Iodine promoted iodosulfonylation of alkynes with sulfonyl hydrazides in an aqueous medium: Highly stereoselective synthesis of (E)-β-iodo vinylsulfones

Article abstract of DOI:10.1039/c8nj01145a

A catalyst-free and metal-free sulfonylation reaction for the preparation of (E)-β-iodo vinylsulfones from alkynes with sulfonyl hydrazides and molecular iodine was efficiently developed under mild and environmentally benign conditions, in water without any ligand or catalyst. The reaction gave a range of structurally diverse β-iodo vinylsulfones with excellent E selectivities and high yields.

Full text of DOI:10.1039/c8nj01145a

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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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Iodine Promoted Iodosulfonylation of Alkynes with
Sulfonyl Hydrazides in an Aqueous Medium: Highly
Stereoselective Synthesis of (E)ꢀβꢀIodo Vinylsulfones
Received 00th January 20xx,
Accepted 00th January 20xx
Yunlei Hou, Liangyu Zhu, Hao Hu, Shaowei Chen, Zefei Li, Yajing Liu*, Ping Gong* [a]
DOI: 10.1039/x0xx00000x
www.rsc.org/
A catalystꢀfree and metalꢀfree sulfonylation reaction for the synthesize 1,1ꢀdiaryl olefin and sulfonylꢀsubstituted 1,3ꢀenynes via
preparation of (E)ꢀβꢀiodo vinylsulfones from alkynes with
sulfonyl hydrazides and molecular iodine was efficiently
developed under mild and environmentally benign conditions, in
water without any ligand or catalyst. The reaction gave a range
of structurally diverse βꢀiodo vinylsulfones with excellent E
selectivities and high yields.
Suzuki–Miyaura and Sonogashira reactions with arylboronic acid
and terminal alkyne. Inomata et al.[9] (Scheme 1, Eq. 3) utilized the
(E)ꢀβꢀiodovinyl sulfones to synthesis corresponding vinyl sulfones in
the presence of 5% PdꢀC under hydrogen atmosphere in methanol.
(E)ꢀβꢀIodovinyl sulfones undergo dehydroiodogenation reactions for
the synthesis of alkynyl sulfones was reported by Liu et al.[10]
(Scheme 1, Eq. 4), which is a versatile and essential building block
in organic and polymer chemistry. Accordingly, the efficient
selective construction of (E)ꢀβꢀiodovinyl sulfones has attracted
considerable interest among organic chemists.
Maximizing the efficiency of reactants and minimizing the
production of waste are primary considerations for improving the
atom economy of a reaction and are important goals of chemists.[1]
To achieve these purposes, great efforts have been made for the
development of green and sustainable procedures, such as metalꢀ
Prior art
free,[2] catalystꢀfree,[3] or aqueousꢀphase reaction strategies[4]
.
I
R
SO2H
(1)
O
S
O
Particularly, the metalꢀfree strategies are very attractive on account
of their being environmentally friendly and inexpensive. In addition,
water serves as excellent supporting medium with numerous
advantages including the ease of product isolation, nontoxicity,
nonflammability, high heat capacity and redox stability.[5]
I2
+
R
R
SO2Na
(2)
I2, TBHP, MeCN, 80 o
C
(3)
(4)
I
O
S
O
NH2
NH
CuI, BPO, DMSO,rt
O
+
+
S
O
Ph
Ar
H2/Pd
PhB(OH)2
TBAI, K2S2O8, MeCN, 80 o
C
(5)
(6)
(1)
(3)
MeOH
Ts Pd(PPh3)4, CsCO3
THF, 60 oC, 8h
Ar
Ar
Ts
7
8
5
I
Our work
Ph
I
I2, H2O, 40 o
metalꢀfree
C
Ar
Ts
O
NH2
NH
O
Ar1
Ar2
Ar2
S
Ar1
S
O
K2CO3
Ph
O
(4)
(2)
Ts
odorless
only water
MeOH, 60 oC, 4h
1
3
4
Ar
Ts
Pd(PPh3)4, CuI, TEA
THF, 60 oC, 4h
6
Scheme 2. Strategies for the synthesis of βꢀiodovinyl sulfones
Scheme 1. Application of βꢀiodovinyl sulfones
βꢀiodovinyl sulfones are valuable structural units in biologically
active molecules and serve as versatile synthetic precursors for a
diverse range of chemical transformations that produce
pharmaceutical and industrially important organic compounds.[6]
Jiang et al.[7] (Scheme 1, Eq. 1) and Xie et al.[8] (Scheme 1, Eq. 2),
respectively, reported that (E)ꢀβꢀiodovinyl sulfones were used to
Generally, the iodosulfonylation using sulfonyl iodides, sulfinic
acids/iodine source (Scheme 2, Eq. 1),[11] sodium sulfinates/iodine
(Scheme 2, Eq. 2),[10] and sulfonyl hydrazides /iodine have all been
known as practical routes to iodogenated vinyl sulfones. However,
the instability of sulfonyl iodides greatly limited the application of
this method to construct βꢀiodovinyl sulfones.[12] Recently, Li et al.
