Catalytic oxidative cleavage of 1,3-diketones to carboxylic acids by aerobic photooxidation with iodine

Article abstract of DOI:10.1055/s-0031-1289891

We report the catalytic oxidative cleavage of 1,3-diketones to the corresponding carboxylic acids by aerobic photooxidation with iodine under irradiation with a high-pressure mercury lamp. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0031-1289891

2
896
LETTER
Catalytic Oxidative Cleavage of 1,3-Diketones to Carboxylic Acids by Aerobic
Photooxidation with Iodine
O
N
xidative Cleava
g
o
e
of 1, 3-Dike
r
tones ihiro Tada, Motoki Shomura, Lei Cui, Tomoya Nobuta, Tsuyoshi Miura, Akichika Itoh*
Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan
Fax +81(58)2308105; E-mail: itoha@gifu-pu.ac.jp
Received 29 August 2011
the succeeding oxidation of 1,2-diketones would make it
Abstract: We report the catalytic oxidative cleavage of 1,3-dike-
tones to the corresponding carboxylic acids by aerobic photooxida-
tion with iodine under irradiation with a high-pressure mercury
lamp.
possible to synthesize carboxylic acids from 1,3-dike-
tones. Herein we report a catalytic oxidative cleavage of
1,3-diketones to carboxylic acids by aerobic photooxida-
tion with iodine under light irradiation with a 400 W mer-
cury lamp (Scheme 1).
Key words: photooxidation, aerobic, iodine, 1,3-diketone, carbox-
ylic acid
O
O
O
O2, hν, cat. I2
Syntheses of carboxylic acids are essential in organic
chemistry because carboxylic acids are versatile com-
pounds or intermediates that can be used in various fields,
such as pharmaceuticals, agrochemicals, paints, lubri-
cants, liquid crystal polymers, cosmetics, and food addi-
tives. Thus, many useful methods have been developed
for the preparation of carboxylic acids including (i) oxida-
tion of alkyl benzenes, primary alcohols, and aldehydes,
OH
Scheme 1
To explore this approach, we selected benzoylacetone (1)
as a test substrate for the optimization of reaction condi-
tions (Table 1). Among the solvents and catalysts exam-
ined, ethyl acetate with I provides benzoic acid (2) most
efficiently (Table 1, entries 1–9). After detailed studies on
the reaction conditions, we found that the efficient reac-
(
ii) reaction of organometallic reagents with carbon diox-
2
ide, (iii) oxidative cleavage of alkenes, alkynes, and vici-
1
nal diols, and (iv) haloform-type reactions, etc. The
conversion of 1,3-diketones into carboxylic acids is a sup-
plementary reaction for the preparation of carboxylic ac-
tion conditions involve I (0.1 equiv) in ethyl acetate for
ten hours (entries 1, 10, and 11). Note that a lower yield
2
4
2
ids. However, it requires a stoichiometric amount of
of 2 was obtained when other light sources, such as a xe-
non lamp (500 W) and a fluorescent lamp (4 × 22 W),
were used instead of a 400 W mercury lamp (Table 1, en-
tries 12 and 13). The fact that compound 2 was not ob-
tained or was obtained only in low yield without iodine,
molecular oxygen, and irradiation confirms the require-
ment of all these conditions for this reaction (Table 1, en-
tries 14–16).
