Notes
J . Org. Chem., Vol. 63, No. 8, 1998 2745
H, dd, J ) 9.3, 5.0 Hz), 4.42 (1 H, d, J ) 7.6 Hz), 4.24-4.12 (2
H, m), 4.04 (1 H, dd, J ) 9.1, 7.6 Hz), 3.83 (1 H, dd, J ) 11.0,
5.3 Hz), 2.39 (1 H, br s), 0.97 (9 H, s); 13C NMR (75 MHz) δ
172.9, 153.9, 134.7, 128.7, 128.6, 127.7, 65.5, 64.9, 61.4, 51.8,
35.7, 25.6; combustion analysis (C16H21NO4: C, 65.96; H, 7.27)
found C, 65.81; H, 7.41.
to afford the â-hydroxyoxazolidinone (2.42 g, 92%) after flash
chromatography (4:1 hexane:EtOAc): TLC analysis (3:2 hexane:
EtOAc) Rf ) 0.42; mp 142-143 °C; [R]D ) +176° (c 1.0, CHCl3);
1H NMR (300 MHz) δ 7.90-7.25 (12 H, m), 5.44 (1 H, dd, J )
5.2, 4.0 Hz), 4.70-4.60 (1 H, m), 4.38 (1 H, dd, J ) 10.5, 9.7
Hz), 4.07 (1 H, d, J ) 8.9 Hz), 3.99-3.90 (2 H, m), 3.36 (1 H, dd,
J ) 7.9, 8.8 Hz), 3.38 (1 H, d, J ) 13.3 Hz), 2.88 (1 H, dd, J )
9.3, 4.0 Hz), 2.55 (1 H, br s); 13C NMR (75 MHz) δ 172.9, 152.6,
135.1, 133.2, 132.7, 132.3, 129.4, 128.9, 128.4, 127.8, 127.7, 127.5,
127.3, 126.7, 126.2, 126.1, 65.8, 65.0, 55.5, 52.0, 37.7; combustion
analysis (C23H21NO4: C, 73.58; H, 5.64) found C, 73.44; H, 5.80.
(4S)-Ben zyl-3-((2R)-3-h yd r oxy-3-m eth yl-2-(2′-n a p h th yl)-
1-oxobu tyl)-2-oxa zolid in on e. (4S)-4-Benzyl-3-(2′-naphthyl)-
1-oxoethyl)-2-oxazolidinone (1.00 g, 2.89 mmol) was condensed
with acetone (0.25 mL, 3.3 mmol) via procedure B using TiCl4
(two 0.33 mL, 3.0 mmol portions) and (i-Pr)2NEt (0.55 mL, 3.2
mmol) to afford the â-hydroxyoxazolidinone (1.00 g, 86%) after
flash chromatography (4:1 hexane:EtOAc): TLC analysis (3:2
hexane:EtOAc) Rf ) 0.52; mp 174-176 °C; [R]D ) +148° (c 1.1,
CHCl3); 1H NMR (300 MHz) δ 8.00 (1 H, s), 7.90-7.25 (11 H,
m), 5.35 (1 H, s), 4.70-4.60 (1 H, m), 4.10-4.00 (2 H, m), 3.94
(1 H, dd, J ) 7.9, 8.8 Hz), 3.45 (1 H, dd, J ) 3.3, 10.0 Hz), 2.84
(1 H, dd, J ) 9.8, 3.6 Hz), 1.55 (3 H, s), 1.18 (3 H, s); 13C NMR
(75 MHz) δ 174.6, 152.6, 135.0, 133.0, 132.7, 132.0, 129.4, 129.3,
128.9, 128.3, 128.0, 127.6, 127.4, 127.3, 126.0, 125.9, 72.8, 65.6,
(4S)-4-Ben zyl-3-((2R)-3-h yd r oxy-3-m et h yl-2-p h en yl-1-
oxobu tyl)-2-oxa zolid in on e. (4S)-4-Benzyl-3-(2-phenyl-1-oxo-
ethyl)-2-oxazolidinone (1.00 g, 3.39 mmol) was condensed with
acetone (0.29 mL, 3.90 mmol) via procedure B using TiCl4 (two
0.39 mL, 3.6 mmol portions) and (i-Pr)2NEt (0.65 mL, 3.7 mmol)
to afford the â-hydroxyoxazolidinone (1.15 g, 96%) after flash
chromatography (0.5% MeOH in CH2Cl2): TLC analysis (3:2
hexane:EtOAc) Rf ) 0.37; mp 133-135 °C; [R]D ) +118° (c 0.99,
