Aerobic photo-oxidative cleavage of the C-C double bonds of styrenes

Article abstract of DOI:10.1016/j.tetlet.2009.05.012

Carbon tetrabromide enables us to carry out oxidative cleavage of the C-C double bonds of styrenes under aerobic photo-irradiation conditions. Oxidative cleavage of the various β-substituted styrenes produced benzoic acid in good yields. Since this reaction is found to be applicable to the α- or β-substituted styrenes, which showed very low reactivity under our previous cleavage reaction condition with FSM-16 and I₂, this reaction can be used complementarily.

Full text of DOI:10.1016/j.tetlet.2009.05.012

Tetrahedron Letters 50 (2009) 4328–4330
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Tetrahedron Letters
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Aerobic photo-oxidative cleavage of the C–C double bonds of styrenes
Shin-ichi Hirashima, Yasuhisa Kudo, Tomoya Nobuta, Norihiro Tada, Akichika Itoh *
Gifu Pharmaceutical University 5-6-1, Mitahora-higashi, Gifu 502-8585, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Carbon tetrabromide enables us to carry out oxidative cleavage of the C–C double bonds of styrenes
Received 4 March 2009
Revised 30 April 2009
Accepted 7 May 2009
Available online 10 May 2009
under aerobic photo-irradiation conditions. Oxidative cleavage of the various b-substituted styrenes pro-
duced benzoic acid in good yields. Since this reaction is found to be applicable to the
a- or b-substituted
styrenes, which showed very low reactivity under our previous cleavage reaction condition with FSM-16
and I
2
, this reaction can be used complementarily.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Aerobic
Photo-oxidation
Carbon tetrabromide
Cleavage of carbon–carbon double bond
Styrenes
Table 1
Oxidative cleavage of a carbon–carbon double bond to the cor-
responding carbonyl compounds is an important method in organ-
ic syntheses, especially in syntheses of natural products and
biologically active compounds. Ozonolysis, in general, has been
used for this purpose; however, ozone is explosive and a special
equipment is necessary to carry out this method.1 Since another
Study of reaction conditions for aerobic photo-oxidative cleavage of b-methylstyrene (1)
O , hν (400W Hg lamp)
2
CO H
2
catalyst
solvent (5 mL)
1 (0.3 mmol)
Catalyst
2
oxidative cleavage with heavy metals such as RuO
quires the expensive or toxic heavy metals, such as RuO
OsO
4
and OsO
4
re-
and
Entry
Amount (equiv)
Solvent
Time (h)
Yield of 2a (%)
4
1
2
3
4
5
6
7
8
9
CBr
CBr4
4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.1
0.2
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
MeOH
10
10
10
10
10
10
10
10
10
10
10
10
10
10
7
41
55
58
61
63
79
81
66
73
78
4
, and a number of stoichiometric oxygen donors to produce
CH Cl2
2
2
the corresponding carboxylic acids or aldehydes, development of
a safe and metal-free method is desirable for these synthetic trans-
formations. With this concern, we have studied the aerobic photo-
CBr
CBr
CBr
CBr
CBr
CBr
CBr
CBr
CBr
CBr
4
4
4
4
4
4
4
4
4
4
2
iPr O
Acetone
MeCN
Hexane
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
3
oxidation, and have already reported oxidative cleavage of the
double bonds of styrenes with FSM-16, a mesoporous silica, and
I
2
under photo-irradiation; however, this method was rather
10
11
12
unsatisfactory when - or b-substituted styrenes were used as
a
b
64
0
0
0
4
substrates. In the course of our further study of this reaction with
other catalysts, we also found that oxidative cleavage of the C–C
double bonds of styrenes occurred in the presence of cat. carbon
c,f
d,f
13
14
CBr4
e,f,g
CBr
CBr
CBr
4
4
4
15
16
17
18
19
20
79
85
70
62
60
57
49
4
tetrabromide (CBr ) under aerobic photo-irradiation conditions
15
10
10
10
10
10
(
Eq. 1). We report herein a detailed study of this single-step
aq HBr
MgBr
ꢀOEt
Br
photo-oxidative cleavage of alkenes.
2
2
2
O
O
R2 O2, cat. CBr4, hν
LiBr
NBS
R1
ð1Þ
+
21
R1
OH
R2
OH
a
All yields are for pure, isolated products.
b
c
d
e
f
The reaction was carried out under irradiation of 500 W Xenon lamp.
The reaction was carried out under irradiation of fluorescent lamp.
The reaction was carried out in the dark.
The reaction was carried out under Ar atmosphere.
Startingmaterial wasrecovered: 51%(entry 12), 63%(entry 13)and35%(entry 14).
(1,2-Dibromo-propyl)-benzene (5%) was obtained.
*
Corresponding author. Tel./fax: +81 58 237 8573.
E-mail address: itoha@gifu-pu.ac.jp (A. Itoh).
g
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.012

