202
Typical Procedure for the Preparation of Conjugated Allenyl Esters 6
To a solution of 2a (247 mg, 0.8 mmol) in EtOH (8 ml) was added 1 N KOH
(0.8 ml) at 0 °C. After stirring at 0 °C for 15 min, 1 N HCl was added to the
Vol. 54, No. 2
Alkaline Hydrolysis of 7a To a solution of 7a (120 mg, 0.46 mmol) in
EtOH (4.6 ml) was added 1 N KOH (0.92 ml) at the room temperature. After
being warmed at 50 °C for 1 h, the reaction mixture was treated with 10%
reaction mixture and extracted with Et2O. The organic layer was washed HCl and then extracted with AcOEt. The extract was washed with brine and
with water, brine and dried over anhydrous MgSO4. The solvent was re-
dried over anhydrous MgSO4. The solvent was removed in vacuo. The
residue was recrystallized from CHCl3–acetone to yield 7ꢀa (91 mg, 86%) as
moved in vacuo to yield 6a (176 mg, 94%) as a pale yellow oil.
Ethyl 2-Methoxy-4-(p-tolyl)-2,3-butadienoate (6a): Pale yellow oil; 1H- colorless prisms.
NMR (200 MHz, CDCl3) d: 1.28 (3H, t, Jꢂ7.1 Hz), 2.36 (3H, s), 3.53 (3H,
2-Methyl-5-(p-tolylmethyl)-4-oxazolecarboxylic acid (7ꢀa): Colorless
s), 4.28 (2H, q, Jꢂ7.1 Hz), 7.08 (1H, s), 7.16 (2H, d, Jꢂ8.1 Hz), 7.27 (2H, d, prisms, mp 162 °C (CHCl3–acetone); 1H-NMR (200 MHz, CDCl3) d: 2.32
Jꢂ8.1 Hz). 13C-NMR (100 MHz, CDCl3) d: 14.25, 21.31, 56.60, 61.63, (3H, s), 2.43 (3H, s), 4.32 (2H, s), 7.12 (2H, d, Jꢂ8.0 Hz), 7.20 (2H, d,
111.28, 127.72, 129.42, 129.48, 131.89, 138.86, 163.49, 197.64; IR (neat) Jꢂ8.0 Hz). 13C-NMR (100 MHz, CDCl3) d: 13.58, 21.06, 31.48, 126.75,
2982, 1932, 1733, 1512, 1447 cmꢁ1. FAB-MS Calcd for C14H17O3 MWꢀH 128.74, 129.41, 133.00, 136.72, 158.63, 160.72, 165.43; IR (KBr) 3423,
233, Found m/z 233 (MꢀꢀH).
2921, 2568, 1730, 1708, 1616, 1594, 1515, 1439, 1352, 1283, 1227, 1186,
Ethyl 2-Methoxy-4-phenyl-2,3-butadienoate (6b): Yellow oil; 1H-NMR 1112, 1069 cmꢁ1. Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06.
(200 MHz, CDCl3) d: 1.28 (3H, t, Jꢂ7.1 Hz), 3.54 (3H, s), 4.28 (2H, q, Found, C, 67.33; H, 5.70; N, 5.69.
Jꢂ7.1 Hz), 7.11 (1H, s), 7.26—7.40 (5H, m); 13C-NMR (100 MHz, CDCl3)
d: 14.23, 56.68, 61.69, 111.43, 127.80, 128.73, 128.89, 131.98, 133.28,
163.39, 198.28; IR (neat) 2982, 1933, 1733, 1493 cmꢁ1. FAB-MS Calcd for
C13H15O3 MWꢀH 219, Found m/z 219 (MꢀꢀH).
Esterification of 7ꢀa To a solution of 7ꢀa (12 mg, 0.05 mmol) in
AcOEt–DMF (10 : 1, v/v) (5 ml) was added triethylamine (0.01 ml, 0.06
mmol) and bromoethane (0.02 ml, 0.27 mmol) at room temperature. After
stirring at room temperature for 48 h, water was added to the reaction mix-
ture and extracted with Et2O. The extract was washed with brine and dried
over anhydrous MgSO4. The solvent was removed in vacuo to yield 7a
Ethyl 2-Methoxy-2,3-heptadienoate (6c): Yellow oil; 1H-NMR (200 MHz,
CDCl3) d: 0.98 (3H, t, Jꢂ7.4 Hz), 3.51 (3H, s), 1.29 (3H, t, Jꢂ7.1 Hz),
1.50—1.61 (2H, m), 2.18—2.23 (2H, m), 4.23—4.30 (2H, m), 6.20 (1H, t, (10 mg, 77%) as a yellow oil.
