Revealing the metal-like behavior of iodine: An iodide-catalysed radical oxidative alkenylation

Article abstract of DOI:10.1039/c4cc00644e

In this work, we have described an alternative alkenylation approach to illustrate the metal-like behaviour of iodine in cross-coupling reactions. Alkenylation could proceed through iodide catalysed radical initiation, radical addition and iodine promoted

Full text of DOI:10.1039/c4cc00644e

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Revealing the metal-like behavior of iodine: an
iodide-catalysed radical oxidative alkenylation†
Shan Tang,a Yong Wu,a Wenqing Liao,a Ruopeng Bai,a Chao Liua and Aiwen Lei*ab
Cite this: Chem. Commun., 2014,
50, 4496
Received 24th January 2014,
Accepted 28th February 2014
DOI: 10.1039/c4cc00644e
www.rsc.org/chemcomm
In this work, we have described an alternative alkenylation approach to coupling reactions,11 we could say that iodine catalysis might serve
illustrate the metal-like behaviour of iodine in cross-coupling reactions. as a promising replacement for transition metal catalysis. However,
Alkenylation could proceed through iodide catalysed radical initiation, little attention has been paid to investigate the metal-like behavior of
radical addition and iodine promoted alkenyl functionality recovery. iodine. Thus, the study for discovering metal-like iodine catalysed
Catalytic HI elimination similar to the b-hydride elimination of transition cross-coupling reactions as well as understanding the behavior of
metals was realized for the radical alkenylation of sulfonyl hydrazides. iodine during catalytic reactions would be of high importance for
Operando IR and cyclic voltammetry experiments were carried out to synthetic organic chemistry. Herein, we report our progress in the
confirm the crucial role of iodine in the radical alkenylation process.
iodide-catalysed radical alkenylation of sulfonyl hydrazides with
simple alkenes (eqn (1)).
Over the past few decades, transition-metal-catalysed cross-coupling
reaction has been proved to be a powerful tool for the construction of
natural, biological, pharmaceutical, and material molecules.1 Their
remarkable capability for electron transfer processes is the major
(1)
The Heck reaction was known to go through transition metal
reason why transition metals are the most widely exploited catalysts. involved alkene insertion and b-hydride elimination of aryl or vinyl
Transition metals usually have moderate redox potentials, which halides (or sulfonates).12 Recently, the radical involved Heck-type
makes it easy for them to gain and lose electrons in cross-coupling reaction has been developed, which offers alkenylation reactions
reactions.2 As a nonmetallic element, iodine has diverse valence with more alternatives.13 Nevertheless, only limited examples have
states as well as moderate redox potentials.2b,3 These features been reported to be successful in radical alkenylation processes.
make it possible for serving as an alternative catalyst for transition In most cases, radical addition to alkenes would end up with
metals. Over the past few years, iodine-catalysed reactions have been hydrogenation or alkene difunctionalization since there is a lack of
increasingly explored.4 Importantly, iodine has been reported to elimination protocols.14 Thus, developing elimination strategies is
catalyze many reactions in which transition metals are used as the key to achieving radical alkenylation. In this work, we describe
catalysts.5 Initiated by Ishihara and Wan, iodine has been applied that HI elimination13e,15 can be realized in a catalytic version for
as an efficient alternative catalyst for transition metals in CDC successful radical alkenylation, which is similar to the b-hydride
reactions for C–O,6 C–N7 and C–C8 bond formations. Interestingly, elimination of transition metals in the traditional Heck reaction.
