EIMS, m/z 232 (9, M+), 230 (9, M+), 151 (31, M+ - Br), 123 (8,
M+ - Br- CO), 41 (100). HRMS: calcd for C10H15O (M+ - Br),
151.1117; found 151.1125.
NMR10 δ 2.73 (dd, 1H, J ) 18.1, 6.7 Hz), 2.35 (m, 1H), 2.14 (t,
2H, J ) 7.5 Hz), 2.08 (dd, 1 H, J ) 18.1, 2.2 Hz), 2.03 (s, 3H),
1.40 (tq, 2H, J ) 7.5, 7.4 Hz), 1.15 (d, 3H, J ) 7.5 Hz), 0.87 (t,
3H, J ) 7.4 Hz); 13C NMR δ 212.3, 168.5, 139.4, 40.9, 39.7, 25.2,
21.8, 17.3, 16.9, 14.2; IR (film) 2961, 2931, 2871, 1698, 1646,
5-Methyl-5-(2-methylpropyl)dihydrofuran-2[3H]-one, 13. To
a stirred solution of ethyl levulinate (1.0 g, 6.94 mmol) in dry
benzene (3 mL) was added dropwise a 2.0 M solution of
isobutylmagnesium bromide (3.81 mL, 7.63 mmol) in diethyl ether
at 0 °C. The resulting solution was stirred for an additional 15 min
at -5 to 0 °C and was then poured into a mixture of concentrated
H2SO4 (2 mL) and ice (ca. 60 g). The mixture was extracted with
ether (2 × 20 mL), and the extract was washed with water (40
mL) and 5% aq. NaHCO3 (40 mL). Combining of the organic
layers, followed by drying (anhydrous MgSO4), concentration under
vacuum, and flash column chromatography (silica gel, 25% ethyl
acetate in hexane), yielded 0.85 g (79%) of the known lactone 134
as a colorless oil: 1H NMR δ 2.62 (ddd, 1H, J ) 18.0, 9.4, 8.6
Hz), 2.55 (ddd, 1H, J ) 18.0, 9.3, 5.9 Hz), 2.08 (ddd, 1H, J )
12.8, 9.3, 8.6 Hz), 2.00 (ddd, 1H, J ) 12.8, 9.4, 5.9 Hz), 1.82 (m,
1H), 1.62 (dd, 1H, J ) 14.4, 6.4 Hz), 1.57 (dd, 1H, J ) 14.4, 6.1
Hz), 1.39 (s, 3H), 0.98 (d, 3H, J ) 6.6 Hz), 0.95 (d, 3H, J ) 6.6
Hz); 13C NMR δ 176.8, 87.1, 49.4, 34.2, 28.9, 25.4, 24.4, 24.2,
24.0; IR (film) 2957, 1771, 1466, 1382, 1368, 1283, 1207, 1163,
1456, 1436, 1385, 1354, 1334 cm-1
.
5-Butyl-5-methyldihydrofuran-2[3H]-one, 17. To a stirred
solution of ethyl levulinate (1.0 g, 6.94 mmol) in dry benzene (3
mL) was added dropwise a 2.0 M solution of butylmagnesium
bromide (4.16 mL, 8.32 mmol) in diethyl ether at 0 °C. The
resulting solution was stirred for an additional 15 min at -5 to 0
°C and was then poured into a mixture of concentrated H2SO4 (2
mL) and ice (ca. 60 g). The mixture was extracted with ether (2 ×
20 mL), and the extract was washed with water (40 mL) and 5%
aq. NaHCO3 (40 mL). Combining of the organic layers, followed
by drying (anhydrous MgSO4), concentration under vacuum, and
flash column chromatography (silica gel, 25% ethyl acetate in
hexane), yielded 1.02 g (94%) of the known lactone 174c as a
colorless oil: 1H NMR δ 2.63 (ddd, 1H, J ) 18.0, 9.3, 8.0 Hz),
2.57 (ddd, 1H, J ) 18.0, 9.2, 6.6 Hz), 2.08 (ddd, 1H, J ) 12.8,
9.2, 8.0 Hz), 1.97 (ddd, 1H, J ) 12.8, 9.3, 6.6 Hz), 1.66 (m, 2H),
1.38 (s, 3H), 1.34 (m, 4H), 0.92 (m, 3H); 13C NMR δ 176.9, 86.9,
40.7, 32.9, 29.2, 26.0, 25.6, 22.9, 13.9; IR (film) 2936, 1770, 1458,
1136, 938 cm-1
.
3-Methyl-2-(2-methylethyl)-cyclopent-2-en-1-one, 14. To a
solution of P2O5 (6.1 g, 43.0 mmol) in 85% H3PO4 (4 mL) at 60-
70 °C was added the lactone 13 (0.85 g, 5.44 mmol). Stirring of
the mixture at 60-70 °C for 2 min resulted in a change of color
from colorless to yellow-brown. The mixture was then stirred at
98 °C under argon for 6 h, after which the hot, dark red-brown
mixture was poured onto ice (ca. 150 g). The mixture was extracted
with ether (2 × 100 mL), and the combined extracts were washed
with water (100 mL), dried over anhydrous MgSO4, and concen-
trated under vacuum. The residue was purified by flash column
chromatography (silica gel, 13% ethyl acetate in hexane) to give
0.62 g (83%) of the known cyclopentenone 144 as a colorless oil:
1H NMR δ 2.79 (sep, 1H, J ) 7.1 Hz), 2.44 (m, 2H), 2.31 (m,
2H), 2.06 (s, 3H), 1.16 (d, 6H, J ) 7.1 Hz); 13C NMR δ 209.4,
168.8, 144.6, 34.5, 31.7, 24.7, 20.3 (2C’s), 17.4; IR (film) 2961,
1382, 1205, 1161, 1137, 939 cm-1
.
