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J.-M. Galano et al. / Tetrahedron 56 (2000) 7477–7481
13.1 mmol) and tert-butyldimethylsilyl chloride (844 mg,
5.60 mmol) were added, and the mixture was stirred for
3 h at rt. The solution was poured into water and extracted
with ether. The combined organic extracts were washed
with water, brine, dried, filtered, and concentrated. Column
chromatography gave 912 mg (92%) of (ϩ)-5.
[a]2D5ϩ34.7 (c 1.0, CHCl3). IR (neat): n 3026, 1687,
ide (748 mg, 6.67 mmol) in toluene (60 ml) was heated
under reflux for 3 h. After the suspension had settled for
3 h at room temperature, the supernatant solution was
added to a solution of (Ϫ)-7 (400 mg, 2.38 mmol) in toluene
(15 ml). The reaction mixture was stirred at rt for 2 h and the
mixture was poured into water and extracted with Et2O. The
organic phase was successively washed with H2O, aq.
NH4Cl and brine, dried over MgSO4 and evaporated under
reduced pressure. Column chromatography gave 316 mg
(80%) of (Ϫ)-1 as a solid. Recrystallisation in n-hexane
(240 mg, needles) gave the product with an improved opti-
cal purity (eeϾ99%). Mp57.5–58.5ЊC; [a]2D5Ϫ295.0 (c
1.0, CHCl3), [lit. [a]DϪ236.0 (c 0.83, CHCl3)10]. IR
1H NMR (200 MHz, CDCl3): d 4.89 (br. s, 1H), 4.82 (br. s,
1H), 4.33 (br. d, J4.0 Hz, 1H), 2.74 (s, 1H), 2.41–2.26 (m,
2H), 2.07–1.69 (m, 2H), 1.16 (s, 3H), 0.98 (s, 3H). 13C
NMR (50 MHz, CDCl3): d 176.6, 139.6, 112.5, 85.1, 59.1,
42.3, 25.3, 25.0, 24.3, 19.8 Anal. Calcd for C10H14O2: C,
72.26; H, 8.49. Found: C, 72.37; H, 8.51.
1
1628, 1250, 1103 cmϪ1. H NMR (200 MHz, CDCl3): d.
5.80 (br. s, 1H), 4.33 (dd, J7.8, 5.0 Hz, 1H), 2.53 (br. dt,
J16.2, 5.1 Hz, 1H), 2.37–1.95 (m, 3H), 1.96 (s, 3H), 0.89
(s, 9H), 0.11 (s, 3H), 0.10 (s, 3H); 13C NMR (50 MHz,
CDCl3)): d 198.4, 164.0, 126.4, 69.4, 34.9, 32.4, 25.5,
20.9, 17.8, Ϫ4.5, Ϫ5.1. Anal. Calcd for C13H24O2Si: C,
64.95; H, 10.06. Found: C, 65.06; H, 10.03.
(KBr): n 3080, 1783, 1652, 1245, 1140, 1045, 900 cmϪ1
.
Methyl (1S,3R)-3-[(tert-butyldimethylsilyl)oxy]-2,2-di-
methyl-6-oxo-cyclohexanecarboxylate 6. To a stirred
suspension of copper(I) iodide (1.38 g, 7.25 mmol) in dry
ether (15 ml) at Ϫ5ЊC, was added dropwise MeLi (1.5 M in
ether, 9.7 ml, 14.5 mmol) under an argon atmosphere. The
mixture was stirred for 1 h at Ϫ5ЊC and a solution of (ϩ)-5
(870 mg, 3.63 mmol) in ether (6 ml) was added dropwise.
The reaction mixture was stirred for a further 1 h at 0ЊC,
HMPA (6 ml, 34.5 mmol) was added dropwise under
vigorous stirring, the mixture was slowly cooled to Ϫ70ЊC
and methyl cyanoformate (1.23 g, 14.5 mmol) in ether
(4 ml) was added dropwise. The solution was allowed to
rise to rt, then poured into a saturated aqueous NH4Cl/
NH4OH solution and extracted with ether. The organic
layers were combined, washed with brine, dried, and evapo-
rated to furnish 1.04 g (91%) of 6 as an oil. This compound
was used in the next step without further purification. IR
(neat): n 1766, 1722, 1262, 1130, 1086, 834 cmϪ1. 1H NMR
(400 MHz, C6D6): d 3.81 (s, 1H), 3.43 (s, 3H), 3.37 (br. t,
J3.2 Hz, 1H), 2.39 (ddd, J14.1, 12.1, 6.9 Hz, 1H), 2.18
(ddd, J14.1, 5.5, 3.6 Hz, 1H), 1.72 (dddd, J14.2, 12.1,
5.5, 2.7 Hz, 1H), 1.51 (dddd, J14.2, 6.9, 3.6, 3.0 Hz, 1H),
1.04 (s, 3H), 1.00 (s, 3H), 0.88 (s, 9H) (min), 0.06 (s, 3H),
-0.03 (s, 3H). 13C NMR (50 MHz, CDCl3): d 206.3, 169.3,
74.6, 61.9, 51.5, 43.6, 35.7, 29.3, 25.8 (3C), 24.7, 22.56,
18.0, Ϫ4.5, Ϫ5.0.
