3902 J. Am. Chem. Soc., Vol. 121, No. 16, 1999
He et al.
pressure to give a brown solid residue. Purification either by silica gel
column chromatography (elution with hexane/EtOAc 8:1) or by
recrystallization from hexane/EtOAc (15:1) gave 10.3 g (80%) of methyl
4-(4′-methoxyphenyloxy)crotonate (5) as white crystals and 1.0 g (8%)
of the SN2′ regioisomer 5a as a light yellow oil: Rf of 5 and 5a, 0.40
and 0.47, respectively (hexane/EtOAc 6:1). 5: mp 53.6-54.3 °C (lit.18
After a solution of 7.9 g of AD-mix-â in 100 mL of tert-butyl alcohol
and 100 mL of water was stirred for 45 min at room temperature, 538
mg (5.7 mmol) of MeSO2NH2 was added, and the reaction mixture
was chilled to 0 °C. At this moment, a solution of 2.1 g (5.7 mmol) of
enyne 8a in 12 mL of Et2O was added. A gentle stream of air was
used for about 1 h to evaporate the Et2O. The heterogeneous solution
was stirred for 48 h at 0 °C, and then 8.5 g (68 mmol) of Na2SO3 was
added. The reaction mixture was allowed to warm to room temperature
and stirred for another 30 min. The product was extracted first with
100 mL of EtOAc, and then with CH2Cl2 (3 × 100 mL). The combined
organic layers were dried over Na2SO4. After the solvents were removed
under vacuum, the yellow solid residue was dissolved in a minimum
volume of CHCl3 and filtered through a pad of silica gel in a sintered
glass funnel to remove the chiral ligand. The pad was washed with
hexane/EtOAc 1:1 (400 mL). The filtrate was concentrated and
lyophilized from benzene to give 2.25 g (96%) of pure diol 9 as a
white solid: mp 91.0-92.3 °C; [R]25D +9.6° (c 1.27, CHCl3); IR (NaCl)
mp 43.0-45.0 °C); IR (NaCl) 1720, 1508, 1443, 1226, 1032, 826 cm-1
;
1H NMR δ 3.74 (s, 3H), 3.75 (s, 3H), 4.63 (dd, 2H, J ) 4.0, 2.0 Hz),
6.18 (dt, 1H, J ) 15.8, 2.0 Hz), 6.82 (s, 4H), 7.06 (dt, 1H, J ) 15.8,
4.1 Hz); 13C NMR δ 51.67, 55.69, 67.16, 114.69, 115.64, 121.43,
143.10, 152.16, 154.22, 166.55. Step b: To a solution of 4.3 g (19.4
mmol) of crotonate 5 in 140 mL of freshly distilled THF was injected
33.5 mL (50.0 mmol, 1.5 M solution in toluene) of DIBAL-H at -78
°C. The reaction mixture was stirred at -78 °C until starting material
5 was consumed (∼1 h) and then was warmed to room temperature.
After MeOH (4 mL) was added dropwise to destroy the excess DIBAL-
H, the reaction mixture was poured into 400 mL of 5% aqueous
potassium sodium tartrate solution and extracted first with 400 mL of
hexane/EtOAc (1:1), then with EtOAc (2 × 200 mL). The combined
extracts were dried (Na2SO4), and the solvents were removed, giving
3.7 g (99%) of pure 4-(4′-methoxyphenyloxy)-(2E)-buten-1-ol (6) as a
white solid: mp 65.3-66.2 °C; IR (NaCl) 3307, 1514, 1237, 1032,
826 cm-1; 1H NMR δ 1.57 (t, 1H, J ) 7.1 Hz), 3.75 (s, 3H), 4.20 (m,
2H), 4.49 (dd, 2H, J ) 5.0, 0.8 Hz), 5.98 (m, 2H), 6.81 (m, 4H); 13C
NMR δ 55.72, 62.91, 68.51, 114.63, 115.65, 126.50, 132.68, 152.64,
153.92. Step c: To a solution of 3.7 g (19.1 mmol) of alcohol 6 and
5.5 g (21.0 mmol) of Ph3P in 150 mL of dry CH2Cl2 was added 4.1 g
(22.9 mmol) of NBS at -23 °C. The reaction mixture was stirred under
N2 at this temperature for 1 h and then warmed to room temperature
for another hour. Hexane (200 mL) was added to precipitate Ph3PO,
and the reaction mixture was passed through a pad of silica gel in a
sintered glass funnel, which was rinsed with 400 mL of hexane/EtOAc
(8:1). Concentration gave 4.8 g (97%) of pure allylic bromide 7 as a
1
3272, 2073, 1508, 1461, 1232, 1055, 814 cm-1; H NMR δ 0.86 (t,
3H, J ) 7.0 Hz), 1.25 (m, 16H), 1.37 (m, 2H), 1.45 (m, 2H), 2.13 (tt,
2H, J ) 7.0, 2.2 Hz), 2.51 (m, 3H), 2.60 (d, 1H, J ) 4.9 Hz), 3.80 (s,
3H), 3.87 (ddt, 1H, J ) 6.0, 5.8, 2.1 Hz), 4.03 (m, 3H), 6.83 (m, 4H);
13C NMR δ 14.11, 55.69, 70.27, 70.43, 70.08, 75.43, 83.47, 114.65,
115.54, 152.48, 154.18; HRMS [FAB, M+] calcd for C25H40O4 m/z
404.2926, found 404.2915. The enantiomeric purity was determined
1
to be 95% ee by H NMR analysis of the bis-Mosher ester of diol 9
(see Figure 1).
