Synthesis of Alkylidenecyclopentenone Prostaglandins
J . Org. Chem., Vol. 67, No. 13, 2002 4405
C28H57NO3Si: C, 65.69; H, 11.22; N, 2.74. Found: C, 65.95;
H, 11.18; N, 2.79.
morpholine N-oxide (297 mg, 2.53 mmol), 4 Å molecular sieves
(845 mg), and tetrapropylammonium perruthenate (29 mg, 84
µmol) were introduced, and the mixture was stirred for an
additional 1 h and 40 min. The reaction was quenched with a
10% solution of sodium thiosulfate, and the organic layer was
washed with brine and a saturated copper sulfate solution.
This was dried over anhydrous MgSO4, filtered, and concen-
trated to dryness. Purification by flash chromatography over
silica gel (cyclohexane/ethyl acetate, 3:1) afforded the cyclo-
pentenone 27 as a colorless oil (661 mg, 89%): [R]D -23 (c 1.4,
CHCl3); IR (CHCl3) 3441, 2957, 1718 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.02 (s, 9H), 0.92 (m, 2H), 1.66 (m, 2H, J ) 7.6 Hz),
1.83 (m, 2H, J ) 7.3 Hz), 2.42 (d, 1H, J ) 18.0 Hz), 2.77 (d,
1H, J ) 18.0 Hz), 3.46 (t, 2H, J ) 6.0 Hz), 4.07 (m, 2H), 4.46
(s, 2H), 5.34 (br s, 1H), 6.18 (d, 1H, J ) 5.7 Hz), 7.03 (t, 2H),
7.30 (t, 2H), 7.48 (d, 1H, J ) 5.4 Hz); 13C NMR (75 MHz,
CDCl3) δ -1.6, 17.7, 24.5, 36.4, 46.9, 61.5, 63.3, 69.6, 72.5,
115.5, 129.5, 133.6, 133.7, 155.3, 164.0, 165.2, 206.4; HRMS
(CI+, NH3) m/z calcd for C21H31O4NFSi 408.2008, found
408.2001. Anal. Calcd for C21H30O4NFSi: C, 61.89; H, 7.42.
Found: C, 61.82; H, 7.52.
{1-[3(R,S)-(4-Flu or oben zyloxy)pr opyl]-3-h ydr oxy-1-pr o-
p en ylp en t-4-en yl}ca r ba m ic Acid 2-(Tr im eth ylsila n yl)-
et h yl E st er (23a a n d 23b ). A 1 M solution of tetrabutyl-
ammonium fluoride in THF (2.2 mL, 2.2 mmol) was added
to a solution of silyl ether 21 (1.017 g, 1.798 mmol) in THF
(25 mL) at 0 °C under an argon atmosphere. After being stirred
for 1 h at 0 °C, the reaction was quenched by brine (30 mL)
and extracted with ether, and the organic layers were dried
over anhydrous magnesium sulfate, filtered, and concentrated
under reduced pressure. Separation by flash chromatography
(cyclohexane/ethyl acetate, 5:1 and then 3:1) gave partially
separated diastereoisomeric alcohols 23a and 23b as colorless
oils (total mass 817.7 mg, 100%). Data for diastereoisomer
23a : IR (CHCl3) 3605, 3384, 2957, 2856, 1718 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.03 (s, 9H), 0.95 (m, 2H), 1.62 (m, 3H, J
) 6.7 Hz), 1.88 (m, 1H), 1.98 (dd, 1H, J ) 6.9 Hz), 2.50 (m,
1H), 3.46 (m, 2H, J ) 2.6, 6.5 Hz), 4.09 (m, 2H), 4.34 (m, 1H),
4.45 (s, 2H), 5.07 (dd, 1H, J ) 1.3, 10.3 Hz), 5.20 (d, 1H, J )
17.0 Hz), 5.50 (br m, 2H), 5.84 (m, 1H), 5.96 (s, 1H), 7.02 (m,
2H), 7.28 (m, 2H). Data for diastereoisomer 23b: IR (CHCl3)
(1S)-(1-Octyl-4-oxocyclop en t-2-en yl)ca r ba m ic Acid 2-
(Tr im eth ylsila n yl)eth yl Ester (28). The diene 24 (347 mg,
0.87 mmol) was dissolved in anhydrous dichloromethane (22
mL) under an argon atmosphere. The Grubbs catalyst 29 was
added (7 mg, 9 µmol), and 50 min later, N-methylmorpholine
N-oxide (153 mg, 1.31 mmol), 4 Å molecular sieves (436 mg),
and tetrapropylammonium perruthenate (15 mg, 43 µmol)
were introduced. After the solution was stirred for 3 h and 20
min, the medium was passed through a short silica gel column
(eluent dichloromethane/ethyl acetate, 10:1) to give the cyclo-
pentenone 28 free from ruthenium. Purification by flash
chromatography on silica gel (cyclohexane/ethyl acetate, 5:1)
gave cyclopentenone 28 as a colorless oil (278 mg, 90%): [R]D
-15 (c 1.1, CDCl3); IR (CHCl3) 3443, 2957, 2930, 2857, 1718,
3590, 3430, 2957, 1718 cm-1 1H NMR (300 MHz, CDCl3) δ
;
0.04 (s, 9H), 0.95 (m, 2H, J ) 3.7, 8.5 Hz), 1.63 (m, 3H), 1.67
(m, 1H), 1.74 (d, 3H, J ) 4.7 Hz), 1.83 (m, 1H, J ) 8.8, 14.7
Hz), 2.04 (m, 1H), 2.10 (dd, 1H, J ) 3.0, 14.7 Hz), 2.20 (m,
1H), 3.44 (m, 2H, J ) 7.1 Hz), 4.09 (m, 2H, J ) 3.7, 8.5 Hz),
4.30 (m, 1H), 4.45 (s, 2H), 5.07 (d, 1H, J ) 10.3 Hz), 5.20 (d,
2H, J ) 17.1 Hz), 5.52 (m, 2H), 5.86 (m, 1H), 7.03 (m, 2H),
7.29 (m, 2H). Data for diastereoisomers 23a and 23b: MS (CI+,
NH3) m/z 434 (M + NH4)+. Anal. Calcd for C24H38FNO4Si: C,
63.82; H, 8.48. Found: C, 63.63; H, 8.48.
