(()-Methyl 2-(5-Ethyl-2-oxo-tetrahydrofuran-3-yl)acrylate
(5a). To a solution of 3a (228 mg, 1.00 mmol) in methanol (15
mL) was added NaBH4 (60 mg, 1.50 mmol) at 0 °C, and the reaction
mixture was stirred for 15 min. The reaction was then quenched
with water. The reaction mixture was extracted with ethyl acetate
(25 mL × 4), and the combined organic layer was washed with
brine and dried over Na2SO4. Concentration of the organic layer
in vacuo followed by silica gel column chromatographic purification
of the residue using a mixture of ethyl acetate/petroleum ether (3:
mmol) in methanol (15 mL) was added NaBH4 (72 mg, 1.80 mmol)
at 0 °C, and the reaction mixture was stirred for 1 h. The reaction
was then quenched with water. The reaction mixture was extracted
with ethyl acetate (25 mL × 4), and the combined organic layer
was washed with brine and dried over Na2SO4. Concentration of
the organic layer in vacuo followed by silica gel column chro-
matographic purification of the residue using a mixture of ethyl
acetate/petroleum ether (3:7) as an eluant gave the mixture of 13
and 14 as a thick oil (the mixture of diastereoisomers was formed
in the ratio of 13/14 ) 15:85, 113 mg, 85%). Major isomer (()-
14: 1H NMR (CDCl3, 200 MHz) δ 1.19 (d, J ) 6 Hz, 3H), 1.20-
2.00 (m, 8H), 2.15-2.30 (m, 1H), 2.85 (dd, J ) 14 and 4 Hz, 1H),
2.90-3.10 (m, 1H), 3.70 (s, 3H), 3.70-3.83 (m, 1H); 13C NMR
(CDCl3, 50 MHz) δ 12.8, 23.9, 25.1, 28.0, 30.0, 37.3, 45.8, 48.6,
51.9, 82.7, 174.8, 176.7; IR (neat) Vmax 1778, 1734, 1450, 1254
cm-1. Anal. Calcd for C12H18O4: C, 63.70; H, 8.02. Found: C,
63.65; H, 8.14.
1
7) as an eluant gave 5a as a thick oil (174 mg, 88%). H NMR
(CDCl3, 200 MHz) δ 1.01 (t, J ) 8 Hz, 3H), 1.55-2.10 (m, 3H),
2.53 (ddd, J ) 12, 10, and 6 Hz, 1H), 3.66 (dd, J ) 12 and 8 Hz,
1H), 3.77 (s, 3H), 4.25-4.50 (m, 1H), 5.84 (s, 1H), 6.40 (s, 1H);
13C NMR (CDCl3, 50 MHz) δ 9.3, 28.2, 35.0, 44.9, 52.1, 80.0,
129.2, 136.1, 165.7, 175.8; IR (neat) Vmax 1771, 1720, 1634, 1439
cm-1. Anal. Calcd for C10H14O4: C, 60.59; H, 7.12. Found: C,
60.76; H, 7.03.
Methyl 2-(2-Oxo-5-phenyl-tetrahydrofuran-3-yl)propanoate
(6 and 7). Starting from 3e (200 mg, 0.72 mmol) and NaBH4 (90
mg, 2.20 mmol), the mixture of 6 and 7 was obtained as a white
solid (the mixture of diastereoisomers was formed in the ratio of
6/7 ) 10:90, 158 mg, 88%). Recrystallization from dichloromethane
furnished the analytically pure major isomer (()-7: mp 79-80
°C; 1H NMR (CDCl3, 200 MHz) δ 1.35 (d, J ) 6 Hz, 3H), 2.08-
2.30 (m, 1H), 2.68 (ddd, J ) 12, 8, and 6 Hz, 1H), 2.85-3.20 (m,
2H), 3.69 (s, 3H), 5.37 (dd, J ) 12 and 6 Hz, 1H), 7.30-7.45 (m,
5H); 13C NMR (CDCl3, 50 MHz) δ 15.1, 34.5, 38.6, 44.1, 51.9,
79.5, 125.7, 128.5, 128.6, 139.1, 173.9, 176.8; IR (neat) Vmax 1774,
1732, 1458 cm-1. Anal. Calcd for C14H16O4: C, 67.73; H, 6.50.
Found: C, 67.89; H, 6.47.
Compounds 5b-e and 12 were prepared similarly using the
previous procedure.
