Synthesis and reactions of (E)- and (Z)-1,3-dibromo-2-methoxypropene

Article abstract of DOI:10.1021/jo991822l

(Z)-1,3-Dibromo-2-methoxypropene is prepared in 90% yield by dehydrohalogenation of 1,2,3-tribromo-2-methoxypropane with diisopropylaminein dichloromethane. The E-isomer can be obtained as the only product in almost quantitative yield by UV irradiation of

Full text of DOI:10.1021/jo991822l

J . Org. Chem. 2000, 65, 3085-3089
3085
Syn th esis a n d Rea ction s of (E)- a n d
(Z)-1,3-Dibr om o-2-m eth oxyp r op en e
Kjetil Røe Edvardsen and Tore Benneche*
Department of Chemistry, University of Oslo, P.O. Box 1033,
Blindern, 0315 Oslo, Norway
Marcus A. Tius
Department of Chemistry, University of Hawaii at Manoa, 2545 The Mall, Honolulu, Hawaii 96822
Received November 29, 1999
(Z)-1,3-Dibromo-2-methoxypropene is prepared in 90% yield by dehydrohalogenation of 1,2,3-
tribromo-2-methoxypropane with diisopropylamine in dichloromethane. The E-isomer can be
obtained as the only product in almost quantitative yield by UV irradiation of the Z-isomer.
Nucleophilic displacement reactions of the allylic bromide and palladium-catalyzed coupling
reactions of the vinylic bromide in (E)- and (Z)-1,3-dibromo-2-methoxypropene have been studied.
In tr od u ction
Resu lts a n d Discu ssion
Treatment of compound 1 with a catalytic amount of
p-toluenesulfonic acid in toluene at 200 °C, gave a 4:1
mixture of the (E)- and (Z)-1,3-dibromo-2-methoxypro-
pene (3a and 3b) in 50% yield. [Note: 3a is (Z) and 3b is
(E)]. The relatively low E/Z-selectivity and yield in this
reaction led us to consider the formation of 3 by dehy-
drobromination of 2 under basic conditions. Compound
2 was prepared in almost quantitative yield by reacting
the acetal 1 with acetyl bromide in dichloromethane at
ambient temperature.
Nucleophilic displacement reactions on 1,3-dihalo-2-
propanones have been widely used to add a three-carbon
unit to organic compounds.1-9 We were interested in
developing a 2-propanone derivative that could undergo
nucleophilic displacement reactions at C-1 and pal-
ladium-catalyzed coupling reactions at C-3. The com-
mercially available 1,3-dibromo-2-propanone was not
considered to be a good candidate for these reactions,
since dialkylation may be a problem with this compound10
and anomalies have been observed in palladium-cata-
lyzed coupling reactions with R-bromo ketones.11
Palladium(0) complexes react easily with vinyl and aryl
halides, especially bromides and iodides.12 â-Bromovinyl
ethers can also be used in palladium-catalyzed reac-
tions.13 This indicated that the keto function in 2-pro-
panone could be masked as an enol ether to get a suitable
substrate for palladium-catalyzed reactions. Thus our
target molecule would be a 1,3-dihalo-2-alkoxypropene.
1,3-Dibromo-2,2-dimethoxypropane 1, which can be readily
prepared in one step from acetone,14 was an obvious
candidate for the preparation of such an enol ether.
A number of bases were examined for the dehydroha-
logenation of 2. Potassium tert-butoxide or potassium
carbonate in DMF gave a nearly 1:1 mixture of 3a and
3b in moderate yields. With amines the yield varied from
0% to >90%. The reactions were in all cases unselective,
except when diisopropylamine in dichloromethane was
used. Then the ratio of the Z- and E-isomers was 93:7
(entry 4, Table 1). The isolated yield of the Z-isomer from
the reaction was 90%.
* Ph: +4722855556.Fax: +4722855441.E-mail: tore.benneche@kjemi.
uio.no.
(1) Gellis, A.; Vanelle, P.; Kaafarani, M.; Benakli, K.; Crozet, M. P.
Tetrahedron 1997, 53, 5471-5484.
(2) Meier, H.; Dai, Y.; Schuhmacher, H.; Kolshorn, H. Chem. Ber.
1994, 127, 2035-2041.
