Reaction of thioketones with (R)-2-vinyloxirane: Regio- and stereoselective formation of (sS)-4-vinyl-1,3-oxathiolanes

Article abstract of DOI:10.1002/ejoc.200400766

The reactions of 4,4′-dimethoxythiobenzophenone (1), 9H-xanthene-9-thione (2), and adamantane-2-thlone (3) with (R)-2-vinyloxirane [(R)-6] in the presence of SiO₂ in anhydrous CH₂Cl ₂ at 0°C or room temperature afforded th

Full text of DOI:10.1002/ejoc.200400766

FULL PAPER
Reaction of Thioketones with (R)-2-Vinyloxirane: Regio- and Stereoselective
Formation of (S)-4-Vinyl-1,3-oxathiolanes
Alexey Fedorov,[a] Changchun Fu,[b] Anthony Linden,[b] and Heinz Heimgartner*[b]
Keywords: Crystal structure / Oxiranes / 1,3-Oxathiolanes / Ring-expansion / Sulfur heterocycles
The reactions of 4,4Ј-dimethoxythiobenzophenone (1), 9H-
xanthene-9-thione (2), and adamantane-2-thione (3) with
rocyclic 1,3-oxathiolanes (S)-12 and (S)-14, respectively. The
structures of (S)-9 and (S)-12 were established by X-ray crys-
(R)-2-vinyloxirane [(R)-6] in the presence of SiO2 in anhy- tallography. In all cases, the nucleophilic thiocarbonyl S atom
drous CH2Cl2 at 0 °C or room temperature afforded the corre-
sponding 4-vinyl-1,3-oxathiolane derivatives (S)-7, (S)-9, and
(S)-11, respectively. The analogous BF3-catalyzed reactions
of (R)-6 with 1,1,3,3-tetramethylindane-2-thione (4) and
2,2,4,4-tetramethyl-3-thioxocyclobutanone (5) in anhydrous
CH2Cl2 at –65 °C or –78 °C yielded the corresponding spi-
attacked predominantly C(2) of the Lewis acid-activated (R)-
2-vinyloxirane ring with inversion of the configuration
through an SN2-type mechanism.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Introduction
In recent years, interest in 1,3-oxathiolanes has increased
remarkably. On the one hand, some nucleoside analogues
containing a 1,3-oxathiolane ring instead of a sugar moiety
show antiviral activities against HIV.[1–4] Another clinically
effective drug is ( )-cis-2-methylspiro[1,3-oxathiolane-5,3Ј-
quinuclidine] hydrochloride hemihydrate, which has been
developed in Japan for treatment of the symptoms of dry
mouth.[5,6] On the other hand, 1,3-oxathiolanes are versatile
carbonyl protecting groups in organic synthesis, because
they can easily be removed under essentially neutral condi-
tions to generate the carbonyl functionality.[7–9] The chemo-
selective protection of aldehydes in the presence of ketone
groups and of aliphatic ketones in the presence of aromatic
ketones has been reported recently.[10,11]
Because of many important applications, convenient and
efficient syntheses of 1,3-oxathiolanes are still sought after.
The methodologies reported so far are summarized in
Scheme 1.
The most widely used procedure for preparing 1,3-oxa-
thiolanes is the acid-catalyzed condensation (acetalization)
of 2-sulfanylethan-1-ols and carbonyl compounds (path a;
see[10,12]). Path b represents the base-catalyzed nucleophilic
substitution of dihalomethane derivatives by 2-sulfanyl-
ethan-1-ols,[13,14] and path c shows the electrochemical
Scheme 1.