2
c
2d
2h
2i
reagents, such as CAN, oxone, PIDA, SnCl , heavy-
4
2
b
2f
metal catalyst [In(OTf) , and MeReO ], high-tempera-
3
3
2
a
ture water conditions, and electrochemical oxidation
2
e,g
conditions. In 1953, conversion of benzoylacetone cat-
alyzed by iodine (only one substrate) was reported, al-
though benzoic acid was obtained only in 18% yield.2
Thus, the development of a mild and efficient protocol for
a metal-free catalytic conversion of 1,3-diketones into the
i
corresponding carboxylic acids is highly desirable. Cur- Table 1 Study of Reaction Conditions
rently, the effective use of light is one of the most impor-
O
O
O
O2, hν (400 W Hg lamp)
tant research topics for the development of new energy-
conversion protocols and energy-using technologies. Fur-
thermore, molecular oxygen has received considerable
attention as an ultimate oxidant because it is photosynthe-
sized by plants, produces little waste, is inexpensive, and
has larger atom efficiency than other oxidants. Consider-
ing these factors, we have developed various aerobic pho-
tooxidation reactions in an oxygen atmosphere and under
catalyst (equiv)
OH
solvent (5 mL)
1
(0.3 mmol)
2
Time (h) Yield (%)a
Entry
Catalyst (equiv)
Solvent
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
hexane
1
2
3
4
5
6
I2 (0.1)
10
10
10
10
10
10
89
47
56
19
44
66
NIS (0.1)
3
light irradiation. We recently reported the tandem oxida-
tion–rearrangement–oxidative decarboxylation of 1,3-
diketones to 1,2-diketones in the presence of a catalytic
LiI (0.1)
CaI (0.1)
3
f
2
amount of I . In the course of this study, we found that
2
Br (0.1)
2
SYNLETT 2011, No. 19, pp 2896–2900
x
x
.x
x
.2
0
1
1
I2 (0.1)
Advanced online publication: 11.11.2011
DOI: 10.1055/s-0031-1289891; Art ID: U06311ST
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidative Cleavage of 1,3-Diketones
2897
Table 1 Study of Reaction Conditions (continued)
Table 2 Oxidative Cleavage of 1,3-Diketones (continued)
O
O
O
O , hν (400 W Hg lamp)
2
O2, hν (400 W Hg lamp)
2
I (0.1 equiv)
catalyst (equiv)
OH
substrate
0.3 mmol)
product
(
EtOAc (5 mL), 24 h
solvent (5 mL)
1
(0.3 mmol)
2
Yield (%)a
Entry Substrate
Product
Entry
Catalyst (equiv)
I2 (0.1)
Solvent
Time (h) Yield (%)a
O
O
O
7
8
9
i-Pr O
10
10
10
10
5
49
46
24
69
57
75b
40c
9
2
5
OH
69
I2 (0.1)
MeCN
MeOH
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
9
10
I2 (0.1)
O
O
O
1
1
1
1
1
1
1
0
1
2
3
4
5
6
I2 (0.05)
6
OH
OH
57
I2 (0.1)
S
S
11
12
I2 (0.1)
10
10
10
10
10
O
O
O
I2 (0.1)
–
7
8
9
80c
I2 (0.1)
I2 (0.1)
0d
13
14
2
O
O
O
0e
a
b
c
d
e
O
70
Isolated yields.
The reaction was carried out with xenon lamp (500 W).
The reaction was carried out with fluorescent lamp (4 × 22 W).
The reaction was carried out under Ar.
O
15
The reaction was carried out in the dark.
O
O
O
73d
OEt
OH
Table 2 Oxidative Cleavage of 1,3-Diketones
O2, hν (400 W Hg lamp)
1
1
6
2
I2 (0.1 equiv)
substrate
product
O
O
O
(
0.3 mmol)
EtOAc (5 mL), 24 h
1
1
0
1
61
40
OH
8
8
18
Entry Substrate
Product
Yield (%)a
84
7
O
O
O
O
O
O
O
1
OH
HO
OH
2
0
1
2
9
MeO
MeO
O
O
O
3
4
OH
O
O
O
1
2
OH
OH
63
2
OH
77
1
2
2
O
5
6
2
O
O
O
0e
1
1
3
4
3
4
OH
89b
91
2
2
3
O
9
O
O
9
OH
1
0f
9
O
O
O
O
O
O
2
24
OH
a
b
c
d
e
f
Isolated yields.
The reaction was carried out for 10 h.
Compound 2 (0.48 mmol) was obtained.
The reaction was carried out with I (0.2 equiv).
Starting material 22 was recovered in 87% yield.
Cl
Cl
7
8
2
Starting material 23 was recovered in 97% yield.
