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Helvetica Chimica Acta – Vol. 90 (2007)
for 10 h. Then the soln. was diluted with AcOEt (400 ml) and washed with sat. aq. NH4Cl soln. and brine,
dried (MgSO4), and concentrated. The residue was purified by FC (AcOEt/hexane 1:9): 5 (31.6 g, 95%)
as a viscous oil, which slowly crystallized upon standing. M.p. 40 – 438 ([4]: M.p. 39 – 43.58). [a]2D5 ¼ ꢀ65.5
(c ¼ 0.81, MeOH) ([4]: [a]2D1 ¼ ꢀ68.7 (c ¼ 0.53, MeOH)). IR (film): 3541, 2952, 2929, 2856, 1704, 1625,
1437, 1248, 1103, 1076, 893, 835, 777. 1H-NMR (CDCl3): 6.57 (m, ¼CH); 4.48 (s, CH); 4.13 (dd, J ¼ 9.2,
3.6, CH); 3.68 (s, Me); 3.64 (dd, J ¼ 4.4, 4.4, CH); 2.56 (dddd, J ¼ 18.4, 4.4, 2.4, 2.4, 1 H); 2.51 (s, OH);
2.17 (ddd, J ¼ 18.0, 1.2, 1.2, 1 H); 0.87 (s, 1 Me3CSi); 0.80 (s, 1 Me3CSi); 0.09 (s, 1 MeSi); 0.08 (s, 1 MeSi);
0.02 (s, 1 MeSi); 0.01 (s, 1 MeSi). 13C-NMR (CDCl3): 167.1; 137.3; 128.5; 70.7; 68.3; 67.6; 51.6; 29.6; 25.74;
25.63; 17.96; ꢀ 4.7; ꢀ 4.86; ꢀ 4.96; ꢀ 5.03. ESI-MS: 439.3 ([M þ Na]þ).
(3R,4S,5R)-3,5-Bis{[(tert-butyl)dimethylsilyl]oxy}-4-methoxycyclohex-1-ene-1-carboxylic Acid
Methyl Ester (6). To a soln. of 5 (30 g, 72 mmol) in DMF/DMSO 1:1 (484 ml), barium oxide (96 g,
625 mmol) and barium hydroxide octahydrate (54 g, 170 mmol) were added at 08. Dimethyl sulfate
(143 ml, 1.51 mol) was then added dropwise at 08 under N2. After stirring for 18 h at 08, the mixture was
treated with conc. aq. ammonia soln. (60 ml), and subsequently neutralized (pH 7) at 08 with 4m HCl.
The resultant soln. was extracted twice with AcOEt, the org. layer washed with brine, dried (Na2SO4),
and concentrated, and the residue purified by FC (AcOEt/hexane 1:10): 6 (25.4 g, 82%). Viscous oil
which slowly crystallized upon standing. M.p. 59 – 608. [a]2D5 ¼ ꢀ32.3 (c ¼ 0.89, MeOH). IR (film): 2942,
1
2736, 2708, 1719, 1650, 1434, 1363, 1338, 1258, 1190, 1110, 952, 845, 780. H-NMR (CDCl3): 6.70 (m,
¼CH); 4.63 (s, CH); 4.15 (dd, J ¼ 8.8, 4.0, CH); 3.70 (s, 1 MeO); 3.47 (s, 1 MeO); 3.26 (dd, J ¼ 4.4, 4.0,
CH); 2.56 (dddd, J ¼ 18.4, 4.4, 2.4, 2.4, 1 H); 2.17 (ddd, J ¼ 18.4, 1.2, 1.2, 1 H); 0.91 (s, 1 Me3CSi); 0.84 (s,
1 Me3CSi); 0.10 (s, 1 MeSi); 0.09 (s, 1 MeSi); 0.06 (s, 1 MeSi); 0.04 (s, 1 MeSi). 13C-NMR (CDCl3): 167.1;
139.2; 127.9; 81.2; 67.8; 67.2; 59.7; 51.6; 30.3; 25.9; 25.7; 18.2; 17.9; ꢀ 4.4; ꢀ 4.73; ꢀ 4.75; ꢀ 4.85. ESI-HR-
MS: 453.7315 (C21H42NaO5Siþ2 ; calc. 453.7223).
