Tetrahedron Letters
Oxidative cleavage of a-sulfonyl ketones to carboxylic acids with
Ce(NH4)2(NO3)6
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Meng-Yang Chang , Chung-Yu Tsai
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Tandem oxidative cleavage of a-sulfonyl arylketones 2 with the combination of Ce(NH4)2(NO3)6 and O2 in
MeCN afforded carboxylic acids 3 in moderate to good yields. The plausible reaction mechanism has been
discussed.
Received 2 July 2014
Revised 25 July 2014
Accepted 9 August 2014
Available online 14 August 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
a-Sulfonyl ketones
Oxidative cleavage
Ce(NH4)2(NO3)6
Introduction
Results and discussion
Sulfonyl groups are useful substituents in synthetic chemistry.
Among the functionalized sulfonyl groups, the skeleton of -sulfo-
nyl ketone (b-ketosulfone) is a versatile intermediate.1 The sulfonyl
group can stabilize the adjacent -carbon atom, thus facilitating
the formation of a new C–C bond via diversified approaches. It is
useful precursor for functional group transformations and
constitutes a diverse structural class associated with important
medicinal applications. Thus, some synthetic routes to access this
scaffold have been developed.2 Among these protocols, nucleo-
As shown in Table 1, entries 1–2 show that 3a was respectively
isolated in 49% and 72% yields with a 1.0 and 2.0 equiv of CAN
under the nitrogen system. It caused an incomplete CAN-mediated
oxidative cleavage of 2a and a different ratio of starting material
was recovered. Under air atmosphere, a 65% yield of 3a was pro-
vided along with phenylglyoxylic acid (26%) by CAN-mediated oxi-
dative cleavage of 2a (entry 3). As suggested by previous reports,6–
a
a
a
10
some reaction conditions of oxidative cleavage were screened.
Entry 4 shows that the combination of FeCl3 and t-BuONO afforded
3a (50%) and phenylglyoxylic acid (37%) under a solvent-free con-
dition.6 Similar results were also described in the combination of I2
and DMSO,7 and CuI and O2,8 or Oxone.9 The ratio values of benzoic
acid 3a/phenylglyoxylic acid were nearly 6/4 (entry 4), 4/6 (entry
5), 8/2 (entry 6), and 7/3 (entry 7). The phenylglyoxylic acid should
be an intermediate for the generation of benzoic acid 3a. Next,
treatment of 2a with DDQ and TEMPO in MeCN produced 3a
philic substitution of
sodium salts (RSO2Na) affording
a
-bromo acetophenones 1 with sulfinic
-sulfonyl ketones 2 with good
a
to excellent yields is an easy methodology (see Scheme 1).3
Cerium ammonium nitrate (CAN, Ce(NH4)2(NO3)6) is one of the
most important oxidants in organic synthesis among various ceriu-
m(IV) complexes, as it is a mild, stable, inexpensive, and easily
operational oxidation reagent.4 It has largely been employed as
the co-oxidant in the presence of molecular oxygen for a variety
of transformations.5 Due to the numerous advantages associated
with this eco-friendly compound, CAN has been explored as a
powerful reagent for different reactions. Many research teams have
successfully developed various useful transformations using this
(26%) and
a-conjugated TEMPO with 2a adduct (58%), as shown
in entry 8.10 When the TEMPO was removed from the oxidation
system, no desired 3a was generated (see entry 9). By screening
different combinations of oxidants and solvents, we found that
the combination of CAN and O2 was an optimal condition to
oxidative cleavage of 2a.
reagent.4 For the application of
a
-sulfonyl ketones3 in this study,
CAN-mediated synthesis of skeleton 3 with dioxygen was chosen
as the key focus, as shown in Scheme 1.
With the results in hand, the CAN-mediated reactions were fur-
ther studied, as shown in Table 2. When CAN-mediated oxidative
cleavage of 2a (Ar = Ph, R = Me) was treated with O2 in MeCN at rt
for 10 h, benzoic acid (3a) resulted in 45% yield and the starting
material 2a was recovered in 47% (see Table 1, entry 1). By elevating
the temperature to reflux, 3a was isolated in 72% yield (entry 2).
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