Lipase-Involved Strategy to the Enantiomers of 4-Benzyl-b-Lactam
3.78 (m, 1H, CHNH2), 7.19–7.36 (m, 5H, aroma.); 13C NMR
FULL PAPERS
References
(D2O, 126 MHz): d¼35.52, 37.85, 49.43, 127.69, 129.11,
129.46, 135.02, 173.98. Similarly, (R)-4 (ee¼98%) was obtained
from (R)-1 in quantitative yield.
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Transformations of (R)- and (S)-1 into (R)- and (S)-5
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Boc2O (0.54 g, 2.5 mmol) in CH2Cl2 (3 mL) was added to a sol-
ution of (R)-1 (0.20 g, 1.2 mmol) and DMAP (0.015 g,
0.12 mmol) in CH2Cl2 (5 mL). After 10 hours, the starting ma-
terial was totally consumed as indicated by TLC. The solvent
was evaporated and the residue was purified on a silica gel col-
umn eluting with ethyl acetate/petroleum ether (1:5). (R)-5
{0.32 g, 1.2 mmol; mp 75–778C; ee¼98%; [a]2D5: ꢁ104.2 (c 1,
CHCl3)} was obtained in 99% yield. HR-MS: Mþ found (Mþ
calculated for C15H19NO3): 261.13690 (261.13649); MS: m/z
(relative intensity)¼261 (0.1), 205 (57), 187 (5), 145 (20), 118
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[8] E. Forro, F. Fülçp, Mini-Rev. Org. Chem. 2004, 1, 93–102.
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1
(40), 91 (20), 57 (100); H NMR (CDCl3, 500 MHz): d¼1.56
[s, 9H, C(CH3)3 ], 2.66–2.69 (dd, J¼16.0, 3.0 Hz, 1H), 2.83–
2.88 (dd, J¼13.5, 8.5 Hz, 1H), 2.92–2.96 (d, J¼16.0, 6.0 Hz,
1H), 3.41–3.44 (dd, J¼13.5, 2.5 Hz, 1H), 4.15–4.18 (m, 1H,
CH2CHN), 7.16–7.33 (m, 5H, arom); 13C NMR (CDCl3,
126 MHz): d¼28.11, 38.42, 41.35, 51.71, 83.31, 127.05, 128.79,
129.24, 135.94, 148.02, 164.27.
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´
[12] S. Park, E. Forro, H. Grewal, F. Fülçp, R. J. Kazlauskas,
Similarly, (S)-5 {ee¼99%; [a]2D5: þ104.4 (c 1, CHCl3)} was
obtained from (S)-1 in 99% yield.
Adv. Synth. Catal. 2003, 345, 986–995.
´
[13] E. Forro, F. Fülçp, Org. Lett. 2003, 5, 1209–1212.
´
[14] E. Forro, F. Fülçp, Tetrahedron: Asymmetry 2004, 15,
573–575.
Transformations of (R)- and (S)-5 into (R)- and (S)-6
´
[15] E. Forro, F. Fülçp, Tetrahedron: Asymmetry 2004, 15,
2875–2880.
(R)-5 (0.29 g, 1.1 mmol) was added to 25% NH3 in methanol
(3 mL) at 08C and the mixture was stirred for 4 hours at 08C.
The solvent was evaporated and the residue was washed with
hexane (6 mL) and CH2Cl2 (6 mL), affording (R)-6 {0.31 g,
1.1 mmol; mp 128–1318C; [a]2D5: þ20.6 (c 1.0, CHCl3)} in
99% yield. HR-MS was not obtained due to too low intensity.
MS: m/z (relative intensity)¼280 (Mþ þ2, 0.1), 205 (12), 187
(15), 161 (7), 146 (26), 118 (70), 100 (100), 91 (80), 77 (8), 58
(70); 1H NMR (DMSO-d6, 500 MHz): d¼1.31 [s, 9H,
C(CH3)3], 2.14–2.18 (dd, J¼14.5, 7 Hz, 1H, CH2CONH2),
2.20–2.24 (dd, J¼14.5, 7.0 Hz, 1H, CH2CONH2), 2.63–2.67
(dd, J¼13.5, 8.0 Hz, 1H, ArCH2), 2.68–2.72 (dd, J¼13.0,
5.5 Hz, 1H, ArCH2), 3.90–3.94 (m, 1H, CH2CHNH), 6.84 (br
s, 1H, NH), 7.15–7.32 (m, 5H, arom); 13C NMR (DMSO-d6,
126 MHz): d¼28.70 [C(CH3)3], 39.48, 40.48, 49.68
(CH2CHNH), 77.92 [C(CH3)3], 126.39, 128.51, 129.66, 139.41,
155.26, 172.75.
´
´
[16] P. Csomos, L. T. Kanerva, G. Bernath, F. Fülçp, Tetrahe-
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Bernath, L. T. Kanerva, Adv. Synth. Catal, 2004, 346,
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`
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Similarly,(S)-6{mp128–1318C;lit. mp125–1298C;[21] [a]D25:
ꢁ20.6 (c 0.9, CHCl3); lit. [a]2D0: ꢁ18.96 (c 2.6, CHCl3)}[21] was
obtained from (S)-5 in 96% yield.
´
´
´
[23] J. Kaman, E. Forro, F. Fülçp, Tetrahedron: Asymmetry
2001, 12, 1881–1886.
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ˆ
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Acknowledgements
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The authors thank the Academy of Finland for financial support
(grant 210263 to L. T. K.).
Adv. Synth. Catal. 2006, 348, 197 – 205
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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