1
monitored by TLC and after the reaction was complete (0.5 h), it
was cautiously quenched by addition of saturated solution of NH4-
Cl (10 mL). It was then poured into water (20 mL) and extracted
with ether (3 × 25 mL). Combined ethereal extracts were washed
with brine (30 mL) and dried (Na2SO4). Evaporation of the solvent
and silica gel column chromatography of the residue using
petroleum ether/EtOAc (7:3) as eluent yielded 4 (1.86 g, 71%) as
a white solid: mp 74-76 °C; [R]D -70.8 (c 1.2, CHCl3); IR (KBr)
941, 837, 776, 702 cm-1; H NMR (400 MHz, CDCl3) δ 7.44-
7.23 (m, 5H), 4.96 (d, J ) 4.8 Hz, 1H), 4.36 (dd, J ) 7.5, 3.3 Hz,
1H), 4.25 (dd, J ) 7.5, 5.4 Hz, 1H), 4.15 (d, J ) 4.5 Hz, 1H), 3.41
(dd, J ) 4.5, 3.3 Hz, 1H), 3.04 (s, 1H), 2.84-2.71 (m, 4H), 2.08-
1.81 (m, 2H), 1.40 (s, 6H), 0.92 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 139.6 (C), 128.5 (CH), 128.0 (CH),
126.9 (CH), 109.6 (C), 80.3 (CH), 79.0 (CH), 74.5 (CH), 74.0 (CH),
52.8 (CH), 31.0 (CH2), 30.5 (CH2), 27.5 (CH3), 27.1 (CH3), 26.1
(CH2), 26.0 (CH3), 18.6 (C), -3.8 (CH3), -4.5 (CH3); HRMS for
C23H38O4S2Si + Na calcd 493.1881, found 493.1879.
1
2939, 2832, 1707, 1651, 1495, 1378, 1265, 1087 cm-1; H NMR
(300 MHz, CDCl3) δ 5.52 (d, J ) 5.7 Hz, 1H), 4.85 (d, J ) 5.7
Hz, 1H), 4.73 (s, 1H), 3.45-3.31 (m, 1H), 3.24-3.10 (m, 1H),
3.16 (s, 3H), 3.00 (s, 3H), 2.66-2.48 (m, 2H), 2.22-1.94 (m, 2H),
1.47 (s, 3H), 1.43 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 200.5
(C), 167.6 (C), 112.1 (C), 79.3 (CH), 76.1 (CH), 39.8 (CH), 36.8
(CH3), 35.8 (CH3), 26.1 (CH3), 25.8 (CH3), 24.9 (CH2), 24.7 (CH2);
HRMS for C13H21NO4S2 + Na calcd 342.0812, found 342.0810.
Anal. Calcd for C13H21NO4S2: C, 48.88; H, 6.63; N, 4.38; S, 20.08.
Found: C, 49.03; H, 6.55; N, 4.48; S, 20.19.
Preparation of (S)-2-(tert-Butyldimethylsilyloxy)-2-((4S,5R)-
5-((R)-(methoxymethoxy)(phenyl)methyl)-2,2-dimethyl-1,3-diox-
olan-4-yl)acetaldehyde (11). A solution of 10 (0.42 g, 0.8 mmol)
in acetonitrile (5.0 mL) was added dropwise over a period of 5
min to a solution of N-bromosuccinimide (0.85 g, 4.8 mmol) in
4:1 mixture of acetonitrile/water (10 mL) at room temperature. The
reaction mixture was stirred for 10 min at same temperature. After
the reaction was complete (TLC), saturated solution of sodium
sulfite (5 mL) was added to the reaction mixture and stirred for 5
min. The reaction mixture was then extracted with ether (3 × 15
mL), and the combined ethereal extracts were washed with 1 M
solution of aqueous sodium bicarbonate (15 mL), water (15 mL),
and brine (20 mL) and dried over Na2SO4. Evaporation of the
solvent and silica gel column chromatography of the residue with
petroleum ether/EtOAc (95:5) as eluent afforded aldehyde 11 (0.32
g, 94%) as colorless oil: [R]D -22.8 (c 1, CHCl3); IR (neat) 2934,
Preparation of ((4S,5S)-5-((R)-(1,3-Dithian-2-yl)(tert-butyldi-
methylsilyloxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)(phenyl)-
methanone (7). To a precooled (-10 °C) solution of the silyl ether
