Metal-free catalyzed synthesis of the (E)-vinyl sulfones via aromatic olefins with arylsulfonyl hydrazides

Article abstract of DOI:10.1016/j.tetlet.2018.02.078

Synthesis of vinyl sulfones from aromatic olefins and arylsulfonyl hydrazides via I₂-TBHP catalyzed system under the N₂ atmosphere is described. Owing to no use of metal, only producing N₂ and water as the byproducts and d

Full text of DOI:10.1016/j.tetlet.2018.02.078

Tetrahedron Letters xxx (2018) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Metal-free catalyzed synthesis of the (E)-vinyl sulfones via aromatic
olefins with arylsulfonyl hydrazides
⇑
Zhenzhen Zhan, Haojie Ma, Daidong Wei, Jinghong Pu, Yixin Zhang, Guosheng Huang
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry,
Lanzhou University, Lanzhou, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis of vinyl sulfones from aromatic olefins and arylsulfonyl hydrazides via I2-TBHP catalyzed sys-
tem under the N2 atmosphere is described. Owing to no use of metal, only producing N2 and water as the
byproducts and directly available reactants, this reaction could validly avoid many disadvantages of the
transition metal catalysts. In addition, the desired product can be collected with moderate to excellent
yields under the suitable conditions.
Received 27 December 2017
Revised 13 February 2018
Accepted 27 February 2018
Available online xxxx
Ó 2018 Published by Elsevier Ltd.
Keywords:
Metal-free
Vinyl sulfones
I2-TBHP
Introduction
of these compounds in different areas, various approaches to pro-
duce vinyl sulfones have been discovered, like addition-elimina-
With the decrease of fossil energy and pollution of the environ-
ment, finding alternative sustainable processes, which are used to
build new structures through functionalization of inactive CAH
bonds, is a requirement for organic chemists.1 In recent years,
cross-coupling reactions have attracted a mass of current interests
due to their potential advantages.2 Especially, transition-metal-
catalyzed CAC and CAheteroatom (N, O, P) bond formations have
been researched by more and more chemists in recent decades.3
Above their supports, we found that transition-metal-catalyzed
cross-coupling reactions require very long reaction time. At the
same time, transition-metal-catalyzed coupling reactions have
many other drawbacks, such as expensive price for transition-
metal catalysts, ligands, toxic catalysts or co-catalysts and so on.4
But in many transition-metal-catalyzed cross-coupling reactions,
there are a few of the efficient constructions of CAS bonds with
high selectivity relatively, probably owing to the deactivation of
the catalyst for the sulfur species.5 So metal-free catalyst probably
is a wonderful possibility for the construction of CAS bonds, avoid-
ing of many disadvantages of transition-metal-catalyzed coupling
reactions.6
tion sequences, the Pd- and Cu-catalyzed cross-coupling
reactions of sulfinate salts with vinyl halides11 and so on. However,
these methods inevitably suffered from certain shortcomings, for
instance, producing a mixture of isomers.12 In recent years, sul-
fonyl hydrazides have received considerable attention (Scheme 1).
In 2014, Jiang and co-workers obtained vinyl sulfone with high
yield by
a copper-catalyzed transformation of styrene with
TsNHNH2 in dimethyl sulfoxide at 100 °C (Scheme 1a),13 obviously,
there are some metal catalyst. Subsequently, Lei and co-workers
achieved parallel reactions with different catalyst (Scheme 1b).14
Last several years, Singh and co-workers synthesized (E)-vinyl sul-
fones by cross-coupling, while cinnamic acids and arylsulfonyl
hydrazides were performed under DBU as base condition
(Scheme 1c).15 In 2015, Yuan and co-works obtained (E)-vinyl sul-
fones via I2-mediated decarboxylative cross-coupling reactions of
sodium sulfinates with cinnamic acids(Scheme 1d).16
Sulfonyl hydrazine, an available synthesis intermediate in
organic compounds, can be used to synthesis hydrazones, hetero-
cycles directly,17 as aryl sources by means of CAS bond cleavage,18
as sulfone and reductants by means of NAS cleavage. Furthermore,
there are also some chemical synthesis by cleavage of the OAS of
sulfonyl hydrazides.19 In comparison to other sulfenylation/sul-
fonation agents, sulfonyl hydrazides are stable in the air and read-
ily accessible. More importantly, N2 and water are the only
byproducts in this reaction.20 Given conventional synthetic strate-
gies and reactants, herein, we reported the method for synthesis of
Vinyl sulfone is an important function group in a great deal of
biologically active molecules and pharmaceuticals.7 For example,
vinyl sulfones are widely used in sortase,8 cysteine proteases,9 pro-
tein tyrosine phosphatases10 and so on. Based on the significance
⇑
Corresponding author.
