Indium-catalyzed direct conversion of lactones into thiolactones using a disilathiane as a sulfur source

Article abstract of DOI:10.3390/molecules23061339

An indium-catalyzed reaction of lactones and a disilathiane leading to thiolactones is described. The direct synthesis of thiolactones from lactones with an appropriate sulfur source is one of the most attractive approaches in organic and pharmaceutical chemistry. In this context, we found an indium-catalyzed direct conversion of lactones into thiolactones in the presence of elemental sulfur and a hydrosilane via formation of the disilathiane in situ. On the basis of the previous reaction, the application utilizing the disilathiane as a sulfur source was performed herein for the efficient synthesis of a variety of thiolactone derivatives from lactones by an indium catalyst.

Full text of DOI:10.3390/molecules23061339

molecules
Article
Indium-Catalyzed Direct Conversion of Lactones into
Thiolactones Using a Disilathiane as a Sulfur Source
ID
Yohei Ogiwara ID , Ken Takano, Shuhei Horikawa and Norio Sakai *
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science,
2641 Yamazaki, Noda, Chiba 278-8510, Japan; yoheiogiwara@rs.tus.ac.jp (Y.O.); 7218534@ed.tus.ac.jp (K.T.);
7216665@alumni.tus.ac.jp (S.H.)
* Correspondence: sakachem@rs.noda.tus.ac.jp; Tel.: +81-4-7123-9890
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 16 May 2018; Accepted: 1 June 2018; Published: 2 June 2018
Abstract: An indium-catalyzed reaction of lactones and a disilathiane leading to thiolactones is
described. The direct synthesis of thiolactones from lactones with an appropriate sulfur source is one
of the most attractive approaches in organic and pharmaceutical chemistry. In this context, we found
an indium-catalyzed direct conversion of lactones into thiolactones in the presence of elemental sulfur
and a hydrosilane via formation of the disilathiane in situ. On the basis of the previous reaction,
the application utilizing the disilathiane as a sulfur source was performed herein for the efficient
synthesis of a variety of thiolactone derivatives from lactones by an indium catalyst.
Keywords: indium catalyst; disilathiane; lactones; thiolactones
1. Introduction
The introduction of a sulfur atom to organic molecules is a significant topic in synthetic
chemistry because it potentially provides complex and important sulfur-containing compounds
directly. Therefore, a search for an undiscovered sulfur source that could be applicable to organic sulfur
chemistry is imperative, and extensive efforts have been devoted to the development of molecular
transformations utilizing a novel sulfur source by many research groups thus far [
our group has demonstrated that the copper-catalyzed construction of diaryl sulfides from aryl iodides
and hexamethyldisilathiane, (Me3Si)2S [ ]. In the reaction, the disilathiane functioned as an effective
1–6]. In this context,
7
S1 source of sulfides, and the results suggested to us that the strategy employing the disilathiane could
be acceptable for any other sulfur-introduction reactions [8–12].
Recently, we also reported the indium-catalyzed reductive conversion of lactones
thiolactones using a combination of elemental sulfur (S8) and a hydrosilane, wherein the generation
of a disilathiane ([Si]2S) from S8 and a hydrosilane is a key process for the formation of thiolactones
(Scheme 1a) [13]. Although the in situ formation strategy of the disilathiane is a useful and an easily
handled procedure, the yields of thiolactones obtained by the method remained at low to moderate
1 into
2
2
2
levels. We envisioned that the problem could be overcome by utilizing the activated disilathiane, which
can be easily prepared from S8 and a hydrosilane in advance. Herein, we describe the indium-catalyzed
direct formation of thiolactones
(Scheme 1b).
2
from lactones
1
using hexamethyldisilathiane as an effective S1 source
Molecules 2018, 23, 1339; doi:10.3390/molecules23061339
www.mdpi.com/journal/molecules

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Scheme 1. Indium-catalyzed conversion of lactones
1 to thiolactones 2 using (a) S8 and a hydrosilane,
and (b) a disilathiane.
2. Results and Discussion
On the bases of our previous study on the InCl3-catalyzed transformation of lactones
thiolactones employing elemental sulfur (S8) and a hydrosilane, optimization studies utilizing
a disilathiane as a sulfur source were initially conducted (Table 1). When -phenyl- -butyrolactone
1 to
2
γ
γ
(
1a) was treated with 1.1 equiv of◦hexamethyldisilathiane, (Me3Si)2S, in the presence of 5 mol % of
InCl3 in 1,2-dichlorobenzene at 80 C for 24 h, the corresponding γ-butyrothiolactone 2a was obtained
in a 77% GC yield (entry 1). The formation of 2a was also observed in cases with other catalysts, such as
InBr3, InI3, In(OAc)3, In(OTf)3, and Cu(OTf)2 in good yields (entries 2–6). Especially, In(OTf)3 proved
to be the most effective catalyst for the reaction, shown in entry 5, which provided 2a in a 99% GC yield
with a 94% isolated yield. In contrast, in the absence of the catalyst, thiolactone was not generated
(entry 7). We next chose chlorobenzene, 1,2-dichloroethane, and toluene as potential solvents for the
transformation based on our previous results [13]. Although these solvents were also acceptable to
the reaction, these yields were not higher than those using 1,2-Cl2C6H4 as a solvent (entries 8–10 vs.
entry 5). The reaction with a lower catalyst loading (1 mol % of In(OTf)3) made it possible to form 2a
in a 97% GC yield with an 83% isolated yield (entry 11), and then a gram-scale application using 1a
(5 mmol) and (Me3Si)2S (5.5 mmol) provided 0.70 g (3.9 mmol) of thiolactone 2a (entry 12). Employing
a stoichiometric amount of TfOH instead of In(OTf)3 catalyst provided thiolactone quantitatively
(entry 13), whereas its application to the TfOH-catalyzed reaction did not proceed well (entry 14).
