Research has found that for certain iodides, some phosphine-free ligand catalysts can efficiently catalyze reactions under milder conditions, such as PdCl2, Pd(OAc)2, Pd/C, etc. At the same time, it can also avoid the impurities formed by ligands during the reaction that complicate the product separation process.
Hiroa【Sakurai, H. J. Org. Chem. 2002, 67, 2721】 and others used water as a solvent at room temperature to catalyze the coupling reaction of iodobenzenes and arylboronic acids with Pd/C, achieving very good results. This method is significant for large-scale production due to its claim of clean production.
D. S. Ennis【D. S. Ennis, Org. Process Res. Dev.1999, 3,248】 and others used Pd/C as a catalyst to carry out large-scale Suzuki-coupling reactions for the production of the antidepressant drug, SB-245570.
Directly using Pd(OAc)2 for the Suzuki coupling reaction【Felix E. Goodson, Organic syntheses, Coll. Vol. 10, p.501; Vol.75,p.61】
4-Methoxy-2′-methylbiphenyl . o-Tolylboronic acid,10.0 g(73.6 mmol),16.8 g(71.8 mmol) of 4-iodoanisole, and 200 mL of acetone are combined in a 1-L, three-necked flask equipped with an efficient stir bar, two stoppers, and a reflux condenser attached to a gas-flow adapter with a stopcock. Potassium carbonate,25.0 g(0.180 mol), is dissolved in 200 mL of water in a separate 250-mL Schlenk flask. In a third flask (25-mL Schlenk flask) 3.30 mg (0.02 mmol, 0.2%) of palladium acetate is dissolved in 10 mL of acetone. All three flasks are then thoroughly degassed by four freeze-pump-thaw cycles. Under an argon backflow, one of the stoppers on the three-necked flask is replaced with a rubber septum, and the carbonate and catalyst solutions are added via cannula to form a biphasic mixture. The top layer turns brown upon the addition of the catalyst. The septum is replaced with the glass stopper and three additional freeze-pump-thaw cycles are applied. The flask is then backfilled with argon, and the reaction is brought to reflux under a positive argon pressure. After 2 hr at reflux the heat source is removed and the reaction is allowed to cool. By this time the brown color has faded and the reaction is a triphasic mixture with copious amounts of palladium black floating between the layers. The reaction is transferred to a 1-L separatory funnel and extracted into diethyl ether(3 × 100 mL). The organic layers are combined, washed with water (1 × 100 mL) saturated with sodium chloride, and dried over magnesium sulfate. Solvent is removed with a rotary evaporator to yield a yellow oil which is distilled (125-130°C,0.10 mm) to give12.8 g of 4-methoxy-2′-methylbiphenyl as a colorless oil (90.3% yield).
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