I2/TBHP-mediated reaction of sulfonylhydrazides with alkynes: Synthesis of (E)-β-iodovinyl sulfones

Article abstract of DOI:10.1016/j.tetlet.2013.03.117

An efficient and simple procedure for the syntheses of (E)-β-iodovinyl sulfones through TBHP mediated reaction of sulfonylhydrazides and iodine with aryl acetylenes has been developed. This method offers several advantages such as high atom economy, envir

Full text of DOI:10.1016/j.tetlet.2013.03.117

Tetrahedron Letters xxx (2013) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
I2/TBHP-mediated reaction of sulfonylhydrazides with alkynes: synthesis of
(E)-b-iodovinyl sulfones
⇑
⇑
Xiaoqing Li , Xiangsheng Xu , Xinhua Shi
College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and simple procedure for the syntheses of (E)-b-iodovinyl sulfones through TBHP mediated
reaction of sulfonylhydrazides and iodine with aryl acetylenes has been developed. This method offers
several advantages such as high atom economy, environmentally benign oxidant, less byproduct, and
easy operation.
Received 10 January 2013
Revised 25 March 2013
Accepted 27 March 2013
Available online xxxx
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
(E)-b-iodovinyl sulfones
Sulfonylhydrazides
TBHP
Sulfonyl radicals
Atom economy
Sulfone-containing molecules have shown interesting biological
activities and are primary components of many drugs on market.1
They are also versatile building blocks in organic synthesis.2 To
construct this type of compounds, addition of sulfonyl radicals to
carbon–carbon multiple bonds is a common strategy,3 of which
sulfonyl halides,4 selenide,5 cyanide,6 azide,7 and sodium sulfinate8
often serve as the sulfonyl radical precursor. Recently, the Tanigu-
chi group developed a new method to generate sulfonyl radical
from sulfonylhydrazide using inexpensive and nontoxic FeCl3 as
catalyst and O2 as oxidant, which allows them to synthesize b-
hydroxysulfones from alkenes.9 Our group also developed a new
approach to generate sulfonyl radical from sulfonylhydrazide using
TBAI (20 mol %) as catalyst and TBHP (2 equiv) as terminal oxidant
Typically, (E)-b-iodovinyl sulfones are synthesized by the addi-
tion of sodium sulfinate to alkynes in the presence of NaI or KI with
stoichiometric amount of Ce(NH4)2(NO3)6 or PhI(OAc)2 as oxidant
(Scheme 2).13 In addition to the sensitivity to air and moisture, this
approach needs relative expensive oxidants with high molecular
weight, which leaves room to further improve the atom economy.
Encouraged by our initial experiment, iodine (0.5 equiv) was
used to replace TBAI of the standard conditions (Scheme 2). To
our delight, (E)-b-iodovinyl sulfone 3aa was isolated in 94% yield
(Table 1, entry 1). Inert atmosphere and dry solvent are not neces-
sary in this process. All iodine atoms are transferred into the prod-
uct, which is also an improvement compared to using NaI or KI.
Therefore, the reactions of various substituted phenylacetylenes
with TsNHNH2 were examined under the same reaction conditions.
Gratifyingly, good to excellent yields were observed with halogen,
trifluoromethyl, methyl, and n-pentyl substituted phenylacetyl-
enes (Table 1, entries 2–8). Electron rich p-MeO phenylacetylene
afforded 3ha in 62% yield (Table 1, entry 9). Heteroaryl acetylenes,
such as pyridyl and thiophenyl acetylenes were also compatible
substrates and delivered the corresponding (E)-b-iodovinyl sulf-
ones (3ia and 3ja) in 56% and 83% yields, respectively, (Table 1, en-
tries 10–11). However, the yield diminished markedly when
aliphatic alkyne was used (Table 1, entry 12).
(Scheme 1).10 Addition of thus obtained sulfonyl radical to
a-
methyl styrene or styrene furnished allylic or vinyl sulfones,
respectively (Scheme 1, Eqs. 1 and 2).10 Encouraged by these re-
sults, we continued our research on sulfonylation of alkynes
(Scheme 1, Eq. 3).
We initiated our investigation of the sulfonylation of phenyl-
acetylene with standard TBAI–TBHP conditions.10,11 However, to
our surprise, (E)-b-iodovinyl sulfone 3aa was isolated as a single
product in 17% yield and, obviously, the catalytic amount TBAI as
the sole source of iodine limited the yield of 3aa (Scheme 1, Eq.
