Palladium-Catalyzed Hydroxylation of Aryl and Heteroaryl Halides Enabled by the Use of a Palladacycle Precatalyst

Reaction Scheme

Abstract

A method for the hydroxylation of aryl and heteroaryl halides, promoted by a catalyst based on a biarylphosphine ligand tBuBrettPhos (L5) and its corresponding palladium precatalyst (1), is described. The reactions allow the cross-coupling of both potassium and cesium hydroxides with (hetero)aryl halides to afford a variety of phenols and hydroxylated heteroarenes in high to excellent yield.

Substrates

Procedure

An oven-dried 20 mL resealable screw-cap test tube equipped with a Teflon-coated magnetic stir bar was charged with tBuBrettPhos (9.7 mg, 0.020 mmol, 2 mol %), KOH (168.3 mg, 3.0 mmol, 3 equiv), and (hetero)aryl halide (if solid) (1.0 mmol, 1 equiv). Tube A was evacuated and backfilled with argon (this process was repeated a total of three times), and degassed deionized water (0.36 mL, 20.0 mmol, 20 equiv) and (hetero)aryl halide (if liquid) (1.0 mmol, 1 equiv) were then added into tube A via syringe. A second oven-dried 10 mL resealable screw-cap test tube (B) equipped with a Teflon- coated magnetic stir bar was charged with tBuBrettPhos-Pd-G3 (17.1 mg, 0.020 mmol, 2 mol %). Tube B was then evacuated and backfilled with argon (this process was repeated a total of three times), and 1,4-dioxane (2.0 mL) was added into tube B via syringe. The reaction mixture in tube B was stirred at rt for homogeneous solution. The precatalyst solution from tube B was transferred into tube A via syringe. The resulting reaction mixture in tube A was stirred at 80 �C in an oil bath for 18 h. After cooling to rt, the crude product was diluted with EtOAc (5 mL) and then acidified with aqueous HCl solution (1 M, 5 mL). The resulting reaction mixture in the capped test tube was agitated until all of the solid was dissolved. The reaction mixture was transferred into a separatory funnel and then neutralized with saturated NaHCO3 solution (5 mL). The organic fraction was isolated, and the aqueous fraction was rinsed with EtOAc concentrated in vacuo. The crude product residue was purified by flash chromatography.

Products

Materials

     
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