Indium-catalyzed direct conversion of dibenzyl ethers to dibenzyl sulfides using elemental sulfur and a hydrosilane and its application to the preparation of benzyl selenides

Article abstract of DOI:10.1246/cl.180242

Described herein is a catalytic system composed of an indium(III) compound, a hydrosilane and an easily handled form of elemental sulfur (S₈) that effectively and directly catalyzes the sulfidation of dibenzyl ethers to produce dibenzyl sulfides. This system could also be applied to selenium in a straightforward conversion to dibenzyl selenides.

Full text of DOI:10.1246/cl.180242

Advance Publication Cover Page
Indium-catalyzed Direct Conversion of Dibenzyl Ethers to Dibenzyl Sulfides Using Elemental
Sulfur and a Hydrosilane and Its Application to the Preparation of Benzyl Selenides
Norio Sakai,* Koji Takada, Masahiro Katayama, and Yohei Ogiwara
Advance Publication on the web April 14, 2018
doi:10.1246/cl.180242
© 2018 The Chemical Society of Japan
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1
Indium-catalyzed Direct Conversion of Dibenzyl Ethers to Dibenzyl Sulfides Using Elemental
Sulfur and a Hydrosilane and Its Application to the Preparation of Benzyl Selenides
Norio Sakai,* Koji Takada, Masahiro Katayama, and Yohei Ogiwara
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science (RIKADAI),
Noda, Chiba 278-8510, Japan
E-mail: sakachem@rs.noda.tus.ac.jp
Described herein is that a catalytic system composed of
catalyst
+
(1)
(2)
S
an indium(III) compound, a hydrosilane and an easily handled
form of elemental sulfur (S8) effectively and directly catalyzes
the sulfidation of dibenzyl ethers to produce dibenzyl sulfides.
This system was also could be applied to selenium in a
straightforward conversion to dibenzyl selenides.
Ar
Ar
S
S
Ar
Ar
Ar
X
X
Ar
= [Metal]2S, P4S10 etc.
catalyst
S
+
S8
Ar
X
X
Ar
(previous work)
Ar
OH HO
[In] / Si-H
[In] / Si-H
Organic sulfur compounds, such as dialkyl sulfides, are
composed of a central skeleton of biologically active
substances and fine chemicals, and the development of a
facile access to these compounds is highly desired in organic
chemistry.1 Thus far, the coupling of alkyl halides with alkyl
thiols in the presence of a base (Williamson-type synthesis)
has been the most efficient approach to dialkyl sulfide
derivatives.2 In these studies, however, one of the reaction
substrates derives from a sulfur moiety (thiol).
+
+
S8
S8
(3)
(4)
Ar
Ar
S
S
Ar
Ar
Ar
(this work)
Ar
O
Ar
Scheme 1 Divergent approaches to dibenzyl sulfide
On the basis of our previous work, when the mixture of
ether 1a and S8 (1 equiv based on S atom) was initially treated
with InI3 (5 mol %) and Et3SiH (2 equiv) in 1,2-
dichloroethane (1,2-DCE) at 80 ˚C for 8 h, the expected
dibenzyl sulfide (2a) was obtained in a 36% yield (entry 1,
Table 1). The product yield was then improved by the effect
of using other haloganated solvents, such as o-
dichlorobenzene (o-DCB) and chlorobenzene (entries 2 and 3).
