Stereoselective Synthesis of Alkenyl Silanes, Sulfones, Phosphine Oxides, and Nitroolefins by Radical C-S Bond Cleavage of Arylalkenyl Sulfides

Article abstract of DOI:10.1021/acs.orglett.7b00126

A radical-mediated approach has been introduced for the C-S bond activation of arylalkenyl sulfides. The protocol provides an efficient approach for the generation of various alkenes including alkenyl silanes, sulfones, phosphine oxides, and nitroolefins. In most cases, these radical substitutions are performed under metal-free conditions with stereospecificity.

Full text of DOI:10.1021/acs.orglett.7b00126

Letter
pubs.acs.org/OrgLett
Stereoselective Synthesis of Alkenyl Silanes, Sulfones, Phosphine
Oxides, and Nitroolefins by Radical C−S Bond Cleavage of
Arylalkenyl Sulfides
Ya-mei Lin, Guo-ping Lu,* Rong-kang Wang, and Wen-bin Yi*
Chemical Engineering College, Nanjing University of Science and Technology, Nanjing, 210094, China
S
* Supporting Information
ABSTRACT: A radical-mediated approach has been intro-
duced for the C−S bond activation of arylalkenyl sulfides. The
protocol provides an efficient approach for the generation of
various alkenes including alkenyl silanes, sulfones, phosphine
oxides, and nitroolefins. In most cases, these radical
substitutions are performed under metal-free conditions with
stereospecificity.
he activation and cleavage of C−S bonds for the
Tconstruction of C−C bonds and C−heteroatom bonds
has attracted much attention in recent years owing to the
stability and ready availability of sulfur species compared to the
corresponding halides used in traditional methods.1 Among
organosulfurs, alkenyl sulfides have great potential to undergo
C−S bond cleavage with the simultaneous installation of an
olefinic part in the products, which are important structural
units in many natural products, pharmaceuticals, and organic
emitter materials.2 Therefore, the approaches have been well
established for the formation of C−C bonds by Cvinyl−S
activation using transition-metal catalysts, organometal re-
agents, or dithioacetal derivatives.3
Figure 1. Strategies for the preparation of Cvinyl−X bonds via the
cleavage of Cvinyl−S bonds.
Nevertheless, there are only a few strategies for the
generation of C−X bonds (X = heteroatom) via Cvinyl−S
bond cleavage including the preparation of enamine from
dithioacetal derivatives (C−N),4 the formation of C−O and
C−S bonds using sodium alcoholates or alkanethiolates as
nucleophile reagents,5 and the synthesis of vinylsilanes using
organosilicon metal reagents (C−Si).6 Several limitations
related to these approaches should be addressed: (1) reagents
preprepared by multistep processes or strong basic and unstable
reagents are required; (2) the substrate scope is limited; (3) the
production of C−heteroatom bonds by Cvinyl−S bond cleavage
has not been well-studied. In order to eliminate these issues, we
envisaged that a radical process may be a better alternative
solution than the previous nucleophilic processes, because thiyl
radicals (especially aryl sulfenyl radicals) are better leaving
groups than thiyl anions (Figure 1).7
On the other hand, the formation of olefinic compounds
with β-heteroatom substituted patterns has also played an
important role in the preparation of pharmaceuticals, natural
products, and organic materials.8 From this perspective, the
further exploration of more practical methods for the
generation of various Cvinyl−heteroatom bonds through C−S
bond cleavage in vinyl sulfides is still desirable and appealing.
Herein, we report several new metal-free radical-mediated
reactions of vinyl sulfides with a wide range of substrates, which
provide new access to olefinic compounds with various
heteroatoms-substitution patterns. To the best of our knowl-
edge, this is the first example of generating Cvinyl−X bonds by
radical-mediated cleavage of Cvinyl−S bonds.
