TABLE 1. Preparation of Vinyl-Substituted â-Diketones
4-Bromobenzoylacetone was synthesized by a modified Shea
method.5 The bromine-substituted â-diketones were synthesized
by modified literature procedures.6,7 The 1-acetyl-4-bromonaph-
thalene was synthesized by standard Friedel-Crafts acylation
of 1-bromonaphthalene with acetyl chloride and aluminum
chloride. The Heck couplings were performed with either a Parr
Instruments HC 677 100 mL reactor (compounds 1a-5a) or a
PPI LC series 300 mL reactor (compounds 3a, 6a, and 7a).
Procedure A. Dimethyl formamide, palladium acetate, tri-
o-tolyl phosphine, triethylamine, and brominated â-diketone
were added to a 100 mL Parr high-pressure reactor with an inner
glass liner. The solution was degassed with nitrogen for 10 min
before the reactor was cooled to -196 °C and ethylene was
condensed for 20 min. The reactor was allowed to warm to room
temperature before heating to 100 °C in an oil bath. The pressure
was bled off until 300 psi was achieved and the reaction was
allowed to proceed for 12 h. The reaction vessel was cooled to
room temperature, the extra pressure bled, and the contents
dissolved in water (50 mL) and ether (50 mL). The aqueous
phase was made acidic by addition of concentrated hydrochloric
acid followed by extraction with ether (2 × 50 mL). The combined
organic phase was rinsed with saturated sodium chloride
solution, and the organic phase was dried over magnesium
sulfate overnight. The solution was filtered, the solvent was
removed by vacuum, and the residue was dissolved in chloroform
(3 mL). The product was isolated by column chromatography
from silica gel (Selecto, mesh size 63-200) with chloroform as
eluent.
Procedure B. 1,4-Dioxane, TTBP, and Cy2NMe were placed
into a 100 mL Schlenk flask and degassed with argon, before
transfer by syringe to a PPI LC series 300 mL reactor containing
Pd2(dba)3 and the brominated â-diketone under an argon
atmosphere. The reactor was charged to 300 psi with ethylene
and the reaction was allowed to stir for 48 h at room tempera-
ture. Upon completion of the reaction the contents were taken
up in water (50 mL) and ether (50 mL) and the aqueous phase
was acidified by addition of concentrated hydrochloric acid and
extracted with ether (2 × 50 mL). The combined organic phase
was rinsed with saturated sodium chloride solution, and the
organic phase was dried over magnesium sulfate overnight. The
solution was filtered, the solvent was removed by vacuum, and
the residue was dissolved in chloroform (3 mL). The product was
isolated by column chromatography from silica gel (Selecto, mesh
size 63-200) with 10% ether in chloroform as eluent.
Synthesis of 4-vinylbenzoylacetone (1a): Procedure A was
employed, using dimethyl formamide (30 mL), palladium acetate
(0.022 g, 0.1 mmol), tri-o-tolyl phosphine (0.060 g, 0.2 mmol),
triethylamine (9.1 g, 90 mmol), 4-bromobenzoylacetone (2.41 g,
10 mmol), and ethylene (1.7 g, 61 mmol). The first band collected
resulted in a yellow powder (1.03 g, 55% yield) upon solvent
removal.
1H NMR (200 MHz, 25 °C, CDCl3): δ 16.12 (s, 1 H), 7.83 (d,
2 H), 7.45 (d, 2 H), 6.70 (dd, 1 H), 6.17 (s, 1 H), 5.82 (d, 1 H),
5.35 (d, 1 H), 2.20 (s, 3 H). Anal. (found/calcd) for C17H14O2: C
76.49/76.57, H 6.33/6.43.
Synthesis of 4-vinyldibenzoylmethane (2a): Procedure A
was employed, using dimethyl formamide (30 mL), palladium
acetate (0.022 g, 0.1 mmol), tri-o-tolyl phosphine (0.060 g, 0.2
mmol), triethylamine (9.1 g, 90 mmol), 4-bromodibenzoyl-
methane (3.03 g, 10 mmol), and ethylene (1.7 g, 61 mmol). The
first band collected resulted in a yellow powder (2.2 g, 88% yield)
upon solvent removal.
1H NMR (200 MHz, 25 °C, CDCl3): δ 16.91 (s, 1 H), 7.98 (m,
4 H), 7.50 (m, 5 H), 6.96 (s, 1 H), 6.86 (dd, 2 H), 5.90 (d, 2 H),
5.40 (d, 2 H). Anal. (found/calcd) for C17H14O2: C 81.71/81.60,
H 5.65/5.64.