Conversion of lactone 1a into thiolactone 2a, and not into the other possible sulfur-containing
compounds, such as the thionolactone 3a and the dithiolactone 4a, can be easily discriminated by
1H and 13C-NMR spectroscopy (Table 2 and Figure 1). In the 1H-NMR spectrum of the thiolactone
2a, a signal for the methine proton (CH) next to the oxygen appeared at 5.01 ppm in CDCl3, which
is clearly different to those of the corresponding protons of 1a (5.52 ppm), 3a (5.86 ppm), and 4a
(5.29 ppm). The chemical shifts of the carbonyl (C=O) or the thiocarbonyl (C=S) in the 13C-NMR
spectrum can also identify the difference between 1a (176.9 ppm in CDCl3), 2a (207.9 ppm), 3a
(221.9 ppm), and 4a (245.3 ppm). For most of the isolated products by this procedure shown below
(e.g., Table 3), therefore, these structures were assigned as thiolactone 2
forms by 1H and 13C-NMR
analyses (The detailed spectral data are summarized in Section 3.4. Product Characterization and the
Supplementary Materials).

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Table 1. Screening of the reaction conditions for the catalytic conversion of 1a to 2a a.
Entry
Catalyst
Solvent
GC Yield of 2a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
InCl3 (5 mol %)
InBr3 (5 mol %)
InI3 (5 mol %)
In(OAc)3 (5 mol %)
In(OTf)3 (5 mol %)
Cu(OTf)2 (5 mol %)
none
In(OTf)3 (5 mol %)
In(OTf)3 (5 mol %)
In(OTf)3 (5 mol %)
In(OTf)3 (1 mol %)
In(OTf)3 (1 mol %)
TfOH (100 mol %)
TfOH (15 mol %)
1,2-Cl2C6H4
1,2-Cl2C6H4
1,2-Cl2C6H4
1,2-Cl2C6H4
1,2-Cl2C6H4
1,2-Cl2C6H4
1,2-Cl2C6H4
ClC6H5
ClCH2CH2Cl
CH3C6H5
1,2-Cl2C6H4
1,2-Cl2C6H4
1,2-Cl2C6H4
1,2-Cl2C6H4
77
62
69
78
99 (94) b
94
0
76
95
59
97 (83) b
78 b,c
99
23
a
Reaction conditions: 1a (0.5 mmol), (Me3Si)2S (0.55 mmol), catalyst (0.005–0.025 mmol), solvent (0.5 mL) at 80 ◦
C
b
c
for 24 h. Isolated yield. 5 mmol scale.
Table 2. Selected 1H and 13C-NMR spectral data (CDCl3, rt) for 1a, 2a, 3a, and 4a.
S
O
S
O
C
C
C
C
O
S
S
O
H
H
H
H
Ph
Ph
Ph
Ph
Thionolactone 3a
Thiolactone 2a
Dithiolactone 4a
Lactone 1a
1H-NMR
13C-NMR
δ 5.52 (OCH)
δ 176.9 (C=O)
δ 5.01 (SCH)
δ 207.9 (C=O)
δ 5.86 (OCH)
δ 221.9 (C=S)
δ 5.29 (SCH)
δ 245.3 (C=S)
(a)
(b)
Figure 1. NMR spectra of 1a–4a: (a b)
) 1H-NMR (500 MHz, CDCl3, rt), ( 13C-NMR (126 MHz, CDCl3, rt).

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Table 3. Indium-catalyzed conversion of lactones 1 to the thiolactones 2.
conditions A
In(OTf)3 (1 mol %)
conditions B
InCl3 (5 mol %)
conditions A or B
lactone 1
thiolactone 2
(Me3Si)2S (1.1 equiv) S8 (1.1 equiv)
80 °C PhSiH3 (0.67 equiv)
1,2-Cl2C6H4, 24 h
120 °C
Isolated Yield of 2 (%)
Entry
Lactone 1
Thiolactone 2
Conditions A a
Conditions B b
O
O
S
O
R
R
1
2
3
4
5
6
7
8
9
1b (R = 2-Me)
1c (R = 3-Me)
1d (R = 4-Me)
1e (R = 2,5-Me2)
1f (R = 4-Ph)
1g (R = 3-MeO)
1h (R = 4-MeO)
1i (R = 4-F)
2b
2c
2d
2e
2f
2g
2h
2i
73
82
64
65
61
79
22
79
87
74
71
55
66
49
n/a c
16
8 d
61
60
1j (R = 4-Cl)
1k (R = 4-Br)
2j
2k
10
60
O
O
O
S
11
1l
2l
36
23
34
O
O
O
S
S
S
12
13
1m
2m
2n
0
O
O
O
S
1n
66 e
n/a c

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Table 3. Cont.
conditions A
In(OTf)3 (1 mol %)
(Me3Si)2S (1.1 equiv) S8 (1.1 equiv)
80 °C PhSiH3 (0.67 equiv)
conditions B
InCl3 (5 mol %)
conditions A or B
lactone 1
thiolactone 2
1,2-Cl2C6H4, 24 h
120 °C
Isolated Yield of 2 (%)
Entry
Lactone 1
Thiolactone 2
Conditions A a
Conditions B b
18 f
85
14
15
1o (R = H)
1p (R = Ph)
O
2o
2p
0
10
O
O
S
Ar
Ar
16
17
18
1q (Ar = Ph)
1r (Ar =
4-MeC6H4)
2q
2r
2s
10 g
14
9
4
n/a c
n/a c
1s (Ar = 4-ClC6H4)
O
O
O
S
88 h
19
1t
2t
23
a
This work:
1
(0.5 mmol), (Me3Si)2S (0.55 mmol), In(OTf)3 (0.005 mmol), 1,2-Cl2C6H4 (0.5 mL) at 80 ◦C for 24 h.