(1S)-(3(R,S)-Hyd r oxy-1-octyl-1-p r op en ylp en tyl-4-en yl)-
tr im eth ylsilyleth yl Ca r ba m a te (24). The same procedure
described for 23a and 23b gave from compound 22 the
compound 24 (374 mg, 100%): IR (CHCl3) 3605, 3388, 2957,
1
1500, 1252 cm-1; H NMR (300 MHz, CDCl3) δ 0.01 (s, 9H),
2929, 2857, 1718, 1516 cm-1
;
1H NMR (300 MHz, CDCl3) δ
0.86 (t, 3H, J ) 5.1 Hz), 0.93 (m, 2H), 1.24 (s, 12H), 1.67 (m,
1H), 1.80 (m, 1H), 2.43 (d, 1H, J ) 18.5 Hz), 2.71 (d, 1H, J )
18.5 Hz), 4.09 (m, 2H), 4.90 (s, 1H), 6.16 (d, 1H, J ) 5.7 Hz),
7.48 (dl, J ) 4.8 Hz); 13C NMR (75 MHz, CDCl3) δ -1.6, 14.0,
17.7, 24.5, 28.5, 29.1, 29.3, 29.6, 31.7, 33.6, 47.0, 51.5, 63.2,
133.6, 155.2, 165.7, 206.6; MS (CI+, NH3) m/z 371 (M + NH4)+.
Anal. Calcd for C19H35NO3Si: C, 64.54; H, 9.98; N, 3.96.
Found: C, 64.89; H, 10.03; N, 3.97.
0.03 (s, 9H), 0.87 (t, 3H, J ) 6.5 Hz), 0.96 (m, 2H), 1.25 (s,
12H), 1.58 (s, 1H), 1.60 (m, 1H), 1.73 (d, 3H, J ) 5.4 Hz), 1.96
(m, 3H), 4.09 (m, 2H), 4.32 (br m, 1H), 5.07 (dd, 1H, J ) 1.1,
10.3 Hz), 5.20 (d, 1H, J ) 17.5 Hz), 5.47 (m, 2H), 5.58 (m, 2H);
MS (CI+, NH3) m/z 398 (M + H)+. Anal. Calcd for C22H43NO3-
Si: C, 66.45; H, 10.90; N, 3.52. Found: C, 66.26; H, 10.76; N,
3.39.
