Notes
J . Org. Chem., Vol. 62, No. 25, 1997 8913
Sta r tin g Ma ter ia ls. (S)- and (R)-lactaldehyde were prepared
in NH3 (21 mL). The excess of Li was quenched after 2 min by
the addition of solid NH4Cl (0.32 g, 6 mmol), and the ammonia
was allowed to distill off at -33 °C under a stream of N2. The
resulting crude product was dried in vacuo, dissolved in 5 mL
of H2O, briefly acidified to pH 3 with the addition of 10% aqueous
HCl, and subsequently made basic (pH 8) with the addition of
solid NaHCO3. Benzylchloroformate (0.43 mL, 3 mmol) was
added to the aqueous mixture. After 4 h, the reaction mixture
was extracted with ethyl acetate, washed with saturated aque-
ous NaCl, dried (MgSO4), and concentrated in vacuo. Flash
chromatography (SiO2, CH2Cl2/acetone 9/1) afforded 7 (0.33 g,
according the reported procedure.1a
(2R,5R,6S)-2-[(S)-1-[(Tr iisop r op ylsilyl)oxy]eth yl]-5-[(S)-
2-oxo-4-p h en yl-1,3-oxa zolid in -3-yl]-6-m eth ylp er h yd r o-1,3-
oxazin -4-on e an d (2R,5R,6R)2-[(S)-1-[(Tr iisopr opylsilyl)oxy]-
et h yl]-5-[(S)-2-oxo-4-p h en yl-3-oxa zolid in -3-yl]-6-m et h yl-
p er h yd r o-1,3-oxa zin -4-on e (5 a n d 6). The acyl chloride 2 was
prepared as described by Evans.9 To a solution of the corre-
sponding commercially available acid (0.26 g, 1.2 mmol) in dry
toluene (5 mL) was added oxalyl chloride (0.16 mL, 1.8 mmol)
in one portion, and the mixture was warmed to 60 °C for 3 h.
The solvent and excess oxalyl chloride were removed in vacuo,
and the resulting crude acid chloride 2 was redissolved in toluene
(5 mL). Meanwhile, a solution of (S)-lactimine 1 was prepared
by the dropwise addition of a heptane solution (5 mL) of (S)-1-
(triisopropylsiloxy)lactaldehyde (0.23 g, 1 mmol) to a cooled
(0 °C) THF solution of lithium bis(trimethyldisilyl)amide
(LHMDSA) (1 mL of a 1 M solution in THF). After the addition
of the aldehyde was complete, the reaction mixture was stirred
at 0 °C for 15 min and at rt for 1 h. The formation of the imine
was confirmed by an infrared spectrum of the reaction mixture
(νCN ) 1685 cm-1). The imine solution was then warmed to rt,
trimethylsilyl chloride (0.13 mL, 1 mmol) was added in one
portion, and this mixture was allowed to stir for 1 h at rt. This
same mixture was cooled to 0 °C, and triethylamine (0.3 mL,
2.0 mmol) was added in one portion. After this mixture was
stirred for 5 min at 0 °C, the toluene solution of 2 was added
very slowly (over 5 min). Stirring was maintained for 30 min
at 0 °C and 1 h at rt. This yellow-orange mixture was then
filtered through Celite, and the solvent was removed in vacuo.
A small sample was removed from the reaction mixture and
concentrated to an oil, and an 1H NMR of this sample was run
to check for the presence of the azadiene species 3. The so
obtained 3 was dissolved in methylene chloride (5 mL) and cooled
at -78 °C, and acetaldehyde (0.11 mL, 2 mmol) in methylene
chloride (2 mL) was added followed by a very slow addition of
boron trifluoride diethyl etherate (0.12 mL, 1 mmol) dissolved
in methylene chloride (10 mL). The reaction was stirred at -78
°C for 3 h and then allowed to warm to rt overnight. The crude
reaction mixture was diluted with methylene chloride (10 mL),
poured into a satured NaHCO3 aqueous solution, and extracted
with more methylene chloride. The organic layers were washed
with brine and then dried over MgSO4. After filtration, the
solvent was removed under reduced pressure and the crude
reaction mixture was purified by flash chromatography on silica
gel eluting with methylene chloride/acetone 9/1. Compounds 5
and 6 were obtained in 66 and 7% yields, respectively, as oils.
