Synthesis of thiabicyclic heterocycles through free radical cyclization of β-thioacrylates

Article abstract of DOI:10.1016/S0040-4020(00)00247-7

8-Aza-3-thiabicyclo[4.3.0]nonanes 7 and 8, 3-thiabicyclo[4.4.0]decanes 18, and 8-thiabicyclo[4.3.0]nonanes 31 were obtained from monocyclic precursors through free radical cyclizations involving a β-thioacrylate system as radical acceptor and a thionocarbonate as radical precursor. Oxidative sulfur extrusion in 3-thiabicyclo[4.4.0]decanes 18 afforded methyl (2-isopropenyl-5-methylcyclohexyl)-2-propenoates 35. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00247-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3425±3437
Synthesis of Thiabicyclic Heterocycles Through Free Radical
Cyclization of b-Thioacrylates
*
Â
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Yaroslav V. Bilokin, Artem Melman, Valerie Niddam, Bellinda Benhamu and Mario D. Bachi
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel
Received 6 January 2000; revised 29 February 2000; accepted 16 March 2000
AbstractÐ8-Aza-3-thiabicyclo[4.3.0]nonanes 7 and 8, 3-thiabicyclo[4.4.0]decanes 18, and 8-thiabicyclo[4.3.0]nonanes 31 were obtained
from monocyclic precursors through free radical cyclizations involving a b-thioacrylate system as radical acceptor and a thionocarbonate as
radical precursor. Oxidative sulfur extrusion in 3-thiabicyclo[4.4.0]decanes 18 afforded methyl (2-isopropenyl-5-methylcyclohexyl)-2-
propenoates 35. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
from the anti-Markovnikov addition of methyl 2-mercapto-
propionate to the isopropenyl group of 1.2 The resulting
sul®des 2 (mixture of C-10 epimers) were selectively
oxidized to sulfoxides 3. Sulfoxides which carry an acidic
methylene group in a b-position undergo facile thermolysis
to give the corresponding sulfenic acids. The emerging
sulfenic acid can be trapped in situ by alkenes or alkynes.12
Extension of this reaction allowed the metathetic trans-
formation of sulfoxides 3 into a,b-unsaturated sulfoxides
5 by heating the former with excess of methyl propiolate.
Selective reduction with Lawesson's reagent of the unsatu-
rated sulfoxide 3 to the corresponding thioenolate,13 was
followed by desilylation and thionocarbonation to give the
desired b-thioacrylate-thionocarbonate derivatives 6.
n-Bu3SnH/AIBN induced free radical cyclization of thiono-
carbonates 6 (1:1 mixture of two epimers at C-10) gave two
The development of a method for temporary sulfur connec-
tion and its application to the synthesis of (2)-a-kainic acid
and to the stereocontrolled functionalization of (2)-carvone
was recently reported.1±5 This method involves three parts:
(i) anchoring stage, in which two reactants are linked
through a sulfur connector; (ii) intramolecular cyclization
through the formation of a new carbon±carbon bond as part
of a sulfur-containing ring; (iii) disconnecting stage in
which the temporary sulfur linker is removed. As part of a
study directed towards the further development of tempor-
ary sulfur connection, methods for the construction of some
bicyclic sulfur-containing systems were investigated. These
compounds are of interest as synthetic intermediates as well
as target compounds for studying their properties.6±8 In this
paper ef®cient syntheses of thiabicyclic compounds through
free radical cyclization of b-thioacrylates are reported.
1
individual products 7 and 8. H NMR spectra indicate that
compounds 7 and 8 have opposite con®guration, not only at
C-7, but also at C-3a. Relative stereochemistry at position
C-3a of isomers 7 and 8 was established on the basis of the
values of JH3a±H7a, which are 11.3 Hz for 7 and 5.5 Hz for 8.
The large difference in coupling constants, JH3±H3aˆ0 Hz vs.
9 Hz in isomers 7 and 8, indicates an opposite con®guration
at C-3 and C-3a. These values led us to assign to 3-H and
3a-H a trans-con®guration in compound 7 and cis in
compound 8. Moreover, relative stereochemistry at posi-
tions C-3a, C-4, and C-7 in isomers 7 and 8 was con®rmed
by NOE-difference 1H NMR. Irradiation at 7a-H in 7
resulted in NOE response at 3a-H (4.8%) and 7-H
(11.2%). Irradiation at 3a-H in 7 resulted in NOE response
at 7a-H (2%) and 4-H (2.6%). NOE experiments for isomer
8 showed that irradiation at 3a-H revealed NOE difference
at 7-H (6.7%), 4-H (4.5%) and no response at 7a-H. While
irradiation at 3-H revealed NOE difference at 4-H (6.3%).
These data indicate the cis-con®guration of 3a-H and 7a-H,
and the trans-con®guration of 3-H and 3a-H in thiopyrano-
pyrrole 7 and opposite con®gurations in isomer 8.
Results and Discussion
Radical-mediated cyclizations are extensively used for the
construction of heterocyclic systems.9 Although there are no
previous reports on the free radical cyclization of b-thio-
acrylates, b-alkoxyacrylates were found to be ef®cient
radical acceptors for the synthesis of oxacycles.10,11 Scheme
1 describes the synthesis of conformationally restricted
kainoids 7 and 8.8 Pyrrolidine derivative 6, carrying the
b-thioacrylate function as radical acceptor and the thiono-
carbonate function as radical precursor was designed as a
key intermediate. It was prepared in a few stages starting
Keywords: cyclization; radicals and radical reactions; sulfoxides; sulfur
heterocycles.
* Corresponding author. Tel.: 1972-8-934-2043; fax: 1972-8-934-4142;
e-mail: mario.bachi@weizmann.ac.il
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00247-7

3426
Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
Scheme 1. Reagents and conditions: (a) HSCH2CH2CO2Me, AIBN, THF, 608C, 4.5 h; (b) m-CPBA, CH2Cl2, 2608C, 2 h; (c) HCuCCO2Me, toluene, re¯ux,
2 h; (d) Lawesson's reagent, THF, 2108C, 50 min; (e) Bu4NF, AcOH, THF, room temp., 20 h; (f) n-BuLi, PhOC(S)Cl, THF, 2788C!room temp., 3 h;
(g) n-Bu3SnH, AIBN, toluene, 1008C, 1.5 h.
Formation of two, rather than four isomers, is attributed to a
different directive effect of the C-10 methyl group in the two
C-10 epimers 6. Indeed, molecular models examination of
intermediate radical 9 indicates the absence of any signi®-
cant non-bonding interaction at the transition state leading
to cis-fused product 7. In contrast, in intermediate radical
10, non-bonding interaction between the C-10 methyl group
and ring hydrogen atoms are lower at the transition state
leading to trans, rather than to the cis-fused product,
therefore formation of compound 8 is favored. In con-
clusion, stereoselectivities in the free radical cyclizations
of the two C-10 epimeric thionocarbonates 6 are very high
and antithetical.
In another line of research, b-thioacrylates 16a and 16b
were synthesized and their free radical cyclization studied
(Schemes 2 and 3). Light-induced addition of thiolacetic
acid to tert-butyl(dimethylsilyl)isopuelegol 12 afforded
Scheme 2. Reagents and conditions: (a) TBDMSTf, 2,6-lutidine, CH2Cl2, 2728C, 1 h; (b) HSC(O)Me, longwave UV lamp, 72 h.

Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
3427
Scheme 3. Reagents and conditions: (a) KOH, MeOH, 08C!room temp., 1.5 h; (b) HCuCCO2Me, MeOH±H2O (10:1), Et3N, 08C!room temp., 24 h;
(c) Bu4NF, THF, room temp., ca. 12 h; (d) PhOC(S)Cl, DMAP, pyridine, THF, 08C!room temp., ca. 12 h; (e) n-Bu3SnH, AIBN, toluene, 958C, 1.5 h.
Scheme 4. Reagents and conditions: (a) HSCH2CH2CO2Me, AIBN, THF, 608C, 8 h; (b) m-CPBA, CH2Cl2, 2608C, 4.5 h; (c) HCuCCO2Me, toluene, re¯ux,
2 h; (d) NaI, (CF3CO)2O, acetone, 08C, 30 min; (e) Bu4NF, THF, room temp., 22 h; (f) PhOC(S)Cl, DMAP, pyridine, THF, 08C!room temp., ca. 12 h.

3428
Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
Scheme 5. Reagents and conditions: (a) m-CPBA, EtOAc, 08C!room temp., 4 h; (b) MPLC.
epimeric acetylsul®des 13 (Scheme 2), which were chroma-
tographically separated into the two diastereomers 13a and
13b. Each of these diastereomers was subjected to the series
of reactions detailed in Scheme 3. Thus, deacetylation
followed by base-induced addition of the resulting thiols
to methyl propiolate, afforded b-thioacrylates 14a and
14b. Desilylation to 15a and 15b followed by thiono-
carbonation affords the corresponding b-thioacrylate-
thionocarbonate derivatives 16a and 16b. n-Bu3SnH/AIBN
induced free radical cyclization of thionocarbonates 16a and
16b afforded respectively thiabicyclic compounds 18a and
18b in high yields. The absence of any monocyclic reduced
compound deriving from direct hydrogen atom transfer
from n-Bu3SnH to incipient radicals 17a and 17b indicate
that the 6-exo ring closure proceeds at high rate. Thus, 6-exo
ring closure of cyclohexyl radicals 17a and 17b proceeds at
the same high regioselectivity as that of the azacyclopentyl
carbon-centered radicals 9 and 10, but at rather lower
stereoselectivity.
