S. Dufour et al. / Tetrahedron 68 (2012) 5102e5108
5107
1.02 (3H, s, 6-Me); dc (125 MHz, CDCl3) 159.9, 133.9, 123.7, 111.2,
47.8, 39.9, 38.3, 36.6, 36.6, 34.8, 32.1, 28.3, 26.6, 25.1, 24.2; EIMS (rel
intensity) m/z 204 (Mþ, 65), 189 (60), 161 (49), 133 (47), 119 (80),
105 (66), 93 (100), 79 (55); EI-HRMS m/z calcd for C15H24 [M]þ
204.1878, found 204.1869.
75.4, 47.4, 37.9, 36.5, 35.0, 29.8, 28.5, 27.7, 24.8, 23.7, 20.8, 20.5;
EIMS (rel intensity) m/z 262 (Mþ,1), 220 (61), 202 (72),187 (44),159
(100), 146 (46), 125 (62), 107 (29), 94 (47), 79 (34); EI-HRMS m/z
calcd for C17H26O2 [M]þ 262.1933, found 262.1932.
4.1.12. (1SR,7RS)-3,6,6,9-Tetramethylbicyclo[5.4.0]undeca-3,8-dien-
4.1.9. (1SR,2RS,10SR)-1-(10-Hydroxy-20-methylprop-20-enyl)-2-(100,100-
dimethylbut-300-enyl)-4-methylcyclohex-3-ene (5b). To a solution of
aldehyde 4 (3.50 g,17.0 mmol) in THF (300 mL) at ꢁ30 ꢀC was added
isopropenylmagnesium bromide (1 M in THF, 25.5 mL 25.5 mmol)
dropwise. The reaction mixture was warmed to room temperature
and stirred for 4 h. The reaction was quenched with aqueous am-
monium chloride (70 mL) and the aqueous layer was extracted with
Et2O (3ꢂ50 mL). The combined organic layers were dried over
MgSO4 filtered and the solvent removed under reduced pressure.
The crude residue was purified by column chromatography, eluting
with petroleum ether/EtOAc (9:1), to give 5b (3.70 g, 88%) as a clear,
colourless oil; Rf 0.74 (diethyl ether/petroleum ether 1:4); IR (neat)
2-one (7b). To a mixture of TPAP (200 mg, 0.57 mmol), NMO
ꢀ
(2.55 g, 21.8 mmol) and 4 A molecular sieves (1.50 g) in CH2Cl2
(150 mL), was added dropwise a solution of alcohol 6b (2.40 g,
10.9 mmol) in CH2Cl2 (20 mL). The mixture was stirred for 3 h at
room temperature and was then filtered through a pad of silica,
eluting with petroleum ether/EtOAc (95:5), to yield the corre-
sponding ketone 7b (1.99 g, 84%) as a clear, colourless oil; Rf 0.42
(diethyl ether/petroleum ether 1:19); IR (neat) nmax 1665, 1654,
1448. 1366, 1084, 872, 798 cmꢁ1
; dH (500 MHz, CDCl3) 6.20 (1H, t, J
5.2, H-4), 5.31 (1H, s, H-8), 2.90 (1H, dt, J 6.6, 3.5, H-1), 2.40e2.35
(2H, m, H-7, H-10), 2.30e2.26 (2H, m, H-5). 2.13e2.09 (1H, m, H-11),
1.80 (3H, s, 9-Me), 1.79e1.76 (1H, m, H-10), 1.65 (3H, s, 3-Me),
1.64e1.56 (1H, m, H-11), 1.04 (3H, s, 6-Me), 0.75 (3H, s, 6-Me); dc
(125 MHz, CDCl3) 206.8, 138.9, 138.2, 135.6, 119.6, 47.4, 47.1, 42.3,
36.7, 28.4, 27.5, 26.5, 25.7, 23.9, 19.9; EIMS (rel intensity) m/z 218
(Mþ, 100), 203 (30), 175 (22), 162 (15), 147 (22), 135 (17), 121 (60),
109 (41), 93 (24), 79 (24); EI-HRMS m/z calcd for C15H22O [M]þ
218.1671, found 218.1663.
