Stereospecific alkyl and alkynyl substitution reactions of epoxy sulfides with organoaluminums with double inversion of the configuration

Article abstract of DOI:10.1021/jo010240c

A regioselective and stereospecific substitution reaction of 1-(phenylthio)-2,3-epoxyalkanes was achieved by using organoaluminum reagents as a nucleophile. Under the influence of trimethylor triethylaluminum, a 1-(phenylthio)-2,3-epoxyalkane underwent substitution at the C2 position to give a product with retention of the configuration. The reaction proceeds through an episulfonium ion intermediate, which gives rise to the C2-substitution products with double inversion of the configuration. Introduction of an alkynyl group was also accomplished by the reaction with dimethyl[2-(trimethylsilyl)ethynyl] aluminum in dichloromethane.

Full text of DOI:10.1021/jo010240c

5388
J . Org. Chem. 2001, 66, 5388-5394
Ster eosp ecific Alk yl a n d Alk yn yl Su bstitu tion Rea ction s of Ep oxy
Su lfid es w ith Or ga n oa lu m in u m s w ith Dou ble In ver sion of th e
Con figu r a tion
Minoru Sasaki, Keiji Tanino, and Masaaki Miyashita*
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, J apan
miyasita@sci.hokudai.ac.jp
Received March 5, 2001
A regioselective and stereospecific substitution reaction of 1-(phenylthio)-2,3-epoxyalkanes was
achieved by using organoaluminum reagents as a nucleophile. Under the influence of trimethyl-
or triethylaluminum, a 1-(phenylthio)-2,3-epoxyalkane underwent substitution at the C2 position
to give a product with retention of the configuration. The reaction proceeds through an episulfonium
ion intermediate, which gives rise to the C2-substitution products with double inversion of the
configuration. Introduction of an alkynyl group was also accomplished by the reaction with dimethyl-
[2-(trimethylsilyl)ethynyl]aluminum in dichloromethane.
Sch em e 1
In tr od u ction
Stereoselective, epoxide-opening reactions have been
recognized as an important transformation in organic
synthesis and are widely used as the key step in natural-
product synthesis.1 Although a variety of regio- and/or
stereoselective reactions via an SN2 process have been
reported so far, the stereospecific alkyl substitution
reaction of epoxides, which proceeds with retention of the
configuration, is scarcely known. On the other hand, in
connection with our studies on the reactions of epoxides
with trialkylaluminums described previously,2 we were
intrigued by the effects of neighboring-group participa-
tion in this type of reaction. We chose 1-(phenylthio)-2,3-
epoxyalkanes as substrates with the goal of inducing
stereospecific substitution reactions with retention of the
configuration as shown in Scheme 1. We envisioned that
a trialkylaluminum would initially act as a Lewis acid
to yield an episulfonium ion intermediate3,4 that would
have an aluminum ate-complex moiety that, in turn,
would undergo the intramolecular migration of the alkyl
group. The reaction, which involves double inversion of
the configuration at the C2 position, should give the
substitution product in a regioselective manner with
retention of the configuration.
J ust when we started experiments based on this
concept, however, Saigo et al. reported the reactions of
1-(phenylthio)-2,3-epoxyalkanes with organoaluminum
reagents.5 They described that the epoxides essentially
undergo substitution reactions at the C2 position with
double inversion of the configuration, which is consistent
with the reaction mechanism involving episulfonium ions.
Through our independent studies, however, we found
that the efficiency in this type of reaction is highly
dependent on the reaction conditions. In certain cases,
the regioselectivity of the C-C bond-formation reaction
can be dramatically changed by employing different
(1) For reviews, see: (a) Posner, G. H. Org. React. 1975, 22, 253-
400. (b) Lipshutz, B. H.; Sengupta, S. Org. React. 1992, 41, 135-631.
(c) Bonini, C.; Righi, G. Synthesis 1994, 225-238.
(2) (a) Miyashita, M.; Shiratani, T.; Kawamine, K.; Hatakeyama,
S.; Irie, H. J . Chem. Soc., Chem. Commun. 1996, 1027-1028. (b)
Miyazawa, M.; Ishibashi, N.; Ohnuma, S.; Miyashita, M. Tetrahedron
Lett. 1997, 38, 3419-3422. (c) Ishibashi, N.; Miyazawa, M.; Miyashita,
M. Tetrahedron Lett. 1998, 39, 3775-3778. (d) Abe, N.; Hanawa, H.;
Maruoka, K.; Sasaki, M.; Miyashita, M. Tetrahedron Lett. 1999, 40,
5369-5372. (e) Hayakawa, H.; Miyashita, M. J . Chem. Soc., Perkin
Trans. 1 1999, 3399-3401.
6
solvents. We report herein our results in detail.
Resu lts a n d Discu ssion
(3) For examples of synthetic reactions via episulfonium ions, see:
(a) Kudo, K.; Saigo, K.; Hashimoto, Y.; Saito, K.; Hasegawa, M. Chem.
Lett. 1992, 1449-1452. (b) Kudo, K.; Hashimoto, Y.; Houchigai, H.;
Hasegawa, M.; Saigo, K. Bull. Chem. Soc. J pn. 1993, 66, 848-856. (c)
Kudo, K.; Hashimoto, Y.; Sukegawa, M.; Hasegawa, M.; Saigo, K. J .
Org. Chem. 1993, 58, 579-587. (d) Liu, C.; Kudo, K.; Hashimoto, Y.;
Saigo, K. J . Org. Chem. 1996, 61, 494-502.
(4) For examples of sulfur-directed ring-opening reactions of ep-
oxides, see: (a) Miyauchi, H.; Nakamura, T.; Ohashi, N. Bull. Chem.
Soc. J pn. 1995, 68, 1731-1737. (b) Miyauchi, H.; Ohashi, N. Bull.
Chem. Soc. J pn. 1995, 68, 3591-3598. (c) Gill, D. M.; Pegg, N. A.;
Rayner, C. M. Tetrahedron 1996, 52, 3609-3630.
Th e Alk yl Su bstitu tion Rea ction s of Disu bstitu t-
ed 1-(P h en ylth io)-2,3-ep oxya lk a n es w ith Tr ia lk yl-
a lu m in u m s. Saigo et al. reported that treatment of cis-
1-(phenylthio)-2,3-epoxyhexane (1a ) with trialkylalumi-
(5) Liu, C.; Hashimoto, Y.; Kudo, K.; Saigo, K. Bull. Chem. Soc. J pn.
1996, 69, 2095-2105.
(6) For a preliminary report of a part of this work, see: Sasaki, M.;
Miyazawa, M.; Tanino, K.; Miyashita, M. Tetrahedron Lett. 1999, 40,
9267-9270.
10.1021/jo010240c CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/11/2001

Substitution Reactions of Epoxy Sulfides
J . Org. Chem., Vol. 66, No. 16, 2001 5389
Ta ble 1. Alk yl Su bstitu tion Rea ction of cis-Ep oxy
nums in hexane at 0 °C induced alkyl substitution
reactions with double inversion of the configuration (eqs
1 and 2).5
Su lfid es
a
b
All products were obtained as a single isomer. Isolated yield.
While the methylation product was obtained in a high
yield, however, the reaction with triethylaluminum re-
sulted in formation of a nearly 1:1 mixture of the desired
product and the reduction product.
