1,3-Oxathiolanes from the reaction of aromatic and enolized thioketones with monosubstituted oxiranes

Article abstract of DOI:10.1002/hlca.200390234

The reactions of 4,4′-dimethoxythiobenzophenone (1) with (S)-2-methyloxirane ((S)-2) and (R)-2-phenyloxirane ((R)-6) in the presence of a Lewis acid such as BF₃·Et₂O, ZnCl₂, or SiO₂ in dry CH₂Cl₂ led to the corresponding 1:1 adducts, i.e., 1,3-oxathiolanes (S)-3 with Me at C(5), and (S)-7 and (R)-8 with Ph at C(4) and C(5), respectively. A 1:2 adduct, 1,3,6-dioxathiocane (4S,8S)-4 and 1,3-dioxolane (S)-9, respectively, were formed as minor products (Schemes 3 and 5, Tables 1 and 2). Treatment of the 1:1 adduct (S)-3 with (S)-2 and BF₃·Et₂O gave the 1:2 adduct (4S,8S)-4 (Scheme 4). In the case of the enolized thioketone 1,3-diphenylprop-1-ene-2-thiol (10) with (S)-2 and (R)-6 in the presence of SiO₂, the enesulfanyl alcohols (1′Z,2S)-11 and (1′E,2S)-11, and (1′Z,2S)-13, (1′E,2S)-13, (1′Z,1R)-15, and (1′E,1R)-15, respectively, as well as a 1,3-oxathiolane (S)-14 were formed (Schemes 6 and 8). In the presence of HCl, the enesulfanyl alcohols (1′Z,2S)-11, (1′Z,2S)-13, (1′E,2S)-13, (1′Z,1R)-15, and (1′E,1R)-15 cyclize to give the corresponding 1,3-oxathiolanes (S)-12, (S)-14, and (R)-16, respectively (Schemes 7, 9, and 10). The structures of (1′E,2S)-11, (S)-12, and (S)-14 were confirmed by X-ray crystallography (Figs. 1-3). These results show that 1,3-oxathiolanes can be prepared directly via the Lewis acid-catalyzed reactions of oxiranes with non-enolizable thioketones, and also in two steps with enolized thioketones. The nucleophilic attack of the thiocarbonyl or enesulfanyl S-atom at the Lewis acid-complexed oxirane ring proceeds with high regio- and stereoselectivity via an S_K2-type mechanism.

Full text of DOI:10.1002/hlca.200390234

Helvetica Chimica Acta ± Vol. 86 (2003)
2833
1
,3-Oxathiolanes from the Reaction of Aromatic and Enolized Thioketones
with Monosubstituted Oxiranes
1
by Changchun Fu ), Anthony Linden, and Heinz Heimgartner*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstr. 190, CH-8057 Z¸rich
The reactions of 4,4'-dimethoxythiobenzophenone (1) with (S)-2-methyloxirane ((S)-2) and (R)-2-
phenyloxirane ((R)-6) in the presence of a Lewis acid such as BF ¥ Et O, ZnCl , or SiO in dry CH Cl led to the
3 2 2 2 2 2
corresponding 1:1 adducts, i.e., 1,3-oxathiolanes (S)-3 with Me at C(5), and (S)-7 and (R)-8 with Ph at C(4) and
C(5), respectively. A 1:2 adduct, 1,3,6-dioxathiocane (4S,8S)-4 and 1,3-dioxolane (S)-9, respectively, were
formed as minor products (Schemes 3 and 5, Tables 1 and 2). Treatment of the 1:1 adduct (S)-3 with (S)-2 and
BF
ene-2-thiol (10) with (S)-2 and (R)-6 in the presence of SiO
1, and (1'Z,2S)-13, (1'E,2S)-13, (1'Z,1R)-15, and (1'E,1R)-15, respectively, as well as a 1,3-oxathiolane (S)-14
were formed (Schemes 6 and 8). In the presence of HCl, the enesulfanyl alcohols (1'Z,2S)-11, (1'Z,2S)-13,
3
¥ Et
2
O gave the 1 :2 adduct (4S,8S)-4 (Scheme 4). In the case of the enolized thioketone 1,3-diphenylprop-1-
2
, the enesulfanyl alcohols (1'Z,2S)-11 and (1'E,2S)-
1
(
(
1'E,2S)-13, (1'Z,1R)-15, and (1'E,1R)-15 cyclize to give the corresponding 1,3-oxathiolanes (S)-12, (S)-14, and
R)-16, respectively (Schemes 7, 9, and 10). The structures of (1'E,2S)-11, (S)-12, and (S)-14 were confirmed by
X-ray crystallography (Figs. 1 ± 3). These results show that 1,3-oxathiolanes can be prepared directly via the
Lewis acid-catalyzed reactions of oxiranes with non-enolizable thioketones, and also in two steps with enolized
thioketones. The nucleophilic attack of the thiocarbonyl or enesulfanyl S-atom at the Lewis acid-complexed
n
oxirane ring proceeds with high regio- and stereoselectivity via an S 2-type mechanism.
1. Introduction. ± Recent studies have shown that 1,3-oxathiolanes are easily
prepared via the Lewis acid-catalyzed reaction of oxiranes with thioketones. The
mechanism of this reaction has been investigated intensively [1 ± 6]. The results
reported so far indicate that the formation of 1,3-oxathiolanes in the case of non-
enolizable thiocarbonyl compounds proceeds with high regio- and stereoselectivity via
an S 2-type mechanism (Scheme 1). With alkyl-substituted oxiranes, the nucleophilic
n
attack occurs at C(3) and leads to the product with retention of configuration, whereas
phenyloxirane is attacked mainly at C(2) under inversion of the configuration.
Scheme 1
R'
S
O
O
O
Lewis Acid
R
R
+
+
R'
R
R
R'
S
S
R
R
(S)
(S)
(R)
Enolizable thioketones exist predominantly in the enethiol form [7][8], and in
extreme cases, e.g. dibenzyl thioketone, only the enethiol form can be detected [9].
1)
Part III of the projected Ph.D. thesis of C. F., University of Zurich. Part I: [1], Part II: [2].

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Helvetica Chimica Acta ± Vol. 86 (2003)
These enethiols undergo different reactions with oxiranes, yielding enesulfanyl
alcohols, but not 1,3-oxathiolanes [10].
The Lewis acid-catalyzed reaction of (1R,4R)-thiocamphor, an enolizable thio-
ketone, with oxiranes gave the expected enesulfanyl alcohols, as well as the spirocyclic
1,3-oxathiolanes, with high regio- and stereoselectivity in good yields. Surprisingly, the
enesulfanyl alcohols cyclized smoothly to 1,3-oxathiolanes in the presence of traces of
HCl [2]. On the basis of the results described above, the preparation of 1,3-
oxathiolanes via the Lewis acid-catalyzed reactions of open chain enethiols with
oxiranes can be performed in two steps (Scheme 2).
Scheme 2
O
OH
Me
Me
H+
O
S
R'
Me
S
SiO2
R
R'
R
SH
R'
R
O
H+
O
S
R'
Ph
S
R
OH
SiO2
R'
Ph
Ph
R
The objective of the present study was to gain more insight into the regio- and
stereoselectivity of the ring-opening of optically active oxiranes by thioketones, in
particular, to establish the scope and limitation of the formation of 1,3-oxathiolanes.
Reactions of 4,4'-dimethoxythiobenzophenone (1) and 1,3-diphenylprop-1-ene-2-thiol
(10), the enethiol of dibenzyl thioketone, with optically active oxiranes were carried
out. In the present paper, the results of the reactions of 1 and 10 with (S)-2-
methyloxirane ((S)-2) and (R)-2-phenyloxirane ((R)-6) are described.
2
. Results. ± 2.1. Reaction of 4,4'-Dimethoxythiobenzophenone (1) with (S)- and
(
R)-2-Methyloxirane ((S)-2 and (R)-2). The reaction of 1 with (S)-2 was carried out in
dry CH Cl at À308 under an N atmosphere in the presence of ZnCl . After 2 h 20 min,
2
2
2
2
the dark blue solution turned to light yellow, and the reaction was quenched with H O.
2
Chromatographic separation gave the 1:1 adduct (S)-3 and the 1:2 adduct (4S,8S)-4, as
well as 4,4'-dimethoxybenzophenone (5) in 47, 7, and 35% yield, respectively. The
reaction of 1 with (R)-2 under the same conditions for 2 h 45 min led to (R)-3, (4R,8R)-
4
, and 5 in 47, 5, and 37% yield, respectively. Treatment of a mixture of 1 and (S)-2 in
dry CH Cl at room temperature for 8 h with silica gel led to (S)-3, (4S,8S)-4, and 5 in
2
2
6
7, 3, and 18% yield, respectively (Scheme 3 and Table 1).
The structures of (S)-3 and (4S,8S)-4 were assigned on the basis of their H- and
C-NMR spectra, and by comparison of these spectra with those described in [6]. The
1
13