Jꢂ6.7 Hz); 13C-NMR (100 MHz, CDCl3) d: 13.39, 13.95, 20.78, 21.65,
Hydrogenation of 2a The mixture of 2a (912 mg, 3 mmol), 5% Pd–
54.26, 63.28, 91.57, 110.19, 165.27, 196.07; FAB-MS Calcd for C10H17O3 BaSO4 (91 mg, 10% w/w), and quinoline (20 mg, 0.15 mmol) in MeOH
MWꢀH 185, Found m/z 185 (MꢀꢀH).
(30 ml) was stirred at room temperature for 1.5 h. The reaction mixture was
Ethyl 2-Methoxy-4-(1-cyclohexen-1-yl)-2,3-butadienoate (6d): Yellow submitted to filtration with celite. The filtrate was concentrated in vacuo to
oil; 1H-NMR (200 MHz, CDCl3) d: 1.29 (3H, t, Jꢂ7.3 Hz), 1.50—1.76 (4H, afford a crude product 9, which was purified by column chromatography on
m), 1.90—2.28 (4H, m), 3.48 (3H, s), 4.27 (2H, q, Jꢂ7.3 Hz), 5.86—6.00 silica gel with n-hexane–AcOEt (85 : 15, v/v) to yield 9 (894 mg, 97%) as a
(1H, m), 6.75 (1H, m); 13C-NMR (100 MHz, CDCl3) d: 14.30, 22.15, 22.28, pale yellow oil.
25.73, 26.10, 56.49, 61.48, 114.72, 128.03, 132.09, 132.33, 163.81, 196.41;
Ethyl (Z)-2-Methoxy-2(-ethoxycarbonyl)-4-(p-tolyl)-3-butenoate (9): Pale
IR (neat) 2932, 1926, 1733, 1446, 1394, 1367, 1280, 1217, 1161, 1131, yellow oil; 1H-NMR (200 MHz, CDCl3) d: 1.19 (6H, t, Jꢂ7.3 Hz), 2.33 (3H,
1040 cmꢁ1. FAB-MS Calcd for C13H19O3 MWꢀH 223, Found m/z 223
(MꢀꢀH).
s), 3.24 (3H, s), 4.07—4.24 (4H, m), 6.14 (1H, d, Jꢂ12.9 Hz), 6.80 (1H, d,
Jꢂ12.9 Hz), 7.12 (2H, d, Jꢂ8.3 Hz), 7.43 (2H, d, Jꢂ8.3 Hz); IR (neat) 2983,
2938, 1740, 1514, 692 cmꢁ1. EI-MS Calcd for C17H22O5 MW 306.1467,
Found m/z 306.1494 (Mꢀ). Anal. Calcd for C17H22O5: C, 66.65; H, 7.24.
1
Ethyl 2-Methoxy-2,3-butadienoate (6e): Yellow oil; H-NMR (400 MHz,
CDCl3) d: 1.31 (3H, dt, Jꢂ0.98, 7.3 Hz), 3.51 (3H, s), 4.28 (2H, dq, Jꢂ0.03,
7.3 Hz), 5.83 (2H, s); 13C-NMR (100 MHz, CDCl3) d: 14.23, 61.61, 93.84, Found, C, 66.16; H, 7.17.
56.69, 127.21, 163.88, 203.38; IR (neat) 2982, 2837, 1942, 1734 cmꢁ1
.
Alkaline Hydrolysis of 9 To a solution of 9 (432 mg, 1.4 mmol) in
EtOH (7 ml) was added 1 N KOH (1.4 ml) at 0 °C. After being stirred at 0 °C
FAB-MS Calcd for C7H11O3 MWꢀH 143, Found m/z 143 (MꢀꢀH).
