8538
M. Nejman et al. / Tetrahedron 61 (2005) 8536–8541
0.04 mol) in THF (50 mL) was added dropwise with stirring
and occasional cooling for ca. 30 min to a suspension of
sodium hydride (1.92 g, 0.08 mol) and the corresponding
sulfone 1 (0.04 mol) in anhydrous THF (100 mL). Stirring
was continued for 2 h at room temperature. The mixture was
then cooled to 10 8C and quenched with saturated NH4Cl aq
(30 mL). Water (20 mL) was then added, the organic layer
was separated, and the aqueous phase was extracted with
CH2Cl2 (3!20 mL). Combined extracts were dried
(MgSO4) and the solvent evaporated in vacuo to give
spectroscopically pure adducts 3a–h.
53.1, 55.8, 61.1, 61.5, 78.6, 155.3, 168.0, 168.45; FAB/MS:
332 (42, MC1), 276 (100), 232 (54%).
4.2.5. Diethyl 2-(1-N-Boc-amino-3-methylbutyl)malon-
ate (3e). Yield 96%, colorless solid, mp 58–60 8C; [Found:
C, 59.0; H, 9.2; N, 4.2. C17H31NO6 requires C, 59.11; H,
9.05; N, 4.05%]; nmax (KBr) 3370, 3000, 2970, 1752, 1720,
1528, 1476, 1450, 1400, 1372, 1320, 1300, 1268, 1236,
1188, 1160, 1070, 1036, 1016, 630, 620 cmK1; dH 0.92 (3H,
d, JZ6.25 Hz, Me2CH), 0.95 (3H, d, JZ6.25 Hz, Me2CH),
1.27 (3H, t, JZ7.1 Hz, CH3CH2O), 1.29 (3H, t, JZ7.1 Hz,
CH3CH2O), 1.41 (9H, s, Me3C), 1.46–1.67 (1H, m,
Me2CH), 3.56 (1H, d, JZ4.25 Hz, CH(CO2Et)), 4.15–4.26
(4H, m, CH3CH2O), 4.27–4.35 (1H, m, CH–NH), 5.33 (1H,
d, JZ10.0 Hz, NH); dC 13.6, 21.5, 22.6, 24.6, 27.9, 42.2,
48.0, 55.1, 60.9, 61.1, 78.5, 154.8, 167.5, 167.9; FAB/MS;
346 (42, MC1), 290 (100), 246 (38%).
4.2.1. Diethyl 2-(N-Boc-aminomethyl)malonate (3a).
Yield 88%, colorless oil; [Found: C, 53.7; H, 7.9; N, 5.0.
C13H23NO6 requires C, 53.97; H, 8.01; N, 4.84%]; nmax
(liquid film) 3400, 3000, 2960, 1730, 1528, 1508, 1488,
1460, 1400, 1374, 1300, 1256, 1170, 1100, 1036, 960, 900,
870, 784, 650 cmK1; dH 1.28 (6H, t, JZ7.1 Hz, CH3CH2O),
1.43 (9H, s, Me3C), 3.60–3.65 (3H, m, CHCH2NH), 4.21
(4H, q, JZ7.1 Hz, CH3CH2O), 5.15 (1H, br s, NH); dC 13.6,
27.9, 38.9, 51.6, 61.2, 79.1, 155.3, 167.8; FAB/MS: 290 (26,
MC1), 234 (100), 190 (78%).
4.2.6. Diethyl 2-(N-Boc-aminocyclohexylmethyl)malon-
ate (3f). Yield 99%, colorless oil; [Found: C, 61.6; H, 9.1;
N, 3.6. C19H33NO6 requires C, 61.43; H, 8.95; N, 3.77%];
nmax (liquid film) 3450, 2990, 2950, 2870, 1736, 1500, 1450,
1400, 1374, 1350, 1316, 1284, 1256, 1174, 1150, 1100,
1046, 1020, 972, 870, 780, 650 cmK1; dH 0.94–1.20 (5H, m,
ring CH2), 1.26 (3H, t, JZ7.0 Hz, CH3CH2O), 1.29 (3H, t,
JZ7.0 Hz, CH3CH2O), 1.40 (9H, s, Me3C), 1.40–1.55 (6H,
m, ring CH2), 3.71 (1H, d, JZ4.0 Hz, CH(CO2Et)), 4.02
(1H, dt, JZ10.0, 4.0 Hz, CHNH), 4.10–4.32 (4H, m,
CH3CH2O), 5.54 (1H, d, JZ10.0 Hz, NH); dC 13.6, 13.7,
25.5, 25.6, 25.8, 29.2, 29.9, 28.0, 41.0, 52.45, 54.7, 61.0,
61.4, 78.5, 155.2, 168.1, 168.45; FAB/MS: 372 (20, MC1),
316 (47), 272 (28%).
4.2.2. Diethyl 2-(1-N-Boc-aminoethyl)malonate (3b).
Yield 94%, colorless solid; [Found: C, 55.6; H, 8.1; N,
4.8. C14H25NO6 requires C, 55.43; H, 8.31; N, 4.62%]; nmax
(liquid film) 3370, 2980, 2930, 1750, 1708, 1528, 1460,
1380, 1368, 1308, 1250, 1176, 1156, 1100, 1080, 1050,
1020, 856, 834, 750, 660, 630 cmK1; dH 1.24–1.32 (6H, m,
CH3CH2O), 1.24–1.32 (3H, m, CH3CH), 1.42 (9H, s,
Me3C), 3.56 (1H, d, JZ4.5 Hz, CH(CO2Et)), 4.13–4.30
(4H, m, CH3CH2O), 4.30–4.45 (1H, m, NHCH), 5.27–5.43
(1H, m, NH); dC 13.8, 18.9, 28.1, 45.75, 55.9, 61.2, 61.35,
79.1, 154.8, 167.55, 168; FAB/MS: 304 (46, MC1), 248
(100), 204 (28%).
