Direct, efficient, and inexpensive formation of α-hydroxyketones from olefins by hydrogen peroxide oxidation catalyzed by the 12-tungstophosphoric acid/cetylpyridinium chloride system

Article abstract of DOI:10.1039/b518200j

The direct ketohydration of a variety of 1-aryl-1-alkenes with H ₂O₂, catalyzed by the inexpensive 12-tungstophosphoric acid/cetylpyridinium chloride system under very mild condition was analyzed. A variety of substituted olefins were oxidized to Α-hydroxyketones in good regioselectivities and yields by this method. The combination of HPA with cetylpyridium chloride (CPC) could catalyze the epoxidation of olefins such as 1-acetone and diols and the oxidative cleavage of 1,2 diols and olefins. It was found that direct ketohydroxyaltion of some olefins with H₂O ₂ could be achieved under similar conditions. It was observed that various 1-aryl-1-alkenes can be oxidized by H₂O₂, to hydroxyketones in the presence of WPA/CPC under mild reaction conditions.

Full text of DOI:10.1039/b518200j

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Direct, efficient, and inexpensive formation of a-hydroxyketones from olefins
by hydrogen peroxide oxidation catalyzed by the 12-tungstophosphoric
acid/cetylpyridinium chloride system
Yanfei Zhang,a Zongxuan Shen,a Jingting Tang,a Yan Zhang,a Lichun Kongb and Yawen Zhang*a
Received 6th January 2006, Accepted 7th February 2006
First published as an Advance Article on the web 13th March 2006
DOI: 10.1039/b518200j
The direct ketohydroxylation of a variety of 1-aryl-1-
alkenes with H2O2, catalyzed by the inexpensive 12-
tungstophosphoric acid/cetylpyridinium chloride system un-
der very mild conditions, was achieved. Various acyloins were
obtained in good yields and high regioselectivies.
chloride (CPC) could catalyze the epoxidation of olefins such as
1-octene, the ketonization of alcohols and diols, and the oxidative
cleavage of 1,2-diols and olefins.5
We have found that direct ketohydroxylation of some olefins
with H2O2 could be achieved under similar conditions. It turns
out that when olefins are treated with hydrogen proxide in
chloroform containing a catalytic amount of WPA (10 mol%)
combined with CPC (30 mol%) as phase-transfer catalyst at
60 ◦C, a-hydroxyketones can obtained in good-to-excellent yields
with good regioselectivities (Scheme 1). There are a number
of interesting features of this methodology worth pointing out:
(i) H3PW12O40 is less expensive and less toxic than RuO4 or OsO4;
(ii) H2O2 as the oxidant is of great advantage to the environment
and industry because it generates H2O as the sole by-product, it has
a high content of active oxygen species, and it is less expensive than
organic peroxides and peracids; (iii) the experiment is easy to carry
out, because no special precautions such as high temperature, inert
gas atmosphere or dry solvents are necessary.
a-Hydroxyketones (acyloins) are important building blocks in
organic synthesis and form parts of the structures of various
biologically active compounds, such as cortisone acetate 1 and
daunomycinone 21,2 (Fig. 1).
Fig. 1 Acyloin substructure in cortisone acetate 1 and daunomycinone 2.
It is known that acyloins can be prepared by the benzoin
condensation, the acyloin condensation, the a-hydroxylation of
carbonyl compounds and the oxidation of diols, whereas the
direct oxidation of C–C double bonds has only rarely been
reported.3 Since, in these cases, toxic cyanide compounds must
be employed, or the reaction must be performed under an inert
atmosphere with dry solvent, the development of an efficient
and convenient method to obtain a-hydroxyketones would be
significant. Recently, a new straightforward oxidation of C–C
double bonds to a-hydroxyketones using catalytic amounts of
RuCl3 and stoichiometric amounts of Oxone under buffered
conditions has been reported by Plietker.4 A variety of substituted
olefins were oxidized to a-hydroxyketones in good-to-excellent
regioselectivities and yields by this method.
Scheme 1
We choose styrene as our working model to study the influences
of the catalyst, phase-transfer catalyst, solvents and temperatures
(Table 1).
