ing Na2S2O3 (2.5 g). The mixture was stirred for 5 minutes then
further diethyl ether (10 ml) was added and the layers were
separated. The organic layer was washed with saturated
NaHCO3 solution (10 ml) and water (10 ml), dried (MgSO4)
and evaporated to give the aldehyde 9 as a clear oil (47 mg, 0.20
mmol, 92%); νmax(film)/cmϪ1 1732 (CO) and 1718 (CO); δH (270
MHz; CDCl3) 1.20 (3H, t, J 7, CH2CH3), 1.34 (3H, s, CH3), 1.36
(3H, s, CH3), 1.80 (2H, m, 3-H2), 2.40 (2H, m, 2-H2), 3.80 (1H,
m, 4-H), 4.05 (1H, m, 5-H), 4.09 (2H, q, J 7, CH2CH3) and 9.65
(1H, d, J 2, CHO).
OCH2CH3), 4.51 (1H, m, 5-H), 5.23 (1H, dddq, J 11.0, 10.0, 2.0
and 1.0, 6-H), 5.80 (1H, dqt, J 14.5, 7.0 and 1.0, 9-H), 6.20 (1H,
tm, J 11.0, 7-H), 6.35 (1H, ddqd, J 14.5, 11.0, 1.5 and 1.0, 8-H);
major compound δC (75 MHz; CDCl3) 14.2 (OCH2CH3), 18.3
(C-10), 26.8 (C-2 or C-3), 27.1, 27.2 (each CH3), 30.6 (C-2 or
C-3), 60.4 (OCH2CH3), 76.7, 80.0 (C-4 and C-5), 108.7 (OCO),
123.9, 126.1, 133.3, 134.3 (C-6, C-7, C-8, C-9), 173.1 (C-1); m/z
(CI) 239.1286 ([MH]ϩ Ϫ C2H6. C13H19O4 requires 239.1283,
10%), 165 (80), 85 (65) and 59 (100).
Deprotection of diene 19 and lactonisation to 2
Ethyl (4S,5S,6Z)-4,5-isopropylidenedioxy-7-iodohept-6-enoate
17
Diene 19 (35 mg, 0.13 mmol) was dissolved in methanol (5 ml)
and a few crystals of toluene-p-sulfonic acid were added. The
mixture was stirred at room temperature for 6 h. Sodium
hydrogen carbonate was added, the mixture was filtered and the
filtrate concentrated in vacuo. Purification by flash column
chromatography afforded lactone 2 (12 mg, 50%) as a clear oil
Tetrapropylammonium perruthenate (25 mg, 5 mol%) was
added in one portion to a stirred suspension of alcohol 16
(0.332 g, 1.4 mmol), N-methylmorpholine N-oxide (0.25 g, 2.1
mmol) and 5 Å molecular sieves (0.5 g) in dichloromethane (20
ml) under a nitrogen atmosphere. After 1.5 h the reaction mix-
ture was filtered through a short pad of silica eluting with a
50% solution of ethyl acetate in petroleum ether. The filtrate
was concentrated in vacuo at room temperature to give the alde-
hyde 9 (0.260 g, 77%) as a clear oil. The aldehyde was used in the
next step without further purification. 2 M Sodium hexameth-
yldisilazide in tetrahydrofuran (2.26 ml, 4.52 mmol) was added
to a suspension of the iodomethyltriphenylphosphonium iod-
ide (2.40 g, 4.52 mmol) in dry tetrahydrofuran (30 ml). The
mixture was stirred at room temperature for 15 min and the
yellow suspension became a deep red solution. The reaction
was cooled to Ϫ78 ЊC and hexamethylphosphoramide (1.5 ml)
was added. The solution was stirred at Ϫ78 ЊC for 15 min and a
solution of the aldehyde (0.26 g, 1.13 mmol) in dry tetrahydro-
furan (10 ml) was added slowly dropwise. The solution was
quenched with petroleum ether (5 ml) at Ϫ78 ЊC after 2 h and
water (50 ml) was added. The mixture was extracted with ethyl
acetate (3 × 50 ml), dried over sodium sulfate, filtered through a
pad of silica eluting with ethyl acetate to remove remaining
hexamethylphosphoramide and concentrated in vacuo. The
crude reaction mixture was purified by dry flash column chro-
matography eluting with 10% ethyl acetate in petroleum ether
to give the title compound 17 (0.100 g, 25%) as a pale yellow oil;
[α]D25 ϩ22.7 (c 0.9, CHCl3); νmax(film)/cmϪ1 2985 (CH), 1736
1
which was judged to be approximately 85% pure by H NMR
spectroscopy; [α]D25 ϩ23.4 (c 0.9, CHCl3); major compound
δH (300 MHz; CDCl3) 1.81 (3H, ddd, J 7.0, 1.5 and 1.0, 10-H3),
2.00–2.35 (2H, m, 3-H2), 2.45–2.70 (2H, m, 2-H2), 4.48
(1H, ddd, J 7.5, 7.0 and 5.5, 4-H), 4.58 (1H, ddd, J 9.0, 5.5 and
1.0, 5-H), 5.32 (1H, dddq, J 11.0, 9.0, 1.5 and 1.0, 6-H), 5.85
(1H, dqt, J 15.0, 7.0 and 1.0, 9-H), 6.18 (1H, tm, J 11.0, 7-H),
6.35 (1H, ddqd, J 15.0, 11.0, 2.0 and 1.0, 8-H); major com-
pound δC (75 MHz; CDCl3) 18.4 (C-10), 23.7 (C-3), 28.5 (C-2),
70.1 (C-5), 82.9 (C-4), 123.9 (C-6), 126.1 (C-8), 133.9 (C-7),
134.0 (C-9), 177.1 (C-1); m/z (EI) 165.0915 ([MH]ϩ Ϫ H2O.
