Novel behavior of thiiranium radical cation intermediates. Reactions of dimethyl disulfide with alkenes in the presence of Pd(OAc)2

Article abstract of DOI:10.3390/50700916

Reaction of dimethyl disulfide (1) with cyclohexene (2a) in AcOH in the presence of Pd(OAc)₂ yields trans-1-acetoxy-2-methylcyclohexane (3a). The equivalent reactions with hex-1-ene (2b) and 2-methylpent-1-ene (2c) or 1-methylcyclohex-1-ene (2d) preferentially give anti-Markovnikov and Markovnikov adducts 4 and 3, respectively, by ace-toxymethylthiolation of the alkene. The Markovnikov regioselectivity 3b/4b for the reaction with 2b (is higher than that for the reaction using AgOAc instead of Pd(OAc)₂, which proceeds via a thiiranium ion. Addition of a polar solvent (MeCN or MeNO₂) to the reactions with 2b or 2c (using Pd(OAc)₂ abnormally decreases the Markovnikov regioselectivity. The total yield of 3 and 4 increases with an increased concentration of AcOH. Compounds 3 and 4 are also formed and the reactions in MeCN or MeNO₂ not containing AcOH. A solution of Pd(OAc)₂ in 1 exhibits λ_max 380 nm (log ε 3.6) assigned to the absorption of a relatively stable sulfonium salt. These indicate that the reactions using Pd(OAc)₂ proceed by S_N2 ring-opening of a new type of thiiranium radical cations paired with ^-OAc via the sulfonium salts. The insensitivity of the 3/4 ratios to the reaction time at 25-60°C in the reactions with 2c-d shows the ring-opening to be controlled kinetically, but the increased ratio with reaction time at 116°C in the reaction with 2b suggests that the ring-opening is thermodynamically governed. The reaction product with 2d also undergoes a skeletal rearrangement to a thietanium radical cation to give 1-acetoxymethyl-2-methylthiocyclohexane.

Full text of DOI:10.3390/50700916

Molecules 2000, 5, 916-926
molecules
ISSN 1420-3049
2000 by MDPI
http://www.mdpi.org
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Novel Behavior of Thiiranium Radical Cation Intermediates.
Reactions of Dimethyl Disulfide with Alkenes in the Presence of
Pd(OAc)2
Hiroshi Takeuchi*, Junnichi Takatori and Shingo Iizuka
Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University,
Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Tel.: +81-78-803-6190, Fax: +81-78-803-6205, E-mail: takeuchi@kobe-u.ac.jp,
URL: http://www.cx.kobe-u.ac.jp/takeuchi/index.html
Received: 8 March 2000; revised form: 7 June 2000 / Accepted: 20 June 2000 / Published: 7 July 2000
Abstract: Reaction of dimethyl disulfide (1) with cyclohexene (2a) in AcOH in the presence
of Pd(OAc) yields trans-1-acetoxy-2-methylcyclohexane (3a). The equivalent reactions
2
with hex-1-ene (2b) and 2-methylpent-1-ene (2c) or 1-methylcyclohex-1-ene (2d) preferen-
tially give anti-Markovnikov and Markovnikov adducts 4 and 3, respectively, by ace-
toxymethylthiolation of the alkene. The Markovnikov regioselectivity 3b/4b for the reaction
with 2b is higher than that for the reaction using AgOAc instead of Pd(OAc) which pro-
2
,
ceeds via a thiiranium ion. Addition of a polar solvent (MeCN or MeNO ) to the reactions
2
with 2b or 2c using Pd(OAc) abnormally decreases the Markovnikov regioselectivity. The
2
total yield of 3 and 4 increases with an increased concentration of AcOH. Compounds 3 and
4
are also formed and the reactions in MeCN or MeNO not containing AcOH. A solution of
2
Pd(OAc) in 1 exhibits λ 380 nm (log ε 3.6) assigned to the absorption of a relatively sta-
2
max
ble sulfonium salt. These indicate that the reactions using Pd(OAc) proceed by S 2 ring-
2
N
−
opening of a new type of thiiranium radical cations paired with OAc via the sulfonium
salts. The insensitivity of the 3/4 ratios to the reaction time at 25-60°C in the reactions with
2
c-d shows the ring-opening to be controlled kinetically, but the increased ratio with reac-
tion time at 116°C in the reaction with 2b suggests that the ring-opening is thermodynami-
cally governed. The reaction product with 2d also undergoes a skeletal rearrangement to a
thietanium radical cation to give 1-acetoxymethyl-2-methylthiocyclohexane.
Keywords: Dimethyl disulfide, Palladium (II) acetate, Acetoxymethylthiolation, Thiiranium
radical cation, Regioselectivity for S 2 ring-opening, Solvent effects, Thietanium radical
N
cation, Skeletal rearrangement.

