The Journal of Organic Chemistry
Note
added at 0 °C under nitrogen atmosphere, and the mixture was
allowed to stir for 30 min at room temperature. Thereafter, 4-methoxy
benzyl bromide (5.49 g, 27.6 mmol) dissolved in dry THF (50 mL)
was added dropwise to the above reaction mixture. After completion of
the reaction (monitored by TLC), it was carefully quenched with ice
pieces at 0 °C and then with a saturated solution of NH4Cl (100 mL).
The reaction mixture was diluted with ethyl acetate (150 mL). The
organic layer was separated and the aqueous layer was extracted with
ethyl acetate (3 × 100 mL). The combined organic layer was washed
with brine (2 × 150 mL), dried over anhydrous Na2SO4, and
evaporated to dryness under reduced pressure to get the crude
product, which was purified by column chromatography over silica gel
(ethyl acetate/hexane = 1:49) to afford the desired product 13 (7.3 g,
((4S,5R)-4-(Benzyloxy)-3-(4-methoxybenzyloxy)-5-methyl-
tetrahydrofuran-2yl)(furan-2-yl)methanol (15). To a stirred
solution of furan (2.6 mL, 34.4 mmol) in dry diethyl ether (52 mL)
was added n-BuLi (12 mL, 24 mmol, 2 M in hexane) dropwise at −15
°C under an argon atmosphere. The reaction mixture was slowly
warmed to 20 °C and stirred for 1 h and then again cooled to 0 °C.
Thereafter, the aldehyde 14 (3.5 g, 9.8 mmol) dissolved in dry diethyl
ether (15 mL) was added to the above reaction mixture, and it was
allowed to stir for 5 h at room temperature. After completion of the
reaction (monitored by TLC), it was cooled to 0 °C and carefully
quenched with saturated NH4Cl solution (50 mL). The two layers
were separated, and the aqueous layer was extracted with ethyl acetate
(2 × 100 mL). The combined organic layers were washed with brine
(2 × 100 mL), dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure to get the crude oil, which on
purification over silica gel column chromatography (ethyl acetate/
hexane = 1:9) afforded alcohol 15 (3.54 g, 85%) as a colorless liquid:
IR (neat) 3410, 2924, 2855, 1713, 1636, 1507, 1453, 1050, 752, 742,
27
91%) as a colorless liquid: [α]D −14.5 (c = 0.9, CHCl3); IR (neat)
2930, 2859, 1612, 1512, 1462, 1362, 1096, 1036, 778, 741, 589 cm−1
;
1H NMR (300 MHz, CDCl3) δ 7.32−7.22 (m, 5H), 7.19 (d, J = 8.3
Hz, 2H), 6.81 (d, J = 9.0 Hz, 2H), 4.50 (ABq, J = 12.0, 18.8 Hz, 2H),
4.38 (dd, J = 3.7, 12.0 Hz, 2H), 4.43−4.05 (m, 1H), 3.91 (d, J = 3.7
Hz, 1H), 3.83 (dd, J = 3.0, 5.2 Hz, 1H), 3.79 (s, 3H), 3.81−3.78 (m,
1H), 3.73−3.66 (m, 2H), 3.54 (dd, J = 7.5, 9.8 Hz, 1H), 1.25 (d, J =
6.7 Hz, 3H), 0.89 (s, 9H), 0.04 (d, J = 1.5 Hz, 6H) ppm; 13C NMR
(75 MHz, CDCl3) 159.2, 138.1, 130.1, 129.3, 128.3, 127.5, 127.4,
113.8, 84.0, 83.9, 71.3, 71.0, 63.8, 55.2, 25.4, 18.3, 14.1, −5.4; HRMS
(ESI) m/z calcd. for C27H40O5Si [M + Na]+ 495.2542, found
495.2532.
1
600 cm−1; H NMR (300 MHz, CDCl3) δ 7.39−7.25 (m, 5H), 7.02
(d, J = 9.0 Hz, 1H), 6.76−6.8 (m, 2H), 6.41−6.24 (m, 3H), 6.21−6.16
(m, 1H), 4.62 (dd, J = 13.5 Hz, 0.6H), 4.60 (dd, J = 6.7, 12.0 Hz,
0.6H), 4.33 (d, J = 6.7 Hz, 0.4H), 4.27 (d, J = 13.5 Hz, 0.4H), 4.07−
4.21 (m, 2.7H), 3.97 (dd, J = 3.0, 12.0, 20.3 Hz, 0.7H), 3.79 (d, J = 2.2
Hz, 1H), 3.78 (s, 3H), 3.59 (dd, J = 3.0, 4.5 Hz, 0.8H), 1.31 (d, J = 6.7
Hz, 1.5H), 1.28 (d, J = 6.0 Hz, 1.2H) ppm; 13C NMR (75 MHz,
CDCl3) 159.3 153.7, 153.6, 142.1, 142.0, 137.6, 137.3, 129.6, 129.5,
129.4, 129.2, 128.5, 128.4, 127.9, 127.8, 127.6, 127.4, 113.8, 113.7,
110.2, 107.6, 107.0, 86.6, 85.3, 83.4, 83.3, 82.7, 81.1, 77.7, 77.3, 71.4,
71.2, 71.1, 71.1, 68.7, 68.2, 55.2, 13.9, 13.4 ppm; MS (ESI) m/z
C25H28O6 [M + Na]+ 447.
