C26H44NO4S2 requires M, 498.2712); νmax/cmϪ1 3436, 1701,
1367, 1340, 1197, 1150, 1119, 1013 and 956; δH 0.90 and 0.95
(each 3 H, d, J 6, Me), 0.93 (6 H, d, J 6, 2 × Me), 1.39 (1 H,
m, 12Ј-H), 1.45 (2 H, m, 11Ј-H2), 1.60 (3 H, s, 9Ј-Me), 1.73 (3
H, s, 5Ј-Me), 1.94 (1 H, m, 13Ј-H), 2.10 (6 H, m, 6Ј-H2, 7Ј-H2
and 10Ј-H2), 2.49 (1 H, m, CHMe2), 2.64 (1 H, br s, OH), 3.45 (1
H, dd, J 15, 8, 2Ј-H), 3.60 (1 H, dd, J 15, 3, 2Ј-HЈ), 3.82 and 3.94
(each 2 H, m, OCH2), 4.40 (2 H, m, 5-H2), 4.72 (1 H, m, 4-H),
4.82 (1 H, d, J 3, OCHO), 4.94 (1 H, dt, J 3, 8, 3Ј-H), 5.10 (1 H,
m, 8Ј-H) and 5.22 (1 H, br d, J 8, 4Ј-H); m/z (CI) 464 (13%), 404
(31) and 386 (17).
oxotetradeca-5,9-trienal 51 (0.28 g, 78%), [α]D ϩ24.8 (c 1 in
CHCl3); νmax/cmϪ1 1721, 1262, 1111, 1034, 823, 741 and 704; δH
0.95 (6 H, m, 2 × Me), 1.0 (9 H, s, Me3CSi), 1.55–2.1 (16 H, m),
2.65 (1 H, dd, J 15, 5, 12-H), 2.93 (1 H, dd, J 15, 7.5, 12-H), 3.1
(2 H, m, 14-H2), 3.78 (6 H, d, J 11, 2 × OMe), 4.87 (1 H, m,
11-H), 5.0 (1 H, m, 6-H), 5.12 (1 H, m, 11-H), 7.38 (6 H, m,
aromatic H), 7.68 (4 H, m, aromatic H) and 9.65 (1 H, m, 1-H);
m/z (EI) 654 (Mϩ, 100%).
A solution of the aldehyde 51 (110 mg, 0.18 mmol) in
acetonitrile (100 cm3) containing lithium chloride (80 mg, 1.9
mmol) was heated to 40 ЊC and DBU (35 cm3, 0.22 mmol) in
acetonitrile (8 cm3) added over 16 h via syringe pump. The reac-
tion was cooled, filtered through a short pad of silica gel and
concentrated under reduced pressure. Flash chromatography of
the residue using light petroleum–ethyl acetate (30:1) as eluent
gave the title compound 52 (30 mg, 31%) containing ca. 15%
of its C(1)-epimer, [α]D ϩ45.6 (c 1.0 in CHCl3) (Found: Mϩ,
528.3414. C35H48O2Si requires M, 528.3423); νmax/cmϪ1 1687,
1662, 1621, 1428, 1111, 1057, 823, 740 and 703; δH (major
diastereoisomer) 0.82 and 0.86 (each 3 H, d, J 6, Me), 1.00 (12
H, s, Me3CSi and Me), 1.45 (2 H, m, 5-H2), 1.50 (3 H, s,
Me), 1.65 (4 H, m, 4-H, CHMe2 and 6-H2), 2.00 (4 H, m, 9-H2
and 10-H2), 2.60 (1 H, dd, J 12, 3, 14-H), 3.00 (1 H, dd, J 12,
9, 14-H), 4.68 (1 H, m, 8-H), 4.84 (1 H, dt, J 3, 8, 13-H), 5.08 (1
H, d, J 8, 12-H), 5.75 (1 H, d, J 15, 2-H), 6.55 (1 H, dd, J 15, 8,
3-H), 7.4 (6 H, m, aromatic H) and 7.7 (4 H, m, aromatic H);
m/z (CI) 529 (Mϩ ϩ 1, 40%) and 471 (10).