Typical Procedure for the Preparation of 2,4,5-Trisubstituted Oxa- for 7 h, the reaction mixture was treated with 1 N HCl (1.4 ml) and then ex-
zoles 7 To a solution of 5a (68 mg, 0.26 mmol) in EtOH (2.6 ml) was
added 1 N KOH (0.26 ml) in one portion at 0 °C. After stirred at 0 °C for
20 min, 1 N HCl was added to the reaction mixture and extracted with Et2O.
The organic layer was washed with brine and dried over anhydrous MgSO4.
The solvent was removed in vacuo. The residue was purified by column
chromatography on silica gel with n-hexane–Et2O (1 : 5, v/v) to yield 7a
(48 mg, 93%) as a yellow oil.
tracted with AcOEt. The extract was washed with saturated NaHCO3, brine
and dried over anhydrous MgSO4. The solvent was removed in vacuo. The
residue was purified by column chromatography on silica gel with n-
hexane–AcOEt (85 : 15, v/v) to yield 9 (151 mg, 35% recovery), 10 (99 mg,
30%), 11 (2.3 mg, 0.7%) and 12 (5.3 mg, 1.6%).
Ethyl (Z)-2-Methoxy-4-(p-tolyl)-3-butenoate (10): Yellow oil; 1H-NMR
(270 MHz, CDCl3) d: 1.32 (3H, t, Jꢂ7.3 Hz), 2.37 (3H, s), 3.31 (3H, s), 4.28
Ethyl 2-Methyl-5-(p-tolylmethyl)-4-oxazolecarboxylate (7a): Yellow oil; (2H, q, Jꢂ7.3 Hz), 4.73 (1H, d, Jꢂ9.6 Hz), 5.63 (1H, dd, Jꢂ9.6 and
1H-NMR (200 MHz, CDCl3) d: 1.40 (3H, t, Jꢂ7.1 Hz), 2.32 (3H, s), 2.41 11.6 Hz), 6.84 (1H, d, Jꢂ11.6 Hz), 7.19 (2H, d, Jꢂ8.3 Hz), 7.32 (2H, d,
(3H, s), 4.30 (2H, s), 4.40 (2H, q, Jꢂ7.1 Hz), 7.12 (2H, d, Jꢂ8.2 Hz), 7.18
Jꢂ8.3 Hz). IR (neat) 2984, 2930, 1750, 1514 cmꢁ1. EI-MS Calcd for
(2H, d, Jꢂ8.2 Hz); 13C-NMR (100 MHz, CDCl3) d: 13.81, 14.40, 21.06, C14H18O3 MW 234.1256, Found m/z 234.1238 (Mꢀ). Anal. Calcd for
31.55, 60.95, 127.29, 128.65, 129.38, 133.31, 136.64, 157.75, 160.04, C14H18O3: C, 71.77; H, 7.74, Found, C, 71.23; H, 7.72.
162.33; IR (CHCl3) 3000, 2925, 1713, 1618, 1372 cmꢁ1. Anal. Calcd for
Ethyl (E)-2-Methoxy-4-(p-tolyl)-3-butenoate (11): Pale yellow oil; 1H-
NMR (200 MHz, CDCl3) d: 1.30 (3H, t, Jꢂ7.3 Hz), 2.34 (3H, s), 3.44 (3H,
C15H17NO3: C, 69.47; H, 6.61N, 5.40. Found, C, 69.11; H, 6.58; N, 5.29.
Ethyl 2-Methyl-5-(phenylmethyl)-4-oxazolecarboxylate (7b): Yellow oil; s), 4.26 (2H, q, Jꢂ7.3 Hz), 4.38 (1H, d, Jꢂ6.9 Hz), 6.14 (1H, dd, Jꢂ6.9,
1H-NMR (200 MHz, CDCl3) d: 1.40 (3H, t, Jꢂ7.1 Hz), 2.42 (3H, s), 4.34 15.8 Hz), 6.74 (1H, d, Jꢂ15.8 Hz), 7.13 (2H, d, Jꢂ7.9 Hz), 7.29 (2H, d,
(2H, s), 4.40 (2H, q, Jꢂ7.1 Hz), 7.15—7.45 (5H, m); 13C-NMR (100 MHz,
CDCl3) d: 13.79, 14.38, 31.97, 61.00, 127.00, 127.43, 128.71, 128.76,
Jꢂ7.9 Hz).