(2R,3R,5E)-Octadecene-1,2,3-triol [(+)-10]. In a 500-mL two-neck
round-bottom flask was collected 160 mL of EtNH2 at -78 °C; then,
1.4 g (200 mmol) of lithium metal (prewashed with hexane, then with
Et2O, and finally with MeOH until it was shiny) was added. After the
blue solution was stirred for 30 min, a solution of 4.5 g (11.1 mmol)
of yne-diol 9 in 50 mL of THF was injected slowly. The reaction
mixture was stirred at this temperature for 10 h under N2 and then was
quenched with 40 mL of MeOH and 160 mL of water. The reaction
mixture was warmed to room temperature, and the product was
extracted with CHCl3 (4 × 150 mL). The extracts were dried over Na2-
SO4 and concentrated. After the brown semisolid residue was dissolved
in 200 mL of CHCl3 and washed with 200 mL of 3 N HCl, the aqueous
layer was further extracted with CHCl3 (2 × 100 mL). The combined
extract was dried (Na2SO4) and concentrated to give a brown solid
that was purified by column chromatography (elution with CHCl3/
MeOH 15:1). The white solid obtained was dissolved in CHCl3 and
filtered through a Cameo filter (Fisher Scientific) to remove the
dissolved silica gel. Concentration gave 2.7 g (81%) of the desired
triol 10 as a white solid: mp 66.5-67.5 °C; [R]25D +4.3° (c 1.5, CHCl3/
1
white solid: mp 60.0-60.5 °C; IR 1501, 1225, 1037, 820 cm-1; H
NMR δ 3.75 (s, 3H), 3.98 (d, 2H, J ) 7.4 Hz), 4.49 (d, 2H, J ) 4.7
Hz), 6.05 (m, 2H), 6.89 (s, 4H); 13C NMR δ 31.73, 55.71, 67.94, 114.63,
115.68, 129.07, 130.40, 152.48, 154.03; HRMS [FAB, M+] calcd for
C11H13BrO2 m/z 256.0099, 258.0079, found 256.0096, 258.0081.
4-Methoxyphenyl 5-Octadecyn-(2E)-enyl Ether (8a). To a solution
of 5.0 g (26.0 mmol) of 1-tetradecyne in 300 mL of THF was injected
16.3 mL (26.0 mmol, 1.6 M solution in hexane; in some reactions, we
used 22.5 mmol instead of 26.0 mmol of n-butyllithium at -23 °C.
The mixture was stirred at this temperature under N2 for 2.5 h and
then warmed to room temperature. A catalytic amount of CuI (300
mg, 1.6 mmol) was added, and the milklike solution was stirred at
room temperature for 15 min, followed by injection of 2.3 g (9.0 mmol)
of allylic bromide 7 in 20 mL of THF. After 1 h, 10% aqueous NaHSO4
solution (100 mL) was added to quench the reaction, and the product
was extracted with hexane/EtOAc (50:1) (3 × 100 mL). After the
combined extracts were dried (Na2SO4), the solvents were removed
under vacuum. The yellow solid residue was purified by column
chromatography (elution with pentane/Et2O 100:1) to give 2.68 g (81%)
of the desired enyne 8a as a white solid; in addition to 8a, 0.52 g (16%)
of the SN2′ isomeric byproduct 8b was also isolated as a yellow oil.