C10H13O2 requires 165.0916, 7%), 137 (8), 119 (7), 115 (30) and
85 (100).
Lactone 2 was further purified by HPLC on a Waters
Nova-Pak C18 8 × 100 mm radially compressed column using
an isocratic elution of 20% acetonitrile, 80% water and 0.01%
TFA, flow rate 2 ml minϪ1. The UV absorbance was monitored
at 210 and 254 nm using a Waters 996 PDA detector. Analysis
of the product 2 by standard gradient confirmed that it was
pure. Found Mϩ 182.0948. C10H14O3 requires M 182.0943;
spectroscopic data as for the natural product.
Acknowledgements
We thank the EPSRC for studentships (S. C. and M. E. R.) and
Xenova Discovery Ltd (now TerraGen Discovery (UK) Ltd)
and Novartis for CASE awards.
This paper is dedicated with fond memories to Leslie
Crombie and to his many contributions to all aspects of
natural product chemistry.
(CO), 1647 (C᎐C); δ (300 MHz; CDCl3) 1.26 (3H, t, J 7.0,
᎐
H
OCH2CH3), 1.40 (3H, s, CH3), 1.43 (3H, s, CH3), 1.92 (1H, dtd,
J 14.0, 8.0 and 6.5, 3-HH), 2.05 (1H, dddd, J 14.0, 9.0, 7.0 and
4.0, 3-HH), 2.47 (1H, ddd, J 16.5, 8.0 and 7.0, 2-HH), 2.53 (1H,
ddd, J 16.5, 9.0 and 6.5, 2-HH), 3.82 (1H, td, J 8.0 and 4.0,
4-H), 4.14 (2H, q, J 7.0, OCH2CH3), 6.25 (1H, t, J 8.0, 6-H),
6.57 (1H, dd, J 8.0 and 1.0, 7-H); δC (75 MHz; CDCl3) 14.3
(OCH2CH3), 26.9 (C-3), 27.0, 27.3 (each CH3), 30.6 (C-2), 60.5
(OCH2CH3), 79.2 (C-4), 82.6 (C-5), 85.9 (C-7), 109.6 (OCO),
137.9 (C-6), 173.0 (C-1); m/z (EI) 339.0092 (Mϩ Ϫ CH3.
C11H16O4I requires 339.0093, 15%), 325 (2), 297 (8), 251 (80),
183 (8), 167 (10), 149 (8), 124 (15), 115 (12) and 97 (100).
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Stille coupling of vinylic iodide 17 and stannane 18
Stannane 18 (0.166 g, 0.56 mmol) in dry tetrahydrofuran (1 ml)
was added to dichlorobis(triphenylphosphine)palladium()
(0.020 g, 10 mol%) in dry tetrahydrofuran (20 ml). Iodide 17
(0.100 g, 0.28 mmol) in dry tetrahydrofuran (1 ml) was added
and the reaction mixture was heated under reflux for 3 h. The
mixture was cooled to room temperature and concentrated
in vacuo. The crude mixture was purified by flash column
chromatography to afford diene 19 (0.040 g, 57%) as a pale
yellow oil which was judged to be approximately 85% pure by
1H NMR spectroscopy; [α]D25 Ϫ12.5 (c 3.4, CHCl3); νmax(film)/
cmϪ1 2985 (CH), 1735 (CO), 1657 (C᎐C); major compound
᎐
δH (300 MHz; CDCl3) 1.25 (3H, t, J 7.0, OCH2CH3), 1.40 (6H,
m, 2 × CH3), 1.80 (3H, m, 10-H3), 1.75–2.05 (2H, m, 3-H2),
2.33–2.54 (2H, m, 2-H2), 3.69 (1H, m, 4-H), 4.13 (2H, q, J 7.0,
2480
J. Chem. Soc., Perkin Trans. 1, 2000, 2475–2481