Synthesis of cyclic sulfides and allylic sulfides by phenylsulfanyl (PhS-) migration of β-hydroxy sulfides

Article abstract of DOI:10.1039/a905497e

New routes to cyclic and spirocyclic sulfides involve aldol reactions of dithioesters or chemoselective Mitsunobu reactions of 1,/i-diols to give 2-hydroxyalkyl sulfides with a terminal SH group. Treatment with acid gives unrearranged cyclic sulfides, or by rearrangement with PhS-migration, spirocyclic thiolanes and allylic sulfides in almost quantitative yield. We comment on the effect of the chain length on the mode of cyclisation and on the surprising differences between an OH group and an SH group as nucleophile towards an episulfonium ion. The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a905497e

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Synthesis of cyclic sulfides and allylic sulfides by phenylsulfanyl
(PhS-) migration of ꢀ-hydroxy sulfides
Jason Eames*ab and Stuart Warren*a
a University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW
b Department of Chemistry, Queen Mary and Westfield College, Mile End Road,
London, UK E1 4NS
Received (in Cambridge, UK) 8th July 1999, Accepted 19th August 1999
New routes to cyclic and spirocyclic sulfides involve aldol reactions of dithioesters or chemoselective Mitsunobu
reactions of 1,n-diols to give 2-hydroxyalkyl sulfides with a terminal SH group. Treatment with acid gives
unrearranged cyclic sulfides, or by rearrangement with PhS-migration, spirocyclic thiolanes and allylic sulfides
in almost quantitative yield. We comment on the effect of the chain length on the mode of cyclisation and on
the surprising differences between an OH group and an SH group as nucleophile towards an episulfonium ion.
In the preceding paper,1 we have reported the type of cyclisation
observed in the acid-catalysed rearrangement of a series of
1,n-diols (n = 2 to 12) with an PhS group adjacent to one alco-
hol to give single compounds (either rearranged cyclic ethers,
unrearranged cyclic ethers or allylic sulfides) in quantitative
yield. Intramolecular capture of episulfonium ions with oxy-
gen2 nucleophiles such as alcohols3 and esters,4 to give stereo-
specifically spirocyclic ethers and lactones is well documented.
Slightly less is known about the use of the more basic nitrogen5
nucleophiles such as amines and sulfonamides to give spiro-
cyclic amines.6 For example, treatment of the β-hydroxy sulfide
anti-1 with TMSOTf in CH2Cl2 gives the episulfonium ion 2
which is captured intramolecularly at the most substituted end
to give the spirocyclic amine anti-3 in essentially quantitative
yield (Scheme 1). This type of 1,2-PhS migration occurs stereo-
Scheme 1 Reagents and conditions: a, TMSOTf, CH2Cl2, Ϫ78 ЊC.
Scheme 2
specifically with inversion of configuration at the migratory
terminus.7
problem was overcome using a masked sulfanyl equivalent
We were interested in extending this cyclisation procedure to
the synthesis of cyclic sulfides and now report the successful use
of a sulfanyl (SH) group as an intramolecular nucleophile8 for
the capture of an episulfonium ion such as 5. The three distinct
products from the rearrangement of the thiol 4 are the spiro-
cyclic sulfide type A (formed with PhS migration by the
hybrid (n ϩ 5)-endo–(n ϩ 4)-exo-tet cyclisation) disfavoured by
Baldwin’s rule,9 the unrearranged cyclic sulfide of type B
from the pure (n ϩ 3)-tet cyclisation (where the position of the
PhS group remains unchanged) and the allylic sulfide type C,
formed by a [1,2]-PhS shift without cyclisation (Scheme 2).
Initial attempts to form the thiol 4, n = 1 by conversion of the
a primary OH group to an SH group by activation and dis-
placement proved fruitless; in some cases chemoselective activ-
ation of the primary OH group promoted [1,4]-PhS migration
and the formation of allylic sulfides1,10,11 (by treatment with
TsCl in pyridine) and in others oxetanes12 (under Ziram
mediated Mitsunobu reaction conditions).13 However, this
(dithioester) as we supposed that reduction of such dithioesters
as 8 would give the required thiol 4, n = 1. These thiols were
eventually synthesised by an aldol reaction with dithioester
enolates.14 Formation of the colourless lithium enolate of
the yellow ethyl dithioester 6 (Fluka 43795) by treatment with
n-BuLi at Ϫ78 ЊC and reaction with the aldehydes 7a–c gave the
corresponding yellow dithioesters 8a–c in good yield as shown
in Table 1. For successful reduction of 8a–c, slow reverse
addition of the dithioesters 8a–c to a solution of LiAlH4 in ether
was required to prevent a reverse aldol reaction. The thiol 4,
n = 1, and the related thiols 9 and 10 were prepared in a reason-
able chemical yield (Scheme 3).
Rearrangement of these thiols 4, n = 1, 9 and 10 with either
TsOH or with TMSOTf in CH2Cl2 gave the type A rearranged
spirocyclic sulfides 11, 12 and 13 in near quantitative yield
(Table 1) via the disfavoured hybrid 6-endo–5-exo-tet cyclisation
(Scheme 4). This mode of cyclisation to form other spirocyclic
heterocycles such as ethers and amines by similar methods is
J. Chem. Soc., Perkin Trans. 1, 1999, 2783–2790
This journal is © The Royal Society of Chemistry 1999
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Table 1 Yields in the synthesis and rearrangement of the thiols 4, n = 1, 9 and 10
Reaction → aldol
Aldehyde
LiAlH4
Thiols
TsOH
TMSOTf
7
R
R
Dithioesters
Spirocyclic sulfides
7a
7b
7c
–(CH2)5–
–(CH2)4–
Me
8a
8b
8c
93%
82%
78%
4, n = 1
99%
83%
79%
11
12
13
99%
99%
98%
99%
99%
98%
9
Me
10
Table 2 Indentification of thiolanes and thiane by 1H NMR and mass spectra
δ/ppm or J/Hz
or mass spectrum
(abundance)
Thiolanes
Thiane
19
11
12
13
18
δ Ha
3.33 (dd)
5.4
10.8
3.64 (dd)
5.2
8.3
3.40 (dd)
5.7
11.6
3.60 (t)
6.9
6.9
2.59 (dd)
2.7
12.0
Jsyn Ha
Janti Ha
191.1 (PhSC6H10)
M Ϫ 191.5
M Ϫ SPh
0%
0%
100%
—
—
100%
—
—
100%
90%
80%
100%
100%
60%
100%
Scheme 3
common.4,6 The 1H NMR spectra of these compounds includes
a double doublet for Ha with surprisingly dissimilar coupling
constants (see Table 2). A more reliable method for determining
which product type was formed was observed from the mass
spectra; the PhSC2H3 group is the base peak, which is character-
istic for rearranged heterocycles of product type A.1
Acid-catalysed rearrangement of the intermediate dithioester
8a gave the spirocyclic thiolactone 15 in 85% yield by simple
hydrolysis of the thionium ion 14. In the 13C NMR spectrum
the C᎐O group appears at δ 205 ppm, which is characteristic of
Scheme 4 Reagents and conditions: a, TsOH, CH2Cl2, reflux; b,
TMSOTf, CH2Cl2, Ϫ78 ЊC.