On the other hand, a number of facile methods have been
achieved to prepare a symmetrical dibenzyl sulfide (DBS) by
combining two benzyl halides and a sulfur source. Most sulfur
sources employed in these cases are generally metal sulfides,
such as Na2S,3 Li2S,4 (MgBr)2S,5 (Bu3Sn)2S,6 (NH4)2S,7 and
P4S10.8 Unfortunately, these involve either high reactivity or
an unpleasant odor, which often leads to the troublesome
handling on a laboratory scale (eq 1 in Scheme 1). To
overcome these drawbacks, a single-step preparation of
dibenzyl sulfides with benzyl halides and an odorless and
economical sulfur source, elemental sulfur (S8), in the
presence of an appropriate promoter has been developed (eq 2
in Scheme 2).9,10 However, these methods are generally
limited to the conversion with a metal catalyst immobilized in
a solid-phase, and the procedure to activate S8 requires either
a multi-step operation with a reducing reagent or an
electrochemical apparatus.3a,11 Therefore, the development of
a facile method for sulfide preparation would be most
welcome. In this context, we studied the activation of S8 with
an indium compound and a hydrosilane, and reported the one-
pot preparation of dibenzyl sulfides from either aromatic
carboxylic acid derivatives or benzyl alcohols and S8 (eq 3 in
Scheme 1).12a
Table 1 Optimization of the reaction conditions
catalyst (5 mol %)
hydrosilane
+
S8
Ph
O
Ph
Ph
S
Ph
solvent (0.5 mL)
100 ˚C, 8 h
1a (0.5 mmol)
(1 equiv)
2a
entry
catalyst
hydrosilane
solvent
yield
(equiv)
(%)a
36
65
58
44
33
40
0
1b
2c
3
InI3
InI3
InI3
InI3
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
TMDS (2)
PhSiH3 (2)
(EtO)3SiH (2)
Et3SiH (4)
1,2-DCE
o-DCB
PhCl
4
5c
PhMe
In(OTf)3
InBr3
InCl3
In(OH)3
CuI
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
6
7
8c
0
9
4
During ongoing study on the molecular transformation
using S8, we found that when a mixture of lactones and S8 was
treated with an indium compound and a hydrosilane,
thiolactones were directly obtained.12b Thus, we applied this
protocol to a direct sulfidation of dibenzyl ethers (eq 4 in
Scheme 1). Herein, we communicate the results. Also, we
disclose that this catalytic system could be applied to
selenium in a direct preparation of dibenzyl selenides.
10
11
12
13
14
15
ZnI2
1
AlCl3
InI3
3
58
53
28
InI3
InI3
InI3
89 (79)
a GC (Isolated) yield. b 80 ˚C. c 1a (0.6 mmol).

2
Toluene showed a relatively better effect in a reductive
reaction with an indium catalyst and a hydrosilane, but that
resulted in a slight decrease in yield, which was probably due
to the low solubility of the elemental sulfur (entry 4). When
sulfidation was attempted using several indium compounds,
the improvement was insignificant (entries 5-8). To display
the utility of the indium compound, other typical Lewis acidic
catalysts, such as CuI, ZnI2, and AlCl3, were then applied to
the sulfidation. As expected, all catalysts were ineffective
(entries 9-11). Also, when the sulfidation was run using
hydrosilanes, such as TMDS (1,1,3,3-tetramethyldisiloxane)
and PhSiH3, an effect equal to that with Et3SiH resulted
(entries 12 and 13), but the use of (EtO)3SiH led to a decrease
in yield (entry 14). Finally, when Et3SiH was increased to 4
equiv, the desired sulfide 2a was isolated in a 79% yield
(entry 15).
Conversion of a variety of dibenzyl ethers 1 to the
corresponding dibenzyl sulfides 2 was then investigated, and
the results are summarized in Table 2. Benzyl ethers with an
alkyl group on the benzene ring, regardless of the substituted
position and size, produced the desired benzyl sulfides 2b-e in
relatively good yields. In similar manner, when using with a
moderate electron-withdrawing halogen group, benzyl ethers
were effectively converted to benzyl sulfides 2f-i. However,
the sulfidation of benzyl ether bonding with a strong electron-
withdrawing group, a trifluoromethyl group, led to a slight
decrease in the product yield. On the other hand, when the
reaction was conducted using substrates with an electron-
donating methylsulfanyl or methoxy group, the former benzyl
ether was converted to the corresponding benzyl sulfide 2k in
a 50% yield, but the latter substrate did not form the desired
benzyl sulfide 2l, but instead led to a complicated mixture.