Ta ble 2. Alk yl Su bstitu tion Rea ction of tr a n s-Ep oxy
Su lfid es
We first examined the solvent effects on the reaction
of 1-(phenylthio)-2,3-epoxyalkanes with trialkylalumi-
nums, and the use of dichloromethane as a solvent was
found to accelerate the reaction rate remarkably. For
example, when a 0.1 M dichloromethane solution of trans-
4-benzyloxy-2,3-epoxy-1-(phenylthio)butane (2b ) was
treated with trimethylaluminum (2 M hexane solution,
3 equiv) at -78 °C for 10 min, the reaction was almost
completed and the desired methylation product, with
double inversion of the configuration, was obtained in a
93% yield. However, the same reaction in hexane gave
only a 7% yield of the product, and a large amount of
the starting material was recovered unchanged (eq 3).
a
b
All products were obtained as a single isomer. Isolated yield.
carbon atoms is extremely important in organic synthe-
sis, particularly in natural-product synthesis.8 Although
considerable efforts have been devoted to the construction
of quaternary carbon atoms, including asymmetric ones,
stereospecific methods are rather limited. Particularly,
a methodology involving double inversion of the config-
uration has not yet been developed. With the excellent
results (shown above) in hand, we envisioned that the
reaction of trisubstituted epoxide, namely, 2-alkyl-1-
(phenylthio)-2,3-epoxyalkanes with trialkylaluminums,
might proceed stereospecifically to provide alkyl substitu-
tion products that have a quaternary carbon atom at the
C2 position. Indeed, we found that the reaction of various
2-alkyl-1-(phenylthio)-2,3-epoxyalkanes with trimethyl-
aluminum in dichloromethane did occur via episulfonium
ions as summarized in Table 3. As can be seen from this
table, all the reactions of trisubstituted trans-epoxy
sulfides with trimethylaluminum proceeded cleanly, giv-
ing rise to products bearing a quaternary carbon atom
at the C2 position in excellent yields (>90%; entries 2,
4, and 6). Similarly, the reactions of the corresponding
cis analogues occurred regioselectively, though their
chemical yields decreased in comparison with those of
the trans analogues (entries 1, 3, and 5). The stereo-
chemistry of products 18a and 18b that have an asym-
metric quaternary carbon atom was unambiguously
confirmed by identification with an authentic sample that
was prepared by our recent method employing γ-alkyl-
γ,δ-epoxy-R,â-unsaturated esters with trialkylaluminum.2c
These results demonstrate that the reaction of 2-alkyl-
Similarly, the reaction of 1a with triethylaluminum
occurred smoothly in a mixture of dichloromethane and
hexane at -30 °C to give the corresponding ethylation
product in a high yield without the formation of an
undesired reduction product. These remarkable solvent
effects may be rationalized by the following consider-
ations: (1) Deoligomerization of organoaluminum re-
agents is accelerated more in dichloromethane than in
hexane to generate the more reactive organoaluminum
species as a Lewis acid and an alkylating agent. (2) The
intermediary episulfonium ions may be effectively sta-
bilized in the more-polar solvent dichloromethane than
in the less-polar hexane.
The reactions of various disubstituted 1-(phenylthio)-
2,3-epoxyalkanes with trialkylaluminums in the same
solvent system are summarized in Tables 1 and 2. As
can be seen from these tables, all the reactions proceeded
stereospecifically with double inversion of the configu-
ration to give the corresponding C2-substitution products
in excellent yields.7 For the reactions of trans-epoxy
sulfides in Table 2, Saigo has already reported similar
results that were obtained using hexane as a solvent.5
Th e R ea ct ion of Tr isu b st it u t ed E p oxy Su lfid es
with Tr im eth ylalu m in u m : Ster eospecific Con str u c-
tion of Asym m etr ic Qu a ter n a r y Ca r bon Atom s.
Stereoselective construction of asymmetric quaternary
(8) For reviews, see: (a) Martin, S. F. Tetrahedron 1980, 36, 419-
460. (b) Fuji, K. Chem. Rev. 1993, 93, 2037-2066. (c) Corey, E. J .;
Guzman-Perez, A. Angew. Chem., Int. Ed. Engl. 1998, 37, 388-401.
(7) The stereochemistry of the products was confirmed by compari-
son with that of authentic samples (see ref 5).

5390 J . Org. Chem., Vol. 66, No. 16, 2001
Ta ble 3. Alk yl Su bstitu tion Rea ction of Tr isu bstitu ted Ep oxy Su lfid es w ith Me3Al
Sasaki et al.
a
Epoxides were treated with 3 equiv of Me3Al in CH2Cl2.
Sch em e 2
Ta ble 4
2,3-epoxysulfides with trimethylaluminum occurred ste-
reospecifically via the corresponding episulfonium ions,
i.e., with double inversion of the configuration. Unfortu-
nately, the use of triethylaluminum was found to give a
1:1 mixture of the desired product and the reduction
product even in the reaction in dichloromethane, pre-
sumably due to severe steric hindrance at the C2 position.
Thus, a new stereospecific methodology for the construc-
tion of asymmetric quaternary carbon atoms with double
inversion of the configuration has been developed, though
it is limited to the use of trimethylaluminum.
entry solvent
R
conditions
19:20 yield (%)
1
2
3
4
5
hexane Et
hexane Et
toluene Et
CH2Cl2 Et
0 °C, 2 h
-78 °C, 2 h
10:90
30:70
78
63
66
62
71
-78 to ca. -50 °C, 5 h 30:70
-78 °C, 1 h
60:40
70:30
CH2Cl2 Me -78 °C, 10 min
a). From these results, it seemed that the more reactive
alkynylaluminum reagents attack the C1 position more
preferentially than do the corresponding trialkylalumi-
num reagents.
Th e Su bstitu tion Rea ction of Ep oxy Su lfid es w ith
Alk yn yla lu m in u m Rea gen ts. Alkynylaluminum re-
agents, which can be easily prepared from the corre-
sponding alkynyllithium and dialkylaluminum chloride,9
have found widespread use in organic synthesis. Inter-
estingly, Saigo et al. have reported that a reaction that
uses an alkynylaluminum reagent showed unique fea-
tures that contrast nicely with those of reactions with
trimethylaluminum (Scheme 2).5 Thus, the reaction
mainly proceeded through migration of the phenylthio
group followed by alkynylation at the C1 position (path
b), while the desired compound, having an alkynyl group
at the C2 position, was obtained as a minor product (path
To explore the synthetic potential of the alkynyl
substitution reaction via episulfonium ions, we investi-
gated the reaction of 1b with dialkyl(alkynyl)aluminum
reagents in detail. As a result, these reactions were found
to exhibit remarkably different regioselectivities depend-
ing on the solvent as well as on the alkynylaluminum
reagents (Table 4). When the reaction with diethyl(1-
hexynyl)aluminum in hexane was carried out at -78 °C,
the ratio of the products 19 and 20 was changed from
10:90 to 30:70 (entries 1 and 2). Although the use of
toluene showed no evident effect on the regioselectivity,
the reaction in dichloromethane caused an inversion of
the ratio to give a 60:40 mixture of 19 and 20 (entry 4).
The effect of the substituents of the aluminum reagents
(9) Zweifel, G.; Miller, J . A. Org. React. 1984, 32, 375-517.

Substitution Reactions of Epoxy Sulfides
J . Org. Chem., Vol. 66, No. 16, 2001 5391
Ta ble 5. Rea ction s of 1-(P h en ylth io)-2,3-ep oxya lk a n es w ith Dim eth yl[2-(tr im eth ylsilyl)eth yn yl]a lu m in u m a
a
b
Reactions were carried out using 3 equiv of dimethyl[2-(trimethylsilyl)ethynyl]aluminum at -78 °C for 10 to ca. 45 min. Determined
by 1H NMR spectra. c Combined isolated yield.
was also investigated, and the reaction with dimethyl-
(1-hexynyl)aluminum in the place of the corresponding
diethylaluminum reagent exhibited slightly better regi-
oselectivity (entry 5).
aldehydes.11 Therefore, the substitution reaction we
present should provide not only unique acyclic stereo-
control but also extremely useful methodologies in or-
ganic synthesis, including that of natural-product syn-
thesis.
