Regio- and stereoselectivity of the SiO2-catalyzed reaction of thiocamphor (=1,7,7-trimethylbicyclo[2.2.1]heptane-2-thione) with optically active monosubstituted oxiranes

Article abstract of DOI:10.1002/hlca.200390182

The reactions of the enolizable thioketone (1R,4R)-thiocamphor (= (1R,4R)-1,7,7-trimethylbicyclo[2.2.1]-heptane-2-thione; 1) with (S)-2-methyloxirane (2) in the presence of a Lewis acid such as SnCl₄ or SiO₂ in anhydrous CH₂Cl₂ led to two diastereoisomeric spirocyclic 1,3-oxathiolanes 3 and 4 with the Me group at C(5′), as well as the isomeric β-hydroxy thioether 5 (Scheme 2). The analogous reactions of 1 with (RS)-, (R)-, and (S)-2-phenyloxirane (7) yielded two isomeric spirocyclic 1,3-oxathiolanes 8 and 9 with Ph at C(4′), an additional isomer 13 bearing the Ph group at C(5′), and three isomeric β-hydroxy thioethers 10, 11, and 12 (Scheme 4). In the presence of HCI, the β-hydroxy thioethers 5, 10, 11, and 12 isomerized to the corresponding 1,3-oxathiolanes 3 and 4 (Scheme 3), and 8, 9, and 13, respectively (Scheme 5). Under similar conditions, an epimerization of 3, 8, and 9 occurred to yield the corresponding diastereoisomers 4, 14, and 15, respectively (Schemes 3 and 6). The structures of 9 and 15 were confirmed by X-ray crystallography (Figs. 1 and 2). These results show that the Lewis acid-catalyzed addition of oxiranes to enolizable thioketones proceeds with high regio- and stereoselectivity via an S_N2-type mechanism.

Full text of DOI:10.1002/hlca.200390182

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Helvetica Chimica Acta Vol. 86 (2003)
Regio- and Stereoselectivity of the SiO2-Catalyzed Reaction of
Thiocamphor (ˆ1,7,7-Trimethylbicyclo[2.2.1]heptane-2-thione) with
Optically Active Monosubstituted Oxiranes
by Changchun Fu1), Anthony Linden, and Heinz Heimgartner*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
The reactions of the enolizable thioketone (1R,4R)-thiocamphor (ˆ(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]-
heptane-2-thione; 1) with (S)-2-methyloxirane (2) in the presence of a Lewis acid such as SnCl4 or SiO2 in
anhydrous CH2Cl2 led to two diastereoisomeric spirocyclic 1,3-oxathiolanes 3 and 4 with the Me group at C(5'),
as well as the isomeric b-hydroxy thioether 5 (Scheme 2). The analogous reactions of 1 with (RS)-, (R)-, and
(S)-2-phenyloxirane (7) yielded two isomeric spirocyclic 1,3-oxathiolanes 8 and 9 with Ph at C(4'), an additional
isomer 13 bearing the Ph group at C(5'), and three isomeric b-hydroxy thioethers 10, 11, and 12 (Scheme 4). In
the presence of HCl, the b-hydroxy thioethers 5, 10, 11, and 12 isomerized to the corresponding 1,3-oxathiolanes
3 and 4 (Scheme 3), and 8, 9, and 13, respectively (Scheme 5). Under similar conditions, an epimerization of 3, 8,
and 9 occurred to yield the corresponding diastereoisomers 4, 14, and 15, respectively (Schemes 3 and 6). The
structures of 9 and 15 were confirmed by X-ray crystallography (Figs. 1 and 2). These results show that the
Lewis acid-catalyzed addition of oxiranes to enolizable thioketones proceeds with high regio- and stereo-
selectivity via an Sn2-type mechanism.
1. Introduction. The formation of 1,3-oxathiolanes via the Lewis acid-catalyzed
reactions of non-enolizable thiocarbonyl compounds with racemic or optically active
oxiranes has been investigated in recent years [1 5]. All results reported previously
indicate that the reactions proceed with high regio- and stereoselectivity via an Sn2-type
mechanism (Scheme 1). For example, the reactions with monosubstituted oxiranes lead
to 5- and 4-substituted 1,3-oxathiolanes with retention and inversion of the config-
uration, respectively.
Scheme 1
With the aim of establishing the scope and limitation of the formation of 1,3-
oxathiolanes, the reactions of some enolizable thioketones with asymmetrically
substituted oxiranes were carried out. In the present paper, the results of the reactions
of (1R,4R)-thiocamphor (ˆ1,7,7-trimethylbicyclo[2.2.1]heptane-2-thione; 1) with (S)-
2-methyloxirane (2), and (RS)-, (R)-, and (S)-phenyloxirane (7) are described.
1
)
Part II of the projected Ph.D. thesis of C. F., University of Zurich. For Part I, see [1].

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2. Results. 2.1. Reaction of (1R,4R)-Thiocamphor (1) with (S)-2-Methyloxirane
(2). On dropping 4 equiv. of 2 into a soln. of 1 and 0.6 equiv. of SnCl4 in anhydrous
CH2Cl2 at À788 under an N2 atmosphere, the color of the yellow soln. turned slowly to
light yellow. After 8min, the reaction was quenched by addition of H O. Chromato-
2
graphic separation of the mixture gave two diastereoisomeric spirocyclic 1,3-
oxathiolanes 3 and 4, and camphor (6) in 51, 8, and 10% yield, respectively, as well
as an unexpected open-chain product 5 in 18% yield. When the reaction was repeated
at room temperature in the presence of silica gel, after 1 d, only 3 and the isomer 5 were
obtained in 16 and 48% yield, respectively. Furthermore, the starting material 1 was
recovered in 10% yield (Scheme 2 and Table 1).
Scheme 2
Table 1. SnCl4- and SiO2-Catalyzed Reactions of 1 with 2 in CH2Cl2
Lewis acid
Temp.
Reaction time
Yield of products [ % ]
3
4
5
6
1
SnCl4
SiO2
À 788
8min
1 d
51
16
8
18
48
10
r.t.
10
The structures of 3, 4, and 5 were assigned on the basis of elemental analyses, 1H-,
13C-, and 2D-NMR, and mass spectra, and by comparison with those of similar
compounds described previously [1 5]. The configurations at C(2) and C(5') of 3 and
4 were determined by means of NOESY spectra relative to the known absolute
configuration of the bicyclic skeleton of the starting material 1. The examination of a
Dreiding model of 3 shows that the spatial distances between HÀC(5') and the
MeÀC(1) group, and between the MeÀC(5') group and HendoÀC(3) are small, which
corresponds well with the NOESY spectrum (600 MHz, C6D6) of 3, which shows one
relevant cross-signal between HÀC(5') at 4.02 3.99 ppm and MeÀC(1) at 1.11 ppm,
and a smaller relevant cross-signal between MeÀC(5') at 1.08ppm and H endoÀC(3) at
1.95 ppm. It is worth mentioning that the difference between the chemical shifts of
HendoÀC(6) at 2.32 ppm and HexoÀC(6) at 1.45 ppm is large (Dd ˆ 0.85 ppm) due to the
proximity of the electronegative O-atom, which means that the O-atom is close to
HendoÀC(6), i.e., in the endo position. These analyses indicate that the absolute
configuration of 3 is (1R,2R,4R,5'S). Similarly, the examination of the Dreiding model
of the diastereoisomer 4 shows that the distance between HÀC(5') and HexoÀC(3) is
small, in accordance with the NOESY spectrum (500 MHz, CDCl3) of 4, which shows a
relevant cross-signal between HÀC(5') at 4.18 4.13 ppm and H exoÀC(3) at 2.33 ppm.

