B(C6F5)3-Catalyzed Hydrodesulfurization Using Hydrosilanes - Metal-Free Reduction of Sulfides

Article abstract of DOI:10.1021/acs.orglett.5b01651

B(C₆F₅)₃-catalyzed hydrodesulfurization of carbon-sulfur bonds was achieved using triethylsilane as the reducing agent. The corresponding products were obtained in good yields under mild reaction conditions. This protocol could be applied to the reduction of sulfides, including benzyl and alkyl sulfides and dithianes, with high chemoselectivities. (Chemical Equation Presented).

Full text of DOI:10.1021/acs.orglett.5b01651

Letter
pubs.acs.org/OrgLett
B(C6F5)3‑Catalyzed Hydrodesulfurization Using Hydrosilanes − Metal-
Free Reduction of Sulfides
Kodai Saito, Kazumi Kondo, and Takahiko Akiyama*
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan
S
* Supporting Information
ABSTRACT: B(C6F5)3-catalyzed hydrodesulfurization of car-
bon−sulfur bonds was achieved using triethylsilane as the
reducing agent. The corresponding products were obtained in
good yields under mild reaction conditions. This protocol
could be applied to the reduction of sulfides, including benzyl
and alkyl sulfides and dithianes, with high chemoselectivities.
he importance of the carbon−sulfur (C−S) bond is
reflected in the extensive use of sulfur-containing building
Tris(pentafluorophenyl)borane B(C6F5)3 is widely used in
organic synthesis, and the combination of B(C6F5)3 and a Lewis
base, in particular, has been recognized as an efficient tool for
the activation of inert molecules.9 The combined use of
B(C6F5)3 and hydrosilanes is also one of the representative
methods for the generation of a silylium cation.10 Piers and
Gevorgyan et al. independently reported the cleavage reaction
of the C−O−H and C−O−C bonds of alcohols and ethers
based on the B(C6F5)3−Et3SiH system.10b,c Subsequent to their
reports, several research groups developed the reduction
reactions of ketones and imines using this system. However,
the application of this method to the cleavage of C−S bonds
had not been reported. We wish to report herein a B(C6F5)3-
catalyzed HDS of C−S bonds using triethylsilane as the
reducing agent. A wide substrate scope was confirmed in the
reactions of benzyl (tertiary C−SR) and alkyl (quaternary C−
SR) sulfides and dithioacetals and dithioketals with high
chemoselectivities.
T
blocks in diverse areas of synthetic organic chemistry. The high
demand for organosulfur compounds is mainly attributed to the
various functions of the sulfur atom attached to the carbon
atom,1 such as stabilizing the adjacent carbanions,2 acting as a
leaving group for reductive metalation,3 acting as an electro-
phile for cross-coupling reaction,4 etc.5 Cleavage of the C−S
bond is important for the removal of the sulfur unit.6 However,
methods for C−S bond cleavage are highly limited due to the
inertness of the bond.
Hydrodesulfurization (HDS), which is the conversion of a
C−SR bond to a C−H bond, is the simplest transformation
reaction of the C−S bond (Figure 1). Although main-group
An initial attempt was carried out with benzyl sulfide 1a and
an excess amount of triethylsilane in the presence of a catalytic
amount of B(C6F5)3 in CDCl3 (Table 1). When 3.0 equiv of
Et3SiH were used for HDS,11 target product 2a was obtained in
98% yield by NMR measurement (entry 1). PhSiH3, Ph3SiH,
and (EtO)3SiH were less effective for this HDS (entries 2−4).
To our delight, 2a was obtained in high yield with a low catalyst
loading in CH2Cl2 (2 mol %, entry 5). When this reaction was
performed in larger scale, 2a was successfully obtained in 92%
isolated yield (entry 6). On the other hand, the use of BF3·
OEt2, which is one of the representative boron Lewis acids, was
not effective, and no 2a was formed (entries 7 and 8). Finally,
the optimum conditions were established as follows: 2 mol %
B(C6F5)3, Et3SiH (3 equiv), and sulfide (1.0 equiv) at room
temperature.