To elucidate the stereochemistry7 of the inseparable 2:1
mixture of two thiabicyclo[4.4.0]decanes 18a-1 and 18a-2,
these compounds were oxidized with m-CPBA (Scheme 5)
to the corresponding trans-fused bicyclic sulfone 22 (major
isomer) and cis-fused bicyclic sulfone 23 (minor isomer)
(separated by MPLC). The stereochemistry of sulfones 22
and 23 was established by detailed NMR analysis which
included spin decoupling experiments, 1D- (1H, 13C/
DEPT), and 2D-NMR spectra (1H/1H, COSY, 1H/13C
HMQC). The same approach was used to elucidate the
stereochemistry of the mixture of thiabicyclo[4.4.0]decanes
18b-1 and 18b-2. It was found that the product of cycliza-
tion of 16b consists of two trans-fused bicyclic isomers
18b-1, which are epimers at C-2, and two cis-fused bicyclic
isomers 18b-2 also epimeric at C-2. A 6:1 ratio of trans-
fused to cis-fused isomers 18b-1 and 18b-2 was established
on the grounds of the NMR spectra of their degradation
products 35 (Scheme 7, 18b!35). It was found that the
NMR spectra for these compounds are identical to those
obtained from the degradation of cyclic sul®des 18a
(Scheme 7, 18a!35). Indeed, oxidation of thia-
bicyclo[4.4.0]decanes 18b-1 and 18b-2 gave, after separa-
tion, pure trans-fused sulfones 24 and 25 and a mixture of
sulfone 25 with cis-fused sulfones 26 (epimers at C-2)
where sulfone 25 constitutes the major component. 1,6-cis
The two diastereomeric menthol derivatives 16a,b were also
obtained by the method based on acrylate/propiolate
metathesis as described in Scheme 4. Thus, TBDMS-
isopulegol 12 was converted in 60% overall yield into
b-thioacrylate-thionocarbontes 16a,b.

Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
3429
Scheme 6. Reagents and conditions: (a) HCuCCO2Et, EtOH±H2O (15:1), Et3N, 08C!room temp., ca. 12 h. (b) PhOC(S)Cl, DMAP, pyridine, THF,
08C!room temp., ca. 12 h. (c) n-Bu3SnH, AIBN, toluene, 958C, 1 h.
and 1,6-trans con®guration assignments for compounds
22±26 was derived from spin coupling constants of the
C-1 and C-6 protons, where JH1eqH6ax (cis),JH1axH6ax
(trans). 1,6-cis Compounds 23 and 26 and 1,6-trans
compounds 22, 24, and 25 exhibited upon irradiation
of the C-2 protons the following relevant coupling
constants: JH1eqH6ax<0 Hz in compounds 23 and 26 and
JH1axH6axˆ10.0±10.9 Hz in sulfones 22, 24, and 25. The
1H NMR spectra of sulfones 23, 24 and 25 exhibited
characteristic signals of C-5 methyl groups at 1.03±
1.07 ppm. The corresponding signals for isomers 22 and
26 are further down®eld and are 1.19, 1.20, and 1.31 ppm.
This pattern derives from the deshielding effect of SO2
group on the juxtaposed 5-CCH3 H-atoms and constitutes
a simple diagnostic tool to differentiate between epimers at
position C-5.
Opposite stereoselectivity was observed in the 5-exo ring
closure of cyclohexyl radical 30. Its precursor, b-thioacry-
late-thionocarbonte 29, was prepared from thiol 27 as
described in Scheme 6. A key mercaptane 27 was prepared
from (1)-pulegone by a known procedure.14 Addition of
mercaptan 27 with ethyl propiolate using catalytic amount
of triethylamine led to a b-thioacrylate 28 in good yield.
This compound was acetylated with chlorothionoformate to
give radical precursor 29. 5-exo Intramolecular radical
cyclization reaction of 29 (n-Bu3SnH/AIBN) afforded
8-thiabicyclo[4.3.0]nonane derivative 31 (90% yield) as a
Scheme 7. Reagents and conditions: (a) CF3SO3CH3, CH2Cl2, 2108C!room temperature, 2.5 h. (b) tBuOK, THF, 08C!room temperature, 2 h; (c) m-CPBA,
EtOAc, 2608C!2408C, 4 h; (d) H2CvCHCO2Me, toluene, 1808C, 62 h.

3430
Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
6:1.5:1.5:1 mixture of four diastereomers (epimers at C-1
and C-9). The ratio 3:1 of 1,6-cis-fused bicyclic sul®de 31a
to 1,6-trans-fused bicycle 31b was determined by NMR on
the grounds of the spin coupling constants where JH1eqH6ax
(cis),JH1axH6ax (trans).
®nyl]ethyl}tetrahydro-1H-1,2-pyrroledicarboxylate (5).
a. Mercaptan addition. A mixture of pyrrolidine 12
(732 mg, 1.66 mmol), methyl b-mercaptopropionate
(300 mg, 2.5 mmol), AIBN (68 mg, 0.42 mmol), and THF
(0.5 mL) was stirred under argon in a sealed tube at 608C for
4.5 h. The reaction mixture was evaporated, the residue was
dissolved in xylene and evaporated to afford compound 2
(pale yellow oil, 900 mg, 97%) as a 1:1 mixture of two
Oxidative sulfur extrusion in thiabicyclic compounds like 7,
8, 18a,b and 31a,b would restore the isopropenyl group and
thus complete a process by which the hydroxyl group
present in starting materials like 1 and 11 is substituted by
an acrylic ester system through temporary sulfur connec-
tion. This is exempli®ed in Scheme 7 for compounds 18a
and 18b. Thus, S-methylation of 18a-1/18a-2 with methyl
tri¯uoromethanesulfonate to sulfonium 32,15 followed by
base induced retro-Michael ring opening, afforded methyl
acrylate 33. Oxidation of the sul®de 33 to sulfoxide 34 using
m-CPBA and subsequent pyrolysis in a sealed tube in
toluene at 1808C produced isopropenyl-acrylate derivatives
35. Similarly the same two cis/trans isopropenyl-acrylates 35
were obtained from thiabicyclo[4.4.0]decanes 18b-1/18b-2.
1
diastereomers. IR (®lm): nmax 1702, 1739 cm21. H NMR:
(2 diastereomers, 2 conformers): d 0.10±0.16 (m, 6H); 0.88
(s, 9H); 0.93±0.96 (m, 3H); 1.43±1.47 (m, 18H); 1.75±2.00
(m, 1H); 2.26 (m, 8H); 3.50±3.75 (m, 4H); 4.05±4.25 (m,
2H). The product was used without further puri®cation in
the next step.
b. Oxidation. To a solution of sul®de 2 (890 mg, 1.6 mmol)
in CH2Cl2 (10 mL) at 2608C under argon was added drop-
wise for 20 min a solution of m-CPBA (326 mg of 85%
reagent, 1.6 mmol) in CH2Cl2 (10 mL). The reaction
mixture was stirred during 2 h at 2608C, slowly warmed
to room temperature, washed with 5% aqueous NaHCO3
(2£5 mL), dried, and evaporated. The residue was
chromatographed (MPLC) to afford a mixture of four
Conclusion
isomeric sulfoxides
1.22 mmol, 76%) and starting sul®de 2 (oil, 199 mg,
3
(pale yellow oil, 703 mg,
Metathesis of acrylates with propiolates in (alkoxycarbonyl-
ethyl)alkyl sulfoxides like 3 and 20 constitutes an excellent
method for the preparation of the corresponding b-sulfoxy-
acrylates like 5 and 21. n-Bu3SnH/AIBN induced free
radical cyclization of b-thioacrylates like 6, 16a,b and 29
affords fused thiabicyclic compounds like 7, 8, 18a,b and
31a,b in high yields. These compounds may serve as inter-
mediates for syntheses through temporary sulfur connection
(e.g. Scheme 7). Bicyclic kainoid derivatives like 7 and 8
are of interest for the preparation of neuroexcitatory amino
acids.8
0.35 mmol, 22%). 3: IR (®lm): nmax 1701, 1739 cm21. H
1
NMR (4 diastereomers, 2 conformers): d 0.11±0.19 (m,
6H); 0.88±089 (m, 9H); 1.05±1.30 (m, 3H); 1.42±1.47
(m, 18H); 2.20±3.21 (m, 9H); 3.50±3.80 (m, 4H); 4.10±
4.30 (m, 2H). Anal. Calcd for C27H51NO8SSi (577.85): C,
56.12; H, 8.90; N, 2.42; S, 5.55. Found: C, 56.20; H, 8.74;
N, 2.50; S, 5.74.
c. Sulfoxide metathesis. A mixture of sulfoxide 3 (320 mg,
0.56 mmol), methyl propiolate (0.5 mL, 5.9 mmol), and
toluene (3 mL) was re¯uxed for 2 h. The reaction mixture
was evaporated to dryness to afford unsaturated sulfoxide 5
as an oil with quantitative yield. IR (®lm): nmax 1702, 1735,
Experimental
1
1610 cm21. H NMR (4 diastereomers, 2 conformers): d
0.00±0.08 (m, 6H); 0.75±0.80 (m, 9H); 0.90±1.18 (m,
3H); 1.30±1.36 (m, 18H); 2.25±3.15 (m, 5H); 3.40±3.75
(m, 4H); 4.01±4.10 (m, 2H); 6.52±6.58 (m, 1H); 7.45±
7.50 (m, 1H). Anal. Calcd for C27H49NO8SSi (575.83): C,
56.32; H, 8.58; N, 2.43; S, 5.57. Found: C, 56.01; H, 8.53;
N, 2.18; S, 5.44.
Thin layer chromatography (TLC) was performed on
aluminum sheets precoated with silica gel (Merck, Kieselgel
60 F-254). Flash-chromatographic separations were
performed on silica gel (Merck, Kieselgel 60, 230±
400 Mesh ASTM). Medium-pressure liquid chromato-
graphy (MPLC) was performed on glass columns (BuÈchi,
B-685, dˆ26 mm, lˆ460 mm) with LiChroprepe 60
(particle size 15±25 mm). Light-induced reaction was
performed by using BLAK-RAYw lamp, Model B-100AP,
lˆ310±400 nm (lmaxˆ365 nm). Unless otherwise stated
NMR spectra were recorded in CDCl3 on Bruker AMX-
400 (400 MHz) spectrometer using TMS as an internal
standard (chemical shifts in ppm). Infrared spectra (IR)
were recorded on Nicolet Protege 460 FT-IR spectrometer.
Elementary analyses were performed by the microanalytical
laboratory of the Hebrew University, Jerusalem. High
resolution mass spectra (HRMS) were recorded using a
VG 7070e high resolution mass spectrometer. Solvents
and glassware were dried and deoxygenated by con-
ventional methods, and all reactions were performed in
atmosphere of argon.