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In addition, HendoÀC(6) and HexoÀC(6) both absorbed at 1.63 1.56 ppm, which implies
that the O-atom is exo-oriented. Therefore, the absolute configuration of 4 is
(1R,2S,4R,5'S).
Acid-Catalyzed Isomerization of 5 with HCl. A solution of 5 in Et2O at À208 was
treated with 4 drops of conc. HCl, and the mixture was stirred for 8h. After the usual
workup, column chromatography yielded 73% of 3 and 8% of 4. The isomerization of
5 also occurred smoothly in CDCl3, which contained traces of DCl, at room
temperature, leading to different ratios of 3 and 4, depending on the conditions. In
the absence of DCl, i.e., after filtration of CDCl3 through Al2O3, no isomerization of 5
was observed (Scheme 3 and Table 2). On the other hand, irradiation of this solution
with sunlight led to extensive isomerization.
Scheme 3
Table 2. Acid-Catalyzed Isomerzation of 5 to Give 3 and 4
Solvent
Conditions
Temp.
Reaction time
Ratio of products
3
4
a
Et2O
addition of HCl
À 208
r.t.
r.t.
r.t.
r.t.
8
h
73
)
8
CDCl3
CDCl3
CDCl3
CDCl3
C6D6
5 min
12 h
12 h
2 h
1
1
:
:
3.8
1.8
filtered through Al2O3
filtered through Al2O3, hn
no reaction
1
no reaction
:
3.5
r.t.
12 h
a) Yields of isolated products.
Epimerization of 3 with HCl. To a solution of 3 in CH2Cl2, five drops of conc. HCl
were added at room temperature. After stirring the mixture for 7.5 h and the usual
workup, chromatographic separation gave the diastereoisomer 4 in 73% yield, and the
starting material 3 was recovered in 7% yield (Scheme 3).
2.2. Reaction of 1 with 2-Phenyloxirane (7). The analogous SnCl4-catalyzed reaction
of 1 with (RS)-7 in CH2Cl2 at À788 for 17 min led to two diastereoisomeric 1,3-
oxathiolanes 8 and 9 in 37 and 21% yield, respectively, whereas the reaction of 1 with
(R)-7 under the same conditions gave only diastereoisomer 8 in 79% yield (Scheme 4).
The reaction of 1 with (R)-7 was repeated at À788 for 20 min, whereupon 8 was formed

Helvetica Chimica Acta Vol. 86 (2003)
2261
in 62% yield. In addition, the b-hydroxy thioether 10 was isolated in 8% yield. After
17 min at À788, the reaction of 1 with (S)-7 gave the two diastereoisomers 8 and 9 in 1
and 45% yield, respectively, as well as a b-hydroxy thioether 11 in 44% yield.
The SiO2-catalyzed reaction of 1 with (R)-7 was carried out at room temperature
for 3 days, and chromatographic separation gave the diastereoisomer 8, and two
unexpected isomers 12 and 13 in 58, 5, and 2% yield, respectively. At 08, after 3 days,
the reaction yielded 51, 6, 10, and 0.7% of 8, 10, 12, and 13, repectively. In addition, the
starting material 1 was recovered in 18% yield (Scheme 4 and Table 3).
Scheme 4
Table 3. SnCl4- and SiO2-Catalyzed Reactions of 1 with 7 in CH2Cl2
Lewis
7
Temp.
Reaction time
Yield of products [ % ]
acid
8
9
10
11
12
13
1
SnCl4
(RS)
(R)
(R)
(S)
(R)
(R)
À 788
À 788
À 788
À 788
r.t.
17 min
17 min
20 min
17 min
3 d
37
79
62
1
58
51
21
8
6
45
44
SiO2
5
2
10
08
3 d
0.7
18
Isomerization of 10, 11, and 12. A solution of 10 in CH2Cl2 under N2 was treated
with one drop of conc. HCl for 2 min at room temperature. The usual workup by
preparative TLC yielded 86% of the spirocyclic compound 8. Similar treatment of 12 in
Et2O with two drops of conc. HCl for 1.5 h at room temperature gave 13 in 50% yield.
The analogous isomerization of 11 in CDCl3 proceeded smoothly at room temperature
by irradiation with sunlight for 2 h, leading to 9 in 77% yield. (Scheme 5).

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 5
Epimerization of 8 to 14, and of 9 to 15. Addition of seven drops of conc. HCl to a
CH2Cl2 solution of 8 at room temperature and stirring the mixture for 42 h yielded 67%
of 14, and 21% of the starting material 8 was recovered. An analogous epimerization of
9 in CDCl3 occurred upon irradiation with sunlight for 5 h at room temperature and led
to 15 in 42% yield. In addition, 32% of the starting material 9 was recovered
(Scheme 6).
The structures of 8 15 were assigned on the basis of their elemental analyses, 1H-,
13C-, and 2D-NMR, and mass spectra, and by comparison with those of similar
compounds described previously (see [1 5] and Sect. 2.1). The configurations of the
spirocyclic 1,3-oxathiolanes 8, 9, 13, 14, and 15 were determined by means of NOESY
spectra, relative to the known absolute configuration of the bicyclic skeleton of the
starting material 1.
The examination of a Dreiding model of 8 shows that the distances between
HÀC(2'') and HÀC(6'') of the Ph group and the Me group at C(1) are small, in
agreement with the NOESY spectrum (600 MHz, C6D6) of 8, which shows one cross-
signal between HÀC(2'')/HÀC(6'') at 7.31 ppm and MeÀC(1) at 1.16 ppm. In addition,
Dd of HendoÀC(6) at 2.47 ppm and HexoÀC(6) at ꢀ 1.50 ppm is 0.97 ppm, which
demonstrates that the O-atom is close to HendoÀC(6), i.e., the O-atom is in the endo-

