5672 J . Org. Chem., Vol. 65, No. 18, 2000
Djung et al.
(()-(1Z)-1-[2,6-Bis(m eth oxy)-4-p yr im id in yl]-1-octen -4-
ol Ca r ba m a te (ester ) (9a ). A mixture of 1.46 g (4.76 mmol)
of alkyne 8 and 714 mg of 5% palladium on barium sulfate in
15.0 mL of pyridine was degassed and flushed with a hydrogen
atmosphere three times. The reaction mixture was stirred
vigorously under 1 atm of hydrogen for 2 h at room temper-
ature, during which time 105 mL (4.7 mmol) of hydrogen was
taken up. The reaction mixture was then filtered through a
pad of Celite, and the filter cake was rinsed with three 50-mL
portions of MeOH. The filtrate was concentrated in vacuo, and
the residue was chromatographed over 50 g of silica gel (eluted
with EtOAc-hexanes, 1:1) to give 1.28 g (87%) of alkene 9a
as a sticky viscous oil: IR (thin film) 3471, 3354, 3190, 2954,
2865, 1718 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.85-0.90 (m,
3H), 1.26-1.37 (m, 4H), 1.53-1.64 (m, 2H), 3.08-3.15 (m, 2H),
3.96 (s, 3H), 4.00 (s, 3H), 4.58 (br s, 2H), 4.86-4.95 (m, 1H),
6.01 (dt, J ) 11.9, 7.2, 1H), 6.25 (s, 1H), 6.30 (d, J ) 11.9,
1H); 13C NMR (75 MHz, CDCl3) δ 13.9 (q), 22.5 (t), 27.4 (t),
33.8 (t), 34.1 (t), 53.7 (q), 54.7 (q), 74.5 (d), 101.3 (d), 128.0 (d),
136.1 (d), 157.0 (s), 164.8 (s), 165.0 (s), 172.2 (s); exact mass
calcd for C15H23N3O4 m/z 309.1688, found m/z 309.1662.
NH4Cl, diluted with 50 mL of EtOAc, dried (MgSO4), and
concentrated in vacuo. The residue was chromatographed over
90 g of silica gel (eluted with EtOAc-hexanes, 3:1, to separate
excess oxaziridine, then EtOAc) to give 120 mg (18%) of
recovered 10a and 364 mg (51%) of alcohol 11 as a white
solid: mp 131-133.5 °C; IR (KBr pellet) 3354, 3107, 2955,
2872, 1725 cm-1 1H NMR (300 MHz, CDCl3) δ 0.85 (t, J )
;
6.9, 3H), 1.25-1.67 (m, 8H), 3.85-4.02 (m, 1H), 3.95 (br s, 6H),
4.13-4.22 (m, 1H), 4.71 (d, J ) 3.2, 1H), 6.63 (s, 1H), 6.93 (br
s, 1H), 1H not observed; 13C NMR (75 MHz, CDCl3) δ 13.8 (q),
22.3 (t), 26.1 (t), 26.7 (t), 34.7 (t), 53.9 (q), 54.7 (q), 54.8 (d),
72.7 (d), 76.8 (d), 98.6 (d), 156.5 (s), 164.8 (s), 170.2 (s), 172.4
(s); calcd for C15H24N3O5 (M + 1) m/z 326.1716, found (M + 1)
m/z 326.1740 (parent not observed).