Synlett 2011, No. 19, 2896–2900 © Thieme Stuttgart · New York

2
898
N. Tada et al.
LETTER
1
5
Next, we investigated the scope and limitation of the oxi- (28) were detected by H NMR. When 26 and 28 were
dative cleavage of 1,3-diketones under the optimal reac- used as substrates under the optimal conditions, benzoic
tion conditions (Table 2). When benzoylacetones were acid (2) was obtained in high yield (Scheme 2, equations
used as a substrate, the corresponding carboxylic acids 1 and 3). These results suggest that 26 and 28 are interme-
were obtained in good to high yields, regardless of an diates in this reaction. On the other hand, when 27 was
electron-donating or electron-withdrawing group at the used as the substrate under the optimal conditions, benzo-
benzene ring (Table 2, entries 1–4). Furthermore, 2-naph- ic acid (2) was only afforded in 13% yield and 87% yield
thoic acid (10) and 3-thiophenecarboxylic acid (12) were of recovered 27 (Scheme 2, equation 2). In contrast, 27
obtained from 9 and 11 in moderate yields (Table 2, en- was converted into benzoic acid (2, 33%) and perbenzoic
tries 5 and 6), respectively. Dibenzoylmethane (13) was acid (29, 30%) without I (Scheme 2, equation 5). Note
2
also oxidized to benzoic acid (2) in 80% yield (Table 2, that in the oxidative cleavage of 13, iodobenzene and io-
entry 7). When 1,3-indandione (14), a cyclic 1,3-diketone, dinated ethyl acetate were detected by GC-MS in the later
was used, phthalic anhydride (15) was obtained in 70% stages of this reaction. These results probably indicated
yield (Table 2, entry 8). 1,3-Keto ester 16 was also con- that benzil (27) is a minor intermediate, and oxidative
verted into benzoic acid (2) in good yield (Table 2, entry conversion of 27 reached completion in the later stages of
6
9
). Note that 2,4-tridecanedione (17) and 1,3-cyclohex- the reaction in the presence of low I concentration.
2
anedione (19), which are aliphatic diketones, also afford- Moreover, 26 and 28 were also oxidized to benzoic acid
ed decanoic acid (18) and glutaric acid (20) in moderate and perbenzoic acid without I (Scheme 2, equations 4
2
yields (Table 2, entries 10 and 11), respectively. In addi- and 6).
tion, 2-hydroxyacetophenone (21) was oxidized to afford
benzoic acid (2) in 63% yield. Under these conditions, ac-
etophenone (22) and didecyl malonate (23) functioned as
poor substrates.
Scheme 3 shows a plausible path of this reaction, which is
postulated by considering the requirement of continuous
irradiation, a catalytic amount of I , and molecular oxygen
2
for the oxidative cleavage of 1,3-diketones. 1,3-Diketone
To clarify the reaction mechanism, the time course of the 13 was initially oxidized to triketone 26 and its monohy-
oxidative cleavage of 13 was studied (Figure 1). It was re- drate by aerobic photooxidation with catalytic amount of
vealed that dibenzoyliodomethane (25), triketone (26, in- iodine.3 Triketone 26 was transferred to benzil (27),
f,7,8
3f,9
10
cluding its monohydrate), benzil (27), and glyoxylic acid glyoxylic acid (28), and perbenzoic acid (29) under light
irradiation and in the presence of oxygen. Moreover, ben-
O
O
O
O2, hν ( 400 W Hg lamp)
OH
OH
OH
OH
I2 (0.1 equiv)
O
(1)
(2)
2
2
6 (0.3 mmol)
EtOAc (5 mL), 24 h
2
83%
O
O
O
O2, hν ( 400 W Hg lamp)
I2 (0.1 equiv)
O
O
EtOAc (5 mL), 24 h
7 (0.3 mmol)
2
2
13%
27 87%
O
O
OH
O2, hν ( 400 W Hg lamp)
I2 (0.1 equiv)
O
(3)
(4)
(5)