Helvetica Chimica Acta Vol. 86 (2003)
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Scheme 6
position. Therefore, the absolute configuration of 8 has been established as
(1R,2R,4R,4'S). Similarly, the NOESY spectrum of 9 (600 MHz, CDCl3) shows one
relevant cross-signal between HÀC(2'')/HÀC(6'') at 7.42 7.40 ppm and MeÀC(1) at
1.08ppm, but the signals of H endoÀC(6) and HexoÀC(6) overlap at 1.62 1.54 ppm,
which implies that the O-atom is exo-oriented. Therefore, it can be deduced that 9
possesses the absolute configuration of (1R,2S,4R,4'R). The structure of 9 was
confirmed by X-ray crystallography (Fig. 1).
The crystals of 9 were enantiomerically pure, and the absolute configuration of the
molecule has been confidently determined independently by the diffraction experi-
ment. The enantiomer defined this way is in agreement with the known configuration of
the camphor moiety, and the configuration of the Ph-substituted C(4') is (R). The
configuration at the spiro C-atom is (S). Therefore, the absolute configuration deduced
by NOESY spectra is in agreement with the X-ray analysis.
The NOESY spectrum (600 MHz, CDCl3) of 13 shows two relevant cross-signals
between HÀC(2'')/HÀC(6'') at 7.40 7.39 ppm and HendoÀC(6) at 2.26 ppm and
MeÀC(1) at 1.04 ppm, as well as one relevant cross-signal between HÀC(5') at
4.86 ppm and HendoÀC(3) at 1.82 ppm. In addition, Dd of HendoÀC(6) (2.26 ppm) and
HexoÀC(6) (ca. 1.51 ppm) is 0.75 ppm, which suggests an endo-oriented O-atom.
Therefore, the absolute configuration of 13 should be (1R,2R,4R,5'R).
The NOESY spectrum (500 MHz, CDCl3) of 14 shows one relevant cross-peak
between HÀC(2'')/HÀC(6'') at 7.45 7.43 ppm and HendoÀC(3) at 2.20 ppm, as well as
one relevant cross-signal between HÀC(4') at 4.51 ppm and MeÀC(1) at 0.99 ppm. In
addition, the signals of HendoÀC(6) and HexoÀC(6) overlap (1.65 1.55 ppm), which
indicates an exo-oriented O-atom. So, it can be inferred that 14 has the absolute
configuration (1R,2S,4R,4'S), i.e., it is the C(2) epimer of 8.
The NOESY spectrum (500 MHz, CDCl3) of 15 shows two relevant cross-peaks
between HÀC(2'')/HÀC(6'') (7.42 7.41 ppm) and HexoÀC(3) (2.61 ppm) as well as

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Helvetica Chimica Acta Vol. 86 (2003)
Fig. 1. ORTEP Plot [6] of the molecular structure of 9 (arbitrary numbering of the atoms; 50% probability
ellipsoids)
HendoÀC(3) (1.86 ppm), and one relevant cross-signal between HÀC(4') (4.46 ppm)
and MeÀC(1) (1.02 ppm). The Dd of HendoÀC(6) (2.13 ppm) and HexoÀC(6) (ca.
1.48ppm) amounts to 0.65 ppm, which indicates an endo-oriented O-atom. According
to the results mentioned above, it can be concluded that the absolute configuration of
15 is (1R,2R,4R,4'R), i.e., 15 is the C(2) epimer of 9. This result was confirmed by X-ray
crystallography (Fig. 2).
The crystals of 15 were enantiomerically pure, and the absolute configuration of the
molecule has been confidently determined independently by the diffraction experi-
ment. The enantiomer defined this way is in agreement with the known configuration of
the camphor moiety. The configurations at the Ph-substituted C(4') and the spiro C-
atom are both (R).
3. Discussion and Conclusions. The results presented show that the enolizable
thioketone 1 reacts with the optically active monosubstituted oxiranes 2 and 7 in the
presence of a Lewis acid to yield spirocyclic 1,3-oxathiolanes, as well as open-chain
enethiol ethers, with high regio- and stereoselectivity. The reactions proceed via an Sn2-
type mechanism, whereby the nucleophilic thiocarbonyl S-atom preferentially attacks
the less hindered C(3)-atom of the activated (S)-2-methyloxirane (1) (OÀC(3)
cleavage), leading to products with retention of configuration (Scheme 2). In the case
of 2-phenyloxirane (7), the preferred attack takes place at C(2) (OÀC(2) cleavage)
with inversion of configuration (Scheme 4).

Helvetica Chimica Acta Vol. 86 (2003)
2265
Fig. 2. ORTEP Plot [6] of the molecular structure of one of the three symmetry-independent molecules of 15
(arbitrary numbering of the atoms; 50% probability ellipsoids)
In contrast to the analogous reaction with non-enolizable thioketones, enethiol
ethers 5, 10, 11, and 12 are formed with thiocamphor (1). Their formation can be
rationalized via intermediates of type A or B (Scheme 7). In the case of non-enolizable
thioketones, the analogous intermediates undergo ring closure to give 1,3-oxathiolanes
exclusively (cf. [1 5]).
Scheme 7
The enethiol ethers isomerize smoothly to give the corresponding spirocyclic 1,3-
oxathiolanes in the presence of traces of HCl or DCl (Schemes 3 and 5). The
mechanism of the isomerization of 5 is depicted in Scheme 8. The CˆC bond of the
sulfanylalkene of 5 is protonated, leading to the thiocarbonylium ion C. The cyclization
of C and subsequent release of a proton yields the spirocyclic 1,3-oxathiolanes 3 and 4,

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Scheme 8
depending upon the nucleophilic attack of the OH group from the si- and re-face side,
respectively (Scheme 8).
The observed epimerizations in the cases of 3/4, 8/14, and 9/15 (Schemes 3 and 6)
can be explained by the acid-catalyzed ring opening of the spirocyclic 1,3-oxathiolanes
according to the mechanism described by Pihlaja [7]. The ring opening of the oxonium
ion D leads to the thiocarbonylium ion C, which undergoes a cyclization by nucleophilic
attack of the OH group from the opposite side to yield the thermodynamically more
stable epimer 4 (Scheme 9).
Scheme 9
We thank the analytical services of our institute for NMR and mass spectra and elemental analyses, Miss J.
Cavegn and Mr. B. B¸rgi for their assistance with the determination of the crystal structures, and the Swiss
National Science Foundation and F. Hoffmann-La Roche AG, Basel, for financial support.
Experimental Part
1. General. See [8]. Optical rotations were recorded on a Perkin-Elmer-241 polarimeter (c ˆ 1, in THF).
HPLC on a Chiralcel OD-H column. IR Spectra: film, in cmÀ1. NMR Spectra: at 300 (1H) and 75.5 MHz (13C) in
CDCl3, if not otherwise stated. Assignment of signals based on 2D NMR spectra.
2. General Procedures for the Reactions of (1R,4R)-Thiocamphor (ˆ1,7,7-Trimethylbicylo[2.2.1]heptane-2-
thione; 1) with Oxiranes (S)-2 and 7. Procedure 1. To the soln. of 1 (ca. 1 mmol) in anh. CH2Cl2 (10 15 ml)
under N2 atmosphere, 0.5 equiv. of SnCl4 was added at À788. This led to little change in the color of the soln.
After stirring the mixture for 15 min at À788, ca. 2 equiv. of oxirane (S)-2 or 7 were added dropwise, whereby