Previous work: (0.5 mmol), S8 (0.55 mmol of S atom), PhSiH3 (0.33 mmol), InCl3 (0.025 mmol), 1,2-Cl2C6H4
(0.5 mL) at 120 ◦C for 24 h. Not applicable. 4-(4-Methoxyphenyl)butanoic acid (30%) was formed. NMR yield.
b
1
c
d
e
f
g
h
7 d. 120 ◦C, 3 days. InCl3 (0.025 mmol, 5 mol %), 120 ◦C, 20 h.
Examination of the In(OTf)3-catalyzed direct transformation of several lactones
conducted under the conditions described for entry 10 in Table 1. The results of the present reaction
utilizing an In(OTf)3/(Me3Si)2S system (conditions A) and our previous yields of thiolactones
1 was then
2
by an InCl3-catalyzed reaction using S8/PhSiH3 (conditions B) [13] are summarized in Table 3.
In most of the substrates, the conditions A showed a better reactivity for the conversion of
1
into
functional groups at the aryl ring, such as methyl, phenyl, methoxy, and halogen, afforded the
corresponding -aryl- -butyrothiolactones 2b 2k (entries 1–10). Among these entries, the yield of a
2 than that of conditions B. Reactions of γ-aryl-γ-butyrolactons 1b–1k bearing various
γ
γ
–
4-methoxy-substituted one 2h was not sufficient (entry 7), probably because of benzylic C–O bond
cleavage prior to the reaction with disilathiane due to the strong electron donation by the 4-methoxy
substituent. Similar results were also obtained in the case of our previous investigation employing an
S8/PhSiH3 system prominently, which provided 4-(4-methoxyphenyl)butanoic acid as a side product
in a 30% yield (entry 7, conditions B). A tetralin and a thiophene ring were also acceptable to
substituents of the butyrolactons 1l and 1m, forming 2l and 2m (entries 11 and 12). The simple
unsubstituted -butyrolactons 1n, phthalide (1o), and its derivative 1p were converted into the
products 2n 2p, respectively (entries 13–15). When -lactones 1q 1t were used as starting substrates,
γ-aryl
γ
–
δ
–
the formation of the expected six-membered thiolactones 2q–2t were observed (entries 16–19).
Finally, the present procedure was evaluated using substrates involving an ester moiety, but not
lactones. When phthalic anhydride (1u) was treated with a disilathiane, the corresponding reaction
proceeded to give thiophthalic anhydride (2u) in a 74% isolated yield (Scheme 2).

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O
O
In(OTf)3 (1 mol %)
+
(Me3Si)2S
O
S
1,2-Cl2C6H4
80 °C, 24 h
1.1 equiv
O
O
1u
2u, 74%
Scheme 2. Reaction of phthalic anhydride.
Although an acyclic ester, the methyl benzoate derivative 1v was not acceptable to the
transformation under the optimal conditions; the use of 5 mol % of InI3 catalyst at 120 ◦C for 20 h
improved the reactivity for the reaction, leading to the expected thioester 2v in a 38% isolated yield.
Along with the formation of the thioester 2v in those conditions, the unexpected dithioester 4v was
also isolated in an 18% yield (Scheme 3).
O
O
S
catalyst
+
+
(Me3Si)2S
O
S
S
1,2-Cl2C6H4
1.1 equiv
1v
2v
4v
0%
0%
In(OTf)3 (1 mol %), 80 °C, 24 h
InI3 (5 mol %), 120 °C, 20 h
38%
18%
Scheme 3. Reaction of an acyclic ester.
3. Materials and Methods
3.1. General Information
1H- and 13C-NMR spectra were recorded on a 300 or 500 MHz spectrometer. Chemical shifts in the
1H- and 13C-NMR spectra were reported in ppm relative to the residual solvent peaks, such as those of
chloroform (
1H and 13C). High-resolution mass spectra (HRMS) were measured using NBA (3-nitrobenzylalcohol)
as a matrix. GC analyses were performed using a DB-5 capillary column (30 m 0.25 mm, film
thickness = 0.25 m). Reactions were monitored by TLC analysis of the reaction aliquots. Column
δ δ δ 0.00 for both
7.26 for 1H and 77.0 for 13C) or of the internal reference tetramethylsilane (
×
µ
chromatography was performed using a silica gel. All indium compounds and hexamethyldisilathiane
were commercially available and were used without further purification. 1,2-Dichlorobenzene was
distilled from CaH2. The lactones 1a, 1f, 1n, 1o, 1q, and 1t, phthalic anhydride (1u), and an ester 1v
were purchased and used without further purification. The lactones 1b and 1l were prepared by the
gallium-catalyzed reductive cyclization of keto acids [14]. The lactones 1c, 1d, 1e, 1g, 1h, 1i, 1j, 1k, 1m,
1p, 1r, and 1s were prepared via a modified literature method [15].
