Chiral 1,4-Morpholine-2,5-diones
955
solution was evaporated under vacuum to dryness. The oily product was recovered pure in 95% yield
1
after purification by silica gel chromatography. H NMR: ꢂ ¼ 1.64 (d, 3H, J ¼ 6.8Hz), 1.69 (d, 3H,
J ¼ 6.8 Hz), 2.87 (dd, 1H, J ¼ 5.4, 17.6Hz), 3.05 (dd, 1H, J ¼ 3.2, 17.6Hz), 4.05 (dd, 1H, J ¼ 3.2,
5.4 Hz), 5.48 (q, 1H, J ¼ 6.8 Hz), 5.76 (q, 1H, J ¼ 6.8 Hz), 7.38 (m, 5ArH) ppm; 13C NMR: ꢂ ¼ 17.2,
18, 37.3, 52.8, 53.5, 75.1, 127.9, 128.9, 129.4, 136.4, 167.5, 168.5, 172.2ppm; [ꢀ]D ¼
86.2ꢁ cm3 gꢃ1 dmꢃ1 (c ¼ 1, CH3OH).
(3S,6R)-3-(E)-But-2-enyl-6-methyl-N-[(S)-1-phenethyl]-1,4-morpholine-2,5-dione
(3c, C17H21NO3)
Obtained in 85% yield by alkylating 1 with (E)-1-bromobut-2-ene. The reaction was worked up after
8 h and the product was isolated pure as an oil after silica gel chromatography. 1H NMR: ꢂ ¼ 1.65 (d,
3H, J ¼ 6.8 Hz), 1.66 (d, 3H, J ¼ 7.1 Hz), 1.68 (d, 3H, J ¼ 7.1 Hz), 2.6 (m, 2H), 3.85 (t, 1H, J ¼ 6.5 Hz),
5 (q, 1H, J ¼ 6.8Hz), 5.4 (m, 1H), 5.6 (m, 1H), 5.85 (q, 1H, J ¼ 7.1 Hz), 7.3 (m, 5H) ppm; 13C NMR:
ꢂ ¼ 16.6, 17.2, 17.4, 17.7, 52.2, 56.4, 73.4, 123.3, 126.9, 128, 128.8, 131.1, 138.8, 166.4, 166.9ppm;
[ꢀ]D ¼ 94.1ꢁ cm3 gꢃ1 dmꢃ1 (c ¼ 1.8, CHCl3).
(3S,6R)-N-[(S)-1-Phenethyl]-3-[3-methylbutyl]-6-methyl-1,4-morpholine-2,5-dione
(3d, C18H23NO3)
Obtained in 86% yield by alkylating 1 with 1-bromo-3-methylbut-2-ene. The reaction was worked up
after 4 h and the product was isolated pure as an oil after silica gel chromatography. 1H NMR: ꢂ ¼ 1.62
(d, 3H, J ¼ 7.2 Hz), 1.64 (d, 3H, J ¼ 6.8 Hz), 1.67 (s, 3H), 1.7 (s, 3H), 2.6 (m, 2H), 3.83 (dd, 1H,
J ¼ 4.9, 8.3Hz), 5.05 (q, 1H, J ¼ 6.8 Hz), 5.15 (m, 1H), 5.85 (q, 1H, J ¼ 7.2Hz), 7.3 (m, 5H) ppm; 13C
NMR: ꢂ ¼ 16.9, 17.5, 18, 25.9, 32, 52.5, 56.4, 73.8, 116.7, 127.2, 128.1, 128.4, 137.5, 138.3, 166.8,
168 ppm; [ꢀ]D ¼ 108.7ꢁ cm3 gꢃ1 dmꢃ1 (c ¼ 1.4, CHCl3).
Benzyl (3R,6S)-[6-methyl-2,5-dioxo-N-((S)-1-phenethyl)-1,4-morpholin-3-yl]acetate
(4a, C22H23NO5)
Obtained in 88% yield by alkylating 2 with benzyl bromoacetate. The benzyl ester was submitted to
1
silica gel chromatography. H NMR: ꢂ ¼ 1.67 (m, 6H), 2.33 (dd, 1H, J ¼ 6.2, 17.2Hz), 2.5 (dd, 1H,
J ¼ 4, 17.2 Hz), 4.62 (dd, 1H, J ¼ 4, 6.2 Hz), 4.95 (m, 2H), 5.24 (q, 1H, J ¼ 6.6 Hz), 5.98 (q, 1H,
J ¼ 7.2 Hz), 7.31 (m, 10H) ppm; 13C NMR: ꢂ ¼ 15.4, 17.2, 36.6, 50.8, 52.2, 67.1, 74.4, 127.2, 128.2,
128.5, 128.6, 128.9, 134.8, 139.5, 166.7, 167.2, 168.9 ppm; the product was not obtained in a suffi-
ciently pure form to measure the specific rotation.
(3R,6S)-[6-Methyl-2,5-dioxo-N-((S)-1-phenethyl)-1,4-morpholin-3-yl]acetic acid
(4b, C15H17NO5)
The benzyl ester 4a was cleaved by hydrogenolysis, following the procedure described for 3b.
After purification by silica gel chromatography, the product was recovered as an oil in 93% yield.
1H NMR: ꢂ ¼ 1.69 (m, 6H), 2.38 (dd, 1H, J ¼ 6.3, 17.1Hz), 2.47 (dd, 1H, J ¼ 4.2, 17.1Hz), 4.63 (dd,
1H, J ¼ 4.2, 6.3 Hz), 5.2 (q, 1H, J ¼ 6.9 Hz), 5.98 (q, 1H, J ¼ 6.9 Hz), 7.4 (m, 5ArH) ppm; 13C-NMR:
ꢂ ¼ 15.5, 17, 36.2, 51.7, 52.3, 74.3, 127.1, 128.3, 128.9, 138.8, 167.1, 167.3, 172.5ppm;
[ꢀ]D ¼ ꢃ144.7ꢁ cm3 gꢃ1 dmꢃ1 (c ¼ 1, CH3OH).
3-N-(p-Methoxybenzyl)glycine ethylester (5, C12H17NO3)
Ethyl bromoacetate (12 cm3, 110 mmol) was dropped to a solution of 15.5cm3 of p-methoxybenzyla-
mine (110 mmol) and 15.3cm3 of triethylamine (110 mmol) in 50 cm3 of CH2Cl2 cooled at 0ꢁC. When