nmax 3560, 1638, 1448, 1371, 994, 900 cmꢁ1
; dH (500 MHz, CDCl3)
5.88 (1H, ddt, J 10.3, 17.0, 7.4, H-300), 5.62 (1H, s, H-3), 5.22 (1H, s, H-
30a), 5.09e5.06 (1H, m, H-400a), 5.07e5.04 (1H, m, H-400b), 4.96 (1H,
s, H-30b), 4.60 (1H, s, H-1), 2.97 (1H, s, OH), 2.39 (1H, br s, H-2),
2.33e2.21 (1H, m, H-5a), 2.21 (2H, d, J 7.4, H-200), 2.15 (1H, br s, H-1),
1.95 (1H, ddd, J 2.9, 7.0, 13.7, H-5b), 1.89 (1H, dd, J 7.0, 18.3, H-6a),
1.73 (6H, s, 20-Me, 4-Me),1.55 (1H, m, H-6b),1.08 (3H, s,100-Me),1.07
(3H, s, 100-Me); dc (125 MHz, CDCl3) 145.0, 138.5, 135.4, 122.6, 117.4,
109.7, 76.4, 45.9, 45.6, 35.6, 33.6, 28.7, 25.6, 24.4, 24.3, 24.0, 20.1;
EIMS (rel intensity) m/z 248 (Mþ,1), 230 (3), 215 (5), 189 (8),177 (9),
147 (18), 137 (21), 121 (15), 109 (45), 95 (100), 81 (28); EI-HRMS m/z
calcd for C17H28O [M]þ 248.2140, found 248.2145.
4.1.13. (1SR,3SR,7RS)-3,6,6,9-Tetramethylbicyclo[5.4.0]undec-8-en-2-
one (8b).8 To a solution of ketone 7b (100 mg, 0.46 mmol) in THF
(4 mL) at ꢁ78 ꢀC was added dropwise a solution of L-Selectride
(1.0 M in THF, 0.60 mL, 0.60 mmol). The solution was stirred while
warming to room temperature over 3 h and then cooled to ꢁ78 ꢀC.
The reaction was reverse quenched by transferring it cold through
a canula into water (20 mL) and the aqueous layer then extracted
with Et2O (2ꢂ20 mL). The combined organic layers were dried over
MgSO4 and filtered before the solvents were removed under re-
duced pressure. The crude residue was passed through a silica gel
plug, eluting with petrol-Et2O (95:5), to give the 8b (93 mg, 92%) as
4.1.10. (1SR,2SR,7RS)-3,6,6,9-Tetramethylbicyclo[5.4.0]undeca-3,8-
dien-2-ol (6b). To a solution of Grubbs’ first generation catalyst
(300 mg, 0.36 mmol) in degassed benzene (450 mL) under N2 at
50 ꢀC was added a solution of 5b (3.70 g, 14.9 mmol) in benzene
(50 mL). The reaction mixture was stirred overnight. The solution
was filtered through a pad of silica under vacuum, eluting with
petroleum ether/EtOAc (95:5), to give the cyclised alkene 6b
(2.49 g, 76%) as a clear, colourless oil; Rf 0.35 (diethyl ether/petro-
leum ether 1:4); IR (neat) nmax 1668, 1446, 1385, 1377, 1362, 1036,
a
1 (1SR,3SR,7RS)-8b : 1.4 (1SR,3RS,7RS)-8b mixture of di-
astereoisomers as analysed by 1H NMR spectroscopy and chiral GC.
Separation of the diastereoisomers was performed by flash column
chromatography using 2% diethyl ether in petroleum ether to yield
clear, colourless oils.
1011, 759 cmꢁ1
; dH (500 MHz, CDCl3) 5.49e5.46 (2H, m, H-4, H-8),
4.41 (1H, dd, J 5.8, 8.4, H-2), 2.19 (1H, br s, H-7), 2.10e2.03 (1H, m,
H-10a), 2.02e1.90 (5H, m, H-10b, H-11, H2-5, H-1), 1.81 (3H, s, 3-
Me), 1.72 (3H, s, 9-Me), 1.67 (1H, d, J 5.8, OH), 1.65e1.61 (1H, m,
H-11b), 0.95 (3H, s, 6-Me), 0.91 (3H, s, 6-Me); dc (125 MHz, CDCl3)
140.9, 135.3, 122.4, 122.3, 72.6, 47.3, 39.4, 38.1, 34.9, 29.9, 28.8, 27.8,
25.1, 23.8, 20.2; EIMS (rel intensity) m/z 220 (Mþ, 33), 218 (47), 203
(30), 177 (14), 161 (40), 135 (100), 125 (36), 119 (69), 107 (37), 93
(45), 79 (33); EI-HRMS m/z calcd for C15H24O [M]þ 220.1827, found
220.1821.
