SCHEME 1
Direct Oxidative Cleavage of r- and
â-Dicarbonyls and r-Hydroxyketones to
Diesters with KHSO5
Jun Yan, Benjamin R. Travis, and Babak Borhan*
Department of Chemistry, Michigan State University,
East Lansing, Michigan 48824
Received August 2, 2004
Abstract: Presented is a methodology to oxidatively cleave
R-hydroxyketones and R- or â-diones using the environmen-
tally benign reagent KHSO5, prepared easily from Oxone,
to diesters in one simple transformation. In addition, we
undertook a mechanistic study to provide a plausible
mechanistic interpretation. These reactions may prove to be
valuable alternatives to other related metal-mediated pro-
cesses.
sodium percarbonate, copper perchlorate, basic peroxide,
bismuth, and rhenium.11-16 In addition, vanadium-based
systems have been reported to convert R-hydroxyketones
or R-diones into the corresponding methyl or ethyl esters
in the presence of the appropriate alcohol.17,18 Herein, we
report a mild and efficient method that utilizes Oxone
as the sole oxidant for the direct transformation of the
aforementioned functional groups to yield diesters in high
yields.
Oxidation of various R- or â-diones and R-hydroxyke-
tones were performed in methanol at rt for 18 h with the
purified (>95%) KHSO5 (see Table 1). It should be noted
that even though KHSO5 was used in all the studies cited
in this report, similar reactivity and yields were obtained
if Oxone (triple salt containing KHSO5) was utilized. As
can be seen from Table 1, oxidation of R-hydroxyketones
and R- and â-diones in methanol provided good to
excellent yields of the desired dimethyl esters. For
instance, R-hydroxyketones (entries 1 and 2) provided
products in 98% and 69% yield, respectively, and cyclic
R-diones (entries 3 and 4) were converted efficiently to
their corresponding dimethyl esters. Cyclic and acyclic
â-diones (entries 5, 8, 9, and 11) afforded the desired
dimethyl esters in 78-99% yield. R-Branching did not
affect the reaction (entries 6 and 10); however, the bis
R-branching in the 1,3-dione 719 did hinder the reaction
significantly providing the tertiary hydroxyketone 7a in
a modest 65% yield. Interestingly, 7a does not undergo
further oxidation without heating, presumably due to
Oxone is a triple salt containing two parts KHSO5, one
part KHSO4, and one part K2SO4. Owing to its nontoxic
“green” nature, affordability, and safety profile, Oxone
has become an increasingly popular reagent for oxidative
transformations such as the oxidation of aldehydes to
acids or esters, oxidative removal of aryl boronic acids
to phenols, and most commonly generation of DMDO for
epoxidations.1-5 Work in our laboratory has previously
focused on the use of Oxone as a co-oxidant for the
oxidative cleavage of olefins and the oxidation of alde-
hydes to acids and esters.1,6-9 Continuing studies with
the Oxone-mediated oxidative cleavage of olefins with a
variety of reactants showed that neither R,â-unsaturated
carbonyls nor R-hydroxyolefins provided the expected
R-ketoacids or R-hydroxyacids, but instead the one-
carbon-deleted carboxylic acid products were isolated.
This also led to the investigation of R-diones, which
cleaved under similar conditions to provide the desired
diacid. Interestingly, a related study by Ashford and
Grega10 reported that â-diones could be oxidatively
cleaved to the corresponding one-carbon-deleted carbox-
ylic acid using Oxone/NaHCO3/acetone/water (Scheme 1).
Oxidative cleavage of R-hydroxyketones, R-diones, and
â-diones to their corresponding dicarboxylic acids is well
precedented with reagents such as calcium hypochlorite,
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10.1021/jo048665x CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/01/2004
J. Org. Chem. 2004, 69, 9299-9302
9299