Initially, we started our investigations by selecting the
reaction of (4-methylphenyl)(styryl)sulfane 1a and triphenylsi-
lane 2a as the model reaction (Table 1). Oxidants play a crucial
role in the reaction. Peroxides are better initiators than other
oxidants, presumably owing to the high reactivity of oxygen free
radicals.8e tert-Butyl peroxybenzoate (TBPB) emerged as the
optimal choice (entries 1−11). After screening different
solvents, t-BuOH resulted in the best yield (entry 11). The
amount of TBPB was also optimized (entries 11−14), and 3
equiv of TBPB could provide the best yield. This result
indicates that the reaction may not include a radical chain cycle
in which the thiyl radical is unable to abstract an H atom from a
silane to generate a silyl radical.7a No byproduct generated by
direct addition−fragmentation from the oxygen-centered
radicals was detected in the protocol.
Received: January 13, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00126
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Organic Letters
Letter
a
a
Table 1. Optimization of Reaction Conditions
Scheme 2. Reactions of Alkenyl Sulfides with Silanes
b
entry
oxidant (equiv)
solvent
yield (%)
1
TBHP (3)
TBHP (4)
TBHP (5)
DTBP (3)
K2S2O8 (3)
Na2S2O8 (3)
H2O2 (3)
mCPBA (3)
I2O5 (3)
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
H2O
45
2
50
3
52
4
48
5
trace
trace
14
6
7
8
11
9
nr
10
11
12
13
14
15
16
17
AIBN
nr
TBPB (3)
TBPB (2)
TBPB (1)
TBPB (0.2)
TBPB (3)
TBPB (3)
CHP (3)
82
78
47
18
52
toluene
t-BuOH
69
trace
a
Conditions: 1a (0.25 mmol), triphenylsilane (0.75 mmol), t-BuOH
b
(1.0 mL), 110 °C, 10 h. Isolated yields.
Scheme 1. Effects of Substituent Groups in S-Substituent
Benzene Ring of Arylalkenyl Sulfides on the Reaction
a
Conditions: vinyl sulfides (0.25 mmol), silane (0.75 mmol), TBPB
(0.75 mmol), t-BuOH (1.0 mL), 110 °C, 10 h, isolated yield.
b
c
Corresponding Z-1 was used. Silane (5 equiv) and TBPB (5 equiv)
d
were used. Cobalt(III) acetylacetonate 20 mol % was used.
Scheme 3. Silylation of Ethynylbenzene via a One-Pot Two-
a
Step Process
Four alkenyl sulfides were chosen to explore the effects of
substituent groups on the reaction. As shown in Scheme 1, no
obvious influence of S-substituent aryl groups in alkenes was
found in the transformation, so 2-(2-(p-tolylthio)vinyl)arenes
were employed in further studies due to consideration of price
and yield.
A series of arylalkenyl sulfides with electron-donating and
-withdrawing groups provided moderate to excellent yields
(3a−3h, 3k−3m) (Scheme 2). The electron-rich vinyl sulfides
led to slightly lower yields (3d, 3l). The reactions of hetero-
and naphthylalkenyl sulfides also proceeded smoothly under
the identical conditions (3i, 3j, 3n). Other silanes could be also
applied in the protocol (3o−3r). However, only a trace yield
was observed in the case of 3r, and the reaction could be
enhanced by adding cobalt(III) acetylacetonate to provide a
poor yield of 3r (15%). In the cases of 3o and 3p, the reactions
could be enhanced by increasing the amount of silane and
oxidant. It was noteworthy that E-alkenyl organosilanes were
isolated as the only product from both Z and E starting
materials in all cases.
a
Conditions: (1) ethynylbenzene (0.25 mmol), p-tolylthiol (0.25
mmol), t-BuOH (1 mL), 110 °C, 1 h; (2) Ph3SiH (0.75 mmol), TBPB
(0.75 mmol), 110 °C, 10 h, isolated yield.
Likewise, vinyl sulfones that are valuable synthetic targets
and a significant motif in natural products and in drug
discovery11 could be generated from vinyl sulfides and sodium
arylsulfinates in the presence of PhI(OAc)2 (Table 2). To
further demonstrate the versatile synthetic utility of the
chemistry, other substrates including diphenylphosphine
oxide, DMSO, and tert-butyl nitrite (TBN) were also applied
in the approach to provide the desired products (5−7)
(Scheme 4). All the substitution reactions are stereospecific
since only E-products are obtained. It should be noted that no
β-methylstyrene is observed in the reaction of DMSO and 1a.
