2867
S. AnkiReddy et al.
Paper
Synthesis
(4S,5R,2E)-5-[(4-Methoxybenzyl)oxy]-4-methylhex-2-enal (4)
[α]D25 –4.0 (c 0.5, CHCl3).
IR (KBr): 3445, 2930, 2857, 1700, 1600, 1512, 1462, 1252, 771 cm–1
1H NMR (500 MHz, CDCl3): δ = 7.43 (dd, J = 8.6, 1.3 Hz, 1 H), 7.25–7.21
(m, 2 H), 6.95–6.84 (m, 3 H), 6.22–6.13 (m, 2 H), 4.51 (d, J = 11.3 Hz, 1
H), 4.38 (d, J = 11.5 Hz, 1 H), 3.81 (s, 3 H), 3.65–3.53 (m, 2 H), 3.52–
3.40 (m, 2 H), 2.83–2.70 (m, 1 H), 2.56–2.41 (m, 2 H), 1.97–1.64 (m, 3
H), 1.12 (d, J = 6.0 Hz, 3 H), 1.08 (d, J = 6.6 Hz, 3 H), 1.06 (d, J = 6.7 Hz,
3 H), 0.93–0.87 (m, 12 H), 0.84 (d, J = 6.9 Hz, 3 H), 0.09–0.04 (m, 6 H).
Dess–Martin periodinane (0.16 g, 0.38 mmol) and NaHCO3 (0.04 g,
0.48 mmol) were added to a solution of alcohol 23 (0.08 g, 0.32
mmol) in CH2Cl2 (10 mL) at 0 °C. After stirring for 30 min, the reaction
was warmed to 25 °C for 1 h. The reaction mixture was then poured
into a solution of Na2S2O3 (20 mL), NaHCO3 (20 mL) and Et2O (50 mL)
and stirred for 30 min. The organic layer was separated and the aq
layer extracted with Et2O (2 × 20 mL). The organic layers were com-
bined, washed with Na2S2O3 (30 mL), NaHCO3 (30 mL) and brine (30
mL), dried over anhydrous Na2SO4, filtered and concentrated under
reduced pressure to provide the aldehyde 4. This aldehyde was used
immediately in the next reaction without further purification.
.
13C NMR (75 MHz, CDCl3): δ = 204.1, 159.1, 147.7, 143.2, 130.8, 129.1,
128.7, 126.5, 113.7, 77.5, 77.2, 70.4, 66.2, 55.2, 42.3, 39.5, 37.7, 34.3,
26.1, 18.3, 16.7, 16.3, 15.5, 15.3, 14.1, 12.6, –3.9, –4.1.
HRMS (ESI): m/z [M + Na]+ calcd for C32H54O5SiNa: 569.3612; found:
569.3612.
(2S,3S,4S,6R,8E,10E,12S,13R)-1,3-Bis[(tert-butyldimethylsilyl)oxy]-
13-[(4-methoxybenzyl)oxy]-2,4,6,12-tetramethyltetradeca-8,10-
dien-7-one (24)
Ethyl (2E,4S,5S,6S,8R,10E,12E,14S,15R)-5-[(tert-Butyldimethylsi-
lyl)oxy]-15-[(4-methoxybenzyl)oxy]-4,6,8,14-tetramethyl-9-oxo-
hexadeca-2,10,12-trienoate (26)
To a solution of phosphonate 5 (0.08 g, 0.14 mmol) in THF (10 mL)
was added Ba(OH)2·8H2O (0.03 g, 0.17 mmol, predried at 120 °C for 2
h). The resulting solution was allowed to stir at r.t. for 30 min. Next, a
solution of the aldehyde 4 (0.03 g, 0.12 mmol) in THF–H2O (40:1, 2
mL) was added to the phosphonate solution, followed by another por-
tion of the THF–H2O mixture (2 mL). After stirring for 30 min, the
mixture was diluted with EtOAc and filtered through a small pad of
Celite. The filtrate was washed with aq NaHCO3, and the organic layer
was separated and the aq layer extracted with EtOAc (2 × 5 mL). The
combined organic layers were dried over anhydrous Na2SO4 and con-
centrated under reduced pressure. The crude residue was purified by
column chromatography (Rf = 0.1, hexane–EtOAc, 9:1) to provide the
product 24 (0.05 g, 80%) as a colorless oil.
Dess–Martin periodinane (16 mg, 0.036 mmol) and NaHCO3 (4 mg,
0.045 mmol) were added to a solution of alcohol 25 (18 mg, 0.03
mmol) in CH2Cl2 (5 mL) at 0 °C. After stirring for 30 min, the mixture
was warmed to 25 °C for 1 h. The reaction mixture was poured into a
solution of Na2S2O3 (5 mL), NaHCO3 (5 mL) and Et2O (5 mL) and then
stirred for 30 min. The organic layer was separated and the aq layer
was extracted with Et2O (2 × 5 mL). The combined organic layer was
washed with Na2S2O3 (5 mL), NaHCO3 (10 mL) and brine (5 mL), dried
over anhydrous Na2SO4, filtered and concentrated under reduced
pressure to provide the corresponding aldehyde. This aldehyde was
used immediately in the next reaction without purification.
[α]D25 –7.8 (c 0.7, CHCl3).
