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J. Augusto R. Rodrigues et al. / Tetrahedron: Asymmetry 16 (2005) 3099–3106
heterocyclic), 178.1 (C@O). HRMS: calcd for
C18H17NO3: 295.12084; found: 295.12071.
139.2(C, aromatic), 167.1 (C, C @O), 173.3 (C, C@O).
HRMS: calcd for: C18H19NO4: 313.13141; found:
313.13139.
4.4.2. Ethyl (4S,5R)-4-benzyl-2-methyl-4,5-dihydrooxaz-
20
D
ole-5-carboxylate 5b. Brown oil, ½a ¼ ꢀ14.5 (c 1.3,
4.5.2. Ethyl (2R,3S)-3-acetylamino-2-hydroxy-4-phenyl-
110–114 ꢁC,
CHCl3); IR (film) mmax: 2923, 1774, 1759, 1738, 1496,
1455, 1367, 1247, 1220, 701, 698 cmꢀ1; MS m/z (%):
247 (3), 206 (5), 188 (1), 174 (10), 156 (42), 144 (5),
133 (10), 112 (20), 103 (10), 84 (100), 77 (20), 65 (20),
butanoate
6b. White
solid,
mp
20
½a ¼ ꢀ38.0 (c 1.3, CHCl3); IR (film) mmax: 3346,
D
2923, 1774, 1759, 1738, 1496, 1455, 1367, 1247, 1220,
701, 698 cmꢀ1; MS m/z (%): 247 (3), 206 (5), 188 (1),
174 (10), 156 (42), 144 (5), 133 (10), 112 (20), 103 (10),
84 (100), 77 (20), 65 (20), 43 (33); 1H NMR
(300 MHz, CDCl3): d 1.25 (3H, t, J 7.1 Hz), 2.02 (3H,
s), 2.93 (1H, m, H-4), 3.40 (1H, d, J 3.7 Hz, OH), 4.07
(br s, 1H, H-2), 4.37 (2H, m), 4.60 (1H, m, H-3), 5.84
(1H, d, J 9.2Hz, NH), 7.30 (5H, m, aromatic); 13C
NMR (75 MHz, CDCl3): d 14.2(CH 3), 14.4 (CH3),
42.0 (CH2, C-4), 62.3 (CH2), 72.9 (CH, C-3), 80.7
(CHOH, C-2), 129.7 (CH, C-8), 128.3 (2CH, aromatic),
130.1 (2CH, aromatic), 137.8 (C, aromatic), 169.9
(C@O, C-13), 174.2(C @O, C-1). HRMS: calcd for
C14H19NO4: 265.13141; found: 265.13242.
1
43 (33); H NMR (300 MHz, CDCl3): d 1.18 (3H, t, J
7.3 Hz), 2.02 (3H, s, H-1), 2.84 (1H, dd, J 14.0 and
7.0 Hz), 3.05 (1H, dd, J 14.0 and 7.0 Hz), 4.11 (2H, q,
J 7.0 Hz), 4.40 (1H, m, H-5), 4.51 (1H, d, J 6.6 Hz, H-
5), 7.23 (5H, m, aromatic); 13C NMR (75 MHz, CDCl3):
d 14.2(CH ), 14.4 (CH3, C-1), 42.0 (CH2), 62.3 (CH2),
3
72.9 (CH, C-4), 80.7 (CH, C-5), 129.7 (CH, C-11),
128.3 (2CH, aromatic), 130.1 (2CH, aromatic), 137.8
(C, heterocyclic), 171.4 (C@O). HRMS: calcd for
C14H17NO3: 247.12084; found: 247.12088.
4.4.3. Ethyl (4S,5R)-4-isopropyl-2-methyl-4,5-dihydroox-
20
D
azole-5-carboxylate 5c. Brown oil, ½a ¼ ꢀ3.2( c
1.6, CHCl3); IR (film) mmax: 2963, 2920, 2880, 1808,
1732, 1016 cmꢀ1; MS m/z (%): 213 (1), 198 (7), 184
(1), 170 (5), 156 (100), 140 (40), 129 (13), 115 (16), 98
(8), 84 (85), 68 (46), 55 (15); 1H NMR (300 MHz,
CDCl3): d 0.98 (6H, m, H-8 and H9), 1.30 (3H, t, J
7.0 Hz, H-12), 1.32–1.99 (3H, m, H-6 and H-7), 2.05
(3H, s, H-1), 4.1 (1H, m, H-4), 4.2(2H, m, H-11), 4.42
(2H, d, J 6.6 Hz, H-5); 13C NMR (75 MHz, CDCl3): d
4.5.3. Ethyl (2R,3S)-3-acetylamino-2-hydroxy-5-methyl-
20
hexanoate 6c. Colorless oil, ½a ¼ þ13.0 (c 1.6,
D
CHCl3); IR (film) mmax: 3335, 2991, 2924, 2820, 1810,
1728, 1203 cmꢀ1; EM m/z (%): 86 (100), 216 (1), 207
(1), 198 (1), 174 (3), 158 (10), 128 (60), 116 (9), 86
(100), 60 (10); 1H NMR (300 MHz, CDCl3): d 0.97
(6H, d, J 6.7 Hz, H-6 and H7), 1.32(3H, t, J 7.1 Hz,
H-9), 1.33–2.21 (3H, m, H-4 and H-5), 1.97 (3H, s, H-
11), 4.18 (1H, d, J 2.5 Hz, H-2), 4.22 (2H, q, J 7.1 Hz,
H-8), 4.44 (2H, m, H-3), 5.63 (1H, d, J 6.8 Hz, H-12);
13C NMR (75 MHz, CDCl3): d 14.1 (CH3, C-9),
22.3 (CH3, C-6 and C-7), 22.8 (CH3, C-11), 24.8 (CH2,
C-5), 41.1 (CH2, C-4), 49.6 (CH, C-3), 62.4 (CH2, C-8),
72.2 (CH, C-2), 169.6 (C, C@O), 173.4 (C, C@O).
