1332 J . Org. Chem., Vol. 66, No. 4, 2001
An et al.
at room temperature for 3 d and washed with 20 mL of water.
The aqueous portion was further extracted with CH2Cl2 (two
10-mL portions), and the combined organic fractions were dried
and concentrated under reduced pressure to give 40 mg (100%)
of 13e,z in a 1:1 ratio. The E/ Z isomers were separated by
chromatography (4:1 hexanes/EtOAc).
(()-Eth yl (E)-4(R*)-t-Bu tyldiph en ylsiloxy-[2(R*),3(R*)]-
d ih yd r oxycyclop en tylid en ea ceta te (16a ). To a solution of
1.176 g (2.897 mmol) of silyl ether 8b in 20 mL of tert-butyl
alcohol was added 1.57 g of 2.5 wt % OsO4 (39.3 mg, 0.155
mmol, 0.05 equiv) in tert-butyl alcohol, followed by 116 mg
(1.04 mmol, 0.36 equiv) of DABCO and a solution of 3.05 g
(9.27 mmol, 3.2 equiv) of K3Fe(CN)6 and 1.28 g (9.27 mmol,
3.2 equiv) of K2CO3 in 20 mL of water. The biphasic reaction
mixture was stirred at room temperature for 50 h, and then
3.9 g of Na2SO3 was added. The resulting mixture was stirred
at room temperature for 3 h, diluted with 100 mL of water,
and extracted with EtOAc (six 100-mL portions). All EtOAc
fractions were combined, dried, and concentrated under re-
duced pressure, and the residue was chromatographed (7:3
hexanes/EtOAc) to afford 805 mg (63%) of the desired triol 16a
and 35 mg (3%) of the all-cis triol. For 16a : 1H NMR δ 1.04
(s, 9), 1.26 (t, 3, J ) 7.1), 2.05-2.09 (m, 1), 2.43 (d, 1, J ) 8.7),
2.77-2.87 (m, 1), 3.09-3.21 (m, 1), 3.83-3.89 (m, 1), 4.14 (q,
2, J ) 7.1), 4.16-4.21 (m, 1), 4.79-4.87 (m, 1), 6.04 (q, 1, J )
2.4), 7.33-7.48 (m, 6), 7.57-7.69 (m, 4). 13C NMR δ 14.5, 19.3,
27.1, 38.2, 60.1, 74.9, 75.6, 76.7, 115.9, 128.0, 130.1, 133.5,
133.8, 135.9, 163.6, 166.7. IR (neat) 3434 (br), 2931, 2858, 1716,
1699, 1428, 1203, 1112, 822, 701 cm-1. MS (FAB+) m/z 441
(MH+). Anal. Calcd. for C25H32O5Si: C, 68.15; H, 7.32. Found:
C, 67.86; H, 7.55.
(()-Eth yl (E)-4-Hyd r oxy-2-cyclop en ten ylid en ea ceta te
(8a ). To a solution of 0.31 g (1.87 mmol) of enone 13e and 0.836
g (2.24 mmol, 1.2 equiv) of CeCl3‚7H2O in 50 mL of MeOH at
-3 °C was added slowly over 2 min 85 mg (2.25 mmol, 1.2
equiv) of NaBH4. The reaction mixture was stirred at room
temperature for 30 min, mixed with 10 mL of 0.5 M aq HCl (5
mmol, 2.7 equiv) and 25 mL of brine, and extracted with ether
(five 30-mL portions). The combined ether fractions were dried
and concentrated under reduced pressure, and the crude
product was purified via chromatography (7:3 hexanes/EtOAc)
to give 296 mg (94%) of allylic alcohol 8a as a viscous, colorless
1
oil. H NMR δ 1.29 (t, 3, J ) 7.1), 1.78-1.80 (m, 1), 2.78 (td,
1, J ) 2.1, 19.4), 3.45 (ddd, 1, J ) 2.2, 6.5, 19.3), 4.18 (q, 2, J
) 7.1), 4.99-5.08 (m, 1), 5.80 (t, 1, J ) 2.2), 6.39 (d, 1, J )
5.4), 6.52 (dd, 1, J ) 2.3, 5.4). 13C NMR δ 14.2, 39.9, 59.8, 75.2,
110.8, 135.7, 147.5, 162.9, 167.4. IR (neat) 3417 (br), 3060,
2981, 2935, 2903, 1698, 1633, 1580, 859 cm-1. HRMS (EI+)
M+ Calcd. for C9H12O3: 168.0786. Found: 168.0789.