9
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Molecules 2000, 5
Introduction
Thiiranium ion intermediates have been generated by reactions of disulfides with alkenes in the
presence of oxidants such as Pb(OAc) [1-4], Mn(OAc) [2-4], Fe(OAc) [2-4] or Cu(OAc) [5], by re-
4
3
3
2
actions of β-thiohalides with AgY [6] and by reactions of thiiranes with RY [6]. The intermediates
−
−
−
−
−
−
which have soft counterions such as BF , PF , SbF , SbCl , FSO and CF CO behave like carbe-
4
6
6
5
3
3
2
nium ions [1] of a weakly bridged strong electrophile, undergoing a rapid ring-opening by the outer
o
nucleophile at low temperature (−20-0 C) to give the observed predominant Markovnikov regioselec-
tivity; in some cases, the skeletal rearrangement or stereoconversion of the thiiranium ions has been
observed. We may infer that the reactions of RSCl with alkenes would generate not a σ-sulfurane but a
−
strongly bridged thiiranium ion pairing tightly with hard Cl [1], and thus the ring-opening by the pair-
−
ing Cl leads to the anti-Markovnikov regioselectivity without undergoing the stereoconversion and
skeletal rearrangement.
In this work, reactions of dimethyl disulfide with 2-alkyl and 2,2-dialkylalkenes in AcOH in the
presence of Pd(OAc) lead to the anti-Markovnikov and Markovnikov regioselectivity products, re-
2
spectively, for the addition to the alkenes. Interestingly, the Markovnikov regioselectivity is lower than
that observed for thiiranium ion intermediates, and is decreased by addition of polar solvents such as
MeCN or MeNO or the nonpolar solvent n-hexane. This novel behavior can be reasonably explained
2
by considering a S 2 ring-opening mechanism of a new type of thiiranium radical cation intermediates
N
−
paired with OAc. Furthermore, the reaction with 1-methylcyclohex-1-ene yields a product via an
anionotropic rearrangement of the thiiranium radical cation intermediate to a thietanium radical cation
intermediate.
Results and Discussion
Reactions with Cyclohexene (2a)
Reaction of dimethyl disulfide (1) with cyclohexene (2a) in AcOH in the presence of Pd(OAc) pro-
2
o
duced only trans-1-acetoxy-2-methylthiocyclohexane (3a) at 25 or 116 C (Table 1). The structure of 3a
was assigned to the trans-form on accord of the fact that the mass spectra of 3a were identical with
those of the product formed by the reaction of cyclohexene oxide with MeSH in benzene (Scheme 1).
The trans-configuration shows that 3a arises from an S 2 ring-opening of a three-membered ring in-
N
o
termediate, and that the intermediate is still stable at 116 C without transforming to the corresponding
carbocation at such a high temperature.
SMe
SMe
Hydrolysis
MeSH
2
a
MeSSMe
O
Pd(OAc)2
in AcOH
in benzene
1
OAc
OH
3
a
Scheme 1.

9
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Molecules 2000, 5
Table 1. Reactions in the presence of Pd(OAc) (0.68 mmol) of dimethyl disulfide (1) (2.0 mmol) with
2
3
3
4
.8 mmol of cyclohexene (2a) and hex-1-ene (2b) in AcOH (10.0 cm ) containing Ac O (1.0 cm ).
2
o
a
Alkene
T/ C
t/h
Yield (%)
Ratio
3/4
3
69
68
4
b
b
2
2
a
a
25
116
0
24
24
-
-
-
-
2
2
2
2
2
2
2
2
2
2
b
b
b
b
b
b
b
b
b
b
2.0
4.0
2.0
24
5.6
8.8
14
16
16
13
20
17
36
76
15
24
32
37
36
29
40
23
34
17
0.37
0.37
0.44
0.43
0.44
0.45
0.50
0.74
1.1
0
25
25
25
96
60
1.0
2.0
1.0
2.0
24
60
116
116
116
4.5
a
The yields are calculated to be 100% when two moles of product is formed from one mole of
1
Pd(OAc) used, and were obtained by GLC analysis; H NMR analysis gave nearly the same results.
b
2
The trans-stereochemistry is assigned by the fact that the compound given by hydrolysis of 3a is
identical with that formed by S 2 reaction of cyclohexene oxide with MeSH in benzene.