Conducting the elimination at other temperatures, i.e.,
at 25 and -78 °C, had little effect on the product
distribution, except in the case of diisopropylamine,
which at 25 °C gave a lower selectivity (70:30 mixture of
3a /3b) than at 0 °C. The reason diisopropylamine, in
contrast to the other amines, gives good selectivity for
the Z-isomer 3a , as well as a good chemical yield, is
unclear. The base strength of the amines in water does
not correlate well with the yield of the elimination
reaction (Table 1). tert-Butylamine, for instance, which
has approximately the same pKBH as diisopropylamine,
(3) Caballero, E.; Guilhot, F.; Lo´pez, J . L.; Medarde, M.; Sahagu´n,
H.; Tome´, F. Tetrahedron Lett. 1996, 37, 6951-6954.
(4) O’Brien, M. K.; Sledeski, A. W.; Truesdale, L. K. Tetrahedron
Lett. 1997, 38, 509-512.
(5) Lavoisier-Gallo, T.; Rodriguez, J . Synth. Commun. 1998, 28,
2259-2269.
(6) Denmark, S. E.; Wu, Z. J . Org. Chem. 1998, 63, 2810-2811.
(7) Menger, F. M.; Persichetti, R. A. J . Org. Chem. 1987, 52, 3451-
3452.
(8) Vollmer, S. H.; Walner, M. B.; Tarbell, K. V.; Colman, R. F. J .
Biol. Chem. 1994, 269, 8082-8090.
(9) Witkowski, A.; J oshi, A. K.; Rangan, V. S.; Falick, A. M.;
Witkowska, H. E.; Smith, S. J . Biol. Chem. 1999, 274, 11557-11563.
(10) Nishizawa, M.; Adachi, K.; Hayashi, Y. Tetrahedron Lett. 1983,
24, 4447-4450.
(11) Pri-Bar, I.; Pearlman, P. S.; Stille, J . K. J . Org. Chem. 1983,
48, 4629-4634.
(12) Tsuji, J . Palladium Reagents and Catalysts; J ohn Wiley &
Sons: Chichester, 1995; p 125 ff.
(13) Abe, S.; Miyaura, N.; Suzuki, A. Bull. Chem. Soc. J pn. 1992,
65, 2863-2865.
(14) Gallucci, R. R.; Going, R. J . Org. Chem. 1981, 46, 2532-2538.
10.1021/jo991822l CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/13/2000

3086 J . Org. Chem., Vol. 65, No. 10, 2000
Edvardsen et al.
Ta ble 2. Alk yla tion s w ith 3a a n d 3b
Ta ble 1. Am in e Ba ses in th e Deh yd r obr om in a tion of 2
entry alkene
NuH
C6H4OH
2-I-C6H4OH
2-I-C6H4OH
PhCH2OH
diethyl malonate
ethyl acetoacetate
product
E/Z yield (%)a
product distribution (%)a
1
2
3
4
5
6
3a
3a
3b
3a
3b
3b
5a
5b
5c
5d
5e
5f
Z
Z
88
83
b,c
entry
base
2,6-lutidine
DMAP
tert-butylamine
diisopropylamine
pKBH
3a
3b
4
E
83
1
2
3
4
5
6
7.36
9.68
10.95
10.96
33
0
7
93
35
67
17
0
3
7
35
33
50
100
90
0
30
0
Z/ Eb
79
E
E
(82)c
67
a
b
ethyldiisopropylamine 11.51
Isolated. Z/ E ratio 5:1. c Crude product.
DBU
14.30d
a
From 1H NMR of the crude product. b In H2O. c For references,
ethynyltrimethylsilane and 1-hexyne could be effected at
ambient temperature under standard conditions (entries
1 and 2, Table 3). Compounds 5b and 5c [note: 5b is (Z)
and 5c is (E)] were reacted with 1.1 equiv of 1-hexyne in
the presence of palladium to determine if the aromatic
iodide could be selectively substituted in the presence of
a â-alkoxy alkenylic bromide. The Z-isomer 5b gave a
4:1 mixture of the monoalkylated 7a and the dialkylated
product 8a (entry 3, Table 3), whereas the E-isomer 5c
gave only the product from reaction at the aromatic iodide
(entry 4). Since these reactions have been conducted
under the same conditions, the results indicate that the
vinylic bromide in the Z-isomer 5b is more reactive than
in the E-isomer 5c in the Sonogashira-Castro reaction.
