F.F. Wong et al. / Tetrahedron 66 (2010) 4068–4072
4071
3.6. Levonorgestrel (6)
1.02–2.31 (m, 19H), 2.56 (s, 1H, C^C–H), 3.49–3.54 (m, 1H, C-3H);
5.35 (d, J¼5.0 Hz, 1H, C]CH); IR (diffuse reflectance) 3430 (br,
OH), 3263 (s), 2936 (s), 2897 (s), 2859 (m), 2826 (m), 1650 (w),
1459 (m), 1436 (m), 1383 (s), 1249 (m), 1200 (w), 1162 (w), 1134
(m), 1053 (s), 1038 (s), 1023 (s), 842 (s), 701 (s), 623 (m), 582 (w),
553 (w), 483 (w); ESIMS m/z 313.0 (MꢀH)ꢀ.
Compound 5 (13.4 g, 44.6 mmol, 1.0 equiv) was dissolved in
anhydrous THF (100 mL) and reacted with lithium trimethylsiyl-
acetylide solution (3.0 equiv) at ꢀ40 ꢁC for 1.0 h. The reaction was
added with TBAF (1.0 M solution in THF, 0.050 equiv, 2.25 mL) and
warmed up to room temperature and stirred for 1.0 h. The reaction
mixture was neutralized with aqueous HCl (1 N) and concentrated
under reduced pressure to remove THF. The aqueous solution was
then added with additional H2O (100 mL) and extracted with EtOAc
(200 mLꢂ2). The organic layer was washed with brine (50 mLꢂ2)
and concentrated under reduced pressure. The resultant light
yellow solids were recrystallized from ethanol to give the desired 4
(12.6 g, 40.3 mmol) in 90% yield: mp (recrystallized from ethanol)
171–174 ꢁC; TLC Rf 0.26 (25% EtOAc in hexanes); 1H NMR (CDCl3,
3.9. 24-Norchol-5-en-22-yn-3b
-ol (12)21
Compound 9 (533 mg, 1.68 mmol, 1.0 equiv) was dissolved in
anhydrous THF (20 mL) and reacted with lithium trimethylsiyla-
cetylide solution (4.0 equiv) at ꢀ40 ꢁC for 1.0 h. The reaction was
added with TBAF (1.0 M solution in THF, 0.050 equiv, 84 mL) and
warmed up to room temperature and stirred for 1.0 h. The reaction
mixture was neutralized with aqueous HCl (1 N) and concentrated
under reduced pressure to remove THF. The aqueous solution was
then added with additional H2O (20 mL) and extracted with EtOAc
(50 mLꢂ2). The organic layer was washed with brine (10 mLꢂ2)
and concentrated under reduced pressure. The resultant light
yellow solids were purified by column chromatography on silica gel
(20% EtOAc in hexanes as eluant) to give the desired 11 (432 mg,
1.26 mmol) in 75% yield: mp (recrystallized from EtOH)
144–146 ꢁC; TLC Rf 0.13 (20% EtOAc in hexanes); 1H NMR (CDCl3,
400 MHz)
d
1.02 (s, 3H, CH3), 0.80–1.11 (m, 4H), 1.00 (t, J¼10.0 Hz,
3H, CH3), 1.12–1.80 (m, 3H), 1.60 (q, J¼10.0 Hz, 2H, CH2), 1.64 (br s,
1H, OH), 1.82–2.56 (m, 12H), 2.60 (s, 1H, C^C–H), 5.89 (s, 1H,
C(]O)CH]C); IR (diffuse reflectance) 3347 (br, OH), 2932
(w, C]C–H),1653 (s, C]O),1617 (m, C]C),1451 (m),1364 (m),1270
(m), 1210 (m), 1131 (m), 1066 (s), 969 (m), 925 (m), 887 (m), 854 (b),
814 (m), 766 (m), 691 (s), 657 (s), 608 (m), 564 (m), 512 (m), 465 (m)
428 (m) cmꢀ1; MS m/z (relative intensity) 312 (Mþ, 100), 283 (20),
265 (12), 245 (76), 229 (35), 217 (15), 203 (16), 187 (18), 160 (22),
135 (27), 105 (44), 91 (70), 79 (46), 67 (32), 55 (28).
