3808 J . Org. Chem., Vol. 67, No. 11, 2002
Wu et al.
amount of DMAP (20 mg) in dry CH2Cl2 (23 mL) was stirred
at ambient temperature for 24 h. The reaction mixture was
then diluted with diethyl ether (50 mL), washed with water
and brine, and dried over Na2SO4. The drying agent was
filtered off, and solvents were removed on a rotary evaporator
to give an oily residue, which was subjected to column
chromatography (eluting with 1:4 EtOAc/hexanes) to yield the
monotosylate (R,R)-8 as a colorless oil (650 mg, 84.3%, along
(3S,4S)-4-Hyd r oxy-3-m eth yld eca n en itr ile ((S,S)-9). The
procedure was the same as that for preparing (R,R)-9: yield
1
89.0%; [R]26 -8.79 (c 1.03, CHCl3); H NMR δ 3.66 (m, 1H),
D
2.49 (dd, J ) 6.9, 16.8 Hz, 1H), 2.31 (dd, J ) 7.4, 16.8 Hz,
1H), 1.95 (m, 1H), 1.69 (br d, J ) 4.9 Hz, 1H, OH), 1.50-1.20
(m, 10H), 1.03 (d, J ) 6.9 Hz, 3H), 0.88 (t, J ) 6.7 Hz, 3H); IR
(film) 3352, 2249 cm-1; MS m/z 184 (M + 1, 7), 166 (61), 115
(9), 97 (58), 69 (65), 55 (100); HRMS calcd for C11H21NO
183.1623, found 183.1593.
with 52 mg of unreacted diol): [R]19 +1.55 (c 3.89, CHCl3);
D
1H NMR δ 7.81 (d, J ) 8.2 Hz, 2H), 7.36 (d, J ) 8.2 Hz, 2H),
4.09 (dd, J ) 8.0, 9.6 Hz, 1H), 3.90 (dd, J ) 6.1, 9.6 Hz, 1H),
3.70 (m, 1H), 2.46 (s, 3H), 1.91 (m, 1H), 1.55-1.20 (m, 10H),
0.91 (t, J ) 6.0 Hz, 3H), 0.89 (d, J ) 7.5 Hz, 3H); IR (film)
3554, 1599, 1466, 1359, 1189 cm-1; MS m/z 287 (M+ - 41, 3.4),
243 (1.1), 216 (3.2), 173 (100), 155 (17.5), 139 (6.7), 115 (8.1),
97 (15), 91 (40).
(4S,5S)-5-Hexyl-4-m eth yld ih yd r ofu r a n -2-on e ((S,S)-1).
The procedure was the same as that for preparing (R,R)-1:
yield 82.9% (from (S,S)-9); [R]26 -56.1 (c 3.56, CHCl3) (lit.8
D
[R]23 -57.6 (c 1.06, CHCl3)); 1H NMR δ 4.45 (br quintet, J ≈
D
4.8 Hz, 1H), 2.70 (dd, J ) 7.8, 17.0 Hz, 1H), 2.60 (m, 1H), 2.20
(dd, J ) 3.7, 17 Hz, 1H), 1.75-1.20 (m, 10H), 1.02 (d, J ) 6.9
Hz, 3H), 0.90 (t, J ) 6.6 Hz, 3H); IR (film) 1774 cm-1; MS m/z
185 (M + 1, 2), 142 (6), 124 (7), 115 (9), 99 (100).
(3R,4R)-4-H yd r oxy-3-m et h yld eca n en it r ile ((R,R)-9).
NaCN (980 mg, 10 mol equiv) was added to a solution of the
tosylate (R,R)-8 (560 mg, 1.7 mmol) in DMSO (5.0 mL)
containing a catalytic amount of NaI (26 mg). The mixture
was stirred at 60 °C overnight before being diluted with water
and extracted with diethyl ether (3 × 50 mL). The combined
ethereal phases were washed with brine and dried over Na2-
SO4. The drying agent was filtered off, and solvents were
removed on a rotary evaporator to give the nitrile (R,R)-9 as
a colorless oil (280 mg, 89.6%): 1H NMR δ 3.63 (m, 1H), 2.49
(dd, J ) 6.9, 16.8 Hz, 1H), 2.31 (dd, J ) 7.7, 16.7 Hz, 1H),
1.96 (m, 1H), 1.65 (br d, J ) 4.7 Hz, OH), 1.50-1.20 (m, 10H),
1.04 (d, J ) 6.6 Hz, 3H), 0.89 (t, J ) 6.8 Hz, 3H); IR (film)
3457, 2251 cm-1; MS m/z 166 (M+ - 17, 5.9), 115 (13), 97 (73),
(2S)-4-Ben zyl-3-((2S,3R)-3-h yd r oxy-2-m eth ylocta n oyl)-
oxa zolid in -2-on e (14). The procedure was the same as that
for preparing 6a : yield 74.5%; [R]14 +51.6 (c 1.8, CHCl3); 1H
D
NMR δ 7.40-7.20 (m, 5H), 4.72 (m, 1H), 4.28-4.18 (m, 2H),
3.96 (m, 1H), 3.78 (dq, J ) 1.9, 7.1 Hz, 1H), 3.27 (dd, J ) 3.3,
13.5 Hz, 1H), 2.85 (br s, 1H, OH), 2.80 (dd, J ) 9.3, 13.5 Hz,
1H), 1.60-1.20 (m, 8H), 1.27 (d, J ) 7.1 Hz, 3H), 0.90 (t, J )
6.5 Hz, 3H); IR (film) 3523, 1782 cm-1; MS m/z 333 (M+, 0.9),
316 (3), 289 (0.5), 262 (1), 244 (14), 233 (17), 200 (6), 178 (16),
157 (3), 142 (23), 134 (11.5), 117 (17), 91 (48), 57 (100); HRMS
calcd for C19H25NO3 (M+ - H2O) 315.1834, found 315.1833.