᎐
C
these thiolactones. Conversely, for dithiocarboxylic esters (such
as ethyl dithioacetate 6) the C᎐S group surprisingly appears at a
96480)13 to give the dithiocarbamates 17, n = 2, 3 and 4 in excel-
lent yield (Table 3). Subsequent reduction (LiAlH4) gave the
longer chain length thiols 4, n = 2, 3 and 4. These thiols 4, n = 2,
3 and 4 were subjected to our standard TsOH rearrangement
conditions4 and these results are presented in Scheme 5. The
thiol 4, n = 2 rearranged exclusively to the thiolane 18 (type
B) in 99% yield, via a pure 5-exo-tet cyclisation (favoured by
Baldwin’s rules).9 The 1H NMR spectrum of 18 included a trip-
let (J = 6.9 Hz) for Ha which is typical for a five-membered
ring,4 as Jgem = Jsyn = Janti (Table 2). The coupling constants in
the spirocyclic thiolanes 11 (type A) are not like this. In the
mass spectrum, fragmentation between the thiolane and the
᎐
much lower field (δC 250 ppm). Spirocyclic sulfides of this type
are not well known, and some have been synthesised by an alkyl
migration in a pinacol rearrangement15 to give 1-thiaspiro[4.4]-
nonanes (e.g. 12), but the same route to the 1-thiaspiro[4.5]-
decane (e.g. 11) is very low yielding. Alternatively, we have syn-
thesised this type of sulfide using [1,4]-SBn participation and
debenzylation.16
The longer chain thiols 4, n = 2, 3 and 4 were synthesised
from the corresponding diols 16, n = 3, 4 and 5 using a chemo-
selective Mitsunobu displacement of the primary alcohol
involving Ziram (zinc dimethyldithiocarbamate, Fluka
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Scheme 5 Reagents and conditions: a, Ziram, DEAD, PPh3, toluene; b, LiAlH4, Et2O; c, TsOH, CH2Cl2, reflux.
Table 3 Yields in the synthesis and rearrangement of the thiols 4, n = 2, 3 and 4
Reaction → Mitsunobu
LiAlH4
Thiols
TsOH
Sulfides
Diols
Dithiocarbamate
16; n = 2
16; n = 3
16; n = 3
17; n = 2
17; n = 3
17; n = 3
85%
83%
90%
4; n = 2
4; n = 3
4; n = 3
76%
75%
69%
18
19
20
99%
99%
98%
Table 4 Yields in the synthesis of allylic sulfide 20 and 22, n = 2 and 3
C6H10SPh group is observed; which is characteristic of this
product type (Table 2).1
Reaction → TsOH
With longer chain length thiol 4, n = 3, acid-catalysed
rearrangement gave the thiane 19, of product type B in near
quantitative yield, via a pure 6-exo-tet cyclisation.1,2 In contrast
to 11 and 18, the thiane 19 has a double doublet for Ha
with typical six-membered ring axial–axial (12 Hz) and axial–
equatorial (2.7 Hz) couplings. In the mass spectrum, fragmen-
tation between the thiane and the C6H10SPh group is again
observed (Table 2). However, in contrast, when the chain length
was even longer 4, n = 4, rearrangement gave the allylic sulfide
20 (of product type C) in near quantitative yield. The chain
length now appears to be too long for efficient cyclisation, and
elimination is now preferred, as the alternative would have been
the unfavourable thiepine.
LiAlH4
Allylic sulfides/
Dithiocarbamate
Allylic sulfides/
thiols 22
Dithiocarbamate
17; n = 2
17; n = 3
17; n = 3
21; n = 2
21; n = 3
21; n = 3
95%
97%
96%
22; n = 2
22; n = 3
20
82%
76%
69%
carbamate functionality serves as a protection against this type
of acid-catalysed cyclisation. Reduction of these allylic dithio-
carbamates 21, n = 2, 3 and 4 gave the allylic sulfides 20 and 22,
n = 2 and 3 of product type C in good yield (Table 4). Allylic
sulfides of this type have potential in [2,3]-sigmatropic
rearrangements of the corresponding sulfoxides and sulfonium
salts.17
However, the alternative product allylic sulfide 20 and 22,
n = 2 and 3 (type C) from the rearrangement of thiols 8 was be
obtained from the same starting materials 17, simply by revers-
ing the order of the reduction and the rearrangement as shown
in Scheme 6. Acid-catalysed rearrangement of these dithiocar-
Conclusion
The acid-catalysed rearrangement of thiols 4, n = 1, 2, 3 and 4
and the corresponding diols 16,1 are broadly rather similar.
However, one example is quite different: rearrangement of thiol
4, n = 2 gave the thiolane 18 of type B, whereas the diol 16, n = 2
gave the tetrahydropyran 25 of type A by attack at the more
substituted end of the episulfonium ion 24 via a hybrid 6-endo–
5-exo-tet cyclisation;1,2 both reactions occur in quantitative
yield. The alternative type B tetrahydrofuran 26 can be pre-
pared by simple ether formation (TsCl–pyridine) from the
original diol (Scheme 7).1,2 However, this tetrahydrofuran 26
does rearrange under the acid-catalysed reaction conditions
(TsOH in CH2Cl2) to give the type A THP 25 in quantitative
yield. Clearly, the THP 25 is the thermodynamic product of the
cyclisation of diol 16, n = 2, whereas the THF 26 has been
shown to be the kinetic product—albeit in a 67:33 ratio 26:25
(determined from the decomposition of a cyclic sulfite).18 Inter-
estingly, the much less basic thiolane 18 does not rearrange to
the thermodynamically preferred thiane (type A) in acid and
must be the kinetic product.
Scheme 6 Reagents and conditions: a, TsOH, CH2Cl2, reflux; b,
LiAlH4, Et2O.
bamates 17, n = 2, 3 and 4 gives the allylic dithiocarbamates 21,
n = 2, 3 and 4 by a simple [1,2]-SPh shift without cyclisation.
Participation by the C᎐S group would require the formation of
a medium ring heterocyclic intermediate and so it is less effi-
cient than that of a dithioester in 8a. Consequently, the dithio-
In the kinetically controlled cyclisations with SH as a nucleo-
phile, it appears that Baldwin’s rules9 are more important and
the 5-exo-tet is more efficient, than when OH is the nucleophile,
᎐
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(3 × 40 ml). The combined organic extracts were dried (MgSO4)
and evaporated under reduced pressure. The residue was puri-
fied by flash chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (1:1) to give the thiol 4, n = 1 (80
mg, 99%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (1:1)]
0.55; νmax (film, CDCl3)/cmϪ1 1580 (SPh); δH(400 MHz, CDCl3)
7.67–7.30 (5 H, m, SPh), 3.42 (1 H, dd, J 9.2 and 2.9, CHOH),
3.04 (1 H, s, OH), 2.84–2.75 (1 H, m, CHAHBSH), 2.59–2.54
(1 H, m, CHAHBSH), 2.03–1.15 (12 H, m, 6 × CH2) and 1.34
(1 H, t, J 4.2, SH); δC(100 MHz, CDCl3) 137.3 (m-SPh), 130.1*
(i-SPh), 129.1 (p-SPh), 128.9 (o-SPh), 73.3 (CHOH), 61.3*
(CSPh), 35.1* (CH2-SH), 30.8*, 30.0*, 26.2*, 22.5*, 21.9* and
21.8* (6 × CH2) (Found Mϩ, 282.1099. C15H22OS2 requires
282.1112); m/z 282.1 (65%, M), 191.1 (95, C6H11SPh), 173.1 (20,
M Ϫ SPh), 155.1 (42, M Ϫ SPh Ϫ H2O), 110.0 (100, PhS ϩ H)
and 81.1 (80, C6H11 Ϫ H).
Scheme 7 Reagents and conditions: a, TsOH, CH2Cl2, reflux.
perhaps because the greater nucleophilicity of the SH group
demands a tighter transition state. Additionally, rearrangement
of diol 16, n = 3 gave a mixture of unrearranged THP (type
B) in 59% and the allylic sulfide (type C) in 13% yield,1,10 while
the thiol 4, n = 3 exclusively gave the type B thiane 19 in near
quantitative yield.
