Manganese catalysed sulfenylation of N-methyl amides with arenesulfonyl hydrazides

Article abstract of DOI:10.1039/c5ob00133a

A convenient oxidative sulfenylation method for the formation of various sulfenyl amides has been reported. Arenesulfonyl hydrazine as a sulfur source in the presence of a manganese salt can activate the sp³ C-H bond of N-methyl amides through a free-radical pathway using di-tert-butyl peroxide (DTBP). This journal is

Full text of DOI:10.1039/c5ob00133a

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Manganese catalysed sulfenylation of N-methyl
amides with arenesulfonyl hydrazides†
Jinwei Sun,a Yi Wang*a and Yi Pana,b,c
Cite this: Org. Biomol. Chem., 2015,
13, 3878
Received 23rd January 2015,
Accepted 12th February 2015
DOI: 10.1039/c5ob00133a
www.rsc.org/obc
A convenient oxidative sulfenylation method for the formation of
various sulfenyl amides has been reported. Arenesulfonyl hydr-
azine as a sulfur source in the presence of a manganese salt can
activate the sp3 C–H bond of N-methyl amides through a free-
radical pathway using di-tert-butyl peroxide (DTBP).
Introduction
Direct C–S bond formation has been extensively studied for
the synthesis of many organosulfur containing natural pro-
ducts and synthetic drugs.1 Significant progress has been
achieved for direct sp2-hybridised C–H bond sulfenylation of
arenes, indoles and pyrazolones for the construction of the
corresponding sulfides.2 The challenge for the activation of
the sp3 C–H bond has also been addressed by free radical
initiated C–S bond formation on the heteroatom-adjacent
carbons.3 Li and Xiang have independently reported direct oxi-
dative sulfenylation of amides3a and ethers3b with disulfides
under metal-free conditions (Schemes 1a and b).
Sulfonyl hydrazides have commonly been used as reduc-
tants and sulfonylation agents but were also recently found to
be valuable in the sulfenylation process.4 This new strategy
could not only avoid smelling volatile sulfur sources such as
thiols,5 thiolates6 and disulfides,7 but also expend the limited
substrate scope of agents like thiourea,8 thiocyanate9 and
metal sulfides.10 Various sulfonyl hydrazide reagents have
been developed in the sulfenylation of indoles,11 aryl
halides,12 activated alkenes13 and aryl acetylenes.14 Yuan
Scheme 1 Approaches on the sp3 C–H bond sulfenylation of hetero-
atom adjacent carbons.
recently reported a palladium catalysed oxidative sulfenylation
of ethers using arenesulfonyl hydrazide.15 Presumably, aryl
sulfide radicals generated in situ from the decomposition of
sulfonyl hydrazides that promoted by palladium catalyst,
although the exact mechanism was not revealed (Scheme 1c).
N,S-Acetals are biologically important molecules present
in numerous natural products such as fusaperazine16 and
β-lactam antibiotics.17 Inspired by Li,3a Xiang3b and Yuan’s15
work, we herein report a radical sulfenylation process of
N-methyl amides with arenesulfonyl hydrazides catalysed by
the inexpensive and non-toxic manganese(II) salt, which shows
higher efficiency than the classic palladium catalysts. Various
N,S-acetals tolerating different amides and sulfenylarenes were
readily obtained (Scheme 1d).
aSchool of Chemistry and Chemical Engineering, Nanjing University, Nanjing,
210093, China. E-mail: yiwang@nju.edu.cn; Fax: +86-25-83309123;
Tel: +86-25-83593153
Results and discussion
We started our attempt with N,N-dimethylacetamide (DMA)
and p-toluenesulfonyl hydrazide in the presence of different
oxidants and catalysts (Table 1). Using DTBP without any cata-
lyst, no reaction was observed (entry 1). As previously