Li and co-workers have demonstrated an I2-catalysed indole for-
As stable solids, sulfonyl hydrazides are readily accessible. Upon
mation via oxidative cyclization of N-aryl enamines, which was known breaking the C–S, C–N and S–N bond structure, they have demon-
to have been catalysed by transition metals before.9 Moreover, the strated versatile reactive characteristics.16 Among these transforma-
iodine catalysis has also been proved to be successful for replacing tions, iodine has been shown to be a good catalyst for initiating the
transition-metals in direct oxidative aminations of azoles with the sulfonyl radical.16b,h,i Following our continuous interest in radical
same efficiency.10 From all these promising results in oxidative alkenylation,13f,g, j,k we found that the combination of KI and TBHP
with DMSO/HOAc as co-solvent gave good results for the oxidative
a College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei
430072, P. R. China. E-mail: aiwenlei@whu.edu.cn; Fax: +86-27-68754067;
Tel: +86-27-68754672
alkenylation for p-toluenesulfonohydrazide (1a) with p-methyl
styrene (2a) under mild conditions. Under these conditions, a 66%
isolated yield of alkenyl sulfone (Scheme 1, 3a) was obtained at room
temperature. Effects of reaction parameters are shown in Table S1,
ESI.† Encouraged by the preliminary results, we tried to explore the
functional group tolerance for the synthesis of various alkenyl
b National Research Center for Carbohydrate Synthesis, Jiangxi Normal University,
Nanchang, Jiangxi 330022, P. R. China
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc00644e
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Scheme 2 Effect of temperature on the reactivity for aliphatic olefin
towards alkenylation.
Scheme 1 Iodide catalysed oxidative radical alkenylation for the synthesis of
alkenyl sulfones. Reaction condition: the reactions were carried out with 1a
(0.33 mmol), 2 (0.30 mmol), KI (40 mol%), TBHP (0.60 mmol, 70% in aqueous
solution), DMSO (0.15 mL), HOAc (0.15 mL), 25–30 1C, 10 h. (a) DMSO (0.5 mL)
and HOAc (0.5 mL) were used to ensure solubility. (b) 80 1C.
sulfones under the standard conditions. First of all, various sub-
stituted sulfonyl hydrazides were tried in this radical alkenylation
process (Scheme 1, 3a–h). Strong electron donating methoxyl groups,
strong electron withdrawing trifluoromethyl groups and halide
groups at the para position were all tolerated and afforded good
yields. When two halide atoms were introduced to the meta and
ortho positions, the reaction proceeded smoothly as well (Scheme 1,
3g). To our pleasure, aliphatic sulfonyl hydrazides were proved to be
good substrates for this reaction (Scheme 1, 3h). Regarding another
widely existing sulfonyl source, sodium sulfinates were applied in
this system. Sodium p-tolylsulfinate (4) was tested with p-methyl
styrene under the standard conditions. Delightfully, the alkenylation
product was obtained in 64% yield (eqn (2)). Next, various olefins
were employed to synthesize alkenyl sulfones. para-tert-Butyl styrene
afforded the coupling product in 64% yield (Scheme 1, 3i). ortho-
Methyl substituent showed a positive effect on the generation of the
product with 79% isolated yield (Scheme 1, 3n). Halide substituents
were well tolerated in this transformation and the reaction proceeded
chemoselectively to afford the desired alkenylation products (Scheme 1,
3j–l, 3o). The trifluoromethyl group at the para position of styrene gave
the alkenylation product in good yields (Scheme 1, 3m). Furthermore,
we tried to apply more electron-deficient olefins as the substrates. We
found that even butyl acrylate could give the desired product in good
selectivity under increased temperature (Scheme 1, 3p).
Scheme 3 Proposed mechanism.
For understanding the role of iodine, we first outlined a radical
involved reaction pathway for this alkenylation process (Scheme 3).
Initially, iodide is oxidized by TBHP under acidic conditions to
generate iodine and tert-butoxyl radical.6b,d Subsequently, tert-butoxyl
radical abstracts hydrogen atom from sulfonyl hydrazide 1, which
initiates the generation of sulfonyl radicals (I-1) with the release
of molecular nitrogen.16b,h Afterwards, the radical addition of I-1
to olefin 2 generates carbon radical I-2.14g,16a,g The key step for
alkenylation is that radical I-2 reacts with in situ generated iodine
to generate b-iodosulfone I-3.18 At last, HI elimination from I-3
affords the final alkenylation product.3,15
Since iodine was believed to be key for alkenylation to occur,
experiments were carried out to confirm the role of iodine in
the reaction system. Firstly, we attempted to use in situ IR to
monitor the reaction between 1a and 2a. The profile of relative
absorbance (ConcIRT) versus time for individual species is
(2)
When 1-octene (2j) was applied as the substrate, iodosulfonyla-
tion product (5) was obtained instead of the desired alkenylation
product (3q). This result showed the possibility for C–I bond
formation in this iodide catalysed system. As expected, 3q turned
out to be the only product when the reaction was conducted at
110 1C, which indicated that HI elimination might be the key to
alkenylation (Scheme 2).17
Fig. 1 2D kinetic profile of the reaction of 1a (3.3 mmol), 2a (3.0 mmol),
TBHP (6.0 mmol) and KI (1.2 mmol) added to DMSO (2.0 mL) and (2.0 mL) at
30 1C in succession; the reaction was monitored by in situ IR spectroscopy.
