Tetrahedron Letters
A novel method for synthesis of a-keto esters with phenyliodine(III)
diacetate
a,b,
⇑
, Jiwei Liu a,b, Yingyi Huang , Lixia Yao b
a
Yuanyuan Xie
a
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, PR China
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid and efficient synthesis of a-keto esters from b-ketonitriles using phenyliodine(III) diacetate is
reported. This protocol gave a-keto esters in good yields. This is the first time to report the application
Received 27 February 2015
Revised 14 April 2015
Accepted 18 April 2015
Available online 29 April 2015
of hypervalent iodine(III) reagents in the synthesis of
a
-keto esters. A plausible reaction mechanism is
proposed.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
a-Keto esters
Phenyliodine(III) diacetate
b-Ketonitrile
Oxidation
Introduction
Surprisingly, the product ethyl phenylglyoxylate 3a was obtained.
In the absence of cyclohex-2-enone, 3a could still be formed in 17%
yield. The origin of the oxyethyl group of 3a was curious and a fur-
ther experiment was carried out. Furthermore, when [bis(trifluo-
roacetoxy)iodo]benzene (PIFA) was used instead of PIDA, the
same product ethyl phenylglyoxylate 3a was obtained, indicating
that the oxyethyl group was not derived from PIDA. Thus, the oxy-
ethyl group is reckoned to be derived from the solvent. Because
there was 1% ethanol as stabilizer in the chloroform, we inferred
that ethanol was the origin of the oxyethyl group. Then, the reac-
tion was carried out using ethanol as solvent and nucleophile. As
expected, the ethyl phenylglyoxylate was obtained in a good yield.
The reaction of 3-oxo-3-phenyl-propionitrile 1a (1 mmol) and
PIDA (1 mmol) in ethanol (8 mL) at room temperature was investi-
gated as a model reaction. While the PIDA was increased to
2.2 mmol, the yield of ethyl phenylglyoxylate 3a was increased
from 37% to 74%. However, further increase of PIDA to 5 mmol
did not improve the yield of 3a any more. The effect of reaction
temperature was also investigated, product 3a being provided in
86% yield at refluxing temperature in 30 min.
a
-Keto esters, which are good precursors of a
-hydroxy esters,1
2
3
heterocycles and chiral compounds, are important intermediates
for pharmaceuticals and organic synthesis. Because of their versa-
tile applications, many methods for the synthesis of
have been developed. In 1959, Corey group reported a direct syn-
thesis of -keto esters by the oxidation of -bromoacetophenone
with selenium dioxide. In 1987, Creary reported that -keto esters
were produced by the reaction of Grignard reagents with diethyl
a-keto esters
a
a
4
a
5
oxalate. Subsequently,
a-keto esters were synthesized from the
6
(
cyanomethylene)triphenyl phosphoran by Wasserman’s group
7
and from phenylacetic acids by Zhao and Lee. More recently, some
8
9
10
2 2 3
new systems such as O /hv/HBr, TEMPO/Ca(OCl) , oxone/AlCl
1
1
and Cu/O
to obtain
2
,
employed in the reaction with the relative substrates
-keto esters, have been reported. However, these
a
reported procedures suffer from some disadvantages such as
expensive reagents, longer reaction time and harsh reaction condi-
tions. Phenyliodine(III) diacetate (PIDA) is a mild, highly selective
and environmentally benign oxidant.12 Herein, we report a facile
and straightforward approach to obtain
a
-keto esters from b-ke-
Under the optimized reaction conditions, a range of b-ketoni-
triles 1 (Table 1) have been employed to demonstrate the scope
of this procedure. As shown in Table 1, all the b-ketonitriles could
tonitriles, PIDA and alcohols under refluxing condition (Scheme 1).
Initially, PIDA was used in the reaction of 3-oxo-3-phenyl-propi-
onitrile with cyclohex-2-enone in chloroform, expecting to produce
afford
a-keto esters in good yields. The para- substituted b-oxo-
3a,4,5,6,7,7a-hexahydro-7-oxo-2-phenyl-3-benzofurancarbonitrile.
benzenepropanenitriles gave better yields than the corresponding
ortho- and meta-substituted analogues. For example, reaction of
4
-methyl-b-oxo-benzenepropanenitrile 1d with PIDA and EtOH,
⇑
gave product 3d in 81% yield, whereas 2-methyl-b-oxo-
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0