Palladium-catalyzed oxidation of vinyl ether to acetate with hydrogen peroxide

Article abstract of DOI:10.1016/j.tetlet.2011.10.015

The selective hydrogen peroxide oxidation of vinyl ethers to give acetates was developed using triphenylphosphine palladium and triethyl amine catalysts under mild reaction conditions.

Full text of DOI:10.1016/j.tetlet.2011.10.015

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Tetrahedron Letters 52 (2011) 6739–6742
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Tetrahedron Letters
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Palladium-catalyzed oxidation of vinyl ether to acetate with hydrogen peroxide
⇑
Yoshihiro Kon , Takefumi Chishiro, Daisuke Imao, Takuya Nakashima, Takashi Nagamine,
⇑
Houjin Hachiya, Kazuhiko Sato
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The selective hydrogen peroxide oxidation of vinyl ethers to give acetates was developed using triphen-
ylphosphine palladium and triethyl amine catalysts under mild reaction conditions.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 16 August 2011
Revised 29 September 2011
Accepted 5 October 2011
Available online 12 October 2011
Keywords:
Oxidation
Palladium catalyst
Green chemistry
Acetate
Hydrogen peroxide
Pd-catalyzed oxidation processes that convert terminal olefins
to methyl ketones using molecular oxygen (O2) with Cu are well
known and powerful methods applied to synthetic organic chem-
istry in industry as well as in the laboratory.1–3 There are also
many reports of Pd-catalyzed oxidation using hydrogen peroxide
(H2O2) as an oxidant for the transformation of terminal alkenes
to methyl ketones.4 In the application of these reactions to other
alkenes having various functional groups, Pd-catalyzed H2O2 oxi-
an oxygen transfer to terminal alkenes via peroxypalladation to af-
ford methyl ketones.4,11 The addition of amines has also been
known to affect a scavenger of free acids to suppress acetal forma-
tion under a transfer vinylation reaction using Pd catalyst.7e We
therefore thought that the addition of a catalytic amount of Pd
compound and amine would show good reactivity for the H2O2
oxidation of vinyl ethers to acetates. Here we report a unique
and a convenient synthesis of acetates by the oxidation of various
vinyl ethers using H2O2 as an oxidant with triphenyl phosphine
palladium and triethylamine catalysts under mild reaction
conditions.
dation of
a,b-unsaturated carbonyl compounds to 1,3-dicarbonyl
compounds has been reported.5 However, the Pd-catalyzed H2O2
oxidation of vinyl ether to acetate has rarely been reported.6 Vinyl
ethers are known to undergo hydrolysis and a vinyl interchange
reaction to produce alcohols and acetals under the Pd-catalyzed
reaction conditions, respectively.7 Design of the process without
generation of alcohols incidental to the cleavage of vinyl ethers is
required for the syntheses of acetates in high yields. Previously,
pyridinium chlorochromate (PCC) oxidation has been reported to
generate acetates from vinyl ethers in good yields.8 But this meth-
od requires more than 2 equiv of PCC toward the substrate to form
the deoxygenated Cr by-products as waste. In a constant search for
a cleaner oxidation reaction, H2O2 is a preferable oxidant because
H2O2 can be used with high atom efficiency and water is a sole
co-product.9 We have developed syntheses of various carbonyl
compounds using Pd and/or Pt catalyst with aqueous H2O2 under
organic solvent-free conditions.10 Previously, it was well known
that Pd–OOH species generated from H2O2 and Pd catalyst undergo
We selected cyclohexyl vinyl ether as a screening substrate,
which is known to generate cyclohexanol by the hydrolysis.7a
Table 1 shows the screening of various palladium catalysts with
Et3N using H2O2 oxidation under organic solvent-free conditions.
Cyclohexyl vinyl ether (2.0 mmol),
a 0.02 molar amount of
PdCl2(PPh3)2, a 0.05 molar amount of Et3N, and a 2.0 molar amount
of aqueous 30% H2O2 were stirred in open air at 30 °C for 2 h to give
cyclohexyl acetate in 83% yield (86% conversion) and 97% selectiv-
ity under organic solvent-free conditions (Table 1, entry 1).12
Hydrolysis of cyclohexyl vinyl ether was found to provide cyclo-
hexanol in only 3% yield. Pd(PPh3)4 catalyst also showed good reac-
tivity for the oxidation of cyclohexyl vinyl ether (66% yield, Table 1,
entry 2). In the reaction using Pd(OAc)2 catalyst, cyclohexyl acetate
was produced in 20% yield (77% conversion), and cyclohexanol was
given in 49% yield (Table 1, entry 4). By the addition of
Pd(OAc)2(PPh3)2 catalyst, cyclohexyl acetate was generated in
60% yield (92% conversion) and cyclohexanol was given in 18%
yield (Table 1, entry 3). In comparing entries 3 and 4, PPh3 ligands
⇑
Corresponding authors. Tel./fax: +81 29 861 4670 (Y.K.), +81 3 5501 0604 (K.S.).
E-mail addresses: y-kon@aist.go.jp (Y. Kon), k.sato@aist.go.jp (K. Sato).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.015

