; Subramanian, L. R. Tetrahedron: Asymmetry 1993, 4,
2333–2334; (b) Garcia Martinez, A.; Teso Vilar, E.; Garcia
Fraile, A.; de la Moya Cerero, S.; Gonzalez-Fleitas de
Diego, J. M.; Subramanian, L. R. Tetrahedron: Asymmetry
1994, 5, 1599–1603; (c) Garcia Martinez, A.; Teso Vilar, E.;
Garcia Fraile, A.; de la Moya Cerero, S.; Martinez Ruiz, P.;
Garcia Alvarez, P. P. Tetrahedron: Asymmetry 1994, 8, 849–
852; (d) Lora Maroto, B.; de la Moya Cerero, S.; Garcia
Martinez, A.; Garcia Fraile, A.; Teso Vilar, E. Tetrahedron:
Asymmetry 2000, 11, 3059–3062.
4.12.1.4. (2E,1R)-1-phenylhex-2-en-1-ol 13j0. Colorless
24
D
1
oil; ½aꢀ ¼ )33.6 (c 0.60, CHCl3); H NMR (400 MHz,
CDCl3): d 7.39–7.25 (m, 5H), 5.76 (dt, J ¼ 15:2, 6.4 Hz,
1H), 5.66 (ddt, J ¼ 15:2, 6.6, and 1.1 Hz, 1H), 5.16 (d,
J ¼ 6:6 Hz, 1H), 2.03 (br q, J ¼ 7:2 Hz, 2H), 1.93 (br,
1H), 1.42 (sextet, J ¼ 7:5 Hz, 2H), 0.90 (t, J ¼ 7:3 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 143.4, 132.6, 132.4,
128.4 (2), 127.4, 126.1 (2), 75.2, 34.2, 22.2, 13.7; IR
(CHCl3): 3600, 3006, 2962, 2931, 2873, 1666, 1602, 1492,
1454, 1379, 968 cmꢁ1; MS (20 eV) m=z: 176 (Mþ, 18), 158
(40), 133 (73), 129 (100), 105 (24), 91 (8), 55 (14); HRMS
calcd for C12H16O (Mþ): 176.1201, found 176.1193.
References and notes
1. (a) Eliel, E. L.; Frazee, W. J. J. Org. Chem. 1979, 44, 3598–
3599; (b) Eliel, E. L.; Lynch, J. E.; Kenan, W. R., Jr.
Tetrahedron Lett. 1981, 22, 2855–2858; (c) Lynch, J. E.;
8. Nokami, J.; Nomiyama, K.; Matsuda, S.; Imai, N.;
Kataoka, K. Angew. Chem., Int. Ed. 2003, 42, 1273–
1276.