Notes
J . Org. Chem., Vol. 61, No. 17, 1996 6011
to -78 °C. Methyl trifluoromethanesulfonate (0.17 mL, 1.5
mmol) was added dropwise to the green solution over a 2 min
period to give 3,5-dimethoxy-1-methyl-4-(1-methylethyl)-2-(tri-
methylsiloxy)benzene. In a separate experiment this compound
was isolated and purified by flash chromatography on silica gel
and shown to have the following properties: mp 29.0-29.5 °C
(hexanes); IR 2955, 1484, 1413, 1237 cm-1; 1H NMR (300 MHz,
CDCl3) δ 6.43 (s, 1H), 3.75 (s, 3H), 3.68 (s, 3H), 3.44 (hept, J )
7.1 Hz, 1H), 2.17 (s, 3H), 1.31 (d, J ) 7.0 Hz, 6H), 0.22 (s, 9H);
13C (75 MHz, CDCl3) δ 152.7, 149.6, 141.3, 127.6, 126.7, 108.8,
60.4, 55.7, 25.4, 21.4 (2C), 16.9, 0.5 (3C); LRMS (CI) m/ e 282
Hz, 1H), 4.07 (s, 3H), 3.38 (s, 3H), 2.54 (hept, J ) 7.0 Hz, 1H),
2.09 (s, 3H), 1.75 (s, 3H), 1.16 (d, J ) 7.0 Hz, 6H). Z-Isomer:
1H NMR (500 MHz, CDCl3) δ 6.0-5.8 (m, 1H), 5.56 (d, J ) 12.0
Hz, 1H), 4.02 (s, 3H), 2.56 (hept, J ) 7.0 Hz, 1H), 2.09 (s, 3H),
1.77 (s, 3H), 1.17 (d, J ) 7.0 Hz, 6H). 4-Acetoxy-3-methoxy-
2-(1-methylethyl)-4-(1-propynyl)-2-cyclobutene-1-one: 1H NMR
(500 MHz, CDCl3) δ 4.17 (s, 3H), 3.50 (s, 3H), 2.56 (hept, J )
7.1 Hz, 1H), 2.09 (s, 3H), 1.93 (s, 3H), 1.17 (d, J ) 7.0 Hz, 6H).
After hexanes (200 mL) were added, the clear solution was
warmed to 69 °C for 2 h. The concentrated yellow product was
then added to sodium hydride (50% in mineral oil, 0.19 g, 4.0
mmol) and cooled to -78 °C. After the addition of THF (30 mL),
the reaction mixture was allowed to warm to 0 °C, maintained
at this temperature for 30 min, and then recooled to -78 °C.
Methyl trifluoromethanesulfonate (0.17 mL, 1.5 mmol) was
added dropwise to the dark brown solution over a 2 min period.
Once the orangish-red mixture was rewarmed to 0 °C and
maintained at this temperature for 30 min, a solution of sodium
hydroxide (5 N, 2 mL, 10 mmol) was added, along with
tetrabutylammonium iodide (0.04 g, 0.20 mmol). After 6 h
hydrchloric acid (5 N, 2 mL) was added. The organic phase of
the mixture was separated, and the aqueous phase was extracted
with diethyl ether (3 × 20 mL). The combined organic phase
was then washed with brine (40 mL), dried (MgSO4), and
concentrated in vacuo. The concentrated product was then
purified by column chromatography (silica gel, 9:1 hexanes/ethyl
acetate) to give the title compound 12 (0.18 g, 44%) as a white
(M, 100), 267 (30), 252 (19); HRMS calcd for
282.1651; found 282.1666.
C15H26O3Si
A THF solution of the above compound was cooled to 0 °C
and stirred for 10 min, and then H2O (1 mL) was added to the
beige solution, followed by TBAF (1.1 M in THF, 1.1 mL, 1.2
mmol). The green solution was poured into 10% NH4Cl (40 mL).
After the organic layer was separated, the aqueous layer was
extracted with diethyl ether (3 × 20 mL). The combined organic
layers were washed with brine (20 mL), dried (MgSO4), and
concentrated in vacuo. The product was then purified by column
chromatography (silica gel, 9:1 hexanes/ethyl acetate) to give
espintanol (1) (0.19 g, 90%) as a white solid: mp 45.0-45.5 °C
1
(cold hexanes) (lit.2 mp 42.3-43.0 °C); IR 3444 cm-1; H NMR
(300 MHz, CDCl3) δ 6.47 (s, 1H), 5.40 (s, 1H), 3.76 (s, 6H), 3.35
(hept, J ) 7.1 Hz, 1H), 2.23 (s, 3H), 1.34 (d, J ) 7.0 Hz, 6H); 13
C
NMR (75 MHz, CDCl3) δ 152.0, 144.8, 141.1, 126.8, 121.4, 110.0,
61.8, 55.8, 25.9, 21.2 (2C), 15.7; LRMS (EI) m/ e 210 (M, 92),
195 (100), 180 (27); HRMS calcd for C12H18O3 210.1256, found;
210.1263.
