Catalytic Asymmetric Oxidation of Heteroaromatic Sulfides
azolyl benzyl sulfides gave a significantly lower enantio-
selectivity than the 1H-benzimidazolyl pyridinylmethyl sul-
fides. The following interesting conclusions can be drawn:
a pyridine ring in the substrate is indispensable for high
enantioselectivities, and the substituents of the benzyl, pyr-
idinylmethyl, or benzimidazolyl moiety have an important
impact on the enantioselectivities.
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Conclusions
We have developed a simple and efficient catalytic asym-
metric oxidation of 1H-benzimidazolyl pyridinylmethyl sul-
fides to 1H-benzimidazolyl pyridinylmethyl sulfoxides with
tert-butyl hydroperoxide in toluene in the presence of a chi-
ral titanium complex formed in situ from Ti(iPrO)4, chiral
diol 3c and water. The chiral sulfoxides were obtained in
high chemical yields with excellent enantiomeric excesses.
Investigations are underway to utilize this method for the
asymmetric synthesis of other chiral sulfoxides exhibiting
important biological activities.
Experimental Section
General Experimental Procedures: In
a typical experiment,
Ti(iPrO)4 (4.5 mg, 0.016 mmol) was added to a solution of ligand
3c (12 mg, 0.032 mmol) in toluene (2 mL) at 25°C. The solution
was stirred for 10 min. Water (5.7 mg, 0.32 mmol) was added to the
mixture, and the solution was stirred for another 10 min. Pyrmeta-
zole sulfide (1a) (105 mg, 0.32 mmol) was then added to the solu-
tion, and the temperature was then adjusted to –20°C; sub-
sequently, tert-butyl hydroperoxide (70%, 96 µL, 0.64 mmol) was
slowly added. After 24 h at –20°C, the solution was extracted three
times with aqueous ammonium hydroxide (12.5% of NH3,
3ϫ5 mL). Subsequently, isobutyl methyl ketone (5 mL) was added
to the combined aqueous extracts. The aqueous phase was adjusted
to pH = 7 with acetic acid, separated and extracted with an ad-
ditional portion of isobutyl methyl ketone (5 mL). The combined
organic solutions were dried with anhydrous Na2SO4, filtered, and
the solvent was removed in vacuo. The residue was purfied by
chromatography on silica gel to afford 2a (101 mg, 92% yield, 96%
ee).
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and full spectroscopic data.
Acknowledgments
We gratefully acknowledge the Shanghai Municipal Committee of
Science and Technology (No. 05DZ19344), the National Natural
Science Foundation of China (No. 20802087), the Knowledge In-
novation Program of the Chinese Academy of Sciences and the
Ministry of Science and Technology of the P. R. China for their
financial support.
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M. Seenivasaperumal, H. Federsel, A. Ertan, K. J. Szabo,
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For details of the experimental procedures, see the Supporting
Information.
Received: November 17, 2008
Published Online: January 21, 2009
Eur. J. Org. Chem. 2009, 987–991
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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