CHCl3); 1H NMR (300 MHz) δ 7.51-7.48 (2 H, m), 7.38-7.20 (8
H, m), 5.13 (1 H, s), 4.68-4.57 (1 H, m), 4.08 (1 H, dd, J ) 9.3,
2.2 Hz), 3.99 (1 H, dd, J ) 7.9, 8.8 Hz), 3.91 (1 H, s), 3.39 (1 H,
dd, J ) 13.4, 3.3 Hz), 2.80 (1 H, dd, J ) 13.4, 9.8 Hz), 1.45 (3 H,
s), 1.06 (3 H, s); 13C NMR (75 MHz) δ 174.7, 152.7, 135.0, 134.4,
130.4, 129.3, 129.0, 128.2, 127.7, 127.4, 72.6, 65.7, 56.4, 55.6,
38.0, 30.0, 26.9; combustion analysis (C21H23NO4: C, 71.37; H,
6.56) found C, 71.25; H, 6.66.
(4S)-4-Ben zyl-3-((2R)-2-(4′-b r om op h en yl)-3-h yd r oxy-1-
oxop r op yl)-2-oxa zolid in on e. (4S)-4-Benzyl-3-(2-(4′-bromo-
phenyl)-1-oxoethyl)-2-oxazolidinone (1.06 g, 2.68 mmol) was
condensed with s-trioxane (280 mg, 3.11 mmol) via procedure B
using TiCl4 (two 0.31 mL, 2.8 mmol portions) and (i-Pr)2NEt
(0.51 mL, 2.95 mmol) to afford the â-hydroxyoxazolidinone (960
mg, 84%) after flash chromatography (4:1 hexane:EtOAc): TLC
56.5, 55.6, 37.9, 30.0, 27.0; HRMS analysis (CI, C25H25NO4
+
H+ ) 404.1862) found m/z 404.1860.
Gen er a l P r oced u r es for th e Hyd r olyses of â-Hyd r oxy-
oxa zolid in on es to â-Hyd r oxy Acid s. (A) P r oced u r e A. To
a cooled (0 °C) solution of the â-hydroxyoxazolidinone (1 equiv)
in THF:water (4:1, ca. 0.05 M) was added 30% aqueous H2O2
(ca. 10 equiv) dropwise followed by the portionwise addition of
LiOH(H2O) (ca. 2 equiv). The resulting mixture was warmed
to rt, stirred for 3 h, and then recooled (0 °C) and quenched by
the addition of excess 1.0 M aqueous Na2SO3. The resulting
mixture was partitioned between CH2Cl2:water. The aqueous
phase was acidified to pH 2 with 1 N aqueous HCl and extracted
three times with EtOAc. These latter organic extracts were
combined, dried (anhydrous Na2SO4), and concentrated. The
crude â-hydroxy acid product was used without further purifica-
tion.
(B) P r oced u r e B. To a cooled (0 °C) solution of the
â-hydroxyoxazolidinone (1 equiv) in THF:water (3:1, ca. 0.2 M)
was added 30% aqueous H2O2 (ca. 10 equiv) dropwise followed
by the portionwise addition of LiOH(H2O) (ca. 2 equiv). The
resulting mixture was warmed to rt and stirred for 3 h. KOH
(ca. 2 equiv) was then added and the resulting mixture was
heated at reflux for 1.5 h. Afterward, the reaction mixture was
recooled (0 °C) and quenched by the addition of excess 1.0 M
aqueous Na2SO3. The resulting mixture was partitioned be-
tween CH2Cl2:water. The aqueous phase was acidified to pH 2
with 1 N aqueous HCl and extracted three times with EtOAc.
