Formal Synthesis of (()-Guanacastepene A
7.31 (m, 3), 6.29 (dd, 1, J ) 6.7, 6.7), 4.36 (dd, 1, J ) 3.4, 3.4),
4.25-4.13 (m, 2), 3.71 (ddd, 1, J ) 11.0, 8.5, 3.1), 3.62 (ddd, 1,
J ) 9.8, 6.1, 6.1), 3.42 (ddd, 1, J ) 11.0, 4.6, 4.6), 3.15 (ddd, 1,
J ) 9.8, 7.3, 5.5), 2.75 (dd, 1, J ) 5.8, 5.8, OH), 2.60-2.44 (m,
2), 1.80-1.60 (m, 2), 1.49-1.44 (m, 4), 0.40 (s, 3), 0.39 (s, 3);
13C NMR 142.4, 139.9, 138.0, 133.9 (2 C), 129.1, 127.8 (2 C),
98.8, 66.0, 62.0, 58.3, 30.1, 29.8, 25.2, 19.3, -2.8, -3.1; IR
26.8, 25.9 (3 C), 25.4, 23.6, 21.9, 19.5, 19.0, 18.2, -2.72, -2.75
(0.5 C), -2.77 (0.5 C), -4.6, -4.7; IR (neat) 1669, 1610; HRMS
(FAB DCM/NBA) calcd for C38H62O4NaSi2 (MNa+) 661.4084,
found 661.4095.
(1â,3r,3a r,6r)-3a ,6-Dim eth yl-6-[(2E)-3-(d im eth ylp h en -
ylsilyl)-5-((t et r a h yd r o-2H -p yr a n -2-yl)oxy)p en t yl]-1,2,3,
3a ,4,5-Hexa h yd r o-3-(1-m eth yleth yl)-1-(ter t-bu tyld im eth -
ylsilyloxy)-7(6H)-a zu len eon e (36ba ). To 2.94 mL of freshly
made LDA (1 M in THF, 2.94 mmol) under N2 at -78 °C was
added a solution of 35ba (1.80 g, 2.8 mmol) in 4 mL of dry
THF. The solution was stirred for 30 min at -78 °C and
another 40 min while slowly warming to room temperature.
The solution was cooled again to -78 °C and dry DMPU (495
µL, 6.2 mmol) was added. The mixture was stirred at -78 °C
for 15 min and dry MeI (0.374 mL, 6.0 mmol) was added. The
solution was stirred overnight while slowly warming to room
temperature. Water was added and the solution was extracted
three times with hexanes. The combined organic layers were
washed with 5 mL of brine and dried (Na2SO4). Concentration
gave 2.03 g of crude 36ba , which was used for the next step.
(neat) 3600-3300, 1616, 1029; HRMS (DEI) calcd for C18H29
-
O3Si (MH+) 321.1886, found 321.1872.
(2E)-1-Iod o-3-(d im eth ylp h en ylsilyl)-5-[(tetr a h yd r o-2H-
p yr a n -2-yl)oxy]p en ten e (26a ). To pure 25a (641 mg, 2.0
mmol) in 4 mL of dry CH2Cl2 under N2 at 0 °C was added 0.558
mL (4.0 mmol) of Et3N and 168 µL (2.2 mmol) of MsCl. The
mixture was stirred at 0 °C for 15 min. Water and citric acid
were added until the pH was 3-4, and the aqueous layer was
separated and discarded. The organic layer was washed with
water three times, dried over Na2SO4, and concentrated to give
851 mg of crude mesylate.
The crude mesylate was dissolved in 8 mL of dry acetone
under N2 and 445 mg (3.0 mmol) of NaI in 4 mL of dry acetone
was added while the mixture stirred vigorously. The mixture
was heated at 45 °C for 15 min and cooled to room tempera-
ture. Water (10 mL) and a small amount of Na2S2O3 were
added. Acetone was removed under reduced pressure and the
aqueous layer was extracted three times with hexanes. The
combined organic layers were dried (Na2SO4) and concentrated
to give 890 mg of crude 26a as a yellow oil, which was used
directly in the next step. The oil turns red slowly in air at room
temperature but can be kept at -4 °C under N2 for a week
without significant change. Although the red color usually does
not affect the chemistry significantly, freshly made crude 26a
is usually used in the next step. An analytical sample was
prepared by flash chromatography on silica gel (25:1 hexanes/
EtOAc) to give pure 26a as a colorless oil: 1H NMR 7.51-
7.46 (m, 2), 7.37-7.32 (m, 3), 6.22 (t, 1, J ) 8.5), 4.45 (dd, 1,
J ) 3.4, 3.4), 4.01 (d, 2, J ) 8.5), 3.77 (ddd, 1, J ) 11.0, 8.2,
3.4), 3.61 (ddd, 1, J ) 9.8, 8.5, 6.1), 3.44 (ddd, 1, J ) 11.0, 4.4,
4.4), 3.27 (ddd, 1, J ) 9.8, 7.8, 7.3), 2.60-2.46 (m, 2), 1.82-
1.72 (m, 1), 1.65 (dddd, 1, J ) 12.8, 12.8, 3.1, 3.1), 1.57-1.45
(m, 4), 0.37 (s, 6); 13C NMR 140.4, 139.5, 137.7, 134.0 (2 C),
129.1, 127.8 (2 C), 98.7, 65.5, 62.1, 30.5, 29.6, 25.4, 19.5, 1.2,
-3.12, -3.18; IR (neat) 2940, 2869, 1032.