On the other hand, the alkynyl group of an aluminum
reagent was found to have a greater influence on the
selectivity. Thus, treatment of 1-(phenylthio)-2,3-epoxy-
alkanes with dimethyl[2-(trimethylsilyl)ethynyl]alumi-
num induced a regioselective substitution at the C2
position as shown in Table 5. It should be noted that the
remarkable solvent effect was again observed in these
cases (entries 1 and 2), which indicates that the use of
dichloromethane is essential for the C2-selective substi-
tution reaction. In contrast to the reactions of trans-1-
(phenylthio)-2,3-epoxyalkanes that occurred regioselec-
tively (>d.s. 85%) at the C2 position, the corresponding
cis analogue was found to react selectively at the C1
position, giving rise to products with predominantly a
sulfenyl shift (entry 5). These results may be explained
by the steric hindrance, the same as in the reactions of
trisubstituted cis-epoxy sulfides with trimethylaluminum
(vide ante).
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were carried out under a
positive pressure of dry argon. Pyridine was distilled from
potassium hydroxide immediately before use. Anhydrous CH2-
Cl2 was purchased from the KANTO Chemical Co., Ltd. Flash
chromatography was performed using Merck silica gel. Ana-
lytical TLC was carried out on 250-µm Merck (Kiesegel 60F-
1
254) silica-gel plates. H and 13C NMR spectra were recorded
at 270 MHz (1H) using CDCl3 with tetramethylsilane as the
internal standard.
Gen er a l P r oced u r e for P r ep a r a tion of 2,3-Ep oxy-1-
a lk a n ols. To a solution of an allylic alcohol in CH2Cl2 was
added m-chloroperbenzoic acid (2 equiv) at -30 °C. After the
solution was stirred for 3-6 h, saturated aqueous (aq) Na2S2O3
and NaHCO3 were added, and the mixture was separated. The
aqueous layer was extracted with CH2Cl2, and the combined
organic layer was successively washed with saturated aq
NaHCO3 and brine and dried over MgSO4. Concentration
under reduced pressure, followed by flash column chromatog-
raphy, afforded a 2,3-epoxy-1-alkanol in a 90-95% yield.
Con clu sion
In conclusion, we have developed stereospecific alkyl
and alkynyl substitution reactions of 1-(phenylthio)-2,3-
epoxyalkanes with organoaluminum reagents, which
proceed via episulfonium ions with double inversion of
the configuration. It is noteworthy that a variety of
optically active epoxy sulfides are readily available from
the corresponding epoxy alcohols.10 Furthermore, the
products having a phenylthio group at the terminal
position can be easily transformed into the corresponding
(2R*,3R*)-2,3-Ep oxy-1-n on a n ol: IR (CHCl3) 3460, 1586,
1
1080 cm-1; H NMR (270 MHz, CDCl3) δ 0.89 (t, J ) 6.6 Hz,
3 H), 1.20-1.66 (m, 11 H), 2.90-2.98 (m, 2 H), 3.63 (ddd, J )
4.1, 7.3, 12.4 Hz, 1 H), 3.92 (ddd, J ) 2.5, 5.3, 12.4 Hz, 1 H);
13C NMR (67.8 MHz, CDCl3) δ 14.14, 22.62, 25.97, 29.12, 31.62,
31.78, 56.04, 58.46, 61.74; HRMS calcd for C9H19O2 [M + H]
159.1385, found 159.1346.
(11) De Lucchi, O.; Miotti, U.; Modena, G. Org. React. 1991, 40, 157-
405.
(12) Nakagawa, I.; Hata, T. J . Chem. Soc., Perkin Trans. 1 1983,
1315-1318.
(10) Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1-299.

5392 J . Org. Chem., Vol. 66, No. 16, 2001
Sasaki et al.
(2R*,3R*)-5-Ben zyloxy-2,3-ep oxy-1-p en ta n ol: IR (neat)
mixture by flash column chromatography afforded 2.7 g (92%)
3430, 1497, 1207, 1101, 1028, 885, 698 cm-1
;
1H NMR (270
of epoxy sulfide 2a : IR (neat) 1686, 1508, 1094, 1026, 694 cm-1
;
MHz, CDCl3) δ 1.63-1.70 (br, 1 H), 1.77-2.01 (m, 2 H), 2.98
(dt, J ) 2.5, 4.9 Hz, 1 H), 3.11 (ddd, J ) 2.3, 4.9, 6.8 Hz, 1 H),
3.58-3.67 (m, 3 H), 3.90 (ddd, J ) 2.6, 5.4, 12.5 Hz, 1 H), 4.52
(s, 2 H), 7.27-7.39 (m, 5 H); 13C NMR (67.8 MHz, CDCl3) δ
32.13, 53.72, 58.41, 61.70, 66.84, 73.10, 127.53 (2 C), 127.57,
128.32 (2 C), 138.07; HRMS calcd for C12H15O3 [M - H]
207.1021, found 207.0996.
1H NMR (270 MHz, CDCl3) δ 2.92 (dd, J ) 6.6, 13.8 Hz, 1 H),
3.12 (dd, J ) 6.0, 13.8 Hz, 1 H), 3.18-3.27 (m, 2 H), 3.42 (dd,
J ) 6.2, 11.2 Hz, 1 H), 3.48 (dd, J ) 4.1, 11.2 Hz, 1 H), 4.49
(d, J ) 11.9 Hz, 1 H), 4.58 (d, J ) 11.9 Hz, 1 H), 7.19-7.44
(m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 33.04, 54.83, 55.90,
67.71, 73.22, 126.84, 127.62 (3 C), 128.27 (2 C), 128.90 (2 C),
130.64 (2 C), 134.67, 137.49; HRMS calcd for C17H18O2S
286.1027, found 286.1052.
(2S *,3R *)-4-Be n zyloxy-2,3-e p oxy-1-(p h e n ylt h io)b u -
t a n e (2b). This compound was prepared from (2R*,3R*)-4-
benzyloxy-2,3-epoxy-1-butanol in a 92% yield: IR (neat) 1686,
1508, 1026, 908, 737 cm-1; 1H NMR (270 MHz, CDCl3) δ 2.90-
2.97 (m, 2 H involving a double doublet at 2.94, J ) 5.6, 13.2
Hz), 3.08-3.12 (m, 1 H), 3.17 (dd, J ) 4.8, 13.2 Hz, 1 H), 3.39
(dd, J ) 5.4, 11.7 Hz, 1 H), 3.61 (dd, J ) 3.0, 11.7 Hz, 1 H),
4.50 (d, J ) 12.0 Hz, 1 H), 4.53 (d, J ) 12.0 Hz, 1 H), 7.18-
7.43 (m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 36.01, 54.45,
57.52, 69.48, 73.10, 126.74, 127.53 (3 C), 128.22 (2 C), 128.85
(2 C), 130.47 (2 C), 134.82, 137.62; HRMS calcd for C17H18O2S
286.1027, found 286.1022.
(2S*,3R*)-2,3-Epoxy-2-m eth yl-1-n on an ol: IR (neat) 3450,
1
1541, 1508, 1040 cm-1; H NMR (270 MHz, CDCl3) δ 0.89 (t,
J ) 6.8 Hz, 3 H), 1.28-1.64 (m, 14 H), 2.85 (t, J ) 6.2 Hz, 1
H), 3.64-3.74 (m, 2 H); 13C NMR (67.8 MHz, CDCl3) δ 14.03,
20.02, 22.53, 26.63, 28.09, 29.07, 31.68, 60.94, 63.82, 64.92;
HRMS calcd for C9H15O [M - CH3 - H2O] 139.1123, found
139.1108.
(2R*,3R*)-2,3-Epoxy-2-m eth yl-1-n on an ol: IR (neat) 3450,
1
1541, 1508, 1040 cm-1; H NMR (270 MHz, CDCl3) δ 0.89 (t,
J ) 7.1 Hz, 3 H), 1.26-1.65 (m, 14 H), 3.04 (t, J ) 6.4 Hz, 1
H), 3.57 (d, J ) 12.1 Hz, 1 H), 3.68 (d, J ) 12.1 Hz, 1 H); 13C
NMR (67.8 MHz, CDCl3) δ 14.07, 14.22, 22.57, 26.43, 28.17,
29.13, 31.74, 60.31, 60.97, 65.46; HRMS calcd for C9H17O2 [M
- CH3] 157.1229, found 157.1194.
