Taber et al.
JOCArticle
(s, 9 H), 0.92 (s, 9 H), 0.31 (s, 3 H), 0.27 (s, 3 H), 0.14 (s, 3 H), 0.00
(s, 3 H); 13C NMR δ u 144.3, 119.9, 86.6, 64.7, 38.8, 32.3, 26.4,
25.5, 18.1, 17.9, 16.4, d 128.9, 128.9, 127.7, 126.9, 82.5, 79.6,
74.4, 73.0, 25.9, 25.8, -4.0, -4.3, -4.8, -5.4; IR (film) 3432,
2932, 2264, 1253, 1078, 834 cm-1; HRMS calcd for C44H63NO4-
Si2Na 748.4193, found 748.4192.
1252, 1073, 834 cm-1; HRMS calcd for C32H61NO4Si2Na
602.4033, found 602.4025. Further elution gave 17aab (41 mg,
35% yield from the enone 16aa): TLC Rf (Et2O/CH2Cl2/petro-
leum ether=1/3/6)=0.33; [R]D þ6.9 (c 1.0, CH2Cl2); 1H NMR δ
5.68-5.81 (m, 2 H), 5.58-5.64 (m, 1 H), 5.37-5.42 (m, 1 H),
4.25-4.29 (m, 1 H), 4.03-4.13 (m, 2 H), 3.82-3.86 (m, 1 H),
3.64-3.70 (m, 1 H), 2.65 (d, 1 H, J=9.6 Hz), 2.42-2.48 (m,1 H),
2.31-2.35 (m, 2 H), 2.18-2.25 (m, 4 H), 1.81-1.86 (m, 1 H),
1.60-1.75 (m, 4 H), 1.49-1.55 (m, 2 H), 1.37-1.44 (m, 1 H),
1.26-1.36 (m, 3 H), 0.88-0.90 (m, 21 H), 0.01-0.09 (m, 12 H);
13C NMR δ u 119.9, 38.6, 37.1, 32.2, 31.8, 26.4, 25.3, 25.2, 22.6,
18.2, 18.1, 16.5, d 136.8, 128.7, 128.0, 127.8, 83.9, 79.7, 74.1,
74.0, 72.6, 25.90 (3), 25.87 (3), 14.1, -4.1, -4.3, -4.6, -4.9; IR
(film) 3449, 2932, 2250, 1254, 1074, 835 cm-1; HRMS calcd for
C32H61NO4Si2Na 602.4037, found 602.4023.
Isofuran 1aaa. To a stirred solution of 17aaa (45 mg,
0.078 mmol) in THF (0.8 mL) was added a 1 M solution of
Bu4NF (1.0 M in THF, 1.0 mL). After an additional 1.5 h at rt,
the reaction mixture was partitioned between CH2Cl2 and H2O.
The organic extract was concentrated to afford the crude triol.
The crude triol was dissolved in EtOH (1.0 mL), and then 15%
aqueous NaOH (2.0 mL) was added. After an additional 16 h at
85 °C, the reaction mixture was cooled to rt and acidified with
NaH2PO4 (0.5 M, 3 mL) and AcOH (3 mL). The mixture was
partitioned beween CH2Cl2 and water. The organic extract was
concentrated, and the residue was chromatographed to give
1aaa (26 mg, 89% yield from 17aaa): TLC Rf (Et2O/0.5 M
aqueous NaH2PO4/HOAc=90/9/1)=0.35; [R]D þ25.0 (c 0.5,
CH2Cl2), [R]D þ35.4 (c 0.58, CH3OH); 1H NMR δ 5.98 (s, 3 H),
5.81-5.82 (m, 2 H), 5.44-5.49 (m, 2 H), 4.08-4.16 (m,4 H),
3.86-3.87 (m, 1 H), 2.35 (s, 1 H), 2.02-2.27 (m, 7 H), 1.70 (s, 2
H), 1.22-1.53 (m, 9 H), 0.86-0.91 (m, 3 H); 13C NMR δ u 36.7,
34.1, 31.8, 26.4, 25.2, 24.4, 22.6, d 137.5, 131.6, 126.0, 125.9,
84.0, 80.4, 73.1, 72.0, 71.8, 30.3, 14.1; the carbonyl carbon was
not observed; IR (film) 3334, 2925, 1708, 1018 cm-1; HRMS
calcd for C20H34O6Na 393.2253, found 393.2246.
