9
594 J . Org. Chem., Vol. 64, No. 26, 1999
J ohnson et al.
added dropwise. The solution was stirred for 35 min, and then
a solution of bromide 20 (1.2 g, 2.7 mmol) in THF (4 mL) was
added to the reaction mixture which was stirred for 20 min at
458.3756. Anal. Calcd for C30
Found: C, 75.68; H, 11.42.
H
53FOSi: C, 75.57; H, 11.20.
13-F lu or o-3-isop r op ylid en -22,23,24,25,26,27-h exa n or -
d a m m a r -20-en e (24). To a solution of TFA (1.05 mL, 13.7
mmol, 93.0 equiv) in DCM (70 mL) that had been degassed
with argon and cooled to -45 °C was added alcohol 3 (70 mg,
0.147 mmol, 1.0 equiv) dropwise over a 30 min period with
vigorous stirring. (Note: Each drop was cooled by contact with
the cold wall of the reaction flask before mixing with the
reaction mixture.) After the addition, the mixture turned a
pale pink and was stirred an additional 10 min at -45 °C.
The reaction was quenched slowly at -45 °C by the addition
of a solution of triethylamine (1.05 mL) in ethanol (3 mL), then
allowed to warm to 24 °C, extracted with saturated NaHCO3
-
78 °C and then warmed over 1 h to 0 °C. The mixture was
stirred at 0 °C for an additional 1.5 h, treated with saturated
NH Cl, and extracted with hexane. The extract was washed
with brine (diluted with water, 1:1) and saturated brine, dried
MgSO ), and concentrated. Flash chromatography of the
residue on silica gel (5-15% ether in hexane) gave â,γ-ester
1 (1.13 g, 85% yield) as a colorless oil: 90% pure by GC; IR
film) 1715, 1630, 1235, 1140, 840 cm-1; 1H NMR δ 5.40 (dt, J
4
(
4
2
(
)
1
4
(
1
10.8, 8.6 Hz, 1H), 5.28-5.20 (m, 1H), 5.12 (t, J ) 6.5 Hz,
H), 5.11 (t, J ) 6.5 Hz, 1H), 4.88 (br, s, 1H), 4.87 (s, 1H),
.14 (q, J ) 7.1 Hz, 2H), 2.98 (t, J ) 7.0 Hz, 1H), 2.28-2.13
m, 4H), 2.13-2.02 (m, 6H), 2.02-1.85 (m, 6H), 1.74 (s, 3H),
and brine, dried (MgSO ), and concentrated to give a white
4
.61 (s, 3H), 1.59 (s, 3H), 1.57 (d, J ) 2.0 Hz, 3H), 1.47 (d, J
gum (85 mg). Flash chromatography (hexane) gave tetracyclic
fluoro diene 24 (31 mg, 55% yield) as a white semisolid. In
other experiments, yields of 60-62% were achieved. An
analytical sample of 24 was recrystallized from acetonitrile
to give colorless crystals: mp 135-137 °C; IR (film) 1625, 900
)
8.6 Hz, 2H), 1.25 (t, J ) 7.1 Hz, 3H), 0.00 (s, 9H); 13C NMR
δ 173.7, 155.9, 153.1, 142.6, 136.0, 134.1, 126.9, 125.7, 125.0,
1
2
23.0, 113.7, 111.3, 111.2, 60.4, 52.5, 39.7, 37.3, 29.7, 29.6, 29.0,
8.7, 28.3, 26.6, 25.2, 20.2, 18.5, 16.0, 15.9, 15.6, 14.2, -1.8;
-
1
1
MS m/z (rel intensity) 490 (25), 213 (37), 135 (89), 81 (100),
cm ; H NMR δ 5.80 (quint, J ) 8.8 Hz, 1 H), 5.04 (d, J )
10.3 Hz, 1 H), 4.99 (d, J ) 17.4 Hz, 1 H), 2.56 (dq, J ) 34.8,
8.9, 1 H), 2.33 (ddd, J ) 14.7, 6.8, 3.4 Hz, 1 H), 2.13-1.92 (m,
3 H), 1.78 (s, 3 H), 1.66 (s, 3 H), 1.8-1.2 (m, 14 H), 1.20 (s, 3
H), 1.10 (s, 3 H), 1.09 (d, J ) 6.4 Hz, 3 H), 0.99 (s, 3 H), 0.83
(s, 3 H); 13C NMR δ 138.6, 138.4, 138.3, 121.5, 116.0, 110.3,
108.6, 54.0, 53.0, 52.9, 51.1, 49.7, 49.5, 41.2, 39.3, 36.7, 35.0,
29.0, 28.6, 28.4, 28.1, 27.2, 24.7, 24.2, 23.9, 23.2, 21.3, 21.2,
19.6, 19.5, 18.3, 17.3, 17.1; MS m/z (rel intensity) 386 (9), 290
7
3 (97); HRMS calcd for C30
Anal. Calcd for C30
3.76; H, 10.32.