HRMS: calcd for C11H21NO4: 231.14706; found:
231.14700.
14.2(CH ), 14.5 (CH3, C-8 and C-9), 22.8 (CH3, C-1),
3
25.2 (CH2, C-7), 46.2(CH 2, C-6), 62.0 (CH2), 70.3
(CH, C-4), 81.6 (CH, C-5), 164.1 (heterocyclic), 171.0
(C@O). HRMS: calcd for C11H19NO3: 213.13649;
found: 213.13632.
4.5. General procedure to obtain the (2R,3S)-3-amino-2-
hydroxyalkanoates 6a–c
To a stirred solution of HCl (0.5 mol Lꢀ1, 10 mL) were
added 4,5-dihydrooxazole-5-carboxylate (0.84 mmol)
5a–c and the solution was kept for 1.5 h at room temper-
ature. Then, a saturated solution of NaHCO3 was added
to pH 9 and the solution stirred overnight. The reaction
product was extracted with dichloromethane (3 ·
20 mL) and the organic phase dried over anhydrous
MgSO4, filtered, and the solvent evaporated. The crude
product was purified by recrystallization in hexane
(3 mL) with 5% ethyl acetate to give white crystals.
4.5.4. (ꢀ)-(2R)-2-Hydroxy-4-phenylbutanoate 8. To a
solution of 3b (182mg, 0.7 mmol) in anhydrous ethanol
(3 mL) were added under argon sodium acetate (57 mg,
0.7 mmol) and 5% palladium on carbon (16 mg). After
stirring for 2h at room temperature, the reaction mix-
ture was filtered over Celite, extracted with ethyl acetate
(3 · 50 mL), and washed with NaCl saturated solution.
The organic phase was dried over anhydrous MgSO4,
filtered, and the solvent removed under reduced pres-
sure. The crude product was purified by silica gel chro-
matography and eluted with hexane and ethyl acetate
4.5.1. Ethyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phen-
(15%) to give
8
(138 mg, 95%). Yellow oil,
20
20
ylpropanoate 6a. White solid, mp 162–164 ꢁC, ½a
¼
½a ¼ ꢀ32.5 (c 2.0, CHCl3); 1H NMR (300 MHz,
D
D
ꢀ21.7 (c 1.0, CHCl3); IR (film) mmax: 3474, 3446, 3005,
2919, 2923, 2807, 1713, 1635, 1450, 1354 cmꢀ1; MS m/
z (%): 222 (100), 194 (11), 193 (66), 166 (4), 165 (15),
145 (2), 132 (2), 119 (20), 105 (72), 89 (93), 91 (89), 89
(93), 77 (70), 65 (50), 51 (60); 1H NMR (300 MHz,
CDCl3): d 1.26 (3H, t, J 7.3 Hz), 3.26 (1H, s), 4.25
(2H, m), 4.62 (1H, d, J 1.9 Hz, H-2), 5.74 (1H, dd, J
2.0 and 9.0 Hz, H-3), 6.98 (1H, d, J 9.0 Hz), 7.24
(10H, m, H-5 aromatic); 13C NMR (75 MHz, CDCl3):
CDCl3): d 1.28 (3H, t, J 7.0 Hz, H-12), 1.90–2.18 (2H,
m, H-4), 2.77 (2H, m, H-3), 4.20 (2H, q, J 7.0 Hz, H-
11), 7.26 (5H, m, aromatic).12
4.5.5. Ethyl (2R,3S)-3-azido-2-hydroxyphenylbutanoate
9. To a solution of the oxirane 4b (200 mg, 0.7 mmol)
in anhydrous dichloromethane (2mL) were added bor-
on trifluoride–diethyl etherate (0.25 mL) and azidotri-
methylsilane (0.08 g, 0.7 mmol) under argon. The
mixture was stirred at room temperature for 3 h. The
reaction mixture was diluted with dichloromethane,
d 14.7 (CH3), 55.2(CH, C-3), 63.3 (CH ), 73.8 (CH,
2
C-2), 127.3–132.1 (CH, aromatic), 134.6 (C, aromatic),