2022
J. Alifantes et al. / Tetrahedron: Asymmetry 13 (2002) 2019–2024
(1H, s); 13C NMR (50 MHz, CDCl3) l 36.0 (CH2), 41.2
(CH), 45.3 (CH), 55.6 (CH), 58.9 (CH), 62.3 (CH), 64.6
(CH), 73.7 (CH), 74.3 (C), 79.6 (C), 85.1 (C), 98.6 (C).
rotations were measured with a Perkin–Elmer polarime-
ter model 341 with a 1 cm cell at a temperature of
20°C. Lipase, type VII (from C. rugosa) was providing
from Amano Enzime USA Co. Ltd.
4.1. exo-(−)-1,8,9,10,11,11-Hexachloropentacyclo-
[6.2.1.13,6.02,7.05,9]dodecan-4-yl acetate, (−)-5
4.3. endo-( )-1,8,9,10,11,11-Hexachloropentacyclo-
[6.2.1.13,6.02,7.05,9]dodecan-4-trimethylsilyloxy ( )-8
Concentrated sulfuric acid (1 mL) was added to a
solution of acetate (+)-4 (1.0 g, 2.5 mmol) in acetic acid
(10 mL) at a temperature of 125°C under magnetic
stirring. After stirring for 1 h, the system was cooled
down and neutralized with 10% aqueous NaHCO3 solu-
tion. A precipitate formed and was separated. An addi-
tional extraction with chloroform was undertaken. The
extract was combined with the precipitate. This solu-
tion was dried with MgSO4, and after concentration of
the filtrates, a mixture of two compounds was obtained
as a white solid. These products were purified by chro-
matography on a silica gel column (hexane/ethyl ace-
tate: 0–20%). The acetate (−)-5 (70% yield) and
compound 6 (30% yield) were obtained. Acetate, (−)-5:
mp 193–194°C (lit.16 194–195°C); [h]2D0 −6.0 (c=1,
To a solution of alcohol ( )-3 (1.0 g, 2.6 mmol) in THF
(70 mL) under nitrogen were added 380 mL of pyridine
and 230 mL of chlorotrimethylsilane. The solution was
stirred at room temperature (20°C) for 24 h. The salt
formed was filtered and the solvent was removed under
vacuum and the half-cage ( )-8 was obtained as a white
solid (93% yield). Anal. calcd: C, 39.56; H, 3.95.
Found: C, 38.89; H, 3.89%. FTIR (KBr) w (cm−1) 842
1
(Si-CH3); H NMR (200 MHz, CDCl3) l 0.20 (9H, s),
1.34 (1H, d, J=9.8 Hz), 1.60 (1H, d, J=9.8 Hz), 2.58
(1H, br s), 2.77–3.04 (3H, m), 3.19 (1H, dd, J=6.4 Hz,
J=4.1 Hz), 4.00 (1H, d, J=6.4 Hz), 7.70 (1H, s); 13C
NMR (50 MHz, CDCl3) l 0.6 (CH3), 37.9 (CH2), 43.6
(CH), 45.2 (CH), 56.6 (CH), 57.1 (CH), 59.3 (CH), 64.8
(CH), 73.5 (C), 80.8 (CH), 81.9 (C), 82.0 (C), 99.2 (C).
1
CH2Cl2). FTIR (film, CHCl3) w (cm−1) 1735 (CꢀO); H
NMR (200 MHz, CDCl3) l 1.51 (1H, d, J=11.0 Hz),
2.09 (3H, s), 2.33 (1H, d, J=11.0 Hz), 2.88–3.15 (5H,
m), 5.50 (1H, s) and 5.80 (1H, s); 13C NMR (50 MHz,
CDCl3) l 21.1 (CH3), 36.5 (CH2), 41.6 (CH), 43.4 (CH),
55.6 (CH), 58.8 (CH), 60.0 (CH), 64.7 (CH), 74.0 (C),
76.4 (CH), 79.6 (C), 84.8 (C), 99.5 (C), 169.8 (CO).
4.4. Hexacyclo[.2.1.13,6.14,10.02,7.05,9]dodecan-4,10-oxo 9
Method A: Into a 250 mL flask equipped with reflux
condenser and under an inert atmosphere was placed
dry THF (88 mL). Small pieces (wire) of lithium (2.3 g,
0.33 mmol) were added along with tert-butyl alcohol
(16 mL, 0.17 mol). The apparatus was then immersed
into an ultrasound bath (45 KHz, 100 Watt) and a
solution of hexachlorinated compound, or acetate ( )-4
(13.6 mmol) of either alcohol ( )-3 in dry THF (10 mL)
was slowly added. The reaction was complete after 5 h
and crushed ice was added under an inert atmosphere.