chemoselective α-acetoxylation of βЈ-hydroxy sulfides fol-
lowed by a cyclization in the presence of BF3·Et2O.[15] Path
d concerns the acid-catalyzed exchange reaction between
2,2-dimethyl-1,3-oxathiolanes and a nonvolatile carbonyl
compound.[7a] This procedure has been improved recently
by use of solid acid catalysts under microwave irradiation
conditions in the absence of a solvent.[16] Paths e and f re-
late to 1,3-dipolar cycloadditions between carbonyl ylides
and thiocarbonyl groups and between thiocarbonyl ylides
[a] Stay at the University of Zürich, July–September 2004; perma-
nent address:
Saint-Petersburg State University,
Universitetskij pr. 26, 198504 Saint Petersburg, Russia
[b] Institute of Organic Chemistry, University of Zürich,
Winterthurerstrasse 190, 8057 Zürich, Switzerland
Fax: +41-44-635 6836
E-mail: heimgart@oci.unizh.ch
Eur. J. Org. Chem. 2005, 1613–1619
DOI: 10.1002/ejoc.200400766
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A. Fedorov, C. Fu, A. Linden, H. Heimgartner
FULL PAPER
and carbonyl compounds, respectively. The 1,3-dipolar spe- 2,2,4,4-tetramethyl-3-thioxocyclobutanone (5) with (R)-vi-
cies can be generated by the pyrolysis of oxiranes possessing nyloxirane [(R)-6] were carried out. In this paper, the results
electron-withdrawing groups[17] and by the extrusion of N2 of these reactions are described.
from 2,5-dihydro-1,3,4-thiadiazoles.[18] Other very useful
precursors of carbonyl and thiocarbonyl ylides are silicon-
based synthons such as chloromethyl (trimethylsilyl)methyl
ethers or their sulfur analogues, which readily react with
Results and Discussion
The reaction of 4,4Ј-dimethoxythiobenzophenone (1)
with (R)-2-vinyloxirane [(R)-6] at a molar ratio of 1:2 was
carried out in anhydrous CH2Cl2 in the presence of SiO2 at
0 °C under N2.[33] After stirring for 17 h, filtration, and us-
ual workup by column chromatography (CC), the 1,3-oxa-
thiolane (S)-7 and 4,4Ј-dimethoxybenzophenone (8) were
obtained in 84 and 12% yields, respectively (Scheme 3). The
enantiomeric excess of (S)-7 (99% ee) was determined by
analytical HPLC (Chiralcel OD-H, hexane/iPrOH, 400:1).
CsF through a 1,3-elimination process to generate the cor-
responding reactive ylides in situ, and these then undergo
[3+2] cycloadditions with C=S or C=O groups to give the
1,3-oxathiolanes.[19,20] As is generally the case in 1,3-dipolar
cycloadditions, regio- and stereoselectivity are important
aspects of these 1,3-oxathiolane syntheses.
The novel synthetic approach to 1,3-oxathiolanes
through the Lewis acid-catalyzed reaction of thioketones
and thiolactones with oxiranes (path g) has been investi-
gated thoroughly over the last few years.[21–28] The results
reported so far for this reaction indicate that it proceeds
with high regio- and stereoselectivity by an SN2-type
mechanism (Scheme 2). In the case of 2-alkyl-substituted
oxiranes, the nucleophilic thiocarbonyl S atom reacts pref-
erentially at C(3) to give the 5-substituted 1,3-oxathiolanes
with retention of the configuration at C(2) of the oxirane.
On the other hand, 2-phenyloxirane is attacked mainly at
C(2) with inversion of the configuration to yield the 4-
phenyl-substituted products. Similar reactions have been
observed with 1,3-thiazole-5(4H)-thiones,[29,30] with cyclic
trithiocarbonates,[31] and with a rhodanine derivative.[32]
1
The structure of (S)-7 was assigned on the basis of H
and 13C NMR spectra, and by comparison of these spectra
with those described previously.[22] The absolute configura-
tion of (S)-7 has been proposed by assuming that the ring-
opening of (R)-6 takes place through nucleophilic attack of
the thiocarbonyl S atom at C(2) of the oxirane and cleavage
of the O–C(2) bond with inversion of the configuration at
C(2).[34]
The analogous reaction of 9H-xanthene-9-thione (2)
with (R)-6 (molar ratio 1:2) in anhydrous CH2Cl2 at room
temperature in the presence of SiO2 occurred much more
slowly. After 68 h, the spirocyclic compound (S)-9 and xan-
thone (10) were obtained in 40 and 21% yields, respectively.
In addition, a 35% yield of the starting material 2 was reco-
vered (Scheme 4). The 1,3-oxathiolane derivative (S)-9 was
almost enantiomerically pure (99% ee, HPLC, Chiralcel
OD-H, hexane/iPrOH, 250:1).
