Synthesis of chiral vinylic sulfoxides by Pd-catalyzed asymmetric sulfinylzincation

Article abstract of DOI:10.1016/j.tet.2003.10.037

Novel asymmetric sulfinylzincation of alkynoates has been accomplished via a Pd-catalyzed sulfinylzincation using 1-alkynyl sulfoxides bearing chiral auxiliaries as a sulfinylating reagent. The reaction proceeded in a highly syn-selective fashion, giving

Full text of DOI:10.1016/j.tet.2003.10.037

Tetrahedron 59 (2003) 9895–9906
Synthesis of chiral vinylic sulfoxides by Pd-catalyzed
asymmetric sulfinylzincation
a
a
b
a
,
Naoyoshi Maezaki,a Suguru Yagi, Shizuka Ohsawa, Hirofumi Ohishi and Tetsuaki Tanaka
,
*
*
aGraduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
bOsaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
Received 7 July 2003; revised 12 October 2003; accepted 14 October 2003
Abstract—Novel asymmetric sulfinylzincation of alkynoates has been accomplished via a Pd-catalyzed sulfinylzincation using 1-alkynyl
sulfoxides bearing chiral auxiliaries as a sulfinylating reagent. The reaction proceeded in a highly syn-selective fashion, giving the (E)-b-
sulfinyl a,b-unsaturated ester exclusively. Among the chiral sulfinylating reagents tested, an isoborneol-type compound (Rs)-4 showed the
best results in terms of both yield and diastereoselectivity. As a result of optimization of the reaction, the selectivity was improved up to 92:8
dr, and stereochemistry of the newly formed sulfur stereogenic center was revealed as (Ss)-configuration.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
The synthesis of chiral sulfoxides has been extensively
studied due to its high ability of asymmetric induction.
Several methods are presently available for the synthesis of
optically active sulfoxides. Representative methods are (1)
optical resolution of racemic sulfoxides, (2) asymmetic
oxidation of sulfides, (3) nucleophilic substitution on chiral
sulfur derivatives.1 Addition of sulfenic acid to an
unsaturated bond affords an alternative option. Aversa and
co-workers reported an asymmetric addition of a sulfenic
acid to unsaturated bonds.2 However, the stereoselectivity
of sulfinylation was not sufficiently high. The asymmetric
addition of a chiral sulfenic anion has not hitherto been
investigated, to the best of our knowledge.3 We have
recently found that unusual sulfinylation proceeds on
treatment of 1-alkynyl sulfoxides with a Pd(0)-catalyst
and Et2Zn, wherein a sulfinylzinc (or zinc sulfenate) species
is assumed to be generated via oxidative addition of the
1-alkynyl sulfoxide to the Pd(0)-catalyst followed by
transmetalation with Et2Zn (Scheme 1).4 This methodology
allows easy introduction of a sulfinyl group into activated
alkynes in a highly syn-selective manner, thereby enabling a
compensative procedure against an anti-selective conjugate
addition of thiolate followed by oxidation to sulfoxide.5
Scheme 1.
rapid sulfinyl-sulfenate tautomerization. We assumed that
the chiral sulfoxides could be synthesized by employing the
sulfenate (sulfinyl) anion with a chiral substitutent (R p) as
shown in Scheme 2.
Scheme 2.
To confirm our working hypothesis to develop a novel
asymmetric reaction, we designed four kinds of chiral
1-alkynyl sulfoxides 1–4 bearing various chiral auxiliaries
(Fig. 1).
In this research, we found that the chirality on the sulfur
atom was lost during the reaction presumably as a result of
Keywords: sulfoxides; asymmetric reaction; palladium catalyst;
sulfinylzincation.
*
Corresponding authors. Tel.: þ81-6-6879-8213; fax: þ81-6-6879-8214;
*
e-mail: maezaki@phs.osaka-u.ac.jp; Tel.: þ81-6-6879-8210; fax: þ81-
6-6879-8214; e-mail: t-tanaka@phs.osaka-u.ac.jp
Figure 1. Structure of chiral sulfinylating reagents.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.10.037

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N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
In this paper, we report the full details of asymmetric
sulfinylzincation using these 1-alkynyl sulfoxides.6
2. Results and discussion
2.1. Preparation of chiral 1-alkynyl sulfoxides
The 1-alkynyl sulfoxide 1 having a stereogenic center
adjacent to the sulfoxide was synthesized starting from
known hydroxylated thiol 5 prepared from ethyl (R)-
mandelate according to the procedure described in the
literature (Scheme 3).7 After conversion of 5 into disulfide 6
with NaIO3 and moist aluminum,8 lithium acetylide
generated from 3,3-dimethylbutyne was reacted with 6 in
the presence of HMPA, giving sulfide 7 in 96% in two steps.
Methylation of the primary alcohol (NaH, MeI) to give 8
followed by m-CPBA oxidation of the sulfide furnished the
sulfoxide 1 as a 57:43 diastereomeric mixture in 76% yield
in two steps.
Scheme 5.
Scheme 6.
changing the procedure as depicted in Scheme 7. The
hydroxylated disulfide 18 was methylated (MeI, KOH) in
62% yield. The resulting disulfide 21 was transformed into a
methyl sulfinate by the reaction with SO2Cl2 in AcOH
followed by methanolysis in pyridine,12 giving 22 as a 5:1
diastereomeric mixture in 54% yield in two steps.13 Finally,
the mixture was treated with 3,3-dimethyl-1-butynyl-
magnesium bromide to give the alkynylsulfoxide (Ss)-4 in
45% yield along with 9% of (Rs)-4.
Scheme 3.
On the other hand, the substrate 2 bearing a stereogenic
center at the b-position of the sulfoxide was synthesized as a
52:48 diastereomeric mixture from known hydroxylated
thiol 97 following the same procedure for 1 (Scheme 4).
Scheme 7.
Scheme 4.
These two procedures shown in Schemes 6 and 7 afforded
the 1-alkynyl sulfoxides with an opposite configuration. The
absolute configuration on the sulfur atom in (Rs)- and (Ss)-4
was assumed by an empirical rule reported by Goodridge
and co-workers.10 They reported that the signal for the H4-
proton in (Rs)-isomers of 3-exo-(alkylsulfinyl)isoborneols
appears at lower field than that of the corresponding (Ss)-
isomers due to anisotropic effect of the SvO bond to the
H4-proton in the (Rs)-isomer.14 Since the stereochemistry
on the sulfoxides in the 3-exo-(alkynylsulfinyl)isoborneol
derivatives is opposite to that in the 3-exo-(alkylsulfinyl)-
isoborneols due to the change of priority groups, the isomers
having the H4-proton at 2.34 and 2.08 ppm were assigned as
(Ss)- and (Rs)-isomers, respectively.
The 1-alkynyl sulfoxides 3 and 4 with the conformationally
restricted chiral auxiliaries were also prepared from the
known mercaptoisoborneol derivatives 139 and 17.10 Thus,
the 1-alkynyl sulfoxide 3 was obtained as a 72:28
diastereomeric mixture by the same method described for
the 1-alkynyl sulfoxide 1 (Scheme 5).
The 1-alkynyl sulfoxide (Rs)-4 was selectively synthesized
by m-CPBA oxidation of alcohol 19 followed by methyl-
ation of the hydroxy group (Scheme 6).11
The diastereomeric (Ss)-4 was also synthesized mainly by

N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
9897
2.2. Asymmetric sulfinylzincation
dioxane using the 1-alkynylsulfoxide (Rs)-4 as a sulfinyl
source. The results are summarized in Table 3.
Asymmetric sulfinylzincation using these 1-alkynyl
sulfoxides 1–4 was applied to the alkynoate, and the results
are summarized in Table 1. A mixture of (R)- and (S)-
sulfoxides was used in the reactions except for entry 4.
Upon treatment of the 1-alkynyl sulfoxides with 2 mol% of
Pd2(dba)3·CHCl3 and Et2Zn in the presence of a
g-functionalized alkynoate, sulfinylzincation proceeded to
give the sulfinylated adducts in moderate yields after
protonation of the resulting b-sulfinylic vinyl anion. The
position of the stereogenic center in the chiral auxiliary
considerably affected the diastereoselectivity. Thus, dia-
stereoselectivity was markedly reduced in the substrates 2
and 3 bearing a stereogenic center far from the sulfoxide
(entries 2 and 3). On the other hand, 1-alkynyl sulfoxides 1
and 4 with a stereogenic center adjacent to the sulfoxide
showed better selectivity. We selected compound (Rs)-4 for
the further study owing to the higher yield and cheapness of
the material.
Table 3. Sulfinylzincation of various alkynoates with (Rs)-4
Entry
R
R0
Product
Yiled (%)
dra
1
2
3
4
5
6
7
8
BnOCH2
AcOCH2
TBSOCH2 Me
BnSCH2
H
Me
Me
BnOCH2
Me
Me
(E,Ss)-26a
26b
26c
26d
26e
99
51
98
100
30
100
82
91:9
92:8b
90:10
Me
Me
Et
91:9b
85:15b,c
90:10b,c
91:9b,c,d
86:14
26f
26f
Et
4-O2NC6H4CH2 26g
72
The reactions were carried out with alkynoate (3 equiv.), Et2Zn (2 equiv.),
and Pd2(dba)3·CHCl3 (2 mol%) in 1,4-dioxane overnight under Ar unless
otherwise stated.
Table 1. Influence of structure of chiral auxiliaries
a
Determined by 1H NMR spectroscopic data.
b
Diastereomeric isomers were inseparable.
10 equiv. of alkynoates were used.
1 equiv. of Et2Zn was used.
c
d
Upon treatment of (Rs)-4 with 3 equiv. of alkynoate and
2 equiv. of Et2Zn and 2 mol% of Pd2(dba)3·CHCl3, the
sulfinylzincation proceeded in good yields in the presence of
various functional group, except that the b-unsubstituted
alkynoate afforded the product in poor yield (entry 5). By
use of one equivalent of Et2Zn, the yield was reduced
(entries 6 and 7). Interestingly, the chirality on the sulfur
atom was reversed during the reactions. The vinylic
sulfoxides with an (S)-sulfoxide were obtained preferen-
tially with ca. 9:1 dr, except that 26e and 26g exhibited
reduced selectivity (ca. 6:1 dr). The selectivity was not
affected even if the (Ss)-isomer of 4 was used, although the
yield was slightly reduced (Scheme 8). The results support
the speculation that the reaction proceeds via the same zinc
sulfenate (or sulfinylzinc) intermediate generated from both
epimers of the 1-alkynylsulfoxide (Ss)- and (Rs)-4.
Entry
Substrate
Product
23
24
25
(E,Ss)-26a
Yiled (%)
dra
1
2
3
4
1
2
63
41
68
69
83:17b
59:41b
72:28b
82:18
3
(Rs)-4
The reactions were carried out with alkynoate (3 equiv.), Et2Zn (2 equiv.),
and Pd2(dba)3·CHCl3 (2 mol%) in THF overnight under Ar.
a
Determined by 1H NMR spectroscopic data.