Helvetica Chimica Acta ± Vol. 86 (2003)
2835
Table 1. ZnCl
2
- and SiO
2
2 2
-Catalyzed Reaction of 1 with (S)-2 and (R)-2 in CH Cl
3
Temp.
Reaction time
Yield [%], specific rotation ([a]2
D
, c ˆ 1, in THF),
and enantiomeric excess (ee) of products (HPLC)
S)-3 (4S,8S)-4
(
5
a
ZnCl
2
, (S)-2
À 308
2 h 20 min
8 h
47, À22.6, 98% ee
67, À22.2, 97% ee
7, À254.8 ), >99% ee
3, À162.1, >99% ee
35
18
SiO , (S)-2
2
r.t.
(
R)-3
(4R,8R)-4
5
a
ZnCl
2
, (R)-2
À 308
2 h 45 min
47, ‡23.8, 98% ee
5, ‡255.7 ), >99% ee
37
a) c ˆ 1, in CH
2
2
Cl .
Scheme 3
Me
Ar
Ar
Ar
Ar
Me
H
O
Ar
Ar
O
CH Cl / N2
Ar
Ar
2
2
5
O
S
S
+
+
+
O
S
Me
O
Me
1
(S)-2
(S)-3
(4S,8S)-4
5
Ar = 4-MeOC6H4
enantiomeric excess (ee) of the products was determined by analytical HPLC
2
(
Chiralcel OD-H, hexane/i-PrOH1000 :1) ).
.2. Reaction of (S)-3 with (S)-2. To explain the formation of the 1:2 adduct
4S,8S)-4, the 1:1 adduct (S)-3 was reacted with (S)-2 at À908 for 7 h in the presence of
2
(
BF ¥ Et O (cf. [6]). After chromatographic separation, the expected 1:2 trans-adduct
3
2
(4S,8S)-4 was obtained in 3% yield. The starting material (S)-3 was recovered in 30%
yield (Scheme 4).
Scheme 4
Me
Ar
Me
H
BF3 . Et2O, CH2Cl2 / N2
O
Ar
Ar
5
O
O
S
+
S
Ar
–90°, 7 h
O
Me
Me
(S)-3
(S)-2
(4S,8S)-4
Ar = 4-MeOC6H4
3% (> 99% ee)
2)
The absolute configurations have been assigned based on the knowledge that ring opening of 2-
methyloxirane (2) occurs via nucleophilic attack at C(3) and cleavage of the OÀC(3) bond under retention
of the configuration at C(2) (see Sect. 2.4 and [2]).

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Helvetica Chimica Acta ± Vol. 86 (2003)
In an analogous reaction of (R)-3 with (S)-2 under the same conditions, no 1:2
adduct was formed, but most of (R)-3 decomposed to 5; only 11% of (R)-3 were
recovered.
2
.3. Reaction of 4,4'-Dimethoxythiobenzophenone (1) with (R)- and (S)-2-Phenyl-
oxirane ((R)- 6 and (S)-6). To a solution of 1 and 0.6 equiv. of BF ¥ Et O in dry CH Cl
2
3
2
2
at À808 under N , 3 equiv. of (S)-6 were added dropwise. The violet color of the
2
solution changed rapidly to light yellow. After 5 min, the reaction was quenched by
addition of H O, and chromatographic workup gave (R)-7, (R)-9, and 5 in 41, 9, and
2
4
5% yield, respectively. Similarly, in the presence of ZnCl at À308 (2 h 50 min), the
2
reaction of 1 with (R)-6 led to (S)-7 in 60% yield. The SiO -catalyzed reaction of 1 with
2
(
R)-6 at room temperature for 1 h 40 min gave (S)-7 in 77% yield, as well as an
unexpected isomer (R)-8 in 2% yield. In addition, 5 was isolated in 19% yield
(
Scheme 5 and Table 2).
Scheme 5
Ar
Ar
Ar
H
Ar
Ar
H
Ar
Ar
H
Ar
Ar
O
2 2
CH Cl / N2
O
5
O
S
+
+
O
+
+
O
S
4
O
4
S
Ar
Ph
Ph
Ph
Ph
1
(R)-6
(S)-7
(R)-8
(S)-9
5
Ar = 4-MeOC6H4
2 2
Table 2. Lewis Acid-Catalyzed Reaction of 1 with (S)-6 and (R)-6 in CH Cl
Yield [%], specific rotation ([a]2
3
, c ˆ 1, in THF),
Temp.
Reaction time
D
and enantiomeric excess (ee) of products (HPLC)
(
R)-7
41, ‡11.4, 94% ee
S)-7
(S)-8
±
(R)-9
9, À7.8
(S)-9
5
BF
3
¥ Et
2
O, ( S)-6
À 808
5 min
45
(
(R)-8
5
ZnCl
2
, (R)-6
À 308
2 h 50 min
1 h 40 min
60, À10.2, 88% ee
77, À11.8, 94% ee
±
±
±
±
19
SiO , (R)-6
2
r.t.
2, À79.4, 92% ee
1
The structures of (R)- and (S)-7, (R)-8, and (R)-9 were assigned on the basis of H-
13
and C-NMR spectra, and by comparison of these spectra with those described in [6].
The ee of the products was determined by analytical HPLC (Chiralcel OD-H, hexane/
3
i-PrOH250 :1) ).
2
.4. Reaction of 1,3-Diphenylprop-1-ene-2-thiol (10) with (S)-2-Methyloxirane ((S)-
2
). The reaction of 10 with (S)-2 was carried out in dry CH Cl at room temperature
2
2
under an N atmosphere in the presence of SiO . After 4 d, filtration and the usual
2
2
workup, CC, and MPLC gave two isomeric products (1'Z,2S)-11 and (1'E,2S)-11 in 46
and 10% yield, repectively (Scheme 6). The ee of the isomers was determined by
HPLC.
3)
The absolute configurations have been assigned based on the knowledge that ring opening of 2-
phenyloxirane (6) takes place via nucleophilic attack at C(2) and cleavage of the OÀC(2) bond under
inversion of the configuration at C(2) (see Sect. 2.6 and [2]).