4-Hydroxy-4-[1Ј-(phenylsulfanyl)cyclohexyl]-1-sulfanylbutane
44, n ؍ 2
LiAlH4 (74 mg, 1.98 mmol) was added to a stirred solution of
the dithiocarbamate 17, n = 2 (0.25 mg, 0.66 mmol) in ether (5
ml) at 0 ЊC. The solution was stirred for 12 hours and poured
onto ice–brine. NaOH (2 ml, 10%) was added and the solution
was extracted with ether (3 × 50 ml). The combined organic
extracts were dried (MgSO4) and evaporated under reduced
pressure. The residue was purified by flash chromatography on
silica gel eluting with light petroleum (40–60 ЊC)–ether (1:1) to
give the thiol 4, n = 2 (0.19 g, 76%) as an oil; Rf [light petroleum
(40–60 ЊC)–ether (1:1)] 0.8; νmax (film, CDCl3)/cmϪ1 3200 (OH);
δH(400 MHz, CDCl3) 7.55–7.25 (5 H, m, SPh), 3.23 (1 H, dd,
J 10.0 and 2.2, CHOH), 3.08 (1 H, d, J 2.2, OH), 2.51 (1 H, q,
J 7.2, CHAHBS), 2.50 (1 H, q, J 7.2, CHAHBS), 2.04–1.16 (14 H,
m, 7 × CH2) and 1.30 (1 H, t, J 7.61); δC(100 MHz, CDCl3)
137.2 (m-SPh), 130.1* (i-SPh), 129.0 (o-SPh), 128.8 (p-SPh),
74.3 (CHO), 61.8* (CSPh), 31.7* (CH2S), 30.6*, 29.6*, 29.2*,
26.2*, 24.7*, 21.8* and 21.8* (7 × CH2) (Found Mϩ, 296.1265.
C16H24OS2 requires M, 296.1268); m/z 296.1 (95%, M), 191.1
(100, C6H10SPh), 110.0 (70, PhSH) and 81.1 (55, C6H9).
In conclusion, we have shown that the shortest chain thiols 4,
n = 1 cyclise to form spirocyclic sulfides 11 of type A, and the
intermediate chain length n = 2 gives the unrearranged type B
cyclic sulfides 18. Clearly five-membered ring formation in both
cases is favoured over other ring sizes (four and six). However,
six-membered ring formation becomes favoured (to give un-
rearranged thiane 19 of type B) over the alternative more
strained seven-membered thiepines of type A. However, allylic
sulfides 20 of type C are formed when the chain length n is too
long for efficient cyclisation. The dithiocarbamates 17, n = 2,3
and 4 also gave the allylic sulfide 21, n = 2, 3 and 4 without
cyclisation as the dithiocarbamate functionality serves as a
protection against cyclisation.
Experimental
All solvents were distilled before use. Tetrahydrofuran (THF)
and ether were freshly distilled from LiAlH4, whilst dichloro-
methane (CH2Cl2) and toluene were freshly distilled from
CaH2. Triphenylmethane was used as the indicator for THF.
n-BuLi was titrated against diphenylacetic acid before use.
All reactions were carried out under nitrogen using oven-
dried glassware. Flash column chromatography was carried
out using Merck Kieselgel 60 (230–400 mesh). Thin layer
chromatography (TLC) was carried out on commercially avail-
able pre-coated plates (Merck Kieselgel 60F254 silica). Proton
and carbon NMR spectra were recorded on a Bruker WM 200,
WM 250 or WM400. Fourier transform spectrometers were
used with an internal deuterium lock. Chemical shifts are
quoted in parts per milllion downfield from tetramethylsilane.
Carbon NMR spectra were recorded with broad proton
decoupling and Attached Proton Test (ATP). The symbol *
after the carbon shift indicates an even number of attached
protons; i.e., CH2 or quaternary carbons. The symbols i-, o-,
m- and p- denote the ipso-, ortho-, meta- and para- positions
respectively for the phenyl ring (PhS group). Mass spectra were
recorded on a AEI Kratos MS30 or MS890 machine using a
DS503 data system for high resolution analysis. All compounds
were isolated using flash column chromatography and were
assumed to have a purity of greater than 98% (determined by
NMR).
5-Hydroxy-5-[1Ј-(phenylsulfanyl)cyclohexyl]-1-sulfanylpentane
4, n ؍ 3
In the same way as 4, n = 2, the dithiocarbamate 17, n = 3 (50
mg, 0.12 mmol) and LiAlH4 (14 mg, 0.37 mmol) in ether (1 ml)
gave, after column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (1:1), the thiol 4, n = 3 (29.2
mg, 75%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (1:1)]
0.65; νmax (film, CDCl3)/cmϪ1 3300 (OH); δH(400 MHz, CDCl3)
7.51–7.30 (5 H, m, SPh), 3.23 (1 H, d, J 9.4, CHOH), 3.06 (1 H,
s, OH), 2.49 (1 H, q, J 7.5, CHAHBS), 2.48 (1 H, q, J 7.5,
CHAHBS), 1.99–1.30 (16 H, m, 8 × CH2) and 1.31 (1 H, t, J 7.7,
SH); δC(100 MHz, CDCl3) 137.2 (m-SPh), 130.1* (i-SPh), 129.0
(p-SPh), 128.8 (o-SPh), 74.5 (CHOH), 61.9* (CSPh), 34.1*
(CH2S), 30.6*, 30.0*, 29.6*, 26.2*, 24.5*, 21.9* and 21.8*
(8 × CH2) (Found Mϩ, 310.1428. C17H26OS2 requires M,
310.1424); m/z 310.1 (100%, M), 201.1 (20, M Ϫ SPh), 191.1
(100, C6H10SPh), 109.0 (20, PhSH) and 81.0 (50, C6H9).
6-Hydroxy-6-[1Ј-(phenylsulfanyl)cyclohexyl]-1-sulfanylhexane
4, n ؍ 4
In the same way as 4, n = 2, the dithiocarbamate 17, n = 4 (0.35
g, 0.85 mmol) and LiAlH4 (93 mg, 2.54 mmol) in ether (5 ml)
gave, after column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (1:1), the thiol 4, n = 4 (0.19 g,
69%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (1:1)] 0.7;
νmax (film, CDCl3)/cmϪ1 3200 (OH); δH(250 MHz, CDCl3) 7.51–
7.27 (5 H, m, SPh), 3.23 (1 H, dd, J 9.3 and 2.3, CHOH), 2.50
(2 H, q, J 7.0, CH2S), 2.09–1.08 (20 H, m, 10 × CH2) and 1.31
(1 H, t, J 10.6, SH); δC(100 MHz, CDCl3) 137.2 (m-SPh), 130.2
3-Hydroxy-3-[1Ј-(phenylsulfanyl)cyclohexyl]-1-sulfanylpropane
4, n ؍ 1
A solution of dithioester dithioacetate 8a (0.1 g, 0.293 mmol) in
ether (5 ml) was slowly added to a stirred solution of LiAlH4
(34 mg, 0.91 mmol) in ether (3 ml) at 0 ЊC. The solution was
stirred for 1 hour and poured onto ice–brine. NaOH (1 ml,
10%) was added and the solution was extracted with ether
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(i-SPh), 129.0 (p-SPh), 128.8 (o-SPh), 74.6 (CHOH), 61.9*
(CSPh), 33.9* (CH2S), 30.6*, 30.45, 29.6*, 28.4*, 26.8*, 26.3*,
24.5*, 21.9* and 21.8* (10 × CH2) (Found Mϩ, 324.1594.
C18H28OS2 requires M, 324.1581); m/z 324.2 (60%, M), 215.1
(30, M Ϫ SPh), 191.1 (100, C6H10SPh), 110.0 (90, PhSH) and
81.1 (80, C6H9).
(i-SPh), 129.1 (p-SPh), 128.7 (o-SPh), 75.1 (CHOH), 55.8*
(CSPh), 53.4* (CH C᎐S), 30.9* (CH S), 24.6 (CH ), 24.42
᎐
2
2
3
(CH3) and 12.0 (CH3CH2) (Found Mϩ, 300.0678. C14H20OS3
requires M, 300.0676); m/z 300.1 (75%, M), 238.0 (50, M Ϫ CH3-
CH2SH), 191.1 (30, M Ϫ SPh), 151.1 (100, C3H6SPh) and 110.0
(30, PhSH).