Dimethyl [(4R,13S,5E,9E)-13-(1Ј,3Ј-dioxolan-2Ј-yl)-4-hydroxy-
6,10,14-trimethyl-2-oxopentadeca-5,9-dienyl]phosphonate 49
Butyllithium (5.6 mmol) in hexane was added to dimethyl
methylphosphonate (0.61 cm3, 5.6 mmol) in tetrahydrofuran
(10 cm3) at Ϫ78 ЊC. After 1 h at this temperature, the amide 47
(700 mg, 1.4 mmol) in tetrahydrofuran (5 cm3) was added and
the mixture stirred for 1 h. Water and ether were added and the
aqueous layer was separated, acidified and extracted with ether.
The combined ethereal extracts were washed with water, dried
(MgSO4) and concentrated under reduced pressure. Flash
chromatography using light petroleum–ethyl acetate–methanol
(5:2:1) as eluent gave the title compound 49 (500 mg, 77%), [α]D
Ϫ5.2 (c 0.5 in CHCl3); νmax/cmϪ1 3400, 1714, 1251, 1118, 1033
and 816; δH 0.88 (6 H, d, J 6, 2 × Me), 1.30 (1 H, m, 13-H), 1.45
(2 H, m, 12-H2), 1.55 (3 H, s, 10-Me), 1.66 (3 H, s, 6-Me), 1.88 (1
H, m, 14-H), 2.02 (6 H, m, 7-H2, 8-H2 and 11-H2), 2.69 (1 H, dd,
J 8, 3, 3-H), 2.80 (1 H, dd, J 16, 8, 3-H), 3.12 (2 H, d, J 23,
1-H2), 3.75 (6 H, d, J 11, 2 × OMe), 3.70 and 3.90 (each 2 H, m,
OCH2), 4.75 (2 H, m, 4-H and 2Ј-H), 5.05 (1 H, m, 9-H) and
5.15 (1 H, br d, J 8, 5-H); m/z (CI) 460 (Mϩ, 8%), 443 (41), 422
(19), 404 (100) and 381 (53).
(1R- and 1S,3R,12S,4E,8E,13E)-12-Isopropyl-1,5,9-trimethyl-
cyclotetradeca-4,8,13-trien-1,3-diols 1 and 2
Methylmagnesium iodide (0.19 mmol; 3 in ether) was added
to the ketone 52 (20 mg, 0.038 mmol) in ether (0.3 cm3) at 0 ЊC.
After 5 h, saturated aqueous NH4Cl and water were added. The
mixture was extracted into ether and the combined ethereal
extracts dried (MgSO4) and concentrated under reduced pres-
sure. The residue was dissolved in tetrahydrofuran and tetra-
butylammonium fluoride (0.12 mmol) in tetrahydrofuran was
added. After 15 h at room temperature, water was added and
the mixture extracted with ether. The organic extracts were
dried (MgSO4) and concentrated under reduced pressure. Flash
chromatography of the residue using benzene–ethyl acetate
(10:1) as eluent gave a mixture of cembratrienediols 1 and 2
(60%). The (1S)- and (1R)-diastereoisomers 1 and 2 were separ-
ated by HPLC using ethyl acetate–light petroleum (1.5:1) as
eluent, ratio 1:2 = 80:20. The synthetic cembratrienediols had
spectroscopic and chromatographic properties identical to
authentic samples; synthetic α-cembratrienediol 1, mp 69–70 ЊC
Dimethyl [(4R,13S,5E,9E)-4-(tert-butyldiphenylsilyloxy)-13-
(1Ј,3Ј-dioxolan-2Ј-yl)-6,10,14-trimethyl-2-oxopentadeca-5,9-
dienyl]phosphonate 50
tert-Butyldiphenylsilyl chloride (0.5 cm3, 2 mmol) was added to
a solution of imidazole (0.38 g, 5.6 mmol) in N,N-dimethyl-
formamide (2 cm3) at room temperature and the mixture stirred
for 30 min. The alcohol 49 (0.84 g, 1.8 mmol) in N,N-
dimethylformamide (2 cm3) was added dropwise and the mix-
ture stirred for 5 h. Water (10 cm3) and ether (20 cm3) were
added and the aqueous layer extracted with ether (3 × 20 cm3).
