A novel synthesis of α-hydroxy- and α,α′- dihydroxyketone from α-iodo and α,α′-diiodo ketone using photoirradiation

Article abstract of DOI:10.1016/j.tetlet.2003.10.082

A novel reaction of α-iodo ketone (α-iodocycloalkanone, α-iodo-β-alkoxy ester, and α-iodoacyclicketone) with irradiation under a high-pressure mercury lamp gave the corresponding α-hydroxyketone in good yields. In the case of α,α′- diiodo ketone, α,α′-dihydroxyketone which little has been reported until now was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxy- and α,α′- dihydroxyketone.

Full text of DOI:10.1016/j.tetlet.2003.10.082

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9307–9311
A novel synthesis of a-hydroxy- and a,a%-dihydroxyketone from
a-iodo and a,a%-diiodo ketone using photoirradiation
C. Akira Horiuchi,a,* Akinori Takeda,a Wen Chai,a Kishoh Ohwada,a Shun-Jun Jib and
T. Tomoyoshi Takahashic
aDepartment of Chemistry, Rikkyo (St. Paul’s) University, Nishi-Ikebukuro, Toshima-Ku, Tokyo 171-8501, Japan
bDepartment of Chemistry and Chemical Engineering, Suzhou University, 1 Shizi St. Suzhou, Jiangsu 215006, PR China
cDepartment of Chemistry, The Jikei University School of Medicine, Kokuryo-cho, Chofu-shi, Tokyo 182-8570, Japan
Received 27 August 2003; revised 22 September 2003; accepted 10 October 2003
Abstract—A novel reaction of a-iodo ketone (a-iodocycloalkanone, a-iodo-b-alkoxy ester, and a-iodoacyclicketone) with
irradiation under a high-pressure mercury lamp gave the corresponding a-hydroxyketone in good yields. In the case of a,a%-diiodo
ketone, a,a%-dihydroxyketone which little has been reported until now was obtained. This reaction affords a new, clean and
convenient synthetic method for a-hydroxy- and a,a%-dihydroxyketone.
© 2003 Elsevier Ltd. All rights reserved.
a-Hydroxyketones are usually prepared by one of the
following methods: a-hydroxylation by treatment of
their enolate forms with a molybdenum peroxide
reagent in THF–hexane at −70°C,1 transformation of
the enamine derivatives of ketones to a-hydroxy deriva-
tives by molecular oxygen,2 and a-hydroxylation of silyl
enol ethers with m-chloroperbenzoic acid,3 or with cer-
tain other oxidizing agents.4
synthesis, which were synthesized by our laboratory by
a new method.9 These iodo ketones are unstable and
sensitive to light. We thus tried to obtain useful prod-
ucts from these iodo compounds. In this series, we have
already shown that the photo-dehydroiodination from
a-iodocycloalkanones in hexane affords a,b-unsatu-
rated ketones as major products, accompanied by pho-
toreduced products as by-products. In the hexane
containing a small amount of water, the substituted
product 2-hydroxycycloalkanone was also obtained.10
In our previous paper, we found that photo-cleavage of
the carbonꢀcarbon bond of a-iodocycloalkanones giv-
ing v,v-dialkoxyalkanoic esters in alcohol gives a-
hydroxyketone as intermediates.11 In order to increase
the yield of a-hydroxyketone, we undertook a closer
inquiry into the reaction conditions. Herein, we report
that the irradiation of a-iodoalkanones 1–12, 22–25 in
solvents containing a small amount of air gave the
a-hydroxyketones 1d–12d, 22d–25d under a high-pres-
sure mercury lamp. The reaction of a-iodo- and a,a%-
diiodo ketone using photoirradiation in alcohols,
hexane, and acetone, etc., in the presence of air
afforded the corresponding a-hydroxy- and a,a%-dihy-
droxyketone in good yield (Scheme 1).
It is known that there has been considerable interest in
the development of direct methods for the synthesis of
a-hydroxyketones using nontoxic hypervalent iodine
reagents, which involve the following methods: reaction
of ketone with iodobenzene diacetate in the presence of
potassium hydroxide in methanol and then hydrolysis
of the dimethylacetals;5 oxidation of enol silyl ether of
acetophenone using the system iodosobenzene/boron
trifluoride etherate/water in methylene chloride at
−40°C;6 and reaction of ketones with [bis(trifluoroace-
toxy)] iodobenzene and trifluoroacetic acid in acetoni-
trile–water under acidic conditions.7
During the course of our studies, we investigated a
novel self-coupling reaction of cyclic ketones with a
high-pressure mercury lamp to give the corresponding
pinacol-type compound in good yields.8 a-Iodocy-
cloalkanones are important as intermediates in organic
The irradiation of a-iodo ketones (1–12) in a solvent at
room temperature under air atmosphere with a 400 W
mercury lamp for 10–12 h gave the corresponding
a-hydroxyketone (1d–12d) in good yields. These results
are summarized in Table 1.
* Corresponding author. Tel.: +81-3-3985 2397; fax: +81-3-3985 2397;
e-mail: horiuchi@rikkyo.ac.jp, cahoriuchi@nifty.com
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.082