(2S((2R,3S,4S,5R)-4-(Benzyloxy)-3-(4-methoxybenzyloxy)-5-
methyl-tetrohydrofuran-2-yl)methanol (8). To a stirred solution
of TBS-ether 13 (7.1 g, 15 mmol) in methanol (40 mL) at 0 °C was
added camphorsulfonic acid (0.17 g, 0.75 mmol) and, the mixture was
stirred for 4 h at room temperature. After completion of the reaction
(monitored by TLC), it was quenched with saturated NaHCO3
solution (25 mL). Methanol was removed under reduced pressure,
and the residual reaction mixture was diluted with ethyl acetate (100
mL) and water (50 mL). The organic layer was separated, and the
aqueous layer was extracted with ethyl acetate (2 × 100 mL). The
combined organic layer was washed with brine (2 × 100 mL), dried
over anhydrous Na2SO4, and concentrated under reduced pressure to
get the crude product, which was purified by silica gel column
chromatography (ethyl acetate/hexane = 1:5) to afford alcohol 8 (4.82
2-(((4S,5R,4S)-4-(Benzyloxy)-3-(4-methoxybenzyloxy)-5-
methyl-tetrahydrofuran-2-yl)methyl)furan (16). To a suspen-
sion of NaH (0.31 g, 13.0 mmol, 60% in mineral oil) in anhydrous
THF (20 mL) was added alcohol 15 (3.1 g, 7.3 mmol) dissolved in
THF (20 mL) at 0 °C under nitrogen atmosphere, and the mixture
was stirred for 30 min at room temperature. To this reaction mixture,
carbon disulfide (0.7 mL, 10.9 mmol) was added at 0 °C, and the
mixture was stirred for 30 min. Methyl iodide (0.75 mL, 12.2 mmol)
was added, and the mixture was slowly warmed to room temperature.
After completion of the reaction (monitored by TLC), it was
quenched with ice pieces at 0 °C. The reaction mixture was diluted
with ethyl acetate (50 mL) and water (30 mL). The organic layer was
separated and the aqueous layer was extracted with ethyl acetate (3 ×
70 mL). The combined organic layers were washed with brine (2 × 75
mL) and dried over anhydrous Na2SO4. After removal of the organic
solvents under reduced pressure, the crude was purified by silica gel
column chromatography (ethyl acetate/hexanes = 1:19) to afford
xanthate 16 (3.4 g, 90%) as a colorless liquid: IR (neat) 3446.6, 2925,
27
g, 92%) as a light yellow liquid: [α]D −61.4 (c = 1.01, CHCl3); IR
(neat) 3447, 2929, 2868, 1718, 1513, 1389, 1248, 1070, 1033, 821,
1
742, 588 cm−1; H NMR (300 MHz, CDCl3) δ 7.34−7.24 (m, 5H),
7.17 (d, J = 8.3 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 4.59 (d, J = 12.0 Hz,
1H), 4.42 (s, 2H), 4.38 (d, J = 12.0 Hz, 1H), 4.13−4.04 (m, 1H), 3.97
(d, J = 3.7 Hz, 1H), 3.90 (dd, J = 3.0, 6.7 Hz, 1H), 3.80 (s, 3H), 3.74
(d, J = 12.0 Hz, 1H), 3.67 (d, J = 3.7 Hz, 1H), 3.56 (m, 1H), 2.09 (br
s, 1H), 1.29 (d, J = 6.0 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3)
159.3, 137.6, 129.6, 129.1, 129.2, 128.4, 127.7, 127.6, 113.9, 84.2, 83.2,
77.4,76.5, 71.5, 71.2, 63.1, 55.2, 13.8 ppm; HRMS (ESI) m/z calcd. for
C21H26O5 [M+Na]+ 381.1677, found 381.1665.
