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J. Elaridi et al. / Tetrahedron: Asymmetry 16 (2005) 1309–1319
167.5, 168.0 (C1, CONH); HRMS (ESI+, MeOH): m/z
calcd for C10H17NO3Na: 222.1106. Found: 222.1103;
C10H17NO3 (199.25) calcd: C, 60.26; H, 8.60; N, 7.03.
Found: C, 60.13; H, 8.88; N, 6.95.
39%); IR (neat): m = 2960, 2871, 2358, 1694, 1645,
1506, 1469, 1369, 1279, 1228, 1170, 1136, 1086, 913,
822, 765, 734 cmꢀ1 1H NMR (300 MHz, CDCl3): d
;
0.92 (d, 6H, J = 6.6 Hz, (CH3)2CH), 1.29 (t, 3H,
J = 7.2 Hz, OCH2CH3), 1.76–1.86 (m, 1H, (CH3)2CH),
2.13 (d, 2H, J = 7.2 Hz, CH2C@), 2.16 (s, 3H, CH3CO),
4.19 (q, 2H, J = 7.1 Hz, OCH2CH3), 7.24 (br d, 1H,
J = 11.1 Hz, NH), 8.06 (d, 1H, J = 12.0 Hz, H3); 13C
NMR (75 MHz, CDCl3): d 14.4 (OCH2CH3), 22.5
((CH3)2CH), 23.6 (CH3CO), 28.2 ((CH3)2CH), 34.5
(CH2C@), 60.5 (OCH2CH3), 112.3 (C2), 132.1 (C3),
168.0, 168.3 (C1, CONH); HRMS (ESI+, MeOH): m/z
calcd for C11H19NO3Na: 236.1263. Found: 236.1257.
4.3.3. Ethyl 3-N-acetylamino-2-methyl-2-propenoate
1c. Prepared from formyl ester 3c (1.09 g, 8.38 mmol),
acetamide (5.00 g, 84.6 mmol) and a catalytic amount of
para-toluenesulfonic acid in toluene (12 mL). Purifica-
tion by flash chromatography on silica gel using light
petroleum and ethyl acetate (1:1) first gave the (Z)-en-
amide Z-1c as an off-white waxy solid (0.20 g, 14%);
mp 42–43 ꢁC; IR (KBr): m = 2980, 2978, 1706, 1682,
1624, 1489, 1439, 1394, 1370, 1342, 1273, 1224, 1194,
1160, 1112, 1031, 982, 946, 859, 780, 734 cmꢀ1
;
1H
4.3.5. Ethyl 3-N-benzoylamino-2-methyl-2-propenoate.
Prepared from formyl ester 3c (1.59 g, 12.2 mmol),
benzamide (4.47 g, 36.9 mmol) and a catalytic amount
of para-toluenesulfonic acid in toluene (70 mL). Purifi-
cation by flash chromatography on silica gel using light
petroleum and ethyl acetate (2:1) first gave the title (Z)-
enamide as an off-white waxy solid (2.41 g, 85%); mp
65–66 ꢁC; IR (KBr): m = 3067, 2981, 2252, 1682, 1633,
1582, 1505, 1480, 1453, 1440, 1393, 1371, 1338, 1278,
1235, 1201, 1150, 1095, 1069, 1028, 912, 868, 844, 800,
NMR (300 MHz, CDCl3): d 1.32 (t, 3H, J = 7.2 Hz,
OCH2CH3), 1.84 (d, 3H, J = 1.5 Hz, CH3C@), 2.13 (s,
3H, CH3CO), 4.22 (q, 2H, J = 7.2 Hz, OCH2CH3),
7.37 (dq, 1H, J = 11.2, 1.3 Hz, H3), 10.40 (br s, 1H,
NH); 13C NMR (75 MHz, CDCl3): d 14.3 (OCH2CH3),
16.1 (CH3C@), 23.8 (CH3CO); 60.5 (OCH2CH3), 104.7
(C2), 134.8 (C3), 168.2, 169.8 (C1, CONH); HRMS
(ESI+, MeOH): m/z calcd for C8H13NO3Na: 194.0793.
Found: 194.0789; C8H13NO3 (171.19) calcd: C, 56.13;
H, 7.65; N, 8.18. Found: C, 56.35; H, 7.67; N, 7.88.