E-mail address: hgs@lzu.edu.cn (G. Huang).
https://doi.org/10.1016/j.tetlet.2018.02.078
0040-4039/Ó 2018 Published by Elsevier Ltd.
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2
Z. Zhan et al. / Tetrahedron Letters xxx (2018) xxx–xxx
Scheme 1. CAS functionalization by aromatic olefins and arylsulfonyl hydrazides.
vinyl sulfones via I2ÀTBHP-catalyzed oxidative cross-coupling
the reaction of 1a with 2a was performed with 1.0 equiv. of I2 as
catalyst, 4.0 equiv. of TBHP as oxidant, and 1, 4-dioxane as the sol-
vent in an open atmosphere at 90 °C for 3 h, the desired product
3aa was isolated in 38% yield as shown in Table 1 (entry 1). At
the same time, we performed the reaction in different solvent, to
our delight, the corresponding product 3aa was collected in 45%
yield in toluene (entry 2). In order to find the best additives, we
between styrenes and sulfonyl hydrazine.
Organisation of the template
Firstly, p-toluenesulfonyl hydrazide (1a) and styrene (2a) were
used as model substrates to examine various reaction conditions,
Table 1
Optimization of reaction conditionsa.
Entry
Catalyst
Solvent
Additive
Oxidant
Yield (%)b
1
2
3
4
5
6
7
8
I2
I2
I2
I2
I2
I2
I2
I2
I2
1,4-Dioxane
Toluene
DMA
no
no
no
Na2CO3
NaOH
KHCO3
DBU
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
No
H2O2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
38
45
38
70
53
60
53
65
Trace
53
76
79
74
70
63
88
65
64
35
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
TEA
9
10
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
I2
c11
d12
d,e13
d,f14
d,g15
d,h16
d,i17
d,h18
d,h19
I2
I2
I2
I2
I2
I2
I2
TABI
I2
a
b
c
d
e
f
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), catalyst (1.0 equiv.), oxidant (4 equiv.), solvent (2 mL), time (3h), temp (90 °C).base (1.0 equiv.) under air atmosphere.
Isolated yield.
Base (2.0 equiv.).
(base (2.0 equiv.) oxidant (2.0 equiv.)).
Catalyst (0.5 equiv.).
i
At 70 °C. gAt 110 °C. hunder N2 atmosphere. under O2 atmosphere. TBHP: tert-butyl hydroperoxide, DMA: N, N-dimethylacetamide, DBU: 1, 5-diazabicycloundec-5-ene,
TEA: triethylamine.
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Z. Zhan et al. / Tetrahedron Letters xxx (2018) xxx–xxx
3
chose Na2CO3, NaOH, KHCO3, DBU and TEA as base, the results
showed that Na2CO3was more favorable than other bases, the yield
of (E)-1-methyl-4-(styrylsulfonyl) benzene (3aa) could be
increased to 70% (entry 4–8). In addition, we found the yield of
3aa did not enhance in absence of oxidant or other oxidants
instead of TBHP (entry 9–10). Next, we optimized the dosages
of the base, oxidant, and catalyst (entry 11–13). We found when
the reaction was performed in an increase in the equiv. of
Na2CO3 to 2.0, 2.0 equiv. of TBHP and 1.0 equiv. of catalyst the
yield of 3aa was achieved to 79% (entry12). Other temperatures
(70 °C and 110 °C) were further tested, however, the yield of 3aa
was not improved (entry 14–15). At last, reaction was respec-
tively performed under the O2 atmosphere and N2 atmosphere
(entry 16–17). To our surprised, the yield of 3aa was improved
to 88% when reaction was carried out under the N2 atmosphere
(entry 16). We use TABI to replace iodine and get the corre-
sponding product in yield (entry 18). And the same time, we
use DTBP to replace TBHP in optimal condition and get the
desired product in 38% yield (entry 19). After all, the use of I2,
TBHP, and Na2CO3 were crucial for this reaction, by using the
optimized reaction conditions [1.0 equiv. of I2, and 2.0 equiv.
of TBHP, 2.0 equiv. of Na2CO3 in toluene, under the N2
atmosphere] (entry 16), the generality of the method was
subsequently explored (See Table 2).
