Aerobic photo-decarboxylation of α-hydroxy carboxylic acid derivatives under visible light irradiation in the presence of catalytic iodine

Article abstract of DOI:10.1016/j.tetlet.2008.02.116

A catalytic amount of iodine enables us to carry out aerobic photo-decarboxylation of α-hydroxy carboxylic acid derivatives to the corresponding carboxylic acids or ketones selectively in high yields under irradiation of vis. This new oxidation is interesting in keeping with the notion of Green Chemistry due to the non-use of heavy metals and halogenated solvents, waste reduction, and the use of molecular oxygen.

Full text of DOI:10.1016/j.tetlet.2008.02.116

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2792–2794
Aerobic photo-decarboxylation of a-hydroxy carboxylic acid derivatives
under visible light irradiation in the presence of catalytic iodine
Hiroki Nakayama, Akichika Itoh *
Gifu Pharmaceutical University 5-6-1, Mitahora-higashi, Gifu 502-8585, Japan
Received 18 January 2008; revised 19 February 2008; accepted 22 February 2008
Available online 4 March 2008
Abstract
A catalytic amount of iodine enables us to carry out aerobic photo-decarboxylation of a-hydroxy carboxylic acid derivatives to the
corresponding carboxylic acids or ketones selectively in high yields under irradiation of vis. This new oxidation is interesting in keeping
with the notion of Green Chemistry due to the non-use of heavy metals and halogenated solvents, waste reduction, and the use of molec-
ular oxygen.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Aerobic; a-Hydroxy carboxylic acid; Iodine; Photo-decarboxylation; Visible light
The notion of Green Chemistry is becoming well estab-
lished, and the development of environmentally benign
processes is the goal of various research projects. The
method using molecular oxygen which possesses a high
atom effect as an oxidant is a way consistent with this
notion. In this background in mind, we have studied aero-
bic photo-oxidation, and found several reactions in the
safe, economical and steady, and the equipment is more
easily installed, if visible light (vis) from a fluorescent lamp
is applicable instead of the high-pressure mercury lamp;
however, unfortunately, among our study, only a trace
amount of the oxidative product was obtained with
FSM-16 mentioned above under irradiation of vis by a
general-purpose fluorescent lamp. This is the driving force
of our continued wide-ranging studies on this oxidation,
and we have found that iodine is suitable for this purpose.
The effective use of vis is a most important research topic at
this time of hoped-for the development of new energy con-
version and energy-using technology, and our new oxida-
tion method is interesting since there have been few
reports about the application of photo-oxidation with vis
by a general-purpose fluorescent lamp to fine chemis-
1
presence of some catalysts. Among them, oxidative
1
o
photo-decarboxylation of a-hydroxy carboxylic acids,
1
o
1m
phenyl acetic acids and N-protected a-amino acids to
afford the corresponding carbonyl compounds in the pres-
2
ence of FSM-16, a mesoporous silica, is environmentally
more benign than the previous methods, which involve
the use of heavy metals and large quantities of complex
3
organic reagents, due to its metal free and usage of recy-
1
a–c,g
clable FSM-16. Although this reaction has the advantages
of both acquisition of safe reagents and easy work-up, UV,
which is irradiated by an expensive high-pressure mercury
lamp and has harmful effect on the human body, is needed
to proceed. As mentioned above, this reaction becomes
try.
We now report our detailed study for visible light
oxidative photo-decarboxylation of a-hydroxy carboxylic
acids in the presence of catalytic iodine.
Table 1 shows the results of study of reaction conditions
for the aerobic photo-decarboxylation conducted with
mandelic acid (1, 0.3 mmol) as test substrate in the presence
of catalysts in typical solvents equipped with an oxygen
balloon under irradiation with 500 W xenon-lamp through
the filter, which absorbs the UV of wavelength less than
*
Corresponding author. Tel.: +81 58 237 3931x222; fax: +81 58 237
5979.
E-mail address: itoha@gifu-pu.ac.jp (A. Itoh).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.116