Helvetica Chimica Acta Vol. 86 (2003)
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the color of the soln. changed moderately in most cases. Then, the reaction was quenched by addition of H2O,
and the mixture was washed with sat. aq. NaCl soln. (3Â). The combined org. layers were dried (MgSO4) and
evaporated in vacuo. The products were separated by chromatography (SiO2; hexane/Et2O or hexane/CH2Cl2;
CC, prep. TLC (PLC)).
Procedure 2. To a soln. of 1 (ca. 1 mmol) and oxirane (S)-2 or (7) (ca. 2 mmol) in dry CH2Cl2 (10 15 ml)
under an N2 atmosphere, 4.5 g of silica gel were added at r.t. After stirring the suspension for 2 3 d at r.t., the
mixture was filtered, and the residue was washed with CH2Cl2 (4Â). Then, the combined filtrate was evaporated
in vacuo. The products were separated as described above.
3. Reactions of 1. 3.1. With (S)-2-Methyloxirane ((S)-2). Reaction of 1 (168mg, 1 mmol) with 2 (232 mg,
4 mmol, or 116 mg, 2 mmol) and 0.6 mmol of SnCl4 (or 4.5 g of SiO2) at À788 or r.t. (CC (hexane/CH2Cl2 10 :1
and hexane/Et2O 3 :1)) yielded (1R,2R,4R,5'S)-1,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]oxa-
thiolane] (3), (1R,2S,4R,5'S)-1,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]oxathiolane] (4), (2S)-1-
[(1'R,4'R)-(1',7',7'-trimethylbicyclo[2.2.1]hept-2'-en-2'-yl)sulfanyl]propan-2-ol (5), and camphor (6). In addi-
tion, the starting material 1 was partly recovered in the case of SiO2 as catalyst (Scheme 2 and Table 1).
Data of 3: Yield: 116 (36) mg (51 (16)%). Colorless oil. [a]2D2 ˆ ‡ 44.3. IR: 2952s, 2932s, 2883m, 1475m,
1454s, 1389s, 1373s, 1348w, 1332w, 1306m, 1274w, 1250w, 1234w, 1195m, 1178w, 1149m, 1112s, 1092s, 1060s, 1046s,
1023w, 1012w, 998m, 953m, 938m, 8 8m4, 8 2w3, 8 0m3 , 747w. 1H-NMR (600 MHz, C6D6): 4.02 3.99 (m,
HÀC(5')); 2.65 (ddd, J ˆ 14.1, 4.4, 3.4, HexoÀC(3)); 2.62 (dd, J ˆ 9.9, 5.4, 1 HÀC(4')); 2.44 (dd, J ˆ 9.8, 7.2, 1
HÀC(4')); 2.32 (ddd, J ˆ 12.8, 9.3, 3.7, HendoÀC(6)); 1.95 (d, J ˆ 14.1, HendoÀC(3)); 1.67 1.66 (m, HexoÀC(5));
1.56 (t, J ˆ 4.6, HÀC(4)); 1.45 (ddd, J ˆ 12.2, 7.4, 4.8, HexoÀC(6)); 1.37 1.33 (m, HendoÀC(5)); 1.11 (s,
MeÀC(1)); 1.08( d, J ˆ 6.0, MeÀC(5')); 1.05 (s, Mesyn); 0.78( s, Meanti). 13C-NMR (150.9 MHz, C6D6): 103.8( s,
C(2)); 78.7 (d, C(5')); 55.7 (s, C(1)); 50.6 (t, C(3)); 49.5 (s, C(7)); 46.6 (d, C(4)); 40.7 (t, C(4')); 30.5 (t, C(6));
28.0 (t, C(5)); 21.3 (q, Mesyn); 21.1 (q, Meanti); 20.4 (q, MeÀC(5')); 15.3 (q, MeÀC(1)). CI-MS (NH3): 228(15),
‡
227 (100, [M ‡ H] ), 171 (8), 170 (67), 169 (7), 153 (7). Anal. calc. for C13H22OS (226.38): C 68.97, H 9.80,
S 14.16; found: C 68.92, H 9.66, S 14.07.
Data of 4: Yield: 18mg (8%). Colorless oil. [ a]2D5 ˆ ‡ 50.9. IR: 2955s, 2930s, 2880s, 1480m, 1450m, 1440m,
1390m, 1380m, 1370m, 1348w, 1335w, 1305w, 1275w, 1255w, 1220w, 1200w, 1175m, 1165m, 1143m, 1130m, 1110m,
1095s, 1080s, 1030s, 998w, 950m, 928w, 8 8 0m, 8 65w, 8 55w, 8 40w, 8 05w, 762w, 740w. 1H-NMR (500 MHz, CDCl3):
4.18 4.13 ( m, HÀC(5')); 2.92 (dd, J ˆ 9.7, 4.9, 1 HÀC(4')); 2.43 (t, J ˆ 9.7, 1 HÀC(4')); 2.33 (ddd, J ˆ 13.4, 4.3,
3.4, HexoÀC(3)); 1.91 (d, J ˆ 13.4, HendoÀC(3)); 1.76 (t-like, J ꢀ 4.5, HÀC(4)); 1.74 1.68( m, HexoÀC(5)); 1.63
1.56 (m, 2 HÀC(6)); 1.34 (d, J ˆ 6.0, MeÀC(5')); 1.22 1.17 (m, HendoÀC(5)); 1.03 (s, Mesyn); 0.89 (s, MeÀC(1));
0.87 (s, Meanti). 13C-NMR (125.8MHz, CDCl 3): 104.8( s, C(2)); 77.6 (d, C(5')); 53.3 (s, C(1)); 51.7 (t, C(3)); 48.1
(s, C(7)); 45.9 (d, C(4)); 38.2 (t, C(4')); 34.7 (t, C(6)); 27.2 (t, C(5)); 21.1 (q, Meanti); 20.8( q, Mesyn); 19.5 (q,
‡
MeÀC(5')); 10.0 (q, MeÀC(1)). CI-MS (NH3): 228(6), 227 (40, [ M ‡ H] ), 171 (11), 170 (100), 153 (10). Anal.
calc. for C13H22OS (226.38): C 68.97, H 9.80, S 14.16; found: C 69.04, H 9.98, S 13.88.
Data of 5: Yield: 41 (108) mg (18 (48)%). Colorless oil. [ a]2D2 ˆ À22.2. IR: 3356m (br., OH), 3059w, 2954s,
2872s, 1561m, 1453m, 1386m, 1375m, 1365m, 1298m, 1255w, 1186w, 1125m, 1107m, 1074m, 1044m, 98 3m, 935m,
906w, 8 76w, 8 20w, 776w, 714w. 1H-NMR: 5.57 (d, J ˆ 3.4, HÀC(3')); 4.00 3.94 (m, HÀC(2)); 2.85 (dd, J ˆ 13.4,
4.0, 1 HÀC(1)); 2.67 (dd, J ˆ 13.4, 8.1, 1 HÀC(1)); 2.35 (t, J ˆ 3.5, HÀC(4')); 2.17 (d, J ˆ 3.5, OH); 1.92 1.83
(m, HexoÀC(5')); 1.55 1.48( m, HexoÀC(6')); 1.27 (d, J ˆ 6.2, 3 HÀC(3)); 1.13 0.97 (m, HendoÀC(5'),
HendoÀC(6')); 1.01 (s, MeÀC(1)); 0.81 (s, Mesyn); 0.78( s, Meanti). 13C-NMR: 143.3 (s, C(2')); 125.3 (d, C(3')); 65.9
(d, C(2)); 56.5 (s, C(1')); 56.4 (s, C(7')); 52.1 (d, C(4')); 40.4 (t, C(1)); 31.7 (t, C(6')); 26.4 (t, C(5')); 22.3 (q, C(3));
.
‡
19.7 (q, Meanti); 19.5 (q, Mesyn); 11.3 (q, MeÀC(1')). EI-MS: 226 (24, M ), 198(50), 184 (16), 169 (24), 168(43),
167 (50), 165 (13), 155 (13), 153 (11), 152 (12), 151 (12), 141 (11), 140 (42), 139 (15), 138(10), 135 (14), 133
(12), 125 (46), 123 (18), 121 (11), 119 (19), 116 (15), 111 (13), 109 (26), 108 (74), 107 (34), 106 (12), 105 (30),
97 (13), 95 (65), 93 (37), 91 (51), 85 (16), 83 (23), 81 (42), 80 (11), 79 (27), 77 (30), 74 (14), 71 (10), 69 (36), 67
(27), 65 (17), 59 (17), 57 (26), 55 (45), 53 (22), 45 (32), 43 (40), 41 (100).
Isomerization of 5 to 3 and 4. Treatment of 5 (60 mg, 0.27 mmol) with 4 drops of conc. HCl in Et2O (15 ml)
at À208 (8h, CC (hexane/CH 2Cl2 10 :1)) yielded 44 mg (73%) of 3 and 5 mg (8%) of 4. Moreover, the
isomerization of 5 to 3 and 4 proceeded very smoothly in NMR tubes in the presence of traces of DCl with
different ratios of 3 to 4, depending upon the conditions, but without DCl (CDCl3 filtered through Alox
(basic)), 5 did not change at all (Scheme 3 and Table 2).
Epimerization of 3 to 4. Treatment of 3 (106 mg, 0.47 mmol) with 5 drops of conc. HCl in CH2Cl2 (6 ml) at
r.t. (7.5 h, CC (hexane/CH2Cl2 10 :1)) yielded 77 mg (73%) of 4, and 8mg (7%) of the starting material 3 was
recovered (Scheme 3).