The ethereal extracts were dried (MgSO4) and concentrated
under reduced pressure. Flash chromatography using light
petroleum–ethyl acetate (1:1) as eluent gave the title compound
50 (70%), [α]D ϩ17.6 (c 1.0 in CHCl3) (Found: Mϩ Ϫ C4H9,
641.3079. C35H52O7PSi requires M, 641.3063); νmax/cmϪ1 1717,
1263, 1187, 1112, 1033, 944, 823, 741 and 704; δH 0.85 (6 H, d, J
6, 2 × Me), 0.92 (9 H, s, Me3CSi), 1.25 (1 H, m, 13-H), 1.45 (2
H, m, 12-H2), 1.46 (3 H, s, 10-Me), 1.58 (3 H, s, 6-Me), 1.85 (7
H, m, 7-H2, 8-H2, 11-H2 and 14-H), 2.65 (1 H, dd, J 15, 6, 3-H),
2.90 (1 H, m, 3-H), 3.10 (2 H, m, 1-H2), 3.74 (6 H, d, J 11,
2 × OMe), 3.85 and 3.95 (each 2 H, m, OCH2), 4.82 (1 H, d,
J 2, 2Ј-H), 4.88 (1 H, m, 4-H), 5.05 (1 H, m, 9-H), 5.13 (1 H, d,
J 8, 5-H) and 7.38–7.67 (10 H, m, aromatic H); m/z (CI) 641
(Mϩ Ϫ 59, 2%).
(lit.,3 65–66 ЊC), [α]D ϩ270 (c
1
in CHCl3) (lit.,3 ϩ281;
lit.,8 ϩ173); νmax/cmϪ1 3389, 1711, 1660, 1444, 1388, 1368, 1165,
1100, 1060, 975 and 733; m/z (CI) 289 (Mϩ Ϫ 17, 100%) and 271
(70); synthetic β-cembratrienediol 2, [α]D ϩ170 (c 1.0 in CHCl3)
(lit.,3 ϩ162); νmax/cmϪ1 3339, 1465, 1430, 1390, 1370, 1170,
1145, 1120, 1097, 1083, 1038, 975 and 924; m/z (CI) 290
(Mϩ Ϫ 16, 15%) and 273 (100).
2-(tert-Butyldiphenylsilyloxymethyl)-3-methylbutyl phenyl
sulfone 54
A mixture of the racemic alcohol (±)-44 (5.0 g, 21 mmol), tert-
butyldiphenylsilyl chloride (6.5 cm3, 25 mmol) and imidazole
(3.4 g, 50 mmol) in tetrahydrofuran–DMF (25 cm3) was stirred
for 15 h at room temperature then diluted with 25 cm3 water.
The reaction was extracted with ether (4 × 50 cm3) and the
combined ethereal extracts washed with brine (50 cm3), dried
(MgSO4) and concentrated under reduced pressure. Flash
chromatography using light petroleum–ethyl acetate (10:1) as
eluent gave the title compound 54 (7.6 g, 75%), as a colourless
oil; νmax/cmϪ1 1471, 1447, 1428, 1307, 1238, 1148, 1111, 1085,
827, 741 and 703; δH 0.76 and 0.80 (each 3 H, d, J 6, Me), 1.02
(9 H, s, Me3CSi), 2.00 (2 H, m, 2-H and 3-H), 3.06 (1 H, dd, J
12, 4, SO2CHH), 3.30 (1 H, dd, J 12, 6, SO2CHH), 3.68 (2 H, d,
(4S,13R,2E,7E,11E)-7,11-Dimethyl-4-isopropyl-13-(tert-butyl-
diphenylsilyloxy)cyclotetradeca-2,7,11-trien-1-one 52
The acetal 50 (0.38 g, 0.55 mmol) in acetone–water (5:1; 12
cm3) was heated under reflux and pyridinium toluene-p-
sulfonate (15 mg, 0.06 mmol) was added. After 15 h, NaHCO3
(3 cm3) was added and the mixture concentrated under reduced
pressure. The aqueous layer was extracted with ether (3 × 20
cm3), dried (MgSO4) and concentrated under reduced pressure.
Flash chromatography using light petroleum–ethyl acetate
(1:1) as eluent gave (2S,11R,5E,9E)-11-(tert-butyldiphenylsilyl-
oxy)-14-(dimethoxyphosphinoyl)-5,9-dimethyl-2-isopropyl-13-
854
J. Chem. Soc., Perkin Trans. 1, 1997