O. Bedel, A. Haudrechy, Y. Langlois
ture was extracted with diethyl ether (3 ϫ 150 mL). The combined 1.4 equiv.) in dichloromethane (60 mL) was added dropwise. After
FULL PAPER
organic layers were dried, filtered and concentrated. The residue
was purified by silica gel column chromatography (heptane/EtOAc,
10 min, the reaction mixture was allowed to warm to room tem-
perature and stirred for 2 h. The mixture was concentrated, and
5:2) to afford the diene 9 as a pale yellow oil (8.4 g, yield 70%). ether was added to the residue. The resulting suspension was fil-
Rf ϭ 0.49 (heptane/EtOAc, 1:1). 1H NMR (200 MHz, CDCl3): δ ϭ tered, and the filtrate was concentrated. Purification by silica gel
6.32 (d, J ϭ 15.6 Hz, 1 H, 2Ј-H), 5.54 (t, J ϭ 7.5 Hz, 1 H, 4Ј-H), column chromatography on silica gel (pentane/ether, 6:1, 4:1, 2:1
5.55Ϫ5.45 (m, 1 H, 1Ј-H), 4.89 (t, J ϭ 4.7 Hz, 1 H, 2ЈЈ-H), 4.53
and 1:1) gave a 1:1 diastereoisomeric mixture of the ester 13 as an
(q, J ϭ 6.4 Hz, 1 H, 4-H), 4.06 (m, J ϭ 6.4, 8 Hz, 1 H, 5-H), oil (10.8 g, yield 86%). Rf ϭ 0.33 (pentane/ether, 4:1). Diastereoiso-
1
3.98Ϫ3.81 [m, 4 H, (OCH2)2], 3.57 (dd, 1 H, 5-H), 2.52 (dd, 2 H, meric mixture. H NMR (250 MHz, CDCl3): δ ϭ 7.60Ϫ7.50 (m, 4
5Ј-H), 1.76 (s, 3 H, 3Ј-Me), 1.42 [s, 3 H, (O)2CMe], 1.37 [s, 3 H,
H, CAr-H), 7.35Ϫ7.20 (m, 6 H, CAr-H), 7.20Ϫ7.10 (m, 2 H,
(O)2CMe] ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 138.6 (C-2Ј), CPMBAr-H), 6.75Ϫ6.68 (m, 2 H, CPMBAr-H), 6.25Ϫ6.16 (dd, 1 H,
135.8 (C-3Ј), 126.9 (C-1Ј), 124.5 (C-4Ј), 109.5 [(O)2CMe2], 104.0 3Ј-H), 5.75Ϫ5.30 (m, 5 H, 5-H, 2 ϫ 6-H, 2Ј-H, 5Ј-H), 4.90Ϫ4.75
(C-2ЈЈ), 77.8 (C-4), 69.9 (C-5), 65.3 [(OCH2)2], 33.6 (C-5Ј), 27.1
(m, 3 H, 2ЈЈ-H, 1Ј-H, 2-H), 4.57Ϫ4.18 (AB system, 2 H, p-Me-
(O2CMe), 26.3 (O2CMe), 13.0 (3Ј-Me) ppm. IR (film): ν˜ ϭ 2985, OC6H4CH2), 3.89Ϫ3.61 [m, 9 H, 2 ϫ SiOCH, (OCH2)2, OMe],
2879, 1650, 1369, 1217, 1135, 1058 cmϪ1. [α]2D0 ϭ ϩ18.1 (c ϭ 1,
CHCl3). MS (electrospray): calcd. for [M ϩ Na] 277.1; found 277.1.
2.38 (m, 2 H, 2 ϫ 6Ј-H), 2.15Ϫ2.0 (m, 2 H, 2 ϫ 4-H), 1.75Ϫ1.65
(m, 2 H, 2 ϫ 3-H), 1.58 (s, 3 H, 4Ј-Me), 0.95 (s, 9 H, tBu) ppm.
13C NMR (62.5 MHz, CDCl3): δ ϭ 172.3, 159.3, 138.8, 138.4,
137.5, 135.6, 135.4, 133.2, 133.1, 129.8, 127.7, 127.2, 127.1, 115.4,
113.8, 103.7, 77.0, 75.8, 71.8, 65.7, 65.0, 55.3, 33.3, 32.4, 32.2, 29.6,
29.5, 26.8, 19.3, 12.5 ppm. IR (film): ν˜ϭ 3071, 2931, 1747, 1613,
1514, 1248, 1113 cmϪ1. HRMS (electrospray): calcd. for [M ϩ Na]
707.3455; found 707.3390.
