A convenient access to β-iodo sulfone by the iodine-mediated iodosulfonylation of alkenes

Article abstract of DOI:10.1039/c5ra07065a

A novel iodine-mediated intermolecular iodosulfonylation reaction of alkenes for dual C-S and C-I bond formation is described. A series of alkenes could be selectively converted into the corresponding β-iodo sulfones, which are versatile building blocks in organic synthesis and medicinal chemistry. Molecular iodine was the iodine source in this reaction.

Full text of DOI:10.1039/c5ra07065a

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A Convenient Access to β-Iodo Sulfone by Iodine-Mediated
Iodosulfonylation of Alkenes
Kai Sun,*a Yunhe Lv,a Zhonghong Zhu,a Yongqing Jiang,a Jiejie Qi,a Hankui Wu,a Zhiguo Zhang,b Guisheng
Zhangb and Xin Wang*a
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
β-iodo sulfone is a versatile building blocks in organic synthesis
50 and medicinal chemistry, as well as valuable intermediates since
the chemical structure can be further elaborated in the
construction of a series of useful active molecules. However,
conevnient and direct synthetic method for β-iodo sulfone is
rare.14,9b Sulfonyl hydrazides have been widely used as
55 reductants and as well as a source of sulfonylation and
arylation,15 And concerning our continuing interest in radical
oxidative cross-coupling reactions,16 we now disclose an iodine-
mediated intermolecular iodosulfonylation reaction of alkenes by
using sulfonylhydrazides as sulfonyl source. 17
A novel iodine-mediated intermolecular iodosulfonylation
reaction of alkenes for daul C–S and C–I bonds formation is
described. A series of alkenes could be selectively converted
10 into the corresponding β-iodo sulfones, which are versatile
building blocks in organic synthesis and medicinal chemistry.
Molecular iodine acted in this reaction as iodine source.
Difunctionalization of alkenes is a class of significant synthetic
transformations that allow for the buildup of molecular
15 complexity in a single procedure.1 Recent, transition-metal-
catalyzed difunctionalization of alkenes provide a powerful
strategy for the synthesis of two new vicinal chemical bonds
60
We started our investigations with styrene 1a and 4-
methylbenzenesulfonohydrazide 2a as model substrates. Several
parameters, such as iodine sources, solvents and temperature
simultaneously,
and
diamination,2
aminooxygenation,3
dioxygenation,4 cyanotrifluoromethylation,5 fluoroamination,6
20 phosphonofluorination,7 and oxysulfonylation8 have been
elegantly demonstrated. Despite of the overall efficiency and
versatility of these transformations, significant limitations such as
costly and toxic metal catalyst that led to the emergence of a
metal-free approach for difunctionalization of alkenes.
25 Difunctionalization of unsaturated bonds via a radical pathway is
an attractive alternative compared to transition-metal-catalyzed
difunctionalization of alkenes.9 Molecular-iodine catalyst, in
combination with TBHP as environmentally benign and
inexpensive co-oxidant, has been increasingly explored in place
30 of rare or toxic heavy metal oxidants in recent years.10 Simple
iodine has broad transformation ability of functional groups and
can be used widely in organic synthesis.11 The advantages of
iodine are operational simplicity, low cost, and less toxicity.
However, research towards the development of iodine-
35 catalyzed/mediated methods for the direct functionalization of C–
H bonds is still in its infancy, and further explore this fascinating
area is highly desirable in synthetic chemistry. 12
Table 1: Screening of Reaction Conditionsa
entry
oxidant
solvent
Iodine
source
yield of 3a / 4
(%) b
1
2
I2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
MeCN
DCE
0/79 c
23/57d
52/0
0/0
I2
3
I2
4
NaI
5
KI
0/0
6
nBu4NI
0/0
7
I2
I2
I2
I2
I2
I2
20/0
0/0
Sulfonyl group is of great importance in medical chemistry,
8
photovoltaic materials,
nonlinearoptics, and synthetic
40 chemistry.13 Therefore, it is valuable to develop new strategies to
introduce sulfonyl groups to the designated molecular
frameworks. Difunctionalization of alkenes to incorporate the
sulfone group is also an attractive target to pursue. Recently, Lei
and co-workers reported an elegant aerobic oxysulfonylation of
45 alkenes using sulfinic acids as sulfonyl group.8a The similar work
was achieved by Itoh group using sodium sulfinates as sulfonyl
group promoted by molecular iodine.8b We noticed that β-iodo
sulfone was eliminated as a possible intermediate in Itoh’s work.
9
EtOH
THF
89/0
79/0
0/0
10
11
12
H2O
EtOH
42/0
65
a Reaction conditions: 1a (0.5 mmol), 2a (0.55 mmol), iodine
o
source (0.25 mmol) and TBHP (1.0 mmol) at 0-20 C for 8 h.
c
b
d
Yield of isolated product. Reaction performed at 80 oC.
Reaction performed at 40 oC.
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Table 3: Scope of Chain and Cyclic Alkenes.a, b
were all conducted to investigate the impact of the reaction
outcome, the results are listed in Table 1. Initially, the reaction of
1a with 2a was performed in EtOAc at 80 oC utilizing molecular
iodine and TBHP (70% in water) combinations, but we can not
detect the iodosulfonylation product 3a. The unexpected