3-Hydroxy-3-[1Ј-(phenylsulfanyl)cyclopentyl]-1-sulfanylpropane
9
Ethyl 3-hydroxy-3-[1Ј-(phenylsulfanyl)cyclohexyl]propanedithio-
ate 8a
In the same way as 4, n = 1, the dithioester 8b (0.11 g, 0.35
mmol) and LiAlH4 (40 mg, 1.05 mmol) in ether (5 ml) gave,
after column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (1:1), the thiol 9 (85 mg, 83%) as
an oil; Rf [light petroleum (40–60 ЊC)–ether (1:1)] 0.75; νmax
(film, CDCl3)/cmϪ1 3200 (OH) and 1550 (SPh); δH(200 MHz,
CDCl3) 7.59–7.28 (5 H, m, SPh), 3.62 (1 H, dt, J 8.4 and 5.9,
CHOH), 2.86 (1 H, d, J 6.0, OH), 2.71–2.51 (2 H, m, CH2S),
1.95–1.51 (10 H, m, 5 × CH2) and 1.38 (1 H, t, J 8.0, SH); δC(50
MHz, CDCl3) 136.8 (m-SPh), 131.7 (i-SPh), 129.0 (p-SPh),
128.8 (o-SPh), 73.4 (CHOH), 67.3 (CSPh), 36.1 (CH2), 34.8,
33.7, 24.8, 22.6 and 22.2 (5 × CH2) (Found Mϩ, 268.0953.
C14H20OS2 requires M, 268.0958); m/z 268.1 (5%, M), 177.1 (50,
C5H8SPh), 159.1 (10, M Ϫ SPh), 110.0 (100, PhSH) and 67.1
(95, C5H7).
n-BuLi (1.77 ml, 1.3 M in hexanes, 2.31 mmol) was added slow-
ly to a stirred solution of ethyl dithioacetate 6 (0.25 g, 0.26 ml,
2.1 mmol) in THF (10 ml) at Ϫ78 ЊC. The solution was stirred
for 20 min. Aldehyde 7a (0.43 g, 1.95 mmol) in THF (5 ml) was
slowly added. The solution was stirred for 30 min. Saturated
NH4Cl (5 ml) was added and the solution was allowed to warm
to room temperature and then extracted with ether (3 × 50 ml).
The combined organic extracts were dried (MgSO4) and evap-
orated under reduced pressure. The residue was purified by
flash chromatography on silica gel eluting with light petroleum
(40–60 ЊC)–ether (9:1) to give the dithioester 8a (0.35 g, 93%) as
a yellow oil; Rf [light petroleum (40–60 ЊC)] 0.27; νmax (film,
CDCl3)/cmϪ1 3400–3100 (OH) and 1100 (CS2Et); δH(400 MHz,
CDCl3) 7.58–7.27 (5 H, m, SPh), 4.03–3.98 (1 H, ddd, J 9.7, 1.5
and 3.4, CHOH), 3.66–3.62 (1 H, dd, J 14.3 and 1.4, CHAHBS),
3.29–3.24 (2 H, dq, J 12.3 and 7.5, CH2S), 3.21–3.26 (1 H, dd,
J 14.4 and 9.7, CHAHBS), 3.10–3.08 (1 H, d, J 7.5, OH), 1.91–
1.19 (10 H, m, 5 × CH2) and 1.36–1.32 (3 H, t, J 7.5, CH3);
3-Hydroxy-4-methyl-4-phenylsulfanyl-1-sulfanylpentane 10
In the same way as 4, n = 1, the dithioester 8c (0.5 g, 1.66 mmol)
and LiAlH4 (0.12 g, 3.33 mmol) in ether (20 ml) gave, after
column chromatography on silica gel eluting with light petrol-
eum (40–60 ЊC)–ether (9:1), the thiol 10 (0.31 g, 79%) as an oil;
Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.16; νmax (film,
CDCl3)/cmϪ1 3300 (OH); δH(400 MHz, CDCl3) 7.52–7.31 (5 H,
m, SPh), 3.44 (1 H, dt, J 9.8 and 2.5, CHOH), 2.95 (1 H, d,
J 2.5, OH), 279 (1 H, m, CHAHBS), 2.58 (1 H, m, CHAHBS),
1.70 (2 H, m, CH2), 1.37 (1 H, t, J 8.0, SH), 1.24 (3 H, s, CH3)
and 1.18 (3 H, s, CH3); δC(100 MHz, CDCl3) 137.4 (m-SPh),
130.2* (i-SPh), 129.2 (p-SPh), 128.8 (o-SPh), 73.5 (CHOH),
55.2* (CSPh), 35.0* (CH2S), 25.8 (CH3), 23.3* (CH2) and 22.1
(CH3) (Found Mϩ, 242.0803. C12H18OS2 requires M, 242.0799);
m/z 242.1 (32%, M), 151.1 (100, C3H6SPh) and 109.0 (30, PhS).
δ (100 MHz, CDCl ) 238.0* (C᎐S), 137.4 (m-SPh), 130.5*
᎐
C
3
(i-SPh), 129.0 (p-SPh), 128.8 (o-SPh), 76.0 (CHOH), 59.1*
(CSPh), 53.4* (CH C᎐S), 30.9*, 30.7*, 30.3*, 30.3* and 21.8*
᎐
2
(5 × CH2), 26.0* (CH2S) and 12.1 (CH3) (Found Mϩ, 340.0982.
C17H24OS3 requires M, 340.0989); m/z 340.1 (45%, M), 231.1
(75, M Ϫ SPh), 213.1 (50, M Ϫ SPh Ϫ H2O), 191.1 (90,
C6H11SPh), 83.1 (100, C6H12) and 81.1 (80, C6H10).
Ethyl 3-hydroxy-3-[1Ј-(phenylsulfanyl)cyclopentyl]propane-
dithioate 8b
In the same way as 8a, n-BuLi (2.01 ml, 1.3 M in hexanes, 2.62
mmol), ethyl dithioacetate 6 (0.28 g, 2.4 mmol) and aldehyde 7b
(0.45 g, 2.18 mmol) in THF (50 ml) gave, after column chrom-
atography on silica gel eluting with light petroleum (40–60 ЊC)–
ether (9:1), the dithioester 8b (0.58 g, 82%) as a yellow oil; Rf
[light petroleum (40–60 ЊC)] 0.30; νmax (film, CDCl3)/cmϪ1 3300
(OH) and 1120 (CS2Et); δH(400 MHz, CDCl3) 7.60–7.25 (5 H,
m, SPh), 4.03–3.98 (1 H, dd, J 9.7 and 1.9, CHOH), 3.66–3.62
(1 H, dd, J 14.2 and 1.7, CHAHBCS), 3.30–3.22 (2 H, m, CH2S),
3.21–3.26 (1 H, dd, J 14.4 and 9.8, CHAHBS), 3.15 (1 H, s, OH),
1.91–1.40 (8 H, m, 5 × CH2) and 1.36–1.32 (3 H, t, J 7.5, CH3);
4-(Phenylsulfanyl)-1-thiaspiro[4.5]decane 11
Toluene-p-sulfonic acid (6 mg, 30 µmol) was added to a stirred
solution of thiol 4; n = 1 (50 mg, 0.18 mmol) in CH2Cl2 (2 ml).
The solution was refluxed for 5 min. The solution was allowed
to cool to room temperature and filtered through a silica plug.
