Tetrahedron Letters
Oxidative kinetic resolution of heterocyclic sulfoxides with a porphyrin-
inspired manganese complex by hydrogen peroxide
b,
Jinchuang Yang a,b, Lianyue Wang b, Ying Lv b, Ning Li b,c, Yue An a, , Shuang Gao
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a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China
b Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
c College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, Henan, China
a r t i c l e i n f o
a b s t r a c t
Article history:
We have successfully reported here the low loading porphyrin-inspired high-valent manganese (IV)-oxo
complex was applied in oxidative kinetic resolution (OKR) of racemic heterocyclic sulfoxides using the
environmentally benign hydrogen peroxide for the first time. This approach allows for rapid OKR
(0.5 h) of a variety of racemic sulfoxides (including pyridine, pyrimidine, pyrazine, thiazole, benzothiazole,
thiophene) in excellent enantioselectivity (up to > 99% ee), simultaneously generating the corresponding
sulfones in high yield (up to 80%). The catalytic system also showed an unexceptionable chemoselectivity
for the sulfoxide substrates with hydroxyl groups in which only the sulfoxide group was oxidized. The
practical utility of the method has been demonstrated in the OKR of gram-scale sulfoxides.
Ó 2017 Elsevier Ltd. All rights reserved.
Received 3 November 2017
Revised 28 November 2017
Accepted 2 December 2017
Available online 5 December 2017
Keywords:
Oxidative kinetic resolution
Heterocyclic sulfoxides
Manganese
Porphyrin-inspired
Sulfone
Introduction
the conversion of racemic sulfoxide. So it is a great of significance
to explore a highly efficient method of OKR of racemic sulfoxides to
The nonracemic sulfoxides are extensively used as chiral auxil-
iaries, ligands and intermediates in modern organic synthesis
chemistry and valuable well-marketed pharmaceutical (e.g.,
esomeprazole, modafinil).1 Therefore, the efficient synthesis of
enantiopure sulfoxides have aroused great interest to numerous
chemists.2 Although the synthesis of chiral sulfoxides is mainly
carried out through the asymmetric oxidation of thioether since
the initial breakthrough completed in asymmetric thioether oxida-
tion by the groups of Kagan and Modena in 1984,3 it is a high
research value how to convert racemic sulfoxides to optically pure
sulfoxides because the synthesis of the racemic sulfoxides is
becoming increasingly concise and can be purchased in lower
prices.4 The tiny sulfones which has wide industrial utility were
often found to form in the most of the process of conventional
asymmetric oxidation of thioether.5 Sulfone moieties are widely
used in medicine (e.g., bicalutamide, eletriptan, and Vioxx), plas-
tics, herbicides, basic organic synthesis and other industries.6 To
date, the method of synthesis of sulfones is really scanty except
sulfides directly oxidized into sulfones in organic synthesis.7 And
the oxidative kinetic resolution (OKR) can be a perfect method to
be used for obtaining both chiral sulfoxides and sulfones from
acquire high ee value of sulfoxides and high yield of sulfones. To
the best of our knowledge, several cases of the OKR of racemic sul-
foxides in the literature involve metal-salen complex (e.g. tita-
nium,1f vanadium,8 iron,9 aluminum,10 and copper11
) with
hydrogen peroxide have been reported. The optical purity of aryl
alkyl sulfoxides up to >99% ee have been achieved (such as
Maguire,12 Zeng and Zhao13 and Chan14). But the above catalytic
systems have apparent disadvantages, including limited substrate
scope or long reaction times (Scheme 1). And the existing report
mostly focused on the OKR of aromatic sulfoxides, the OKR of hete-
rocyclic sulfoxides have not been reported yet. As we all know, the
sulfoxide substances with heteroatoms are more difficult to be car-
ried out in a electrophilic reaction. Therefore, to develop a efficient
catalytic system for the OKR of heterocyclic sulfoxides is still an
attractive target.
We have developed a porphyrin-inspired manganese complexes
with hydrogen peroxide way to conduct catalytic oxidation of sul-
fide to chiral sulfoxide.15 We found a oxidation kinetic resolution
process should exist in the oxidation reaction. Here we reported
a high-efficiency method of OKR involves porphyrin-inspired man-
ganese complexes with hydrogen peroxide to applicate in the
desymmetrization of racemic heterocyclic sulfoxides. With the
low-loading catalyst (0.01 equiv), higher efficiency(0.5 h), more
moderate reaction condition(ꢀ30 °C), and more green oxidant
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Corresponding authors.
0040-4039/Ó 2017 Elsevier Ltd. All rights reserved.