N
Reactions with Hex-1-ene (2b)
o
The reaction with hex-1-ene (2b) at 0-60 C gave preferentially the anti-Markovnikov adduct 4b,
o
and the 3b/4b ratio was observed to increase with temperature (Table 1). The ratio at 0-60 C was al-
o
most insensitive to the reaction time whereas the ratio at 116 C was enhanced in the prolonged reaction
(
Table 1). The insensitivity of the ratio to the reaction time means that the reaction is controlled kineti-
o
o
cally at 0-60 C, but thermodynamically governed at 116 C. In fact, when a mixture of 3b/4b = 0.34
o
o
was treated in AcOH, the ratio 3b/4b at 25 C did not change for 24 h , but the ratio at 116 C increased
to 1.4 or 6.6 after 2 h or 24 h, respectively. The preferential formation of anti-Markovnikov adduct at
o
0
-60 C suggests that the kinetic S 2 ring-opening of the final three-membered ring intermediate is
N
principally affected by steric factors (Scheme 2).
Formation of Thiiranium Radical Cations II and II’ from Sulfonium Salts I and I’
From the above trans-addition, the final intermediate for the formation of the products should be
logically three membered ring intermediates. As an oxidant Pd(OAc) can act in two ways. The first
2
action is electron transfer: One electron transfer from 1 to Pd(OAc) forms a disulfide radical cation
2
[
7], and the radical cation and/or a sulfenium ion [8] arising from the radical cation should generate a
thiiranium ion as the final intermediate by attack on the alkene. As seen in Tables 1 and 4, the reaction
using Pd(OAc) shows higher Markovnikov regioselectivity (3b/4b = 0.44) at 25°C than that observed
2
at 25°C (0.27) in the reaction via a thiiranium ion [9] using AgOAc instead of Pd(OAc) . Furthermore,
2

9
19
Molecules 2000, 5
the Markovnikov regioselectivity 3/4 for the reaction using Pd(OAc) is unusually decreased on
2
dilution with a polar solvent (MeCN or MeNO ) while that using AgOAc is increased on dilution with
2
MeNO (Table 3). These data show that the reaction using Pd(OAc) does not proceed via a thiiranium
2
2
ion, and thus this action for Pd(OAc) can be ruled out. Another action is coordination. Pd(OAc)
2
2
coordinates to 1 to give sulfonium ions I and I’ (Scheme 2). The sulfonium ions undergo a homolytic
S-S scission by spontaneous or induced (by AcOH) decomposition to give MeS• and thiiranium radical
cations II and II’ which bond with the Pd atom (Scheme 2). If a heterolytic S-S scission of I and I’
occurs, then thiiranium ion intermediates should be formed by reaction with sufenium fragment. Thus,
the heterolytic scission can be excluded. Therefore, the latter action predominates and II and II’ as the
final intermediates should be formed by the homolytic S-S scission of I and I’ (Scheme 2). The
following evidence supports the fact that the products are formed via thiiranium radical cations II and
II’ from sulfonium ions I and I’.
2
3
R2
R3
R R
1
+
1
R C=CH
Pd(OAc)2
in AcOH
R @C
CH
MeS SMe OAc
2
MeS-SMe
+
OAc
1
PdOAc and Pd
S Me
I and I'
PdOAc and Pd
Dimerization
MeS
II
and II'
AcOH
AcOH
1
2
3
a: R =H; R +R = -(CH ) -
R2
R2
R3
2
4
R3
1
2
3
b: R =H; R =n-Bu; R =H
1
1
R C
CH
R C
CH
1
2
3
c: R =Me; R =n-Pr; R =H
1
2
3
SMe OAc
OAc SMe
d: R =Me; R +R = -(CH ) -
2
4
3
4
Scheme 2.
A solution containing Pd(OAc) in AcOH also containing Ac O (9.1% v/v) shows λ 397 nm (log
2
2
max
o
o
ε 2.3) at 25 C while a solution made by dissolving Pd(OAc) in 1 at 25 C has λ
380 nm (log ε 3.6).
max
2
The species with λmax 380 nm shows the half life-time ca. 30 h in 1, so that the species could not be the
+
−
unstable disulfide radical cation [7] but rather a sulfonium salt I [MeS-S (Me)PdOAc] OAc. When
different oxidants AgOAc and AlCl are dissolved in 1, we can observe the same λ 375 nm with a
3
max
very short lifetime. Thus, the species with λmax 375 nm might be the disulfide radical cation, which
would be independent of oxidative metals [7]. Considering that the intermediate using AlCl can bring
3
about an aromatic methylthiolation [7] whereas that using AgOAc is not subject to the aromatic meth-
ylthiolation but can react with alkene to form a thiiranium ion [9], we can regard the following: a very
small amount of the disulfide radical cation and a more large amount of a sulfonium ion [MeS-
+
−
S (Me)Ag] OAc (this has no visible absorption due to a σ S-Ag bond) are generated as the intermedi-
ates when AgOAc is dissolved in 1. Dissolving AlCl in 1, the disulfide radical cation is only formed
3
as the intermediate.