The solvent was removed under reduced pressure. The residue
was purified by flash column chromatography on silica gel
eluting with light petroleum (40–60 ЊC)–ether (9:1) to give the
thiolane 11 (47 mg, 99%) as an oil; Rf [light petroleum
(40–60 ЊC)–ether (9:1)] 0.34; νmax (film, CDCl3)/cmϪ1 1600
(SPh); δH(400 MHz, CDCl3) 7.47–7.20 (5 H, m, SPh), 3.35–3.29
(1 H, dd, J 10.8 and 5.4, CHSPh), 2.92–2.84 (1 H, m, CHAHBS),
2.80–2.73 (1 H, m, CHAHBS), 2.52–2.44 (1 H, m, CHAHB-
CH2S), 2.25–2.14 (1 H, m, CHAHBCH2S), 2.01–1.92 (1H, dt,
J 12.7 and 3.65, CHAHBC) and 1.72–1.20 (9 H, m, CHAHBC
and 4 × CH2); δC(100 MHz, CDCl3) 131.9 (m-SPh), 129.0
(p-SPh), 126.9 (o-SPh), 76.5* (CSCH2), 62.4 (CSPh), 39.2*
(SCH2), 35.4*, 35.0*, 30.9*, 27.4*, 25.7* and 25.6* (6 × CH2)
(Found Mϩ, 264.1004. C15H20S2 requires M, 264.1006); m/z
264.1 (35%, M), 155.1 (100, M Ϫ SPh) and 109 (15, SPh).
δ (100 MHz, CDCl ) 238.1* (C᎐S), 137.4 (m-SPh), 130.4*
᎐
C
3
(i-SPh), 129.2 (p-SPh), 128.7 (o-SPh), 76.0 (CHOH), 59.1*
(CSPh), 53.3* (CH C᎐S), 30.9*, 30.7*, 21.8* and 21.8* (4 ×
᎐
2
CH2), 26.1* (CH2S) and 12.1 (CH3); m/z 326.1 (50%, M), 217.1
(100, M Ϫ SPh), 177.1 (80, C5H8SPh).
Ethyl-3-hydroxy-4-methyl-4-phenylsulfanylpentanedithioate 8c
In the same way as 8a, n-BuLi (1.7 ml, 1.3 M in hexane, 2.21
mmol), ethyl dithioacetate 6 (0.26 g, 0.27 ml, 2.22 mmol) and
aldehyde 7c (0.4 g, 2.22 mmol) in THF (30 ml) gave, after col-
umn chromatography on silica gel eluting with light petroleum
(40–60 ЊC)–CH2Cl2 (1:1), the dithioester 8c (0.51 g, 78%) as an
oil; Rf [light petroleum (40–60 ЊC)–CH2Cl2 (1:1)] 0.4; νmax (film,
CDCl3)/cmϪ1 1050 (CS2); δH(400 MHz, CDCl3) 7.56–7.30 (5 H,
m, SPh), 4.01 (1 H, dt, 9.8 and 1.9, CHOH), 3.48 (1 H, dd,
J 14.2 and 1.6, CHAHBCS), 3.27 (2 H, m, CH2S), 3.15 (1 H, d,
J 2.7, OH), 3.11 (1 H, dd, J 14.2 and 9.7, CHAHBCS), 1.31 (3 H,
t, J 7.4, CH3CH2), 1.30 (3 H, s, CH3) and 1.26 (3 H, s, CH3);
TMSOTf mediated rearrangement of the thiol 4, n ؍ 1 to give
thiolane 11
TMSOTf (43 mg, 37 µl, 0.18 mmol) was added to a stirred
solution of thiol 4, n = 1 (50 mg, 0.18 mmol) in CH2Cl2 (5 ml) at
Ϫ78 ЊC. The solution was then allowed to warm to room tem-
perature. Saturated NH4Cl (1 ml) was added and the solution
δ (100 MHz, CDCl ) 236.0* (C᎐S), 137.6* (m-SPh), 130.5*
᎐
C
3
J. Chem. Soc., Perkin Trans. 1, 1999, 2783–2790
2787

View Article Online
was extracted with ether (3 × 10 ml). The combined organic
extracts were dried (MgSO4) and evaporated under reduced
pressure. The residue was purified by flash column chrom-
atography on silica gel eluting with light petroleum (40–60 ЊC)–
ether (1:1) to give the thiolane 11 (47 mg, 99%) as an oil; identi-
cal spectroscopically to that obtained previously.
(i-SPh), 132.7 (m-SPh), 129.3 (p-SPh), 127.9 (o-SPh), 65.6*
(CSCH ), 57.6 (CHSPh), 47.9* (CH C᎐S), 38.0*, 33.8*, 25.4*,
᎐
2
2
25.1* and 23.4* (5 × CH2); m/z 218 (4%, M Ϫ CS2), 136.0 (70,
C H SPh), 109.1 (100, PhS) and 88.0 (30, CH (C᎐S)S).
᎐
2
3
2
1-(N,N-Dimethyldithiocarbamoyl)-4-hydroxy-4-[1Ј-(phenyl-
sulfanyl)cyclohexyl]butane 17, n ؍ 2
4-(Phenylsulfanyl)-1-thiaspiro[4.4]nonane 12
DEAD (0.12 g, 0.12 ml, 0.71 mmol) was added to a stirred
solution of diol 16, n = 2 (0.1 g, 0.36 mmol), Ziram (0.22 g,
0.714 mmol) and PPh3 (0.18 g, 0.71 mmol in toluene (2 ml)).
The solution was stirred for 12 hours. The solution was filtered
through a silica plug and the solvent was removed under
reduced pressure. The residue was purified by flash column
chromatography on silica gel eluting with light petroleum (40–
60 ЊC)–ether (1:1) to give the dithiocarbamate 17, n = 2 (0.11 g,
85%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (1:1)] 0.55;
In the same way as 11, the thiol 9 (20 mg, 74.6 µmol) and
toluene-p-sulfonic acid (2.6 mg, 1.5 µmol) in CH2Cl2 (1 ml)
gave, after column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (9:1), the spirocyclic sulfide
12 (18.2 mg, 99%) as an oil; Rf [light petroleum (40–60 ЊC)–
ether (9:1)] 0.5; νmax (film, CDCl3)/cmϪ1 3300 (OH); δH(200
MHz, CDCl3) 7.47–7.23 (5 H, m, SPh), 3.64 (1 H, dd, J 8.3
and 5.1, CHSPh), 3.13–3.34 (2 H, m, CH2S), 2.54–2.37 (1 H,
m, CHAHB) and 2.26–1.64 (11 H, 10 × CH2 and CHAHB);
δC(100 MHz, CDCl3) 135.9* (i-SPh), 131.6 (m-SPh), 129.0 (o-
SPh), 126.9 (p-SPh), 66.0* (CS), 60.4 (CHSPh), 40.4*
(CH2S), 37.2*, 36.4*, 28.1*, 24.5* and 24.4* (5 × CH2)
(Found Mϩ, 250.0832. C14H18S2 requires M, 250.0849); m/z
250.1 (70%, M), 141.1 (100, M Ϫ SPh), 109.1 (80, PhS) and
67.1 (55, C5H7).
νmax (film, CDCl3)/cmϪ1 1254 (C᎐S); δ (400 MHz, CDCl ) 7.54–
᎐
H
3
7.23 (5 H, m, SPh), 3.50 (3 H, s, NCH3), 3.30 (3 H, s, NCH3),
3.28 (3 H, m, CH2S and CHO), 3.05 (1 H, d, J 2.8, OH) and
2.05–1.11 (14 H, m, 7 × CH2); δC(100 MHz, CDCl3) 197.4*
(C᎐S), 137.5 (m-SPh), 130.1* (i-SPh), 129.0 (p-SPh), 128.5
᎐
(o-SPh), 74.4 (CHOH), 61.6* (CSPh), 45.2 (NCH3), 41.4
(NCH3), 37.6* (CH2S), 30.5*, 29.8*, 29.7*, 26.6*, 26.2*, 21.8*
and 21.6* (7 × CH2) (Found (M Ϫ SPh)ϩ, 274.1297. C13H24-
OS2N requires M Ϫ SPh, 274.1299); m/z 274.1 (35%, M Ϫ
SPh), 191.1 (20, C6H10SPh), 110.0 (10, PhSH), 88.0 (100,
C3H5SN) and 81.1 (20, C6H9).