(()-Methyl 2-(5-Butyl-2-oxo-tetrahydrofuran-3-yl)acrylate
(5b). Starting from 3b (256 mg, 1.00 mmol) and NaBH4 (60 mg,
1
1.50 mmol), 5b was obtained as a thick oil (192 mg, 85%). H
NMR (CDCl3, 200 MHz) δ 0.89 (t, J ) 8 Hz, 3H), 1.15-1.50 (m,
4H), 1.50-1.85 (m, 2H), 1.85-2.07 (m, 1H), 2.53 (ddd, J ) 13, 8
and 6 Hz, 1H), 3.55-3.75 (m, 1H), 3.75 (s, 3H), 4.30-4.50 (m,
1H), 5.83 (s, 1H), 6.38 (s, 1H); 13C NMR (CDCl3, 50 MHz) δ
13.8, 22.3, 27.2, 35.0, 35.4, 44.9, 52.0, 78.8, 129.1, 136.0, 165.6,
175.8; IR (neat) Vmax 1771, 1720, 1634, 1439 cm-1. Anal. Calcd
for C12H18O4: C, 63.70; H, 8.02. Found: C, 63.61; H, 7.92.
(()-Methyl 2-(5-Heptyl-2-oxo-tetrahydrofuran-3-yl)acrylate
(5c). Starting from 3c (298 mg, 1.00 mmol) and NaBH4 (60 mg,
(()-2-(2-Oxo-octahydrobenzofuran-3-yl)propanoic acid (15).
A solution of the mixture of 13 and 14 (70 mg, 0.30 mmol) in
AcOH/HCl (3:1) (10 mL) was refluxed for 6 h. The reaction mixture
was allowed to cool to room temperature and concentrated in vacuo,
and the resulting solution was washed with ethyl acetate (10 mL
× 3). The combined organic layer was washed with brine, dried
over Na2SO4, and concentrated in vacuo to give a mixture of
diastereomers as a white solid (60 mg, 92%). Recrystalization from
ethyl acetate furnished the analytically pure major isomer 15: mp
1
1.50 mmol), 5c was obtained as a thick oil (220 mg, 82%). H
NMR (CDCl3, 200 MHz) δ 0.87 (t, J ) 6 Hz, 3H), 1.27 (bs, 10H),
1.40-1.85 (m, 2H), 1.85-2.10 (m, 1H), 2.54 (ddd, J ) 12, 10,
and 6 Hz, 1H), 3.66 (dd, J ) 12 and 8 Hz, 1H), 3.78 (s, 3H), 4.30-
4.50 (m, 1H), 5.85 (s, 1H), 6.41 (s, 1H); 13C NMR (CDCl3, 50
MHz) δ 14.0, 22.5, 25.2, 29.1, 29.2, 31.7, 35.4, 35.6, 44.9, 52.1,
78.9, 129.2, 136.1, 165.7, 175.8; IR (neat) Vmax 1771, 1720, 1632,
1439 cm-1. Anal. Calcd for C15H24O4: C, 67.14; H, 9.01. Found:
C, 66.98; H, 8.93.
1
215-216 °C; H NMR (CDCl3, 200 MHz) δ 1.00-1.30 (m, 2H),
1.29 (d, J ) 6 Hz, 3H), 1.35-1.85 (m, 4H), 2.20-2.45 (m, 2H),
2.55-2.75 (m, 1H), 3.00-3.15 (m, 2H), 4.45-4.55 (m, 1H); 13C
NMR (acetone-d6, 100 MHz) δ 16.9, 20.4, 23.0, 23.7, 28.0, 36.5,
38.0, 51.3, 78.1, 176.9, 177.6; IR (neat) Vmax 2700-2500, 1757,
1697, 1464, 1377 cm-1. Anal. Calcd for C11H16O4: C, 62.25; H,
7.60. Found: C, 62.37; H, 7.56.
(()-Methyl 2-(5-Decyl-2-oxo-tetrahydrofuran-3-yl)acrylate
(5d). Starting from 3d (340 mg, 1.00 mmol) and NaBH4 (60 mg,
1
1.50 mmol), 5d was obtained as a thick oil (248 mg, 80%). H
NMR (CDCl3, 200 MHz) δ 0.87 (t, J ) 6 Hz, 3H), 1.25 (bs, 16H),
1.40-1.85 (m, 2H), 1.85-2.10 (m, 1H), 2.54 (ddd, J ) 12, 10,
and 6 Hz, 1H), 3.55-3.75 (m, 1H), 3.78 (s, 3H), 4.30-4.50 (m,
1H), 5.85 (s, 1H), 6.41 (s, 1H); 13C NMR (CDCl3, 50 MHz) δ
14.0, 22.6, 25.2, 29.2, 29.3, 29.4, 29.5, 29.6, 31.8, 35.4, 35.6, 44.9,
52.1, 78.9, 129.1, 136.1, 165.7, 175.8; IR (neat) Vmax 1774, 1734,
1634, 1439 cm-1. Anal. Calcd for C18H30O4: C, 69.64; H, 9.74.