Stereochemistry was not determined.
b
To improve the selectivity, solvent effect on the sulfinyl-
zincation was examined. We found that dioxane was the
best solvent, giving (E,Ss)-26a with 91:9 dr (Table 2).
Therefore, dioxane was used in the following experiments.
Table 2. Solvent effect on sulfinylzincation
Entry
Solvent
Temperature (8C)
Yiled (%)
dra
Scheme 8.
1
2
3
4
Toluene
Et2O
THF
2788C to rt
2788C to rt
2788C to rt
08C to rt
86
69
69
99
86:14
88:12
82:18
91:9
Stereochemistry of the adducts was determined as follows.
The geometry of the olefins was deduced as (E)-configur-
ation based on our previous results,4 and was confirmed by
lactone formation on treatment of two isomers of 26c with
TFA (Scheme 9). The stereochemistry of the sulfoxide was
Dioxane
The reactions were carried out with alkynoate (3 equiv.), Et2Zn (2 equiv.),
and Pd2(dba)3·CHCl3 (2 mol%) in solvent overnight under Ar.
a
Determined by 1H NMR spectroscopic data.
1
assumed by the above-mentioned empirical rule. In the H
Next, we examined the asymmetric sulfinylzincation of
various alkynoate derivatives (3 equiv.) with Et2Zn
(2 equiv.) and 2 mol% of catalytic Pd2(dba)3·CHCl3 in
NMR spectra, the major product (Ss)-26c and the corre-
sponding lactone (Ss)-27 showed a downfield shift in
comparison with the minor adduct (Rs)-26c and the lactone

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N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
Scheme 9.
(Rs)-27 in signals due to the H4-protons in the isoborneol
skeleton.
This speculation was confirmed by X-ray single crystal
analysis of the g-lactone (Ss)-27 (Fig. 2).
Scheme 10.
sence of Et3N in MeOH. Unexpectedly, the reaction
proceeded with low selectivity, giving (Z)-29 in 67% yield
along with 31% of (E)-29. In addition, the diastereo-
selectivity of m-CPBA oxidation of (Z)- and (E)-29 was also
very poor. These results are in sharp contrast to the finding
that the sulfinylzincation proceeds with high diastereo- and
syn-selectivity (Table 3, entry 1). The stereochemistry of the
products was confirmed by the empirical rule and NOE
experiments.
Figure 2. ORTEP drawing of (Ss)-27.
The diastereoselectivity in the sulfinylzincation can be
interpreted as follows. In the preferred conformers of the
zinc sulfenate and sulfinylzinc species, the smallest lone
pair electron would situate at the most crowded space near
one of the C7-Me and C2-MeO groups (Fig. 3). The X-ray
data of (Ss)-27 supports this speculation. Although inter-
mediate (b) seems to be more stable than intermediate (a) by
Table 4 shows the chemical shifts of the H4-proton in the
adducts 26a–g. The chemical shifts are varied ranging from
2.27 to 2.42 for major adducts, and ranging from 1.63 to
1.86 for minor adducts. Accordingly, the major and minor
sulfoxides are assumed to possess (Ss)- and (Rs)-configur-
ation, respectively, by the above-mentioned empirical
rule.10
Table 4. Comparison of chemical shifts due to H4-proton for adducts
26a–g
Compound
Substrate
Major [(Ss)-form] (ppm)
Minor [(Rs)-form] (ppm)
26a
26b
26c
26d
26e
26f
2.27
2.38
2.27
2.37
2.42
2.39
2.27
1.79
1.68
1.86
1.63
a
–
a
–
1.82
26g
a
Not assigned due to overlap with other signals.
Addition of thiolate to alkynoates is known to proceed in an
anti-selective fashion. To compare the stereochemical
outcome with the sulfinylzincation, conjugate addition of
thiol 28 was investigated (Scheme 10). The disulfide 21 was
reduced with Zn and AcOH to give the thiol 28, which was
reacted with methyl 4-benzyloxy-2-butynoate in the pre-
Figure 3. Plausible reaction mechanism for the asymmetric sulfinylzinca-
tion reaction (only relevant protons are shown).

N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
9899
the coordination of the methoxy group to the zinc cation,
both lone pair electrons on the sulfur atom are shielded by
the isoborneol moiety in the intermediate (b). Therefore, the
reaction occurred at the pro-R lone pair electrons in the
intermediate (a) having the least steric demand (Fig. 3(a)
and (b)). In comparison with the sulfinylzinc intermediates
(c) and (d), the intermediate (c) with an unshielded zinc
anion would preferentially react with alkynoates rather than
the intermediate (d) (Fig. 3(c) and (d)). Thus, the reactions
would proceed via intermediate (a) or (c) to give sulfoxides
with (Ss)-configuration.
2-H), 3.99 (dd, J¼11.6, 7.0 Hz, 2H, 2-H), 7.23–7.37 (m,
10H, Ar-H). 13C NMR (75 MHz) d: 57.36 (2C), 64.64 (2C),
128.18 (2C), 128.38 (4C), 128.77 (4C), 138.05 (2C). IR
3321 (OH), 3027 (vCH), 2872 (CH), 1378 (t-Bu). MS
(FAB) m/z: 329 (MNaþ). HRMS (FAB) calcd for
C16H18NaO2S2 (MNaþ): 329.0646. Found: 329.0652.
4.1.2. (S)-2-(3,3-Dimethyl-1-butynylthio)-2-phenyl-
ethanol (7). n-BuLi (1.59 M in hexane) (12.2 mL,
19.43 mmol) was added slowly to a solution of 3,3-
dimethyl-1-butyne (2.40 mL, 19.4 mmol) in THF (20 mL)
with stirring at 2788C. After 30 min, HMPA (3.40 mL,
19.4 mmol) and the disulfide 6 (1.70 g, 5.55 mmol) was
successively added to the mixture. After 15 min, the
reaction was quenched with saturated NH4Cl aqueous
solution. The organic layer was separated and the aqueous
layer was extracted with AcOEt. The combined organic
layers were washed with brine prior to drying and solvent
evaporation. The residue was chromatographed on silica gel
with hexane–AcOEt (9:1) to give 7 (1.25 g, 96%) as a
colorless powder. Mp 40.0–41.58C. [a]2D3¼215.1 (c 1.20,
3. Conclusion
In conclusion, we have investigated a Pd-catalyzed asym-
metric sulfinylzincation using 1-alkynyl sulfoxides bearing
chiral auxiliaries. We found that the isoborneol derivative
(Rs)-4 was the most efficient chiral auxiliary among those
we tested. The addition to various alkynoates proceeded in a
highly syn-selective fashion and the diastereoselectivities
exceeded 90:10 dr in many cases. The absolute configur-
ation of the resulting sulfoxide depended on that of the
chiral auxiliary rather than that of the original sulfoxide.
1
CHCl3). H NMR (500 MHz) d: 1.18 (s, 9H, t-Bu), 4.04–
4.18 (m, 3H, H-1 and 2), 7.23–7.37 (m, 5H, Ar-H). 13C
NMR (75 MHz) d: 28.57, 30.62 (3C), 54.02, 64.18, 64.72,
104.58, 127.84 (2C), 127.88, 128.39 (2C), 137.56. IR 3379
(OH), 3024 (vCH), 2967 (CH), 1362 (t-Bu). MS (FAB)
m/z: 235 (MHþ). HRMS (FAB) calcd for C14H19OS (MHþ):
235.1157. Found: 235.1175.
4. Experimental
4.1. General
4.1.3. (S)-1-Methoxy-2-(3,3-dimethyl-1-butynylthio)-2-
phenylethane (8). 60% NaH (62 mg, 1.54 mmol) was
added to a solution of 7 (300 mg, 1.28 mmol) in DMF
(3 mL) with stirring at 08C. After stirring at room
temperature for 1 h, MeI (0.12 mL, 1.92 mmol) was added
to the mixture. The whole was stirred at this temperature for
4 h. The reaction was quenched with water and extracted
with AcOEt. The extract was washed with brine prior to
drying and solvent evaporation. The residue was chromato-
graphed on silica gel with hexane–AcOEt (95:5) to give 8
(276 mg, 87%) as a colorless oil. [a]2D1¼þ36.1 (c 1.24,
CHCl3). 1H NMR (500 MHz) d: 1.17 (s, 9H, t-Bu), 3.39 (s,
3H, OCH3), 3.91 (d, J¼7.3 Hz, 2H, H-1), 4.20 (t, J¼7.3 Hz,
1H, H-2), 7.28–7.51 (m, 5H, Ar-H). 13C NMR (75 MHz) d:
28.68, 30.76 (3C), 51.58, 58.93, 65.40, 74.15, 104.73,
127.83, 127.99 (2C), 128.38 (2C), 138.15. IR 3029 (vCH),
2968 (CH), 1362 (t-Bu). MS (FAB) m/z: 249 (MHþ). HRMS
(FAB) calcd for C15H21OS (MHþ): 249.1313. Found:
249.1318.
Melting points are uncorrected. Optical rotations were
1
measured using a JASCO DIP-360 digital polarimeter. H
NMR spectra were recorded in CDCl3 solution at 300 or
500 MHz with a JMN-AL-300 or a JEOL JNM-GX500
spectrometer, respectively. 13C NMR spectra were recorded
in CDCl3 at 75 or 125 MHz with a JEOL JMN-AL-300 or a
JEOL JNM-GX500 spectrometer, respectively. Chemical
1
shifts of H NMR are expressed in ppm downfield from
tetramethylsilane as an internal standard (d¼0). Chemical
shifts of 13C NMR are expressed as ppm in CDCl3 as an
internal standard (d¼77). IR spectra were measured with a
Horiba FT-210 IR spectrometer. EI-MS spectra were taken
with a JMS-600H mass spectrometer. FAB-MS spectra were
measured by a JEOL JMS-700. Kanto Chemical Silica Gel
60 was used as an adsorbent for column chromatography.
All air- or moisture-sensitive reactions were carried out in
flame-dried glassware under Ar or N2 atmosphere. All
organic extracts were dried over anhydrous MgSO4, filtered,
and concentrated with a rotary evaporator under reduced
pressure unless otherwise cited.
4.1.4. (2S)-1-Methoxy-2-(3,3-dimethyl-1-butynylsul-
finyl)-2-phenylethane (1). m-CPBA (containing 30% of
water) (158 mg, 0.64 mmol) was added to a solution of the
sulfide 8 (150 mg, 0.64 mmol) in CH2Cl2 (2 mL) with
stirring at 08C. After 1.5 h, the reaction was quenched with
1N NaOH. The mixture was extracted with AcOEt and the
extract was washed with brine prior to drying and solvent
evaporation. The residue was chromatographed on silica gel
with hexane–AcOEt (4:1) to give 1 (147 mg, 87%) as a
colorless oil (57:43 diasteromeric mixture). 1H NMR
(500 MHz) d: 1.13 (s, 0.43£9H, t-Bu), 1.14 (s, 0.57£9H,
t-Bu), 3.42 (s, 0.57£3H, OCH3), 3.46 (s, 0.43£3H, OCH3),
3.96–4.31 (m, 3H, H-1 and 2), 7.35–7.51 (m, 5H, Ar-H).
