purified by chromatography (SiO2, 1:4, EtOAc in hexanes) to
0 °C. The resulting slurry was stirred at 0 °C for 36 h, before
Na2SO3 (1 g) was added. The mixture was stirred for 30 min,
and then extracted with ethyl acetate (3 × 5 mL). The combined
organic layers were washed with saturated aqueous NaCl (15
mL), dried (Na2SO4), filtered, and concentrated. The residue was
purified by chromatography (SiO2, 1:8 to 1:3, EtOAc in hexanes)
to afford 6A (26 mg, 26%) and 6B (58 mg, 58%).
afford 3 (1.69 g, 91%) as a colorless oil; [R]25 +46.3 (c 2.01,
D
CHCl3) {lit.12 [R]20D +43.1 (c 1.65, CHCl3)}; 1H NMR (CDCl3 400
MHz) δ 5.25 (d, J ) 8.9 Hz, 1H), 4.95 (dd, J ) 6.7, 8.8 Hz, 1H),
4.22 (dd, J ) 6.7, 12.1 Hz, 1H), 3.57 (m, 2H), 1.78 (s, 3H), 1.73
(s, 3H), 1.51 (s, 3H), 1.40 (s, 3H); 13C NMR (CDCl3 100 MHZ) δ
139.5, 119.5, 108.6, 78.5, 74.2, 62.7, 28.4, 26.4, 25.7, 18.8.
(4R,5S)-4-(Ben zyloxym eth yl)-2,2-d im eth yl-5-(2-m eth yl-
p r op -1-en yl)-1,3-d ioxola n e (4). Sodium hydride (60% in min-
eral oil, 80 mg, 2.0 mmol) was added to a solution of 3 (186 mg,
1.0 mmol) in THF (10 mL) at 25 °C. The suspension was stirred
at 25 °C for 20 min before benzyl bromide (300 mg, 1.75 mmol)
was added. The resulting mixture was stirred for 12 h before
the addition of water (20 mL). The heterogeneous solution was
extracted with EtOAc (3 × 20 mL) and the combined organic
layers were dried (Na2SO4), filtered, and concentrated. The
residue was purified by chromatography (SiO2, 1:20, EtOAc in
hexanes) to afford 4 (263 mg, 95%) as a colorless oil; [R]25D +34.5
(c 3.30, CH2Cl2); 1H NMR (CDCl3 400 MHz) δ 7.33 (m, 5H), 5.20
(d, J ) 9.2 Hz, 1H), 4.92 (dd, J ) 5.5, 9.2 Hz, 1H), 4.61 (d, J )
12.4 Hz, 1H), 4.53 (d, J ) 12.4 Hz, 1H), 4.35 (dd, J ) 6.1, 9.1
Hz, 1H), 3.50 (m, 2H), 1.76 (s, 3H), 1.70 (s, 3H), 1.50 (s, 3H),
1.40 (s, 3H); 13C NMR (CDCl3 100 MHZ) δ 138.6, 138.5, 128.7
(2C), 128.1 (2C), 128.0, 120.2, 108.7, 77.3, 74.4, 73.8, 70.1, 28.5,
26.5, 25.9, 18.6; IR (film) νmax 2980, 2929, 2909, 2852, 1454, 1372,
1244, 1214, 1070, 1050, 1024, 737 cm-1; HRMS (ESI+) m/z
294.2067 (M + NH4+, C17H28NO3 requires 294.2069).
(S)-1-((4R,5R)-5-(Ben zyloxym eth yl)-2,2-d im eth yl-1,3-d i-
oxola n -4-yl)-1-m eth oxy-2-m eth ylp r op a n -2-ol (8). Potassium
tert-butoxide (28 mg, 0.25 mmol) was added to a solution of 6A
(68 mg, 0.21 mmol) in anhydrous THF (4 mL) at 25 °C under
argon. The mixture was stirred for 20 min before addition of
iodomethane (15 µL, 35 mg, 0.25 mmol). The resulting mixture
was stirred for 10 h at 25 °C before water (10 mL) was added.
The heterogeneous solution was extracted with EtOAc (3 × 10
mL), and the combined organic layers were dried (Na2SO4),
filtered, and concentrated. The residue was purified by chro-
matography (SiO2, 1:4, EtOAc in hexanes) to afford 6A (9 mg)
and 8 (51 mg, 86%); [R]25 +15.1 (c 1.03, CH2Cl2); 1H NMR
D
(CDCl3 400 MHz) δ 7.35 (m, 5H), 4.61 (d, J ) 7.6 Hz, 1H), 4.53
(d, J ) 7.6 Hz, 1H), 4.37 (m, 2H), 3.66 (app t, J ) 8.5 Hz, 1H),
3.51 (s, 3H), 3.45 (dd, J ) 3.5, 9.3 Hz, 1H), 3.19 (m, 2H), 1.42 (s,
3H), 1.38 (s, 3H), 1.16 (s, 3H), 1.14 (s, 3H); 13C NMR (CDCl3
100 MHz) δ 137.1, 129.0 (2C), 128.7, 128.6 (2C), 107.6, 85.0, 78.0,
76.2, 74.2, 72.3, 69.4, 61.8, 29.3, 28.6, 25.9, 23.3; IR (film) νmax
3472, 2970, 2929, 2873, 2822, 1454, 1383, 1250, 1214, 1147,
1127, 1091, 1060, 737, 702 cm-1; HRMS (ESI+) m/z 342.2282
(M + NH4+, C18H32NO5 requires 342.2280).