(1S,5R)-cis-3-Hydroxy-2,2-dimethyl-6-methylenecyclo-
hexanemethanol ((Ϫ)-8). A solution of (Ϫ)-1 (150 mg,
0.88 mmol) in dry ether (3 ml) was slowly added to a stirred
slurry of LiAlH4 (86 mg, 2.26 mmol) in dry ether (5 ml) at
0ЊC. The solution was allowed to rise to rt. After 1 h 30 min,
Celite (10 g) and Na2SO4·10H2O (5 g) were added and the
solution was stirred for a further 30 min. The mixture was
filtered through a pad of MgSO4 and concentrated. A
column chromatography of the oil afforded 146 mg (95%)
of pure (Ϫ)-8. [a]2D5Ϫ54.0 (c 1.0, CHCl3). IR (neat): n
1
3500, 1641, 1086, 1005, 890 cmϪ1. H NMR (200 MHz,
CDCl3): d 4.92 (s, 1H), 4.73 (s, 1H), 3.91 and 3.67 (ABX,
J10.8, 7.5, 2.3 Hz, 2H), 3.45 (dd, J5.1, 3.5 Hz, 1H), 2.61
(br. s, 2×OH), 2.55–2.41 (m, 1H), 2.13–1.79 (m, 3H), 1.62
(dq, J13.4, 5.5 Hz, 1H). 13C NMR (50 MHz, CDCl3): d
148.1, 110.2, 73.9, 62.8, 54.6, 38.6, 30.5, 21.4, 27.7, 29.2
Anal. Calcd for C10H18O2: C, 70.55; H, 10.66. Found: C,
70.31; H, 10.69.
(1S,5R)-8,8-Dimethyl-2-methylene-6-oxabicyclo[3.2.1]-
octane ((Ϫ)-2). (Ϫ)-Karahana ether. p-Toluenesulphonyl
chloride (133 mg, 0.70 mmol) was added to a stirred solu-
tion of diol (Ϫ)-8 (100 mg, 0.65 mmol) in dry pyridine
(4 ml) at 0ЊC and the mixture was allowed to rise to rt.
After stirring for 3 h, the mixture was poured into water
and extracted with Et2O. The organic phase was washed
with 1 M HCl, saturated NaHCO3, brine and dried over
MgSO4. After filtration, concentration in vacuo (bath temp
3–4ЊC) furnished an oil. Column chromatography afforded
the bicyclic ether (Ϫ)-2 as a colorless liquid with a pleasant
camphor-like odor (81 mg, 81% yield). [a]2D5Ϫ68.0 (c 1.0,
pentane), [lit. [a]DϪ70.3 (c 1.02, pentane),10 Ϫ47.5 (c
0.30, pentane),11 Ϫ65.5 (c 0.44, pentane)12]. IR (neat): n
3066, 1645, 1240, 1042, 890 cmϪ1. (200 MHz, CDCl3): d
4.62 (t, J2.2 Hz, 1H), 4.53 (t, J2.2 Hz, 1H), 4.01 (dd,
J8.2, 4.3 Hz, 1H), 3.78 (d, J8.2 Hz, 1H), 3.73 (d,
J3.5 Hz, 1H), 2.50–2.33 (m, 1H), 2.29 (d, J4.3 Hz,
1H), 2.10 (dd, J15.6, 6.4 Hz, 1H), 1.80–1.50 (m, 2H),
1.05 (s, 3H), 0.93 (s, 3H). 13C NMR (50 MHz, CDCl3): d
149.0, 107.5, 82.4, 71.1, 53.9, 42.2, 28.5, 25.8, 25.4, 20.8
Anal. Calcd for C10H16O: C, 78.90; H, 10.59. Found: C,
78.67; H, 10.61.
(1S,5R)-8,8-Dimethyl-6-oxabicyclo[3.2.1]octane-2,7-dione
((Ϫ)-7). A suspension of ester 6 (850 mg, 2.70 mmol) and
p-toluenesulfonic acid monohydrate (617 mg, 3.24 mmol)
in toluene (20 ml) was placed in an oil bath equilibrated at
110ЊC. After 30 min, the solution was cooled to rt and
filtered through a pad of Celite. The filter-cake was washed
with CH2Cl2 and the solvent evaporated. Column chromato-
graphy gave 427 mg (94%) of (Ϫ)-7 as a solid. An analy-
tical sample was recrystallized from n-hexane–ether (4:1).
(Ϫ)-7. Mp112–113ЊC. [a]2D5Ϫ302.0 (c 1.0, CHCl3), [lit.
[a]2D2Ϫ236.0 (c 0.83, CHCl3)10]. IR (neat): d 1785, 1730,
1130, 960 cmϪ1. 1H NMR (200 MHz, CDCl3): d 4.46 (br. s,
1H), 2.98 (s, 1H), 2.65–2.30 (m, 3H), 2.13–1.95 (m, 1H),
1.24 (s, 3H), 1.06 (s, 3H). 13C NMR (50 MHz, CDCl3): d
200.0, 171.7, 84.1, 66.5, 45.5, 33.4, 25.0, 24.9, 19.6. Anal.
Calcd for C9H12O3: C, 64.27; H, 7.19. Found: C, 64.12; H,
7.17.
(1S,5R)-8,8-Dimethyl-2-methylene-6-oxabicyclo[3.2.1]octan-
7-one ((Ϫ)-1). (Ϫ)-Karahana lactone. A solution of
Ph3PϩMeIϪ (2.40 g, 5.95 mmol) and potassium tert-butox-