6400 J . Org. Chem., Vol. 63, No. 18, 1998
Notes
sium carbonate, and distilled. Commercially available com-
pounds were used without further purification. Compound 6
was prepared as described.17d
186 °C (ethanol); [R]25 ) -10.6 (c ) 1.0, CH2Cl2); IR (KBr) ν
D
3335, 1740 (CdO), 1633 cm-1 (CdO), 1H NMR (CDCl3) 7.42-
6.89 (m, 9H), 5.68 (d, 1H, J ) 8.4 Hz), 5.31 (dd, 1H, J ) 4.9, 8.4
Hz), 4.25 (m, 1H), 3.84 (s, 3H), 2.72 (m, 2H), 2.31 (m, 1H), 1.96
(m, 1H), 1.57 (s, 9H); 13C NMR (CDCl3) 164.1, 156.3, 140.7, 128.5,
128.2, 126.1, 118.7, 114.3, 80.5, 58.9, 57.2, 55.4, 31.5, 29.6, 28.2.
Anal. Calcd for C23H28N2O4 (396.48): C, 69.67; H, 7.11; N, 7.06.
Found: C, 69.65; H, 6.95; N, 7.06.
cis-(3S,4R)-3-[(4S,5R)]-4,5-Dip h en yl-2-oxooxa zolid in -3-
yl]-1-[(m eth oxycar bon yl)m eth yl]-4-styr ylazetidin -2-on e (9).
Triethylamine (1.45 mL, 16.6 mmol) was added at -78 °C to a
solution of the acid chloride 6 (3.47 g, 11 mmol) in dry methylene
chloride (50 mL). After 20 min, a solution of the imine 7 (2.48
g, 12.2 mmol) in dry toluene (50 mL) was added dropwise at the
same temperature. The cooling bath was removed, and the
resulting mixture was stirred,under nitrogen atmosphere at 0
°C for 2 h. Then the reaction mixture was successively washed
with water (100 mL), 1 N HCl (50 mL), and a saturated aqueous
solution of NaHCO3 (100 mL). The organic layer was dried over
MgSO4 and filtered, and the solvent was evaporated under
reduced presure to afford a crude material that was purified by
flash column chromatography (silica gel, 230-400 mesh, meth-
ylene chloride and methylene chloride/ethyl acetate 10:1 as
eluants) to give the desired product: 71% (3.8 g); mp 194-196
P r ep a r a tion of th e Lor a ca r bef In ter m ed ia te 14. To a
mixture of the â-lactam 11 (0.31 g, 0.85 mmol) in carbon
tetrachloride (5 mL), acetonitrile (5 mL), and water (7.5 mL)
was added at room-temperature periodic acid (2.75 g, 12 mmol).
The biphasic mixture was stirred until both phases became clear,
and ruthenium trichloride hydrate (350 mg, 0.17 mmol) was
added. Stirring was continued until no starting material was
detected by TLC (4 h). The reaction mixture was cooled to 0
°C, and diethyl ether (50 mL) was added with vigorous stirring
for 10 min. The organic phase was separated and the aqueous
layer extracted with diethyl ether (2 × 30 mL). The combined
organic layers were washed with brine (30 mL), dried, filtered,
and concentrated. The residue was dissolved in ethyl acetate
(10 mL), dicyclohexylamine (0.121 g, 0.67 mmol) was added, and
the resulting mixture was stirred at room temperature over-
night. The resulting crystals were filtered, and then a biphasic
mixture of ethyl acetate (10 mL) and a solution of KHSO4 (0.14
g, 1 mmol) in water (10 mL) was added. The mixture was stirred
until the dicyclohexylammonium salt was completely dissolved.
The aqueous phase was extracted with ethyl acetate (2 × 20
mL), and the organic phases were dried and evaporated under
reduced presure to give the desired product 14: yield 65%; mp
°C; [R]25 ) +77.6 (c ) 1.0, CH2Cl2); IR (NaCl) ν 1760 (CdO),
D
1740 cm-1 (CdO); 1H NMR (CDCl3) 7.45-6.89 (m, 15H), 6.75
(d, 1H, J ) 16.0 Hz), 6.37 (dd, 1H, J ) 8.9, 16.0 Hz), 5.82 (d,
1H, J ) 8.4 Hz), 5.06 (d, 1H, J ) 8.4 Hz), 4.66 (dd, 1H, J ) 5.1,
8.9 Hz), 4.58 (d, 1H, J ) 5.1 Hz), 4.45 (d, 1H, J ) 18.2 Hz), 3.70
(s, 3H), 3.65 (d, 1H, J ) 18.2 Hz); 13C NMR (CDCl3) 168.3, 164.1,
157.4, 137.9, 135.4, 133.9, 133.1, 128.6, 126.7, 125.9, 122.4, 80.1,
65.4, 63.8, 62.0, 52.2, 41.2. Anal. Calcd for C29H26N2O5
(482.54): C, 72.18; H, 5.43; N, 5.80. Found: C, 72.33; H, 5.14;
N, 5.78.
