358
Vol. 53, No. 4
less crystals: mp 95—97 °C (hexane/CHCl3) (lit.18,19) mp 94—96 °C, 92—
mixture at 0 °C. After being stirred at room temperature for 24 h, the reac-
tion mixture was diluted with CHCl3 and washed with H2O. The organic
phase was dried over Na2SO4 and concentrated at reduced pressure. Purifica-
tion of the residue by MCC (hexane/AcOEt 3 : 1) afforded 6c (1.29 g, 62%)
as a colorless oil; IR (CHCl3) cmꢀ1: 3369, 1652. 1H-NMR (200 MHz,
CDCl3) d: 1.47 (6H, s), 3.80 (2H, s), 3.84 (3H, s), 7.35 (1H, br s). MS (EI)
m/z: 208 (Mꢅ), 210 (Mꢅꢅ2).
1
93 °C); IR (CHCl3) cmꢀ1: 3433, 1645. H-NMR (300 MHz, CDCl3) d: 0.46,
1.15, 1.40 and 1.48 (each 3H, d, Jꢄ7 Hz), 3.35 and 3.80 (each 1H, sept,
Jꢄ7 Hz), 5.11 (1H, s), 7.24—7.38 (5H, m). HR-MS (EI) m/z: 235.1545
(Calcd for C14H21NO2 (Mꢅ): 235.1571). These spectral data are identical
with those reported.18,19)
(Z)-1-(2-Furyl)-2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-phenyl-
ethanone O-Methyloxime (11) To a solution of 2b (462 mg, 2 mmol) in
CH2Cl2 (10 ml) was added 2,6-lutidine (0.47 ml, 4 mmol) and then added
dropwise a solution of TBDMSOTf (0.69 ml, 3 mmol) in CH2Cl2 (1 ml).
After being stirred at room temperature for 1 h, the reaction mixture was di-
luted with H2O and extracted with AcOEt. The organic phase was washed
with H2O, dried over Na2SO4, and concentrated at reduced pressure. Purifi-
cation of the residue by MCC (hexane/AcOEt 20 : 1) afforded 11 (690 mg,
quant.) as colorless crystals mp 86—88 °C (hexane/CHCl3); 1H-NMR
(300 MHz, CDCl3) d: ꢀ0.08 and 0.00 (each 3H, s), 0.80 (9H, s), 3.98 (3H,
s), 6.18 (1H, dd, Jꢄ3.5, 2 Hz), 6.52 (1H, s), 6.62 (1H, dd, Jꢄ3.5, 1 Hz),
7.06—7.22 (3H, m), 7.25 (1H, dd, Jꢄ2, 1 Hz), 7.30—7.37 (2H, m). HR-MS
(EI) m/z: 345.1758 (Calcd for C19H27NO3Si (Mꢅ): 345.1760). Anal. Calcd
for C19H27NO3Si: C, 66.05; H, 7.88; N, 4.05, Found: C, 66.02; H, 7.71; N,
4.03.
Preparation of Hydroximates 1a—c To
a solution of 6a—c
(12.8 mmol) in MeCN (100 ml) was added Ph3P (19.2 mmol) under a nitro-
gen atmosphere at room temperature. After being stirred at the same temper-
ature for 10 min, CBr4 (19.2 mmol) was added to the reaction mixture. After
refluxing for 3 h, the resulting solution was concentrated at reduced pressure.
Purification of the residue by FCC (hexane→hexane/AcOEt 10 : 1) afforded
the hydroximoyl bromide 7a—c. After being characterized by NMR spectra,
7a—c were immediately subjected to the following reaction. To a suspen-
sion of NaH (60% oil suspension) (32 mmol) in THF (40 ml) was added a
solution of benzyl alcohol (48 mmol) in THF (40 ml) under a nitrogen at-
mosphere at 0 °C. After being stirred at room temperature for 20 min, a solu-
tion of the hydroximoyl bromide 7a—c (16 mmol) in THF (80 ml) was
added to reaction mixture at room temperature. After being stirred at the
same temperature for 4 h, the reaction mixture was cooled at 0 °C, diluted
with H2O and extracted with CH2Cl2. The organic phase was washed with
H2O, dried over Na2SO4, and concentrated at reduced pressure. Purification
of the residue by MCC afforded 1a—c.