Synthesis of 3-vinyldibenzoylmethane (3a): Procedure
A was employed, using dimethyl formamide (30 mL), palladium
acetate (0.022 g, 0.1 mmol), tri-o-tolyl phosphine (0.060 g, 0.2
mmol), triethylamine (9.1 g, 90 mmol), 3-bromodibenzoyl-
methane (3.03 g, 10 mmol), and ethylene. The first band collected
resulted in a yellow powder (2.2 g, 88% yield) upon solvent
removal.
Heck yield
compd
and prepa
vinyl 1H NMR (δ)
1a
2a
3a
4a
5a
6a
7a
55% (a, d)
45% (b, d)
50% (b, d)
62% (b, d)
56% (b, d)
97% (c, e)
32% (c, e)
6.70 (dd, 1 H), 5.82 (d, 1 H), 5.35 (d, 1 H)
6.86 (dd, 1 H), 5.90 (d, 1 H), 5.40 (d, 1 H)
6.79 (dd, 1 H), 5.91 (d, 1 H), 5.36 (d, 1 H)
6.80 (dd, 2 H), 5.90 (d, 2 H), 5.40 (d, 2 H)
6.77 (dd, 2 H), 5.92 (d, 2 H), 5.40 (d, 2 H)
7.20 (dd, 1 H), 5.91 (d, 1 H), 5.62 (d, 1 H)
6.74 (dd, 1 H), 5.86 (d, 1 H), 5.43 (d, 1 H)
a Key: (a) bromomethyl methylbenzoate, NaH, acetone; (b)
benzaldehyde, acetophenone, NaOH, Br2, NaOMe; (c) sodium
alkoxide, aromatic acetyl, ethyl trifluoroacetate; (d) â-diketone,
Pd(OAc)2, TPP, TEA, ethylene, DMF; (e) â-diketone, Pd2DBA3,
TBPP, 1,4-dioxane, ethylene, Cy2NMe.
respectively, yield without hydrogenation of the vinyl
group or autopolymerzation. The coupling reaction re-
quired 48 h for complete consumption of the halogenated
precursor. Two equivalents of Cy2NMe was needed to
neutralize the hydrogen bromide generated during the
reaction and labile proton of the enolate tautomer of the
â-diketones. Compounds 6a and 7a were both susceptible
to autopolymerization within days despite addition of
stabilizer and storage at -20 °C. To stabilize the com-
pounds for both characterization and storage both 6a and
7a were converted to copper(II) bis â-diketonate salts by
addition of a methanolic solution of copper(II) chloride
hexahydrate to a methanol solution of the â-diketone. The
copper(II) complex of 7a was found to be stable indefi-
nitely at room temperature; however, the copper(II)
complex of 6a would still autopolymerize at -20 °C after
several weeks. Normally, copper(II) complexes are known
for quenching or retarding free-radical polymerizations.
It is quite interesting to see that 6a could stabilize the
redox couple of copper(II) to the point where free-radical
polymerization would propagate at -20 °C. Thus 6a
should be used immediately upon isolation for subsequent
chemical reactions.
Compound 3a was prepared by the low-temperature
Heck method for comparison. The yield was the same as
the high-temperature Heck method, but there was no
evidence of hydrogenation to the vinyl moiety.
In conclusion, a number of new vinyl-substituted aryl
â-diketones were prepared by Heck coupling in fair to
good yield. The aryl groups varied from benzene deriva-
tives to polyaromatic hydrocarbons to heterocycles. High-
temperature Heck coupling was found to work adequately
for preparing vinyl-substituted aryl â-diketones from
benzene derivatives; however, the products did suffer
from partial hydrogenation of the vinyl group. The high-
temperature Heck coupling also failed to give any product
with the electron-rich polyaromatic and heterocyclic
substrates. A low-temperature Heck coupling devised by
Fu succeeded in preparing vinyl-substituted aryl â-dike-
tones from those electron-rich substrates without hydro-
genation of the vinyl group.10 The low-temperature
method was also shown to work well with the benzene
derivatives without the hydrogenation suffered by the
high-temperature method.
Experimental Section
General. 1,4-Dioxane (anhydrous; Sure-Seal; Aldrich), Pd2-
(dba)3 (Aldrich), and TTBP (10 wt % solution in hexane: Sure-
Seal; Strem), and Cy2NMe (Aldrich) were used as received.
9038 J. Org. Chem., Vol. 70, No. 22, 2005