Checked by Joseph Fortunak and Ian Fleming.
1. Procedure
Caution! The reaction described in Section (Step) A (Note 1) should be carried out in a well-ventilated hood because bromine is toxic.
A.
(Z)-β-Bromostyrene. In a
1-L, round-bottomed flask equipped with a
magnetic stirring bar are placed
30.8 g (0.100 mol) of erythro-α,β-dibromo-β-phenylpropionic acid (Note
1),
13.0 g (0.200 mol) of sodium azide (Note
2), and
500 mL of dry N,N-dimethylformamide (Note
3). The reaction mixture is stirred at room temperature for 8 hr and poured into a mixture of
300 mL of ether and 300 mL of water. The organic layer is separated, washed with three 100-mL portions of water, dried over
magnesium sulfate, and filtered. After evaporation of the filtrate with a
rotary evaporator, the residual liquid is distilled under reduced pressure, giving
13.5–13.9 g (
74–76%) of
(Z)-β-bromostyrene, bp
54–56°C (1.5 mm) (Note
4).
B.
2-(N,N-Dimethylamino)phenyllithium. A
100-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar and a
reflux condenser connected to a
nitrogen-inlet tube is capped with
serum stoppers and flushed with
nitrogen. The flask is charged with
18.2 g (0.150 mol) of N,N-dimethylaniline (Note
5) and
33.4 mL (0.050 mol) of a 1.50 M solution of butyllithium in
hexane (Note
6). While a continuous positive
nitrogen pressure is maintained, the solution is heated at reflux (in a 90–95°C bath) with stirring for 20 hr and then cooled to room temperature (Note
7).
C.
(Z)-β-[2-(N,N-Dimethylamino)phenyl]styrene. A
1-L. three-necked, round-bottomed flask equipped with a magnetic stirring bar, a reflux condenser connected to a nitrogen-inlet tube, and a
300-mL, pressure-equalizing dropping funnel is capped with serum stoppers. The flask is flushed with
nitrogen and charged with
0.433 g (0.0025 mol) of palladium chloride (Note
8),
2.62 g (0.010 mol) of triphenylphosphine (Note
9) and
300 mL of benzene (Note
10). While a continuous positive
nitrogen pressure is maintained, the mixture is stirred at gentle reflux for 30 min, and then
4.25 mL (0.0060 mol) of a 1.41 M solution of methyllithium in ether (Note
11) is added with a
syringe. After an additional 10 min at reflux,
9.15 g (0.050 mol) of (Z)-β-bromostyrene as prepared in Section A is added in one portion with syringe, and the mixture is heated at reflux for 10 min. The solution of
2-(N,N-dimethylamino)phenyllithium prepared as described in Section B is transferred to the dropping funnel with a syringe and diluted by adding
150 mL of benzene (Note
10) and (Note
12). The resulting solution is then added dropwise to the mixture with stirring at reflux over a period of 30 min (Note
13). After additional stirring for 10 min, the resulting red solution is cooled to room temperature with the help of an
ice bath and quenched by adding
100 mL of saturated aqueous ammonium chloride. The organic layer is separated, washed successively with 100 mL of water and
100 mL of saturated aqueous sodium chloride, and then dried over
magnesium sulfate and filtered. The solvent is evaporated with a rotary evaporator, and the residue is distilled under reduced pressure to give a forerun
(ca. 11 g) of excess N,N-dimethylaniline, bp
31–51°C (1 mm), followed by
7.4–7.5 g (
66–67%) of
(Z)-β-[2-(N,N-dimethylamino)phenyl]styrene, bp
90.0–92.0°C (0.035 mm),
82–84°C (0.01 mm), as a pale-yellow liquid (Note
14).
2. Notes
1.
erythro-α,β-Dibromo-β-phenylpropionic acid is prepared from
trans-cinnamic acid (mp 133–134°C) (Nakarai Chemicals, Japan) by the method used for
ethyl α,β-dibromo-β-phenylpropionate (Abbott T. W.; Althousen, D.
Org. Synth., Coll. Vol. II 1943, 270) in
83% yield, mp
199–200°C. The checkers used
benzene (400 mL per mol) in place of the
carbon tetrachloride, because the mixture was then easier to stir and the reaction was more reproducible. The yield before purification was
89% (mp
174–191°C); the yield after recrystallization was
81% (mp
198–199°C). Crude material could be used without appreciable loss of yield.
2.
Sodium azide from Wako Pure Chemical Ind., Japan, was used without purification.