8a: mp 53.0-53.8 °C; Rf 0.51 (hexane/EtOAc 20:1); IR (NaCl) 1508,
1
MeOH 10:1); IR (NaCl) 3342, 1461 cm-1; H NMR δ 0.85 (t, 3H, J
) 7.0 Hz), 1.25 (m, 20H), 2.03 (dt, 2H, J ) 6.9, 6.8 Hz), 2.27 (m,
4H), 2.60 (d, 1H, J ) 5.5 Hz), 3.55 (dt, 1H, J ) 5.0, 3.7 Hz), 3.64 (m,
1H), 3.67 (dd, 1H, J ) 11.5, 5.2 Hz), 3.73 (dd, 1H, J ) 11.5, 3.6 Hz),
5.40 (dt, 1H, J ) 15.2, 7.5 Hz), 5.57 (dt, 1H, J ) 15.2, 6.5 Hz); 13C
NMR δ 14.11, 64.96, 72.03, 73.03, 124.84, 135.13; HRMS [FAB,
MH+] calcd for C18H37O3 m/z 301.2742, found 301.2735.
(2R,3R)-1,3-O-Benzylidene-(5E)-octadecene-1,2,3-triol [(+)-11].
To a solution of 245 mg (0.8 mmol) of ene-triol 10 and 252 mg (2.4
mmol) of benzaldehyde in 40 mL of CH2Cl2 was added 20 mg (0.1
mmol) of p-TsOH‚H2O. The reaction mixture was stirred at room
temperature for 4 h under N2, quenched by addition of 30 mg (0.22
mmol) of K2CO3, and stirred for another 10 min. After the solvent
was removed, the slurry was purified by column chromatography
(elution with hexane/EtOAc 6:1). The top spot (Rf 0.40, hexane/EtOAc
6:1), acetal 11, was isolated as a waxy solid, and the 1,2- and 2,3-O-
benzylidene isomers were combined and allowed to equilibrate again
with the 1,3-O-benzylidene derivative by the addition of 5 mg (0.025
mmol) of p-TsOH‚H2O, 100 mg (0.9 mmol) of benzaldehyde, and 8
mL of CH2Cl2. The combined yield of the desired acetal 11 in the two
1
1454, 1237, 1032, 826 cm-1; H NMR δ 0.86 (t, 3H, J ) 7.0 Hz),
1.24 (m, 16H), 1.37 (m, 2H), 1.50 (m, 2H), 2.15 (tt, 2H, J ) 7.0, 2.3
Hz), 2.95 (m, 2H), 3.75 (s, 3H), 4.45 (dd, 2H, J ) 5.7, 1.3 Hz), 5.78-
5.84 (m, 1H), 5.93-5.99 (m, 1H), 6.81 (m, 4H); 13C NMR δ 14.11,
55.69, 68.80, 76.31, 83.05, 114.57, 115.63, 126.40, 129.33, 152.79,
153.82; HRMS [FAB, M+] calcd for m/z C25H38O2 370.2872, found
370.2874. 8b: Rf 0.59 (hexane/EtOAc 20:1); IR (NaCl) 1502, 1467,
1
1232, 1044, 826 cm-1; H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.24 (m,
16H), 1.36 (m, 2H), 1.49 (dt, 2H, J ) 14.9, 7.1 Hz), 2.20 (dt, 2H, J )
7.0, 2.1 Hz), 3.49 (m, 1H), 3.75 (s, 3H), 3.85 (t, 1H, J ) 8.4 Hz), 4.00
(dd, 1H, J ) 8.9, 6.1 Hz), 5.20 (dt, 1H, J ) 10.1, 1.4 Hz), 5.45 (dt,
1H, J ) 17.0, 1.5 Hz), 5.92 (ddd, 1H, J ) 17.0, 10.2, 5.8 Hz), 6.82
(m, 4H); 13C NMR δ 14.12, 35.99, 55.70, 71.84, 77.16, 85.03, 114.57,
115.96, 116.71, 135.08, 152.77, 154.01; HRMS [FAB, M+] calcd for
C25H38O2 m/z 370.2872, found 370.2881.
runs was 276 mg (84%): [R]25 +16.9° (c 4.13, CHCl3); IR (NaCl)
D
1
3436, 1085, 1026, 744, 691 cm-1; H NMR δ 0.85 (t, 3H, J ) 7.0
Hz), 1.24 (m, 20H), 2.00 (dt, 2H, J ) 6.9, 6.6 Hz), 2.39 (t, 2H, J )
7.1 Hz), 2.57 (d, 1H, J ) 11.6 Hz), 3.49 (d, 1H, J ) 11.6 Hz), 3.84 (t,
1H, J ) 7.1 Hz), 4.03 (dd, 1H, J ) 11.8, 0.9 Hz), 4.22 (dd, 1H, J )
11.8, 1.7 Hz), 5.41 (dt, 1H, J ) 15.2, 7.0 Hz), 5.55 (s, 1H), 5.59 (dt,
(2R,3R)-1-(4 -Methoxyphenyloxy)-5-octadecyne-2,3-diol [(+)-9].