The structure of (S)-9 was assigned on the basis of ele-
mental analysis and spectroscopic data, and was confirmed
by X-ray crystallography (Figure 1). The crystals of (S)-9
were enantiomerically pure and the absolute configuration
of the molecule was determined independently by the dif-
fraction experiment and found to be (4S). Therefore, the
ring-opening of the oxirane occurred by an SN2 mechanism.
The reaction of adamantane-2-thione (3) with (R)-6 in a
Scheme 2.
The reaction of 2-vinyloxirane with thiocarbonyl com-
pounds, which could lead to five- or seven-membered het- molar ratio of 1:2 was also carried out in anhydrous
erocycles, has not been reported so far. With the aim of CH2Cl2 under N2 and in the presence of SiO2. Because 3
further extending the scope of the reactions of thioketones was more reactive than 2, a reaction temperature of 0 °C
with oxiranes, reactions of 4,4Ј-dimethoxythiobenzo- was chosen and the mixture was stirred for 28 h. Filtration
phenone (1), 9H-xanthene-9-thione (2), adamantane-2- and the usual workup by column chromatography (CC)
thione (3), 1,1,3,3-tetramethylindane-2-thione (4), and gave the spiroheterocycle (S)-11 in 32% yield, and the start-
Scheme 3.
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Regio- and Stereoselective Formation of (S)-4-Vinyl-1,3-oxathiolanes
FULL PAPER
Scheme 4.
The structure of (S)-11 was again assigned on the basis
of elemental analysis and spectroscopic data, and, from the
reaction mechanism postulated above, the absolute configu-
ration of (S)-11 was assumed to be (4ЈS).
Under the reaction conditions used for the transforma-
tion of 1–3 (i.e., 0–20 °C and SiO2 as catalyst), only very
slow formation of 1,3-oxathiolane was observed with the
sterically crowded 1,1,3,3-tetramethylindane-2-thione (4).
Therefore, a stronger Lewis acid was used: the BF3-cata-
lyzed reaction of 4 with (R)-6 (molar ratio 1:4) in anhydrous
CH2Cl2 at –65 °C for 6 h under N2 afforded the spirocyclic
compound (S)-12 and ketone 13 in 44 and 4% yields,
respectively. The starting material 4 was recovered in 20%
yield (Scheme 6). The ee value of (S)-12 (98%) was deter-
mined by analytical HPLC (Chiralcel OD-H, hexane/
iPrOH, 750:1).
The structure of (S)-12 was assigned on the basis of ele-
mental analysis and spectroscopic data, particularly NMR
experiments (HSQC, HSQC-TOCSY, and HMBC), and
was established by X-ray crystallography (Figure 2). The
crystals of (S)-12 were enantiomerically pure, and the abso-
lute configuration of the molecule was determined indepen-
dently by the diffraction experiment and found to be (4ЈS).
There are two symmetry independent molecules in the
asymmetric unit. Both are of the same enantiomorph and
Figure 1. ORTEP plot[35] of the molecular structure of (S)-9 (arbi-
trary numbering of the atoms; displacement ellipsoids with 50%
probability).
ing material 3 was recovered in 8% yield (Scheme 5). The
ee value of (S)-11 was determined by analytical HPLC (Chi-
ralcel OD-H, hexane) to be Ͼ99.9%.
Scheme 5.
Scheme 6.
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A. Fedorov, C. Fu, A. Linden, H. Heimgartner
FULL PAPER
have almost identical conformations, with a r.m.s. fit of the ee), and the inversion has been demonstrated in the cases
corresponding atoms of 0.06 Å.
of (S)-9 and (S)-12 by X-ray crystallography. Therefore, the
reaction proceeds analogously to that reported for thiocar-
bonyl compounds with (R)-2-phenyloxirane.[23–26,30]
The thiocarbonylium ion A is a likely intermediate in the
nucleophilic attack of the thiocarbonyl S atom at the C(2)
atom (O–C(2) cleavage) of the activated (R)-6. Cyclization
of A by the intramolecular addition of the O atom gives the
expected 1,3-oxathiolane (S)-15. The formation of ketones
8, 10, and 13 can be explained by the hydrolysis of the cor-
responding intermediates of type A. An alternative explana-
tion is the Lewis acid-catalyzed decomposition of (S)-15,
which produces the carbonyl compound and 2-vinylthiirane
(for analogous reactions see[21,29,31]).