Reaction of the E-isomer 5b with an excess of alkyne gave
the dialkylated product 8b in good yield (entry 5). The
diynes 8a and 8b should be well suited for further
elaboration in the side chain.
d
see Experimental Section. Calculated.
gave only 10% elimination (entry 3, Table 1). Ethyldi-
isopropylamine, which is a stronger base than diisopro-
pylamine, also gave less elimination than diisopropyl-
amine (entry 5). The base strength seems to be of some
importance, because weak bases such as 2,6-lutidine and
DMAP gave low yields in the elimination while the strong
and nonnucleophilic base DBU gave complete elimination
(entries 1, 2, and 6). DMAP is a stronger base than 2,6-
lutidine but gave no elimination. The reason may be that
DMAP is acting like a nucleophile, giving a substitution
product that is hydrolyzed to 4 during the workup.
The stereochemistry of the compounds 3a and 3b was
determined by NOE.
The Heck reaction is one of the more impotant reac-
tions in contemporary organic synthesis.16 In this reaction
the regeneration of the catalyst is normally achieved by
a â-hydride elimination.16 In some cases a â-substituent
other than a hydride may be eliminated, e.g., a bromide17
or a TMS group.18 In the latter case the TMS group is
eliminated in preference to a â-hydrogen. We wanted to
investigate if 5b could be cyclized in a Heck process. We
assumed that the oxidative addition of palladium(0)
would be more rapid to the iodide in the 2-position of the
aromatic ring than to the vinylic bromide in the side
chain. The coupling reaction of 5b with 1-hexyne (vide
supra) supports this view. If the reaction mechanism
involved addition of an aromatic palladium complex to
the double bond of the side chain, only a 6-endo-trig
cyclization seemed resonable. The new palladium com-
plex would then have the possibility for a â-hydride
elimination or a â-bromide elimination. When 5b was
treated with palladium(0) under standard Heck condi-
tions, only 9 was isolated (58% yield); no other elimina-
tion products were observed (Scheme 1). Reacting 5c in
the same way gave almost the same result (61% yield of
9). The amine is possibly the stoichiometric reducing
agent.
The thermal stability of 3 was investigated by heating
a 93:7 mixture of 3a and 3b from ambient temperature
to 135 °C. The temperature was increased by 10 °C every
30 min, at which point samples were taken and analyzed
1
by H NMR. When the temperature had reached 100 °C
the Z/ E-ratio had changed to 75:25 without noticeable
decomposition. Further heating led to decomposition
without any change in the isomer ratio.
Irradiation of 3a in hexane with a low-pressure UV
lamp resulted in complete conversion of the Z-isomer to
the E-isomer. The yield in the conversion was almost
quantitative.
The elimination reaction with diisopropylamine gives
access to nearly pure 3a , and photoisomerization gave
3b. With a convenient source of both geometrical isomers
of 3, the nucleophilic displacement reactions of the allylic
bromide were examined.
Alkylation of oxygen nucleophiles (entries 1-4, Table
2) and active methylene compounds (entries 5 and 6) with
3 under basic conditions was successful. Double bond
isomerization was observed only with the anion of benzyl
alcohol (entry 4). Products from a SN2′ process could not
be detected in the reaction mixture.
The effectiveness of the intramolecular Heck reaction
of 5 to 9 was compared to an intermolecular Heck
reaction.Treatment of 5b and 5c with methyl acrylate
led in both cases to 9, the product of intramolecular
Alkenyl halides are useful substrates for the Sono-
(16) Metal-catalyzed Cross-coupling Reactions; Bra¨se, S., Meijere,
A., Eds.; Wiley-VCH: New York, 1998.
gashira-Castro reaction.15 The coupling of 5a with
(17) Grigg, R.; Stevenson, P.; Worakun, T. Tetrahedron 1988, 44,
2049-2054.
(18) Hallberg, A.; Westerlund, C. Chem. Lett. 1982, 1993-1994.
(15) Tsuji, J . Palladium Reagents and Catalysts; J ohn Wiley &
Sons: Chichester, 1995; p 168.

(E)- and (Z)-1,3-Dibromo-2-methoxypropene
J . Org. Chem., Vol. 65, No. 10, 2000 3087
Ta ble 3. P a lla d iu m -Ca ta lyzed Cou p lin g Rea ction s of Alk yn es w ith 5a or 5b
yield (%)a
entry
alkene
X
R
equiv. alkyn
product
E/Z
6
7
8
1
2
3
4
5
5a
5a
5b
5c
5b
H
H
I
I
I
TMS
Bu
Bu
Bu
TMS
1.1
1.1
1.1
1.1
4.0
6a
6b
7a /8a
7b
8b
Z
Z
Z
E
Z
45
67
0
0
0
60
67
0
16
0
72
a
Isolated.
