11592
K. Mandelt et al. / Tetrahedron 60 (2004) 11587–11595
GC [column B, 175 8C; retention times (min): 3.08 (18b),
3.61 (18a)]. Colourless liquids. 18a: H NMR (200 MHz,
dZ11.96 (t), 18.69 (t), 22.06 (q), 25.74 (t), 31.47 (d), 33.82
(t), 34.08 (t), 50.72 (d), 75.87 (s); MS (CI): m/eZ140 (100,
1
C
CDCl3, CHCl3 int): dZ0.97 (d, JZ7 Hz, 3H), 1.27 (s, 3H),
1.45–1.70 (m, 2H), 1.85–2.05 (m, 1H), 2.24–2.45 (m, 1H),
2.72 (symm m, 1H), 10.7–11.7 (br s, 1H, COOH); 13C NMR
(50 MHz, CDCl3, CDCl3 int): dZ15.28 (q), 16.83 (q), 23.92
(t), 28.63 (t), 35.86 (d), 45.39 (s), 184.49 (s); MS (EI): m/eZ
128 (7, MC), 87 (100). C7H12O2 requires C, 65.60; H, 9.44.
Found: C, 65.56; H, 9.62. 18b: 1H NMR (300 MHz, CDCl3,
CHCl3 int): dZ1.06 (d, JZ7 Hz, 3H), 1.38 (s, 3H), 1.50–
1.72 (m, 2H), 2.00–2.15 (m, 1H), 2.20–2.37 (m, 1H), 2.45–
2.58 (m, 1H), COOH not detected; 13C NMR (75 MHz,
CDCl3, CDCl3 int): dZ17.15 (q), 23.66 (t), 24.39 (q), 27.36
(t), 40.68 (d), 47.55 (s), 182.66 (s); MS (EI): m/eZ128
(8, MC), 87 (100). C7H12O2 requires C, 65.60; H, 9.44.
Found: C, 65.25; H, 9.70.
MCNH4KH2Oe ). C9H16O requires C, 77.09; H, 11.50.
Found: C, 77.15; H, 11.33. 29b: 1H NMR (300 MHz,
CDCl3, CHCl3 int): dZ1.07 (d, JZ7 Hz, 3H), 1.40–1.60
(m, 2H), 1.72 (br s, 1H, OH), 1.70–1.85 (m, 1H), 1.85–2.06
(m, 6H), 2.06–2.18 (m, 1H), 2.46–2.52 (m, 2H); 13C NMR
(50 MHz, C6D6, C6D6 int): dZ12.85 (t), 17.00 (q), 20.04 (t),
26.80 (t), 32.63 (d), 36.03 (t), 36.41 (t), 44.20 (d), 76.37
(s, hidden in CDCl3); MS (CI): m/eZ140 (93, MC
C
NH4KH2Oe ), 123 (100). C9H16O requires C, 77.09; H,
11.50. Found: C, 77.05; H, 11.29.
3.1.6.2. rel-(10R,20R)-10,20-Dimethyl-[1,10-bicyclobutyl]-
1-ol (30a) and rel-(10R,20S)-10,20-dimethyl-[1,10-bicyclo-
butyl]-1-ol (30b). Yield 90 mg (6%) 30a and 50 mg (3%)
30b; Rf 0.22 (30a) and 0.29 (30b). Colourless liquids. 30a:
1H NMR (300 MHz, CDCl3, CHCl3 int): dZ0.92 (d, JZ
7 Hz, 3H), 1.00 (s, 3H), 1.30–1.56 (m, 3H), 1.46 (s, 1H,
OH), 1.76–1.94 (m, 5H), 2.16–2.42 (m, 3H); 13C NMR
(75 MHz, CDCl3, CDCl3 int): dZ12.37 (t), 14.01 (q), 16.67
(q), 23.64 (t), 26.28 (t), 31.56 (t), 31.58 (t), 31.76 (d), 45.14
(s), 80.85 (s); MS (EI): m/eZ154 (1, MC), 84 (100). HRMS
3.1.5.3. 1,2,2-Trimethyl-cyclobutanecarboxylic acid (23)
and 4,5-dimethyl-hex-4-enoic acid (26). Yield 1.14 g
(80%) of a 1:1-mixture of 23 and 26. Pure samples were
obtained by preparative GC [column B, 6 min 180 8C,
20 8C/min to 220 8C; retention times (min): 4.68 (23), 8.85
(26)]. 23: colourless solid, mp 115–117 8C. 1H NMR
(200 MHz, CDCl3, CHCl3 int): dZ1.03 (s, 3H), 1.12
(s, 3H), 1.33 (s, 3H), 1.44–1.54 (m, 2H), 1.75 (ddd, JZ
10, 10, 9 Hz, 1H), 2.50 (ddd, JZ10, 10, 9 Hz, 1H); 13C
NMR (50 MHz, CDCl3, CDCl3 int): dZ19.90 (q), 23.85 (q),
25.40 (t), 25.53 (q), 30.07 (t), 40.51 (s), 48.58 (s), 182.83 (s);
MS (EI): m/eZ142 (4, MC), 56 (100). C8H14O2 requires C,
67.35; H, 9.92. Found: C, 67.35; H, 9.77. 26: colourless
liquid.17 Spectral data have not yet been reported and were
1
m/e (MC) calcd 154.1358, obsd 154.1357. 30b: H NMR
(300 MHz, CDCl3, CHCl3 int): dZ1.03 (s, 3H), 1.04 (d, JZ
7 Hz, 3H), 1.30–1.45 (m, 1H), 1.50–1.85 (m, 5H), 1.90–2.20
(m, 5H), 2.55–2.67 (m, 1H); 13C NMR (75 MHz, CDCl3,
CDCl3 int): dZ14.78 (t), 17.77 (q), 23.26 (q), 23.62 (t),
27.92 (t), 32.29 (t), 33.52 (t), 39.35 (d), 45.30 (s), 81.58 (s);
MS (EI): m/eZ154 (2, MC), 84 (100). HRMS m/z (MC)
calcd 154.1358, obsd 154.1357.