The latter result agreed with our previous results wherein the
indium-catalyzed reductive transformation of a typical
reducible substrate, such as an aromatic ester with a p-
methoxy group, was unsuccessful.12b However, no reasonable
explanation for this failure could be determined.
(eq 2 in Scheme 2). Consequently, the existence of benzyl
carbon was essential to sulfidation.13
InI3 (5 mol %)
Ph
O
Et3SiH (4 equiv)
Ph
S
+
(1)
(2)
S8
o-DCB (0.5 mL)
100 ˚C, 8 h
Ph
(0.5 mmol)
Ph
3: NR
(1 equiv)
InI3 (5 mol %)
BuMe2SiH (4 equiv)
O
S
+
S8
o-DCB (1 mL)
100 ˚C, 8 h
(1 equiv)
(1 mmol)
4: 26%
Scheme 2 Conversion of aliphatic ether derivatives
With selenium, we further attempted to use the present
method to directly prepare dibenzyl selenide derivatives.14 For
example, when benzyl ether (1a) was treated with selenium,
the corresponding dibenzyl selenide (5a) was obtained in a
65% yield (Scheme 3). Thus, the catalytic system proved
useful. Also, benzyl ether with a p-bromo substituent was
converted to dibenzyl selenide 5b in a 56% yield.
InI3 (5 mol %)
Et3SiH (4 equiv)
+
Ar
O
Ar
Se
Ar
Se
Ar
o-DCB (0.5 mL)
100 ˚C, 8 h
(1 equiv)
(0.5 mmol)
5a: 65% (Ar = Ph)
5b: 56% (Ar = p-BrC6H4)
Scheme 3 Application to the preparation of dibenzyl selenides
To clarify the reaction path of sulfidation, two control
experiments were attempted (Scheme 4). Based on our
previous studies, we assumed that a key intermediate in the
reaction would be disilathiane, which is derived from
elemental sulfur and a hydrosilane in the presence of an
indium catalyst.15 When the mixture of benzyl ether (1a) and
hexamethyldisilathiane was treated with only InI3, the
corresponding sulfide 2a was formed in a high yield (eq 1 in
Scheme 4). The result strongly supports that a disilathiane
functions as an actual sulfur source. Also, when an
unsymmetrical dibenzyl ether derivative was subjected to the
same optimal conditions, unsymmetrical dibenzyl sulfide 6
and symmetrical dibenzyl ethers 2g and 2a were obtained in
43, 21 and 22% NMR yields, respectively (eq 2 in Scheme 4).
Table 2 Conversion of dibenzyl ethers 1 to dibenzyl sulfides 2a
InI3 (5 mol %)
Et3SiH (4 equiv)
+
S8
Ar
O
Ar
Ar
S
Ar
o-DCB (0.5 mL)
100 ˚C, 8 h
(1 equiv)
1 (0.5 mmol)
2
2b: 63%
2c: 61%
2d: 74%
2e: 90%
2f: 67%b
2g: 80%
(Ar = o-Me-C6H4)
(Ar = m-Me-C6H4)
(Ar = p-Me-C6H4)
(Ar = p-t-Bu-C6H4)
(Ar = o-Cl-C6H4)
(Ar = p-Cl-C6H4)
2h: 94%
2i: 80%
(Ar = p-F-C6H4)
(Ar = p-Br-C6H4)
InI3 (5 mol %)
S
(1)
+
2j: 48%b (Ar = p-CF3-C6H4)
1a
Ph
S
Ph
Me3Si
SiMe3
o-DCB (0.5 mL)
100 ˚C, 8 h
(1 equiv)
2a: 94% (GC)
2k: 50%
2l: CM
(Ar = p-MeS-C6H4)
(Ar = p-MeO-C6H4)
Ph
S
Ar
a Isolated yield. b 120 ˚C.