Figure 1. HDS of organosulfur compounds and concepts presented in
this work.
metal reagents7 or transition metal catalysts,8 including Raney
nickel, are typically employed for the cleavage of the C−S bond
of sulfides, those reagents are generally flammable and difficult
to handle and require use of more than their stoichiometric
amounts. In addition, the chemoselective reduction of the C−S
bond is rather difficult by previous methods. Therefore, work is
ongoing to develop a novel method for the activation and
transformation of the C−S bond by means of an easily available
and handled nonmetal catalyst.
Next, we explored the substrate scope of this HDS reaction
(Scheme 1). Both aryl and alkyl sulfides 1a−1c underwent
highly efficient HDS to afford 2-ethylnaphthalene (2a) (85−
Received: June 6, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01651
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Organic Letters
Letter
a
and quantitative yields, respectively. 1f derived from 1-indanol
also participated in HDS to furnish Indane (2f) in 73% yield,
which is a volatile material, and the formation of 2f was
Table 1. Examination of Reaction Conditions
1
confirmed by H NMR measurement. Next, we examined the
chemoselectivity of the present HDS reaction. Benzyl sulfide 1g
bearing a 4-bromophenyl group gave 4-butylbromobenzene
(2g) in 83% yield without affecting the C−Br bond. Substrate
1h bearing a 2-thienyl group, which has potential coordinating
ability to a Lewis acid and is easily cleaved by using Raney
nickel, also worked well. Alkenyl12 and alkynyl groups were not
affected under the reaction conditions. Alkyl sulfides 1k and 1l
connected to a quaternary carbon atom were reduced to
hydrocarbons in good yields. Allylsulfide 1m could be
employed for this HDS to afford the product in high yield
involving the isomerization of a double bond. In contrast,
primary benzyl sulfide 1n, secondary alkyl sulfide 1o, aryl
sulfides 1p and 1q, and propargyl sulfide 1r did not undergo
HDS at all.
Gevorgyan et al. reported the demethylation of anisole
derivatives using B(C6F5)3 and Et3SiH.10d When we subjected
benzyl sulfides 1s and 1t bearing a methoxy group to the
reactions, both methyl ether and aryl sulfide were readily
cleaved to afford silyl-protected phenols in 95% and 82% yields,
respectively (Scheme 2). Interestingly, the HDS rate was higher
than the demethylation rate when a competition experiment
using 1.5 equiv of Et3SiH was performed.
b
entry
B(C6F5)3
20 mol %
hydrosilane
yield (%)
1
2
3
4
Et3SiH
PhSiH3
Ph3SiH
(EtO)3SiH
Et3SiH
Et3SiH
Et3SiH
Et3SiH
98
71
49
20 mol %
20 mol %
20 mol %
no reaction
d
c
5
e
2 mol %
99 (95)
c
6
2 mol %
92
f
7
8
BF3·OEt2 (20 mol %)
BF3·OEt2 (100 mol %)
0
f
0
a
Conditions: Reactions were carried out with 1a (0.1 mmol), Et3SiH
(0.3 mmol), and B(C6F5)3 in CDCl3 (0.7 mL) at rt for 30 min. NMR
yields. Isolated yields. Reaction time was 1 h in CH2Cl2. 1a (5
b
c
d
e
f
mmol) was used in CH2Cl2. No reaction.
Scheme 1. Substrate Scope for HDS of Sulfides Using
B(C6F5)3−Et3SiH System
a b
,
a
Scheme 2. HDS of Substrates Bearing Methoxy Group
a
Conditions: Reactions were carried out with starting material (0.1
mmol), Et3SiH (0.3 mmol), and B(C6F5)3 (2 mol %) in CDCl3 (0.7
mL) at room temperature (details in Supporting Information).