2268
Helvetica Chimica Acta Vol. 86 (2003)
3.2. With 2-Phenyloxirane (7). Reaction of 1 (168mg, 1 mmol) with 7 (240 mg, 2 mmol) and 0.5 mmol SnCl4
(or 4.5 g of SiO2) at À 788, 08, or r.t. (CC (hexane/CH2Cl2 10 :1 and hexane/Et2O 3 :1)) gave (1R,2R,4R,4'S)-
1,7,7-trimethyl-4'-phenylspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]oxathiolane] (8), (1R,2S,4R,4'R)-1,7,7-trimethyl-
4'-phenylspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]oxathiolane] (9), (2S)-2-phenyl-2-[(1'R,4'R)-(1',7',7'-trimethylbi-
cyclo[2.2.1]hept-2'-en-2'-yl)sulfanyl]ethanol (10), (2R)-2-phenyl-2-[(1'R,4'R)-(1',7',7'-trimethylbicyclo[2.2.1]-
hept-2'-en-2'-yl)sulfanyl]ethanol (11), (1R)-1-phenyl-2-[(1'R,4'R)-(1',7',7'-trimethylbicyclo[2.2.1]hept-2'-en-2'-
yl)sulfanyl]ethanol (12), and (1R,2R,4R,5'R)-1,7,7-trimethyl-5'-phenylspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]oxa-
thiolane] (13). In addition, the starting material 1 was partly recovered when SiO2 was used as a catalyst at 08
(Scheme 4; for yields see Table 3).
Data of 8: Colorless oil. [a]2D3 ˆ À119.0. IR: 3080w, 3058w, 3020m, 2980s, 2950s, 2865s, 1600m, 1583w,
1490m, 1472m, 1450s, 1388s, 1369m, 1350w, 1304m, 1272m, 1250m, 1191m, 1150w, 1111m, 1078s, 1040m, 1025m,
1015m, 1000w, 98 5w, 958m, 935m, 911w, 8 8 0m, 8 60w, 8 10m, 795w, 758m, 724w, 700s. 1H-NMR (600 MHz, C6D6):
7.31 (d-like, J ˆ 7.2, HÀC(2''), HÀC(6'')); 7.10 (t-like, J ꢀ 7.7, H ÀC(3''), HÀC(5'')); 7.02 (t-like, J ꢀ 7.3,
HÀC(4'')); 4.36 (dd, J ˆ 5.8, 2.8, HÀC(4')); 4.01 (dd, J ˆ 9.4, 2.8, 1 HÀC(5')); 3.77 (dd, J ˆ 9.4, 5.9, 1 HÀC(5'));
2.54 (ddd, J ˆ 13.7, 7.8, 3.2, HexoÀC(3)); 2.47 (ddd, J ˆ 12.8, 9.3, 3.6, HendoÀC(6)); 1.79 (d, J ˆ 13.7, HendoÀC(3));
1.69 1.63 (m, HexoÀC(5), HÀC(4)); 1.52 1.47 (m, HexoÀC(6)); 1.32 1.28( m, HendoÀC(5)); 1.16 (s,
MeÀC(1)); 1.03 (s, Mesyn); 0.78( s, Meanti). 13C-NMR (150.9 MHz, C6D6): 143.6 (s, C(1'')); 129.0 (d, C(3''),
C(5'')); 128.2 (d, C(2''), C(6'')); 127.5 (d, C(4'')); 106.1 (s, C(2)); 75.8( t, C(5')); 54.9 (s, C(1)); 54.0 (d, C(4')); 51.0
(t, C(3)); 49.0 (s, C(7)); 47.0 (d, C(4)); 31.2 (t, C(6)); 28.0 (t, C(5)); 21.6 (q, Mesyn); 20.6 (q, Meanti); 14.9 (q,
‡
MeÀC(1)). CI-MS (NH3): 290 (21), 289 (100, [M ‡ H] ), 202 (11), 170 (42), 104 (12). Anal. calc. for C18H24OS
(288.45): C 74.95, H 8.39, S 11.12; found: C 74.87, H 8.13, S 10.88.
Data of 9: Colorless crystals. M.p. 79.4 79.78. [a]2D3 ˆ ‡86.5. IR (KBr): 3060w, 3031w, 3012w, 2985m, 2956s,
2884m, 2886s, 1616w, 1602w, 1540w, 1498w, 1490w, 1480m, 1456s, 1387m, 1370m, 1351w, 1342w, 1304w, 1277w,
1246w, 1156w, 1137w, 1112w, 1082s, 1057w, 1042s, 1011m, 990w, 953m, 937m, 913w, 8 71m, 8 36m, 8 07m, 772m,
1
757m, 735w, 701s. H-NMR (600 MHz, CDCl3): 7.42 7.40 (m, HÀC(2''), HÀC(6'')); 7.32 7.29 (m, HÀC(3''),
HÀC(5'')); 7.24 7.21 (m, HÀC(4'')); 4.49 (dd, J ˆ 6.0, 3.9, HÀC(4')); 4.28( dd, J ˆ 9.4, 6.1, 1 HÀC(5')); 4.18( dd,
J ˆ 9.4, 3.9, 1 HÀC(5')); 2.45 (ddd, J ˆ 13.4, 4.4, 3.3, HexoÀC(3)); 2.03 (d, J ˆ 13.4, HendoÀC(3)); 1.82 (t, J ˆ 4.5,
HÀC(4)); 1.77 1.72 (m, HexoÀC(5)); 1.62 1.54 (m, 2 HÀC(6)); 1.27 1.22 (m, HendoÀC(5)); 1.08(2 s, Mesyn