Helvetica Chimica Acta ± Vol. 86 (2003)
2837
Scheme 6
SH
Ph
OH
Me
H
OH
O
SiO2, CH2Cl2 / N2
r.t., 4 d
Me
+
S
+
S
H
Ph
Me
Ph
(
Ph
Ph
Ph
10
(S)-2
(1'Z,2S)-11
(1'E,2S)-11
(Z)/(E) 3:1)
46% (98% ee)
10% (89% ee)
The structures of (1'Z,2S)-11 and (1'E,2S)-11 were assigned on the basis of the
1
13
elemental analyses, IR, 1D-NOESY, H- and C-NMR, and mass spectra, and that of
(
(
1'E,2S)-11 was confirmed by X-ray crystallography (Fig. 1). The IR spectra of
1'Z,2S)-11 and (1'E,2S)-11 showed typical broad absorptions for the OHgroup at 3396
À1
and 3480 cm , respectively, which indicate that the two isomers are not cyclic 1,3-
oxathiolanes, but open-chain alcohols. The 1D-NOESY spectrum of (1'Z,2S)-11, on
irradiation of HÀC(2') at 6.7 ppm, showed NOE signals for PhCH at 3.88 ppm and for
2
2
arom. H(Ph ÀC(2')) at 7.35 ppm, and irradiation of PhCH at 3.8 ppm led to NOE
2
signals for HÀC(2') at 6.69 ppm, 2 HÀC(1) at 2.76 and 2.47 ppm, and 2 arom. Hof
PhCH at 7.32 ppm. The formation of (1'Z,2S)-11 proceeded with retention of the
2
configuration at C(2) because the nucleophilic attack of the enesulfanyl S-atom took
place at C(3) of (S)-2. Therefore, the analyses mentioned above indicate that (1'Z,2S)-
11 should have the (Z,S)-configuration.
Fig. 1. ORTEP Plot [11] of the molecular structure of (1'E,2S)-11 (arbitrary numbering of the atoms;
displacement ellipsoids with 50% probability)

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Helvetica Chimica Acta ± Vol. 86 (2003)
Similarly, the 1D-NOESY spectrum of (1'E,2S)-11, on irradiation of HÀC(2') at
6
2
.7 ppm, led to NOE signals for 2 arom. H(Ph ÀC(2')) at 7.22 ppm, and for 2 HÀC(1) at
.96 and 2.70 ppm, respectively, and irradiation of PhCH at 3.8 ppm showed no NOE
2
signal for HÀC(2'). In analogy to (1'Z,2S)-11, (1'E,2S)-11 has been formed with
retention of the configuration at C(2). Therefore, (1'E,2S)-11 has the (E,S)-
configuration, which was then confirmed by X-ray crystallography (Fig. 1). The
absolute configuration of the molecule has been confidently determined independently
by the diffraction experiment. The compound has the expected (2S)-configuration, and
the ethylene group is (E)-configured. The OHgroup forms an intermolecular H-bond
with the OHO-atom of an adjacent molecule, thereby linking the molecules into
extended one-dimensional chains, which run parallel to the y-axis and have a graph set
motif [12] of C(3).
2
.5. Cyclization of (1'Z,2S)-11 to 1,3-Oxathiolane (S)-12. A solution of (1'Z,2S)-11
in dry CH Cl was treated with HCl gas at room temperature for 30 min. After
2
2
chromatographic workup, (S)-12 was obtained in 88% yield (Scheme 7). The ee was
determined by HPLC.
Scheme 7
Ph
Ph
OH
Me
Me
H
HCl(gas), CH2Cl2 / N2
r.t., 30 min
5
S
O
H
S
Ph
Ph
(1'Z,2S)-11
(S)-12
88% (98% ee)
The structure of (S)-12 was deduced from the elemental analysis, 1H- and
C-NMR, and mass spectra, and was then confirmed by X-ray crystallography (Fig. 2).
13
In the crystal structure, there are two symmetry-independent molecules in the
asymmetric unit. Both are of the same enantiomer and have very similar conforma-
tions, although there are slight differences in the puckering of the five-membered ring.
In both molecules, the five-membered ring has a half-chair conformation distorted
towards an envelope conformation, but the atom that is closest to being the envelop
flap is different in each molecule, being C(4) in molecule A and C(5) in molecule B. In
molecule A, the deviation of atoms C(4) and C(5) from the plane defined by S(1),
C(2), and C(3) is À0.459(1) and 0.179(2) ä, respectively. In molecule B, the
corresponding deviations are 0.214(2) and À0.457(2) ä for C(24) and C(25),
respectively. The absolute configuration of the molecule has been determined
independently by the diffraction experiment. The compound has the expected (S)-
configuration.
2
.6. Reaction of 1,3-Diphenylprop-1-ene-2-thiol (10) with (R)-2-Phenyloxirane
(
(R)-6). The reaction of 10 with (R)-6 in dry CH Cl at room temperature for 10 d
2
2
under an N atmosphere in the presence of SiO gave four open chain products,
2
2
(
1'Z,2S)-13, (1'E,2S)-13, (1'Z,1R)-15, and (1'E,1R)-15, and one 1,3-oxathiolane (S)-14
in 22, 9, 2, 1, and 1% yield, repectively. In addition, 10 was recovered in 40% yield
Scheme 8). The ee values were determined by HPLC. They show that the reaction
(

Helvetica Chimica Acta ± Vol. 86 (2003)
2839
Fig. 2. ORTEP Plot [11] of the molecular structure of one of the two symmetry-independent molecules of (S)-12
arbitrary numbering of the atoms; displacement ellipsoids with 50% probability)
(
took place with partial racemization. For example, in the case of the main product
(1'Z,2S)-13 with 50% ee, the reaction occurred with a stereoselectivity of only 75%.
Scheme 8
Ph
H
SH
O
SiO2, CH2Cl2 / N2
r.t., 10 d
S
S
+
H
OH
+
Ph
OH
Ph
Ph
Ph
Ph
Ph
Ph
Ph
10
(R)-6
(1'Z,2S)-13
(1'E,2S)-13
((Z )/(E) 3:1)
22% (50% ee)
9% (82% ee)
Ph
Ph
Ph
H
Ph
H
O
S
S
+
S
4
+
H
OH
+
Ph
OH
Ph
Ph
Ph
Ph
(S)-14
(1'Z,1R)-15
(1'E,1R)-15
1% (85% ee)
2%
1%
The structures of the products were assigned on the basis of their elemental
1
13
analyses, IR, 1D-NOESY, H- and C-NMR, and mass spectra, and that of (S)-14 was
confirmed by X-ray crystallography (Fig. 3). In the crystal structure, there are two
symmetry-independent molecules in the asymmetric unit. Both are of the same
enantiomer and have very similar conformations. The absolute configuration of the
molecule has been determined independently by the diffraction experiment. The
compound has the expected (S)-configuration. The five-membered ring in molecule B

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840
Helvetica Chimica Acta ± Vol. 86 (2003)
has an envelope conformation, with C(35) being the envelope flap and with a deviation
of 0.577(2) ä from the plane defined by the other four ring atoms. The five-membered
ring in molecule A has a similar conformation, although it is distorted slightly towards a
half-chair conformation twisted on C(4)ÀC(5) with C(4) and C(5) being 0.164(2) and
À0.445(2) ä, respectively, from the plane defined by the other three ring atoms.
Fig. 3. ORTEP Plot [11] of the molecular structure of one of the two symmetry-independent molecules of (S)-14
(arbitrary numbering of the atoms; displacement ellipsoids with 50% probability)
The IR spectra of (1'Z,2S)-13, (1'E,2S)-13, (1'Z,1R)-15, and (1'E,1R)-15 showed
À1
typical broad absorptions for the OHgroup at 3407, 3403, 3406, and 3376 cm
,
respectively. The 1D-NOESY spectrum of (1'Z,2S)-13, on irradiation of HÀC(2') at
6
.6 ppm, showed NOE signals for PhCH at 3.67 ppm, 2 arom. H(Ph ÀC(2')) at
2
7.51 ppm, and 2 arom. Hof PhCH at 7.15 ppm. The formation of (1'Z,2S)-13 proceeded
2
mainly (75% selectivity) with inversion of configuration at C(2). Therefore, the
nucleophilic attack of the enesulfanyl S-atom at C(2) of (R)-6 occurs preferentially via
an S 2-type process. The analyses mentioned above indicate that (1'Z,2S)-13 has the
n
4
(
Z,S)-configuration ).
An analogous 1D-NOESY experiment led to the conclusion that (1'E,2S)-13 has
the (E,S)-configuration.
Similarly, the 1D-NOESY spectrum of (1'Z,1R)-15, on irradiation of HÀC(2') at
6
.76 ppm, showed NOE signals for PhCH at 3.82 ± 3.75 ppm, and 2 arom. H
2
(
PhÀC(2')) at 7.56 ppm. The formation of (1'Z,1R)-15 should have proceeded with
retention of configuration at C(2) because the nucleophilic attack of the enesulfanyl S-
atom took place at C(3) of (R)-6. For this reason, (1'Z,1R)-15 should have the (Z,R)-
4)
The absolute configuration at C(2) of the major enantiomer of (1'Z,2S)-13 follows from the cyclization to
S)-14 (see Sect. 2.7).
(

