Indium(I) iodide promoted cleavage of dialkyl disulfides - Application of the Michael addition of thiolate anions to conjugated carbonyl compounds and regioselective ring opening of epoxides

Article abstract of DOI:10.1139/V06-065

Indium(I) iodide promotes cleavage of dialkyl disulfides generating thiolate anions that then undergo facile addition to α,β-unsaturated ketones, aldehydes, carboxylic esters, and nitriles under neutral conditions producing corresponding β-ketosulfides or β-cyanosulfides. This strategy has also been used for the regioselective nucleophilic ring opening of epoxides by thiolate anions in presence of indium(III) chloride producing corresponding β-hydroxyphenyl sulfides. The reactions are in general, very clean, high yielding, and reasonably fast. Thus, simple and convenient procedures for the synthesis of β-ketosulfides or β-cyanosulfides and β-hydroxyalkyl sulfides have been developed using this cleavage reaction.

Full text of DOI:10.1139/V06-065

762
Indium(I) iodide promoted cleavage of dialkyl
disulfides — Application of the Michael addition of
thiolate anions to conjugated carbonyl compounds
and regioselective ring opening of epoxides
Brindaban C. Ranu and Tanmay Mandal
Abstract: Indium(I) iodide promotes cleavage of dialkyl disulfides generating thiolate anions that then undergo facile
addition to α,β-unsaturated ketones, aldehydes, carboxylic esters, and nitriles under neutral conditions producing corre-
sponding β-ketosulfides or β-cyanosulfides. This strategy has also been used for the regioselective nucleophilic ring
opening of epoxides by thiolate anions in presence of indium(III) chloride producing corresponding β-hydroxyphenyl
sulfides. The reactions are in general, very clean, high yielding, and reasonably fast. Thus, simple and convenient pro-
cedures for the synthesis of β-ketosulfides or β-cyanosulfides and β-hydroxyalkyl sulfides have been developed using
this cleavage reaction.
Key words: indium(I) iodide, Michael addition, β-ketosulfide, β-cyanosulfide, epoxide, β-hydroxy sulfide.
Résumé : L’iodure d’indium(I) facilite le clivage des disulfures d’alkyles et génère la formation d’anions thiolates
qui peuvent ensuite s’additionner facilement sur des cétones, des aldéhydes, des esters carboxyliques et des nitriles
α,β-insaturés, dans des conditions neutres, pour conduire à la formation des β-céto ou β-cyanosulfures correspondants.
On a aussi utilisé cette stratégie pour l’ouverture de cycle nucléophile et régiosélective d’époxydes par des anions thio-
lates en présence de chlorure d’indium(III) qui conduisent à la formation des sulfures de β-hydroxyphényle. Les réac-
tions sont, en général, très propres et elles donnent des rendements élevés rapidement. Des méthodes simples et faciles
utilisant cette réaction de clivage permettent donc de synthétiser des β-cétosulfures ou des β-cyanosulfures ainsi que
des sulfures de β-hydroxyalkyles.
Mots clés : iodure d’indium(I), addition de Michael, β-cétosulfure, β-cyanosulfure, époxyde, β-hydroxysulfure.
[Traduit par la Rédaction] Ranu and Mandal 770
Introduction
to report here the results of our earlier communication (4c)
in detail together with this new observation (Scheme 1).
The β-oxy- and β-hydroxy-sulfides are very useful mole-
cules as they constitute a common structural component in a
vast group of natural products (5). Some of the synthetic
molecules are found to have biological and pharmaceutical
activities (6). These molecules are also very useful interme-
diates in organic synthesis (7). Many methods are available
in the literature for the synthesis of β-oxy- (8) and β-
hydroxy-sulfides (9) and these are primarily based on reac-
tion with thiols under base or acid catalysis. However, many
of them suffer from disadvantages of harsh reaction condi-
tions, poor regioselectivity, unsatisfactory yields, long reac-
tion times, and are associated with undesirable side reactions
owing to the oxidation of thiol or rearrangement of
epoxides. Since β-oxy- and β-hydroxy-sulfides have become
increasingly useful and important in organic synthesis, de-
velopment of simple, efficient, and mild procedures for their
The importance of indium reagents in organic synthesis
has been well-demonstrated through novel protocols for
carbon–carbon bond formation, rearrangements, and a vari-
ety of other useful transformations over past few years (1)
and increasing interest in this area is continuing (2). As a
part of our activities in indium-mediated reactions (3), we
are constantly looking for new indium reagents and we re-
ported the application of indium(I) iodide (4) for the cleav-
age of diphenyl diselenide and disulfide followed by in situ
condensation with alkyl halide (4a, 4b). We also communi-
cated the cleavage of dialkyl disulfides promoted by InI fol-
lowed by subsequent Michael addition of thiolate anions to
conjugated carbonyl compounds (4c). We have now discov-
ered another application of this protocol for regioselective
ring opening of epoxides by thiolate anions in presence of
indium(III) chloride to provide β-hydroxy sulfides. We wish
Received 21 December 2005. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 17 May 2006.
B.C. Ranu1 and T. Mandal. Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
Kolkata – 700 032, India.
1Corresponding author (e-mail: ocbcr@iacs.res.in).
Can. J. Chem. 84: 762–770 (2006)
doi:10.1139/V06-065
© 2006 NRC Canada

Ranu and Mandal
763
Scheme 1.
Scheme 2.
