A simple and effective method for α-hydroxylation of β-dicarbonyl compounds using oxone as an oxidant without a catalyst

Article abstract of DOI:10.1002/ejoc.201000940

Oxone has been found to be a highly efficient reagent for the introduction of a hydroxy group at the α position of a variety of β-dicarbonyl compounds in the homogeneous solvent mixture of water and 1,4-dioxane at 60 °C. We have developed a simple and effective method for the α-hydroxylation of β-dicarbonyl compounds using Oxone as anoxidant in the homogeneous solvent mixture of water and 1,4-dioxane at 60 °C without a catalyst. Copyright

Full text of DOI:10.1002/ejoc.201000940

FULL PAPER
DOI: 10.1002/ejoc.201000940
A Simple and Effective Method for α-Hydroxylation of β-Dicarbonyl
Compounds Using Oxone as an Oxidant without a Catalyst
Jun Yu,[a] Jian Cui,[a] and Chi Zhang*[a]
Keywords: Synthetic methods / Oxidation / Hydroxylation / Enols
Oxone has been found to be a highly efficient reagent for the
of β-dicarbonyl compounds in the homogeneous solvent mix-
introduction of a hydroxy group at the α position of a variety
ture of water and 1,4-dioxane at 60 °C.
sulfur-[20] and selenium-containing[21] compounds. More re-
cently, the ability of Oxone has also been demonstrated in
the oxidation of alcohols to the corresponding aldehydes
and ketones catalysed by TEMPO and nBu4NBr,[22] the oxi-
dation of aldehydes to the corresponding acids or esters,[23]
the deprotection of acetals and tert-butyldimethylsilyl
ethers,[24] the oxidative cleavage of olefins, alkynes, α- or β-
diketones and α-hydroxy ketones,[25] the oxygenation of the
C–H bond[26] and the oxidation of iodoarenes to hyper-
valent iodine compounds.[27] However, to the best of our
knowledge, the use of Oxone for the α-hydroxylation of β-
dicarbonyl compounds has never been reported before.
Herein, we report a simple and effective protocol for the α-
hydroxylation of β-dicarbonyl compounds using Oxone as
a stoichiometric oxidant under mild conditions without the
aid of a catalyst.
Introduction
α-Hydroxy β-dicarbonyl moieties are common structural
units in many natural products and pharmaceuticals, for
example, kjellmanianone,[1] hamigeran A,[2] (–)-praman-
icin[3] and doxycycline.[4] They also serve as starting materi-
als or key intermediates in the synthesis of a variety of natu-
ral products.[5] To date, a number of methods have been
developed for the preparation of α-hydroxy β-dicarbonyl
moieties.[6] Among them, the direct oxidation of readily
available β-dicarbonyl compounds is the most convenient
and a number of oxidizing agents have been employed for
this transformation. Examples include the stoichiometric
application of Pb(OAc)4,[7] oxodiperoxymolybdenum(pyrid-
ine)hexamethylphosphoramide (MoOPH),[8] m-CPBA,[9]
oxaziridines[10] and 2-iodoxybenzoic acid (IBX).[11] How-
ever, Pb(OAc)4 and MoOPH are toxic agents and the use
of m-CPBA, oxaziridines and IBX leads to the formation
of large quantities of organic by-products that have to be
removed by chromatographic techniques. Dimethyldioxir-
Results and Discussion
[13]
ane (DMDO)[12] and H2O2 can also be used for the oxi-
Initially, the hydroxylation of methyl 1-oxo-1,2,3,4-tetra-
dation of β-dicarbonyl compounds. These two oxidants are hydronaphthalene-2-carboxylate (1a) at room temperature
viewed as “green oxidants” because the only by-product using 3.0 equiv. of Oxone in the homogeneous solvent mix-
from each oxidant in the reaction is acetone or water. On ture of water and acetonitrile (1:3, v/v) was examined.
the other hand, the metal-catalysed α-hydroxylation of β- Methyl 2-hydroxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-
dicarbonyl compounds with molecular oxygen as the oxi- carboxylate (2a) was formed in 70% yield with the conver-
dant has received much attention.[14]
sion of 1a being 75% after 24 h. When the reaction tem-
Oxone is a cheap, safe, stable, and easily handled oxidiz- perature was elevated from room temperature to 60 °C, the
ing reagent that has found widespread use in organic syn- reaction was completed within 10 h and afforded 2a in 87%
thesis.[15] The most impressive use of Oxone is in the ef- yield. The effect of volume ratio of water and acetonitrile
ficient preparation of dimethyldioxirane (DMDO), which was then investigated at 60 °C (Table 1). Substrate 1a was
can epoxidize olefins readily.[16] Oxone is also well known first subjected to 3.0 equiv. of Oxone in acetonitrile alone
for its oxidation of boron-,[17] nitrogen-,[18] phosphorus-,[19] and the reaction gave little conversion of 1a due to the poor
solubility of Oxone in acetonitrile (Table 1, entry 1). The
[a] The State Key Laboratory of Elemento-Organic Chemistry, The
Research Institute of Elemento-Organic Chemistry, Nankai
University,
use of a 1:1 mixture of water and acetonitrile led to the
formation of 2a in 91% yield within 4 h (entry 3). The best
result was obtained when a 3:1 mixture of water and aceto-
nitrile was employed, with 2a being obtained in 94% yield
within 2.5 h (entry 4). The reaction was also carried out in
water alone, which gave 2a in 84% yield after 11 h (entry 5).
