Preparation and reactivity studies of 1,2-bis-triisopropylsilanylsulfanyl-alkenes

Article abstract of DOI:10.1016/S0040-4020(01)00517-8

The cross-coupling reaction of bis-triisopropylsilyl disulfide 1 on alkynes yielded 1,2-bis-triisopropylsilanylsulfanyl-alkenes 2, a new chemical class. A series of tri and tetrasubstituted olefins 2 were prepared and their behavior toward electrophiles was studied. The triisopropylsilyl groups could be readily removed by treatment with TBAF at 0°C for 1 h or cesium acetate at 70°C for 2 h. Soft and hard electrophiles were submitted to 2 under these conditions. The electrophiles can either react to yield double-addition products with alkyl and activated halides, epoxides and acyl chlorides or cyclic adducts with chloroformate derivatives. In the latter case, 1,3-dithiol-2-ones or 1,3-dithiol-2-thiones are prepared.

Full text of DOI:10.1016/S0040-4020(01)00517-8

TETRAHEDRON
Pergamon
Tetrahedron 57 82001) 5739±5750
Preparation and reactivity studies of
1,2-bis-triisopropylsilanylsulfanyl-alkenes
p
Yves Gareau, Melanie Tremblay, Danny Gauvreau and Helene Juteau
Â
 Á
Merck Frosst Canada & Co., P.O. Box 1005, Pointe-Claire, Dorval, Que., Canada H9R 4P8
Received 19 March 2001;accepted 11 May 2001
AbstractÐThe cross-coupling reaction of bis-triisopropylsilyl disul®de 1 on alkynes yielded 1,2-bis-triisopropylsilanylsulfanyl-alkenes 2, a
new chemical class. A series of tri and tetrasubstituted ole®ns 2 were prepared and their behavior toward electrophiles was studied. The
triisopropylsilyl groups could be readily removed by treatment with TBAF at 08C for 1 h or cesium acetate at 708C for 2 h. Soft and hard
electrophiles were submitted to 2 under these conditions. The electrophiles can either react to yield double-addition products with alkyl and
activated halides, epoxides and acyl chlorides or cyclic adducts with chloroformate derivatives. In the latter case, 1,3-dithiol-2-ones or
1,3-dithiol-2-thiones are prepared. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
There has been several reports showing the use of transition
metal catalyst in chemical reactions involving thiolates,1
sul®des2 and disul®des.3 In 1997, we published our own
ꢀ1†
results on the palladium-catalyzed reaction of a new disul-
®de 1 and terminal alkynes that yielded 1,2-bis-methyl-
sulfanyl-alkenes 3 after treatment with methyl iodide±
TBAF 8Eq. 81)).4 The initial addition reaction 8alkyne!2)
was an extension of a more speci®c reaction 8alkyne!4)
described by Ogawa, Sonoda et al. in 1991 8Eq. 82)).3c For
this transformation, they reported high yields of 4 if
ꢀ2†
aromatic disul®des and diselenides were used. The con®g-
uration of 4 was such that the newly formed substituents
were always cis to each other. In the case of aliphatic disul-
®des, the results were much less attractive since the yields
were very low 80±20%) and therefore greatly limits the
possibility of the reaction. In our previous report on the
preparation of vinyl 1,2-bis-methylsulfanyl-alkenes 3, we
opened the way for a much more ¯exible reaction of the
iodide oxidation of the commercially available thiol. A
palladium cross-coupling reaction between alkynes and
2. Results and discussion
Disul®de 1 is a bright yellow solid easily prepared4 by
series of mono and disubstituted alkynes were converted
disul®de 1. At that time, we did not pay any special attention
to Z-1,2-bis-triisopropylsilanylsulfanyl-alkenes. Thus, the
to the intermediate 2. In only one example 8Rˆt-butyl), such
desired alkyne was treated with 1.1 equiv. of 1 and
a compound was isolated by ¯ash chromatography in a
0.05 equiv. of 8Ph3)4Pd in a 1.0 M solution of toluene at
modest yield of 55%. We would like to report herein our
results on the scope and limitations for the preparation and
tion conditions varied with the volatility of the substrate
the reactivity of such intermediates.
ca. 908C under nitrogen for approximately 15 h. The reac-
and/or the degree of substitution on the triple bond. For
volatile starting materials, the reaction was performed in a
sealed tube using excess alkyne toward electrophiles.
Less reactive disubstituted alkynes were run at higher
concentration and temperature. At the end of each reaction,
the solvent was removed and the crude oil was rapidly
passed through a short pad of silica gel. This reaction is
Keywords: alkynes;electrophiles;double-addition products.
Corresponding author. Tel.: 11-514-428-3001;fax: 11-514-428-4900;
e-mail: yves_gareau@merck.com
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020801)00517-8

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Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
Table 1. Preparation of Z-1,2-bis-triisopropylsilanylsulfanyl-alkenes from alkynes
quite general and the yields are usually quite satisfactory.
Some low yields were not always indicative of the effec-
tiveness of the reaction but re¯ected mainly the dif®culty of
the puri®cation. Simple aliphatic alkynes usually worked
quite nicely, yet the highly bulky t-butyl acetylene gave
3,3-dimethyl-1,2-bis-triisopropylsilanylsulfanyl-but-1-ene
9 in 70% isolated yield. Many functional groups such as
alcohol, ester, acetate and halide were tolerated 8Table 1)
while carboxylic acids were one group that gave poor results
8not shown). Disubstituted alkynes also worked but in
general lower yields are obtained. These silylated vinyl-
sul®des are fairly stable and could be stored for months at
room temperature.
With all these 1,2-bis-triisopropylsilanylsulfanyls in hand
we examined, in a more general way than previously
reported their reactivity toward electrophiles after TBAF
deprotection. The two substrates selected for this study
were 1-81,2-bis-triisopropyl silanylsulfanyl-vinyl)-cyclo-
hexene 8 and 1,2-bis-triisopropylsilanylsulfanyl-dec-1-ene
5. The electrophiles examined varied from activated and
non-activated halides to epoxides 8Table 2). Therefore, to
a 08C solution of 8 in toluene±DMF was added 2.5 equiv. of
the halide followed by 2.5 equiv. of TBAF and the reaction
mixture was left stirring for 1 h. The ®nal product obtained
corresponded to an addition of the electrophile on both
sulfur atoms as expected. The reaction worked satisfactorily

Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
5741
Table 2. Double-addition products of electrophiles to Z-1,2-bis-trisopropylsilanylsulfanyl-alkenes
a
To the starting material in toluene±DMF 81:1, 0.5 M) at 08C was added the electrophile followed by TBAF. The mixture was stirred 1 h at 08C.
b To the starting material in toluene±CH3CN 81:1, 0.5 M) was added the electrophile followed by cesium acetate. The mixture was stirred 2 h at 708C.
Table 3. Double-addition products from a one-pot 2-step reaction
a
Cesium acetate was used to remove the silyl groups.
b TBAF was used to remove the silyl groups.

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Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
Table 4. Double-addition products of acyl chlorides to Z-1,2-bis-triisopropylsilanylsulfanyl-alkenes
a
The reaction was performed at 08C.
The reaction was performed at 2788C.
b
with iodo and bromopropionate in 60 and 54% isolated
yield. For activated halides such as 2-bromoacetophenone,
the yield was slightly higher and reached 70%. Finally,
reagents that had two electrophilic sites led to cyclic
adducts. With 1.2 equiv. of 1,3-dibromoacetone, the
7-membered ring ketone 19 was formed in only 34%
yield. We then looked at epoxides versus substrate 5.
We did experience a lot of problems using TBAF and
1,2-epoxy-7-octene and decided to search for a different
deprotecting agent. We found that cesium acetate was
ef®cient enough to remove the silyl groups but at higher
temperature. Therefore a mixture of 5, 2.5 equiv. of the
epoxide and 2.5 equiv. of cesium acetate were heated to
708C for 2 h. The expected diol 20 was isolated in 71%.
We did not encounter the same success with other type of
epoxides. For example, cyclopentene oxide did not furnish
any trace of compound under these conditions although
this could be explained by the reduced reactivity of 1,2-
disubstituted epoxides. Having a different method to remove
the triisopropylsilyl groups, we decided to examine the
cesium acetate conditions with other aliphatic and benzylic
halides. As can be seen in Table 2, benzyl bromide seems to
be superior over benzyl chloride while there is no difference
between the iodo and bromopropane. Overall, the yields
were in the range 66±76%.
Interestingly, the ®nal products of double addition could
Scheme 1.

Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
5743
Table 5. Preparation of 1,3-dithiol-2-ones from Z-1,2-bis-triisopropylsilanylsulfanyl-alkenes and phenyl chlorothiolformate
a
Reaction was performed at2238C.
also come from a one-pot 2-step reaction if one decided to
start from the alkyne in the following way. The catalyzed
cross-coupling addition of the alkyne and reagent 1 was run
at 908C for 15 h followed by treatment of the mixture with
either TBAF/halide or cesium acetate/halide. Table 3 shows
three examples obtained from 1-decyne in such a way.
Typically, the overall yields 865±69%) for this 2-step
process are in the same limit as the ones achieved from
compound 5 with similar electrophiles.
of acetyl chloride. In some instances, these conditions were
still not suf®cient. Propionyl chloride is an example, which
gave too many undesirable side products, and we were not
able to isolate the bis-addition product in satisfactory purity.
Sterically hindered a-hydrogen acyl chlorides like t-butyl-
acetyl chloride gave limited side products and a higher yield
of 28 could be achieved. Obviously, these problems can be
overcome by using acyl chlorides that possess no a-hydro-
gen. Pivaloyl chloride and p-toluoyl chloride fall in this
category and as can be seen in Table 4, these electrophiles
usually behaved very well with different substrates. We then
turned our attention to phosgene, an even more reactive
electrophile. This, we anticipated would lead to 1,3-
dithiol-2-one 34 8Scheme 1). In fact, phosgene was not
the best choice for this type of reaction with low yield of
34. Triphosgene, a solid phosgene equivalent was more
appropriate but yet, the yields were not satisfactory. Finally,
we found that something less reactive would be good
enough for our purpose. Phenyl chlorothiolformate was
the reagent of choice for this transformation. Table 5
summarized the end result for this conversion with seven
bis-triisopropylsilyl-alkenes. The yields are generally good
particularly for the t-butyl derivative 38 with 88%. Also,
some reactions were run at 2238C for optimum yields,
So far we have focused our efforts on soft electrophiles.
However some hard electrophiles could also be used. For
instance, when substrate 2 was subjected to acyl chlorides
and TBAF, the corresponding bis-thiolester was isolated in
reasonably good yield. The choice of the temperature at
which the reaction was performed proved to be important
for two reasons. First, the yield can be increased if the
reaction is carried out at lower temperature 82238C) and
second, the ®nal compounds are easier to purify since they
are less contaminated by impurities coming from side reac-
tions. In basic media, acyl chlorides having a-hydrogen are
know to be converted to ketenes5 which are prone to fast
oligomerization.6 This problem can be greatly reduced by
running the reaction at 2238C or even 2788C as in the case

5744
Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
Table 6. Preparation of 1,3-dithiol-2-thiones from Z-1,2-bis-triisopropylsilanylsulfanyl-alkenes and thiophosgene or phenyl chlorothionoformate
a
The reaction was performed at2238C.
mainly in the cases of tetrasubstituted ole®ns. Other chloro-
formates 8phenyl chloroformate, 4-nitrophenyl chlorofor-
mate and 4-methoxyphenyl chloroformate) were tested
with less success.
tion to this came from compound 46 838%). However this
reaction still can be enhanced if one use phenyl chloro-
thionoformate instead of thiophosgene. This time the yield
increased to 55% using the same conditions and reached
78% at 2238C. The superiority of this reagent can be seen
in all the other substrates given in Table 6. In particular, the
reaction was highly ef®cient with trisubstituted ole®ns with
isolated yields between 85 and 94% 842±45).
In the same vein, 1,3-dithiol-2-thiones 8the sulfur analogues
of 34) could be prepared by two different reagents. Under
the standard reaction conditions 82.3 equiv. of TBAF at 08C
for 1 h) thiophosgene was much more ef®cient than phos-
gene to give the cyclic adduct. The yields are very consistent
and remained in the 55% range 8Table 6). The only excep-
The probable mechanism for this reaction 8and most likely
phenyl chloroformate) is described in Scheme 2. Starting
Scheme 2.

Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
5745
with 5, the ®rst attack of one of the thiolates on the chloro-
thionoformate gives 49 followed by the expulsion of the
chloride ion. Subsequently, an intramolecular attack from
the other thiolate on the thione resulted in the cyclic product
44 888%) together with phenol as a side product. It did make
sense to presume that the chloride ion would be expulsed
before the phenol group. This was con®rmed when the
reaction was repeated with an excess of chlorothiono-
formate. The major compound is still 44 871%) but a second
product 850) which corresponds to the addition of two
equivalents of chlorothionoformate could be isolated in
12% yield.
4.2.2. ,2,3-Bis-triisopropylsilanylsulfanyl-allyl)-benzene
,6). To solution of 3-phenyl-1-propyne 8200 mg,
a
1.70 mmol) in 2 mL of benzene was added disul®de 1
8685 mg, 1.81 mmol) followed by Pd8PPh3)4 8100 mg,
0.09 mmol). Puri®cation on a short pad of silica gel using
30% of toluene in hexane afforded 736 mg 886%) of
1
compound 6 as a light yellow oil. H NMR 8300 MHz,
CDCl3) d 7.18 8m, 5H), 5.93 8s, 1H), 3.62 8s, 2H), 1.37
8m, 3H), 1.18 8d, Jˆ7.2 Hz, 18H), 1.09 8m, 3H), 0.98 8d,
Jˆ6.4 Hz, 18H); 13C NMR 875 MHz, CDCl3) d 138.7,
130.7, 129.2, 128.2, 126.2, 48.6, 18.6, 18.2, 13.9, 12.5;
HRMS calcd for C27H50S2Si21H1: 495.2971. Found:
495.2969.
3. Conclusion
4.2.3. ,1,2-Bis-triisopropylsilanylsulfanyl-vinyl)-cyclo-
hexane ,7). To a solution of cyclohexylethyne 1.00 g,
9.24 mmol) in 10 mL of benzene was added disul®de 1
83.85 g, 10.2 mmol) followed by Pd8PPh3)4 8534 mg,
0.46 mmol). Puri®cation on a short pad of silica gel using
A collection of 1,2-bis-triisopropylsilanylsulfanyl-alkenes 2
was prepared. They represent a new class of compounds and
the reactivity of these species toward electrophiles was
investigated. These bis-triisopropylsilanylsulfany-alkenes
are readily deprotected with either cesium acetate at 708C
or TBAF at 08C and trapped with a wide variety of soft
electrophiles to produce products of double addition. Hard
electrophiles such as acyl chlorides and chloroformates
were also captured by 2 to generate 1,3-dithiol-2-ones or
1,3-dithiol-2-thiones.
1
hexane afforded 3.04 g 867%) of 7. H NMR 8300 MHz,
CDCl3) d 6.22 8s, 1H), 2.02 8m, 3H), 1.77 8m, 2H), 1.67
8m, 1H), 1.27 8m, 6H), 1.11 8m, 41H); 13C NMR 875 MHz,
acetone-d6) d 139.0, 122.5, 51.3, 34.5, 28.1, 27.7, 19.7,
19.4, 15.2, 14.0;HRMS calcd for C 26H54S2Si21H1:
486.3284. Found: 486.3284.
4.2.4. 1-,1,2-Bis-triisopropylsilanylsulfanyl-vinyl)-cyclo-
hexene ,8). To a solution of 1-ethynylcyclohexene
8450 mg, 4.24 mmol) in 4.2 mL of benzene was added disul-
®de 1 81.69 g, 4.45 mmol) followed by Pd8PPh3)4 8245 mg,
0.21 mmol). Puri®cation on a short pad of silica gel using
4. Experimental
4.1. Data for compounds
1
hexane afforded 1.62 g 877%) of compound 8. H NMR
4.1.1. Bis,triisopropylsilyl)disul®de ,1). To 9.75 g of tri-
isopropylsilanethiol in 50 mL of benzene was added
portionwise sodium hydride 81.05 equiv.) and the resulting
suspension was allowed to stir for 10 min. A solution of
iodine in 150 mL of benzene was added until a slight pink
color remained. The suspension was ®ltered through celite
and the solvent evaporated to yield an orange oil. The crude
oil was crystallized overnight in hexane at 258C to give
8300 MHz, CDCl3) d 6.57 8s, 1H), 6.31 8m, 1H), 2.14 8m,
4H), 1.59 8m, 4H), 1.29 8m, 6H), 1.12 8m, 36H); 13C NMR
875 MHz, CDCl3) d 138.1, 133.1, 126.7, 123.9, 27.2, 25.6,
23.0, 22.2, 18.5, 18.3, 13.9, 12.7;HRMS calcd for
C26H52S2Si21H1: 485.3127. Found: 485.3126.
4.2.5. 3,3-Dimethyl-1,2-bis-triisopropylsilanylsulfanyl-
but-1-ene ,9). To a solution of 3,3-dimethyl-1-butyne
81.56 g, 19.0 mmol) in 10 mL of benzene was added disul-
®de 1 84.0 g, 10.6 mmol) followed by Pd8PPh3)4 8610 mg,
0.53 mmol). Puri®cation on a short pad of silica gel using
1
7.63 g 879%) of bright yellow crystals 84). Mp: 388C. H
NMR 8CDCl3, 400 MHz) d 1.16 86H, d, Jˆ7.4 Hz) and 1.40
81H, m, Jˆ7.4 Hz); 13C NMR 8CDCl3, 100 MHz) d 12.96
and 18.66;Anal. calcd for C 18H42S2Si2: C, 57.07;H, 11.18;
S, 16.93. Found: C, 57.43;H, 11.55;S, 16.50.
1
hexane afforded 3.39 g 870%) of the title compound 9. H
NMR 8300 MHz, CDCl3) d 6.53 8s, 1H), 1.50 8m, 3H), 1.28
8m, 3H), 1.14 8m, 45H); 13C NMR 875 MHz, CDCl3) d
141.8, 122.6, 40.3, 30.2, 18.9, 18.4, 14.2, 12.7;HRMS
calcd for C24H52S2Si21H1: 461.3127. Found: 461.3128.
4.2. General procedure for the addition of bis-triiso-
propylsilyl disul®de 1 to alkynes
4.2.6. 5-Chloro-1,2-bis-triisopropylsilanylsulfanyl-pent-
1-ene ,10). To a solution of 5-chloro-1-pentyne 8630 mL,
6.03 mmol) in 6 mL of toluene was added disul®de 1
82.50 g, 6.57 mmol) followed by Pd8PPh3)4 8346 mg,
0.31 mmol). Puri®cation on a short pad of silica gel using
hexane afforded 2.21 g 876%) of the title compound 10. 1H
NMR 8500 MHz, CDCl3) d 6.39 8s, 1H), 3.49 8t, Jˆ6.2 Hz,
2H), 2.47 8t, Jˆ6.8 Hz, 2H), 2.03 8m, 2H), 1.3 8m, 6H), 1.12
8m, 36H); 13C NMR 8125 MHz, CDCl3) d 129.9, 125.6,
43.8, 39.2, 30.7, 18.5, 18.3, 13.9, 12.6;HRMS calcd for
C23H49ClS2Si21H1: 480.2503. Found: 480.2502.
4.2.1. 1,2-Bis-triisopropylsilanylsulfanyl-dec-1-ene ,5).
To a solution of 1-decyne 8500 mg, 3.61 mmol) in 3.6 mL
of toluene was added bis-triisopropylsilyl disul®de 1
81.44 g, 3.81 mmol) followed by Pd8PPh3)4 8200 mg,
0.18 mmol). The solution was stirred at 908C overnight
and then cooled to rt. After evaporation to dryness, the
product was puri®ed on a short pad of silica gel using
hexane to yield 1.80 g 896%) of the desired compound 5
1
as a yellow oil. H NMR 8300 MHz, CDCl3) d 6.25 8s,
1H), 2.28 8t, Jˆ7.2 Hz, 2H), 1.55 8m, 2H), 1.31 8m, 16H),
1.14 8m, 36H), 0.88 8m, 3H); 13C NMR 875 MHz, CDCl3) d
132.5, 122.9, 42.7, 31.8, 29.4, 29.2, 28.7, 28.5, 22.6, 18.5,
18.3, 14.0, 13.9, 12.7;HRMS calcd for C 28H60S2Si21H1:
517.3753. Found: 517.3753.
4.2.7. Acetic acid 10,11-bis-triisopropylsilanylsulfanyl-
undec-10-enyl ester ,11). To a solution of 10-undecyn-1-yl