cis-(3S,4R)-3-[(4S,5R)-4,5-Dip h en yl-2-oxooxa zolid in -3-
yl]-1-(4-m eth oxyp h en yl)-4-styr yla zetid in -2-on e (10). The
title compound was prepared from the acid chloride 6 (6.3 g, 20
mmol), the imine 8 (4.26 g, 18 mmol), and triethylamine (41
mmol) following the above procedure. The resulting crude was
washed with ethyl acetate and the solid residue recrystallized
128-130 °C; [R]25 ) +8.0 (c ) 1.0, MeOH); IR (KBr) ν 3334
D
(NH), 1761 (CdO), 1748 (CdO), 1677 cm-1 (NHCOO); 1H NMR
(CDCl3) 5.43 (d, 1H, J ) 8.1 Hz), 5.11 (dd, 1H, J ) 8.01, 4.7
Hz), 4.15 (d, 1H, J ) 18.1 Hz), 3.95 (dt, 1H, J ) 4.7, 8.8 Hz),
3.87 (d, 1H, J ) 18.1 Hz), 3.74 (s, 3H), 2.34 (m, 2H), 2.00 (m,
1H), 1.81 (m, 1H), 1.43 (s, 9H); 13C NMR (CDCl3) 176.7, 168.2,
167.3, 155.3, 80.7, 59.8, 58.7, 52.5, 41.4, 29.6, 28.1, 23.3. Anal.
Calcd for C14H22N2O7 (330.33): C, 50.90; H, 6.71; N, 8.47.
Found: C, 50.79; H, 6.58; N, 8.57.
from ethyl acetate: yield 60%; mp 262-264 °C; [R]25 ) +55.9
D
(c ) 1.0, CH2Cl2); IR (NaCl) ν 1743 cm-1 (CdO); 1H NMR (CDCl3)
7.44-6.89 (m, 19H, arom), 6.82 (d, 1H, J ) 16.3 Hz), 6.41 (dd,
1H, J ) 8.8, 16.3 Hz), 5.84 (d, 1H, J ) 8.6 Hz), 5.14 (d, 1H, J )
8.6 Hz), 4.83 (dd, 1H, J ) 5.3, 8.8 Hz), 4.64 (d, 1H, J ) 5.3 Hz),
3.75 (s, 3H); 13C NMR (CDCl3) 161.2, 156.9, 137.7, 136.2, 134.7,
134.0, 131.9, 129.4, 129.2, 129.1, 128.8, 128.7, 128.5, 127.6, 126.7,
124.6, 119.1, 114.9, 81.0, 66.1, 63.6, 62.18, 56.11. Anal. Calcd
for C33H28N2O4 (516.59): C, 76.72; H, 5.46; N, 5.42. Found: C,
76.91; H, 5.37; N, 5.41.
cis-(3S,4R)-3-[(ter t-Bu toxyca r bon yl)a m in o]-4-(2-p h en yl-
eth yl)a zetid in -2-on e (13). A solution of ceric ammonium
nitrate (CAN) (1.54 g, 2.8 mmol) in water (30 mL) was added to
a mixture of â-lactam 12 (0.37 g, 0.94 mmol) in acetonitrile (50
mL) cooled at 0 °C. The reaction mixture was stirred for 45 min
and then was diluted with water (200 mL) and extracted with
ethyl acetate (100 mL). The organic phase was washed with
5% sodium bicarbonate (50 mL), and the aqueous phase was re-
extracted with ethyl acetate (50 mL). The combinated organic
phases were washed with 10% sodium sulfite (30 mL), 5%
sodium bicarbonate (30 mL), and brine (30 mL). The organic
layer was dried, the solvent was evaporated under reduced
pressure, and the product was purified by flash chromatography
(silica gel 230-400 mesh; CH2Cl2/EtAcO 10:1 and then CH2Cl2/
EtAcO 2:1) to obtain the desired product: yield 82%; mp 130-
Gen er a l P r oced u r e for Sim u lta n eou s Hyd r ogen olysis
a n d N-Boc P r otection of â-La cta m s 9 a n d 10. Pearlman’s
catalyst (Acros, 200 mg) and di-tert-butyl dicarbonate (0.65 g, 3
mmol) were added successively to a solution of the corresponding
3-oxazolidinyl-â-lactam (1 mmol) in THF (30 mL). The resulting
mixture was stirred at room temperature under a hydrogen
atmosphere (120 psi) for 48 h. Then the mixture was filtered
through Celite, and after evaporation of the filtrate under
reduced pressure, the resulting crude was purified by chroma-
tography to give the desired product.