(()-E t h yl (E)-4-t-Bu t yld ip h en ylsiloxy-2-cyclop en t e-
n ylid en ea ceta te (8b). To a solution of 410 mg (2.44 mmol)
of alcohol 8a in 3 mL of DMF were added 581 mg (8.54 mmol,
3.5 equiv) of imidazole and 2 g (7.31 mmol, 3 equiv) of tert-
butyldiphenylsilyl chloride. The reaction mixture was stirred
at room temperature for 2 h, then diluted with 50 mL of brine
and 50 mL of ether. The aqueous layer was extracted with
ether (one 50 mL-portion followed by two 25-mL portions), the
combined organic layers were washed with water, dried, and
concentrated under reduced pressure, and the residue was
chromatographed (9:1 hexanes/Et2O) to give 939 mg (95%) of
(()-Eth yl (E)-[2(R*),3(S*),4(R*)]-Tr ih yd r oxycyclop en -
tylid en ea ceta te (16b). A solution of 46 mg (0.104 mmol) of
silyl ether 16a in 2 mL of 5 M ethanolic HCl was stirred at
room temperature for 62 h. After ethanol was removed under
reduced pressure, the crude product was chromatographed
(EtOAc f 10:1 EtOAc/MeOH) to give 20 mg (95%) of triol 16b
1
as a colorless film. H NMR (MeOH-d4) δ 1.28 (t, 3, J ) 7.1),
2.60-2.73 (m, 1), 3.21 (tdd, 1, J ) 2.5, 6.2, 20.2), 3.84-3.88
(m, 1), 4.08 (d, 1, J ) 6.3), 4.15 (q, 2, J ) 7.1), 4.62-4.68 (m,
1), 5.94-6.00 (m, 1). 13C NMR (MeOH-d4) δ 14.8, 38.4, 61.1,
74.3, 76.5, 77.8, 115.5, 166.5, 168.5. IR (neat) 3370 (br), 2923,
1696, 1666, 1213, 1042 cm-1. MS (EI+) m/z 202 (M+). Anal.
Calcd. for C9H14O5: C, 53.46; H, 6.98. Found: C, 53.11; H, 7.29.
(()-Eth yl (E)-[2(R*),3(S*)]-O-Isop r op ylid en e-4(R*)-h y-
d r oxycyclop en t ylid en ea cet a t e (17). A mixture of 91 mg
(0.45 mmol) of triol ester 16b and 0.75 g of Bio-Rad AG 50W-
X4 resin in 5 mL of acetone was stirred at room temperature
for 20 h, then diluted with 10 mL of EtOAc and filtered. After
solvent was removed under reduced pressure, the colorless
residue was chromatographed (1:1 hexanes/EtOAc and 2:1
EtOAc/MeOH) to afford 78 mg of acetonide 17 (94% overall
yield) as a colorless oil along with 22 mg of recovered starting
1
8b as a colorless, viscous oil. H NMR δ 1.07 (s, 9), 1.26 (t, 3,
J ) 7.1), 2.90 (td, 1, J ) 2.2, 19.0), 3.34 (ddd, 1, J ) 2.0, 6.3,
19.0), 4.16 (q, 2, J ) 7.2), 4.95-5.00 (m, 1), 5.72 (t, 1, J ) 2.2),
6.23 (d, 1, J ) 5.7), 6.26 (dd, 1, J ) 1.9, 5.5) 7.30-7.50 (m, 6),
7.64-7.78 (m, 4). 13C NMR δ 14.5, 19.2, 25.4, 40.5, 59.8, 77.0,
110.8, 127.8, 127.9, 129.9, 133.7, 134.2, 135.3, 135.8, 135.9,
147.6, 162.8, 167.4. IR (neat) 3070, 2958, 2931, 2893, 2857,
1703, 1634, 1214, 1110, 1064, 702 cm-1. MS (EI+) m/z 406
(M+). Anal. Calcd. for C25H30O3Si: C, 73.85; H, 7.44. Found:
C, 73.89; H, 7.66.
(()-Eth yl (E)-[2(S*),3(R*)]-Ep oxy-4(R*)-h yd r oxycyclo-
p en tylid en ea ceta te (14). To a solution of 281 mg (1.67 mmol)
of hydroxycyclopentenylidene 8a in 50 mL of toluene at 0 °C
was added slowly 1.08 g (3.57-5.44 mmol, 2.1-3.2 equiv) of
57-86% pure m-CPBA. The mixture was allowed to warm to
room temperature over 1 h and then was stirred for 23 h. After
toluene was removed under reduced pressure, the residue was
chromatographed (1:1 hexanes/EtOAc, Rf ) 0.26) to give 217
mg (70%) of epoxide 14 as a colorless oil. 1H NMR δ 1.27 (t, 3,
J ) 7.2), 2.11 (ddd, 1, J ) 3.0, 6.6, 18.4), 2.70-3.25 (br s, 1),
3.56 (ddd, 1, J ) 1.8, 8.1, 18.3), 3.72 (d, 1, J ) 2.7), 3.83-3.87
(m, 1), 4.11-4.22 (m, 2), 4.32-4.40 (m, 1), 5.99-6.02 (m, 1).
