J. S. Yadav, P. Dutta, B. Ganganna, E. Srinivas
FULL PAPER
was stirred at room temperature for 30 min. Then, a solution of
alcohol 3 (17 mg, 0.119 mmol) in toluene (0.5 mL) and DMAP
(7 mg, 53 μmol) were added at 0 °C. The resulting solution was
stirred at room temperature for 3 h and then quenched by the ad-
dition of a saturated aqueous NaHCO3 solution (1.0 mL). The or-
ganic layer was separated, and the aqueous layer was extracted with
ethyl acetate (2ϫ 5 mL). The combined organic layers were washed
with brine (5 mL), dried with anhydrous Na2SO4, filtered, and con-
centrated under reduced pressure. Purification of the residue by
flash column chromatography (EtOAc/PE, 30:70) afforded com-
pound 3a (20 mg, 75%) as a colorless oil; Rf = 0.5 (EtOAc/PE,
(ddd, J = 7.5, 10.5, 17.1 Hz, 1 H), 8.19–8.23 (m, 2 H), 8.27–8.31
(m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.4, 55.5, 73.5,
78.6, 93.9, 120.2, 123.5, 130.7, 133.6, 135.9, 150.4, 164.0 ppm.
HRMS (ESI): calcd. for C14H17O6NNa [M + Na]+ 318.0948; found
318.0971.
(2R,3S)-3-(Methoxymethoxy)pent-4-en-2-ol (14): The p-nitrobenzo-
ate ester (90 mg, 0.3 mmol) was dissolved in MeOH (4 mL), and
K2CO3 (50 mg, 0.6 mmol) was added. The mixture was stirred at
room temperature for 12 h and then poured into a saturated aque-
ous ammonium chloride solution (5 mL). The resulting mixture
was extracted with Et2O (3ϫ 10 mL). The combined organic layers
were washed with water (15 mL) and brine (15 mL), dried with
anhydrous Na2SO4, and concentrated in vacuo. The residue was
purified by flash chromatography (EtOAc/PE, 20:80) to give
alcohol 14 (36 mg, 82%) as a colorless liquid; Rf = 0.2 (EtOAc/PE,
40:60). [α]2D0 = –3.3 (c = 0.16, CHCl ). IR (neat): ν = 2920, 2845,
˜
3
1760, 1730, 1094, 1043, 857, 756 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 1.81 (qd, J = 7.0, 1.2 Hz, 3 H), 1.85 (q, J = 1.2 Hz, 3
H), 2.04–2.11 (m, 1 H), 2.27–2.36 (m, 1 H), 2.47–2.60 (m, 2 H),
4.68 (ddd, J = 4.4, 6.0, 7.9 Hz, 1 H), 5.35 (d, J = 10.5 Hz, 1 H),
5.39–5.48 (m, 2 H), 5.88 (ddd, J = 6.6, 10.5, 17.2 Hz, 1 H), 6.92
(qq, J = 1.4, 7.0 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
12.0, 14.5, 23.7, 28.0, 75.0, 80.0, 120.0, 128.1, 131.7, 138.7, 166.6,
176.7 ppm. HRMS (ESI): calcd. for C12H16O4Na [M + Na]+
247.0940; found 247.0935.
20:80). [α]2D0 = +48.5 (c = 0.24, CHCl ). IR (neat): ν = 2923, 2855,
˜
3
1717, 1457, 1259, 799 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.15
(d, J = 6.0 Hz, 3 H), 3.38 (s, 3 H), 3.81–3.98 (m, 2 H), 4.60 (d, J
= 6.8 Hz, 1 H), 4.72 (d, J = 6.8 Hz, 1 H), 5.25–5.38 (m, 2 H), 5.76
(ddd, J = 7.6, 10.6, 17.4 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 17.8, 55.6, 69.3, 81.8, 94.2, 120.1, 133.8 ppm.