(2S)-4-Ben zyl-3-[(2S,3R)-3-(t er t -b u t ylca r b on yloxy)-2-
m eth ylocta n oyl]oxa zolid in -2-on e (17). To a solution of 14
(666 mg, 2.0 mmol) in dry CH2Cl2 (10 mL) were added a
catalytic amount of 4-(dimethylamino)pyridine (DMAP, ca. 20
mg), NEt3 (1.0 mL, 7.0 mmol), and, with cooling (ice-water
bath), pivaloyl chloride (0.5 mL, 4.0 mmol). The mixture was
stirred at ambient temperature (ca. 8 °C) for 48 h before being
diluted with ether, washed with water and brine, and dried
over anhydrous Na2SO4. The oily residue after removal of
drying agent and solvents was chromatographed (eluting with
1:8 EtOAc/hexanes) to give 17 as a colorless oil (800 mg, 95.9
69 (77), 55 (100); [R]19 +9.4 (c 0.72, CHCl3); HRMS calcd for
D
C
11H21NO 186.1623, found 186.1631.
(4R,5R)-5-Hexyl-4-m eth yld ih yd r ofu r a n -2-on e ((R,R)-1).
The crude nitrile (R,R)-9 (130 mg, 0.71 mmol) from the above
step (without chromatographic purification) was directly dis-
solved in EtOH (5.0 mL) and treated with 2 N NaOH (1 mL)
at reflux for 8 h. Solvents were removed on a rotary evaporator.
To the residue were added THF (10 mL) and (with cooling on
ice-water bath) aqueous H2SO4 (0.73 M, ca. 2 mL) until
pH ) 1-2. The mixture was stirred at ambient temperature
(10 °C) overnight before being diluted with diethyl ether,
washed with aqueous NaHCO3, water, and brine, and dried
over Na2SO4. After removal of the drying agent and solvents,
column chromatography of the residue on silica gel (eluting
with 1:4 EtOAc/hexanes) gave (R,R)-1 as a fragrant colorless
oil (110 mg, 84.1% over two steps): [R]12D +56.7 (c 2.47, CHCl3)
yield): [R]14 +40.1 (c 4.78, CHCl3); 1H NMR δ 7.40-7.18 (m,
D
5H), 5.24 (m, 1H), 4.67 (t, J ) 10.3 Hz, 0.6H), 4.51 (m, 0.4H),
4.40 (dd, J ) 4.2, 11.0 Hz, 0.6H), 4.30 (t, J ) 8.8 Hz, 0.4H),
4.15 (dd, J ) 2.2, 8.8 Hz, 0.4H), 3.95 (dq, J ) 3.3, 7.1 Hz, 0.4H),
3.82-3.60 (lump, 0.6H), 3.25-3.16 (m, 1H), 3.06 (dd, J ) 14,
6.3 Hz, 0.6H), 2.77 (dd, J ) 13, 9.8 Hz, 0.4H), 2.58-2.48 (lump,
0.6H), 1.78-1.10 (m, including several s, 17H altogether), 1.02
(d, J ) 7.4 Hz, 3H), 0.89 (t, J ) 7.0 Hz, 3H); IR (film) 1776,
1703 cm-1; MS m/z 417 (M+, 1.6), 316 (21.3), 315 (23.5), 244
(26.2), 241 (14.7), 218 (24.6), 200 (43.7), 178 (14.5), 139 (77.4),
(lit.8 [R]22 +59.8 (c 0.40, CHCl3)); 1H NMR δ 4.42 (m, 1H),
D
2.63 (dd, J ) 7.8, 16.8 Hz, 1H), 2.56 (m, 1H), 2.16 (dd, J )
3.7, 16.8 Hz, 1H), 1.70-1.20 (m, 10H), 0.98 (d, J ) 7.1 Hz,
3H), 0.86 (t, J ) 6.8 Hz, 3H); IR (film) 1779 cm-1; MS m/z 142
(M+ - 42, 14), 105 (10), 92 (28), 91 (40), 86 (23), 83 (15), 69
(28), 57 (100).