13C NMR δ 14.5, 34.2, 59.3, 60.5, 60.7, 71.7, 117.7, 156.4, 165.7.
IR (neat) 3413 (br), 2983, 1712, 1668, 1222, 857 cm-1. MS (EI+)
m/z 184 (M+). Anal. Calcd. for C9H12O4: C, 58.69; H, 6.57.
Found: C, 58.38; H, 6.52.
(()-Eth yl (E)-[2(R*),3(R*),4(R*)]-Tr ih yd r oxycyclop en -
tylid en ea ceta te (15). A mixture of 125 mg of epoxide 14 (0.68
mmol) and 5 mL of 0.75 M aq H2SO4 (3.75 mmol, 5.5 equiv)
was stirred at room temperature for 20 min, then neutralized
to pH 7 with 1 M NaHCO3. After water was removed via
lyophilization, the residue was chromatographed (EtOAc) to
yield 126 mg (92%) of triol ester 15. 1H NMR (MeOH-d4) δ
1.27 (t, 3, J ) 7.2), 2.77-2.90 (m, 1), 2.98-3.12 (m, 1), 3.67
(dd, 1, J ) 4.4, 8.9), 4.06-4.12 (m, 1), 4.15 (q, 2, J ) 7.2), 4.51
(td, 1, J ) 2.4, 9.0), 5.95 (q, 1, J ) 2.4). 13C NMR (MeOH-d4)
δ 14.8, 37.8, 61.1, 70.5, 78.5, 79.4, 115.6, 164.9, 168.3. IR (neat)
3366 (br), 2925, 1710, 1455, 1207, 1113 cm-1. MS (FAB+) m/z
203 (MH+). Anal. Calcd. for C9H14O5: C, 53.46; H, 6.98.
Found: C, 53.37; H, 7.28.
1
material. H NMR δ 1.22-1.32 (m, 3), 1.34 (s, 3), 1.41 (s, 3),
2.18-2.32 (br s, 1), 2.90-3.06 (m, 1), 3.25 (d, 1, J ) 18.2), 4.17
(q, 2, J ) 7.1), 4.37 (d, 1, J ) 4.7), 4.47 (d, 1, J ) 5.3), 4.95 (d,
1, J ) 5.3), 6.09 (s, 1). 13C NMR δ 14.3, 24.8, 26.8, 37.1, 60.4,
73.9, 82.3, 84.3, 111.9, 119.5, 160.5, 166.7. IR (neat) 3466 (br),
2986, 2933, 1716, 1374, 1212, 1158, 1039, 861 cm-1. MS (EI+)
m/z 242 (M+). Anal. Calcd. for C12H18O5: C, 59.49; H, 7.49.
Found: C, 59.61; H, 7.84.
(()-Eth yl [4(S*),5(R*)]-O-Isopr opyliden e-3(R*)-h ydr oxy-
1-cyclop en ten ea ceta te (18). To a solution of 300 µL (2.14
mmol, 10.6 equiv) of dry diisopropylamine in 2 mL of dry THF
in a flame-dried flask under Ar at -70 °C was slowly added
600 µL of 1.6 M n-BuLi in hexanes (0.96 mmol, 4.7 equiv),
and the mixture was stirred for 10 min. A solution of 49 mg
(0.20 mmol) of acetonide 17 in 2 mL of dry THF was added
slowly over 10 min. The reaction mixture was allowed to warm
to -35 °C over 20 min, mixed with 5 mL of 1 M aq HCl, and
partitioned between 30 mL of brine and 25 mL of ether. The
aqueous portion was extracted with ether, and the combined
organic layer was dried and concentrated under reduced
pressure to give 45 mg of yellow residue, which was chromato-
graphed (1:1 hexanes/EtOAc) to afford 23 mg (47%) of the
desired isomerized acetonide 18 and 9 mg (16%) of the enol
ether 19. For 18: 1H NMR δ 1.28 (t, 3, J ) 7.1), 1.35 (s, 3),
1.36 (s, 3), 2.09-2.17 (m, 1), 3.13-3.30 (m, 2), 4.17 (q, 2, J )
7.1), 4.53 (d, 1, J ) 5.5), 4.70 (s, 1), 5.23 (d, 1, J ) 5.5), 5.74 (s,
1). 13C NMR δ 14.4, 26.3, 27.6, 34.3, 61.2, 80.0, 85.0, 86.3,
112.1, 130.9, 142.5, 170.7. IR (neat) 3414 (br), 2986, 2935, 1738,