6 (0.8 g, 1.8 mmol) in dry THF (12 mL) was added a freshly
prepared THF solution of PhMgBr (4.5 mL of 0.5 M solution in
THF, 2.2 mmol) dropwise under argon atmosphere. The reaction
mixture was stirred for 0.5 h at the same temperature. It was then
cautiously quenched by addition of saturated NH4Cl (15 mL). The
reaction mixture was then extracted with ether (3 × 20 mL), and
the combined ethereal extracts were washed with brine (25 mL)
and dried (Na2SO4). Evaporation of the solvent and silica gel
column chromatography of the residue with petroleum ether/EtOAc
(95:5) as eluent afforded ketone 7 (0.83 g, 96%) as a white solid:
mp 68-69 °C; [R]D +21.6 (c 1.2, CHCl3); IR (KBr) 2931, 2690,
1597, 1451, 1371, 1257, 1057, 845, 778, 688 cm-1; 1H NMR (300
MHz, CDCl3) δ 8.08 (d, J ) 7.5 Hz, 2H), 7.63-7.42 (m, 3H),
5.24 (d, J ) 6.6 Hz, 1H), 4.83 (t, J ) 6.3 Hz, 1H), 4.32 (d, J ) 3.6
Hz, 1H), 4.00 (t, J ) 4.8 Hz, 1H), 2.92-2.67 (m, 4H), 2.07-1.98
(m, 1H), 1.93-1.75 (m, 1H), 1.52 (s, 3H), 1.32 (s, 3H), 0.90 (s,
9H), 0.19 (s, 3H), 0.11 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
197.4 (C), 135.7 (C), 133.4 (CH), 129.4 (CH), 128.4 (CH), 111.1
(C), 78.9 (CH), 78.3 (CH), 75.5 (CH), 51.8 (CH), 31.3 (CH2), 30.4
(CH2), 26.9 (CH3), 26.1 (CH2), 26.0 (CH3), 25.9 (CH3), 18.4 (C),
-4.2 (CH3), -4.4 (CH3); HRMS for C23H36O4S2Si + Na calcd
491.1724, found 491.1722. Anal. Calcd for C23H36O4S2Si: C, 58.93;
H, 7.74; S, 13.68. Found: C, 58.94; H, 7.61; S, 13.79.
Preparation of (R)-((4R,5S)-5-((R)-(1,3-Dithian-2-yl)(tert-bu-
tyldimethylsilyloxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)(phe-
nyl)methanol (9). To a precooled (0 °C) solution of 8 (0.6 g, 1.3
mmol) in dry THF (12 mL) were added triphenylphosphine (0.5 g,
1.9 mmol) and p-nitrobenzoic acid (0.3 g, 1.9 mmol) under argon
atmosphere and allowed to stir for 10 min. DIAD (0.3 mL, 0.3
mmol) was introduced in the reaction mixture over period of 15
min at the same temperature. The reaction mixture was warmed to
room temperature and stirred at room temperature for 2 h. After
the reaction was complete (TLC), solvent was removed under
reduced pressure and the crude ester thus obtained was purified by
column chromatography to yield the corresponding p-nitrobenzoate
ester (0.73 g, 92%) as pale yellow solid (for characterization, see
the Supporting Information).
2859, 1737, 1467, 1375, 1253, 1217, 1151, 1084, 922, 839 cm-1
;
1H NMR (400 MHz, CDCl3) δ 9.65 (s, 1H), 7.39-7.28 (m, 5H),
4.76 (d, J ) 6.1 Hz, 1H), 4.56 (s, 3H), 4.43 (dd, J ) 7.6, 2.0 Hz,
1H), 4.31 (dd, J ) 7.4, 6.3 Hz, 1H), 3.87 (d, J ) 1.3 Hz, 1H), 3.38
(s, 1H), 1.37 (s, 3H), 1.35 (s, 3H), 0.93 (s, 9H), 0.04 (s, 3H), 0.01
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 203.3 (C), 137.9 (C), 128.5
(CH), 128.3 (CH), 127.7 (CH), 110.3 (C), 94.1 (CH2), 79.8 (CH),
78.6 (CH), 78.1 (CH), 77.6 (CH), 56.0 (CH3), 27.2 (CH3), 26.7
(CH3), 25.8 (CH3), 18.2 (C), -4.5 (CH3), -5.1 (CH3); HRMS for
C22H36O6Si + Na calcd 447.2181, found 447.2179.