O
(a)
O
InI , RSSR
[ -SR]
THF , reflux
(1a)
SR
SR
R2
OH
(b)
(RS)2InI
InI
+ RSSR
O
OH
InI , RSSR
R2
Cl3In
R2
(1b)
R2
[ -SR]
InCl3(cat)
THF , reflux
R1
R1
R1
O
SR
SR
R1
synthesis are highly desirable. Thus, we sought an alterna-
tive approach replacing thiol by a more stable sulphur re-
agent and we found that dialkyl disulfide can do this job
more efficiently (Scheme 1).
occurred under the reaction process to produce the corre-
sponding α-thiophenyl α,β-unsaturated ketones, although in
β-methyl epoxyketone (Table 2, entry 18), a minor product
(20%) from the β attack was isolated. However, in the case
of α-methyl-α,β-epoxyketone (Table 2, entry 19) α-methyl-
α-thiophenyl-β-hydroxyketone was obtained, as dehydra-
tion is not feasible.
In general, the reactions are considerably fast, clean, and
high yielding. Presumably, these reactions are going through
the intermediacy of bis(phenylthiophenyl)iodoindium(III),
formed readily by the oxidative insertion of equimolar quan-
tities of InI to diphenyl disulfide, which then releases thiolate
anion to trigger the Michael addition and epoxide cleavage
under the catalysis of InCl3 (Scheme 2). It has also been ob-
served that the epoxide cleavage reactions did not proceed at
all without the presence of InCl3.
In conclusion, this one-pot procedure for the synthesis of
β-oxy- and β-hydroxyalkyl sulfides has been developed in-
volving indium(I) iodide mediated cleavage of diorganyl di-
sulfides and subsequent reaction with conjugated carbonyl
compounds and epoxides. The significant advantages offered
by this method are operational simplicity, relatively fast re-
action, neutral and mild reaction conditions, general applica-
bility, high regio- and stereo-selectivity, and good yields.
Thus, it provides a better and practical alternative to the ex-
isting procedures (8, 9). Moreover, this constitutes a novel
approach demonstrating the synthetic potential of indium(I)
iodide, and further useful applications of this reagent are in
progress.
Results and discussion
The experimental procedures for both of these reactions
are very simple and convenient. A solution of dialkyl disulfide
and activated alkene in THF was heated under reflux in the
presence of indium(I) iodide and the Michael adduct was
isolated by the usual workup. On the other hand, a stirred
solution of indium(I) iodide, dialkyl disulfide, and epoxide
in dry THF was heated under reflux in the presence of a cat-
alytic amount of indium trichloride (5 mol%) (TLC) and
quenched with a few drops of water. Extraction with ether
and the usual workup produced a pure product.
Several α,β-unsaturated ketones, aldehydes, and carboxylic
esters underwent facile Michael additions to dithiolate an-
ions generated by the cleavage of disulfides by this proce-
dure to provide the corresponding adducts in high yields.
Conjugated nitriles were also found to react with the thiolate
anions, although the yields are relatively low compared with
those with carbonyl compounds. The results are summarized
in Table 1. Aliphatic as well as aromatic disulfides are found
to undergo cleavage and subsequent reaction. On the other
hand, both cyclic and acyclic conjugated carbonyl com-
pounds participate in this reaction as Michael acceptors.
A wide range of structurally diverse epoxides underwent
cleavages by reaction with dialkyl or diaryl disulfides by this
procedure to provide the corresponding β-hydroxysulfides in
high yields. The results are summarized in Table 2. The
cleavages are highly regio- and stereo-selective. As ex-
pected, attack of thiolate anion occurred at the less-hindered
carbon atom of the terminal alkyl-substituted epoxides (Ta-
ble 2, entries 1–5). However, an aryl-substituted epoxide
(Table 2, entry 6) attack occurs at the benzylic carbon atom.
The cyclic epoxides (Table 2, entries 7–12) produced stereo-
specifically trans-diequatorial β-hydroxysulfides. In case of
open-chain, α-keto aryl epoxides (Table 2, entries 13–15)
thiolate anion also stitched at the benzylic carbon producing
the corresponding γ -keto-β-hydroxysulfides. In all cases,
the syn orientation of hydroxy and thiophenyl were observed
Experimental
General experimental procedure
Representative procedure for the cleavage of diphenyl
disulfide and subsequent reaction with methyl vinyl
ketone (Table 1, entry 2)
Indium(I) iodide (121 mg, 0.5 mmol) was added to a solu-
tion of diphenyl disulfide (109 mg, 0.5 mmol) in freshly dis-
tilled tetrahydrofuran (2.5 mL) under an argon atmosphere
followed by the addition of methyl vinyl ketone (70 mg,
1 mmol). The reaction mixture was heated under reflux for
2.5 h (TLC). THF was then evaporated off and the residue
was quenched with water and extracted with diethyl ether
(3 × 10 mL). The ether extract was washed with water and
1
as revealed by their coupling constants in H NMR. The
nonaromatic cyclic α-keto epoxides (Table 2, entries 16–18)
underwent the attack of thiolate anion to the epoxycarbon
atom α to the carbonyl group and simultaneous dehydration
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Can. J. Chem. Vol. 84, 2006
Table 1. InI-mediated cleavage of disulfides followed by Michael addition.
Entry
Disulfide
Substrate Time (h) Product
Yield (%)a Ref.
