2
836
C. Song et al. / Tetrahedron: Asymmetry 14 (2003) 2833–2838
−
1
1
.3. Methyl (3R,4R,5R,6R)-5,6-dihydroxy-3,4-isopropyl-
(KBr)/cm 3521, 3444, 2954, 2927, 2894, 2856, 1716,
165, 1276, 1251, 1209, 1126, 1051; lH (270 MHz) 0.12
(3 H, s), 0.16 (3 H, s), 0.93 (9 H, s), 1.38 (3 H, s), 1.45
(3 H, s), 2.85 (1 H, d, J 2.0), 3.77 (1 H, dd, J 7.3, 3.3),
idenedioxycyclohex-1-ene-1-carboxylate 9 and methyl
(
1S,2R,3S,4S)-1,2-dihydroxy-3,4-isopropylidenedioxycy-
clohex-5-ene-1-carboxylate 10
3
.81 (3 H, s), 4.32 (1 H, t, J 7.3), 4.54 (1 H, dd, J 3.3,
To a solution of diene 8 (2.92 g, 13.88 mmol) in
tert-butanol (18 ml) and water (2 ml) at 0°C were
added N-methylmorpholine N-oxide (1.95 g, 16.65
mmol) and osmium tetroxide (100 mg, 0.39 mmol). The
mixture was stirred at 0°C for 8 h. Aqueous sodium
thiosulfate was added, the mixture was stirred at room
temperature for 30 min and then filtered through Celite.
The filtrate was diluted with water (30 ml) and
extracted with ethyl acetate (3×80 ml). The organic
phases were combined and dried (Na SO ). Concentra-
2.0), 4.84 (1 H, dd, J 7.3, 3.3), 7.03 (1 H, d, J 3.3); l
C
(67.8 MHz) (4.94, (4.51, 18.02, 25.23, 25.75, 27.59,
52.24, 66.36, 72.52, 73.12, 75.84, 109.57, 131.99, 137.48,
+
165.94; m/z HRMS (CI, NH
). Found: MH 359.1894,
3
C H O Si requires 359.1890. Microanalysis: Found:
17 31
6
C, 57.06; H, 8.51. C H O Si requires C, 56.95; H,
17 30
6
8
.43%).
1
.5. Methyl (3R,4R,5S,6S)-5-tert-Butyldimethylsilyl-
oxy-6-fluoro-3,4-isopropylidenedioxycyclohex-1-ene-1-
2
4
carboxylate 12
tion under reduced pressure followed by column chro-
matography of the residue using petrol–ethyl acetate
N,N-Diethylaminosulfur trifluoride (1.80 ml, 13.59
(
2:3) as eluent afforded the diol 9 (1.29 g, 38%) and diol
mmol) was added to a solution of the monosilyl ether
the 10 (1.18 g, 35%) as colourless solids. Both diols
were recrystallised (separately) from petrol–diethyl
ether and gave colourless crystals. Data for 9: m.p.
1
1 (590 mg, 1.65 mmol) in dichloromethane (25 ml).
The reaction mixture was stirred at room temperature
for 4 h, then quenched with water (50 ml). The aqueous
phase was extracted with dichloromethane (3×50 ml).
The combined organic extracts were dried (Na SO )
−
1
9
3
1
7–99°C; [h] =−31.3 (c 0.80, CHCl ); w
(KBr)/cm
D
3
max
436, 2987, 2940, 2917, 1716, 1656, 1434, 1380, 1268,
205, 1162, 1041; lH (270 MHz) 1.40 (3 H, s), 1.43 (3
2
4
and concentrated under reduced pressure. Chromatog-
raphy on silica gel with petrol–diethyl ether (5:1) as
eluent yielded the title compound 12 (547.2 mg, 92%) as
a colourless oil, [a] =+41.1 (c 1.22, CHCl ); w
H, s), 3.55–3.62 (1 H, br s), 3.81 (3 H, s), 3.93–3.98 (1
H, m), 4.10–4.14 (1 H, br s), 4.45 (1 H, t, J 6.6), 4.68 (1
H, br s), 4.83 (1 H, dd, J 5.9, 3.3), 6.95 (1 H, d, J 3.3);
lC (67.8 MHz) 25.42 (Me), 27.59, 52.25, 65.22, 70.69,
D
3
max
−1
(
film)/cm 2954, 2931, 2857, 1731, 1664, 1463, 1371,
7
1.91, 75.17, 109.85, 131.30, 136.85, 166.54; m/z HRMS
+
3 4 11 20 6
1249, 1108, 1072, 840; l
H
(270 MHz) 0.13 (6 H, s), 0.86
(CI, NH ), Found: MNH 262.1288, C H NO
(
9 H, s), 1.40 (6 H, s), 3.84 (3 H, s), 4.24 (1 H, t, J 4.6),
requires 262.1291. Microanalysis: Found: C, 54.07; H,
4
4
2
.37–4.45 (1 H), 4.68–4.74 (1 H, m), 5.15 (1 H, d, JFH
.67. C H O requires C, 54.09; H, 6.60%. Data for
11 16 6
6.2), 6.95–7.02 (1 H, m); l (67.8 MHz) −5.08, 17.90,
C
D
3
max
5.54, 26.35, 27.86, 52.27, 68.89 (d, JFC 25.96), 71.15 (d,
−1
JFC 2.08), 74.62 (d, JFC 2.08), 84.42 (d, JFC 174.46),
1
440, 1380, 1245, 1137, 1035; l (270 MHz) 1.41 (3 H,
H
1
1
3
11.08, 127.06 (d, JFC 17.65), 139.50 (d, JFC 6.23),
s), 1.53 (3 H, s), 3.24 (1 H, d, J 6.6), 3.84 (3 H, s),
+
65.59 m/z HRMS (CI, NH3), Found: MNH4
3
6
.95–4.05 (1 H, m), 4.03 (1 H, s), 4.33 (1 H, dd, J 9.2,
.6), 4.73–4.77 (1 H, m), 5.89 (1 H, d, J 9.9), 6.11 (1 H,
78.2109, C H FNO Si requires 378.2112.