3.2. General Procedure A for the Indium-Catalyzed Conversion of Lactones or Their Derivatives 1 into
Thiolactones 2 Using a Disilathiane (In the Case of 1 in Solid State at Room Temperature)
To a screw-capped tube, lactone or the derivative
1 (0.50 mmol) was added. The tube was sealed
and moved into a glovebox, then In(OTf)3 (2.8 mg, 0.0050 mmol) was added. The tube was sealed
again and removed from the glovebox. 1,2-Dichlorobenzene (0.5 mL) and hexamethyldisilathiane
(98.1 mg, 0.550 mmol) were successively added, and after the tube was sealed, the mixture was heated
at 80 ◦C for 24 h. The resulting mixture was cooled to room temperature and chloroform was added.
The mixture was transferred into a round-bottom flask, which was then evaporated under reduced
pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc)
followed by gel permeation chromatography (GPC) in some cases.

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3.3. General Procedure B for the Indium-Catalyzed Conversion of Lactones 1 into Thiolactones 2 Using a
Disilathiane (In the Case of 1 in Liquid State at Room Temperature)
To a screw-capped tube, In(OTf)3 (2.8 mg, 0.0050 mmol) was added in a glovebox. The tube was
then sealed and removed from the glovebox, and 1,2-dichlorobenzene (0.5 mL), lactone
1 (0.50 mmol),
and hexamethyldisilathiane (98.1 mg, 0.550 mmol) were added in this order. After the tube was sealed,
◦
the mixture was heated at 80 C for 24 h. The resulting mixture was cooled to room temperature
and chloroform was added. The mixture was transferred into a round-bottom flask, which was
then evaporated under reduced pressure. The crude material was purified by silica gel column
chromatography (hexane/EtOAc) followed by gel permeation chromatography (GPC) in some cases.
3.4. Product Characterization
Dihydro-5-phenyl-2(3H)-thiophenone (2a) [13].
General procedure A was followed with
5-phenyldihydrofuran-2-one (1a, 80.2 mg). Column chromatography (10/1 hexane/EtOAc) afforded
1
2a as a colorless oil (73.4 mg, 83%): H-NMR (CDCl3, 500 MHz)
δ
2.24–2.32 (m, 1 H, CH2), 2.59–2.82
(m, 3 H, CH2, CH2), 5.01 (dd, J = 10.0, 5.5 Hz, 1 H, CH), 7.30–7.44 (m, 5 H, ArH); 13C-NMR (CDCl3,
126 MHz) δ 35.0, 42.9, 54.3, 127.4, 128.1, 128.9, 139.4, 207.9; MS (EI) m/z (%) 178 (M+, 78), 117 (100).
Dihydro-5-(2-methylphenyl)-2(3H)-thiophenone (2b) [13]. General procedure B was followed with
5-(2-methylphenyl)dihydrofuran-2-one (1b, 89.9 mg). Column chromatography (10/1 hexane/EtOAc)
1
afforded 2b as a colorless oil (69.7 mg, 73%): H-NMR (CDCl3, 500 MHz)
δ
2.26–2.34 (m, 1 H, CH2),
2.42 (s, 3 H, CH3), 2.55–2.61 (m, 1 H, CH2), 2.67–2.74 (m, 1 H, CH2), 2.78–2.84 (m, 1 H, CH2), 5.25 (dd,
J = 9.5, 5.5 Hz, 1 H, CH), 7.19–7.27 (m, 3 H, ArH), 7.56 (d, J = 8.0 Hz, 1 H, ArH); 13C-NMR (CDCl3,
126 MHz)
δ
19.5, 33.4, 42.7, 50.3, 126.5, 126.7, 127.8, 130.7, 135.7, 137.2, 208.0; MS (EI) m/z (%) 192 (M+,
82), 117 (100).
Dihydro-5-(3-methylphenyl)-2(3H)-thiophenone (2c) [13]. General procedure B was followed with
5-(3-methylphenyl)dihydrofuran-2-one (1c, 92.3 mg). Column chromatography (10/1 hexane/EtOAc)
1
afforded 2c as a dark yellow oil (81.9 mg, 82%): H-NMR (CDCl3, 500 MHz)
δ 2.23–2.31 (m, 1 H, CH2),
2.37 (s, 3 H, CH3), 2.57–2.81 (m, 3 H, CH2, CH2), 4.97 (dd, J = 10.0, 5.5 Hz, 1 H, CH), 7.13 (d, J = 7.5 Hz,
1 H, ArH), 7.21–7.28 (m, 3 H, ArH); 13C-NMR (CDCl3, 126 MHz)
128.7, 128.9, 138.6, 139.3, 208.0; MS (EI) m/z (%) 192 (M+, 100).
δ 21.4, 35.0, 42.9, 54.3, 124.4, 128.1,
Dihydro-5-(4-methylphenyl)-2(3H)-thiophenone (2d) [13]. General procedure A was followed with
5-(4-methylphenyl)dihydrofuran-2-one (1d, 87.5 mg). Column chromatography (10/1 hexane/EtOAc)
1
afforded 2d as a colorless oil (61.3 mg, 64%): H-NMR (CDCl3, 500 MHz)
δ
2.21–2.29 (m, 1 H, CH2),
2.35 (s, 3 H, CH3), 2.56–2.78 (m, 3 H, CH2, CH2), 4.96 (dd, J = 10.0, 5.5 Hz, 1 H, CH), 7.17 (d, J = 8.0 Hz,
2 H, ArH), 7.30 (d, J = 8.0 Hz, 2 H, ArH); 13C-NMR (CDCl3, 126 MHz)
129.5, 136.4, 137.9, 208.0; MS (EI) m/z (%) 192 (M+, 82), 117 (100).