Sch em e 1
Sch em e 2
cyclization, and 10a or 10b as the minor product (38%
vs 16% and 40% vs 20%, respectively). Compounds 10a
and 10b could, however, be prepared in good yields (92%
and 72%, respectively) from methyl 3-(2-hydroxyphenyl)-
acrylate19 and 3a or 3b. Compounds 10a and 10b do not
cyclize under the reaction conditions used in the Heck
reaction.
Sch em e 3
Compound 9 was also obtained when 5b or 5c was
reacted with hexabutylditin in the presence of palladium-
(0) at 110 °C in toluene. In the former case the yield was
42%, and in the latter case it was 68%. Molecular models
indicate that the cyclization of the E-isomer 5c is much
easier for steric reasons than the cyclization of the
Z-isomer 5b, hence the better yield in the case of 5c
compared to 5b. Double bond isomerization in 5 most
likely takes place at 110 °C, and an E-isomer is probably
also the cyclizing species in the case of 5b.
Alkylation of diethyl malonate with 2 equiv of 3b gave
the dialkylated malonate 11 in 82% yield (Scheme 2).
Treatment of 11 with palladium gave the cyclized product
12 in 65% yield, as the only product. The methoxy groups
probably block anything other than a 7-endo-trig cycliza-
tion. Also in this case is a â-bromide elimination preferred
to a â-hydride elimination. The formation of a conjugated
system may be of importance in this matter. The reaction
is performed with an excess of triphenylphosphine, which
presumably is also functioning as a reducing agent in
addition to being a ligand.
The first step in this reaction is believed to be oxidative
addition of palladium(0) to the alkenyl halide. Little
information on the rate of the oxidative additon of
palladium(0) to an alkenyl halide having an electron-
donating substituent in the â-position is available, but
the methoxy group was expected to reduce the rate of
the oxidative addition since a similar observation has
been made in aromatic systems.21 Compound 5a did,
however, react with 2-tributylstannylthiophene in DCE
at 50 °C for 25 h to give the coupled product as a 1:1
mixture of E/ Z-isomers in 73% yield. (Scheme 3).
Treatment of the enol ether 13 with acid gave the
ketone 14. (Scheme 3). The synthesis of 14 from 1,3-
dibromo-2-methoxypropene is in essence the same as
The palladium-catalyzed reaction of organotin reagents
with alkenyl halides (Stille reaction) is very versatile.20
(19) Heck, R. F. Org. React. 1982, 27, 345-390.
(20) Farina, V.; Krishnamurthy, V.; Scott, W. J . Org. React. 1997,
50, 1-652.
(21) Fauvarque, J . F.; Pflu¨ger, F.; Troupel, M. J . Organomet. Chem.
1981, 208, 419-427.

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-
(22) King, J . F.; Hillhouse, J . H.; Skonieczny, S. Can. J . Chem. 1984,
62, 1977-1995.
(23) Leffek, K. T.; Pruszynski, P.; Thanapaalasingham, K. Can. J .
Chem. 1989, 67, 590-595.
(24) Pritchard, J . G.; Long, F. A. J . Am. Chem. Soc. 1957, 79, 2365-
2368.
(25) Bunting, J . W.; Stefanidis, D. J . Am. Chem. Soc. 1990, 112,
779-786.
(26) Hall, F. N.; Sprinkle, M. R. J . Am. Chem. Soc. 1932, 54, 3469-
3485.
(27) Gruen, L.; Laskowski, M., J r.; Scheraga, H. A. J . Am. Chem.
Soc. 1959, 81, 3891-3901.

(E)- and (Z)-1,3-Dibromo-2-methoxypropene
J . Org. Chem., Vol. 65, No. 10, 2000 3089
(EI): m/z 460/458/456 (0.14/0.25/0.14, M+), 385 (7, [M -
EtO2C]+), 379 (12, [M - Br]+), 377 (12, [M - Br]+).