,
MeÀC(1)); 0.91 (s, Meanti). 13C-NMR (150.9 MHz, CDCl3): 142.5 (s, C(1'')); 128.7 (d, C(3''), C(5'')); 127.8( d,
C(2''), C(6'')); 127.3 (d, C(4'')); 107.6 (s, C(2)); 77.1 (t, C(5')); 54.2 (s, C(1)); 51.2 (t, C(3)); 51.1 (d, C(4')); 48.6 (s,
C(7)); 46.0 (d, C(4)); 34.9 (t, C(6)); 27.2 (t, C(5)); 21.2 (q, Meanti); 20.9 (q, Mesyn); 10.7 (q, MeÀC(1)). CI-MS
‡
(NH3): 290 (6), 289 (78, [M ‡ H] ), 256 (9), 202 (8), 171 (11), 170 (100), 164 (49), 104 (9). Anal. calc. for
C18H24OS (288.45): C 74.95, H 8.39, S 11.12; found: C 75.08, H 8.15, S 10.94.
Crystals of 9 suitable for the X-ray crystal-structure determination were grown from Et2O/MeOH.
Data of 10: Colorless oil. [a]2D2 ˆ ‡69.4. IR: 3385m (br., OH), 3062w, 3029w, 2982m, 2953s, 2871s, 1601w,
1582w, 1561w, 1493m, 1470m, 1453s, 1386m, 1375m, 1365m, 1290w, 1279w, 1253w, 1202w, 1184w, 1134w, 1106w,
1
1075m, 1054s, 1018m, 98 1m, 906w, 8 75w, 8 20w, 78 3w, 757w, 737w, 715w, 698s. H-NMR: 7.35 7.18( m, 5 arom.
H); 5.58( d, J ˆ 3.4, HÀC(3')); 4.11 (t, J ˆ 6.6, HÀC(2)); 3.85 3.79 (br. s, 2 HÀC(1)); 2.24 (t, J ˆ 3.5, HÀC(4'));
1.81 1.74 (m, OH, HexoÀC(5')); 1.47 1.39 (m, HexoÀC(6')); 1.05 0.89 (m, HendoÀC(5'), HendoÀC(6')); 0.94 (s,
MeÀC(1)); 0.69 (s, Mesyn); 0.67 (s, Meanti). 13C-NMR: 142.0 (s, C(1'')); 139.0 (s, C(2')); 128.7 (d, C(3''), C(5''));
128.5 (d, C(4'')); 128.0 (d, C(2''), C(6'')); 127.7 (d, C(3')); 65.8( t, C(1)); 56.9 (s, C(1')); 56.0 (s, C(7')); 52.2 (d,
C(2)); 52.1 (d, C(4')); 31.5 (t, C(6')); 26.3 (t, C(5')); 19.6 (q, Meanti); 19.4 (q, Mesyn); 11.4 (q, MeÀC(1')). CI-MS
‡
(NH3): 290 (20), 289 (100, [M ‡ H] ), 170 (8), 169 (14).
Data of 11: Colorless oil. [a]2D2 ˆ À185.2. IR: 3377m (br., OH), 3062w, 3029w, 2985m, 2953s, 2870s, 1601w,
1584w, 1561m, 1492m, 1471m, 1452s, 1386s, 1374m, 1365m, 1297m, 1253w, 1205w, 1185w, 1134w, 1106w, 1056s,
1019m, 98 1m, 933w, 906w, 8 75w, 8 21w, 78 4w, 757w, 737w, 716w, 698s. 1H-NMR: 7.38 7.22 ( m, 5 arom. H); 5.61
(d, J ˆ 3.4, HÀC(3')); 4.24 (t, J ˆ 6.7, HÀC(2)); 3.92 (t, J ˆ 6.5, 2 HÀC(1)); 2.28( t, J ˆ 3.5, 1 HÀC(4')); 1.85 (t,
J ˆ 6.6, OH); 1.79 1.70 (m, HexoÀC(5')); 1.41 (ddd, J ˆ 12.1, 8.6, 3.3, HexoÀC(6')); 1.00 (s, MeÀC(1)); 0.91 0.68
(m, HendoÀC(5'), HendoÀC(6')); 0.78( s, Mesyn); 0.74 (s, Meanti). 13C-NMR: 141.4 (s, C(1'')); 139.1 (s, C(2')); 128.5
(d, C(3''), C(5'')); 128.2 (d, C(4'')); 127.9 (d, C(2''), C(6'')); 127.5 (d, C(3')); 65.9 (t, C(1)); 56.6 (s, C(1')); 55.8( s,
C(7')); 52.5 (d, C(2)); 52.1 (d, C(4')); 31.1 (t, C(6')); 26.0 (t, C(5')); 19.5 (q, Meanti); 19.3 (q, Mesyn); 11.2 (q,
‡
MeÀC(1')). CI-MS (NH3): 291 (7), 290 (20), 289 (100, [M ‡ H] ), 169 (18). Anal. calc. for C18H24OS (288.45):
C 74.95, H 8.39, S 11.12; found: C 74.79, H 8.26, S 11.03.
Data of 12: Colorless oil. [a]2D2 ˆ À1.0. IR: 3407m (br., OH), 3063w, 3028w, 2982m, 2953s, 2871m, 1561w,
1495w, 1472w, 1455m, 1386m, 1373w, 1365w, 1298w, 1189w, 1133w, 1106w, 1080w, 1054m, 1046m, 1027m, 98 3m,
908w, 8 75w, 8 20w, 777w, 754w, 713w, 698s. 1H-NMR (600 MHz, CDCl3): 7.39 7.35 (m, 4 arom. H); 7.31 7.28( m,

