Ag-catalyzed sulfonylation-peroxidation of alkenes with sulfonyl hydrazides and T-hydro

Article abstract of DOI:10.1016/j.tetlet.2018.09.045

The sulfonylation-peroxidation of alkenes with sulfonyl hydrazides and T-hydro was developed. The Ag-catalyzed three-component peroxidation provides a method for synthesis of a variety of β-sulfonyl peroxides, which could be converted into various sulfone derivatives.

Full text of DOI:10.1016/j.tetlet.2018.09.045

Accepted Manuscript
Ag-catalyzed Sulfonylation-Peroxidation of Alkenes with Sulfonyl hydrazides
and T-Hydro
Ran Xu, Zhiping Li
PII:
S0040-4039(18)31136-5
https://doi.org/10.1016/j.tetlet.2018.09.045
TETL 50284
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
26 July 2018
12 September 2018
18 September 2018
Please cite this article as: Xu, R., Li, Z., Ag-catalyzed Sulfonylation-Peroxidation of Alkenes with Sulfonyl
hydrazides and T-Hydro, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.09.045
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Ag-catalyzed Sulfonylation-Peroxidation of
Alkenes with Sulfonyl hydrazides and T-
Hydro
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Ran Xu and Zhiping Li

1
Tetrahedron Letters
Ag-catalyzed Sulfonylation-Peroxidation of Alkenes with Sulfonyl hydrazides and T-
Hydro
Ran Xu and Zhiping Li
Department of Chemistry, Renmin University of China, Beijing 100872, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The sulfonylation-peroxidation of alkenes with sulfonyl hydrazides and T-hydro was developed.
The Ag-catalyzed three-component peroxidation provides a method for synthesis of a variety of
β-sulfonyl peroxides, which could be converted into various sulfone derivatives.
2013 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Sulfonylation
Peroxidation
Difunctionalization
Sulfonyl hydrazide
Alkene
1,2-Difunctionalization of alkenes allows the introduction of
two functional groups across the carbon-carbon double bonds in
a single operation and thus attracts great attention in organic
synthesis.1 Organic peroxides have received considerable
attention in pharmacy, biochemistry and food chemistry.2 They
are not only versatile oxidants but also play as key reactive
intermediates in synthetic chemistry.3 The major approaches to
synthesize organic peroxides include autoxidation,4 metal-
catalyzed peroxidation5 of active C-H bonds, and cycloaddition
of singlet oxygen with alkenes.6 In these reactions, the peroxy
group of peroxides was introduced into certain molecules as the
only one functional group (Scheme 1a).7 In 2011, we reported the
acylation-peroxidation of alkenes,8 in which an acyl and a peroxy
groups are introduced selectively across the C=C double bond of
alkene (Scheme 1b). Importantly, the method was successfully
applied for total synthesis of natural products clavilactone A, B,
and D.9 The three-component peroxidation of alkenes with a
peroxy and another functional group is growing up as an
attractive strategy for the synthesis of a variety of functionalized
organic peroxides,10 including acylation-peroxidation,8,11
alkoxycarbonylation-peroxidation,12 alkylation-peroxidation,13
perfluoroalkylation-peroxidation,14 phosphoryl ation-
peroxides, we envisioned that a new sulfonylation-peroxidation
of alkenes could be developed. Herein, we would like to report
the first Ag-catalyzed sulfonylation-peroxidation of alkenes
(Scheme 1d). The method provides an efficient route
tosynthesize -sulfonyl peroxides, which could be converted into
various sulfone derivatives smoothly.
peroxidation,15 iodination-peroxidation,16 bisperoxidation,17
silylation-peroxidation18 (Scheme 1c).
The sulfonyl group is of great importance in medical
chemistry, materials and synthetic chemistry.19 In various
sulfonylation reactions, oxysulfonylation of alkenes20 to
introduce a sulfonyl group and an oxygen group presents an
attractive method for synthesis of multifunctional sulfonyl
derivatives. According to these excellent works and in the course
Scheme 1. Methods for synthesis of organic peroxides.
———
of exploring new reactions to synthesize functional organic
 Corresponding author. Tel.: +86-10-6251-5101; fax: +86-10-6251-6444; e-mail: zhipingli@ruc.edu.cn