During the reaction of 1 with 2b using Pd(OAc) , we obtained a small amount of a dark reddish
2
-
1
−
powdery precipitate having υmax (KBr)/cm 2900 and 2980 (C-H), 1577 and 1410 (−CO ), 1050,
2
+
−
1
020, 950, 930 and 652 (C-S). This precipitate might be a sulfonium salt I’ [MeS-S (Me)Pd] OAc;
−
-1
this salt does not have OAc attached to Pd since the carbonyl of Pd(OAc) appears at ca. 1610 cm .
2

9
20
Molecules 2000, 5
Considering that one mole of product is formed from one mole of Pd(OAc) , then we observe that the
2
total yield of 3 and 4 is more than 100%. Thus, the generation of the two species I and I’ from one
mole of Pd(OAc) is reasonable.
2
The novel behavior for the reaction using Pd(OAc) instead of AgOAc (i.e. the high 3b/4b ratio us-
2
ing Pd(OAc) relative to AgOAc and the decreased 3b/4b ratio upon addition of polar solvent) as de-
2
scribed above is probably due to the higher positive charge on the C -carbon of II than that of the cor-
2
responding thiiranium ion since II contains a positive Pd atom; the effect of polar solvent is explained
below. The possibility that the final intermediate is a thiiranium dication formed by attack of thiira-
nium ion on Pd(OAc) can be excluded on account of charge-repulsion between the positive species on
2
the attack.
Reactions with 2-Methylpent-1-ene (2c)
The reaction with 2-methylpent-1-ene 2c gave the Markovnikov regioselectivity exhibiting 3c/4c of
ca. 1.8 at 0-60°C, and the ratio was almost insensitive to reaction time (Table 2). The time-insensitivity
reflects the product stability, and means that the ring-opening of the intermediates IIc and II’c is con-
trolled kinetically. The Markovnikov regioselectivity indicates that the ring-opening of IIc and II’c is
o
mostly governed electronically. The reaction with 2c at 116 C is described below.
Table 2. Reactions of dimethyl disulfide 1 (2.0 mmol) with 2-methylpent-1-ene 2c and
3
1
-methylcylohex-1-ene 2d of 4.8 mmol in the presence of Pd(OAc) (0.68 mmol) in AcOH (10 cm )
2
3
containing Ac O (1.0 cm ).
2
o
a
Alkene
T/ C
t/h
Yield (%)
Ratio
3/4
1.8
1.8
1.8
2.0
1.8
1.8
3.7
3.5
3.0
2.8
2.7
2.2
3
4
5
0
2
2
2
2
2
2
c
c
c
c
c
c
0
2.0
4.0
2.0
24
15
20
18
34
24
47
15
26
30
39
38
44
8.5
11
10
17
13
26
4.1
7.4
10
14
14
20
0
0
25
25
60
60
0
0
0
2.0
4.0
2.0
4.0
2.0
24
0
0
2
2
2
2
2
2
d
d
d
d
d
d
3.2
2.8
5.3
3.5
3.5
4.1
0
25
25
60
60
2.0
4.0
a
The yields are calculated as shown in Table 1. The products 3d or 4d correspond to trans-1-
acetoxy-1- or -2-methyl-2-methylthiocyclohexane, respectively.

9
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Molecules 2000, 5
Reactions with 1-Methylcyclohex-1-ene (2d)
The reaction with 1-methylcyclohex-1-ene (2d) at 25-60°C gives predominantly Markovnikov trans-
adduct (3d/4d = 3.7-2.2) (Table 2). This can be also interpreted by the idea that the S 2 ring-opening of IId
N
and II’d occurs under preferential electronic control. A slightly lower ratio in the prolonged reaction (Table 2)
is presumably due to the thermodynamic instability of 3d compared to 4d.
We obtained 1-acetoxymethyl-2-methylthiocyclohexane (5d) in the reaction with 2d, but did not obtain the
corresponding 5c in the reaction with 2c (Table 2). According to the molecular model, the S-atom of IId and
II’d is closer to the 2-methyl carbon than that of IIc and II’c, so IId and II’d may rearrange to the thietanium
radical cations IIId and III’d by a concerted reaction involving C
2
-S bond breaking and hydride migration of
the 2-methyl group, leading to 5d (Scheme 3). A similar anionotropic rearrangement from thiiranium ion to
thietanium ion has been proposed for the concerted reaction involving C
2
-S breaking and methyl migration at
tertiary carbon [10-14].
H
CH2
CH2
OAc
OAc
Me
Me
+
S
+
S
PdOAcandPd
PdOAcand Pd
IIId and III'd
I I d and II ' d
AcOH
CH OAc
2
SMe
5d
Scheme 3.
o
The reaction with 2c or 2d at 116 C gave many unidentified products according to GLC analysis. A stable
tertiary carbocation is probably formed by bridge-cleavage of IIc and II’c or IId and II’d at a high tempera-
o
ture such as 116 C, hence this result. But IIa and II’a or IIb and II’b, which cannot generate a tertiary car-
o
bocation by the cleavage are still bridged at 116 C, thus yielding 3a or 3b and 4b by the S
N
2 ring-opening.
