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mmol), ethyl acrylate (0.450 g, 4.48 mmol), and Novozym 435 (0.50
g, ∼890 mg/mmol) in diisopropyl ether (5 mL) was agitated on an
orbital shaker at 120 rpm for 30 h. The reaction mixture was filtered,
the filtrate was concentrated in vacuo, and the residue was column
chromatographed (silica gel, 0−25% EtOAc/hexane) to furnish pure
27 (0.171 g, 71%). colorless oil; [α]2D3 −7.1 (c 1.13, CHCl3); IR: 3479,
3065, 3030, 1728, 1714, 1657, 985 cm−1; 1H NMR: δ 1.22 (d, J = 6.2
Hz, 3H), 1.25 (d, J = 6.4 Hz, 3H), 1.54−1.80 (m, 8H), 3.51 (broad s,
1H), 3.68−3.79 (m, 1H), 4.29−4.35 (merged m and d, J = 11.8 Hz,
2H), 4.58 (d, J = 11.8 Hz, 1H), 4.88−5.06 (m, 2H), 5.16−5.25 (m,
2H), 5.66−5.83 (m, 2H), 5.95−6.15 (m, 2H), 6.38 (dd, J = 1.6, 17.2
Hz, 1H), 6.88 (dd, J = 5.0, 15.8 Hz, 1H), 7.29−7.33 (m, 5H); 13C
NMR: δ 20.0, 31.1, 31.4, 31.6, 32.0, 70.0, 70.5, 70.7, 70.9, 80.0, 117.5,
120.8, 127.4, 127.7, 128.3, 128.7, 130.6, 138.5, 138.6, 149.5, 165.9,
166.0. Anal. Calcd for C25H34O6: C, 69.74; H, 7.96%. Found: C, 69.44;
H, 7.94%.
(5S,8R,13S,16R)-Pyrenophorol Monobenzyl Ether 28. A
stirred solution of 27 (0.142 g, 0.33 mmol) and Grubbs’ II catalyst
(20 mol %) in degassed CH2Cl2 (10 mL) was refluxed for 72 h. The
reaction mixture was concentrated in vacuo, and the residue was
subjected to preparative tlc to obtain pure 28 (57 mg, 61% based on
conversion) and recovered 27 (40 mg). colorless oil; [α]2D5 −39.0 (c
1.07, CHCl3); IR: 3470, 1713, 1643 cm−1; 1H NMR: δ 1.24 (t, J = 6.2
Hz, 6H), 1.60−1.86 (m, 9H), 3.78−3.88 (m, 1H), 4.13−4.22 (m, 1H),
4.37 (d, J = 12.0 Hz, 1H), 4.55 (d, J = 12.0 Hz, 1H), 5.03−5.17 (m,
2H), 5.91 (d, J = 16.0 Hz, 2H), 6.74 (dd, J = 7.8, 16.0 Hz, 1H), 6.82
(dd, J = 6.8, 15.6 Hz, 1H), 7.32 (s, 5H); 13C NMR: δ 13.9, 18.4, 29.7,
30.9, 33.4, 43.7, 69.8, 70.7, 77.2, 79.2, 83.4, 124.5, 127.7, 128.6, 146.9,
178.1. Anal. Calcd for C23H30O6: C, 68.64; H, 7.51%. Found: C, 68.56;
H, 7.78%.
Ethyl (2Z,4E,6R,9S)-6-tert-Butyldimethylsilyloxy-9-para-
methoxybenzyloxydeca-2,4-dienoate 31. To a cooled (0 °C)
and stirred suspension of hexane-washed NaH (0.142 mg, 2.95 mmol,
50% suspension in oil) in THF (5 mL) was added ethyl
diphenylphosphonoacetate (0.750 g, 2.36 mmol) in THF (5 mL).
After 1 h, the solution was cooled to −78 °C, 30 (0.77 g, 1.96 mmol)
in THF (5 mL) was injected into it, and stirring continued at −78 °C
for 3 h. The mixture was poured into ice−water and extracted with
Et2O (3 × 10 mL). The ether layer was washed with H2O (2 × 10
mL) and brine (1 × 5 mL), dried, and concentrated in vacuo to get a
residue, which, on column chromatography (silica gel, 0−10% EtOAc/
hexane), furnished pure 31 (0.620 g, 68%). colorless liquid; [α]D24
−12.9 (c 1.00, CHCl3); IR: 1716, 1641 cm−1; 1H NMR: δ 0.04 and 0.1
(two s, 6H), 0.90 (s, 9H), 1.16 (d, J = 6.0 Hz, 3H), 1.27 (t, J = 7.6 Hz,
3H), 1.48−1.74 (m, 4H), 3.47−3.53 (m, 1H), 3.80 (s, 3H), 4.15−4.22
(m, 3H), 4.39−4.50 (m, 2H), 5.64 (d, J = 11.4 Hz, 1H), 5.96 (dd, J =
6.3, 15.3 Hz, 1H), 6.54 (t, J = 11.4 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H),
7.26 (d, J = 8.4 Hz, 2H), 7.42 (dd, J = 11.4, 15.3 Hz, 1H); 13C NMR: δ
−4.8, −4.3, 14.3, 18.2, 19.6, 22.7, 25.9, 29.7, 30.2, 31.7, 32.1, 33.7, 55.2,
59.9, 69.9, 72.7, 73.0, 74.1, 74.5, 113.7, 117.5, 125.6, 129.2, 131.1,
144.2, 146.8, 159.1, 166.3. Anal. Calcd for C26H42O5Si: C, 67.49; H,
9.15%. Found: C, 67.74; H, 9.21%.