Table 1 Effects of the catalyst, solvent, and temperature on the ketohy-
droxylation of styrenea
Entry
Catalyst
Solvent
T/◦C
Yield (%)b
Heteropoly acids (HPA) such as 12-molybdophopsphoric acid
(MPA) or 12-tungstophosphoric acid (WPA) are often used, not
only for the oxidation of organic substrates, but also for many
acid-catalyzed reactions, because they possess the dual catalytic
functions of oxidizing ability and strong acidity.5 It has been
reported that the combination of HPA with cetylpyridinium
1
2
3
4
5
6
7
8
9
WPA/CPC
WPA
CHCl3
CHCl3
CHCl3
CH2Cl2
CH3CN
PhCH3
H2O
60
60
60
40
60
60
60
86.4
nd
42.4
62.5
36.4
73.9
nd
CWPc
WPA/CPC
WPA/CPC
WPA/CPC
WPA/CPC
WPA/CPC
WPA/CPC
CHCl3
CHCl3
−20
nd
10
4
aKey Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry and Chemical Engineering, Suzhou University, Suzhou, 215123,
China. E-mail: zhangyw@suda.edu.cn; Fax: +86 0512 65880305; Tel: +86
0512 65880339
a All reactions were performed on a 6.5 mmol scale in CHCl3 (15 mL)
using WPA (H3PW12O40, 0.4 mol%), CPC (1.2 mol%) and 10 equiv. of
H2O2 (30%), and were stopped after 24 h. b Isolated yields (nd = not
determined). c CWP: prepared according to ref. 5.
bCollege of Chemistry and Life Science, Zhejiang Normal University, Jinhua,
321004, China. E-mail: sky35@zjnu.cn
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To evaluate the potential of H3PW12O40 for the ketohydroxyla-
tion of styrene, three different catalyst systems were tested (entries
1–3). Combination of WPA with CPC produced in situ was found
to be more effective than [p-C6H5NC16H33]3[PO4(WO3)4] (CWP).
When the WPA/CPC combination (which produces CWP with
evolution of hydrogen chloride) was employed as the catalyst, the
reaction medium is acidic, while in the CWP-catalyzed reaction,
the medium is not acidic. The fact that ketohydroxylation pro-
ceeded more rapidly with the WPA/CPC combination suggested
that the tungsten-catalyzed reaction is accelarated in acidic media.
WPA alone could not catalyze the ketohydroxylation of styrene
(entry 2), probably due to its poor solubility in organic solvents.
Therefore, the reaction was conducted in various solvents using
the WPA/CPC catalyst. It was observed that chloroform was the
best solvent. The same reaction in toluene or acetonitrile led
to a considerable decrease of the yield (entries 1, 4–7). A lower
temperature decreased the conversion significantly (entry 9), while
no reaction was found at −20 ◦C.
It is noteworthy that the insoluble WPA/CPC dissolved slowly
under the action of H2O2, to form the real catalyst, which
subsequently led to homogeneous catalytic direct oxidation of
C–C double bond. During the reaction, the system gradually
changed from turbid to clear. The infrared spectra (Fig. 2) showed
that the H2O2-treated WPA/CPC (spectrum 2) has a peroxo-bond
absorption peak m(O–O) at 840 cm−1 and 846 cm−1, while CWP
itself (spectrum 1) does not have a peroxo-bond absorption peak
at about 840 cm−1. Instead, an absorption peak at 895 cm−1, which
corresponds to the asymmetric vibration of W–O–W, was found.
Scheme 2 A proposed mechanism.
A mechanistic explanation is proposed as shown in Scheme 2.
According to previous mechanistic research on the WPA/CPC-
catalyzed epoxidation of olefins with hydrogen peroxide, when
mixed with commercially available 35% H2O2, H3[PW12O40] is
Fig. 2 Infrared spectra of (1) CWP, (2) H2O2 (30%)-treated CWP, and (3)
recovered H2O2 (30%)-treated catalyst.