cis-(3S,4R)-3-[(ter t-Bu toxyca r bon yl)a m in o]-4-(2-p h en yl-
eth yl)-1-[(m eth oxycar bon yl)m eth yl]azetidin -2-on e (11). The
title compound was prepared from 9 (0.48 g, 1 mmol) following
the general procedure in a yield of 84%. The white solid was
purified by flash chromatography (silica gel, 230-400 mesh,
methylene chloride and methylene chloride/ethyl acetate 10:1):
mp 100-103 °C; [R]25D ) +4.8 (c ) 1.0, CH2Cl2); IR (KBr) ν 3339
(NH), 1746 (CdO), 1729 (CdO), 1685 cm-1 (NHCO); 1H NMR
(CDCl3) 7.32-7.16 (m, 5H), 5.45 (d, 1H, J ) 8.7 Hz), 5.16 (dd,
1H, J ) 8.7, 5.0 Hz), 4.09 (d, 1H, J ) 18.1 Hz), 3.93 (dt, 1H, J
) 8.0, 5.0 Hz), 3.72 (s, 3H), 3.72 (d, 1H, J ) 18.1 Hz), 2.6 (m,
2H), 1.9 (m, 2H), 1.45 (s, 9H); 13C NMR (CDCl3) 168.2, 167.1,
155.0, 140.8, 128.4, 128.3, 128.2, 128.1, 126.1, 80.3, 59.9, 59.0,
52.3, 41.6, 31.9, 30.5, 28.1. Anal. Calcd for C19H26N2O5
(362.43): C, 62.96; H, 7.23; N, 7.72. Found: C, 63.04; H, 7.11;
N, 7.68.
132 °C (ethanol); [R]25 ) +62.1 (c ) 1.0, CH2Cl2); IR (KBr) ν
D
3337 (NH), 1737 (CdO), 1685 cm-1 (CdO); 1H NMR (CDCl3)
7.30-7.15 (m, 5H), 6.33 (s, 1H), 5.46 (d, 1H, J ) 8.2 Hz), 5.04
(dd, 1H, J ) 4.7, 8.2 Hz), 3.76 (m, 1H), 2.63 (m, 2H), 1.78 (m,
2H), 1.43 (s, 9H); 13C NMR (CDCl3) 169.0, 155.9, 141.4, 129.1,
128.9, 126.7, 80.9, 60.7, 55.2, 33.0, 32.8, 28.8. Anal. Calcd for
C16H22N2O3 (290.36): C, 66.18; H, 7.63; N, 9.64. Found: C,
66.24; H, 7.78; N, 9.53.
Ack n ow led gm en t. Financial support of this work
by Comisio´n Interministerial de Ciencia y Tecnolog´ıa
(Project SAF 95/0749), and in part by Gobierno Vasco
(Project PI 95/93). Grants from Gobierno Vasco to L.D.
and A.K. are gratefully acknowledged.
1
Su p p or tin g In for m a tion Ava ila ble: Representative H
and 13C NMR spectra of compounds 9, 11, 12, and 14 (4 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
cis-(3S,4R)-3-[(ter t-Bu toxyca r bon yl)a m in o]-4-(2-p h en yl-
eth yl)-1-(4-m eth oxyp h en yl)a zetid in -2-on e (12). The title
compound was prepared from 10 (0.52 g, 1 mmol) following the
general procedure in a yield of 80%. The white solid was purified
by flash chromatography (silica gel, 230-400 mesh, methylene
chloride and methylene chloride/ethyl acetate 10:1): mp 184-
J O980515X