solid: mp 103.0-104.0 °C; IR 3487 cm-1 1H NMR (500 MHz,
;
CDCl3) δ 6.63 (s, 1H), 5.23 (s, 1H), 3.77 (s, 3H), 3.69 (s, 3H),
3.39 (s, J ) 7.0 Hz, hept), 2.22 (s, 3H), 1.35 (d, J ) 7.0 Hz, 6H);
13C NMR (125 MHz, CDCl3) δ 150.6, 145.0, 143.7, 134.2, 127.5,
115.2, 61.6, 61.1, 26.1, 22.3 (2C), 16.4; LRMS (CI) m/ e 210 (M,
100), 195 (21), 180 (5); HRMS calcd for C14H24O3Si 210.1256;
found 210.1262.
3,4-Dim et h oxy-5-m et h yl-2-(1-m et h ylet h yl)p h en ol (10).
Under an atmosphere of nitrogen, tert-butyllithium (1.7 M in
pentane, 2.5 mL, 4.2 mmol) was added in a dropwise fashion to
anhydrous THF (10 mL) at -78 °C. After 5 min, 2-bromopro-
pene (0.19 mL, 2.1 mmol) was added dropwise to this solution
over a 2 min period. After an additional 5 min, the resulting
lithium reagent was added via cannula to at -78 °C to an
anhydrous THF (20 mL) solution of 6 (0.31 g, 2.0 mmol). Upon
addition of methyl trifluoromethanesulfonate (0.36 mL, 3.2
mmol), the yellow solution gradually turned clear as it was
allowed to warm to 0 °C and maintained at this temperature
for 10 min. After the solution was recooled to -78 °C, it was
poured into a solution of 5% NaHCO3 (20 mL). The organic layer
was separated; the aqueous layer was extracted with diethyl
ether (3 × 20 mL). The combined organic phase was then
washed with brine (40 mL), dried (MgSO4), and concentrated
in vacuo to give crude 3,4-dimethoxy-4-(1-methylethenyl)-2-(1-
methylethyl)-2-cyclobuten-1-one (9) [1H NMR (500 MHz, CDCl3)
δ 5.20 (s, 1H), 5.04 (s, 1H), 3.96 (s, 3H), 3.36 (s, 3H), 2.54 (hept,
J ) 7.0 Hz, 1H), 1.75 (s, 3H), 1.14 (d, J ) 7.0 Hz, 6H)]. Hexanes
(200 mL) were added, and the clear solution was warmed to 69
°C for 2 h. The product was then purified by column chroma-
tography (silica gel, 9:1 hexanes/ethyl acetate) to give the title
compound 10 (0.38 g, 70%) as a white solid: mp 52.5-53.5 °C
3,4-Dim et h oxy-6-m et h yl-2-(1-m et h ylet h yl)p h en ol (14).
Under an atmosphere of nitrogen, tert-butyllithium (1.7 M in
pentane, 2.5 mL, 4.2 mmol) was added in a dropwise fashion to
anhydrous THF (10 mL) at -78 °C. After 5 min, 1-bromo-1-
propene (as a mixture of E- and Z-isomers) (0.18 mL, 2.1 mmol)
was added dropwise to this solution over a 2 min period. After
an additional 5 min, the resulting lithium reagent was added
via cannula to a -78 °C anhydrous THF (20 mL) solution of
3-methoxy-4-(1-methylethyl)-3-cyclobutene-1,2-dione 6 (0.31 g,
2.0 mmol). Upon addition of methyl trifluoromethanesulfonate
(0.4 mL, 3.2 mmol), the yellow solution gradually turned clear
as it was allowed to warm to 0 °C and maintained at this
temperature for 10 min. After the solution was recooled to -78
°C, it was poured into a cold solution of 5% NaHCO3 (20 mL).