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Y. Kon et al. / Tetrahedron Letters 52 (2011) 6739–6742
Table 1
Various palladium catalysts tested for the oxidation of cyclohexyl vinyl ether using H2O2 with Et3Na
Entry
Palladium catalyst
Conversionb (%)
Yieldb (%)
1
2
3
4
5
PdCl2(PPh3)2
Pd(PPh3)4
Pd(OAc)2(PPh3)2
Pd(OAc)2
Pd(OAc)2 + 4 PPh3
PdCl2(PCy3)2
86
83
92
77
100
0
83
66
60
20
65
0
6
7
8
9
[1,2-Bis(diphenylphosphino)ethane] palladium(II) dichloride
Bis[1,2-bis(diphenylphosphino)ethane] palladium
Pd(acac)2
9
27
0
6
17
0
c
10
11
12
PdCl2
Pd/C
Pd black
18
0
0
2
0
0
a
Reaction conditions: cyclohexyl vinyl ether (2.0 mmol), 30% H2O2 (4.0 mmol), palladium catalyst (0.040 mmol), Et3N (0.10 mmol),
30 °C, 1500 rpm, 2 h, unless otherwise stated.
b
Yield and conversion on the basis of cyclohexyl vinyl ether, determined by GLC analysis with biphenyl as an internal standard.
acac = acetylacetonato.
c
clearly accelerated the reaction and inhibited the generation of
cyclohexanol caused by the cleavage of vinyl ether. The reaction
using Pd catalyst with bulky phosphine ligands such as tricyclo-
hexylphosphine (PCy3) and bidentate phosphine ligands such as
1,2-bis(diphenylphosphino)ethane resulted in low yields due to
steric hindrance (0–17% yields, Table 1, entries 6–9). PdCl2 catalyst
also showed low reactivity because of the lower solubility toward
the organic (substrate) phase (2% yield, Table 1, entry 10). Solid Pd
catalysts such as Pd/C and Pd black showed no reactivity due to the
decomposition of H2O2 catalyzed by Pd/C and Pd black with low
contact with substrate under organic solvent-free conditions (Ta-
ble 1, entries 11 and 12). The addition of Pd(OAc)2 catalyst and
PPh3 also showed good catalytic activity to generate cyclohexyl
acetate in 65% yield (100% conversion) to the same extent as that
of Pd(OAc)2(PPh3)2 catalyst (Table 1, entry 5). The reactions of
other metal catalysts having PPh3 ligands such as Ni(PPh3)4 and
Pt(PPh3)4 did not proceed in contrast to that of Pd(PPh3)4 (0% yield
(0% conversion) for Ni(PPh3)4 and 1% yield (2% conversion) for
Pt(PPh3)4).
Table 2 shows the screening of amines with PdCl2(PPh3)2 cata-
lyst. When we carried out the reaction without amine, the cleavage
of cyclohexyl vinyl ether occurred, cyclohexanol was given in 56%
yield, and the desired cyclohexyl acetate was generated in only 2%
yield (Table 2, entry 1). The addition of a 0.05 molar amount of
Et3N improved the selectivity to give cyclohexyl acetate in 83%
yield (Table 1, entry 1 and Table 2, entry 2). In the case of using
n-Pr2NH and n-HexNH2, cyclohexyl acetate was provided in 52%
yield for n-Pr2NH, and in 8% yield for n-HexNH2 (Table 2, entries