Di(tert-butyl) (2Sp,3Rp,4Sp)-3-phenoxythiocarbonyloxy-
4-{1-methyl-2-[(E)-2-methyloxycarbonyl-1-ethenylsulfa-
nyl]ethyl}tetrahydro-1H-1,2-pyrroledicarboxylate (6).
a. Sulfoxide reduction. A mixture of unsaturated sulfoxide
5 (541 mg, 0.94 mmol), Lawesson's reagent (378 mg,
0.54 mmol), and THF (10 mL) was stirred at 2108C for
50 min. After TLC revealed full consumption of starting
material, the reaction was diluted with hexane (15 mL)
and the formed suspension was ®ltered through silica gel
(2 cm). The ®ltrate was evaporated and the residue was
chromatographed (MPLC) to afford a corresponding
unsaturated sul®de (oil, 304 mg, 60%). IR (®lm): nmax
1
1582, 1707, 1739 cm21. H NMR (270 MHz, 2 diastereo-
mers, 2 conformers): d 0.13±0.25 (m, 6H); 0.87, 0.89 (2£s,
9H); 0.96±1.19 (m, 3H); 1.43±1.48 (m, 18H); 1.90±2.10,
2.50±3.15 (m, 5H); 3.50±3.80 (m, 4H); 4.09±4.22 (m, 2H);
5.68±5.77 (m, 1H); 7.62±7.68 (m, 1H).
Di(tert-butyl) (2Sp,3Rp,4Sp)-3-tert-butyldimethylsilyloxy-
4-{1-methyl-2-[(E)-2-methyloxycarbonyl-1-ethenylsul-

Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
3431
b. Desilylation. A mixture of the unsaturated sul®de
(260 mg, 0.46 mmol), AcOH (27 mg, 0.46 mmol), and
Bu4NF (1 M solution in THF, 1 mL) was kept for 20 h,
diluted with 1:1 EtOAc/hexane mixture (5 mL) and chro-
matographed (¯ash chromatography, EtOAc/hexane, 1:1).
Fractions containing the corresponding alcohol were
combined, evaporated (IR (®lm): nmax 1581, 1683, 1703,
1737, 3447 cm21), and used at the next stage.
major), 2.51 (dd, Jˆ7.3, 15.8 Hz, minor), total 1H; 2.68
(dd, Jˆ7.7, 15.8 Hz, minor), 2.69 (dd, Jˆ7.6, 15.9 Hz,
major), total 1H; 3.31 (dd, Jˆ5.0, 11.0, major), 3.32 (dd,
Jˆ5.0, 11.0, minor), total 1H; 3.36 (s, major), 3.38 (s,
minor), total 3H; 3.47 (dd, Jˆ2.0, 10.7, minor), 3.77 (d,
Jˆ11.2 Hz, major), total 1H; 3.56 (dt, Jˆ3.5, 7.5 Hz,
minor), 3.63 (dt, Jˆ2.8, 7.5 Hz, major), total 1H; 4.68
(d, Jˆ9.4 Hz, major), 4.78 (d, Jˆ8.7 Hz, minor), total
1H. Anal. Calcd for C21H35NO6S (429.57): C, 58.72; H,
8.21; N, 3.26; S, 7.46. Found: C, 58.39; H, 8.43; N, 3.03;
S, 7.38.
c. Thionocarbonation. A solution of the alcohol and phenan-
throline (ca. 1 mg) in THF was cooled to 2788C, and a
solution of n-BuLi (1.6 M solution in hexane, 0.4 mL,
0.54 mmol) was added followed by the neat PhOC(S)Cl.
After 1.5 h at 2788C the reaction mixture was slowly
warmed to room temperature, and stirred 1.5 h at 258C.
The reaction mixture was diluted with hexane (4 mL), the
formed suspension was ®ltered through silica (4 cm). The
®ltrate was evaporated and puri®ed by MPLC (EtOAc/
hexane, 3:7) to afford thionocarbonate 6 (yellow-red oil,
190 mg, 0.33 mmol, 45% from unsaturated sulfoxide 5).
1H NMR (2 diastereomers, 2 conformers): d 1.11, 1.26
(2£d, Jˆ6.9 Hz, 3H); 1.44±1.51 (m, 18H); 2.6±3.0 (m,
4H); 3.20, 3.90 (2£m, 1H); 3.70, 3.71 (2£d, 3H); 4.62,
4.64 (2£d, major, Jˆ6.2 Hz), 4.73 (m, minor), total 1H;
5.75 (m, 2H); 7.09±7.45 (m, 5H); 7.62 (m, 1H). Anal.
Calcd for C28H39NO8S2 (581.74): C, 57.81; H, 6.76; N,
2.41; S, 11.02. Found: C, 57.49; H, 6.73; N, 2.07; S, 10.95.
(2R)- and (2S)-2-[(1S,2R,4R)-2-tert-Butyldimethylsilyl-
oxy-4-methylcyclohexyl]propyl ethanethioates (13a)
and (13b). To a cold (2728C) solution of (2)-isopulegol
11 (5.0 mL, 29.5 mmol) in methylene chloride (40 mL)
were added in rapid succession 2,6-lutidine (5.2 mL,
44.5 mmol) and tert-butyldimethylsilyl tri¯ate (7.5 mL,
32.6 mmol). The reaction mixture was stirred at the same
temperature for 1 h. The temperature was allowed to rise to
08C, and hexane (75 mL) was added. The emulsion was
washed with 1 N HCl (25 mL), saturated NaHCO3
(2£50 mL), dried (NaHCO3 and Na2SO4), and evaporated.
Flash chromatography (hexane) afforded the silylated
1
alcohol 12 (7.91 g, quant.) as a colorless oil. H NMR
(250 MHz): d 0.01, 0.04 (2£s, 6H); 0.86 (s, 9H); 0.91 (d,
Jˆ6.4 Hz, 3H); 0.98±1.11 (m, 1H); 1.24±1.53 (m, 2H);
1.57±1.67 (m, 3H); 1.69 (s, 3H); 1.84±1.97 (m, 2H); 3.49
(ddd, Jˆ10.3, 10.3, 4.4 Hz, 1H); 4.75 (br s, 2H). 13C NMR:
d 24.6, 17.4, 20.2, 21.7, 25.2, 29.9, 31.0, 33.7, 44.5, 52.9,
72.7, 110.4, 147.2. HRMS (CI) Calcd for C16H32OSi
(MH1): 269.2301. Found: (MH1): 269.2307. The silylated
alcohol 12 (2.473 g, 9.2 mmol) and thiolacetic acid (2.7 mL,
37.8 mmol) were deoxygenated and the reaction mixture
was irradiated with a longwave UV lamp for 72 h. An
excess of thiolacetic acid was removed in vacuum. The
residue was puri®ed by ¯ash chromatography (toluene±
hexane, 1:1) to give recovered starting compound 12
(945 mg, 3.5 mmol, 38%) and two separated sul®des 13a
(yellow-red oil, 1.175 g, 3.4 mmol, 60% based on reacted
12) and 13b (yellow oil, 786 mg, 2.3 mmol, 40% based on
reacted 12).
Di(tert-butyl) (3Sp,3aSp,4Rp,7Sp,7aRp)- and di(tert-butyl)
(3Sp,3aRp,4Sp,7Rp,7aRp)-7-methyl-4-methyloxycarbonyl-
methylperhydrothiopyrano[3,4-c]pyrrole-2,3-dicarboxyl-
ates (7) and (8). A solution of thionocarbonate 6 (155 mg,
0.27 mmol), n-Bu3SnH (100 mg, 0.35 mmol), AIBN
(11 mg, 0.07 mmol) in toluene (15 mL) was heated at
1008C for 1.5 h. The reaction mixture was washed with
5 N NaOH to remove PhOH, aqueous NaHCO3, dried, and
evaporated. The residue was dissolved in MeCN (30 mL)
and extracted with hexane to remove organotin compounds.
The MeCN solution was evaporated and the residue was
separated by MPLC (EtOAc/hexane, 2:3) to afford two
isomers. High Rf isomerÐcompound 7 (amorphous color-
less solid, 60 mg, 52%). IR (®lm): nmax 1702, 1742 cm21
.
1H NMR (C6D6, 2 conformers): d 0.39 (d, Jˆ6.9 Hz, major),
0.44 (d, Jˆ6.9 Hz), total 3H; 1.41 (s, 9H); 1.53 (s, minor),
1.54 (s, major), total 9H; 1.76 (m, 2H); 2.09 (m, 1H); 2.31
(dd, Jˆ5.8, 11.3 Hz, 1H); 2.39 (dd, Jˆ8.8, 15.8 Hz, minor),
2.41 (dd, Jˆ8.8, 15.8 Hz, major), total 1H; 2.58 (m, major),
2.70 (m, minor), total 1H; 2.73 (dd, Jˆ2.4, 15.8 Hz, minor),
2.74 (dd, Jˆ3.4, 15.8 Hz, major), total 1H; 3.10 (m, 2H);
3.35 (s, major), 3.36 (s, minor), total 3H; 3.60 (dd, Jˆ8.5,
10.1 Hz, minor), 3.77 (dd, Jˆ8.5, 10.6, major), total 1H;
4.31 (s, major), 4.50 (s, minor), total 1H. Anal. Calcd for
C21H35NO6S (429.57): C, 58.72; H, 8.21; N, 3.26; S, 7.46.
