Direct access to β-seleno sulfones at room temperature through selenosulfonylation of alkenes

Article abstract of DOI:10.1007/s11426-016-0412-0

A new protocol has been developed for the formation of C?Se and C?S bonds by the direct selenosulfonylation of alkenes. This protocol is operationally simplistic, has a wide substrate scope, uses readily available seleno and sulfonyl sources, and is amenable to gram-scale synthesis. This reaction represents a significant addition to the limited number of reactions available for the intermolecular selenide difunctionalization of alkenes and would be useful for the synthesis of sulfur- and selenium-containing molecules.

Full text of DOI:10.1007/s11426-016-0412-0

SCIENCE CHINA
Chemistry
doi: 10.1007/s11426-016-0412-0
•
COMMUNICATIONS •
Direct access to β-seleno sulfones at room temperature through
selenosulfonylation of alkenes
1,2*
1
1
1
1
3*
Kai Sun , Yunhe Lv , Zuodong Shi , Fangfang Fu , Chong Zhang & Zhiguo Zhang
1
College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang 455000, China
2
Henan Province Key Laboratory of New Opto-Electronic Functional Materials, Anyang 455000, China
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China
3
Received October 8, 2016; accepted December 5, 2016; published online January 4, 2017
A new protocol has been developed for the formation of C−Se and C−S bonds by the direct selenosulfonylation of alkenes.
This protocol is operationally simplistic, has a wide substrate scope, uses readily available seleno and sulfonyl sources, and is
amenable to gram-scale synthesis. This reaction represents a significant addition to the limited number of reactions available for
the intermolecular selenide difunctionalization of alkenes and would be useful for the synthesis of sulfur- and selenium-containing
molecules.
alkenes, selenosulfonylation, difunctionalization, metal-free conditions, β-seleno sulfones
Citation:
Sun K, Lv Y, Shi Z, Fu F, Zhang C, Zhang Z. Direct access to β-seleno sulfones at room temperature through selenosulfonylation of alkenes. Sci China
Chem, doi: 10.1007/s11426-016-0412-0
Selenium-containing structures can be found in a diverse
range of drug candidates, biologically active compounds, and
functional organic materials [1]. Moreover, the facile conver-
sion of selenides to other functional groups and their ability
to favor or even facilitate further synthetic transformations
represent additional assets that render selenation reactions
indispensable [2]. The development of new synthetic routes
for the introduction of selenium groups into organic com-
pounds would therefore be of significant synthetic value.
Alkenes are simple and abundant bulk commodities, and the
vicinal difunctionalization of these feedstock materials is of
great importance for the introduction of molecular complex-
ity in a single procedure [3]. However, compared with the
well-established transition metal-catalyzed reactions for the
difunctionalization of specific substrates [4], further research
is still needed for the discovery of complementary organocat-
alyst-mediated difunctionalization approaches. Furthermore,
the development of sustainable approaches for the synthetic
introduction of selenium-containing functional groups via
the organocatalyst-mediated seleno-difunctionalization of
alkenes is an attractive topic.
The sulfonyl group has attracted considerable interest from
researchers working in a variety of different fields, includ-
ing medical chemistry, photovoltaic materials, nonlinear op-
tics, and synthetic chemistry [5]. Significant progress has
recently been made towards exploring the difunctionaliza-
tion of alkenes using a sulfonylation-based transformation,
such as an oxysulfonylation reaction [6]. The difunctional-
ization of alkenes to incorporate selenium and sulfone groups
in a single step represents an attractive transformation, which
could provide a unique and convenient method for the in-
troduction of two synthetically versatile functionalities into
an unsaturated substrate. However, a review of the literature
revealed that very few reactions have been reported for the
selenosulfonylation of alkenes (Scheme 1(a)) [7]. Based on
the nucleophilic attack to a seleniranium intermediate, we re-
cently achieved the highly regioselective selenoamination of
*
Corresponding authors (email: sunk468@nenu.edu.cn; zhangzg@htu.cn)
©
Science China Press and Springer-Verlag Berlin Heidelberg 2017
chem.scichina.com link.springer.com