The aqueous layer was separated and extracted with diethyl
ether (3 × 20 mL). The combined organic phase was then
washed with brine (40 mL), dried (MgSO4), and concentrated
in vacuo to give a mixture of the E- and Z-isomers of 3,4-
dimethoxy-2-(1-methylethyl)-4-(1-propenyl)-2-cyclobuten-1-one
(13a ,b) along with the 4-propynyl analog 13c in a ratio of 1:5:4,
respectively. These were not isolated in a pure state but shown
to have the following properties from analysis of spectral data
obtained on the partially purified products. E-Isomer: 1H NMR
(500 MHz, CDCl3) δ 6.0-5.8 (m, 1H), 5.58 (d, J ) 15.6 Hz, 1H),
4.00 (s, 3H), 3.38 (s, 3H), 2.54 (hept, J ) 7.0, 1H), 1.75 (d, J )
6.6 Hz, 3H), 1.16 (d, J ) 6.9 Hz, 6H). Z-Isomer: 1H NMR (300
MHz, CDCl3) δ 5.9 (m, 1H), 5.59 (d, J ) 10.1 Hz, 1H), 4.00 (s,
3H), 3.40 (s, 3H), 2.52, (hept, J ) 7.0 Hz, 1H), 1.77 (d, 3H), 1.18
(d, J ) 7.0 Hz, 6H). 3,4-Dimethoxy-2-(1-methylethyl)-4-(1-pro-
pynyl)-2-cyclobuten-1-one: 1H NMR (500 MHz, CDCl3) δ 4.14
(s, 3H), 3.50 (s, 3H), 2.50 (hept, J ) 7.0 Hz, 1H), 1.94 (s, 3H),
1.16 (d, J ) 6.9 Hz, 6H). After hexanes (200 mL) was added,
the clear solution was warmed to 69 °C for 2 h. The concentrated
product was then purified by column chromatography (silica gel,
9:1 hexanes/ethyl acetate) to give the title compound 14 (0.26 g,
70%) as a white solid: mp 53.0-54.0 °C; IR 3452 cm-1; 1H NMR
(500 MHz, CDCl3) δ 6.29 (s, 1H), 5.11 (s, 1H), 3.85 (s, 3H), 3.79
(s, 3H), 3.45 (hept, J ) 7.1 Hz, 1H), 2.18 (s, 3H), 1.35 (d, J )
7.1, 6H); 13C NMR (125 MHz, CDCl3) δ 151.8, 150.3, 145.3, 129.9,
126.0, 112.9, 61.0, 60.3, 25.2, 21.3 (2C), 15.6; LRMS (CI) m/ e
210 (M, 100) 195 (20), 169 (10); HRMS calcd for C12H18O3
210.1256; found 210.1252.
1
(hexanes); IR 3387 cm-1; H NMR (500 MHz, CDCl3) δ 6.29 (s,
1H), 5.04 (s, 1H), 3.85 (s, 3H), 3.78 (s, 3H), 3.44 (hept, J ) 7.1
Hz, 1H), 2.18 (s, 3H), 1.35 (d, J ) 7.1 Hz, 6H); 13C NMR (125
MHz, CDCl3) δ 151.8, 150.5, 145.2, 129.3, 126.1, 113.0, 61.0, 60.3,
25.2, 21.3 (2C), 15.6; LRMS (EI) m/ e 210 (M, 81), 195 (100),
180 (39); HRMS calcd for C12H18O3 210.125;, found 210.1249.
2,4-Dim et h oxy-5-m et h yl-3-(1-m et h ylet h yl)p h en ol (12).
Under an atmosphere of nitrogen, tert-butyllithium (1.7 M in
pentane, 2.47 mL, 4.2 mmole) was added in a dropwise fashion
to anhydrous THF (10 mL) at -78 °C. After 5 min, 1-bromo-
1-propene (as a mixture of E- and Z-isomers) (0.18 mL, 2.1 mmol)
was added dropwise to this solution over a 2 min period. After
an additional 5 min, the resulting lithium reagent was added
via cannula to a -78 °C anhydrous THF (20 mL) solution of 6
(0.31 g, 2.0 mmol). Once acetic anhydride (0.23 mL, 2.4 mmol)
was added, the solution was allowed to warm to 0 °C, maintained
at this temperature for 10 min, recooled to -78 °C, and poured
into a cold solution of 5% NaHCO3 (20 mL). The organic layer
was separated and the aqueous layer was extracted with diethyl
ether (3 × 20 mL). The combined organic phase was then
washed with brine (40 mL), dried (MgSO4), and concentrated
in vacuo to give a mixture of the E- and Z-isomers of 11 along
with a small amount of the 4-propynyl analog. E-Isomer: 1H
NMR (500 MHz, CDCl3) δ 5.9-5.7 (m, 1H), 5.57 (d, J ) 12.0
3,4-Dim eth oxy-6-m eth yl-2-(1-m eth yleth yl)ph en ol (14) Us-
in g (E)-1-Br om op r op en e. Under an atmosphere of nitrogen,