Found: C, 58.79; H, 8.21; N, 3.26; S, 7.46. Low Rf isomerÐ
compound 8 (oil, 41 mg, 35%). IR (®lm): nmax all identical
to high Rf isomer. 1H NMR (C6D6, 2 conformers): d 0.47 (d,
Jˆ6.4 Hz, major), 0.55 (d, Jˆ6.4 Hz, minor), total 3H; 1.13
(m, 1H); 1.26 (m, 1H); 1.54 (s, major), 1.58 (s, minor), total
18H; 1.77 (dd, Jˆ3.7, 14.1 Hz, major), 1.84 (dd, Jˆ3.8,
14.1 Hz, minor), total 1H; 1.91 (dd, Jˆ11.1, 14.0 Hz,
major), 1.93 (dd, Jˆ10.1, 14.0 Hz, minor), total 1H; 2.29
(ddd, Jˆ2.8, 5.5, 9.4 Hz, major), 2.36 (ddd, Jˆ3.6, 5.5,
8.9 Hz, minor), total 1H; 2.44 (dd, Jˆ7.4, 15.9 Hz,
13a: yellow±red oil, IR (neat): nmax 2954, 2925, 2850, 1690,
1258, 1095 cm21. 1H NMR: d 0.05, 0.07 (2£s, 6H); 0.87 (s,
9H); 0.90 (d, Jˆ6.6 Hz, 3H); 0.79±1.08 (m, 3H); 0.95 (d,
Jˆ7.0 Hz, 3H); 1.28 (m, 1H); 1.38 (m, 1H); 1.62±1.68 (m,
2H); 1.88 (m, 1H); 2.15 (m, 1H); 2.70 (dd, Jˆ12.7, 10.9 Hz,
1H); 2.95 (dd, Jˆ12.7, 3.7 Hz, 1H); 3.50 (ddd, Jˆ10.3,
10.3, 4.3 Hz, 1H). 13C NMR: d 24.8, 23.6, 17.5, 18.0,
22.2, 24.6, 26.0, 30.6, 31.5, 31.8, 31.9, 34.5, 45.4, 50.3,
71.9, 196.2. HRMS (CI) Calcd for C18H37O2SSi (MH1):
345.2284. Found (MH1): 345.2288.
13b: yellow oil, IR (neat): nmax 2962, 2923, 2869, 1706,
1
1262, 1106 cm21. H NMR: d 0.02, 0.05 (2£s, 6H); 0.81
(d, Jˆ7.0 Hz, 3H); 0.86 (s, 9H); 0.89 (d, Jˆ6.5 Hz, 3H);
0.93±1.05 (m, 3H); 1.29±1.44 (m, 2H); 1.55 (dddd, Jˆ13.0,
3.3, 3.3, 3.3 Hz, 1H); 1.63 (m, 1H); 1.85 (m, 1H); 2.21
(dddd, Jˆ21.4, 7.1, 7.1, 2.2 Hz, 1H); 2.77 (dd, Jˆ13.1,
7.6 Hz, 1H); 2.87 (dd, Jˆ13.1, 7.6 Hz, Hz, 1H); 3.37
(ddd, Jˆ10.2, 10.2, 4.3 Hz, 1H). 13C NMR: d 24.9, 23.6,
13.5, 18.0, 22.3, 23.0, 25.9, 30.6, 31.2, 31.6, 34.2, 34.6,

3432
Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
45.2, 47.8, 71.7, 195.9. HRMS (CI) Calcd for C18H37O2SSi
(MH1): 345.2284. Found (MH1): 345.2272.
48.04 (E), 51.12 (Z), 51.28 (E), 71.69 (E), 71.79 (Z), 112.32
(Z), 113.26 (E), 147.39 (E), 150.93 (Z), 167.11 (E/Z).
HRMS (CI) Calcd for C20H39O3SSi (MH1): 387.2389.
Found (MH1): 387.2330.
Methyl (E/Z)-3-[(2R)-2-((1S,2R,4R)-2-tert-butyldimethyl-
silyloxy-4-methylcyclohexyl)propylsulfanyl]-2-propeno-
ate (14a). To thioate 13a (1.20 g, 3.5 mmol) at 08C was
Methyl (E/Z)-3-[(2R)-2-((1S,2R,4R)-2-phenoxythiocar-
bonyloxy-4-methylcyclohexyl)propylsulfanyl]-2-pro-
penoate (16a). Method A. A mixture of compound 14a
(1.10 g, 2.84 mmol) and tetrabutylammonium ¯uoride
(1 M solution in THF, 7.1 mL) was stirred at room tempera-
ture overnight. The solution was poured into 35 mL of a
phosphate buffer (pH 5.8) and extracted with ethyl acetate
(3£30 mL). The organic layer was dried (Na2SO4), the
solvent was evaporated, and ¯ash chromatography
(EtOAc/hexane, 3:7) of the residue gave alcohol 15a (oil,
774 mg, quant.). 1H NMR (250 MHz, E/Z isomers): d 0.68±
1.02 (m, 3H); 0.80 (d, Jˆ6.5 Hz, 3H); 0.95 (d, Jˆ6.9 Hz,
3H); 1.13±1.39 (m, 2H); 1.49±1.57 (m, 2H); 1.85 (br d,
Jˆ12.0 Hz, 1H); 2.07 (m, 1H); 2.43 (dd, Jˆ13.0, 9.9 Hz,
1H); 2.92 (dd, Jˆ13.0, 4.4 Hz, Z), 2.96 (dd, Jˆ13.0, 4.4 Hz,
E), total 1H; 3.39 (ddd, Jˆ10.5, 10.5, 4.2 Hz, 1H); 3.60 (s,
E), 3.61 (s, Z), total 3H; 5.71 (d, Jˆ15.1 Hz, E), 5.72 (d,
Jˆ10.2 Hz, Z), total 1H; 7.11 (d, Jˆ10.2 Hz, Z), 7.60 (d,
Jˆ15.1 Hz, E), total 1H. To a solution of alcohol 15a
(767 mg, 2.82 mmol), pyridine (1.0 mL, 12.9 mmol), and
DMAP (69 mg, 0.56 mmol) in THF (5 mL) at 08C was
added by syringe pump a solution of phenyl chlorothiono-
formate (2.0 mL, 9.28 mmol) in THF (2 mL). The addition
was complete within 30 min. The temperature was allowed
to rise to room temperature and the reaction mixture was
stirred overnight. The reaction mixture was diluted with
hexane (12 mL) and the formed suspension was ®ltered
trough silica gel (4.5 cm). The ®ltrate was evaporated and
puri®ed by MPLC (EtOAc/hexane, 1:9) to afford phenoxy-
thiocarbonyl derivative 16a (red oil, 944 mg, 82%) as a
mixture of two isomers (E/Z, 1:4). IR (neat): nmax 2952,
added
a
deoxygenated solution of KOH (0.25 g,
4.4 mmol) in methanol (2.5 mL). The temperature was
allowed to rise to room temperature and the reaction mixture
was stirred for 1.5 h (TLC control). The reaction mixture
was quenched with 15 mL of a phosphate buffer (pH 5.5)
and hexane (10 mL) was added. The aqueous layer was
extracted with hexane (3£30 mL). The combined hexane
solution was dried over Na2SO4 and evaporated to afford
deprotected thiol (1.05 g, quant.). The crude thiol was
dissolved in MeOH±H2O mixture (10:1, 10 mL), cooled
to 08C and methyl propiolate (0.43 mL, 5.0 mmol) and
catalytic amount of triethylamine (2 drops of a mixture: 1
drop of NEt3 in 10 drops of MeOH) were added. The reac-
tion mixture was stirred for 24 h at room temperature,
diluted with benzene (100 mL) and evaporated. The residue
was puri®ed by ¯ash chromatography (EtOAc/hexane, 1:20)
to give the unsaturated sul®de 14a (oil, 1.11 g, 82% from
13a) as a mixture of two isomers (E/Z, 1:6). IR (neat): nmax
2954, 2924, 2854, 1701, 1577, 1255, 1162 cm21. H NMR
1
(E/Z isomers): d 0.05, 0.07 (2£s, E), 0.07, 0.08 (2£s, Z),
total 6H; 0.88 (s, 9H); 0.83±1.06 (m, 3H); 0.90 (d,
Jˆ6.7 Hz, 3H); 1.04 (d, Jˆ7.0 Hz, 3H); 1.37 (m, 2H);
1.63 (m, 2H); 1.90 (m, 1H); 2.19 (m, 1H); 2.53 (dd,
Jˆ12.6, 10.4 Hz, Z), 2.54 (dd, Jˆ10.8, 10.8 Hz, E), total
1H; 2.90 (dd, Jˆ11.7, 4.0 Hz, E), 2.90 (dd, Jˆ11.4,
4.4 Hz, Z), total 1H; 3.50 (ddd, Jˆ10.4, 10.4, 4.2 Hz, 1H);
5.71 (d, Jˆ15.1 Hz, E), 5.81 (d, Jˆ10.2 Hz, Z), total 1H;
7.13 (d, Jˆ10.2 Hz, Z), 7.74 (d, Jˆ15.1 Hz, E), total 1H. 13C
NMR (E/Z isomers): d 24.41 (E), 24.20 (Z), 23.55 (E),
23.39 (Z), 16.70 (Z), 17.34 (E), 18.05 (E/Z), 22.18 (E/Z),
25.32 (E), 25.76 (Z), 25.94 (E), 26.00 (Z), 31.52 (Z), 32.04
(E), 33.82 (E/Z), 34.48 (Z), 35.69 (E), 40.41 (E/Z), 45.37
(E), 45.45 (Z), 49.45 (Z), 49.93 (E), 51.11 (Z), 51.32 (E),
72.07 (E), 72.22 (Z), 111.89 (Z), 112.78 (E), 148.13 (E),
151.82 (Z), 167.10 (E/Z). HRMS (CI) Calcd for
C20H39O3SSi (MH1): 387.2389. Found (MH1): 387.2330.