(S)-1-((4S,5R)-5-(Ben zyloxym eth yl)-2,2-d im eth yl-1,3-d i-
oxola n -4-yl)-2-m eth ylp r op a n e-1,2-d iol (6A) a n d (R)-1-((4S,-
5R)-5-(Ben zyloxym eth yl)-2,2-d im eth yl-1,3-d ioxola n -4-yl)-
2-m eth ylp r op a n e-1,2-d iol (6B). Osmium tetraoxide (10 mg/
mL in toluene, 0.1 mL) was added to a solution of olefin 4 (62
mg, 0.22 mmol) in acetone (1 mL) and H2O (1 mL). The mixture
was stirred at 25 °C for 15 min before addition of 4-methylmor-
pholine N-oxide (59 mg, 0.9 mmol). The resulting solution was
stirred at 25 °C until TLC showed the consumption of 4 (∼8 h).
Water (10 mL) was added and the mixture was extracted with
EtOAc (3 × 10 mL). The combined organic layers were washed
with saturated aqueous NaCl (20 mL), dried (Na2SO4), filtered,
and concentrated. The residue was purified by chromatography
(SiO2, 1:8 to 1:3, EtOAc in hexanes) to afford 6B (20 mg) as a
higher Rf compound and 6A (38 mg) as a lower Rf compound
(S)-1-((4R,5R)-5-(Hyd r oxym eth yl)-2,2-d im eth yl-1,3-d iox-
ola n -4-yl)-1-m eth oxy-2-m eth ylp r op a n -2-ol (9). Palladium on
charcoal (10%, 20 mg) was added to a solution of 8 (173 mg,
0.53 mmol) in EtOAc (2 mL). The mixture was stirred under
hydrogen (1 atm) at 25 °C for 12 h, diluted with EtOAc (10 mL),
and filtered through a plug of Celite. The filtrate was concen-
trated and the residue purified by chromatography (SiO2, 1:1,
EtOAc in hexanes) to afford 9 (120 mg, 96%) as a colorless oil;
[R]25 +51.5 (c 2.12, CH2Cl2); 1H NMR (CDCl3 400 MHz) δ 4.36
D
(dd, J ) 5.3, 8.1 Hz, 1H), 4.21 (ap. q, J ) 5.2 Hz, 1H), 3.75 (dt,
J ) 4.8, 10.8 Hz, 1H), 3.62 (m, 1H), 3.59 (t, 3H), 3.24 (d, J ) 8.0
Hz, 1H), 3.20 (br t, J ) 5.0 Hz, 1H), 3.06 (s, 1H), 1.47 (s, 3H),
1.39 (s, 3H), 1.30 (s, 3H), 1.24 (s, 3H); 13C NMR (CDCl3 100 MHz)
δ 107.8, 84.5, 78.1, 77.6, 73.1, 62.1, 62.0, 28.9, 28.5, 25.9, 24.7;
IR (film) νmax 3390, 2980, 2924, 1460, 1372, 1244, 1214, 1157,
1122, 1091, 1045, 927, 876 cm-1; HRMS (ESI+) m/z 252.1811
(M + NH4+, C11H26NO5 requires 252.1811).
(84% total yield). 6B: [R]25 -0.1 (c 0.97, CH2Cl2); 1H NMR
D
(CDCl3 400 MHz) δ 7.36 (m, 5H), 4.59 (s, 2H), 4.40 (ddd, J )
3.5, 5.3, 9.3 Hz, 1H), 4.25 (dd, J ) 5.4, 9.6 Hz, 1H), 3.83 (d, J )
4.0 Hz, 1H), 3.72 (app t, J ) 9.6 Hz, 1H), 3.51 (m, 2H), 3.16 (s,
1H), 1.39 (s, 3H), 1.36 (s, 3H), 1.28 (s, 3H), 1.26 (s, 3H); 13C NMR
(CDCl3 100 MHz) δ 136.9, 129.1 (2C), 128.8, 128.5 (2C), 109.7,
78.1, 76.3, 74.4, 73.9, 72.8, 69.0, 28.4, 26.0, 25.7, 25.5; IR (film)
(3a S,7S,7a S)-7-Meth oxy-2,2,6,6-tetr am eth yldih ydr o-3a H-
[1,3]d ioxolo[4,5-c]p yr a n -4(6H)-on e (10). Pyridinium chloro-
chromate (151 mg, 0.7 mmol) was added to a solution of 9 (53
mg, 0.23 mmol) in CH2Cl2 (2 mL) at 25 °C. The mixture was
stirred at 25 °C for 8 h and filtered through a plug of silica gel
(3 × 0.5 cm) and eluted with CH2Cl2. The eluent was concen-
νmax 3462, 2980, 2929, 2868, 1455, 1373, 1219, 1163, 1075, 958,
+
850, 732, 691 cm-1; HRMS (ESI+) m/z 328.2097 (M + NH4
,
trated to afford 10 (43 mg, 82%) as white solid; [R]25 +40.3 (c
C
17H30NO5 requires 328.2124).