Ethyl (2Z,4E,6R,9S)-6-tert-Butyldimethylsilyloxy-9-hydroxy-
deca-2,4-dienoate 32. To a solution of 31 (0.620 g, 1.34 mmol)
in CH2Cl2−H2O was added DDQ (0.394 g, 1.74 mmol). After stirring
for 3 h at room temperature, the reaction mixture was filtered through
a pad of Celite. The filtrate was dried and concentrated in vacuo to get
a residue, which, on column chromatography (silica gel, 0−10%
EtOAc/hexane), furnished pure 32 (0.353 g, 77%). colorless liquid;
[α]2D4 −7.2 (c 0.82, CHCl3); IR: 3415, 1715, 1641 cm−1; H NMR: δ
1
0.07 (s, 6H), 0.89 (s, 9H), 1.18 (d, J = 6.3 Hz, 3H), 1.22 (t, J = 6.3 Hz,
3H), 1.31−1.69 (m, 4H), 2.04 (broad s, 1H), 3.78−3.81 (m, 1H), 4.19
(q, J = 7.0 Hz, 2H), 4.29−4.35 (m, 1H), 5.65 (d, J = 11.9 Hz, 1H),
5.98 (dd, J = 15.4, 6.3 Hz, 1H), 6.56 (t, J = 11.9 Hz, 1H), 7.39−7.46
(m, 1H); 13C NMR: δ −4.8, −4.3, 14.3, 18.2, 22.7, 23.4, 25.9, 29.7,
31.9, 33.8, 34.4, 59.9, 67.8, 72.8, 114.0, 117.6, 125.8, 139.2, 144.0,
146.3, 166.3. Anal. Calcd for C18H34O4Si: C, 63.11; H, 10.00%. Found:
C, 63.18; H, 9.84%.
(2Z,4E,6R,9S)-6-tert-Butyldimethylsilyloxy-9-hydroxydeca-
2,4-dienoic acid 33. A solution of 32 (0.080 g, 0.234 mmol) and
aqueous 1 M LiOH (0.351 mL, 0.351 mmol) in THF:H2O (1:1, 10
mL) was stirred at 0 °C for 6 h. Removal of solvent in vacuo gave a
residue, which was purified by preparative thin layer chromatography
(silica gel, 40% EtOAc/hexane) to afford 33 (60 mg, 82%). viscous
liquid; [α]2D4 −6.98 (c 1.39, CHCl3); IR: 3500- 2500, 1693, 1639 cm−1;
1H NMR: δ 0.04 (s, 3H), 0.06 (s, 3H), 0.90 (s, 9H), 1.18 (d, J = 6.2
(5S,8R,13S,16R)-Pyrenophorol 2. A mixture of 28 (40 mg, 0.1
mmol) and TiCl4 (11.0 μL, 0.1 mmol) in CH2Cl2 (5 mL) was stirred
at room temperature until the completion of the reaction (cf. TLC, 30
min). After concentration in vacuo, the residue was purified by
preparative thin layer chromatography to get pure (5S,8R,13S,16R)-2
9f
25
(23 mg, 74%). sticky solid; [α]2D5 −2.9 (c 1.00, acetone), (lit. [α]D
1
−3.2 (c 0.25, acetone); IR: 3440, 1714, 1651, 985 cm−1; H NMR: δ
1.26 (d, J = 6.6 Hz, 6H), 1.64−1.93 (m, 8H), 2.30 (broad s, 2H),
4.26−4.32 (m, 2H), 5.10−5.17 (m, 2H), 5.98 (dd, J = 1.6, 15.6 Hz,
2H), 6.90 (dd, J = 5.2, 15.6 Hz, 2H); 13C NMR: δ 18.2, 28.9, 30.5,
69.8, 70.4, 122.2, 149.5, 165.0. Anal. Calcd for C16H24O6: C, 61.52; H,
7.74%. Found: C, 61.45; H, 7.92%.