(1â,3r,3a r)-6-[(2E)-3-(Dim eth ylp h en ylsilyl)-5-((tetr a h y-
d r o-2H-p yr a n -2-yl)oxy)p en tyl]-1,2,3,3a ,4,5-h exa h yd r o-3a -
m eth yl-3-(1-m eth yleth yl)-1-(ter t-bu tyld im eth ylsilyloxy)-
7(6H)-a zu len eon e (35ba ). To 3.15 mL of freshly made LDA
(1 M in THF, 3.15 mmol) under N2 at -78 °C was added a
solution of 23b (1.013 g, 3 mmol) in 5 mL of dry THF. The
solution was stirred at -78 °C for 20 min and dry DMPU (527
µL, 6.6 mmol) was added. The mixture was stirred at -78 °C
for another 10 min and was added via cannula to a stirred
solution of pure 26a (2.073 g, 4.5 mmol) in 10 mL of dry THF
at -78 °C under N2. The solution was stirred overnight while
slowly warming to room temperature. Water was added and
the solution was extracted three times with hexanes. The
combined organic layers were washed with 5 mL of brine and
dried (Na2SO4). Concentration gave 2.64 g of crude 35ba . Flash
chromatography on silica gel (20:1 hexanes/EtOAc) gave
recovered 26a (0.368 g, 0.8 mmol) and 1.802 g (94%) of pure
35ba as a colorless oil: 1H NMR 7.50-7.46 (m, 2), 7.34-7.28
(m, 3), 5.90 (d, 1, J ) 1.8), 5.83 (dd, 1, J ) 6.7, 6.7), 4.60 (ddd,
1, J ) 8.5, 3.6, 1.8), 4.46-4.42 (m, 1), 3.81-3.73 (m, 1), 3.58-
3.48 (m, 1), 3.43 (ddd, 1, J ) 10.4, 5.2, 5.2), 3.24-3.15 (m, 1),
2.74 (dddd, 1, J ) 7.3, 7.3, 6.7, 6.7), 2.56 (ddd, 1, J ) 14.7, 6.1,
6.1), 2.55-2.40 (m, 2), 2.36 (ddd, 1, J ) 14.7, 7.9, 7.3), 2.02-
1.90 (m, 2), 1.88-1.81 (m, 1), 1.81-1.60 (m, 6), 1.60-1.43 (m,
5), 1.07 (s, 3), 0.99 (d, 3, J ) 6.1), 0.92 (d, 3, J ) 6.1), 0.91 (s,
9), 0.34 (s, 6), 0.087 (s, 3), 0.084 (s, 3); 13C NMR 205.9, 170.5,
142.0, 138.78 (0.5 C), 138.76 (0.5 C), 136.58 (0.5 C), 136.54
(0.5 C), 134.0 (2 C), 128.8, 127.6 (2 C), 123.4, 98.62 (0.5 C),
98.59 (0.5 C), 72.9, 66.6, 62.1, 53.91 (0.5 C), 53.89 (0.5 C), 52.1,
48.3, 36.8, 36.3, 31.1, 30.6, 30.24 (0.5 C), 30.19 (0.5 C), 28.7,
An analytical sample was prepared by flash chromatography
on silica gel (25:1 hexanes/EtOAc) to give a trace of 37ba ,
followed by pure 36ba as a colorless liquid: 1H NMR 7.50-
7.46 (m, 2), 7.34-7.28 (m, 3), 5.90 (dd, 1, J ) 7.0, 7.0), 5.81 (d,
1, J ) 1.8), 4.51 (ddd, 1, J ) 5.2, 5.2, 1.8), 4.46-4.42 (m, 1),
3.82-3.74 (m, 1), 3.57-3.49 (m, 1), 3.43 (ddd, 1, J ) 10.4, 5.2,
5.2), 3.24-3.16 (m, 1), 2.53 (ddd, 1, J ) 14.7, 3.7, 3.0), 2.52-
2.42 (m, 1), 2.47 (dddd, 1, J ) 7, 7, 7, 7), 2.37 (dd, 1, J ) 14.7,
7.9), 2.00-1.83 (m, 3), 1.82-1.69 (m, 4), 1.69-1.57 (m, 2),
1.57-1.43 (m, 5), 1.15 (s, 3), 0.98 (d, 3, J ) 6.7), 0.95 (s, 3),
0.90 (s, 9), 0.89 (d, 3, J ) 6.7), 0.342 (s, 3), 0.336 (s, 3), 0.08 (s,
6); 13C NMR 209.0, 166.8, 140.8, 138.8, 137.0, 133.9 (2 C),
128.8, 127.6 (2 C), 122.5, 98.7, 72.7, 66.8, 62.1, 53.0, 51.0, 48.2,
38.0, 37.3, 34.4, 31.1, 30.6, 30.17 (0.5 C), 30.15 (0.5 C), 28.7,
25.8 (3 C), 25.4, 24.7, 23.6, 22.1, 21.2, 19.5, 18.1, -2.65 (0.5
C), -2.68 (0.5 C), -2.71 (0.5 C), -2.75 (0.5 C), -4.6, -4.7; IR
(neat) 1674, 1643, 1611; HRMS (FAB DCM/NBA) calcd for
C
39H64O4NaSi2 (MNa+) 675.4241, found 675.4221.