In order to obtain both high regio- and stereoselectivity
and high yield, a weak Lewis acid (e.g., SiO2) is recom-
mended for the reaction of (R)-6 with aromatic and reactive
aliphatic thioketones such as 1, 2, and 3, but a strong Lewis
acid (e.g., BF3·Et2O) is needed for the reaction with steri-
cally hindered thioketones such as 4 and 5.
Figure 2. ORTEP plot[35] of the molecular structure of one of the
two symmetry-independent molecules of (S)-12 (arbitrary number-
ing of the atoms; displacement ellipsoids with 50% probability).
In analogy to the experiment with 4, the reaction of
2,2,4,4-tetramethyl-3-thioxocyclobutanone (5) with (R)-6
(molar ratio 1:2) in anhydrous CH2Cl2 at –78 °C under N2
was catalyzed with BF3. After 45 min and the usual
workup, the spirocyclic 1,3-oxathiolane (S)-14 was obtained
in 71% yield with 99.6% ee (HPLC, Chiralcel OD-H, hex-
ane/iPrOH, 400:1) (Scheme 7).
The structure of (S)-14 was assigned as usual, and it has
been assumed that the molecules have the (7S) configura-
tion.
Experimental Section
General: See.[36] The thioketones 1,[37] 2,[38] 3,[39] 4,[40] and 5[41] were
prepared by thionation of the corresponding ketones by literature
procedures. Optical rotations: Perkin–Elmer 241 polarimeter (c =
1, in THF). IR spectra: film or KBr (cm–1). NMR spectra: at 300
(1H) and 75.5 MHz (13C) in CDCl3, if not otherwise stated. Enan-
tiomeric excesses (ee) were determined by analytical HPLC on a
Chiralcel OD-H column.
Conclusions
The nucleophilic attack of the thiocarbonyl S atom at the
Lewis acid-activated (R)-2-vinyloxirane [(R)-6] could occur,
in principle, at C(2) and C(3) through an SN2 mechanism
to give 1,3-oxathiolanes, or at C(2Ј) through an SN2Ј
mechanism to afford seven-membered heterocycles. How-
ever, the results presented show that, in all cases, the ring-
enlarged product is formed by the nucleophilic attack of the
thiocarbonyl S atom at C(2) of the Lewis acid-complexed
(R)-2-vinyloxirane ring through an SN2-type mechanism
General Procedure for the Reactions of 4,4Ј-Dimethoxythiobenzo-
phenone (1), 9H-Xanthene-9-thione (2), and Adamantane-2-thione
(3) with (R)-2-Vinyloxirane [(R)-6]: Silica gel (SiO2, Uetikon-
Chemie Chromatographiegel C-560 (4.5 g) was added at 0 °C or at
room temperature to a solution of 1, 2, or 3 (ca. 1 mmol) and (R)-
6 (ca. 2 mmol) in dry CH2Cl2 (15 mL) under N2. After the suspen-
sion had been stirred at 0 °C or room temperature for 17–68 h, the
mixture was filtered and the residue was washed with AcOEt (4×).
(Scheme 8). The stereoselectivity is very high (98–99.9% Then, the combined filtrate was evaporated in vacuo, and the prod-
Scheme 7.
Scheme 8.
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Regio- and Stereoselective Formation of (S)-4-Vinyl-1,3-oxathiolanes
FULL PAPER
ucts were separated by column chromatography (CC; SiO2; hexane/
AcOEt, hexane/Et2O, or hexane/CH2Cl2).
Crystals of (S)-9 suitable for X-ray crystal structure determination
were grown from CH2Cl2/hexane.
(S)-4Ј-Vinylspiro[tricyclo[3.3.1.13,7]decane-2,2Ј-[1,3]oxathiolane]
[(S)-11]: Treatment of 3 (140 mg, 0.84 mmol) with (R)-6 (117 mg,
1.67 mmol) and SiO2 (3.8 g) in dry CH2Cl2 (9 mL) at 0 °C, 28 h,
and CC (SiO2, hexane/CH2Cl2, 10:1) yielded (S)-11 (64 mg, 32%).
In addition, 8% of 3 were recovered.