1
as follows: H NMR (300 MHz, CDCl3, CHCl3 int): dZ
1.63 (s, 6H), 1.65 (s, 3H), 2.36 (s, 4H); 13C NMR (50 MHz,
CDCl3, CDCl3 int): dZ17.98 (q), 20.08 (q), 20.63 (q), 29.60
(t), 32.87 (t), 125.34 (s), 125.94 (s), 180.14 (s); MS (EI):
m/eZ142 (98, MC), 83 (100).
3.1.6.3. rel-(1R,2S)-10,2-Dimethyl-[1,10-bicyclobutyl]-1-
ol (32a). Yield 841 mg (59%); Rf 0.24. Colourless liquid.
1H NMR (300 MHz, CDCl3, CHCl3 int): dZ1.00 (d, JZ
7 Hz, 3H), 1.07 (s, 3H), 1.42 (br s, 1H, OH), 1.45–1.57
(m, 3H), 1.60–2.20 (m, 7H), 2.40 (symm m, 1H); 13C NMR
(75 MHz, CDCl3, CDCl3 int): dZ14.09 (t), 15.37 (q), 21.36
(q), 22.40 (t), 28.27 (t), 28.43 (t), 28.47 (t), 33.57 (d), 43.76
(s), 80.99 (s); MS (EI): m/eZ154 (60, MC), 137 (100).
C10H18O requires C, 77.87; H, 11.76. Found: C, 78.15; H,
11.81.
3.1.6. Synthesis of the [1,10-bicyclobutyl]-1-ols 29a,b,
30a,b, 32a and 33
A suspension of finely powdered dry CeCl3 (4.93 g,
20 mmol) in THF (85 ml) was stirred under argon overnight.
After addition of the appropriate cyclobutanone (10 mmol),
stirring was continued for 2 h until the mixture was cooled
to K78 8C and the appropriate Grignard reagent (15 mmol)
was added. After 15 min at K78 8C and 4 h at room
temperature the mixture was hydrolyzed with 2 N HCl
(50 ml). The aqueous phase was extracted with ether
(4!40 ml), and the combined organic phases were washed
with saturated sodium bicarbonate (60 ml), brine (60 ml)
and dried (MgSO4). The solvents were distilled off on a
rotary evaporator (bath temperature 20 8C/14 Torr) and the
residue was chromatographed on silica gel (0.05–0.20 mm)
in pentane/ether 3:1 (32a) and 5:1 (29a,b, 30a,b, 33)
respectively.
3.1.6.4. 10,2,2-Trimethyl-[1,10-bicyclobutyl]-1-ol (33).
Yield 460 mg (27%); Rf 0.32. Colourless liquid. H NMR
1
(300 MHz, CDCl3, CHCl3 int): dZ0.98 (s, 3H), 1.02
(s, 3H), 1.19 (s, 3H), 1.40 (s, 1H, OH), 1.30–1.48 (m,
2H), 1.53–2.04 (m, 6H), 2.30 (symm m, 1H), 2.40 (symm m,
1H); 13C NMR (50 MHz, CDCl3, CDCl3 int): dZ15.32 (t),
20.82 (q), 24.47 (q), 24.99 (q), 27.37 (t), 29.35 (t), 30.00 (t),
31.52 (t), 43.00 (s), 44.24 (s), 82.96 (s); MS (EI): m/eZ168
(16, MC), 151 (100). C11H20O requires C, 78.77; H, 12.01.
Found: C, 78.51; H, 11.98.
3.1.7. 6-Methyl-spiro[3.4]octan-5-one (36)
3.1.6.1. rel-(10R,20R)-20-Methyl-[1,10-bicyclobutyl]-1-ol
(29a) and rel-(10R,20S)-20-methyl-[1,10-bicyclobutyl]-1-ol
(29b). Yield 297 mg (42%) 29a and 237 mg (34%) 29b; Rf
0.14 (29a) and 0.23 (29b). Colourless liquids. 29a: 1H NMR
(300 MHz, CDCl3, CHCl3 int): dZ1.07 (d, JZ7 Hz, 3H),
1.30–1.55 (m, 2H), 1.60 (s, 1H, OH), 1.55–2.16 (m, 9H),
2.16–2.30 (m, 1H); 13C NMR (50 MHz, CDCl3, CDCl3 int):
To a solution of diisopropylamine (8.1 g, 80 mmol) in THF
(160 ml) was added at 5–10 8C under nitrogen with stirring a
1.6 M solution of n-butyllithium in hexane (50 ml,
80 mmol) followed by neat 824 (9.9 g, 80 mmol). The
mixture was stirred for 0.5 h at room temperature, until it
was cooled to K78 8C and methyl iodide (56.8 g,
400 mmol) was added. Afterwards, the mixture was held