Effects of Solvent and Concentration of AcOH
The total yield of 3 and 4 in the reaction with 2b or 2c in AcOH–CH
2
Cl
2
increases with an increase in the
concentration of AcOH, and 3b and 4b are also produced in the reaction in MeCN or MeNO
2
not containing
AcOH (Table 3). These indicate that 3 and 4 are formed by the S 2 attack on II and II’ of both AcOH and
N
–
AcO pairing with II and II’ (Scheme 2).
In the reaction with 2b or 2c, the Markovnikov regioselectivity 3/4 was interestingly decreased upon dilu-
tion with CH Cl or the polar solvents MeCN or MeNO , and it was also depressed on dilution with nonpolar
n-hexane (Table 3). By contrast, in the reaction of 1 with 2b using AgOAc instead of Pd (OAc) , the Mark-
ovnikov regioselectivity for the ring-opening of thiiranium ion was increased on dilution with MeNO (Table
).
2
2
2
2
2
3

9
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Molecules 2000, 5
Table 3. Effects of solvents on the reaction of dimethyl disulfide (1) (2.0 mmol) with hex-1-ene (2b)
(
4.8 mmol) or 2-methylpent-1-ene (2c) (4.8 mmol) in the presence of Pd(OAc) (0.68 mmol) at 25°C
2
for 24 h.
a
3
Alkene
Solvent (cm )
Yield (%)
Ratio
AcOH CH Cl n-C
H
MeCN
MeNO2
3
4
3/4
0.43
0.41
0.38
0.34
0.38
0.24
0.19
0.31
0.27
0.34
2.0
2
2
6
14
2
2
2
2
2
2
2
2
b
b
b
b
b
b
b
b
10
9.0
5.0
1.0
5.0
0
0
0
0
0
0
0
0
10
0
0
0
0
0
0
0
0
0
0
0
0
0
0
16
12
10
6.5
5.3
4.1
3.2
13
5.2
5.4
34
31
24
16
32
15
17
47
37
29
26
19
14
17
17
42
19
16
17
18
18
19
20
12
13
27
1.0
5.0
9.0
0
0
0
0
0
0
5.0
0
0
0
0
0
0
0
10
5.0
0
5.0
10
0
0
b
2
b
b
0
0
b
2
5.0
10
0
0
5.0
0
2
c
0
0
2
2
2
2
2
2
2
c
c
c
c
c
c
c
9.0
5.0
1.0
9.0
5.0
1.0
5.0
1.0
5.0
9.0
0
0
0
1.7
0
0
1.3
0
0
0.84
1.6
1.0
5.0
9.0
0
0
0
0
1.3
0
0
1.3
0
5.0
1.7
a
The yields are calculated to be 100% when two moles of product is formed from one mole of
3
Pd(OAc) and from two moles of AgOAc, and were obtained by GLC analysis; Ac O (1.0 cm ) is
2
2
added to these reactions, but Ac O is not used in the reactions with only MeCN or MeNO .
2
2
b
AgOAc (1.36 mmol) instead of Pd(OAc) was used in this reaction.
2
The decreased Markovnikov regioselectivity observed on dilution with the polar solvents suggests
that the solvation with the polar solvent occurs strongly at the highly charged C-2 of II and II’ rather
than at the low charged C-3, suppressing the S 2 reactivity at C-2 relative to the C-3. The depressed
N
3
b/4b ratio upon dilution with nonpolar n-hexane allows us to infer that this dilution transforms the
solvent separated ion-pair of II and II’ into a tight ion-pair in which the counteranion interacts to a
greater extent with the more positive C-2 of II and II’ than the less positive C-3 to decrease the SN2
reactivity more at the C-2 than the C-3, leading to the observed results.
Effects of Oxidants
As described above, the oxidative attack of Pd(OAc) on 1 may form the sulfonium salts I and I’,
2
giving thiiranium radical cations II and II’ and MeS• (Scheme 2); MeS• dimerizes to give 1 because

9
23
Molecules 2000, 5
of an unfavorable reaction with 2 [15]. An addition of Cu(OAc) to the reaction with 2b using
2
Pd(OAc) resulted in rather suppressed yields of 3b and 4b (Tables 1 and 4). The use of Cu(OAc) ,
2
2
Mn(OAc) or Pb(OAc) instead of Pd(OAc) in the reaction with 2b did not yield the products 3b and
3
4
2
4
b (Table 4); Cu(OAc) forms a complex with the alkene, and thus it would not operate as oxidizing
2
agent. Mn(OAc) is not effective since it oxidizes AcOH [16]. Pb(OAc) is too strong an oxidant to be
3
4
effective, giving a lot of unidentified products. PdSO is difficult to dissolve in AcOH, so that it could
4
scarcely be effective. The use of H SO gave many unidentified products due to the strong acidity,
2
4
leading to only a trace of the target products. Since AgOAc is complexed with alkene, it would be not
so effective for the reaction.
