3088 J . Org. Chem., Vol. 65, No. 10, 2000
Edvardsen et al.
ature for 4 h before a saturated solution of NH4Cl was added,
followed by diethyl ether. The aqueous phase was extracted
with diethyl ether, and the combinded organic phase was
washed with brine and water, dried (MgSO4), and evaporated.
The crude product was purified by silica gel chromatography
with hexane/ethyl acetate 7:1 as eluent to afford 3b as a
performing a nuceophilic substitution at C-1 and a
palladium-catalyzed reaction on C-3 of 1,3-dibromo-2-
propanone.
Con clu sion
1
colorless oil (0.92 g, 45%). H NMR (300 MHz, CDCl3): δ 3.62
Diisopropylamine was the only base among a number
of amines that showed high selectivity and gave a good
chemical yield in the dehydrohalogenation of 2. Photo-
isomerization of the Z-isomer of 3 gives access to the
E-isomer. Nucleophilic displacement reactions of the
allylic bromide in 3 occur mostly without any double bond
isomerization, and the vinylic bromide of 3 could be
utilized for palladium-catalyzed coupling reactions. The
reactions performed indicate that 1,3-dibromo-2-meth-
oxypropene might be a useful three-carbon unit for
organic synthesis.
(3H, s), 4.10 (2H, s), 5.35 (1H, s). 13C NMR (75 MHz, CDCl3):
δ 28.4, 56.4, 82.0, 156.4. MS (EI): m/z 232/230/228 (15/33/17,
M+), 151 (98, [M - Br]+), 149 (100, [M - Br]+). HRMS (EI):
calcd for C4H7OBr3 227.8790, found 227.8787.
Meth od 2. Compound 3a (120 mg, 0. 53 mmol) in dry
hexane (10 mL) was irradiated with a low-pressure mercury
lamp for 5 h under N2 at ambient temperature. The solvent
was evaporated off, and the crude product (120 mg) was
analyzed by TLC, GLC, and 1H NMR, which showed that a
complete isomerzation to 3b had taken place. Only minor
1
impurities (<5%) were observed by H NMR and GLC.
Gen er a l P r oced u r e for th e P r ep a r a tion of 5a -d . The
alcohol (1.5 mmol) in dry DME (2 mL) was added to sodium
hydride (1.6 mmol) in dry DME (2 mL) at 0 °C under N2. After
15 min at 0 °C a solution of 3a or 3b in dry DME (2 mL) was
added. The mixture was stirred at ambient temperature for
18 h before a mixture of NH4Cl (aqueous) and diethyl ether
was added. The aqueous phase was extracted with diethyl
ether, and the combinded organic phase was washed with
brine and water, dried (MgSO4), and evaporated. The crude
product was purified by silica gel chromatography.
Exp er im en ta l Section
Gen er a l Meth od s. All air- and moisture-sensitive reactions
were performed under an atmosphere of dry nitrogen. All
solvents were dried over the standard drying agents and
freshly distilled prior to use. For flash chromatography, 400-
1
230 mesh silica gel 60 was employed. H NMR spectra were
recorded at 200, 300, or 500 MHz, and the 13C NMR spectra
were recorded at 75 MHz. Mass spectra, under electron impact
conditions, were recorded at 70 eV ionizing energy. UV
reactions were conducted in a quartz immersion well reactor
using a low-pressure mercury lamp from Applied Photophysics
(model 3020; 90% of the radiation at 254 nm). pKBH: ethyldi-
isopropylamine,22 DBU,23 2,6-lutidine,24 DMAP,25 diisopropyl-
amine,26 and tert-butylamine.27
3-Meth oxy-2H-ch r om en e (9). Meth od 1. Ethyldiisopro-
pylamine (71 mg, 0.55 mmol) and compound 5b (81 mg, 0.22
mmol) were added to a mixture of palladium acetate (10 mg,
0.045 mmol) and lithium chloride (10 mg, 0.24 mmol) in DMF
(3 mL) under N2 at ambient temperature. The mixture was
stirred at 50 °C for 44 h, cooled, and diluted with diethyl ether.
NH4Cl (aqueous) was added, and the aqueous phase was
extracted with diethyl ether. The combined organic phase was
washed with brine and water and dried (MgSO4). Evaporation
gave the crude product, which was purified by silica gel
chromatography using hexane/ethyl acetate 5:1 as eluent to
afford 9 as a colorless oil (22 mg, 61%). 1H NMR (300 MHz,
CDCl3): δ 3.72 (3H, s), 4.58 (2H, s), 5.51 (1H, s), 6.76-6.93
(4H, m).13C NMR (300 MHz, CDCl3): δ 55.0, 65.9, 92.9, 115.2,
121.8, 123.4, 125.4, 126.1, 151.0, 152.8. MS(EI): m/z 162 (95,
M+), 161 (100, [M - H]+), 147 (21, [M - CH3]+), 131 (52, [M -
OCH3]+). HRMS (EI): calcd for C10H10O2 162.0680, found
162.0672.