Data for (S)-11: Colorless oil. [α]2D5 = –153.1 (99.9% ee). 1H NMR:
δ = 5.85–5.73 (m, CH=CH2), 5.17 (ddd, J = 16.9, 1.3, 0.7 Hz, 1 H
of =CH2), 5.02 (ddd, J = 9.9, 1.3, 1.0 Hz, 1 H of =CH2), 4.22 [dd,
J = 9.3, 5.4 Hz, 1 H–C(5Ј)], 4.08–4.00 [m, H–C(4Ј)], 3.90 [dd, J =
9.3, 6.1 Hz, 1 H–C(5Ј)], 2.19–2.07 (br. m, 4 H), 1.87–1.71 (br. m, 8
H), 1.64–1.56 (br. m, 2 H) ppm. 13C NMR (150.9 MHz): δ = 137.1
(d, CH=CH2), 116.1 (t, CH=CH2), 103.0 [s, C(2)], 73.7 [t, C(5Ј)],
52.6 [d, C(4Ј)], 40.3, 40.1 [2 d, C(1), C(3)], 37.4 [t, C(6)], 36.8, 36.5,
34.3 [3 t, C(4), C(8), C(9), C(10)], 26.9, 26.2 [2 d, C(5), C(7)] ppm.
General Procedure for the Reactions of 1,1,3,3-Tetramethylindane-
2-thione (4) and 2,2,4,4-Tetramethyl-3-thioxocyclobutanone (5) with
(R)-2-Vinyloxirane [(R)-6]: BF3·Et2O (0.5 equiv.) was added at
–65 °C or –78 °C under N2 to a solution of 4 or 5 (ca. 1 mmol) in
dry CH2Cl2 (10–15 mL), leading to little change in the color of the
soln. After the mixture had been stirred for 15 min at –65 °C or
–78 °C, respectively, (R)-6 (2 equiv.) was added dropwise, where-
upon the color of the solution changed moderately. Then, the reac-
tion was quenched by addition of H2O (4 mL) or aqueous
NaHCO3 solution (5%), and the mixture was washed with satu-
rated aqueous NaCl solution (3×). The organic layers were com-
bined and dried over MgSO4, and the solvents were evaporated in
vacuo. The products were separated by column chromatography
(CC; SiO2, hexane/CH2Cl2 or hexane/Et2O).
IR (film): ν = 3081 w, 2910 s, 2854 s, 1636 m, 1469 m, 1451 m,
˜
(S)-2,2-Bis(4-methoxyphenyl)-4-vinyl-1,3-oxathiolane [(S)-7]: Treat-
ment of 1 (258 mg, 1 mmol) with (R)-6 (140 mg, 2 mmol) and SiO2
(4.5 g) at 0 °C, 17 h, and CC (SiO2, hexane/AcOEt, 4:1) yielded
(S)-7 (276 mg, 84%) and 4,4Ј-dimethoxybenzophenone (8, 30 mg,
12%).
1417 w, 1373 w, 1358 w, 1350 w, 1309 w, 1276 w, 1249 w, 1226 w,
1197 w, 1174 w, 1103 m, 1084 m, 1046 m, 1019 w, 995 m, 962 m,
917 m, 892 m, 879 w, 851 m, 802 w, 732 w cm–1. CI-MS (NH3):
239 (5), 238 (14), 237 (88) [M + H]+, 169 (12), 168 (100), 151 (8).
C14H20OS (236.37): calcd. C 71.14, H 8.53; found C 70.91, H 8.20.
1
Data for (S)-7: Colorless oil. [α]2D5 = –105.5 (99% ee). H NMR: δ
(S)-1,1,3,3-Tetramethyl-4Ј-vinylspiro[indane-2,2Ј-[1,3]oxathiolane]
[(S)-12]: Treatment of 4 (204 mg, 1 mmol) with (R)-6 (280 mg,
4 mmol) and BF3·Et2O (1 mmol) at –65 °C, 6 h, and CC (SiO2,
hexane/CH2Cl2, 4:1) yielded (S)-12 (120 mg, 44%) and 1,1,3,3-tet-
ramethylindan-2-one (13, 8 mg, 4%). In addition, 20% of 4 were
recovered.