13C NMR (75 MHz) (major) d: 28.23, 29.76 (3C), 59.31,
4.1.1. Bis[(S)-2-hydroxy-1-phenylethyl]disulfide (6). A
mixture of
5 (1.73 g, 11.2 mmol), NaIO3 (4.50 g,
22.7 mmol), and 17% wet alumina (11.23 g) in hexane–
toluene (1:1) (150 mL) was vigorously stirred at room
temperature under Ar. After 1 h, the mixture was filtered
and the solid was rinsed with AcOEt. The combined organic
layers were washed with 5% NaHSO3 aqueous solution and
brine prior to drying and solvent evaporation. The crude was
chromatographed on silica gel with n-hexane–AcOEt (7:3)
to give 6 (1.75 g, quant) as a colorless oil. [a]2D2¼þ134.0 (c
1
2.13, CHCl3). H NMR (500 MHz) d: 2.04 (br s, 2H, OH),
3.74 (t, J¼7.0 Hz, 2H, 1-H), 3.95 (dd, J¼11.6, 7.0 Hz, 2H,

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N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
69.59, 69.83, 74.79, 113.06, 128.36 (2C), 128.73, 129.39
(2C), 132.56. (minor) d: 28.23, 29.73 (3C), 59.19, 69.27,
71.57, 74.39, 113.82, 128.19 (2C), 128.69, 129.57 (2C),
131.69. IR 3032 (vCH), 2971 (CH), 2195 (CuC), 1363
(t-Bu), 1065 (SvO). MS (FAB) m/z: 265 (MHþ). HRMS
(FAB) calcd for C15H21O2S (MHþ): 265.1262. Found:
265.1254. Anal. calcd for C15H20O2S: C, 68.14; H, 7.62; S,
12.13. Found: C, 67.74; H, 7.67; S, 12.27.
128.84 (2C), 138.75. (minor) d: 28.34, 30.03 (3C), 56.87,
64.10, 76.42, 78.78, 112.06, 126.55 (2C), 128.43, 128.87
(2C), 138.91. IR 3030 (vCH), 2972 (CH), 2193 (CuC),
1363 (t-Bu), 1063 (SvO). MS (FAB) m/z: 265 (MHþ).
HRMS (FAB) calcd for C15H21O2S (MHþ): 265.1262.
Found: 265.1267.
4.1.9. (1S,2R)-Bis(2-hydroxybornane-10-yl)disulfide
(14). In a manner similar to that described for 6, the thiol
13 (1.50 g, 8.05 mmol) was converted into 14 (1.48 g, 99%)
as a colorless oil. The spectral data was identified with the
reported data.15
4.1.5. Bis[(S)-2-hydroxy-2-phenylethyl]disulfide (10). In
a manner similar to that described for 6, the thiol 5 (1.78 g,
11.5 mmol) was converted into 10 (1.78 g, quant) as a
colorless powder. Mp 75.0–76.08C. [a]2D4¼þ169.0 (c 1.20,
1
CHCl3). H NMR (500 MHz) d: 2.43 (br s, 2H, OH), 2.96
4.1.10. (1S,2R)-2-Hydroxy-10-(3,3-dimethyl-1-butynyl-
thio)bornane (15). In a manner similar to that described
for 7, the disulfide 14 (2.61 g, 7.03 mmol) was converted
into 15 (1.84 g, quant) as a colorless powder. Mp 34.0–
36.08C. [a]2D2¼þ48.1 (c 0.95, CHCl3). 1H NMR (500 MHz)
d: 0.80 (s, 3H, CH3), 0.99–1.08 (m, 1H), 1.04 (s, 3H, CH3),
1.21 (s, 9H, t-Bu), 1.32–1.37 (m, 1H), 1.47 (td, J¼11.6,
4.3 Hz, 1H), 1.64–1.81 (m, 4H), 2.48 (d, J¼3.7 Hz, 1H),
2.55 (d, J¼13.4 Hz, 1H, H-10), 3.15 (d, J¼13.4 Hz, 1H,
H-10), 4.29 (dt, J¼7.9, 4.3 Hz, 1H, H-2). 13C NMR
(75 MHz) d: 19.88, 20.53, 26.92, 28.71, 30.64, 30.80
(3C), 36.01, 38.96, 45.67, 47.76, 53.25, 68.93, 76.39,
101.62. IR 3550 (OH), 2966 (CH), 1362 (t-Bu). MS (FAB)
m/z: 267 (MHþ). HRMS (FAB) calcd for C16H27OS (MHþ):
267.1783. Found: 267.1794.
(dd, J¼14.0, 9.2 Hz, 2H, H-1), 3.08 (dd, J¼14.0, 3.1 Hz,
2H, H-1), 4.98 (dd, J¼9.2, 3.1 Hz, 2H, H-2), 7.28–7.38 (m,
10H, Ar-H). 13C NMR (75 MHz) d: 47.73 (2C), 72.06 (2C),
125.87 (4C), 127.96 (2C), 128.55 (4C), 142.04 (2C). IR
3361 (OH), 3029 (vCH), 2910 (CH). MS (FAB) m/z: 329
(MNaþ). HRMS (FAB) calcd for C16H18NaO2S2 (MNaþ):
329.0646. Found: 329.0665.
4.1.6. (S)-2-(3,3-Dimethyl-1-butynylthio)-1-phenyl-
ethanol (11). In a manner similar to that described for 7,
the disulfide 10 (1.70 g, 5.55 mmol) was converted into 11
(541 mg, 42%) as a colorless oil. [a]2D2¼223.4 (c 0.41,
CHCl3). 1H NMR (500 MHz) d: 1.26 (s, 9H, t-Bu), 2.80 (dd,
J¼13.4, 9.2 Hz, 1H, H-2), 3.02 (dd, J¼13.4, 3.1 Hz, 1H,
H-2), 2.82 (br s, 1H, OH), 4.99 (dt, J¼9.2, 3.1 Hz, 1H, H-1),
7.29–7.41 (m, 5H, Ar-H). 13C NMR (75 MHz) d: 28.70,
30.86 (3C), 44.54, 65.78, 72.13, 102.96, 125.81 (2C),
127.93, 128.51 (2C), 141.79. IR 3379 (OH), 3029 (vCH),
2968 (CH), 1362 (t-Bu). MS (FAB) m/z: 257 (MNaþ).
HRMS (FAB) calcd for C14H18NaOS (MNaþ): 257.0976.
Found: 257.0980.
4.1.11. (1S,2R)-2-Methoxy-10-(3,3-dimethyl-1-butynyl-
thio)bornane (16). In a manner similar to that described
for 8, the alcohol 15 (300 mg, 1.14 mmol) was converted
into 16 (262 mg, 82%) as a colorless oil. [a]2D0¼2135.6 (c
1
1.10, CHCl3). H NMR (300 MHz) d: 0.85 (s, 3H, CH3),
0.99 (s, 3H, CH3), 1.03–1.08 (m, 1H), 1.22 (s, 9H, t-Bu),
1.26–1.43 (m, 1H), 1.57–1.81 (m, 5H), 2.63 (d, J¼12.3 Hz,
1H, SCH2), 3.07 (d, J¼12.3 Hz, 1H, SCH2), 3.23 (s, 3H,
OCH3), 3.38 (dd, J¼7.9, 3.3 Hz, 1H, 2-H). 13C NMR
(75 MHz) d: 20.22, 20.41, 27.14, 28.64, 30.95, 30.98 (3C),
36.51, 37.48, 45.54, 47.91, 53.41, 56.31, 69.43, 85.42,
100.33. IR 2931 (CH), 1362 (t-Bu). MS (FAB) m/z: 303
(MNaþ). HRMS (FAB) calcd for C17H28NaOS (MNaþ):
303.1759. Found: 303.1756.
4.1.7. (S)-1-Methoxy-2-(3,3-dimethyl-1-butynylthio)-1-
phenylethane (12). In a manner similar to that described
for 8, the alcohol 11 (150 mg, 0.64 mmol) was converted
into 12 (147 mg, 93%) as a colorless oil. [a]2D1¼220.7 (c
1
1.05, CHCl3). H NMR (500 MHz) d: 1.24 (s, 9H, t-Bu),
2.87 (dd, J¼13.1, 4.9 Hz, 1H, H-2), 3.00 (dd, J¼13.1,
8.5 Hz, 1H, H-2), 3.30 (s, 3H, OCH3), 4.41 (dd, J¼8.5,
4.9 Hz, 1H, 1-H), 7.30–7.39 (m, 5H, Ar-H). 13C NMR
(75 MHz) d: 28.71, 31.00 (3C), 42.86, 57.16, 66.82, 81.71,
102.55, 126.69 (2C), 128.14, 128.57 (2C), 140.17. IR 3028
(vCH), 2968 (CH), 1362 (t-Bu). MS (FAB) m/z: 271
(MNaþ). HRMS (FAB) calcd for C15H20NaOS (MNaþ):
271.1133. Found: 271.1131.
4.1.12. (1S,2R)-2-Methoxy-10-(3,3-dimethyl-1-butynyl-
sulfinyl)bornane (3). In a manner similar to that described
for 1, the sulfide 16 (260 mg, 0.93 mmol) was converted
into 3 (275 mg, quant) as a colorless oil (72:28 dia-
1
stereomeric mixture). H NMR (500 MHz) d: 0.88 (s, 3H,
CH3), 1.04 (s, 0.28£3H, CH3), 1.05 (s, 0.72£3H, CH3),
1.00–1.86 (m, 7H), 1.295 (s, 0.72£9H, t-Bu), 1.300 (s,
0.28£9H, t-Bu), 3.04 (d, J¼12.8 Hz, 0.72H, H-10), 3.09 (d,
J¼12.8 Hz, 0.28H, H-10), 3.23 (s, 0.28£3H, OCH3), 3.25 (s,
0.72£3H, OCH3), 3.28 (d, J¼12.8 Hz, 0.28H, H-10), 3.35
(dd, J¼7.3, 3.1 Hz, 0.72H, H-2), 3.54 (dd, J¼7.3, 3.1 Hz,
0.28H, H-2), 4.12 (d, J¼12.8 Hz, 0.72H, H-10). 13C NMR
(75 MHz) (major) d: 20.12, 20.21, 27.31, 28.31, 29.87 (3C),
30.72, 37.74, 44.48, 48.76, 50.17, 56.03, 57.93, 77.20,
85.17, 111.61. (minor) d: 20.07, 20.21, 27.43, 28.28, 29.97
(3C), 31.29, 37.52, 44.41, 48.77, 50.87, 55.85, 58.65, 77.63,
85.23, 111.45. IR 2931 (CH), 2193 (CuC), 1363 (t-Bu),
1063 (SvO). MS (FAB) m/z: 297 (MHþ). HRMS (FAB)
calcd for C17H29O2S (MHþ): 297.1888. Found: 297.1885.