D
6A: [R]25 -38.5 (c 0.28, CH2Cl2); 1H NMR (CDCl3 400 MHz)
1
0.6, CH2Cl2); H NMR (CDCl3 400 MHz) δ 4.75 (d, J ) 8.4 Hz,
D
δ 7.33 (m, 5H), 4.63 (d, J ) 9.0 Hz, 1H), 4.57 (d, J ) 9.0 Hz,
1H), 4.42 (m, 2H), 3.80 (d, J ) 5.5 Hz, 2H), 3.40 (dd, J ) 1.3,
8.4 Hz, 1H), 2.83 (d, J ) 8.4 Hz, 1H), 2.71 (s, 1H), 1.51 (s, 3H),
1.39 (s, 3H), 1.24 (s, 3H), 1.12 (s, 3H); 13C NMR (CDCl3 100 MHz)
δ 138.0, 128.9 (2C), 128.4 (2C), 128.3, 109.0, 76.8, 76.0, 74.1,
74.0, 73.4, 69.5, 27.4, 27.3, 26.0, 25.1; IR (film) νmax 3482, 2986,
2934, 2868, 1454, 1373, 1219, 1091, 743, 697 cm-1; HRMS (ESI+)
m/z 328.2100 (M + NH4+, C17H30NO5 requires 328.2124).
Oxid a tion of 4 w ith AD-m ix-r. 4 (676 mg, 2.45 mmol) in
t-BuOH (24 mL) was added to a mixture of AD-mix R (4.2 g)
and methanesulfonamide (285 mg, 3 mmol) in H2O (24 mL) at
0 °C. The resulting slurry was stirred at 0 °C for 48 h, before
Na2SO3 (10 g) was added. The mixture was stirred for 15 min,
and then extracted with ethyl acetate (3 × 50 mL). The combined
organic layers were washed with saturated aqueous NaCl (100
mL), dried (Na2SO4), filtered, and concentrated. The residue was
purified by chromatography (SiO2, 1:8 to 1:3, EtOAc in hexanes)
to afford 6A (353 mg, 46%) and 6B (312 mg, 41%).
1H), 4.49 (dd, J ) 6.0, 8.4 Hz, 1H), 3.57 (s, 3H), 3.26 (d, J ) 6.0
Hz, 1H), 1.52 (s, 3H), 1.47 (s, 3H), 1.42 (s, 3H), 1.36 (s, 3H); 13
C
NMR (CDCl3 100 MHz) δ 169.3, 111.7, 84.9, 82.5, 77.8, 72.0,
59.4, 27.8, 27.0, 25.3, 22.5; IR (film) νmax 2991, 2939, 2914, 2873,
1741, 1465, 1383, 1352, 1260, 1214, 1137, 1065, 1060, 1024, 973,
876 cm-1; HRMS (ESI+) m/z 248.1497 (M + NH4+, C11H22NO5
requires 248.1498).
(3a S,7S,7a S)-7-Meth oxy-2,2,6,6-tetr a m eth yltetr a h yd r o-
3a H-[1,3]d ioxolo[4,5-c]p yr a n -4-ol (11). A solution of diisobu-
tylaluminum hydride (1 M in hexane, 180 µL, 0.18 mmol) was
added dropwise to a solution of 10 (35 mg, 0.15 mmol) in
anhydrous CH2Cl2 (2 mL) at -78 °C. The mixture was stirred
for 30 min at -78 °C before addition of saturated potassium
sodium tartrate aqueous solution (3 mL). The mixture was
warmed to 25 °C and stirred until layers separated (∼1 h). The
aqueous phase was extracted with CH2Cl2 (3 × 5 mL), and the
combined organic layers were dried (Na2SO4), filtered, and
concentrated. The residue was purified by chromatography
(SiO2, 1:1, EtOAc in hexane) to give 11 (31 mg, 89%) as a 3:1
mixture of anomers; [R]25D -1.6 (c 0.7, CH2Cl2); 1H NMR (CDCl3
400 MHz) δ 5.12 (d, J ) 4.0 Hz, major 1H), 5.11 (d, J ) 2.7 Hz,
Oxid a t ion of 4 w it h AD-m ix-â. 4 (90 mg, 0.32 mmol) in
t-BuOH (3 mL) was added to a mixture of AD-mix â (500 mg)
and methanesulfonamide (30 mg, 0.31 mmol) in H2O (3 mL) at
J . Org. Chem, Vol. 69, No. 21, 2004 7377