Direct α-hydroxylation of ketones catalyzed by organic-inorganic hybrid polymer

Article abstract of DOI:10.1246/cl.2006.1094

Direct α-hydroxylation of ketones using molecular oxygen was accomplished by organic-inorganic hybrid polymers. A newly prepared Cu-piperazine hybrid polymer was tolerant to the basic conditions, and with employment of lithium hydroxide smoothly catalyzed

Full text of DOI:10.1246/cl.2006.1094

1094
Chemistry Letters Vol.35, No.10 (2006)
Direct ꢀ-Hydroxylation of Ketones Catalyzed
by Organic–Inorganic Hybrid Polymer
Takayoshi Arai,1 Toru Sato,2 Hiroshi Noguchi,2 Hirofumi Kanoh,1
Katsumi Kaneko,1 and Akira Yanagisawaꢀ1
1Department of Chemistry, Faculty of Science, Chiba University, Inage 263-8522
2Graduate School of Science and Technology, Chiba University, Inage 263-8522
(Received June 27, 2006; CL-060723; E-mail: ayanagi@faculty.chiba-u.jp)
Direct ꢀ-hydroxylation of ketones using molecular oxygen
Table 1. Direct ꢀ-hydroxylation of ketone 1 under basic condi-
tions
was accomplished by organic–inorganic hybrid polymers. A
newly prepared Cu-piperazine hybrid polymer was tolerant to
the basic conditions, and with employment of lithium hydroxide
smoothly catalyzed the ꢀ-hydroxylation of ketones. In the
present catalytic process not only tetralone derivatives, but also
acyclic ketones were converted to the ꢀ-hydroxy ketones in
good yield.
O2
Cu-bpy (10 mol % as Cu)
Base (0.5 equiv.)
P(OEt)3 (0.8 equiv.)
O
O
OH
Me
Me
EtOH, 80 °C, 1 h
1
2
Entry
Base
Yield/%
1
2
3
4
5
—
no reaction
piperazine
DBU
no reaction
ꢀ-Hydroxy carbonyls are valuable building blocks in organ-
ic synthesis and impressive structural motifs in a variety of
biologically active natural products. The biological importance
of the ꢀ-hydroxy carbonyl functionality has inspired the devel-
opment of a number of catalytic processes.1 Among the various
useful processes, the oxidation of a carbon center adjacent to
carbonyls is a beneficial route to prepare the fascinating
functionality, and the ultimate oxidant would be the molecular
oxygen from the viewpoint of the promotion of sustainable
chemistry.2
In the course of our recent effort to apply the organic–inor-
ganic hybrid polymer directed toward organic synthesis, we have
succeeded in the catalytic synthesis of ꢀ-hydroxy ketones using
the molecular oxygen as the oxidant.3 Thus, in the previous
report, the hybrid polymer ‘‘{[Cu(bpy)(BF4)2(H2O)2](bpy)}n
(bpy = 4,40-bipyridine)’’4 abbreviated as ‘‘Cu-bpy’’ shows ac-
tivity to provide the ꢀ-hydroxy ketones from the trimethylsilyl
enolates (Scheme 1).5,6
Although the Cu-bpy catalyst showed remarkable catalytic
activity, one drawback is the requirement of preformation of
the silyl enolate of the ketones before enforcing the target reac-
tion. One apparent way to solve this problem is the use of car-
bonyl compounds directly. We report herein that the direct mo-
lecular oxygen derived ꢀ-hydroxylation of ketones using the or-
ganic–inorganic hybrid polymers under the basic conditions.
Toward the development of direct ꢀ-hydroxylation of
ketones, initially, we screened various bases to generate the
enolate in situ. The results are summarized in Table 1. Among
the bases tested, lithium hydroxide monohydrate smoothly pro-
moted the reaction of 2-methyl-1-tetralone (1) to give ꢀ-hydroxy
ketone 2 in 82% yield in 1 h (Entry 5).7 The use of amine bases
31
7
NaOH
LiOH–H2O
82
resulted in lower chemical conversions (Entries 2 and 3).
Though we succeeded in the first direct ꢀ-hydroxylation us-
ing the hybrid polymer, it was revealed that the Cu-bpy catalyst
was dissolved in the reaction media under the basic conditions.
This makes the recovery and reuse of catalyst difficult. More se-
riously, the catalytic activity dramatically declined after dissolv-
ing. For example, the reaction using sodium hydroxide was com-
pletely disrupted within 1 h under the reaction conditions. To
overcome the problem, we decided to prepare new organic–inor-
ganic hybrid polymers in structural variation of the ligand frame-
work. With the analogous method for the preparation of the Cu-
bpy complex, a series of hybrid polymers were prepared, and the
catalytic activities were examined as summarized in Table 2.