6: 43% (NMR)
InI3 (5 mol %)
Et3SiH (4 equiv)
+
The current method was then applied to the direct
sulfidation of an aliphatic ether without a benzylic position
and to a cyclic ether with a benzylic position (Scheme 2).
First, when 3-phenylpropyl ether was treated with S8 under
the optimal conditions, the desired sulfidation did not proceed
to recover the starting ether (eq 1 in Scheme 2). In contrast,
when a mixture of isochroman and S8 was subjected to the
conditions using BuMe2SiH, direct sulfidation occurred to
produce the corresponding thioisochroman 4 in a 26% yield
+
S8
Ph
O
Ar
(2)
Ar
S
Ar
o-DCB (0.5 mL)
100 ˚C, 8 h
(0.5 mmol)
Ar = p-Cl-C6H4
(1 equiv)
2g: 21% (NMR)
+
Ph
S
Ph
2a: 22% (NMR)
Scheme 4 Control experiments

3
6
7
D. N. Harpp, M. Gingras, Tetrahedron Lett. 1987, 28, 4373.
(a) S. K. Maity, N. C. Pradhan, A. V. Patwardhan, J. Mol. Catal. A:
Chem. 2006, 250, 114. (b) J. E. Bittell, J. L. Speier, J. Org. Chem.
1978, 43, 1687.
These results showed that a carbon-oxygen bond cleavage at
the benzyl position occurred during the series of sulfidation.
Based on these findings, a plausible reaction path of the
direct sulfidation of dibenzyl ether is shown in Scheme 5.
Initially, the reaction of S8 and a hydrosilane in the presence
of an indium catalyst in-situ generates the corresponding
disilathiane derivative A with the release of hydrogen gas.
Then, disilathiane A reacts with a dibenzyl ether activated by
an indium catalyst to form benzyl silyl ether B and benzyl
silyl sulfide C. From this step, two paths are expected. One
path is the substitution of benzyl silyl ether B with benzyl
silyl sulfide C through a crossed-condensation to produce a
final unsymmetrical (or symmetrical) dibenzyl sulfide.16 The
other path involves the self-condensation of two benzyl silyl
sulfides C to yield a final symmetrical dibenzyl sulfide.
8
9
G. Turkoglu, M. E. Cinar, T. Ozturk, Synthesis 2016, 48, 3618.
For the example of the preparation of benzyl sulfides using S8, see:
(a) A. Rostami, A. Rostami, N. Iranpoor, M. A. Zolfigol,
Tetrahedron Lett. 2016, 57, 192; See also for the selected review
and papers of the preparation of diaryl sulfides with S8, see also:
(b) T. B. Nguyen, Adv. Synth. Catal. 2017, 359, 1066. (c) J.-T. Yu,
H. Guo, Y. Yi, H. Fei, Y. Jiang, Adv. Synth. Catal. 2014, 356, 749.
(d) H.-Y. Chen, W.-T. Peng, Y.-H. Lee, Y.-L. Chang, Y.-J. Chen,
Y.-C. Lai, N.-Y. Jheng, H.-Y. Chen, Organometallics 2013, 32,
5514. (e) M. Arisawa, T. Ichikawa, M. Yamaguchi, Org. Lett. 2012,
14, 5318-5321. (f) Y. Jiang, Y. Qin, S. Xie, X. Zhang, J. Dong, D.
Ma, Org. Lett. 2009, 11, 5250.
10
For selected examples of the preparation of sulfides with an
odorless sulfur source, thiorea or
a stable sulfur source,
dithiooxamide, see: (a) H. Firouzabadi, N. Iranpoor, F. Gorginpour,
A. Samadi, Eur. J. Org. Chem. 2015, 2914. (b) J. Feng, G. Lu, M.
Lv, C. Cai, Asian J. Org. Chem. 2014, 3, 77. (c) G.-P. Lu, C. Cai,
Green Chem. Lett. Rev. 2012, 5, 481. (d) F. Ke, Y. Qu, Z. Jiang, Z.