1
2866, 1646, 1511, 1456, 1247, 1075, 1034, 866, 742, 700 cm−1; H
NMR (300 MHz, CDCl3) δ 7.35−7.26 (m, 5H), 7.25−7.15 (m, 2H),
6.82 (dd, J = 4.5, 8.3 Hz, 1H), 6.81 (dd, J = 2.2, 6.7 Hz, 1H), 6.25 (dd,
J = 3.7, 11.3 Hz, 0.7H), 6.24 (dd J = 3.7, 9.8 Hz, 0.7H), 5.07 (d, J = 8.3
Hz, 1H), 4.36−4.60 (m, 3H), 4.28 (dd, J = 6.7, 12.0 Hz, 1H), 4.21−
4.05 (m, 2H), 3.90 (d, J = 3.0, 3.8 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 1H),
3.70 (dd, J = 3.7, 14.3 Hz, 1H), 3.70 (dd, J = 3.7, 14.3 Hz, 1H), 3.69
(dd, J = 2.2, 18.8 Hz, 1H), 2.42 (2 × s, 3H), 1.28 (m, 3H) ppm; 13C
NMR (75 MHz, CDCl3) 188.6, 188.2, 159.3, 159.2, 152.3, 150.8,
142.1, 142.0, 141.8, 138.0, 129.7, 129.6, 129.4, 129.3, 129.3, 128.3,
128.2, 127.7, 127.6, 127.5, 127.4, 113.8, 113.7, 110.5, 110.4, 110.2,
110.1, 108.8, 108.2, 108.1, 108.0, 85.3, 85.1, 84.7, 84.2, 84.1, 83.6, 83.5,
83.4, 82.8, 78.0, 77.8, 77.7, 71.6, 71.3, 71.2, 55.2, 47.5, 44.4, 44.3, 14.4,
14.3, 14.2 ppm; HRMS (ESI) m/z calcd. for C27H30O6S2 [M + Na]+
537.1381, found 537.1372.
2-(((4S,5R)-4-(Benzyloxy)-3-(4-methoxybenzyloxy)-5-meth-
yl-tetrahydrofuran-2-yl)methyl)furan (7). Compound 15 (3.8 g,
7.3 mmol) was taken in toluene (50 mL) and Bu3SnH (3.2 g, 11.0
mmol) followed by a catalytic amount of AIBN (100 mg, 0.6 mmol)
added under a nitrogen atmosphere, and the mixture was stirred under
reflux conditions for 8 h. After completion of the reaction (monitored
by TLC), toluene was removed under reduced pressure, and the
((2S,3R,4S,5R)-4-(Benzyloxy)-3-(4-methoxybenzyloxy)-5-
methyl-tetrahydrofuran-2-carbaldehyde (14). To a stirred sol-
ution of alcohol 8 (4.1 g, 11.45 mmol) in dry CH2Cl2 (50 mL) was
added Dess−Martin periodinane (7.2 g, 17.1 mmol) at 0 °C under a
nitrogen atmosphere. After 1 h (monitored by TLC), the reaction
mixture was filtered through a Celite bed and washed thoroughly with
CH2Cl2 (2 × 50 mL). The filtrate was washed with sodium
thiosulphate (2 × 50 mL) and brine (2 × 50 mL) and dried over
anhydrous Na2SO4. After removal of the organic layer under reduced
pressure, the crude aldehyde 14 was obtained (3.85 g, 96%) as a light
red liquid and immediately used for the next step: [α]D27 −8.0 (c = 1.3,
CHCl3); IR (neat) 2929, 1724, 1610, 1512, 1455, 1249, 1082, 1032,
699 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.56 (s, 1H), 7.32−7.13 (m,
7H), 6.84 (d, J = 8.7 Hz, 2H), 4.55 (d, J = 11.7 Hz, 1H), 4.42 (dd, J =
11.7, 15.6 Hz, 2H), 4.33 (m, 1H), 4.21 (d, J = 13.7 Hz, 1H), 4.10 (br s,
1H), 3.80 (s, 3H), 3.61 (d, J = 2.97 Hz, 1H), 1.32 (d, J = 6.8 Hz, 3H)
ppm; 13C NMR (75 MHz, CDCl3) 203.7, 159.4, 129.4, 128.4, 127.9,
127.6, 113.9, 87.0, 85.0, 81.1, 78.3, 71.4, 71.3, 55.2, 13.9 ppm; HRMS
(ESI) m/z calcd. for C21H24O5 [M + Na]+ 379.1526, found 379.1532.
9838
dx.doi.org/10.1021/jo201570h|J. Org. Chem. 2011, 76, 9835−9840