1832
M. T. Crimmins et al. / Tetrahedron 58 ,2002) 1817±1834
room temperature and stirred for 30 min. After ®ltering the
suspension through Celite, the solution was dried over
Na2SO4. Concentration in vacuo and puri®cation by ¯ash
chromatography provided 0.161 g &94%) of epoxide 43: 1H
NMR &300 MHz, CDCl3) d 5.53±5.38 &m, 2H), 4.20 &m,
1H), 4.02 &dt, J11.1, 4.5 Hz, 1H), 3.93 &m, 1H), 3.84 &m,
1H), 3.76 &ddd, J10.2, 5.4, 3.0 Hz, 1H), 3.64 &ddd, J12.8,
7.7, 2.1 Hz, 1H), 3.20 &m, 1H), 3.03±2.83 &m, 3H), 3.00 &m,
1H), 2.22±2.00 &m, 4H), 1.78±1.49 &m, 3H), 0.95 &t, J
7.8 Hz, 9H), 0.86 &t, J7.5 Hz, 3H), 0.61&m, 6H); 13C
NMR &75 MHz, CDCl3) d 5.1, 7.0, 10.5, 23.6, 28.8, 32.9,
37.8, 55.9, 57.3, 60.9, 71.2, 75.1, 82.1, 82.3, 86.0, 127.5,
127.8; IR &®lm) 3740±3140 &br), 2960, 1460, 1270, 1245,
4H), 1.78±1.48 &m, 2H), 0.95 &t, J8.0 Hz, 9H), 0.86 &t,
J7.5 Hz, 3H), 0.62 &m, 6H); 13C NMR &75 MHz, CDCl3)
d 5.1, 7.0, 10.5, 23.6, 28.6, 32.9, 36.9, 64.7, 71.3, 73.8, 80.1,
82.0, 82.2, 82.3, 86.2, 127.3, 128.1; IR &®lm) 3700±3160
&br), 3320, 2960, 1465, 1270, 1245 cm21; [a]25 222.5 &c
D
0.64, CH2Cl2); Anal. Calcd for C21H36O4Si: C, 66.27; H,
9.53. Found: C, 65.52; H, 9.45.
6.1.36. 2,4,6-Triisopropyl-benzenesulfonic acid ꢀ1R)-1-
ꢀꢀ2R,3aS,5R,6R,10aS)-5-ethyl-6-triethylsilanyloxy-2,3,
3a,5,6,7,10,10a-octahydro-furo[3,2-b]oxonin-2-yl)-prop-
2-ynyl ester ꢀ19). Into a 25 mL ¯ask equipped with a re¯ux
condenser was placed alcohol 45 &0.0840 g, 0.221mmol)
and 5 mL of dichloromethane. 4-Dimethylaminopyridine
&0.0940 g, 0.769 mmol) and 2,4,6-triisopropylbenzenesulfo-
nyl chloride &0.167 g, 0.551 mmol) were added, and the
solution was heated to re¯ux for 2.5 h. The solution was
cooled to room temperature and ®ltered through a plug of
silica gel washing with dichloromethane. The ®ltrate was
condensed in vacuo, and puri®cation by ¯ash chroma-
1060 cm21; [a]27 236.7 &c 0.64, CH2Cl2).
D
6.1.34. [ꢀ2R,3aS,5R,6R,10aS)-2-ꢀꢀ2S,3R)-3-Chloromethyl-
oxiranyl)-5-ethyl-2,3,3a,5,6,7,10,10a-octahydro-furo-
[3,2-b]oxonin-6-yloxy]-triethyl-silane ꢀ44). Into a 25 mL
¯ask equipped with a re¯ux condenser was placed epoxy
alchohol 43 &0.0630 g, 0.158 mmol) and 5 mL of dichloro-
methane. Triphenylphosphine &0.050 g, 0.19 mmol) was
added followed by N-chlorosuccinimide &0.026 g, 0.19
mmol), and the solution was heated to re¯ux for 1h. The
solution was cooled and poured into half-saturated brine
with dichloromethane. The layers were separated, and the
aqueous layer was extracted with dichloromethane. The
organic layers were dried over Na2SO4 and concentrated
in vacuo. Puri®cation by ¯ash chromatography provided
0.0550 g &84%) of epoxy chloride 44: 1H NMR &300
MHz, CDCl3) d 5.53±5.38 &m, 2H), 4.23 &dt, J7.4,
3.3 Hz, 1H), 4.01 &dt, J11.1, 4.5 Hz, 1H), 3.84 &m, 1H),
3.77 &m, 1H), 3.56 &d, J5.4 Hz, 2H), 3.30 &dt, J5.4,
2.1Hz, 1H), 3.02±2.80 &m, 4H), 2.23±2.00 &m, 4H),
1.78±1.39 &2H), 0.95 &t, J8.0 Hz, 9H), 0.85 &t, J
7.5 Hz, 3H), 0.62 &m, 6H); 13C NMR &75 MHz, CDCl3) d
5.1, 7.0, 10.5, 23.6, 28.8, 32.9, 37.7, 44.3, 54.7, 60.5, 71.2,
74.5, 82.0, 82.4, 85.9, 127.5, 127.9; IR &®lm) 2960, 1465,
1
tography provided 0.137 g &96%) of trisylate 46: H NMR
&400 MHz, CDCl3) d 7.14 &s, 2H), 5.52±5.37 &m, 2H), 5.07
&dd, J5.2, 2.0 Hz, 1H), 4.38 &dd, J12.8, 7.2 Hz, 1H),
4.17±4.00 &m, 3H), 3.84±3.72 &m, 2H), 2.98±2.82 &m,
4H), 2.30±2.15 &m, 2H), 2.26 &d, J2.0 Hz, 1H), 2.11±
2.02 &m, 2H), 1.67 &m, 1H), 1.55 &m, 1H), 1.25 &m, 18H),
0.95 &t, J8.0 Hz, 9H), 0.85 &t, J7.4 Hz, 3H), 0.61&m,
6H); 13C NMR &100 MHz, CDCl3) d 5.1, 7.0, 10.6, 23.6,
23.8, 24.6, 24.7, 28.5, 29.7, 32.9, 34.2, 36.8, 71.2, 71.4,
77.2, 77.8, 82.2, 82.6, 86.4, 123.6, 127.2, 128.1, 130.5,
150.7, 153.7; IR &®lm) 3300, 2970, 1605, 1460, 1355,
1185, 1070 cm21; [a]25 234.0 &c 0.72, CH2Cl2); Anal.
