A mild and efficient Nef reaction for the conversion of nitro to carbonyl group by dimethyldioxirane (DMD) oxidation of nitronate anions

Article abstract of DOI:10.1055/s-1998-1947

DMD oxidation of nitronate onions, generated in situ from the corresponding nitroalkanes, affords the corresponding carbonyl products. Highest yields were obtained when one equivalent of water was added before the oxidation with DMD.

Full text of DOI:10.1055/s-1998-1947

December 1998
SYNLETT
1335
A Mild and Efficient Nef Reaction for the Conversion of Nitro to Carbonyl Group by
Dimethyldioxirane (DMD) Oxidation of Nitronate Anions
a
l
a,
Chantu R. Saha-Möller
a
Institut für Organische Chemie, Universität Würzburg, am Hubland, D-97074 Würzburg, Germany
Tel: +49-931-8885340; Fax: +49-931-8884756; E-mail: adam@chemie.uni-wuerzburg.de
b
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 1 September 1998
Abstract: DMD oxidation of nitronate anions, generated in situ from
the corresponding nitroalkanes, affords the corresponding carbonyl
products. Highest yields were obtained when one equivalent of water
was added before the oxidation with DMD.
Nitroalkanes are useful building blocks in organic synthesis since the
1
nitro group may be transformed into numerous functionalities, most
importantly, into the carbonyl group which is known as the Nef
2
reaction. The Nef reaction was originally carried out under acidic
1,2
conditions, e.g. with strong acid such as aqueous HCl. To avoid such
3
4
drastic conditions, some oxidative methods with KMnO , K S O ,
4
2 2 8
5 1
6
7
TM
O , O , and most recently, Caroate (known also as Oxone ) have
3
2
been developed. However, all these stoichiometric methods usually give
only moderate yields of the carbonyl products, especially when an
8
aldehyde is formed. Bartlett et al. reported the first metal-catalyzed
t
oxidation in which BuOOH/VO(acac) was employed, but concentrated
2
t
BuOOH (90%) is required. Clearly, a milder and more efficient method
for such conversions is still in demand, and we presently demonstrate
that dimethyldioxirane serves this purpose well.
Dioxiranes, especially dimethyldioxirane (DMD) and methyl-
9,10
(trifluoromethyl)dioxirane (TFD), either in the isolated form
or
generated in situ, have been established as very powerful yet highly
11
selective oxidants. The regeneration of the carbonyl functionality
12
12
13
from acetals, orthoesters and hydrazones by DMD or TFD is well-
14
known in the literature. Recently, we reported that the DMD oxidation
of σ adducts generated from the addition of the carbanion of 2-
H
phenylpropionitrile to nitroarenes which can be considered as
cyclohexadiene nitronates produces high yields of phenols,
a
transformation which is mechanistically akin to the Nef reaction. We
envisaged that the DMD oxidation of the nitronate anions derived from
nitroalkanes should lead to the corresponding carbonyl products as a
convenient and efficient alternative to the traditional Nef reaction, as
confirmed by the high yields in Table 1.
When a slight excess of DMD was added as acetone solution to the
nitronate anion 2a, generated in situ from the nitroalkane 1a, a good
yield of the keto ester 3a was obtained (entry 1). Without DMD, no
conversion of the nitronate to the carbonyl product 3a took place (data
not shown). Since we have observed a pronounced water effect in the
H
14
DMD oxidation of σ adducts derived from nitroarenes,
one
In summary, the DMD oxidation of nitronate anions provides a mild and
efficient alternative to the traditional Nef reaction. Since the required
equivalent of water was intentionally added to the nitronate prior to
DMD and an excellent yield of the keto ester 3a was obtained (entry 2);
however, the reverse addition of water and DMD was ineffective (entry
3). A similar water effect was found for substrate 1b (entries 4-6). In
this way, very good yields of the carbonyl products 3c-e were also
obtained from the corresponding nitro compounds 1c-1e (entries 7-9).
Noteworthy is that the aldehyde 3e was prepared in good yield with the
present method (entry 9). The beneficial water effect in enhancing the
oxidation yield is presumably due to the increased reactivity of DMD
nitro compounds are conveniently prepared by the Michael addition of
15,16
simple nitroalkanes to α,β-unsaturated carbonyl derivatives,
this
transformation is recommended for its high yields and convenient
24
workup. Of interest for preparative applications, the keto diester 3d
5
has been used in natural product synthesis and is now readily available
in high yield by the DMD oxidation of the nitronate 2d.
Acknowledgement: Generous financial support of the Deutsche
Forschungsgemeinschaft (Schwerpunktprogramm: Peroxidchemie) and
the Fonds der Chemischen Industrie is gratefully appreciated. M.
Makosza thanks the Alexander von Humboldt Foundation for the
22
through hydrogen-bonding with water, as suggested by experimental
and theoretical studies.
23

1336
LETTERS
SYNLETT
research award which made this collaboration possible. C.-G. Z. thanks
the DAAD (Deutscher Akademischer Austauschdienst) for a doctoral
fellowship.
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(24) General Procedure: To a solution of the nitroalkane (1.0 mmol)
in THF (10 mL, freshly distilled over potassium) was added
t-BuOK (123 mg, 1.1 mmol) and the mixture was stirred at room
temperature (ca. 20 °C) for 5 min. Then H O (18.0 µL, 1.0 mmol)
2
was added, stirred for 2 min, and a solution of DMD (1.2 mmol,
0.07-0.10 M) in acetone (dried over molecular sieves 4Å) was
added in one portion. After 5 min, the reaction mixture was
neutralized with aqueous NH Cl (0.5 mL) and dried over MgSO .
4
4
The MgSO was removed by filtration and washed with acetone
4
(3×10 mL). The crude product, obtained after evaporation (20 °C,
30 mbar) of the solvent, was purified by silica gel chromatography
with 30-50% ether in petroleum ether (b.p. 30-50 °C) as eluent
(1:1 EtOAc/n-hexane was used for 3d).
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