1
2928, 2869, 1707, 1581, 1498, 1292, 1208, 1167 cm21. H
NMR (E/Z isomers): d 0.85±0.99 (m, 1H); 0.95 (d,
Jˆ6.5 Hz, 3H); 1.06 (d, Jˆ6.9 Hz, E), 1.07 (d, Jˆ6.9 Hz,
Z), total 3H; 1.08±1.29 (m, 2H); 1.52 (m, 1H); 1.69±1.87
(m, 3H); 1.99 (m, 1H); 2.26±2.34 (m, 1H); 2.50 (dd,
Jˆ13.2, 10.4 Hz, Z), 2.60 (dd, Jˆ13.2, 10.4 Hz, E), total
1H; 2.94 (dd, Jˆ13.2, 4.2 Hz, Z), 2.99 (dd, Jˆ13.2,
4.2 Hz, E), total 1H; 3.66 (s, E), 3.72 (s, Z), total 3H; 5.23
(ddd, Jˆ10.9, 10.9, 4.4 Hz, E), 5.26 (ddd, Jˆ10.9, 10.9,
4.4 Hz, Z), total 1H; 5.76 (d, Jˆ15.2 Hz, E), 5.81 (d,
Jˆ10.1 Hz, Z), total 1H; 7.04±7.08 (m, 2H); 7.24±7.29
(m, 1H); 7.35±7.42 (m, 2H); 7.11 (d, Jˆ10.1 Hz, Z), 7.68
(d, Jˆ15.2 Hz, E), total 1H. 13C NMR (E/Z isomers): d
16.78 (Z), 16.94 (E), 22.28 (E/Z), 26.33 (Z), 27.16 (E),
31.60 (E), 31.66 (Z), 34.40 (Z), 35.38 (E/Z), 37.19 (E),
39.77 (E/Z), 40.68 (E/Z), 46.69 (E), 46.73 (Z), 51.58 (Z),
51.73 (E), 84.83 (E), 84.98 (Z), 112.92 (Z), 113.89 (E),
122.36 (Z), 122.43 (E), 126.91 (E), 127.00 (Z), 129.88
(E), 129.95 (Z), 147.87 (E), 151.66 (Z), 153.66 (E/Z),
166.03 (E), 167.42 (Z), 194.47 (E), 194.75 (Z). HRMS
(CI) Calcd for C21H29O4S2 (MH1): 409.1507. Found
(MH1): 409.1497.
Methyl (E/Z)-3-[(2S)-2-((1S,2R,4R)-2-tert-butyldimethyl-
silyloxy-4-methylcyclohexyl)propylsulfanyl]-2-propeno-
ate (14b). Compound 14b (oil, 661 mg, 81%) was obtained
as a mixture of two isomers (E/Z, 1:6) from thioate 13b
(727 mg, 2.1 mmol) as described above for the synthesis
of 14a, after puri®cation by ¯ash chromatography
(EtOAc/hexane, 1:20). IR (neat): nmax 2951, 2927, 2856,
1707, 1579, 1256, 1166 cm21. H NMR (E/Z isomers): d
1
0.03, 0.05 (2£s, 6H); 0.86 (s, 9H); 0.86 (d, Jˆ7.1 Hz, Z),
0.87 (d, Jˆ7.1 Hz, E), total 3H; 0.89 (d, Jˆ6.5 Hz, Z), 0.90
(d, Jˆ6.5 Hz, E), total 3H; 0.96±1.06 (m, 2H); 1.23±1.54
(m, 4H); 1.63 (m, 1H); 1.87 (m, 1H); 2.37 (m, 1H); 2.61±
2.76 (m, 2H); 3.40 (ddd, Jˆ10.3, 10.3, 4.3 Hz, E), 3.41
(Jˆ10.2, 10.2, 4.3 Hz, Z), total 1H; 5.72 (d, Jˆ15.1 Hz,
E), 5.82 (d, Jˆ10.2 Hz, Z), total 1H; 7.08 (d, Jˆ10.2 Hz,
Z), 7.69 (d, Jˆ15.1 Hz, E), total 1H. 13C NMR (E/Z
isomers): d 24.86 (E/Z), 23.66 (E/Z), 12.96 (Z), 13.45
(E), 17.99 (E/Z), 22.23 (E/Z), 22.95 (E), 23.08 (Z), 25.79
(E), 25.85 (Z), 30.29 (E), 31.42 (Z), 31.48 (E), 31.60 (Z),
34.19 (Z), 38.05 (E), 42.30 (E/Z), 45.15 (E/Z), 47.88 (Z),
Methyl (E/Z)-3-[(2S)-2-((1S,2R,4R)-2-phenoxythiocar-
bonyloxy-4-methylcyclohexyl)propylsulfanyl]-2-pro-
penoate (16b). Method A. Compound 16b (red oil, 456 mg,
67%) was obtained as a mixture of two isomers (E/Z, 1:4)

Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
3433
1
from sulfanylpropenoate 14b (644 mg, 1.67 mmol) as
described above for the synthesis of 16a, after puri®cation
by MPLC (EtOAc/hexane, 1:9), through the intermediacy of
20 (439 mg, quant.) as a mixture of four diastereomers. H
NMR (250 MHz, 4 diastereomers): d 0.06, 0.07, 0.09, 0.11
(4£s, 6H); 0.87±1.47 (m, 16H); 1.23±1.55 (m, 3H); 1.65
(m, 2H); 1.82±1.93 (m, 2H); 2.33±3.09 (m, 7H); 4.43 (ddd,
Jˆ10.2, 10.2, 4.2 Hz), 4.49 (ddd, Jˆ10.2, 10.2, 4.2 Hz),
total 1H; 3.73 (s, 3H). A mixture of sulfoxides 20
(407 mg, 1.0 mmol), methyl propiolate (0.88 mL,
11 mmol), and toluene (6 mL) was re¯uxed for 2 h. The
reaction mixture was evaporated to dryness and puri®ed
by ¯ash chromatography (EtOAc/hexane, 3:7) to afford
unsaturated E-sulfoxide 21 (362 mg, 90%) as a mixture of
four diastereomers. 1H NMR (250 MHz, 4 diastereomers): d
0.06, 0.08, 0.09, 0.11 (4£s, 6H); 0.84±1.94 (m, 23H); 2.31±
3.12 (m, 2H); 3.48 (ddd, Jˆ10.3, 10.3, 4.2 Hz, 1H); 3.82,
3.85 (2£s, 3H); 6.67 (d, Jˆ15.0 Hz, 1H); 7.62 (d,
Jˆ15.0 Hz, 1H). HRMS (CI) Calcd for C20H39O4SSi
(MH1): 403.2338. Found: (MH1): 403.2320. To a cold
(08C) solution of unsaturated sulfoxide 21 (396 mg,
0.98 mmol) and sodium iodide (367 mg, 2.45 mmol) in
acetone (2.5 mL) was added dropwise a solution of
tri¯uoroacetic anhydride (513 mg, 2.44 mmol) in acetone
(2.5 mL). The reaction mixture was stirred at 08C for
30 min, evaporated, dissolved in water, and extracted with
diethyl ether. The organic layer was washed with 10%
aqueous sodium thiosulfate and water, dried (Na2SO4) and
evaporated to afford a mixture of silylated and desilylated
unsaturated sul®des, which were directly used at the next
stage. A mixture of unsaturated sul®des and tetrabutylam-
monium ¯uoride (1 M solution in THF, 4.9 mL) was stirred
for 22 h, diluted with EtOAc/hexane (1:1, 16 mL), evapo-
rated and puri®ed by ¯ash chromatography (EtOAc/hexane,
1
15b: H NMR (250 MHz, E/Z isomers): d 0.71±1.04 (m,
3H); 0.83 (d, Jˆ6.4 Hz, 3H); 0.86 (d, Jˆ6.7 Hz, 3H); 1.27±
1.39 (m, 2H); 1.46 (m, 1H); 1.59 (m, 1H); 1.91 (br d,
Jˆ12.0 Hz, 1H); 2.31 (m, 1H); 2.56±2.74 (m, 2H); 3.32
(ddd, Jˆ10.4, 10.4, 4.3 Hz, 1H); 3.63 (s, E), 3.65 (s, Z),
total 3H; 5.67 (d, Jˆ15.1 Hz, E), 5.75 (d, Jˆ10.2 Hz, Z),
total 1H; 7.07 (d, Jˆ10.2 Hz, Z), 7.64 (d, Jˆ15.1 Hz, E),
total 1H.
16b: IR (neat): nmax 2955, 2931, 2869, 1714, 1582, 1496,
1293, 1199 cm21. 1H NMR (E/Z isomers): d 0.89±1.01 (m,
1H); 0.96 (d, Jˆ6.5 Hz, E), 0.97 (d, Jˆ6.5 Hz, Z), total 3H;
0.99 (d, Jˆ7.0 Hz, E), 1.00 (d, Jˆ7.0 Hz, Z), total 3H; 1.08±
1.31 (m, 2H); 1.54 (m, 1H); 1.63±1.79 (m, 2H); 1.84±1.97
(m, 1H); 2.11±2.25 (m, 1H); 2.33 (m, 1H); 2.67±2.81 (m,
2H); 3.69 (s, E), 3.74 (s, Z), total 3H; 5.18 (ddd, Jˆ10.8,
10.8, 4.4 Hz, Z), 5.22 (ddd, Jˆ10.8, 10.8, 4.4 Hz, E), total
1H; 5.77 (d, Jˆ15.1 Hz, E), 5.81 (d, Jˆ10.1 Hz, Z), total
1H; 7.04±7.08 (m, 2H); 7.24±7.29 (m, 1H); 7.35±7.42 (m,
2H); 7.08±7.11 (m, 2H); 7.24±7.31 (m, 1H); 7.35±7.44 (m,
2H); 7.10 (d, Jˆ10.1 Hz, Z), 7.71 (d, Jˆ15.1 Hz, E), total
1H. HRMS (CI) Calcd for C21H29O4S2 (MH1): 409.1507.
Found (MH1): 409.1500.