Helvetica Chimica Acta ± Vol. 86 (2003)
2841
configuration. The analogous experiments with (1'E,1R)-15 indicated that it has the
E,R)-configuration.
.7. Cyclization of (1'Z,2S)-13 and (1'E,2S)-13 to 1,3-Oxathiolane (S)-14. Treatment
of a solution of (1'Z,2S)-13 in dry CH Cl with HCl gas at room temperature for 45 min
(
2
2
2
yielded 88% of (S)-14 with 59% ee (HPLC). Furthermore, treatment of (1'Z,2S)-13
with SiO in CH Cl at room temperature for 12 d gave 9% of (S)-14, and (1'Z,2S)-13
2
2
2
was recovered in 58% yield.
An analogous treatment of (1'E,2S)-13 with HCl under the conditions mentioned
above gave (S)-14 in 95% yield with 67% ee (HPLC) (Scheme 9).
Scheme 9
Ph
Ph
HCl(gas),
H
HCl(gas),
CH2Cl2 / N2
H
CH Cl / N
2
S
O
2
2
S
H
OH
S
Ph
OH
4
r.t., 45 min
88%
Ph
r.t., 45 min
95%
Ph
Ph
Ph
Ph
Ph
(1'Z,2S)-13
(S)-14
(1'E,2S)-13
2
.8. Cyclization of (1'Z,1R)-15 and (1'E,1R)-15 to 1,3-Oxathiolane (R)-16. A
solution of (1'Z,1R)-15 in dry CH Cl at room temperature was treated for 30 min with
2
2
HCl gas. After usual workup, TLC yielded 52% of (R)-16. An analogous reaction with
1'E,1R)-15 for 2 h gave (R)-16 in 40% yield (Scheme 10). In both cases, the ee value
(
was determined by HPLC to be 90%.
Scheme 10
Ph
Ph
Ph
HCl(gas),
H
Ph
HCl(gas),
CH2Cl2 / N2
5
H
CH2Cl2 / N2
S
O
S
H
Ph
OH
OH
S
r.t., 30 min
Ph
r.t., 2 h
40%
52%
Ph
Ph
Ph
(1'Z,1R)-15
(R)-16
(1'E,1R)-15
90% ee
3
. Discussion and Conclusions. ± The results presented show that 1,3-oxathiolanes
can be prepared not only by the Lewis acid-catalyzed reactions of oxiranes with non-
enolizable thioketones, but with enolized thioketones as well. For example, the
aromatic thioketone 1 reacts with the optically active monosubstituted oxiranes (S)-2
and (R)-6 in the presence of a Lewis acid to yield 1,3-oxathiolanes with high regio- and
stereoselectivity. The weaker the Lewis acid, the higher the yield of the 1,3-oxathiolane
(
1
Schemes 3 and 5, and Tables 1 and 2). However, in the case of the enolized thioketone
0, the analogous reactions yielded mainly the open-chain enesulfanyl alcohols, which,
in turn, in the presence of HCl, easily cyclized to give 1,3-oxathiolanes, again with high
regio- and stereoselectivity in most cases.
We assume that the reactions proceed via an S 2-type mechanism, whereby the
N
nucleophilic thiocarbonyl or enesulfanyl S-atom favorably attacks the C(3)-atom

2
842
Helvetica Chimica Acta ± Vol. 86 (2003)
(
OÀC(3) cleavage) of the activated (S)-2-methyloxirane ((S)-2) with retention of
configuration, but, in the case of (R)-2-phenyloxirane ((R)-6), the preferred attack
took place at the C(2)-atom (OÀC(2) cleavage) mainly with inversion of configuration.
In the presence of SiO , the aromatic thioketone 1 is more reactive than the
2
enethiol 10. On the other hand, 10 is more stable than 1, as 10 was partially recovered
even when the reaction was performed at room temperature for 10 d, while no trace of
1
could be detected after 1 h 40 min at room temperature.
The reaction mechanisms for the −direct× and −indirect× formation of 1,3-
oxathiolanes are depicted in Scheme 11. In the case of non-enolizable thioketones,
the reaction with the complexed oxirane A leads to the unstable thiocarbonylium ion B,
which undergoes in situ ring closure to give 1,3-oxathiolanes of type (S)-3 (Scheme 11).
On the other hand, enolized thioketones and A form sulfonium ions C, which can be
stabilized by a H-transfer to give the hydroxy sulfides 11. In the presence of a strong
acid such as HCl, the enethiol group is protonated to give thiocarbonylium ion D, which
cyclizes to (S)-12.
Scheme 11
O
L.A.–
Me
Me
Ar2C=S
Ar
Ar
O
Ar
S
S
L.A.–
Ar
B
(S)-3
Ar = 4-MeOC6H4)
O
(
SH
Me
PhCH
L.A.–
Me
OH
A
H
O
Ph
PhHC
S
PhHC
S
Me
Ph
Ph
C
(2S)-11
H+
Ph
Ph
OH
Me
Me
O
S
Ph
S
Ph
(S)-12
D
It is worth mentioning that the control experiments showed that (S)-2 reacts only
with (S)-3, leading to the 1:2 trans-adduct (4S,8S)-4 (Scheme 4), but does not react
with (R)-3. No 1:2 cis-adduct (4R,8S)-4 was obtained from the reaction of (R)-3 with
(
S)-2. These results confirm the assumption presented in [6].
We thank the analytical services of our institute for NMR and mass spectra, and elemental analyses, Miss J.
Cavegn for her assistance with the determination of the crystal structures, and the Swiss National Science
Foundation and F. Hoffmann-La Roche AG, Basel, for financial support.

