New Preparation and Reactions of Arylaluminum Reagents Using Barbier Conditions
08 April 2009 (online)
The reaction of various aryl bromides with magnesium turnings, LiCl and R2AlCl (R = Et, i-Bu) provides at room temperature arylaluminum reagents in high yields. These organometallic species undergo readily 1,4-additions, acylations, allylations, and Pd-catalyzed cross-couplings with various aryl iodides and bromides.
organoaluminum - cross-coupling - 1,4-addition - acylation - Barbier reaction
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References and Notes
Preparation of Aluminum Reagent 1f
A dry argon-flushed Schlenk flask equipped with a magnetic stirrer and a rubber septum was charged with anhyd LiCl (106 mg, 2.5 mmol), and the flask was dried with a heating gun for 3-5 min on high vacuum (1 mbar). To this flask was added the magnesium turnings (122 mg, 5.0 mmol), and the flask was evacuated and refilled with argon. After the addition of freshly distilled THF (3 mL), magnesium turnings were activated with DIBAL-H (0.2 mL, 0.1 M solution in THF, 0.02 mmol). After heating for about 1 min and then cooling to 25 ˚C, i-Bu2AlCl soln (2.2 mmol, 0.8 M in heptane) was added. Finally, 4-bromoanisole (374 mg, 2.0 mmol) was added in one portion at 25 ˚C. After 3 h at this temperature, the reaction mixture was cannulated to a new Schlenk flask for the trapping reaction with an electrophile.
The ²7Al NMR spectra of 1a obtained by our method and by the reaction of p-lithioanisole and 4a give the same chemical shift (δ = 178.16 ppm, in THF and Et2O).15
Preparation of 3-(4-Methoxy-phenyl)cyclohexanone (4a)
The freshly made aluminum reagent 1a was cannulated into a dry argon-flushed Schlenk flask equipped with a magnetic stirrer and a rubber septum at -10 ˚C. To this was added CuCN˙2LiCl (0.2 mL, 1 M in THF, 0.2 mmol), and the reaction mixture was stirred for 5 min. After the addition of cyclohex-2-enone (115 mg, 1.2 mmol) and then TMSCl (239 mg, 2.2 mmol), the cooling bath was removed and the mixture was stirred for 4 h at 25 ˚C. The reaction was quenched with AcOH (360 mg, 6.0 mmol) at -30 ˚C and then kept at 25 ˚C for 15 min. The mixture was extracted three times with EtOAc, washed with aq sat. NaHCO3, H2O, and sat. NaCl soln. The combined organic layers were dried over Na2SO4, and the solvents were removed under reduced pressure to furnish the crude product, which was further purified by column chromatography (SiO2) to obtain a light yellow oil (72% yield, 176 mg).
Typical Procedure: Preparation of Ethyl 4′-Methoxy-biphenyl-2-carboxylate (8b) A dry Schlenk flask equipped with a magnetic stirrer and a rubber septum was charged with ethyl 2-bromobenzoate (366 mg, 1.6 mmol), PEPPSIi-Pr (13.6 mg, 2 mol%). The flask was thoroughly flushed with argon, and freshly distilled THF (0.5 mL) was added to it through the rubber septum. The resultant mixture was stirred at 25 ˚C for 5 min before the aluminum reagent 1f was slowly cannulated into the flask. After 1 h, the reaction was quenched with aq 2 N HCl at -30 ˚C and then kept at 25 ˚C for 10 min. The mixture was extracted three times with EtOAc, washed with aq sat. NaHCO3, H2O, and sat. NaCl soln. The combined organic layers were dried over Na2SO4, and the solvents were removed under reduced pressure to furnish the crude product, which was further purified by column chromatog-raphy (SiO2) to obtain a light yellow oil (95% yield, 389 mg).