V. Lecomte et al. / Tetrahedron 59 (2003) 2169–2176
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small pieces and introduced into a three-necked flask under
argon. Diethyl ether (1 ml) was then added and, slowly,
p-bromo-N,N-dimethylaniline (1.2 g; 6 mmol) diluted in
2 ml of diethyl ether. The mixture was stirred for 2 h at the
reflux temperature. Compound 7 (777 mg; 2 mmol) in 12 ml
toluene were added to the lithium derivative solution. The
mixture was stirred at room temperature for 4.5 h and then
hydrolysed. The organic layer was separated and the
aqueous layer extracted with dichloromethane. The organic
layers were combined, dried on magnesium sulfate, and
evaporated. The crude product was crystallized in cyclo-
hexane and filtered. The solid was introduced into a solution
of THF (10 ml) and HCl 0.2 M (10 ml), and the mixture was
stirred for 15 min. The solvent was evaporated, then toluene
was added. The resulting chlorohydrate precipitate was
filtered and washed with toluene to give 250 mg (25%
yield—30% conversion) of a blue powder. 1H NMR
(200 MHz, CD3OD) d 1.16 (s, 3H, CH3-18), 1.45 (s, 3H,
CH3-19), 3.59 (s, 6H, CH3–Nþ), 5.58 (s, 1H, H6), 7.60
–7.89 (m, Harom) ppm; 13C NMR (50 MHz, CD3OD) d 15.2,
23.1, 23.8, 33.0, 34.5, 36.3, 37.3, 43.5, 47.4, 52.0, 52.2,
59.6, 64.2, 80.6, 121.2, 122.8, 127.9, 129.9, 142.1, 156.4,
176.2, 202.4 ppm; IR (NaCl, CH2Cl2) 1633, 1720, 2315,
2858, 2914, 2941, 3415, 3468 cm21. Anal. calcd for
C27H36NO3Cl: C 70.01, H 8.23. Found C 70.33, H 7.95.
6.2.3. (1S,5R)- and (1R,5S)-1-Butyl-3,3,5-trimethylcyclo-
hexan-1-ol 20. Viscous oil, 74% yield (100% conversion).
1H NMR (200 MHz, CDCl3) d 0.66–0.82 (m, 3H), 0.86 (d,
J¼6.6 Hz, 3H, CH3-5), 0.86 (s, 3H, CH3-3), 1.08 (s, 3H,
CH3-3), 1.23–1.43 (m, 7H), 1.59 (bd, 1H), 1.92 (17 lines,
1H, H-5) ppm; 13C NMR (50 MHz, CDCl3) d 14.0, 22.4,
23.2, 24.0, 25.1, 27.3, 31.1, 34.4, 45.4, 45.9, 48.5, 48.6, 73.1
(C-1) ppm; MS (ICP/NH3 70 eV) m/z 216 ([MþNH4]þ),
198 ([Mz2H2OþNH4]þ), 181([Mz2H2OþH]þ); IR (NaCl,
neat) 759, 1216, 1457, 2930, 2953, 3464 cm21. Anal. calcd
for C13H26O: C 78.72, H 13.21. Found C 78.53, H 13.33.
6.2.4. 11b-Hydroxy-11a-n-butyl-3,3,17,17-(ethylenedi-
oxy)-androst-5-ene 8e. White powder: mp 1308C, 88%
yield (100% conversion); 1H NMR (200 MHz, CDCl3) d 0.88
(t, J¼6.6 Hz, 2H), 1.05 (s, 3H, CH3-18), 0.25–1.38 (m, 5H),
1.38 (s, 3H, CH3-19), 1.50–2.25 (m, 10H), 2.60 (dd, J¼2.5 Hz,
14.5 Hz, 1H), 3.85–3.95 (m, 8H, CH2-ketal), 5.31 (m, 1H,
H-6) ppm; 13C NMR (50 MHz, CDCl3) d 14.0, 15.2, 21.3, 23.2,
23.5, 27.1, 30.9, 32.6, 33.1, 33.9, 37.3, 41.1, 41.6, 44.4, 46.3,
47.6, 49.6, 53.7, 64.1–64.9 (C-ketal), 77.4 (C11), 108.8–118.9
(C3-C7), 121.6 (C6), 142.2 (C5) ppm; MS (ICP/NH3 70 eV)
m/z 446 (Mþz), 428 ([M2H2O]þz), 389, 346, 327, 284, 257,
232, 129, 99, 85, 57; IR (KBr) 2872, 2952, 3503 cm21. Anal.
calcd for C27H42O5: C 72.61, H 9.48. Found C 72.63, H 9.44.
6.2. General procedure for the addition of n-buLi and
tert-buLi to ketones 1, 2, 4 and 7
6.2.5. 11b-Hydroxy-11a-tert-butyl-3,3,17,17-(ethylene-
dioxy)-androst-5-ene 8f. White powder, 85% yield (98%
conversion). H NMR (200 MHz, CDCl3) d 0.97 (s, 9H,
1
The ketone (0.5 mmol) and the dry solvent (3 ml) were
introduced into a three-necked flask under argon. n-BuLi
resp. tert-BuLi (1.5 mmol) was added slowly by syringe.