5746
Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
acetate 8720 mg, 3.66 mmol) in 3.7 mL of toluene was
added disul®de 81.53 g, 4.04 mmol) followed by
To a solution of 3-hexyne 82.4 mL, 21.1 mmol) in 6 mL of
toluene was added disul®de 1 84.0 g, 10.6 mmol) followed
by Pd8PPh3)4 8610 mg, 0.53 mmol). The mixture was stirred
at 1308C for 15 h. Puri®cation on a short pad of silica gel
using hexane afforded 3.52 g 872%) of compound 16 as a
1
Pd8PPh3)4 8200 mg, 0.18 mmol). Puri®cation on a short
pad of silica gel using 2% ethyl acetate in hexane afforded
1.75 g 883%) of the desired compound 11 as an orange oil.
1H NMR 8500 MHz, CDCl3) d 6.25 8s, 1H), 4.05 8t, Jˆ
6.8 Hz, 2H), 2.28 8t, Jˆ7.3 Hz, 2H), 2.04 8s, 3H), 1.59 8m,
4H), 1.28 8m, 16H), 1.13 8m, 36H); 13C NMR 8125 MHz,
CDCl3) d 171.1, 132.4, 123.1, 64.5, 42.7, 29.4, 29.3, 29.2,
28.7, 28.5, 28.4, 25.8, 20.9, 18.5, 18.3, 13.9, 12.6;HRMS
calcd for C31H64O2S2Si21H1: 588.3886. Found: 588.3888.
1
light yellow oil. H NMR 8500 MHz, CDCl3) d 2.36 8q,
Jˆ7.4 Hz, 4H), 1.31 8m, 6H), 1.11 8m, 42H); 13C NMR
8125 MHz, CDCl3) d 137.5, 32.4, 18.7, 13.8, 13.2;HRMS
calcd for C24H52S2Si21H1: 461.3127. Found: 461.3128.
4.2.13. 3-[2-Cyclohex-1-enyl-2-,2-methoxycarbonyl-ethyl-
sulfanyl)-vinylsulfanyl]-propionic acid methyl ester ,17).
To a solution of compound 8 8520 mg, 1.10 mmol) in
2.4 mL of toluene:DMF 81:1) at 08C, was added methyl-3-
iodopropionate 8575 mg, 2.71 mmol) or methyl 3-bromo-
propionate 8450 mg, 2.71 mmol) followed by solid TBAF
8700 mg, 2.71 mmol). The solution was stirred 1 h at 08C
and then quenched with ammonium acetate 825%), washed
with water and brine. The organic phase was dried over
MgSO4, ®ltered and evaporated to dryness. Flash chroma-
tography using 20% ethyl acetate in hexane, afforded
220 mg 860%) of the title compound 17 when 3-iodopropio-
4.2.8. 10,11-Bis-triisopropylsilanylsulfanyl-undec-10-enoic
acid methyl ester ,12). To a solution of methyl-10-unde-
cynoate 8954 mg, 4.86 mmol) in 4.8 mL of toluene was
added disul®de
1 81.99 g, 5.25 mmol) followed by
Pd8PPh3)4 8278 mg, 0.24 mmol). Puri®cation on a short
pad of silica gel using 2% ethyl acetate in hexane afforded
1.73 g 860%) of the desired compound 12. 1H NMR
8300 MHz, CDCl3) d 6.25 8s, 1H), 3.66 8s, 3H), 2.28 8m,
4H), 1.57 8m, 4H), 1.29 8m, 14H), 1.12 8m, 36H); 13C NMR
875 MHz, CDCl3) d 174.0, 132.4, 122.9, 51.2, 42.6, 33.9,
29.1, 28.9, 28.5, 28.4, 24.8, 18.4, 18.2, 13.8, 12.6;HRMS
calcd for C30H62O2S2Si21H1: 574.3730. Found: 574.3729.
1
nate was used as electrophile. H NMR 8300 MHz, CDCl3)
d 6.43 8s, 1H), 6.15 8m, 1H), 3.66 8s, 3H), 3.64 8s, 3H), 2.97
8t, Jˆ7.4 Hz, 2H), 2.81 8t, Jˆ7.6 Hz, 2H), 2.64 8t, Jˆ7.4 Hz,
2H), 2.51 8t, Jˆ7.6 Hz, 2H), 2.14 8m, 4H), 1.64 8m, 2H),
1.53 8m, 2H); 13C NMR 875 MHz, CDCl3) d 172.4, 171.9,
134.4, 131.8, 131.5, 126.8, 51.8, 51.6, 35.4, 34.5, 28.8, 28.1,
26.7, 25.7, 22.7, 22.1;HRMS calcd for C 16H24O4S21H1:
345.1194. Found: 345.1196.
4.2.9. 10,11-Bis-triisopropylsilanylsulfanyl-undec-10-en-
1-ol ,13). To a solution of 10-undecyn-1-ol 8816 mg,
4.85 mmol) in 4.8 mL of toluene was added disul®de 1
82.00 g, 5.41 mmol) followed by Pd8PPh3)4 8270 mg,
0.24 mmol). Puri®cation on a short pad of silica gel using
8% ethyl acetate in hexane afforded 1.44 g 854%) of the title
compound 13. 1H NMR 8500 MHz, CDCl3) d 6.25 8s, 1H),
3.63 8t, Jˆ6.6 Hz, 2H), 2.28 8t, Jˆ7.3 Hz, 2H), 1.56 8m,
4H), 1.29 8m, 16H), 1.13 8m, 36H); 13C NMR 8100 MHz,
CDCl3, at 320 K) d 133.1, 123.1, 63.0, 42.9, 32.9, 29.5,
29.4, 28.8, 28.7, 25.8, 18.6, 18.4, 14.1, 12.9;HRMS calcd
for C29H62OS2Si21H1: 546.3781. Found: 546.3780.
4.2.14. 2-[2-Cyclohex-1-enyl-2-,2-oxo-2-phenyl-ethylsul-
fanyl)-vinylsulfanyl]-1-phenyl-ethanone ,18). Following
the procedure used for compound 17;to a solution of
8
8500 mg, 1.03 mmol) in 2 mL of toluene/DMF 81:1) at
08C was added 2-bromoacetophenone 8513 mg, 2.58
mmol) and solid TBAF 8675 mg, 2.58 mmol). After puri®-
cation by ¯ash chromatography using 2% ethyl acetate in
toluene, 295 mg 870%) of the desired compound 18 was
obtained. 1H NMR 8300 MHz, CDCl3) d 7.93 8d, Jˆ
7.5 Hz, 2H), 7.79 8d, Jˆ7.5 Hz, 2H), 7.55±7.31 8m, 6H),
6.59 8s, 1H), 6.14 8m, 1H), 3.95 8s, 2H), 3.87 8s, 2H), 2.05
8m, 4H), 1.57 8m, 2H), 1.47 8m, 2H); 13C NMR 875 MHz,
CDCl3) d 194.6, 193.9, 135.6, 134.7, 133.6, 133.4, 132.9,
131.7, 131.0, 128.6, 128.5, 128.4, 128.2, 127.4, 38.7, 38.3,
26.3, 25.6, 22.5, 21.8;HRMS calcd for C 24H24O2S21H1:
409.1296. Found: 409.1296.
4.2.10. 2,3-Bis-triisopropylsilanylsulfanyl-but-2-ene ,14).
To a solution of 2-butyne 81.65 mL, 21.1 mmol) in 6 mL of
toluene was added disul®de 1 84.0 g, 10.6 mmol) followed
by Pd8PPh3)4 8610 mg, 0.53 mmol). The mixture was stirred
at 1008C for 15 h. Puri®cation on a short pad of silica gel
using hexane afforded 2.31 g 850%) of the desired
compound 14 as a yellow oil. 1H NMR 8300 MHz,
CDCl3) d 2.12 8s, 6H), 1.30 8m, 6H), 1.16 8m, 36H); 13C
NMR 875 MHz, CDCl3) d 129.8, 26.4, 18.6, 13.8;HRMS
calcd for C22H48S2Si21H1: 433.2814. Found: 433.2814.
4.2.15. 2-Cyclohex-1-enyl-[1,4]dithiepin-6-one ,19).
Following the procedure used for compound 17;to a solu-
tion of 8 8700 mg, 1.44 mmol) in 2.8 mL of toluene/DMF
81:1) at 08C was added 1,3-dibromoacetone 8373 mg,
1.73 mmol) and solid TBAF 8943 mg, 3.61 mmol). Puri®-
cation by ¯ash chromatography using 40% toluene in hex-
ane afforded 110 mg 834%) of the desired compound 19. 1H
NMR 8300 MHz, CDCl3) d 6.21 8s, 1H), 6.14 8s, 1H), 4.04
8s, 2H), 3.94 8s, 2H), 2.17 8m, 4H), 1.67 8m, 2H), 1.57 8m,
2H); 13C NMR 875 MHz, CDCl3) d 200.3, 137.0, 135.7,
127.7, 114.1, 39.9, 37.9, 27.4, 25.7, 22.7, 21.8;HRMS
calcd for C11H14OS21H1: 227.0564. Found: 227.0565.
4.2.11. 2,3-Bis-triisopropylsilanylsulfanyl-hex-2-ene ,15).
To a solution of 2-hexyne 82.1 mL, 18.5 mmol) in 5.3 mL of
toluene was added disul®de 1 83.51 g, 9.24 mmol) followed
by Pd8PPh3)4 8534 mg, 0.46 mmol). The mixture was stirred
at 1308C for 15 h. Puri®cation on a short pad of silica gel
using hexane afforded 1.79 g 842%) of the desired
compound 15 as an orange oil. 1H NMR 8500 MHz,
CDCl3) d 2.34 8m, 2H), 2.13 8s, 3H), 1.57 8m, 2H), 1.31
8m, 6H), 1.13 8m, 36H), 0.92 8t, Jˆ7.7 Hz, 3H); 13C NMR
8125 MHz, CDCl3) d 134.7, 131.4, 41.9, 26.1, 21.6, 18.7,
18.6, 13.9, 13.8, 13.7;HRMS calcd for C 24H52S2Si21H1:
461.3127. Found: 461.3128.
4.2.16. 1-[2-,2-Hydroxy-hex-5-enylsulfanyl)-dec-1-enyl-
sulfanyl]-hex-5-en-2-ol ,20). To a solution of 5 890 mg,
4.2.12. 3,4-Bis-triisopropylsilanylsulfanyl-hex-3-ene ,16).

Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
5747
0.17 mmol) in 0.34 mL of toluene/acetonitrile 81:1) was
added 1,2-epoxy-5-hexene 848 mg, 0.44 mmol) and cesium
acetate 884 mg, 0.44 mmol). The mixture was heated at
708C for 2 h then cooled to rt. The reaction was diluted
with ethyl acetate, washed with ammonium acetate 825%),
water and brine. The organic phase was then dried over
MgSO4, ®ltered and evaporated. After puri®cation by ¯ash
chromatography with 20% ethyl acetate in hexane, 48 mg
871%) of compound 20 was obtained as a 1:1 diastereomeric
brine. The organic phase was dried over MgSO4, ®ltered
and evaporated to dryness. Puri®cation by ¯ash chroma-
tography using 2% ethyl acetate in hexane afforded
405 mg 865%) of the desired compound 23. 1H NMR
8300 MHz, CDCl3) d 6.07 8s, 1H), 4.13 8m, 4H), 2.73 8t,
Jˆ7.1 Hz, 4H), 2.46 8dd, Jˆ7.3, 9.0 Hz, 4H), 2.24 8t,
Jˆ7.6 Hz, 2H), 2.00±1.83 8m, 4H), 1.49 8m, 2H), 1.25
8m, 16H), 0.88 8t, Jˆ6.5 Hz, 3H); 13C NMR 875 MHz,
CDCl3) d 172.9, 172.7, 131.9, 127.3, 60.2, 60.1, 36.6,
33.0, 32.7, 32.5, 31.7, 30.4, 29.2, 29.1, 28.8, 28.4, 25.4,
24.9, 22.5, 14.1, 13.9;HRMS calcd for C 22H40O4S21H1:
433.2446. Found: 433.2448.
1
mixture. H NMR 8400 MHz, CDCl3) d 6.18 8s, 1H), 5.82
8m, 2H), 5.02 8m, 4H), 3.69 8m, 1H), 3.55 8m, 1H), 3.31 8d,
Jˆ2.3 Hz, 0.5H), 3.05 8m, 1H), 2.92 8m, 2H), 2.66 8m,
1.5H), 2.49 8m, 1H), 2.21 8m, 6H), 1.55 8m, 6H), 1.25 8m,
10H), 0.87 8t, Jˆ6.8 Hz, 3H); 13C NMR 875 MHz, CDCl3)
characteristic peaks are: d 138.0, 137.9, 137.8, 133.0, 132.2,
130.0, 129.8, 114.9, 114.8, 114.7, 70.1, 69.6, 68.9, 68.5;
HRMS calcd for C22H40O2S21H1: 401.2548. Found: 401.
2546.
4.2.20. 2-[2-,2-Hydroxy-ethylsulfanyl)-dec-1-enylsulfanyl]-
ethanol ,24). Following the procedure used for compound
23;to a solution of 1-decyne 8200 mg, 1.45 mmol) in
1.5 mL of toluene was added disul®de 1 8575 mg, 1.52
mmol) and Pd8PPh3)4 884 mg, 0.07 mmol). After 15 h, the
reaction mixture was diluted with 1.5 mL of DMF followed
by the addition of 2-iodoethanol 8282 mL, 3.62 mmol) and
cesium acetate 8694 mg, 3.62 mmol). Puri®cation by ¯ash
chromatography using 60% ethyl acetate in hexane afforded
283 mg 867%) of the desired compound 24. Mp: 41.38C. 1H
NMR 8300 MHz, CDCl3) d 6.22 8s, 1H), 3.77 8t, Jˆ5.7 Hz,
2H), 3.65 8t, Jˆ5.5 Hz, 2H), 2.84 8m, 4H), 2.24 8t, Jˆ
7.5 Hz, 2H), 1.52 8m, 2H), 1.27 8m, 10H), 0.88 8t, Jˆ
6.6 Hz, 3H); 13C NMR 875 MHz, CDCl3) d 132.5, 129.6,
61.3, 60.1, 36.9, 36.6, 34.6, 31.7, 29.2, 29.1, 28.8, 28.4,
22.5, 14.0;HRMS calcd for C 14H28O2S21H1: 293.1609.
Found: 293.1608.
4.2.17. 1-[2-,2-Methylsulfanyl-benzene)-dec-1-enylsul-
fanyl]-methyl-benzene ,21). Following the procedure
used for compound 20;to a solution of 5 8500 mg,
0.97 mmol) in 2 mL of toluene/DMF 81:1) was added
benzyl bromide 8345 mL, 2.90 mmol) or benzyl chloride
8239 mL, 2.90 mmol) and cesium acetate 8464 mg,
2.42 mmol). After ¯ash chromatography using 20% toluene
in hexane, 280 mg 875%) of compound 21 was isolated
1
when benzyl bromide was used as electrophile. H NMR
8300 MHz, CDCl3) d 7.25 8m, 10H), 6.06 8s, 1H), 3.87 8s,
4H), 2.08 8t, Jˆ7.2 Hz, 2H), 1.36 8m, 2H), 1.21 8m, 10H),
0.87 8t, Jˆ6.9 Hz, 3H); 13C NMR 875 MHz, CDCl3) d
138.0, 137.9, 132.7, 128.7, 128.6, 128.4, 128.2, 127.3,
127.0, 126.8, 37.9, 37.6, 35.9, 31.8, 29.2, 29.1, 28.8, 28.2,
22.6, 14.0;HRMS calcd for C 24H32S21H1: 385.2024.
Found: 387.2023.
4.2.21. 2-Octyl-6,7-dihydro-5H-[1,4]dithiepine ,25). To a
solution of 1-decyne 8200 mg, 1.45 mmol) in 1.5 mL of
toluene was added disul®de 1 8575 mg, 1.52 mmol) and
Pd8PPh3)4 884 mg, 0.07 mmol). The mixture was heated at
908C overnight then cooled to rt. The reaction was diluted
with 9.4 mL of THF, cooled to 08C and 1,3-diiodopropane
8185 mL, 1.59 mmol) followed by TBAF 83.6 mL, 3.6
mmol, 1.0 M/THF) were added. After 1 h at 08C, the reac-
tion was diluted with ethyl acetate, washed with ammonium
acetate 825%), water and brine. The organic phase was dried
over MgSO4, ®ltered and evaporated to dryness. Puri®cation
by ¯ash chromatography using hexane afforded 249 mg
4.2.18. 1,2-Bis-propylsulfanyl-dec-1-ene ,22). Following
the procedure used for compound 20;to a solution of
5
8800 mg, 1.55 mmol) in 3 mL of toluene/acetonitrile 81:1)
was added 1-iodopropane 8377 mL, 3.87 mmol) or 1-bromo-
propane 8422 mL, 4.64 mmol) and cesium acetate 8742 mg,
3.87 mmol). After ¯ash chromatography using 10% toluene
in hexane, 326 mg 873%) of compound 22 was obtained
1
1
when 1-iodopropane was used as electrophile. H NMR
869%) of compound 25. H NMR 8300 MHz, CDCl3) d
8300 MHz, CDCl3) d 6.04 8s, 1H), 2.67 8t, Jˆ7.3 Hz, 4H),
2.24 8t, Jˆ7.5 Hz, 2H), 1.49±1.72 8m, 6H), 1.28 8m, 10H),
1.05 8t, Jˆ7.3 Hz, 6H), 0.88 8t, Jˆ7.0 Hz, 3H); 13C NMR
875 MHz, CDCl3) d 131.9, 126.8, 36.8, 36.0, 33.2, 31.7,
29.3, 29.1, 28.8, 28.4, 23.5, 23.2, 22.5, 13.9, 13.3, 13.1;
HRMS calcd for C16H32S21H1: 289.2024. Found:
289.2023.
5.82 8s, 1H), 3.36 8m, 4H), 2.14 8m, 4H), 1.47 8m, 2H),
1.27 8m, 10H), 0.88 8t, Jˆ6.8 Hz, 3H); 13C NMR 8100
MHz, CDCl3) d 137.8, 115.1, 40.5, 31.7, 31.5, 31.4, 29.2,
29.1, 28.7, 28.6, 22.5, 14.0;HRMS calcd for C 13H24S21H1:
245.1398. Found: 245.1398.
4.2.22. 2,2-Dimethyl-thiopropionic acid S-[1-,2,2-di-
methyl-propionylsulfanylmethylene)-nonyl] ester ,27).
To a solution of compound 5 8249 mg, 0.48 mmol) in
1.2 mL of toluene at 08C was added pivaloyl chloride
8130 mL, 1.06 mmol) followed by TBAF 81.2 mL, 1.2
mmol, 1.0 M/THF). The mixture was stirred at 08C for
1 h, diluted with ethyl acetate, washed with ammonium
acetate 825%), water, bicarbonate and brine. The organic
phase was then dried over MgSO4, ®ltered and evaporated.
Puri®cation by ¯ash chromatography using 30% toluene in
hexane afforded 125 mg 870%) of the desired compound 27
as a yellow oil. 1H NMR 8300 MHz, CDCl3) d 7.18 8s, 1H),
2.41 8t, Jˆ7.3 Hz, 2H), 1.52 8m, 2H), 1.26 8m, 28H), 0.88 8t,
4.2.19. 4-[2-,3-Ethoxycarbonyl-propylsulfanyl)-dec-1-
enylsulfanyl]-butyric acid ethyl ester ,23). To a solution
of 1-decyne 8200 mg, 1.45 mmol) in 1.5 mL of toluene was
added disul®de 1 8575 mg, 1.52 mmol) and Pd8PPh3)4
884 mg, 0.07 mmol). The solution was stirred at 908C over-
night and cooled to rt. The reaction mixture was diluted with
1.5 mL of DMF followed by the addition of ethyl 4-bromo-
butyrate 8518 mL, 3.62 mmol) and cesium acetate 8694 mg,
3.62 mmol). The reaction was stirred at 708C for 2 h and
cooled to rt. After dilution with ethyl acetate, the solution
was washed with ammonium acetate 825%), water and