reported a procedure through the tertꢀbutyl hydroperoxide (TBHP)ꢀ
mediated reaction of aryl acetylenes with sulfonyl hydrazides in the
presence of I2 (Scheme 2, Eq. 3).[13] Subsequently, Liu et al. utilized
sulfonyl hydrazides as sulfonyl source, and developed a novel CuIꢀ
catalyzed tandem reaction with aryl acetylenes for the stereoselective
synthesis of (Z)ꢀβꢀiodovinyl sulfones (Scheme 2, Eq. 4).[14] More
recently, Xie et al. reported the preparation of (E)ꢀβꢀiodovinyl
sulfones through TBAI/K2S2O8ꢀfacilitated reaction of sulfonyl
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hydrazides with aryl acetylene in MeCN (Scheme 2, Eq. 5).[15] ring, reacted smoothly with phenylacetylene, affording the
However, most of them proceeded via a dangerous oxidant, a metal corresponding (E)ꢀβꢀiodovinyl sulfones 4aa–4af in good to excellent
catalyst, or
a toxic organic solvent was employed in these yields, while also exhibiting high stereoselectivities. In addition, 2ꢀ
aforementioned reactions. Therefore, the development of green naphthylꢀsubstituted sulfonyl hydrazide was also tested in the
methods for the synthesis of βꢀiodovinyl sulfones with high reaction and afforded the desired product 4ag in yield of 70%.
selectivity under mild reactions is still highly desirable. Continuing Interestingly, the reaction with arylsulfonyl hydrazide 1n bearing an
with our interest in the sulfonyl hydrazideꢀbased chemistry, we amide group also proceeded smoothly to produce the desired allylic
focused our attention to the development of a new method for the sulfone product 4an in a yield of 83%, indicating that the
synthesis of (E)ꢀβꢀiodovinyl sulfones, and we now report the results transformation was not affected by the N–H group. Notably, the
of our investigation, waterꢀmediated sulfonylation and iodination of corresponding product (4al) was obtained in a relatively low yield
aryl acetylenes with sulfonyl hydrazides and molecular iodine (30%) when 4ꢀnitrobenzenesulfonohydrazide (1l) was used as the
(Scheme 2, Eq. 6).
substrate. However, when thiopheneꢀ2ꢀsulfonyl hydrazide was
employed, βꢀiodovinyl sulfones was not obtained, which might be
caused by the instability of the corresponding sulfone radicals.
Initially, we investigated the model reaction of 4ꢀmethylphenylꢀ
sulfonyl hydrazide (1a) with iodine (2a) and phenylacetylene (3a)
under various conditions and the results are summarized in Table 1.
To our delight, the corresponding βꢀiodo vinylsulfone 4aa was
obtained in 38% yield (Table 1, entry 1) at 25 °C in water for 3 h.
In order to improve the yield, different equivalents of iodine were
tested. Increasing the number of equivalents of iodine (2a) from 0.5
to 2.0 (Table 1, entries 1−4) led to a significant increase in product
yields. Screening of the temperature indicated 40 °C to be optimal
with the expected product 4aa obtained in 80% yield. Raising the
temperature to 80 °C had no effect on the yield (Table 1, entries
Table 2. Substrate scope of various sulfinate hydrazides [a.b]
5−7). Next, the effect of the solvent on the reaction efficiency was
examined (Table 1, entries 8–13). Among all the solvents tested,
apparently, H2O was determined to be the most efficient reaction
medium for the investigated transformation. Nevertheless, no
product was obtained when the reaction was performed separately in
THF, DMF, toluene and acetone (Table 1, entries 9–12).
Consequently, the standard reaction conditions used for further
investigations were 1 (1.0 equiv.), 2 (2.0 equiv.), and 3 (1.1 equiv.)
in H2O at 40 °C for 3 h. The stereochemistry and precise
configuration of 4aa was unambiguously confirmed as (E)ꢀβꢀiodo
vinylsulfones (see Supporting Information, SI).
I
O
S
O
4al, 30%
NO2
Table 1. Optimization of reaction conditions[a]
[a] Reaction conditions: unless otherwise noted, all reactions were performed
with 1 (1.0 equiv.), 2a (2.0 equiv.), and 3a (1.1 equiv.) in 5 mL of H2O at 40
°C for 3 h; [b] Isolated yield.
The scope of the transformation with respect to alkynes (3) was
also evaluated under the optimized reaction conditions (Table 3).
Generally, various arylꢀsubstituted terminal alkynes were found to
be suitable reaction partners for this difunctionalization process. The
position of the substituents on the aryl ring affected the reactivity.
For example, pꢀsubstituted 3d and 3g afforded the desired products
4da and 4ga in 71% and 75% yields. In contrast, oꢀ or mꢀsubstituted
3e and 3h exhibited a decreased conversion, indicating that pꢀ
substitution on the aryl ring is favorable. Interestingly, the
heterocyclic compound 2ꢀethynylthiophene reacted smoothly,
affording the corresponding (E)ꢀβꢀiodo vinylsulfone 4ba in 78%
yield. However, 1ꢀethynylꢀ4ꢀnitrobenzene gave only trace amounts
of product 4ia, making it unsuitable for further investigation.
