Bodner et al.
21%), and the byproduct dihydropyranone 1016 (6.7 mg, 20%).
The pure R-acetate was recrystallized from EtOAc/hexanes (1/
1, slow evaporation through Parafilm), providing crystals for
X-ray analysis.14 Data for 8R: Rf ) 0.35 (80% EtOAc/hexanes).
into saturated aqueous NaHCO3 and extracted with CH2Cl2.
The organic extract was washed with brine (×1), dried
(MgSO4), filtered, and concentrated. The residue was chro-
matographed (20% EtOAc/hexanes, 70 mL SiO2), affording
Cbz-protected oxazolidinone 16R (103 mg, 92%) as a clear oil
that solidified on standing in the freezer at -20 °C. Rf ) 0.51
(40% EtOAc/hexanes). Mp: 89-91 °C. IR (thin film): 1832,
1805, 1733 cm-1. 1H NMR (300 MHz, CDCl3): δ 7.48-7.30 (m,
5H), 5.78 (dddd, J ) 17.0, 10.3, 6.7, 6.7 Hz, 1H), 5.32 (AB, JAB
) 12.3 Hz, ∆νAB ) 23.6 Hz, 2H), 5.31 (s, 1H), 5.08-4.97 (m,
2H), 4.60 (dd, J ) 7.9, 7.9 Hz, 1H), 4.36 (d, J ) 4.4 Hz, 1H),
3.90-3.85 (m, 1H), 3.78-3.67 (m, 3H), 3.61 (ddd, J ) 9.6, 6.6,
6.6 Hz, 1H), 3.35 (ddd, J ) 9.6, 6.5, 6.5 Hz, 1H), 2.10 (m, 2H),
1.65 (m, 2H), 1.48 (s, 3H), 1.43 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 151.6, 151.4, 137.6, 134.3, 128.7, 128.2, 115.2, 100.2,
95.3, 72.6, 72.0, 69.2, 67.4, 61.9, 59.9, 58.6, 30.0, 28.9, 28.3,
18.9. HRMS (FAB): m/z calcd for C23H30NO8 (M + H)+
448.1971, found 448.1956.
1
Mp: 168-170 °C. IR (thin film): 3326, 1766, cm-1. H NMR
(300 MHz, CDCl3): δ 6.34 (br s, 1H), 6.14 (s, 1H), 4.66 (dd, J
) 7.8, 7.8 Hz, 1H), 4.11 (d, J ) 7.8 Hz, 1H), 4.02-3.88 (m,
2H), 3.84-3.62 (m, 2H), 2.14 (s, 3H), 1.54 (s, 3H), 1.44 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 169.1, 158.3, 100.5, 90.9, 75.2,
71.5, 63.1, 61.9, 55.8, 29.1, 21.1, 19.2. HRMS (FAB): m/z calcd
for C12H18NO7 (M + H)+ 288.1083, found 288.1092. Data for
8â: Rf ) 0.28 (80% EtOAc/hexanes). Mp: 199-203 °C. IR (thin
1
film): 3306, 1755 cm-1. H NMR (300 MHz, CDCl3): δ 6.09
(d, J ) 3.0 Hz, 1H), 5.91 (br s, 1H), 4.69 (dd, J ) 7.8, 7.8 Hz,
1H), 4.30 (dd, J ) 10.7, 7.2 Hz, 1H), 4.22 (dd, J ) 8.4, 3.0 Hz,
1H), 3.97 (dd, J ) 11.0, 5.4 Hz, 1H), 3.74 (dd, J ) 10.5, 10.5
Hz, 1H), 3.50 (ddd, J ) 10.4, 10.4, 5.4 Hz, 1H), 2.17 (s, 3H),
1.54 (s, 3H), 1.43 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.5,
158.8, 100.3, 90.0, 76.1, 70.8, 65.9, 62.7, 52.8, 29.0, 21.3, 19.1.
HRMS (FAB): m/z calcd for C12H18NO7 (M + H)+ 288.1083,
found 288.1086. Data for 10: Rf ) 0.18 (40% EtOAc/hexanes).