Tianjin 300071, P. R. China
Fax: +86-22-23499247
E-mail: zhangchi@nankai.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000940.
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α-Hydroxylation of β-Dicarbonyl Compounds
Table 1. The effect of the volume ratio of water and acetonitrile on good substrate under the standard conditions in which the
the hydroxylation of methyl 1-oxo-1,2,3,4-tetrahydronaphthalene-
desired product 2e was obtained in only 40% yield with the
conversion of 1e being 48%. However, the use of water/
2-carboxylate (1a).[a]
acetonitrile (3:1, v/v) and 3.0 equiv. of Oxone successfully
resulted in the formation of 2e in 70% yield after 24 h (en-
try 5). The cyclic aliphatic β-keto esters 1f–1i were also
readily oxidized to the corresponding desired products 2f–
2i in moderate-to-good yields (entries 6–9). Notably, the
benzyl group was well tolerated under the reaction condi-
tions (entry 7). For the reactions of β-diketones 1j–1o, both
the aromatic and aliphatic β-diketones were efficiently
transformed into the corresponding α-hydroxylated β-di-
ketones 2j–2o in good-to-excellent yields (entries 10–15).
This new hydroxylation protocol was also effectively ap-
plied to β-ketoamides 1p–1t and the reactions provided the
expected products 2p–2t in good-to-excellent yields (en-
tries 16–20).
Entry
H2O/CH3CN [mL/mL]
Time [h]
Yield [%][b]
1
2
3
4
5
0:10
2.5:7.5
5:5
7.5:2.5
10:0
24
10
4
2.5
11
20[c]
87
91
94
84[d]
[a] 1 mmol of 1a was used. [b] Isolated yield. [c] The conversion of
1a was 21%. [d] The conversion of 1a was 98 %.
A screening study of the amounts of Oxone and organic
solvent was then conducted still using 1a as the model sub-
strate (Table 2). The results shown in Table 2 (Table 2, en-
tries 1–5) indicate that 1.1 equiv. of Oxone are enough for
completion of the reaction although a longer reaction time
7 h was required. Among the screened organic solvents, 1,4-
dioxane gave the highest yield (98%) within the shortest
reaction time (4 h) (entry 6) whereas the use of THF led to
little conversion of 1a (entry 7). The solvent mixtures of
water/DMF (3:1, v/v) and water/acetone (3:1, v/v) were also
found to be good solvent systems with yields similar to
those in water/1,4-dioxane being obtained, but prolonged
reaction times were needed (entries 8 and 9 vs. entry 6).
The acyclic substrate ethyl 2-methyl-3-oxo-3-phenyl-
propanoate (1u; Figure 1) was also tested in water/1,4-di-
oxane (3:1, v/v) and water/acetonitrile (3:1, v/v). The reac-
tions turned out to be too sluggish to be synthetically via-
ble. This is largely the consequence of the lower enol con-
tent of 1u compared with cyclic β-dicarbonyl compounds
as the cyclic substrates tend to enolize more readily than
the open-chain compounds.[12a,28] Other acyclic substrates
including 1v, 1w, 1x, 1y and 1z also failed to give the corre-
sponding α-hydroxylated products for similar reasons.[29]
Table 2. Screening of the amounts of Oxone and organic solvents.[a]
Figure 1. Structures of 1u–z.
Entry
Oxone [equiv.]
Solvent
Time [h] Yield [%][b]
It is known that Oxone itself can epoxidize alkenes in
aqueous methanol.[30] Thus, as proposed for other hydrox-
ylation reactions,[12a,14e,28] the mechanism for the present
transformation may involve the epoxidation of the enol
form of 1a by Oxone to form the hydroxy-epoxide interme-
diate A and subsequent ring-opening to produce the α-hy-
droxylated β-dicarbonyl compound 2a (Scheme 1).[31]
1
2
3
4
5
6
7
8
9
3.0
2.0
1.5
1.1
0.6
1.1
1.1
1.1
1.1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
1,4-dioxane
THF
2.5
3.3
5
7
24
4
26
17
17
94
95
97
96
90[c]
98
18[d]
94[e]
96
DMF
acetone
[a] 1 mmol of 1a and the indicated amount of Oxone were used.
[b] Isolated yield. [c] The conversion of 1a was 98%. [d] The conver-
sion of 1a was 19%. [e] The conversion of 1a was 98 %.