5748
Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
Jˆ6.1 Hz, 3H); 13C NMR 875 MHz, CDCl3) d 202.2, 202.0,
131.2, 128.4, 47.1, 46.6, 39.3, 31.8, 29.3, 29.1, 28.9, 28.0,
27.2, 27.1, 22.6, 14.0;HRMS calcd for C 20H36O2S21H1:
373.2235. Found: 373.2237.
202.1, 135.5, 128.1, 47.8, 47.1, 46.6, 31.8, 27.2, 27.1, 26.2,
25.9;HRMS calcd for C 18H30O2S21H1: 343.1765. Found:
343.1765.
4.2.27. 2,2-Dimethyl-thiopropionic acid S-[1-cyclohex-1-
enyl-2-,2,2-dimethyl-propionylsulfanyl)-vinyl] ester ,32).
Following the procedure used for compound 27;to a solu-
tion of 8 8296 mg, 0.61 mmol) in 1.5 mL of toluene at
2238C was added pivaloyl chloride 8180 mL, 1.46 mmol)
followed by TBAF 81.5 mL, 1.5 mmol, 1.0 M/THF). After
¯ash chromatography using 50% toluene in hexane, 114 mg
4.2.23. 3,3-Dimethyl-thiobutyric acid S-[1-,3,3-dimethyl-
butyrylsulfanylmethylene)-nonyl] ester ,28). Following
the procedure used for compound 27;to a solution of
5
8200 mg, 0.39 mmol) in 1 mL of toluene at 2238C was
added t-butyl acetyl chloride 8130 mL, 0.93 mmol) followed
by TBAF 81.0 mL, 1.0 mmol, 1.0 M/THF). After ¯ash
chromatography using 20% toluene and 1% ethyl acetate
in hexane, 137 mg 887%) of compound 28 was obtained.
1H NMR 8500 MHz, CDCl3) d 7.23 8s, 1H), 2.45 8s, 4H),
2.41 8t, Jˆ6.9 Hz, 2H), 1.50 8m, 2H), 1.26 8m, 10H), 1.07 8s,
9H), 1.03 8s, 9H), 0.88 8t, Jˆ7.1 Hz, 3H); 13C NMR
8125 MHz, CDCl3) d 193.6, 193.5, 130.9, 128.3, 56.9,
56.5, 39.2, 31.9, 31.8, 31.7, 29.6, 29.3, 29.1, 28.9, 28.0,
22.6, 14.1;HRMS calcd for C 22H40O2S21H1: 401.2548.
Found: 401.2546.
1
855%) of compound 32 was obtained as a yellow oil. H
NMR 8500 MHz, CDCl3) d 7.45 8s, 1H), 6.17 8m, 1H),
2.35 8m, 2H), 2.15 8m, 2H), 1.72 8m, 2H), 1.57 8m, 2H),
1.31 8s, 9H), 1.25 8s, 9H); 13C NMR 8125 MHz, CDCl3) d
202.0, 201.8, 135.1, 129.7, 127.9, 127.3, 47.2, 46.6, 27.2,
27.1, 26.2, 25.9, 22.6, 21.8;HRMS calcd for
C18H28O2S21H1: 341.1609. Found: 341.1609.
4.2.28. 2,2-Dimethyl-thiopropionic acid S-[2-,2,2-
dimethyl-propionylsulfanyl)-1-ethyl-but-1-enyl]
ester
,33). Following the procedure used for compound 27;to a
solution of 16 8305 mg, 0.65 mmol) in 1.6 mL of toluene at
2238C was added pivaloyl chloride 8190 mL, 1.56 mmol)
and TBAF 81.6 mL, 1.6 mmol, 1.0 M/THF). After ¯ash
chromatography using 4% toluene in hexane, 140 mg
4.2.24. 4-Methyl-thiobenzoic acid S-[1-,4-methylphenyl-
sulfanylmethylene)-nonyl] ester ,29). Following the
procedure used for compound 27;to a solution of
5
8207 mg, 0.41 mmol) in 1 mL of toluene at 2238C was
added p-toluoyl chloride 8125 mL, 0.93 mmol) followed
by TBAF 81.0 mL, 1.0 mmol, 1.0 M/THF). After ¯ash
chromatography using 3% ethyl acetate in hexane 152 mg
1
868%) of compound 33 was obtained as a colorless oil. H
NMR 8500 MHz, CDCl3) d 2.52 8q, Jˆ7.5 Hz, 4H), 1.24 8s,
18H), 1.11 8t, Jˆ7.5 Hz, 6H); 13C NMR 8125 MHz, CDCl3)
d 204.2, 141.4, 46.8, 29.0, 27.3, 13.2;HRMS calcd for
C16H28O2S21H1: 317.1609. Found: 317.1608.
1
886%) of compound 29 was obtained. H NMR 8500 MHz,
CDCl3) d 7.92 8d, Jˆ8.2 Hz, 2H), 7.82 8d, Jˆ8.2 Hz, 2H),
7.56 8s, 1H), 7.25 8d, Jˆ8.0 Hz, 2H), 7.23 8d, Jˆ8.1 Hz,
2H), 2.57 8t, Jˆ7.4 Hz, 2H), 2.41 8s, 3H), 2.37 8s, 3H),
1.61 8m, 2H), 1.28 8m, 10H), 0.87 8t, Jˆ7.1 Hz, 3H); 13C
NMR 8125 MHz, CDCl3) d 187.2, 186.9, 144.7, 144.6,
134.0, 133.7, 131.0, 129.3, 129.1, 127.7, 127.4, 39.5, 31.8,
29.3, 29.1, 28.9, 28.1, 22.6, 21.6, 21.6, 14.0;HRMS calcd
for C26H32O2S21H1: 441.1922. Found: 441.1924.
4.3. General procedure for the preparation of 1,3-dithiol-
2-one
4.3.1. 4-Cyclohexyl-[1,3]dithiol-2-one ,35). To a solution
of 7 8350 mg, 0.63 mmol) in 1.4 mL of toluene at 08C was
added phenyl chlorothiolformate 891 mL, 0.68 mmol)
followed by TBAF 81.6 mL, 1.6 mmol, 1.0 M/THF). The
mixture was stirred 1 h, diluted with ethyl acetate and
washed with ammonium acetate 825%), water and brine.
The organic phase was then dried over MgSO4, ®ltered
and evaporated. The compound was isolated by ¯ash
chromatography using 25% toluene and 1% ethyl acetate
in hexane to yield 95 mg 875%) of 35 as a yellow oil
4.2.25. Thioacetic acid S-,2-acetylsulfanyl-2-cyclohexyl-
vinyl) ester ,30). Following the procedure used for
compound 27;to a solution of 7 8306 mg, 0.63 mmol) in
1.5 mL of toluene at 2788C was added acetyl chloride
8105 mL, 1.48 mmol) and TBAF 81.5 mL, 1.5 mmol,
1.0 M/THF). After ¯ash chromatography using 4% ethyl
acetate in hexane, 93 mg 857%) of compound 30 was
1
1
which was identical to an authentic sample by H and 13C
obtained. H NMR 8300 MHz, DMSO-d6) d 7.18 8s, 1H),
NMR.7
2.39 8s, 3H), 2.37 8s, 3H), 2.25 8m, 1H), 1.72 8m, 4H), 1.63
8m, 1H), 1.32±1.11 8m, 5H); 13C NMR 8100 MHz, DMSO-
d6, at 325 K) d 196.4, 195.7, 140.4, 132.7, 51.9, 36.5, 35.5,
35.2, 30.6, 30.4;HRMS calcd for C 12H18O2S21H1:
259.0826. Found: 259.0827.
4.3.2. 4-Cyclohex-1-enyl-[1,3]dithiol-2-one ,36). Follow-
ing the procedure used for compound 35;to a solution of 8
8461 mg, 0.95 mmol) in 2.3 mL of toluene at 2238C, was
added phenyl chlorothiolformate 8138 mL, 1.02 mmol)
followed by TBAF 82.3 mL, 2.3 mmol, 1.0 M/THF). The
compound was isolated by ¯ash chromatography using
50% toluene in hexane to yield 121 mg 861%) of compound
36 as a white solid which was identical to an authentic
4.2.26. 2,2-Dimethyl-thiopropionic acid S-[1-cyclohexyl-
2-,2,2-dimethyl-propionylsulfanyl)-vinyl] ester ,31).
Following the procedure used for compound 27;to a solu-
tion of 7 8260 mg, 0.53 mmol) in 1.3 mL of toluene at
2238C was added pivaloyl chloride 8150 mL, 1.23 mmol)
followed by TBAF 81.3 mL, 1.3 mmol, 1.0 M/THF). After
¯ash chromatography using 40% toluene in hexane, 141 mg
1
sample by H and 13C NMR.7
4.3.3. 4-Octyl-[1,3]dithiol-2-one ,37). Following the pro-
cedure used for compound 35;to a solution of 5 8404 mg,
0.77 mmol) in 1.9 mL of toluene at 08C was added phenyl
chlorothiolformate 8115 mL, 0.85 mmol) followed by
TBAF 81.9 mL, 1.9 mmol, 1.0 M/THF). The compound
1
877%) of compound 31 was obtained as a colorless oil. H
NMR 8500 MHz, CDCl3) d 7.26 8s, 1H), 2.21 8m, 1H), 1.87
8m, 2H), 1.76 8m, 2H), 1.65 8m, 1H), 1.29 8s, 9H), 1.27 8m,
5H), 1.23 8s, 9H); 13C NMR 8125 MHz, CDCl3) d 202.4,

Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
5749
was isolated by ¯ash chromatography using 30% toluene in
hexane to yield 111 mg 863%) of compound 37 as a yellow
¯ash chromatography using 2% ethyl acetate in hexane to
afford 100 mg 856%) of the desired compound 42.
1
oil which was identical to an authentic sample by H- and
13C NMR.7
Method B: To a solution of 7 8343 mg, 0.62 mmol) in
1.4 mL of toluene at 08C was added phenyl chlorothiono-
formate 895 mL, 0.68 mmol) followed by TBAF 81.6 mL,
1.6 mmol, 1.0 M/THF). The mixture was stirred for 1 h at
08C then diluted with ethyl acetate and washed with
ammonium acetate 825%), water and brine. The organic
phase was dried over MgSO4, ®ltered and evaporated to
dryness. After ¯ash chromatography using 30% toluene
and 1% ethyl acetate in hexane, 126 mg 894%) of compound
42 was obtained as an orange solid. Mp: 64±658C. 1H NMR
8500 MHz, CDCl3) d 6.64 8s, 1H), 2.59 8m, 1H), 1.98 8m,
2H), 1.84 8m, 2H), 1.74 8m, 1H), 1.35 8m, 4H), 1.22 8m, 1H);
13C NMR 875 MHz, CDCl3) d 213.3, 154.7, 120.4, 41.0,
33.8, 25.9, 25.4. Elemental analysis calcd for C9H12S3: C,
49.95;H, 5.59;S, 44.46. Found: C, 49.89;H, 5.51;S, 44.47.
4.3.4. 4-t-Butyl-[1,3]dithiol-2-one ,38). Following the
procedure used for compound 35;to a solution of
9
8454 mg, 0.98 mmol) in 2.4 mL of toluene at 08C, was
added phenyl chlorothiolformate 8148 mL, 1.1 mmol)
followed by TBAF 82.5 mL, 2.5 mmol, 1.0 M/THF). The
compound was isolated by ¯ash chromatography using
30% toluene in hexane to yield 150 mg 888%) of compound
38 as a yellow oil which was identical to an authentic
1
sample by H and 13C NMR.7
4.3.5. 4,5-Dimethyl-[1,3]dithiol-2-one ,39).8 Following the
procedure used for compound 35;to a solution of 14
8505 mg, 1.15 mmol) in 2.9 mL of toluene at 2238C, was
added phenyl chlorothiolformate 8175 mL, 1.27 mmol)
followed by TBAF 82.9 mL, 2.9 mmol, 1.0 M/THF). The
compound was puri®ed by ¯ash chromatography using
40% toluene in hexane to yield 121 mg 871%) of compound
4.4.2. 4-Cyclohex-1-enyl-[1,3]dithiole-2-thione ,43).
Following method A, with compound
8 8430 mg,
0.88 mmol), thiophosgene 882 mL, 1.06 mmol) and TBAF
82.0 mL, 2.0 mmol, 1.0 M/THF) in 2.2 mL of toluene,
111 mg 859%) of compound 43 was obtained after ¯ash
chromatography using 2% ethylacetate in hexane. Follow-
ing method B, with compound 8 8250 mg, 0.52 mmol),
phenyl chlorothionoformate 878 mL, 0.57 mmol) and
TBAF 81.3 mL, 1.3 mmol, 1.0 M/THF) in 1.3 mL of
toluene, 98 mg 889%) of compound 43 was obtained as a
orange solid. Mp: 107±1088C. 1H NMR 8300 MHz, CDCl3)
d 6.71 8s, 1H), 5.95 8t, Jˆ4.0 Hz, 1H), 2.28 8m, 2H), 2.21
8m, 2H), 1.74 8m, 2H), 1.64 8m, 2H); 13C NMR 875 MHz,
CDCl3) d 212.3, 148.5, 131.2, 129.4, 119.5, 26.1, 25.8, 22.1,
21.5;HRMS calcd for C 9H10S31H1: 215.0023. Found:
215.0023.
1
39. Mp: 44.5±45.28C. H NMR 8500 MHz, CDCl3) d 2.15
8s, 6H); 13C NMR 8125 MHz, CDCl3) d 192.2, 122.8, 13.8;
HRMS calcd for C5H6OS21H1: 146.9938. Found:
146.9939.
4.3.6. 4-Methyl-5-propyl-[1,3]dithiol-2-one ,40). Follow-
ing the procedure used for compound 35;to a solution of 15
8400 mg, 0.87 mmol) in 2.2 mL of toluene at 2238C, was
added phenyl chlorothiolformate 8129 mL, 0.95 mmol) and
TBAF 82.2 mL, 2.2 mmol, 1.0 M/THF). The compound was
puri®ed by ¯ash chromatography using 40% toluene in
hexane to yield 102 mg 867%) of compound 40 as a yellow
1
oil. H NMR 8300 MHz, CDCl3) d 2.52 8t, Jˆ7.4 Hz, 2H),
2.15 8s, 3H), 1.58 8m, 2H), 0.97 8t, Jˆ7.3 Hz, 3H); 13C NMR
8125 MHz, CDCl3) d 192.3, 128.8, 122.6, 30.4, 23.3, 13.8,
4.4.3. 4-Octyl-[1,3]dithiole-2-thione ,44). Following
method A, with compound 5 8500 mg, 0.97 mmol),
thiophosgene 888 mL, 1.16 mmol) and TBAF 82.2 mL,
2.2 mmol, 1.0 M/THF) in 2.4 mL of toluene, 138 mg
858%) of compound 44 was obtained after ¯ash chroma-
tography using 2% ethyl acetate in hexane. Following
method B, with compound 5 8305 mg, 0.59 mmol), phenyl
chlorothionoformate 888 mL, 0.64 mmol) and TBAF
81.5 mL, 1.5 mmol, 1.0 M/THF) in 1.4 mL of toluene,
120 mg 888%) of compound 44 was obtained as an orange
13.4;HRMS calcd for C H10OS21H1: 175.0251. Found:
175.0251.
7
4.3.7. 4,5-Diethyl-[1,3]dithiol-2-one ,41). Following the
procedure used for compound 35;to a solution of 16
8398 mg, 0.86 mmol) in 2.2 mL of toluene at 2238C, was
added phenyl chlorothiolformate 8130 mL, 0.95 mmol)
followed by TBAF 82.2 mL, 2.2 mmol, 1.0 M/THF). The
compound was puri®ed by ¯ash chromatography using
20% toluene in hexane to yield 61 mg 840%) of compound
41. 1H NMR 8500 MHz, CDCl3) d 2.57 8q, Jˆ7.5 Hz, 4H),
1.19 8t, Jˆ7.5 Hz, 6H); 13C NMR 8125 MHz, CDCl3) d
1
oil. H NMR 8300 MHz, CDCl3) d 6.64 8s, 1H), 2.61 8t,
Jˆ7.5 Hz, 2H), 1.61 8m, 2H), 1.27 8m, 10H), 0.89 8t, Jˆ
6.7 Hz, 3H); 13C NMR 875 MHz, CDCl3) d 213.5, 148.5,
122.0, 31.6, 31.2, 29.7, 29.0, 28.9, 28.7, 22.5, 14.0;HRMS
calcd for C11H18S31H1: 247.0649. Found: 247.0648.
192.3, 129.6, 22.0, 14.9;HRMS calcd for C H10OS21H1:
7
175.0251. Found: 175.0251.
4.4.4. Side-product ,50). Following method B, with
compound 5 8400 mg, 0.77 mmol), phenyl chlorothiono-
formate 8235 mL, 1.72 mmol) and TBAF 81.9 mL,
1.9 mmol, 1.0 M/THF) in 1.9 mL of toluene, 140 mg
871%) of compound 44 was obtained and 48 mg 812%) of
the title compound 50 as a yellow oil. 1H NMR 8400 MHz,
CDCl3) d 7.53 8s, 1H), 7.42 8m, 4H), 7.33 8m, 2H), 7.11 8m,
4H), 2.62 8t, Jˆ7.4 Hz, 2H), 1.65 8m, 2H), 1.26 8m, 10H),
0.87 8t, Jˆ6.6 Hz, 3H); 13C NMR 8100 MHz, CDCl3) d
209.1, 208.4, 154.3, 154.2, 134.7, 133.8, 129.6, 129.6,
126.8, 126.8, 122.0, 121.9, 39.0, 31.8, 29.3, 29.2, 28.9,
4.4. General procedure for the preparation of 1,3-dithiol-
2-thione
4.4.1. 4-Cyclohexyl-[1,3]dithiole-2-thione ,42). Method A:
To a solution of 7 8400 mg, 0.82 mmol) in 2 mL of toluene
at 08C was added thiophosgene 869 mL, 0.91 mmol)
followed by TBAF 81.9 mL, 1.9 mmol, 1.0 M/THF). The
mixture was stirred 1 h at 08C then diluted with ethyl
acetate. The organic phase was washed with ammonium
acetate 825%), water, brine and dried over MgSO4. After
evaporation to dryness, the compound was puri®ed by

