Preparation of α-sulfonylethanone oximes from oxidized hydroxylamine

Article abstract of DOI:10.1002/ejoc.201200133

Alkenes react with substituted N-hydroxysulfonamides and tetrabutylammonium periodate under metal catalyst free conditions to give oximes in good to high yields. The reaction proceeds in a one-pot manner, giving rise to the formation of intermolecular C-N

Full text of DOI:10.1002/ejoc.201200133

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201200133
Preparation of α-Sulfonylethanone Oximes from Oxidized Hydroxylamine
Nan Liu,[a] Ping Yin,[a] Yue Chen,[b] Yong Deng,[a] and Ling He*[a]
Keywords: Sulfur / Nitrogen oxides / Radicals / Alkenes / Domino reactions
Alkenes react with substituted N-hydroxysulfonamides and
tetrabutylammonium periodate under metal catalyst free
conditions to give oximes in good to high yields. The reaction
proceeds in a one-pot manner, giving rise to the formation
of intermolecular C–N and C–S bonds simultaneously. The
method is mild, highly efficient, and convenient.
we report, for the first time, a practical process for synthe-
sizing various sulfonylethanone oximes through a one-pot
cascade oxidation–addition reaction of olefin derivatives by
using N-hydroxysulfonamides as a nitrogen and sulfur
source to give tosylethanone oximes in good yields
(Scheme 1).
Introduction
The formation of carbon–nitrogen bonds from olefins is
considered to be an important strategy in organic synthesis
that has found wide applications in the synthesis of many
substances such as drugs, materials, natural products, and
agrochemicals.[1] For some years, we have been interested in
and have reported advancements in the construction of C–
N bonds.[2] Recently, we found that NO is a practical amin-
ation reagent and can be used to react with olefins. On the
basis of these former works, we wish to report a new
method to synthesize oximes from olefins.
There are various ways to produce NO free radicals, for
example, from organic nitrates and nitrites,[3] N-nitroso
compounds,[4] metal–NO complexes,[5] C-nitroso com-
pounds,[6] and N-hydroxyureas.[7] To date, there are few re-
ported reactions that involve the release of NO for the syn-
thesis of oximes from olefins.[8] In 2001, W. B. Motherwell
and co-workers reported that thionitrites can be used as the
nitrogen source in these reactions.[8d] Recently, Prateeptong-
kum and co-workers[8a] reported the first iron-catalyzed
synthesis of oximes from styrenes. However, the methods
described in these works have drawbacks, for example, low
yields and limited varieties of nitrogen sources. Therefore,
we wish to report a new NO-releasing reagent to improve
this type of reaction. Due to the interest in the biological
effects of nitric oxide and the chemical reactivity and bio-
logical activity of sulfonyl-containing compounds, we de-
cided to use N-sulfonyl hydroxylamine as a novel NO-re-
leasing reagent[9] to give rise to the formation of intermo-
lecular C–N and C–S bonds simultaneously. In this paper,
Scheme 1. The preparation of α-sulfonyl oximes by using oxidized
hydroxylamine.
Results and Discussion
Initially, we carried out a set of experiments by using N-
4-methylbenzenesulfonyl hydroxylamine[10] and styrene as
model substrates and iodosylbenzene (PhI=O) as the oxi-
dant to optimize the reaction conditions; the results are
summarized in Table 1. In this reaction, the hydroxylamine
was not stable in the presence of the oxidant; thus, a low
temperature was selected. Considering previous re-
ports,[8a–8c] a series of catalysts were tested, and a moderate
amount of the expected product was formed when
Hg(OAc)2 was used as the catalyst (Table 1, Entries 1–4).
We probed the solvent effect and found that dichloro-
methane was considerably superior to acetonitrile, tetra-
hydrofuran, and dichloroethane (Table 1, Entries 5–7). Sub-
sequently, we attempted to identify the optimal oxidant,
and the preliminary results showed that [hydroxy(tosyloxy)-
iodo]benzene (HTIB) was more effective than PhI=O,
PhI(OAc)2, Dess–Martin periodinane, 2-iodoxybenzoic
acid (IBX), and HTIB[11](Table 1, Entries 1, 8–12). How-
ever, we found that the temperature had a pronounced im-
pact, and when tetrabutylammonium periodate (nBu4NIO4)
was used as oxidant and the temperature ranged from –20
to 40 °C, there was a better yield than that obtained with
[a] Key Laboratory of Drug-Targeting and Drug-Delivery Systems
of the Ministry of Education, Department of Medicinal
Chemistry, West China School of Pharmacy, Sichuan University,
Chengdu, Sichuan 610041, P. R. China
Fax: +86-28-85502940
E-mail: lhe2001@sina.com
[b] Department of Nuclear Medicine, Affiliated Hospital, Luzhou
Medical College,
No. 25 Taiping Street, Luzhou, Sichuan 646000, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200133.
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N. Liu, P. Yin, Y. Chen, Y. Deng, L. He
SHORT COMMUNICATION
HTIB as oxidant (Table 1, Entries 13–19). Given the toxic- Table 2. Scope and limitations.[a]
ity of mercuric acetate, we decided to use catalyst-free con-
ditions and found that the reaction proceeded equally well
without the catalyst (Table 1, Entries 18 and 19). Finally,
the optimum results were obtained when hydroxylamine
(1.2 equiv.), the oxidant (1.2 equiv.), and the alkene
(1.0 equiv.) were allowed to react in dichloromethane at
–20 °C for 1 h and then at reflux for 2 h.
Table 1. Optimization of the reaction conditions.[a]
Entry
Catalyst
Oxidant