Isofuran 1aab. The reaction was performed with the alcohol
17aab (36 mg, 0.062 mmol) in the same manner as described for
the preparation of isofuran 1aaa to give isofuran 1aab (24 mg,
92% yield from 17aab): TLC Rf (Et2O/0.5 M aqueous NaH2-
PO4/HOAc=90/9/1)=0.38; [R]D þ15.6 (c 0.48, CH2Cl2), [R]D
þ23.1 (c 0.50, CH3OH); 1H NMR δ 5.71-5.88 (m, 3 H), 5.43-
5.48 (m, 3 H), 4.05-4.20 (m, 4 H), 3.89 (s, 1 H), 2.36 (s, 2 H),
2.04-2.27 (m, 6 H), 1.70-1.73 (m, 2 H), 1.43-1.57 (m, 3 H),
1.25-1.36 (m, 7 H), 0.86-0.89 (m, 3 H); 13C NMR δ u 178.1,
36.5, 34.2, 32.0, 31.8, 26.4, 25.2, 24.4, 22.6, d 136.5, 131.3, 126.2,
126.2, 83.1, 80.3, 72.7, 72.3, 71.8, 30.3, 14.1; the carbonyl carbon
was not initially observed, but when 1aab was prepared by
saponification of the ester 18aab, the carbonyl was evident; IR
(film) 3447, 3034, 2926, 1708, 1240, 1018 cm-1; HRMS calcd for
C20H34O6Na 393.2253, found 393.2246.
Ester 18aab. To a stirred solution of isofuran 1aab (8 mg,
0.021 mmol) in MeOH/benzene (1:4, 0.5 mL) was added tri-
methylsilyl diazomethane (2.0 M in Et2O, 50 uL). The mixture
was stirred at room temperature for 20 min. The mixture was
concentrated, and the residue was chromatographed to afford the
ester 18aab (8 mg, 96% yield from the isofuran 1aab): TLC Rf
(acetone/CH2Cl2=4/1)=0.38; [R]D þ23.8 (c 0.38, CH2Cl2), [R]D
þ23.1 (c 0.55, CH3OH); 1H NMR δ 5.81-5.87 (m, 1 H), 5.73 (dd,
J=15.6 and 5.2 Hz, 1 H), 5.44-5.51 (m, 2 H), 4.88 (s, 1 H), 4.79 (s,
1 H), 4.18-4.20 (m, 1 H), 4.11-4.16 (m, 2 H), 4.02-4.08 (m, 1 H),
3.85-3.90 (m, 1 H), 3.70-3.85 (m, 1 H), 3.67 (s, 3 H), 2.32 (t, 2 H,
J=7.2 Hz), 2.03-2.29 (m, 5 H), 1.66-1.74 (m, 3 H), 1.41-1.60 (m,
2 H), 1.21-1.38 (m, 6 H), 0.87 (t, 3 H, J=6.4 Hz); 13C NMR
δ u 174.0, 36.5, 34.0, 33.4, 32.2, 31.7, 26.7, 25.3, 24.7, 22.6, d 136.4,
131.2, 126.5, 126.2, 83.1, 80.2, 72.8, 72.2, 71.8, 51.5, 14.1; HRMS
calcd for C21H36O6Na 407.2404, found 407.2410.
Alcohol 14aa. To a stirred solution of 4aa (20 mg,
0.0275 mmol) in CH2Cl2 (4 mL) was added diethyl aluminum
chloride (1 N in hexane, 0.15 mL, 0.15 mmol) at - 78 °C. After
an additional 10 min, the reaction mixture was quenched with
water and filtered through a pad of silica gel, washing with
methanol. The filtrate was concentrated, and the residue was
chromatographed to give the desired alcohol 14aa (11.2 mg,
84% yield from the ether 4aa): TLC Rf (MTBE/petroleum ether
=3/7)=0.32; [R]D -5.2 (c 1.0, CH2Cl2); 1H NMR δ 5.58-5.61
(m, 1 H), 5.38-5.41 (m, 1 H), 4.50 (dd, 1 H, J=6.0 and 13.2 Hz),
3.79-3.83 (m, 2 H), 3.72-3.75 (m, 2 H), 3.63-3.68 (m, 1 H),
2.32-2.40 (m, 4 H), 2.17-2.25 (m, 4 H), 1.78-1.83 (m, 1 H),
1.70-1.76 (m, 2 H), 0.88 (s, 18 H), 0.07 (s, 12 H); 13C NMR δ u
119.7, 62.7, 38.1, 32.5, 26.5, 25.3, 18.1, 18.0, 16.5, d 128.8, 127.7,
81.1, 79.4, 73.8(2), 25.9, 25.8, -4.2, -4.4, -4.6, -5.2; IR (film)
2932, 2256, 1254, 1079, 835 cm-1; HRMS calcd for C25H49NO4-
Si2Na 506.3098, found 506.3097.