The reason may be because the methyl radical has high
reactivity, so it can react with methyl sulfinic acid or another
radical quickly to form a methyl sulfonyl radical or other side
products, respectively.12
To further demonstrate the potential of this methodology,
the stereospecific silylation of ethynylbenzene via a one-pot
two-step route was also achieved to derive E-isomer 3a
(Scheme 3), in which p-tolylthiol was first added and then
displaced. However, Z-isomers are the main products in various
transition-metal-catalyzed reactions of alkyne with silanes.10
Further radical trapping experiments were also performed.
All the reactions shown in Scheme 5 were inhibited in the
presence of the radical trap TEMPO. Based on these results, it
could be concluded that all these transformations may involve
free radical processes. As a representative example, a tentative
mechanism for the reaction of triphenylsilane and arylalkenyl
B
DOI: 10.1021/acs.orglett.7b00126
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 2. Reactions of Alkenyl Sulfides and Sodium
Arylsulfinates
Scheme 6. A Tentative Pathway for the Reaction of
Triphenylsilane and Arylalkenyl Sulfide
a
b
entry
Ar1
Ar2
4
yield (%)
c
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
4-MeC6H4
4-MeOC6H4
4-FC6H4
4a
4b
4c
4d
4e
4f
80, 78
42
91
97
84
95
63
4-MeOC6H4
4-ClC6H4
4-FC6H4
2-pyridyl
Ph
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
Ph
in the final product 3. There is no radical chain cycle in the
addition−elimination pathway since a stoichiometric oxidant is
required in the process.7a The elimination step may be a slow
step, and the removed thiyl radical may react with arylthiol or
triphenylsilane to afford the corresponding disulfide or
thiosilane in the presence of an oxidant,14 which are observed
by GC-MS as the byproducts. Other transformations may have
similar mechanisms.12,15
4g
4h
4i
d
37
Ph
74
a
Conditions: 1 (0.25 mmol), sodium arylsulfinates (0.75 mmol),
b
PhI(OAc)2 (0.50 mmol), DMF (1 mL), 100 °C, 10 h. Isolated yield.
c
d
1c instead of 1a was used. (2,2-Diphenylvinyl)(p-tolyl)sulfane is
used as the starting material.
In summary, a newly developed approach for stereoselective
synthesis of β-heteroatom substituted arylalkenes via C−S bond
cleavage has been disclosed. In most cases, these alkenes are
generated through a radical process under metal-free
conditions, and only E-products are derived in these processes.
The chemistry not only provides a new application of vinyl
sulfides in organic synthesis but also develops a useful method
for the activation of C−S bonds, which may promote the
discovery of other new types of cleavage and transformation of
C−S bonds to useful motifs.
Scheme 4. Transformations of Alkenyl Sulfides 1 via C−S
Bond Cleavage
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b00126.
Experimental details and copies of NMR spectra of all
products (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: glu@njust.edu.cn.
*E-mail: yiwb@njust.edu.cn.
ORCID
Guo-ping Lu: 0000-0003-4476-964X
Wen-bin Yi: 0000-0003-4606-7668
Notes
Scheme 5. Radical Trapping Experiments
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the Natural Science Foundation of
China (21402093, 21476116) and Jiangsu (BK20140776,
BK20141394), Chinese Postdoctoral Science Foundation
(2016T90465, 2015M571761), and Priority Academic Program
Development of Jiangsu Higher Education Institutions for
financial support.
sulfide was proposed (Scheme 6), although the detailed
mechanisms of these reactions remain to be elucidated. First,
a silicon radical 813 derived from triphenylsilane in the presence
of TBPB is added to the arylalkenyl sulfide generating a radical
intermediate 9.8e The release of the thiyl radical from 9 results
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