3 and 4). These results indicate that the high basicity of an amine
such as tertiary amine is required to accelerate the reaction. Hin-
dered tertiary amines having long alkyl chains showed low reactiv-
ities to give cyclohexyl acetate in 7% yield for n-Hex3N, and in 4%
yield for n-Oct3N (Table 2, entries 5 and 6). N-methylpiperidine,
N-methylpyrrolidine, and 2,2,6,6-tetramethylpiperidine showed
high reactivity to give cyclohexyl acetate in 80%, 74%, and 71%
yields, respectively (Table 2, entries 7–9). However, in the case of
1,4-diazabicyclo[2,2,2]octane having less hindered tertiary amine,
cyclohexyl acetate was produced in only 37% yield (Table 2, entry
10). Cyclohexyl acetate was generated in 2%, 3%, and 8% yields for
using pyridine, N-methylpyrrole, and 2,20-bipyridine, respectively,
(Table 2, entries 12–14). Aromatic amines are less effective for this
reaction, even in the case of 4-dimethylaminopyridine, which is
known as a strong base (Table 2, entry 11).
Table 2
Various amines tested for the oxidation of cyclohexyl vinyl ether using H2O2 with
PdCl2(PPh3)2
a
Entry
Amine
Conversionb (%)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
None
Et3N
n-Pr2NH
n-HexNH2
n-Hex3N
n-Oct3N
N-Methylpiperidine
N-Methylpyrrolidine
2,2,6,6-Tetramethylpiperidine
1,4-Diazabicyclo[2,2,2]octane
4-Dimethylaminopyridine
Pyridine
66
86
55
23
12
11
82
81
80
41
59
8
2
83
52
8
7
4
80
74
71
37
52
2
N-Methylpyrrole
2,20-Bipyridine
10
34
3
8
a
Reaction conditions: cyclohexyl vinyl ether (2.0 mmol), 30% H2O2 (4.0 mmol),
PdCl2(PPh3)2 (0.040 mmol), amine (0.10 mmol), 30 °C, 1500 rpm, 2 h, unless
otherwise stated.
b
Yield and conversion on the basis of cyclohexyl vinyl ether, determined by GLC
analysis with biphenyl as an internal standard.
This process is well applicable to the oxidation of various vinyl
ethers to give the corresponding acetates in good yields (Table 3).
Oxidation of benzyl vinyl ether gave benzyl acetate in 71% yield
with 91% selectivity (Table 3, entry 3). The reaction of cyclohexyl
vinyl ether and benzyl vinyl ether also proceeded under dimethyl-
acetamide (DMA) solution to give the corresponding acetates in
87% and 72% yields, respectively (Table 3, entries 2 and 4).3 How-
ever, the oxidation of cyclohexyl vinyl ether under DMA solution
accelerated the reactivity, and the selectivity of cyclohexyl acetate
decreased slightly compared to that under organic solvent-free
conditions (Table 2, entries 1 and 2). The reaction of cyclohexylm-
ethyl vinyl ethers gave the corresponding acetates in 60% and 90%
yields with excellent selectivities (>99% selectivities, Table 3, en-
tries 5 and 6). On the other hand, it was difficult to oxidize alkyl

