+
+
Synthesis of (-)-Galbonolide B
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7099
NMR (CDCl3) δ -1.3, 10.7, 13.0, 16.7, 18.9, 27.6, 35.7, 42.8, 66.2,
68.2, 84.8, 92.8, 115.9, 130.8, 137.9, 145.3. HRMS (EI) calcd for
C18H36Si1O3 328.2344, found 328.2499.
Deprotected 26. To a solution of 26 (467 mg, 0.778 mmol) in
DMSO (20 mL) were added Et4NF (1.16 g, 7.77 mmol) and 2 g of
powdered 4 Å molecular sieves. The mixture was stirred at 90 °C
overnight and was then acidified with 1 N HCl. After aqueous workup
(ether) and concentration in Vacuo, the mixture was dissolved in ether
(20 mL) to which ethereal CH2N2 was added until a steady yellow
color was obtained. The mixture was stirred for another 5 min, and
nitrogen was passed through the mixture to remove the excess CH2N2.
The mixture was concentrated in Vacuo and chromatographed to give
Ethyl Ester 24. To a solution of oxalyl chloride (5.6 mL, 0.064
mol) in CH2Cl2 (150 mL) at -78 °C was slowly added DMSO (6.1
mL, 0.086 mol). The mixture was stirred at -78 °C for 15 min. To
this mixture was added desilylated 21 (3.5 g, 0.011 mol) in 50 mL of
CH2Cl2. The mixture was stirred at -78 °C for 1 h, and NEt3 (14.9
mL, 0.107 mol) was added. The mixture was stirred at -78 °C for
another 15 min. After aqueous workup (CH2Cl2) and chromatography,
3.24 g (93% yield) of the aldehyde was obtained, which was used
directly in the next step.
190.2 mg (52% yield from 26) of the deprotected compound: [R]25
D
+7.6° (c 0.29, EtOAc). IR 3477, 1741, 1610. 1H NMR (C6D6) δ 0.84
(3H, t, J ) 7.5), 0.93 (3H, d, J ) 6.6), 1.47 (2H, m), 1.71 (3H, s), 1.72
(3H, s), 1.98 (1H, dd, J ) 7.3, 13.5), 2.07 (3H, s), 2.12 (1H, dd, J )
6.6, 13.5), 2.47 (6H, s), 2.52 (1H, d, J ) 13.9), 2.53 (1H, m), 2.64
(1H, d, J ) 13.9), 3.38 (3H, s), 3.74 (1H, t, J ) 6.4), 3.82 (1H, d, J )
8.1), 4.28 (1H, J ) 8.1), 4.93 (1H, s), 5.03 (1H, s), 5.11 (1H, d, J )
9.4), 5.80 (1H, s), 6.46 (1H, s), 6.70 (2H, s). 13C NMR (C6D6) δ 10.2,
13.6, 17.4, 20.3, 20.6, 20.9, 28.3, 31.6, 46.1, 46.2, 51.6, 73.3, 78.8,
85.3, 103.7, 115.1, 126.3, 128.3, 128.6, 129.6, 130.4, 136.0, 138.5,
138.8, 140.8, 144.4, 173.1. HRMS (EI) calcd for C29H42O5 470.3032,
found 470.3080.
To a mixture of LiCl (1.69 g, 0.040 mol) and phosphonate 31 (8.52
mL, 0.040 mol) in CH3CN (100 mL) was added DBU (4.46 mL, 0.030
mol). The mixture was stirred at room temperature until a clear solution
was obtained and was then cooled to 0 °C. To this mixture was added
the aldehyde obtained above (3.24 g, 9.94 mmol) in 30 mL of CH3-
CN. The mixture was stirred at 0 °C for another hour and was
concentrated in Vacuo. After aqueous workup (CH2Cl2) and chroma-
tography, 3.87 g (95% yield) of 24 was obtained: [R]25 -21.6° (c
D
0.38, CHCl3). IR 1644, 1712. 1H NMR (CDCl3) δ 0.00 (9H, s), 0.87
(3H, t, J ) 7.4), 0.92 (2H, m), 0.95 (3H, d, J ) 6.9), 1.27 (3H, t, J )
7.1), 1.50-1.65 (2H, m), 1.66 (3H, s), 1.77 (3H, s), 2.06 (1H, dd, J )
7.5, 13.5), 2.13 (1H, dd, J ) 6.9, 13.5), 2.58 (1H, m), 3.49 (1H, m),
3.74 (1H, m), 3.85 (1H, t, J ) 6.9), 4.16 (2H, AB q, J ) 7.2), 4.57
(2H, AB q, J ) 6.7), 4.86 (1H, s), 5.00 (1H, d, J ) 1.1), 5.73 (1H, s),
6.51 (1H, d, J ) 9.9). 13C NMR (CDCl3) δ -1.4, 10.4, 12.4, 12.8,
14.3, 18.1, 19.4, 26.6, 32.1, 44.7, 60.4, 65.1, 83.1, 91.7, 115.7, 126.4,
129.0, 137.2, 142.9, 147.2, 168.4. HRMS (EI) calcd for C23H42Si1O4
410.2762, found 410.2752.