4.1.8. (2S)-1-Methoxy-2-(3,3-dimethyl-1-butynylsul-
finyl)-1-phenylethane (2). In a manner similar to that
described for 1, the sulfide 12 (100 mg, 0.40 mmol) was
converted into 2 (104 mg, 98%) as a colorless oil (52:48
1
diasteromeric mixture). H NMR (500 MHz) d: 1.25 (s,
0.48£9H, t-Bu), 1.33 (s, 0.52£9H, t-Bu), 3.19 (dd, J¼13.7,
11.0 Hz, 0.48H, H-2), 3.21 (dd, J¼12.8, 4.6 Hz, 0.52H,
H-2), 3.24 (s, 0.52£3H, OCH3), 3.30 (s, 0.48£3H, OCH3),
3.44 (dd, J¼13.7, 2.4 Hz, 0.48H, H-2), 3.63 (dd, J¼12.8,
8.9 Hz, 0.52H, H-2), 4.64 (dd, J¼8.9, 4.6 Hz, 0.52H, H-1),
4.65 (dd, J¼11.0, 2.4 Hz, 0.48H, H-1), 7.33–7.42 (m, 5H,
Ar-H). 13C NMR (125 MHz) (major) d: 28.48, 29.91 (3C),
56.80, 65.22, 76.36, 78.82, 113.00, 126.61 (2C), 128.56,

N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
9901
Anal. calcd for C17H28O2S: C, 68.87; H, 9.52; S, 10.82.
Found: C, 68.60; H, 9.36; S, 10.67.
gel with hexane–ether (98:2) to give 21 (88 mg, 62%) as a
colorless powder. Mp 77.5–80.08C. [a]2D5¼254.1 (c 1.03,
CHCl3). 1H NMR (300 MHz) d: 0.78 (s, 6H, CH3), 0.88 (s,
6H, CH3), 1.08 (s, 6H, CH3), 1.03–1.14 (m, 4H, H-5 and 6),
1.45–1.58 (m, 2H, H-5), 1.72–1.85 (m, 2H, H-6), 2.02 (d,
J¼4.2 Hz, 2H, H-4), 3.247 (s, 4H, H-2 and 3), 3.42 (s, 6H,
OCH3). 13C NMR (125 MHz) d: 11.64 (2C), 21.04 (2C),
21.66 (2C), 28.59 (2C), 33.74 (2C), 46.96 (2C), 50.36 (2C),
52.75 (2C), 61.16 (2C), 65.59 (2C), 91.38 (2C). IR 2950
(CH), 557 (S-S). MS (FAB) m/z: 421 (MNaþ). HRMS
(FAB) calcd for C22H38NaO2S2 (MNaþ): 421.2211. Found:
421.2219.
4.1.13. (1R,2S,3R)-Bis(2-hydroxybornane-3-yl)disulfide
(18). In a manner similar to that described for 6, the thiol
17 (250 mg, 1.34 mmol) was converted into 18 (248 mg,
quant) as a colorless powder. The spectral data was
identified with the reported data.16
4.1.14. (1R,2S,3R)-2-Hydroxy-3-(3,3-dimethyl-1-
butynylthio)bornane (19). In a manner similar to that
described for 7, the disulfide 18 (250 mg, 0.67 mmol) was
converted into 19 (142 mg, 80%) as a colorless oil.
[a]2D8¼þ22.7 (c 1.03, CHCl3). 1H NMR (500 MHz) d:
0.80 (s, 3H, CH3), 0.96 (s, 3H, CH3), 1.10 (s, 3H, CH3), 1.22
(s, 9H, t-Bu), 1.06–1.26 (m, 2H, H-5 and 6), 1.48–1.54 (m,
1H, H-6), 1.78–1.84 (m, 1H, H-5), 1.95 (d, J¼4.3 Hz, 1H,
H-4), 2.32 (d, J¼3.4 Hz, 1H, OH), 3.38 (d, J¼7.3 Hz, 1H,
H-3), 3.83 (dd, J¼7.3, 3.4 Hz, 1H, H-2). 13C NMR
(125 MHz) d: 11.53, 21.14, 21.43, 28.67, 28.78, 29.75,
30.93 (3C), 33.25, 45.86, 48.14, 51.57, 61.16, 79.93, 101.27.
IR 3542 (OH), 2983 (CH), 2164 (CuC), 1361 (t-Bu). MS
(FAB) m/z: 289 (MNaþ). HRMS (FAB) calcd for
C16H26NaOS (MNaþ): 289.1602. Found: 289.1603.
4.1.17. (1R,2S,3R)-2-Methoxy-3-(methoxysulfinyl)-
bornane (22). SO2Cl2 (200 mg, 1.50 mmol) was added
dropwise to a solution of the disulfide 21 (200 mg,
0.50 mmol) and acetic acid (60 mg, 1.00 mmol) in CH2Cl2
(2 mL) with stirring at 2108C. The mixture was stirred at
room temperature for 2 h and then at 358C for 1 h. The
solvent was evaporated and the residue was dissolved in
MeOH (2 mL) and pyridine (158 mg, 2.00 mmol) was
added to the mixture. The whole was stirred at room
temperature fro 2 h. The reaction was quenched with 1N
HCl and the mixture was extracted with AcOEt. The organic
layer was washed with water and brine prior to drying and
solvent evaporation. The residue was chromatographed on
silica gel with hexane–AcOEt (85:15) to give 22 (134 mg,
54%) as a colorless oil (4:1 diastreomeric mixture). 1H
NMR (300 MHz) d: 0.81 (s, 0.8£3H, CH3), 0.82 (s, 0.2£3H,
CH3), 0.96 (s, 3H, CH3), 0.99–1.09 (m, 2H, H-5 and 6), 1.12
(s, 0.8£3H, CH3), 1.16 (s, 0.2£3H, CH3), 1.47–1.58 (m, 1H,
H-6), 1.72–1.88 (m, 1H, H-5), 2.05 (d, J¼3.1 Hz, 0.8H,
H-4), 2.22 (d, J¼4.4 Hz, 0.2H, H-4), 3.02 (d, J¼7.9 Hz,
0.8H, H-3), 3.08 (d, J¼7.9 Hz, 0.2H, H-3), 3.34 (d,
J¼8.1 Hz, 0.2H, H-2), 3.38 (s, 0.2£3H, OCH3), 3.41 (d,
J¼8.1 Hz, 0.8H, H-2), 3.44 (s, 0.8£3H, OCH3), 3.71 (s,
0.8£3H, S(O)2CH3), 3.83 (s, 0.2£3H, S(O)2CH3). 13C NMR
(125 MHz) (major) d: 10.92, 20.45, 21.09, 27.81, 32.75,
46.64, 48.52, 50.37, 52.62, 61.46, 78.66, 90.12. (minor) d:
11.01, 20.70, 27.96, 32.96, 46.63, 46.80, 47.14, 50.39,
50.61, 55.04, 61.00, 90.31. IR 2948 (CH), 1132 (SvO). MS
(FAB) m/z: 247 (MNaþ). HRMS (FAB) calcd for
C12H23O3S (MHþ): 247.1368. Found: 247.1370.
4.1.15. (Rs,1R,2S,3R)-2-Methoxy-3-(3,3-dimethyl-1-
butynylsulfinyl)bornane [(Rs)-4]. m-CPBA (containing
30% of water) (679 mg, 2.75 mmol) was added to a solution
of 19 (734 mg, 2.75 mmol) in CH2Cl2 (5 mL) with stirring
at 08C. After 1.5 h, the reaction was quenched with 1N
NaOH. The mixture was extracted with AcOEt and the
extract was washed with brine prior to drying and solvent
evaporation. 60% NaH (165 mg, 4.13 mmol) was added to a
solution of the crude sulfoxide in DMF (3 mL) with stirring
at 08C. After stirring at room temperature for 1 h, MeI
(0.34 mL, 5.50 mmol) was added to the mixture. The whole
was stirred at this temperature for 12 h. The reaction was
quenched with water and extracted with AcOEt. The extract
was washed with brine prior to drying and solvent
evaporation. The residue was chromatographed on silica
gel with hexane–AcOEt (4:1) to give (Rs)-4 (639 mg, 78%
in two steps) as a colorless powder. Mp 92.0–95.08C.
[a]2D5¼257.1 (c 1.02, CHCl3). 1H NMR (500 MHz) d: 0.79
(s, 3H, CH3), 0.97 (s, 3H, CH3), 1.02 (s, 3H, CH3), 1.08–
1.12 (m, 1H, H-5 or 6), 1.13–1.22 (m, 1H, H-5 or 6), 1.30 (s,
9H, t-Bu), 1.55 (td, J¼12.2, 3.7 Hz, 1H, H-6), 1.80–1.88
(m, 1H, H-5), 2.08 (d, J¼4.3 Hz, 1H, H-4), 3.45 (s, 2H, H-2
and 3), 3.49 (s, 3H, OCH3). 13C NMR (125 MHz) d: 11.14,
20.48, 21.08, 28.00, 28.32, 30.00 (3C), 32.87, 46.39, 50.78,
51.06, 61.92, 76.87, 79.43, 89.74, 112.17. IR 2964 (CH),
2156 (CuC), 1371 (t-Bu), 1057 (SvO). MS (FAB) m/z:
297 (MHþ). HRMS (FAB) calcd for C17H29O2S (MHþ):
297.1888. Found: 297.1904. Anal. calcd for C17H28O2S: C,
68.87; H, 9.52; S, 10.82. Found: C, 68.73; H, 9.40; S, 10.64.