C4H9S
n
n-C4H9S-S-n-C4H9
1
8a
3.0
85
O
O
O
C6H5S
10
2
C6H5S-SC6H5
2.5
86
O
(p-Cl)C6H4S
C6H5CH2S
C6H5S
(p-Cl)C6H4S-SC6H4(p-Cl)
3
2.5
3.0
85
82
O
O
O
11
C6H5CH2S-SCH2C6H5
4
O
C6H5S-SC6H5
8e
5
6
2.5
3.0
85
81
O
O
O
(p-Cl)C6H4S
(p-Cl)C6H4S-SC6H4(p-Cl)
O
C6H5S
C6H5S-SC6H5
2.5
7
82
80
O
O
O
(p-Cl)C6H4S
C6H5S
8
9
(p-Cl)C6H4S-SC6H4(p-Cl)
3.0
O
C6H5S-SC6H5
2.25
80
78
90
O
O
O
(pCl)C6H4S
(p-Cl)C6H4S-SC6H4(p-Cl)
3.0
2.5
10
11
O
O
O
C4H9S
n
8e
n-C4H9S-S-n-C4H9
O
C6H5S
O
O
O
11
C6H5S-SC6H5
12
13
14
95
92
89
1.5
2.0
2.5
O
(p-Cl)C6H4S
(p-Cl)C6H4S-SC6H4(p-Cl)
C6H5CH2S-SCH2C6H5
8f
C6H5CH2S
O
11
dried (Na2SO4). The aqueous extract containing indium de-
rivatives was discarded, although in relatively large-scale re-
actions indium salts may be recovered. Evaporation of the
solvent left the crude product, which was purified by column
chromatography over silica gel (hexane–ether, 95:5) to pro-
vide the pure addition product, 4-phenylsulfanylbutan-2-one
(155 mg, 86%) as a colourless liquid. IR (neat, cm–1) ν:
7.22 (m, 2H), 7.26–7.35 (m, 3H). 13C NMR (75 MHz,
CDCl3) δ: 27.9, 30.5, 43.5, 126.7, 127.9, 129.4 (2C), 130.0
(2C). These values are in good agreement with those re-
ported for this compound (10). Several Michael adducts are
known and are identified by comparison of their spectro-
scopic data with those reported. The new compounds are
characterized by their spectroscopic data and elemental anal-
ysis. The data for a few selective representative compounds
are provided here.
1
1716, 1477. H NMR (300 MHz, CDCl3) δ: 2.14 (s, 3H),
2.76 (t, J = 7.26 Hz, 2H), 3.13 (t, J = 7.26 Hz, 2H), 7.20–
© 2006 NRC Canada

Ranu and Mandal
Table 1 (concluded).
765
Entry
Disulfide
Substrate Time (h) Product
Yield (%)a Ref.
C6H5S
H
H
H
H
8e
15
C6H S-SC6H5
2.5
3.0
3.5
92
5
O
O
O
O
(p-Cl)C6H4S
H
(p-Cl)C6HS-SC6H4(p-Cl)
16
17
90
82
4
O
C6H CH2S
H
5
C6H CH2S-SCH2C6H5
5
O
C4H9S
n
H
H
n-C4H9S-S-n-C4H9
C6H5S-SC6H5
4.0
3.0
3.5
3.0
8e
80
18
19
20
21
O
O
C6H S
H
H
5
80
( 61:39 )b
O
O
O
(p-Cl)C6HS
H
H
4
(p-Cl)C6HS-SC6H4(p-Cl)
78
4
( 59:41 )b
O
O
H
H
H
C6H S-SC6H5
80
5
( 53:47 )b
C6H5S
O
O
H
(p-Cl)C HS-SC H (p-Cl)
3.5
4.0
22
23
76
6
4
6 4
( 51:49 )b
(p-Cl)C6H4S
O
OCH3
OCH3
C6H5S
C6H5S-SC6H5
8e
73
O
O
OCH3
OCH3
OCH3
(p-Cl)C6H4S
(p-Cl)C HS-SC H (p-Cl)
4.25
5.0
70
60
24
25
6
4
6 4
O
O
O
OCH3
C6H5S
C6H5S-SC6H5
8e
8e
O
C6H5S
CN
CN
CN
C6H S-SC6H5
4.0
4.5
26
27
72
65
5
CN
(p-Cl)C6H4S
(p-Cl)C6HS-SC6H4(p-Cl)
4
CN
C6H5S
C6H5S-SC6H5
28
5.0
55
CN
1
aYields refer to those of pure isolated products characterized by spectroscopic data (IR and H and 13C NMR).
1
bRatio of diastereoisomers as determined by H NMR.
4-(4-Chlorophenylsulfanylbutan-2-one (Table 1, entry 3)
4-(4-Chlorophenylsulfanyl)-4-methyl-pentan-2-one
(Table 1, entry 6)
Colourless liquid. IR (neat, cm–1) ν: 1438, 1477, 1578,
1
1716. H NMR (300 MHz, CDCl3) δ: 2.14 (s, 3H), 2.73 (t,
Colourless liquid. IR (neat, cm–1) ν: 1438, 1473, 1573,
J = 7.2 Hz, 2H), 3.10 (t, J = 7.2 Hz, 2H), 7.25 (s, 4H). 13C
NMR (75 MHz, CDCl3) δ: 28.1, 30.5, 43.3, 129.5 (2C),
131.2 (2C), 132.8, 134.7, 206.7. Anal. calcd. for
C10H11ClOS: C 55.94, H 5.16; found: C 55.81, H 5.09.
1715. H NMR (300 MHz, CDCl3) δ: 1.36 (s, 6H), 2.11 (s,
1
3H), 2.62 (s, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.41 (d, J =
8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ: 28.1 (2C), 32.0,
47.2, 54.2, 128.8 (2C), 129.8, 136.9, 138.7 (2C), 206.2.
© 2006 NRC Canada

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Can. J. Chem. Vol. 84, 2006
Table 2. Cleavages of epoxides by dialkyl and diaryl disulfides.