Acetate 27. The deprotected compound obtained above (165.2 mg,
0.351 mmol) was dissolved in 10 mL of pyridine and 5 mL of acetic
anhydride. DMAP (10 mg, 0.082 mmol) was added, and the mixture
was stirred at room temperature for 1 h. The mixture was concentrated
in Vacuo and chromatographed to give 178.2 mg (99% yield) of 27:
[R]25 +1.4° (c 0.18, EtOAc). IR 1733, 1610. 1H NMR (C6D6) δ
D
0.76 (3H, t, J ) 7.5), 0.90 (3H, d, J ) 6.7), 1.46-1.63 (2H, m), 1.67
(3H, s), 1.75 (3H, s), 1.76 (3H, s), 1.92 (1H, dd, J ) 8.0, 13.5), 2.07
(3H, s), 2.10 (1H, dd, J ) 6.4, 13.5), 2.46 (6H, s), 2.54 (1H, d, J )
14.0), 2.55 (1H, m), 2.64 (1H, d, J ) 14.0), 3.39 (3H, s), 3.83 (1H, d,
J ) 8.3), 4.30 (1H, d, J ) 8.3), 4.91 (1H, s), 5.01 (1H, s), 5.10 (1H,
d, J ) 9.4), 5.22 (1H, t, J ) 6.9), 5.92 (1H, s), 6.46 (1H, s), 6.69 (2H,
s). 13C NMR (C6D6) δ 9.96, 13.8, 17.3, 20.3, 20.7, 20.9, 26.0, 31.4,
45.9, 46.2, 51.5, 73.2, 80.4, 85.3, 103.6, 115.5, 128.3, 128.6, 129.1,
129.7, 130.4, 136.0, 136.0, 138.5, 138.7, 143.9, 169.3, 173.0. HRMS
(EI) calcd for C31H44O6 512.3138, found 512.3126.
Alcohol 32. To a solution of 24 (3.60 g, 8.78 mmol) in CH2Cl2
(200 mL) at -78 °C was added DIBAL-H (44 mL of a 1 M solution
in hexanes, 44 mmol). The mixture was stirred at -78 °C for 2 h.
EtOAc (20 mL) was added to quench the excess DIBAL-H. The
mixture was warmed to room temperature. MeOH (10 mL) was added
at 0 °C, followed by saturated NH4Cl solution (300 mL) and cold 1 N
HCl (100 mL). After aqueous workup and chromatography, 3.10 g
(96% yield) of the desired alcohol 32 was obtained: [R]25D -48.5° (c
0.48, CHCl3). IR 3413, 1621. 1H NMR (CDCl3) δ 0.00 (9H, s), 0.87
(3H, t, J ) 7.3), 0.89 (3H, d, J ) 6.4), 0.92 (2H, m), 1.50-1.65 (2H,
m), 1.60 (3H, d, J ) 0.9), 1.66 (3H, d, J ) 1.2), 1.99-2.08 (2H, m),
2.48 (1H, m), 3.50 (1H, m), 3.74 (1H, m), 3.86 (1H, t, J ) 6.8), 3.94
(2H, s), 4.58 (2H, AB q, J ) 6.8), 4.84 (1H, s), 4.98 (1H, s), 5.18 (1H,
d, J ) 9.4), 5.75 (1H, s). 13C NMR (CDCl3) δ -1.4, 10.4, 12.7, 13.7,
18.1, 20.5, 26.5, 31.4, 45.6, 65.1, 68.8, 83.2, 91.5, 115.2, 129.7, 132.0,
133.4, 136.4, 143.8.
Cyclization Product 28. To a solution of 27 (91.2 mg, 0.178 mmol)
in THF (100 mL) at 0 °C was added LiHMDS (1.07 mL of a 1 M
THF solution, 1.07 mmol). This mixture was added over 1 h to a two-
necked flask containing 100 mL of THF under reflux. After the
addition was complete, the mixture was stirred under reflux for another
hour. The mixture was concentrated in Vacuo. After aqueous workup
and purification by PTLC, 64.1 mg (75% yield) of 28 was obtained:
[R]25D -7.5° (c 0.067, EtOAc). IR 1742, 1712, 1607. 1H NMR (C6D6)
δ 0.85 (3H, t, J ) 7.5), 0.91 (3H, d, J ) 6.7), 1.46 (1H, m), 1.47 (3H,
s), 1.58 (3H, s), 1.62 (1H, m), 1.98 (1H, dd, J ) 8.5, 13.1), 2.07 (3H,
s), 2.27 (1H, dd, J ) 2.5, 13.1), 2.32 (6H, s), 2.56 (1H, m), 2.6 (2H,
AB q, J ) 14.4), 3.23 (1H, d, J ) 16.2), 3.91 (1H, d, J ) 8.3), 3.95
(1H, d, J ) 16.2), 4.15 (1H, d, J ) 8.3), 4.87 (1H, s), 5.01 (1H, d, J
) 2.0), 5.19 (1H, d, J ) 9.2), 5.38 (1H, dd, J ) 4.2, 7.4), 5.89 (1H, s),
6.02 (1H, d, J ) 1.3), 6.69 (2H, s). 13C NMR (C6D6) δ 9.5, 15.8,
16.3, 20.3, 20.9, 21.1, 26.4, 33.8, 45.6, 45.6, 47.2, 72.1, 77.9, 88.9,
102.0, 115.3, 126.4, 127.6, 128.3, 130.4, 134.2, 137.1, 138.3, 139.0,
144.2, 165.4, 204.0. HRMS (EI) calcd for C30H40O5 480.2876, found
480.2900.
