688
K. C. Nicolaou et al. / Bioorg. Med. Chem. 7 (1999) 665±697
2954, 2928, 2856, 1682, 1472, 1448, 1253, 1090, 994,
1
20% ether in hexanes); [a]2d2 16.8 (c 0.7, CHCl3); IR
(thin ®lm) nmax 3058, 2951, 2856, 1693, 1471, 1253,
1079, 1004, 836, 706 cm 1; 1H NMR (600 MHz, CDCl3)
d 7.46±7.43 (m, 5H, Ph), 7.29±7.19 (m, 10H, Ph), 6.19 (s,
1H, CHCCH3), 5.49 (dd, J=7.0, 7.0 Hz, 1H,
CCHCH2), 4.18 (dd, J=6.3, 6.1 Hz, 1H, CHOSi), 3.85
(dd, J=7.6, 2.5 Hz, 1H, CHOSi), 3.70 (dd, J=6.7,
2.0 Hz, 1H, CHOSi), 3.67 (ddd, J=9.6, 4.8, 4.8 Hz, 1H,
CH2OSi), 3.59 (ddd, J=9.7, 7.9. 7.9 Hz, 1H, CH2OSi),
3.45 (d, J=11.2 Hz, 1H, CH2OTr), 3.42 (d, J=11.2 Hz,
1H, CH2OTr), 3.08 (qd, J=6.8, 6.8 Hz, 1H,
CH3CH(CO)), 2.27 (ddd, J=14.4, 7.2, 7.2 Hz, 1H,
CCHCH2CHOSi), 2.23 (ddd, J=14.5, 6.2, 6.2 Hz, 1H,
CCHCH2CHOSi), 1.97 (m, 2H, CH2C(CH2OTr)CH),
1.79 (s, 3H, CHC(CH3)), 1.57 (m, 1H), 1.46 (m, 1H),
1.25 (m, 3H), 1.17 (s, 3H, C(CH3)2), 1.01 (d, J=6.8 Hz,
3H, CH(CH3)), 0.95 (s, 3H, C(CH3)2), 0.87 (s, 18H,
SiC(CH3)3), 0.86 (s, 18H, SiC(CH3)3), 0.09±0.03 (m,
24H, Si(CH3)2); 13C NMR (150.9 MHz, CDCl3) d 218.2,
150.2, 144.3, 138.7, 128.6, 127.7, 126.8, 121.5, 86.5, 77.5,
77.4, 77.3, 74.0, 67.1, 60.9, 53.6, 45.1, 38.7, 38.0, 34.6,
31.0, 29.3, 26.5, 26.2, 26.1, 25.9, 25.8, 24.4, 19.7, 19.5,
18.5, 18.3, 18.2, 18.1, 17.5, 15.1, 3.6, 3.7, 3.8, 4.0,
836, 775, 706, 668, 632 cm
;
1H NMR (600 MHz,
CDCl3) d 7.45±7.43 (m, 5H, Ph), 7.30±7.19 (m, 10H,
Ph), 6.19 (s, 1H, CHCCH3), 5.51 (dd, J=7.0, 6.9 Hz,
1H, CCHCH2), 4.18 (dd, J=6.3, 6.2 Hz, 1H, CHOSi),
3.88 (dd, J=7.5, 2.6 Hz, 1H, CHOSi), 3.65 (m, 1H,
CH2OSi), 3.59 (m, 1H, CH2OSi), 3.46 (d, J=11.2 Hz,
1H, CH2OTr), 3.43 (d, J=11.2 Hz, 1H, CH2OTr), 3.27
(m, 1H, CH3CH(CO)), 3.22 (d, J=9.3 Hz, 1H,
CHOH), 2.32±2.18 (m, 2H, CCHCH2CHOSi), 2.00
(m, 2H, CH2(C)CH2OTr), 1.80 (s, 3H, CHC(CH3)),
1.66 (m, 2H), 1.46 (m, 2H), 1.27 (m, 1H, CH(CH3), 1.19
(s, 3H, C(CH3)2), 1.07 (s, 3H, C(CH3)2), 0.99 (d,
J=6.8 Hz, 3H, CH(CH3)), 0.89 (s, 9H, SiC(CH3)3), 0.87
(s, 9H, SiC(CH3)3), 0.86 (s, 9H, SiC(CH3)3), 0.71 (d,
J=6.7 Hz, 3H, CH(CH3)), 0.10 (s, 3H, Si(CH3)2), 0.07
(s, 3H, Si(CH3)2), 0.04 (s, 3H, Si(CH3)2), 0.03 (s, 6H,
Si(CH3)2),
0.01 (s, 3H, Si(CH3)2); 13C NMR
(150.9 MHz, CDCl3) d 222.1, 150.1, 144.1, 138.6, 128.5,
127.6, 126.7, 121.1, 86.4, 77.4, 74.8, 74.1, 67.1, 60.4,
54.0, 41.2, 37.9, 35.4, 34.7, 33.0, 29.2, 26.2, 26.0, 25.9,
25.7, 23.0, 20.6, 19.8, 18.4, 18.3, 18.2, 15.4, 9.6, 3.5,
3.9, 4.7, 4.8,
5.1; HRMS (FAB), calcd for
C60H97IO6Si3 (M+Cs+) 1257.4692, found 1257.4639.