(2S*,3R*)-2,3-Epoxy-1-(ph en ylth io)n on an e (3). This com-
pound was prepared from (2R*,3R*)-2,3-epoxy-1-nonanol in a
(2S *,3R *)-5-B e n zy lo x y -2,3-e p o x y -2-m e t h y l-1-p e n -
ta n ol: IR (neat) 3440, 1560, 1508, 1205, 1094, 1036, 885, 698
100% yield: IR (neat) 1655, 1508, 1088, 1026, 910, 691 cm-1
;
1
cm-1; H NMR (270 MHz, CDCl3) δ 1.43 (s, 3 H), 1.70-1.85
1H NMR (270 MHz, CDCl3) δ 0.88 (t, J ) 7.1 Hz, 3 H), 1.20-
1.50 (m, 10 H), 2.65-2.70 (m, 1 H), 2.86-2.95 (m, 2 H involving
a double doublet at 2.91, J ) 6.5, 16.0 Hz), 3.17 (dd, J ) 6.9,
16.0 Hz, 1 H), 7.19-7.43 (m, 5 H); 13C NMR (67.8 MHz, CDCl3)
δ 14.03, 22.47, 25.62, 28.93, 31.61, 31.63, 36.15, 56.97, 59.29,
126.38, 128.71 (2 C), 128.98 (2 C), 135.12; HRMS calcd for
(m, 1 H), 2.09 (ddd, J ) 3.8, 6.8, 14.7 Hz, 1 H), 2.81 (dd, J )
4.1, 9.6 Hz, 1 H), 3.15 (dd, J ) 2.6, 10.6 Hz, 1 H), 3.45-3.70
(m, 4 H), 4.54 (d, J ) 11.8 Hz, 1 H), 4.55 (d, J ) 11.8 Hz, 1 H),
7.28-7.40 (m, 5 H); 13C NMR (67.8 MHz, CDCl3) δ 20.38, 29.03,
60.46, 62.28, 64.06, 66.58, 73.52, 127.88 (2 C), 128.03, 128.43
(2 C), 136.92; HRMS calcd for C13H15O2 [M - H3O] 203.1072,
found 203.1045.
C
15H22OS 250.1391, found 250.1415.
(2S*,3R*)-5-Ben zyloxy-2,3-ep oxy-1-(p h en ylt h io)p en -
ta n e (4). This compound was prepared from (2R*,3R*)-5-
(2R *,3R *)-5-B e n zy lo x y -2,3-e p o x y -2-m e t h y l-1-p e n -
ta n ol: IR (neat) 3440, 1508, 1497, 1205, 1097, 876, 698 cm-1
;
benzyloxy-2,3-epoxy-1-pentanol in a 98% yield: IR (neat) 1583,
1H NMR (270 MHz, CDCl3) δ 1.29 (s, 3 H), 1.66 (dd, J ) 4.6,
8.4 Hz, 1 H), 1.78-2.01 (m, 2 H), 3.19 (dd, J ) 5.4, 6.9 Hz, 1
H), 3.58 (dd, J ) 8.4, 12.0 Hz, 1 H), 3.64 (dd, J ) 5.7, 7.0 Hz,
2 H), 3.68 (dd, J ) 4.6, 12.0 Hz, 1 H), 4.54 (s, 2 H), 7.23-7.39
(m, 5 H); 13C NMR (67.8 MHz, CDCl3) δ 14.33, 28.94, 57.86,
60.87, 65.41, 67.30, 72.99, 127.41 (3 C), 128.18 (2 C), 138.00;
HRMS calcd for C13H16O2 [M - H2O] 204.1150, found 204.1161.
(2S*,3R*)-5-Ben zyloxy-2,3-epoxy-2-eth yl-1-pen tan ol: IR
1
1481, 1101, 1026, 907, 694 cm-1; H NMR (270 MHz, CDCl3)
δ 1.67-1.89 (m, 2 H), 2.86 (bt, J ) 4.8 Hz, 1 H), 2.91-3.01
(m, 2 H), 3.09-3.19 (m, 1 H), 3.50 (dd, J ) 1.5, 5.8 Hz, 1 H),
3.52 (dd, J ) 2.3, 5.8 Hz, 1 H), 4.48 (s, 2 H), 7.17-7.42 (m, 10
H); 13C NMR (67.8 MHz, CDCl3) δ 32.18, 36.19, 56.89, 57.08,
66.64, 72.94, 126.51, 127.42 (3 C), 128.21 (2 C), 128.82 (2 C),
130.07 (2 C), 135.18, 138.04; HRMS calcd for C18H20O2S
300.1184, found 300.1165.
1
(neat) 3450, 1647, 1508, 1094, 1043, 912, 698 cm-1; H NMR
(2R*,3R*)-2,3-E p oxy-2-m et h yl-1-(p h en ylt h io)n on a n e
(5a ). This compound was prepared from (2S*,3R*)-2,3-epoxy-
2-methyl-1-nonanol in a 94% yield: IR (neat) 1655, 1585, 1090,
1026, 691 cm-1; 1H NMR (270 MHz, CDCl3) δ 0.88 (t, J ) 6.9
Hz, 3 H), 1.20-1.50 (m, 13 H involving a singlet at 1.43), 2.76-
2.79 (m, 1 H), 3.01 (d, J ) 12.9 Hz, 1 H), 3.15 (d, J ) 12.9 Hz,
1 H), 7.17-7.42 (m, 5 H); 13C NMR (67.8 MHz, CDCl3) δ 14.06,
21.96, 22.52, 26.57, 28.48, 29.07, 31.63, 38.50, 59.90, 65.10,
126.18, 128.69 (2 C), 129.72 (2 C), 136.15; HRMS calcd for
(270 MHz, CDCl3) δ 0.97 (t, J ) 7.4 Hz, 3 H), 1.63 (dq, J )
7.4, 14.7 Hz, 1 H), 1.73-1.95 (m, 2 H), 2.09 (ddt, J ) 2.9, 4.0,
14.7 Hz, 1 H), 2.84 (dd, J ) 4.1, 9.6 Hz, 1 H), 3.14 (dd, J )
2.9, 10.6 Hz, 1 H), 3.45 (dd, J ) 2.9, 11.9 Hz, 1 H), 3.58 (ddd,
J ) 2.7, 9.4, 11.0 Hz, 1 H), 3.66 (dt, J ) 4.3, 9.4 Hz, 1 H), 3.75
(dd, J ) 10.6, 11.9 Hz, 1 H), 4.53 (d, J ) 11.9 Hz, 1 H), 4.56
(d, J ) 11.9 Hz, 1 H), 7.27-7.40 (m, 5 H); 13C NMR (67.8 MHz,
CDCl3) δ 8.45, 26.28, 28.81, 60.93, 61.88, 63.46, 66.63, 73.49,
127.86 (2 C), 127.90, 128.39 (2 C), 136.93; HRMS calcd for
C
16H24OS 264.1548, found 264.1546.
C
14H17O2 [M - H3O] 217.1229, found 217.1258.
(2S*,3R*)-2,3-E p oxy-2-m et h yl-1-(p h en ylt h io)n on a n e
(2R*,3R*)-5-Ben zyloxy-2,3-epoxy-2-eth yl-1-pen tan ol: IR
1
(neat) 3450, 1655, 1508, 1099, 910, 698 cm-1; H NMR (270
MHz, CDCl3) δ 0.98 (t, J ) 7.7 Hz, 3 H), 1.49 (dq, J ) 7.7,
14.3 Hz, 1 H), 1.70-1.86 (m, 3 H), 1.99 (ddt, J ) 4.7, 7.1, 14.3
Hz, 1 H), 3.20 (dd, J ) 4.7, 7.5 Hz, 1 H), 3.61 (dd, J ) 8.2,
12.2 Hz, 1 H), 3.65 (dd, J ) 5.9, 7.0 Hz, 2 H), 3.76 (dd, J )
4.6, 12.2 Hz, 1 H), 4.54 (s, 2 H), 7.27-7.38 (m, 5 H); 13C NMR
(67.8 MHz, CDCl3) δ 9.34, 21.93, 28.75, 58.10, 62.91, 63.90,
67.54, 73.14, 127.54 (3 C), 128.28 (2 C), 138.08; HRMS calcd
for C14H17O2 [M - H3O] 217.1229, found 217.1229.