(2S)-7-(1Ј,3Ј-Dioxolan-2Ј-yl)-5-methyl-3,5-heptadiene-1,2-diol (10):
The diene 9 (8.3 g, 31 mmol) was dissolved at 0 °C in a solution of
trifluoroacetic acid (0.1%) in acetic acid (160 mL). After 4 h, tolu-
ene (100 mL) was added, and the reaction mixture was concen-
trated under reduced pressure, this operation being repeated twice.
Purification by silica gel column chromatography (EtOAc/heptane,
1:1 and then 3:1) gave the expected diol 10 (5.11 g, yield 76% and
Methyl (1R,2R)-2-[3Ј-(1ЈЈ,3ЈЈ-Dioxolan-2ЈЈ-yl)-1Ј-methyl-1Ј-propen-
1Ј-yl]-1-[(4-methoxybenzyl)oxy]-3-cyclohexene-1-carboxylate (15b):
The ester 13 (10.5 g, 15 mmol) was dissolved under argon in dry
toluene (100 mL) and the mixture was then cooled to Ϫ78 °C. A
solution of KHMDS in toluene (0.5 ) was added dropwise
(40 mL, 20 mmol) over 15 min. After 45 min, freshly distilled
TMSCl (3.8 mL, 30 mmol, 2 equiv.) was added and the resulting
mixture was stirred for 5 min. The mixture was warmed to room
temperature and stirred for an additional 3 h. The solution was
then transferred by cannula to a flask containing Grubbs catalyst
(1 g, 1.5 mmol, 0.1 equiv.) in CH2Cl2 (900 mL). This solution was
heated at 40 °C for 2 h. After cooling, the reaction was quenched
with 10% aqueous NH4Cl solution and the layers were separated.
The aqueous layer was extracted with dichloromethane, the com-
bined organic layers were dried and filtered, and the solvent was
removed under reduced pressure. The crude product was esterified
with diazomethane, and the resulting methyl ester was purified by
silica gel column chromatography (pentane/ether, 4:1) to give the
ester 15b as a colourless oil (4.22 g, yield 70%). Rf ϭ 0.52 (ether/
1
15% of recovered starting material). Rf ϭ 0.43 (EtOAc). H NMR
(200 MHz, CDCl3): δ ϭ 6.37 (d, J ϭ 15.8 Hz, 1 H, 4-H), 5.63Ϫ5.55
(m, 2 H, 6-H, 3-H), 4.92 (t, J ϭ 4.7 Hz, 1 H, 2Ј-H), 4.29 (m, 1 H,
2-H), 4.00Ϫ3.80 [m, 4 H, (OCH2)2], 3.75Ϫ3.45 (m, 2 H, 1-Ha, 1-
Hb), 2.54 (dd, J ϭ 6.9 Hz, 2 H, 7-H), 2.25Ϫ2.00 (br. s, 2 H, OH),
1.77 (s, 3 H, 5-Me) ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 136.7
(C-4), 135.6 (C-5), 126.2 (C-3), 125.5 (C-6), 103.7 (C-2Ј), 73.3 (C-
2), 66.5 (C-1), 65.0 [(OCH2)2], 33.2 (C-7), 12.7 (5-Me) ppm. IR
(film): ν˜ ϭ 3428, 2887, 1650, 1404, 1134, 1027 cmϪ1. [α]2D0 ϭ ϩ7.1
(c ϭ 0.95, CHCl3). MS MS (electrospray): calcd. for [M ϩ Na]
237.2; found 237.2.
(2S) 1-[(tert-Butyldiphenylsilyl)oxy]-7-(1Ј,3Ј-dioxolan-2Ј-yl)-5-
methyl-3,5-heptadien-2-ol (11): DMAP (250 mg, 2 mmol, 10%) and
triethylamine (3.72 mL, 26.8 mmol, 1.3 equiv.) were added to a
solution of diol 10 (4.4 g, 20.6 mmol) in dry THF (200 mL). The
mixture was cooled to 0 °C. A solution of tert-butyldiphenylsilyl
chloride (6 mL, 22.9 mmol, 1.11 equiv.) in dry THF (50 mL) was
added dropwise. After 3 h, the solvent was removed under reduced
pressure and the crude product was purified by silica gel column
chromatography (EtOAc/heptane, 4:6). Allylic alcohol 11 was iso-
lated (7.7 g, yield 82%). Rf ϭ 0.63 (EtOAc/heptane, 1:1). 1H NMR
(200 MHz, CDCl3): δ ϭ 7.69Ϫ7.64 (m, 4 H, ar-H), 7.42Ϫ7.35 (m,
6 H, ar-H), 6.31 (d, J ϭ 15.4 Hz, 1 H, 4-H), 5.56Ϫ5.45 (m, 2 H,
3-H, 6-H), 4.90 (t, J ϭ 4.8 Hz, 1 H, 2Ј-H), 4.4Ϫ4.25 (m, 1 H, 2-
H), 3.99Ϫ3.80 [m, 4 H, (OCH2)2], 3.71Ϫ3.55 (m, 2 H, 1-Ha, 1-Hb),
2.52 (dd, 2 H, 7-H), 1.72 (s, 3 H, 5-Me), 0.93 (s, 9 H, tBu) ppm.