OH
O
InI , RSSR
R2
R2
R1
R1
THF , InCl3( mol%)
5
reflux
Time (h)
SR
Yield (%)a Ref.
R
Entry Epoxide
Product
OH
O
SC6H5
1
3.0
4.0
4.5
98
78
80
9g
9b
C6H5
( )5
( )5
OH
O
SCH2C6H5
SC6H4(p-Cl)
SC6H5
C6H5CH2
C6H4(p-Cl)
2
3
( )5
( )5
( )5
OH
O
( )5
OH
O
Cl
Cl
C6H5
C6H5
4
5
2.5
3.0
76
80
9g
9g
OH
O
C6H5O
C6H5
SC6H5
C6H5O
O
SC6H5
OH
C6H5
OH
6
7
2.75
4.5
60
69
9b
9b
C6H5
n-C4H9
O
SC4H9-n
OH
C6H5
O
O
8
9
3.0
3.0
3.5
82
80
82
9e
SC6H5
OH
C6H4(p-Cl)
SC6H4(p-Cl)
OH
C6H5
10
9g
O
SC6H5
OH
C6H4(p-Cl)
11
12
3.5
3.5
72
78
O
SC6H4(p-Cl)
OH
C6H5
O
9g
SC6H5
Anal. calcd. for C12H15ClOS: C 59.37, H 6.23; found: C
59.22, H 6.09.
3H), 2.12 (s, 3H), 2.55 (dd, J1 = 8.5 Hz, J2 = 17.0 Hz, 1H),
2.75 (dd, J1 = 5.3 Hz, J2 = 17.0 Hz, 1H), 3.63–3.72 (m, 1H),
7.22–7.35 (m, 3H), 7.39–7.49 (m, 2H). 13C NMR (75 MHz,
CDCl3) δ: 20.9, 30.5, 38.1, 50.2, 127.1, 128.8 (2C), 132.3
(2C), 134.1, 206.4. Anal. calcd. for C11H14OS: C 68.00, H
7.26; found: C 67.73, H 7.11.
4-Phenylsulfanylpentan-2-one (Table 1, entry 7)
Colourless liquid. IR (neat, cm–1) ν: 1438, 1477, 1583,
1
1714. H NMR (300 MHz, CDCl3) δ: 1.28 (d, J = 6.6 Hz,
© 2006 NRC Canada

Ranu and Mandal
767
Table 2 (concluded).
Yield (%)a Ref.
R
Entry Epoxide
Time (h)
Product
O
SC6H5
O
O
C6H5
C6H5
C6H5
13 C6H5
C6H5
2.25
2.5
81
(syn)
OH
OH
O
O
O
SC6H5
C H
6
C6H5
C6H5
80
14
5
(52:48) b
OMe
OMe
O
SC6H5
O
O
C2H5O
C6H5
15 C2H5O
C6H5
5.5
85
70
75
C6H5
(syn)
OH
SC6H5
O
O
O
C6H5
16
17
18
3.25
3.0
O
O
SC6H5
C6H5
9e
O
O
O
O
SC6H5
OH
75 9ec
(80 : 20)
+
C6H5
O
2.75
SC6H5
18a
18b
O
O
C6H5S
C6H5
O
19
3.0
76 9e
HO
1
aYields refer to pure isolated products characterized by spectroscopic data (IR and H and 13C NMR).
1
bThe ratio was determined by H NMR spectroscopic data.
cCorresponds to compound 18a.
4-(4-Chlorophenylsulfanyl)pentan-2-one (Table 1, entry 8)
Colourless liquid. IR (neat, cm–1) ν: 1475, 1716. 1H NMR
(300 MHz, CDCl3) δ: 1.27 (d, J = 6.5 Hz, 3H), 2.12 (s, 3H),
2.55 (dd, J1 = 8.3 Hz, J2 = 17.2 Hz, 1H), 2.72 (dd, J1 =
5.3 Hz, J2 = 17.2 Hz, 1H), 3.65 (m, 1H), 7.26 (d, J = 8.6 Hz,
2H), 7.33 (d, J = 8.6 Hz, 2H). 13C NMR (75 MHz, CDCl3)
δ: 20.9, 30.5, 38.4, 50.0, 129.0 (2C), 132.5, 133.4, 133.6
(2C), 206.2. Anal. calcd. for C11H13ClOS: C 57.76, H 5.73;
found: C 57.84, H 5.81.
5-Phenylsulfanyl-hexan-3-one (Table 1, entry 9)
Colourless liquid. IR (neat, cm–1) ν: 1477, 1712. 1H NMR
(300 MHz, CDCl3) δ: 1.03 (t, J = 7.3 Hz, 3H), 1.27 (d, J =
6.7 Hz, 3H), 2.39 (q, J = 14.8 Hz, 2H), 2.53 (dd, J = 8.5 Hz,
16.9 Hz, 1H), 2.73 (dd, J = 5.3 Hz, 16.9 Hz, 1H), 3.71 (m,
1H), 7.23–7.32 (m, 3H), 7.38–7.42 (m, 2H). 13C NMR
(75 MHz, CDCl3) δ: 7.5, 20.9, 36.6, 38.2, 48.9, 124.5, 127.1
(2C), 132.2 (2C), 134.2, 209.2. Anal. calcd. for C12H16OS: C
69.19, H 7.74; found: C 68.93, H 7.60.