2
Sun et al. Sci China Chem
a)
Table 1 Optimization of the reaction conditions
b)
Entry
Oxidant
Additive
no
Solvent
THF
THF
THF
THF
THF
THF
THF
THF
Yield (%)
29
1
2
3
4
5
6
7
8
9
(NH
(NH
(NH
4
4
4
)
)
)
2
2
2
2
S
S
S
2
2
2
O
O
O
8
8
8
c)
no
trace
Scheme 1 Selenosulfonylation reactions of alkenes.
d)
No
trace
K
2
S
O
8
No
36
0
Oxone
TBHP
No
alkenes [8]. Inspired by this result, and as part of our ongoing
interest in the development of new methods for the formation
of C–X (X=N, S, I) bonds [9], we herein disclose our lat-
No
17
71
22
78
55
0
K S
2
K S
2
K S
2
K S
2
K S
2
K S
2
K S
2
O
2 8
O
2 8
O
2 8
O
2 8
O
2 8
O
2 8
O
2 8
KI
est work on the KI/K
2
S
2
8
O -mediated selenosulfonylation of
2 3
Na CO
alkenes under mild conditions (Scheme 1(b)). This new ap-
proach avoids the need for pre-prepared S–Se regents and ex-
hibits wide substrate scope, high functional group tolerance,
making it a useful tool with numerous potential applications
in synthetic chemistry.
KI
KI
KI
KI
KI
3
CH CN
10
EtOAc
DCE
11
e)
1
2
3
CH
3
CN
CN
72
All reagents were used as received from commercial
sources, unless otherwise specified or prepared as described
in the literature. All reagents were weighed and handled in
air.
f)
1
CH
3
89
a) Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), diphenyl dise-
lenide (0.3 mmol), oxidant (0.6 mmol), and additive (0.2 equiv.) in solvent
2.0 mL) for 12 h. b) Yield of the isolated product. c) Sodium p-toluenesul-
fonate 4 was used as the sulfonyl reagent. d) Tosyl chloride 5 was used as
the sulfonyl reagent. e) Reaction performed at 40 °C. f) Reaction performed
at 20 °C.
(
1
13
H and C NMR spectra were respectively recorded at 400
and 100 MHz, using tetramethylsilane as an internal refer-
ence. Chemical shifts (δ) and coupling constants (J) were
expressed in ppm and Hz, respectively.
Styrene 1a (0.3 mmol), 4-methyl benzene sulfonyl hy-
drazine 2a (0.6 mmol), diphenyl diselenide (0.3 mmol),
tive (Table 1, entries 5 and 6). After detailed additive screen-
ing, we found that 20% KI led to marked improvements in
the transformation, with the isolated yield of 3a increasing to
71% (Table 1, entry 7). In a separate experiment, we noted
K
2
S
2
O
8
(0.6 mmol), KI (0.2 equiv.), and CH CN (2.0
3
mL) at 20 °C for 12 h (monitored by thin-layer chro-
matography (TLC)), quenched with water, extracted with
dichloromethane (5×3 mL), and dried over anhydrous
that the addition of Na
come of the reaction (Table 1, entry 8). We also evaluated the
effects of several different solvents. We found that CH CN
2
CO
3
had an adverse impact on the out-
3
Na
2
SO
4
. The solvent was removed under reduced pressure,
was the best solvent for this transformation (Table 1, entry
9). EtOAc also performed well, whereas the non-polar sol-
vent DCE failed to afford any of the desired product (Table 1,
entries 10 and 11). The reaction temperature was determined
to be critical to the success of this reaction. Pleasingly, de-
creasing the temperature of the reaction to 20 °C led to a con-
siderable increase in the yield of 3a to 89% when the reaction
and the residue was purified by a shot flash silica gel column
chromatography (EtOAc/petro ether=1:8) to give compound
3
a as a white solid (111.1 mg, 89%).
For our initial study, we chose styrene 1a and diphenyl
diselenide as model substrates, which were reacted with
various sulfonyl reagents, including 4-methylbenzenesul-
fon-hydrazide 2a, sodium p-toluenesulfonate 4, and tosyl
chloride 5. Pleasingly, this reaction proceeds as anticipated
with 4-methylbenzenesulfonhydrazide 2a in the presence
was conducted in CH
3
CN with KI and K
2
S
2
8
O (Table 1, entry
13). The optimal catalytic system for the selenosulfonyla-
tion of styrene was therefore determined to be as follows: 1a
of (NH
4
)
2
S
2
O
8
in tetrahydrofuran (THF) at 60 °C, affording
(0.3 mmol), 2a (0.6 mmol), KI (0.06 mmol), and K
2
S
2
O (0.6
8
the desired product 3a in 29% yield (Table 1, entry 1). In
contrast, only trace quantities of the desired product 3a were
obtained when 4 and 5 were used as the sulfonyl reagents
mmol) in CH CN (2.0 mL) at 20 °C under air for 12 h.
3
With the optimized reaction conditions in hand (Table 1,
entry 13), we turned our attention to the scope with respect
to the alkenes and sulfonyl hydrazides. As shown in Table 2,
various substituents on the benzene ring of styrene were well
tolerated, including electron-withdrawing (–F, –Cl, –Br, and
(
Table 1, entries 2 and 3). Encouraged by this result, we also
tested K , oxone, and t-butylhydroperoxide (TBHP) as
oxidizing agents in the reaction. The yield of 3a improved to
2
S
2
O
8
3
4
6% when K
2
S
2
O
8
was added to the reaction (Table 1, entry
–NO
2
) and -donating groups (–CH
3
, –CH Cl, and –t-butyl).
2
), whereas oxone and TBHP proved to be much less effec-
Some of these functional groups are useful for further syn-