3.86 (3H, s), 3.89 (3H, s), 4.54 (2H, s), 4.67 (2H, s), 5.61 (1H,
s), 6.11 (1H, s), 6.90-7.01 (10H, m), 7.27-7.31 (6H, m). 13C
NMR (75 MHz, CDCl3): δ 56.1, 57.1, 66.1, 66.8, 88.2, 106.7,
114.8, 114.9, 121.4, 121.7, 125.2, 125.8, 126.1, 129.5, 129.6,
137.7, 148.6, 153.0, 157.7, 158.1. MS (EI): m/z 246 (11, M+),
153 (100, [M - PhO]+). HRMS (EI): calcd for C14H14O2S
246.0715, found 246.0716.
Diet h yl (3E,5E)-3,6-Dim et h oxycycloh ep t a -3,5-d ien e-
1,1-d ica r boxyla te (12). Compound 11 (55 mg, 0.12 mmol) in
dry acetonitrile (2 mL) was added to a mixture of palladium
acetate (5 mg, 0.024 mmol), triphenylphosphine (44 mg, 0.17
mmol), and K2CO3 (48 mg, 0.35 mmol) in dry acetonitrile (10
mL) under N2 at ambient temperature. The mixture was
heated under reflux for 24 h, cooled, and a mixture of 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 3:1 as eluent to
1-P h en oxy-3-(2-th ien yl)p r op a n on e (14). Compound 13
(17 mg, 0.069 mmol) was dissolved in dioxane (1.2 mL), and
10% HCl (0.25 mL) was added. The mixture was stirred at
ambient temperature for 13 h before diethyl ether and a
saturated solution of Na2CO3 (aqueous) were added. The
aqueous phase was extracted with diethyl ether, and the
combined organic phase was washed with water and dried (Mg
SO4). The crude product was purified by silica gel chromatog-
raphy using hexane/ethyl acetate 15:1 as eluent to afford 14
1
afford 12 as a colorless oil (22 mg, 65%). H NMR (300 MHz,
CDCl3): δ 1.20 (6 H, t, J ) 7.1 Hz), 2.80 (4H, s), 3.49 (6H, s),
4.15 (4H, q, J ) 7.1 Hz), 4.87 (2 × 1H, s). 13C NMR (75 MHz,
CDCl3): δ 13.9, 37.7, 54.7, 60.4, 61.5, 94.1, 155.1, 170.6. MS-
(EI): m/z 298 (35, M+), 253 (5, [M - EtO]+), 195 (26, [M -
EtO2C/2 × CH3]+). HRMS (EI): calcd for C15H22O6 298.1416,
found 298.1402.
1
as a colorless oil (6 mg, 40%). H NMR (300 MHz, CDCl3): δ
4.11 (2H, s), 4.62 (2H, s), 6.86-6.99 (5H, m), 7.21-7.32 (3H,
m). 13C NMR (75 MHz, CDCl3): δ 40.0, 72.0, 87.7, 114.5, 121.9,
125.4, 127.1, 127.2, 129.7, 157.6, 203.6. MS (EI): m/z 232 (45,
M+), 139 (46, [M - PhO]+). HRMS (EI): calcd for C13H12O2S
232.0558, found 232.0553.
2-Meth oxy-3-(2-th ien yl)a llyloxyben zen e (13). A mixture
of compound 5b (241 mg, 1.0 mmol) and 2-thienyltributyltin
(0.76 g, 2.0 mmol) in dry degassed DCE (4 mL) was added to
a solution of bis(triphenylphosphine)palladium dichloride (40
mg, 0.05 mmol) in dry degassed DCE (2 mL) under N2 at
ambient temperature. The mixture was stirred at 50 °C for
25 h, diluted with DCE, and added to a saturated aqueous
solution of KF. 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/chloroform
2:1 as eluent to afford 13 as a colorless oil (0.18 g, 73%, as 1:1
Ack n ow led gm en t. M.A.T. is grateful to Sea Grant
(Institutional Grant NA86RG0041) for generous sup-
port.
Su p p or tin g In for m a tion Ava ila ble: Experimental data
for 5a -f, 6a and 6b, 7a and 7b, 8a and 8b, and 10a and 10b;
copy of 1H NMR spectrum of 5e; copies of 1H and 13C NMR
spectra of 2, 3a ,b, 5a -d , 6a ,b, 7a ,b, 8a ,b, 9, 10a ,b, and 11-
14. This material is available free of charge via the Internet
at http://pubs.acs.org.
1
mixture of the E/ Z isomers). H NMR (300 MHz, CDCl3): δ
J O991822L