Ethyl 2-Methoxy-4-(p-tolyl)-2-butenoate (12): Pale yellow oil; H-NMR
1
136.36, 157.47, 160.14, 162.28; IR (neat) 3030, 2982, 1708, 1616, (270 MHz, CDCl3) d: 1.30 (3H, t, Jꢂ7.3 Hz), 2.31 (3H, s), 3.53 (2H, d,
1376 cmꢁ1. Anal. Calcd for C14H15N3O: C, 68.54; H, 6.17; N, 5.71. Found, Jꢂ7.6 Hz), 3.72 (3H, s), 4.21 (2H, q, Jꢂ7.3 Hz), 6.38 (1H, t, Jꢂ7.6 Hz),
C, 68.26; H, 6.24; N, 5.53.
7.10 (4H, s).
Ethyl 2-Methyl-5-(1-cyclohexen-1-ylmethyl)-4-oxazolecarboxylate (7d):
Biomimetic Reactions of 2 with EtSH To a solution of 2a (247 mg,
0.8 mmol) in EtOH (8 ml) was added 1 N KOH (0.8 ml) in one portion at
Colorless crystalline powder, mp 30—31 °C (n-hexane–Et2O); 1H-NMR
(200 MHz, CDCl3) d: 1.38 (3H, t, Jꢂ7.1 Hz), 1.45—1.78 (4H, m), 1.86— 0 °C. After being stirred at 0 °C for 15 min, EtSH (0.07 ml, 0.9 mmol) was
2.15 (4H, m), 2.45 (3H, s), 3.63 (2H, s), 4.37 (2H, q, Jꢂ7.1 Hz), 5.46—5.58
added. After being stirred at 0 °C for 80 min, 1 N HCl (0.8 ml) was added and
(1H, m); 13C-NMR (100 MHz, CDCl3) d: 13.85, 14.38, 22.08, 22.71, 25.24, then the reaction mixture was poured into water and extracted with Et2O.
28.20, 34.23, 60.81, 124.37, 127.83, 132.97, 157.64, 159.82, 162.33; IR The extract was washed with brine and dried over anhydrous MgSO4. The
(CHCl3) 3010, 2949, 1718, 1612, 1375, 1342 cmꢁ1. Anal. Calcd for solvent was removed in vacuo. The residue was purified by column chro-
C14H19NO3: C, 67.43; H, 7.69; N, 5.62. Found, C, 67.30; H, 7.92; N, 5.41.
matography on silica gel with n-hexane–AcOEt (7 : 3, v/v) to yield 13a
Ethyl 2,5-Dimethyl-4-oxazolecarboxylate (7e): Yellow oil; 1H-NMR (147 mg, 61%) as a pale yellow oil.
(200 MHz, CDCl3) d: 1.39 (3H, t, Jꢂ7.1 Hz), 2.44 (3H, s), 2.59 (3H, s), 4.37
Ethyl (E)-2-Methoxy-3-ethylthio-4-(p-tolyl)-3-butenoate (13a): Pale yel-
(2H, q, Jꢂ7.1 Hz). 13C-NMR (100 MHz, CDCl3) d: 11.88, 13.71, 14.40, low oil; 1H-NMR (270 MHz, CDCl3) d: 1.32 (3H, t, Jꢂ7.3 Hz), 1.33 (3H, t,
60.81, 127.39, 156.07, 159.43, 162.45. IR (neat) 2999, 1710, 1620, 1340 Jꢂ7.3 Hz), 2.36 (3H, s), 2.77—3.02 (2H, m), 3.29 (3H, s), 4.29 (2H, q,
cmꢁ1. EI-MS Calcd for C8H11NO3 MW 169.0739, Found m/z 169.0736
Jꢂ7.3 Hz), 4.96 (1H, s), 6.81 (1H, s), 7.13 (2H, d, Jꢂ7.9 Hz), 7.26 (2H, d,
Jꢂ7.9 Hz); IR (neat) 2926, 2825, 1752, 1607, 1510, 1447, 1369, 1265,
(Mꢀ).