4.1.18. (Ss,1R,2S,3R)-2-Methoxy-3-(3,3-dimethyl-1-
butynylsulfinyl)bornane [(Ss)-4]. EtMgBr (3 M in ether)
(0.33 mL, 1.20 mmol) was added slowly to a solution of 3,3-
dimethyl-1-butyne (0.12 mL, 1.00 mmol) in ether (2 mL)
with stirring at room temperature under N2. A solution of 22
(100 mg, 0.41 mmol) in toluene (5 mL) was added to the
mixture. The whole was stirred at 608C for 5 h. The reaction
was quenched with saturated NH4Cl aqueous solution. The
organic layer was separated and the aqueous layer was
extracted with AcOEt. The combined organic layers were
washed with water and brine prior to drying and solvent
evaporation. The residue was chromatographed on silica gel
with hexane–AcOEt (85:15) to give (Rs)-4 (55 mg, 45%) as
a colorless powder along with (Rs)-4 (11 mg, 9%). Mp
63.0–65.08C. [a]D28¼þ55.2 (c 1.15, CHCl3). 1H NMR
(300 MHz) d: 0.84 (s, 3H, CH3), 0.98 (s, 3H, CH3), 1.02–
1.16 (m, 1H, H-5 or 6), 1.20–1.45 (m, 1H, H-5 or 6), 1.23 (s,
3H, CH3), 1.32 (s, 9H, t-Bu), 1.50–1.61 (m, 1H, H-6),
1.80–1.93 (m, 1H, H-5), 2.34 (d, J¼4.4 Hz, 1H, H-4), 3.37
4.1.16. Bis[(1R,2S,3R)-2-methoxybornane-3-yl]disulfide
(21). The disulfide 18 (135 mg, 0.36 mmol) and MeI
(0.13 mL, 20.8 mmol) were added to a solution of KOH
(264 mg, 4.00 mmol) in DMSO (2 mL) with stirring at room
temperature. After 2 h, water was added to the mixture and
the mixture was extracted with AcOEt. The organic layer
was washed with brine prior to dying and solvent
evaporation. The residue was chromatographed on silica

9902
N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
(s, 3H, OCH3), 3.39 (d, J¼7.9 Hz, 1H, H-3), 3.71 (d,
J¼7.9 Hz, 1H, H-2). 13C NMR (125 MHz) d: 11.24, 20.32,
21.24, 28.28, 30.10, 30.29 (3C), 32.67, 45.39, 47.37, 51.07,
61.62, 78.25, 79.52, 80.67, 109.81. IR 2964 (CH), 2158
(CuC), 1371 (t-Bu), 1055 (SvO). MS (FAB) m/z: 297
(MHþ). HRMS (FAB) calcd for C17H29O2S (MHþ):
297.1888. Found: 297.1879.
(vCH), 2948 (CH), 1716 (CvO), 1105 (SvO). MS (FAB)
m/z: 389 (MHþ). HRMS (FAB) calcd for C21H25O5S
(MHþ): 389.1423. Found: 389.1406.
4.2.3. Methyl (E)-4-benzyloxy-3-[[(1S,2R)-2-methoxy-
bornane-10-yl]sulfinyl]-2-butenoate (25). Pale yellow oil
(72:28 diastereomeric mixture). 1H NMR (500 MHz) d:
0.74 (s, 0.28£3H, CH3), 0.81 (s, 0.72£3H, CH3), 0.93 (s,
0.28£3H, CH3), 1.02 (s, 0.72£3H, CH3), 0.80–1.84 (m,
7H), 2.32 (d, J¼12.8 Hz, 0.72H, SCH2), 3.02–3.10 (m,
0.28£2H, SCH2), 3.14 (s, 0.72£3H, OCH3), 3.23 (s,
0.28£3H, OCH3), 3.40–3.62 (m, 1H, CHO), 3.60 (d,
J¼12.8 Hz, 0.72H, SCH2), 3.755 (s, 0.28£3H, CO2CH3),
3.760 (s, 0.72£3H, CO2CH3), 4.50–5.00 (m, 4H, CH2-
OCH2Ph), 6.64 (s, 0.28H, H-2), 6.66 (s, 0.72H, H-2), 7.28–
7.37 (m, 5H, Ar-H). 13C NMR (75 MHz) (major) d: 20.10,
20.33, 27.49, 31.58, 37.55, 44.68, 48.83, 51.36, 51.82,
55.60, 55.67, 64.88, 73.49, 85.41, 119.79, 127.91 (2C),
127.98, 128.35 (2C), 128.39, 137.12, 163.64. (minor) d:
20.08, 20.31, 27.19, 29.20, 30.30, 38.12, 44.92, 51.76,
53.73, 56.16, 67.14, 73.64, 77.20, 85.96, 118.15, 126.85,
127.83 (2C), 128.01 (2C), 128.40 136.78, 164.77. IR 2952
(CH), 1716 (CvO), 1041 (SvO). MS (FAB) m/z: 421
(MHþ). HRMS (FAB) calcd for C23H33O5S (MHþ):
421.2049. Found: 421.2037. Anal. calcd for C23H32O5S:
C, 65.68; H, 7.67; S, 7.62. Found: C, 65.66; H, 7.63; S, 7.40.
4.2. General procedure of sulfinylzincation with 1–3
(Table 1)
Et2Zn (0.99 M in hexane) (0.30 mL, 0.30 mmol) was slowly
added to a solution of the 1-alkynyl sulfoxide 1 (42 mg,
0.15 mmol), methyl 4-benzyloxy-2-butynoate (92 mg,
0.45 mmol), and Pd2(dba)3·CHCl3 (3 mg, 0.003 mmol) in
THF (0.2 mL) with stirring at 2788C. The stirring was
continued at this temperature for 10 min and at room
temperature for 2 h. The reaction was quenched with
saturated NH4Cl aqueous solution. The organic layer was
separated and the aqueous layer was extracted with AcOEt.
The combined organic layers were washed with brine prior
to drying and solvent evaporation. The residue was
chromatographed on silica gel with hexane–AcOEt (4:1)
to give 23 (36 mg, 63%) as a pale yellow oil (83:17
diastereomeric mixture).
4.2.1. Methyl (E)-4-benzyloxy-3-[(1S)-(2-methoxy-1-phe-
nylethyl)sulfinyl]-2-butenoate (23). Pale yellow oil (83:17
diastereomeric mixture). H NMR (500 MHz) d: 3.20 (s,
4.3. General procedure of sulfinylzincation with 4
(Table 3)
1
0.83£3H, OCH3), 3.44 (s, 0.17£3H, OCH3), 3.57 (s,
0.83£3H, CO2CH3), 3.77 (s, 0.17£3H, CO2CH3), 3.71–
3.82 (m, 1.17H, CH2OMe), 4.05 (dd, J¼11.0, 8.0 Hz,
0.83H, CH2OMe), 4.53–4.70 (m, 1.51H, CHS, CH2Ph, and
4-H), 4.55 (d, J¼11.3 Hz, 0.83H, CH2Ph), 4.60 (d,
J¼11.3 Hz, 0.83H, CH2Ph), 4.82 (dd, J¼16.5, 2.1 Hz,
0.17H, 4-H), 4.88 (dd, J¼15.6, 2.1 Hz, 0.83H, 4-H), 5.11
(dd, J¼15.6, 2.1 Hz, 0.83H, 4-H), 5.76 (t, J¼2.1 Hz, 0.17H,
2-H), 6.50 (t, J¼2.1 Hz, 0.83H, 2-H), 7.06–7.42 (m, 10H,
Ar-H). 13C NMR (75 MHz) (major) d: 29.22, 51.80, 58.21,
65.83, 67.01, 68.25, 73.81, 118.09, 128.02 (2C), 128.07,
128.48 (2C), 128.72 (2C), 128.82 (2C), 134.93, 136.92,
161.03, 164.81. (minor) d: 31.67, 51.55, 59.02, 66.17, 67.81,
70.42, 73.92, 119.49, 128.01 (2C), 128.11, 128.51 (2C),
128.56 (2C), 128.70 (2C), 134.93, 136.78, 161.64, 164.26.
IR 3030 (vCH), 2929 (CH), 1716 (CvO), 1116 (SvO).
MS (FAB) m/z: 389 (MHþ). HRMS (FAB) calcd for
C21H25O5S (MHþ): 389.1423. Found: 389.1421.
Et2Zn (0.99 M in hexane) (0.20 mL, 0.20 mmol) was slowly
added to a solution of the 1-alkynyl sulfoxide (Rs)-4 (30 mg,
0.10 mmol), methyl 4-benzyloxy-2-butynoate (61 mg,
0.30 mmol), and Pd2(dba)3·CHCl3 (2 mg, 0.002 mmol) in
1,4-dioxane (0.5 mL) with stirring at 08C. The stirring was
continued at this temperature for 10 min and at room
temperature for 12 h. The reaction was quenched with
saturated NH4Cl aqueous solution. The organic layer was
separated and the aqueous layer was extracted with AcOEt.
The combined organic layers were washed with water and
brine prior to drying and solvent evaporation. The residue
was chromatographed on silica gel with hexane–AcOEt
(85:15) to give (E,Rs)-26a (43 mg, 99%) as a pale yellow oil
(91:9 diastereomeric mixture). Analytical sample was
purified by column chromatography with hexane–AcOEt
(9:1).
4.3.1. Methyl (E)-4-benzyloxy-3-[[(1R,2S,3R)-2-
methoxybornane-3-yl]sulfinyl]-2-butenoate
4.2.2. Methyl (E)-4-benzyloxy-3-[(1S)-(2-methoxy-2-phe-
nylethyl)sulfinyl]-2-butenoate (24). Pale yellow oil (59:41
diastereomeric mixture). H NMR (500 MHz) d: 3.07 (s,
[(E)-26a].
Compound (E,Ss)-26a. Pale yellow powder. Mp 50.0–
51.08C. [a]2D6¼223.5 (c 1.06, CHCl3). 1H NMR (500 MHz)
d: 0.81 (s, 3H, CH3), 0.84–0.98 (m, 2H, H-50 and 60), 0.94
(s, 3H, CH3), 1.23 (s, 3H, CH3), 1.42–1.51 (m, 1H, H-60),
1.77–1.85 (m, 1H, H-50), 2.27 (d, J¼4.3 Hz, 1H, H-40), 3.18
(d, J¼7.9 Hz, 1H, H-20 or 30), 3.23 (s, 3H, OCH3), 3.49 (d,
J¼7.9 Hz, 1H, H-20 or 30), 3.77 (s, 3H, CO2CH3), 4.57 (d,
J¼11.3 Hz, 1H, CH2Ph), 4.66 (d, J¼11.3 Hz, 1H, CH2Ph),
4.71 (d, J¼12.8, 1H, H-4), 4.92 (d, J¼12.8, 1H, H-4), 6.58
(s, 1H, H-2), 7.27–7.37 (m, 5H, Ar-H). 13C NMR
(125 MHz) d: 11.52, 20.95, 21.08, 29.66, 32.86, 45.08,
47.23, 50.93, 51.90, 61.07, 61.74, 71.21, 73.39, 90.92,
124.07, 127.85 (2C), 127.88, 128.37 (2C), 137.51, 160.23,
164.71. IR 2953 (CH), 1718 (CvO), 1024 (SvO). MS
1
0.41£3H, OCH3), 3.25–3.36 (m, 1H, CH2S), 3.33 (s,
0.59£3H, OCH3), 3.59 (t, J¼11.6 Hz, 0.59H, CH2S), 3.65–
3.80 (m, 0.41H, CH2S), 3.73 (s, 0.59£3H, CO2CH3), 3.77 (s,
0.41£3H, CO2CH3), 4.49–5.04 (m, 5H, CH2Ph, CHOCH3,
and H-4), 6.57 (t, J¼1.8 Hz, 0.59H, H-2), 6.61 (t, J¼1.8 Hz,
0.41H, H-2), 7.25–7.42 (m, 10H, Ar-H). 13C NMR
(75 MHz) (major) d: 29.22, 51.86, 56.03, 62.64, 66.64,
73.60, 76.78, 118.33, 126.66 (2C), 127.83 (2C), 128.34,
128.45 (2C), 136.85, 128.73 (2C), 139.69, 164.37, 164.67.