S.-i. Hirashima et al. / Tetrahedron Letters 50 (2009) 4328–4330
4329
Table 2
Aerobic photo-oxidative cleavage of C–C double bonds
O ,
h
ν
(400W Hg lamp)
4
2
CBr (0.3 equiv.)
substrate
0.3 mmol)
product
(
EtOAc (5 mL), 10h
Entry
1
Substrate
Product
Yielda (%)
81
R = Me: 1a
R = Ph: 1b
CO H
b
R
2
2
71
3
4
5
6
R = CH
R = NO
R = COMe: 1e
R = COPh: 1f
2
OH: 1c
: 1d
77
71
88
2
2
b
82
CO H
2
7
82
3
4
MeO
R
MeO
t
8
9
0
1
R = Bu: 5a
CO H 6a
62
56
60
2
R = OMe: 5b
R = Cl: 5c
R = NO
4
6
6
1
1
c
d
c
2
: 5d
R
16
CO H
2
1
2
18
7
8
O
d
1
1
3
4
R
R = Me: 9
R = Ph: 11
10
12
38
R
d
48
CO H
2
1
5
32e
1
0
10
13
14
a
All yields are for pure, isolated products.
b
c
The yield was calculated as 2 equiv of benzoic acid.
-Nitrophenacyl bromide was also obtained in 20% yield.
The reaction was carried out with 0.1 equiv of aq HBr.
4
d
e
4
The reaction was carried out with 0.6 equiv of CBr in hexane for 24 h.
hv
1
2
)
)
CBr4
Ar
Br
+
CBr3
O
solvent
or
OH
Br
Br
O2
R
O
O
H O
2
R
R
R
R
Ar
Ar
Ar
H
17
Br
Br
H O
2
1
5
16
solvent
or
O
O
O2
O
O
H
H O
2
R
R
R
Ar
Ar
Ar
Ar
Br
Br
O
O
O
1
8
20
21
O
22
OH
path a hv
path b
BrCHR
H O
2
O
O
hv
R
Ar
Ar
1
9
O
O2
23
solvent
R
or
H O
hv
2
Ar CO3
Ar CO H
Ar CO H
3
2
2
4
25
26
solvent
or
O
OH
O
O
O
O2
H2O
hv
3
)
BrCHR
Br CHR
Br CHR
Br CR
Br
+
RCO
H O
2
Scheme 1. Plausible path of aerobic photo-oxidative cleavage of C–C double bonds.