Table 4. Effects of oxidants in the reactions of dimethyl disulfide (1) (2.0 mmol) with hex-1-ene (2b)
3
3
(
4.8 mmol) in the presence of oxidant in AcOH (10 cm ) containing Ac O (1.0 cm ) at 25°C for 24 h.
2
a
Oxidant
Oxidant/mmol
Yield (%)
Ratio
3
b
4b
3b/4b
Pd(OAc) +Cu(OAc)
b
7.7
0
17
0
0.45
2
2
Cu(OAc)2
0.68
0.68
0.68
1.36
2.4
-
H SO4
2
trace
trace
5.2
0
trace
trace
19
-
PdSO4
-
AgOAc
0.27
Mn(OAc)3
Pb(OAc)4
0
-
-
2.4
0
0
a
The yields are calculated to be 100% when two moles of product are formed from one mole
Pd(OAc) or Cu(OAc) and from two moles AgOAc.
2
2
b
Pd(OAc) (0.60 mmol) and Cu(OAc) (3.6 mmol) were used, and the yields are obtained on the
2
2
basis of Pd(OAc)2.
Experimental
General
1
IR spectra were obtained on a JASCO Cooperation A-302 spectrometer. H NMR spectra were
taken with a Nippondenshi PMX-60SI instrument (J values are given in Hz). GLC-MS were recorded
with a Shimadzu QP-5000 spectrometer linked to a Shimadzu GC-17A; the column (15 m × 0.25 mm,
coated with a 0.25 µm film of DB-1) is made by J & W Scientific. GLC was performed with a Shima-
dzu GC-8A using a glass column (1m × 3 mm) packed with 10% SE-30 on 60-80 mesh Chromosorb W
(AW-DMCS). Two runs agreed within 3% error for the yields of the products, which were determined
by replicate GLC analyses. The isolation or separation (as a mixture) of the products was done by thin
layer chromatography (using Merck Silicagel 60PF254). AcOH, CH Cl , MeCN, MeNO , n-hexane
2
2
2
and ethyl acetate were purified by standard methods before use. The following compounds were rea-
gent grade (Nacalai Tesque), and used without further purification: Ac O, H SO , Pd(OAc) ,
2
2
4
2
Cu(OAc) , PdSO , AgOAc, Mn(OAc) , Pb(OAc) , dimethyl disulfide (1), cyclohexene (2a), hex-1-ene
2
4
3
4
(2b), 2-methylpent-1-ene (2c) and 1-methyl-cyclohex-1-ene (2d).

9
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Molecules 2000, 5
Experimental procedures
Reactions of dimethyl disulfide (1) with cyclohexene (2a), hex-1-ene (2b), 2-methylpent-1-ene (2c) and
-methylcyclohex-1-ene (2d) in AcOH containing Ac O in the presence of Pd(OAc)
1
2
2
A mixture of 1 and alkene (2a, 2b, 2c or 2d) was added to a mixture of AcOH and Ac O in the
2
presence of Pd(OAc) with stirring (using a magnetic stirrer) under the conditions described in Tables 1
2
and 2. After the reaction, any precipitate formed was filtered off, and aqueous Na CO was added to the
2
3
filtrate until the solution reached pH > 7. The organic layer was extracted with ethyl acetate. The yields
of products 3a-d, 4b-d and 5d were determined by GLC analysis, and the results are summarized in
Tables 1 and 2. Product 3a was isolated by thin layer chromatography, and the structure was confirmed
as follows.
Trans-1-acetoxy-2-methylthiocyclohexane (3a)
-1
Liquid, υmax (neat)/cm 2930, 2860, 1734, 1450, 1375, 1235 and 1048; δ (CDCl ) 1.08-1.09 (8H,
H
3
m, CH ), 2.06 (3H, s, Me), 2.09 (3H, s, Me), 2.33-2.80 (1H, m, SCH) and 4.85-5.08 (1H, m, OCH);
2
+
GLC-MS, m/z 188 (M ), 128, 113, 81, 80, 79, 77, 61 and 53. The GC-MS mass spectra for the com-
pound which is formed by hydrolysis of 3a in aq. NaOH were identical with those for the product [i.e.