(2E,4R,7S)-4-Hydroxy-7-para-methoxybenzyloxyoct-2-enal
29. A mixture of (3R,6S)-17 (0.690 g, 2.76 mmol), acrolein (0.92 mL,
13.80 mmol), and Hoveyda Grubbs’ II catalyst (86 mg, 0.14 mmol) in
CH2Cl2 (20 mL) was stirred for 22 h at room temperature. After
concentrating the mixture in vacuo, the residue was subjected to
column chromatography (silica gel, 0−25% EtOAc/hexane) to give
pure 29 (0.682 g, 89%). colorless liquid; [α]2D6 +16.6 (c 1.01, CHCl3);
Hz, 3H), 1.48−1.68 (m, 4H), 2.34 (broad s, 1H), 3.75−3.85 (m, 1H),
4.28−4.36 (m, 1H), 5.66 (d, J = 11.0 Hz, 1H), 6.04 (dd, J = 15.4, 6.0
Hz, 1H), 6.65 (t, J = 11.4 Hz, 1H), 7.45 (dd, J = 15.4, 11.4 Hz, 1H);
13C NMR: δ −4.7, −4.2, 18.1, 23.1, 25.9, 29.7, 33.5, 33.9, 66.9, 72.5,
1
IR: 3426, 2729, 1688 cm−1; H NMR: δ 1.23 (d, J = 6.0 Hz, 3H),
1.66−1.83 (m, 5H), 3.44−3.61 (m, 2H), 3.82 (s, 3H), 4.36 (d, J = 11.2
Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H), 6.25−6.37 (m, 1H), 6.80 (dd, J =
4.2, 15.6 Hz, 1H), 6.86−6.93 (m, 2H), 7.25−7.31 (m, 2H), 9.57 (d, J
= 7.8 Hz, 1H); 13C NMR: δ 19.2, 19.7, 32.4, 55.3, 70.3, 70.7, 74.4,
113.8, 113.9, 129.3, 129.5, 130.1, 130.8, 159.4, 193.7. Anal. Calcd for
C16H22O4: C, 69.04; H, 7.97%. Found: C, 68.93; H, 7.89%.
(2E,4R,7S)-4-tert-Butyldimethylsilyloxy-7-para-methoxyben-
zyloxyoct-2-enal 30. Silylation of 29 (1.08 g, 3.88 mmol) with
TBSCl (0.700 g, 4.66 mmol), imidazole (0.400 g, 5.83 mmol), and
DMAP (catalytic) in CH2Cl2 (30 mL), followed by the usual isolation,
afforded pure 30 (1.23 g, 81%). colorless liquid; [α]2D8 −12.7 (c 1.00,
CHCl3); IR: 2722, 1692 cm−1; 1H NMR: δ 0.06 (s, 3H), 0.10 (s, 3H),
0.95 (s, 9H), 1.22 (d, J = 6.2 Hz, 3H), 1.47−1.78 (m, 4H), 3.49−3.55
(m, 1H), 3.84 (s, 3H), 4.36−4.57 (m, 3H), 6.23−6.35 (m, 1H), 6.81
(dd, J = 4.4, 15.4 Hz, 1H), 6.87−6.95 (m, 2H), 7.26−7.31 (m, 2H),
9.60 (d, J = 7.8 Hz, 1H); 13C NMR: δ −4.9, −4.7, 18.1, 19.5, 25.7,
32.9, 33.2, 55.2, 69.9, 71.6, 74.2, 113.7, 129.1, 130.7, 130.9, 159.1,
160.0, 193.6. Anal. Calcd for C22H36O4Si: C, 67.30; H, 9.24%. Found:
C, 67.26; H, 9.41%.
126.0, 126.4, 137.9, 142.4, 175.0. Anal. Calcd for C16H30O4Si: C,
61.11; H, 9.61%. Found: C, 61.04; H, 9.76%.
(3Z,5E,7R,10R)-7-tert-Butyldimethylsilyloxy-10-methyl-
7,8,9,10-tetrahydrooxecin-2-one 34. To a cooled (0 °C) and
stirred solution of 33 (0.210 g, 0.67 mmol) and PPh3 (0.352 g, 1.34
mmol) in anhydrous toluene (96 mL) was slowly added DIAD (0.26
mL, 1.34 mmol). The reaction mixture was stirred at room
temperature for 16 h and concentrated in vacuo, and the residue
was purified by preparative thin layer column chromatography (silica
gel, 20% EtOAc/hexane) to furnish 34 (130 mg, 73% based on
conversion) along with unreacted 33 (20 mg). colorless liquid; [α]D24
−51.8 (c 0.4, CHCl3); IR: 1702, 1643, 1360 cm−1; 1H NMR: δ 0.04 (s,
3H), 0.08 (s, 3H), 0.89 (s, 9H), 1.32 (d, J = 6.2 Hz, 3H), 1.46−1.59
(m, 2H), 1.78−2.01 (m, 2H), 4.02−4.15 (m, 1H), 4.75−4.93 (m, 1H),
5.58 (d, J = 11.6 Hz, 1H), 5.90 (dd, J = 8.2, 15.4 Hz, 1H), 6.49 (t, J =
11.6 Hz, 1H), 7.09 (dd, J = 15.4, 11.6 Hz, 1H); 13C NMR: δ −4.8,
−4.0, 18.2, 20.9, 25.8, 29.7, 33.7, 35.1, 72.1, 75.3, 119.6, 126.2, 141.9,
146.1, 166.2. Anal. Calcd for C16H28O3Si: C, 64.82; H, 9.52%. Found:
C, 64.47; H, 9.22%.
H
dx.doi.org/10.1021/jo5012575 | J. Org. Chem. XXXX, XXX, XXX−XXX