Methyl (E)-3-[(2RS)-2-((1S,2R,4R)-2-phenoxythiocarbo-
nyloxy-4-methylcyclohexyl)propylsulfanyl]-2-propeno-
ates (16a,b). Method B. A mixture of compound 12
(750 mg, 2.79 mmol), methyl b-mercaptopropionate
(503 mg, 4.18 mmol), AIBN (117 mg, 0.71 mmol) and
THF (0.8 mL) was deoxygenated and re¯uxed under
argon for 4.5 h. Then the reaction mixture was cooled to
room temperature and additional methyl b-mercaptopropio-
nate (335 mg, 2.79 mmol), AIBN (117 mg, 0.71 mmol) and
THF (0.3 mL) were added and the mixture was re¯uxed for
3.5 h (TLC monitoring). The reaction mixture was evapo-
rated and puri®ed by ¯ash chromatography (EtOAc/hexane,
1:5) to afford sul®de 19 (colorless oil, 954 mg, 88%) as a
1
3:7) to afford E-alcohols 15a,b in a quantitative yield. H
NMR data of the compound have been compared to the data
of the samples 15a and 15b obtained from sul®des 14a and
14b and are identical with their E-isomers. To a solution of
alcohols 15a,b (256 mg, 0.94 mmol), pyridine (0.33 mL,
4.3 mmol), and DMAP (23 mg, 0.19 mmol) in THF
(2 mL) at 08C was added by syringe pump a solution of
phenyl chlorothionoformate (0.7 mL, 3.25 mmol) in THF
(1 mL). The addition was complete within 30 min. The
temperature was allowed to rise to room temperature and
the reaction mixture was stirred overnight. The reaction
mixture was diluted with hexane (5 mL) and the formed
suspension was ®ltered trough silica gel (2.5 cm). The
®ltrate was evaporated and puri®ed by MPLC (EtOAc/
hexane, 1:9) to afford E-phenoxythiocarbonyl derivatives
16a,b (red oil, 287 mg, 75%) as a mixture of two isomers
1
mixture of two diastereomers at C-2. H NMR (250 MHz,
epimers at C-2): d 0.05, 0.07, 0.09 (3£s, 6H); 0.83 (d,
Jˆ6.9 Hz), 1.02 (d, Jˆ6.9 Hz), total 3H; 0.89 (s, 9H);
0.91 (d, Jˆ6.9 Hz, 3H); 0.84±1.05 (m, 1H); 1.25±1.48
(m, 3H); 1.63 (m, 2H); 1.88 (m, 1H); 2.05±2.32 (m, 2H);
2.46 (d, Jˆ7.5 Hz, 1H); 2.58±2.70 (m, 3H); 2.73±2.80 (m,
2H); 4.43 (ddd, Jˆ10.3, 10.3, 4.3 Hz), 4.45 (ddd, Jˆ10.3,
10.3, 4.3 Hz), total 1H; 3.70, 3.72 (2£s, 3H). 13C NMR
(epimers at C-2): d 24.55, 23.77, 23.57, 13.34, 17.47,
17.94, 17.99, 19.64, 22.21, 22.79, 25.03, 25.80, 25.94,
26.60, 27.99, 29.92, 31.47, 32.41, 34.22, 34.50, 34.56,
34.80, 35.89, 37.91, 38.20, 45.19, 45.41, 47.45, 50.08,
51.62, 71.79, 71.99, 172.39. To a solution of sul®des 19
(427 mg, 1.1 mmol) in methylene chloride (6 mL) at
2608C under argon was added dropwise for 20 min a solu-
tion of m-CPBA (348 mg of 54.5% reagent, 1.1 mmol) in
methylene chloride (6 mL). The reaction mixture was stir-
red for 4 h at 2608C and a saturated solution of sodium
bisulphite (3 mL) was added. The reaction mixture was
slowly warmed to room temperature, washed with 5%
aqueous sodium bicarbonate (3£5 mL), dried, and evapo-
rated. The residue was puri®ed by ¯ash chromatography
(EtOAc/hexane, gradient from 3:7 to 1:1) to afford sulfoxide
1
(epimers at C-2). H and 13C NMR data of the compound
have been compared to the data of the samples 16a and 16b
obtained from alcohols 15a and 15b and are identical with
their E-isomers.
Free radical cyclizations of thionocarbonates 16a and
16b
(1R,2S,5R,6S,9R)- and (1S,2R,5R,6S,9R)-5,9-Dimethyl-3-
thiabicyclo[4.4.0]decane-2-acetic acid methyl esters
(18a-1) and (18a-2). A 0.025 M solution of thionocarbonate
16a (915 mg, 2.24 mmol) in toluene (90 mL) was placed in
a ¯ask equipped with a re¯ux condenser and a magnetic bar,
under argon atmosphere. The solution was heated to 958C,
and individual 0.93 M solution of n-Bu3SnH (1.5 mL,
5.6 mmol, 2.5 equiv.) and a 0.07 M solution AIBN

3434
Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
(68 mg, 0.4 mmol, 0.18 equiv.) in toluene (6 mL) were
slowly added (syringe pump, 1 h). The heating at 958C
was continued until disappearance of starting material
(TLC). When the reaction was ®nished, the solvent was
removed under vacuum, and the residue was puri®ed by
¯ash chromatography (EtOAc/hexane, 1:9) to afford thia-
bicyclodecane 18a (oil, 476 mg, 83%) as a mixture of two
gave the mixture of corresponding sulfones 22 and 23 or
24±26. The isomers were further separated by MPLC
(EtOAc/hexane, 3:7).
(1R,2S,5R,6S,9R)-5,9-Dimethyl-3,3-dioxo-3-thiabicyclo-
[4.4.0]decane-2-acetic acid methyl ester (22). White
needles, mp 88±898C. IR (nujol): nmax 1735, 1300,
1
1
isomers (ratio 18a-1/18a-2, 2:1). H NMR (2 isomers): d
1132 cm21. H NMR: d 0.72 (ddd, Jˆ11.9, 11.9, 11.9 Hz,
0.54 (ddd, Jˆ11.8, 11.8, 11.8 Hz, major), 0.85±1.70 (m,
major1minor), total 8H; 0.81 (d, Jˆ6.5 Hz, minor), 0.86
(d, Jˆ6.5 Hz, major), total 3H; 0.94 (d, Jˆ7.0 Hz, minor),
1.05 (d, Jˆ6.9 Hz, major), total 3H; 1.76±1.85 (m, 1H);
1.90 (ddddt, Jˆ10.5, 10.5, 6.9, 6.9, 6.9 Hz, major), 2.01
(m, 1H, minor), total 1H; 2.14 (dd, Jˆ13.4, 3.4 Hz,
minor), 2.21 (dd, Jˆ15.3, 8.4 Hz, minor), 2.26 (dd,
Jˆ15.3, 8.6 Hz, major), 2.39 (dd, Jˆ13.3, 3.2 Hz, major),
total 2H; 2.68 (dd, Jˆ13.4, 12.1 Hz, minor), 2.71 (dd,
Jˆ15.3, 4.9 Hz, minor), 2.78 (dd, Jˆ15.3, 4.5 Hz, major),
3.07 (dd, Jˆ13.2, 2.9 Hz, major), total 2H; 2.86 (ddd,
Jˆ10.2, 8.6, 4.6 Hz, major), 3.56 (ddd, Jˆ10.7, 6.7,
3.9 Hz, minor), total 1H; 3.69, 3.70 sh (2£s, 3H). 13C
NMR (2 epimers): d 12.71 (major), 19.39 (CH2, minor),
19.98 (minor), 22.74 (major1minor), 26.70 (minor), 30.52
(CH2, minor), 31.91 (CH2, major), 32.80 (major), 33.02
(major), 34.15 (minor), 34.83 (CH2, major), 35.40 (CH2,
minor), 37.68 (minor), 37.68 (CH2, major), 37.91 (CH2,
major), 38.22 (CH2, minor), 38.68 (CH2, minor), 38.93
(CH2, major), 40.60 (major), 42.81 (minor), 43.95 (major),
44.78 (minor), 45.14 (major), 51.74 (major), 51.78 (minor),
172.41 (minor), 172.48 (major). HRMS (CI) Calcd for
C14H25O2S (MH1): 257.1575. Found (MH1): 257.1560.
1H); 0.89 (d, Jˆ6.5 Hz, 3H); 0.91 (dddd, Jˆ12.8, 12.8,
12.8, 3.4 Hz, 1H); 1.19 (d, Jˆ7.4 Hz, 3H); 1.24±1.38 (m,
2H); 1.47 (dddd, Jˆ11.6, 10.7, 3.4, 3.4 Hz, 1H); 1.54 (dddd,
Jˆ12.8, 3.2, 3.2, 3.2 Hz, 1H); 1.64±1.76 (m, 2H); 1.88
(dddd, Jˆ10.9, 10.9, 10.9, 3.5 Hz, 1H); 2.30 (m, 1H);
2.49 (dd, Jˆ17.4, 6.8 Hz, 1H); 3.06 (d, Jˆ14.3 Hz, 1H);
3.07 (dd, Jˆ17.4, 3.4 Hz, 1H); 3.22 (ddd, Jˆ10.9, 6.8,
3.4 Hz, 1H); 3.23 (dd, Jˆ14.3, 5.2 Hz, 1H); 3.73 (s, 3H).
13C NMR: d 13.24, 22.28, 28.05, 30.54, 31.57, 33.69, 34.15,
38.17, 38.64, 43.62, 52.41, 56.70, 61.95, 171.53. HRMS
(CI) Calcd for C14H24O4S (MH1): 289.1474. Found
(MH1): 289.1486.
(1S,2R,5R,6S,9R)-5,9-Dimethyl-3,3-dioxo-3-thiabicyclo-
[4.4.0]decane-2-acetic acid methyl ester (23). White
amorphous solid. IR (nujol): nmax 1735, 1296, 1139 cm21
.
1H NMR: d 0.82 (d, Jˆ6.4 Hz, 3H); 0.94 (dddd, Jˆ12.8,
12.8, 12.8, 3.8 Hz, 1H); 1.05 (d, Jˆ7.1 Hz, 3H); 1.20 (ddd,
Jˆ13.9, 12.2, 4.4 Hz, 1H); 1.38 (dddd, Jˆ13.2, 13.2, 13.2,
3.8 Hz, 1H); 1.53 (m, 1H); 1.56±1.67 (m, 2H); 1.68 (dddd,
Jˆ13.0, 3.6, 3.6, 3.6 Hz, 1H); 1.86 (m, 1H); 2.21 (m, 1H);
2.46 (dd, Jˆ16.9, 6.8 Hz, 1H); 2.48 (m, 1H); 2.85 (dd,
Jˆ15.6, 14.2 Hz, 1H); 2.87 (dd, Jˆ22.4, 14.2 Hz, 1H);
3.09 (dd, Jˆ16.9, 3.8 Hz, 1H); 3.67 (ddd, Jˆ10.7, 6.8,
3.8 Hz, 1H); 3.74 (s, 3H). 13C NMR: d 18.62, 18.88,
22.28, 26.49, 28.76, 33.07, 34.48, 36.78, 41.21, 41.40,
52.40, 52.42, 54.68, 171.38. HRMS (CI) Calcd for
C14H24O4S (MH1): 289.1474. Found (MH1): 289.1471.