(minor) d: 31.69, 51.81, 56.93, 59.88, 67.91, 73.65, 75.29,
117.47, 126.61 (2C), 127.98 (2C), 128.21, 128.49 (2C),
128.71 (2C), 136.80, 139.24, 163.97, 164.77. IR 3029

N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
9903
(FAB) m/z: 421 (MHþ). HRMS (FAB) calcd for C23H33O5S
(MHþ): 421.2049. Found: 421.2033. Anal. calcd for
C23H32O5S: C, 65.68; H, 7.67; S, 7.62. Found: C, 65.76;
H, 7.60; S, 7.34.
(s, 3H, CH3), 1.00–1.10 (m, 2H, H-50 and 60), 1.12 (s, 3H,
CH3), 1.47–1.54 (m, 1H, H-60), 1.64–1.76 (m, 1H, H-50),
1.86 (d, J¼4.4 Hz, 1H, H-40), 3.12 (d, J¼7.5 Hz, 1H, H-20 or
30), 3.44 (d, J¼7.5 Hz, 1H, H-20 or 30), 3.53 (s, 3H, OCH3),
3.78 (s, 3H, CO2CH3), 4.68 (d, J¼13.6 Hz, 1H, H-4), 5.12
(d, J¼13.6 Hz, 1H, H-4), 6.47 (s, 1H, H-2). 13C NMR
(125 MHz) d: 25.32, 25.28, 11.28, 18.54, 20.65, 22.00,
25.95 (3C), 28.56, 32.63, 46.86, 48.67, 50.67, 51.94, 56.27,
62.17, 77.77, 90.72, 122.86, 163.65, 164.63. IR 2953 (CH),
1724 (CvO), 1045 (SvO). MS (FAB) m/z: 445 (MHþ).
HRMS (FAB) calcd for C22H41O5SSi (MHþ): 445.2444.
Found: 445.2449.
Compound (E,Rs)-26a. Pale yellow oil. [a]2D7¼þ37.0 (c
1.07, CHCl3). 1H NMR (500 MHz) 0.73 (s, 3H, CH3), 0.83–
1.22 (m, 2H, H-50 and 60), 0.96 (s, 3H, CH3), 1.05 (s, 3H,
CH3), 1.46 (ddd, J¼12.5, 12.0, 3.5 Hz, 1H, H-60), 1.57–1.60
(m, 1H, H-50), 1.79 (d, J¼3.6 Hz, 1H, H-40), 3.17 0 (d,
J¼7.3 Hz, 1H, H-20 or 30), 3.43 (d, J¼7.9 Hz, 1H, H-2 or
30), 3.53 (s, 3H, OCH3), 3.76 (s, 3H, CO2CH3), 4.60 (s, 2H,
CH2Ph), 4.64 (d, J¼12.8 Hz, 1H, H-4), 4.90 (d, J¼12.8 Hz,
1H, H-4), 6.53 (s, 1H, H-2), 7.28–7.35 (m, 5H, Ar-H). 13C
NMR (75 MHz) d: 11.17, 20.50, 21.70, 28.11, 32.50, 46.75,
48.80, 50.64, 51.93, 61.85, 62.05, 73.41, 77.33, 90.53,
124.32, 127.75, 127.96 (2C), 128.24 (2C), 137.30, 161.19,
164.34. IR 2950 (CH), 1724 (CvO), 1024 (SvO). MS
(FAB) m/z: 421 (MHþ). HRMS (FAB) calcd for C23H33O5S
(MHþ): 421.2049. Found: 421.2043.
4.3.4. Methyl (E)-4-benzylthio-3-[[(1R,2S,3R)-2-
methoxybornane-3-yl]sulfinyl]-2-butenoate (26d). Pale
yellow oil. 1H NMR (500 MHz) d: 0.77 (s, 0.09£3H,
CH3), 0.84 (s, 0.91£3H, CH3), 0.96–1.17 (m, 2H, H-50 and
60), 0.98 (s, 0.91£3H, CH3), 1.08 (s, 0.09£3H, CH3), 1.25 (s,
0.09£3H, CH3), 1.29 (s, 0.91£3H, CH3), 1.48–1.54 (m, 1H,
H-600), 1.63 (d, J¼4.3 Hz, 0.09H, H-40), 1.69–1.91 (m, 1H,
H-5 ), 2.37 (d, J¼4.3 Hz, 0.91H, H-40), 3.25 (d, J¼13.4 Hz,
0.09H, CH2Ph), 3.25 (s, 3H, OCH3), 3.26 (d, J¼7.3 Hz,
0.09H, H-20 or 30), 3.43 (d, J¼0 7.3 Hz, 0.09H, H-20 or 30),
3.29 (d, J¼8.5 Hz, 0.91H, H-2 or 30), 3.32 (d,0 J¼13.4 Hz,
0.09H, CH2Ph), 3.41 (d, J¼8.0 Hz, 0.91H, H-2 or 30), 3.45
(s, 3H, CO2Me), 3.64 (d, J¼12.8 Hz, 0.91H, H-4), 3.80 (d,
J¼12.8 Hz, 0.09H, H-4), 3.84 (d, J¼12.8 Hz, 0.91H,
CH2Ph), 3.88 (d, J¼12.8 Hz, 0.91H, CH2Ph), 3.99 (d,
J¼12.8 Hz, 0.09H, H-4), 4.26 (d, J¼12.8 Hz, 0.91H, H-4),
6.32 (s, 0.09H, H-2), 6.51 (s, 0.91H, H-2), 7.23–7.35 (m,
5H, Ar-H). 13C NMR (125 MHz) (major): d: 11.78, 20.61,
21.09, 24.84, 28.47, 32.90, 37.65, 45.80, 47.42, 51.38,
51.90, 61.01, 73.04, 90.73, 122.27, 127.18, 128.52 (2C),
128.99 (2C), 137.58, 162.42, 164.90. IR 2951 (CH), 1716
(CvO), 1038 (SvO). MS (FAB) m/z: 437 (MHþ). HRMS
(FAB) calcd for C23H33O4S2 (MHþ): 437.1820. Found:
437.1827.
4.3.2. Methyl (E)-4-acetoxy-3-[[(1R,2S,3R)-2-methoxy-
bornane-3-yl]sulfinyl]-2-butenoate (26b). Pale yellow
1
oil. H NMR (500 MHz) d: 0.78 (s, 0.08£3H, CH3), 0.85
(s, 0.92£3H, CH3), 0.94–1.16 (m, 2H, H-50 and 60), 1.01 (s,
0.92£3H, CH3), 1.12 (s, 0.08£3H, CH3), 1.26 (s, 0.08£3H,
CH3), 1.28 (s, 0.92£3H, CH3), 1.51–1.75 (m, 1H, H-60),
1.68 (d, J¼4.3 Hz, 0.08H, H-40), 1.87–1.92 (m, 01H, H-50),
2.10 (s, 03H, A0c), 2.38 (d, J¼4.3 Hz, 0.92H, H-4 ), 3.29 (s,
2H, H-2 and 3 ), 3.30 (s, 3H, OCH3), 3.80 (s, 3H, CO2CH3),
5.03 (d, J¼12.8 Hz, 0.08H, H-4), 5.13 (d, J¼12.8, 0.92H,
H-4), 5.40 (d, J¼12.8 Hz, 0.92H, H-4), 5.56 (d, J¼12.8 Hz,
0.08H, H-4), 6.55 (s, 0.08H, H-2), 6.67 (s, 0.92H, H-2). 13C
NMR (125 MHz) (major) d: 11.83, 20.66, 20.70, 21.15,
28.64, 33.02, 45.67, 47.27, 51.41, 52.22, 55.80, 61.11,
73.18, 90.83, 125.97, 157.99, 164.33, 169.94. IR 2956 (CH),
1749 (CvO), 1740 (CvO), 1030 (SvO). MS (FAB) m/z:
373 (MHþ). HRMS (FAB) calcd for C18H29O6S (MHþ):
373.1685. Found: 373.1684.
4.3.5. Methyl (E)-3-[[(1R,2S,3R)-2-methoxybornane-3-
yl]sulfinyl]propenoate (26e). Pale yellow oil. 1H NMR
(300 MHz) d: 0.81 (s, 0.15£3H, CH3), 0.87 (s, 0.85£3H,
CH3), 1.01 (s, 0.15£3H, CH3), 1.03 (s, 0.85£3H, CH3),
1.04–1.12 (m, 2H, H-50 and 60), 1.26 (s, 0.15£3H, CH3),
1.30 (s, 0.85£3H, CH3), 1.45–1.57 (m, 1H, H-60), 1.84–
1.92 (m, 1.15H, H-40 and 50), 2.42 (d, 0J¼4.40Hz, 0.85H,
H-40), 3.07 (d, J¼8.1 Hz, 0.15H, H-2 or 3 ), 3.09 (d,
J¼8.1 Hz0, 0.85H, H-20 or 30), 3.40 (d, J¼8.1 Hz, 0.85H,
H-20 or 3 ), 3.45 (s, 0.85£3H, OCH3), 3.51 (d, J¼8.1 Hz,
0.15H, H-20 or 30), 3.55 (s, 0.15£3H, OCH3), 3.81 (s, 3H,
CO2CH3), 6.66 (d, J¼5.1 Hz, 0.15H, H-2), 6.71 (d,
J¼5.5 Hz, 0.85H, H-2), 7.78 (d, J¼4.9, 0.15H, H-3), 7.85
(d, J¼5.1, 0.85H, H-3). 13C NMR (125 MHz) (major): d:
11.77, 20.28, 21.30, 28.32, 32.78, 45.94, 47.42, 51.39,
52.20, 60.98, 75.85, 90.39, 124.67, 152.16, 164.87. IR 2954
(CH), 1724 (CvO), 1057 (SvO). MS (FAB) m/z: 301
(MHþ). HRMS (FAB) calcd for C15H25O4S (MHþ):
301.1474. Found: 301.1487.
4.3.3. Methyl (E)-4-(tert-butyldimethylsilyloxy)-3-
[[(1R,2S,3R)-2-methoxybornane-3-yl]sulfinyl]-2-buteno-
ate (26c). Compound (Ss)-26c. Pale yellow powder. Mp
63.0–65.58C. [a]D28¼234.4 (c 1.03, CHCl3). 1H NMR
(500 MHz) d: 0.14 (s, 3H, SiCH3), 0.15 (s, 3H, SiCH3), 0.83
(s, 3H, CH3), 0.87–1.05 (m, 2H, H-50and 60), 0.92 (s, 9H,
Sit-Bu), 0.93 (s, 3H, CH3), 1.24 (s, 3H, CH3), 1.49–1.56 (m,
1H,0H-60), 1.72–1.93 (m, 1H, H-50), 2.27 (d, J¼4.2 Hz, 1H,
H-4 ), 3.31 (d, J¼8.0 Hz, 1H, H-20 or 300), 3.30 (s, 3H,
OCH3), 3.62 (d, J¼8.0 Hz, 1H, H-20 or 3 ), 3.78 (s, 3H,
CO2CH3), 4.76 (d, J¼13.0 Hz, 1H, H-4), 5.11 (d,
J¼13.0 Hz, 1H, H-4), 6.47 (s, 1H, H-2). 13C NMR
(125 MHz) d: 25.63, 25.46, 11.40, 18.17, 20.88, 21.14,
25.73 (3C), 28.92, 32.88, 45.11, 47.20, 50.93, 51.74, 54.88,
61.22, 70.31, 91.02, 123.32, 161.53, 164.56. IR 2954 (CH),
1718 (CvO), 1024 (SvO). MS (FAB) m/z: 445 (MHþ).