Sun et al. Sci China Chem
3
a), b)
Table 2 Scope of the alkenes and benzenesulfonyl hydrazides
hydrazides [11] and diphenyl diselenides. As expected, these
reactions proceeded smoothly, affording the corresponding
products 3r–3u in good yields (61%–81%).
To demonstrate the synthetic utility of this selenosulfony-
lation reaction, we conducted a gram-scale reaction under the
optimized conditions using 1a, 2a, and diphenyl diselenide,
which gave the desired product 3a in an isolated yield of 78%
(Scheme 2(a)). We subsequently showed that 3a could be
converted to the corresponding vinyl sulfone H in 79% yield
using known transformations (Scheme 2(b)) [7].
K
2
S
2
O
8
is a good initiator of free seleno radicals. To de-
termine whether K was acting as a radical initiator in
this reaction, we added 2 equiv. of the radical scavenger
2
S
2
O
8
2,6-di-tert-butyl-4-methylphenol (BHT) to the reaction of 1a,
2a, and diphenyl diselenide under the standard conditions.
After 3 h, the desired selenosulfonylation product 3a was ob-
tained in 76% yield, which argues against the possibility of a
pathway involving the initial addition of a free seleno radical
to alkenes pathway (Scheme 3(a)). It is likely that the K
2
S O
2 8
will oxidize the iodide ion to I , which could easily reacted
2
with the tosylhydrazine to give an N-iodo-N-tosyldiazene.
Nucleophilic attacked by the PhSe portion of the phenyldise-
lenide to N-iodo-N-tosyldiazene will generate Back’s reagent
(
TsSO
stead of KI, no reaction occurred (Scheme 3(b)). In addition,
we prepared the TsSO SePh according to Back’s work and
2
SePh) in situ. However, when I was introduced in-
2
2
was then reacted with 1a, only a small amount of 3a could be
detected (Scheme 3(c)). The pH of the reaction mixture was
a) Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), diphenyl diselenide
(
2 2 8 3
0.3 mmol), K S O (0.6 mmol), and KI (0.2 equiv.) in CH CN (2.0 mL) at
2
0 °C for 4–12 h. b) Yield of the isolated product.
thetic diversification. For example, the chloromethyl group
–CH Cl) in 1n could be readily converted to a –CH , –CH
OH, –CH CN, –CHO, or –CH N(Me) group. Organo-chloro
(
2
3
2
-
2
2
2
and -bromo substituents are reactive and can be difficult to
retain during transition metal-catalyzed or organocatalytic re-
actions [10]. Therefore, these groups were well tolerated un-
der our reaction conditions, further highlighting the synthetic
utility of the current protocol. Substrates with substituents at
different positions of their benzene ring, including o-chloro-,
m-chloro-, and p-chloro-, all transformed smoothly to give
the corresponding seleno-sulfonylated products 3c, 3d, and
Scheme 2 Gram-scale synthesis and functionalization of the selenosulfony-
lation product.
3
g, respectively. Notably, the reaction of the sterically bulky
substrate 1,6-dichloro-2-vinylbenzene 1j also proceeded well
to afford the corresponding β-iodo sulfone 3j in 92% yield.
1
-(Allyloxy)-2-chlorobenzene 1o, 1-(allyloxy)-4-chloro-
benzene 1p, and 1-(allyloxy)-4-methyl-benzene 1q also
reacted well to give the desired products 3o, 3p, and 3q with
high yields of 84%, 86%, and 79%, respectively, thereby
greatly expanding upon the substrate scope of this reaction.
In addition, we also briefly tested the scope of sulfonyl
Scheme 3 Reactions determining the reaction mechanism.

4
Sun et al. Sci China Chem
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Acknowledgments This work was supported by the National Natural
Science Foundation of China (U1504210), the China Postdoctoral Science
Foundation (2015M572110), and Jilin Province Key Laboratory of Organic
Functional Molecular Design & Synthesis (130028651).
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Supporting information The supporting information is available online
at http://chem.scichina.com and http://link.springer.com/journal/11426.
The supporting materials are published as submitted, without typesetting
or editing. The responsibility for scientific accuracy and content remains
entirely with the authors.
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