KONIDENA ET AL.
3
ꢀ
was added at 0 C and stirred for 5 hr. The reaction mixture
(m, 2H), 1.83–1.63 (m, 4H), 1.47–1.21 (m, 7H), 1.17 (d,
3H), 1.13 (m, 1H); 13C NMR (75 MHz, CDCl3): δ160.3,
135.6, 130.3, 128.9, 120.1, 114.3, 75.6, 72.3, 56.7, 54.3,
40.1, 36.6, 31.3, 29.1, 28.2, 27.4, 25.6, 24.3, 24.0, 22.3;
HRMS (ESI): m/z calculated for C22H34O2S2Na [M + Na]+
417.2001 found 417.2008.
ꢀ
was quenched with aq. Na2SO4 (20 mL) at 0 C dropwise
and stirred for an additional 2 hr. It was filtered through
celite and extracted with EtOAc (4 × 20 mL), dried
(Na2SO4), and concentrated, and the residue was purified by
column chromatography (Silica gel, 60–120 mesh, 25%
EtOAc in pet. ether) to give an inseparable mixture of alco-
hols as colorless oil. The mixture of alcohols in EtOAc
(5 mL) was treated with solid NaHCO3 (0.5 g) and a cata-
lytic amount of PtO2 under H2 gas pressure. After 2 hr, the
reaction mixture was diluted with EtOAc (50 mL), filtered
through celite, dried (Na2SO4), and concentrated, and the
residue was purified by column chromatography (Silica gel,
60–120 mesh, 25% EtOAc in pet. ether) to afford alcohol
5.4 | (E)-methyl 3-(2-((R)-7-(4-methoxybenzyloxy)
octyl)-1,3-dithian-2-yl)acrylate (9)
ꢀ
Ozone was bubbled through a cooled (−78 C) solution of
8 (3.1 g, 7.86 mmol) in CH2Cl2 (30 mL) until the pale blue
color persisted. Excess ozone was removed with Me2S
ꢀ
(2 mL) and stirred for 15 min at 0 C. The reaction mixture
6 (4.2 g, 71%) as a yellow liquid; [α]25 = +8.7 (c 0.74,
was concentrated under reduced pressure to give aldehyde,
which was used for further reaction.
D
CHCl3); IR (neat): 3540, 3,070, 3,025 2,958, 2,836, 1,470,
1,310, 1,280, 970 cm−1 1H NMR (300 MHz, CDCl3): δ
;
A solution of the above aldehyde in benzene (50 mL)
was treated with (methoxy- carbonylmethylene)triphenyl
phosphorane (3.14 g, 9.44 mmol) at reflux temperature.
After 2 hr, the solvent was evaporated, and the residue was
purified by column chromatography (60–120 Silica gel, 8%
EtOAc in pet. ether) to furnish 9 (2.95 g, 83%) as a yellow
7.21 (d, 2H, J = 8.6 Hz), 6.79 (d, 2H, J = 8.6 Hz), 4.51 (d,
1H, J = 11.0 Hz), 4.41 (d, 1H, J = 11.0 Hz), 3.77 (s, 3H),
3.71 (t, 2H, J = 6.3 Hz), 3.43 (m, 1H), 2.06 (brs, 1H),
1.51–1.44 (m, 3H), 1.40–1.27 (m, 7H), 1.14 (d, 3H,
J = 6.0 Hz); 13C NMR (75 MHz, CDCl3): δ 160.1, 130.1,
128.3, 114.3, 75.4, 72.3, 62.4, 56.7, 36.3, 32.8, 31.3, 28.2,
26.3, 22.3; HRMS (ESI): m/z calculated for C16H26O3Na
[M + Na]+ 289.1883 found 289.1888.
liquid; [α]25 = −56.1 (c 0.74, CHCl3); IR (neat): 3067,
D
3,082, 2,955, 2,870, 2,840, 1,695, 1,602, 1,440, 1,350,
1
1,220, 980 cm−1; H NMR (CDCl3, 300 MHz): δ 7.24 (d,
2H, J = 8.2 Hz), 6.87 (d, 1H, J = 15.6 Hz), 6.77 (d, 2H,
J = 8.2 Hz), 5.81 (d, 1H, J = 15.6 Hz), 4.51 (d, 1H,
J = 10.9 Hz), 4.42 (d, 1H, J = 10.9 Hz), 3.73 (s, 3H), 3.69
(s, 3H), 3.39 (m, 1H), 2.87–2.71 (m, 4H), 1.97–1.86 (m,
2H), 1.77–1.64 (m, 3H), 1.54–1.43 (m, 2H), 1.41–1.20 (m,
7H), 1.17 (d, 3H, J = 6.0 Hz); 13C NMR (75 MHz, CDCl3):
δ 171.2, 160.3, 145.3, 130.1, 129.6, 128.7, 125.3, 114.3,
75.7, 72.3, 68.3, 56.3, 52.3, 49.3, 36.1, 31.2, 29.4, 29.0,
26.2, 25.8, 24.2, 21.2; HRMS (ESI): m/z calculated for
C24H36O4S2Na [M + Na]+ 475.2055 found 475.2061.