In the optimal reaction conditions, various styrenes having var-
ious substitution groups underwent a smooth sulfono functional-
ization and the desired products were obtained in excellent
yields. Some styrenes which have electron-withdrawing sub-
stituents on the phenyl ring could be performed smoothly to afford
the corresponding products in available yields (3ba-3fa), obvi-
ously, the yield of product was declined when o-styrenes (2-F, 2-
Cl) with p-toluenesulfonyl hydrazide was performed relative to
p-styrenes (4-F, 4-Cl, 4-Br), perhaps primary reason is steric hin-
drance. In addition, we did other styrenes with electron-donating
group on the phenyl ring (4-Me, 2-Me, 4-t-Bu, 2, 5-2Me), and the
yields of the corresponding products ranged from 73% to 80%
(3ga-3ja). When
a-Methyl-styrene was reacted, we did not get
desired product ((E)-1-methyl-4-((2-phenylprop-1-en-1-yl) sul-
fonyl) benzene (3k’a), however, we collected another product (1-
methyl-4-((2-phenylallyl) sulfonyl) benzene) (3ka). What is more,
when styrene with electron-donating group on the phenyl ring (4-
OCH3) was performed, only trace desired product was detected
(3la). In addition, we also did some heterocyclic compound and
other substituted groups, 2-vinypyridine, 2, 3, 4, 5, 6-pentafluo-
rostyrene, the corresponding yields ranged from 50 to 73% (3ma-
3na) (See Table 3).
At the same time, sulfonyl hydrazides with electron-withdraw-
ing group or electron-donating group on the phenyl ring (3-F, 3-Br,
Table 2
Scope of the reaction with styrene.
Using 1 (0.24 mmol), 2a (0.2 mmol), I2 (100 mol%), Na2CO3 (2.0 equiv.), TBHP (2.0 equiv.) in toluene under N2 atmosphere at 90 °C for 3 h.
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Z. Zhan et al. / Tetrahedron Letters xxx (2018) xxx–xxx
Table 3
Scope of the reaction with sulfonyl hydrazides.
Using 1a (0.24 mmol), 2 (0.2 mmol), I2 (100 mol%), Na2CO3 (2.0 equiv), TBHP (2.0 equiv) in toluene under N2 atmosphere at 90 °C
for 3 h.
Scheme 2. Some controlling experiment.
4-OCH3, 4-H) also could be performed, and yields of corresponding
products range from 62% to 94% (3ab-3af). And then we chose
thiophene-2-sulfonohydrazide as the substrate, but the yield of
product was 19%. We performed the methanesulfonyl hydrazide
and styrene in the optimal condition, the corresponding product
3 ag was collected in 95% yield. That showed the reaction was suit-
able for alkyl sulfonyl hydrazides.
Afterwards, the radical addition reaction of I-1 and olefin 2 gener-
ates carbon radical I-2.22 The most important step for alkenylation
is that radical I-2 reacts with in situ generated iodine to generate
iodosulfone I-3 and then HI elimination from I to 3 affords the final
alkenylation product under the base.23 At last, iodide is oxidized by
TBHP under basic conditions to generate iodine and tert-butoxyl
radical.24
In order to further explore possible reaction mechanism, we did
some controlling experiments (Scheme 2). The reaction of styrenes
with p-toluenesulfonyl hydrazide were performed under the stan-
dard conditions in the presence of radical inhibitors 2,2,6,6-tetram-
Conclusions
ethyl-1-piperidinyloxy
(TEMPO)
or
2,6-di-tert-butyl-4-
In conclusion, the pathway to synthesize (E)-vinyl sulfone
from available aromatic olefin and arylsulfonyl hydrazides was
developed. The reaction was carried through an I2 –TBHP
catalyzed radical addition result, and an abundance of groups
methylphenol (BHT) respectively, the reaction was suppressed
obviously, which indicated a radical reaction pathway be involved
possible.
Based on the results of control experiments, a possible reaction
mechanism was proposed in Scheme 3. Initially, tert-butyl
hydroperoxide is decomposed into tertiary butyl free radicals, sub-
sequently, tert-butoxyl radical abstracts hydrogen atom from sul-
fonyl hydrazide 1a, which leads to the generation of sulfonyl
radicals (I-1), water, and the release of molecular nitrogen.15,21
was well tolerated. This transformation provides
a general
method to the functionalization of styrenes, and the same time,
N2 and water as byproduct, so this reaction shows its
unexceptionable application prospect in organic synthesis area.
What is more, the reaction provides good chemoselectivity and
stereoselectivity.
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Z. Zhan et al. / Tetrahedron Letters xxx (2018) xxx–xxx
5
Scheme 3. Possible reaction mechanism.
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Supplementary data associated with this article can be found, in
the online version, at https://doi.org/10.1016/j.tetlet.2018.02.078.
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