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Y. Kon et al. / Tetrahedron Letters 52 (2011) 6739–6742
6741
Table 3
Catalytic H2O2 oxidation of various vinyl ethers with PdCl2(PPh3)2 and Et3Na
Entry Vinyl ether
Acetate ester
Conversionb (%) Yieldb (%)
(isolated yield%)
Selectivityd (%) H2O2 efficiencye (%)
c
1
86
100
83 (75)
87
97
87
42
44
2f
3
78
100
71 (70)
72
91
72
36
36
4f
5
6
60
90
60 (60)
>99
>99
30
45
90 (91)g
7
78
93
34
66
44
71
17
33
8f
9
48
100
36
72
75
72
18
36
10f
11
41
88
24
62
59
70
12
31
12f
13
27
82
8
49
30
60
4
25
14f
15
40
87
24
51
60
59
12
26
16f
17
0
0
53
0
0
53
0
0
>99
0
0
27
18f
19h
a
b
c
Reaction conditions: vinyl ether (2.0 mmol), 30% H2O2 (4.0 mmol), PdCl2(PPh3)2 (0.040 mmol), Et3N (0.10 mmol), 30 °C, 1500 rpm, 2 h, unless otherwise stated.
Yield and conversion on the basis of cyclohexyl vinyl ether, determined by GLC analysis with biphenyl as an internal standard.
Acetates (mol)/vinyl ethers (mol) ꢁ 100 (%).
d
e
f
Yield/conversion (%).
Yield/2 (%) because the amount of H2O2 (mol) using this reaction was twice as much as that of vinyl ether (mol).
Using DMA (2 ml) as organic solvent at 60 °C.
Two gram-scale, isolated yield.
Using dichloromethane (0.5 ml) as organic solvent at 40 °C.
g
h
vinyl ethers to generate the corresponding acetates in this catalytic
system under organic solvent-free conditions. For example, the
yields of n-propyl, n-butyl, i-butyl, and t-pentyl vinyl ethers were
34%, 36%, 24%, and 8%, respectively (selectivities were 44%, 75%,
59%, and 30%, respectively, Table 3, entries 7, 9, 11, and 13). Under
the reaction conditions with DMA solution at 60 °C, alkyl vinyl
ethers were oxidized to generate acetates in good yields (66%,
72%, 62%, and 49% for n-propyl, n-butyl, i-butyl, and t-pentyl vinyl
ethers, respectively, Table 3, entries 8, 10, 12, and 14). Oxidation of
2-chloroethyl vinyl ether gave 2-chloroethyl acetate in 51% yield
under DMA solution (Table 3, entry 16). Oxidation of cholesteryl vi-
nyl ether generated cholesteryl acetate in 53% yield with >99%
selectivity under dichloromethane solution (Table 3, entry 19).
The reaction could be explained by the same mechanism of Pd-
catalyzed H2O2 oxidation of terminal alkenes reported previously.4
The initial step was suggested to be the formation of the PdII–OOH
species11 regardless of the valence of the employed Pd catalyst (Pd0
and/or PdII). Through the coordination of vinyl ether to Pd metal,
Pd–OOH species underwent an oxygen transfer to vinyl ether via
peroxypalladation to afford the corresponding acetate. Deoxygen-
ated Pd–OH species was reoxidized by H2O2 to regenerate the
Pd–OOH species. The addition of amine would work effectively to
avoid the reduction of Pd–OH to metallic palladium by coordina-
tion to Pd–OH species and to scavenge the HCl produced by the re-
leased Clꢀ from PdCl2(PPh3)2. The effect of PPh3 ligands might be
the stabilization of cationic Pd species through the catalytic cycle
and the acceleration of vinyl ether coordination to Pd metal.
In summary, the oxidation of vinyl ether to acetate using 30%
H2O2 aqueous solution with PdCl2(PPh3)2 and Et3N catalysts was
carried out. Cyclohexyl vinyl ether, cyclohexylmethyl vinyl ethers,
and benzyl vinyl ether were effectively oxidized by this catalytic
system to generate the corresponding acetates in good yields with
excellent selectivities under organic solvent-free conditions. This
catalytic system was also successfully applied to various alkyl vinyl
ethers under DMA and/or dichloromethane solution in moderate to
good yields.
Acknowledgment
This work was partially supported by the New Energy and
Industrial Technology Development Organization (NEDO), Japan.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.10.015.

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Y. Kon et al. / Tetrahedron Letters 52 (2011) 6739–6742
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References and notes
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with 12% yield of desired cyclohexyl acetate.