9308
C. A. Horiuchi et al. / Tetrahedron Letters 44 (2003) 9307–9311
Scheme 1.
Table 1. Photochemical reaction of a-iodo ketone in the presence of air
Run
Substrate
n
Solvent
Base (mol. equiv.)
Time (h)
Product (%)a
a
b
c
d
e
1
2
3
4
5
6
7
8
1
1
2
2
3
3
5
7
7
Me2CO
Me2CO
MeOH
Me2CO
MeOH
Me2CO
Me2CO
MeOH
Me2CO
Me2CO
Me2CO
Me2CO
Me2CO
Me2CO
Me2CO
Me2CO
Me2CO
MeOH
MeOH
EtOH
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (1)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
10
10
12
10
12
10
10
12
10
12
10
12
10
12
10
10
10
48
12
24
72
68
10
41
t
35
t
24
t
t
t
t
t
t
t
t
t
t
t
t
t
t
4
t
4
t
3
t
t
3
t
5
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
49
56
42
60
35
70
95
47
95
70
81
30
87
31
89c
92c
94c
85
62
52
86
85
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
2%b
3
3%b
4
5
5%b
6
7
9
10
t
15
t
t
t
t
t
t
t
t
t
t
t
10
11
12
13
14
15
16
17
18
19
20
21
22
7
8
8%b
9
9%b
10
11
12
26%
26%
26%
26%
26%
(exo:endo=40:60)c
(exo:endo=40:60)c
(exo:endo=33:67)c
(exo:endo=43:57)c
(exo:endo=43:57)c
Me2CO
MeCN
t
t
t
t
Reaction conditions: Substrate (0.1 mmol) in solvent (10 ml) was irradiated by a high pressure mercury lamp (400W) under air.
a Yields were determined by GLC.
b KI (0.1 mmol) was used.
c Product ratio was determined from the peak area ratio of the NMR spectrum. t=trace.