Data for (S)-12: Colorless crystals. M.p. 59.3–59.6 °C. [α]2D5 = –81.1
(98% ee). 1H NMR (600 MHz): δ = 7.23–7.16 (m, 4 arom. H),
5.81–5.75 (m, CH=CH2), 5.34 (d, J = 16.9 Hz, 1 H of =CH2), 5.17
(d, J = 10.1 Hz, 1 H of =CH2), 4.27 [dd, J = 8.9, 5.9 Hz, 1 H–
C(5Ј)], 4.20–4.16 [m, H–C(4Ј)], 3.80 [t-like, J Ϸ 8.9 Hz, 1 H–C(5Ј)],
1.43, 1.42, 1.36, 1.35 (4 s, 4 Me) ppm. 13C NMR (150.9 MHz): δ =
148.5, 148.1 (2 s, 2 arom. C), 134.3 (d, CH=CH2), 127.1, 127.0,
122.6, 122.4 (4 d, 4 arom. CH), 118.3 (t, CH=CH2), 113.9 [s, C(2)],
76.6 [t, C(5Ј)], 53.0 [d, C(4Ј)], 52.2, 51.5 [2 s, C(1), C(3)], 31.9, 30.6,
= 7.45 (AAЈ of AAЈXXЈ, J = 8.9 Hz, 2 arom. H), 7.38 (AAЈ of
AAЈXXЈ, J = 8.9 Hz, 2 arom. H), 6.84 (XXЈ of AAЈXXЈ, J =
8.9 Hz, 2 arom. H), 6.82 (XXЈ of AAЈXXЈ, J = 8.9 Hz, 2 arom.
H), 5.87–5.75 (m, CH=CH2), 5.18 (d-like, J Ϸ 16.9 Hz, 1 H of
=CH2), 5.04 (dd, J = 9.9, 1.1 Hz, 1 H of =CH2), 4.38–4.23 [m, H–
C(4), 1 H–C(5)], 3.86–3.77 [m, 1 H–C(5)], 3.80, 3.79 (2 s, 2
Me) ppm. 13C NMR: δ = 159.0, 158.9 (2 s, 2 arom. C), 136.7, 136.6
(2 s, 2 arom. C), 136.4 (d, CH=CH2), 128.4, 128.1 (2 d, 4 arom.
CH), 116.5 (t, CH=CH2), 113.1 (d, 4 arom. CH), 100.3 [s, C(2)],
74.2 [t, C(5)], 55.2 (q, 2 Me), 54.8 [d, C(4)] ppm. IR (film): ν =
˜
3076 w, 3036 w, 3001 w, 2956 m, 2933 m, 2908 w, 2870 w, 2836 m,
1635 w, 1607 s, 1583 m, 1508 s, 1463 m, 1441 m, 1415 m, 1303 s,
1250 s, 1172 s, 1113 m, 1066 s, 1034 s, 988 m, 921 m, 879 w, 824 s,
793 m, 730 w cm–1. CI-MS (NH3): 331 (6), 330 (18), 329 (83) [M
+ H]+, 244 (17), 243 (100). C19H20O3S (328.43): calcd. C 69.48, H
6.14, S 9.76; found C 69.27, H 6.20, S 9.85.
23.4, 22.2 (4 q, 4 Me) ppm. IR (KBr): ν = 3082 w, 3069 w, 3041 w,
˜
3016 w, 2990 m, 2958 s, 2930 m, 2866 m, 1639 m, 1586 w, 1479 s,
1465 m, 1448 m, 1416 w, 1380 w, 1373 m, 1359 m, 1311 w, 1248 w,
1200 w, 1171 w, 1126 m, 1076 s, 1045 m, 1026 m, 993 m, 984 m,
965 m, 952 m, 912 s, 871 w, 803 w, 754 s, 741 m cm–1. CI-MS
(NH3): 294 (7), 293 (20), 292 (100) [M + NH4]+, 276 (15), 275 (75)
[M + H]+, 206 (17), 160 (6). C17H22OS (274.42): calcd. C 74.40, H
8.08, S 11.68; found C 74.23, H 8.16, S 11.46.
(S)-4-Vinylspiro[1,3-oxathiolane-2,9Ј-[9ЈH]xanthene] [(S)-9]: Treat-
ment of 2 (89 mg, 0.42 mmol) with (R)-6 (59 mg, 0.84 mmol) and
SiO2 (1.9 g) in dry CH2Cl2 (6 mL) at room temperature, 68 h, and
CC (SiO2, hexane/Et2O, 4:1) yielded (S)-9 (48 mg, 40%) and xan-
thone (10, 17 mg, 21%). In addition, 35% of 2 were recovered.