EtOAc (5 mL), 24 h
2
2
8 (0.3 mmol)
87%
O
O
O
O
O2, hν ( 400 W Hg lamp)
OOH
O
6 (0.3 mmol)
EtOAc (5 mL), 24 h
2
51%
O
29 30%
O
O
O2, hν ( 400 W Hg lamp)
OH
OH
OOH
OOH
O
EtOAc (5 mL), 24 h
2
2
7 (0.3 mmol)
2
2
33%
O
29 30%
O
O
OH
O2, hν ( 400 W Hg lamp)
O
(6)
EtOAc (5 mL), 24 h
8 (0.3 mmol)
67%
29 2%
Scheme 2 Study of reaction intermediate
Synlett 2011, No. 19, 2896–2900 © Thieme Stuttgart · New York

LETTER
Oxidative Cleavage of 1,3-Diketones
2899
hν, O2
I2
O
O
O
O
hν, O2
O
1
)
OH
O
Ph
Ph
Ph
Ph
Ph
O
13
2
6
28
hν, O2
hν, O2
hν, O2
O
O
O
hν, O2
HI
Ph
Ph
Ph
OOH
Ph
OH
2
9
2
O
2
7
hν
O2, hν
2
)
HI
I2
I•
Scheme 3 Plausible path
tion with a 400 W mercury lamp. This mild and efficient
reaction is significantly important because of the use of
inexpensive molecular iodine as the catalyst and molecu-
lar oxygen as the terminal oxidant.
References and Notes
(
1) (a) Larock, R. C. Comprehensive Organic Transformations,
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2
B.; March, J. March’s Advanced Organic Chemistry, 6th ed.;
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(
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(
(
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(
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2
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(
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2
9
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Figure 1 Time course of oxidative cleavage of 1,3-diketones
zil (27)11 and glyoxylic acid (28)12 were converted into
perbenzoic acid (29). Finally, perbenzoic acid (29) was re-
duced to benzoic acid (2). Iodine was regenerated by aer-
obic photooxidation of hydrogen iodide.
Inagaki, S. Synlett 2002, 522. (o) Itoh, A.; Kodama, T.;
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4) Typical Procedure
(
A solution of benzoylacetone (1, 0.3 mmol) and I (0.03
2
mmol) in dry EtOAc (5 mL) in a Pyrex test tube, purged with
In conclusion, we have developed the catalytic oxidative
cleavage of 1,3-diketones to carboxylic acids through io-
dine-catalyzed aerobic photooxidation under light irradia-
an O balloon, was stirred and irradiated externally with 400
2
W high-pressure mercury lamp for 10 h. The reaction
Synlett 2011, No. 19, 2896–2900 © Thieme Stuttgart · New York

2
900
N. Tada et al.
LETTER
mixture was concentrated under reduced pressure. The pure
product 2 was obtained by preparative TLC.
(8) Since the reaction did not proceed when using methylene
blue, a singlet-state molecular oxygen generator, instead of
iodine, singlet-state molecular oxygen is probably not an
active species for this reaction.
(
(
(
5) These compounds were identified by comparison with
1
authentic samples, and yields were determined by H NMR
with internal standard.
6) Benzil(27) was obtained as major product in the presence of
(9) Benzilic acid rearrangement of triketone to benzil, see:
(a) Gurumurthy, R.; Narasimhan, K. Indian J. Chem., Sect.
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R. B.; Schofield, C. J. Angew. Chem. Int. Ed. 2009, 48, 2796.
(11) Photooxidation of a-diketones, see: (a) Sawaki, Y.
Tetrahedron 1985, 41, 2199. (b) Sawaki, Y.; Foote, C.
J. Org. Chem. 1983, 48, 4934. (c) Sawaki, Y. Bull. Chem.
Soc. Jpn. 1983, 56, 3464. (d) Biro, C. W. Chem. Commun.
1968, 1537.
0
.5 equiv of Ca(OH) under visible-light irradiation. See ref.
2
3f.
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