(()-(4R*,6R*)-6-Bu tyl-4-[(S*)-(2,6-bism eth oxy-4-p yr im -
id in yl)h yd r oxym et h yl]t et r a h yd r o-2H -1,3-oxa zin -2-on e
(12). To a suspension of 72 mg (0.22 mmol) of alcohol 11 were
added 163 mg (0.975 mmol) of 4-nitrobenzoic acid and 281 mg
(1.07 mol) of diethyl azodicarboxylate. The reaction mixture
immediately became homogeneous and was stirred at room
temperature for 21 h. The solvent was removed in vacuo, and
the residue was chromatographed over 50 g of silica gel (eluted
first with EtOAc-hexanes, 3:7, to separate residual triph-
enylphosphine, then with EtOAc-hexanes, 3:1) to provide 84
mg (80%) of the 4-nitrobenzoate of alcohol 12 as a white
foam: IR (KBr pellet) 3251, 3125, 2952, 2871, 1733, 1704,
(()-(4R*,6S*)-6-Bu tyl-4-[(2,6-m eth oxy-4-p yr im id in yl)-
m eth yl]tetr a h yd r o-2H-1,3-oxa zin -2-on e (10a ). To a solu-
tion of 1.52 g (4.92 mmol) of carbamate 9a in 165 mL of dry
THF at room temperature was added 297 mg (7.43 mmol) of
a 60% dispersion of NaH in mineral oil. The reaction mixture
was heated to reflux for 2 h, then cooled to room temperature,
and quenched by addition of 2.0 mL of saturated aqueous NH4-
Cl. The reaction mixture was then dried (MgSO4) and concen-
trated in vacuo. The residue was chromatographed over 40 g
of silica gel (eluted with EtOAc-hexanes, 1:1) to give 1.10 g
(72%) of 10a as a white solid: mp 108-110 °C; IR (KBr pellet)
3366, 3224, 3119, 2955, 2861, 1708 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.91 (t, J ) 7.1, 3H), 1.30-1.63 (m, 5H), 1.67-1.77
(m, 2H), 1.98-2.05 (m, 1H), 2.69 (dd, J ) 14.3, 8.9, 1H), 2.79
(dd, J ) 14.3, 4.0, 1H), 3.88-3.96 (m, 1H), 3.97 (s, 3H), 4.00
(s, 3H), 4.20-4.28 (m, 1H), 6.22 (br s, 2H); 13C NMR (75 MHz,
CDCl3) δ 13.5 (q), 22.0 (t), 26.3 (t), 32.8 (t), 34.4 (t), 42.4 (t),
49.4 (d), 53.4 (q), 54.4 (q), 76.4 (d), 100.7 (d), 154.2 (s), 164.9
(s), 167.2 (s), 171.6 (s); exact mass calcd for C15H23N3O4 m/z
309.1688, found m/z 309.1711.
1525, 1358 cm-1 1H NMR (300 MHz, CDCl3) δ 0.90 (t, J )
;
7.1, 3H), 1.37-1.71 (m, 7H), 1.96 (dd, J ) 13.5, 5.2, 1H), 3.98
(s, 3H), 4.01 (s, 3H), 4.21-4.31 (m, 2H), 5.73 (d, J ) 4.7 Hz,
1H), 5.87 (br s, 1H), 6.45 (s, 1H), 8.27 (d, J ) 9.1, 2H), 8.33 (d,
J ) 9.1, 2H); 13C NMR (75 MHz, CDCl3) δ 13.7 (q), 22.3 (t),
26.7 (t), 29.6 (t), 34.5 (t), 52.4 (d), 54.1 (q), 55.0 (q), 76.1 (d),
77.0 (d), 100.3 (d), 123.6 (d), 131.1 (d), 134.1 (s), 150.8 (s), 154.4
(s), 163.7 (s), 164.7 (s), 165.6 (s), 172.3 (s); exact mass calcd
for C22H26N4O8 m/z 474.1750, found m/z 474.1743.
To a suspension of 75 mg (0.158 mmol) of the aforemen-
tioned 4-nitrobenzoate in 3.0 mL of MeOH at room tempera-
ture was added 190 mg (1.37 mmol) of potassium carbonate.
The reaction mixture was stirred for 10 min and then filtered
through a short column of silica gel (eluted with EtOAc-
hexanes, 1:1) to provide 32 mg (62%) of alcohol 12 as a white
solid: mp 149-152 °C; IR (KBr pellet) 3271, 3092, 2955, 1688
cm-1; 1H NMR (300 MHz, CDCl3) δ 0.88 (t, J ) 7.0, 3H), 1.24-
1.78 (m, 8H), 3.63-3.70 (m, 1H), 3.97 (s, 3H), 3.98 (s, 3H),
4.14-4.17 (m, 1H), 4.31 (d, J ) 6.5, 1H), 4.32-4.48 (br s, 1H),
6.06 (br s, 1H), 6.45 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 13.8
(q), 22.4 (t), 26.7 (t), 29.5 (t), 34.7 (t), 54.1 (q), 54.9 (q), 55.0
(d), 75.1 (d), 76.6 (d), 99.4 (d), 154.8 (s), 165.2 (s), 169.0 (s),
172.3 (s); exact mass calcd for C15H23N3O5 m/z 325.1638, found
m/z 325.1621.