(5b). This compound was prepared from (2R*,3R*)-2,3-epoxy-
2-methyl-1-nonanol in a 95% yield: IR (neat) 1655, 1541, 1067,
1026, 691 cm-1; 1H NMR (270 MHz, CDCl3) δ 0.88 (t, J ) 7.1
Hz, 3 H), 1.20-1.50 (m, 13 H involving a singlet at 1.39), 2.67
(t, J ) 6.0 Hz, 1 H), 2.93 (d, J ) 13.5 Hz, 1 H), 3.15 (d, J )
13.5 Hz, 1 H), 7.20-7.41 (m, 5 H); 13C NMR (67.8 MHz, CDCl3)
δ 14.06, 16.14, 22.50, 26.10, 28.49, 29.01, 31.65, 43.22, 59.61,
63.44, 126.35, 128.68 (2 C), 130.12 (2 C), 135.66; HRMS calcd
for C16H24OS 264.1548, found 264.1522.
(2R*,3R*)-2,3-E p oxy-1-(p h en ylt h io)h exa n e (1a ) a n d
(2S*,3R*)-2,3-E p oxy-1-(p h en ylt h io)-h exa n e (1b ). These
compounds were previously reported by other groups.5
Typ ica l P r oced u r e for th e P r ep a r a tion of 2,3-Ep oxy-
1-(phenylthio)alkanes from 2,3-Epoxy-1-alkanols:12 (2S*,3S*)-
4-Ben zyloxy-2,3-ep oxy-1-(p h en ylth io)bu ta n e (2a ). To a
solution of (2R*,3S*)-4-benzyloxy-2,3-epoxy-1-butanol (2.0 g,
10.3 mmol) and diphenyl disulfide (4.5 g, 20.6 mmol) in dry
pyridine (15 mL) was added tributylphosphine (5.1 mL, 20.6
mmol) at 0 °C. After being stirred for 30 min, the mixture was
concentrated under reduced pressure. Purification of the crude
(2R*,3R*)-5-Ben zyloxy-2,3-epoxy-2-m eth yl-1-(ph en ylth -
io)pen tan e (6a). This compound was prepared from (2S*,3R*)-
5-benzyloxy-2,3-epoxy-2-methyl-1-pentanol in a 93% yield: IR
1
(neat) 1583, 1481, 1094, 1026, 910, 696 cm-1; H NMR (270
MHz, CDCl3) δ 1.43 (s, 3 H), 1.62-1.90 (m, 2 H), 2.93-2.96
(m, 1 H), 3.00 (d, J ) 13.0 Hz, 1 H), 3.14 (d, J ) 13.0 Hz, 1 H)
3.59 (t, J ) 6.3 Hz, 2 H), 4.50 (s, 2 H), 7.15-7.40 (m, 10 H);
13C NMR (67.8 MHz, CDCl3) δ 21.96, 29.25, 38.59, 59.95, 62.46,
67.30, 73.00, 126.32, 127.46 (3 C), 128.22 (2 C), 128.80 (2 C),
129.82 (2 C), 136.03, 138.07; HRMS calcd for C19H22O2S
314.1340, found 314.1359.

Substitution Reactions of Epoxy Sulfides
J . Org. Chem., Vol. 66, No. 16, 2001 5393
(2S*,3R*)-5-Ben zyloxy-2,3-ep oxy-2-m eth yl-1-(p h en ylth -
io)pen tan e (6b). This compound was prepared from (2R*,3R*)-
5-benzyloxy-2,3-epoxy-2-methyl-1-pentanol in a 92% yield: IR
treating 2a with trimethylaluminum: IR (neat) 3450, 1583,
1481, 1026, 908, 696 cm-1; 1H NMR (270 MHz, CDCl3) δ 1.02
(d, J ) 6.9 Hz, 3 H), 1.85-2.00 (m, 1 H), 2.46 (d, J ) 4.0 Hz,
1 H), 2.77 (dd, J ) 8.7, 12.9 Hz, 1 H), 3.36 (dd, J ) 4.0, 12.9
Hz, 1 H), 3.43 (dd, J ) 7.4, 9.4 Hz, 1 H), 3.59 (dd, J ) 3.1, 9.4
Hz, 1 H), 3.66-3.74 (m, 1 H), 4.54 (d, J ) 12.0 Hz, 1 H), 4.56
(d, J ) 12.0 Hz, 1 H), 7.11-7.39 (m, 10 H); 13C NMR (67.8
MHz, CDCl3) δ 15.68, 36.34, 37.02, 72.38, 73.41 (2 C), 125.49,
127.62 (2 C), 127.73, 128.37 (2 C), 128.61 (2 C), 128.71 (2 C),
136.97, 137.67; HRMS calcd for C18H22O2S 302.1340, found
302.1369.
1
(neat) 1583, 1481, 1101, 1026, 907, 694 cm-1; H NMR (270
MHz, CDCl3) δ 1.40 (s, 3 H), 1.70-1.89 (m, 2 H), 2.85 (t, J )
5.7 Hz, 1 H), 2.96 (d, J ) 13.7 Hz, 1 H), 3.14 (d, J ) 13.7 Hz,
1 H), 3.50 (t, J ) 6.4 Hz, 2 H), 4.48 (s, 2 H), 7.15-7.40 (m, 10
H); 13C NMR (67.8 MHz, CDCl3) δ 16.46, 29.35, 43.15, 59.71,
60.95, 67.18, 73.00, 126.46, 127.44 (3 C), 128.23 (2 C), 128.80
(2 C), 130.14 (2 C), 135.77, 138.11; HRMS calcd for C19H22O2S
314.1340, found 314.1358.
(3R*,4R*)-1-Ben zyloxy-3,4-ep oxy-4-[(p h en ylth io)m eth -
yl]h exa n e (7a ). This compound was prepared from (2S*,3R*)-
5-benzyloxy-2,3-epoxy-2-ethyl-1-pentanol in a 97% yield: IR
(2S*,3R *)-1-Be n zyloxy-3-(p h e n ylt h io)m e t h yl-2-p e n -
ta n ol (11a ). This compound was obtained in a 97% yield by
treating 2a with triethylaluminum: IR (neat) 3450, 1583,
1481, 1026, 908, 696 cm-1; 1H NMR (270 MHz, CDCl3) δ 0.90
(t, J ) 7.4 Hz, 3 H), 1.40-1.62 (m, 2 H), 1.65-1.78 (m, 1 H),
2.40 (d, J ) 3.8 Hz, 1 H), 3.00 (dd, J ) 6.8, 12.9 Hz, 1 H), 3.20
(dd, J ) 4.8, 12.9 Hz, 1 H), 3.48 (dd, J ) 7.7, 9.4 Hz, 1 H),
3.57 (dd, J ) 3.3, 9.4 Hz, 1 H), 3.88-3.95 (m, 1 H), 4.55 (s, 2
H), 7.12-7.39 (m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 11.27,
22.48, 33.77, 42.20, 71.12, 72.77, 73.41, 125.59, 127.63, 127.72
(2 C), 128.37 (2 C), 128.71 (2 C), 128.83 (2 C), 137.09, 137.72;
HRMS calcd for C19H24O2S 316.1497, found 316.1508.