Eth yl 13-F lu or o-2-isop r op ylid en -5,9,14-tr im eth yl-19-
t r im e t h ylsilyl)n on a d e ca -5(E ),9(E ),13(Z),17(Z)-t e t r a -
en oa te (22). To a solution of potassium tert-butoxide (0.22 g,
.8 mmol) in THF (15 mL), from which oxygen had been
H
51FO
2
Si 490.3644, found 490.3660.
H
51FO Si: C, 73.41; H, 10.47. Found: C,
2
7
(
1
rigorously excluded and replaced with argon at 0 °C, was added
a solution of â,γ-ester 21 (1.0 g, 2.04 mmol) in THF (5 mL).
The reaction mixture was stirred for 40 min at 0 °C, cooled to
(42), 121 (100), 95 (92); HRMS calcd for C27
found 386.3359. Anal. Calcd for C27
Found: C, 83.49; H, 11.32.
A mixture of compounds 25 (C-17 epimers) from chromato-
graphic separation gave the following data: H NMR δ 5.90
(quint, J ) 7.1 Hz, 1 H), 5.38 (br s, 1H), 4.96 (d, J ) 6.1 Hz,
1 H), 4.89 (d, J ) 17. Hz, 1 H), 2.94 (dd, J ) 8, 18 Hz, 0.5 H),
2.41 (dt, J ) 17, 6 Hz, 1 H), 2.3-2.0 (m, 3 H), 1.81 (s, 3 H),
1.68 (s, 3 H), 1.9-1.0 (m, 14 H), 1.56 (s, 3 H), 1.21 (s, 3 H),
1.15 (s, 3 H), 1.08 (s, 1.5 H), 0.98 (s, 1.5 H), 0.95 (s, 1.5 H),
0.90 (s, 1.5 H), 0.89 (s, 1.5 H).
H
43F 386.3351,
H43F: C, 83.88; H, 11.21.
-
78 °C, and stirred for 15 min before the reaction was
quenched with saturated NH Cl (3 mL), and then warmed to
4 °C, diluted with hexane (30 mL), washed with saturated
4
1
2
NH
4
Cl and brine, dried (MgSO
4
), filtered through silica gel,
and concentrated to give ester 22 (0.98 g, 98% yield) as a
colorless oil (97/3, 22/21, by GC): IR (film) 1695, 1630, 1235,
-
1
1
8
5
2
45 cm ; H NMR δ 5.40 (dt, J ) 10.0, 8.6 Hz, 1H), 5.28-
.20 (m, 1H), 5.12 (br, t, J ) 6.5 Hz, 2H), 4.19 (q, J ) 7.1 Hz,
H), 2.36 (m, 2H), 2.30-2.12 (m, 4H), 2.12-1.95 (m, 10H), 1.97
(
s, 3H), 1.80 (s, 3H), 1.62 (s, 3H), 1.61 (s, 3H), 1.57 (d, J ) 2.5
Hz, 3H), 1.46 (d, J ) 8.6 Hz, 2H), 1.30 (t, J ) 7.1 Hz, 3H),
.00 (s, 9H); C NMR δ 169.7, 155.5, 153.1, 142.0, 136.0, 134.7,
27.8, 126.9, 125.7, 124.5, 123.0, 111.3, 111.2, 59.9, 39.6, 38.9,
9.6, 29.0, 28.7, 26.7, 25.2, 22.9, 21.7, 18.5, 16.0, 15.5, 14.3,
3-Isop r op ylid en e-22,23,24,25,26,27-h exa n or d a m m a r -
20-en e (27). To a suspension of sodium-potassium alloy (200
mg, 22%-78%) in toluene (6 mL) was added dicyclohexano-18-
crown-6 (800 mg, 2.15 mmol). The resultant blue-black mixture
was stirred for 10 min at 25 °C, and a solution of fluoro
tetracycle 24 (83 mg, 0.215 mmol) in toluene (1 mL) was added
dropwise. After 1.5 h the reaction mixture was diluted with
hexane, quenched with 2-propanol, washed with water and
brine, dried (Na SO ), filtered, and concentrated. Flash chro-
1
3
0
1
2
-
1.8; MS m/z (rel intensity) 490 (11), 135 (30), 95 (32), 73 (100);
HRMS calcd for C30 Si 490.3644, found 490.3642. Anal.
Si: C, 73.41; H, 10.47. Found: C, 73.09;
H
51FO
2
Calcd for C30
H, 10.61.
