6510
H. Uehara et al. / Tetrahedron 58 (2002) 6493–6512
2.27 (1H, dt, J¼12.0, 5.0 Hz), 2.58–2.64 (1H, m), 2.85 (1H,
dd, J¼9.5, 4.5 Hz), 2.98–3.04 (1H, m), 3.17 (1H, ddd,
J¼11.0, 9.0, 5.0 Hz), 3.23 (1H, dd, J¼9.0, 3.0 Hz), 3.29
(1H, t, J¼9.5 Hz), 3.45 (1H, td, J¼9.0, 3.0 Hz), 3.65 (1H, d,
J¼10.0 Hz), 3.69–3.76 (2H, m), 3.76 (1H, q, J¼8.0 Hz),
3.79 (3H, s), 3.86 (1H, td, J¼8.0, 5.0 Hz), 4.14–4.21 (2H,
m), 4.29 (1H, d, J¼11.0 Hz), 4.55 (1H, d, J¼11.0 Hz), 4.62
(1H, d, J¼11.5 Hz), 4.68 (1H, d, J¼11.5 Hz), 4.81 (1H, d,
J¼6.5 Hz), 4.84 (1H, d, J¼6.5 Hz), 6.81–6.88 (3H, m),
7.20–7.24 (2H, m), 7.25–7.38 (5H, m); MALDI-TOF MS,
calcd for C47H66O11Na 829.450 (MþNaþ), found 829.459.
chromatography (hexane/EtOAc 12:1–3:1) gave the epoxy
alcohol 70 (174 mg, 223 mmol) in 97% yield. 70: colorless
oil; Rf¼0.70 (hexane/EtOAc 1:1); [a]2D9¼231.6 (c 0.994,
CHCl3); IR (film) n 3479, 2929, 2873, 1613, 1514, 1455,
1
1380, 1249, 1176, 1101, 1073, 1037, 822, 735 cm21; H
NMR (500 MHz, CDCl3) d 0.87 (3H, d, J¼6.5 Hz, Me57),
1.03 (3H, d, J¼6.0 Hz, Me56), 1.08 (3H, d, J¼7.0 Hz,
Me54), 1.14 (3H, d, J¼7.5 Hz, Me55), 1.27 (3H, s, Me53),
1.39 (1H, q, J¼11.5 Hz, H40), 1.45–1.61 (3H, m, H37, 47,
48), 1.64–1.99 (10H, m, H32£2, 35£2, 36, 37, 50£2,
51£2), 2.09–2.14 (1H, m, H43), 2.32 (1H, dt, J¼12.0,
5.0 Hz, H40), 2.87 (1H, dd, J¼9.5, 4.5 Hz, H42), 3.06 (1H,
td, J¼9.5, 4.5 Hz, H38), 3.20 (1H, t, J¼6.0 Hz, H31), 3.22–
3.28 (1H, m, H39), 3.31 (1H, t, J¼9.5 Hz, H46), 3.30–3.35
(1H, m, H34), 3.49–3.54 (1H, m, H33), 3.56 (1H, dd,
J¼12.5, 8.0 Hz, H29), 3.65 (1H, d, J¼9.5 Hz, H45), 3.68
(1H, dd, J¼12.5, 4.0 Hz, H29), 3.72–3.81 (3H, m, H41, 44,
52), 3.79 (3H, s, MPM), 3.86 (1H, td, J¼8.0, 4.5 Hz, H52),
4.31 (1H, d, J¼11.0 Hz, MPM), 4.54 (1H, d, J¼11.0 Hz,
MPM), 4.62 (1H, d, J¼11.5 Hz, BOM), 4.68 (1H, d,
J¼11.5 Hz, BOM), 4.81 (1H, d, J¼7.0 Hz, BOM), 4.85 (1H,
d, J¼7.0 Hz, BOM), 6.84–6.87 (2H, m, MPM), 7.20–7.38
(7H, m, MPM, BOM); 13C NMR (125 MHz, CDCl3) d 13.3,
14.2, 15.6, 19.9, 24.2, 26.2, 27.9, 33.2, 34.8, 38.4, 38.7,
39.5, 40.5, 41.7, 44.0, 55.1, 57.6, 59.9, 65.5, 67.2, 69.0,
70.9, 71.1, 74.2, 78.2, 80.0, 81.7, 81.8, 81.9, 83.6, 86.7,
93.4, 108.2, 113.6, 127.4, 127.9, 128.2, 129.5, 130.3, 138.0,
159.1; MALDI-TOF MS, calcd for C45H64O11Na 803.435
(MþNaþ), found 803.439.