A variety of cyclic β-dicarbonyl compounds, including β-
keto esters, β-diketones and β-ketoamides, were studied in
α-hydroxylation reactions using the optimal reaction condi-
tions (Table 2, entry 6); the results are summarized in
Table 3. Methyl 1-oxoindane-2-carboxylate (1b) and its two
derivatives 1c and 1d were readily converted into the corre-
sponding α-hydroxylated products 2b, 2c and 2d in 87, 86
and 80% yields, respectively (Table 3, entries 2–4). The
seven-membered-ring-containing substrate 1e was not a Scheme 1. Proposed mechanism for the hydroxylation reaction.
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FULL PAPER
Table 3. α-Hydroxylation of β-dicarbonyl compounds by Oxone.[a]
[a] Unless otherwise indicated, the reactions were conducted with 1 mmol of β-dicarbonyl compounds and 1.1 mmol of Oxone in a
solvent mixture of water and 1,4-dioxane (3:1, v/v) at 60 °C. [b] Isolated yield. [c] The conversion of 1d was 88%. [d] The reaction was
carried out in H2O/CH3CN (3:1, v/v) using 3.0 mmol of Oxone at 60 °C. [e] The conversion of 1e was 82%. [f] The reaction was carried
out in H2O/CH3CN (3:1, v/v). [g] The reaction was carried out in H2O/CH3CN (3:1, v/v) using 2.0 mmol of Oxone at 40 °C. [h] 1.5 mmol
of Oxone was used.
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α-Hydroxylation of β-Dicarbonyl Compounds
H, OCH3), 4.02 (s, 1 H, OH), 7.42 (d, J = 8.0 Hz, 1 H, aromatic
CH), 7.50 (s, 1 H, aromatic CH), 7.74 (d, J = 8.0 Hz, 1 H, aromatic
CH) ppm. 13C NMR (100 MHz): δ = 38.89 (CH2), 53.63 (CH3),
Conclusions
A simple and convenient method for the direct α-hydrox-
ylation of β-dicarbonyl compounds using Oxone as oxidant 80.37 (C), 126.37 (CH), 126.73 (CH), 129.06 (CH), 131.93 (C),
142.85 (C), 153.50 (C), 171.51 (CO), 199.37 (CO) ppm.
without a catalyst has been developed. Considering the sim-
plicity and efficiency of the present method, the cost effec-
tiveness, ready availability and ease of handling of Oxone,
this method is an attractive method for synthesizing α-hy-
droxylated β-dicarbonyl compounds.
Ethyl 2-Hydroxy-5-methoxy-1-oxo-2,3-dihydro-1H-indene-2-carb-
oxylate (2d): (Table 3, entry 4); yield 200 mg (80%); white solid,
m.p. 72–73 °C. 1H NMR (400 MHz, CDCl3): δ = 1.17 (t, J =
6.8 Hz, 3 H, CH2CH3), 3.17 (d, J = 17.2 Hz, 1 H, CHH), 3.66 (d,
J = 17.2 Hz, 1 H, CHH), 3.89 (s, 3 H, OCH3), 4.02 (br. s, 1 H,
OH), 4.19 (t, J = 6.8 Hz, 2 H, CH2CH3), 6.90 (s, 1 H, aromatic
CH), 6.93 (d, J = 8.4 Hz, 1 H, aromatic CH), 7.71 (d, J = 8.4 Hz,
1 H, aromatic CH) ppm. 13C NMR (100 MHz): δ = 13.93 (CH3),
39.22 (CH2), 55.74 (CH3), 62.61 (CH2), 80.56 (C), 109.54 (CH),
116.17 (CH), 126.56 (C), 127.01 (CH), 155.37 (C), 166.34 (C),
Experimental Section
General: Oxone was purchased from Alfa Aesar. The known α-
hydroxy β-dicarbonyl compounds were identified by comparison of
their 1H and 13C NMR spectra with those reported in the literature.
The 1H NMR spectra were recorded at 400 MHz and the 13C
NMR spectra at 100 MHz using a Bruker AV400 instrument with
CDCl3 as solvent. IR spectra were recorded with a FT-IR Bruker
EQUINOX55 spectrometer in KBr pellets. High-resolution mass
spectroscopy (HRMS) was performed with a high-resolution ESI–
FTICR mass spectrometer (Varian 7.0 T). The petroleum ether
(PE) used had the range of boiling point 60–90 °C.
171.61 (CO), 198.78 (CO) ppm. IR (KBr): ν = 3396, 2971, 2945,
˜
2923, 1748, 1698, 1596, 1490, 1466, 1440, 1425, 1389, 1366, 1310,
1269, 1188, 1152, 1090, 1054, 1023, 1006, 935, 893, 846, 657, 558,
495 cm–1. HRMS (ESI): calcd. for C13H14O5Na [M + Na]+
273.0733; found 273.0739.