+
trans-1-hydroxy-2-methylthiocyclohexane; m/z 146 (M ), 98, 87, 81, 80, 79, 70, 61, 57, and 55] given
by a reaction of cyclohexene oxide with MeSH in benzene. This indicates that product 3a has a trans-
configuration.
The products 3b and 4b were not isolated but rather obtained as a mixture by thin layer chromatog-
-1
raphy. This mixture showed the following spectral data: υmax (neat) /cm 2930, 2870, 1744, 1460,
380, 1240, 1040 and 818; δ (CDCl ) 0.85-1.88 (9H, m, MeCH CH CH ), 2.08 (3H, s, SMe or
1
H
3
2
2
2
OCOMe), 2.12 (3H, s, OCOMe or SMe), 2.48-2.78 (br, SCH of 3b), 2.78-2.3.08 (br, SCH of 4b), 4.18
2
(
ABq, J=6 Hz, OCH of 4b) and 4.88-5.23 (m, OCH of 3b). The products 3b and 4b have the follow-
2
+
+
ing mass spectra by GLC-MS: m/z for 3b 130 (M –AcOH), 115 [M − (AcOH+Me)], 87 (n-
+
+
+
BuCH OH)), 82 (radical cation of n-BuC≡CH), 67, 61 (MeSCH ) and 55 (C H ); m/z for 4b 130,
2
4
7
115, 88, 87, 82, 67, 61 and 55. The fact that the relative intensity of m/z 130 and 87 to m/z 55 is higher
in 3b than in 4b also suggests these structures. The observation that the GLC peak for 3b has a shorter
retention time than that for 4b supports the fact that the AcO group for 3b is more shielded by non po-
lar groups than the AcO group for 4b. The yields of 3b and 4b were obtained using the assumption that
these compounds have the same GLC response factors. A mixture (33 mg) containing 3b and 4b
3
3
(
3b/4b = 0.34) was treated in AcOH (10 cm ) containing Ac O (1.0 cm ) at 25°C for 24 h and at 116°C
2
for 2 h or 24 h. Product 3c was isolated by thin layer chromatography, and the structure was confirmed
by the following spectra.
2-Acetoxy-2-methyl-1-methylthiopentane (3c)
-1
Liquid, υmax (neat) /cm 2920, 2870, 1732, 1435, 1370, 1240, 1198, 1140, 1030 and 950; δ
H
(
CDCl ) 0.77-1.88 (7H, m, MeCH CH ), 1.47 (3H, s, Me), 1. 96 (3H, s, OCOMe), 2.11 (3H, s, SMe)
3 2 2
+
+
and 2.98 (2H, s, SCH ); m/z 130 (M –AcOH), 101 [M −(AcOH+Et)], 87, 82, 67, 61, 59, 55 and 53.
2
Compound 4c was obtained as a mixture with 3c, and the proposed structure was supported by the

9
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Molecules 2000, 5
GLC-MS results; the GLC peak for 4c has a longer retention time than that for 3c because the AcO
group of 4c is less shielded by non polar groups than the AcO group of 3c, and the mass spectra for 4c
+
showed the following peaks: m/z 130, 117 (M −CH OAc), 101, 83, 82, 67, 61, 59, 55 and 53). The
2
peak m/z 117 is not observed for 3c, and the appearance of this peak is in good agreement with the pro-
posed anti-Markovnikov structure of 4c. The yield of 4c was determined using the assumption that 4c
has the same GLC response factor as 3c.
The products 3d, 4d and 5d were also obtained as a mixture, and the mixture indicated the follow-
-1
ing spectra: υmax (neat) /cm 2920, 2860, 1728, 1440, 1368, 1242, 1173, 1147, 1112, 1040 and 1025;
δ (CDCl ) 4.75-4.05 (m, OCH of 4d), 4.05 (s, CH OCOMe of 5d), 2.45-2.75 (m, SCH of 3d and 5d),
H
3
2
2
.16 (3H, s, SMe), 2.00 (3H, s, OCOMe), 1.56 (s, Me) and 1.05-1.65 (m, CH of 5d and CH ). The
2
+
GLC-MS for these products exhibited the following separate mass spectra: m/z for 3d 202 (M ), 142
+
+
+
(M −AcOH), 113, 95 [M −(AcOH+SMe)], 94, 93, 79, 77, 67, 55 and 53; m/z for 4d 202(M ), 142,
+
+
1
7
13, 95, 94, 93, 79, 77, 67, 55 and 53; m/z for 5d 202 (M ), 163, 142, 129 (M −CH OAc), 95, 94, 81,
2
9, 77, 67, 61, 55 and 53. The comparatively strong peak for m/z 129 was observed for 5d but for nei-
1
ther 3d nor 4d, and the H NMR spectra for the mixture of 3d, 4d and 5d showed a peak at 4.05 ppm
(
singlet, CH OCOMe). These results lend strong support to the structure of 5d. Considering 2a to be
2
trans-compound, 3d and 4d should also have trans-configuration. The low retention time of 3d com-
pared to 4d and the high relative-intensity for m/z 142 of 3d relative to 4d support the proposed struc-
tures for 3d and 4d. The configuration for 5d is not unambiguous, but it seems reasonable to assume it
to be in a trans-form in which the SMe and CH OAc groups are located at the stable equatorial posi-
2
tions. The yields of 3d, 4d and 5d were also determined with the assumption that these compounds
have identical GLC response factors.
