Kengo Akagawa and Kazuaki Kudo
COMMUNICATIONS
and 3). However, the reaction rate gradually de- Acknowledgements
creased in further recycling, while the enantioselectiv-
ity was completely maintained (entry 4).
In conclusion, through the exploration of the pep-
tide catalyst for the efficient asymmetric epoxidation
in aqueous media, we have found the novel terminal
The authors thank Mr. Masahiro Yamashina, Mr. Akihiro
Yabe, and Mr. Jeng-Kae Tan for experimental assistance.
sequence d-Pro-Ach-[Ala
(1-Pyn)]3. Introducing un- References
natural amino acid Ala(1-Pyn) with the hydrophobic
AHCTUNGTRENNUNG
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and bulky aromatic ring was particularly effective.
The present study demonstrates that even though the
catalytic ability is not sufficient, the peptide catalysis
always has potential for improving it simply by chang-
ing sequences, and a resin-supported peptide offers an
easy way of screening them. It is expected that the
result obtained in this study will further be applied to
other reactions. Research from such a viewpoint is
under way in our laboratory.
Experimental Section
General Procedure for the Asymmetric Epoxidation
of a,b-Unsaturated Aldehydes (Table 3)
To a mixture of the substrate aldehyde (0.05 mmol) and the
resin-supported peptide (0.01 mmol of the terminal prolyl
group) in THF (0.33 mL) and H2O (0.66 mL), 30 wt% hy-
drogen peroxide aqueous solution (7.3 mL) was added at
08C. After the resulting mixture had been stirred for 12–
48 h, the catalyst was filtered off and washed with chloro-
form. To the filtrate solution, water was added, and the
whole extracted with chloroform. The organic layer was
dried over anhydrous magnesium sulfate, and the solvent
was removed under reduced pressure. The residue was dis-
solved in ethanol (1 mL), and sodium borohydride
(0.25 mmol) was added. After the mixture had been stirred
for 30 min, saturated aqueous ammonium chloride solution
was added. The resulting solution was extracted with chloro-
form. The organic layer was dried over anhydrous magnesi-
um sulfate, and the solvent was removed under reduced
pressure. In entries 1–8, the crude product was purified
using preparative TLC (hexane/ethyl acetate=2/1) to afford
the epoxy alcohol. In entries 9 and 10, to the crude epoxy al-
cohol in dichloromethane (1 mL), pyridine (30 mL) and 3,5-
dinitrobenzoyl chloride (15 mg) were added. After the mix-
ture had been stirred for 1 h, 10% aqueous citric acid was
added. The resulting solution was extracted with ethyl ace-
tate and the organic layer was successively washed with
H2O and saturated aqueous sodium bicarbonate. The organ-
ic layer was dried over anhydrous magnesium sulfate, and
the solvent was removed under reduced pressure. The crude
product was purified using preparative TLC (hexane/ethyl
acetate=2/1) to afford the 3,5-dinitrobenzoate esters.
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Enantiomeric excesses and the absolute configurations of
the major products were determined according to the litera-
ture (ref.[5]). In the examination of the reusability of the
peptide catalyst (entries 2–4), the recovered catalyst by fil-
tration was dried under vacuum, and used for the next reac-
tion.
846
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Adv. Synth. Catal. 2011, 353, 843 – 847