IR (KBr): 2930, 2857, 1720, 1589, 1512, 1252, 836 cm–1
A solution of triethyl phosphonoacetate (6 mg, 0.025 mmol) in THF (5
mL) was added slowly to a stirred solution of NaH (2 mg, 0.05 mmol)
in THF (5 mL) at 0 °C under N2. The mixture was stirred at 0 °C for 30
min. Next, the mixture was cooled to 0 °C and the above crude alde-
hyde in THF (5 mL) was added dropwise over 10 min. The resulting
mixture was stirred at 0 °C for 30 min and then quenched with sat.
NH4Cl solution (5 mL). The product was extracted with EtOAc (3 × 5
mL), and the combined organic layer dried over Na2SO4. The solvent
was removed under reduced pressure and the crude residue was pu-
rified by silica gel column chromatography (10% EtOAc–hexane) to af-
ford (E)-olefin ester 26 (14 mg, 90% over 2 steps) as a colorless liquid.
.
1H NMR (500 MHz, CDCl3): δ = 7.26–7.17 (m, 3 H), 6.92–6.85 (m, 3 H),
6.20–6.13 (m, 2 H), 4.51 (d, J = 11.4 Hz, 1 H), 4.38 (d, J = 11.4 Hz, 1 H),
3.80 (s, 3 H), 3.69–3.63 (m, 1 H), 3.47–3.33 (m, 3 H), 2.88–2.78 (m, 1
H), 2.55–2.45 (m, 1 H), 1.90–1.55 (m, 4 H), 1.12 (d, J = 6.2 Hz, 3 H),
1.11 (d, J = 6.2 Hz, 3 H), 1.06 (d, J = 6.7 Hz, 3 H), 0.93–0.85 (m, 21 H),
0.82 (d, J = 6.8 Hz, 3 H), 0.04–0.01 (m, 12 H).
13C NMR (75 MHz, CDCl3): δ = 175.9, 159.1, 147.5, 146.0, 129.3, 129.1,
128.4, 126.6, 113.7, 74.5, 70.4, 66.4, 60.4, 55.2, 42.5, 39.0, 37.9, 37.6,
26.1, 25.9, 21.0, 18.7, 18.3, 18.2, 16.7, 16.0, 14.2, 11.5, –3.8, –4.3, –5.3
(2 C).
[α]D25 –13.7 (c 0.7, CHCl3).
IR (KBr): 2960, 2857, 1717, 1635, 1594, 1252, 772 cm–1
.
HRMS (ESI): m/z [M + Na]+ calcd for C38H68O5Si2Na: 683.4474; found:
683.4471.
1H NMR (500 MHz, CDCl3): δ = 7.43 (dd, J = 8.3, 1.5 Hz, 1 H), 7.25–7.18
(m, 2 H), 6.98 (dd, J = 15.8, 7.5 Hz, 1 H), 6.87 (d, J = 8.3 Hz, 2 H), 6.22–
6.15 (m, 3 H), 5.76 (dd, J = 15.8, 1.5 Hz, 1 H), 4.51 (d, J = 11.3 Hz, 1 H),
4.38 (d, J = 11.3 Hz, 1 H), 4.22–4.10 (m, 3 H), 3.81 (s, 3 H), 3.50–3.42
(m, 1 H), 2.81–2.66 (m, 1 H), 2.59–2.44 (m, 2 H), 1.67–1.53 (m, 3 H),
1.28 (t, J = 6.7 Hz, 3 H), 1.12 (d, J = 6.7 Hz, 3 H), 1.06 (d, J = 6.7 Hz, 3 H),
1.05 (d, J = 6.9 Hz, 3 H), 1.03 (d, J = 6.8 Hz, 3 H), 0.93–0.87 (s, 9 H), 0.82
(d, J = 6.0 Hz, 3 H), 0.07–0.02 (m, 6 H).
13C NMR (75 MHz, CDCl3): δ = 195.1, 159.0, 152.2, 147.6, 143.1, 141.2,
129.1, 128.6, 126.5, 120.1, 113.7, 78.7, 77.5, 70.3, 60.1, 55.2, 42.5,
42.1, 41.0, 37.5, 34.6, 26.0, 18.3, 16.6, 16.1, 15.4, 15.1, 14.2, 14.1, –3.8
(2 C).
(2S,3S,4S,6R,8E,10E,12S,13R)-3-[(tert-Butyldimethylsilyl)oxy]-1-
hydroxy-13-[(4-methoxybenzyl)oxy]-2,4,6,12-tetramethyltetra-
deca-8,10-dien-7-one (25)
To a solution of compound 24 (0.035 g, 0.05 mmol) in a mixture of
MeOH (6 mL) and CH2Cl2 (6 mL) was added CSA (0.12 g, 0.053 mmol),
in one portion, at 0 °C. After 1 h, the reaction was quenched by the
addition of sat. aq NaHCO3 solution (10 mL), and the aq layer was ex-
tracted with CH2Cl2 (3 × 15 mL). The combined organic layers were
washed with brine (10 mL), dried over MgSO4, filtered, and the sol-
vent was removed in vacuo. Column chromatography (20% EtOAc–PE)
yielded alcohol 25 (0.024 mg, 85%) as a colorless oil.
HRMS (ESI): m/z [M + Na]+ calcd for C36H58O6SiNa: 637.3877; found:
637.3877.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2860–2868