Helvetica Chimica Acta ± Vol. 86 (2003)
2843
Experimental Part
1
. General. See [13]. Optical rotations: Perkin-Elmer 241 polarimeter (c ˆ 1, in THF). IR Spectra: film or
À
1
1
1
3
3
KBr, cm . NMR Spectra: at 300 ( H) and 75.5 MHz ( C) in CDCl . Enantiomeric excesses were determined by
anal. HPLC on a Chiralcel OD-H column.
2
. General Procedures for the Reactions of 4,4'-Dimethoxythiobenzophenone (1) and 1,3-Diphenylprop-1-
enethiol 10 with Methyl- and Phenyloxiranes 2 and 6. Procedure 1: To the soln. of 1 (ca. 1 mmol) in dry CH Cl
10 ± 15 ml) under N , 0.5 equiv. of BF ¥ Et O or ZnCl
was added at À808 or À308. In general, this led to a more
or less pronounced change in the color of the soln. After stirring the mixture for 15 min at the selected temp., ca.
equiv. of (S)-2 or (R)-6 were added dropwise, whereby the color of the soln. changed again rapidly in most
cases. Then, the reaction was quenched by addition of H O, and the mixture was washed with sat. aq. NaCl soln.
3Â). The combined org. layers were dried (MgSO ) and evaporated i.v. The products were separated by
chromatography (SiO ; hexane/Et O or hexane/CH Cl ; CC or prep. TLC (PLC)).
Procedure 2: To the soln. of 1 or 10 (ca. 1 mmol), and 2 or 6 (ca. 2 mmol) in dry CH
, 4.5 g of silica gel (SiO ) were added at r.t. After stirring the suspension for 2 h ± 10 d at r.t., the mixture was
filtered, and the residue was washed with CH Cl
(4Â). Then, the combined filtrate was evaporated i.v., and the
products were separated as described above.
. Reactions of 1. 3.1. With (S)- and (R)-2-Methyloxirane ((S)-2 and (R)-2, resp.; see [6]). Reaction of 1
258 mg, 1 mmol) with (S)-2 (290 mg, 5 mmol) and 1.2 mmol of ZnCl (or 4.5 g of SiO
) at À308 (or r.t.), 2 h
0 min (or 8 h), and CC (hexane/Et O 10 : 1) yielded (S)-2,2-bis(4-methoxyphenyl)-5-methyl-1,3-oxathio-
2
2
(
2
3
2
2
2
2
(
4
2
2
2
2
2
2
Cl (10 ± 15 ml) under
N
2
2
2
2
3
(
2
2
2
2
lane ((S)-3), (4S,8S)-2,2-bis(4-methoxyphenyl)-4,8-dimethyl-1,3,6-dioxathiocane ((4S,8S)-4), and 4,4'-
dimethoxybenzophenone (5) (Scheme 3 and Table 1; for spectroscopic characterization of the products,
see [6]).
The analogous reaction with (R)-2, ZnCl
4R,8R)-4 together with 5 (Table 1).
2
, À308, 2 h 45 min gave the enantiomeric products (R)-3 and
(
3
.2. Reaction of (S)-3 with (S)-2. Treatment of (S)-3 (138 mg, 0.44 mmol) with (S)-2 (511 mg, 8.8 mmol) in
the presence of 0.39 mmol of BF ¥ Et O 10 :1), yielded 4 mg (3%) of
O at À908, 7 h and CC (hexane/Et
4S,8S)-4 with ca. 100% ee. In addition, 41 mg (30%) of (S)-3 were recovered.
An analogous reaction of (R)-3 (167 mg, 0.53 mmol) with (S)-2 (145 mg, 2.5 mmol) in the presence of
.55 mmol of BF ¥ Et
O at À908, 1 h 25 min, did not give the expected cis-product (4R,8S)-4; most of (R)-3
3
2
2
(
0
3
2
decomposed to 5. Only 19 mg (11%) of (R)-3 were recovered.
.3. With (R)- and (S)-2-Phenyloxirane ((R)-6 and (S)-6, resp.). Reaction of 1 (258 mg, 1 mmol) with (R)-
(360 mg, 3 mmol) and 1.0 mmol of ZnCl (or 4.5 g of SiO O 10 :1 and
), at À308 (r.t.), and CC (hexane/Et
/hexane 4 :1) yielded (S)-2,2-bis(4-methoxyphenyl)-4-phenyl-1,3-oxathiolane ((S)-7), (R)-2,2-bis(4-me-
3
6
2
2
2
C
6 6
H
thoxyphenyl)-5-phenyl-1,3-oxathiolane ((R)-8), (S)-2,2-bis(4-methoxyphenyl)-4-phenyl-1,3-dioxolane ((S)-9),
and 5 (Scheme 5 and Table 2; for spectroscopic characterization, see [6]).
2
3
Data of (R)-8: Colorless oil. [a]
D
ˆ À79.4 (92% ee). IR (film): 3065w, 3035w, 3002w, 2954w, 2933m, 2907w,
2
7
836m, 1608s, 1583m, 1509s, 1463m, 1456m, 1441m, 1414w, 1303s, 1251s, 1172s, 1114w, 1035s, 1007m, 910m, 828s,
1
35m, 699s. H-NMR: 7.58 ± 7.45 (AA' of AA'BB', J ˆ 8.9, 2 arom. H); 7.48 (m, 2 arom. H); 7.39 ± 7.30 (m, 5 arom.
H); 6.86 (BB' of AA'BB', J ˆ 8.9, 2 arom. H); 6.80 (BB' of AA'BB', J ˆ 9.0, 2 arom. H); 5.04 (dd, J ˆ 9.1, 5.9,
HÀC(5)); 3.80, 3.76 (2s, 2 MeO); 3.42 (dd, J ˆ 10.2, 5.9, 1 HÀC(4)); 3.25 (dd, J ˆ 10.2, 9.1, 1 HÀC(4)).
1
3
C-NMR: 159.1, 159.0 (2s, 2 arom. C); 139.7, 137.2, 137.0 (3s, 3 arom. C); 128.7, 128.6, 128.2, 127.9, 126.3 (5d, 9
arom. CH); 113.4, 113.3 (2d, 4 arom. CH); 98.6 (s, C(2)); 83.3 (d, C(5)); 55.3 (2q, 2 MeO); 42.2 (t, C(4)). ESI-
‡
‡
MS (MeOH/CH
calc. for C23
. Reactions of 10. 4.1. With (S)-2-Methyloxirane ((S)-2). Reaction of 10 (226 mg, 1 mmol) with (S)-2
116 mg, 2 mmol) and 4.5 g of SiO at r.t., 4 d, and CC (hexane/Et O 2 :1) yielded 181 mg (64%) of (Z/E,2S)-1-
(1'-benzyl-2'-phenylethenyl)sulfanyl]propan-2-ol ((Z/E,2S)-11). Separation of the two isomers by MPLC
hexane/Et O 3 :1) gave 132 mg (46%) of (1'Z,2S)-11 and 27 mg (10%) of (1'E,2S)-11 (Scheme 6).
Data of (1'Z,2S)-11: Colorless crystals. M.p. 36.0 ± 37.28. [a]
2
Cl
2
): 401 (10, [M ‡ Na] ), 379 (31, [M ‡ H] ), 333 (100), 307 (47), 243 (58), 112 (37). Anal.
H O S (378.49): C 72.99, H5.86, S 8.47; found: C 72.84, H6.09, S 8.39.
22 3
4
(
[
(
2
2
2
2
2
D
ˆ ‡13.6 (98% ee). IR (film): 3396m (br.,
OH), 3083w, 3060m, 3026m, 2971m, 2927m, 1599m, 1573w, 1493s, 1453s, 1445m, 1373w, 1266w, 1184w, 1124m,
1
1
6
109m, 1074m, 1031m, 935m, 751s, 697s. H-NMR (600 MHz, CDCl
3
): 7.53 (d, J ˆ 7.5, 2 arom. H); 7.35 ± 7.30 (m,
arom. H); 7.27 ± 7.22 (m, 2 arom. H); 6.69 (s, HÀC(2')); 3.80 ± 3.73 (m, PhCH ); 3.63 ± 3.60 (m, HÀC(2)); 2.76
2
(
dd, J ˆ 13.7, 3.6, 1 HÀC(1)); 2.47 (dd, J ˆ 13.7, 8.5, 1 HÀC(1)); 2.03 (d, J ˆ 3.0, OH); 1.09 (d, J ˆ 6.3, Me).
1
3
C-NMR: 138.6, 136.5 (2s, 2 arom. C); 134.4 (s, C(1')); 132.4 (d, C(2')); 129.2, 128.8, 128.6, 128.1, 127.2, 126.7 (6d,
‡
1
0 arom. CH); 66.3 (d, C(2)); 44.8 (t, PhCH
2
); 40.7 (t, C(1)); 21.7 (q, Me). CI-MS (NH
3
): 302 (36, [M ‡ NH
4
] ),