4.5.5. Allyl alcohol 69. To a solution of the a,b-unsaturated
ester 68 (194 mg, 240 mmol) in CH2Cl2 (2.4 ml) at 2608C
was added DIBAL (0.8 ml, 0.93 M in hexane, 0.74 mmol)
over 10 min. After being stirred for 20 min at 2608C, the
reaction mixture was quenched with EtOAc at 2608C,
diluted with EtOAc, and stirred with aqueous saturated
Rochelle’s salt for 2 h. The mixture was extracted with
EtOAc (£3), and the combined organic layer was washed
with brine and dried over MgSO4. Concentration and flash
column chromatography (hexane/EtOAc 1:0–5:1) afforded
the allyl alcohol 69 (175 mg, 229 mmol) in 95% yield. 69:
colorless oil; Rf¼0.25 (hexane/EtOAc 3:1); [a ]3D0¼236.0
(c 0.985, CHCl3); IR (film) n 3469, 2927, 2873, 1612, 1514,
1
1454, 1249, 1178, 1101, 1074, 1038, 754 cm21; H NMR
(500 MHz, CDCl3) d 0.88 (3H, d, J¼6.5 Hz, Me57), 1.03
(3H, d, J¼6.0 Hz, Me56), 1.07 (3H, d, J¼7.5 Hz, Me54),
1.14 (3H, d, J¼7.0 Hz, Me55), 1.30 (1H, q, J¼11.5 Hz,
H40), 1.66 (3H, s, Me53), 1.45–1.95 (11H, m, H35£2, 36,
37£2, 47, 48, 50£2, 51£2), 2.03–2.14 (2H, m, H32, 43),
2.26 (1H, dt, J¼12.0, 5.0 Hz, H40), 2.45–2.51 (1H, m,
H32), 2.85 (1H, dd, J¼9.0, 4.5 Hz, H42), 3.01 (1H, td,
J¼9.5, 3.5 Hz, H38), 3.16 (1H, ddd, J¼11.5, 9.0, 5.0 Hz,
H39), 3.23 (1H, td, J¼9.0, 2.0 Hz, H34), 3.31 (1H, t,
J¼9.5 Hz, H46), 3.37 (1H, td, J¼9.0, 2.5 Hz, H33), 3.65
(1H, d, J¼9.0 Hz, H45), 3.69–3.75 (2H, m, H41, 44), 3.76
(1H, q, J¼7.5 Hz, H52), 3.79 (3H, s, MPM), 3.86 (1H, td,
J¼7.5, 4.5 Hz, H52), 3.98–4.04 (2H, m, H29£2), 4.29 (1H,
d, J¼11.0 Hz, MPM), 4.55 (1H, d, J¼11.0 Hz, MPM), 4.62
(1H, d, J¼11.5 Hz, BOM), 4.68 (1H, d, J¼11.5 Hz, BOM),
4.81 (1H, d, J¼6.5 Hz, BOM), 4.84 (1H, d, J¼6.5 Hz,
BOM), 5.48 (1H, t, J¼7.0 Hz, H31), 6.84–6.87 (2H, m,
MPM), 7.20–7.38 (7H, m, MPM, BOM); 13C NMR
(125 MHz, CDCl3) d 13.4, 14.0, 15.7, 20.0, 24.2, 26.5,
28.1, 32.6, 34.9, 38.5, 39.3, 39.5, 40.5, 41.8, 44.2, 55.2,
67.3, 68.9, 69.0, 70.9, 71.2, 74.4, 78.3, 80.3, 81.8, 81.9,
82.0, 86.0, 86.7, 93.5, 108.3, 113.7, 122.9, 127.5, 128.0,
128.2, 129.5, 130.4, 136.5, 138.1, 159.1; MALDI-TOF MS,
calcd for C45H64O10Na 787.440 (MþNaþ), found 787.445.