(2S*,3S*)-1-Ben zyloxy-3-m et h yl-4-(p h en ylt h io)-2-b u -
ta n ol (10b). This compound was obtained in a 96% yield by
treating 2b with trimethylaluminum: IR (neat) 3450, 1583,
1
(neat) 1655, 1508, 1099, 1026, 908, 696 cm-1; H NMR (270
MHz, CDCl3) δ 0.92 (t, J ) 7.4 Hz, 3 H), 1.67-1.93 (m, 4 H),
2.99 (dd, J ) 5.1, 7.3 Hz, 1 H), 3.00 (d, J ) 13.0 Hz, 1 H), 3.20
(d, J ) 13.0 Hz, 1 H), 3.61 (dd, J ) 5.6, 6.9 Hz, 2 H), 4.51 (s,
2 H), 7.16-7.40 (m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 8.72,
27.54, 29.18, 36.21, 61.12, 63.09, 67.46, 73.13, 126.35, 127.53,
127.57 (2 C), 128.29 (2 C), 128.85 (2 C), 129.86 (2 C), 136.21,
138.12; HRMS calcd for C20H24O2S 328.1497, found 328.1498.
(3R*,4S*)-1-Ben zyloxy-3,4-ep oxy-4-[(p h en ylth io)m eth -
yl]h exa n e (7b). This compound was prepared from (2R*,3R*)-
5-benzyloxy-2,3-epoxy-2-ethyl-1-pentanol in a 93% yield: IR
1
(neat) 1583, 1481, 1101, 1026, 910, 696 cm-1; H NMR (270
1
MHz, CDCl3) δ 1.01 (t, J ) 7.6 Hz, 3 H), 1.62-1.92 (m, 4 H),
2.92 (dd, J ) 5.1, 7.1 Hz, 1 H), 2.98 (d, J ) 13.8 Hz, 1 H), 3.20
(d, J ) 13.8 Hz, 1 H), 3.51 (dd, J ) 5.9, 7.1 Hz, 2 H), 4.48 (s,
2 H), 7.14-7.40 (m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 9.14,
22.53, 28.90, 39.57, 61.22, 62.68, 67.25, 72.94, 126.28, 127.39
(3 C), 128.16 (2 C), 128.71 (2 C), 129.88 (2 C), 135.93, 138.05;
HRMS calcd for C20H24O2S 328.1497, found 328.1492.
1481, 1092, 1026, 897, 696 cm-1; H NMR (270 MHz, CDCl3)
δ 1.04 (d, J ) 6.9 Hz, 3 H), 1.87 (dq, J ) 3.8, 6.9 Hz, 1 H), 2.27
(d, J ) 3.6 Hz, 1 H), 2.55 (dd, J ) 7.3, 13.0 Hz, 1 H), 3.14 (dd,
J ) 6.4, 13.0 Hz, 1 H), 3.43-3.53 (m, 2 H), 3.97-4.04 (m, 1
H), 4.54 (s, 2 H), 7.12-7.64 (m, 10 H); 13C NMR (67.8 MHz,
CDCl3) δ 14.05, 35.46, 37.52, 71.69, 72.76, 73.34, 125.62, 127.59
(2 C), 127.67, 128.34 (2 C), 128.73 (2 C), 128.78 (2 C), 136.65,
137.70; HRMS calcd for C18H22O2S 302.1340, found 302.1365.
(2S *,3S *)-1-Be n zyloxy-3-(p h e n ylt h io)m e t h yl-2-p e n -
ta n ol (11b). This compound was obtained in a 95% yield by
treating 2b with triethylaluminum: IR (neat) 3450, 1583,
Typ ica l P r oced u r e for th e Alk yl Su bstitu tion Rea c-
tion of 2,3-Ep oxy-1-(p h en ylth io)a lk a n es: (2S*,3R*)-5-
Ben zyloxy-2-m eth yl-1-(p h en ylth io)-3-p en ta n ol (14). To a
solution of epoxy sulfide 4 (90 mg, 0.3 mmol) in CH2Cl2 (6 mL)
was added a 1.0 M hexane solution of Me3Al (0.9 mL, 0.9 mmol)
at -30 °C. After the solution was stirred for 10 min, water
and aq 3 M HCl were added sequentially, and the mixture
was separated. The aqueous layer was extracted with CH2-
Cl2, and the combined organic layer was washed with brine
and dried over MgSO4. Concentration under reduced pressure
followed by flash column chromatography afforded 87 mg
(91%) of alcohol 14: IR (neat) 3450, 1583, 1481, 1092, 1026,
1
1481, 1090, 1026, 908, 692 cm-1; H NMR (270 MHz, CDCl3)
δ 0.93 (t, J ) 7.4 Hz, 3 H), 1.43-1.60 (m, 2 H), 1.67-1.75 (m,
1 H), 2.34 (d, J ) 3.8 Hz, 1 H), 2.91 (dd, J ) 5.9, 12.9 Hz, 1
H), 3.10 (dd, J ) 6.8, 12.9 Hz, 1 H), 3.46-3.57 (m, 2 H), 4.03-
4.11 (m, 1 H), 4.55 (s, 2 H), 7.12-7.38 (m, 10 H); 13C NMR
(67.8 MHz, CDCl3) δ 11.71, 21.59, 34.27, 42.12, 70.87, 72.49,
73.27, 125.56, 127.55 (2 C), 127.60, 128.27 (2 C), 128.67 (2 C),
128.69 (2 C), 136.77, 137.70; HRMS calcd for C19H24O2S
316.1497, found 316.1508.
1
910, 696 cm-1; H NMR (270 MHz, CDCl3) δ 1.03 (d, J ) 6.9
Hz, 3 H), 1.57-1.66 (m, 1 H), 1.74-1.92 (m, 2 H), 2.79 (dd, J
) 7.7, 12.9 Hz, 1 H), 2.91 (d, J ) 2.8 Hz, 1 H), 3.17 (dd, J )
6.3, 12.9 Hz, 1 H), 3.61-3.76 (m, 2 H), 3.99 (dq, J ) 2.8, 9.9
Hz, 1 H), 4.51 (s, 2 H), 7.11-7.38 (m, 10 H); 13C NMR (67.8
MHz, CDCl3) δ 13.66, 33.67, 37.24, 38.36, 69.63, 73.03, 73.32,
125.43, 127.52 (2 C), 127.61, 128.30 (2 C), 128.55 (2 C), 128.66
(2 C), 136.89, 137.62; HRMS calcd for C19H24O2S 316.1497,
found 316.1510.
(2S*,3R*)-2-Meth yl-1-(p h en ylth io)-3-n on a n ol (12). This
compound was obtained in a 93% yield by treating 3 with
trimethylaluminum: IR (neat) 3410, 1585, 1481, 1092, 914,
1
691 cm-1; H NMR (270 MHz, CDCl3) δ 0.88 (t, J ) 6.9 Hz, 3
H), 1.00 (d, J ) 6.9 Hz, 3 H), 1.25-1.43 (m, 11 H), 1.72-1.86
(m, 1 H), 2.85 (dd, J ) 7.2, 12.8 Hz, 1 H), 3.10 (dd, J ) 6.8,
12.8 Hz, 1 H), 3.75-3.81 (m, 1 H), 7.13-7.37 (m, 5 H); 13C
NMR (67.8 MHz, CDCl3) δ 13.27, 14.15, 22.66, 26.24, 29.31,
31.85, 34.57, 37.80 (2 C), 73.23, 125.63, 128.73 (2 C), 128.80
(2 C), 136.77; HRMS calcd for C16H26OS 266.1704, found
266.1702.