6-Ethoxycarbonyl-6-hydroxy-6,7,8,9-tetrahydro-5-oxo-5H-benzo-
cycloheptene (2e): (Table 3, entry 5);[14g] yield 174 mg (70%);
colourless oil. 1H NMR (400 MHz, CDCl3): δ = 1.13 (t, J = 7.2 Hz,
3 H, CH2CH3), 1.92–2.09 (m, 3 H, CH2CHHCH2), 2.52–2.59 (m,
1 H, CH2CHHCH2), 2.86–3.03 (m, 2 H, CH2CHHCH2), 4.13 (q,
J = 7.2 Hz, 2 H, CH2CH3), 4.43 (s, 1 H, OH), 7.18 (d, J = 7.6 Hz,
1 H, aromatic CH), 7.29 (t, J = 7.6 Hz, 1 H, aromatic CH), 7.42 (t,
J = 7.6 Hz, 1 H, aromatic CH), 7.50 (d, J = 7.6 Hz, 1 H, aromatic
CH) ppm. 13C NMR (100 MHz): δ = 13.75 (CH3), 22.65 (CH2),
33.95 (CH2), 34.06 (CH2), 62.04 (CH2), 81.82 (C), 126.47 (CH),
129.31 (CH), 129.47 (CH), 132.20 (CH), 137.26 (C), 139.86 (C),
170.62 (CO), 204.35 (CO) ppm.
Typical Procedure for α-Hydroxylation of β-Dicarbonyl Compounds:
Oxone (677 mg, 1.1 mol) was added to a stirred mixture of methyl
1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1a; 204 mg,
1 mmol) in a mixture of water (7.5 mL) and 1,4-dioxane (2.5 mL)
in a 25 mL rounded-bottomed flask at room temperature. The reac-
tion flask was then placed in an oil bath (60 °C) and the reaction
was monitored by TLC. After 4 h the reaction mixture was cooled
to room temperature and diluted with dichloromethane (50 mL).
Then the mixture was washed with satd. aqueous NaHCO3 (10 mL)
and satd. aqueous Na2S2O3 (10 mL). The separated aqueous phase
was extracted with dichloromethane (20 mL) twice. The combined
organic layers were washed with brine, dried with anhydrous
Na2SO4 and concentrated in vacuo to afford the crude product
which was purified by flash column chromatography (PE/EtOAc,
9:1) to give 216 mg of 2a[14d] in 98% yield as a white solid; m.p.
Ethyl 1-Hydroxy-2-oxocyclopentanecarboxylate (2f): (Table 3, en-
1
try 6);[14d] yield 91 mg (53%); colourless oil. H NMR (400 MHz,
CDCl3): δ = 1.29 (t, J = 7.2 Hz, 3 H, CH2CH3), 2.08–2.12 (m, 3
H, CH2CHHCH2), 2.44–2.51 (m, 3 H, CH2CHHCH2), 3.40 (br. s,
1 H, OH), 4.26 (q, J = 7.2 Hz, 2 H, CH2CH3) ppm. 13C NMR
(100 MHz): δ = 14.01 (CH3), 18.35 (CH2), 34.71 (CH2), 35.80
(CH2), 62.54 (CH2), 79.72 (C), 171.56 (CO), 213.37 (CO) ppm.
1
69–70 °C (ref.[14d] 68 °C). H NMR (400 MHz, CDCl3): δ = 2.22–
Benzyl 1-Hydroxy-2-oxocyclopentanecarboxylate (2g): (Table 3, en-
2.29 (m, 1 H, CHH), 2.70–2.75 (m, 1 H, CHH), 3.12–3.15 (m, 2
H, CH2), 3.75 (s, 3 H, OCH3), 4.35 (s, 1 H, OH), 7.27 (d, J =
7.6 Hz, 1 H, aromatic CH), 7.36 (t, J = 7.6 Hz, 1 H, aromatic CH),
7.54 (t, J = 7.6 Hz, 1 H, aromatic CH), 8.05 (d, J = 7.6 Hz, 1 H,
aromatic CH) ppm. 13C NMR (100 MHz): δ = 25.52 (CH2), 32.67
(CH2), 53.00 (CH3), 77.66 (C), 126.96 (CH), 128.19 (CH), 128.93
(CH), 130.06 (C), 134.44 (CH), 143.99 (C), 170.99 (CO), 194.54
(CO) ppm.
1
try 7);[32] yield 152 mg (65%); colourless oil. H NMR (400 MHz,
CDCl3): δ = 2.03–2.15 (m, 3 H, CH2CHHCH2), 2.41–2.52 (m, 3
H, CH2CHHCH2), 3.80 (s, 1 H, OH), 5.16–5.28 (m, 2 H, CH2),
7.29–7.39 (m, 5 H, aromatic C5H5) ppm. 13C NMR (100 MHz): δ
= 18.32 (CH2), 34.66 (CH2), 35.77 (CH2), 67.96 (CH2), 79.84 (C),
126.90 (CH), 128.03 (CH), 128.45 (CH), 128.57 (CH), 128.63 (CH),
134.68 (C), 171.40 (CO), 213.22 (CO) ppm.