2
2
844
Helvetica Chimica Acta ± Vol. 86 (2003)
‡
‡
86 (20), 285 (100, [M ‡ H] ), 268 (8), 267 (40, [M À H
2
O ‡ H] ), 228 (20). Anal. calc. for C18
H20OS (284.42):
C 76.01, H7.09, S 11.27; found: C 75.94, H6.96, S 11.07.
2
2
Data of (1'E,2S)-11: Colorless crystals. M.p. 67.5 À 70.88. [a] ˆ ‡2.6 (89% ee). IR (KBr): 3480s (br., OH),
D
3
1
7
079w, 3057w, 3025w, 2973m, 2920s, 2854m, 1611s, 1599m, 1573w, 1495s, 1487s, 1452s, 1424s, 1398m, 1367m,
342m, 1316m, 1285m, 1261w, 1248w, 1222w, 1192w, 1182w, 1156w, 1123s, 1080m, 1046s, 1032s, 944m, 853m,
66m, 743m, 717s, 695s. H-NMR (600 MHz, CDCl
1
3
): 7.33 ± 7.21 (m, 10 arom. H); 6.73 (s, HÀC(2')); 3.94 (br. s,
); 2.96 (dd, J ˆ 13.6, 3.7, 1 HÀC(1)); 2.70 (dd, J ˆ 13.6, 8.5, 1 HÀC(1)); 2.23 (br.
3
HÀC(2)); 3.91 ± 3.81 (m, PhCH
2
1
s, OH); 1.26 (d, J ˆ 6.3, Me). C-NMR: 138.4, 136.8 (2s, 2 arom. C); 135.9 (s, C(1')); 128.6, 128.5, 128.4, 128.2
2
(4d, 8 arom. CH); 128.1 (d, C(2')); 126.9, 126.5 (2d, 2 arom. CH); 65.7 (d, C(2)); 41.0 (t, C(1)); 38.1 (t, PhCH );
‡
‡
‡
2
2
2.1 (q, Me). CI-MS (NH
28 (15). Anal. calc. for C18
Crystals of (1'E,2S)-11 suitable for X-ray crystal-structure analysis were grown from Et
.2. Cyclization of (1'Z,2S)-11 t o S( )-2,2-Dibenzyl-5-methyl-1,3-oxathiolane ((S)-12). Treatment of
1'Z,2S)-11 (80 mg, 0.35 mmol) in CH Cl (10 ml) with HCl gas at r.t., 30 min, and CC (hexane/Et O 20 :1)
yielded 70 mg (88%) of (S)-12 (Scheme 7). Colorless crystals. M.p. 66.7 ± 67.98. [a]
ˆ À14.3 (98% ee). IR
KBr): 3082w, 3058w, 3027m, 2985m, 2945m, 2925m, 2886m, 2847w, 1600w, 1493s, 1452s, 1440m, 1430m, 1379m,
3
): 302 (30, [M ‡ NH
20OS (284.42): C 76.01, H7.09, S 11.27; found: C 76.04, H7.13, S 11.34.
O/hexane.
4
] ), 286 (21), 285 (100, [M ‡ H] ), 267 (32, [M À H O ‡ H] ),
2
H
2
4
(
2
2
2
2
2
D
(
1
7
2
349w, 1337w, 1313w, 1235m, 1222m, 1165m, 1135m, 1088s, 1078s, 1062s, 1030w, 1017m, 991m, 950m, 809m, 755s,
1
00vs, 636m, 608m. H-NMR: 7.35 ± 7.18 (m, 10 arom. H); 4.06 ± 3.95 (m, HÀC(5)); 3.24 ± 2.90 (m, 2 PhCH
2
);
1
3
.56 (dd, J ˆ 10.3, 4.1, 1 HÀC(4)); 1.80 (dd, J ˆ 10.2, 9.8, 1 HÀC(4)); 1.18 (d, J ˆ 6.0, Me). C-NMR: 137.1, 137.0
(2s, 2 arom. C); 131.6, 131.0, 127.9, 127.3 (4d, 8 arom. CH); 126.5, 126.3 (2d, 2 arom. CH); 97.1 (s, C(2)); 79.7 (d,
‡
C(5)); 49.0, 47.7 (2t, 2 PhCH
H] ), 229 (17), 228 (100), 193 (9). Anal. calc. for C18
H7.26, S 11.05.
2
); 40.3 (t, C(4)); 18.9 (q, Me). CI-MS (NH
3
): 302 (4, [M ‡ NH
4
] ), 285 (4, [M ‡
‡
H20OS (284.42): C 76.01, H7.09, S 11.27; found: C 75.97,
Crystals of (S)-12 suitable for X-ray crystal-structure analysis were grown from Et
.3. With (R)-2-Phenyloxirane ((R)-6). Reaction of 10 (452 mg, 2 mmol) with (R)-6 (360 mg, 3 mmol) and
.8 g of SiO at r.t., 10 d, and CC and MPLC (hexane/CH Cl 15 :1, hexane/Et O 3 :1) yielded 150 mg (22%) of
1'Z,2S)-2-[(1'-benzyl-2'-phenylethenyl)sulfanyl]-2-phenylethanol ((1'Z,2S)-13), 60 mg (9%) of (1'E,2S)-2-[(1'-
2
O/MeOH.
4
4
(
2
2
2
2
benzyl-2'-phenylethenyl)sulfanyl]-2-phenylethanol ((1'E,2S)-13), 5 mg (1%) of (S)-2,2-dibenzyl-4-phenyl-1,3-
oxathiolane ((S)-14), 14 mg (2%) of (1'Z,1R)-2-[(1'-benzyl-2'-phenylethenyl)sulfanyl]-1-phenylethanol
((1'Z,1R)-15), and 9 mg (1%) of (1'E,1R)-2-[(1'-benzyl-2'-phenylethenyl)sulfanyl]-1-phenylethanol ((1'E,1R)-
1
5). In additon, 10 was recovered in 40% yield (Scheme 8).
2
2
Data of (1'Z,2S)-13: Colorless oil. [a]
D
ˆ À2.6 (50% ee). IR (film): 3407m (br., OH), 3080w, 3060m,
1
3
027m, 2927m, 2868w, 1600m, 1492s, 1453s, 1383w, 1181w, 1075m, 1054s, 1030s, 751s, 697vs. H-NMR: 7.52 ± 7.49
(
m, 2 arom. H); 7.35 ± 7.15 (m, 13 arom. H); 6.64 (s, HÀC(2')); 4.19 (t, J ˆ 6.6, HÀC(2)); 3.75 ± 3.67 (m, 2
13
HÀC(1), PhCH ); 1.66 (t, J ˆ 6.7, OH). C-NMR: 138.9, 138.6, 136.5 (3s, 3 arom. C); 134.4 (s, C(1')); 133.4 (d,
2
C(2')); 129.3, 129.0, 128.6, 128.5, 128.1, 128.0 (6d, 12 arom. CH); 127.7, 127.2, 126.7 (3d, 3 arom. CH); 66.0 (t,
‡
C(1)); 52.4 (d, C(2)); 45.5 (t, PhCH
2
). CI-MS (NH
3
): 365 (15), 364 (57, [M ‡ NH
4
‡
] ), 349 (8), 348 (26), 347
‡
‡
(
(
100, [M ‡ H] ), 346 (12, [M À H
2
O ‡ NH
4
] ), 330 (11), 329 (50, [M À H
2
O ‡ H] ), 313 (12), 228 (21), 227
14). Anal. calc. for C23
Data of (1'E,2S)-13: Colorless oil. [a]
027m, 2927m, 2868w, 1601m, 1573w, 1494s, 1452s, 1384w, 1285w, 1182w, 1076m, 1051s, 1030m, 746s, 698vs.
H22OS (346.49): C 79.73, H6.40, S 9.25; found: C 79.54, H6.47, S 9.21.
2
2
D
ˆ ‡126.2 (82% ee). IR (film): 3403m (br., OH), 3080w, 3060m,
3
1
H-NMR: 7.34 ± 7.13 (m, 15 arom. H); 6.80 (s, HÀC(2')); 4.29 (t, J ˆ 6.8, HÀC(2)); 3.89 (t, J ˆ 6.7, 2 HÀC(1));
1
3
3
.79 (s, PhCH
2
); 1.84 (t, J ˆ 6.7, OH). C-NMR: 138.9, 138.3, 136.7 (3s, 3 arom. C); 135.2 (s, C(1')); 131.9 (d,
C(2')); 129.3, 128.7, 128.6, 128.5, 128.4, 128.2 (6d, 12 arom. CH); 127.8, 127.1, 126.5 (3d, 3 arom. CH); 65.8 (t,
C(1)); 53.6 (d, C(2)); 38.5 (t, PhCH
[
‡
2
). CI-MS (NH
3
): 365 (9), 364 (32, [M ‡ NH
4
] ), 349 (8), 348 (27), 347 (100,
‡
‡
‡
M ‡ H] ), 346 (8, [M À H
2
O ‡ NH
4
] ), 330 (14), 329 (52, [M À H
2
O ‡ H] ), 313 (6), 228 (13), 227 (8). Anal.
calc. for C23H22OS (346.49): C 79.73, H6.40, S 9.25; found: C 79.53, H6.52, S 9.25.
2
2
Data of (S)-14: Colorless crystals. M.p. 90.0 ± 93.68. [a]
D
ˆ À23.9 (85% ee). IR (KBr): 3085w, 3062m,
3
1
3
030s, 2943m, 2916m, 2871w, 1602m, 1584w, 1494s, 1453s, 1435m, 1324w, 1275w, 1230m, 1209w, 1156w, 1093s,
1
081s, 1031m, 991m, 753s, 699vs, 646m. H-NMR: 7.39 ± 7.03 (m, 15 arom. H); 4.19 (dd, J ˆ 9.1, 5.8, HÀC(4));
.96 (dd, J ˆ 8.5, 5.8, 1 HÀC(5)); 3.71 (dd, J ˆ 9.0, 8.6, 1 HÀC(5)); 3.33 ± 3.24 (m, PhCH
2
); 3.19 ± 3.07 (m,
1
3
2
PhCH ). C-NMR: 137.6, 137.0, 136.8 (3s, 3 arom. C); 131.34, 131.30 (2d, 4 arom. CH); 128.4, 127.93, 127.89,
1
27.7 (4d, 8 arom. CH); 127.5, 126.7, 126.5 (3d, 3 arom. CH); 99.3 (s, C(2)); 77.8 (t, C(5)); 54.3 (d, C(4)); 47.9, 47.8
‡
‡
(
2t, 2 PhCH
100). Anal. calc. for C23
Crystals of (S)-14 suitable for X-ray crystal-structure analysis were grown from Et
2
). CI-MS (NH
22OS (346.49): C 79.73, H6.40, S 9.25; found: C 79.70, H6.18, S 9.12.
O/MeOH.
3
): 364 (7, [M ‡ NH ] ), 347 (6, [M ‡ H] ), 313 (11), 286 (7), 255 (6), 229(34), 228
4
(
H
2