(1R,2RS,5S,6S,9R)- and (1S,2RS,5S,6S,9R)-5,9-Dimethyl-
3-thiabicyclo[4.4.0]decane-2-acetic acid methyl esters
(18b-1) and (18b-2). Thiabicyclodecanes 18b (oil,
228 mg, 89%) were obtained as a mixture of four isomers
(ratio 18b-1/18b-2, 6:1) as described above for the synthesis
of 18a, after puri®cation by ¯ash chromatography (EtOAc/
(1R,2S,5S,6S,9R)-5,9-Dimethyl-3,3-dioxo-3-thiabicyclo-
[4.4.0]decane-2-acetic acid methyl ester (24). White
needles, mp 148±1518C. IR (nujol): nmax 1736, 1287,
1
hexane, 1:9). H NMR (4 diastereomers): d 0.57 (ddd,
Jˆ12.4, 12.4, 12.4 Hz), 0.71 (ddd, Jˆ12.3, 12.3, 12.3 Hz),
0.64±0.96 (m), total 4H; 0.85 (d, Jˆ6.4 Hz), 0.86 (d,
Jˆ6.6 Hz), total 3H; 0.94 (d, Jˆ6.6 Hz), 0.95 (d,
Jˆ6.6 Hz), total 3H; 1.12±1.54 (m, 3H); 1.65±2.04 (m,
3H); 2.17±2.27 (m), 2.25 (dd, Jˆ15.5, 8.2 Hz), total 1H;
2.36±2.58 (m), 2.42 (dd, Jˆ13.5, 3.6 Hz), 2.51 (dd, Jˆ13.6,
11.2 Hz), total 2H; 2.63±2.83 (m), 2.70 (dd, Jˆ15.2,
4.8 Hz), 2.77 (dd, Jˆ15.4, 4.9 Hz), total 1H; 2.87±2.99
(m), 2.86 (ddd, Jˆ10.2, 8.3, 5.0 Hz), 3.42 (m), total
1H; 3.68, 3.69. 3.70, 3.72 (4£s, 3H). HRMS (CI)
Calcd for C14H25O2S (MH1): 257.1575. Found (MH1):
257.1557.
1
1137 cm21. H NMR: d 0.72 (ddd, Jˆ11.8, 11.8, 11.8 Hz,
1H);, 0.83±1.02 (m, 3H); 0.90 (d, Jˆ6.5 Hz, 3H); 1.07 (d,
Jˆ6.7 Hz, 3H); 1.39 (m, 1H); 1.56±1.78 (m, 3H); 1.97±
2.08 (m, 2H); 2.49 (dd, Jˆ17.3, 7.2 Hz, 1H); 2.80 (dd,
Jˆ14.0, 12.8 Hz, 1H); 3.07 (dd, Jˆ14.0, 3.4 Hz, 1H); 3.10
(dd, Jˆ17.3, 3.5 Hz, 1H); 3.27 (ddd, Jˆ11.0, 7.2, 3.5 Hz,
1H); 3.75 (s, 3H). 13C NMR: d 19.39, 22.28, 28.02, 29.64,
32.16, 34.06, 35.17, 37.91, 44.58, 46.81, 52.44, 57.20,
61.00, 171.48. HRMS (CI) Calcd for C14H24O4S (MH1):
289.1474. Found (MH1): 289.1470.
(1R,2R,5S,6S,9R)-5,9-Dimethyl-3,3-dioxo-3-thiabicyclo-
[4.4.0]decane-2-acetic acid methyl ester (25). White
Oxidation of 3-thiabicyclo[4.4.0]decanes 18a and 18b to
sulfones
amorphous solid. IR (nujol): nmax 1736, 1301, 1135 cm21
.
1H NMR: d 0.74 (ddd, Jˆ12.4, 12.4, 12.4 Hz, 1H); 0.83±
1.01 (m, 3H); 0.90 (d, Jˆ6.5 Hz, 3H); 1.03 (d, Jˆ6.7 Hz,
3H); 1.48 (m, 1H); 1.56 (dddd, Jˆ12.6, 2.5, 2.5, 2.5 Hz,
1H); 1.75 (m, 1H); 1.94 (m, 1H); 2.05 (dddd, Jˆ12.6, 3.3,
3.3, 3.3 Hz, 1H); 2.30 (m, 1H); 2.64 (dd, Jˆ17.0, 6.1 Hz,
1H); 2.69 (dd, Jˆ14.5, 12.6 Hz, 1H); 2.84 (dd, Jˆ17.0,
6.2 Hz, 1H); 2.85 (d, Jˆ14.5 Hz, 1H); 3.51 (ddd, Jˆ9.6,
6.1, 3.4 Hz, 1H); 3.75 (s, 3H). 13C NMR: d 19.14, 22.19,
29.86, 30.35, 32.23, 34.37, 35.87, 39.40, 39.83, 41.93,
General procedure: To a solution of thiabicyclodecanes 18a
or 18b (51 mg, 0.2 mmol) in ethyl acetate (5 mL) at 08C was
added m-CPBA (160 mg of 65% reagent, 3 equiv.), and the
reaction mixture was slowly warmed to room temperature
and stirred for 4 h. The resulting mixture was poured into
EtOAc/hexane (1:1 mixture, 20 mL), washed with saturated
sodium bisulphite and NaHCO3 solutions, dried (Na2SO4),
and evaporated. Flash chromatography (EtOAc/hexane, 3:7)

Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
3435
52.47, 53.60, 60.04, 170.81. HRMS (CI) Calcd for
C14H24O4S (MH1): 289.1474. Found (MH1): 289.1477.
31 (105 mg, 90%) as a mixture of four diastereomers
(6:1.5:1.5:1) with overall ratio of cis/trans isomers 31a/
31b, 3:1. H NMR (4 isomers): d 0.79±0.91 (m, 1H); 0.87
1
(1S,2RS,5S,6S,9R)-5,9-Dimethyl-3,3-dioxo-3-thiabicyclo-
[4.4.0]decane-2-acetic acid methyl esters (26) occur as a
mixture with sulfone 25 and exhibited characteristic H
(d, Jˆ6.4 Hz, major), 0.88 (d, Jˆ6.4 Hz, minor), 0.93 (d,
Jˆ6.5 Hz, minor), 0.94 (d, Jˆ6.5 Hz, minor), total 3H;
1.07±1.91 (m, 8H); 1.23 (t, Jˆ7.1 Hz, minor), 1.24 (t,
Jˆ7.1 Hz, minor), 1.27 (t, Jˆ7.1 Hz, major), 1.29 (t,
Jˆ7.1 Hz, minor), total 3H; 1.39 (s, minor), 1.40 (s,
minor), 1.45 (s, major), 1.46 (s, minor), total 3H; 2.12 (m,
minor), 2.42 (m, major1minor), 2.93 (m, minor), total 1H;
2.38 (dd, Jˆ16.0, 10.0 Hz, minor), 2.41 (dd, Jˆ16.0,
6.8 Hz, minor), 2.46 (dd, Jˆ16.0, 10.0 Hz, major), 2.66
(dd, Jˆ16.0, 14.6 Hz, minor), 2.68 (dd, Jˆ16.0, 8.5 Hz,
minor), 2.82 (dd, Jˆ16.0, 3.8 Hz, major), 2.83 (dd,
Jˆ16.0, 3.2 Hz, minor), 2.84 (dd, Jˆ16.0, 4.3 Hz, minor),
total 2H; 3.33 (ddd, Jˆ9.9, 9.9, 4.0 Hz, minor), 3.72 (ddd,
Jˆ14.6, 7.2, 5.4 Hz, minor), 3.76 (ddd, Jˆ10.5, 10.5,
3.8 Hz, major), 3.89 (ddd, Jˆ11.3, 9.3, 4.0 Hz, minor),
total 1H; 4.10±4.20 (4£q, Jˆ7.1 Hz, 2H). 13C NMR
(major isomer): d 14.20, 22.42, 24.43, 26.00, 26.18,
26.83, 34.24, 34.44, 35.20, 42.22, 44.98, 47.35, 53.70,
54.91, 60.60. HRMS (CI) Calcd for C15H27O2S (MH1):
271.1732. Found (MH1): 271.1719.
1
NMR peaks at d 1.20, 1.31 (2£d, Jˆ7.4 Hz, 3H); and
3.02±3.29 (m, 1H).
Ethyl (E/Z)-3-[1-((1R,2R,4R)-2-hydroxy-4-methylcyclo-
hexyl)-1-methylethylsulfanyl]-2-propenoate (28). Thiol
2714 (641 mg, 3.4 mmol) was dissolved in EtOH±H2O
mixture (15:1, 10 mL). The temperature was reduced to
08C and ethyl propiolate (0.5 mL, 4.9 mmol) and catalytic
amount of triethylamine (two drops of a mixture: one drop
of NEt3 in 10 drops of EtOH) were added. The reaction
mixture was stirred for 12 h at room temperature, diluted
with benzene (100 mL) and evaporated. The residue was
puri®ed by ¯ash chromatography (EtOAc/hexane, 1:20) to
give the unsaturated sul®de 28 (oil, 691 mg, 71%) as a
mixture of two isomers (E/Z, 1:4.6). 1H NMR (E/Z isomers):
d 0.85 (m, 1H); 0.89 (d, Jˆ6.5 Hz, Z), 0.90 (d, Jˆ6.5 Hz,
E), total 3H; 0.95±1.16 (m, 2H); 1.27 (t, Jˆ7.1 Hz, 3H);
1.45 (m, 1H); 1.46 (s, Z), 1.47 (s, E), total 3H; 1.50 (s, Z),
1.52 (s, E), total 3H; 1.51 (m, 1H); 1.67 (m, 1H); 1.85±1.96
(m, 2H); 2.46 (br s, Z), 2.58 (br s, E), total 1H; 3.66 (m, 1H);
4.17 (q, Jˆ7.1 Hz, 2H, E), 4.18 (q, Jˆ7.1 Hz, 2H, Z), total
2H; 5.87 (d, Jˆ10.5 Hz, Z), 5.95 (d, Jˆ15.4 Hz, E), total
1H; 7.36 (d, Jˆ10.5 Hz, Z), 7.87 (Jˆ15.4 Hz, E), total 1H.