13C NMR (62.5 MHz, CDCl3): δ ϭ 136.7 (C-4), 135.7 (C-5), 135.6
(CAr), 133.2 (CqAr), 129.9 (CAr), 127.8 (CAr), 125.9 (C-3), 125.2 (C-
6), 103.8 (C-2Ј), 73.1 (C-2), 68.1 (C-1), 65.0 [(OCH2)2], 33.3 (C-7),
26.9 [SiϪpC(Me)3], 19.3 [SiϪpC(Me)3], 12.7 (5-Me) ppm. IR
(film): ν˜ ϭ 3467, 2930, 2858, 1589, 1472, 1427, 1391, 1362, 1191,
1113, 1044 cmϪ1. [α]2D0 ϭ ϩ4.2 (c ϭ 0.5, CHCl3). MS (electrospray):
calcd. for [M ϩ Na] 475.2; found 475.2.
1
pentane, 1:1). H NMR (200 MHz, CDCl3): δ ϭ 7.20 (d, J ϭ 8.3
Hz, 2 H, CAr-H), 6.77 (d, J ϭ 8.3 Hz, 2 H, CAr-H), 5.90Ϫ5.77 (m,
1 H, 2Ј-H), 5.45Ϫ5.32 (m, 1 H, 3-H), 5.22Ϫ5.12 (m, 1 H, 4-H),
4.76 (t, J ϭ 4.9 Hz, 1 H, 2ЈЈ-H), 4.49Ϫ4.31 (AB system, J ϭ 10.7
Hz, 2 H, ArCH2), 4.00Ϫ3.77 [m, 4 H, (OCH2)2], 3.75 (s, 3 H,
OMe), 3.72 (s, 3 H, COOMe), 3.33 (m, 1 H, 2-H), 2.33 (t, J ϭ 5.8
Hz, 2 H, 3Ј-H), 2.20Ϫ1.95 (m, 4 H, 5-H, 6-H), 1.6 (s, 3 H, 1Ј-Me)
ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 174.3 (COOMe), 159.1
(CqAr-OMe), 138.4 (CqAr), 131.5 (C-1Ј), 128.9 (CAr), 127.7 (C-3),
126.8 (C-4), 122.6 (C-2Ј), 113.8 (CAr), 104.5 (C-2ЈЈ), 82.5 (C-1),
66.1 (ArCH2O), 65.2 [(OCH2)2], 55.5 (C-2), 52.6 (ArOMe), 52.0
(COOMe), 33.4 (C-3Ј), 26.9 (C-5), 22.6 (C-6), 16.5 (1Ј-Me) ppm.
IR (film): ν˜ ϭ 3024, 2951, 2838, 1744, 1613, 1514, 1249, 1131 cmϪ1
.
[α]2D0 ϭ ϩ15.5 (c ϭ 0.88, CHCl3). HRMS (electrospray): calcd. for
[M ϩ Na] 425.1940; found 425.1930.
(2R/S,1ЈS)-1Ј-{[(tert-Butyldiphenylsilyl)oxy]methyl}-6Ј-(1ЈЈ,3ЈЈ-di-
oxolan-2ЈЈ-yl)-4Ј-methyl-2Ј,4Ј-hexadien-1Ј-yl 2-[(4-Methoxybenzyl)-
(1ЈR,3S,3aS,7aR)-3-[2Ј-(1ЈЈ,3ЈЈ-Dioxolan-2ЈЈ-yl)-1Ј-iodoethyl]-7a-
[(4-methoxybenzyl)oxy]-3-methyl-3a,6,7,7a-tetrahydro-2-benzo-
oxy]-5-hexenoate (13): Allylic alcohol 11 (8.2 g, 18 mmol), acid 12 furan-1(3H)-one (16): Acid 15a (1.07 g, 2.75 mmol) was dissolved
(7 g, 28 mmol, 1.4 equiv.) and DMAP (460 mg, 3.6 mmol) were dis-
solved in dichloromethane (220 mL) and the mixture was cooled
to 0 °C. A solution of dicyclohexylcarbodiimide (5.8 g, 28 mmol,
under argon in dry THF (10 mL). A solution of freshly prepared
N-iodosuccinimide (0.8 g, 3.5 mol, 1.3 equiv.) in THF (5 mL) was
added rapidly. After 2 h, the reaction was quenched with 5% aque-
3816
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2004, 3813Ϫ3819