H51FO
2
2
4
1
4-F lu or o-3-isop r op ylid en -2,6,10,15-t et r a m et h yl-20-
t r im et h ylsilyl)eicosa -6(E),10(E),14(Z),18(Z)-t et r a en -2-
ol (3). To a solution of ester 22 (0.94 g, 1.92 mmol) in ether
20 mL) was added methyllithium (6.9 mL, 1.4 M in ether,
matography of the residue on silica gel (hexane) gave diene
27 (59 mg, 74% yield) as a solid, 90% pure by GC. An analytical
sample of 27 was recrystallized from acetonitrile to give
(
-
1
(
colorless crystals: mp 126-128 °C; IR (KBr) 1625, 900 cm ;
1
9
.66 mmol) dropwise at -20 °C. The reaction mixture was
allowed to reach 10 °C, stirred at this temperature for 1 h,
and then cooled to -10 °C, diluted with ether (30 mL), and
4
quenched with saturated NH Cl (5 mL). The organic layer was
H NMR δ 5.64 (quint., J ) 8.6 Hz, 1H), 4.91 (d, J ) 16.8 Hz,
1H), 4.88 (d, J ) 9.7 Hz, 1H), 2.32 (ddd, J ) 14.7, 6.8, 3.4 Hz,
1H), 2.20-1.85 (m, 5H), 1.79 (s, 3 H), 1.66 (s, 3H), 1.6-1.2
(m, 14H), 1.20 (s, 3H), 1.10 (s, 3H), 0.95 (s, 3H), 0.86 (s, 3H),
0.80 (s, 3H); 13C NMR δ 144.0, 138.9, 121.4, 112.9, 54.1, 51.0,
49.4, 48.1, 45.8, 41.3, 40.4, 39.3, 36.7, 35.0, 31.2, 28.9, 28.6,
24.8, 24.6, 24.3, 23.9, 23.2, 22.4, 20.1, 19.8, 15.8, 15.1; MS m/z
(rel intensity) 368 (18), 272 (100), 95 (93); HRMS calcd for
4
washed with brine, dried (MgSO ), filtered, and concentrated.
Flash chromatography of the residue on silica gel (4-10%
ether in hexane) gave ketone 23 (0.18 g, 20% yield) and alcohol
3
(0.66 g, 72% yield) as colorless oils. Data for ketone 23: 1
H
NMR δ 5.39 (dt, J ) 10.0, 8.6 Hz, 1H), 5.28-5.20 (m, 1H),
C
27
H
44 368.3445, found 368.3443. Anal. Calcd for C27
H44: C,
5
2
1
0
3
.13 (br, t, J ) 6.5 Hz, 2H), 2.34 (m, 2 H), 2.25 (s, 3H), 2.22-
.12 (m, 4H), 2.10-1.95 (m, 10H), 1.82 (s, 3H), 1.76 (s, 3H),
.61 (s, 3H), 1.56 (d, J ) 2.5 Hz, 3H), 1.46 (d, J ) 8.6 Hz, 2H),
.00 (s, 9H). Data for alcohol 3 (unstable on GC): IR (film)
400, 1235, 1140, 840 cm-1; 1H NMR δ 5.39 (dt, J ) 10.0, 8.6
87.97; H, 12.03. Found: C, 88.33; H, 11.85.
3-Isop r op ylid en -22,23,24,25,26,27-h exa sn or d a m m a r -
20-on e (28). A mixture of palladium chloride (5 mg, 0.028
mmol) and copper chloride (10 mg, 0.075 mmol) in DMF (2
mL) and water (0.2 mL) was stirred for 1 h under an oxygen
atmosphere at 25 °C. Then a solution of diene 27 (45 mg, 0.122
mmol) in ether (1 mL) was added, and the reaction mixture
was heated at 60 °C for 3 h and then diluted with water and
extracted with hexanes-ether (1:1). The organic layer was
Hz, 1 H), 5.28-5.20 (m, 1 H), 5.13 (br, t, J ) 6.5 Hz, 2H), 2.28-
2
3
.12 (m, 6 H), 2.12-2.02 (m, 6 H), 2.02-1.95 (m, 4 H), 1.92 (s,
H), 1.70 (s, 3H), 1.63 (s, 3 H), 1.61 (s, 3 H), 1.57 (d, J ) 2.5
Hz, 3 H), 1.47 (d, J ) 7.7 Hz, 2 H), 1.42 (s, 6 H), 0.00 (s, 9 H);
1
3
C NMR δ 155.6, 153.2, 138.6, 136.0, 135.6, 128.1, 126.9,
25.7, 124.1, 123.0, 111.3, 111.2, 74.2, 40.1, 39.7, 30.9, 30.1,
9.7, 29.6, 29.0, 28.7, 26.6, 25.3, 22.8, 18.5, 16.0, 15.6, -1.8;
2 4
extracted with brine, dried (Na SO ), and concentrated. Flash
1
2
chromatography of the residue on silica gel (0-5% ether in
hexane) gave ketone 28 (40 mg, 85% yield) as a solid, 92% pure
by GC. An analytical sample of 28 was crystallized from
acetonitrile to give colorless needles: mp 141-142 °C; IR (film)
MS m/z (rel intensity) 458 (54), 136 (68), 109 (73), 73 (100);
HRMS calcd for C30
+
H
2
51FSi (M - H O) 458.3744, found