The mixture was stirred at room temperature for 30 min,
after which water was added. After usual work-up the crude
product obtained was compared with literature data:
(1S,2S,5R)-1-butyl-2-isopropyl-5-methyl-cyclohexan-1-ol
18,12 (1S,2S,5R)-1-tert-butyl-2-isopropyl-5-methyl-cyclo-
hexan-1-ol 19,12 (1S,5R)- and (1R,5S)-1-tert-butyl-3,3,5-
trimethylcyclohexan-1-ol 2113 or fully characterized.
CH3–tert-butyl), 1.04 (s, 3H, CH3-18), 1.46 (s, 3H, CH3-19),
3.90–4.12 (m, 8H, CH2-ketal), 5.39 (s, 1H, H6) ppm; 13C
NMR (50 MHz, CDCl3) d 17.2, 19.7, 23.3, 26.9, 31.3, 33.3,
33.8, 36.1, 38.1, 42.3, 43.0, 44.4, 44.9, 45.4, 51.4, 64.3,
65.2, 80.6, 109.2, 119.9, 122.9, 144.8 ppm; MS (EI 70 eV)
m/z 446 (Mþz), 428 ([M2H2O]þz), 389, 346, 327, 284, 199,
121, 99, 84, 75, 57, 49, 43; IR (KBr) 1370, 1468, 2876,
2957, 3535 cm21. Anal. calcd for (C27H42O5þ1/3AcOEt) C
71.49, H 9.46. Found C 71.46, H 9.64.
6.2.6. 11b-Hydroxy-11a-methyl-3,3,17,17-(ethylene-
(140 mg;
6.2.1. (1R,2S)-2-endo-Hydroxy-2-exo-butyl-1,3,3-tri-
methylbicyclo[2.2.1]heptane 16. Viscous oil, 76% yield
(100% conversion). H NMR (200 MHz, CDCl3) d 0.86–
dioxy)-androst-5-ene 8g. Compound
7
0.33 mmol) and dry THF (10 ml) were introduced into a
three-necked flask under argon. ‘Salt-free’ methyllithium
(1 mmol; 1.6 M) was added slowly and the yellow mixture
was then stirred at room temperature for 0.5 h. After
hydrolysis, the organic phase was washed, dried and the
solvent was evaporated. The product was purified on a silica
gel chromatographic column (petroleum ether/ethyl acetate
6/4) to give 122 mg (84%) of a white powder (mp 1768C) in
agreement with Ref. 29 and 1H NMR (200 MHz, CDCl3) d
1.03 (s, 3H, CH3), 1.34 (s, 3H), 1.43 (s, 3H), 1.60–2.26 (m,
15H), 2.58 (bd, J¼14.3 Hz, 1H), 3.92 (m, 8H, ketal), 5.27
(bs, 1H) ppm; 13C NMR (50 MHz, CDCl3) d 15.2, 21.0,
23.4, 31.0, 32.7, 33.9, 37.2, 38.1, 40.5, 41.5, 44.8, 50.0,
50.4, 56.7, 64.0–65.0, 75.3, 108.7, 119.5, 121.4, 141.7 ppm;
MS (EI 70 eV) m/z 404 (Mþz), 386 ([M2H2O]þz), 346, 284,
1
0.94 (m), 0.96 (s, 3H), 0.99 (s, 3H), 1.05 (s, 3H), 1.08 (bd,
1H), 1.23–1.75 (m), 1.98 (m, 1H) ppm; 13C NMR (50 MHz,
CDCl3) d 14.0, 18.0, 22.5, 23.7, 24.8, 27.1, 27.5, 30.6, 35.4,
40.9, 44.2, 50.1, 52.5 (C1), 80.9 (C2) ppm; MS (EI 70 eV)
m/z 210 (Mþz), 192 ([Mþz2H2O]), 181, 167, 153, 135, 128,
109, 81, 69, 57, 43, 41; IR (NaCl, neat) 995, 1105, 1375,
1458, 2871, 2963, 3509, 3630 cm21. Anal. calcd for
C14H26O: C 79.94, H 12.46. Found C 79.74, H 12.64.
6.2.2. (1R,2S)-2-endo-Hydroxy-2-exo-tert-butyl-1,3,3-tri-
methylbicyclo[2.2.1]heptane 17. White powder: mp
1
1108C, 58% yield (70% conversion). H NMR (200 MHz,
CDCl3) d 0.85–1.01 (m, 2H), 1.03 (s, 3H), 1.06 (d, J¼
1.7 Hz, 1H), 1.11 (s, 6H), 1.28 (s, 3H), 1.29 (s, 3H), 1.32 (s,
3H), 1.35–2.11 (m, 5H) ppm; 13C NMR (50 MHz, CDCl3) d
22.4, 23.3, 23.5, 26.3, 29.5, 30.0, 30.3, 35.7, 41.5, 43.6,
49.6, 51.1, 54.3, 84.8 ppm; MS (EI 70 eV) m/z 210 (Mþz),
193 ([M2H2OþH]þ); IR (NaCl, neat) 984, 1050, 1476,
2938, 3627 cm21. Anal. calcd for C14H26O: C 79.94, H
12.46. Found C 79.27, H 12.65.
99, 86; IR (KBr) 1118, 2879, 2945, 2965, 3507 cm21
.
Acknowledgements
The authors wish to thank B. McGlinchey for her assistance
in translating the manuscript.