Li, D. Wu, X. Zhou, Org. Lett. 2011, 13, 454. (d) S. Fujisaki, I.
Fujiwara, Y. Norisue, S. Kajigaeshi, Bull. Chem. Soc. Jpn. 1985,
58, 2429.
[In]
S
+
S8
2Si-H
Si
Si
-
H2
Ar
O
Ar
A
[In]
11
(a) M. Khanmoradi, M. Nikoorazm, A. Ghorbani-Choghamarani,
Appl. Organomet. Chem. 2017, 31, e3693. (b) A. Ghorbani-
Choghamarani, Z. Taherinia, New J. Chem. 2017, 41, 9414. (c) P.
B. Ribeiro Neto, S. O. Santana, G. Levitre, D. Galdino, J. L.
Oliveira, R. T. Ribeiro, M. E. S. B. Barros, L. W. Bieber, P. H.
Menezes, M. Navarro, Green Chem. 2016, 18, 657. (d) A. Ogawa,
N. Takami, M. Sekiguchi, N. Sonoda, T. Hirao, Heteroat. Chem
1998, 9, 581.
Ar
OSi
Ar
S-Si
Ar
S-Si
B
C
C
[In]
[In]
crossed-condensation
self-condensation
Si-O-Si
Si-S-Si
Ar
S
Ar
Ar
S
Ar
12
13
14
(a) T. Miyazaki, M. Katayama, S. Yoshimoto, Y. Ogiwara, N.
Sakai, Tetrahedron Lett. 2016, 57, 676. (b) N. Sakai, S. Horikawa,
Y. Ogiwara, Synthesis 2018, 50, 565.
When the sulfidation of benzyl methyl ether was carried out with
the optimal conditions, the corresponding benzyl methyl sulfide
was produced in a 21% (NMR) yield.
For selectied examples of the prepration of selenides, see: (a) T.
Wirth, Angew. Chem. Int. Ed. 2000, 39, 3740. (b) F. Shibahara, T.
Kanai, E. Yamaguchi, A. Kamei, T. Yamauchi, T. Murai, Chem.
Asian J. 2014, 9, 237. (c) F. Shibahara, R. Sugiura and T. Murai,
Org. Lett., 2009, 11, 3064. (d) A. Krief, M. Derock, Tetrahedron
Lett. 2002, 43, 3083. (e) N. Taniguchi, Tetrahedron 2012, 68,
10510. (f) K. Yanada, T. Fujita, R. Yanada, Synlett 1998, 971. (g) J.
A. Gladysz, J. L. Hornby, J. E. Garbe, J. Org. Chem. 1978, 43,
1204.
Scheme 5 Plausible reaction mechanism for the sulfidation of dibenzyl
ether derivatives
In summary, we have demonstrated an indium-catalyzed
direct sulfidation of dibenzyl ether derivatives using elemental
sulfur leading to dibenzyl sulfide derivatives. The present
protocol could also be applied to selenium for a one-pot
conversion to dibenzyl selenide derivatives. A primary feature
of the series of sulfidation involves that a decoupling of a
carbon-oxygen bond and a coupling of a carbon-sulfur bond
simultaneously occurs to generate a benzyl silyl sulfide
intermediate that could function as a key intermediate. Further
investigation into the substrate scope of direct sulfidation and
the reaction mechanism involving the possibility of a
reversible reaction is now in progress.
15
16
T. Miyazaki, K. Nishino, S. Yoshimoto, Y. Ogiwara, N. Sakai, Eur.
J. Org. Chem. 2015, 1991.
For example of the substitution with a thiosialne, see: Y. Nishimoto,
A. Okita, M. Yasuda, A. Baba, Org. Lett. 2012, 14, 1846.
We deeply thank Shin-Etsu Chemical Co., Ltd., for the
gift of hydrosilanes.
Supporting
Information
is
also
available
on
http://dx.doi.org/######.
References and Notes
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3
4
5