Isolated yields.
To further test the flexibility of this methodology, attempts
were made to perform HDS of dithioacetals (Scheme 3). It is
known that dithioacetals are useful umpolungs of carbonyl
groups and applicable skeletons for the construction of
additional C−C bonds.2,13 The Raney nickel catalyzed HDS
of dithianes is frequently used for the conversion of a
dithioacetal unit into a methylene unit. However, methods
for the conversion of a dithioacetal into a methylene unit are
limited to transition metal catalyzed reactions or main-group
metal-mediated reactions.14 Dithioacetals 4a, 4b, and 4c
underwent selective cleavage of one of the C−S bonds to
furnish 5a, 1o, and 5c in high yields. The results indicate that
HDS of dithioacetals has similar chemoselectivity to that of the
former sulfides. Encouraged by the results, we examined HDS
of dithiolane and dithiane. Use of 4d and 4e, which were
a
Conditions: Reactions were carried out with starting material 1 (0.1
mmol, Ar = p-ClC6H4), Et3SiH (0.3 mmol), and B(C6F5)3 (2 mol %)
in CDCl3 (0.7 mL) at room temperature (details in Supporting
b
c
Information). Isolated yields. NMR yields. Et3SiH (0.6 mmol) and
B(C6F5)3 (10 mol %) were used. Et3SiH (0.6 mmol) and B(C6F5)3
(20 mol %) were used. Et3SiH (0.6 mmol) was used. Isomer ratio is
3.4/1 (details in Supporting Information).
d
e
f
95% yields). Ethyl and isopropyl group substituted benzyl
sulfides 1d and 1e afforded target products 2d and 2e in 96%
B
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a
Scheme 3. HDS of Dithioacetal Derivatives
Scheme 5. Proposed Reaction Mechanism
intermediate in path A. The intermediate is rapidly reduced by
the hydride on the borate to give the product involving the
regeneration of B(C6F5)3. As another plausible reaction
pathway, a substitution reaction by hydroborate via the sulfide
intermediate activated by the silylium cation in an SN2 manner
could also occur (path B).15
In summary, we have applied the B(C6F5)3−Et3SiH system
to HDS of various sulfides via the silylium cation catalyzed
activation of the sulfur atom. Benzyl sulfides as well as
secondary and tertiary sulfides were selectively reduced to
hydrocarbons. On the other hand, among the alkyl sulfides,
tertiary ones were removed by employing the same conditions.
The highly chemoselective HDS could be applied to the
deprotection reaction of dithioacetals. Dithioketals were
converted into the corresponding hydrocarbons, and a ring-
opening thiol-bridged sulfide bond was obtained by the
reaction of dithioacetals. Further investigation of the mecha-
nism of and application to the synthesis of more complex
molecules is underway in our laboratory.
a
Conditions: Reactions were carried out with starting material (0.1
mmol), Et3SiH (0.3−0.6 mmol), and B(C6F5)3 (2 mol %) in CDCl3
(0.7 mL) at room temperature (details in Supporting Information).
Isolated yields.
derived from 2-acetylnaphthalene, furnished 2a in 98% and
93% yields, respectively. Meanwhile, treatment of dithiane 4f
and 4g, which are synthesized from 2-naphthalenecarbaldehyde,
resulted in the formation of ring-opening thiols 5f and 5g in
quantitative and 98% yields, respectively. Although the
transformations had been reported, all of them required a
catalytic amount of transition metal or more than the
stoichiometric amount of metal reagents.14
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, analytical data for all new com-
pounds, NMR spectra for the products. The Supporting
Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.orglett.5b01651.
To prove the utility of this HDS, we examined the
deuteration reaction of a C−S bond based on this HDS
method (Scheme 4). When substrates 1b and 4d were treated
a
Scheme 4. HDS Using Et3SiD
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: takahiko.akiyama@gakushuin.ac.jp.
Notes
The authors declare no competing financial interest.
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