Data for (S)-9: Colorless crystals. M.p. 72.3–72.9 °C. [α]2D5 = –129.1
1
(99% ee). H NMR: δ = 8.03–8.00 (m, 1 arom. H), 7.92–7.89 (m,
Crystals of (S)-12 suitable for X-ray crystal structure determination
1 arom. H), 7.40–7.33 (m, 2 arom. H), 7.25–7.18 (m, 4 arom. H),
6.06–5.94 (m, CH=CH2), 5.39 (d, J = 16.8 Hz, 1 H of =CH2), 5.23
(d, J = 10.0 Hz, 1 H of =CH2), 4.64–4.57 [m, H–C(4)], 4.50 [dd, J
= 9.4, 5.7 Hz, 1 H–C(5)], 4.16 [dd, J = 9.3, 7.9 Hz, 1 H–C(5)] ppm.
13C NMR: δ = 151.0, 150.6 (2 s, 2 arom. C), 133.7 (d, CH=CH2),
129.6, 129.5, 128.7, 128.0 (4 d, 4 arom. CH), 125.2, 124.4 (2 s, 2
were grown from Et2O/MeOH.
(S)-1,1,3,3-Tetramethyl-7-vinyl-5-oxa-8-thiaspiro[3.4]octan-2-one
[(S)-14]: Treatment of 5 (70 mg, 0.45 mmol) with (R)-6 (63 mg,
0.90 mmol) and BF3·Et2O (0.22 mmol) at –78 °C, 45 min, and CC
(SiO2, hexane/Et2O, 30:1) yielded (S)-14 (72 mg, 71%).
arom. C), 123.3, 123.2 (2 d, 2 arom. CH), 118.5 (t, CH=CH2), 116.7 Data for (S)-14: Colorless oil. [α]2D5 = –139.2 (99.6% ee). 1H NMR:
(d, 2 arom. CH), 89.0 [s, C(2)], 76.0 [t, C(5)], 55.4 [d, C(4)] ppm. IR
δ = 5.81–5.70 (m, CH=CH2), 5.25 (ddd, J = 16.9, 1.1, 0.9 Hz, 1 H
of =CH2), 5.10 (ddd, J = 10.0, 1.1, 0.4 Hz, 1 H of =CH2), 4.11 [dd,
J = 8.8, 5.5 Hz, 1 H–C(6)], 4.07–4.00 [m, H–C(7)], 3.77 [dd, J =
8.8, 5.7 Hz, 1 H–C(6)], 1.30, 1.28, 1.19, 1.17 (4 s, 4 Me) ppm. 13C
(KBr): ν = 3084 w, 3037 w, 3012 w, 2971 w, 2923 w, 2864 m, 1634
˜
w, 1598 s, 1570 m, 1482 m, 1471 s, 1445 s, 1418 m, 1355 w, 1317 s,
1288 s, 1243 s, 1208 m, 1184 m, 1150 m, 1100 m, 1055 s, 1038 m,
991 m, 940 s, 918 m, 884 s, 868 m, 792 m, 757 s, 738 m, 724 m cm–1. NMR: δ = 220.9 [s, C(2)], 136.1 (d, CH=CH2), 117.0 (t, CH=CH2),
ESI-MS (MeOH): 413 (20), 307 (7), 306 (18), 305 (88) [M + Na]+,
304 (35), 284 (20), 283 (100) [M + H]+, 219 (35), 214 (8), 213 (45),
197 (6). C17H14O2S (282.36): calcd. C 72.31, H 5.00; found C 72.42,
H 5.01.
100.7 [s, C(4)], 76.4 [t, C(6)], 65.6, 65.5 [2 s, C(1), C(3)], 52.2 [d,
C(7)], 24.6, 24.0, 17.7, 17.3 (4 q, 4 Me) ppm. IR (film): ν = 3085
˜
w, 2967 m, 2931 w, 2868 w, 1774 s, 1637 w, 1463 m, 1444 w, 1420
w, 1380 w, 1364 w, 1250 w, 1205 w, 1142 w, 1096 s, 1028 m, 986 w,
Eur. J. Org. Chem. 2005, 1613–1619
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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A. Fedorov, C. Fu, A. Linden, H. Heimgartner
FULL PAPER
927 m, 892 w, 811 w, 733 w, 701 w cm–1. CI-MS (NH3): 228 (13),
227 (100) [M + H]+, 156 (18), 71 (5). C12H18O2S (226.34): calcd. C
63.68, H 8.02, S 14.17; found C 63.51, H 7.89, S 14.08.