Solvent Temperature
[°C]
Yield
[%][b]
1
2
3
Hg(OAc)2
AgOAc
Cu(OAc)2
Cu(CF3SO3)
PhI=O
PhI=O
PhI=O
CH2Cl2
CH2Cl2
CH2Cl2
–40
–40
–40
40
trace
0
4
PhI=O
CH2Cl2
–40
25
2
5
6
7
8
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
PhI=O
PhI=O
PhI=O
CH3CN
THF
DME
–40
–40
–40
trace
trace
37
0
Hg(OAc)2 PhI(OAc)2 CH2Cl2
–40
9
Hg(OAc)2 nBu4NIO4 CH2Cl2
–40
–40
–40
–40
–20
0
–20 to 40
–20
20
0
52
0
50
28
Ͻ10
38
60
70
70
80
80
10
11
12
13
14
15
16
17
18[c]
19[c]
20[d]
21[d,e]
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
IBX
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
HITB
DMP
HITB
HITB
HITB
Hg(OAc)2 nBu4NIO4 CH2Cl2
Hg(OAc)2 nBu4NIO4 CH2Cl2
Hg(OAc)2 nBu4NIO4 CH2Cl2
nBu4NIO4 CH2Cl2
0
–20 to 40
–20 to 40
–20 to 40
–20 to 40
–
nBu4NIO4 CH2Cl2
nBu4NIO4 CH2Cl2
[a] Unless otherwise noted, all reactions were carried out by using
the molar ratio of hydroxylamine/oxidant/substrate 2:2:1.
=
[b] Yield of isolated product. [c] –20 °C for 15 min and reflux for
1 h. [d] –20 °C for 1 h and reflux for 2 h. [e] Molar ratio of hydrox-
ylamine/oxidant/substrate = 1.2:1.2:1.
A probable mechanism for the formation of oximes is
described in Scheme 2.[8d] First, hydroxylamine is oxidized
by nBu4NIO4 at a low temperature to release NO free radi-
cal A and sulfonyl free radical B. Then, styrene first reacts
[a] All reactions were carried out with molar ratio hydroxylamine/
oxidant/substrate = 1.2:1.2:1, –20 °C for 1 h to reflux for 2 h.
[b] E/Z = 1:1. [c] Yield of isolated product.
Scheme 2. Proposed mechanism.
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α-Sulfonylethanone Oximes from Oxidized Hydroxylamine
with B and subsequent capture of A by the carbon-centered (Table 2, Entry 19); however, the 1,4-addition compound
radical gives intermediate D, which can afford the product was not formed; only the reaction with the unhindered
through quick intramolecular hydrogen transfer. This double bond was observed.
mechanism is supported by successful capture of NO free
Finally, we investigated the scope of the use of sulfonyl
radicals by using morpholine as a capturing reagent (see hydroxylamine (Table 3, Entries 1–6) under the optimized
the Supporting Information). Moreover, when oxygen was reaction conditions with p-chlorostyrene as the model al-
present, a red-brown gas was obtained, and if this gas was kene. As expected, the corresponding oximes were obtained
allowed to flow through the tube into an aqueous solution in low to excellent yields. Different substituted benzenesulf-
of FeSO4, the solution color changed from light green to onyl hydroxylamines were more reactive than alkyl-substi-
brown, which proves the presence of NO free radicals.
tuted sulfonyl hydroxylamines and gave the corresponding
Having determined the optimized conditions, we ex- addition products in higher yields (Table 3, Entries 1–4).
plored the scope of this NO free radical addition by utiliz- Possibly, the instabilities of the alkyl-substituted nitrogen
ing a variety of alkenes as substrates (Table 2). Different sources resulted in lower yields of the oximes. Hydroxyl-
para-, meta-, and ortho-substituted styrene derivatives gave amine lacking the sulfonyl group (Table 3, Entries 5 and 6)
the desired products in good yields (Table 2, Entries 1–15). did not afford the corresponding oximes.
In general, no significant electronic effects were observed
for electron-rich and electron-poor styrenes. On the other
hand, the reactivity of the substrates suffered significantly
from steric hindrance; for instance, 2,6-disubstituted and
Conclusions
In summary, we have developed an efficient procedure
for the addition of NO free radicals through the oxidation
of hydroxylamine to form the corresponding oximes. These
α-sulfonylethanone oximes are prepared from a cheap and
environmentally friendly TsNHOH reagent and a mild oxi-
dant, nBu4NIO4. The versatility, convenient operation, low
cost, and environmental friendliness of this method, in ad-
dition to the high yields, make it viable for use both in labo-
ratory research and in industrial production. Currently, we
are exploring the scope of this reaction and the application
of this free radical addition reaction with regard to the syn-
thesis of pharmaceutical compounds.
multisubstituted alkenes (Table 2, Entries 20–23) did not af-
ford the corresponding oximes under identical conditions.
However, cyclic alkenes could afford excellent yields, and
the stereoconfiguration of the corresponding oximes had a
Z/E ratio of 1:1 (Table 2, Entry 18). In addition, ethyl acryl-
ate and 1-phenylpropenone afforded moderate yields of the
target products (Table 2, Entries 16 and 17). It is possible
that the steric hindrance and electronic effects of the carb-
onyl group makes the reactions with these compounds more
sluggish than the reactions with styrene derivatives.
Remarkably, conjugated diene compounds were con-
verted into the corresponding oximes in good yields
Supporting Information (see footnote on the first page of this arti-
Table 3. Effect of hydroxylamine in the reaction.[a]
cle) General procedure for the imidation of tertiary amines; charac-
1
terization data, including H NMR and 13C NMR spectra.
Acknowledgments
This work was financially supported by the National Natural Sci-
ence Foundation of China (NSFC) (grant number 21072131).
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Received: February 6, 2012
Published Online: April 4, 2012
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