TMSOTf mediated rearrangement of the thiol 9 to give thiolane
12
In the same way as 11, the thiol 9 (20 mg, 74.6 µmol) and
TMSOTf (16.4 mg, 14 µl, 74.6 µmol) in CH2Cl2 (5 ml) gave,
after column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (9:1), the spirocyclic sulfide 12 (19
mg, 99%) as an oil; identical spectroscopically to that obtained
previously.
1-(N,N-Dimethyldithiocarbamoyl)-5-hydroxy-5-[1Ј-(phenyl-
sulfanyl)cyclohexyl]pentane 17, n ؍ 3
In the same way as 17, n = 2, the diol 16, n = 3 (0.21 g, 0.71
mmol), Ziram (0.33 g, 1.07 mmol), PPh3 (0.37 g, 1.42 mmol)
and DEAD (0.25 g, 0.23 ml, 1.42 mmol) in toluene (3 ml) gave,
after column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (1:1), the dithiocarbamate 17, n = 3
(0.23 g, 83%) as an oil; Rf [light petroleum (40–60 ЊC)–ether
(1:1)] 0.4; νmax (film, CDCl3)/cmϪ1 1275 (C᎐S); δ (400 MHz,
2,2-Dimethyl-3-(phenylsulfanyl)thiolane 13
In the same way as 11, the thiol 10 (50 mg, 0.20 mmol) and
toluene-p-sulfonic acid (3.8 mg, 20 µmol) in CH2Cl2 (1 ml) gave,
after column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (9:1), the spirocyclic sulfide 13 (49
mg, 98%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)]
0.45; νmax (film, CDCl3)/cmϪ1 broad 1580 (SPh); δH(400 MHz,
CDCl3) 7.55–7.20 (5 H, m, SPh), 3.39 (1 H, dd, J 11.6 and 5.7,
CHSPh), 2.94–2.81 (2 H, m, CH2S), 2.57–2.49 (1 H, m,
CHAHB), 2.26–2.15 (1 H, m, CHAHB), 1.48 (3 H, s, CH3) and
1.42 (1 H, m, CH3); δC(100 MHz, CDCl3) 131.9 (m-SPh), 129.0
(o-SPh), 127.0 (p-SPh), 62.2 (CHSPh), 54.0* (CSCH2), 36.1*
(CH2S), 29.3 (CH3), 27.6* (CH2) and 27.4 (CH3) (Found Mϩ,
224.0696. C12H16S2 requires M, 224.0693); m/z 224.1 (60%, M),
135.0 (10, C2H2SPh) and 115.1 (100, M Ϫ SPh).
᎐
H
CDCl3) 7.52–7.25 (5 H, m, SPh), 3.54 (3 H, s, NCH3), 3.32 (3 H,
s, NCH3), 3.29–3.19 (3 H, m, CH2S and CHOH), 3.04 (1 H, br
s, OH) and 2.02–1.19 (16 H, m, 8 × CH2); δC(100 MHz, CDCl3)
197.6* (C᎐S), 137.2 (m-SPh), 130.2* (i-SPh), 129.0 (p-SPh),
᎐
128.8 (o-SPh), 74.6 (CHOH), 61.9* (CSPh), 45.2 and 41.4
(2 × NCH3), 37.5* (CH2S), 30.6*, 30.1*, 29.6*, 28.8*, 26.7*,
26.2*, 21.9* and 21.8* (8 × CH2) (Found Mϩ, 397.1549.
C20H31OS3N requires M, 397.1567); m/z 397.2 (10%, M), 288.1
(80, M Ϫ SPh), 277.2 (10, M Ϫ S2CN(CH3)2 ϩ H), 206 (60,
M Ϫ C6H10SPh), 191.1 (100, C6H10SPh), 121.0 (75, S2CN-
(CH3)2), 109 (25, PhSH) and 81.0 (20, C6H9).
1-(N,N-Dimethyldithiocarbamoyl)-6-hydroxy-6-[1Ј-(phenyl-
sulfanyl)cyclohexyl]hexane 17, n ؍ 4
TMSOTf mediated rearrangement of the thiol 10 to give thiolane
13
In the same way as 17, n = 2, the diol 16, n = 4 (1.3 g, 4.2 mmol),
Ziram (1.92 g, 3 mmol), PPh3 (2.21 g, 8.44 mmol) and DEAD
(1.42 g, 1.32 ml, 8.44 mmol) in toluene (15 ml) gave, after
column chromatography on silica gel eluting with light petrol-
eum (40–60 ЊC)–ether (1:1), the dithiocarbamate 17, n = 4 (1.56
g, 90%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (1:1)]
In the same way as 11, the thiol 10 (0.2 g, 0.83 mmol) and
TMSOTf (0.18 mg, 0.16 ml, 0.83 mmol) in CH2Cl2 (2 ml) gave,
after column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (9:1), the thiolane 13 (0.18 g, 98%)
as an oil; identical spectroscopically to that obtained previously.
0.4; νmax (film, CDCl3)/cmϪ1 1270 (C᎐S); δ (250 MHz, CDCl )
᎐
H
3
4-(Phenylsulfanyl)-1-thiaspiro[4.5]decan-2-one 15
7.56–7.28 (5 H, m, SPh), 3.53 and 3.34 (6 H, s, 2 × NCH3), 3.25
(2 H, t, J 7.3, CH2S), 3.22 (1 H, m, CHOH), 3.07 (1 H, d, J 1.9,
OH) and 2.05–1.13 (18 H, m, 10 × CH2); δC(62.5 MHz, CDCl3)
In the same way as 11, the dithioacetate 8a (0.15 g, 0.44 mmol)
and toluene-p-sulfonic acid (17 mg, 88 µmol) in CH2Cl2 (2 ml)
gave, after column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (9:1), the spirocyclic sulfide 15
(0.12 g, 85%) as an oil; Rf [light petroleum (40–60 ЊC)–ether
(9:1)] 0.2; νmax (film, CDCl3)/cmϪ1 1150 (CS2); δH(400 MHz,
CDCl3) 7.46–7.25 (5 H, m, SPh), 3.72 (1 H, t, J 8.9, CHSPh),
2.94 (2 H, double AB quartet, J 9.0, CH2CS) and 2.19–1.20 (10
197.6* (C᎐S), 137.2 (m-SPh), 130.1* (i-SPh), 128.9 (p-SPh),
᎐
128.8 (o-SPh), 74.6 (CHOH), 61.9* (CSPh), 45.1 and 41.40
(2 × NCH3), 37.6* (CH2S), 30.6*, 30.4*, 29.6*, 29.1*, 28.5*,
27.0*, 26.2*, 21.8* and 21.8* (9 × CH2) (Found Mϩ, 411.1690.
C21H33OS3N requires M, 411.1724); m/z 411.1 (50%, M), 302.2
(30, M Ϫ SPh), 220.1 (45, M Ϫ C6H10SPh), 191.1 (50, C6H10-
SPh) and 88.0 (100, C3H5NS).