(1S)-(4S)-{1-[3-(4-F lu or oben zyloxy)p r op yl]-4-h yd r oxy-
cyclop en t-2-en yl}ca r ba m ic Acid 2-(Tr im eth ylsila n yl)-
eth yl Ester (25a) an d (1S)-(4R)-{1-[3-(4-Flu or oben zyloxy)-
pr opyl]-4-h ydr oxycyclopen t-2-en yl}car bam ic Acid 2-(Tr i-
m eth ylsila n yl)eth yl Ester (25b). The mixture of dienes 23a
and 23b (32.5 mg, 72 µmol) was dissolved in dichloromethane
(2 mL) under an argon atmosphere. The Grubbs catalyst 29
(1.2 mg, 1.5 µmol) was then introduced into the flask. After
the solution was stirred 10 min, the solvent was removed
under reduced pressure, and the residue was purified by flash
chromatography over silica gel (cyclohexane/ethyl acetate, 1:1),
giving cyclopentenols 25a (13.2 mg, 45%) and 25b (13.7 mg,
47%). Data for 25a : [R]D -36 (c 1, CHCl3); IR (CHCl3) 3613,
(1R,4S)- a n d (1S,4R)-4-[3-(4-F lu or oben zyloxy)p r op yl]-
4-[2-(tr im eth ylsila n yl)eth oxyca r bon yla m in o]cyclop en t-
2-en ecar boxylic Acid 2,2,2-Tr iflu or o-1-m eth oxy-1-ph en yl-
eth yl Ester (30a a n d 30b). To a solution of cyclopentenol
25b (9.5 mg, 23 µmol) in anhydrous dichloromethane (0.3 mL)
were added DMAP (11 mg, 92 µmol) and triethylamine (5 mL,
32 µmol). To this solution was then added, under argon,
(R)-MTPACl (9 mg, 34.5 µmol) in 0.3 mL of anhydrous
dichloromethane. After being stirred for 30 min, the reaction
was quenched by addition of a saturated aqueous NaHCO3
solution. After extraction with dichloromethane, the organic
layers were dried (MgSO4), filtered, and evaporated under
reduced pressure. The residue obtained was purified by flash
column chromatography (cyclohexanes/ethyl acetate, 10:1) and
gave diastereoisomers esters 30a and 30b (11.5 mg, 79%) in
3443, 2956, 2861, 1703 cm-1 1H NMR (300 MHz, CDCl3) δ
;
0.02 (s, 6H), 0.92 (m, 2H), 1.67 (m, 3H), 1.77 (dd, 1H, J ) 3.6,
14.2 Hz), 1.86 (m, 2H), 2.51 (q, 1H, J ) 7.3, 14.1 Hz), 3.48 (t,
2H), 4.07 (t, 2H), 4.46 (s, 2H), 4.97 (br s, 1H), 5.05 (m, 1H),
5.90 (s, 2H), 7.03 (m, 2H), 7.30 (m, 2H). Data for 25b: [R]D
-35 (c 1, CHCl3); IR (CHCl3) 3437, 2955, 2861, 1703 cm-1; 1H
NMR (300 MHz, CDCl3) δ 0.02 (s, 9H), 0.91 (m, 2H), 1.66 (m,
5H), 2.03 (d, 1H, J ) 15.0 Hz), 2.35 (dd, 1H, J ) 6.4, 15.0 Hz),
3.47 (m, 2H), 4.06 (m, 2H), 4.47 (s, 2H), 4.60 (br s, 1H), 5.43
(s, 1H), 5.58 (d, 1H, J ) 5.4 Hz), 6.00 (d, 1H, J ) 5.4 Hz), 7.04
(m, 2H), 7.30 (m, 2H). Data for 25a and 25b: HRMS (CI+,
NH3) m/z calcd for C21H33FNO4Si 410.5853, found 410.5850.
{1-[3-(4-F lu or ob en zyloxy)p r op yl]-4-oxocyclop en t -2-
en yl}ca r ba m ic Acid 2-(Tr im eth ylsila n yl)eth yl Ester (27).
The diene 23a and 23b (764 mg, 1.69 mmol) was dissolved in
anhydrous dichloromethane (43 mL) under an argon atmo-
sphere, and the Grubbs catalyst 29 (13 mg, 16 µmol) was
added. After 1 h of stirring at room temperature, N-methyl-
1
an 81:19 ratio (as determined by H NMR spectroscopy): 1H
NMR (300 MHz, CDCl3) δ 0.00 (s, 9H), 0.92 (m, 2H), 1.58 (m),
1.86 (m, 2H), 2.07 (dd, 0.81H, J ) 4.2, 14.2 Hz), 2.50 (dd,
0.19H, J ) 7.2 Hz), 2.57 (dd, 0.81H, J ) 7.2, 14.2 Hz), 3.45 (t,
2H, J ) 6.4 Hz), 3.54 (s, 3H), 4.06 (m, 2H), 4.44 (s, 2H), 4.85
(s, 0.19H), 4.92 (s, 0.81H), 5.78 (m, 1H), 5.92 (m, 0.81H), 5.99
(m, 0.19H), 6.14 (d, 0.81H), 6.21 (sl, 0.19H), 7.03 (t, 2H), 7.28
(m, 2H), 7.39 (m, 3H), 7.53 (m, 2H).
(7S)-7-{2-[3-(4-F lu or oben zyloxy)p r op yl]-5-oxo-2-[2-(tr i-
m eth ylsila n yl)eth oxyca r bon yla m in o]cyclop en t-3-en yl}-
7-h yd r oxyh ep ta n oic Acid Meth yl Ester (31). A solution
of 1,1,1,3,3,3-hexamethyldisilazane (HMDS) (89 mL, 420 µmol)
in anhydrous THF (1 mL) under an argon atmosphere was
cooled to 0 °C. Then, a 1.6 M BuLi solution in hexane (262
µL, 420 mmol) was introduced. After 10 min, this solution was
cooled to -78 °C, and a solution of the ketone 27 (71.4 mg,