10.1002/ejoc.201700936
European Journal of Organic Chemistry
FULL PAPER
Ethyl 3-(acetyloxy)-2-(4-methoxybenzoyl)butanoate (4c). Colorless oil.
Two isomers. Ratio 1:1; 1H NMR (CDCl3, 400 MHz) one isomer: δ 1.14 (t.
J = 7.2 Hz, 3H), 1.27 (d, J = 6.0 Hz, 3H), 1.88 (s, 3H), 3.87 (s, 3H), 4.15
(q, J = 7.2 Hz, 2H), 4.54 (m, 1H), 5.61-5.64 (m, 1H), 6.93-6.96 (m, 2H),
7.98-8.02 (m, 2H); second isomer: 1.14 (t. J = 7.2 Hz, 3H), 1.39 (d, J =
6.0 Hz, 3H), 2.00 (s, 3H), 3.87 (s, 3H), 4.15 (q, J = 7.2 Hz, 2H), 4.54 (m,
1H), 5.65-5.75 (m, 1H), 6.93-6.96 (m, 2H), 7.98-8.02 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ 190.5, 169.7, 169.6, 167.2, 167.1, 164.2, 164.0,
131.2, 131.1, 129.3, 129.3, 114.0, 113.9, 69.9, 69.1, 61.6, 61.5, 59.2,
58.8, 55.5, 55.5, 21.0, 20.9, 18.5, 18.0, 13.9, 13.9; HR ESIMS (M+Na)+
calcd for C16H20O6Na 331.1158, found 331.1157.
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Molander, G.
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Patel, H.D. Synth. Commun. 2014, 44, 2756-2788; h) Voskressensky,
L.G. Festa, A. A. Varlamov, A.V. Tetrahedron 2014, 70, 551-572; i) Bigi,
F. Quarantelli, C. Curr. Org. Synth. 2012, 9, 31-39.
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913-917.
Ethyl 3-(acetyloxy)-2-benzoylbutanoate (4d). Colorless oil. Two
isomers. Ratio 1:1; 1H NMR (CDCl3, 400 MHz) one isomer: δ 1.15 (t. J =
7.2 Hz, 3H), 1.29 (d, J = 6.0 Hz, 3H), 1.88 (s, 3H), 4.17 (q, J = 7.2 Hz,
2H), 4.59 (m, 1H), 5.64-5.66 (m, 1H), 7.46-7.50 (m, 2H), 7.57-7.60 (m,
1H), 7.98-7.8.02 (m, 2); second isomer: 1.16 (t. J = 7.2 Hz, 3H), 1.39 (d,
J = 6.4 Hz, 3H), 1.99 (s, 3H), 4.17 (q, J = 7.2 Hz, 2H), 4.59 (m, 1H), 5.67-
5.70 (m, 1H), 7.46-7.50 (m, 2H), 7.57-7.60 (m, 1H), 7.98-7.8.02 (m, 2);
13C NMR (100 MHz, CDCl3): δ 192.3, 192.2, 169.7, 167.0, 166.8, 136.3,
133.8, 133.6, 128.8, 128.7, 128.6, 69.0, 61.7, 61.6, 59.3, 59.0, 21.0, 18.5,
14.0, 13.9; HR ESIMS (M+Na)+ calcd for C15H18O5Na 301.1051, found
301.1052.
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Synthesis of ethyl 3-methyl-2-(4-nitrobenzoyl)oxirane-2-carboxylate
(6). To a solution of 2-(4-nitrobenzoyl)-but-2-enoic acid ethyl ester (3b)
(88 mg, 0.33 mmol) in dry DCM (10 mL), KOH (110 mg, 2.00 mmol) and
m-CPBA (232 mg, 1.32 mmol) were successively added. After stirring for
16 hours the reaction was filtered using Celite, solvent was removed in
vacuum. The resulting residue was purified by column chromatography
(silica gel, eluent: ethyl acetate/hexanes) to afford the desired product 6
as a colorless liquid (51 mg, 0.18 mmol) with 56% yield; 1H NMR (CDCl3,
400 MHz) δ major isomer: δ 1.19 (t. J = 7.2 Hz, 3H), 1.30 (d, J = 5.6 Hz,
3H), 3.76 (q, J = 5.6 Hz, 1H), 4.22 (q, J = 7.2 Hz, 2H), 8.17 (d, J = 9.2 Hz,
2H), 8.33 (d, J = 9.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 189.9, 166.6,
139.3, 130.2, 123.9, 70.0, 63.0, 62.9, 59.5, 15.1, 13.8; HR ESIMS
(M+Na)+ calcd for C13H13NO6Na 302.0641, found 302.0630; Elementary
analysis calcd. for C13H13NO6; C 55.92%, H 4.69%, N 5.02% found C
55.89, H 4.75%, N 4.96%.
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General procedure for enzyme-catalyzed synthesis of ethyl 3-
methyl-2-(4-nitrobenzoyl)oxirane-2-carboxylate (6). A mixture of the
ethyl 3-(4-nitrophenyl)-3-oxopropanoate (237 mg, 1 mmol), vinyl acetate
(3 mmol), and Novozym 435 (200 mg) in acetonitrile (5 mL) was shaken
at 200 rpm at 40 °C for 120 hours. The reaction was monitored by TLC.
Then, UHP (1.5 mmol) and phenylacetic acid (272 mg, 2.00 mmol) were
added, and the mixture was stirred for 48 hours. Next, the mixture was
filtered and the residue was washed with ethyl acetate. The combined
organic phase was concentrated under vacuum. The resulting residue
was purified by column chromatography (silica gel, eluent: ethyl
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acetate/hexanes)
to
afford
the
desired
3-methyl-2-(4-
nitrobenzoyl)oxirane-2-carboxylate (6) with 29% yield.
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Acknowledgements
[19] a) Hangarge, R. V.; Sonwane, S. A.; Jarikote, D. V.; Shingare, M. S.
Green Chem. 2001, 3, 310-312; b) Kaupp, G.; Naimi-Jamal, M. R.;
Schmeyers, J. Tetrahedron 2003, 59, 3753-3760.
This work was supported by Polish National Science Center
project No. 2014/14/M/ST5/00030.
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Keywords: Knoevenagel condensation • promiscuity •
hydrolases • biocatalysis • tandem reaction
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2nd ed.; John Wiley
& Sons: Toronto, 1999; e) Ebitani, K.
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