Found: C, 69.57; H, 9.88.
(E)-Methyl 2-(2-Oxo-4,5,6,7-tetrahydrobenzofuran-3(2H)-
ylidene)propanoate (16). To a solution of a mixture of 9 and 10
(125 mg, 0.50 mmol) in methanol (5 mL) was added NaOMe (27
mg, 0.50 mmol) at room temperature, and the reaction mixture was
stirred for 1 h. The reaction mixture was concentrated in vacuo,
diluted with ethyl acetate (15 mL), and acidified with 2 N HCl.
The aqueous layer was extracted with ethyl acetate (10 mL × 2),
and the combined organic layer was washed with brine and dried
over Na2SO4. Concentration of the organic layer in vacuo followed
by silica gel column chromatographic purification of the residue
using a mixture of ethyl acetate/petroleum ether (2:8) as an eluant
(()-Methyl 2-(2-Oxo-5-phenyl-tetrahydrofuran-3-yl)acrylate
(5e). Starting from 3e (200 mg, 0.72 mmol) and NaBH4 (45 mg,
1.10 mmol), 5e was obtained as a white solid (160 mg, 90%). Mp
1
127-128 °C; H NMR (CDCl3, 200 MHz) δ 2.30-2.50 (m, 1H),
2.83 (ddd, J ) 12, 10, and 6 Hz, 1H), 3.65-3.75 (m, 1H), 3.80 (s,
3H), 5.42 (dd, J ) 10 and 6 Hz, 1H), 5.91 (s, 1H), 6.45 (s, 1H),
7.30-7.50 (m, 5H); 13C NMR (CDCl3, 50 MHz) δ 38.1, 45.6, 52.2,
79.7, 125.9, 128.6, 128.7, 129.7, 135.7, 138.8, 165.5, 175.5; IR
(neat) Vmax 1771, 1728, 1632, 1439 cm-1. Anal. Calcd for
C14H14O4: C, 68.28; H, 5.73. Found: C, 68.22; H, 5.71.
1
gave 16 as a white solid (95 mg, 87%). Mp 88-89 °C; H NMR
(CDCl3, 200 MHz) δ 1.55-1.90 (m, 4H), 2.03 (s, 3H), 2.29 (t, J
) 6 Hz, 2H), 2.53 (t, J ) 6 Hz, 2H), 3.91 (s, 3H); 13C NMR (CDCl3,
50 MHz) δ 13.8, 21.4, 21.8, 23.4, 27.3, 52.5, 109.1, 119.6, 145.4,
157.7, 163.3, 166.4; IR (CHCl3) Vmax 1736, 1719, 1647 cm-1. Anal.
Calcd for C12H14O4: C, 64.85; H, 6.35. Found: C, 65.03; H, 6.52.
(()-Methyl 2-(2-Oxo-octahydrobenzofuran-3-yl)acrylate (12).
Starting from a mixture of 9 and 10 (150 mg, 0.60 mmol) and
NaBH4 (36 mg, 0.90 mmol), 12 was obtained as a thick oil (116
Acknowledgment. M.M.B. thanks CSIR, New Delhi, for
the award of a research fellowship.
1
mg, 88%). H NMR (CDCl3, 200 MHz) δ 1.15-1.65 (m, 4H),
1.75-2.35 (m, 4H), 3.36 (d, J ) 14 Hz, 1H), 3.65-3.90 (m, 2H),
3.79 (s, 3H), 5.77 (s, 1H), 6.46 (s, 1H); 13C NMR (CDCl3, 50 MHz)
δ 24.0, 25.1, 27.4, 30.1, 50.1, 50.3, 52.2, 83.0, 129.2, 134.9, 166.0,
175.5; IR (neat) Vmax 1769, 1732, 1632, 1445 cm-1. Anal. Calcd
for C12H16O4: C, 64.27; H, 7.19. Found: C, 64.41; H, 7.23.
Methyl 2-(2-Oxo-octahydrobenzofuran-3-yl)propanoate (13
and 14). To a solution of a mixture of 9 and 10 (150 mg, 0.60
Supporting Information Available: 1H and 13C NMR spectra
of 3a-e, 5a-e, 6 + 7, 9 + 10, 12, 13 + 14, 15, and 16. X-ray
crystallographic data for compounds (()-7 and (()-15 in CIF
format. This material is available free of charge via the Internet at
JO0619128
1012 J. Org. Chem., Vol. 72, No. 3, 2007