4.5.7. Vinyl epoxide 72. To a solution of epoxy alcohol 70
(174 mg, 223 mmol) and Et3N (0.6 ml, 4.4 mmol) in
(CH2Cl)2 (0.6 ml) and DMSO (0.6 ml) at 08C was added
SO3·pyridine complex (220 mg, 1.4 mmol). After being
stirred for 40 min at rt, the mixture was diluted with
EtOAc and aqueous NH4Cl, and extracted with EtOAc
(£3). The organic layer was washed with brine and dried
over MgSO4, and concentrated. The residue was purified
by florisil column chromatography to afford the aldehyde,
which was subjected to the next reaction without further
purification. A mixture of triphenylphosphonium bromide
(394 mg, 1.10 mmol) in THF (0.6 ml) was treated with
NaHMDS (0.9 ml, 1 M in THF, 0.9 mmol) at 08C for
15 min. To the resultant yellow suspension at 08C was
added dropwise a solution of the aldehyde in THF
(2.3 ml). The reaction mixture was stirred at 08C for
45 min, quenched with aqueous saturated NH4Cl, and
extracted with EtOAc (£3). The organic layer was
washed with brine and dried over MgSO4. Concentration
and flash column chromatography (hexane/EtOAc 1:0–
10:1) gave the vinyl epoxide 72 (148 mg, 191 mmol) in
86% yield over 2 steps. 72: colorless oil; Rf¼0.60
(hexane/EtOAc 3:1); [a ]2D9¼245.0 (c 1.070, CHCl3); IR
(film) n 2929, 2874, 1612, 1514, 1455, 1249, 1176, 1102,
4.5.6. Epoxy alcohol 70. To a solution of allyl alcohol 69
(175 mg, 229 mmol), D-(2)-DET (40 ml, 230 mmol), and
activated powdered MS4 A (100 mg) in CH2Cl2 (3.0 ml) at
2508C was added Ti(Oi-Pr)4 (50 ml, 170 mmol). After
10 min, TBHP (0.8 ml, 3 M in CH2Cl2, 2.4 mmol) was
added to the mixture, and the reaction temperature kept
below 2408C for 3 h. The mixture was diluted with Et2O
(8 ml), and 30% aqueous NaOH saturated with NaCl (4 ml)
were added. The mixture was stirred overnight at rt, and
then diluted with aqueous saturated NH4Cl and extracted
with EtOAc (£3). The organic layer was washed with brine
and dried over MgSO4. Concentration and flash column
1074, 1038, 755 cm21 1H NMR (500 MHz, CDCl3) d
;
0.87 (3H, d, J¼6.5 Hz, Me57), 1.03 (3H, d, J¼6.0 Hz,
Me56), 1.06 (3H, d, J¼6.5 Hz, Me54), 1.14 (3H, d,
J¼7.0 Hz, Me55), 1.35 (1H, q, J¼11.5 Hz, H40), 1.39
(3H, s, Me53), 1.45–1.97 (13H, m, H32£2, 35£2, 36,
37£2, 47, 48, 50£2, 51£2), 2.10–2.14 (1H, m, H43),
2.30 (1H, dt, J¼12.5, 5.0 Hz, H40), 2.87 (1H, dd, J¼9.0,
4.5 Hz, H42), 3.02 (1H, t, J¼6.5 Hz, H31), 3.03–3.08
(1H, m, H38), 3.23 (1H, ddd, J¼9.0, 7.0, 4.5 Hz, H39),