The (E)-isomer E-1c was then eluted and isolated as
an off-white solid (0.61 g, 43%); mp 114–116 ꢁC; IR
(KBr): m = 2992, 1712, 1667, 1631, 1528, 1476, 1397,
1366, 1335, 1272, 1208, 1138, 1032, 987, 970, 886, 853,
780, 734, 700, 676, 648 cmꢀ1 1H NMR (300 MHz,
;
CDCl3): d 1.35 (t, 3H, J = 7.1 Hz, OCH2CH3), 1.92 (d,
3H, J = 1.2 Hz, CH3C@), 4.27 (q, 2H, J = 7.1 Hz,
OCH2CH3), 7.46–7.59 (m, 3H, H30, 40, 50), 7.61–7.65
(m, 1H, H3), 7.93–7.96 (m, 2H, H20, 60), 11.47 (br d,
1H, J = 10.5 Hz, NH); 13C NMR (75 MHz, CDCl3): d
14.4 (OCH2CH3), 16.2 (CH3C@), 60.7 (OCH2CH3),
105.7 (C2), 127.7, 128.9, 132.7 (ArCH), 132.8 (C10),
135.4 (C3), 164.5, 170.1 (C1, CONH); HRMS (ESI+,
MeOH): m/z calcd for C13H15NO3Na: 256.0950. Found:
256.0939; C13H15NO3 (233.11) calcd: C, 66.94; H, 6.48;
N, 6.00. Found: C, 67.16; H, 6.42; N, 5.95. The title
(E)-isomer was then eluted and isolated as an off-white
solid (0.26 g, 9%); mp 89–91 ꢁC; IR (KBr): m = 3178,
2978, 2363, 1703, 1646, 1579, 1560, 1515, 1482, 1450,
1395, 1368, 1353, 1264, 1208, 1184, 1138, 1074, 1041,
1027, 1001, 922, 902, 875, 798, 754, 702, 654,
1
694 cmꢀ1; H NMR (300 MHz, CDCl3): d 1.29 (t, 3H,
J = 7.2 Hz, OCH2CH3), 1.82 (d, 3H, J = 1.5 Hz,
CH3C@), 2.18 (s, 3H, CH3CO), 4.20 (q, 2H,
J = 7.1 Hz, OCH2CH3), 7.20 (br d, 1H, J = 9.9 Hz,
NH), 8.00 (apparent dd, 1H, J = 12.0, 1.5 Hz, H3); 13C
NMR (75 MHz, CDCl3):
d 10.7 (CH3C@), 14.4
(OCH2CH3), 23.5 (CH3CO), 60.6 (OCH2CH3), 108.0
(C2), 131.8 (C3), 168.2, 168.4 (C1, CONH); HRMS
(ESI+, MeOH): m/z calcd for C8H13NO3Na: 194.0793.
Found: 194.0787.
4.3.4. Ethyl 3-N-acetylamino-2-isobutyl-2-propenoate
1d. Prepared from formyl ester 3d (1.00 g, 5.81 mmol),
acetamide (3.50 g, 59.2 mmol) and a catalytic amount of
para-toluenesulfonic acid in toluene (30 mL). Purifica-
tion by flash chromatography on silica gel using light
petroleum, dichloromethane and ethyl acetate (4:1:1)
first gave the (Z)-enamide Z-1d as a brown oil (0.10 g,
8%); IR (neat): m = 2958, 2870, 2360, 1716, 1682, 1628,
1467, 1372, 1346, 1290, 1269, 1188, 1095, 1031, 933,
1
636 cmꢀ1; H NMR (300 MHz, CDCl3): d 1.32 (t, 3H,
J = 7.1 Hz, OCH2CH3), 1.93 (d, 3H, J = 1.5 Hz,
CH3C@), 4.24 (q, 2H, J = 7.2 Hz, OCH2CH3), 7.49–
7.53 (m, 2H, H30, 50), 7.58–7.64 (m, 1H, H40), 7.80 (br
d, 1H, J = 12.0 Hz, NH), 7.83–7.87 (m, 2H, H20, 60),
8.23 (apparent dd, 1H, J = 12.0, 1.2 Hz, H3); 13C
NMR (75 MHz, CDCl3):
d 10.9 (CH3C@), 14.5
(OCH2CH3), 60.7 (OCH2CH3), 100.1 (C2), 127.4,
129.2, 132.0, 132.9 (ArCH, C3), 133.0 (C10), 162.3,
168.3 (C1, CONH); HRMS (ESI+, MeOH): m/z calcd
for C13H15NO3Na: 256.0950. Found: 256.0943;
C13H15NO3 (233.11) calcd: C, 66.94; H, 6.48; N, 6.00.
Found: C, 67.14; H, 6.26; N, 5.99.
822, 786 cmꢀ1 1H NMR (300 MHz, CDCl3): d 0.86
;
(d, 6H, J = 6.6 Hz, (CH3)2CH), 1.31 (t, 3H, J = 7.2 Hz,
OCH2CH3), 1.67–1.80 (m, 1H, (CH3)2CH), 2.06 (d,
2H, J = 7.0, Hz, CH2C@), 2.14 (s, 3H, CH3CO), 4.21
(q, 2H, J = 7.1 Hz, OCH2CH3), 7.32 (d, 1H, J =
11.1 Hz, H3), 10.48 (br d, 1H, J = 9.9 Hz, NH); 13C
NMR (75 MHz, CDCl3): d 14.3 (OCH2CH3), 22.3
((CH3)2CH), 23.8 (CH3CO), 28.3 ((CH3)2CH), 39.5
(CH2C@), 60.4 (OCH2CH3), 108.4 (C2), 135.7 (C3),
168.4, 169.8 (C1, CONH); HRMS (ESI+, MeOH): m/z
calcd for C11H19NO3Na: 236.1263. Found: 236.1261;
C11H19NO3 (213.27) calcd: C, 61.95; H, 8.98; N, 6.57.
Found: C, 61.91; H, 8.90; N, 6.28. The (E)-isomer E-
1d was then eluted and isolated as a brown oil (0.48 g,
4.3.6. (2Z)-Ethyl 3-N-acetylamino-2-methyl-2-butenoate
Z-4. Prepared from ketoester 5 (2.08 g, 74.4 mmol),
acetamide (2.56 g, 43.3 mmol) and a catalytic amount
of para-toluenesulfonic acid in toluene (20 mL). Purifica-
tion by flash chromatography on silica gel using light
petroleum and ethyl acetate (2:1) gave the (Z)-enamide
Z-4 as a yellow oil (0.84 g, 32%); IR (neat): m = 3059,
2982, 2360, 1728, 1660, 1548, 1454, 1373, 1266, 1225,