These latter organic extracts were combined, dried (anhydrous
Na2SO4), and concentrated. The crude â-hydroxy acid product
was used without further purification.
analysis (4:1 hexane:EtOAc) Rf ) 0.44; mp 78-82 °C; [R]D
)
+146° (c 2.4, CHCl3); 1H NMR (300 MHz) δ 7.50-7.25 (9 H, m),
5.20 (1 H, dd, J ) 4.8, 4.0 Hz), 4.70-4.60 (1 H, m), 4.20 (1 H,
dd, J ) 8.9, 2.0), 4.08-4.00 (2 H, m), 3.84 (1 H, dd, J ) 4.8, 6.0
Hz), 3.31 (1 H, dd, J ) 3.2, 10.1), 2.85 (1 H, dd, J ) 9.3, 4.4 Hz),
2.42 (1 H, br s); 13C NMR (75 MHz) δ 172.5, 152.6, 134.9, 133.8,
131.8, 130.5, 129.4, 128.9, 127.4, 121.9, 65.9, 64.8, 55.5, 51.3,
37.7; HRMS analysis (CI, C19H18NO4Br + H+ ) 404.0497), found
m/z 404.0496.
(4S)-4-Ben zyl-3-((2R)-2-(4′-b ip h en yl)-3-h yd r oxy-1-oxo-
p r op yl)-2-oxa zolid in on e. (4S)-4-Benzyl-3-(2-(4′-biphenyl)-1-
oxoethyl)-2-oxazolidinone (1.10 g, 2.97 mmol) was condensed
with s-trioxane (310 mg, 3.44 mmol) via procedure B using TiCl4
(two 0.34 mL, 3.1 mmol portions) and (i-Pr)2NEt (0.57 mL, 3.3
mmol) to afford the â-hydroxyoxazolidinone (1.03 g, 87%) after
flash chromatography (4:1 hexane:EtOAc): TLC analysis (3:2
hexane:EtOAc) Rf ) 0.45; mp 152-154 °C; [R]D ) +148° (c 1.0,
1
CHCl3); H NMR (300 MHz) δ 7.60-7.25 (14 H, m), 5.32 (1 H,
dd, J ) 4.8, 4.0 Hz), 4.70-4.63 (1 H, m), 4.18-4.08 (1 H, m),
4.12 (1 H, dd, J ) 2.4, 6.8 Hz), 4.07 (1 H, dd, J ) 8.0, 8.9 Hz),
3.98-3.90 (1 H, m), 3.36 (1 H, dd, J ) 3.6, 10.1 Hz), 2.89 (1 H,
dd, J ) 9.3, 4.4 Hz), 2.42 (1 H, br s); 13C NMR (75 MHz) δ 172.9,
152.7, 140.7, 140.4, 135.0, 133.76, 129.4, 129.2, 128.9, 128.7,
127.4, 127.3, 126.9, 65.9, 65.0.0, 55.5, 51.6, 37.8; HRMS analysis
(CI, C25H23NO4 + H+ ) 402.1705) found m/z 402.1704.