(2R*,3R*)-2-Meth yl-1-ph en ylth io-3-h exan ol (8). This com-
pound was obtained in a 96% yield by treating 1a with
trimethylaluminum: IR (neat) 3400, 1583, 1481, 1112, 1026,
1
691 cm-1; H NMR (270 MHz, CDCl3) δ 0.93 (bt, J ) 6.6 Hz,
(3S*,4R*)-3-(P h en ylth io)m eth yl-4-decan ol (13). This com-
pound was obtained in a 94% yield by treating 3 with
3 H), 1.05 (d, J ) 6.9 Hz, 3 H), 1.26-1.59 (m, 5 H), 1.75-1.88
(m, 1 H), 2.80 (dd, J ) 8.2, 12.7 Hz, 1 H), 3.21 (dd, J ) 4.4,
12.7 Hz, 1 H), 3.50-3.60 (br, 1 H), 7.12-7.37 (m, 5 H); 13C
NMR (67.8 MHz, CDCl3) δ 14.15, 15.95, 19.05, 36.22, 36.97,
38.86, 74.81, 125.60, 128.72 (2 C), 128.74 (2 C), 136.94; HRMS
calcd for C13H20OS 224.1235, found 224.1266.
triethylaluminum: IR (neat) 3420, 1585, 1481, 1119, 1026,
1
889, 691 cm-1; H NMR (270 MHz, CDCl3) δ 0.88 (t, J ) 6.9
Hz, 3 H), 0.95 (t, J ) 7.4 Hz, 3 H), 1.28-1.66 (m, 14 H), 2.96
(dd, J ) 5.5, 12.8 Hz, 1 H), 3.08 (dd, J ) 7.3, 12.8 Hz, 1 H),
3.82-3.90 (m, 1 H), 7.13-7.37 (m, 5 H); 13C NMR (67.8 MHz,
CDCl3) δ 12.14, 14.14, 21.38, 22.67, 26.34, 29.34, 31.86, 33.91,
34.74, 44.81, 72.54, 125.64, 128.71 (2 C), 128.81 (2 C), 136.85;
HRMS calcd for C17H28OS 280.1861, found 280.1868.
(3R*,4R*)-3-(P h en ylth io)m eth yl-4-h exan ol (9). This com-
pound was obtained in a 91% yield by treating 1a with
triethylaluminum: IR (neat) 3420, 1583, 1481, 1026, 691 cm-1
;
1H NMR (270 MHz, CDCl3) δ 0.91-0.96 (m, 6 H), 1.24-1.66
(m, 8 H), 2.98 (dd, J ) 6.4, 12.5 Hz, 1 H), 3.13 (dd, J ) 4.6,
12.5 Hz, 1 H), 3.68-3.78 (m, 1 H), 7.13-7.37 (m, 5 H); 13C
NMR (67.8 MHz, CDCl3) δ 11.53, 14.07, 19.24, 22.63, 33.88,
36.61, 44.87, 72.24, 125.53, 128.61 (2 C), 128.72 (2 C), 137.05;
HRMS calcd for C14H22OS 238.1391, found 238.1387.
(3R *,4S *)-1-Be n zyloxy-4-(p h e n ylt h io)m e t h yl-3-h e x-
a n ol (15). This compound was obtained in a 91% yield by
treating 4 with triethylaluminum: IR (neat) 3450, 1583, 1481,
1092, 1026, 910, 696 cm-1; 1H NMR (270 MHz, CDCl3) δ 0.94
(t, J ) 7.4 Hz, 3 H), 1.47-1.70 (m, 4 H), 1.77-1.92 (m, 1 H),
2.89 (dd, J ) 6.0, 12.7 Hz, 1 H), 2.99 (d, J ) 2.3 Hz, 1 H), 3.14
(dd, J ) 6.5, 12.7 Hz, 1 H), 3.61-3.77 (m, 2 H), 4.05-4.09 (m,
1 H), 4.50 (d, J ) 12.0 Hz, 1 H), 4.52 (d, J ) 12.0 Hz, 1 H),
(2S*,3R*)-1-Ben zyloxy-3-m et h yl-4-(p h en ylt h io)-2-b u -
ta n ol (10a ). This compound was obtained in a 95% yield by

5394 J . Org. Chem., Vol. 66, No. 16, 2001
Sasaki et al.
7.11-7.37 (m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 12.12,
21.73, 33.15, 34.35, 45.13, 69.83, 72.23, 73.40, 125.49, 127.58
(2 C), 127.67, 128.37 (2 C), 128.56 (2 C), 128.71 (2 C), 137.09,
137.70; HRMS calcd for C20H26O2S 330.1653, found 330.1640.
2,2-Dim eth yl-1-(p h en ylth io)-3-n on a n ol (16). This com-
pound was obtained in a 95% yield by treating 5b with
trimethylaluminum: IR (neat) 3460, 1583, 1481, 1119, 1026,
Concentration under reduced pressure followed by flash
column chromatography afforded 82 mg (94%) of a 91:9
mixture of alcohols 21b and 22b: IR (neat) 3450, 1583, 1481,
1
1250, 1117, 1026, 910, 691 cm-1; H NMR (270 MHz, CDCl3)
δ 0.16 (s, 9 H), 0.92 (t, J ) 7.1 Hz, 3 H), 1.23-1.66 (m, 5 H),
2.64 (ddd, J ) 2.7, 6.8, 7.8 Hz, 1 H), 3.16 (dd, J ) 7.8, 13.4
Hz, 1 H), 3.21 (dd, J ) 6.8, 13.4 Hz, 1 H), 3.75-3.85 (m, 1 H),
7.16-7.49 (m, 5 H), with peaks due to 22b at 0.15 (s), 3.35
(dt, J ) 4.1, 7.0 Hz), and 3.87-3.94 (m); 13C NMR (67.8 MHz,
CDCl3) δ 0.19 (3 C), 14.03, 19.08, 35.81, 38.12, 39.75, 70.29,
89.84, 103.98, 126.22, 128.86 (2 C), 129.65 (2 C), 135.73; HRMS
calcd for C17H26OSSi 306.1474, found 306.1481.
(3S*,4R*)-3-(P h en ylt h io)m et h yl-1-(t r im et h ylsilyl)-1-
d ecyn -4-ol (23). Treatment of 3 with dimethyl[2-(trimethyl-
silyl)ethynyl]aluminum afforded an 85:15 mixture of alcohols
23 and 24 in an 87% yield: IR (neat) 3450, 1583, 1481, 1250,
1119, 1026, 907, 691 cm-1; 1H NMR (270 MHz, CDCl3) δ 0.16
(s, 9 H), 0.88 (t, J ) 6.9 Hz, 3 H), 1.20-1.70 (m, 11 H), 2.60-
2.68 (m, 1 H), 3.15 (dd, J ) 7.8, 13.4 Hz, 1 H), 3.21 (dd, J )
6.7, 13.4 Hz, 1 H), 3.74-3.83 (m, 1 H), 7.16-7.64 (m, 5 H),
with peaks due to 24 at 0.15 (s), 3.35 (dt, J ) 4.1, 7.0 Hz), and
3.86-3.91 (m); 13C NMR (67.8 MHz, CDCl3) δ 0.18 (3 C), 14.17,
22.63, 25.75, 29.17, 31.77, 35.78, 35.94, 39.66, 70.54, 89.82,
103.99, 126.21, 128.84 (2 C), 129.65 (2 C), 135.72; HRMS calcd
for C20H32OSSi 348.1943, found 348.1953.
1
691 cm-1; H NMR (270 MHz, CDCl3) δ 0.89 (t, J ) 6.8 Hz, 3
H), 1.00 (s, 6H), 1.25-1.60 (m, 10H), 1.66 (6s, 1H), 2.91 (d, J
) 12.0 Hz, 1H), 3.11 (d, J ) 12.0 Hz, 1H), 3.45-3.55 (m, 1H),
7.12-7.38 (m, 5 H); 13C NMR (67.8 MHz, CDCl3) δ 14.19, 22.57,
22.71, 23.71, 27.04, 29.40, 31.32, 31.93, 39.33, 44.69, 76.53,
125.63, 128.72 (2 C), 129.00 (2 C), 137.73; HRMS calcd for
C17H28OS 280.1861, found 280.1875.
5-Ben zyloxy-2,2-d im et h yl-1-(p h en ylt h io)-3-p en t a n ol
(17). This compound was obtained in a 91% yield by treating
6b with trimethylaluminum: IR (neat) 3500, 1583, 1481, 1092,
1
1026, 910, 698 cm-1; H NMR (270 MHz, CDCl3) δ 1.00 (s, 3
H), 1.02 (s, 3 H), 1.70-1.78 (m, 2 H), 2.94 (d, J ) 12.1 Hz, 1
H), 3.09 (d, J ) 2.6 Hz, 1 H), 3.14 (d, J ) 12.1 Hz, 1 H), 3.61-
3.79 (m, 3 H), 4.50 (d, J ) 11.8 Hz, 1 H), 4.53 (d, J ) 11.8 Hz,
1 H), 7.10-7.38 (m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 22.30
(2 C), 23.62, 30.87, 39.13, 44.28, 70.20, 73.44, 125.48, 127.62
(2 C), 127.68, 128.37 (2 C), 128.68 (2 C), 128.91 (2 C), 137.66,
138.01; HRMS calcd for C20H26O2S 330.1653, found 330.1672.