3-Methyl-2-propylcyclopent-2-en-1-one, 18. To a solution of
P2O5 (3.0 g, 21.1 mmol) in 85% H3PO4 (2 mL) at 60-70 °C was
added the lactone 17 (0.4 g, 2.56 mmol). Stirring of the mixture at
60-70 °C for 2 min resulted in a change of color from colorless
to yellow-brown. The mixture was then stirred at 98 °C under argon
for 6 h, after which the hot, dark red-brown mixture was poured
onto ice (ca. 75 g). The mixture was extracted with ether (2 × 50
mL), and the combined extracts were washed with water (50 mL),
dried over anhydrous MgSO4, and concentrated under vacuum. The
residue was purified by flash column chromatography (silica gel,
13% ethyl acetate in hexane) to give 0.29 g (83%) of the known
cyclopentenone 184cd as a colorless oil: 1H NMR δ 2.48 (m, 2H),
2.36 (m, 2H), 2.15 (t, 2H, J ) 7.6 Hz), 2.05 (s, 3H), 1.40 (tq, 2H,
J ) 7.6, 7.3 Hz), 0.88 (t, 3H, J ) 7.3 Hz); 13C NMR δ 209.7,
170.2, 140.5, 34.3, 31.5, 25.0, 21.6, 17.2, 14.0; IR (film) 2960,
1695, 1637, 1385, 1340 cm-1
.
3,5-Dimethyl-2-(2-methylethyl)-cyclopent-2-en-1-one, 15. To
a stirred solution of the cyclopentenone 14 (0.22 g, 1.56 mmol)
and HMPA (0.35 mL, 2.02 mmol) in THF (10 mL) was added
dropwise a 2.0 M solution of LDA (0.93 mL, 1.87 mmol) in THF
at -78 °C. The mixture was then stirred for 30 min, after which
iodomethane (0.19 mL, 3.11 mmol) was added to the reaction
mixture. The solution was allowed to warm to 21 °C. After 10 h,
the reaction was quenched by saturated NH4Cl. The mixture was
extracted with diethyl ether, dried over MgSO4, and purified by
flash column chromatography (silica gel, 13% ethyl acetate in
hexane) to give 0.12 g (50%) of the methylated cyclopentenone
15 as a colorless oil: 1H NMR δ 2.78 (sep, 1H, J ) 7.1 Hz), 2.69
(dd, 1H, J ) 18.3, 6.8 Hz), 2.28 (m, 1H), 2.04 (dd, 1 H, J ) 18.3,
2.4 Hz), 2.04 (s, 3H), 1.16 (d, 3H, J ) 7.1 Hz), 1.15 (d, 3H, J )
7.1 Hz), 1.13 (d, 3H, J ) 7.4 Hz); 13C NMR δ 211.8, 166.8, 143.4,
40.8, 39.6, 24.7, 20.4, 20.2, 17.3, 16.5; IR (film) 2960, 2929, 2872,
1698, 1648, 1442, 1385, 1072 cm-1
.
3,5-Dimethyl-2-propylcyclopent-2-enone, 16. To a stirred solu-
tion of the cyclopentenone 18 (0.20 g, 1.41 mmol) and HMPA (0.32
mL, 1.83 mmol) in THF (10 mL) was added dropwise a 2.0 M
solution of LDA (0.92 mL, 1.83 mmol) in THF at -78 °C. The
mixture was then stirred for 30 min, after which iodomethane (0.18
mL, 2.82 mmol) was added to the reaction mixture. The solution
was allowed to warm to 21 °C. After 10 h, the reaction was
quenched by saturated NH4Cl. The mixture was extracted with
diethyl ether, dried over MgSO4, and purified by flash column
chromatography (silica gel, 13% ethyl acetate in hexane) to give
1
0.10 g (45%) of the cyclopentenone 16 as a colorless oil: H NMR10
δ 2.73 (dd, 1H, J ) 18.1, 6.7 Hz), 2.35 (m, 1H), 2.14 (t, 2H, J )
7.5 Hz), 2.08 (dd, 1 H, J ) 18.1, 2.2 Hz), 2.03 (s, 3H), 1.40 (tq,
2H, J ) 7.5, 7.4 Hz), 1.15 (d, 3H, J ) 7.5 Hz), 0.87 (t, 3H, J )
7.4 Hz); 13C NMR δ 212.3, 168.5, 139.4, 40.9, 39.7, 25.2, 21.8,
17.3, 16.9, 14.2; IR (film) 2961, 2931, 2871, 1698, 1646, 1456,
1696, 1639, 1457, 1436, 1385, 1340, 957 cm-1
.
3,5-Dimethyl-2-propylcyclopent-2-enone, 16, from 9. To a
stirred solution of the bromide 9 (15 mg, 0.07 mmol) and
tributylstannane (0.02 mL, 0.07 mmol) in benzene (5 mL) was
added a catalytic amount of AIBN (1 mg). The mixture was heated
under reflux for 2 h. The solution was allowed to cool to 21 °C
and quenched by saturated NH4Cl. The mixture was extracted with
diethyl ether, dried over MgSO4, and purified by flash column
chromatography (silica gel, 13% ethyl acetate in hexane) to give 9
mg (91%) of the known cyclopentenone 165 as a colorless oil: 1H
1436, 1385, 1354, 1334 cm-1
.
Acknowledgment. We thank the National Science Founda-
tion (CHE 0614591) for generous support of this work.
Supporting Information Available: Spectral data for all new
compounds. This material is available free of charge via the Internet
(10) The proton NMR data given in ref 5 for compound 16 are incorrect,
but the carbon NMR data match those of our synthetic material perfectly.
JO071104W
8568 J. Org. Chem., Vol. 72, No. 22, 2007