(3R,4S,5R)-3,5-Dihydroxy-4-methoxycyclohex-1-ene-1-carboxylic Acid Methyl Ester (7). A mixture
of 6 (20 g, 46.4 mmol), AcOH (120 ml, 2.08 mol), tetrahydrofuran (40 ml, 0.488 mol), and H2O (40 ml,
2.22 mol) was stirred at 408 for 36 h. Then the mixture was concentrated and the residue purified by FC
(AcOEt): 7 (8.4 g, 90%). Viscous oil. [a]2D5 ¼ ꢀ104 (c ¼ 0.96, MeOH). IR (neat): 3420, 2952, 1707, 1653,
1439, 1263, 1100, 1042, 750, 666. 1H-NMR (CDCl3): 6.84 (ddd, J ¼ 4.0, 2.0, 2.0, ¼CH); 4.50 (dd, J ¼ 4.4,
4.4, CH); 4.09 (ddd, J ¼ 8.0, 8.0, 5.6, CH); 3.72 (s, 1 MeO); 3.49 (s, 1 MeO); 3.26 (dd, J ¼ 8.4, 4.4, CH);
2.82 (dd, J ¼ 18.0, 5.2, 1 H); 2.48 (br. s, 2 OH); 2.21 (dddd, J ¼ 18.4, 8.4, 2.0, 1.2, 1 H). 13C-NMR (CDCl3):
166.7; 136.1; 130.3; 82.0; 65.2; 63.5; 58.1; 52.0; 31.3. ESI-HR-MS: 225.1967 (C9H14NaOþ5 ; calc. 225.1961).
(4S,5R)-5-Hydroxy-4-methoxy-3-oxocyclohex-1-ene-1-carboxylic Acid Methyl Ester (8). To a soln. of
7 (8 g, 39.6 mmol) in DMF (133 ml), PDC (17.9 g, 47.7 mmol) was added slowly at 108. After being stirred
at 158 for 2 h, the soln. was diluted with AcOEt (250 ml). The resultant mixture was washed with sat. aq.
NH4Cl soln. and brine, dried (Na2SO4), and concentrated. The residue was purified by FC (AcOEt/
hexane 1:1): 8 (6.73 g, 85%). Light yellow oil. [a]2D5 ¼ ꢀ101.7 (c ¼ 0.55, MeOH) ([3]: [a]D ¼ ꢀ142.0 (c ¼
1.12, CHCl3)). IR (neat): 3438, 2955, 2838, 1724, 1694, 1438, 1258, 1195, 1130, 738, 665. 1H-NMR
(CDCl3): 6.73 (d, J ¼ 2.8, ¼CH); 4.02 (ddd, J ¼ 20.0, 10.0, 5.2, CH); 3.82 (s, 1 MeO); 3.66 (d, J ¼ 10.4,
CH); 3.65 (s, 1 MeO); 3.16 (dd, J ¼ 18.8, 5.2, 1 H); 2.82 (br. s, OH); 2.57 (ddd, J ¼ 18.8, 9.6, 3.2, 1 H).
13C-NMR (CDCl3): 198.0; 165.9; 144.8; 132.3; 87.3; 69.7; 60.3; 52.9; 32.4. ESI-MS: 223.1 ([ M þ Na]þ).
(4S,5R)-5-{[(tert-Butyl)dimethylsilyl]oxy}-4-methoxy-3-oxocyclohex-1-ene-1-carboxylic Acid Meth-
yl Ester (9). To a soln. of 8 (6.5 g, 32.5 mmol) in DMF (100 ml) at 08, 1H-imidazole (3.5 g, 51.4 mmol),
DMAP (1.1 g, 9 mmol), and tBuMe2SiCl (5.9 g, 39.4 mmol) were added sequentially. After being stirred
for 12 h at 08, the soln. was diluted with AcOEt (200 ml) and washed with sat. aq. NH4Cl soln. and brine,
dried (Na2SO4), and concentrated. The residue was purified by FC (AcOEt/hexane 1:10): 9 (9.19 g,
90%). Light yellow oil. [a]2D5 ¼ ꢀ77.4 (c ¼ 0.80, MeOH) ([3]: [a]D ¼ ꢀ78.7 (c ¼ 1.21, CHCl3)). IR (neat):
2954, 2930, 2857, 1727, 1697, 1250, 1135, 1117, 836, 779, 666. 1H-NMR (CDCl3): 6.72 (m, ¼CH); 4.12 (ddd,
J ¼ 8.4, 7.2, 4.8, CH); 3.82 (s, 1 MeO); 3.54 (s, CH); 3.51 (s, 1 MeO); 2.93 (ddd, J ¼ 18.4, 4.8, 0.8, 1 H); 2.58
(ddd, J ¼ 18.8, 7.2, 2.4, 1 H); 0.86 (s, Me3CSi); 0.07 (s, 1 MeSi); 0.06 (s, 1 MeSi). 13C-NMR (CDCl3): 198.1;
166.4; 144.5; 131.7; 86.0; 70.6; 59.8; 52.7; 33.2; 25.7; 18.0; ꢀ 4.7; ꢀ 5.0. ESI-MS: 337.2 ([M þ Na]þ).
(3S,4R,5R)-5-{[(tert-Butyl)dimethylsilyl]oxy}-3-hydroxy-4-methoxycyclohex-1-ene-1-carboxylic
Acid Methyl Ester (10). A soln. of 9 (9.0 g, 28.6 mmol) and CeCl3 · 7 H2O (10.6 g, 28.6 mmol) in MeOH
(220 ml) was stirred for 0.5 h at 258 and then cooled to ꢀ 208. NaBH4 (1.1 g, 28.6 mmol) was added. After