38: (minor) colorless oil; Rf=0.38 (silica gel, 20% ether
in hexanes); [a]2d2 11.9 (c 2.9, CHCl3); IR (thin ®lm)
nmax 3501, 2954, 2930, 2856, 1682, 1469, 1254, 1088,
4.9, 5.0,
5.2, 5.3; HRMS (FAB), calcd for
C66H111IO6Si4 (M+Cs+) 1371.5557, found 1371.5523.
Alcohol 40. To a solution of tetra-silyl ether 39
(180 mg, 0.145 mmol) in THF (1.5 mL) at 0ꢀC was
added HFꢁ pyr. in pyr./THF mixture (prepared from a
stock solution containing 420 mL HFꢁ pyr., 1.14 mL pyr.
and 2.00 mL THF) (1.5ꢀmL) and the resulting solution
was stirred for 2 h at 0 C. More HFꢁ pyr. in the pyr./
THF mixture (0.5 mL) was then added and stirring was
continued for additional 1 h at 0ꢀC. The reaction was
quenched by careful addition of saturated aqueous
NaHCO3 and the product was extracted with EtOAc
(3Â25 mL). The combined organic extracts were then
dried (MgSO4) and concentrated under reduced pres-
sure. Flash column chromatography (silica gel 30%
ether in hexanes) furnished alcohol 40 as a pale yellow
oil (137 mg, 84%). Rf=0.36 (silica gel, 40% ether in
hexanes); [a]d22 26.0 (c 0.3, CHCl3); IR (thin ®lm) nmax
1
836, 776, 705, 670 cm 1; H NMR (500 MHz, CDCl3) d
7.46±7.44 (m, 5H, Ph), 7.31±7.21 (m, 10H, Ph), 6.21 (s,
1H, CHC(CH3)), 5.52 (dd, J=7.0, 6.9 Hz , 1H,
CCHCH2), 4.20 (dd, J=6.5, 6.5 Hz, 1H, CHOSi), 3.88
(dd, J=7.5, 2.5 Hz, 1H, CHOSi), 3.67 (m, 1H,
CH2OSi), 3.60 (m, 1H, CH2OSi), 3.46 (s, 2H, CH2OTr),
3.30±3.21 (m, 2H, CHOH, CH3CH(CO)), 2.30±2.25
(m, 2H, CCHCH2CHOSi), 2.05±1.93 (m, 2H,
CH2C(CH2OTr)CH), 1.81 (s, 3H, CHC(CH3)), 1.63
(m, 1H, CH(CH3)), 1.45 (m, 2H), 1.24 (m, 2H), 1.19 (s,
3H, C(CH3)2), 1.05 (s, 3H, C(CH3)2), 1.01 (d, J=6.9 Hz,
3H, CH(CH3)), 0.89 (s, 9H, SiC(CH3)3), 0.88 (obscured
d, 3H, CH(CH3)), 0.88 (s, 18H, SiC(CH3)3), 0.11 (s, 3H,
Si(CH3)2), 0.07 (s, 3H, Si(CH3)2), 0.06 (s, 3H, Si(CH3)2),
0.04 (s, 6H, Si(CH3)2), 0.01 (s, 3H, Si(CH3)2); 13C NMR
(125.7 MHz, CDCl3) d 221.8, 150.1, 144.2, 138.6, 128.7,
127.8, 126.9, 121.6, 86.5, 77.4, 77.3, 75.0, 74.0, 67.1,
60.5, 53.9, 53.4, 41.6, 37.8, 35.4, 34.7, 32.9, 29.0, 26.1,
25.9, 25.7, 23.2, 20.2, 19.8, 18.3, 18.2, 18.1, 15.4, 10.5,
3.7, 4.1, 4.9, 5.0, 5.3; HRMS (FAB), calcd for
C60H97IO6Si3 (M+Cs+) 1257.4692, found 1257.4749.