(3R*,4S*)-1-Ben zyloxy-4-m eth yl-4-(p h en ylth io)m eth yl-
3-h exa n ol (18a ). This compound was obtained in a 78% yield
by treating 7a with trimethylaluminum: IR (neat) 3500, 1583,
1481, 1090, 1026, 698 cm-1; 1H NMR (270 MHz, CDCl3) δ 0.88
(t, J ) 7.6 Hz, 3 H), 0.97 (s, 3 H), 1.43-1.79 (m, 4 H), 2.91 (d,
J ) 11.9 Hz, 1 H), 3.01 (d, J ) 2.8 Hz, 1 H), 3.10 (d, J ) 11.9
Hz, 1 H), 3.61-3.83 (m, 3 H), 4.50 (d, J ) 11.9 Hz, 1 H), 4.54
(d, J ) 11.9 Hz, 1 H), 7.11-7.38 (m, 10 H); 13C NMR (67.8
MHz, CDCl3) δ 8.17, 20.37, 27.91, 30.74, 41.19, 41.33, 70.19,
73.38, 76.20, 125.53, 127.58 (2 C), 127.63, 128.34 (2 C), 128.68
(2 C), 128.96 (2 C), 137.93, 137.70; HRMS calcd for C21H28O2S
344.1810, found 344.1835.
(3S*,4S*)-1-Ben zyloxy-3-(p h en ylth io)m eth yl-5-(tr im e-
th ylsilyl)-4-p en tyn -2-ol (25). Treatment of 2b with dimethyl-
[2-(trimethylsilyl)ethynyl]aluminum afforded an 85:15 mixture
of alcohols 25 and 26 in a 94% yield: IR (neat) 3450, 1583,
1439, 1250, 1092, 1026, 908, 696 cm-1 1H NMR (270 MHz,
;
CDCl3) δ 0.13 (s, 9 H), 2.13 (d, J ) 7.3 Hz, 1 H), 2.85 (ddd, J
) 2.8, 7.0, 7.8 Hz, 1 H), 3.19 (d, J ) 7.0 Hz, 1 H), 3.19 (d, J )
7.8 Hz, 1 H), 3.51 (dd, J ) 5.4, 9.6 Hz, 1 H), 3.60 (dd, J ) 6.8,
9.6 Hz, 1 H), 4.10 (ddt, J ) 2.8, 5.4, 6.8 Hz, 1 H), 4.54 (s, 2 H),
7.15-7.49 (m, 10 H), with peaks due to 26 at 0.15 (s), 3.36
(dt, J ) 5.7, 7.0 Hz), 3.70 (dd, J ) 5.4, 9.5 Hz), 3.75 (dd, J )
3.8, 9.5 Hz), 3.94-4.03 (m), and 4.47 (s); 13C NMR (67.8 MHz,
CDCl3) δ 0.13 (3 C), 35.37, 36.48, 68.99, 72.38, 73.29, 89.77,
103.47, 126.25, 127.55 (2 C), 127.61, 128.28 (2 C), 128.84 (2
C), 129.76 (2 C), 135.53, 137.71; HRMS calcd for C22H28O2SSi
384.1579, found 384.1569.
(3R*,4R*)-1-Ben zyloxy-4-m eth yl-4-(p h en ylth io)m eth yl-
3-h exa n ol (18b). This compound was obtained in a 97% yield
by treating 7b with trimethylaluminum: IR (neat) 3500, 1583,
1
1479, 1090, 1026, 910, 696 cm-1; H NMR (270 MHz, CDCl3)
δ 0.86 (t, J ) 7.6 Hz, 3 H), 0.95 (s, 3 H), 1.41-1.53 (m, 2 H),
1.70-1.77 (m, 2 H), 2.96 (d, J ) 11.9 Hz, 1 H), 3.02 (d, J ) 3.0
Hz, 1 H), 3.17 (d, J ) 11.9 Hz, 1 H), 3.62-3.83 (m, 3 H), 4.50
(d, J ) 11.7 Hz, 1 H), 4.54 (d, J ) 11.7 Hz, 1 H), 7.10-7.38
(m, 10 H); 13C NMR (67.8 MHz, CDCl3) δ 8.00, 19.50, 28.08,
30.74, 40.72, 41.37, 70.16, 73.38, 75.51, 125.44, 127.59 (2 C),
127.64, 128.35 (2 C), 128.65 (2 C), 128.89 (2 C), 137.71, 137.95;
HRMS calcd for C21H28O2S 344.1810, found 344.1818.
Typ ica l P r oced u r e for th e Alk yn yl Su bstitu tion Rea c-
tion of 2,3-Ep oxy-1-(p h en ylth io)a lk a n es: (3S*,4R*)-3-
(P h en ylth io)m eth yl-1-(tr im eth ylsilyl)-1-h exyn -4-ol (21b).
To a solution of (trimethylsilyl)acetylene (0.17 mL, 1.2 mmol)
in CH2Cl2 (4 mL) was added a 1.5 M hexane solution of
butyllithium (0.80 mL, 1.2 mmol) at 0 °C. After the solution
was stirred for 30 min, a 1.0 M hexane solution of Me2AlCl
(1.2 mL, 1.2 mmol) was added at 0 °C. After this solution was
stirred for 30 min, the mixture was cooled to -78 °C. To this
was added a solution of (2S*,3R*)-2,3-epoxy-1-(phenylthio)-
hexane (1b) (58 mg, 0.3 mmol) in CH2Cl2 (2 mL), and the
mixture was stirred for 10 min. Water and aq 3 M HCl were
added sequentially, and the mixture was separated. The
aqueous layer was extracted with CH2Cl2, and the combined
organic layer was washed with brine and dried over MgSO4.
(4R*,5R*)-5-(P h en ylth io)-8-(tr im eth ylsilyl)-7-octyn -4-
ol (22a ). Treatment of 1a with dimethyl[2-(trimethylsilyl)-
ethynyl]aluminum afforded an 83:17 mixture of alcohols 22a
and 21a in a 93% yield: IR (neat) 3430, 1583, 1479, 1439, 1250
1
cm-1; H NMR (270 MHz, CDCl3) δ 0.15 (s, 9 H), 0.93 (t, J )
7.2 Hz, 3 H), 1.26-1.68 (m, 4 H), 2.28 (d, J ) 6.1 Hz, 1 H),
2.58 (dd, J ) 6.3, 17.3 Hz, 1 H), 2.70 (dd, J ) 7.6, 17.3 Hz, 1
H), 3.21 (ddd, J ) 4.0, 6.3, 7.6 Hz, 1 H), 3.92 (dq, J ) 4.0, 6.1
Hz, 1 H), 7.24-7.33 (m, 3 H), 7.46-7.52 (m, 2 H), with peaks
due to 21a at 2.72-2.83 (m) and 3.73-3.81 (m); 13C NMR (67.8
MHz, CDCl3) δ 0.10 (3 C), 13.98, 19.12, 24.37, 36.77, 55.29,
72.18, 87.21, 104.12, 127.30, 128.92 (2 C), 132.45 (2 C), 134.36;
HRMS calcd for C17H26OSSi 306.1474, found 306.1483.
Ack n ow led gm en t. Financial support from the Min-
istry of Education, Science, Sports and Culture of J apan
(a Grant-in-Aid for Scientific Research (A) (No. 12304042)
and a Grant-in-Aid for Scientific Research on Priority
Areas (No. 706: Dynamic Control of Stereochemistry))
is gratefully acknowledged.
J O010240C