H. Miyaoka et al. / Tetrahedron 62 (2006) 4103–4109
4107
(c 1.04, CHCl3); IR (neat) cmK1: 2954, 2930, 2858, 1746,
1649, 1604, 1580, 1496; H NMR (400 MHz, CDCl3) d:
purified by silica gel column chromatography (hexane/
AcOEtZ10:1) to give a,b-unsaturated ester 9 (56.0 mg,
95% yield, two steps) as a colorless oil: [a]2D5 C47.6 (c 1.11,
CHCl3); IR (neat) cmK1: 2954, 2930, 2857, 1722, 1647,
1
7.93 (2H, m), 7.48 (1H, m), 7.40 (2H, m), 4.44 (1H, d, JZ
8.6 Hz), 4.28 (1H, d, JZ11.4 Hz), 4.25 (1H, d, JZ11.4 Hz),
4.23 (1H, d, JZ8.6 Hz), 3.84 (1H, d, JZ10.0 Hz), 3.63 (1H,
d, JZ10.0 Hz), 2.05 (3H, s), 0.85 (9H, s), 0.06 (3H, s), 0.03
(3H, s); 13C NMR (100 MHz, CDCl3) d: 170.9, 164.9,
131.5, 128.4, 128.3, 127.5, 74.7, 71.9, 66.5, 65.9, 25.7, 20.9,
18.1, K5.5. K5.5; ESIMS m/z: 364 (MCCH, 100);
HRESIMS m/z: 364.1948 (Calcd for C19H30NO4Si: MCC
H, 364.1944). Anal. Calcd for C19H29NO4Si: C, 62.78; H,
8.04; N, 3.85. Found: C, 62.76; H, 7.87; N, 3.75.
1
1580, 1496; UV (EtOH) nm: 242 (3 15,300); H NMR
(400 MHz, CDCl3) d: 7.95 (2H, m), 7.49 (1H, m), 7.41 (2H,
m), 7.15 (1H, d, JZ15.8 Hz), 6.11 (1H, d, JZ15.8 Hz), 4.61
(1H, d, JZ8.4 Hz), 4.19 (2H, q, JZ7.1 Hz), 4.19 (1H, d,
JZ8.4 Hz), 3.76 (1H, d, JZ9.9 Hz), 3.71 (1H, d, JZ
9.9 Hz), 1.28 (3H, t, JZ7.1 Hz), 0.84 (9H, s), 0.06 (3H, s),
0.01 (3H, s); 13C NMR (100 MHz, CDCl3) d: 166.4, 164.8,
148.1, 131.6, 128.4, 128.3, 127.5, 121.9, 75.9, 74.0, 67.6,
60.4, 25.7, 18.1, 14.2, K5.4, K5.5; ESIMS m/z: 390 (MCC
H, 100); HRESIMS m/z: 390.2089 (Calcd for C21H32NO4Si:
MCCH, 390.2101). Anal. Calcd for C21H31NO4Si: C,
64.75; H, 8.02; N, 3.60. Found: C, 64.47; H, 8.06; N, 3.47.
3.1.8. (S)-[4-(tert-Butyldimethylsiloxymethyl)-2-phenyl-
4,5-dihydrooxazol-4-yl]methanol (8). To a solution of
acetate 7 (3.61 g, 9.93 mmol) in MeOH (49.7 mL) was
added K2CO3 (497 mg, 3.60 mmol). After stirring at rt for
10 min, the reaction mixture was diluted with Et2O and then
washed with saturated aqueous NH4Cl, water and finally
saturated aqueous NaCl. The organic layer was dried over
MgSO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica gel column chromato-
graphy (hexane/AcOEtZ2:1) to give alcohol 8 (3.14 g, 98%
yield) as colorless needles: mp: 90 8C; [a]2D5 K6.6 (c 1.01,
CHCl3); IR (KBr) cmK1: 3214, 2954, 2929, 2657, 1640,
3.1.10. Ethyl (S)-3-[4-(tert-butyldimethylsiloxymethyl)-
2-phenyl-4,5-dihydrooxazol-4-yl]-propionate (10). A
solution of a,b-unsaturated ester 9 (114 mg, 305 mmol) in
EtOH (3.05 mL) was hydrogenated with 10% Pd/C
(30.5 mg). The mixture was stirred at rt under a balloon
pressure of H2 for 30 min. The reaction mixture was diluted
with Et2O, filtered through Celite, and the filtrate
concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (hexane/
AcOEtZ8:1) to give ester 10 (112 mg, 98% yield) as a
1
1604, 1496; H NMR (400 MHz, CDCl3) d: 7.84 (2H, m),
7.45 (1H, m), 7.35 (2H, m), 4.46 (1H, d, JZ8.4 Hz), 4.36
(1H, d, JZ8.4 Hz), 3.82 (1H, dd, JZ11.3, 4.0 Hz), 3.81
(1H, d, JZ9.8 Hz), 3.73 (1H, dd, JZ11.3, 6.2 Hz), 3.61
(1H, d, JZ9.8 Hz), 0.86 (9H, s), 0.07 (3H, s), 0.03 (3H, s);
13C NMR (100 MHz, CDCl3) d: 165.4, 131.5, 128.3, 128.2,
127.3, 76.2, 72.0, 66.6, 65.9, 25.7, 18.1, K5.5, K5.5;
ESIMS m/z: 322 (MCCH, 100); HRESIMS m/z: 322.1866
(Calcd for C17H28NO3Si: MCCH, 322.1838). Anal. Calcd
for C17H27NO3Si: C, 63.51; H, 8.47; N, 4.36. Found: C,
63.28; H, 8.43; N, 4.08.