3). The structure of 3aa was unambiguously confirmed by single
crystal X-ray diffraction (Fig. 1).12
Phenyl and p-bromophenyl substituted sulfonylhydrazides 2b,c
were also examined in the reaction with phenylacetylene 1a
(Scheme 3), smoothly led to the corresponding (E)-b-iodovinyl
sulfones 3ab and 3ac in 86% and 88% yields, respectively.
Based on results described above and the previous reports,10,13
⇑
Corresponding authors. Tel./fax: +86 571 88320799.
E-mail addresses: xqli@zjut.edu.cn (X. Li), future@zjut.edu.cn (X. Xu).
a
plausible mechanism is proposed (Scheme 4). Initially,
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.03.117
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2
X. Li et al. / Tetrahedron Letters xxx (2013) xxx–xxx
TBAI (20 mol%),
Ts
Ts
TBHP (2.0 equiv.)
TsNHNH2
+
(1)
(2)
MeCN, 80 oC, 20h
74%
31%
TBAI (20 mol%),
TBHP (2.0 equiv.)
TsNHNH2
+
MeCN, 80 oC, 20h
Ts
TBAI (20 mol%),
TBHP (2.0 equiv.)
MeCN, 80 oC, 20h
(3)
+
TsNHNH2
I
Ts
3aa
, 17%
Scheme 1. Reactions of TsNHNH2 with multiple bonds.
PhC CH, Ce(NH4)2(NO3)6, NaI,
Ar, anhyd MeCN
Table 1 (continued)
I
Entry
Substrates
Products
Yield (%)b
SO2Na
PhC CH, PhI(OAc)2, KI
MeCN
I
Ts
Ts
Ts
Ts
I , TBHP
PhC CH,
2
SO2NHNH2
open air, MeCN
This work
Cl
3ca
I
Br
Scheme 2. Synthesis of (E)-b-iodovinyl sulfones.
1d
4
5
6
84
93
94
Table 1
Scope of the reaction with alkynesa
Br
Cl
3da
I
I2 (0.5 equiv.),
I
TBHP (2.0 equiv.)
R
TsNHNH2
+
Ts
R
MeCN, 80 oC, 1h
1
2a
3
Cl
1e
3ea
F3C
I
Entry
1
Substrates
Products
Yield (%)b
I
Ts
F3C
Ts
F3C
Me
1a
94
1f
CF3
Ts
3fa
3aa
I
I
F
1g
Ts
1b
7
8
75
84
2
3
88
93
Me
F
3fa
I
3ba
C5H11
Cl
Ts
1h
1c
C5H11
3ga
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X. Li et al. / Tetrahedron Letters xxx (2013) xxx–xxx
3
t-BuOOH
Table 1 (continued)
Entry Substrates
t-BuO
+
OH
Products
Yield (%)b
t-BuO
+
t-BuOOH
t-BuOO
+
t-BuOH
I
MeO
t-BuOOH
t-BuOOH
Ts
1i
or
or
O
S
O
9
62
56
t-BuOH
NH2
t-BuOH
R
N
or
or
H2O
MeO
H2O
3ha
O
I
R
NHNH2
S
t-BuOO
N
O
O
S
Ts
or
2
R
1j
10
NH
N
t-BuO
O
or
N
3ia
OH
N2
t-BuOOH
I
or
O
S
O
N
S
t-BuOH
R
N
Ts
11
12
83
22
or
1k
O
S
O
S
H2O
R
3ja
I2
I
O
I
R
S
1l
O
Ar
O
Ar
S
(1)
(2)
radical
O
Ts
R
Ar
I
addition
1
3la
3
I
ref 13a
I2
a
Reaction conditions: 0.5 mmol of aryl acetylenes (1), 0.6 mmol of TsNHNH2
(2a), 0.25 mmol of I2, 2 equiv of TBHP (70% aqueous solution) in 2.0 mL of MeCN at
80 °C for 1 h.
I
b
O
O
S
O
Isolated yield.
Ar
O
R
S
R
I
Ar
S
O
O
R
ref. 13b
a
-N-hydrogens of sulfonylhydrazides are abstracted by free radi-
3
I
cals generated from the homolysis of TBHP,14 to generate sulfonyl
radicals. Then, the addition of resulting sulfonyl radicals to aryl
acetylenes and subsequent trapping of the C-centered alkenyl rad-
icals intermediate I with I2 or iodine free radicals afford (E)-b-iod-
ovinyl sulfones 3 (Scheme 4, Eq. 1).13a It is also possible that 3 is
formed via the addition of arenesulphonyl iodides, which was gen-
erated from the reaction of sulfonyl radicals with I2 or iodine free
radicals, to aryl acetylenes (Scheme 4, Eq. 2).13b
Scheme 4. Possible mechanism.
In conclusion, a highly efficient synthetic method for the prep-
aration of (E)-b-iodovinyl sulfones has been developed. The reac-
tion is environmentally benign in adoption of inexpensive TBHP
and iodine, which are highly atom-economically transferred into
products leaving nontoxic tert-butanol as the side product. No
need of inert atmosphere or dry solvent also allows easy experi-
mental operation. Further investigation of the sulfonylation with
sulfonylhydrazides as the sulfonyl radical precursor is underway
in our laboratory.
Acknowledgements
This project is supported by the National Science Foundation of
China (21102130) and the Key Innovation Team of Science & Tech-
nology in Zhejiang Province (2010R50018 and 2011R50017). We
also thank Dr. Guilin Zhuang for helpful assistance in obtaining
X-ray data.
Figure 1. Crystal structure of compound 3aa.
I
I2 (0.5 equiv.),
TBHP (2.0 equiv.)
S
O
X
+
X
SO2NHNH2
O
MeCN, 80 oC, 1h
1a
2b
, X = H
3ab
, X = H, 86%
2c, X = Br
3ac, X = Br, 88%
Scheme 3. Reactions of various sulfonylhydrazides.
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X. Li et al. / Tetrahedron Letters xxx (2013) xxx–xxx
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