Facile aerobic photo-oxidative synthesis of α-diketones from alkynes

Article abstract of DOI:10.1016/j.tetlet.2010.12.029

We report a useful method for facile aerobic photo-oxidative synthesis of α-diketones from alkynes with MgBr₂·OEt₂. This procedure provides a practical synthetic method of α-diketones using easily handled bromine sources, harmless visible light, and molecular oxygen as terminal oxidant.

Full text of DOI:10.1016/j.tetlet.2010.12.029

Tetrahedron Letters 52 (2011) 875–877
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Tetrahedron Letters
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Facile aerobic photo-oxidative synthesis of
a
-diketones from alkynes
⇑
Tomoya Nobuta, Norihiro Tada, Kasumi Hattori, Shin-ichi Hirashima, Tsuyoshi Miura, Akichika Itoh
Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
We report a useful method for facile aerobic photo-oxidative synthesis of
a
-diketones from alkynes with
Received 27 September 2010
Revised 3 December 2010
Accepted 8 December 2010
Available online 13 December 2010
MgBr2ÁOEt2. This procedure provides a practical synthetic method of
bromine sources, harmless visible light, and molecular oxygen as terminal oxidant.
Ó 2010 Elsevier Ltd. All rights reserved.
a-diketones using easily handled
Keywords:
Aerobic
Photo-oxidation
MgBr2ÁOEt2
a-Diketones
Alkynes
Table 1
a-Diketones play an important role as versatile building blocks
Study of reaction conditions for aerobic photo-oxidation
in organic synthesis. For example, they react with 3-oxoglutarates
to afford cis-bicyclo[3.3.0]octane-3,7-diones1 that are precursors of
polyquinanes.
a-Diketones also have been used as precursors of
various heteroaromatics, since they react with acyl hydrazides or
1,2-diaminobenzenes that result in 1,2,4-triazines2 or quinoxa-
lines,3 respectively. Moreover, 2,4,5-trisubstituted imidazoles, hav-
ing pharmaceutical activities, can be prepared by coupling with
Entry
Bromine source (equiv)
Solvent
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (0.2)
MgBr2ÁOEt2 (0.5)
MgBr2ÁOEt2 (1.5)
MgBr2ÁOEt2 (–)
MgBr2ÁOEt2 (1.0)
MgBr2ÁOEt2 (1.0)
Br2 (1.0)
aq. HBr (1.0)
LiBr (1.0)
NaBr (1.0)
AlBr3 (1.0)
NiBr2 (1.0)
SrBr2 (1.0)
SmBr2 (1.0)
YbBr3 (1.0)
Acetone
CH2Cl2
Benzene
THF
20
20
20
20
20
20
20
24
24
24
24
24
24
24
20
20
20
20
20
20
20
20
20
9
aldehydes.4 Most popular syntheses of
a
-diketones are the oxida-
13
14
17
31
48
51
71b
21
45
54
n.r.
n.r.c
n.r.d
5
tion of alkynes which can be easily obtained by Sonogashira cou-
pling; however, the oxidations require rare metal reagents (Mn,5
Cr,6 Ru,7 Re8 or Pd9), high temperature,10 large excess of strong
acid11,12 or expensive halogen sources,13 and complex and intracta-
ble reagents.14,15 As such, from the green chemistry angle, more
Hexane
EtOAc
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
environmentally friendly synthetic methods of
a-diketones are in
demand. With these perspectives, we have studied environmen-
tally benign oxidation with molecular oxygen, and already re-
ported aerobic photo-oxidative syntheses of carboxylic acids
from methyl aromatics or alcohols in the presence of catalytic
amounts of MgBr2ÁOEt2.16 In the course of our additional studies
of this photo-oxidation, we also found that alkynes are oxidized
36
3
to their corresponding
a-diketones successfully under similar
n.r.
32
31
11
55
36
a
b
c
1H NMR analysis.
Isolated yield.
The reaction was carried out in the dark.
Scheme 1.
⇑
Corresponding author.
d
The reaction was carried out under Ar atmosphere.
E-mail address: itoha@gifu-pu.ac.jp (A. Itoh).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.12.029

876
T. Nobuta et al. / Tetrahedron Letters 52 (2011) 875–877
Table 2
Aerobic photo-oxidative synthesis of
a-diketones from alkynes
O2, hν (VIS)
MgBr2·OEt2
substrate
(0.3 mmol)
product
MeCN (5 mL), 24 h
Entry
1
Substrate
MgBr2ÁOEt2 (equiv)
Product
Yielda (%)
71
O
1.0
1.0
1.5
1.5
1.5
O
O
Cl
Br
Ac
Cl
Br
Ac
2
3
4
5
70
60
68
56
O
O
O
O
O
O
O2N
O2N
O2N
O2N
O
O
6
1.0
56
O
O
MeO
MeO
Me
7
8
1.0
1.5
30b
56
O
O
Me
O
Me
Me
O
9
1.0
n.r.
O
O
10
11
12
1.0
1.0
1.0
1.0
33
N
N
O
O
32
N
N
O
O
Bu
n.r.
n.r.
Bu
O
O
C6H11
C6H11
C6H11
13
C6H11
O
a
Isolated yields.
31% of starting material was recovered.
b
conditions (Scheme 1). This novel method is interesting in a view
point of green chemistry due to the use of harmless visible light
from general-purpose fluorescent lamp, molecular oxygen as ter-
minal oxidants, and easily handled bromine sources such as
MgBr2ÁOEt2. Herein, we report our detailed study of the aerobic
substrate.17 In this protocol, better results were obtained when
using MgBr2ÁOEt2 (1.0 equiv) as bromine sources and MeCN as
solvent (entries 1–11 and 15–23).18 The fact that benzil (2) was
not obtained without MgBr2ÁOEt2, irradiation, or molecular oxygen
shows the necessity of all of these ingredients for this reaction (en-
tries 12–14).
photo-oxidative synthesis of a-diketones from alkynes.
Table 1 shows the results of optimization of reaction conditions
for aerobic photo-oxidation using diphenylacetylene (1) as a test
Table 2 presents the scope and limitation of this oxidation un-
der the optimized reaction conditions mentioned above. In general,