5: [R]20D ) +113.5 (c 1.22, CHCl3); IR (CHCl3) 1758, 1684, 1521
67%) as an oil: [R]20 ) +10.6 (c 2.03, CHCl3); IR (CHCl3) cm-1
D
1723, 1685, 1510, 1437. 1H NMR 7.35 (s, 5H), 6.35 (s, 1H), 5.15
(m, 3H), 4.90 (d, 1H, J ) 3.4), 4.38 (dd, 1H, J ) 3.5, 9.15), 4.10
(m, 2H), 1.22 (d, 3H, J ) 6.3), 1.12 (d, 3H, J ) 6.1), 1.04 (s,
21H); 13C NMR 167.9, 156.4, 136.2, 128.6, 128.3, 128.2, 84.2,
73.5, 68.3, 67.4, 54.3, 18.0, 18.0, 16.2, 15.9, 12.3; MS m/z 464
(M+), 421 (M+ - 43), 377, 287, 186. Anal. Calcd for C24H40N2O5-
Si: C, 62.03; H, 8.68. Found: C, 62.23; H, 8.70.
(2S,5S,6R) 2-[(R)-1-[(Tr iisopr opylsilyl)oxy]eth yl]-5-[(ben -
zyloxyca r b on yl)a m in o]-6-m et h ylp er h yd r o-1,3-oxa zin -4-
on e (en t-7). This compound was obtained by following the
above-reported procedure for 7 starting from en t-6: [R]20
-11.2 (c 1.63, CHCl3).
)
D
D-Th r eon in e N-(Ca r boben zyloxy)m eth yl Ester 8. Com-
pound 7 (0.2 g, 0.43 mmol) was dissolved in MeOH (20 mL). The
solution was cooled at 0 °C, and 5 mL of a previously prepared
satured solution of HCl in MeOH was added. After 30 min the
solvent was removed in vacuo, a satured solution of NaHCO3
was added, and the mixture was extracted with ethyl acetate.
A simple filtration on silica gel (CH2Cl2/acetone 9/1) yielded the
target compound 8 in almost quantitative yield. Spectral data
of this compound are superimposable with the authentic, com-
mercially available (Aldrich), enantiomer: [R]20D ) +18.0 (c 1.19
CH3OH); mp 90 °C; IR (CHCl3) 3450, 1725, 1520, 1463 cm-1; 1H
NMR (CDCl3) 7.30 (s, 5H), 5.72 (d, 1H, J ) 8.5), 5.07 (s, 2H),
4.30 (m, 2H), 3.69 (s, 3H), 2.57 (bs, 1H), 1.17 (d, 3H, J ) 6.5).
L-Th r eon in e N-(Ca r b ob en zyloxy)m et h yl E st er en t-8.
This compound was obtained from en t-7 by following the same
procedure as described for 7: [R]20 ) -17.00 (c 1.33 CH3OH).
D
Isom er iza tion of Com p ou n d 7 To Give 9. Compound 7
(0.11 g, 0.237 mmol) was treated with DBU (0.036 g, 0.237 mmol)
in DMF (3 mL) at 80 °C; after the TLC spot-test (CH2Cl2/acetone
9/1) showed complete disappearance of the starting material
(overnight), the reaction mixture was poured in sodium acetate
buffer (pH 5) (5 mL) and extracted with ethyl acetate. Removal
of the solvent yielded the target compound 9 in quantitative
yield: [R]20 ) -25.00 (c 1.04 CHCl3); IR (CHCl3) 1728, 1686,
D
1
cm-1; H NMR 7.33 (s, 5H), 6.20 (s, 1H), 5.10 (dd, 1H, J ) 6.1,
1
1518 cm-1; H NMR 7.33 (s, 5H), 6.28 (s, 1H), 5.47 (d, 1H, J )
8.6), 4.72 (d, 1H, J ) 3.7), 4.62 (t, 1H, J ) 8.6), 4.15-4.07 (m,
7.8), 5.11 (s, 2H), 4.95 (bs, 1H), 4.03 (dq, 1H, J ) 3.2, 6.1), 3.83
(m, 2H), 1.32 (d, 3H, J ) 5.9), 1.14 (d, 3H, J ) 6.1), 1.04 (s,
21H); 13C NMR 168.9, 156.8, 136.2, 128.5, 128.1, 128.0, 85.1,
74.1, 68.8, 67.2, 56.5, 18.8, 18.0, 18.0, 15.6, 12.2; MS m/z 464
(M+), 421, 377, 276, 187, 91. Anal. Calcd for C24H40N2O5Si: C,
62.03; H, 8.68. Found: C, 62.17; H, 8.69.