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Can. J. Chem. Vol. 84, 2006
9.75 (d, J = 2.3 Hz, 1H, minor). 13C NMR (75 MHz, CDCl3)
δ: 11.9 (major), 12.0 (minor), 13.6 (major), 13.7 (minor),
19.3 (major), 19.3 (minor), 20.2 (major), 20.5 (minor), 34.1
(minor), 34.6 (major), 49.2 (major), 49.8 (minor), 56.5 (mi-
nor), 56.9 (major), 127.2, 128.9 (2C), 132.3 (2C), 134.8,
203.5 (major), 204.1 (minor). Anal. calcd. for C14H20OS: C
71.14, H 8.53; found: C 70.93, H 8.39.
5-(4-Chlorophenylsulfanyl)hexan-3-one (Table 1, entry 10)
Colourless liquid. IR (neat, cm–1) ν: 1475, 1714. 1H NMR
(300 MHz, CDCl3) δ: 1.03 (t, J = 7.3 Hz, 3H), 1.26 (d, J =
6.7 Hz, 3H), 2.39 (q, J = 14.3 Hz, 2H), 2.52 (dd, J = 8.3 Hz,
16.4 Hz, 1H), 2.69 (dd, J = 5.5 Hz, 16.3 Hz, 1H), 3.68 (m,
1H), 7.25 (d, J = 8.5 Hz, 2H), 7.33 (d, J = 8.5 Hz, 2H). 13C
NMR (75 MHz, CDCl3) δ: 7.5, 20.9, 36.6, 38.5, 48.8, 128.9
(2C), 132.8, 132.9, 133.3 (2C), 208.9. Anal. calcd. for
C12H15ClOS: C 59.37, H 6.23; found: C 59.21, H 6.07.
3-(4-Chlorophenylsulfanyl)-2-ethyl-hexanal (Table 1,
entry 22)
Colourless liquid obtained as a mixture of diastereo-
3-(4-Chlorophenylsulfanyl)butanal (Table 1, entry 16)
Colourless liquid. IR (neat, cm–1) ν: 1437, 1475, 1724. 1H
NMR (300 MHz, CDCl3) δ: 1.34 (d, J = 6.6 Hz, 3H), 2.54–
2.73 (m, 2H), 3.63–3.69 (m, 1H), 7.23–7.37 (m, 4H), 9.74 (t,
J = 1.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ: 21.5, 38.2,
50.4, 128.1, 129.6 (2C), 132.3, 134.7 (2C), 200.5. Anal.
calcd. for C10H11ClOS: C 55.94, H 5.16; found: C 55.73, H
5.07.
1
isomers (51:49). IR (neat, cm–1) ν: 1475, 1722, 2719. H
NMR (300 MHz, CDCl3) δ: 0.88, 0.94 (m, 6H), 1.49–1.84
(m, 6H), 2.32–2.36 (m, 1H), 3.31–3.37 (m, 1H), 7.28 (d, J =
7.8 Hz, 2H), 7.34 (d, J = 7.8 Hz, 2H), 9.66 (d, J = 2.7 Hz,
1H, minor), 9.73 (d, J = 2.2 Hz, 1H, major). 13C NMR
(75 MHz, CDCl3) δ: 11.9 (major), 12.0 (minor), 13.6 (ma-
jor), 13.6 (minor), 19.2 (major), 19.3 (minor), 20.2 (major),
20.5 (minor), 34.0 (major), 34.6 (minor), 49.6 (major), 50.2
(minor), 56.8 (major), 56.4 (minor), 129.1 (2C), 133.3,
133.4, 133.6 (2C), 203.3 (major), 203.6 (minor). Anal. calcd.
for C14H19ClOS: C 62.09, H 7.07; found: C 61.89, H 6.94.
3-Benzylsulfanyl-butanal (Table 1, entry 17)
IR (neat, cm–1) ν: 1477, 1724. 1H NMR (300 MHz,
CDCl3) δ: 1.33 (d, J = 6.8 Hz, 3H), 2.55–2.61 (m, 2H),
3.13–3.19 (m, 1H), 3.78 (s, 2H), 7.24–7.33 (m, 5H), 9.66 (s,
1H). 13C NMR (75 MHz, CDCl3) δ: 21.3, 33.6, 35.2, 50.1,
127.1, 128.5 (2C), 128.7 (2C), 137.9, 200.5. Anal. calcd. for
C11H14OS: C 68.0, H 7.26; found: C 68.09, H 7.17.
3-(4-Chlorophenylsulfanyl)propionic acid methyl ester
(Table 1, entry 24)
Colourless liquid. IR (neat, cm–1) ν: 1477, 1737. 1H NMR
(300 MHz, CDCl3) δ: 2.59 (t, J = 7.5 Hz, 2H), 3.13 (t, J =
7.5 Hz, 2H), 3.67 (s, 3H), 7.19–7.29 (m, 4H). 13C NMR
(75 MHz, CDCl3) δ: 29.7, 34.4, 52.3, 129.5 (2C), 131.8
(2C), 134.1, 134.2, 172.4. Anal. calcd. for C10H11ClO2S: C
52.06, H 4.77; found: C 52.11, H 4.71.
2-Methyl-3-phenylsulfanyl-pentanal (Table 1, entry 19)
Obtained as a mixture of diastereoisomers (61:39). IR
(neat, cm–1) ν: 1447, 1722, 2721. 1H NMR (300 MHz,
CDCl3) δ: 1.08 (t, J = 7.2 Hz, 3H), 1.20 (d, J = 7.2 Hz, 3H),
1.54–1.67 (m, 2H), 2.55–2.59 (m, 1H), 3.39–3.45 (m, 1H),
7.22–7.33 (m, 3H), 7.41–7.44 (m, 2H), 9.68 (d, J = 1.6 Hz,
1H major), 9.69 (d, J = 1.0 Hz, 1H, minor). 13C NMR
(75 MHz, CDCl3) δ: 9.7 (minor), 10.1 (major), 11.8 (major),
12.1 (minor), 24.2 (major), 26.2 (minor), 49.1 (minor), 49.7
(major), 51.3 (major), 52.7 (minor), 127.2, 128.9 (2C), 132.3
(2C), 133.2, 203.5. Anal. calcd. for C12H16OS: C 69.19, H
7.74; found: C 69.03, H 7.60.