500 MHz)
d 0.97 (s, 3H, CH3), 1.01 (s, 3H, CH3), 1.10–2.30 (m, 23H),
2.52 (s, 1H, C^C–H), 3.50–3.54 (m, 1H, C3-H), 5.35 (d, J¼5.5 Hz, 1H,
C]CH); IR (diffuse reflectance) 3391 (br, OH), 2931 (s), 2898 (s),
2868 (s), 1672 (w), 1623 (w), 1450 (m), 1370 (s), 1249 (w), 1195 (w),
1127 (m), 1042 (s), 1024 (s), 953 (m), 919 (m), 870 (m), 841 (s), 808
(m), 759 (w), 736 (w), 651 (m), 592 (w), 571 (w), 500 (w), 457 (w);
ESIMS m/z 341.0 (MꢀH)ꢀ.
3.7. 5a,l7a-Pregn-20-yne-3b,17b
-diol (10)19
Compound 7 (503 mg, 1.74 mmol, 1.0 equiv) was dissolved in
anhydrous THF (20 mL) and reacted with lithium trimethylsiyla-
cetylide solution (4.0 equiv) at ꢀ40 ꢁC for 1.0 h. The reaction was
added with TBAF (1.0 M solution in THF, 0.050 equiv, 87 mL) and
Acknowledgements
warmed up to room temperature and stirred for 1.0 h. The reaction
mixture was neutralized with aqueous HCl (1 N) and concentrated
under reduced pressure to remove THF. The aqueous solution was
then added with additional H2O (20 mL) and extracted with EtOAc
(50 mLꢂ2). The organic layer was washed with brine (10 mLꢂ2)
and concentrated under reduced pressure. The resultant light
yellow solids were purified by column chromatography on silica gel
(20% EtOAc in hexanes as eluant) to give the desired 10 (358 mg,
1.13 mmol) in 65% yield: mp (recrystallized from EtOAc)
261–262 ꢁC; TLC Rf 0.12 (20% EtOAc in hexanes); 1H NMR (CDCl3,
We are grateful to the China Medical University (CMU96-126 &
CMU98-S-40) and the National Science Council of Republic of China
(NSC98-2221-E-039-003-) for financial support.
Supplementary data
Supplementary data associated with this article can be found, in
clude MOL files and InChIKeys of the most important compounds
described in this article.
500 MHz) d 0.82 (s, 3H, CH3), 0.90 (s, 3H, CH3), 0.92–1.95 (m, 22H),
2.56 (s, 1H, C^C–H), 3.56–3.61 (m, 1H, C-3H); IR (diffuse
reflectance) 3429 (br, OH), 3264 (s), 2929 (s), 2857 (s), 1468 (m),
1446 (m), 1381 (s), 1127 (s), 1051 (s), 1025 (s), 976 (m), 841 (m), 701
(s), 638 (m), 615 (m), 554 (m), 473 (m) cmꢀ1; ESIMS m/z 315.0
(MꢀH)–.
References and notes
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3.8. 17
a
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b
,17
b
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added with TBAF (1.0 M solution in THF, 0.050 equiv, 89 mL) and
warmed up to room temperature and stirred for 1.0 h. The reaction
mixture was neutralized with aqueous HCl (1 N) and concentrated
under reduced pressure to remove THF. The aqueous solution was
then added with additional H2O (20 mL) and extracted with EtOAc
(50 mLꢂ2). The organic layer was washed with brine (10 mLꢂ2)
and concentrated under reduced pressure. The resultant light
yellow solids were purified by column chromatography on silica
gel (15% EtOAc in hexanes as eluant) to give the desired 11
(398 mg, 1.27 mmol) in 71% yield: mp (recrystallized from
acetone/ether) 241–242 ꢁC; TLC Rf 0.19 (20% EtOAc in hexanes); 1H
´
Quinkert, G. Helv. Chim. Acta 1985, 68, 1054–1068; (g) Ferrin˜To, S.; Lopez-
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9. For examples, see: (a) Sierra, M. A.; Torres, M. R. J. Org. Chem. 2007, 72, 4213–
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B. K. Tetrahedron 1991, 47, 2871–2878; (c) Ramı´rez-Lo´pez, P.; de la Torre, M. C.;
NMR (CDCl3, 500 MHz)
d 0.86 (s, 3H, CH3), 1.03 (s, 3H, CH3),