Helvetica Chimica Acta ± Vol. 86 (2003)
2845
Data of (1'Z,1R)-15: Colorless oil. [a]2
2
ˆ ‡13.0. IR (film): 3406m (br., OH), 3084w, 3061m, 3027m,
D
1
2
7
925m, 1600m, 1493s, 1453s, 1193w, 1079w, 1056m, 1029m, 751s, 698vs. H-NMR (600 MHz, CDCl
3
): 7.56 (d, J ˆ
.7, 2 arom. H); 7.36 ± 7.22 (m, 11 arom. H); 7.16 ± 7.15 (m, 2 arom. H); 6.76 (s, HÀC(2')); 4.48 (dd, J ˆ 9.3, 2.2,
HÀC(1)); 3.82 ± 3.75 (m, PhCH
2
); 2.99 (dd, J ˆ 13.9, 3.3, 1 HÀC(2)); 2.70 (dd, J ˆ 13.9, 9.5, 1 HÀC(2)); 2.41 (s,
1
3
OH). C-NMR (150.9 MHz, CDCl
3
): 142.1, 138.6, 136.4 (3s, 3 arom. C); 134.0 (s, C(1')); 132.9 (d, C(2')); 129.3,
1
28.9, 128.6, 128.4, 128.2 (5d, 10 arom. CH); 127.8, 127.3, 126.8 (3d, 3 arom. CH); 125.7 (d, 2 arom. CH); 72.1 (d,
]‡), 346 (11, [M À H
O ‡ NH
] ), 331
‡
C(1)); 45.0 (t, PhCH
2
); 41.2 (t, C(2)). CI-MS (NH
3
): 364 (11, [M ‡ NH
4
2
4
‡
(
8), 330 (26), 329 (100, [M À H
2
O ‡ H] ), 244 (7), 228 (32), 227 (14), 170 (7).
2
2
Data of (1'E,1R)-15: Colorless oil. [a]
D
ˆ ‡16.4. IR (film): 3376s (br., OH), 3083w, 3061m, 3028m, 2954m,
1
2
925m, 1601m, 1573w, 1494s, 1453s, 1431w, 1287w, 1196w, 1077m, 1054s, 1029s, 918m, 749s, 698vs. H-NMR
(
600 MHz, CDCl
3
): 7.37 ± 7.22 (m, 15 arom. H); 6.80 (s, HÀC(2')); 4.81 (dd, J ˆ 9.4, 3.4, HÀC(1)); 3.93 ± 3.83 (m,
13
PhCH
(
2
); 3.18 (dd, J ˆ 13.9, 3.4, 1 HÀC(2)); 2.93 (dd, J ˆ 13.8, 9.4, 1 HÀC(2)); 2.65 (br. s, OH ). C-NMR
150.9 MHz, CDCl ): 142.3, 138.3, 136.7 (3s, 3 arom. C); 135.5 (s, C(1')); 128.7 (d, C(2')); 128.62, 128.57, 128.50,
3
1
28.47, 128.2 (5d, 10 arom. CH); 128.0, 127.0, 126.6 (3d, 3 arom. CH); 125.8 (d, 2 arom. CH); 71.7 (d, C(1)); 44.4
]‡), 363 (15), 346 (9, [M À H
O ‡ NH
] ), 331 (8),
‡
(
t, C(2)); 38.1 (t, PhCH
2
). CI-MS (NH
3
): 364 (15, [M ‡ NH
4
2
4
‡
3
30 (26), 329 (100, [M À H
2
O ‡ H] ), 295 (6), 228 (13), 178 (6).
4
.4. Cyclization of (1'Z,2S)-13 or (1'E,2S)-13 t o (S )-14. Treatment of (1'Z,2S)-13 (24 mg, 0.07 mmol) in
Cl (15 ml) with HCl gas at r.t., 45 min, and TLC (hexane/CH Cl 1:2) yielded 21 mg (88%) of (S)-14.
Cl (7 ml) with 2.4 g of SiO at r.t., 12 d, and TLC
1:1) gave 4 mg (9%) of (S)-14. Compound (1'Z,2S)-13 was recovered in 58% yield (26 mg,
CH
2
2
2
2
Similarly, treatment of (1'Z,2S)-13 (45 mg, 0.13 mmol) in CH
hexane/CH Cl
6% ee).
An analogous treatment of (1'E,2S)-13 (22 mg, 0.06 mmol) in CH
and TLC (hexane/CH Cl 1:2) yielded 21 mg (95%) of (S)-14.
.5. Cyclization of (1'Z,1R)-15 or (1'E,1R)-15 t o R( )-2,2-Dibenzyl-5-phenyl-1,3-oxathiolane ((R)-16).
Treatment of (1'Z,1R)-15 (11.5 mg, 0.03 mmol) in CH Cl (15 ml) with HCl gas at r.t., 30 min, and TLC (hexane/
CH Cl 1:1) yielded 6 mg (52%) of (R)-16.
An analogous treatment of (1'E,1R)-15 (5 mg, 0.01 mmol) in CH
TLC (hexane/CH Cl 4 :1) yielded 2 mg (40%) of (R)-16 (Scheme 10).
Data of (R)-16: Colorless crystals. M.p. 86.5 ± 94.08. [a]
2
2
2
(
6
2
2
2
2
Cl (15 ml) with HCl gas at r.t., 45 min,
2
2
4
2
2
2
2
2
2
Cl (15 ml) with HCl gas at r.t., 2 h, and
2
2
2
2
D
ˆ ‡6.1 (90% ee). IR (KBr): 3087w, 3061w,
3
1
029m, 2951w, 2938w, 2920m, 2860m, 2843w, 1602w, 1491m, 1450m, 1441w, 1428w, 1343w, 1327w, 1308w, 1237m,
1
206m, 1143m, 1096s, 1071s, 1041m, 1031w, 853m, 754s, 739s, 702vs, 696vs, 608m. H-NMR: 7.40 ± 7.13 (m, 15
arom. H); 4.76 (dd, J ˆ 10.4, 4.3, HÀC(5)); 3.34 ± 3.06 (m, 2 PhCH ); 2.90 (dd, J ˆ 10.5, 4.3, 1 HÀC(4)); 2.33 (t,
2
1
3
J ˆ 10.4, 1 HÀC(4)). C-NMR: 138.7, 136.8, 136.7 (3s, 3 arom. C); 131.7, 131.1 (2d, 4 arom. CH); 128.4, 128.2,
1
28.0, 127.5, 126.7, 126.6, 126.1 (7d, 11 arom. CH); 96.8 (s, C(2)); 84.9 (d, C(5)); 49.0, 47.6 (2t, 2 PhCH
2
); 40.7 (t,
‡
C(4)). CI-MS (NH
C 79.73, H6.40, S 9.25; found: C 79.65, H6.68, S 9.15.
3
): 365 (8), 364 (32, [M ‡ NH
4
] ), 229 (17), 228 (100). Anal. calc. for C23
H
22OS (346.49):
5
6. X-Ray Crystal-Structure Determination of (1'E,2S)-11, (S)-12, and (S)-14 (Table 3 and Figs. 1 ± 3) ). All
measurements were performed on a Nonius KappaCCD diffractometer [14] with graphite-monochromated
MoK radiation (l 0.71073 ä ) and an Oxford Cryosystems Cryostream 700 cooler. The data collection and
a
refinement parameters are given in Table 3, and views of the molecules are shown in Figs. 1 ± 3. Data reductions
were performed with HKL Denzo and Scalepack [15]. The intensities were corrected for Lorentz and
polarization effects, and, in the case of (S)-12, an absorption correction based on the multi-scan method [16] was
applied. The structures were solved by direct methods with SIR92 [17], which revealed the positions of all non-
H-atoms. In the case of (S)-12 and (S)-14, there were two symmetry-independent molecules in the asymmetric
unit. The atomic coordinates of the two molecules were tested carefully for a relationship from a higher
symmetry space group with the program PLATON [18], but none could be found. The non-H-atoms were
refined anisotropically. For (1'E,2S)-11, the OHH-atom was placed in the position indicated by a difference-
electron-density map, and its position was allowed to refine together with an isotropic displacement parameter.
All remaining H-atoms, and all the H-atoms of (S)-12 and (S)-14 were fixed in geometrically calculated
positions (d(CÀH) ˆ 0.95 ä) and each was assigned a fixed isotropic displacement parameter with a value equal
5)
CCDC-207086 ± 207088 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 Crystal-
lographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK (fax: ‡44-(0)1223-336033; e-mail:
deposit@ccdc.cam.ac.uk)).