Helvetica Chimica Acta Vol. 86 (2003)
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1 arom. H); 5.69 (d, J ˆ 3.4, HÀC(3')); 4.76 (dd, J ˆ 9.6, 1.7, 1 HÀC(1)); 3.08( dd, J ˆ 13.7, 3.2, 1 HÀC(2)); 2.85
(dd, J ˆ 13.7, 9.7, 1 HÀC(2)); 2.68(br. s, OH); 2.39 (t, J ˆ 3.4, HÀC(4')); 1.92 1.89 (m, HexoÀC(5')); 1.55 1.51
(m, HexoÀC(6')); 1.09 1.01 (m, HendoÀC(5'), HendoÀC(6')); 1.04 (s, MeÀC(1)); 0.84 (s, Mesyn); 0.80 (s, Meanti).
13C-NMR (105.9 MHz, CDCl3): 142.5 (s, C(1'')); 142.3 (s, C(2')); 128.6 (d, C(3''), C(5'')); 127.9 (d, C(4'')); 127.2
(d, C(3')); 125.8( d, C(2''), C(6'')); 71.3 (d, C(1)); 56.8( s, C(1')); 56.0 (s, C(7')); 52.2 (d, C(4')); 40.9 (t, C(2)); 31.5
(t, C(6')); 26.5 (t, C(5')); 19.7 (q, Meanti); 19.5 (q, Mesyn); 11.4 (q, MeÀC(1')). CI-MS (NH3): 291 (6), 290 (20),
‡
289 (100, [M ‡ H] ), 171 (13).
Data of 13: Colorless oil. [a]2D2 ˆ À116.7. IR: 3088w, 3066w, 3031w, 2984s, 2952s, 2928s, 2873m, 1607w,
1498w, 1477w, 1454s, 1433w, 1390m, 1371m, 1320w, 1305w, 1273w, 1251w, 1211w, 1193m, 1143w, 1113m, 1082s,
1070s, 1049m, 1029m, 997w, 960w, 936w, 919w, 8 8 8w, 8 32w, 8 06w, 765m, 742m, 697s. 1H-NMR (600 MHz, CDCl3):
7.40 7.39 (m, HÀC(2''), HÀC(6'')); 7.36 7.34 (m, HÀC(3''), HÀC(5'')); 7.31 7.28( m, HÀC(4'')); 4.86 (dd,
J ˆ 10.5, 4.5, HÀC(5')); 3.22 (dd, J ˆ 10.2, 4.5, 1 HÀC(4')); 2.70 (t, J ˆ 10.4, 1 HÀC(4')); 2.45 (ddd, J ˆ 13.8, 4.7,
3.0, HexoÀC(3)); 2.26 (ddd, J ˆ 13.0, 9.3, 3.8, HendoÀC(6)); 1.82 (d, J ˆ 13.8, HendoÀC(3)); 1.77 (t, J ˆ 4.7,
HÀC(4)); 1.74 1.68( m, HexoÀC(5)); 1.53 1.48( m, HexoÀC(6)); 1.26 (ddd, J ˆ 12.3, 9.4, 4.8, HendoÀC(5)); 1.04
(s, MeÀC(1)); 0.98( s, Mesyn); 0.91 (s, Meanti). 13C-NMR (105.9 MHz, CDCl3): 139.9 (s, C(1'')); 128.5 (d, C(3''),
C(5'')); 127.9 (d, C(4'')); 126.0 (d, C(2''), C(6'')); 102.9 (s, C(2)); 82.1 (d, C(5')); 54.3 (s, C(1)); 50.8( t, C(3)); 48.2
(s, C(7)); 46.6 (d, C(4)); 41.7 (t, C(4')); 30.4 (t, C(6)); 27.0 (t, C(5)); 21.0 (q, Mesyn); 20.2 (q, Meanti); 12.6 (q,
‡
MeÀC(1)). CI-MS (NH3): 289 (37, [M ‡ H] ), 171 (12), 170 (100). Anal. calc. for C18H24OS (288.45): C 74.95,
H 8.39, S 11.12; found: C 74.72, H 8.08, S 11.41.
Isomerization of 10 to 8, of 11 to 9, and of 12 to 13. Treatment of 10 (21 mg, 0.07 mmol) with 1 drop of conc.
HCl in CH2Cl2 (10 ml) at r.t. (2 min, prep. TLC (hexane/CH2Cl2 4 :1)) yielded 18mg (86%) of 8. Irradiation of
11 (13 mg, 0.045 mmol) in CDCl3 (1 ml) with sunlight at r.t. (2 h, prep. TLC (hexane/CH2Cl2 4 :1)) gave 10 mg
(77%) of 9. Treatment of 12 (30 mg, 0.10 mmol) with 2 drops of conc. HCl in Et2O (15 ml) at r.t. (1.5 h, prep.
TLC (hexane/CH2Cl2 20 :1)) yielded 15 mg (50%) of 13 (Scheme 5).
Epimerization of 8 to 14, and of 9 to 15. Treatment of 8 (82 mg, 0.28 mmol) with 7 drops of conc. HCl in
CH2Cl2 (10 ml) at r.t. (42 h, PLC (hexane/CH2Cl2 15 :1)) yielded 55 mg (67%) of (1R,2S,4R,4'S)-1,7,7-trimethyl-
4'-phenylspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]oxathiolane] (14), and 17 mg (21%) of the starting material 8 was
recovered. An analogous epimerization of 9 (143 mg, 0.50 mmol) in CDCl3 (5 ml) by irradiation with sunlight at
r.t. (5 h, prep. HPLC (chiral phase, hexane)) gave 60 mg (42%) of (1R,2R,4R,4'R)-1,7,7-trimethyl-4'-
phenylspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]oxathiolane] (15), and 46 mg (32%) of the starting material 9 was
recovered (Scheme 6).
Data of 14: Colorless oil. [a]2D2 ˆ À43.2. IR: 3080w, 3060w, 3025m, 2950s, 2930s, 2880s, 1600m, 1490m,
1480m, 1450s, 1388s, 1370m, 1355w, 1330w, 1305m, 1293w, 1278w, 1245w, 1205w, 1195w, 1160w, 1140w, 1110m,
1085s, 1050s, 1025m, 1015m, 1000m, 955m, 945m, 915w, 8 74m, 8 60w, 8 38m, 8 05m, 760s, 736w, 699s. 1H-NMR
(500 MHz, CDCl3): 7.45 7.43 (m, HÀC(2''), HÀC(6'')); 7.35 7.31 (m, HÀC(3''), HÀC(5'')); 7.28 7.24 ( m,
HÀC(4'')); 4.51 (dd, J ˆ 8.6, 6.2, HÀC(4')); 4.39 (dd, J ˆ 9.4, 6.2, 1 HÀC(5')); 3.89 (t-like, J ꢀ 9.0, 1 HÀC(5'));
2.52 (ddd, J ˆ 13.4, 4.5, 3.2, HexoÀC(3)); 2.20 (d, J ˆ 13.4, HendoÀC(3)); 1.85 (t, J ˆ 4.5, HÀC(4)); 1.80 1.73 (m,
HexoÀC(5)); 1.65 1.55 (m, 2 HÀC(6)); 1.30 1.25 (m, HendoÀC(5)); 1.07 (s, Mesyn); 0.99 (s, MeÀC(1)); 0.91 (s,
Meanti). 13C-NMR (125.8MHz, CDCl 3): 139.4 (s, C(1'')); 128.5 (d, C(3''), C(5'')); 128.0 (d, C(2''), C(6'')); 127.4
(d, C(4'')); 107.4 (s, C(2)); 77.3 (t, C(5')); 54.0 (s, C(1)); 52.6 (d, C(4')); 51.7 (t, C(3)); 48.3 (s, C(7)); 45.9 (d,
C(4)); 34.7 (t, C(6)); 27.1 (t, C(5)); 21.1 (q, Meanti); 20.7 (q, Mesyn); 10.1 (q, MeÀC(1)). CI-MS (NH3): 290 (7),
‡
289 (35, [M ‡ H] ), 202 (16), 171 (11), 170 (100), 104 (8). Anal. calc. for C18H24OS (288.45): C 74.95, H 8.39,
S 11.12; found: C 74.84, H 8.21, S 11.15.
Data of 15: Colorless crystals. M.p. 43.5 45.08. [a]2D2 ˆ ‡29.6. IR: 3085w, 3063w, 3029m, 2985s, 2954s, 2870s,
1601m, 1493m, 1477m, 1452s, 1390s, 1372m, 1331w, 1305m, 1273m, 1249w, 1205m, 1193m, 1164w, 1113m, 1084s,
1051m, 1037m, 1019m, 1002m, 976m, 956m, 936m, 913w, 8 8m1, 8 61m, 8 20m, 8 08m, 759s, 698s. 1H-NMR
(500 MHz, CDCl3): 7.42 7.41 (m, HÀC(2''), HÀC(6'')); 7.32 7.29 (m, HÀC(3''), HÀC(5'')); 7.25 7.22 (m,
HÀC(4'')); 4.46 (dd, J ˆ 9.3, 5.8, HÀC(4')); 4.33 (dd, J ˆ 9.2, 5.8, 1 HÀC(5')); 3.68( t, J ˆ 9.3, 1 HÀC(5')); 2.61
(ddd, J ˆ 13.8, 4.6, 3.1, HexoÀC(3)); 2.13 (ddd, J ˆ 13.0, 9.3, 3.7, HendoÀC(6)); 1.86 (d, J ˆ 13.8, HendoÀC(3)); 1.79
(t, J ˆ 4.7, HÀC(4)); 1.74 1.70 (m, HexoÀC(5)); 1.51 1.45 (m, HexoÀC(6)); 1.29 1.25 (m, HendoÀC(5)); 1.02 (s,
MeÀC(1)); 0.96 (s, Mesyn); 0.90 (s, Meanti). 13C-NMR (125.8MHz, CDCl 3): 138.4 (s, C(1'')); 128.8 (d, C(3''),
C(5'')); 128.4 (d, C(2''), C(6'')); 127.7 (d, C(4'')); 105.6 (s, C(2)); 76.1 (t, C(5')); 55.0 (d, C(4')); 54.6 (s, C(1)); 51.0
(t, C(3)); 48.6 (s, C(7)); 46.5 (d, C(4)); 30.0 (t, C(6)); 27.3 (t, C(5)); 21.2 (q, Mesyn); 20.4 (q, Meanti); 13.3 (q,
‡
MeÀC(1)). CI-MS (NH3): 290 (6), 289 (26, [M ‡ H] ), 171 (12), 170 (100), 104 (7). Anal. calc. for C18H24OS
(288.45): C 74.95, H 8.39, S 11.12; found: C 75.10, H 8.22, S 11.04.
Crystals of 15 suitable for X-ray crystal-structure determination were grown from EtOH.