(-)-Menthyl 2-Amino-2-N-((benzyloxy)carbonyl)-2-N,3-
O-carbonyl-2-deoxy-4,6-O-isopropylidene-r-D-mannopy-
ranoside (21a). The NPG 16R (27.1 mg, 0.0605 mmol),
activated 4 Å molecular sieves (104 mg), and (-)-menthol (19.0
mg, 0.122 mmol) were stirred in CH2Cl2 (3.0 mL), and IDCP
(115 mg, 0.245 mmol) was added. After the mixture was stirred
in the dark at 23 °C for 17 h, 10% w/w aqueous Na2S2O3 (6
mL) was added with vigorous stirring, discharging the yellow-
orange color of the reaction mixture. The mixture was filtered
through a pad of Celite, rinsing with CH2Cl2 and water. The
filtrate was transferred to a separatory funnel, and the layers
were shaken and separated. The organic layer was washed
with saturated aqueous CuSO4 (×1) and saturated aqueous
NaHCO3 (×1), dried (MgSO4), filtered, and concentrated. The
residue was chromatographed (10% f 15% f 20% EtOAc/
hexanes, 15 mL of SiO2), affording the glycosylated product
21a (22.3 mg, 71%) and iodoetherification byproduct 33aR (4.8
mg, 11%).23 Data for 21a: Rf ) 0.38 (30% EtOAc/hexanes). IR
1
IR (thin film): 1701, 1591 cm-1. H NMR (300 MHz, CDCl3):
δ 7.28 (dd, J ) 6.0, 0.6 Hz, 1H), 5.44 (d, J ) 6.0 Hz, 1H), 4.49
(d, J ) 13.1 Hz, 1H), 4.27 (m, 1H), 4.13-4.00 (m, 2H), 1.56 (s,
3H), 1.52 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 189.7, 161.3,
106.2, 100.8, 73.9, 71.0, 61.2, 28.6, 18.6. HRMS (FAB): m/z
calcd for C9H13O4 (M + H)+ 185.0814, found 185.0817.
4-Pentenyl 2-Amino-2-N,3-O-carbonyl-2-deoxy-4,6-O-
isopropylidene-D-mannopyranosides (2). The glucal 3-car-
bamate 1 (1.012 g, 4.42 mmol), activated 4 Å molecular sieves
(2.01 g), PhIO (1.950 g, 8.86 mmol), Rh2(OAc)4 (110 mg, 0.250
mmol), and 4-penten-1-ol (1.80 mL, 17.7 mmol) were stirred
in CH2Cl2 (40 mL) at 23 °C for 25 h. The mixture was filtered
through Celite and washed with EtOAc, and the filtrate was
1
concentrated. The crude material was analyzed by H NMR
and chromatographed (40% f 50% f 60% EtOAc/hexanes, 300
mL of SiO2), providing the R-NPG 2R (552 mg, 40%), together
with the byproduct dihydropyranone 10 (89.5 mg, 21%) and
the â-NPG 2â (284 mg, 21%). The yields of the R-NPG 2R and
the byproduct dihydropyranone 10 were calculated on the basis
of the integration data from the 1H NMR spectrum of the
chromatographed material. Data for 2R: Rf ) 0.31 (60%
EtOAc/hexanes). Mp: 120-122 °C. IR (thin film): 3293, 1755
cm-1. 1H NMR (300 MHz, CDCl3): δ 6.28 (br s, 1H), 5.80 (dddd,
J ) 17.0, 10.3, 6.7, 6.7 Hz, 1H), 5.10-4.93 (m, 2H), 4.84 (s,
1H), 4.62 (dd, J ) 8.0, 8.0 Hz, 1H), 4.10 (d, J ) 7.8 Hz, 1H),
3.90 (m, 2H), 3.78 (dd, J ) 10.4, 10.4 Hz, 1H), 3.65 (m, 2H),
3.38 (ddd, J ) 9.6, 6.5, 6.5 Hz, 1H), 2.12 (m, 2H), 1.68 (m,
2H), 1.52 (s, 3H), 1.44 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
159.5, 137.7, 115.2, 100.1, 97.0, 75.7, 71.8, 67.3, 62.0, 60.3, 56.5,
30.1, 29.0, 28.4, 19.0. HRMS (FAB): m/z calcd for C15H24NO6
(M + H)+ 314.1604, found 314.1598. Data for 2â: Rf ) 0.20
(thin film): 1833, 1805, 1733 cm-1 1H NMR (300 MHz,
.
CDCl3): δ 7.50-7.31 (m, 5H), 5.46 (s, 1H), 5.34 (s, 2H), 4.62
(dd, J ) 7.9, 7.9 Hz, 1H), 4.39 (d, J ) 7.9 Hz, 1H), 3.90-3.80
(m, 2H), 3.78-3.66 (m, 2H), 3.32 (ddd, J ) 10.6, 10.6, 4.4 Hz,
1H), 2.16 (qqd, J ) 6.9, 6.9, 2.5 Hz, 1H), 1.98 (m, 1H), 1.64
(m, 2H), 1.50 (s, 3H), 1.44 (s, 3H), 1.40-0.80 (m, 5H), 0.91 (d,
J ) 7.0 Hz, 3H), 0.89 (d, J ) 6.4 Hz, 3H), 0.77 (d, J ) 6.9 Hz,
3H). 13C NMR (75 MHz, CDCl3): δ 151.9 (s), 151.5 (s), 134.5
(s), 128.7 (o), 128.6 (o), 128.2 (o), 100.3 (o), 96.9 (o), 82.2 (o),
72.8 (o), 72.1 (o), 69.2 (t), 61.8 (t), 60.0 (o), 58.98 (o), 48.5 (o),
43.0 (t), 34.1 (t), 31.6 (o), 30.0 (o), 25.6 (o), 23.0 (t), 22.3 (o),
21.1 (o), 18.9 (o), 16.0 (o). HRMS (FAB): m/z calcd for C28H40-
NO8 (M + H)+ 518.2754, found 518.2769.