17
33
5
dd, J 9.9, 4.0); lC (67.8 MHz) 25.32, 27.68, 53.33,
1
.6. (3R,4R,5S,6S)-5-tert-Butyldimethylsilyloxy-6-
7
1
2
2.35, 72.88, 74.56, 76.14, 109.97, 127.98, 129.41,
73.99; m/z HRMS (CI, NH3). Found: MNH4
fluoro-3,4-isopropylidenedioxycyclohex-1-ene-1-car-
+
boxylic acid 13
62.1289, C H NO requires 262.1291. Microanalysis:
1
1
20
6
Found: C, 54.06; H, 6.67. C H O requires C, 54.09;
H, 6.60%.
1
1
16
6
Lithium hydroxide (127 mg, 5.3 mmol) was added to a
solution of ester 12 (190.2 mg, 0.53 mmol) in dioxane (1
ml) and water (1 ml). The reaction mixture was stirred
at room temperature for 1 h, diluted with water (15 ml)
and diethyl ether (20 ml), and acidified with Amberlite
IR-120(plus) ion-exchange resin. After stirring for 15
min, the mixture was filtered and the filtrate was
extracted with diethyl ether (2×60 ml). The combined
ethereal extracts were dried (Na SO ) and evaporated
1
6
.4. Methyl (3R,4R,5R,6R)-5-tert-butyldimethylsilyloxy-
-hydroxy-3,4-isopropylidenedioxycyclohex-1-ene-1-
carboxylate 11
tert-Butyldimethylsilyl trifluoromethanesulfonate (0.76
ml, 3.3 mmol) was added dropwise to a stirred solution
of diol 9 (767 mg, 3.14 mmol) and triethylamine (0.88
ml, 6.28 mmol) in dichloromethane (60 ml) at −78°C,
the reaction mixture was stirred at −78°C for 50 min,
and was then quenched with water (40 ml). The mixture
was allowed to warm to room temperature and
extracted with dichloromethane (3×40 ml). The com-
bined organic extracts were dried (Na SO ), filtered and
2
4
to afford the acid 13 (169 mg, 92%) as an oil, [a] =
D
−
1
+
44.4 (c 0.63, CHCl ); w
(film)/cm 2956, 2931,
3
max
2
892, 2857, 1725, 1660, 1455, 1382, 1255, 1122; l (270
H
MHz) 0.13 (3 H, s), 0.14 (3 H, s), 0.87 (9 H, s), 1.40 (6
H, s), 4.26 (1 H, dd, J 5.3, 4.6), 4.43 (1 H, ddd, J 10.6,
4.6, 3.3), 4.74 (1 H, dd, J 8.9, 3.6), 5.15 (1 H, dd, JFH
46.2, J 3.6), 7.08 (1 H, t, J 2.6), 8.00–8.50 (1 H, br s);
lC (67.8 MHz) (5.17, 17.82, 25.46, 26.24, 27.74, 68.83
(d, JFC 25.96), 71.10 (d, JFC 2.07), 74.55, 84.08 (d, JFC
2
4
evaporated to dryness. Chromatography of the residue
on silica gel with petrol–diethyl ether (3:1) gave the
monosilyl ether 10 (878.3 mg, 78%) as a white solid,
which was recrystallised from petrol as colourless crys-
tals, m.p. 66–67.5°C; [h] =−79.3 (c 0.92, CHCl ); w
174.45), 111.11, 126.82 (d, JFC 17.66), 140.87 (d, J
FC
+
6.23), 168.77; m/z HRMS (ES). Found: M −H
345.1541, C H FO Si requires 345.1533.
D
3
max
16 26
5