3-(4-Chlorophenylsulfanyl)propionitrile (Table 1, entry 27)
Pale yellow gummy liquid. IR (neat, cm–1) ν: 1431, 1477,
1
2243. H NMR (300 MHz, CDCl3) δ: 2.55–2.61 (m, 2H),
3.07–3.13 (m, 2H), 7.25–7.37 (m, 4H). 13C NMR (75 MHz,
CDCl3) δ: 18.1, 30.4, 117.6, 129.5 (2C), 131.6, 132.7 (2C),
133.9. Anal. calcd. for C9H8ClNS: C 54.68, H 4.08, N 7.09;
found: C 54.49, H 4.01, N 7.02.
2-Methyl-3-phenylsulfanyl-propionitrile (Table 1, entry 28)
Pale yellow liquid. IR (neat, cm–1) ν: 1438, 1481, 1583,
3-(4-Chlorophenylsulfanyl)-2-methyl-pentanal (Table 1,
entry 20)
1
2241. H NMR (300 MHz, CDCl3) δ: 1.40 (d, J = 6.9 Hz,
Colourless liquid obtained as a mixture of diastereo-
3H), 2.71–2.78 (m, 1H), 2.93–3.02 (m, 1H), 3.12–3.28 (m,
1H), 7.23–7.35 (m, 3H), 7.38–7.43 (m, 2H). 13C NMR
(75 MHz, CDCl3) δ: 17.1, 26.0, 38.2, 121.4, 127.4, 129.3
(2C), 131.1 (2C), 137.0. Anal. calcd. for C10H11NS: C 67.75,
H 6.25, N 7.90; found: C 75.43, H 6.16, N 7.81.
isomers (59:41). IR (neat, cm–1) ν: 1475, 1724, 2721. H
1
NMR (300 MHz, CDCl3) δ: 1.04 (t, J = 7.2 Hz, 3H), 1.20
(d, J = 7.21 Hz, 3H), 1.62–1.73 (m, 2H), 2.63–2.67 (m, 1H),
3.34–3.40 (m, 1H), 7.26 (d, J = 8.3 Hz, 2H), 7.37 (d, J =
8.3 Hz, 2H), 9.67 (d, J = 1.6 Hz, 1H, minor), 9.68 (d, J =
1.0 Hz, 1H, major). 13C NMR (75 MHz, CDCl3) δ: 9.7 (ma-
jor), 10.2 (minor), 11.8 (minor), 12.1 (major), 24.2 (minor),
26.2 (major), 48.9 (major), 49.6 (minor), 51.7 (minor), 52.9
(major), 129.1 (2C), 133.4, 133.5 (2C), 133.6, 203.2. Anal.
calcd. for C12H15ClOS: C 59.37, H 6.23; found: C 59.41, H
6.17.
General procedure for the synthesis of ␤-
hydroxyalkyl/aryl sulfides
Representative procedure for 1-phenylsulfanyloctan-2-ol
(Table 2, entry 1)
To a stirred solution of indium(I) iodide (121 mg,
0.5 mmol) and diphenyldisulphide (109 mg, 0.5 mmol) in
dry THF (2.5 mL) was added 1-octene oxide (128 mg,
1 mmol) and indium trichloride (11.05 mg, 5 mol%) under
nitrogen. The reaction mixture was heated under reflux for
3 h (TLC) and quenched with a few drops of water. THF
was then evaporated off and the residual mixture was then
extracted with ether (3 × 20 mL). The combined ether ex-
2-Ethyl-3-phenylsulfanyl-hexanal (Table 1, entry 21)
Colourless liquid obtained as a mixture of diastereo-
isomers (53:47). IR (neat, cm–1) ν: 1479, 1720, 2715. H
1
NMR (300 MHz, CDCl3) δ: 0.88–0.96 (m, 6H), 1.51–1.71
(m, 6H), 2.33–2.37 (m, 1H), 3.35–3.43 (m, 1H), 7.21–7.32
(m, 3H), 7.38–7.43 (m, 2H), 9.66 (d, J = 2.7 Hz, 1H, major),
© 2006 NRC Canada

Ranu and Mandal
769
tract was washed with brine and dried (Na2SO4). Evapora-
tion of the solvent left the crude product, which was purified
by column chromatography over silica gel (hexane–ether,
85:15) to furnish the pure product, 1-thiophenyloctan-2-ol as
a colourless oil (233 mg, 98%). The product was identified
CDCl3) δ: 3.74 (s, 3H, major), 3.78 (s, 3H, minor), 4.57 (d,
J = 2.64 Hz, 1H, minor), 4.64 (d, J = 2.58 Hz, 1H, major),
5.42 (d, J = 2.64 Hz, 1H, minor), 5.45 (d, J = 2.58 Hz, 1H,
major), 6.74 (d, J = 7.32 Hz, 2H, minor), 6.86 (d, J =
8.70 Hz, 2H, major), 7.04–7.07 (m, 4H, (2H for major and
2H for minor)), 7.29–7.32 (m, 4H (2H for major and 2H for
minor)), 7.41–7.50 (m, 8H (4H for major and 4H for mi-
nor)), 7.62–7.64 (m, 4H (2H for major and 2H for minor)),
7.66 (d, J = 8.70 Hz, 2H, major), 7.84 (d, J = 7.32 Hz, 2H,
minor). 13C NMR (75 MHz, CDCl3) δ: 55.5 (major), 55.6
(minor), 57.3 (minor), 58.4 (major), 75.2 (minor), 77.1 (ma-
jor), 113.9 (minor, 2C), 114.3 (major, 2C), 127.6 (minor),
127.8 (major), 128.1 (minor), 128.2 (major), 128.8 (major,
2C), 128.9 (minor, 2C), 129.1 (major, 2C), 129.2 (minor,
2C), 129.4 (major, 2C), 129.5 (minor, 2C), 129.9 (minor,
2C), 130.1 (minor), 130.4 (major, 2C), 130.5 (major), 132.8
(minor, 2C), 133.3 (major, 2C), 134.2 (minor), 134.5 (ma-
jor), 134.7 (minor), 135.1 (major), 159.5 (minor), 159.7 (major),
199.1 (minor), 199.7 (major). Anal. calcd. for C22H20O3S: C
72.50, H 5.53; found: C 72.41, H 5.43.