reported,15 Pd(II) was able to promote the sulfenylation reac-
bState Key Laboratory of Coordination, Nanjing University, Nanjing, 210093, China
cCollaborative Innovation Center of Advanced Microstructures, Nanjing, 210093,
China
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c5ob00133a
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Table 1 Optimisation of reaction conditionsa
Entry
Oxidant (eq.)
Catalyst (mol%)
Isolated yieldb (%)
1
2
3
4
5
6
7
8
DTBP (2.0)
DTBP (2.0)
DTBP (2.0)
DTBP (2.0)
DTBP (2.0)
DTBP (2.0)
CAN (2.0)
PhI(OAc)2 (2.0)
BQ (2.0)
K2S2O8 (2.0)
TBHP (2.0)c
DCP (2.0)
DTBP (0.5)
DTBP (1.0)
DTBP (3.0)
DTBP (2.0)
DTBP (2.0)
N.A.
PdCl2 (2.0)
FeCl3·6H2O (2.0)
CuI (2.0)
N.D.
45
23
N.D.
N.D.
86
N.D.
N.D.
N.D.
15
18
58
56
72
Cu(OTf)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (2.0)
Mn(OAc)2 (1.0)
Mn(OAc)2 (0.5)
9
10
11
12
13
14
15
16d
17
Scheme 2 Reactions of N,N-dimethylacetamide with various
arenesulfonylhydrazides.
83
70
56
a Catalytic conditions: arenesulfonyl hydrazide 2 (0.5 mmol), DMA 3
(2 mL, 20 mmol, also served as the solvent), oxidant, catalyst,
8 h. b Isolated yield based on 2. c 70% in water solution. d Reaction
time 24 h.
tion but in a disappointing 45% yield (entry 2) according to lit-
erature precedents.15 Other metal catalysts such as FeCl3, CuI
and Cu(OTf)2 failed to provide satisfactory results (entries
3–5). To our delight, Mn(OAc)2 was able to promote the reac-
tion in the presence of DTBP (entry 6, 86% yield). We attribu-
ted the efficiency of manganese to the employment of amides
as the solvent, compared with palladium that usually used in
cycloalkanes or ethers.
Scheme 3 Reactions of other amides with arenesulfonyl hydrazides.
Other oxidants including CAN, PhI(OAc)2 and benzo-
quinone did not afford the desired product (entries 7–9), while
K2S2O8, TBHP or dicumyl peroxide (DCP) showed very low con-
version (entries 10–12). After evaluating the loading of the cata-
lyst and oxidant (entries 13–17), the conditions were set as 2
equivalents of DTBP with 2 mol% of Mn(OAc)2 (entry 6).
Under the optimised conditions, the scope of this arene-
sulfenylation reaction was explored. As shown in Scheme 2, arene-
sulfonyl hydrazides bearing both electron-withdrawing and
electron-donating substituents could react with N,N-dimethyl-
acetamide to form sulfenyl amides in 80–91% yields (1b–1g). To
our delight, heteroarene sulfonyl hydrazides such as thiophene
and pyridine derivatives displayed high reactivity towards the
target sulfenyl amide products in over 80% yield (1h, 1i).18
It was found that propionamides and isobutyramides could
Scheme 4 Control experiments.
also be employed for such transformation to obtain highly yield with two regioisomers in a 2 : 1 ratio in favour of the
substituted sulfenyl amide products with good yields primary carbon (Scheme 2, 1w).
(Scheme 3). Interestingly, when the two substituents on the
nitrogen atom were different, the reaction tended to happen
To understand the mechanism for such arenesulfenylation,
a control reaction with phenylsulfonyl hydrazide and
on the less substituted side. Using N-methyl pyrrolidone, the Mn(acac)2 was carried out. Expectedly, disulfide was obtained
corresponding sulfenyl amides were obtained with 78% overall in 68% yield (Scheme 4a), suggesting that the decomposition
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Acknowledgements
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (no. 21402088
and no. 21472082) and the Fundamental Research Funds for
the Central Universities (no. 2062014749).
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