Enone 16aa. To a stirred solution of 14aa (64 mg, 0.13 mmol)
in CH2Cl2 (1.5 mL) was added Dess-Martin periodinane
(111 mg, 0.26 mmol). After an additional 40 min at rt, the
reaction mixture was directly poured on the silica gel and
chromatographed to afford the crude aldehyde (53 mg).
To a stirred suspension of NaH (26 mg, 0.66 mmol) in THF
(5 mL) was added dimethyl 2-oxoheptylphosphonate 15
(244 mg, 1.10 mmol) at 0 °C. After an additional 1 h at 0 °C, a
solution of the crude aldehyde (53 mg) in THF (1 mL) was
added. After an additional 40 min at 0 °C, the mixture was
partitioned between CH2Cl2 and saturated aqueous NH4Cl. The
organic extract was dried (Na2SO4) and concentrated. The
residue was chromatographed to afford 16aa (64 mg, 84% yield
from 14aa): TLC Rf (MTBE/petroleum ether=3/7)=0.73; [R]D
þ5.9 (c 1.0, CH2Cl2); 1H NMR δ 6.79 (dd, 1 H, J=4.2 and 16.0
Hz), 6.26 (dd, 1 H, J=1.6 and 16.0 Hz), 5.59-5.64 (m, 1 H),
5.39-5.45 (m, 1 H), 4.42-4.46 (m, 1 H), 4.28 (dt, 1 H, J=1.6 and
5.6 Hz), 3.86 (q, 1 H, J=5.2 Hz), 3.74 (q, 1 H, J=7.2 Hz), 2.54-
2.58 (m, 2 H), 2.43-2.50 (m, 1 H), 2.19-2.35 (m, 6 H), 1.82-
1.89 (m, 1 H), 1.70-1.77 (m, 2 H), 1.59-1.66 (m, 2 H), 1.25-
1.37 (m, 4 H), 0.86-0.90 (m, 21 H), 0.09 (s, 6 H), 0.05 (s, 3 H),
0.02 (s, 3 H); 13C NMR δ u 200.5, 119.7, 39.9, 38.3, 32.4, 31.5,
26.3, 25.3, 23.8, 22.5, 18.1, 18.0, 16.5, d 142.7, 130.8, 128.9,
127.6, 82.3, 80.1, 74.3, 73.8, 25.9, 25.8, 13.9, -4.1, -4.3, -4.7, -
5.0; IR (film) 3442, 2929, 2250, 1641, 833, 775 cm-1; HRMS
calcd for C32H59NO4Si2Na 600.3880, found 600.3876.
Alcohols 17aaa and 17aab. To a stirred solution of 16aa
(118 mg, 0.20 mmol) in MeOH (6 mL) was added CeCl3 7H2O
3
(74 mg, 0.20 mmol). After 5 min, NaBH4 (12 mg) was added. The
mixture was stirred for an additional 30 min at rt, and then the
reaction mixture was filtered through a pad of silica gel, washing
with MTBE, the filtrate was concentrated, and the residue was
chromatographed to give the desired alcohol 17aaa (45 mg, 38%
yield from the enone 16aa): TLC Rf (Et2O/CH2Cl2/petroleum
1
ether = 1/3/6) = 0.23; [R]D þ4.5 (c 1.0, CH2Cl2); H NMR δ
5.75-5.82 (m, 2 H), 5.58-5.62 (m, 1 H), 5.36-5.43 (m, 1 H),
4.28-4.31 (m, 1 H), 4.06-4.15 (m, 2 H), 3.84 (q, 1 H, J=4.8 Hz),
3.66 (q, 1 H, J=7.2 Hz), 2.65 (d, 1 H, J=9.6 Hz), 2.39-2.47 (m, 1
H), 2.30-2.34 (m, 2 H), 2.17-2.27 (m, 4 H), 1.83-1.87 (m, 1 H),
1.68-1.76 (m, 2 H), 1.50-1.56 (m, 4 H), 1.26-1.43 (m, 4 H),
0.87-0.90 (m, 21 H), 0.03-0.08 (m, 12 H); 13C NMR δ u: 119.8,
38.3, 37.1, 32.3, 31.8, 26.4, 25.3, 25.2, 22.6, 18.2, 18.1, 16.5 d:
136.3, 128.7, 127.9, 127.6, 83.5, 79.7, 74.3, 74.0, 72.4, 25.9 (3),
25.9 (3), 14.1, -4.1, -4.3, -4.6, -4.9; IR (film) 2931, 2250, 1464,
J. Org. Chem. Vol. 74, No. 15, 2009 5521