3422, 2928, 2855, 1690, 1490, 1471, 1448, 1360, 1252,
1086, 1004, 986, 836, 774, 706 cm
;
1H NMR
1
(600 MHz, CDCl3) d 7.44±7.42 (m, 5H, Ph), 7.29±7.20
(m, 10H, Ph), 6.19 (s, 1H, CHCCH3), 5.49 (dd, J=7.1,
7.1 Hz, 1H, CCHCH2), 4.17 (dd, J=6.2, 6.0 Hz, 1H,
CHOSi), 4.03 (dd, J=6.6, 3.7 Hz, 1H, CHOSi), 3.73
(dd, J=7.2, 1.7 Hz, 1H, CHOSi), 3.65 m, 2H, CH2OH),
3.45 (d, J=11.7 Hz, 1H, CH2OTr), 3.42 (d, J=11.7 Hz,
1H, CH2OTr), 3.06 (qd, J=6.9, 6.9 Hz, 1H,
CH3CH(CO)), 2.28 (ddd, J=14.7, 7.3, 7.3 Hz, 1H,
CCHCH2CHOSi), 2.22 (ddd, J=14.7, 6.3, 6.3 Hz, 1H,
CCHCH2CHOSi), 1.98 (m, 2H, CH2C(CH2OTr)CH),
1.79 (s, 3H, CHC(CH3)), 1.56 (m, 2H), 1.24 (m, 3H),
1.18 (s, 3H, C(CH3)2), 1.03 (d, J=6.9 Hz, 3H,
CH(CH3)), 0.97 (s, 3H, C(CH3)2), 0.87 (3 singlets, 27H,
SiC(CH3)3), 0.81 (d, J=6.7 Hz, 3H, CH(CH3)), 0.10 (s,
3H, Si(CH3)2), 0.04 (s, 9H, Si(CH3)2), 0.03 (s, 3H,
Si(CH3)2), 0.00 (s, 3H, Si(CH3)2); 13C NMR
(150.9 MHz, CDCl3) d 219.2, 150.0, 144.1, 138.5, 128.5,
127.6, 126.7, 121.4, 86.4, 77.5, 77.4, 77.3, 73.1, 67.2,
60.2, 53.7, 45.2, 38.6, 38.4, 34.7, 30.9, 29.4, 26.6, 26.3,
tetra-(Silylether) 39. Alcohol 37 (1.136 g of a 9:1 mix-
ture with aldehyde 35, 0.933 mmol, 1.0 equiv) was dis-
solved in CH2Cl2 (5.0 mL), cooled to 20ꢀC and treated
with 2,6-lutidine (470 mL, 4.04 mmol, 4.3 equiv) and
tert-butyldimethylsilyl tri¯uoromethanesulfonate (695mL,
3.03 mmol, 3.2 equiv). The mixture was then stirred for
2.5 h with slow warming to 0ꢀC. The reaction was then
quenched with saturated aqueous NaHCO3 (25 mL) and
the aqueous phase was extracted with ether (3Â25 mL).
The combined organic extracts were washed with brine
(250 mL), dried (MgSO4) and concentrated under
reduced pressure. Flash column chromatography (silica
gel, 4!9% ether in hexanes) furnished tetra-(silylether)
39 as a colorless oil (1.04 g, 90%). Rf=0.91 (silica gel,