Preparation of ((1S)-2-Hydroxy-1-((4S,5R)-5-((R)-(meth-
oxymethoxy)(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-
pent-4-enyloxy)(tert-butyl)dimethylsilane (12 and 13). To a pre-
cooled (0 °C) solution of allylmagnesium bromide (0.5 M solution
in ether, 3 mL, 1.5 mmol) in dry ether (6.0 mL) was added a
solution of ZnCl2 (0.5 M solution in ether, 4 mL, 2 mmol) dropwise
under argon atmosphere. The reaction mixture was warmed to room
temperature and after stirring for 5 min at room temperature, it
was cooled to -78 °C and 11 (0.35 g, 0.82 mmol) in ether (3.0
mL) was added dropwise over period of 15 min. Progress of the
reaction was monitored by TLC and after the reaction was complete
(15 min), it was cautiously quenched by addition of saturated
solution of NH4Cl (5 mL) and poured in to water (10 mL). The
reaction mixture was then extracted with ether (3 × 15 mL) and
the combined ethereal extracts were washed with brine (20 mL)
and dried (Na2SO4). Evaporation of the solvent and silica gel
column chromatography of the residue with petroleum ether/EtOAc
(9:1) as eluent afforded an inseparable diastereomeric mixture (dr
80:20) of homoallylic alcohols 12 and 13 (0.34 g, 91%) as a
colorless oil: IR (neat) 3509, 2933, 1642, 1465, 1374, 1251, 1149,
1080 cm-1; H NMR (400 MHz, CDCl3) δ 7.44-7.26 (m, 5H),
1
5.93-5.76 (m, 1H), 5.20-5.09 (m, 2H), 4.81-4.75 (m, 1H), 4.65-
4.50 (m, 2H), 4.40-4.19 (m, 1H), 4.26-4.20 (m, 1H), 3.68-3.81
(m, 1H), 3.37 (S, 1H), 3.07 (d, J ) 5.9 Hz, 1H), 2.44-2.22 (m,
2H), 1.44-1.35 (m, 6H), 0.94-0.90 (m, 9H), 0.11-0.01 (m, 6H);
13C NMR (100 MHz, CDCl3) δ 137.8, 135.1, 135.0, 128.7, 128.4,
128.2, 128.18, 128.1, 127.8, 117.6, 117.4, 109.9, 79.8, 79.6, 78.4,
77.9, 77.8, 75.0, 74.4, 72.4, 55.9, 55.8, 38.7, 38.6, 27.4, 27.3, 27.0,
26.9, 26.2, 25.9, 18.5, 18.3, -3.9, -4.3, -4.4, -4.6; HRMS for
C25H42O6Si + Na calcd 489.2651, found 489.2648.
To a methanol (12 mL) solution of the p-nitrobenzoate ester (0.77
g, 1.24 mmol) obtained above was added K2CO3 (0.34 g, 2.5 mmol)
and the mixture stirred for 0.5 h at room temperature. After the
reaction was complete (TLC), the reaction mixture was poured in
to water (15 mL) and extracted with diethyl ether (3 × 20 mL).
Combined ethereal extracts were washed with brine (25 mL) and
dried over Na2SO4. Evaporation of the solvent and silica gel column
chromatography of the residue using petroleum ether/EtOAc (9:1)
as eluent afforded 9 (0.55 g, 94%) as a colorless oil: [R]D -13.2
(c 1, CHCl3); IR (neat) 3450, 2931, 1471, 1371, 1252, 1132, 1068,
Preparation of (4R,5S)-Dihydro-5-((4R,5R)-5-((R)-(meth-
oxymethoxy)(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-
2918 J. Org. Chem., Vol. 73, No. 7, 2008