H. Nakayama, A. Itoh / Tetrahedron Letters 49 (2008) 2792–2794
2793
Table 1
Table 2
Study of reaction conditions of aerobic photo-decarboxylation
Aerobic photo-decarboxylation of various a-hydroxy carboxylic acid
derivatives
hv (500W xenon-lamp)
HO CO H
O
2
catalyst, O -balloon
hv (500W xenon-lamp)
2
Ph
H
Ph OH
solvent (5 mL)
substrate
0.3 mmol)
I (5 mol%), O -balloon
1
(0.3 mmol)
2
2
2
product
(
EtOAc (5 mL)
a
Entry
Solvent
Catalyst (mol %)
Time (h)
Yield (%)
a
Entry Substrate
Time Product
h)
Yield
(%)
1
2
3
4
5
6
7
8
9
Acetone
MeCN
Hexane
MeOH
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(1)
(10)
—
5
5
5
5
5
5
5
5
38
35
0
Trace
0
70
65
34
77
82
62
59
6
(
HO CO H
O
2
1
2
1
3
15
15
2
4
82
84
H
OH
CH
2
Cl
2
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
HO CO H
O
2
b
H
OH
c
MeO
Cl
MeO
Cl
10
15
5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
a
HO CO H
2
O
3
4
5
6
H
5
7
9
15
24
24
OH
6
8
84
5
15
15
15
5
5
5
5
5
5
5
d
(5)
(5)
0
3
HO CO H
O
O
2
e
b
86
CI
4
(5)
52
55
70
3
25
24
68
57
NIS (5)
LiI (5)
NaI (5)
KI (5)
CsI (5)
CaI
Br
HO CO H
2
b
10 86
(5)
(5)
HO CO H
2
2
11 24
—
0
2
5
H
4
All yields were for pure, isolated products.
a
b
All yields were for pure, isolated products.
The reaction was carried out under the irradiation of 400 W Hg-lamp.
The reaction was carried out under the irradiation of fluorescent lamp.
The reaction was carried out in the dark.
b
c
2
The reaction was carried out in the presence of 1 mol % of I .
d
e
The reaction was carried out under Ar.
for 24 h (entries 4 and 5). Unfortunately, 2-hydroxy-n-octa-
noic acid (11), an aliphatic substrate, was intact under this
reaction condition (entry 6).
4
3
70 nm. Among the solvents and lamps examined, ethyl
Scheme 1 shows a plausible path of this oxidation,
which is postulated by considering the necessity of contin-
uous irradiation, a catalytic amount of iodine and molecu-
lar oxygen in this reaction. a-Hydroxy carboxylic acid 12
initially reacts with iodine to generate 13, which transforms
acetate and 500 W xenon-lamp were found to be most
effective (entries 1–8). The yield of 2 was increased when
the reaction time was extended up to 15 h (entry 10).
Although 5 mol % of iodine was required to give 2 in high
yield, an excess amount of iodine inhibited this oxidation
(
entries 6, 11 and 12). On the other hand, the result that,
without iodine, irradiation or molecular oxygen, 2 was
not obtained or was obtained only in low yield shows the
necessity of all of the foregoing conditions for this reaction
I2
.
HO CO H
HO CO2I
Ar
HO CO2
2
hv
1)
Ar
R
R
Ar
R
.
1
.
2
HI
Ar
13
I
14
CO2
(
entries 13–15). Although iodine, lithium iodide and cal-
cium iodide were found to be superior to other catalysts
we examined, we exclusively used iodine, which is metal-
free and inexpensive, as an iodo source. On the other hand,
product 2 was obtained only in moderate yield when using
bromine (entries 6, 16–23).
Table 2 shows the results of this decarboxylation using
several substrates under the reaction conditions mentioned
above. Mandelic acid derivatives (1, 3 and 5) produced to
the corresponding benzoic acids (2, 4 and 6), respectively,
in high yields regardless of electron-donating group or elec-
tron-withdrawing group at aromatic nucleus (entries 1–3).
Acetophenone (8) and benzophenone (10) were obtained
in 86% yield when atrolactic acid (7) and benzilic acid (9)
were used as substrates in the presence of 1 mol % of iodine
.
I
HO
Ar
O
R
R
1
5
HI
16
O
HI
O
hν, O2
2)
16
Ar
OOH
Ar
OH
(
R = H)
17
IOH
18
hv, O2
3)
HI
I2 + H O
2
hv, O2
IOH + HI
I2 + H O
2
Scheme 1. Plausible path of the aerobic photo-decarboxylation.

