Rapid microwave-promoted solvent-free oxidation of α-methylene ketones to α-diketones

Article abstract of DOI:10.1016/S0040-4039(02)01130-9

A convenient and rapid method for the oxidation of α-methylene ketones to α-diketones has been described involving the reaction of pyridine N-oxide with α-nosyloxy ketone intermediates.

Full text of DOI:10.1016/S0040-4039(02)01130-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5661–5663
Rapid microwave-promoted solvent-free oxidation of a-methylene
ketones to a-diketones
Jong Chan Lee,* Hong-Jun Park and Jin Young Park
Department of Chemistry, Chung-Ang University, Seoul 156-756, South Korea
Received 2 May 2002; revised 3 June 2002; accepted 7 June 2002
Abstract—A convenient and rapid method for the oxidation of a-methylene ketones to a-diketones has been described involving
the reaction of pyridine N-oxide with a-nosyloxy ketone intermediates. © 2002 Elsevier Science Ltd. All rights reserved.
Much effort for the efficient preparation of 1,2-dike-
tones has been made due to their biological activity and
usefulness as precursors for many useful organic trans-
a-bromo ketones with DMSO in the presence of
6
sodium carbonate. Between these two methods, sele-
nium dioxide has been most successfully applied for the
oxidation of a-methylene ketones to a-diketones. How-
ever, this method has suffered from inherent vigorous
reaction conditions and inconvenient purification steps
due to the difficulty in removal of the concomitantly
generated selenium. Furthermore, the above two reac-
tions always required either strong acidic or basic reac-
tion conditions, which limits their applications to
sensitive ketones. To the best of our knowledge, the
only method for the oxidation of a-methylene ketones
to a-diketones under neutral reaction conditions was
reported by oxidation of enamino ketone intermediates
1
formations. While a wide variety of methods are
described in literature for the preparation of a-dike-
2
tones, little attention has been paid to the synthesis of
a-diketones from a-methylene ketones. Oxidation of a
reactive benzylic group to a carbonyl functions can be
easily achieved using appropriate oxidants, such as
3
pyridinium chlorochromate and potassium permanga-
4
nate. By contrast, there has been relatively few reports
concerning the conversion of unactivated a-methylene
ketones to the corresponding a-diketones. The repre-
sentative examples include the selenium dioxide oxida-
5
7
tion of ketones in acetic acid and the reaction of
with singlet oxygen. Although this method provided
O
R2
R1
N
O
O
HNIB
O
O
R2
O S O
R2
R1
R1
microwave
microwave
30 sec
NO2
O
1
- 2 min
NO2
O2N
O
O S
O
HO
I
NO2
HNIB =
Scheme 1.
Keywords: a-diketones; N-oxides; hypervalent elements; microwave heating; oxidations.
*
Corresponding author. Tel.: +82-2-820-5202; fax: +82-2-825-4736; e-mail: jclee@cau.ac.kr
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01130-9