4.2.7. Diethyl 2-(N-Boc-aminophenylmethyl)malonate
(3g). Yield 81%, colorless solid, mp 69–70 8C; [Found: C,
62.3; H, 7.6; N, 4.0. C19H27NO6 requires C, 62.45; H, 7.45;
N, 3.83%]; nmax (KBr) 3400, 2990, 2950, 1728, 1688, 1520,
1390, 1368, 1316, 1296, 1256, 1236, 1172, 1012, 754,
700 cmK1; dH 1.13 (3H, t, JZ7.1 Hz, CH3CH2O), 1.26 (3H,
t, JZ7.1 Hz, CH3CH2O), 1.41 (9H, s, Me3C), 3.88 (1H, d,
JZ4.7 Hz, CH(CO2Et)), 4.01–4.29 (4H, m, CH3CH2O),
5.49 (1H, br s, CHNH), 6.18 (1H, br s, NH), 7.20–7.36 (5H,
m, Harom); dC 13.5, 13.6, 27.95, 53.15, 56.6, 61.2, 61.5, 79.2,
126.0, 127.2, 128.2, 139.4, 154.7, 166.8, 167.7; FAB/MS:
366 (1, MC1), 266 (40%).
4.2.3. Diethyl 2-(1-N-Boc-aminopropyl)malonate (3c).
Yield 98%, colorless solid mp 53–55 8C; [Found: C, 56.9;
H, 8.5; N, 4.2. C15H27NO6 requires C, 56.77; H, 8.57; N,
4.41%]; nmax (KBr) 3360, 2976, 2936, 1736, 1688, 1532,
1460, 1390, 1368, 1320, 1290, 1244, 1230, 1176, 1150,
1120, 1100, 1070, 1010, 650, 620 cmK1; dH 0.95 (3H, t, JZ
7.4 Hz, CH3CH2CH), 1.27 (3H, t, JZ7.1 Hz, CH3CH2O),
1.29 (3H, t, JZ7.1 Hz, CH3CH2O), 1.42 (9H, s, Me3C),
1.50–1.68 (2H, m, CH3CH2CH), 3.60 (1H, d, JZ4.3 Hz,
CH(CO2Et)), 4.10–4.30 (2H, m, CH3CH2O), 4.10–4.30 (1H,
m, NHCH), 5.40 (1H, d, JZ10.1 Hz, NH); dC 10.5, 13.7,
13.8, 28.0, 51.5, 54.6, 61.1, 61.3, 78.7, 155.2, 167.7, 168.15;
FAB/MS: 318 (1, MC1), 262 (7), 219 (23%).
4.2.8. Diethyl 2-(N-Boc-amino-(4-methoxyphenyl)
methyl)malonate (3h). Yield 99%, colorless solid, mp
64–66 8C; [Found: C, 60.5; H, 7.6; N, 3.4. C20H29NO7
requires C, 60.74; H, 7.39; N, 3.54%]; nmax (KBr) 3390,
2990, 1744, 1728, 1684, 1520, 1368, 1300, 1250, 1172,
1104, 1024, 832, 630, 620 cmK1; dH 1.16 (3H, t, JZ7.1 Hz,
CH3CH2O), 1.26 (3H, t, JZ7.1 Hz, CH3CH2O), 1.41 (9H, s,
Me3C), 3.78 (3H, s, CH3O), 3.84 (1H, d, JZ5.0 Hz),
CH(CO2Et)), 4.00–4.30 (4H, m, CH3CH2O), 5.42 (1H, br s,
CHNH), 6.12 (1H, br s, NH), 6.84 (2H, d, JZ8.7 Hz,
Harom), 7.22 (2H, d, JZ8.7 Hz, Harom); dC 13.8, 13.9, 28.2,
52.9, 55.2, 57.0, 61.5, 61.8, 79.5, 113.8, 127.4, 131.7,
158.85, 154.9, 167.0, 168.0; FAB/MS: 396 (1, MC1), 294
(11), 279 (38), 180 (100%).
4.2.4. Diethyl 2-(1-N-Boc-amino-2-methylpropyl)malon-
ate (3d). Yield 98%, colorless oil; [Found: C, 58.2; H, 8.7;
N, 4.4. C16H29NO6 requires C, 57.99; H, 8.82; N, 4.23%];
nmax (liquid film) 3440, 3390, 2980, 2930, 2910, 1724, 1500,
1470, 1392, 1368, 1348, 1280, 1264, 1232, 1172, 1100,
1090, 1034, 1010, 870, 660, 630 cmK1; dH 0.93 (3H, d, JZ
6.4 Hz, Me2CH), 0.96 (3H, d, JZ6.4 Hz, Me2CH), 1.27
(3H, t, JZ7.1 Hz CH3CH2O), 1.29 (3H, t, JZ7.1 Hz,
CH3CH2O), 1.41 (9H, s, Me3C), 1.64–1.82 (1H, m,
Me2CH), 3.69 (1H, d, JZ4.3 Hz, CH(CO2Et)), 3.94–4.05
(1H, m, CH–NH), 4.10–4.30 (4H, m, CH3CH2O), 5.55 (1H,
d, JZ10.5 Hz, NH); dC 13.7, 13.8, 19.0, 19.6, 28.0, 31.8,