The organic phase was extracted with ethyl ether and
this solution was washed with water, dried over magne-
sium sulfate, filtered and the solvents were evaporated.
Compound 9 (68% yield) was obtained as an oil.
1
Birdcage 6: mp 290°C (lit.16 287–289°C); H NMR (200
MHz, CDCl3) l 1.69 (1H, d, J=11.5 Hz), 1.90 (1H, d,
J=11.5 Hz), 3.05–3.23 (6H, m); 13C NMR (50 MHz,
CDCl3) l 39.8 (CH2), 43.4 (2CH), 54.4 (2CH), 58.4
(2CH), 78.2 (2C), 83.5 (2C), 97.5 (C).
4.2. endo- or exo-(+)-1,8,9,10,11,11-Hexachloropenta-
cyclo-[6.2.1.13,6.02,7.05,9]dodecan-4-ol (+)-3 and (+)-7
1.0 g (2.3 mmol) of acetate (+)-4 or acetate (−)-5 was
dissolved in a mixture of tetrahydrofuran (20 mL) and
CH3OH (50 mL). A saturated solution of K2CO3 was
added and the reaction was stirred at room temperature
(20°C) for 2 h. The mixture was washed three times
with CHCl3 (20 mL) and the combined organic phases
were dried with MgSO4. After concentration of the
solvent, alcohol (+)-3 or alcohol (+)-7 was obtained
(yield >95%) as a white solid. Alcohol (+)-3: mp 258–
Method B: A solution of the alcohol ( )-3, acetate ( )-4
or trimethylsilyl ether ( )-8 (13.1 mmol) in dry ethanol
(2.2 mL, 37.5 mmol) and dry THF (25 mL) was added
in small portions to a solution of sodium (4.0 g, 173.9
mmol) in ammonia (150 mL) at −78°C, and the reac-
tion mixture was stirred for 12 min. Then, the mixture
was treated with saturated aqueous ammonium chlo-
ride solution (25 mL). The ammonia was evaporated
and the usual ethereal extraction sequence followed to
produce the compound 9 (75% yield) as an oil. After
slow crystallization in CHCl3 a white solid was
obtained. Mp 190–192°C (lit.14 191–193°C). Anal.
calcd: C, 82.77; H, 8.04. Found: C, 82.49; H, 8.24%.
1
260°C dec., [h]D20 +1.0 (c=1, CH2Cl2); H NMR (200
MHz, CDCl3) l 1.40 (1H, d, J=10.8 Hz), 1.62 (1H, d,
J=10.8 Hz), 2.68 (1H, br s), 2.90–3.16 (3H, m), 3.26
(1H, dd, J=5.9 Hz, J=3.9 Hz), 4.23 (1H, d, J=5.9
Hz), 7.43 (1H, s); 13C NMR (50 MHz, CDCl3) l 38.0
(CH2), 42.9 (CH), 44.1 (CH), 56.0 (CH), 56.3 (CH),
58.5 (CH), 64.6 (CH), 72.7 (C), 79.8 (CH), 81.1 (C),
83.3 (C), 99.3 (C); Anal. calcd: C, 37.60; H, 2.61.
Found: C, 37.58; H, 2.59. Alcohol (+)-7: mp 217°C
(lit.16 218°C), [h]D20 +1.0 (c=1, CH2Cl2). FTIR (KBr) w
1
FTIR (KBr) w (cm−1) 1093 (CꢁOꢁC); H NMR (200
MHz, CDCl3) l 1.14–3.13 (12H, overlapping signals),
4.44 (2H, d, J=9.8 Hz); 13C NMR (50 MHz, CDCl3) l
41.7 (2CH2), 38.2 (2CH), 43.0 (CH), 47.6 (2CH), 51.1
(2CH), 56.6 (CH), 86.4 (2CH).
1
(cm−1) 3471 (C−OH); H NMR (200 MHz, CDCl3) l
1.43 (1H, d, J=10.9 Hz), 2.64 (1H, d, J=10.9 Hz),
2.72–2.79 (2H, m), 3.00–3.11 (3H, m), 5.02 (1H, s), 5.42