5
662
J. C. Lee et al. / Tetrahedron Letters 43 (2002) 5661–5663
high yields of a-diketones, somewhat exotic reaction
conditions limits its practical applications. Therefore,
development of a more convenient method for the
conversion of a-methylene ketones to a-diketones
under neutral reaction conditions is required.
After cooling down the reaction mixture to ambient
temperature, pyridine N-oxide (0.114 g, 1.2 mmol)
was added and irradiated for an additional 30 s. The
reaction mixture was extracted with dichloromethane
(
2×25 mL) and washed with water (2×30 mL). The
dichloromethane layer was separated and dried over
Microwave-assisted organic syntheses attracted much
attention because of their fast reaction rates, higher
purity of products, and ease of manipulation. In par-
MgSO . After evaporation of the solvent, the residue
4
was purified by flash column chromatography (SiO2,
ethyl acetate:hexane=1:3) to give the desired a-dike-
tone. Both symmetrical and unsymmetrical a-dike-
tones were successfully prepared and the results are
summarized in Table 1. In general, the reactions were
completed within 3 min exposure to microwave irradi-
ation and the yields were fairly high, without any
observable by-products. Moreover, the present
method proved to work well for an acid sensitive
ketone (entry 7), which illustrated the mildness of
reaction conditions. The somewhat lower yield (45%)
for the 4-heptanone (entry 9) may be due to the
slight decomposition of 3-nosyloxy-4-heptanone inter-
mediate under the present reaction conditions.
Replacing HNIB with [hydroxy(tosyloxy)iodo]benzene
8
ticular, the use of solvent-free microwave-irradiated
procedures for organic synthesis have attracted con-
siderable interest in recent years due to their efficient
9
and environmentally benign conditions.
Recently, we have reported the highly efficient
microwave-assisted
a-organosulfonyloxylation
of
1
0
ketones in solvent-free conditions. Taking advantage
of these results, we wish to report here a facile and
efficient microwave-assisted oxidation of a-methylene
ketones to a-diketones under neutral reaction condi-
tions. Reaction of ketones with [hydroxy(p-nitroben-
11
zenesulfonyloxy)iodo]benzene (HNIB) under micro-
wave irradiation for 1–2 min produced a-nosyloxy
ketone intermediates, which can then undergo substi-
tution reactions with pyridine N-oxide in solvent-free
conditions under microwave irradiation to give a-
diketones (Scheme 1). A general procedure is as fol-
lows: ketone (1.0 mmol) and HNIB (0.507 g, 1.2
mmol) were placed in a 50 mL glass tube. The reac-
tion mixture was immersed in an alumina bath inside
domestic microwave oven and irradiated (600 W)
three times for a period of 30 s with 10 s intervals.
12
(HTIB) under the same reaction conditions, the
yields of oxidations were reduced to 20% on average
over prolonged reaction times, which can be
explained by the decreased leaving ability of the -OTs
group compared to the -ONs group. The oxidation
reaction mechanism probably involves nucleophilic
substitution of -ONs by pyridine N-oxide to form
a-oxypyridinium ketone salt followed by removal of
the a-proton to carbonyl group. Interestingly, the
conversion of deoxybenzoin to benzil occurred spon-
taneously by microwave irradiation of a-nosyloxy
deoxybenzoin intermediate without use of pyridine N-
oxide (entry 8). By analogy with the formation of
Table 1. Conversion of ketones to a-diketones under
microwave irradiation
13
diketones from a-mesyloxy ketones, this oxidation
process presumably occurred via abstraction of reac-
tive benzylic hydrogen by a sulfonyl oxygen in the
a-nosyloxy deoxybenzoin intermediate. Application of
this method for oxidation of a-methyl ketones to a-
keto aldehyde were unsuccessful to provide compli-
cated side reaction products.
Entry Ketones
Product
Yield
a
(
%)
1
2
3
4
5
6
7
C H COCH CH
C H COCOCH
3
83
6
5
2
3
6
5
C H COCH CH CH
C H COCOCH CH
65
78
80
90
85
70
6
5
2
2
3
6
5
2
3
p-MeC H COCH CH
p-MeC H COCOCH
6 4 3
6
4
2
3
p-MeOC H COCH CH p-MeOC H COCOCH
6
4
2
3
6
4
3
In summary, we have developed a facile, mild, and
remarkably fast reaction method for the oxidation of
a-methylene ketones to a-diketones under solvent-free
microwave irradiation reaction conditions. The advan-
tages of the present method include rapid reaction
rates, ease of manipulation, and mild neutral reaction
conditions should provide an added flexibility for the
preparation of a-diketones over existing methods.
Extensions of this chemistry to other skeletal frame-
works are currently underway.
p-BrC H COCH CH
p-BrC H COCOCH
6
4
2
3
6
4
3
p-ClC H COCH CH
p-ClC H COCOCH
6
4
2
3
6 4
3
p-PhCH OC H COCH - p-PhCH OC H COCOCH
2
6
4
2
2
6
4
3
CH3
8
9
PhCOCH Ph
PhCOCOPh
85b
2
O
O
45
O
O
O
O
1
0
64
Acknowledgements
a
We thank the KOSEF for financial support (R01-
1999-00036).
Isolated yields after flash column chromatography.
The product was obtained without use of pyridine N-oxide.
b

J. C. Lee et al. / Tetrahedron Letters 43 (2002) 5661–5663
5663
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