HRMS (FAB) calcd for C22H41O5SSi (MHþ): 445.2444.
Found: 445.2475. Anal. calcd for C22H40O5SSi: C, 59.42;
H, 9.07; S, 7.21. Found: C, 59.73; H, 8.96; S, 6.87.
4.3.6. Ethyl (E)-3-[[(1R,2S,3R)-2-methoxybornane-3-
1
yl]sulfinyl]-2-butenoate (26f). Pale yellow oil. H NMR
(500 MHz) d: 0.77 (s, 0.1£3H, CH3), 0.85 (s, 0.9£3H, CH3),
0.98 (s, 0.1£3H, CH3), 1.00 (s, 0.9£3H, CH3), 0.97–1.10
(m, 2H, H-50 and 60), 1.26 (s, 0.1£3H, CH3), 1.30 (s,
Compound (Rs)-26c. Pale yellow oil. [a]2D8¼þ6.6 (c 1.05,
1
CHCl3). H NMR (500 MHz) d: 0.12 (s, 3H, SiCH3), 0.13
(s, 3H, SiCH3), 0.77 (s, 3H, CH3), 0.90 (s, 9H, Sit-Bu), 0.97

9904
N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
0.9£3H, CH3), 1.30 (t, J¼7.0 Hz, 3H, CH2CH3), 1.50–1.58
(m, 1H, H-60), 1.73–1.95 (m, 1.1H, H-40 and 50), 2.37 (d,
J¼1.8 Hz, 0.1£3H, H-4), 2.39 (d, J¼4.3 Hz, 0.9H, H-4),
2.39 (d, J0¼1.2 Hz, 0.9£3H, H-4), 3.00 (d, 0J¼7.3 Hz, 0.1H,
H-20 or 3 ), 3.15 (d, J¼7.9 Hz, 0.9H, H-2 or 30), 3.24 (d,
J¼7.9 Hz, 0.9H, H-20 or 30), 3.27 (s, 0.9£3H, OCH3), 3.49
(d, J¼7.3 Hz, 0.1H, H-20 or 30), 3.54 (s, 0.1£3H, OCH3),
4.23 (q, J¼7.0 Hz, 2H, CH2CH3), 6.33 (d, J¼1.8 Hz,
0.1H, H-2), 6.45 (d, J¼1.2 Hz, 0.9H, H-2). 13C NMR
(125 MHz) (major): d: 10.48, 11.77, 14.16, 20.56, 21.09,
28.53, 32.96, 45.61, 47.27, 51.51, 60.62, 61.16, 71.61,
90.70, 121.54, 161.69, 164.97. IR 2956 (CH), 1718 (CvO),
1035 (SvO). MS (FAB) m/z: 329 (MHþ). HRMS
(FAB) calcd for C17H29O4S (MHþ): 329.1787. Found:
329.1793.
CH3), 1.35 (s, 3H, CH3), 1.50–1.64 (m, 1H, H-60), 1.86–
2.04 (m, 1H, H-50), 2.48 (d, J¼4.6 Hz, 1H, H-40), 3.38 (s,
3H, OCH3), 3.44 (d, J¼8.2 Hz, 1H, H-20 or 30), 3.48 (d,
J¼8.2 Hz, 1H, H-20 or 30), 5.01 (dd, J¼17.7, 1.7 Hz, 1H,
H-4), 5.09 (dd, J¼17.7, 1.7 Hz, 1H, H-4), 6.52 (t, J¼1.7 Hz,
1H, H-2). 13C NMR (125 MHz) d: 12.38, 20.06, 21.25,
28.18, 32.88, 45.56, 47.39, 51.87, 60.90, 69.65, 74.07,
90.51, 120.98, 170.27, 174.41. IR 2951 (CH), 1747 (CvO)
1053 (SvO). MS (FAB) m/z: 299 (MHþ). HRMS (FAB)
calcd for C15H23O4S (MHþ): 299.1317. Found: 299.1317.
Anal. calcd for C15H22O4S: C, 60.38; H, 7.43; S, 10.75.
Found: C, 60.31; H, 7.27; S, 10.63.
4.3.9. 4-[(Rs)-[(1R,2S,3R)-2-methoxybornane-3-yl]sul-
finyl]-5H-furan-2-one [(Rs)-27]. In a manner similar to
that described for (Ss)-27, the ester (Rs)-26c (150 mg,
0.34 mmol) was converted into (Rs)-27 (78 mg, 77%) as a
pale yellow oil. Mp 174.0–176.08C (diisopropyl ether).
[a]2D8¼211.7 (c 1.01, CHCl3). 1H NMR (500 MHz) d: 0.80
(s, 3H, CH3), 1.01 (s, 3H, CH3), 1.04–1.16 (m, 2H, H-50 and
60), 1.08 (s, 3H, CH3), 1.56–1.61 (m, 1H, H-60), 1.59 (d,
J¼4.3 Hz, 1H, H-40), 1.80–1.87 (m, 1H, H-50), 3.29 (d,
J¼7.3 Hz, 1H, H-20 or 30), 3.54 (s, 3H, OCH3), 3.56 (d,
J¼7.3 Hz, 1H, H-20 or 30), 5.05 (dd, J¼18.3, 1.8 Hz, 1H,
H-4), 5.29 (dd, J¼18.3, 1.8 Hz, 1H, H-4), 6.40 (t, J¼1.8 Hz,
1H, H-2). 13C NMR (125 MHz) d: 10.99, 20.47, 21.63,
28.25, 32.49, 46.99, 49.30, 50.93, 62.22, 69.68, 76.64,
90.10, 122.05, 170.26, 171.50. IR 2956 (CH), 1751 (CvO),
1055 (SvO). Anal. calcd for C15H22O4S: C, 60.38; H, 7.43;
S, 10.75. Found: C, 60.28; H, 7.32; S, 10.59.
4.3.7. 4-Nitrobenzyl (E)-4-benzyloxy-3-[[(1R,2S,3R)-2-
methoxybornane-3-yl]sulfinyl]-2-butenoate (26g). Com-
pound (Ss)-26g. Pale yellow oil. [a]2D5¼27.3 (c 0.93,
1
CHCl3). H NMR (300 MHz) d: 0.81 (s, 3H, CH3), 0.86–
0.99 (m, 2H, H-50 and 60), 0.94 (s, 3H, CH3), 1.22 (s, 3H,
CH3), 1.41–1.51 (m, 1H, H-60), 1.77–1.86 (m, 1H, H-50),
2.27 (d, J¼4.4 Hz, 1H, H-40), 3.19 (d, J¼8.1 Hz, 1H,0H-20 or
30), 3.24 (s, 3H, OCH3), 3.44 (d, J¼8.0 Hz, 1H, H-2 or 30),
4.54 (d, J¼11.6 Hz, 1H, CH2Ph), 4.62 (d, J¼11.6 Hz, 1H,
CH2Ph), 4.72 (dd, J¼12.8, 0.9 Hz, 1H, H-4), 4.89 (dd,
J¼12.8, 0.9 Hz, 1H, H-4), 5.29 (s, 2H, CO2CH2Ar), 6.66 (s,
1H, H-2), 7.27–7.38 (m, 5H, Ar-H), 7.51 (d, J¼8.8 Hz, 2H,
Ar-H), 8.21 (d, J¼8.8 Hz, 2H, Ar-H). 13C NMR (125 MHz):
d: 11.53, 21.02, 21.08, 28.69, 32.86, 45.02, 47.24, 50.94,
61.07, 62.24, 65.11, 71.29, 73.47, 90.96, 122.88, 123.77,
127.85 (2C), 128.02 (2C), 128.29 (2C), 128.43 (2C), 137.29,
142.54, 147.74, 162.18, 163.73. IR 2954 (CH), 1724
(CvO), 1522 (NvO), 1346 (NvO), 1022 (SvO). MS
(FAB) m/z: 542 (MHþ). HRMS (FAB) calcd for
C29H36NO7S (MHþ): 542.2212. Found: 542.2222.
4.3.10. (1R,2S,3R)-2-methoxybornane-3-thiol (28). Acetic
acid (0.60 mL, 9.52 mmol) was added to a mixture of 21
(466 mg, 1.17 mmol) and Zn (900 mg, 13.8 mmol) in
toluene (5 mL) with stirring at 1108C for 4 h. After cooling,
the mixture was filtrated and the solid was rinsed with
AcOEt. The combined filtrates were washed with water and
brine prior to drying and solvent evaporation. The residue
was chromatographed on silica gel with hexane–AcOEt
Compound (Rs)-26g. Pale yellow oil. 1H NMR (300 MHz)
d: 0.74 (s, 3H, CH3), 0.88–1.01 (m, 2H, H-50 and 60), 0.97
(s, 3H, CH3), 1.05 (s, 3H, CH3), 1.42–1.65 (m, 2H, H-50 and
60), 01.82 0(d, J¼4.0 Hz, 1H, H-40), 3.10 (d, J¼7.3 Hz, 1H,
H-2 or 3 ), 3.43 (d, J¼7.7 Hz, 1H, H-20 or 30), 3.53 (s, 3H,
OCH3), 4.57 (s, 2H, CH2Ph), 4.64 (dd, J¼13.4, 1.1 Hz, 1H,
H-4), 4.87 (dd, J¼13.4, 1.1 Hz, 1H, H-4), 5.27 (s, 2H,
CO2CH2Ar), 6.63 (t, J¼1.1 Hz, 1H, H-2), 7.21–7.36 (m,
5H, Ar-H), 7.50 (d, J¼8.8 Hz, 2H, Ar-H), 8.20 (d,
J¼8.8 Hz, 2H, Ar-H). IR 2954 (CH), 1720 (CvO), 1527
(NvO), 1348 (NvO), 1034 (SvO). MS (FAB) m/z: 542
(MHþ). HRMS (FAB) calcd for C29H36NO7S (MHþ):
542.2212. Found: 542.2197.
1
(99:1) to give 28 (343 mg, 73%) as a colorless oil. The H
NMR data was identified with the reported data.17
[a]2D6¼279.9 (c 1.03, CHCl3).