3−
oxidized to {PO4[WO(O2)2]4} , which was identified as the real
catalyst.7 This peroxo tungsten complex behaves as a 1,3-dipolar
reagent, M+–O–O−, which reacts with the olefin to form a five-
membered dioxametallocycle adduct. Degradation of the adduct
produces the corresponding epoxide8 and a PW3 species, which
quickly turns to the peroxo tungsten catalyst in the presence
of hydrogen peroxide. The electrophilic attack of the peroxo
tungsten complex on the above epoxide results in the formation of
a six-membered cyclic intermediate, which degrades to produce
the final oxidation product, a hydroxyketone, together with a
PW3 moiety, which is oxidized back to the peroxo tungsten
catalyst and then enters the next cycle. As evidence for the above
mechanism, phenyloxirane could be oxidized to the corresponding
hydroxyketone in high yield under the reaction conditions (entry
19, Table 3). The fact that 1,1-disubstituted and trisubstituted
ethylenes did not give hydroxyketones is another piece of evidence
for this, because, according to the above mechanistic explanation,
a hydrogen atom a- to the phenyl group is necessary. In the absence
After extraction of the product, the aqueous phase was evap-
orated, which allowed the recovery of the catalyst. As shown in
Table 2, the recovered catalyst can be recycled at least once without
significant loss of activity.
Table 2 Recycling the catalyst for the ketohydroxylation of styrene
Run a
Yield (%) b
1
2
3
4
86.4
81.8
71.5
64.7
a All reactions were performed under the conditions of entry 1, Table 1,
except that the catalyst was recovered from the preceding run. b Isolated
yield.
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Table 3 WPA/CPC-catalyzed oxidation of various olefinsa
Entry
1c
Substrate
Product
Time/h
24
Yield (%)b
86.4
2
3
48
24
74.6
75.7
4
5
48
48
73.0
78.5
6
7
17
20
75.6
79.4
8
9
48
48
20, 22
76.2
10
11
12
12
76.7
80.7
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Table 3 (Contd.)
Entry
Substrate
Product
Time/h
15
Yield (%)c
12
87.8
13
24
24
87.5
14
15
nd
nd
—
—
—
24
24
24
16
17
nd
nd
18
19
—
24
nd
2
3
93.1
a All reactions were performed on a 2 mmol scale in CHCl3 (15 mL) using WPA (H3PW12O40, 10 mol%), CPC (30 mol%), and 10 equiv. of H2O2 (30%) at
60 ◦C. b Isolated yields (nd = not determined). c The reaction was carried out under the conditions given in Table 1.
of WPA, styrene was not oxidized at all, even after 20 h of stirring
with CPC/hydrogen peroxide at 60 ◦C. This excludes a radical
pathway.
are ketohydroxylated much faster than electron-poor starting
materials; in fact, no reaction was observed with those alkenes
that had moderately strong electron-withdrawing groups on C2
(entries 15–18).
However, when extended to substrates other than styrene, the
above conditions did not work. It was found that the amount
of WPA and CPC must be increased to 10 mol% and 30 mol%,
respectively, for the reaction to proceed at an acceptable rate.
We investigated the direct oxidation of various olefins under
the modified conditions.6 Table 3 shows the results of an in-
tense screening of scope and limitations. It is important that
many electron-rich alkenes were successfully transformed into
the corresponding acyloins with remarkably high regioselectivities
and yields (entries 1–7). We were even not able to detect any
regioisomeric products from the crude mixtures. All the substrates
that gave hydroxyketones as the products were 1-aryl-1-alkenes. In
other words, an aromatic ring attached to the terminal sp2 carbon
is necessary for the hydroxyketonization to occur. Without this
kind of substituent, only epoxidation was observed (entries 12–
14). 1,1-Disubstituted and trisubstituted ethylenes cleaved during
the course of oxidation (entries 9–11). It is noteworthy that the
conversion is strongly dependent on the electronic properties
of the C–C double bond. In general, electron-rich substrates
In conclusion, we have demonstrated that various 1-aryl-1-
alkenes can be oxidized by H2O2 to hydroxyketones in the presence
of WPA/CPC under mild reaction conditions.
Acknowledgements
The authors are grateful to the Key Laboratory of Organic
Synthesis of Jiangsu Province, China, for financial support.
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12-tungstophosphate acid (0.60 g, 0.21 mmol), CPC (0.21 g, 0.62 mmol)
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was washed with brine (100 mL), dried over Na2SO4, filtered and
concentrated to a colorless oil. Pure product was obtained by silica gel
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1482 | Org. Biomol. Chem., 2006, 4, 1478–1482
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