Ethyl 1-Hydroxy-2-oxocyclohexanecarboxylate (2h): (Table 3, en-
try 8):[14d] yield 112 mg (60%); colourless oil. 1H NMR (400 MHz,
CDCl3): δ = 1.30 (t, J = 7.2 Hz, 3 H, CH2CH3), 1.61–1.91 (m, 4
H, CH2CH2CH2CH2), 2.04–2.08 (m, 1 H, CH2CH2CHHCH2),
2.53–2.72 (m, 3 H, CH2CH2CHHCH2), 4.25 (q, J = 7.2 Hz, 2 H,
CH2CH3), 4.34 (s, 1 H, OH) ppm. 13C NMR (100 MHz): δ = 13.96
(CH3), 21.94 (CH2), 27.01 (CH2), 37.65 (CH2), 38.86 (CH2), 62.05
(CH2), 80.66 (C), 170.06 (CO), 207.28 (CO) ppm.
Methyl 2-Hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2b):
(Table 3, entry 2);[32] yield 179 mg (87%); white solid, m.p. 131 °C
(ref.[10b] 132–133 °C[10b]). 1H NMR (400 MHz, CDCl3): δ = 3.19
(d, J = 17.6 Hz, 1 H, CHH), 3.68 (d, J = 17.6 Hz, 1 H, CHH), 3.67
(s, 3 H, OCH3), 3.95 (s, 1 H, OH), 7.37 (t, J = 7.6 Hz, 1 H, aromatic
CH), 7.43 (d, J = 7.6 Hz, 1 H, aromatic CH), 7.61 (t, J = 7.6 Hz,
1 H, aromatic CH), 7.73 (d, J = 7.6 Hz, 1 H, aromatic CH) ppm.
13C NMR (100 MHz): δ = 39.23 (CH2), 53.47 (CH3), 80.35 (C),
125.33 (CH), 126.46 (CH), 128.16 (CH), 133.49 (C), 136.19 (CH),
152.19 (C), 171.90 (CO), 200.83 (CO) ppm.
Methyl 1-Hydroxy-2-oxocycloheptanecarboxylate (2i): (Table 3, en-
try 9)[13] yield 115 mg (62%); colourless oil. 1H NMR (400 MHz,
CDCl3): δ = 1.25–1.39 (m, 1 H, carbocyclic ring CH), 1.46–1.51
(m, 2 H, carbocyclic ring CH2), 1.81–1.86 (m, 2 H, carbocyclic ring
CH2), 1.97–2.01 (m, 1 H, carbocyclic ring CH), 2.10–2.16 (m, 1 H,
carbocyclic ring CH), 2.24–2.31 (m, 1 H, carbocyclic ring CH),
Methyl
5-Chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carb-
oxylate (2c): (Table 3, entry 3);[33] yield 206 mg (86%); white solid,
m.p. 132–133 °C. 1H NMR (400 MHz, CDCl3): δ = 3.24 (d, J =
17.6 Hz, 1 H, CHH), 3.71 (d, J = 17.6 Hz, 1 H, CHH), 3.75 (s, 3
Eur. J. Org. Chem. 2010, 7020–7026
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J. Yu, J. Cui, C. Zhang
FULL PAPER
2.57–2.62 (m, 1 H, carbocyclic ring CH), 2.94–3.01 (m, 1 H, carbo-
1.60–1.76 (m, 2 H, carbocyclic ring CH2), 1.78–1.91 (m, 2 H, carbo-
cyclic ring CH2), 2.08–2.11 (m, 1 H, carbocyclic ring CH), 2.24 (s,
cyclic ring CH), 3.77 (s, 3 H, OCH3), 4.33 (s, 1 H, OH) ppm. 13C
NMR (100 MHz): δ = 23.56 (CH2), 27.21 (CH2), 30.10 (CH2), 3 H, CH3), 2.42–2.46 (m, 1 H, carbocyclic ring CH), 2.66–2.72 (m,
34.48 (CH2), 39.84 (CH2), 53.02 (CH3), 83.49 (C), 171.03 (CO), 2 H, carbocyclic ring CH2), 4.64 (s, 1 H, OH) ppm. 13C NMR
209.49 (CO) ppm.
(100 MHz): δ = 21.63 (CH2), 25.47 (CH2), 27.20 (CH2), 38.40
(CH2), 39.35 (CH3), 85.30 (C), 207.38 (CO), 208.94 (CO) ppm.