2H), 4.05-3.90 (m, 2H), 1.28 (d, 3H, J ) 6.5), 1.00 (m, 24H); 13
C
NMR 165.8, 158.7, 137.4, 129.0, 128.6, 127.5, 86.1, 75.0, 70.6,
68.6, 61.5, 55.9, 17.9, 17.8, 16.3, 12.1; MS m/z 433 (M+ - 43),
389, 275, 186, 106. Anal. Calcd for C25H40N2O5Si: C, 62.99; H,
8.46. Found: C, 62.87; H, 8.45.
6: [R]20D ) +66.6 (c 0.90, CHCl3); IR (CHCl3) 1759, 1684, 1521
Com p ou n d en t-9. This compound was obtained in quantita-
tive yield starting from en t-7 by following the procedure reported
1
cm-1; H NMR 7.40 (s, 5H), 6.28 (s, 1H), 5.15 (dd, 1H, J ) 8.6,
9.8), 4.83 (m, 2H), 4.70 (t, 1H, J ) 8.6), 4.20 (dd, 1H, J ) 8.6,
9.8), 4.06 (dq, 1H, J ) 4.5, 6.1), 3.05 (d, 1H, J ) 8.8), 1.21 (d,
3H, J ) 6.1), 1.08 (d, 3H, J ) 6.1), 1.02 (s, 21H); 13C NMR 168.0,
158.6, 136.5, 129.6, 129.2, 128.3, 82.9, 70.5, 69.5, 67.6, 63.9, 58.6,
18.6, 18.0, 18.0, 17.3, 12.3; MS m/z 433 (M+ - 43), 389, 275,
186, 106. Anal. Calcd for C25H40N2O5Si: C, 62.99; H, 8.46.
Found: C, 63.19; H, 8.47.
for 9: [R]20 ) +24.00 (c 0.85 CHCl3).
D
D-a llo-Th r eon in e N-(Ca r boben zyloxy)m eth yl Ester 10.
This compound was obtained in quantitative yield starting from
9 and following the procedure reported for 8. Spectral data were
superimposable with the reported ones: [R]20 ) -14.2 (c 1.12
D
CHCl3) (lit.7e ) -14.5 (c 10 CHCl3); mp 55 °C; IR (CHCl3) 1700,
1500 cm-1; 1H NMR (CDCl3) 7.35 (m, 5H), 5.67 (d, 1H, J ) 8.2),
5.13 (s, 2H), 4.43 (dd, 1H, J ) 8.0, 3.6), 4.15 (m, 1H), 3.77 (s,
3H), 2.0 (bs, 1H), 1.19 (d, 3H, J ) 6.5).
(2S,5S,6R)-2-[(R)-1-[(Tr iisop r op ylsilyl)oxy]eth yl]-5-[(R)-
2-oxo-4-p h en yl-1,3-oxa zolid in -3-yl]-6-m eth ylp er h yd r o-1,3-
oxazin -4-on e an d (2S,5S,6S)2-[(R)-1-[(Tr iisopr opylsilyl)oxy]-
et h yl]-5-[(R)-2-oxo-4-p h en yl-1,3-oxa zolid in -3-yl]-6-m et h -
ylp er h yd r o-1,3-oxa zin -4-on e (en t-5 a n d en t-6). Following
the same procedure described for 5 and 6, en t-5 and en t-6 were
obtained starting from (R)-(triisopropylsiloxy)lactaldehyde and
(R)-oxazolidinone (66% yield, 90/10 diastereomeric ratio en t-5/
L-a llo-Th r eon in e N-(Ca r boben zyloxy)m eth yl Ester en t-
10. This compound was obtained, in quantitative yield, following
the same procedure as described for 10: [R]20 ) +14.0 (c 0.85
D
CHCl3).
en t-6). en t-5: [R]20D ) -112.7 (c 0.70, CHCl3). en t-6: [R]20
-65.4 (c 0.70, CHCl3).
)
Ack n ow led gm en t . This investigation was sup-
ported by “Progetto Strategico Tecnologie Chimiche
Innovative”, awarded by the CNR-Rome. M.P. thanks
Glaxo-Wellcome, Verona, for financial support.
D
(2R,5R,6S)-2-[(S)-1-[(Tr iisopr opylsilyl)oxy]eth yl]-5-[(ben -
zyloxyca r b on yl)a m in o]-6-m et h ylp er h yd r o-1,3-oxa zin -4-
on e (7). A THF/t-BuOH (10:1, 6 mL) solution of 5 (0.476 g, 1
mmol) was added at -78 °C to a solution of Li (42 mg, 6 mmol)
J O971395G