R. Rossi et al. / Tetrahedron 56 (2000) 479–487
485
Methyl (Z)-5-tributylstannyl-2-penten-4-ynoate 30. A
flame-dried reaction vessel, which was maintained under
an argon atmosphere, was charged with a degassed solution
of 28 (15.85 g, 87.18 mmol) in THF (200 ml) and bis(tri-
butyltin)oxide, 29 (24.24 g, 40.70 mmol). A 1 M THF
solution of TBAF (1.74 ml, 1.74 mmol) was added and a
mild exothermic effect was observed. The mixture was then
stirred at 65ЊC for 4.5 h at which time the volatiles were
removed in vacuo (0.01 Torr). The residue was diluted with
hexane (250 ml) and filtered over Celite. The filtrate was
concentrated in vacuo to give compound 30 (30.41 g, 87%
yield) as a red oil. MS, m/z (%): 343 (100), 341 (71), 339
filtrate was extracted repeatedly with Et2O (5×100 ml).
The collected organic extracts were washed with water
(3×100 ml), dried, concentrated in vacuo and the residue
was purified by MPLC on silica gel, using a mixture of
hexane and Et2O (70:30) as eluent, to give compound 32
(2.71 g, 73% yield) as a yellow liquid. MS, m/z (%): 165
(58), 149 (19), 106 (17), 91 (14), 89 (20), 85 (100), 67
(18), 63 (17), 57 (11). IR (film): n 2188, 1728, 1439,
1
1200, 1179, 1156, 1131, 1037, 1027, 984, 954 cmϪ1. H
NMR (200 MHz, CDCl3): d 6.38 (1H, dt, J11.5 Hz,
H-2), 6.02 (1H, dq, J15.5 and 2.0 Hz, H-6), 4.66 (1H, t,
J3.0 Hz, H-20), 4.34 (1H, ddd, J15.1, 4.8 and 1.6 Hz,
H-60), 4.09 (1H, ddd, J15.1, 4.8 and 1.6 Hz, H-60),
4.00–3.70 (1H, m, H-8), 3.60–3.45 (1H, m, H-8), 3.77
(3H, s, COOCH3), 1.95–1.45 ppm (6H, m, H-30, H-40
and H-50). Anal. Calcd for C14H18O4: C, 67.18; H, 7.25.
Found: C, 67.44; H, 6.95. GLC analysis showed that
compound 32 had purity higher than 97.5%. It must also
be noted that in a second preparation according to the above
reported procedure compound 32 was synthesized in 70%
yield.
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(42), 229 (27), 199 (20), 171 (20), 151 (62). H NMR
(200 MHz, CDCl3): d 6.18 (1H, d, J11.6 Hz, H-2 or
H-3), 6.01 (1H, d, J11.6 Hz, H-3 or H-2), 3.75 3H, s,
COOCH3), 1.70–1.48 (3×2H, m, CH2), 1.45–1.15 (3×2H,
m, CH2), 1.06 (3×2H, t, J7.6 Hz, CH2-Sn), 0.91 ppm
(3×3H, t, J7.2 Hz, CH3). GLC/MS analysis showed that
compound 30 was 92% chemically pure and had stereoiso-
meric purity higher than 97%. This crude compound was
used in the next step without any further purification and
characterization.
Methyl (2Z,6E)-8-hydroxy-2,6-octadien-4-ynoate 33.
p-Toluenesulfonic acid monohydrate (0.40 g, 2.10 mmol)
was added to a solution of compound 32 (5.46 g,
21.84 mmol) in methanol (60 ml) and the mixture was
stirred for 8 h at room temperature. It was then diluted
with Et2O (400 ml) and washed repeatedly with a saturated
aqueous NaHCO3 solution (5×50 ml) and brine (4×100 ml).
The organic extract was dried and concentrated in vacuo and
the residue was purified by MPLC on silica gel, using a
mixture of Et2O and petroleum ether (70:30) as eluent, to
give compound 33 (3.23 g, 89% yield) as a colourless oil.