2-Acetyl-2-hydroxy-2,3-dihydro-1H-inden-1-one (2j): (Table 3, en-
try 10);[32] yield 175 mg (92%); white solid, m.p. 60–61 °C (2j was
N,N-Diethyl-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carbox-
amide (2p): (Table 3, entry 16); yield 245 mg (99%); white solid,
1
reported as a dark oil in ref.[32]). H NMR (400 MHz, CDCl3): δ
1
= 2.08 (s, 3 H, CH3), 2.26 (d, J = 17.6 Hz, 1 H, CHH), 3.64 (d, J
= 17.6 Hz, 1 H, CHH), 4.54 (s, 1 H, OH), 7.48 (t, J = 7.6 Hz, 1 H,
aromatic CH), 7.56 (d, J = 7.6 Hz, 1 H, aromatic CH), 7.72 (t, J
= 7.6 Hz, 1 H, aromatic CH), 7.83 (d, J = 7.6 Hz, 1 H, aromatic
CH) ppm. 13C NMR (100 MHz): δ = 23.92 (CH2), 38.56 (CH3),
87.16 (C), 125.27 (CH), 126.65 (CH), 128.50 (CH), 134.28 (C),
136.45 (CH), 151.92 (C), 201.42 (CO), 203.67 (CO) ppm.
m.p. 60–61 °C. H NMR (400 MHz, CDCl3): δ = 0.93–1.18 (m, 6
H, CH2CH3CH2CH3), 2.76–2.87 (m, 2 H, CH2CH3CH2CH3),
3.23–3.46 (m, 4 H, CH2CH3CH2CH3, CH2), 4.55 (br. s, 1 H, OH),
7.36–7.43 (m, 2 H, aromatic C2H2), 7.60 (t, J = 7.6 Hz, 1 H, aro-
matic CH), 7.78 (d, J = 7.6 Hz, 1 H, aromatic CH) ppm. 13C NMR
(100 MHz): δ = 12.39 (CH3), 12.81 (CH3), 40.94 (CH2), 41.10
(CH2), 41.23 (CH2), 78.47 (C), 125.22 (CH), 126.87 (CH), 128.29
(CH), 134.17 (C), 135.93 (CH), 151.01 (C), 170.26 (CO), 201.37
2-Acetyl-2-hydroxy-3,4-dihydro-2H-naphthalen-1-one (2k): (Table 3,
entry 11)[32] yield 202 mg (99%); white solid, m.p. 59–60 °C (ref.[14g]
58.5–59.5 °C). 1H NMR (400 MHz, CDCl3): δ = 2.13–2.20 (m, 1
H, CHHCH2), 2.26 (s, 3 H, CH3), 2.55–2.60 (m, 1 H, CHHCH2),
3.07–3.10 (m, 2 H, CHHCH2), 4.74 (s, 1 H, OH), 7.23 (d, J =
7.6 Hz, 1 H, aromatic CH), 7.31 (t, J = 7.6 Hz, 1 H, aromatic CH),
7.50 (t, J = 7.6 Hz, 1 H, aromatic CH), 7.99 (d, J = 7.6 Hz, 1 H,
aromatic CH) ppm. 13C NMR (100 MHz): δ = 24.86 (CH2), 25.28
(CH2), 32.11 (CH3), 81.63 (C), 126.70 (CH), 127.56 (CH), 128.79
(CH), 130.29 (C), 134.29 (CH), 144.01 (C), 196.44 (CO), 206.98
(CO) ppm.
(CO) ppm. IR (KBr): ν = 3547, 3412, 3017, 2976, 2940, 1720, 1638,
˜
1619, 1463, 1381, 1361, 1326, 1301, 1257, 1215, 1186, 1143, 1080,
963, 948, 920, 900, 878, 849, 749, 702, 686, 639, 605, 564, 469 cm–1.
HRMS (ESI): calcd. for C14H17NO3Na [M + Na]+ 270.1101; found
270.1098.
2-Hydroxy-2-(piperidin-1-ylcarbonyl)-2,3-dihydro-1H-inden-1-
one (2q): (Table 3, entry 17); yield 254 mg (98%); white solid, m.p.