oxysulfonylation product 4 was obtained in 79% yield (Table 1,
entry 1). To our delight, the reaction could gave a low yield of 3a
when we decreased the temperature to 40 oC, although 4 was still
the main product (Table 1, entry 2). The yield of 3a could be
5
10 increased to 52% when the reaction was performed at room
temperature, and any of 4 can not be detected (Table 1, entry 3).
Other iodine sources, such as NaI, KI and nBu4NI were tested,
but all of them completely do not work (Table 1, entries 4–6). A
variety of solvents were subsequently tested (Table 1, entries 7–
15 11). EtOH was clearly the best choice for this catalytic system
and the yield of 3a was improved to 89% (Table 1, entry 9).
Meanwhile, THF was also good choice for this procedure and
gave the desired 3a in 79% yield (Table 1, entry 10). Further
screening revealed that the yield of 3a was decreased severely
a Reaction conditions: 5 (0.5 mmol), 2a (0.55 mmol), molecular-
30 iodine source (0.25 mmol) and TBHP (1.0 mmol) at 0-20 oC for 8
h. b Yield of isolated product.
20 Table 2: Scope of Styrene and Propylene. a, b
when TBHP was absent (Table 1, entries 12). Obviously, TBHP
plays a pivotal role in the catalytic cycle, although the exact
35 reason need to be revealed.
Using the optimized conditions, we next explored the scope
and generality of the process. As shown in Table 2, Various
substitutents on the benzene ring of styrene were well tolerated
such as electron-withdrawing groups (F, Cl, Br and CO2Me) and
40 -donating groups (Me and t-buyl). Some of these functional
groups are useful for further synthetic diversification.
Substitution groups on aromatic ring at different positions, such
as 2-Cl, 3-Br, 4-F, 4-Cl and 4-Br did not show obvious yield
disparity during this iodine-mediated procedure, thus affording
45 the corresponding iodosulfonylation products in good-to-high
yields (72−92%). Notably, the reaction of sterically bulky 1,6-
dichloro-2-vinylbenzene 1k also reacted smoothly, affording the
corresponding β-iodo sulfone 3k in 92% yield. Other than 4-
methylbenzenesulfonohydrazide, benzenesulfonohydrazide and
50 4-chlorobenzenesulfonohydrazide were suitable sulfonyl source
and provided the desired products 3l and 3m in high yields (89%
and 88%). In addition, the reactivity of several allylbenzene
derivatives (1n, 1o, 1p and 1q) were investigated, and the
corresponding products 3n, 3o, 3p and 3q were obtained in good
55 yields (88−95%).
I
I
O
S
I
O
S
O
S
O
O
O
3a, 8h, 89%
3b, 6h, 92%
3c, 6h, 93%
I
I
O
I
O
O
S
O
S
S
O
O
F
Br
Cl
3d, 8h, 83%
3e, 8h, 78%
3f, 12h, 81%
I
O
I
Cl
I
O
O
S
O
Br
S
O
S
O
O
O
3g, 12h, 79%
3h, 8h, 72%
3i, 12h, 92%
I
O
I
I
Cl
O
O
S
S
O
S
O
O
Iodosulfonylation of alkenes is an important chemical process
because the corresponding products are useful for further
transformation. Encouraged by these results, we further
investigated the scope of other easily accessible chain and cyclic
60 olefins. As shown in Table 3, pent-1-ene 5a was effective
substrate and gave the desired product 6a in 76% yield. Notably,
substrates bearing sensitive substituents, such as 4-bromobut-1-
ene 5b, 3-chloroprop-1-ene 5c, methyl acrylate 5d and prop-2-en-
1-ol 5e, can still provide the desired products in moderate to good
65 yields (71−87%). 2,5-dihydrofuran 5f was also subjected to the
process, thus affording the corresponding 6f in 84% yield. Finally,
this reaction can be scaled up to gram level, which suggests that it
can be potentially applied in chemical industry (eqn 1).
Cl
, 8h, 88%
, 12h, 92%
3k
, 6h, 89%
3l
3j
Cl
I
O
I
O
I
S
O
O
S
O
S
O
HO
3m, 6h, 88%
3n, 5h, 90%
3o, 5h, 95%
I
I
O
O
S
S
MeO
O
O
MeO
MeO
3p, 5h, 88%
3q, 5h, 89%
Having established the scope of the method, a preliminary
70 study on the reaction mechanism was performed. 2,2,6,6-
a
Reaction conditions: 1 (0.5 mmol), 2 (0.55 mmol), molecular-
o
iodine source (0.25 mmol) and TBHP (1.0 mmol) at 0-20 C for
25 5-12 h. b Yield of isolated product.
2
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bProf. Z Guo, and Prof. G Zhang
35 College of Chemistry and Chemical Engineering
Henan normal university Xinxiang, Henan 453007, P. R. China
† Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
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Scheme 1: Proposed reaction mechanism.
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80
85
In conclusion, we reported an iodosulfonylation reaction
20 between alkenes and sulfonyl hydrazides using molecular iodine
as iodine source and sulfonyl hydrazides as sulfonyl source. This
reaction also provides an important method for preparing β-iodo
sulfones, which are versatile building blocks and valuable
intermediates in organic synthesis and medicinal chemistry. The
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up operation make this reaction attractive in industrial production.
Further mechanistic studies are underway and will be
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30 aProf. K Sun,* Y Lv, Z Zhu, Y Jiang, J Qi, H Wu, and Prof. X Wang
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E-mail: sunk468@nenu.edu.cn; wangx933@nenu.edu.cn
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