4.3.11. Methyl (Z)-4-benzyloxy-3-[[(1R,2S,3R)-2-meth-
oxybornane-3-yl]thio]-2-butenoate [(Z)-29] and methyl
(E)-4-benzyloxy-3-[[(1R,2S,3R)-2-methoxybornane-3-
yl]thio]-2-butenoate [(E)-29]. Et3N (0.17 mL, 1.20 mmol)
was added to a solution of 28 (200 mg, 1.00 mmol) and
methyl 4-benzyloxy-2-butynoate (204 mg, 1.00 mg) in
MeOH (5 mL) with stirring at room temperature. The
stirring was continued at this temperature overnight. The
mixture was diluted with AcOEt, and washed with water
and brine prior to drying and solvent evaporation. The
residue was chromatographed on silica gel with hexane–
AcOEt (97:3) to give (Z)-29 (270 mg, 67%) and (E)-29
(126 mg, 31%) each as a colorless oil. (Z)- 29: [a]2D6¼þ1.7
(c 1.01, CHCl3). 1H NMR (300 MHz) d: 0.76 (s, 3H, CH3),
0.91 (s, 3H, CH3), 0.94–1.08 (m, 2H, H-50 and 60), 1.14 (s,
3H, CH3), 1.42–1.53 (m, 1H, H-60), 1.65–1.75 (m, 2H, H-40
and 50), 3.17 (d, J¼7.5 Hz, 1H, H-200 or 300), 3.37 (s, 3H,
OCH3), 3.65 (d, J¼7.5 Hz, 1H, H-2 or 3 ), 3.72 (s, 3H,
CO2CH3), 4.23 (d, J¼13.6 Hz, 1H, CH2Ph), 4.30 (d,
J¼13.6 Hz, 1H, CH2Ph), 4.56 (d, J¼1.6 Hz, 2H, H-4),
4.3.8. 4-[(Ss)-[(1R,2S,3R)-2-methoxybornane-3-yl]sul-
finyl]-5H-furan-2-one [(Ss)-27]. A mixture of (Ss)-26c
(150 mg, 0.34 mmol) and TFA-water (9:1) (1 mL) in
CH2Cl2 (2 mL) was stirred at room temperature for 4
days. Water was added to the mixture and the mixture was
extracted with AcOEt. The extract was washed with water
and brine prior to drying and solvent evaporation. The
residue was chromatographed on silica gel with hexane–
AcOEt (3:2) to give (Ss)-27 (78 mg, 77%) as a colorless
needles. Mp 196.0–198.08C (diisopropyl ether).
1
[a]2D8¼þ106 (c 1.00, CHCl3). H NMR (300 MHz) d: 0.89
(s, 3H, CH3), 1.03–1.14 (m, 2H, H-50 and 60), 1.08 (s, 3H,

N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
9905
6.05 (t, J¼1.6 Hz, 1H, H-2), 7.28–7.39 (m, 5H, Ar-H). 13
C
4.3.13. Methyl (E,Rs)-4-benzyloxy-3-[[(1R,2S,3R)-2-
methoxybornane-3-yl]sulfinyl]-2-butenoate [(E,Rs)-29]
and methyl (E,Ss)-benzyloxy-3-[[(1R,2S,3R)-2-methoxy-
bornane-3-yl]sulfinyl]-2-butenoate [(E,Ss)-29]. In a man-
ner similar to that described for 1, the sulfide (E)-29 (60 mg,
0.15 mmol) was converted into (E,Rs)-26a (30 mg, 48%)
and (E,Ss)-26a (13 mg, 21%) each as a colorless oil. The
data of these compounds were identified with those of the
corresponding products synthesized by sylfinylzincation.
NMR (125 MHz) d: 11.67, 21.12, 21.28, 28.25, 33.41,
47.23, 50.27, 50.72, 50.91, 53.20, 61.16, 71.97, 72.22,
91.53, 112.31, 127.82 (3C), 128.42 (2C), 137.29, 156.92,
166.22. IR 2948 (CH), 1709 (CvO). MS (FAB) m/z: 405
(MHþ). HRMS (FAB) calcd for C23H33O4S (MHþ):
405.2100. Found: 405.2075.
Compound (E)-29. [a]2D2¼215.5 (c 1.34, CHCl3). 1H NMR
(300 MHz) d: 0.80 (s, 3H, CH3), 0.95 (s, 3H, CH3), 1.10–
1.25 (m, 2H, H-50 and 60), 1.15 (s, 3H, CH3), 1.53–1.61 (m,
1H, H-60), 1.80–1.89 (m, 2H, H-40 and 50), 3.28 (d,
J¼7.7 Hz, 1H, H-20 or 30), 3.33 (d, J¼7.7 Hz, 1H, H-20 or
30), 3.41 (s, 3H, OCH3), 3.67 (s, 3H, CO2CH3), 4.59 (s, 2H,
CH2Ph), 4.85 (d, J¼1.3 Hz, 2H, H-4), 5.45 (t, J¼1.3 Hz,
1H, H-2), 7.24–7.41 (m, 5H, Ar-H). 13C NMR (125 MHz)
d: 11.51, 20.64, 21.25, 28.40, 33.47, 47.23, 50.26, 50.58,
50.88, 53.23, 61.57, 69.54, 72.95, 91.25, 108.16, 127.57,
127.86 (2C), 128.26 (2C), 137.93, 163.82, 165.19. IR 2949
(CH), 1705 (CvO). MS (FAB) m/z: 405 (MHþ). HRMS
(FAB) calcd for C23H33O4S (MHþ): 405.2100. Found:
405.2108.
4.4. X-Ray analysis
Crystal data for (Rs)-27. C15H22O4S, M¼298.39, ortho-
rhombic, space group P212121, a¼12.520(6), b¼14.047(6),
3
˚
˚
c¼8.703(6) A, volume¼1530.5(14) A , Z¼4, Dc¼
1.295 g cm23, m¼1.973 mm21, crystal dimensions 0.5£
0.3£0.2 mm3, F(000)¼640, T¼293(2) K, u¼4.73–67.338.
1513 reflections measured, unique reflections 1510
[Rint¼0.0797], min and max. Absorption correction factor
0.816 and 1.000, R1¼0.0566, wR2¼0.1067 for 1331
reflections with I.2s(I) and R1¼0.0701, wR2¼0.1737 for
all reflections and 186 refined parameters. Final electron
density 0.433 and 20.433 e A23, S¼1.898, absolute Flack
˚
4.3.12. Methyl (Z,Rs)-4-benzyloxy-3-[[(1R,2S,3R)-2-
methoxybornane-3-yl]sulfinyl]-2-butenoate [(Z,Rs)-26a]
and methyl (Z,Ss)-benzyloxy-3-[[(1R,2S,3R)-2-methoxy-
structure parameter 0.08(6).
The data set was collected on a Rigaku AFC5R diffract-
˚
bornane-3-yl]sulfinyl]-2-butenoate [(Z,Ss)-26a]. In
a
ometer with Cu·Ka radiation (l¼1.5418 A). The structure
manner similar to that described for 1, the sulfide (Z)-29
(150 mg, 0.37 mmol) was converted into (Z,Rs)-26a
(106 mg, 68%) and (Z,Ss)-26a (41 mg, 27%) each as a
colorless oil. (Z,Rs)-26a: [a]2D8¼þ53.7 (c 1.27, CHCl3). 1H
NMR (300 MHz) d: 0.73 (s, 3H, CH3), 0.86–1.20 (m, 2H,
H-50 and 60), 0.97 (s, 3H, CH3), 1.11 (s, 3H, CH3), 1.48 (td,
J¼12.2, 3.7 Hz, 1H, H-60), 1.58 (d, J¼4.0 Hz, 1H,0 H-400),
1.61–1.72 (m, 1H, H-50), 3.25 (d, J¼7.5 Hz, 1H, H-2 or 3 ),
3.43 (d, J¼7.5 Hz, 1H, H-20 or 30), 3.50 (s, 3H, OCH3), 3.76
(s, 3H, CO2CH3), 4.50 (dd, J¼14.9, 1.5 Hz, 1H, H-4), 4.57
(dd, J¼14.9, 1.5 Hz, 1H, H-4), 4.56 (d, J¼11.9 Hz, 1H,
CH2Ph), 4.63 (d, J¼11.9 Hz, 1H, CH2Ph), 6.60 (t,
J¼1.5 Hz, 1H, H-2), 7.27–7.39 (m, 5H, Ar-H). 13C NMR
(75 MHz) d: 11.22, 20.64, 21.66, 28.46, 32.50, 46.89, 48.28,
50.62, 51.95, 61.97, 63.78, 72.89, 73.05, 90.50, 124.90,
127.68 (2C), 127.86, 128.39 (2C), 137.16, 156.00, 164.07.
IR 2953 (CH), 1728 (CvO), 1028 (SvO). MS (FAB) m/z:
421 (MHþ). HRMS (FAB) calcd for C23H33O5S (MHþ):
421.2049. Found: 421.2049.
was solved by direct methods using SHELX-9718 and
refined by full matrix least squares on F 2 by SHELXL-97.19
Non-hydrogen atoms were refined by anisotropic tempera-
ture factor and hydrogens were isotropic. The hydrogens
were placed by riding method. The molecular views were
realized by ORTEP-III.20
Crystal and data collections parameters were deposited with
the Cambridge Crystallographic Data Center. The data will
be sent on quoting the CCDC-213314 number (e-mail:
deposit@ccdc.cam.ac.uk).
References
1. Carren˜o, M. C. Chem. Rev. 1995, 95, 1717–1760.
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`
M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolo, F.
1
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J¼4.4 Hz, 1H, H-4 ), 3.25 (s, 2H, H-2 and 30), 3.31 (s, 3H,
OCH3), 3.76 (s, 3H, CO2CH3), 4.44 (dd, J¼14.9, 1.5 Hz,
1H, H-4), 4.58 (d, J¼11.7 Hz, 1H, CH2Ph), 4.66 (d,
J¼11.7 Hz, 1H, CH2Ph), 4.67 (dd, J¼14.9, 1.5 Hz, 1H,
H-4), 6.49 (t, J¼1.5 Hz, 1H, H-2), 7.29–7.39 (m,
5H, Ar-H). 13C NMR (75 MHz) d:11.36, 21.05, 21.21,
28.94, 32.75, 45.73, 47.39, 50.52, 51.90, 61.29, 64.75,
73.12, 73.47, 91.24, 122.45, 127.74 (2C), 127.97, 128.49
(2C), 137.32, 159.70, 164.47. IR 2950 (CH), 1716 (CvO),
1030 (SvO). MS (FAB) m/z: 421 (MHþ). HRMS
(FAB) calcd for C23H33O5S (MHþ): 421.2049. Found:
421.2013.
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N. Maezaki et al. / Tetrahedron 59 (2003) 9895–9906
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