Six- and Eightfold Palladium-Catalyzed Cross-Coupling Reactions of Hexa- and Octabromoarenes (original) (raw)

2004, Chemistry - A European Journal

General procedure for the preparation of catechol boronates 2 (GP 1): A 1 M solution of catecholborane in THF (10 mmol) was added to the respective alkyne 3 (10 mmol) at ambient temp. and the mixture heated at 70 °C for the stated time. The reaction mixture was cooled to ambient temp. and distilled in vacuo. General procedure for the preparation of pinacol boronates 4 (GP 2): A solution of BH 3 •SMe 2 (20 mmol, 10 M in dimethyl sulfide) was added dropwise to a solution of pinacol (20 mmol, 2.36 g) in CH 2 Cl 2 (2 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 1 h, then warmed up to ambient temp., and stirred until the evolution of hydrogen had ceased. The respective alkyne 3 (6 mmol) was slowly added with vigorous stirring at 0 °C. The reaction mixture was warmed to ambient temp. and stirred for the stated time. Then diethyl ether (150 mL), and a solution of NH 4 Cl (250 mL) was added with stirring. The organic layer was washed quickly with a solution of NH 4 Cl (100 mL), dried (MgSO 4), and the solvents were removed in vacuo. The residue was purified by flash column chromatography. General procedure for the preparation of methyl ketones 6 (GP 3): A solution of methyllithium (1.66 M, 66 mL, 0.11 mol) in diethyl ether was added at 0 °C to a stirred solution of the respective carboxylic acid 5 (50.0 mmol) in ether (250 mL), the mixture was stirred for an additional 30 min at this temp. and for 4 h at 20 °C. The reaction mixture was poured slowly with vigorous stirring into a solution of conc. HCl (25 mL) in ice water (500 mL). The aq. layer was extracted with diethyl ether (3 × 80 mL), and the combined 2 organic layers were washed with NaHCO 3 solution (100 mL), dried (MgSO 4) and concentrated. General procedure for the preparation of terminal alkynes 3 (GP 4): A solution of the respective methyl ketone 6 (25 mmol) in THF (30 mL) was slowly added at-78 °C to a solution of lithium diisopropylamide (LDA), freshly prepared from diisopropylamine (30 mmol) in THF (30 mL) and n-butyllithium (28 mmol) in hexane. After 1 h of stirring at this temperature, diethyl chlorophosphate (28 mmol) was added, and the mixture slowly warmed to ambient temp. and stirred for an additional 3 h. This mixture was added to a second LDA solution, prepared from diisopropylamine (50 mmol) in THF (50 mL) and nBuLi (50 mmol) at-78 °C, slowly warmed to room temp. and stirred for 12 h. Then the reaction was quenched with water (100 mL). The aq. layer was extracted with pentane (3 × 80 mL), the combined organic layers were washed with ice-cold 1 N HCl (2 × 50 mL), water (2 × 50 mL) and portions of a solution of NaHCO 3 until pH 8, dried (MgSO 4) and concentrated. General procedure for the preparation of alkenylstannanes 19 (GP 5): Freshly distilled tri-n-butyltin hydride (5 mmol) and azoisobutyronitrile (0.5 mmol) were added to the respective alkyne 3 (10 mmol) in a screw-capped Pyrex bottle and were stirred at 80 °C for 24 h. Then the reaction mixture was filtered through a bed of Celite. 2-[(E)-2-(Adamantyl)ethenyl]-1,3,2-benzodioxaborol (2b): According to GP 1, compound 3b (570 mg, 3.56 mmol) was treated with a solution of catecholborane in THF (4 mL, 4 mmol). Twofold Kugelrohr distillation yielded 2b (956 mg, 96%) as a colorless solid.