5750
Y. Gareau et al. / Tetrahedron 57 .2001) 5739±5750
28.1, 22.6, 14.1;HRMS calcd for C 24H28O2S41H1:
477.1050. Found: 477.1049.
4.4.8. 4,5-Diethyl-[1,3]dithiole-2-thione ,48). Following
method B, with compound 16 8410 mg, 0.89 mmol), phenyl
chlorothionoformate 8144 mL, 1.04 mmol) and TBAF
82.2 mL, 2.2 mmol, 1.0 M/THF) in 2.2 mL of toluene at
2238C, 60 mg 835%) of compound 48 was obtained as a
yellow oil after ¯ash chromatography using 3% ethyl
4.4.5. 4-t-Butyl-[1,3]dithiole-2-thione ,45). Following
method A, with compound 9 8687 mg, 1.49 mmol), thio-
phosgene 8136 mL, 1.79 mmol) and TBAF 81.5 mL,
1.5 mmol, 1.0 M/THF) in 3.7 mL of toluene, 145 mg
851%) of compound 45 was obtained after ¯ash chroma-
tography using 2% ethyl acetate in hexane. Following
method B, with compound 9 8450 mg, 0.99 mmol), phenyl
chlorothionoformate 8150 mL, 1.11 mmol) and TBAF
82.5 mL, 2.5 mmol, 1.0 M/THF) in 2.5 mL of toluene,
161 mg 885%) of compound 45 was obtained as an orange
solid. Mp: 86±878C. 1H NMR 8300 MHz, CDCl3) d 6.65 8s,
1H), 1.34 8s, 9H); 13C NMR 875 MHz, CDCl3) d 213.6,
1
acetate in hexane. H NMR 8500 MHz, CDCl3) d 2.62 8q,
Jˆ7.5 Hz, 4H), 1.22 8t, Jˆ7.5 Hz, 6H); 13C NMR 8125
MHz, CDCl3) d 211.7, 141.6, 21.8, 15.2;HRMS calcd for
C7H10S31H1: 191.0023. Found: 191.0023.
References
1. 8a) Rane, A. M.;Miranda, E. I.;Soderquist, J. A. Tetrahedron
Lett. 1994, 35, 3225. 8b) Cristau, H. J.;Chabaud, B.;
Labaudiniere, R.;Christol, H. J. Org. Chem. 1986, 51, 875.
8c) Murahashi, S.;Yamamura, M.;Yanagisawa, K.;Mita, N.;
Kondo, K. J. Org. Chem. 1979, 44, 2408. 8d) Arnould, J. C.;
Didelot, M.;Cadilhac, C.;Pasquet, M. J. Tetrahedron Lett.
1996, 37, 4523. 8e) Foa, M.;Santi, R.;Garavaglia, F.
J. Organomet. Chem. 1981, 206, C29±C32. 8f) BaranÄano, D.;
Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 2937. 8g) Mann, G.;
BaranÄano, D.;Hartwig, J. F.;Rheingold, A. L.;Guzei, I. A.
J. Am. Chem. Soc. 1998, 120, 9205.
159.5, 120.0, 36.8, 30.9;HRMS calcd for C H10S31H1:
7
191.0023. Found: 191.0023.
4.4.6. 4,5-Dimethyl-[1,3]dithiole-2-thione ,46).9 Follow-
ing method A, with compound 14 8300 mg, 0.69 mmol),
thiophosgene 864 mL, 0.83 mmol) and TBAF 81.6 mL,
1.6 mmol, 1.0 M/THF) in 1.7 mL of toluene, 42 mg 838%)
of compound 46 was obtained after ¯ash chromatography
using 2% ethyl acetate in hexane. Following method B, with
compound 14 8500 mg, 1.15 mmol), phenyl chlorothiono-
formate 8176 mL, 1.27 mmol) and TBAF 82.9 mL,
2.9 mmol, 1.0 M/THF) in 2.9 mL of toluene at 2238C,
145 mg 878%) of compound 46 was obtained as a yellow
solid after ¯ash chromatography using 40% toluene in
hexane. Mp: 88±908C. 1H NMR 8300 MHz, CDCl3) d
2.18 8s, 6H); 13C NMR 875 MHz, CDCl3) d 211.5, 134.7,
13.2;HRMS calcd for C 5H6S31H1: 162.9710. Found:
162.9710.
2. 8a) Dubois, M. R. Chem. Rev. 1989, 89, 1. 8b) Kondo, T.;
Mitsudo, T. Chem. Rev. 2000, 100, 3205.
3. 8a) Kano, K.;Takeuchi, M.;Hashimoto, S.;Yoshida, Z. Chem.
Lett. 1990, 1381. 8b) Antebi, S.;Alper, H. Tetrahedron Lett.
1985, 26, 2609. 8c) Kuniyasu, H.;Ogawa, A.;Miyazaki, S.;
Ryu, I.;Kambe, N.;Sonoda, N. J. Am. Chem. Soc. 1991, 113,
9796.
4. Gareau, Y.;Orellana, A. Synlett 1997, 803.
5. Brady, W. T. Tetrahedron 1981, 37, 2949.
6. 8a) Newman, M. S.;Arkell, A.;Fukunaga, T. J. Am. Chem. Soc.
1960, 82, 2498. 8b) Rodd, E. H. The Chemistry of Carbon
Compounds, Vol. 1;Elsevier: Amsterdam, 1951 8527pp).
4.4.7. 4-Methyl-5-propyl-[1,3]dithiole-2-thione ,47).
Following method B, with compound 15 8404 mg,
0.88 mmol), phenyl chlorothionoformate 8132 mL, 0.96
mmol) and TBAF 82.2 mL, 2.2 mmol, 1.0 M/THF) in
2.2 mL of toluene at 2238C, 105 mg 863%) of compound
47 was obtained as a yellow oil after ¯ash chromatography
Â
8c) Marko, I.;Ronsmans, B.;Hesbain-Frisque, A.;Dumas, S.;
Ghosez, L. J. Am. Chem. Soc. 1985, 107, 2192.
7. Gareau, Y.;Beauchemin, A. Heterocycles 1998, 48, 2003.
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Soc. 1983, 105, 4519.
1
using 40% toluene in hexane. H NMR 8500 MHz, CDCl3)
d 2.52 8t, Jˆ7.5 Hz, 2H), 2.18 8s, 3H), 1.98 8t, Jˆ7.3 Hz,
3H), 1.61 8m, 2H); 13C NMR 8125 MHz, CDCl3) d 211.7,
140.8, 134.5, 30.2, 23.5, 13.4, 13.3;HRMS calcd for
C7H10S31H1: 191.0023. Found: 191.0023.
9. Merlic, C. A.;Baur, A.;Tantillo, D. J.;Brown, S. E.
Commun. 1999, 29, 2953.
Synth.