2
Tetrahedron Letters
Sulfonyl radicals can be generated from a range of sulfonyl
reactions under the optimized reaction conditions (Scheme 2).
We found that a variety of styrene derivatives reacted smoothly
with p-toluenesulfonyl hydrazide (1a) and T-hydro (3) smoothly
to give the corresponding products (4a-4j) in good isolated yields.
Both electron-donating and electron-withdrawing substituents on
the benzene ring of styrene derivatives had no obvious influence
for the reactions. Acrylate derivatives also led to the desired
sulfonylation-peroxidation products, while the efficiency of the
transformation is much lower than styrenes. For example, methyl
methacrylate (2k) reacted with 1a and 3 to afford the
precursors, such as sulfonyl hydrazides, sulfonyl chloride,
sodium sulfonates, sulfinic acids, and others.21 We chose sulfonyl
hydrazides as sulfonyl radical precursors because they are
noncorrosive, easilly handling, and compatible with water.22 The
reaction of p-toluenesulfonyl hydrazide (1a), styrene (2a) and
tert-butyl hydroperoxide (3, 70% in water, T-hydro) was
investigated to find the optimal reaction conditions for the
sulfonylation-peroxidation (Table 1). Various metal catalysts for
the reaction were screened (entries 1-5). The results revealed that
metal catalysts CuCl2, CoCl2 and AgNO3 gave the sulfonylation-
peroxidation product (4a) in comparable yields (entries 3-5). The
yields of 4a were increased with the increasing of the amount of
3 (entries 6-8) and a 96% yield of 4a was achieved by using
AgNO3 catalyst (entry 8). The efficiency of the reaction was
slight lower when the loading of AgNO3 catalyst was reduced
(entries 9 and 10). However, the desired transformation was
completely shut down in the absence of catalyst (entry 11).
Ag2CO3 was also applicable, albeit in a low yield (entry 12).
Other explored solvents for the reaction such as DCE, PhMe, and
THF provided much inferior results (entries 13-15), indicating
that solvent has great effect on the efficiency of the reaction.
corresponding product (4k) in 44% yield. Moreover, other
arylsulfonyl hydrazides including benzenesulfonyl hydrazide
(1b), 4-fluorobenzenesulfonyl hydrazide (1c), 4-
chlorobenzenesulfonyl hydrazide (1d), and 4-
bromobenzenesulfonyl hydrazide (1e) were also applicable under
the reaction conditions and provided the desired products (4l-4o)
in good yields. In addition, internal alkenes such as E-alkene (2’)
and Z-alkene (2’’) were used to react with 1a and 3 (Scheme 3).
The reactions gave the expected product (4p) with excellent
diastereoselectivities. These results suggested that (1) the
reaction is proceeding step by step; (2) the sulfonylation is a
faster step while the peroxidation is a rate-determination step.
Table 1. Optimization of the reaction conditionsa
entry
1
3 (equiv)
cat.
solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCE
yield of 4a (%)b
3
3
3
3
3
5
5
5
5
5
5
5
5
5
5
FeCl2
FeCl3
CuCl2
CoCl2
AgNO3
CuCl2
CoCl2
AgNO3
AgNO3
AgNO3
-
42
2
54
3
72
4
70
5
71
6
83
7
82
8
96
9
89c
87d
N.D.e
61
10
11
12
13
14
15
Ag2CO3
AgNO3
AgNO3
AgNO3
40
PhMe
THF
13
<5
Scheme 2. Scope of alkenes and sulfonyl hydrazides. Reaction
conditions: 1 (1.0 mmol), 2 (0.5 mmol), 3 (70% in water, 2.5 mmol),
AgNO3 (10 mol %), MeCN (3.0 mL), 85 ℃, 1 h, under N2. Isolated
yields were reported.
a Reaction conditions: 1a (1.0 mmol), 2a (0.5 mmol), 3 (70% in water, T-
hydro), cat. (10 mol %), solvent (3.0 mL), 85 ℃, 1 h, under N2.
b Reported yields was based on 2a and determined by 1H NMR using an
internal standard.
c cat. (5 mol %).
d cat. (2.5 mol %).
e Not Detected.
We subsequently investigated the scopes of sulfonyl
hydrazides (1) and alkenes (2) for the sulfonylation-peroxidation