1
103–105 °C. H NMR (400 MHz, CDCl3): δ = 1.37–1.59 (m, 6 H,
CH2CH2CH2CH2CHH), 2.91–2.92 (m, 2 H, CH2CH2CH2CH2-
CHH), 3.30 (d, J = 17.6 Hz 1 H, CHH), 3.42–3.47 (m, 2 H, CHH,
CH2CH2CH2CH2CHH), 3.80–3.84 (m, 1 H, CH2CH2CH2CH2-
CHH), 4.71 (br. s, 1 H, OH), 7.42–7.48 (m, 2 H, aromatic C2H2),
7.65 (t, J = 7.6 Hz, 1 H, aromatic CH), 7.84 (d, J = 7.6 Hz, 1 H,
aromatic CH) ppm. 13C NMR (100 MHz): δ = 24.11 (CH2), 25.22
2-Benzoyl-2-hydroxycyclopentanone (2l): (Table 3, entry 12); yield
145 mg (71%); yellow solid, 96–98 °C. 1H NMR (400 MHz,
CDCl3): δ = 1.99–2.07 (m, 1 H, carbocyclic ring CH), 2.10–2.20
(m, 2 H, carbocyclic ring CH2), 2.43–2.52 (m, 1 H, carbocyclic ring
CH), 2.61–2.69 (m, 2 H, carbocyclic ring CH2), 4.14 (s, 1 H, OH), (CH2), 40.83 (CH2), 44.77 (CH2), 46.52 (CH2), 78.27 (C), 125.26
7.46 (t, J = 7.6 Hz, 2 H, aromatic C2H2), 7.58 (t, J = 7.6 Hz, 1 H, (CH), 126.92 (CH), 128.23 (CH), 133.93 (C), 135.89 (CH), 150.96
aromatic CH), 7.97 (d, J = 7.6 Hz, 2 H, aromatic C2H2) ppm. 13C
(C), 169.20 (CO), 200.92 (CO) ppm. IR (KBr): ν = 3349, 3069,
˜
NMR (100 MHz): δ = 17.77 (CH2), 35.49 (CH2), 36.07 (CH2), 3031, 2951, 2854, 1721, 1636, 1608, 1461, 1421, 1368, 1322, 1295,
85.29 (C), 128.46 (CH), 129.63 (CH), 133.23 (C), 133.54 (CH),
1279, 1250, 1236, 1206, 1151, 1137, 1125, 1096, 1079, 1046, 1008,
955, 930, 912, 860, 811, 742, 706, 684, 658, 602, 561, 524, 494,
470 cm–1. HRMS (ESI): calcd. for C15H17NO3Na [M + Na]+
282.1101; found 282.1101.
199.92 (CO), 215.81 (CO) ppm. IR (KBr): ν = 3446, 2986, 2959,
˜
2936, 2874, 2834, 1741, 1663, 1597, 1449, 1439, 1398, 1349, 1319,
1275, 1234, 1171, 1133, 1088, 1058, 1006, 963, 934, 914, 894, 780,
710, 686, 641, 503 cm–1. HRMS (ESI): calcd. for C12H12NO3Na
[M + Na]+ 227.0679; found 227.0681.
2-Hydroxy-2-(morpholin-4-ylcarbonyl)-2,3-dihydro-1H-inden-1-
one (2r): (Table 3, entry 18); yield 245 mg (94%); white solid, m.p.
130–132 °C. 1H NMR (400 MHz, CDCl3): δ = 3.23–3.58 (m, 10 H,
CH2, morpholine ring C4H8), 5.12 (br. s, 1 H, OH), 7.37–7.43 (m,
2 H, aromatic C2H2), 7.60 (t, J = 7.6 Hz, 1 H, aromatic CH), 7.77
(d, J = 7.6 Hz, 1 H, aromatic CH) ppm. 13C NMR (100 MHz): δ
= 40.60 (CH2), 43.75 (CH2), 46.17 (CH2), 66.04 (CH2), 66.71
(CH2), 78.99 (C), 125.40 (CH), 126.92 (CH), 128.47 (CH), 133.81
(C), 136.16 (CH), 150.69 (C), 169.84 (CO), 201.23 (CO) ppm. IR
2-Benzoyl-2-hydroxycyclohexanone (2m): (Table 3, entry 13);[11]
yield 166 mg (76%); white solid, m.p. 65–66 °C (2m was reported
1
as a yellow oil in ref.[11]). H NMR (400 MHz, CDCl3): δ = 1.68–
1.80 (m, 4 H, carbocyclic ring C2H4), 2.08–2.12 (m, 1 H, carbocy-
clic ring CH), 2.71–2.76 (m, 2 H, carbocyclic ring CH2), 2.81–2.84
(m, 1 H, carbocyclic ring CH), 4.86 (s, 1 H, OH), 7.42 (t, J =
8.0 Hz, 2 H, aromatic C2H2), 7.54 (t, J = 8.0 Hz, 1 H, aromatic
CH), 8.04 (d, J = 8.0 Hz, 2 H, aromatic C2H2) ppm. 13C NMR
(100 MHz): δ = 21.87 (CH2), 27.38 (CH2), 39.75 (CH2), 39.96
(CH2), 84.98 (C), 128.26 (CH), 129.72 (CH), 133.10 (CH), 134.10
(C), 197.78 (CO), 209.93 (CO) ppm.
(KBr): ν = 3357, 2999, 2863, 1712, 1637, 1609, 1465, 1450, 1419,
˜
1361, 1326, 1361, 1326, 1301, 1245, 1209, 1199, 1186, 1111, 1082,
1048, 1026, 908, 864, 735, 588 cm–1. HRMS (ESI): calcd. for
C14H15NO3Na [M + Na]+ 268.0944; found 268.0950.