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as a reactive intermediate for the radical elimination of carbon
radical to generate alkenyl sulfone.
(3)
(4)
We have demonstrated that iodine behaves as a metal in the
alkenyl functionality recovery of carbon radicals. This system pro-
vides both a mild and easy-to-handle method for the synthesis of
biologically useful alkenyl sulfones.19 During the reaction, iodide was
oxidized under acidic conditions, which is crucial for initiating the
dehydrogenation of sulfonyl hydrazides to generate sulfonyl radical.
Subsequently, catalytic HI elimination similar to the b-hydride
elimination of transition metals was realized for the alkenylation
for sulfonyl radicals from various sulfonyl hydrazides. Importantly,
this work provides an example for applying iodine as a promising
alternative catalyst for transition metals in cross-coupling reactions.
Detailed mechanistic investigations as well as employing the HI
elimination protocol to achieve alkenylation for other radicals are
underway in our laboratory and will be reported in due course.
This work was supported by the 973 Program (2012CB725302),
the National Natural Science Foundation of China (21390400,
21025206, 21272180 and 21302148), and the Research Fund for
the Doctoral Program of Higher Education of China
(20120141130002) and the Program for Changjiang Scholars and
Innovative Research Team in University (IRT1030).
Fig. 2 Cyclic voltammetry in DMSO with nBu4NBF4 (0.1 M) under N2 at
room temperature. The scan rate is v = 0.5 V sÀ1 at a steady gold disk
electrode. (a) None; (b) nBu4NI; (c) toluenesulfonohydrazide; (d) sodium
p-tolylsulfinate.
shown in Fig. 1. Before the addition of KI, signals of the starting
materials remained steady except for changes from delustra-
tion when one material was added. This phenomenon
indicates that it is hard for sulfonyl hydrazide to undergo
dehydrogenation spontaneously at mild temperature. When
KI was added to the reaction, the absorbance of 1a and 2b
decreased immediately. At the same time, the reaction color
turned to purple rapidly, which might suggest the formation
of I2. Furthermore, cyclic voltammetry (CV) experiments were
carried out to study the redox potential of sulfonyl hydrazide.
In the presence of toluenesulfonohydrazide (1a) in DMSO, no
obvious oxidation peak was observed below 1.0 V [Fig. 2(c)]. It
means that direct one-electron oxidation of sulfonyl hydrazide
is not that easy at room temperature. These results were
consistent with our assumption that the iodide oxidation
was the key to initiating the sulfonyl radical from sulfonyl
hydrazide at mild temperature.
Since I2 was proposed to be generated in the reaction,
experiments were carried out to confirm the role of I2 in the
reaction system. I2 was used directly as the oxidant in the absence
of peroxides. Little product was observed for the oxidative alkenyla-
tion of p-methyl styrene (2a) with p-toluenesulfonohydrazide (1a)
(eqn (3)). This result might be explained by the assumption that
sulfonyl radical from sulfonyl hydrazide needed to be initiated
by the tert-butoxyl radical according to the proposed mechanism.
On the other hand, the alkenylation did proceed in the case of
sodium p-toluenesulfonate (4) with a 28% yield (eqn (4)). CV
experiments were also carried out for 4 and iodide. In the
presence of sodium p-tolylsulfinate (4) in DMSO, an obvious
oxidative peak was detected at 0.40 V [Fig. 2(d), Epa1]. At the same
time, the oxidative peak of IÀ was also observed at 0.43 V
[Fig. 2(b), Epa2], suggesting single-electron-transfer could happen
between I2 and sodium p-tolylsulfinate to generate sulfonyl
radical. Since the alkenylation of sodium sulfionate could be
realized just in the presence of I2, we could see that I2 served
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