δ 21.0, 35.0, 42.9, 54.1, 127.2,
Dihydro-5-(2,5-dimethylphenyl)-2(3H)-thiophenone (2e) [13]. General procedure A was followed with
5-(2,5-dimethylphenyl)dihydrofuran-2-one (1e, 94.5 mg). Column chromatography (10/1 hexane/EtOAc)
1
afforded 2e as a yellow oil (66.6 mg, 65%): H-NMR (CDCl3, 500 MHz)
δ 2.24–2.31 (m, 1 H, CH2), 2.33
(s, 3 H, CH3), 2.36 (s, 3 H, CH3), 2.53–2.58 (m, 1 H, CH2), 2.65–2.73 (m, 1 H, CH2), 2.76–2.82 (m, 1 H,
CH2), 5.22 (dd, J = 10.0, 5.5 Hz, 1 H, CH), 7.01 (d, J = 7.5 Hz, 1 H, ArH), 7.07 (d, J = 7.5 Hz, 1 H, ArH),
7.36 (s, 1 H, ArH); 13C-NMR (CDCl3, 126 MHz)
δ 19.0, 21.0, 33.4, 42.7, 50.3, 127.1, 128.5, 130.6, 132.5,
136.2, 136.9, 208.1; MS (EI) m/z (%) 206 (M+, 85), 131 (100).
Dihydro-5-([1,10-biphenyl]-4-yl)-2(3H)-thiophenone (2f). General procedure A was followed with
5-[1,10-Biphenyl]-4-yldihydro-2(3H)-furanone (1f
,
96.2 mg).
hexane/EtOAc) and GPC afforded 2f as a colorless solid (61.6 mg, 61%): m.p. 120–121 ◦C; 1H-NMR
(CDCl3, 500 MHz) 2.78–2.36 (m, 1 H, CH2), 2.63–2.83 (m, 3 H, CH2, CH2), 5.05 (dd, J = 10.0, 5.5 Hz, 1 H,
CH), 7.35–7.61 (m, 9 H, ArH); 13C-NMR (CDCl3, 126 MHz)
35.0, 42.9, 54.1, 127.0, 127.5, 127.6, 127.9,
Column chromatography (10/1
δ
δ

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128.8, 138.4, 140.4, 141.1, 207.8; MS (EI) m/z (%) 254 (M+, 100); HRMS (EI) calcd for [M]+ (C16H14OS)
m/z 254.0765, found 254.0771.
Dihydro-5-(3-methoxyphenyl)-2(3H)-thiophenone (2g) [13]. General procedure B was followed with
5-(3-methoxyphenyl)dihydrofuran-2-one (1g, 100.9 mg). Column chromatography (10/1 hexane/EtOAc)
1
afforded 2g as a yellow oil (86.4 mg, 79%): H-NMR (CDCl3, 500 MHz)
δ 2.21–2.30 (m, 1 H, CH2),
2.59–2.78 (m, 3 H, CH2, CH2), 3.81 (s, 3 H, CH3), 4.96 (dd, J = 10.0, 5.5 Hz, 1 H, CH), 6.85 (dd, J = 8.0,
3.0 Hz, 1 H, ArH), 6.97 (s, 1 H, ArH), 7.00 (d, J = 8.0 Hz, 1 H, ArH), 7.28 (dd, J = 8.0, 8.0 Hz, 1 H, ArH);
13C-NMR (CDCl3, 126 MHz)
m/z (%) 208 (M+, 100).
δ 34.8, 42.7, 54.2, 55.2, 113.1, 113.3, 119.6, 129.8, 140.9, 159.8, 207.8; MS (EI)
Dihydro-5-(4-methoxyphenyl)-2(3H)-thiophenone (2h) [13]. General procedure B was followed with
5-(4-methoxyphenyl)dihydrofuran-2-one (1h, 97.7 mg). Column chromatography (10/1 hexane/EtOAc)
◦
afforded 2h as a colorless solid (23.2 mg, 22%): m.p. 74–75 C; 1H-NMR (CDCl3, 500 MHz)
δ 2.21–2.29
(m, 1 H, CH2), 2.56–2.59 (m, 1 H, CH2), 2.65–2.80 (m, 2 H, CH2, CH2), 3.81 (s, 3 H, CH3), 4.97 (dd,
J = 10.5, 5.5 Hz, 1 H, CH), 6.90 (d, J = 8.0 Hz, 2 H, ArH), 7.35 (d, J = 8.0 Hz, 2 H, ArH); 13C-NMR (CDCl3,
126 MHz)
δ
35.2, 43.1, 54.0, 55.3, 114.2, 128.6, 131.3, 159.4, 208.1; MS (EI) m/z (%) 208 (M+, 79), 147 (100).
Dihydro-5-(4-fluorophenyl)-2(3H)-thiophenone (2i) [13]. General procedure B was followed with
5-(4-fluorophenyl)dihydrofuran-2-one (1i, 96.3 mg). Column chromatography (10/1 hexane/EtOAc)
1
afforded 2i as a pale green oil (82.3 mg, 79%): H-NMR (CDCl3, 297 MHz)
δ
2.17–2.29 (m, 1 H, CH2),
2.56–2.82 (m, 3 H, CH2, CH2), 4.99 (dd, J = 9.8, 5.0 Hz, 1 H, CH), 7.03–7.08 (m, 2 H, ArH), 7.38–7.42 (m,
2 H, ArH); 13C-NMR (CDCl3, 75 MHz)
δ 35.1, 42.8, 53.5, 115.7 (d, JC–F = 20.9 Hz), 129.0 (d, JC–F = 9.0 Hz),
135.2 (d, JC–F = 3.7 Hz), 162.3 (d, JC–F = 246.8 Hz), 207.4; MS (EI) m/z (%) 196 (M+, 72), 135 (100).