To our delight, the hybrid polymer derived from piperazine
(Cu-piperazine) showed remarkable catalytic activity to provide
ꢀ-hydroxy ketone 2 in 79% yield, and the complex did not dis-
solve in EtOH under the basic conditions (Entry 4).8 After the
reaction completed, the catalyst was recovered in 81% yield
by centrifugation. The survived catalytic activity was confirmed
Table 2. A series of hybrid polymers and the catalyst activitiesa
O2
Cu-diamine hybrid polymer
(10 mol % as Cu)
LiOH–H2O (0.5 equiv.)
P(OEt)3 (0.8 equiv.)
1
2
EtOH, 80 °C
Entry
Diamine
pyrazine
Yield/%
Solubility
1
2
3
4
5
no reaction
soluble
1) cat. Cu-bpy, O2
2) P(OEt)3
Me3SiO
R1
O
p-phenylenediamine
p-xylylenediamine
piperazine
67
68
79
65
insoluble
insoluble
insoluble
insoluble
R2
OH
R2 R3
up to 85%
R1
EtOH–H2O, 0 °C
R3
DABCO
Scheme 1. Organic–inorganic hybrid polymer catalyzed syn-
thesis of ꢀ-hydroxy ketones from the trimethylsilyl enolates.
aCatalyst amount was calculated as the similar structure to
{[Cu(bpy)(BF4)2(H2O)2](bpy)}n (bpy = 4,40-bipyridine).
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.10 (2006)
1095
Table 3. Cu-piperazine-catalyzed direct ꢀ-hydroxylation of
ketones
current conditions. This fact suggests that the selective reaction
was performed from the thermodynamic enolate.9
In conclusion, we have disclosed the direct ꢀ-hydroxylation
of ketones using molecular oxygen. The newly prepared Cu-
piperazine complex is durable against the strong base, and the
reaction proceeds smoothly with the coexistence of lithium
hydroxide.
O2
Cu-diamine hybrid polymer
(10 mol % as Cu)
LiOH–H2O, P(OEt)3
O
O
OH
R2
R2
R1
R1
R3
R3
EtOH, 80 °C
Cu-bpya
Time/h Yield/%
Cu-piperazineb,c
Entry
1
Substrate
Time/h Yield/%
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology of the Japanese Government, and by
grants from the Graduate School of Science and Technology,
and Venture Business Laboratory, Chiba University.
1
14.5
84
14.5
77
O
2
3
9
65
9
76
MeO
O
References and Notes
9
9
60
74
9
9
72
60
1
Recent reviews of the synthesis of ꢀ-hydroxy ketones: A. B. Jones,
in Comprehensive Organic Synthesis, ed. by B. M. Trost, I.
Fleming, Pergamon, Oxford, 1991, Vol. 7, p. 151.
MeO
O
2
Recent progress in the synthesis of ꢀ-hydroxy kenones: a) H.
Yamamoto, M. Tsuda, S. Sakaguchi, Y. Ishii, J. Org. Chem.
4
´
1997, 62, 7174. b) A. Solladie-Cavallo, P. Lupattelli, L. Jierry,
P. Bovicelli, F. Angeli, R. Antonioletti, A. Klein, Tetrahedron
O
5
6
11
12
2
18
12
53
71
´
Lett. 2003, 44, 6523. c) H. Sunden, M. Engqvist, J. Casas, I.
Ibrahem, A. Cordova, Angew. Chem., Int. Ed. 2004, 43, 6532.
´
3
4
T. Arai, H. Takasugi, T. Sato, H. Noguchi, H. Kanoh, K. Kaneko,
A. Yanagisawa, Chem. Lett. 2005, 34, 1590.
O
67
a) S. Ohnishi, T. Ohmori, T. Ohkubo, H. Noguchi, L. Di, Y.
Hanzawa, H. Kanoh, K. Kaneko, Appl. Surf. Sci. 2002, 196, 81.
b) D. Li, K. Kaneko, Chem. Phys. Lett. 2001, 335, 50. c) A. J.
Blake, S. J. Hill, P. Hubberstey, W.-S. Li, J. Chem. Soc., Dalton
Trans. 1997, 913.