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Helvetica Chimica Acta Vol. 86 (2003)
6. X-Ray Crystal-Structure Determination of 9 and 15 (Table 4, and Figs. 1 and 2)2). All measurements were
performed on a Nonius KappaCCD diffractometer [9] with graphite-monochromated MoKa radiation (l ˆ
0.71073 ä) and an Oxford Cryosystems Cryostream 700 cooler. The data collection and refinement parameters
are given in Table 4, and views of the molecules are shown in Figs. 1 and 2. Data reduction was performed with
HKL Denzo and Scalepack [10]. The intensities were corrected for Lorentz and polarization effects, but not for
absorption. The structures were solved by direct methods with SIR92 [11], which revealed the positions of all
non-H-atoms. There are three symmetry-independent molecules in the asymmetric unit of 15. The atomic
coordinates of the molecules were tested carefully for a relationship from a higher-symmetry space group with
the program PLATON [12], but none could be found. All are of the same stereoisomer, and molecules B and C
have almost identical conformations. Molecule A differs slightly by a twist of ca. 188 in the orientation of the Ph
ring with respect to its orientation in molecules B and C. The non-H-atoms of each structure were refined
anisotropically. All of the H-atoms were placed in geometrically idealized positions, and each was assigned a
fixed isotropic displacement parameter with a value equal to 1.2 Ueq of its parent C-atom (1.2 Ueq for the Me
Table 4. Crystallographic Data of Compounds 9 and 15
9
15
Crystallized from
Et2O/MeOH
C18H24OS
288.45
colorless, needle
0.10 Â 0.12 Â 0.280.25
160(1)
EtOH
C18H24OS
288.45
colorless, prism
 0.28  0.32
160(1)
Empirical formula
Formula weight [g molÀ1
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
]
Crystal system
Space group
orthorhombic
P212121
orthorhombic
P212121
Z
4
12
Reflections for cell determination
2q Range for cell determination [8]
2597
6085
4 55
4
60
Unit cell parameters
a [ä]
7.4031(1)
10.0944(1)
20.6428(3)
1542.63(3)
1.242
11.1418(1)
15.8380(2)
27.0675(3)
4776.43(9)
1.203
b [ä]
c [ä]
V [ä3]
DX [g cmÀ3
]
m (MoKa) [mmÀ1
2qmax [8]
]
0.204
60
0.198
55
Scan type
Total reflections measured
f and w
37157
f and w
61270
Symmetry-independent reflections
Reflections with I > 2s (I)
Parameters refined
4501
3640
183
10952
7086
551
R [on F; I > 2s (I) reflections]
wR
Goodness-of-fit
0.0407
0.0449
0.0353a)
1.547
0.0846b)
0.969
Secondary extinction coefficient
Final Dmax/s
1.3(2) Â 10À6
1.4(2) Â 10À3
0.0003
0.001
D1 (max; min) [e äÀ3
]
0.31; À0.33
0.34; À0.25
b
a) wR(F) (wˆ[s2(Fo)‡(0.01Fo)2]À1, I > 2s(I) reflections). ) wR(F2) (w ˆ [s2(Fo2)‡(0.0258P)2]À1, where
Pˆ(Fo2 ‡ 2Fc2)/3, all independent reflections).
2
)
CCDC-203514 and -203515 contain the supplementary crystallographic data for this paper. These data can
be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax: ‡44-(0)1223-336033; e-
mail: deposit@ccdc.cam.ac.uk).

Helvetica Chimica Acta Vol. 86 (2003)
2271
groups in 15). Refinement of the structure was carried out on F (for 9) and F2 (for 15) by full-matrix least-
squares procedures, which minimized the function Sw(j Fo jÀj Fc j )2 and Sw(Fo2 À Fc2)2, resp. A correction for
secondary extinction was applied in each case. Refinement of the absolute structure parameter [13] yielded
values of 0.01(5) and À0.03(4), resp., which confidently confirms that the refined coordinates represent the true
enantiomorph. Neutral-atom-scattering factors for non-H-atoms were taken from [14a], and the scattering
factors for H-atoms were taken from [15]. Anomalous dispersion effects were included in Fc [16]; the values for
f' and f'' were those of [14b]. The values of the mass attenuation coefficients are those of [14c]. All calculations
for 9 were performed with the teXsan crystallographic software package [17], and those for 15 employed
SHELXL97 [18].
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Received February 12, 2003