(()-(1R*,7R*,8a R*)-7-Bu tyl-1-(2,6-d im eth oxy-4-p yr im -
id in yl)tetr a h yd r o-3H,5H-oxa zolo[3,4-c][1,3]oxa zin e-3,5-
d ion e (13). To a solution of 56 mg (0.17 mmol) of alcohol 11
and 33 mg (0.22 mmol) of 1,1′-carbonyldiimidazole in 2.0 mL
of dry benzene at room temperature was added 5 mg (0.04
mmol) of 4-DMAP. The reaction mixture was heated to reflux
for 4 h. The solvent was removed under reduced pressure, and
the residue was chromatographed over 20 g of silica gel (eluted
with EtOAc-hexanes, 1:1) to give 34 mg (57%) of carbamate
13 as a colorless glass: IR (thin film) 2955, 2872, 1819, 1713
cm-1; 1H NMR (300 MHz, CDCl3) δ 0.87 (t, J ) 7.0, 3H), 1.11
(dd, J ) 13.8, 12.0, 1H), 1.25-1.56 (m, 6H), 2.18 (dt, J ) 13.8,
2.9, 1H), 3.96 (s, 3H), 3.99 (s, 3H), 4.39-4.42 (m, 1H), 4.74
(ddd, J ) 12.0, 8.1, 3.5, 1H), 5.43 (d, J ) 8.1, 1H), 6.42 (s, 1H);
13C NMR (75 MHz, CDCl3) δ 13.7 (q), 22.2 (t), 26.7 (t), 29.2 (t),
34.7 (t), 54.3 (q), 55.3 (q), 56.1 (d), 75.9 (d), 79.6 (d), 99.6 (d),
146.4 (s), 151.0 (s), 163.5 (s), 165.5 (s), 172.6 (s); exact mass
calcd for C16H21N3O6 m/z 351.1430, found m/z 351.1423.
(()-(4R*,6S*)-6-Bu tyl-4-[(2,6-bisben zyloxy-4-p yr im id i-
n yl)m eth yl]tetr a h yd r o-2H-1,3-oxa zin -2-on e (10b). To a
solution of 960 mg (2.72 mmol) of carbamate 9b in 70 mL of
dry THF at room temperature was added 125 mg (3.13 mmol)
of a 60% dispersion of NaH in mineral oil. The reaction mixture
was heated to reflux for 1.5 h, then cooled to room temperature,
and quenched by addition of 1.0 mL of saturated aqueous NH4-
Cl. The reaction mixture was then diluted with 30 mL of
EtOAc, dried (MgSO4), and concentrated in vacuo to give 882
mg (92%) of 10b as a white solid, mp 110-113 °C, which was
used without further purification: IR (KBr pellet) 3354, 3119,
3025, 2947, 2840, 1696 cm-1 1H NMR (200 MHz, CDCl3) δ
;
0.87-0.94 (m, 3H), 1.34-1.70 (m, 7H), 1.89-2.00 (m, 1H),
2.72-2.76 (m, 2H), 3.83-3.96 (m, 1H), 4.12-4.26 (m, 1H), 5.41
(s, 2H), 5.42 (s, 2H), 6.17 (br s, 1H), 6.28 (s, 1H), 7.33-7.50
(m, 10H); 13C NMR (75 MHz, CDCl3) δ 13.7 (q), 22.2 (t), 26.5
(t), 32.8 (t), 34.5 (t), 42.8 (t), 49.4 (d), 68.1 (t), 69.0 (t), 76.5 (d),
101.3 (d), 127.7 (d), 127.9 (d), 128.0 (d), 128.2 (d), 128.3 (d),
135.7 (s), 136.3 (s), 154.3 (s), 164.3 (s), 167.6 (s), 171.2 (s), one
carbon not observed; exact mass calcd for C27H31N3O4 m/z
416.2314, found m/z 461.2324.
(()-(4R*,6R*)-6-Bu tyl-4-[(R*)-(2,6-bism eth oxy-4-p yr im -
id in yl)h yd r oxym et h yl]t et r a h yd r o-2H -1,3-oxa zin -2-on e
(11). To a solution of 680 mg (2.20 mmol) of 10a in 20.0 mL of
dry THF at -70 °C was added 1.85 mL (4.63 mmol) of a 2.5 M
solution of n-BuLi in hexanes. The reaction mixture was
warmed to -40 °C for 1 h in an acetonitrile-dry ice bath. After
the reaction mixture was cooled to -70 °C, a solution of 863
mg (3.30 mmol) of (()-trans-2-(phenylsulfonyl)-3-phenylox-
aziridine16 in 7.0 mL of dry THF, precooled in a dry ice-
acetone bath, was added. After stirring for 75 min, the reaction
was quenched by addition of 1 mL of saturated aqueous
(()-(1R*,7S*,8a S*)-7-Bu t yl-1-(2,6-d im et h oxy-4-p yr im -
id in yl)tetr a h yd r o-3H,5H-oxa zolo[3,4-c][1,3]oxa zin e-3,5-
d ion e (14). To a solution of 57 mg (0.18 mmol) of alcohol 12
and 37 mg (0.23 mmol) of 1,1′-carbonyldiimidazole in 3.0 mL
of dry benzene at room temperature was added 5 mg (0.04
mmol) of 4-DMAP. The reaction mixture was heated to reflux