2-Acetyl-2-hydroxycyclopentanone (2n): (Table 3, entry 14);[32] yield
89 mg (63%); white solid, m.p. 58–59 °C (2n was reported as a yel-
3-Acetyl-1-benzyl-3-hydroxypyrrolidin-2-one (2s): (Table 3, en-
try 19);[14b] yield 191 mg (82%); white solid, m.p. 83–85 °C (ref.[14b]
84.5 °C).1H NMR (400 MHz, CDCl3): δ = 2.05–2.17 (m, 1 H,
CHHCHH), 2.29 (s, 3 H, CH3), 2.40–2.46 (m, 1 H, CHHCHH),
3.29–3.32 (m, 2 H, CH2), 4.42 (d, J = 14.8 Hz, 1 H, CHHCHH),
4.55 (d, J = 14.8 Hz, 1 H, CHHCHH), 5.01 (s, 1 H, OH), 7.22–
7.35 (m, 5 H, aromatic C5H5) ppm. 13C NMR (100 MHz): δ =
24.95 (CH2), 30.73 (CH3), 43.38 (CH2), 47.27 (CH2), 83.54 (C),
127.82 (CH), 127.97 (CH), 128.75 (CH), 135.10 (C), 171.69 (CO),
1
low oil in ref.[32]). H NMR (400 MHz, CDCl3): δ = 1.96–2.05 (m,
1 H, carbocyclic ring CH), 2.06–2.14 (m, 2 H, carbocyclic ring
CH2), 2.24 (s, 3 H, CH3), 2.41–2.47 (m, 3 H, carbocyclic ring
CH2CH), 4.23 (s, 1 H, OH) ppm. 13C NMR (100 MHz): δ = 17.91
(CH2), 25.29 (CH2), 34.28 (CH2), 35.65 (CH3), 85.87 (C), 207.30
(CO), 215.14 (CO) ppm.
2-Acetyl-2-hydroxycyclohexanone (2o): (Table 3, entry 15);[14b] yield
105 mg (67%); colourless oil. 1H NMR (400 MHz, CDCl3): δ = 207.63 (CO) ppm.
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α-Hydroxylation of β-Dicarbonyl Compounds
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Acknowledgments
This work was financially supported by the National Natural Sci-
ence Foundation of China (grant numbers 20572046 and
20872064), the Program for New Century Excellent Talents in Uni-
versity (NCET-07-0461) and the Tianjin Natural Science Founda-
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One referee of this article believed that the substrates and prod-
ucts may be the possible catalysts in our hydroxylation reac-
tions because Oxone can potentially oxidize the substrates or
products to give a dioxirane compound that can be used for
the hydroxylation of the β-dicarbonyl compounds. However, it
is known that the use of Oxone (2KHSO5·KHSO4·K2SO4) for
the preparation of dioxirane compounds requires strict pH
control within the range of 7–11 (either in situ generated dioxi-
rane or isolated one, see ref.[34]). The high pH value not only
enhances the nucleophilicity of Oxone towards ketone to pro-
duce the intermediate B but also favours the shift of the equi-
Eur. J. Org. Chem. 2010, 7020–7026
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7025

J. Yu, J. Cui, C. Zhang
FULL PAPER
librium (between B and C) to the formation of intermediate
C, which can lead to the effective formation of the dioxirane
compound.
of 1a and 1.1 equiv. of Oxone in a mixture of water and 1,4-
dioxane (3:1, v/v) at 60 °C. After 4 h, 1a was completely con-
verted into 1b in 95% yield. More importantly, the formation
of the epoxide was not observed in the reaction and the trans-
stilbene was recovered in 98% yield. This result further demon-
strated that the dioxirane compound was not formed in our
hydroxylation system. Therefore we believe that the mechanism
shown in Scheme 1 is still preferable. This referee also sug-
gested that we expand the substrate scope to linear β-dicar-
bonyl compounds using acetone as the co-solvent. Thus, sub-
strate 1u was treated with 1.1 equiv. of Oxone in a mixture of
water and acetone (3:1, v/v) at 60 °C. The presence of acetone
did not improve the efficiency of the reaction with the conver-
sion of the starting material 1u being only 9% after 24 h. This
result also indicates that the dioxirane is not the active species
in the hydroxylation reactions.
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Am. Chem. Soc. 2009, 131, 4562–4563.
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Org. Chem. 2004, 69, 8165–8167.
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We tested the acidity of the mixture of Oxone in water/1,4-
dioxane (3:1, v/v) by using pH test paper, which indicated that
our hydroxylation system was strongly acidic. In this strongly
acidic environment, the formation of intermediates B and C
are greatly inhibited. Hence we believe that the dioxirane com-
pound and the Baeyer–Villiger product cannot be formed in
our hydroxylation system (in fact neither the dioxirane nor the
Baeyer–Villiger products were detected in these hydroxylation
reactions). To further exclude the possibility of dioxirane as the
active species in our hydroxylation reactions, trans-stilbene (an
olefin usually used for epoxidation) was treated with 1.0 equiv.
Received: July 4, 2010
Published Online: November 4, 2010
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Eur. J. Org. Chem. 2010, 7020–7026