Acknowledgments
We thank the analytical services of our institute for NMR and mass
spectra and for elemental analyses, Mr. B. Bürgi for his assistance
with the determination of the crystal structures, and the Swiss
National Science Foundation and F. Hoffmann–La Roche AG, Ba-
sel, for financial support.
X-ray Crystal Structure Determination of (S)-9 and (S)-12 (Figure 1
and Figure 2):[42] All measurements were performed on a Nonius
KappaCCD area-detector diffractometer[43] by use of graphite-mo-
nochromated Mo-Kα radiation (λ, 0.71073 Å) and an Oxford
Cryosystems Cryostream 700 cooler. The data collection and re-
finement parameters are given below, and views of the molecules
are shown in Figures 1 and 2. Data reduction was performed with
HKL Denzo and Scalepack.[44] The intensities were corrected for
Lorentz and polarization effects, and an absorption correction
based on the multi-scan method[45] was applied. The structures
were solved by direct methods with SIR92,[46] which revealed the
positions of all non-H atoms. In (S)-12, there are two symmetry-
independent molecules in the asymmetric unit. The atomic coordi-
nates of the two molecules were tested carefully for a relationship
from a higher symmetry space group with the program PLA-
TON,[47] but none could be found. The non-H atoms of (S)-9 and
(S)-12 were refined anisotropically. All of the H atoms were placed
in geometrically calculated positions and refined by use of a riding
model in which each H atom was assigned a fixed isotropic dis-
placement parameter with a value equal to 1.2 Ueq of its parent C
atom (1.5 Ueq for the methyl group in (S)-12). The refinement of
each structure was carried out on F2 using full-matrix least-squares
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2 2
procedures, which minimized the function Σw(Fo2 – Fc ) . A correc-
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Crystal Data for (S)-9: C17H14O2S, M = 282.36, colorless, tablet,
crystal dimensions 0.08×0.25×0.30 mm3, orthorhombic, space
group P212121, Z = 4, a = 8.9261(3) Å, b = 9.7256(4) Å, c =
15.6448(4) Å, V = 1358.15(8) Å3, DX = 1.381 g·cm–3, μ(Mo-Kα) =
0.236 mm–1, T = 160 K, φ and ω scans, transmission factors (min./
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symmetry independent reflections 3125, reflections with I Ͼ 2σ(I)
2744, reflections used in refinement 3125, parameters refined 182,
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2
0.0853 (w = [σ2(Fo2) + (0.0407P)2 + 0.3488P]–1, where P = (Fo
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+ 2Fc )/3), goodness of fit 1.058, secondary extinction coefficient
0.006(2), final Δmax./σ 0.001, Δρ (max./min.) = 0.20/–0.29 e·Å–3.
Crystal Data for (S)-12: C17H22OS, M = 274.42, colorless, prism,
crystal dimensions 0.15×0.20×0.27 mm3, monoclinic, space group
C2, Z = 8, a = 19.7743(4), b = 8.2890(2), c = 19.7925(4) Å, β =
109.813(1)°, V = 3052.1(1) Å3, DX = 1.194 g·cm–3, μ(Mo-Kα) =
0.203 mm–1, T = 160 K, φ and ω scans, transmission factors (min./
max.) 0.908/0.974, 2θ(max.) = 55°, total reflections measured 37032,
symmetry independent reflections 7017, reflections with I Ͼ 2σ(I)
5175, reflections used in refinement 7013, parameters refined 352,
restraints 1, R (on F; I Ͼ 2σ(I) reflections) = 0.0454, wR(F2) (all
reflections) = 0.1184 (w = [σ2(Fo2) + (0.0573P)2 + 0.9687P]–1,
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1618
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 1613–1619

Regio- and Stereoselective Formation of (S)-4-Vinyl-1,3-oxathiolanes
FULL PAPER
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Received: October 16, 2004
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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