R. Matsubara et al. / Tetrahedron 60 (2004) 9769–9784
9779
organic layer was washed with brine and dried over
anhydrous MgSO4. After the solvent was evaporated, the
residue was dissolved in EtOH (3.0 mL), and a 48% HBr
aqueous solution (0.3 mL) was added to the solution. The
mixture was stirred at rt for 1.5 min, and then the reaction
was quenched by addition of saturated aqueous NaHCO3 at
0 8C. The reaction mixture was allowed to warm to rt. The
mixture was extracted with CH2Cl2, and the organic layer
was washed with brine and dried over anhydrous MgSO4.
After the solvents were evaporated, the crude product was
purified by chromatography on silica gel to afford the
desired compound 7.
144.4, 173.7, 197.1. IR (neat) 3483, 2981, 1742, 1682, 1606,
1405, 1365, 1212, 1098, 1044, 813, 578 cmK1; HRMS
(FAB). Exact mass calcd for C13H17O4 [MCH]C,
237.1127. Found 237.1120; HPLC, Daicel Chiralcel ADH,
hexane/iPrOHZ4/1, flow rateZ0.3 mL/min: tRZ36.1 min
(S), tRZ38.2 min (R).
5.2.5. (2S)-2-Hydroxy-4-naphthalen-2-yl-4-oxo-butyric
1
acid ethyl ester (7e). H NMR (CDCl3) dZ1.28 (t, 3H,
JZ7.1 Hz), 3.52 (d, 1H, JZ5.9 Hz), 3.59 (dd, 1H, JZ6.1,
17.3 Hz), 3.66 (dd, 1H, JZ3.9, 17.3 Hz), 4.28 (q, 2H, JZ
7.1 Hz), 4.73 (dt, 1H, JZ4.2, 5.4 Hz), 7.50–7.65 (m, 2H),
7.82–8.20 (m, 4H), 8.45 (s, 1H); 13C NMR (CDCl3) dZ
14.1, 42.3, 61.9, 67.3, 123.6, 126.9, 127.8, 128.6, 128.8, 129.6,
130.2, 132.4, 133.8, 135.8, 173.9, 197.5. IR (neat) 3481, 3058,
2982, 1741, 1681, 1627, 1469, 1369, 1209, 1097, 1045, 859,
824, 749, 477 cmK1; HRMS (FAB). Exact mass calcd for
C16H17O4 [MCH]C, 273.1127. Found 273.1125; HPLC,
Daicel Chiralcel ADH, hexane/iPrOHZ4/1, flow rateZ
0.5 mL/min: tRZ27.0 min (S), tRZ30.4 min (R).
5.2. Analytical data for 7
5.2.1. (2S)-2-Hydroxy-4-oxo-4-phenyl-butyric acid ethyl
1
ester (7a). H NMR (CDCl3) dZ1.27 (t, 3H, JZ7.1 Hz),
3.29 (brs, 1H), 3.44 (dd, 1H, JZ6.1, 17.6 Hz), 3.52 (dd, 1H,
JZ3.9, 17.6 Hz), 4.25 (q, 2H, JZ7.1 Hz), 4.61–4.67 (m,
1H), 7.44–7.50 (m, 2H), 7.54–7.60 (m, 1H), 7.92–7.98 (m,
2H); 13C NMR (CDCl3) dZ14.0, 42.1, 61.8, 67.1, 128.1,
128.6, 133.5, 136.4, 173.7, 197.5. IR (neat) 3475, 3063,
2983, 1737, 1687, 1597, 1580, 1449, 1368, 1213, 1098,
1045, 860, 759, 690, 582, 499 cmK1; HRMS (FAB). Exact
mass calcd for C12H15O4 [MCH]C, 223.0970. Found
223.0972; HPLC, Daicel Chiralcel ADH, hexane/iPrOHZ
4/1, flow rateZ0.5 mL/min: tRZ19.9 min (S), tRZ22.2 min
(R).