T. Nobuta et al. / Tetrahedron Letters 52 (2011) 875–877
877
-dibromoketones 7, which can be detected by 1H NMR. The
corresponding -diketones are given by hydrolysis of 7.
In conclusion, we have developed a facile and practical method
for the preparation of -diketones by aerobic photo-oxidation of
Table 3
a,a
Study of efficient wavelength of light
a
O
O2, hν (300 W Xe lamp)
MgBr2·OEt2 (1.0 equiv)
Ph
a
Ph
Ph
Ph
MeCN (5 mL), 24 h
alkynes. This method is of great value from the view point of syn-
thetic organic chemistry as a harmless visible light irradiation from
a general purpose fluorescent lamp and molecular oxygen are used.
Further application of this photooxidation to other reactions is now
in progress in our laboratory.
1 (0.3 mmol)
O
2
Entry
h
m
(nm)
Yielda (%)
Recovery of 1
2
1
2
3
4
5
6
7
Xe lamp (all)
397
60
0
Trace
100
50
445
499
558
589
35
42
0
0
0
References and notes
50
100
100
99
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a
1H NMR analysis.
-
O2 O2
H2O O2
Br-
Br
Br
Br2
HBr
(1)
MgBr2
Solvent
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Br
OO
Ar
Br
Ar'
HOO
Ar
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O2
HBr
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Ar'
Ar
Ar
Ar'
Ar'
3
4
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Br2
HBr
HBr
HBr
H2O
H O
Ar
Br
O
Br
Br
O
O
Ar'
Ar
Ar
Ar'
Ar'
Br Br
6
7
Scheme 2. Plausible path of aerobic photo-oxidative syntheses of
a-diketones
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sponding
a-diketone only in low yield (entries 1–8). For 2-meth-
ylbiphenylacetylene, possessing a methyl group at the ortho
position of benzene ring, the product was not obtained under this
condition (entry 9). In addition, 2-(2-phenylethynyl) pyridine and
3-(2-phenylethynyl) pyridine, heterocyclic compounds, produced
the corresponding
a-diketones in low yields, respectively (entries
10 and 11). Unfortunately, monoarylacetylenes, such as 1-phe-
nyl-1-hexyne, and dialkylacetylenes, such as 6-undecyne, were in-
tact under this condition (entries 12 and 13).
Table 3 shows the results of the study of efficient wavelength
for this aerobic photo-oxidative synthesis of
a-diketones. Among
our examination, visible lights, especially 445 nm and 499 nm,
were effective for this reaction.19
Scheme 2 shows a plausible path of this oxidation, which is pos-
tulated by the necessity of molecular oxygen and continuous irra-
diation.20 Observation of yellow color in the reaction mixture
suggests the generation of bromine in this reaction system. We
guess that the vinyl radical species 3 is generated by the addition
of bromine radical to alkynes. Bromine radical is formed by contin-
uous aerobic photo-oxidation of the MgBr2ÁOEt2. Mg2+ is thought to
catalyze the electron transfer from bromine anion to oxygen, and
also to stabilize OÁ2À, which is generated by electron transfer from
bromine anion under photo-irradiation, by the formation of their
1:1 complex.21 The radical species 3 traps molecular oxygen to
afford hydroperoxides 5 through peroxy radical species 4. Hydro-
peroxides 5 are reduced by HBr, which is generated in situ, to
provide bromoenols 6. Molecular bromine reacts with 6 to afford
17. Typical procedure:
A solution of diphenylacetylene (1, 0.3 mmol) and
MgBr2ÁOEt2 (0.3 mmol) in dry MeCN (5 mL) in a pyrex test tube, purged with
an O2-balloon, is stirred and irradiated externally with four 22 W fluorescent
lamps, which are equipped in the distance of 65 mm, for 24 h. The reaction
mixture is washed with aq. Na2S2O3 and brine, concentrated in vacuo, and
purified by PTLC.
18. When the reaction was carried out in the presence of catalytic amount of Br2
(0.2 equiv), benzil (2) was obtained only in 3% yield along with 70% of
recovered diphenylacetylene (1) and a lot of by-products. Therefore, we think
that Br2 was probably trapped by triple bond of diphenylacetylene (1) and the
reaction did not proceed efficiently.
19. 300 W Xenon lamp (ASAHI SPECTRA MAX-301) was used.
20. The reaction did not proceed when 1.0 equiv of galvinoxyl, which is a radical
scavenger, was added.
21. Fukuzumi, S.; Ohkubo, K. Chem. Eur. J. 2000, 6, 4532–4535.