(2S,3S)-3-(Methoxymethoxy)pent-4-en-2-ol (6): To a stirred solu-
tion of allyl methoxymethyl ether (1.93 g, 19.0 mmol) in dry THF
(15 mL) was added sBuLi (1.3 m in cyclohexane, 9.7 mL,
12.64 mmol) dropwise at –78 °C over a period of 10 min. The
brown reaction mixture was stirred at the same temperature for
30 min, and then a solution of (+)-Ipc2BOMe (4.0 g, 12.6 mmol)
in dry THF (10 mL and then 2 mL rinse) was added by syringe.
The brown color disappeared, and the colorless solution was again
stirred for 1 h. Sequentially, BF3·OEt2 (1.5 mL, 14.0 mmol) and
acetaldehyde (0.35 mL, 6.32 mmol) were added, and the reaction
mixture was stirred for 3 h at the same temperature and then
quenched by the addition of an aqueous saturated NaHCO3 solu-
tion (8 mL) and 30% H2O2 (4 mL). The resulting mixture was
stirred at room temp. for 30 min. The organic layer was separated,
and the aqueous layer was extracted with diethyl ether (2ϫ 30 mL).
The combined organic layers were washed with brine (30 mL),
dried with anhydrous Na2SO4, and concentrated in vacuo to give
a colorless oil. The crude residue was purified by flash column
chromatography (EtOAc/PE, 20:80) to yield product 6 (0.64 g,
70%) as a colorless oil; Rf = 0.2 (EtOAc/PE, 20:80). [α]2D0 = +12.1
(2R,3S)-2-(tert-Butyldimethylsilyloxy)-3-(methoxymethoxy)pent-4-
ene (4): To a stirred solution of alcohol 14 (100 mg, 0.68 mmol) in
dry DCM (4 mL) were added imidazole (79 mg, 1.16 mmol) and
tert-butyldimethylsilyl chloride (154 mg, 1.02 mmol) followed by
DMAP (8 mg, 0.068 mmol) at 0 °C. The reaction mixture was
warmed to room temperature and stirred for 3 h, whereupon TLC
analysis indicated complete consumption of starting material. The
reaction mixture was then diluted by the addition of water (4 mL),
and the aqueous phase was extracted with DCM (2ϫ 10 mL). The
combined organic layers were washed with brine (15 mL) and dried
with Na2SO4, and the organic solvent was evaporated under re-
duced pressure. The crude residue was purified by flash chromatog-
raphy (EtOAc/PE, 5:95) to give silyl ether 4 (160 mg, 90%) as a
colorless oil; Rf = 0.5 (EtOAc/PE, 10:90). [α]2D0 = +57.5 (c = 0.36,
CHCl ). IR (neat): ν = 2928, 2856, 1254, 1101, 1036, 832, 775 cm–1.
˜
3
1H NMR (300 MHz, CDCl3): δ = 0.02–0.11 (m, 6 H), 0.88 (s, 9
H), 1.15 (d, J = 6.0 Hz, 3 H), 3.37 (s, 3 H), 3.77–3.90 (m, 2 H),
4.58 (d, J = 6.4 Hz, 1 H), 4.70 (d, J = 6.4 Hz, 1 H), 5.19–5.32 (m,
2 H), 5.73 (ddd, J = 7.4, 10.8, 17.0 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = –4.7, –4.6, 18.1, 19.6, 25.8, 55.4, 70.7, 81.6,
93.9, 118.7, 135.5 ppm. HRMS (ESI): calcd. for C13H28O3NaSi [M
+ Na]+ 283.1699; found 283.1718.
(c = 0.44, CHCl ). IR (neat): ν = 2928, 1368, 1255, 1189, 1094,
˜
3
980, 831, 776 cm–1. H NMR (500 MHz, CDCl3): δ = 1.16 (d, J =
1
6.3 Hz, 3 H), 3.40 (s, 3 H), 3.68–3.74 (m, 1 H), 3.75–3.80 (m, 1 H),
4.59 (d, J = 6.6 Hz, 1 H), 4.74 (d, J = 6.6 Hz, 1 H), 5.29–5.32 (m,
1 H), 5.32–5.35 (m, 1 H), 5.66 (ddd, J = 7.8, 9.9, 17.7 Hz, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 18.4, 55.7, 69.5, 82.9,
94.0, 120.1, 134.6 ppm. HRMS (ESI): calcd. for C7H14O3Na [M +
Na]+ 169.0835; found 169.0843.