2
846
Helvetica Chimica Acta ± Vol. 86 (2003)
to 1.2Ueq of its parent C-atom. Refinements of the structures were carried out on F using full-matrix least-
2
squares procedures, which minimized the function Sw(j F
o
jÀj F
c
j ) . A correction for secondary extinction was
applied in the case of (S)-12 and (S)-14. In (1'E,2S)-11, (S)-12, and (S)-14, four, eight, and eight reflections,
respectively, whose intensities were considered to be extreme outliers, were omitted from the final refinement.
Refinements of the absolute structure parameter [19] yielded values of À 0.03(5), À0.01(3), and 0.02(3) for
(
1'E,2S)-11, (S)-12, and (S)-14, respectively, which confidently confirm that the refined coordinates represent
the true enantiomorph in each case. Neutral atom scattering factors for non-H-atoms were taken from [20a],
and the scattering factors for H-atoms were taken from [21]. Anomalous dispersion effects were included in F
c
[22]; the values for f' and f'' were those of [20b]. The values of the mass attenuation coefficients are those of
[20c]. All calculations were performed with the teXsan crystallographic software package [23].
Table 3. Crystallographic Data of Compounds (1'E,2S)-11, (S)-12, and (S)-14
(
1'E,2S)-11
(S)-12
Et O/MeOHEt
(S)-14
Crystallized from
Et O/hexane
2
2
2
O/MeOH
Empirical formula
Formula weight [g mol
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
C
284.42
colorless, needle
0.10 Â 0.10 Â 0.30
160(1)
18
H
20OS
C
284.42
colorless, needle
0.05 Â 0.12 Â 0.32
160(1)
18
H
20OS
C
346.49
colorless, needle
0.07 Â 0.17 Â 0.22
160(1)
23
H
22OS
À1
]
Crystal system
monoclinic
monoclinic
monoclinic
Space group
P2
1
P2
1
P2
1
Z
2
4
4
Reflections for cell determination
2474
25173
4295
2
q range for cell determination [8]
4 ±60
2 ±60
4 ±55
Unit cell parameters a [ä]
8.3752(2)
5.3164(1)
17.5394(5)
99.953(1)
769.20(3)
1.228
15.0307(2)
5.8975(1)
17.1689(2)
91.9977(6)
1520.99(4)
1.242
9.5943(1)
19.5143(1)
9.7674(1)
96.0664(3)
1818.47(3)
1.265
b [ä]
c [ä]
b [8]
3
V [ä ]
À3
D
X
[g cm
]
À1
m (MoK ) [mm
a
]
0.204
0.206
0.185
2
q
(max) [8]
60
60
55
Total reflections measured
Symmetry independent reflections
Reflections used [I > 2s (I)]
Parameters refined
Final R
22113
4484
3532
44192
8726
7178
361
0.0389
0.0330
0.005
43766
8302
7387
451
0.0344
0.0311
0.005
185
0.0427
0.0409
0.015
1.359
±
0.0007
0.22; À0.28
wR
2
2 À1
Weights: p in w ˆ [s (F
o
) ‡ (pF
o
) ]
Goodness-of-fit
1.594
1.661
À6
À6
Secondary extinction coefficient
1.8(2) Â 10
1.6(2) Â 10
Final Dmax/s
D1 (max; min) [e ä
0.001
0.0004
À3
]
0.34; À0.17
0.20; À0.19
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Received April 1, 2003