5.2.6. (2S)-2-Hydroxy-3-methyl-4-oxo-4-phenyl-butyric
acid ethyl ester (7f, syn/anti mixture). 1H NMR syn
(CDCl3) dZ1.26 (t, 3H, JZ7.0 Hz), 1.29 (d, 3H, JZ
7.0 Hz), 3.28 (br, 1H), 3.93 (dq, 1H, JZ4.2, 7.0 Hz), 4.25
(q, 2H, JZ7.0 Hz), 4.58 (d, 1H, JZ4.2 Hz), 7.40–7.65 (m,
3H), 7.90–8.05 (m, 2H); anti (CDCl3) dZ1.20 (t, 3H, JZ
7.1 Hz), 1.36 (d, 3H, JZ7.3 Hz), 3.61 (d, 1H, JZ8.3 Hz),
3.98 (dq, 1H, JZ4.6, 7.1 Hz), 4.10–4.25 (m, 2H), 4.39 (dd,
1H, JZ4.6, 8.3 Hz), 7.40–7.65 (m, 3H); 13C NMR syn
(CDCl3) dZ12.1, 14.0, 44.3, 61.9, 71.6, 128.4, 128.7, 133.3,
135.7, 173.1, 201.6; anti (CDCl3) dZ14.0, 14.1, 44.0, 61.5,
73.1, 128.3, 128.7, 133.4, 135.9, 173.1; IR (neat) syn 3480,
3063, 2978, 2936, 1734, 1678, 1596, 1579, 1449, 1369,
1217, 1133, 1062, 1023, 1001, 975, 952, 862, 794, 708; anti
3481, 3059, 2981, 2941, 1738, 1685, 1588, 1454, 1372,
1255, 1209, 1144, 1092, 1024, 973, 701 cmK1; HRMS
(FAB). Exact mass calcd for C13H17O4 [MCH]C,
237.1127. Found 237.1118; HPLC, Daicel Chiralcel ASC
ADHCAD, hexane/iPrOHZ4/1, flow rateZ0.5 mL/min:
tRZ46.7 min (2S,3S), tRZ50.6 min (2R,3R), tRZ54.3 min
(2S,3R), tRZ61.9 min (2R,3S).
5.2.2. (2S)-2-Hydroxy-4-(4-methoxy-phenyl)-4-oxo-
1
butyric acid ethyl ester (7b). H NMR (CDCl3) dZ1.28
(t, 3H, JZ7.1 Hz), 3.41 (dd, 1H, JZ5.9, 17.4 Hz), 3.48 (dd,
1H, JZ4.0, 17.4 Hz), 3.48 (brd, 1H, JZ6.8 Hz), 3.87 (s,
3H), 4.26 (q, 2H, JZ7.1 Hz), 4.60–4.70 (m, 1H), 6.91–6.97
(m, 2H), 7.90–7.97 (m, 2H); 13C NMR (CDCl3) dZ14.0,
41.7, 55.4, 61.7, 67.3, 113.8, 129.5, 130.4, 163.8, 173.8,
196.1. IR (neat) 3483, 2979, 2841, 1739, 1677, 1600, 1575,
1512, 1465, 1421, 1368, 1265, 1172, 1099, 1027, 988, 895,
834, 737, 579 cmK1; HRMS (FAB). Exact mass calcd for
C13H17O5 [MCH]C, 253.1076. Found 253.1097; HPLC,
Daicel Chiralcel ADH, hexane/iPrOHZ4/1, flow rateZ
0.4 mL/min: tRZ43.1 min (S), tRZ45.7 min (R).