2794
H. Nakayama, A. Itoh / Tetrahedron Letters 49 (2008) 2792–2794
to radical species 14 by irradiation with 500 W xenon-
lamp. The corresponding carbonyl compound 16 is formed
from 14 through decarboxylation and elimination of
hydrogen iodide with iodo radical (Eq. 1). When 16 is alde-
hyde (R = H), further oxidation proceeds, and the corre-
sponding carboxylic acid 18 is generated through peracid
Hashimoto, S.; Masaki, Y. Synlett 2005, 2639–2640; (k) Itoh, A.;
Hashimoto, S.; Kuwabara, K.; Kodama, T.; Masaki, Y. Green Chem.
2
005, 7, 830–832; (l) Itoh, A.; Kodama, T.; Hashimoto, S.; Masaki, Y.
Synthesis 2003, 2289–2291; (m) Itoh, A.; Kodama, T.; Inagaki, S.;
Masaki, Y. Chem. Lett. 2000, 542–543; (n) Itoh, A.; Kodama, T.;
Inagaki, S.; Masaki, Y. Org. Lett. 2000, 2, 2455–2457; (o) Itoh, A.;
Kodama, T.; Inagaki, S.; Masaki, Y. Org. Lett. 2000, 2, 331–333.
2. (a) Inagaki, S.; Koiwai, A.; Suzuki, N.; Fukushima, Y.; Kuroda, K.
Bull. Chem. Soc. Jpn. 1996, 69, 1449–1457; (b) Inagaki, S.; Fukushima,
Y.; Kuroda, K. J. Chem. Soc., Chem. Commun. 1993, 680–682.
. (a) Farhadi, S.; Zaringhadam, P.; Sahamieh, R. Z. Tetrahedron Lett.
2006, 47, 1965–1968; (b) Favier, I.; Dunach, E. Tetrahedron 2003, 59,
1823–1830; (c) Jain, S. L.; Sharma, V. B.; Sain, B. Synth. Commun.
5
,6
1
7 (Eq. 2). Iodine is regenerated by aerobic photo-oxida-
tion of hydrogen iodide or hypoiodous acid (Eq. 3).
In conclusion, we have found the oxidative photo-decar-
boxylation of a-hydroxy carboxylic acid derivatives to the
corresponding carboxylic acids or ketones selectively in
high yields. This new oxidation is interesting in keeping
with the notion of Green Chemistry due to the non-use
of heavy metals and halogenated solvents, waste reduction,
and the use of molecular oxygen.
3
2
003, 33, 3875–3878; (d) Blay, G.; Fernandez, I.; Formentin, P.; Pedro,
J. R.; Rpsello, A. R.; Ruiz, R.; Journaux, Y. Tetrahedron Lett. 1998,
9, 3327–3330. and references cited therein.
3
4
. A typical procedure follows: A dry ethyl acetate solution (5 mL) of the
mandelic acid (1, 0.3 mmol) and I2 (0.015 mmol) in a pyrex test tube
2
equipped with an O -balloon was irradiated without stirring condition
for 15 h with a 500 W xenon-lamp through the filter which absorbs the
UV of wavelength less than 370 nm, which was set from the test tube in
the distance of 45 cm. The reaction mixture was concentrated under
reduced pressure. The pure product was obtained by purification with
preparative TLC.
References and notes
1. (a) Sugai, T.; Itoh, A. Tetrahedron Lett. 2007, 48, 9096–9099; (b)
Hirashima, S.; Itoh, A. Photochem. Photobiol. Sci. 2007, 55, 861–864;
(
c) Hirashima, S.; Itoh, A. Green Chem. 2007, 9, 318–320; (d) Sugai, T.;
5. Kaneda, K.; Ueno, S.; Imanaka, T.; Shimotsuma, E.; Nishiyama, Y.;
Ishii, Y. J. Org. Chem. 1994, 59, 2915–2917.
Itoh, A. Tetrahedron Lett. 2007, 48, 2931–2934; (e) Kuwabara, K.;
Itoh, A. Synthesis 2006, 1949–1952; (f) Hirashima, S.; Hashimoto, S.;
Masaki, Y.; Itoh, A. Tetrahedron 2006, 62, 7887–7891; (g) Nakayama,
H.; Itoh, A. Chem. Pharm. Bull. 2006, 54, 1620–1621; (h) Hirashima,
S.; Itoh, A. Synthesis 2006, 1757–1759; (i) Itoh, A.; Hashimoto, S.;
Kodama, T.; Masaki, Y. Synlett 2005, 2107–2109; (j) Itoh, A.;
6. Although the corresponding carboxylic acid was obtained in 45% yield
under the same reaction conditions when using benzaldehyde as a
substrate, the yield was reduced to 22% yield without iodine. This
suggests that hydrogen iodide, generated from iodine, promotes the
transformation of 17 and 18.