COMMUNICATION
DOI: 10.1002/chem.201302307
Electrochemical Synthesis of the Aryl a-Ketoesters from Acetophenones
Mediated by KI
Zhenlei Zhang,[a] Jihu Su,[b] Zhenggen Zha,*[a] and Zhiyong Wang*[a]
a-Ketoesters play an essential role in biological processes.
They serve as the backbones in some natural products,[1]
such as the 3-deoxy-2-ulosonic acids and their derivatives.[2]
In addition, a-ketoesters are also used as key intermediates
for the synthesis of highly valued substrates.[3]
currence of the haloform reaction without any chemical
waste.
Initially the reaction was carried out in an undivided cell,
while MeOH was employed as the solvent, acetophenone as
the model substrate, and amine as the additive under an
oxygen atmosphere. It was found that the acetophenone can
be oxidized into 2-oxo-2-phenylacetaldehyde (see Table S1
in the Supporting Information). Then we screened various
amines and tert-butylamine was found to be the most effec-
tive additive to afford the desired product with a yield of
64% (see Table S1 in the Supporting Information). To our
knowledge, the 2-oxo-2-phenylacetaldehyde could be an in-
termediate and further transformed into a hemiacetal in the
presence of alcohol. Then this hemiacetal can be converted
into the a-ketoester under electrochemical oxidation. To en-
hance the anode oxidation, we increased the electric current
from 20 to 40 mA. As expected, the a-ketoester was ob-
tained in 30% yield (Table 1, entry 1), which encouraged us
to further optimize the reaction conditions.
Over the past several decades, chemists have paid great
attention to the synthesis of a-ketoesters. Classical methods
include oxidation of a-hydroxy esters with various kinds of
oxidant,[4] oxidation of methyl 2-phenylacetate,[5] Friedel–
Crafts acylation,[6] hydrolysis and esterification of acyl cya-
nides,[7] hydrolysis of 2-aryl-2-nitroacetates,[8] and other
methods.[9] However, these protocols usually require stoi-
chiometric amounts of metal oxidants, and thus a large
amount of waste is formed in the reaction. It has been
known that electrochemistry is a green method for fine
chemical synthesis.[10] Recently the synthesis of esters from
aldehydes and the corresponding alcohols was realized by
virtue of an anode oxidation in the presence of N-heterocy-
clic
carbine
(NHC)/1,8-diazabicycloACTHUGNETRNNU[G 5.4.0]undec-7-ene
(DBU).[11] In our laboratory, we have been attempting to
prepare a-ketoesters from aryl ketones and the correspond-
ing alcohols by an anode oxidation. We conceive that this
oxidation of methyl ketones in the presence of potassium
iodide could avoid the waste pollution under electrochemi-
cal conditions.
Previously, the reaction of methyl ketones with iodine was
a typical haloform reaction, affording carboxylic acids or
esters with a loss of one carbon atom.[12] It is a challenge to
functionalize the methelene of methyl ketones without
losing the methyl carbon atom. Herein, we describe a novel
method to synthesize a-ketoesters via an anode oxidation
from acetophenones under mild conditions inhibiting the oc-
Under the electric current of 40 mA, the reaction base
amine was examined again. After examination of various
amines, 2,2,6,6-tetramethylpiperidine (TMP) was the best
choice for this reaction (see Table S2 in the Supporting In-
formation). From the result of Table S2, it was found that
only the amines with a large steric hindrance could catalyze
the reaction well. Perhaps the amines without steric hin-
drance could be converted into a-ketoamides.[13] Subse-
quently, we attempted to improve the hemiacetal yield by
the addition of some additive. At first, we assumed that this
additive could catalyze the formation of hemiacetal. This
meant that the additive should be an acidic compound. At
the same time, this additive could not protonize the amine
in the reaction mixture. Therefore ammonium acetate, nitro-
alkanes, and phenols were examined in the reaction. To our
delight, when two equivalents of nitromethane were added
to the reaction, a significant increase in yield was observed
(Table 1, entry 3). When more than two equivalents of nitro-
methane was added, the yield decreased a little. Inspired by
this result, other nitro compounds were examined and it was
found that the p-nitrophenol was the best additive for this
transformation, giving the a-ketoester with a high yield of
81% (entry 10). The dosage of p-nitrophenol in this reaction
was also very important. When the amount of p-nitrophenol
was increased from 0.5 to 1.0 equivalents, the reaction yield
was decreased to 78% although the reaction time was pro-
longed to 3 h (entry 11). When the p-nitrophenol was de-
[a] Z. Zhang,+ Z. Zha, Prof. Dr. Z. Wang
Hefei National Laboratory for Physical Sciences at Microscale
CAS Key Laboratory of Soft Matter Chemistry and
Department of Chemistry, Univ Sci & Technol China
Hefei, Anhui, 230026 (P.R. China)
Fax : (+86)551-3603185
[b] Prof. Dr. J. Su+
Hefei National Laboratory for Physical Sciences at Microscale
and Department of Modern Physics, Univ Sci & Technol China
Hefei, Anhui, 230026 (P.R. China)
[+] These two authors have the equal contribution to this manuscript.
Supporting information for this article is available on the WWW
Chem. Eur. J. 2013, 19, 17711 – 17714
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
17711