4. Gas chromatographic analysis of the distillate (10% PEG-20M on 60–80-mesh, Celite 545 AW, 1-m × 4-mm column, column temperature 100–220°C, injection temperature 200°C) shows that the product is 100% isomerically pure. The spectral properties of the
(Z)-β-bromostyrene are as follows: IR (neat) cm
−1: strong absorptions at 3095, 3040, 1620, 1500, 1450, 1333, 1032, 930, 920, 830, 770, and 700;
1H NMR (CHCl
3) δ: 6.43 (doublet, 1 H,
J = 8, PhCH=C), 7.08 (doublet, 1 H,
J = 8, PhC=CHBr), 7.22–7.85 (multiplet, 5 H, aromatic). The checkers also purified the residual oil before distillation by filtration in
250 mL of pentane through three times its weight of silica gel (70–230-mesh) followed by evaporation. The yield before distillation was then reproducibly
84%, distillation was avoided, and the next step proceeded with undiminished yield.
7. The resulting cloudy, yellowish orange solution should be used within 3–4 hr.
8.
Palladium chloride from Inuisho Precious Metal Company, Japan, was used without purification.
10.
Benzene is distilled over
benzophenone ketyl and stored under a
nitrogen atmosphere.
14. Gas chromatographic analysis of the product (5% silicone SE 30 on 80–100-mesh Chromosorb W AB, 0.5-m × 4-mm column, column temperature 100–250°C, injection temperature 180°C) shows that the product is at least 98% (
Z)-isomer. The spectral properties of the (
Z)-alkene are as follows; IR (neat) cm
−1: strong absorptions at 3070, 3025, 2950, 2870, 2835, 2780, 1600, 1490, 1450, 1320, 1190, 1160, 1140, 1100, 1050, 950, 780, 750, and 690;
1H NMR (CCl
4) δ: 2.76 (singlet, 6 H, CH
3-N), 6.38 (doublet, 1 H,
J = 12.3, PhC=CH), 6.63 (doublet, 1 H,
J = 12.3, PhCH=C), 6.50–7.30 (multiplet, 9 H, aromatic).
3. Discussion
This procedure illustrates a general method for the preparation of alkenes from the palladium(O)-catalyzed reaction of vinyl halides with organolithium compounds,
7 which can be prepared by various methods, including direct regioselective lithiation of hydrocarbons.
8 The method is simple and has been used to prepare a variety of alkenes stereoselectively. Similar stoichiometric organocopper reactions sometimes proceed in a nonstereoselective manner
9 and in low yields.
10 Nickel catalysts can be used efficiently for the reaction of alkenyl halides with Grignard reagents but not with organolithium compounds.
11 Highly reactive zerovalent
palladium catalyst can be directly generated in situ from
PdCl2–
PPh3–
CH3Li.
Tetrakis(triphenylphosphine)palladium can be used alternatively. Grignard reagents undergo the reaction as well with vinyl halides. Organolithium compounds require the limited reaction conditions under which the elimination of alkenyl halides producing lithium acetylides is slower than the cross-coupling reaction.
7 The choice of
benzene as a solvent and the dilution of the solution satisfy the above conditions. The palladium-catalyzed alkylation of aryl halides with organolithium compounds proceeds efficiently without such difficulty.
7 Similar reactions with lithium thiolates give the corresponding alkenyl sulfides.
7 Representative reactions of organolithium compounds are shown in Table I.
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
benzophenone ketyl
erythro-α,β-Dibromo-β-phenylpropionic acid
(Z)-C6H5CH=CHBr
CH3Li
C4H9Li
C6H5SLi
(Z)-C6H5CH=CHSC6H5
C2H5SLi
(Z)-C6H5CH=CHSC2H5
(E)-C6H5CH=CHBr
Benzene (71-43-2)
ether (60-29-7)
ammonium chloride (12125-02-9)
sodium bicarbonate (144-55-8)
sodium chloride (7647-14-5)
bromine (7726-95-6)
carbon tetrachloride (56-23-5)
nitrogen (7727-37-9)
nickel (7440-02-0)
palladium (7440-05-3)
methyl bromide (74-83-9)
xylene (106-42-3)
N,N-dimethylaniline (121-69-7)
Pentane (109-66-0)
sodium azide (26628-22-8)
β-bromostyrene (103-64-0)
palladium chloride,
palladium dichloride
Lithium wire (7439-93-2)
magnesium sulfate (7487-88-9)
Ethyl α,β-dibromo-β-phenylpropionate (5464-70-0)
butyllithium (109-72-8)
N,N-dimethylformamide (68-12-2)
hexane (110-54-3)
Methyllithium (917-54-4)
calcium hydride (7789-78-8)
triphenylphosphine,
triphenyl phosphine (603-35-0)
2-Butanol (78-92-2)
(Z)-β-Bromostyrene (103-64-0)
phenylacetylide
Tetrakis(triphenylphosphine)palladium (14221-01-3)
2,2'-biquinoline (119-91-5)
(Z)-β-[2-(N,N-Dimethylamino)phenyl]styrene,
Benzenamine, N,N-dimethyl-2-(2-phenylethenyl)-, (Z)- (70197-43-2)
2-(N,N-Dimethylamino)phenyllithium
trans-cinnamic acid (140-10-3)
(Z)-1,4-diphenyl-1-buten-3-yne
cTetrakis-(triphenylphosphine)palladium
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