1
by comparison of its spectroscopic data (IR and H and 13C
NMR) with the reported values (8g).
This procedure was followed for all the reactions listed in
Table 2. All the products are adequately characterized by
1
their spectroscopic data (IR and H and 13C NMR). The val-
ues for the known compounds are in good agreement with
those reported (Table 2). The spectroscopic data and elemen-
tal analysis for new compounds that are not available in the
literature are provided here.
1-(4-Chlorophenylsulfanyl)octan-2-ol (Table 2, entry 3)
Colourless liquid. IR (neat, cm–1) ν: 1439, 1479, 1580,
1
3467. H NMR (300 MHz, CDCl3) δ: 0.87 (t, J = 6.36 Hz,
3H), 1.26–1.41 (m, 7H), 1.42–1.53 (m, 3H), 2.36 (bs, 1H),
2.84 (dd, J = 8.49, 13.56 Hz, 1H), 3.08 (dd, J = 3.39 Hz,
13.56 Hz, 1H), 3.62–3.70 (m, 1H), 7.23–7.32 (m, 4H). 13C
NMR (75 MHz, CDCl3) δ: 14.4, 22.9, 25.9, 29.6, 32.1, 36.5,
42.7, 69.9, 129.5 (2C), 131.6 (2C), 132.9, 134.5. Anal. calcd.
for C14H21ClOS: C 61.63, H 7.76; found: C 61.50, H 7.61.
2-Hydroxy-3-phenyl-3-phenylsulfanyl propionic acid ethyl
ester (Table 2, entry 15)
Colourless liquid. IR (neat, cm–1) ν: 1439, 1479, 1583,
1
1732, 3484. H NMR (300 MHz, CDCl3) δ: 1.07 (t, J =
2-(4-Chlorophenylsulfanyl)cyclohexanal (Table 2, entry 9)
7.20 Hz, 3H), 2.88 (bs, 1H), 3.99 (q, J = 7.20 Hz, 2H), 4.49
(d, J = 3.69 Hz, 1H), 4.52 (d, J = 3.69 Hz, 1H), 7.11–7.18
(m, 6H), 7.28–7.33 (m, 4H). 13C NMR (75 MHz, CDCl3) δ:
13.9, 56.5, 61.8, 72.6, 127.4, 127.9, 128.2 (2C), 128.3 (2C),
128.7 (2C), 132.1 (2C), 134.2, 136.4, 171.8. Anal. calcd. for
C17H18O3S: C 67.52, H 6.00; found: C 67.45, H 5.91.
Colourless liquid. IR (neat, cm–1) ν: 1446, 1477, 1581,
1
3398. H NMR (300 MHz, CDCl3) δ: 1.17–1.38 (m, 4H),
1.67–1.79 (m, 2H), 2.03–2.12 (m, 2H), 2.70–2.77 (m, 1H),
2.80 (s, 1H), 3.30 (ddd, J = 4.20, 9.86, 10.01 Hz, 1H), 7.23–
7.26 (m, 2H), 7.35–7.39 (m, 2H). 13C NMR (75 MHz,
CDCl3) δ: 24.6, 26.4, 32.9, 34.3, 56.9, 72.4, 129.4 (2C),
131.7, 134.3, 135.3 (2C). Anal. calcd. for C12H15ClOS: C
59.37, H 6.23; found: C 59.21, H 6.11.
1-Phenylsulfanyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-
2-one (Table 2, entry 16)
Yellowish liquid. IR (neat, cm–1) ν: 1439, 1477, 1582,
1
2-(4-Chlorophenylsulfanyl)cycloheptanol (Table 2, entry 11)
1674, 3477. H NMR (300 MHz, CDCl3) δ: 0.97–1.51 (m,
Colourless liquid. IR (neat, cm–1) ν: 1438, 1478, 1582,
4H), 1.52–2.13 (m, 5H), 2.44–2.83 (m, 3H), 3.59–3.69 (m,
1H), 7.07–7.44 (m, 5H). 13C NMR (75 MHz, CDCl3) δ:
25.3, 27.2, 28.2, 34.6, 35.2, 37.0, 41.0, 125.3, 127.2 (2C),
128.9 (2C), 137.2, 137.4, 174.0, 195.1. Anal. calcd. for
C16H18OS: C 74.38, H 7.02; found: C 74.25, H 6.92.