H, m, 5 × CH ); δ (100 MHz, CDCl ) 20.8* (C᎐S), 134.3*
᎐
2
C
3
2788
J. Chem. Soc., Perkin Trans. 1, 1999, 2783–2790

View Article Online
2-[1Ј-(Phenylsulfanyl)cyclohexyl]thiolane 18
5-Cyclohexenyl-5-(phenylsulfanyl)pentyl N,N-dimethyldithio-
carbamate 21, n ؍ 3
In the same way as 11, the thiol 4, n = 2 (10 mg, 33.7 µmol) and
toluene-p-sulfonic acid (1.1 mg, 6.7 µmol) in CH2Cl2 (1 ml)
gave, after column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (9:1), the thiolane 18 (9.3 mg,
99%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)]
0.6; νmax (film, CDCl3)/cmϪ1 1550 (SPh); δH(400 MHz, CDCl3)
7.53–7.27 (5 H, m, SPh), 3.56 (1 H, t, J 6.9, CHS), 2.78 (2 H, dd,
J 7.7 and 4.8, CH2S) and 2.18–1.20 (14 H, m, 7 × CH2); δC(100
MHz, CDCl3) 137.5 (m-SPh), 131.6* (i-SPh), 128.9 (p-SPh),
128.7 (o-SPh), 58.9 (CHS), 57.7* (CS), 33.2* (CH2S), 32.5*,
31.7*, 31.2*, 31.1*, 26.1*, 21.9* and 21.9* (7 × CH2) (Found
Mϩ, 278.1158. C16H22S2 requires M, 278.1162); m/z 278.1 (70%,
M), 191.1 (95, C6H10SPh), 169.1 (100, M Ϫ SPh), 87.0 (70,
M Ϫ C6H10SPh) and 81.1 (30, C6H9).
In the same way as 11, the dithiocarbamate 17, n = 3 (40 mg, 0.1
mmol) and toluene-p-sulfonic acid (3.4 mg, 20 µmol) in CH2Cl2
(1 ml) gave, after column chromatography on silica gel eluting
with light petroleum (40–60 ЊC)–ether (1:1), the allylic dithio-
carbamate 21, n = 3 (37 mg, 97%) as an oil; Rf [light petroleum
(40–60 ЊC)–ether (1:1)] 0.8; νmax (film, CDCl3)/cmϪ1 1280
(C᎐S); δ (250 MHz, CDCl ) 7.48–7.16 (5 H, m, SPh), 5.25 (1 H,
᎐
H
3
s, CH᎐C), 3.62–3.50 (4 H, m, NCH and CHSPh), 3.35 (3 H, s,
᎐
3
NCH3), 3.24 (2 H, t, J 7.1, CH2S) and 1.94–1.10 (14 H, m,
7 × CH ); δ (62.5 MHz, CDCl ) 210.0* (C᎐S), 137.0* (C᎐CH),
᎐
᎐
2
C
3
135.5* (i-SPh), 133.2 (m-SPh), 128.6 (o-SPh), 126.9 (p-SPh),
125.9 (CH᎐C), 57.1 (CSPh), 45.2 and 41.3 (2 × NCH ), 37.4*
᎐
3
(CH2S), 32.0*, 28.3*, 27.0*, 25.2*, 23.8*, 22.7* and 22.6*
(7 × CH2) (Found Mϩ, 379.1441. C20H29S3N requires M,
379.1462); m/z 379.1 (30%, M), 270.1 (70, M Ϫ SPh), 110.0 (40,
PhSH) and 88.0 (100, C3H5SN).
2-[1Ј-(Phenylsulfanyl)cyclohexyl]thiane 19
In the same way as 11, the thiol 4, n = 3 (25 mg, 80.6 µmol) and
toluene-p-sulfonic acid (3 mg, 16.1 µmol) in CH2Cl2 (1 ml) gave,
after column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (9:1), the thiane 19 (23.3 mg, 99%)
as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.75; νmax
(film, CDCl3)/cmϪ1 1580 (SPh); δH(400 MHz, CDCl3) 7.51–7.22
(5 H, m, SPh), 2.72–2.60 (2 H, m, CH2S), 2.59 (1 H, dd, J 12.0
and 2.7, CHS) and 2.00–1.23 (16 H, m, 8 × CH2); δC(100 MHz,
CDCl3) 137.7 (m-SPh), 131.5* (i-SPh), 128.7 (p-SPh), 128.5
(o-SPh), 58.3* (CSPh), 51.5 (CHS), 32.9* (CH2S), 31.8*, 30.2*,
29.2*, 27.6*, 27.4*, 25.8* and 22.0* (8 × CH2) (Found Mϩ,
292.1318. C17H25S2 requires M, 292.1319); m/z 292.1 (15%, M),
191.1 (100, C6H10SPh), 183.1 (70, M Ϫ SPh), 109.0 (10, PhSH),
109.0 (20, PhSH), 101.0 (60, M Ϫ C6H10SPh) and 81.1 (40,
C6H9).
6-Cyclohexenyl-6-(phenylsulfanyl)hexyl N,N-dimethyldithio-
carbamate 21, n ؍ 4
In the same way as 11, the dithiocarbamate 17, n = 4 (50 mg,
0.12 mmol) and toluene-p-sulfonic acid (23 mg, 0.12 mmol) in
CH2Cl2 (1 ml) gave, after column chromatography on silica gel
eluting with light petroleum (40–60 ЊC)–ether (1:1), the allylic
dithiocarbamate 21, n = 4 (45 mg, 96%) as an oil; Rf [light
petroleum (40–60 ЊC)–ether (1:1)] 0.8; νmax (film, CDCl3)/cmϪ1
3350 (OH) and 1275 (C᎐S); δ (250 MHz, CDCl ) 7.45–7.18
᎐
H
3
(5 H, m, SPh), 5.36 (1 H, br s, CH᎐C), 3.53 (3 H, s, NCH ), 3.50
᎐
3
(1 H, t, J 7.6, CHSPh), 3.35 (3 H, s, NCH3), 3.26 (2 H, t, J 7.2,
CH2S) and 2.28–1.26 (16 H, m, 8 × CH2); δC(62.5 MHz, CDCl3)
197.5* (C᎐S), 135.6* (C᎐CH), 131.14* (i-SPh), 133.0 (m-SPh),
᎐
᎐
128.7 (o-SPh), 126.8 (p-SPh), 125.4 (CH᎐C), 57.2 (CHSPh),
᎐
6-Cyclohexenyl-6-(phenylsulfanyl)-1-sulfanylhexane 20
45.2 and 41.4 (2 × CH3N), 37.5* (CH2S), 32.3*, 28.6*, 28.5*,
27.2*, 25.2*, 23.7*, 22.5* and 19.6* (8 × CH2) (Found Mϩ,
393.1614. C21H31S3N requires M, 393.1618); m/z 393.2 (20%,
M), 284.1 (40, M Ϫ PhS), 109.0 (40, PhS) and 88.0 (100,
C3H5NS).
In the same way as 11, the thiol 4, n = 4 (30 mg, 92.6 µmol) and
toluene-p-sulfonic acid (3.2 mg, 18.5 µmol) in CH2Cl2 (1 ml)
gave, after column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (9:1), the allylic sulfide 20 (27
mg, 98%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)]
0.9; νmax (film, CDCl3)/cmϪ1 1600 (SPh); δH(250 MHz, CDCl3)
4-Cyclohexenyl-4-(phenylsulfanyl)-1-sulfanylbutane 22, n ؍ 2
7.34–7.14 (5 H, m, SPh), 5.24 (1 H, br s, CH᎐C), 3.49 (1 H, t,
J 7.6, CHSPh), 2.57 (2 H, t, J 7.2, CH2S), 2.21–1.23 (16 H, m,
8 × CH2) and 1.55 (1 H, s, SH); δC(62.5 MHz, CDCl3) 135.7*
In the same way as 4, n = 2, the allylic dithiocarbamate 21, n = 2
(0.13 g, 0.38 mmol) and LiAlH4 (28 mg, 0.38 mmol) in ether
(5 ml) gave, after column chromatography on silica gel eluting
with light petroleum (40–60 ЊC)–ether (1:1), the allylic sulfide
22, n = 2 (85 mg, 82%) as an oil; Rf [light petroleum (40–60 ЊC)–
ether (9:1)] 0.8; νmax (film, CDCl3)/cmϪ1 1550 (SPh); δH(250
MHz, CDCl ) 7.46–7.25 (5 H, m, SPh), 5.25 (1 H, br s, CH᎐C),
3.48 (1 H, t, J 7.2, CHSPh), 2.52 (2 H, q, J 7.7, CH2S), 2.19–
1.24 (10 H, m, 5 × CH2) and 1.34 (1 H, t, J 7.8, SH); δC(62.5
MHz, CDCl3) 133.2* (i-SPh), 133.1* (m-SPh), 128.4 (o-SPh),
᎐
(C᎐CH), 135.6* (i-SPh), 133.1 (m-SPh), 128.3 (o-SPh), 126.8
᎐
(p-SPh), 125.4 (CH᎐C), 57.2 (CHSPh), 35.6* (CH S), 32.3*,
᎐
2
31.0*, 30.0*, 29.7*, 29.1*, 23.8*, 22.7* and 22.5* (8 × CH2)
(Found Mϩ, 306.1478. C18H26S2 requires M, 306.1475); m/z
306.1 (95%, M), 197.1 (70, M Ϫ SPh), 115.1 (20, M Ϫ C6H10-
SPh), 109.0 (20, PhS) and 81.1 (55, C6H9).