(R)-5-[(1R,4S,5R,E)-5-(tert-Butyldimethylsilyloxy)-1-hydroxy-4-
(methoxymethoxy)hex-2-enyl]dihydrofuran-2(3H)-one (15): Azeo-
tropically dried compound 3 (50 mg, 0.352 mmol) and compound
4 (137 mg, 0.704 mmol) were dissolved in about 2.5 mL of dry
DCM, and the solution was degassed by using argon. To that solu-
tion was added Grubbs-II catalyst (30 mg, 35 μmol), and the light
brown solution was heated at reflux for 2 h. After cooling to room
temperature, the volatiles were removed under reduced pressure.
(2R,3S)-3-(Methoxymethoxy)pent-4-en-2-yl 4-Nitrobenzoate (De-
rived from 6): A mixture of 6 (60 mg, 0.41 mmol), p-nitrobenzoic
acid (0.34 g, 2.05 mmol), and PPh3 (0.65 g, 2.46 mmol) in dry tolu-
ene (10 mL) was stirred at room temperature for 30 min. Then, The residue was subjected to flash column chromatography
DIAD (0.49 mL, 2.46 mmol) was added dropwise, and the resulting
yellow mixture was stirred for an additional 2 h. The toluene was
evaporated, and the mixture was purified by silica gel flash column
chromatography (EtOAc/PE, 12:88) to give the p-nitrobenzoate
(97 mg, 80%) as a light yellow oil; Rf = 0.5 (EtOAc/PE, 20:80).
(EtOAc/PE, 40:60) to afford compound 15 (79 mg, 60%) as a color-
less oil; Rf = 0.3 (EtOAc/PE, 50:50). [α]2D0 = +13.3 (c = 0.24,
CHCl ). IR (neat): ν = 2925, 2855, 1772, 1461, 1254, 1097,
˜
3
833 cm–1. H NMR (500 MHz, CDCl3): δ = 0.06 (s, 3 H), 0.07 (s,
1
3 H), 0.88 (s, 9 H), 1.14 (d, J = 6.3 Hz, 3 H), 2.10–2.28 (m, 2 H),
2.35–2.68 (m, 2 H), 3.37 (s, 3 H), 3.83–3.93 (m, 2 H), 4.14 (t, J =
[α]2D0 = +17.2 (c = 0.68, CHCl ). IR (neat): ν = 2921, 1722, 1270,
˜
3
1
1100, 1028, 800, 718 cm–1. H NMR (500 MHz, CDCl3): δ = 1.40 5.8 Hz, 1 H), 4.46 (dt, J = 7.3, 5.6 Hz, 1 H), 4.59 (d, J = 6.7 Hz, 1
(d, J = 6.6 Hz, 3 H), 3.37 (s, 3 H), 4.23 (dd, J = 4.0, 7.5 Hz, 1 H),
4.61 (d, J = 6.9 Hz, 1 H), 4.73 (d, J = 6.9 Hz, 1 H), 5.29 (dq, J =
6.6, 4.1 Hz, 1 H), 5.36–5.38 (m, 1 H), 5.38–5.41 (m, 1 H), 5.82
H), 4.65 (d, J = 6.7 Hz, 1 H), 5.74 (dd, J = 6.1, 15.7, Hz, 1 H), 5.80
(dd, J = 6.9, 15.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ
= –4.7, –4.6, 18.1, 19.6, 23.8, 25.8, 28.5, 55.5, 70.7, 74.4, 80.2, 82.5,
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Eur. J. Org. Chem. 2015, 6891–6899