Conversion of Z-2-Hydroxyoxime Ethers 2b and 11 into Oxazolidi-
nones 13 (Table 2, Entry 1): To a solution of 2b (300 mg, 1.3 mmol) in
THF (30 ml) was added SMEAH (65% in toluene) (7.74 ml, 5.72 mmol)
under a nitrogen atmosphere at ꢀ30 °C. The reaction mixture was stirred at
the same temperature for 2 h. After being heated at 60 °C for 3 h, the reac-
tion mixture was cooled to room temperature. The reaction mixture was
diluted with 10% aqueous NaOH and extracted with CHCl3. The or-
ganic phase was washed with H2O, dried over Na2SO4, and concentrated
at reduced pressure to afford the crude amino alcohols 12 (threo : ery-
throꢄꢂ99 : ꢃ1). To a solution of the crude amino alcohols in MeCN
(20 ml) were added DMAP (190 mg, 1.3 mmol) and (Boc)2O (672 mg,
2.86 mmol) at room temperature. After being stirred at the same temperature
for 1 h, the reaction mixture was concentrated at reduced pressure. Purifica-
tion of the residue by MCC (hexane/AcOEt 2 : 1) afforded trans-13 (280 mg,
1
Ethyl [Bromo(methoxyimino)methyl]acetate (7a) A colorless oil; H-
NMR (200 MHz, CDCl3). d: 1.38 (3H, t, Jꢄ6 Hz), 4.20 (3H, s), 4.40 (2H, q,
Jꢄ6 Hz).
N-Methoxy-2-furancarboximidoyl Bromide (7b) A colorless oil; 1H-
NMR (200 MHz, CDCl3) d: 4.15 (3H, s), 6.48 (1H, dd, Jꢄ4, 2 Hz), 6.89
(1H, dd, Jꢄ4, 1 Hz), 7.52 (1H, dd, Jꢄ2, 1 Hz).
2-Chloro-N-methoxy-4,4-dimethyl-2-oxazolidinecarboximidoyl Bro-
mide (7c) A colorless oil; 1H-NMR (200 MHz, CDCl3) d: 1.49 (6H, s),
3.82 (2H, s), 4.11 (3H, s), 6.60 (1H, br s).
Ethyl (Z)-[(Methoxyimino)(phenylmethoxy)]acetate (1a) A colorless
oil; IR (CHCl3) cmꢀ1: 1732, 1649. 1H-NMR (200 MHz, CDCl3) d: 1.30 (3H,
t, Jꢄ7 Hz), 3.96 (3H, s), 4.30 (2H, q, Jꢄ7 Hz), 5.32 (2H, s), 7.31—7.47
(5H, m). HR-MS (CI) m/z: 238.1084 (Calcd for C12H15NO4ꢅ1 (QMꢅ):
238.1079).
Phenylmethyl (Z)-N-Methoxy-2-furancarboximidate (1b) A colorless
oil; IR (CHCl3) cmꢀ1: 1609. 1H-NMR (200 MHz, CDCl3) d: 3.95 (3H, s),
5.29 (2H, s), 6.38 (1H, dd, Jꢄ3.5, 2 Hz), 6.62 (1H, dd, Jꢄ3.5, 1 Hz), 7.26—
7.42 (5H, m), 7.44 (1H, dd, Jꢄ2, 1 Hz). HR-MS (EI) m/z: 231.0893 (Calcd
for C13H13NO3 (Mꢅ): 231.0895).
1
67%). The ratio of trans- to cis-adducts was determined by H-NMR spec-
trum.
(Table 2, Entry 2): To a suspension of LiAlH4 (985 mg, 25.6 mmol) in
Et2O (20 ml) was added a solution of 11 (220 mg, 0.64 mmol) in Et2O (5 ml)
with stirring under a nitrogen atmosphere at 0 °C. After being stirred at the
same temperature for 12 h, usual work-up afforded the crude amino alcohols
12 (threo : erythroꢄ3 : 97). To a solution of the crude amino alcohols in
MeCN (10 ml) were added DMAP (94 mg, 0.64 mmol) and (Boc)2O
(331 mg, 1.41 mmol) at room temperature. After being stirred at the same
temperature for 1 h, the reaction mixture was concentrated at reduced pres-
sure. Purification of the residue by MCC (hexane/AcOEt 2 : 1) afforded cis-
and trans-13 (97 : 3) (124 mg, 59%). The ratio of trans- to cis-adducts 13
was determined by 1H-NMR spectrum.
Phenylmethyl (Z)-4,5-Dihydro-N-methoxy-4,4-dimethyl-2-oxazolecar-
boximidate (1c)
A :
colorless oil; IR (CHCl3) cmꢀ1 1649. 1H-NMR
(300 MHz, CDCl3) d: 1.33 (6H, s), 3.93 (3H, s), 4.01 (2H, s), 5.43 (2H, s),
7.30—7.46 (5H, m). HR-MS (EI) m/z: 262.1327 (Calcd for C14H18N2O3
(Mꢅ): 262.1316).
General Procedure for Imino 1,2-Wittig Rearrangement A solution
of Z-hydroximate 1a—c (1 mmol) in THF (5 ml) was added with stirring at
temperature shown in Table 1 to a LDA solution, prepared from diisopropy-
lamine (2 mmol or 4 mmol) and n-BuLi (1.65 M in hexane) (2 mmol or
4 mmol) under nitrogen atmosphere. After being stirred at the same tempera-
ture for 1 or 2 h, the reaction mixture was diluted with saturated aqueous
NH4Cl and extracted with CH2Cl2. The organic phase was washed with H2O,
dried over Na2SO4, and concentrated at reduced pressure. In the case of 1b
and 1c, purification of the residue by MCC (hexane/AcOEt 7 : 1) afforded 2b
(217 mg, 94%) and 2c (131 mg, 50%), respectively. On the other hand, the
residue in reaction of 1a was purified by MCC (hexane/AcOEt 3 : 1) to give
the amide 10 (94 mg, 40%).