(4S)-4-Ben zyl-3-((2R)-3-h yd r oxy-2-(1′-n a p h t h yl)-1-oxo-
p r op yl)-2-oxa zolid in on e. (4S)-4-Benzyl-3-(2-(1′-naphthyl)-1-
oxopropyl)-2-oxazolidinone (2.50 g, 7.24 mmol) was condensed
with s-trioxane (756 mg, 8.39 mmol) via procedure B using TiCl4
(two 0.83 mL, 7.6 mmol portions) and (i-Pr)2NEt (1.39 mL, 7.96
mmol) to afford the â-hydroxyoxazolidinone (2.60 g, 96%) after
flash chromatography (5:1 hexane:EtOAc): TLC analysis (3:2
hexane:EtOAc) Rf ) 0.36; mp 54-56 °C; [R]D ) +228° (c 1.08,
CHCl3); 1H NMR (300 MHz) δ 8.28 (1 H, d, J ) 8.4 Hz), 7.81 (1
H, d, J ) 8.1 Hz), 7.75 (1 H, dd, J ) 6.4, 2.6 Hz), 7.60-7.42 (2
H, m), 7.40-7.19 (7 H, m), 6.02 (1 H, dd, J ) 9.1, 4.3 Hz), 4.75-
4.64 (1 H, m), 4.25 (1 H, dd, J ) 11.2, 9.3 Hz), 4.04 (1 H, dd, J
) 9.1, 2.4 Hz), 4.00-3.87 (2 H, m), 3.35 (1 H, dd, J ) 13.4, 3.1
Hz), 2.88 (1 H, dd, J ) 13.4, 9.3 Hz), 2.80-2.40 (1 H, br s); 13C
NMR (75 MHz) δ 173.6, 152.6, 135.1, 134.0, 131.5, 131.3, 129.4,
128.9, 128.7, 128.4, 127.3, 126.7, 125.9, 125.0, 124.5, 123.3, 65.9,
(2R)-2-Ben zyl-3-h yd r oxy-3-m eth ylbu ta n oic Acid . (4R)-
4-Benzyl-3-((2R)-2-benzyl-3-hydroxy-3-methyl-1-oxobutyl)-2-
oxazolidinone (530 mg, 1.45 mmol) was hydrolyzed via procedure
A using 30% aqueous H2O2 (1.18 mL, 11.6 mmol) and LiOH-
(H2O) (120 mg, 2.9 mmol) to afford crude â-hydroxy acid (240
mg, 80%), which was used without further purification: TLC
analysis (1:1 hexane:EtOAc) Rf ) 0.10; mp 96-98 °C; [R]D
)
1
-29° (c 1.05, acetone); H NMR (300 MHz, acetone-d6) δ 7.34-
7.14 (5 H, m), 3.06-2.91 (2 H, m), 2.73 (1 H, dd, J ) 5.7, 9.3
Hz), 1.35 (6 H, s); 13C NMR (75 MHz, acetone-d6) δ 179.4, 139.0,
128.7, 128.4, 126.4, 71.5, 58.0, 33.7, 28.7, 26.7; combustion
analysis (C12H16O3: C, 69.21; H, 7.74) found C, 69.27; H, 7.59.
(2S,3S)-2-Ben zyl-3-h yd r oxy-3-p h en ylp r op a n oic Acid .28
(4S)-4-tert-Butyl--3-((2R)-2-benzyl-3-hydroxy-3-phenyl-1-oxopro-
64.4, 55.6, 48.3, 37.7; HRMS analysis (CI, C23H21NO4 + H+
376.1548) found m/z 376.1541.
)
(25) CAS Registry Number (racemate) 51439-23-7; see: Gladiali, S.;
Chelucci, G.; Marchetti, M.; Azzena, U. Chim. Ind. (Milan) 1985, 67,
387-91.
(26) CAS Registry Number (racemate) 529-64-6; see: Cox, R. J . O.
H., David J . Chem. Soc., Perkin Trans. 1 1991, 2537-40.
(27) CAS Registry Number (racemate) 6343-61-9; see: Meier, I. K.;
Schwartz, J . J . Org. Chem. 1990, 55, 5619-24.
(4S)-4-Ben zyl-3-((2R)-3-h yd r oxy-2-(2′-n a p h t h yl)-1-oxo-
p r op yl)-2-oxa zolid in on e. (4S)-3-(2-(2′-Naphthyl)-1-oxoethyl)-
4-benzyl-2-oxazolidinone (2.42 g, 7.02 mmol) was condensed with
s-trioxane (733 mg, 8.14 mmol) via procedure B using TiCl4 (two
0.81 mL, 7.4 mmol portions) and (i-Pr)2NEt (1.22 mL, 7.7 mmol)