Meth od 2. A mixture of compound 5c (66 mg, 0.18 mmol)
and hexabutylditin (133 mg, 0.23 mmol) in dry toluene (5 mL)
was added to a solution of tetrakis(triphenylphosphine)-
palladium (10 mg, 0.01 mmol) in dry toluene (4 mL) under
N2. The mixture was stirred at 110 °C for 24 h, cooled to room
temperature, and diluted with toluene before a saturated
solution of KF was added. The organic phase was filtered
through a short pad of Celite, and the Celite was washed with
pentane. The aqueous phase was extracted with pentane, and
the combined organic phase was washed with brine and water
and dried (MgSO4). Evaporation gave the crude product, which
was purified by silica gel chromatography using hexane/ethyl
acetate 5:1 as eluent to afford 9 as a colorless oil (21 mg, 68%).
Dieth yl 2,2-Bis[(E)-3-br om o-2-m eth oxya llyl]m a lon a te
(11). Diethyl malonate (46 mg, 0.29 mmol) in dry DME (1 mL)
was added to sodium hydride (22 mg, 95% in paraffin, 0.87
mmol) in dry DME (3 mL) at 0 °C under N2. The mixture was
stirred at 0 °C for 15 min before a solution of 3b in dry DME
(1 mL) was added. The mixture was stirred at ambient
temperature for 37 h before a mixture of aqueous NH4Cl
(aqueous) and diethyl ether was added. The aqueous phase
was extracted with diethyl ether, and the combined organic
phase was washed with brine and water, dried (MgSO4), and
evaporated. The crude product was purified by silica gel
chromatography using hexane/ethyl acetate 7:1 as eluent to
afford 11 as a colorless oil (110 mg, 85%). 1H NMR (300 MHz,
CDCl3): δ 1.20 (6H, t, J ) 7.1 Hz), 3.08 (4H, s), 3.47 (6H, s),
4.12 (4H, q, J ) 7.1 Hz), 5.19 (2 × 1H, s). 13C NMR (75 MHz,
CDCl3): δ 13.9, 33.6, 55.1, 55.2, 61.4, 80.4, 155.9, 170.3. MS-
1,2,3-Tr ibr om o-2-m eth oxyp r op a n e (2). Acetyl bromide
in dry dichloromethane (10 mL of 1 M, 10 mmol) was added
to a solution of 1 (1.29 g, 4.9 mmol) in dry dichloromethane
under N2 at 0 °C. The mixture was stirred for 4 h at ambient
temperature before the solvent was removed under reduced
pressure. The crude product was sufficiently pure to be used
in the next step but could be purified by Kugelrohr distillation
(1.14 g, 75%). Oven temperature: 68-70 °C/0.1-0.2 mmHg.
1H NMR (300 MHz, CDCl3): δ 3.54 (3H, s), 4.04 (2H, s). 13C
NMR (75 MHz, CDCl3): δ 36.2, 54.9, 104.0.
(Z)-1,3-Dib r om o-2-m et h oxyp r op en e (3a ). Diisopropyl-
amine (0.71 mL, 5.0 mmol) was added dropwise to a solution
of 2 (1.52 g, 4.9 mmol) in dry dichloromethane (10 mL) at 0
°C under N2. The mixture was stirred at ambient temperature
for 4 h before a saturated solution of NH4Cl was added,
followed by diethyl ether. The aqueous phase was extracted
with diethyl ether. The combinded organic phase was dried
(MgSO4) and evaporated. The crude product was purified by
silica gel chromatography with hexane/ethyl acetate 7:1 as
eluent to afford 3a as a colorless oil (1.01 g, 90%). 1H NMR
(300 MHz, CDCl3): δ 3.85 (3H, s), 4.00 (2H, s), 5.62 (1H, s).
13C NMR (75 MHz, CDCl3): δ 27.7, 56.9, 89.1, 153.1. MS (EI):
m/z 232/230/228 (16/31/16, M+), 151 (97, [M - Br]+), 149 (100,
[M - Br]+). HRMS (EI): calcd for C4H6OBr2 227.8790, found
227.8785.
(E)-1,3-Dibr om o-2-m eth oxyp r op en e (3b). Meth od 1.
Compound 2 (2.77 g, 8.9 mmol) in dry DMF (15 mL) was added
to a mixture of K2CO3 (1.25 g, 9 mmol) in dry DMF (15 mL) at
0 °C under N2. The mixture was stirred at ambient temper-
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