O
7
71
13
79
13
O
8
9
15.5
15.5
33
49
15.5
15.5
67
56
5
6
Remarkable metal-catalyzed synthesis of ꢀ-hydroxy ketones from
the silyl enolates: a) T. V. Lee, J. Toczek, Tetrahedron Lett. 1982,
23, 2917. b) T. Takai, T. Yamada, O. Rhode, T. Mukaiyama,
Chem. Lett. 1991, 281.
OMe
O
Selected examples of the applications of organic–inorganic hybrid
polymer to organic synthesis: a) C. Bianchini, E. Farnetti, M.
Graziani, J. Kaspar, F. Vizza, J. Am. Chem. Soc. 1993, 115,
1753. b) M. Fujita, Y. J. Kwon, S. Washizu, K. Ogura, J. Am.
Chem. Soc. 1994, 116, 1151. c) J. S. Seo, D. Whang, H. Lee,
S. I. Jun, J. Oh, Y. J. Jeon, K. Kim, Nature 2000, 404, 982. d) S.
Takizawa, H. Somei, D. Jayaprakash, H. Sasai, Angew. Chem.,
Int. Ed. 2003, 42, 5711. e) R. Dorta, L. Shimon, D. Milstein,
J. Organomet. Chem. 2004, 689, 751. f) X. Wang, K. Ding, J.
Am. Chem. Soc. 2004, 126, 10524. g) H. Guo, X. Wang, K. Ding,
Tetrahedron Lett. 2004, 45, 2009. h) Y. Liang, Q. Jing, X. Li. L.
Shi, K. Ding, J. Am. Chem. Soc. 2005, 127, 7694. i) S.-H. Cho,
B. Ma, S. T. Nguyen, J. T. Hupp, T. E. Albrecht-Schmitt, Chem.
Commun. 2006, 2563.
aLiOH–H2O (0.5 equiv.) and P(OEt)3 (0.8 equiv.) were used. bLiOH–H2O
(0.3 equiv.) and P(OEt)3 (0.8 equiv.) were used. cCatalyst amount was
calculated as similar structure to {[Cu(bpy)(BF4)2(H2O)2](bpy)}n (bpy =
4,40-bipyridine).
in the second use in the promotion of the reaction (68% yield).
Encouraged by the success of the Cu-piperazine-catalyzed
synthesis of ꢀ-hydroxy ketone, the synthetic procedure was
optimized. The amount of LiOH could be reduced to 0.3 equiv.
for obtaining the synthetically useful chemical yield (2: 77% for
14.5 h). Under the optimized conditions, the generality of the
new direct method was examined in Table 3.
Various advantages were realized in the correlation of the
catalytic activity with that obtained by using the original Cu-
bpy catalyst. In the reaction of a sterically hindered substrate
such as 2-propyl-1-tetralone (Entry 5), which shows relatively
lower reactivity, the Cu-piperazine complex catalyzed the ꢀ-hy-
droxylation in 53% yield, despite the fact that the Cu-bpy was
hard to promote the reaction (only 2%). In the reaction of 1-
methyl-2-tetralone, only the tertiary carbon center adjacent to
the carbonyl group was oxidized at 80 ꢁC (Entry 6). Not only
the cyclic ketones, but also acyclic ketones were transformed
to the corresponding ꢀ-hydroxy ketones, and the chemical yields
were higher than those obtained using Cu-bpy (Entries 8 and 9).
In the reaction of 2-benzylcyclohexan-1-one, only 2-benzyl-
2-hydroxycyclohexan-1-one was obtained in 13% under the
7
8
Though the aerobic oxidation of metal enolates has been reported,1
ꢀ-hydroxylation of 1 does not proceed without use of Cu-bpy
catalyst.
Preparation of Cu-piperazine catalyst: To the solution of
Cu(BF4)2–6H2O (237 mg, 1 mmol) in H2O (25 mL) was added pi-
perazine (172 mg, 2 mmol). After standing 17 days, the resulting
insoluble residue was collected by centrifugation (3000 rpm),
and dried under reduced pressure to give the Cu-piperazine
complex (144 mg, ca. 35% yield as similar structure to {[Cu(bpy)-
(BF4)2(H2O)2](bpy)}n).
The catalysis using Cu-bpy for the kinetic trimethylsilyl enolate of
2-benzylcyclohexanone provided 2-benzyl-6-hydroxycyclohexan-
1-one in ca. 3% yield under the reaction conditions similar to those
reported in Ref. 3, while 2-benzyl-2-hydroxycyclohexan-1-one
was not obtained at all.
9
Published on the web (Advance View) August 29, 2006; doi:10.1246/cl.2006.1094