Data for 37ba : 1H NMR 7.49-7.44 (m, 2), 7.34-7.28 (m,
3), 5.73 (dd, 1, J ) 6.1, 4.3), 4.61 (br d, 1, J ) 4.3), 4.44-4.39
(m, 1), 3.79-3.71 (m, 1), 3.56-3.45 (m, 1), 3.45-3.37 (m, 1),
3.20-3.11 (m, 1), 2.64-2.53 (m, 2), 2.53-2.33 (m, 3), 2.04-
1.94 (m, 1), 1.89-1.67 (m, 6), 1.76 (s, 3), 1.67-1.44 (m, 6), 1.39
(ddd, 1, J ) 12.8, 12.8, 4.9), 0.98 (d, 3, J ) 6.7), 0.88 (d, 3, J
) 6.7), 0.88 (s, 3), 0.88 (s, 9), 0.33 (s, 6), 0.10 (s, 3), 0.09 (s, 3);
13C NMR 214.2, 156.03 (0.5 C), 155.99 (0.5 C), 141.2 (0.5 C),
141.18 (0.5 C), 138.44 (0.5 C), 138.42 (0.5 C), 137.36 (0.5 C),
137.34 (0.5 C), 133.9 (2 C), 131.3, 128.8, 127.6 (2 C), 98.50 (0.5
C), 98.47 (0.5 C), 71.6, 66.4, 61.90 (0.5 C), 61.89 (0.5 C), 55.4,
52.70 (0.5 C), 52.68 (0.5 C), 47.2, 36.9, 35.9, 30.74 (0.5 C), 30.71
(0.5 C), 30.5, 30.2, 27.5, 27.2, 25.7 (3 C), 25.4, 23.8, 22.4, 22.1,
19.40 (0.5 C), 19.37 (0.5 C), 17.9, 17.3, -2.77 (0.5 C), -2.83,
-2.87 (0.5 C), -3.9, -4.8; IR (neat) 1677, 1612.
(1â,3r,3a r,6r)-3a ,6-D im e t h y l-6-(5-h y d r o x y -3-o x o -
p en tyl)-1,2,3,3a ,4,5-h exa h yd r o-3-(1-m eth yleth yl)-1-(ter t-
bu tyld im eth ylsilyloxy)-7(6H)-a zu len eon e (41). To a solu-
tion of 762 mg (77%, 3.4 mmol) of m-CPBA in 5 mL of CH2Cl2
was added dropwise a solution of crude 36ba (2.03 g, from 2.8
mmol of 35ba ) in 5 mL of CH2Cl2 while stirring at 0 °C. The
solution was stirred at CH2Cl2 for 30 min and at room
temperature for another 1 h. Saturated Na2SO3 solution (5 mL)
and NaHCO3 solution (10 mL) in water were added, and the
mixture was stirred vigorously for 1 h. The organic layer was
separated and the water layer was extracted three times with
hexanes. The combined organic layers were dried (Na2SO4) and
concentrated to give 2.13 g of crude epoxide.
The crude epoxide (2.13 g, from 2.8 mmol of 35ba ) was
dissolved in 5 mL of dry CH2Cl2 and transferred to a dry
polyethylene tube equipped with a rubber septum. To this
solution was added dropwise 0.5 mL of pyr‚(HF)x at 0 °C while
stirring vigorously. The mixture was stirred for 5 min and
another 0.5 mL of pyr‚(HF)x was added. The mixture was
J . Org. Chem, Vol. 68, No. 3, 2003 1039