5.3 | 2-((R)-7-(4-Methoxybenzyloxy)octyl)-2-vinyl-
1,3-dithiane (8)
To a stirred solution of 6 (4.0 g, 15.03 mmol) in CH2Cl2
(50 mL), CBr4 (5.97 g, 18.04 mmol) and Ph3P (5.9 g,
22.54 mmol) were added at 0 ꢀC and stirred at room temper-
ature for 3 hr. The reaction mixture was evaporated, and the
residue was purified by column chromatography (60–120
Silica gel, 5% EtOAc in pet. ether) to afford 7 (3.6 g, 74%)
as a colorless syrup.
To
a
stirred solution of 2-vinyldithiane (1.76 g,
5.5 | (E)-3-(2-((R)-7-(4-Methoxybenzyloxy)octyl)-
1,3-dithian-2-yl)acrylic acid (10)
ꢀ
12.07 mmol) in dry THF (30 mL) cooled at −78 C was
added a 1.6M solution of n-BuLi in hexane (9.0 mL,
13.16 mmol) dropwise. The reaction mixture was stirred at
To a solution of 9 (2.7 g, 5.97 mmol) in THF: MeOH: water
(3:1:1, 20 mL), LiOH (0.21 g, 8.96 mmol) was added and
stirred at room temperature for 4 hr. The pH of the reaction
mixture was adjusted to acidic with 1N HCl solution and
extracted with ethyl acetate (30 mL). Organic layers were
washed with water (15 mL), brine (15 mL), dried (Na2SO4),
evaporated under reduced pressure, and purified the residue
through column chromatography (60–120 Silica gel, 30%
EtOAc in pet. ether) to give 10 (2.0 g, 79%) as a colorless
ꢀ
ꢀ
−20 C for 1.5 hr. After cooling to −78 C, a solution of
bromide 7 (3.6 g, 10.97 mmol) in THF (5 mL) wasꢀadded
dropwise, and the mixture was maintained at −30 C for
2 hr. The reaction was quenched with water (100 mL), and
the mixture was extracted with Et2O (2 × 100 mL). The
combined extracts were washed with brine (100 mL), dried
(Na2SO4), and concentrated. The residual oil was purified by
column chromatography on silica gel chromatography
(60–120 Silica gel, 10% EtOAc in pet. ether) to give
oil; [α]25 = −48.4 (c 0.74, CHCl3); IR (neat): 3570, 3,060,
D
8 (3.3 g, 77%) as a colorless oil; [α]25 = −78.2 (c 0.74,
3,032 2,965, 2,880, 2,840, 1,690, 1,605, 1,420, 1,350,
D
1
1,270, 940, 730, 678 cm−1; H NMR (CDCl3, 300 MHz): δ
CHCl3); IR (neat): 3090, 3,065 2,925, 2,840, 2,460, 1,610,
1,440, 1,370, 1,240, 950, 740, 676 cm−1; H NMR (CDCl3,
1
7.19 (d, 2H, J = 8.5 Hz), 6.84 (d, 1H, J = 15.6 Hz,), 6.81
(d, 2H, J = 8.5 Hz), 5.79 (d, 1H, J = 15.5 Hz), 4.48 (s, 2H),
3.73 (s, 3H), 3.51 (m, 1H), 2.91–2.77 (m, 4H), 1.93–1.81
(m, 2H), 1.77–1.51 (m, 5H), 1.44–1.21 (m, 7H), 1.19 (d,
300 MHz): δ 7.19 (d, 2H, J = 8.0 Hz), 6.79 (d, 2H,
J = 8.60 Hz), 5.83 (m, 1H), 5.03–4.91(m, 2H), 4.47 (s, 2H),
3.73 (s, 3H), 3.41 (m, 1H), 2.82–2.66 (m, 4H), 2.05–1.96