Entry
1
I2 (equiv.)
0.5
Solvent
H2O
Temp. (°
C) Yield (%)[b]
38
25
2
1.0
H2O
25
55
3
4
5
6
7
8
9
10
11
12
13
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
H2O
H2O
H2O
H2O
H2O
25
25
40
60
80
40
40
40
40
40
40
63
73
80
81
80
MeCN
THF
DMF
Acetone
Toluene
1,4ꢀDioxane
15
n.d.[c]
n.d.
n.d.
n.d.
25
[a] Reaction conditions: unless otherwise noted, all reactions were performed
with 1a (1.0 equiv.), 2a (0.5ꢀ2.0 equiv.), and 3a (1.1 equiv.) in the indicated
solvent (5 mL) for 3 h; [b] Isolated yield; [c] n.d. = not detected.
Table 3. Substrate scope of various terminal acetylenes[a.b]
Under the optimized reaction conditions, the scope of substituted
arylsulfonyl hydrazides (1) was first examined using iodine 2a and
phenylacetylene 3a as standard substrates (Table 2). A variety of
arylsulfonyl hydrazides, bearing electronꢀdonating groups (Me,
MeO) or electronꢀwithdrawing groups (F, Cl, and Br) on the aryl
2 | J. Name., 2012, 00, 1-3
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I
radical B to the terminal alkyne (3) takes place chemoselectively to
form the vinyl sulfone radicals C and D. Subsequently, sulfonyl
iodide (A), molecular iodine, or iodine radical may approach the
vinyl sulfone radical D more readily than vinyl sulfone radical C to
avoid a steric repulsion from the sulfonyl group to provide the
desired βꢀiodovinyl sulfone (4).
H2O, 40 oC, 3 h
O
S
NH2
NH
O
2
Ar2
S
+
I2
+
Ar
O
4
O
3
2a
1a
Conclusions
An efficient, molecular iodineꢀpromoted MCR of alkynes and
sulfonyl hydrazide for the synthesis of (E)ꢀβꢀiodo vinylsulfone
derivatives has been developed. The developed protocol provides an
alternative and highly attractive route to various (E)ꢀβꢀiodo
vinylsulfones from the simple and readily available starting materials,
and especially it avoids the use of any transitionꢀmetal catalyst, and
toxic or potentially dangerous oxidants. Further studies regarding the
scope and synthetic applications of this reaction are being pursued in
our laboratory and will be reported in due course.
[a] Reaction conditions: unless otherwise noted, all reactions were performed
with 1a (1.0 equiv.), 2a (2.0 equiv.), and 3 (1.1 equiv.) in 5 mL of H2O at 40
°C for 3 h; [b] Isolated yield.
Experimental Section
A mixture of sulfonyl hydrazides (0.27 mmol), alkyne (0.30 mmol),
and iodine (0.54 mmol) in water (3.0 mL) was placed in a test tube
equipped with a magnetic stirring bar. The reaction mixture was
stirred at 40 °C for 3h. After the reaction was completed, the mixture
was quenched by the addition of satd aq Na2S2O3 (8 mL). Further
stirring was followed by extraction with ethyl acetate (3 × 10 mL).
The organic phase was separated, washed with brine, dried (MgSO4),
filtered, and concentrated in vacuo to give the crude product, which
was purified by column chromatography on silica gel with a mixture
Scheme 3. Control experiments
To get an insight into the mechanism of the sulfonylation process,
controlled experiments were conducted. Radical trapping experiment
was conducted to elucidate whether the reaction involves radical
species. When the radical scavenger (2,2,6,6ꢀtetramethylꢀ
piperidinyloxy, TEMPO) was employed under standard conditions,
the reaction was inhibited in less than 10% yield, which indicated
that a radical pathway should be involved (Scheme 3, Eq 1).
Subsequently, according to Liu’s work[10], when a pꢀtoluenesulfinic
acid sodium salt was used as the substrate instead of 1a under the
standard conditions, the reaction proceeded with a 78% yield
(Scheme 3, Eq. 2), indicating that the sulfinate radical maybe an
intermediate in this process.
of ethyl acetate/petroleum (1:10, v/v) to afford the desired product 4
.
Acknowledgements
We are grateful to the Program for Innovative Research Team of the
Ministry of Education and Program for Liaoning Innovative
Research Team in University (IRT1073) for financial support.
Notes and references
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Scheme 4. Plausible reaction mechanism
On the basis of control experiment results and previous reports[2ꢀ5,
16], a possible mechanism for the crossꢀcoupling reaction is proposed
in Scheme 4. The sulfonyl hydrazide (1) reacts with iodine (2a) to
give a sulfonyl iodide intermediate (A) that could undergo homolytic
cleavage to yield a sulfonyl radical B. Addition of the sulfonyl
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An efficient, molecular iodineꢀpromoted MCR of alkynes and sulfonyl hydrazide for the synthesis
of (E)ꢀβꢀiodo vinylsulfone derivatives has been developed.