117 (28.0), 91 (27.5), 85 (42.4), 57 (100); HRMS calcd for C24H35
NO5 417.2515, found 417.2502.
-
(2R,3R)-3-(ter t-Bu t ylca r b on yloxy)-2-m et h yloct a n -1-
ol (18). To a solution of 17 (660 mg, 1.58 mmol) in a 1:2 (v/v)
mixture of THF and EtOH (10 mL) containing CaCl2 (10 mmol)
was added NaBH4 (308 mg, 6.32 mmol). The mixture was
stirred at ambient temperature (1-4 °C) overnight. When TLC
showed the disappearance of the starting 17, the excess
hydride was destroyed with dilute HCl and the reaction
mixture was extracted with ether three times. The combined
ethereal phases were washed with water and brine and then
dried over anhydrous Na2SO4. The oily residue after removal
of drying agent and solvents was chromatographed (eluting
with 1:5 EtOAc/hexanes) to afford 18 as a colorless oil (110
mg, 28.5% yield): [R]14D +16.7 (c 1.07, CHCl3); 1H NMR δ 5.09
(m, 1H), 3.44 (m, 1H), 2.96 (m, 1H), 1.88 (m, 1H), 1.72 (m,
1H), 1.55-1.20 (m, 8H), 1.22 (s, 9H), 0.89 (t, J ) 6.4 Hz, 3H),
0.82 (d, J ) 6.9 Hz, 3H); IR (film) 3445, 1735 cm-1; MS m/z
227 (M+ - 17, 79.8), 177 (3.9), 159 (1.9), 143 (40.7), 125 (61.3),
103 (34.3), 85 (43.0), 57 (100); HRMS calcd for C14H27O2
(M+ - 17) 227.2011, found 227.2040.
(2R)-4-P h en yl-3-((2R,3S)-3-h yd r oxy-2-m et h yln on a n o-
yl)oxa zolid in -2-on e (11). The procedure was the same as
that for preparing 6a , except with 10 in place of 4a : yield
79.3%; [R]14 -70.6 (c 0.89, CHCl3); 1H NMR δ 7.40-7.20 (m,
D
5H), 5.46 (dd, J ) 4.0, 8.7 Hz, 1H), 4.72 (t, J ) 8.8 Hz, 1H),
4.27 (dd, J ) 4.0, 8.9 Hz, 1H), 3.94 (m, 1H), 3.82 (m, 1H), 2.77
(br s, 1H), 1.65-1.20 (m, 10H), 1.17 (d, J ) 7.1 Hz, 3H), 0.89
(br t, J ) 6.8 Hz, 3H); IR (film) 3533, 1783, 1698 cm-1; MS
m/z 334 (M + 1), 316 (49), 219 (47), 164 (62), 120 (49), 104
(100); HRMS calcd for C19H26NO3 (M - 17) 316.1913, found
316.1921.
(2S,3S)-3-Hyd r oxy-2-m eth yln on a n yl Tosyla te ((S,S)-8).
The reduction of 11 (79.7% yield) followed the same procedure
for that of 6a , and tosylation of (S,S)-7 used the same
procedure as that for preparing (R,R)-8: yield 79.9%; [R]13
)
D
-2.0 (c 3.75, CHCl3); 1H NMR δ 7.81 (d, J ) 8.1 Hz, 2H), 7.36
(d, J ) 8.1 Hz, 2H), 4.09 (dd, J ) 7.7, 9.6 Hz, 1H), 3.90 (dd,
J ) 6.0, 9.6 Hz, 1H), 3.70 (m, 1H), 2.46 (s, 3H), 1.90 (m, 1H),
1.55-1.20 (m, 10H), 0.89 (t, J ) 6.0 Hz, 3H), 0.86 (d, J ) 6.9
Hz, 3H); IR (film) 3351, 1598, 1494, 1357, 1176 cm-1; MS m/z
287 (M+ - 41, 4.3), 243 (1.5), 216 (3.6), 173 (100), 155 (22.6),
139 (18.3), 115 (7.9), 97 (17.4), 91 (43.7).
(2S)-4-Ben zyl-3-[(2S,3R)-3-(ter t-bu tyld im eth ylsila n yl-
oxy)-2-m eth ylocta n oyl]oxa zolid in -2-on e (19). With cooling
(ice-water bath) and stirring, TBSOTf (1.7 mL, ca. 7.4 mmol)
was added to a mixture of 14 (950 mg, 2.8 mmol) and 2,6-
lutidine (1.4 mL, 12 mmol) in dry CH2Cl2 (30 mL). The bath