MS, m/z (%): 151 (6), 137 (13), 106 (72), 95 (17), 79 (51),
77 (100), 63 (37), 53 (15), 51 (24). IR (film): n 2187, 1712,
(E)-3-Iodo-1-tetrahydropyranyloxy-2-propene 31.
p-Toluenesulfonic acid monohydrate (1.37 g, 7.23 mmol)
was added to a solution of (E)-3-iodo-2-propen-1-ol, 18
(16.33 g, 88.80 mmol) and 3,4-dihydro-2H-pyran (14.90 g,
177.57 mmol) in dry CH2Cl2 (145 ml) which was stirred at
0ЊC. After stirring the reaction mixture for 4 h at room
temperature, solid NaHCO3 (5.0 g) was added and the
mixture was stirred for 15 min. It was then poured into a
large excess of a saturated aqueous NaHCO3 solution
(300 ml) and extracted with Et2O (4×100 ml). The organic
extract was dried and concentrated in vacuo and the residue
was purified by MPLC on silica gel, using a mixture of
hexane and Et2O (95:5) as eluent, to give compound
31 (20.59 g, 86% yield) as a pale yellow liquid. MS,
m/z (%): 167 (39), 85 (100), 67 (14), 57 (10), 55 (24),
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1603, 1441, 1238, 1205, 1182, 953, 911 cmϪ1. H NMR
(200 MHz, CDCl3): d 6.43 (1H, dt, J15.8 and 4.8 Hz,
H-7), 6.29 (1H, dd, J11.4 and 2.3 Hz, H-3), 6.09 (1H, d,
J11.4 Hz, H-2), 6.01 (1H, dq, J15.8 and 2.0 Hz, H-6),
4.26 (2H, br s, H-8), 3.77 (3H, s, COOCH3), 2.78 ppm (1H,
br s, OH). Anal. Calcd for C9H10O3: C, 65.05; H, 6.06.
Found: C, 64.96; H, 6.19.
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43 (18), 41 (28). H NMR (200 MHz, CDCl3): d 6.65
(1H, dt, J14.4 and 5.6 Hz, H-2), 6.39 (1H, d,
J14.4 Hz, H-1), 4.65 (1H, d, J3.3 Hz, H-20), 4.15
(1H, ddd, J13.5, 5.1 and 1.4 Hz, H-3), 3.96 (1H, dd,
J5.1 and 1.4 Hz, H-3), 3.90–3.73 (1H, m, H-60), 3.56–
3.48 (1H, m, H-60), 2.00–1.35 ppm (6H, m, H-30, H-40 and
H-50). Anal. Calcd for C8H13IO2: C, 35.84; H, 4.89. Found:
C, 36.01; H, 5.02.
(2Z,6E)-8-Hydroxy-2,6-octadien-4-ynoic acid 14. A 1 M
aqueous LiOH solution (60 ml, 60.0 mmol) was added to a
solution of compound 33 (3.12 g, 18.80 mmol) in THF
(90 ml) which was cooled to 0ЊC. The resulting mixture
was stirred at room temperature for 22 h and then concen-
trated in vacuo. The residue was diluted with water (300 ml)
and extracted repeatedly with Et2O (4×50 ml). The resulting
aqueous solution was cooled to 0ЊC, acidified with 10%
H2SO4 and extracted repeatedly with Et2O (5×100 ml).
The collected organic extracts were washed with water,
dried and concentrated in vacuo to give compound 14
(2.20 g, 77% yield) as a pale yellow solid. Mp 140–
144ЊC. MS, m/z (%): 152 (62), 123 (100), 121 (27), 96
Methyl (2Z,6E)-8-tetrahydropyranyloxy-2,6-octadien-4-
ynoate 32. A degassed solution of 31 (4.01 g, 14.93 mmol)
in anhydrous DMF (20 ml) and a degassed solution of
compound 30 (6.84 g, 17.17 mmol) in anhydrous DMF
(20 ml) were sequentially added to a degassed solution of
PdCl2(PhCN)2 (0.286 g, 0.746 mmol) in anhydrous DMF
(110 ml) which was stirred under argon. The resulting
mixture was stirred at room temperature for 5 h at which
time the reaction was complete. It was then poured into a
large excess of water (300 ml) and extracted repeatedly with
Et2O (5×100 ml). The collected organic extracts were
washed with water (4×80 ml) and concentrated under
reduced pressure. The residue was diluted with Et2O
(100 ml), treated with a 6 M aqueous KF solution
(300 ml) and the resulting mixture was stirred for 1 h at
room temperature. It was the filtered over Celite and the
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(38), 95 (45), 82 (66), 77 (39), 67 (29), 65 (25). H NMR
(200 MHz, CDCl3): d 10.70 (1H, br s, COOH), 6.50–6.30
(2H, m, H-3 and H-7), 6.14 (1H, d, J11.5 Hz, H-2),
6.00 (1H, dq, J15.8 and 2.0 Hz, H-6), 4.22 ppm (3H,
br s, H-8 and OH). This crude compound was used in
the next step without any further purification and
characterization.