D
Calcd for C36H58O6SSi: C, 66.83; H, 9.04. Found: C,
66.68; H, 8.94.
6.1.37. [ꢀ2R,3aS,5R,6R,10aS)-2-ꢀꢀ3R)-3-Bromo-propa-
1,2-dienyl)-5-ethyl-2,3,3a,5,6,7,10,10a-octahydro-furo-
[3,2-b]oxonin-6-yloxy]-triethyl-silane ꢀ47). Into a 50 mL
¯ask was added lithium bromide &0.260 g, 2.99 mmol) and
cuprous bromide &0.428 g, 2.98 mmol) and 12 mL of THF.
The solution was allowed to stir at room temperature for
20 min. Into a separate 25 mL ¯ask equipped with a re¯ux
condenser was placed trisylate 46 &0.0680 g, 0.105 mmol) in
3 mL of THF. The LiCuBr2 solution &0.25 M in THF,
2.1mL, 0.53 mmol) was added via syringe, and the solution
was heated to re¯ux for 8.5 h. The mixture was cooled to
room temperature and quenched by the addition of saturated
NH4Cl. The mixture was extracted with diethyl ether, and
the organic layer was washed with brine. The combined
aqueous layers were extracted with diethyl ether. The
combined organic layers were dried over Na2SO4 and
concentrated in vacuo. Puri®cation by ¯ash chromatography
1250, 1070, 980 cm21; [a]25 233.9 &c 0.74, CH2Cl2);
D
Anal. Calcd for C21H37ClO4Si: C, 60.48; H, 8.94. Found:
C, 60.27; H, 8.89.
6.1.35. ꢀ1R)-1-ꢀꢀ2R,3aS,5R,6R,10aS)-5-Ethyl-6-triethyl-
silanyloxy-2,3,3a,5,6,7,10,10a-octahydro-furo[3,2-b]oxo-
nin-2-yl)-prop-2-yn-1-ol ꢀ45). Into a 50 mL ¯ask was
added 8 mL of THF and diisopropylamine &0.34 mL,
2.4 mmol), and the solution was cooled to 2408C. Butyl
lithium &1.6 M in hexanes, 1.43 mL, 2.29 mmol) was
added dropwise via syringe. After 15 min chloride 44
&0.119 g, 0.286 mmol) in 4 mL of THF was added dropwise
via syringe. The solution was warmed to 2308C, where it
was maintained for 30 min. The reaction was quenched by
the addition of half-saturated NH4Cl, and the solution was
warmed to room temperature. The mixture was poured into
ethyl acetate, and the layers were separated. The organic
layer was washed with brine, and the combined aqueous
layers were extracted with ethyl acetate. The combined
organic layers were dried over Na2SO4 and concentrated
in vacuo. Puri®cation by ¯ash chromatography gave
0.0950 g &87%) of propargylic alcohol 45: 1H NMR
&300 MHz, CDCl3) d 5.55±5.38 &m, 2H), 4.28 &dd, J
14.0, 6.3 Hz, 1H), 4.17 &dd, J6.0, 1.8 Hz, 1H), 4.06 &dt,
J11.1, 4.5 Hz, 1H), 3.86±3.73 &m, 2H), 3.02±2.85 &m,
3H), 2.43 &d, J2.4 Hz, 1H), 2.39 &s, 1H), 2.23±2.00 &m,
2
provided 0.0042 g &9%) of a propargylic bromide SN
addition byproduct and 0.0361g &78%) of an 8:1mixture
of isomeric bromallenes in favor of the desired diastereomer
47: 1H NMR &300 MHz, CDCl3) d 6.05 &dd, J5.7, 1.7 Hz,
1H), 5.54±5.40 &m, 2H), 5.36 &dd, J5.7, 5.7 Hz, 1H), 4.77
&m, 1H), 4.03 &dt, J11.4, 4.5 Hz, 1H), 3.85 &m, 1H), 3.76
&ddd, J10.1, 5.4, 2.9 Hz, 1H), 3.03±2.84 &m, 3H), 2.27±
2.00 &m, 4H), 1.77±1.50 &m, 2H), 0.95 &t, J8.0 Hz, 9H),
0.87 &t, J7.5 Hz, 3H), 0.61&m, 6H); 13C NMR &75 MHz,
CDCl3) d 5.1, 7.0, 10.5, 23.8, 28.6, 33.0, 40.3, 71.2, 73.6,
73.7, 81.2, 82.0, 86.0, 101.8, 127.5, 127.9, 201.5; IR &®lm)