Effects of solvents and concentration of AcOH on the reaction of dimethyl disulfide (1) with hex-1-ene
(2b) or 2-methylpent-1-ene (2c)
The reaction of dimethyl disulfide (1) with hex-1-ene (2b) or 2-methylpent-1-ene (2c) was per-
formed similarly using various solvents under the conditions indicated in Table 3. Analysis and char-
acterization of the products were carried out as described above. The results are summarized in Table
3
.
Effects of oxidants in the reaction of dimethyl disulfide (1) with hex-1-ene (2b)
The reaction of dimethyl disulfide (1) with hex-1-ene (2b) was also conducted with a variety of oxi-
dants under the conditions shown in Table 4. The yields of 3b and 4b were determined by the same
procedure as that described above, and the results are summarized in Table 4.
References and Notes
1
2
3
4
.
.
.
.
Smit, W. A.; Zefirov, N. S.; Bodrikov, I. V.; Krimer, M. Z. Acc. Chem. Res. 1979, 12, 282.
Trost, B. M.; Ochiai, M.; McDougal, P. G. J. Am. Chem. Soc. 1978, 100, 7103.
Bewick, A.; Mellor, J. M.; Owton, W. M. J. Chem. Soc., Perkin Trans. 1 1985, 1039.
E. Samii, Z. K. M. A.; Ashmawy, M. I. A.; Mellor, J. M. Tetrahedron Lett. 1986, 27, 52859.

9
26
Molecules 2000, 5
5.
6.
7.
Bewick, A.; Mellor, J. M.; Milano, D.; Owton, W. M. J. Chem. Soc., Perkin Trans. 1 1985, 1045.
Bewick, A.; Coe, D. E.; Mellor, J. M.; Owton, W. M. J. Chem. Soc., Perkin Trans. 1 1985, 1033.
It has been reported that the disulfide radical cation is highly reactive in solution, regardless of
whether it is generated by chemical, photochemical or electrochemical oxidation, and thus the
spectral confirmation is difficult in solution; Marti, V.; Fernandez, L.; Garcia, H.; Roth, H. D. J.
Chem. Soc., Perkin Trans. 2 1999, 145. We have recently observed that the disulfide radical cation
(from MeSSMe) with λmax 375 nm is not capable of dissociation into a sulfenium ion, and under-
goes an aromatic methylthiolation; the details will be published in the near future.
A sulfenium ion seems to be formed in the first instance, but this formation would be impossible
because a very unstable sulfenium ion can be generated when it interacts directly with the un-
shared electron-pair of a compound formed by dissociation from the precursor; In fact, arylsu-
fenium ions are generated by interaction with both the unshared electron-pair of amine and the
counterion: Takeuchi, H.; Oya, H.; Yanase, T.; Itou, K.; Adachi, T.; Sugiura, H.; Hayashi, N. J.
Chem. Soc., Perkin Trans. 2 1994, 827.
8
.
.
9
Unpublished data; in the near future we will publish the details in which the reaction of 1 with
+
–
alkene using AgOAc proceeds via the thiiranium ion formed from [MeS-S (Me)Ag] OAc because
of the formation of MeSAg.
1
1
1
1
1
1
0. Mueller, H. Angew. Chem. Int. Ed. Engl. 1969, 8, 482.
1. Lucchini, V.; Modena, G.; Pasquato, L. J. Am. Chem. Soc. 1988, 110, 6900.
2. Lucchini, V.; Modena, G.; Pasquato, L. J. Am. Chem. Soc. 1991, 113, 6600.
3. Huang, X.; Batchelor, R. J.; Einstein, F. W. B.; Bennet, A. J. J. Org. Chem. 1994, 59, 7108.
4. Luccchini, V.; Modena, G.; Pasi, M.; Pasquato, L. J. Org. Chem. 1997, 62, 7018.
5. Ogawa, A.; Tanaka, H.; Yokoyama, H.; Obayashi, R.; Yokoyama, K.; Sonoda, N. J. Org. Chem.
1
992, 57, 111.
1
6. Fristad, W. E.; Peterson, J. R. J. Org. Chem. 1985, 50, 10.
Sample Availability: Available from the authors.
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2000 by MDPI (http://www.mdpi.org).