3
Scheme 3. Reaction conditions: 1a (1.0 mmol), 2 (0.5 mmol), 3
(70% in water, 2.5 mmol), AgNO3 (10 mol %), MeCN (3.0 mL), 85
℃, 1 h, under N2. Isolated yields were reported.
Scheme 5. Pathways for selective deprotonation of 4a.
The reduction of the peroxyl bond of 4a was investigated (eq
2). The corresponding alcohol 7 was generated in 83% yield by
using ammonium formate as a hydrogen donor and palladium on
carbon as catalyst. However, the formation of 7 was
Epoxides are highly useful intermediates and building blocks
for organic synthesis. Guiding by our interesting on epoxidation
of peroxides,9,23 we studied epoxidation of the sulfonylation-
peroxidation products (4) by using NaH as base (Scheme 4). To
our satisfaction, disubstituted epoxides (5a-5e) were obtained in
exclusive trans-selectivity due to the steric hindrance. However,
trisubstituted epoxide (5f) was formed in 1:1 diastereoisomers.
accompanied by the presence of 10% yield of 6 as by-product.
To gain insights into the reaction mechanism, the radical
scavengers 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and
butylated hydroxytoluene (BHT) were added to the reactions
under the standard conditions (eqs 3 and 4). The formation of the
product 4a was inhibited and a BHT-adduct product 8 was
identified (eq 4). The results indicated that the three-component
reaction is initiated by radical addition of a sulfonyl radical to
alkene.
Scheme 4. Epoxidation of 4. Reaction conditions: 4 (0.5 mmol),
NaH (1.0 mmol), THF (5.0 mL), 0 ℃, 5 h, under N2. Isolated yields
were reported. Diastereomeric ratio (d.r.) was determined by 1H
NMR using an internal standard.
In contrast, 4a was selectively transformed into 1-phenyl-2-
tosylethanone (6) in the presence of DBU as base catalyst (eq 1).
We rationalized that deprotonation of Ha is principally favorable
in the case of both NaH and DBU (Scheme 5). The generation of
the intermediate A is irreversible and thus undergoes
intramolecular cyclization to give the epoxide 5a. Furthermore,
the cyclization should be the rate determining step of epoxidation
because the intermediate B did not undergo the cyclization. On
the other hand, the carbonyl product 6 was formed via the
intermediate C because the Kornblum-DeLaMare (K-D)
rearrangement is a fast step and pushes the equilibrium to C by
deprotonation of Hb.
On the basis of the results and previous reports, a tentative
reaction mechanism is proposed by using the reaction of 1a,
2a and 3 (Scheme 6). Tert-butoxy radical (t-BuO·) and tert-
butylperoxy radical (t-BuOO·) are generated in the presence
of silver catalyst (eqs a and b), in which tert-butylperoxy
radical (t-BuOO·) and silver are in equilibrium with silver
tert-butylperoxy D (eq b). Oxidation of 1a by t-BuO· gives
tosyl radical E, which adds to 2a to form the radical
intermediate F. Tert-butylperoxy group transfer from silver
tert-butylperoxy D to F delivers the final three-component
product 4a. Alternatively, radical cross-coupling of F and t-
BuOO· will also give 4a.

4
Tetrahedron Letters
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Scheme 6. Proposed reaction mechanism.
In conclusion, we have developed silver-catalyzed
sulfonylation-peroxidation of alkenes with sulfonyl hydrazides
and T-hydro. A variety of -sulfonyl peroxides were synthesized
by the developed three-component peroxidation strategy. In
addition, epoxidation and reduction of the obtained β-sulfonyl
peroxides were studied. Further studies on the scope, mechanism,
and synthetic applications of this sulfonylation-peroxidation of
alkenes are in progress.
Acknowledgment. Financial support from the National
Natural Science Foundation of China (21672259).
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5
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Highlights
The sulfonylation-peroxidation of alkenes is
developed.
β-Sulfonyl peroxides were synthesized by the three-
component peroxidation of alkenes.
β-Sulfonyl peroxides were converted into sulfone
derivatives under mild conditions.