Dihydro-5-(4-chlorophenyl)-2(3H)-thiophenone (2j) [13]. General procedure A was followed with
5-(4-chlorophenyl)dihydrofuran-2-one (1j, 98.1 mg). Column chromatography (10/1 hexane/EtOAc)
afforded 2j as a colorless solid (85.5 mg, 87%): m.p. 45–48 ◦C; 1H-NMR (CDCl3, 500 MHz)
δ
2.18–2.26
(m, 1 H, CH2), 2.59–2.80 (m, 3 H, CH2, CH2), 4.97 (dd, J = 10.0, 5.5 Hz, 1 H, CH), 7.34–7.35 (m, 4 H,
ArH); 13C-NMR (CDCl3, 126 MHz)
34.9, 42.7, 53.5, 128.7, 129.0, 133.8, 138.0, 207.2; MS (EI) m/z (%)
214 (M++2, 23), 212 (M+, 63), 117 (100).
δ
Dihydro-5-(4-bromophenyl)-2(3H)-thiophenone (2k) [13]. General procedure A was followed with
5-(4-bromophenyl)dihydrofuran-2-one (1k, 120.1 mg). Column chromatography (10/1 hexane/EtOAc)
◦
afforded 2k as a colorless solid (96.1 mg, 74%): m.p. 58–60 C; 1H-NMR (CDCl3, 500 MHz)
δ
2.18–2.26
(m, 1 H, CH2), 2.58–2.80 (m, 3 H, CH2, CH2), 4.95 (dd, J = 10.0, 5.5 Hz, 1 H, CH), 7.30 (d, J = 7.0 Hz, 2 H,
ArH), 7.50 (d, J = 7.0 Hz, 2 H, ArH); 13C-NMR (CDCl3, 126 MHz)
34.9, 42.7, 53.6, 122.0, 129.1, 132.0,
138.6, 207.2; MS (EI) m/z (%) 258 (M+ + 2, 59), 256 (M+, 58), 117 (100).
δ
Dihydro-5-(5,6,7,8-tetrahydronaphthalen-2-yl)-2(3H)-thiophenone (2l) [13]. General procedure B was
followed with 5-(5,6,7,8-Tetrahydronaphthalen-2-yl)dihydrofuran-2(3H)-one (1l, 96.8 mg). Column
1
chromatography (10/1 hexane/EtOAc) and GPC afforded 2l as a colorless oil (37.4 mg, 36%): H-NMR
(CDCl3, 500 MHz)
δ 1.78–1.81 (m, 4 H, CH2), 2.23–2.31 (m, 1 H, CH2), 2.55–2.80 (m, 7 H, CH2, CH2),
4.94 (dd, J = 10.5, 5.5 Hz, 1 H, CH), 7.07 (d, J = 8.0 Hz 1 H, ArH) 7.12–7.15 (m, 2 H, ArH); 13C-NMR
(CDCl3, 126 MHz) δ 23.0, 23.1, 29.1, 29.4, 35.0, 43.0, 54.3, 124.4, 128.1, 129.6, 136.4, 137.3, 137.7, 208.3;
MS (EI) m/z (%) 232 (M+, 100).
Dihydro-5-(thiophen-2-yl)-2(3H)-thiophenone (2m).
General procedure B was followed with
dihydro-5-(3-thienyl)-2(3H)-furanone (1m, 89.0 mg). Column chromatography (10/1 hexane/EtOAc)
1
afforded 2m as a light green oil (22.3 mg, 23%): H-NMR (CDCl3, 500 MHz)
δ 2.34–2.42 (m, 1 H, CH2),
2.65–2.85 (m, 3 H, CH2, CH2), 5.29 (dd, J = 7.5, 5.5 Hz, 1 H, CH), 6.97 (dd, J = 5.0, 3.5 Hz, 1 H, ArH),
7.07 (d, J = 3.5 Hz, 1 H, ArH), 7.27 (dd, J = 5.0, 3.5 Hz, 1 H, ArH); 13C-NMR (CDCl3, 126 MHz)
δ 35.6,
42.3, 49.1, 125.3, 125.6, 126.9, 143.7, 207.0; MS (EI) m/z (%) 184 (M+, 64), 123 (100); HRMS (EI) calcd for
[M]+ (C8H8OS2) m/z 184.0017, found 184.0011.

Molecules 2018, 23, 1339
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Thiophthalide (2o) [16]. General procedure A was followed with phthalide (1o, 67.6 mg). Column
chromatography (10/1 hexane/EtOAc) afforded 2o as a colorless solid (26.8 mg, 18%): m.p. 68–70 ◦C;
1H-NMR (CDCl3, 500 MHz)
δ 4.48 (s, 2 H, CH2), 7.48 (dd, J = 7.5, 7.5 Hz, 1 H, ArH), 7.55 (d, J = 7.0 Hz,
1 H, ArH), 7.63 (dd, J = 7.5, 7.5 Hz, 1 H, ArH), 7.85 (d, J = 7.5 Hz, 1 H, ArH); 13C-NMR (CDCl3, 126 MHz)
δ 34.6, 123.9, 126.3, 128.0, 133.1, 135.8, 147.0, 198.0; MS (EI) m/z (%) 150 (M+, 89), 121 (100).
3-Phenyl-benzo[c]thiophen-1(3H)-one (2p) [13].