4
330
S.-i. Hirashima et al. / Tetrahedron Letters 50 (2009) 4328–4330
Table 1 shows the data for study of catalysts with b-methylsty-
substrate without bromo source, we infer that there are two paths
4
rene (1), which resulted in poor yield under our previous method,
and, among our examination, benzoic acid (2) was produced most
efficiently when using CBr as catalysts and ethyl acetate as solvent
to produce acyl radical 19 through cleavage of C–C bond of phena-
cyl bromides (path a) or 1,2-dicarbonyl compounds (path b) under
photo-irradiation, namely Norrish Type I reaction. We think that
this reaction mainly proceeds through path a, since only 35% of
benzoic acid was produced when using benzil as substrate without
4
5
(
entries 1–7 and 17–21). The optimal result was obtained in the
presence of 0.3 equiv of CBr (entries 7–10). That no oxidation pro-
4
ceeded without irradiation of UV and that only additional reaction
of bromine to the double bond proceeded without molecular oxy-
gen show the necessity of both for this reaction (entries 13 and 14).
The yield of 2 was little affected by extension of the reaction time,
and 500 W Xenon lamp or fluorescent lamp was less effective than
CBr
In conclusion, we report a practical method for CBr
aerobic photo-oxidative cleavage of carbon-carbon double bonds.
Since this reaction is found to be applicable to the - or b-substi-
tuted styrenes, which showed very low reactivity under our previ-
ous cleavage reaction condition with FSM-16 and I2, this reaction
can be used complementarily. Further studies on the use of bro-
mo-catalyst and additional applications of the photo-oxidation
are currently underway in our laboratory.
4
under photo-irradiation conditions.
4
-catalyzed
a
4
00 W high-pressure mercury lamp (entries 11, 12 and 16).
Table 2 shows the results for limitation and scope of this oxida-
tion under the reaction conditions mentioned above. Oxidative
cleavage of the various b-substituted styrenes 1 produced benzoic
acid (2) in good yields (entries 1–7). On the other hand, since non-
substituted styrenes, 5 and 7, were found to be liable to form the
polymers or other unidentified by-products under this reaction
condition, yield of the corresponding products, 4, 6 and 8, was gen-
erally modest (entries 8–12). Corresponding acetophenone (10)
and benzophenone (12), which are unstable under this condition,
were obtained only in modest yield when using 9 and 11, a-substi-
tuted styrenes, as substrates (entries 13 and 14). Surprisingly, we
found that 1-dodecene (13), a non-conjugated alkene which was
intact under our previous condition with FSM-16 and I , afforded
2
References and notes
1.
Comprehensive Organic Transformations: A Guide to Functional Group Preparations;
Larock, R. C., Ed.; Wiley-VCH: New York, 1999.
2. (a) Kogan, V.; Quintal, M. M.; Neumann, R. Org. Lett. 2005, 7, 5039–5042; (b) Travis,
B. R.; Narayan, R. S.; Borhan, B. J. Am. Chem. Soc. 2002, 124, 3824–3825; (c)
Berkowitz, L. M.; Rylander, P. N. J. Am. Chem. Soc. 1958, 80, 6682–6684; (d) Pappo,
R.; Allen, D. S.; Lemieux, R. U.; Johnson, W. S. J. Org. Chem. 1956, 21, 478–479.
3. (a) Itoh, A.; Hashimoto, S.; Kodama, T.; Masaki, Y. Synlett 2005, 2107–2109; (b)
Itoh, A.; Hashimoto, S.; Masaki, Y. Synlett 2005, 2639–2640; (c) Hirashima, S.;
Itoh, A. Synthesis 2006, 1757–1759; (d) Hirashima, S.; Hashimoto, S.; Masaki, Y.;
Itoh, A. Tetrahedron 2006, 62, 7887–7891; (e) Hirashima, S.; Itoh, A. J. Synth. Org.
Chem. Jpn. 2008, 66, 748–756.
the corresponding carboxylic acid 14 in 32% yield.
Scheme 1 shows a plausible path of this oxidation, which is pos-
tulated by considering the detectable intermediates, phenacyl bro-
mides 18, and the necessity of continuous irradiation, bromo
source and molecular oxygen in this reaction. Benzyl radical spe-
cies 15 is generated by addition of bromo radical, formed by het-
4. Itoh, A.; Kodama, T.; Masaki, Y.; Inagaki, S. Synlett 2002, 522–524.
5.
A typical procedure is as follows: A solution of b-methylstyrene (1a, 0.3 mmol)
and CBr (0.09 mmol) in dry EtOAc (5 mL) in a pyrex test tube, purged with an
balloon, was stirred and irradiated externally with a 400 W high-pressure
mercury lamp for 10 h. The reaction mixture was concentrated in vacuo, and
0% NaOH aqueous solution was added. The aqueous solution was washed with
Et O, and then acidified with 2 N HCl aqueous solution, which was extracted
with Et O. The organic layer was washed with brine and dried over MgSO , and
4
O
2
1
erolysis of CBr
radical species 15 traps molecular oxygen to afford 18 via peroxy-
radical 16 and hydroperoxide 17. Since 26 (Ar = 4-BrC ) was ob-
tained in 82% yield when using 18 (Ar = 4-BrC , R = H) as
4
, to the double bond of styrenes. The resulting
2
2
4
H
6 4
concentrated in vacuo. The product obtained is pure without further
purification.
6
H
4