4-Pentenyl 2-Amino-2-N-((benzyloxy)carbonyl)-2-deoxy-
4,6-O-isopropylidene-3-O-methoxycarbonyl-r-D-mannopy-
ranoside (24r). Using conditions B (Table 3): a solution of
N-Cbz oxazolidinone 16R (77.3 mg, 0.173 mmol) in MeOH (4.0
mL) was cooled to -15 °C (bath temperature), giving a white
suspension. Cesium carbonate (61.5 mg, 0.189 mmol) was
added, and the -15 °C bath was replaced with a 0 °C bath,
giving a homogeneous solution. After 10 min saturated aque-
ous NH4Cl (5 mL) was added, followed by enough water to
solubilize all salts. The mixture was extracted with EtOAc
(×1), and the organic layer was dried (MgSO4), filtered, and
concentrated. The residue was chromatographed (20% f 30%
f 40% f 50% f 60% EtOAc/hexanes, 40 mL of SiO2),
providing the desired methyl carbonate 24R (38.7 mg, 47%)
and the N-H oxazolidinone byproduct 2R (23.3 mg, 30%). Data
for 24R: Rf ) 0.41 (30% EtOAc/hexanes). IR (thin film): 3338,
1754, 1726 cm-1; a minor rotamer was evident in the carbonate
methyl resonance of the 1H NMR spectrum. 1H NMR (300
MHz, CDCl3): δ 7.43-7.29 (m, 5H), 5.80 (dddd, J ) 17.0, 10.3,
6.7, 6.7 Hz, 1H), 5.20-4.85 (m, 6H), 4.76 (s, 1H), 4.48 (dd, J )
8.8, 4.1 Hz, 1H), 3.90-3.70 (m, 6.5H), 3.65 (ddd, J ) 9.5, 6.6,
6.6 Hz, 1H), 3.48 (br s, 0.5H), 3.39 (ddd, J ) 9.5, 6.5, 6.5 Hz,
1H), 2.14 (apparent q, J ) 7.1 Hz, 2H), 1.71 (apparent pentet,
(60% EtOAc/hexanes). IR (thin film): 3305, 1760 cm-1 1H
.
NMR (300 MHz, CDCl3): δ 5.80 (dddd, J ) 17.0, 10.3, 6.7, 6.7
Hz, 1H), 5.40 (br s, 1H), 5.07-4.97 (m, 2H), 4.70 (d, J ) 2.7
Hz, 1H), 4.57 (dd, J ) 7.6, 7.6 Hz, 1H), 4.14 (dd, J ) 7.3, 3.2
Hz, 1H), 4.10 (dd, J ) 10.3, 7.3 Hz, 1H), 3.98-3.87 (m, 2H),
3.79 (dd, J ) 10.5, 10.5 Hz, 1H), 3.52 (ddd, J ) 9.5, 6.6, 6.6
Hz, 1H), 3.27 (ddd, J ) 10.2, 5.5, 5.5 Hz, 1H), 2.13 (m, 2H),
1.71 (m, 2H), 1.51 (s, 3H), 1.42 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 158.6, 137.7, 115.1, 100.0, 97.5, 76.3, 71.4, 69.1, 65.0,
62.3, 54.5, 30.0, 28.9, 28.6, 18.9. HRMS (FAB): m/z calcd for
C15H24NO6 (M + H)+ 314.1604, found 314.1602.
4-Pentenyl 2-Amino-2-N-((benzyloxy)carbonyl)-2-N,3-
O-carbonyl-2-deoxy-4,6-O-isopropylidene-r-D-mannopy-
ranoside (16r). To a solution of oxazolidinone 2R (77.8 mg,
0.249 mmol) in THF (3.5 mL) were added Et3N (95 µL, 0.69
mmol) and DMAP (4.0 mg, 0.33 mmol), followed by benzyl
chloroformate (85 µL, 0.60 mmol). The cloudy mixture was
stirred at 23 °C during 4 h, with additional portions of reagents
added at 1 h intervals: Et3N (3 × 95 µL) and benzyl
chloroformate (3 × 85 µL). The reaction mixture was poured
3994 J. Org. Chem., Vol. 70, No. 10, 2005