5.2.3. (2S)-4-(4-Chloro-phenyl)-2-hydroxy-4-oxo-butyric
acid ethyl ester (7c). 1H NMR (CDCl3) dZ1.28 (t, 3H, JZ
7.1 Hz), 3.42 (dd, 1H, JZ6.1, 17.3 Hz), 3.49 (dd, 1H, JZ
3.9, 17.3 Hz), 3.41–3.47 (brd, 1H), 4.26 (q, 2H, JZ7.1 Hz),
4.62–4.70 (m, 1H), 7.42–7.48 (m, 2H), 7.86–7.93 (m, 2H);
13C NMR (CDCl3) dZ14.1, 42.2, 62.0, 67.1, 129.0, 129.6,
134.8, 140.1, 173.7, 196.3. IR (neat) 3480, 2982, 1739,
5.2.7. (2S)-2-Hydroxy-4-(4-methoxy-phenyl)-3-methyl-4-
oxo-butyric acid ethyl ester (7g, syn/anti mixture). H
1
NMR syn (CDCl3) dZ1.28 (t, 3H, JZ7.1 Hz), 1.29 (d, 3H,
JZ7.1 Hz), 3.35 (br, 1H), 3.84–3.96 (m, 4H), 4.27 (q, 2H,
JZ7.1 Hz), 4.58 (t, 1H, JZ4.2 Hz), 6.96 (apparent d, 2H,
JZ9.0 Hz), 7.30–7.45 (m, 5H), 7.95 (apparent d, 2H, JZ
8.8 Hz); anti (CDCl3) dZ1.19 (t, 3H, JZ7.1 Hz), 1.36 (d,
3H, JZ7.3 Hz), 3.75 (d, 1H, JZ9.3 Hz), 3.88 (s, 3H), 3.94
(dq, 1H, JZ4.6, 7.3 Hz), 4.15 (apparent dq, 2H, JZ3.2,
7.1 Hz), 4.36 (dd, 1H, JZ4.6, 9.3 Hz), 6.92–6.99 (m, 2H),
7.90–7.97 (m, 2H); 13C NMR syn (CDCl3) dZ12.3, 14.0,
43.7, 55.4, 61.8, 71.7, 113.9, 128.5, 130.7, 163.7, 173.1,
200.4; anti (CDCl3) dZ14.0, 14.6, 43.2, 55.5, 61.4, 73.4,
113.9, 128.7, 130.8, 163.8, 173.2, 201.9; IR (neat) syn 3477,
2979, 2935, 2850, 1730, 1670, 1600, 1573, 1510, 1463,
1420, 1308, 1261, 1173, 1125, 1027, 976, 843, 770, 604;
anti 3478, 2979, 2941, 2843, 1738, 1671, 1599, 1580, 1510,
1457, 1419, 1370, 1308, 1257, 1216, 1172, 1092, 1026, 974,
841 cmK1; HRMS (FAB). Exact mass calcd for C14H19O5
[MCH]C, 267.1232. Found 267.1232; HPLC, Daicel
1684, 1590, 1573, 1402, 1213, 1093, 1045, 820, 531 cmK1
;
HRMS (FAB). Exact mass calcd for C12H14ClO4 [MCH]C,
257.0580. Found 257.0584; HPLC, Daicel Chiralcel ADH,
hexane/iPrOHZ4/1, flow rateZ0.5 mL/min: tRZ24.2 min
(S), tRZ26.5 min (R).
5.2.4. (2S)-2-Hydroxy-4-oxo-4-p-tolyl-butyric acid ethyl
1
ester (7d). H NMR (CDCl3) dZ1.28 (t, 3H, JZ7.1 Hz),
2.41 (s, 3H), 3.44 (dd, 1H, JZ5.9, 17.4 Hz), 3.51 (dd, 1H,
JZ4.0, 17.4 Hz), 3.45–3.55 (brs, 1H), 4.26 (q, 2H, JZ
7.1 Hz), 4.66 (dt, 1H, JZ4.2, 5.5 Hz), 7.26 (apparent d, 2H,
JZ8.0 Hz), 7.85 (apparent d, 2H, JZ8.2 Hz); 13C NMR
(CDCl3) dZ14.0, 21.6, 42.0, 61.7, 67.2, 128.2, 129.3, 133.9,