13C NMR (E/Z isomers): d 14.27 (E), 14.29 (Z); 21.77 (E),
21.80 (Z); 26.65 (E/Z); 27.00 (E), 27.29 (Z); 28.87 (Z), 29.27
(E); 31.22 (E), 31.25 (Z); 34.44 (E), 34.54 (Z); 45.28 (E),
45.41 (Z); 50.48 (E/Z); 51.83 (Z), 51.94 (E); 60.00 (Z). 60.21
(E); 72.47 (Z), 72.55 (E); 113.27 (Z), 116.40 (E); 144.27 (E),
144.92 (Z); 165.53 (E), 166.53 (Z). HRMS (CI) Calcd for
C15H27O3S (MH1): 287.1681. Found (MH1): 287.1660.
Methyl (E)-3-[(1RS,2R,5R)-5-methyl-2-((1R)-1-methyl-
2-methylsulfanylethyl)cyclohexyl]-2-propenoate
(33).
To a solution of in thiabicyclodecanes 18a-1/18a-2
(141 mg, 0.55 mmol) in methylene chloride (5 mL) at
2108C was added methyl tri¯uoromethanesulfonate
(0.3 mL, 2.65 mmol). The reaction mixture was warmed
to room temperature, stirred for 2.5 h, and evaporated to
give sulfonium salt 32 as a dark-brown oil. The crude salt
was suspended in THF (4 mL) and cooled to 08C. Potassium
tert-butoxide (1.0 M solution in THF, 0.6 mL) was added
dropwise. After stirring for 2 h at room temperature (TLC),
the reaction mixture was quenched with glacial acetic acid
(0.2 mL) and evaporated. The residue was dissolved in
water (10 mL) and hexane (10 mL), and aqueous layer
was extracted with hexane (2£10 mL). The combined
organic layers were dried (Na2SO4), the solvent was evapo-
rated, and ¯ash chromatography (EtOAc/hexane, 1:20) of
the residue gave the title compound 33 (112 mg, 76%) as a
2:1 mixture of epimers at C-1. IR (neat): nmax 2956, 2919,
Ethyl (E/Z)-3-[1-((1R,2R,4R)-2-phenoxythiocarbonyloxy-
4-methylcyclohexyl)-1-methylethylsulfanyl]-2-propenoate
(29). Compound 29 (red oil, 630 mg, 69%) was obtained as
a mixture of two isomers (E/Z, 1:3.3) from alcohol 28
(619 mg, 2.16 mmol) as described above for the synthesis
of 16a, after puri®cation by MPLC (EtOAc/hexane, 1:9). 1H
NMR (E/Z isomers): d 0.88±1.06 (m, 1H); 0.97 (d,
Jˆ6.4 Hz, 3H); 1.09±1.38 (m, 2H); 1.29 (t, Jˆ7.1 Hz, Z),
1.30 (t, Jˆ7.1 Hz, E), total 3H; 1.43 (s, Z), 1.46 (E), total
3H; 1.54 (m, 1H); 1.58 (s, Z), 1.59 (E), total 3H; 1.75 (m,
1H); 2.02 (m, 1H); 2.16±2.37 (m, 2H); 4.21 (q, Jˆ7.1 Hz,
Z), 4.22 (q, Jˆ7.1 Hz, E), 5.36 (ddd, Jˆ10.6, 10.6, 4.7 Hz,
E), 5.37 (ddd, Jˆ10.6, 10.6, 4.7 Hz, Z), total 1H; 5.89 (d,
Jˆ10.5 Hz, Z), 5.97 (d, Jˆ15.4 Hz, E), total 1H; 7.30 (d,
Jˆ10.5 Hz, Z), 7.86 (Jˆ15.4 Hz, E), total 1H; 7.08±7.47
(m, 5H). HRMS (CI) Calcd for C22H31O4S2 (MH1):
423.1664. Found (MH1): 423.1653.
1
2857, 1732, 1659, 1431, 1272, 1173 cm21. H NMR (2
epimers, major and minor):d 0.82 (d, Jˆ6.4 Hz, minor),
0.87 (d, Jˆ6.5 Hz, major), total 3H; 0.87±1.09 (m, 3H);
1.24±1.82 (m, 6H); 1.99 (s, major), 2.05 (s, minor), total
3H; 2.11 (dd, Jˆ12.7, 10.5 Hz, major), 2.20 (dddd, 1H,
Jˆ10.9, 3.2, 3.2, 3.2 Hz, major), 2.37 (dd, Jˆ12.4, 7.7 Hz,
minor), 2.50 (dd, Jˆ12.7, 3.8 Hz, major), 2.61 (dd, Jˆ12.4,
3.4 Hz, minor), 2.73 (m, minor), total 3H; 3.71 (s, major),
3.72 (s, minor), total 3H; 5.80 (d, Jˆ15.6 Hz, major), 5.87
(d, Jˆ15.6 Hz, minor), total 1H; 6.74 (dd, Jˆ15.6, 9.9 Hz,
major), 7.19 (dd, Jˆ15.6, 9.9 Hz, minor), total 1H. 13C
NMR (2 epimers): d 15.86 (major), 16.51 (minor), 17.00
(minor), 17.72 (major), 22.25 (major), 22.52 (minor), 25.37
(CH2, minor), 25.77 (CH2, major), 26.91 (minor), 32.03
(major), 34.35 (major), 34.86 (CH2, major), 35.32 (CH2,
minor), 35.77 (minor), 36.94 (CH2, major), 39.89 (minor),
40.37 (CH2, minor), 41.86 (CH2, major), 41.97 (CH2,
minor), 44.11 (major), 44.24 (minor), 46.47 (major), 51.32
(minor1major), 120.39 (major), 121.59 (minor), 150.47
(minor), 153.59 (major), 166.91 (minor), 166.94 (major).
(1S,3R,6R,9RS)- and (1R,3R,6R,9RS)-3,7,7-Trimethyl-8-
thiabicyclo[4.3.0]nonane-9-acetic acid ethyl esters (31a)
and (31b). The synthesis of 8-thiabicyclo[4.3.0]nonanes 31
was performed starting from thionocarbonate 29 (182 mg,
0.43 mmol), n-Bu3SnH (0.29 mL, 1.08 mmol, 2.5 equiv.),
and AIBN (14 mg, 0.09 mmol, 0.2 equiv.) using reaction
conditions described for preparation of 18a to give after
¯ash chromatography (EtOAc/hexane, 1:9) bicyclic sul®de

3436
Y. V. Bilokin et al. / Tetrahedron 56 (2000) 3425±3437
HRMS (CI) Calcd for C15H27O2S (MH1): 271.1732. Found
(MH1): 271.1721.
evaporated. The residue was puri®ed by ¯ash chromato-
graphy (EtOAc/hexane, 2:3) to afford a mixture of four
diastereomeric sulfoxides used at the next stage. A solution
of sulfoxides (98 mg, 0.34 mmol) and methyl acrylate
(4 mL) in toluene (4 mL) was heated at 1808C for 62 h in
a sealed tube. The mixture was evaporated and puri®ed by
¯ash chromatography (EtOAc/hexane, 1:1) to afford title
compound 35 (colorless oil, 32 mg, 41%, from 11b) as a
mixture of two epimers at C-1 (ratio 35a/35b, 6:1). 1H NMR
data of the compound have been compared to the data of the
sample obtained from sul®de 33 and are identical.
Methyl (E)-3-[(1S,2R,5R)- and (E)-3-[(1R,2R,5R)-2-iso-
propenyl-5-methylcyclohexyl]-2-propenoates (35a) and
(35b) from sul®de 33. To a solution of sul®de 33 (49 mg,
0.18 mmol) in ethyl acetate (1 mL) at 2608C under argon
was added dropwise for 20 min a solution of m-CPBA
(53 mg of 65% reagent, 0.2 mmol) in ethyl acetate
(5 mL). The reaction mixture was stirred for 4 h at
2408C, slowly warmed to room temperature, washed with
5% aqueous NaHCO3 (3£10 mL), dried (Na2SO4), and
evaporated. The residue was puri®ed by ¯ash chromato-
graphy (EtOAc/hexane, 3:7) to afford quantitatively a
mixture of four isomeric sulfoxides 34 used at the next
stage. A solution of 34 (50 mg, 0.17 mmol) and methyl
acrylate (2 mL) in toluene (2 mL) was heated at 1808C for
62 h in a sealed tube. The mixture was then evaporated and
puri®ed by ¯ash chromatography (EtOAc/hexane, 1:1) to
afford title compound 35 (colorless oil, 19 mg, 47%, from
33) as a mixture of two epimers at C-1 (ratio 35a/35b, 2:1).
1H NMR (two epimers, 35aÐmajor and 35bÐminor): d
0.87 (d, Jˆ6.5 Hz, minor), 0.92 (d, Jˆ6.5 Hz, minor), total
3H; 0.90±1.03 (m, 2H); 1.31±1.51 (m, 2H); 1.62 (s, major),
1.70 (s, minor), total 3H; 1.63±1.90 (m, 3H); 2.04±2.25 (m),
2.81 (m), total 2H; 3.72 (s, major), 3.73 (minor), total 3H;
4.65 (m, minor), 4.70 (m, major), 4.80 (m, minor), total 2H;
5.75 (dd, Jˆ15.7, 1.0 Hz, major), 5.82 (dd, Jˆ15.8, 1.3 Hz,
minor), total 1H; 6.79 (dd, Jˆ15.7, 8.4 Hz, major), 7.05 (dd,
Jˆ15.8, 8.3 Hz, minor), total 1H. 13C NMR (2 epimers): d
19.28 (major), 22.27 (minor), 22.38 (major), 22.50 (minor),
25.76 (minor), 27.06 (minor), 31.82 (major), 34.61 (major),
35.15 (minor), 39.57 (minor), 40.59 (major), 40.70 (minor),
43.41 (major), 46.52 (minor), 50.59 (major), 51.31
(minor1major), 110.23 (minor), 111.35 (major), 119.33
(major), 121.15 (minor), 147.68 (minor1major), 150.17
(minor), 153.12 (major), 167.34 (minor1major). HRMS
(CI) Calcd for C14H23O2 (MH1): 223.1698. Found (MH1):
223.1657.
Acknowledgements
This research was supported by The Israel Science
Foundation, founded by The Israel Academy of Sciences
and Humanities and by Minerva Science Foundation,
Germany.
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