C. A. Horiuchi et al. / Tetrahedron Letters 44 (2003) 9307–9311
9309
As can be seen from Table 1, it was found that the
reaction containing triethylamine (molar equivalent)
gives preferentially the a-hydroxyketone. Thus, in order
to discuss the reactivity of the a-iodocyclicketone, it
was compared with that of the bromo derivatives. The
reaction of a-bromo ketone did not give a-hydroxyke-
tone. So, the following experiment was attempted. The
reaction of a-bromo ketone with KI gave the corre-
sponding a-hydroxyketone (runs 3, 5, 8, 12, and 14).
On the basis of these results, it was found that in the
case of the bromo ketone with KI, the yields of a-
hydroxy ketone are lower. However, in the case of
nonoccurrence of a-iodination, i.e., a-iodocamphor,
this reaction can not be applied to the synthesis of
a-hydroxycamphor. In order to overcome this problem,
we tried the reaction of a-bromocamphor (26%) with KI.
As can be seen from Table 1 (runs 18–22), it was found
that a-hydroxycamphor was obtained in good yields.
We further developed the reaction conditions to
decrease the reduced ketone and v-formyl alkanoic
acid. These results are summarized in Table 2. As can
be seen from Table 2, it was found that amines of
i-Pr2NH, Et3N, and n-Pr3N are effective. Moreover, in
the case of absence of triethylamine, a-hydroxyketone
was not obtained, and v-formylcarboxylic acid was
formed.
Table 2. Effects of some amines for photochemical reaction of a-iodo ketone
Run
Substrate
n
Base (mol. equiv.)
Time (h)
Product (%)a
a
b
c
d
e
1
2
3
4
5
6
7
8
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5%
5
5
5
5
5
5
5
5
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
i-Pr2NH (1)
Et3N (1)
n-Pr3N (1)
Et2NH (1)
PhNMe2 (1)
C5H5N (1)
C5H5N (10)
C5H5N (50)
C4H5NH (1)
C4H5NH (10)
t-BuOK (1)
NaOH (1)
NH3 (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
Et3N (1)
0
10
10
10
43
50
10
10
15
40
40
10
20
20
10
15
15
25
62
17
17
18
12
10
10
10
10
10
10
10
10
t
t
t
t
10
16
16
11
9
4
t
t
t
t
t
t
t
t
t
t
t
t
t
t
2
7
t
t
t
t
t
7
t
6
15
9
8
2
3
2
95
95
95
90
85
17
24
43
30
37
33
2
90
95
68
63
83
87
90
77
77
47
5
0
0
0
0
0
45
43
30
46
0
0
0
0
0
0
0
0
0
0
0
0
0
42
41
45
52
53
28
59
70
t
2
4
4
13
10
11
6
22
58
93
5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
7
t
t
4
t
t
t
t
t
t
t
3
9
t
2
t
t
12
t
7
t
3
50
t
3
2
3
8
4
5
4
5
0
0
0
0
0
0
0
5
9
2
13
8
t
t
t
t
17
13
3
12
Reaction conditions: Substrate (0.1 mmol) in acetone (10 ml) was irradiated by a high pressure mercury lamp (400 W) under air.
a Yields were determined by GLC. t=trace.
Scheme 2.

9310
C. A. Horiuchi et al. / Tetrahedron Letters 44 (2003) 9307–9311
Thus, this reaction affords hydroxydiosphenol12,13 in
buchu oil from the leaves of Barosma betulina Bartl.
(mountain buchu) (Scheme 2).
a-iodo-b-alkoxy esters (22–25) in acetone gave the cor-
responding a,a%-dihydroxyketones (13f–21f) and a-
hydroxy-b-alkoxy esters (22d–25d) in good yield. These
results are summarized in Table 3.
Moreover, it is interesting that in the case of a,a%-diiodo
ketones, a,a%-dihydroxyketones were obtained in good
yields. The reaction of a,a%-diiodo ketones (13–21) and
From these results, it is considered that the reaction
proceeds by two pathways (Fig. 1); in the absence of
Table 3. Photochemical reaction of a-iodo-b-alkoxy ester and a,a%-diiodo ketone
Run
Substrate
R1
R2
Time (h)
Product (%)
1
2
3
4
5
6
7
8
13 (cis/trans=95/5)
14 (cis/trans=90/10)
15 (cis/trans=75/25)
16 (cis/trans=62/38)
Me
Et
n-C3H7
n-C4H9
Me
Me
Et
5
6
6
6
5
3
3
5
5
13f (47, cis/trans=50/50)a,b
14f (58, cis/trans=50/50)a,b
15f (65, cis/trans=50/50)a,b
16f (73, cis/trans=50/50)a,b
17f (70, cis/trans=50/50)a,b
18f (t)
n-C3H7
n-C4H9
n-C7H15
n-C3H7
n-C4H9
17 (cis/trans=54/46)
18
19
20
21
22
23
24
25
H2
H2
19f (t)
CH2-(CH2)2-CH2
CH2-(CH2)7-CH2
Me
Me
Ph
Ph
20f (82, cis/trans=87/13)a,b
21f (54, cis/trans=90/10)a,b
22d (65, syn/anti=81/19)a,b
23d (62, syn/anti=80/20)a,b
24d (72, syn/anti=84/16)a,b
25d (75, syn/anti=81/10)a,b
9
10
11
12
13
Me
Et
Me
Et
10
10
8
8
Reaction conditions: Substrate (0.1 mmol) in solvent (10 ml) was irradiated by a high pressure mercury lamp (400W) under air.
a Yields were determined by GLC.
b KI (0.1 mmol) was used.
Figure 1. Pathway from a-iodocyclododecanone into a-hydroxyketone.

C. A. Horiuchi et al. / Tetrahedron Letters 44 (2003) 9307–9311
9311
air, hydroxyl ion attacks at C2 preferentially and 2-
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