colorless oil: [a]D25 K6.2 (c 1.04, CHCl3); IR (neat) cmK1
:
2954, 2930, 2857, 1737, 1649, 1604, 1496; 1H NMR
(400 MHz, CDCl3) d: 7.91 (2H, m), 7.47 (1H, m), 7.39 (2H,
m), 4.44 (1H, d, JZ8.6 Hz), 4.10 (2H, dq, JZ7.1, 2.2 Hz),
4.08 (1H, d, JZ8.6 Hz), 3.68 (1H, d, JZ9.9 Hz), 3.61 (1H,
d, JZ9.9 Hz), 2.42 (1H, ddd, JZ16.3, 10.1, 6.3 Hz), 2.36
(1H, ddd, JZ16.3, 9.9, 6.3 Hz), 2.07 (1H, ddd, JZ14.0,
10.1, 6.3 Hz), 1.95 (1H, ddd, JZ14.0, 9.9, 6.3 Hz), 1.20
(3H, t, JZ7.1 Hz), 0.84 (9H, s), 0.05 (3H, s), 0.01 (3H, s);
13C NMR (100 MHz, CDCl3) d: 173.6, 163.8, 131.3, 128.3,
128.2, 127.8, 74.4, 73.5, 68.2, 60.4, 31.0, 29.0, 25.7, 18.1,
14.1, K5.4, K5.5; ESIMS m/z: 392 (MCCH, 100);
HRESIMS m/z: 392.2265 (Calcd for C21H34NO4Si: MCC
H, 392.2257). Anal. Calcd for C21H33NO4Si: C, 64.41; H,
8.49; N, 3.58. Found: C, 64.53; H, 8.47; N, 3.47.
3.1.9. Ethyl (S,E) 3-[4-(tert-butyldimethylsiloxymethyl)-
2-phenyl-4,5-dihydrooxazol-4-yl]acrylate (9). To a cold
(K78 8C) solution of TFAA (65.9 mL, 474 mmol) in CH2Cl2
(1.0 mL) was added DMSO (44.8 mL, 632 mmol). Following
stirring at K78 8C for 30 min, a solution of alcohol 8
(50.7 mg, 158 mmol) in CH2Cl2 (580 mL) was added.
Following stirring at K78 8C for 30 min, Et3N (110 mL,
790 mmol) was added. The mixture was warmed to rt for
over 15 min and then stirred for 20 min. The reaction
mixture was diluted with Et2O and then washed with
saturated aqueous NaHCO3, water and finally saturated
aqueous NaCl. The organic layer was dried over MgSO4,
filtered, and concentrated under reduced pressure to give the
crude aldehyde. The crude aldehyde was used for the next
reaction without further purification.
3.1.11. Ethyl (R)-3-(4-hydroxymethyl-2-phenyl-4,5-
dihydrooxazol-4-yl)propionate ((R)-6). To TBS ether 10
(66.0 mg, 176 mmol) was added TBAF (1.0 M in THF,
530 mL, 527 mmol). After stirring at rt for 5 min saturated
aqueous NH4Cl was added to the reaction mixture. The
mixture was diluted with AcOEt and then washed with
water and saturated aqueous NaCl. The organic layer was
dried over MgSO4, filtered, and concentrated under reduced
pressure. The residue was purified by silica gel column
chromatography (CHCl3/AcOEtZ2:1) to give alcohol (R)-6
(38.6 mg, 79% yield) as a colorless oil: [a]2D5 K14.6 (c 1.23,
CHCl3). Anal. Calcd for C15H19NO4: C, 64.97; H, 6.91; N,
5.05. Found: C, 65.11; H, 7.09; N, 4.90.
To a suspension of NaH (55%, 20.7 mg, 474 mmol) in THF
(1.0 mL) was added (iPrO)2P(O)CH2CO2Et (120 mL,
553 mmol) at 0 8C. Following stirring at 0 8C for 45 min, a
solution of the above crude aldehyde in THF (580 mL) was
added to this mixture at K78 8C. The mixture was
subsequently warmed to 0 8C for over 15 min. The reaction
mixture was diluted with Et2O and then washed with
saturated aqueous NH4Cl, water, and saturated aqueous
NaCl. The organic layer was dried over MgSO4, filtered,
and concentrated under reduced pressure. The residue was
3.1.12. Methyl (S)-4-(2-ethoxycarbonylethyl)-2-phenyl-
4,5-dihydrooxazole-4-carboxylate (11). To a solution of
alcohol (R)-6 (28.8 mg, 104 mmol) in H2O–CH2Cl2 (2/1,
330 mL) were added TEMPO (4.9 mg, 31.2 mmol) and
BAIB (100 mg, 312 mmol). After stirring at rt for 75 min,
the reaction mixture was diluted with CHCl3 and then