(1SR,3RS,7RS)-8b. Chiral GC; 44.88 min; Rf 0.45 (diethyl ether/
petroleum ether 1:19); IR (neat) nmax 1701, 1452, 1389, 1376, 1365,
755 cmꢁ1
; dH (500 MHz, CDCl3) 5.47 (1H, br s, H-8), 2.90e2.84 (1H,
m, H-3), 2.68 (1H, br s, H-7), 2.42 (1H, ddd, J 3.0, 6.2, 11.9, H-1), 2.18
(1H, ddd, J 2.8, 6.2, 13.9, H-11a), 2.02 (1H, dd, J 5.9, 17.6, H-10a),
1.93e1.86 (1H, m, H-10b), 1.70 (3H, s, 9-Me), 1.67 (1H, dq, J 13.9, 4.8,
H-4a), 1.58e1.44 (3H, m, H-5, H-11b), 1.36e1.28 (1H, m, H-4b), 1.05
(3H, d, J 6.6, 3-Me), 1.00 (3H, s, 6-Me), 0.69 (3H, s, 6-Me); dC
(125 MHz, CDCl3) 216.2, 135.3, 122.0, 51.4, 44.3, 43.8, 42.1, 37.9, 31.7,
31.0, 29.7, 24.0, 23.0, 20.2, 17.0; EIMS (rel intensity) m/z 220 (Mþ,
79), 205 (12), 163 (6), 151 (19), 123 (100), 107 (13), 94 (53), 79 (32),
69 (12), 56 (26); EI-HRMS m/z calcd for C15H24O [M]þ 220.1827,
found 220.1827.
4.1.11. (1SR,2SR,7RS)-2-Acetoxy-3,6,6,9-tetramethylbicyclo[5.4.0]un-
deca-3,8-diene (10). Alcohol 6b (20 mg, 0.091 mmol) was added to
a solution of pyridine (0.5 mL) and acetyl chloride (0.25 ml) in Et2O
(10 mL) and refluxed overnight. The reaction was diluted with Et2O
(30 mL), extracted with water (50 mL), washed with aqueous HCl
(1 M, 20 mL), and brine (20 mL) and the ethereal solution dried
(MgSO4), filtered and the solvent removed in vacuo to yield 10
(20 mg, 84%) as a clear, colourless oil; Rf 0.32 (diethyl ether/pe-
troleum ether 1:9); IR (neat) nmax 1736, 1669, 1436, 1370, 1237,
(1SR,3SR,7RS)-8b. Chiral GC; 42.01, 42.25 min; Rf 0.42 (diethyl
ether/petroleum ether 1:19); IR (neat) nmax 1702, 1451, 1389, 1375,
1365, 1187, 865 cmꢁ1
; dH (500 MHz, CDCl3) 5.59 (1H, br s, H-8),
2.80e2.78 (1H, m, H-1), 2.70 (1H, d sextet, J 2.5, 6.6, H-3), 2.19 (1H,
br s, H-7), 2.09 (1H, ddd, J 1.7, 5.4, 10.0, H-11a), 1.90e1.86 (1H, m, H-
10a), 1.83 (1H, t, J 10.0, H-11b), 1.81e1.77 (1H, m, H-5a), 1.74 (3H, s,
9-Me), 1.75e1.70 (1H, m, H-10b), 1.45 (1H, dq, J 14.5, 3.8, H-4a),
1.36e1.30 (1H, m, H-4b), 1.27 (1H, dt, J 14.5, 3.5, H-5b), 1.10 (3H, s, 6-
Me), 0.98 (3H, d, J 6.6, 3-Me), 0.87 (3H, s, 6-Me); dC (125 MHz,
CDCl3) 219.4, 134.4, 122.4, 48.1, 46.4, 45.3, 37.3, 36.1, 31.6, 30.9, 29.7,
27.0, 24.8, 24.0, 17.1; EIMS (rel intensity) m/z 220 (Mþ, 80), 205 (18),
177 (10), 163 (6), 151 (23), 123 (100), 107 (18), 94 (63), 79 (37), 55
1029 cmꢁ1
; dH (500 MHz, C6D6) 5.61 (1H, br d, J 7.4, H-2), 5.57 (1H, s,
H-8), 5.52, (1H, t, J 7.2, H-4), 2.27 (1H, br s, H-7), 2.22 (1H, br s, H-1),
2.10 (1H, dd, J 7.2, 14.2, H-5a), 2.00e1.94 (1H, m, H-5b), 1.90 (3H,
obscured m, H2-10, H-11a), 1.89 (3H, s, MeCO2), 1.76 (3H, s, 3-Me),
1.73 (3H, s, 9-Me), 1.52e1.48 (1H, m, H-11b), 0.99 (3H, s, 6-Me), 0.96
(3H, s, 6-Me); dc (125 MHz, CDCl3) 170.6, 137.5, 135.3, 124.1, 122.2,