1
3473. H NMR (300 MHz, CDCl3) δ: 1.46–1.61 (m, 4H),
1.69–1.77 (m, 2H), 1.99–2.25 (m, 2H), 2.27–2.40 (m, 2H),
2.41 (s, 1H), 3.64 (ddd, J = 3.21, 8.73, 9.87 Hz, 1H), 4.02–
4.09 (m, 1H), 7.24–7.38 (m, 4H). 13C NMR (75 MHz,
CDCl3) δ: 22.0, 25.0, 26.9, 32.6, 35.3, 66.1, 79.2, 126.4,
127.7, 129.5 (2C), 133.5 (2C). Anal. calcd. for C13H17ClOS:
C 60.80, H 6.67; found: C 60.62, H 6.51.
2-Hydroxy-3,5,5-trimethyl-3-phenylsufanyl-cyclohexanone
(Table 2, entry 18b)
Colourless liquid. IR (neat, cm–1) ν: 1439, 1477, 1582,
1
3-Hydroxy-1,3-diphenyl-2-phenylsulfanyl-propan-1-one
(Table 2, entry 13)
1740. H NMR (300 MHz, CDCl3) δ: 1.15 (s, 3H), 1.27 (s,
3H), 1.42 (s, 3H), 1.81–1.86 (m, 1H), 2.25–2.34 (m, 2H),
2.53–2.59 (m, 1H), 4.44 (s, 1H), 7.15–7.26 (m, 5H). 13C
NMR (75 MHz, CDCl3) δ: 26.3, 30.7, 31.1, 32.9, 47.1, 54.7,
56.8, 71.3, 128.0, 129.0 (2C), 133.2, 133.8, 134.2, 220.7.
Anal. calcd. for C15H20O2S: C 68.14, H 7.62; found: C
67.95, H 7.48.
Yellow oil. IR (neat, cm–1) ν: 1438, 1477, 1597, 1683,
1
3460. H NMR (300 MHz, CDCl3) δ: 2.94 (bs, 1H), 4.64 (d,
J = 2.58 Hz, 1H), 5.48 (d, J = 2.58 Hz, 1H), 7.10–7.13 (m,
2H), 7.20–7.24 (m, 6H), 7.45–7.62 (m, 4H), 7.62–7.68 (m,
3H). 13C NMR (75 MHz, CDCl3) δ: 58.0, 75.1, 128.2, 128.5
(2C), 128.6, 128.7 (2C), 129.0 (2C), 129.2 (2C), 129.3 (2C),
129.4, 129.5, 133.3 (2C), 134.5, 135.9, 198.9. Anal. calcd.
for C21H18O2S: C 75.42, H 5.42; found: C 75.31, H 5.33.
3-Hydroxy-5-isopropenyl-2-methyl-2-phenylsulfanyl-
cyclohexanone (Table 2, entry 19)
Colourless liquid. IR (neat, cm–1) ν: 1439, 1474, 1646,
1
2-Hydroxy-3-(4-methoxy-phenyl)-1-phenyl-3-phenyl-
sulfanyl-propan-1-one (as a mixture of diastereomers,
52:48) (Table 2, entry 14)
1696, 3464. H NMR (300 MHz, CDCl3) δ: 1.18 (s, 3H),
1.76 (s, 3H), 1.89–1.97 (m, 1H), 2.32–2.42 (m, 2H), 2.57
(bs, 1H), 2.84–2.94 (m, 1H), 3.30–3.41 (m, 1H), 4.18–4.20
(m, 1H), 4.79 (d, J = 0.75 Hz, 2H), 7.24–7.35 (m, 5H). 13C
NMR (75 MHz, CDCl3) δ: 18.8, 20.4, 33.4, 39.2, 41.7, 59.9,
Yellowish, low-melting solid; mp 40–43 °C. IR (neat, cm–1)
ν: 1438, 1477, 1581, 1682, 3465. 1H NMR (300 MHz,
© 2006 NRC Canada

770
Can. J. Chem. Vol. 84, 2006
and S. Samanta. J. Org. Chem. 68, 7130 (2003); (h) B.C.
Ranu, A. Das, and A. Hajra. Synthesis, 1012 (2003); (i) B.C.
Ranu and S. Samanta. Tetrahedron, 59, 7901 (2003); ( j) B.C.
Ranu, R. Jana, and S. Samanta. Adv. Synth. Catal. 346, 446
(2004); (k) B.C. Ranu and A. Das. Adv. Synth. Catal. 347, 712
(2005).
76.0, 110.3, 129.0 (2C), 129.6, 129.7, 136.5 (2C), 147.0,
208.5. Anal. calcd. for C16H20O2S: C 69.53, H 7.29; found:
C 69.43, H 7.13.
Acknowledgements
4. (a) B.C. Ranu, T. Mandal, and S. Samanta. Org. Lett. 5, 1439
(2003); (b) B.C. Ranu and T. Mandal. J. Org. Chem. 69, 5793
(2004); (c) B.C. Ranu and T. Mandal. Synlett, 1239 (2004);
(d) B.C. Ranu and A. Das. Tetrahedron Lett. 45, 6875 (2004).
5. (a) E.J. Corey, D.A. Clark, G. Goto, A. Marfat, C.
Mioskowski, C. Samuelsson, and S. Hammarstrom. J. Am.
Chem. Soc. 102, 3663 (1980); (b) E.J. Corey, D.A. Clark, and
G. Goto. Tetrahedron Lett. 21, 3143 (1980).
We are pleased to acknowledge the financial support from
the Council of Scientific and Industrial Research (CSIR),
New Delhi (Grant No. 01(1936)/04) for this investigation.
TM is also thankful to CSIR for his fellowship.
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© 2006 NRC Canada