1,1-Dimethylethyl trans-4-(2-Furyl)-2-oxo-5-phenyl-3-oxazolidinecar-
boxylate (trans-13) A colorless oil; IR (CHCl3) cmꢀ1: 1815. 1H-NMR
(300 MHz, CDCl3) d: 1.39 (9H, s), 5.10 (1H, d, Jꢄ5.5 Hz), 5.47 (1H, d,
Jꢄ5.5 Hz), 6.37 (1H, dd, Jꢄ3.5, 1 Hz), 6.42 (1H, dd, Jꢄ3.5, 2 Hz), 7.30—
7.34 (2H, m), 7.38—7.44 (3H, m), 7.48 (1H, dd, Jꢄ2, 1 Hz). HR-MS (EI)
m/z: 329.1270 (Calcd for C18H19NO5 (Mꢅ): 329.1262).
1,1-Dimethylethyl
cis-4-(2-Furyl)-2-oxo-5-phenyl-3-oxazolidinecar-
boxylate (cis-13) A colorless oil; IR (CHCl3) cmꢀ1: 1815. 1H-NMR
(300 MHz, CDCl3) d: 1.41 (9H, s), 5.50 (1H, d, Jꢄ7.5 Hz), 5.74 (1H, d,
Jꢄ7.5 Hz), 6.03 (1H, br d, Jꢄ3.5 Hz), 6.11 (1H, dd, Jꢄ3.5, 2 Hz), 7.10—
7.16 (3H, m), 7.20—7.24 (3H, m). HR-MS (EI) m/z: 329.1281 (Calcd for
C18H19NO5 (Mꢅ): 329.1262).
(E)-1-(2-Furyl)-2-hydroxy-2-phenylethanone O-Methyloxime (2b)
4-Methyl 3-(1,1-Dimethylethyl) trans-2-Oxo-5-phenyl-3,4-oxazoli-
dinedicarboxylate (15)21) To a solution of trans-13 (280 mg, 0.85 mmol)
in CCl4–MeCN–H2O (2 : 2 : 3) (9.1 ml) was added NaIO4 (1.48 g, 6.9 mmol)
and RuCl3·xH2O (5.3 mg, 0.025 mmol) at room temperature. After being
stirred at the same temperature for 1 h, the reaction mixture was diluted with
H2O and extracted with AcOEt. The organic phase was washed with H2O,
dried over Na2SO4, and concentrated at reduced pressure to afford the crude
trans-carboxylic acid. To a solution of the crude trans-carboxylic acid in
MeOH (20 ml) was added a solution of CH2N2 (2.1 mmol) in Et2O, prepared
according to a usual method, at 0 °C. After being stirred at the same temper-
ature for 1 h, the reaction mixture was concentrated at reduced pressure. Pu-
rification of the residue by MCC (hexane/AcOEt 3 : 1) afforded trans-15
(251 mg, 92%) as colorless crystals mp 123—125 °C (hexane/CHCl3); IR
(CHCl3) cmꢀ1: 1815, 1757. 1H-NMR (300 MHz, CDCl3) d: 1.51 (9H, s),
Colorless crystals: mp 100—101 °C (hexane/CHCl3); IR (CHCl3) cmꢀ1
:
3538. 1H-NMR (300 MHz, CDCl3) d: 3.79 (1H, d, Jꢄ8 Hz), 3.95 (3H, s),
6.12 (1H, d, Jꢄ8 Hz), 6.42 (1H, dd, Jꢄ4, 2 Hz), 6.77 (1H, dd, Jꢄ4, 1 Hz),
7.24—7.35 (5H, m), 7.48 (1H, dd, Jꢄ2, 1 Hz). HR-MS (EI) m/z: 231.0890
(Calcd for C13H13NO3 (Mꢅ): 231.0895. Anal. Calcd for C13H13NO3: C,
67.52; H, 5.67; N, 6.06, Found: C, 67.69; H, 5.77; N, 6.03.
(E)-1-[(4,5-Dihydro-4,4-dimethyl)-2-oxazolyl]-2-hydroxy-2-phenyl-
ethanone O-Methyloxime (2c) A colorless oil; IR (CHCl3) cmꢀ1: 3316.
1H-NMR (300 MHz, CDCl3) d: 1.24 and 1.37 (each 3H, s), 4.00 (2H, s),
4.10 (3H, s), 6.35 (1H, br d, Jꢄ8 Hz), 6.59 (1H, br d, Jꢄ8 Hz), 7.40—7.65
(5H, m). HR-MS (EI) m/z: 262.1337 (Calcd for C14H18N2O3 (Mꢅ):
262.1316).
a-Hydroxy-N,N-bis(1-methylethyl)benzeneacetamide (10)18,19) Color-