᎐
3
4-Cyclohexenyl-4-(phenylsulfanyl)butyl N,N-dimethyldithio-
carbamate 21, n ؍ 2
127.0 (p-SPh), 125.0 (CH᎐C), 56.8 (CHSPh), 32.5* (CH S),
᎐
2
31.2*, 30.9*, 25.5*, 25.2*, 23.8* and 22.6* (6 × CH2) (Found
Mϩ, 278.1145. C16H22S2 requires M, 278.1162); m/z 278.1 (10%,
M), 244.1 (65, M Ϫ H2S), 169.0 (50, M Ϫ SPh), 110.0 (50,
PhSH) and 87.0 (100, C4H7S).
In the same way as 11, the dithiocarbamate 17, n = 2 (64 mg,
0.16 mmol) and toluene-p-sulfonic acid (5.73 mg, 33.3 µmol) in
CH2Cl2 (1 ml) gave, after column chromatography on silica gel
eluting with light petroleum (40–60 ЊC)–ether (1:1), the allylic
dithiocarbamate 21, n = 2 (57.9 mg, 95%) as an oil; Rf [light
petroleum (40–60 ЊC)–ether (1:1)] 0.82; νmax (film, CDCl3)/cmϪ1
5-Cyclohexenyl-5-(phenylsulfanyl)-1-sulfanylpentane 22, n ؍ 3
In the same way as 4, n = 2, the allylic dithiocarbamate 21, n = 3
(50 mg, 0.13 mmol) and LiAlH4 (10 mg, 0.26 mmol) in ether
(5 ml) gave, after column chromatography on silica gel eluting
with light petroleum (40–60 ЊC)–ether (9:1), the allylic sulfide
22, n = 3 (29.2 mg, 76%) as an oil; Rf [light petroleum (40–
60 ЊC)–ether (9:1)] 0.78; νmax (film, CDCl3)/cmϪ1 1600 (SPh);
δH(250 MHz, CDCl3) 7.35–7.17 (5 H, m, SPh), 5.25 (1 H, br s,
1570 (SPh) and 1270 (C᎐S); δ (250 MHz, CDCl ) 7.40–7.16 (5
᎐
H
3
H, m, SPh), 5.26 (1 H, br s, CH᎐C), 3.53 (4 H, m, NCH and
᎐
3
CHSPh), 3.29 (3 H, s, NCH3), 3.26 (2 H, t, J 6.7, CH2S) and
2.20–1.41 (12 H, m, 6 × CH2); δC(100 MHz, CDCl3) 197.3*
(C᎐S), 135.3* (C᎐CH), 133.3 (m-SPh), 129.1* (i-SPh), 128.4
᎐
᎐
(o-SPh), 127.0 (p-SPh), 125.8 (CH᎐C), 56.8 (CHSPh), 45.2 and
᎐
41.4 (2 × CH3), 37.2* (CH2S), 31.6*, 26.8*, 25.2*, 23.8*, 22.7*
and 22.5* (6 × CH2) (Found Mϩ, 365.1299. C19H27S3N requires
M, 365.1305); m/z 365.1 (5%, M), 277.1 (10, M Ϫ C3H5NS),
256.1 (80, M Ϫ SPh) and 88.0 (100, C3H5NS).
CH᎐C), 3.49 (1 H, t, J 7.5, CHSPh), 2.51 (2 H, q, J 7.2, CH S)
and 2.16–1.20 (14 H, m, 7 × CH2); δC(62.5 MHz, CDCl3) 135.6*
(i-SPh), 133.2 (m-SPh), 128.4 (o-SPh), 126.9 (p-SPh), 125.6
᎐
2
(CH᎐C), 57.1 (CHSPh), 33.7* (CH S), 31.9*, 26.3*, 25.2*,
᎐
2
J. Chem. Soc., Perkin Trans. 1, 1999, 2783–2790
2789

View Article Online
24.4*, 23.8*, 22.7* and 22.5* (7 × CH2) (Found Mϩ, 292.1319.
C17H24S2 requires M, 292.1319); m/z 292.1 (70%, M), 191.1 (45,
C6H10SPh), 183.1 (M Ϫ SPh), 109.0 (20, PhS) and 87.0 (100,
C4H7S).
4 V. K. Aggarwal, I. Coldham, S. McIntyre and S. Warren, J. Chem.
Soc., Perkin Trans. 1, 1991, 451.
5 I. Coldham and S. Warren, Tetrahedron Lett., 1989, 30, 5937.
6 I. Coldham and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1993,
1637.
7 Inversion also occurs at the migratory origin, see V. K. Aggarwal,
I. Coldham, S. McIntye, F. H. Sansbury, M.-J. Villa and S. Warren,
Tetrahedron Lett., 1988, 29, 4885.
8 Preliminary communication: J. Eames, R. V. H. Jones and S.
Warren, Tetrahedron Lett., 1996, 37, 707.
9 J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 734.
10 L. Djakovitch, J. Eames, R. V. H. Jones, S. McIntyre and S. Warren,
Tetrahedron Lett., 1995, 36, 1723.
11 J. Eames, M. A. de las Heras, R. V. H. Jones and S. Warren,
Tetrahedron Lett., 1996, 37, 1117.
6-Cyclohexenyl-6-(phenylsulfanyl)-1-sulfanylhexane 20
In the same way as 4, n = 2, the dithiocarbamate 21, n = 4 (20
mg, 50 µmol) and LiAlH4 (5.6 mg, 0.15 mmol) in ether (5 ml)
gave, after column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (1:1), gave the allylic sulfide
20 (10.7 mg, 69%) as an oil; identical spectroscopically to that
obtained previously.
12 J. Eames and S. Warren, Tetrahedron Lett., 1996, 36, 3525.
13 P. Rollin, Tetrahedron Lett., 1986, 27, 4169; Synth. Commun., 1986,
16, 611.
Acknowledgements
14 A. I. Meyers and R. D. Walkup, Tetrahedron, 1985, 41, 5089.
15 L. A. Paquette, U. Dullweber and B. M. Branan, Heterocycles, 1994,
37, 189.
16 J. Eames, N. Kuhnert, R. V. H. Jones and S. Warren, Tetrahedron
Lett., 1998, 39, 1247.
We thank the EPSRC for a grant (to J. E.) and Ray V. H. Jones
(Zeneca Process Technology Department, Grangemouth) for a
CASE award (to J. E.).
17 R. C. Hartley, S. Warren and I. C. Richards, Tetrahedron Lett.,
1992, 33, 8155.
18 J. Eames, N. Kuhnert, F. H. Sansbury and S. Warren, Synlett, 1999,
1211.
References
1 L. Djakovitch, J. Eames, D. J. Fox, F. H. Sansbury and S. Warren,
J. Chem. Soc., Perkin Trans. 1, 1999, 2771.
2 F. H. Sansbury and S. Warren, Tetrahedron Lett., 1991, 28, 3425.
3 V. K. Aggarwal and S. Warren, Tetrahedron Lett., 1986, 27, 101.
Paper 9/05497I
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J. Chem. Soc., Perkin Trans. 1, 1999, 2783–2790