Tetrahedron Letters
Simple and clean synthesis of ketones from internal olefins using
PdCl2/N,N-dimethylacetamide catalyst system
Takato Mitsudome a, Syuhei Yoshida a, Yamato Tsubomoto a, Tomoo Mizugaki a, Koichiro Jitsukawa a,
Kiyotomi Kaneda a,b,
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a Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan
b Research Center for Solar Energy Chemistry, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple catalytic system consisting of PdCl2 and N,N-dimethylacetamide enabled clean and selective
synthesis of ketones from internal olefins using molecular oxygen. Various functionalized internal olefins
were directly and regioselectively oxidized; C atoms of C@C bonds far from substituted moieties were
preferably oxidized.
Received 12 December 2012
Revised 8 January 2013
Accepted 11 January 2013
Available online 17 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Regioselective oxidation
Internal olefin
N,N-Dimethylacetamide
Palladium
Carbonyl groups are important moieties for the construction of
carbon-skeletons and synthetic intermediates.1 Oxygenation of ole-
fins is one of the most straightforward routes to synthesize car-
bonyl compounds. For example, Wacker–Tsuji oxidation is known
as a powerful method for converting terminal olefins into the corre-
sponding methyl ketones and is generally catalyzed by palladium
salts combined with copper salts under aerobic conditions.2–6 De-
spite high efficiency, conventional Wacker–Tsuji oxidation has lim-
ited substrate scope for only terminal olefins and does not show
high activity for internal olefins.7–9 Thus, oxygenation of internal
olefins to ketones is usually conducted via hydration followed by
the oxidation of alcohols (Fig. 1, Eq. 2),10 or hydroboration followed
by oxidation (Fig. 1, Eq. 3).11 These synthetic routes for the forma-
tion of ketones require multiple steps, resulting in the production
of large amounts of waste. Therefore, the development of clean
and highly efficient synthetic methods of ketones from internal ole-
fins is desired.
Recently, we found that the combination of PdCl2 and N,N-
dimethylacetamide (DMA) as the solvent functioned as a clean
and efficient catalyst system for Cu-free Wacker-type oxidation
of terminal olefins, and the in situ generated Pd0 species was di-
rectly reoxidized to PdII species by molecular oxygen.12 Moreover,
this simple catalytic system was successfully applied to direct
oxidation of internal olefins to the corresponding ketones (Fig. 1,
Eq. 1).13 This finding will open up new routes for direct synthesis
of various ketones. If the oxidation of internal olefins occurs regio-
selectively, a more powerful synthetic method could be realized.
Herein, we report a simple and clean method for selective synthe-
sis of ketones from internal olefins. The PdCl2/DMA system pro-
moted highly regioselective oxidation of internal olefins having
functional groups with O2 as a green oxidant.14 The oxygen atoms
were introduced to the C atoms of C@C bonds far from functional
groups (Scheme 1).
Initially, oxidation of (Z)-2-nonenyl acetate was carried out in
the presence of PdCl2 and water in DMA solvent under 6 atm
of O2. Interestingly, (Z)-2-nonenyl acetate was regioselectively
oxidized to 1-acetoxy-3-nonanone in 83% yield with over 99%
selectivity, and trace amounts of the regioisomer 1-acetoxy-2-
nonanone were formed (Table 1, entry 1). The excellent regioselec-
tivity is a sharp contrast to the result obtained from the oxidation
of internal olefins without the acetoxyl group; the use of (E)-2-
nonene afforded non-selective formation of both 2-nonanone and
3-nonanone (production ratio of 2-/3-nonanone = 56/44) (entry 6).
To gain more insight into the acetate-oriented high regioselectiv-
ity, various nonenyl acetates were tested in the PdCl2/DMA catalytic
system (Table 1, entries 1–5). The oxidation of nonenyl acetates
proceeded efficiently and the oxygen atoms were incorporated into
the original olefinic position of the starting materials. This showed
that the migration of C@C bonds in the starting materials did not
occur. The highest regioselectivity was obtained in the case of (Z)-
2-nonenyl acetate and the regioselectivity gradually decreased with
increasingthe number of methylene carbon (m) between C@C bonds
and the acetoxyl moiety. In all the test substrates with the acetoxyl
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Corresponding author.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.