Iodo Compound 25. To a mixture of the alcohol obtained above
(1.05 g, 2.85 mmol), PPh3 (1.50 g, 5.72 mmol) and imidazole (389
mg, 5.72 mmol) in ether (30 mL) and CH3CN (10 mL) at -30 °C was
added I2 (1.45 g, 5.71 mmol). The mixture was stirred at -30 °C for
30 min and was then filtered through a plug of silica gel. The filtrate
was concentrated in Vacuo and the crude iodo compound 25 obtained
(1.50 g) was used in the next step directly without further purification.
Methyl Ester 26. To a mixture of the crude iodo compound 25
obtained above (1.50 g) and acetal 23 (5.71 g, 22.8 mmol) in THF
(150 mL) and HMPA (50 mL) at -78 °C was added LiHMDS (25.7
mL of a 1 M solution in THF, 25.7 mmol). The mixture was stirred
at -78 °C for 1 h. After aqueous workup and chromatography, 1.28
g (75% from 32) of 26 was obtained: [R]25D -28.2° (c 0.65, EtOAc).
IR 1749, 1614. 1H NMR (C6D6) δ -0.01 (9H, s), 0.93 (3H, t, J )
7.3), 0.93 (3H, d, J ) 7.1), 0.94 (2H, m), 1.57 (1H, m), 1.75 (1H, m),
1.77 (3H, s), 1.77 (3H, s), 1.93 (1H, dd, J ) 8.2, 13.2), 2.07 (3H, s),
2.15 (1H, dd, J ) 5.7, 13.2), 2.47 (6H, s), 2.54 (1H, d, J ) 13.8), 2.58
(1H, m), 2.65 (1H, d, J ) 13.8), 3.40 (3H, s), 3.52 (1H, m), 3.83 (1H,
m), 3.83 (1H, d, J ) 8.3), 3.99 (1H, t, J ) 6.7), 4.3 (1H, d, J ) 8.3),
4.59 (1H, d, J ) 6.8), 4.74 (1H, d, J ) 6.8), 4.95 (1H, s), 5.04 (1H, s),
5.12 (1H, d, J ) 9.1), 5.86 (1H, s), 6.46 (1H, s), 6.69 (2H, s). 13C
NMR (C6D6) δ -1.3, 10.6, 13.0, 17.4, 18.3, 20.2, 20.3, 20.9, 27.1,
31.4, 46.0, 46.2, 51.5, 65.2, 73.2, 83.3, 85.3, 92.1, 103.6, 115.4, 128.3,
128.6, 129.6, 130.4, 136.1, 137.5, 138.5, 138.7, 144.1, 173.0. HRMS
(EI) calcd for C35H56Si1O6 600.3756, found 600.3800.
Compound 29. To a solution of 28 (32.0 mg, 0.0667 mmol) in
anhydrous DMF (2.5 mL) at 0 °C was added KOt-Bu (0.077 mL of a
1 M THF solution, 0.077 mmol). The mixture was stirred at 0 °C for
10 min. MeI (0.021 mL, 0.337 mmol) was added at 0 °C and stirring
was continued for 1 h. The mixture was concentrated in Vacuo and
was purifed by PTLC to give 30.3 mg (92% yield) of 29: [R]25D +20.2°
(c 0.19, EtOAc). IR 1749, 1712, 1607. 1H NMR (C6D6) δ 0.76 (3H,
t, J ) 7.3), 0.85 (3H, d, J ) 6.9), 1.46 (3H, d, J ) 6.9), 1.51 (3H, s),
1.52 (2H, m), 1.56 (3H, s), 1.84 (1H, dd, J ) 10.6, 12.8), 2.07 (3H, s),
2.08 (1H, dd, J ) 2.7, 12.8), 2.39 (6H, s), 2.40 (1H, m), 2.71 (1H, d,
J ) 16.5), 3.0 (1H, d, J ) 16.5), 4.05 (1H, d, J ) 8.7), 4.26 (1H, q,
J ) 6.9), 4.75 (1H, s), 4.78 (1H, d, J ) 8.4), 4.98 (1H, d, J ) 2.0),
5.00 (1H, d, J ) 9.6), 5.27 (1H, t, J ) 6.3), 5.96 (1H, s), 6.07 (1H, s),
6.70 (2H, s). 13C NMR (C6D6) δ 9.5, 15.3, 16.1, 18.9, 20.4, 20.9, 22.4,
26.1, 35.8, 43.7, 45.6, 47.0, 69.7, 79.8, 88.2, 102.6, 114.5, 127.7, 128.3,