General procedure A was followed with
3-phenylisobenzofuran-1-one (1p, 105.9 mg). Column chromatography (10/1 hexane/EtOAc) afforded
◦
2p as a pale yellow solid (7.5 mg, 85%): m.p. 87–88 C; 1H-NMR (CDCl3, 500 MHz)
δ 5.91 (s, 1 H, CH),
7.25–7.36 (m, 6 H, ArH), 7.48 (dd, J = 7.5, 7.5 Hz, 1 H, ArH), 7.56 (dd, J = 7.5, 7.5 Hz, 1 H, ArH), 7.86
(d, J = 7.5 Hz, 1 H, ArH); 13C-NMR (CDCl3, 126 MHz)
δ 54.6, 123.6, 126.6, 128.29, 128.33, 128.4, 129.1,
133.6, 135.7, 138.8, 151.2, 197.2; MS (EI) m/z (%) 226 (M+, 100).
Tetrahydro-6-phenyl-2H-benzothiopyran-2-one (2q) [13]. General procedure A was followed with
tetrahydro-6-phenyl-2H-pyran-2-one (1q, 89.3 mg). Colum chromatography (10/1 hexane/EtOAc)
1
afforded 2q as an orange oil (9.7 mg, 10%): H-NMR (CDCl3, 500 MHz)
δ 1.94–2.10 (m, 2 H, CH2),
2.14–2.19 (m, 1 H, CH2), 2.37–2.41 (m, 1 H, CH2), 2.57–2.43 (m, 1 H, CH2), 2.59–2.78 (m, 1 H, CH2), 4.65
(dd, J = 11.0, 4.0 Hz, 1 H, CH), 7.29–7.32 (m, 1 H, ArH), 7.35–7.39 (m, 4 H, ArH); 13C-NMR (CDCl3,
126 MHz)
δ
22.7, 32.4, 40.5, 50.5, 127.7, 128.1, 128.9, 140.4, 201.3; MS (EI) m/z (%) 192 (M+, 59), 104 (100).
Tetrahydro-6-(4-methylphenyl)-2H-thiopyran-2-one (2r). General procedure A was followed with
tetrahydro-6-(4-methylphenyl)-2H-Pyran-2-one (1r, 92.3 mg).
hexane/EtOAc) and GPC afforded 2r as a colorless oil (9.5 mg, 9%): H-NMR (CDCl3, 500 MHz)
Column chromatography (10/1
1
δ
1.93–2.07 (m, 2 H, CH2), 2.15–2.17 (m, 1 H, CH2), 2.35 (s, 3 H, CH3), 2.37–2.44 (m, 1 H, CH2), 2.72–2.76
(m, 1 H, CH2), 4.61 (dd, J = 11.0, 3.5 Hz, 1 H, CH), 7.17 (d, J = 7.5 Hz, 2 H, ArH), 7.26 (d, J = 7.5 Hz, 2 H,
ArH); 13C-NMR (CDCl3, 126 MHz)
δ 21.1, 22.7, 32.4, 40.5, 50.2, 127.5, 129.5, 137.4, 137.9, 201.6; MS (EI)
m/z (%) 206 (M+, 62), 118 (100); HRMS (EI) calcd for [M]+ (C12H14OS) m/z 206.0765, found 206.0766.
6-(4-Chlorophenyl)tetrahydro-2H-thiopyran-2-one (2s). General procedure A was followed with
6-(4-chlorophenyl)tetrahydro-2H-pyran-2-one (1s, 107.5 mg).
hexane/EtOAc) and GPC afforded 2s as a colorless oil (4.8 mg, 4%): H-NMR (CDCl3, 500 MHz)
Column chromatography (10/1
1
δ
1.93–2.02 (m, 2 H, CH2), 2.04–2.19 (m, 1 H, CH2), 2.34–2.39 (m, 1 H, CH2), 2.56–2.63 (m, 1 H, CH2),
2.73–2.78 (m, 1 H, CH2), 4.62 (dd, J = 11.0, 4.5 Hz, 1 H, CH), 7.30–7.35 (m, 4 H, ArH); 13C-NMR (CDCl3,
126 MHz)
(M+, 23), 138 (100); HRMS (EI) calcd for [M]+ (C11H11OSCl) m/z 226.0219, found 226.0241.
δ
22.6, 32.4, 40.5, 49.7, 129.0, 129.1, 133.9, 139.0, 200.8; MS (EI) m/z (%) 226 (M++2, 20), 210
1,4-Dihydro-3H-2-benzothiopyran-3-one (2t) [13]. General procedure A was followed with
1,4-dihydro-3H-2-benzopyran-3-one (1t, 74.3 mg). Column chromatography (10/1 hexane/EtOAc)
◦
1
afforded 2t as a pale yellow solid (40.9 mg, 50%): m.p. 90–93 C; H-NMR (CDCl3, 500 MHz)
δ
3.79 (s, 2 H, CH2), 4.22 (s, 2 H, CH2), 7.21–7.32 (m, 4 H, ArH); 13C-NMR (CDCl3, 126 MHz)
126.6, 127.4, 128.0, 128.7, 133.7, 134.2, 202.9; MS (EI) m/z (%) 164 (M+, 14), 104 (100).
δ 34.2, 49.2,
Phthalic thioanhydride (2u) [17]. General procedure A was followed with phthalic anhydride (1u, 77.3 mg).
Column chromatography (10/1 hexane/EtOAc) afforded 2u as a yellow solid (56.1 mg, 74%): m.p.
68–70 ◦C; 1H-NMR (CDCl3, 500 MHz) 7.81–7.83 (m, 2 H, ArH), 7.97–7.99 (m, 2 H, ArH); 13C-NMR
δ
(CDCl3, 126 MHz) δ 123.8, 135.0, 138.7, 189.8; MS (EI) m/z (%) 164 (M+, 100).
S-Methyl 4-methylbenzothioate (2v). General procedure A was followed with methyl 4-methylbenzoate (1v
,
75.0 mg). Column chromatography (100/1 hexane/EtOAc) afforded 2v as a red oil (31.8 mg, 38%):
1H-NMR (CDCl3, 500 MHz)
δ 2.40 (s, 3 H, CH3), 2.46 (s, 3 H, CH3), 7.24 (d, J = 14.5 Hz, 2 H, ArH), 7.87
(d, J = 14.5 Hz, 2 H, ArH); 13C-NMR (CDCl3, 126 MHz)
(EI) m/z (%) 166 (M+, 5), 119 (100).
δ 11.6, 21.7, 127.2, 129.2, 134.5, 144.1, 192.1; MS
Methyl 4-methylbenzodithioate (4v) [18]. General procedure A was followed with methyl 4-methylbenzoate
1v, 75.0 mg). Column chromatography (100/1 hexane/EtOAc) afforded 4v as an orange oil (15.9 mg,
(

Molecules 2018, 23, 1339
10 of 11
1
18%): H-NMR (CDCl3, 500 MHz)
δ
2.38 (s, 3 H, CH3), 2.77 (s, 3 H, CH3), 7.18 (d, J = 13.5 Hz, 2 H,
ArH), 7.94 (d, J = 13.5 Hz, 2 H, ArH); 13C-NMR (CDCl3, 126 MHz)
228.8; MS (EI) m/z (%) 182 (M+, 22), 135(100).
δ 20.5, 21.5, 126.8, 129.0, 142.6, 143.2,
5-[1,10-Biphenyl]-4-yldihydro-2(3H)-furanone (1f). A colorless solid: m.p. 100–102 ◦C; 1H-NMR (CDCl3,
500 MHz) 2.19–2.29 (m, 1 H, CH2), 2.66–2.72 (m, 3 H, CH2), 5.54–5.57 (m, 1 H, CH), 7.35–7.46 (m, 5 H,
ArH), 7.58–7.62 (m, 4 H, ArH); 13C-NMR (CDCl3, 126 MHz)
δ
δ
29.0, 30.9, 81.0, 125.8, 127.1, 127.45, 127.53,
128.8, 138.3, 140.4, 141.4, 176.9; MS (EI) m/z (%) 238 (M+, 100); HRMS (EI) calcd for [M]+ (C16H14O2)
m/z 238.0994, found 238.1002.
Tetrahydro-6-(4-methylphenyl)-2H-pyran-2-one (1r). A colorless solid: m.p. 81–83 ◦C; 1H-NMR (CDCl3,
500 MHz)
δ 1.80–1.88 (m, 1 H, CH2), 1.92–1.98 (m, 2 H, CH2), 2.09–2.14 (m, 1 H, CH2), 2.34 (s, 3 H,
CH3), 2.51–2.56 (m, 1 H, CH2), 2.57–2.71 (m, 1 H, CH2), 5.30 (dd, J = 10.5, 3.5 Hz, 1 H, CH), 7.17 (d,
J = 7.5 Hz, 2 H, ArH), 7.22 (d, J = 7.5 Hz, 2 H, ArH); 13C-NMR (CDCl3, 126 MHz)
δ 18.4, 21.0, 29.3, 30.3,
81.5, 125.5, 129.1, 136.6, 137.8, 171.4; MS (EI) m/z (%) 190 (M+, 42), 118 (100); HRMS (EI) calcd for [M]+
(C12H14O2) m/z 190.0994, found 190.0995.
Tetrahydro-6-(4-chlorophenyl)-2H-pyran-2-one (1s). An orange solid: m.p. 91–98 ◦C; 1H-NMR (CDCl3,
500 MHz) δ 1.77–1.85 (m, 1 H, CH2), 1.96–2.01 (m, 2 H, CH2), 2.12–2.16 (m, 1 H, CH2), 2.53–2.60 (m, 1 H,
CH2), 2.67–2.73 (m, 1 H, CH2), 5.32 (dd, J = 10.5, 3.0 Hz, 1 H, CH), 7.28 (d, J = 8.5 Hz, 2 H, ArH), 7.34
(d, J = 8.5 Hz, 2 H, ArH); 13C-NMR (CDCl3, 126 MHz) δ 18.4, 29.3, 30.4, 80.8, 127.0, 128.6, 133.9, 138.2,
171.0; MS (EI) m/z (%) 212 (M++2, 7), 210 (M+, 23), 70 (100); HRMS (EI) calcd for [M]+ (C11H11O2Cl)
m/z 210.0448, found 210.0449.
4. Conclusions
An indium-catalyzed formation of thiolactones from lactones and a disilathiane was developed.
A disilathiane was found to be a novel and an effective sulfur source for this type of conversion, and a
wide range of lactone derivatives were successfully converted into the corresponding thiolactones.
1
Supplementary Materials: The following are available online: H and 13C-NMR spectra of 2a
–2m; 2o–2v; 4v; 1f;
1r and 1s.
Author Contributions: N.S. conceived and designed the experiments; K.T. and S.H. performed the experiments;
Y.O., K.T. and S.H. analyzed the data; Y.O. and N.S. wrote the paper.
Acknowledgments: The authors deeply thank Shin-Etsu Chemical Co., Ltd., for the gift of hydrosilanes
and chlorosilanes.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the all compounds are available from the authors.
©
2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).