Cascade Palladium Catalysis: A Predictable and Selectable Regiocontrolled Synthesis of N-Arylbenzimidazoles

Reaction Scheme

Abstract

A wide-ranging study�of Suzuki reactions which use nitrogen-containing heterocycles is described (see scheme). This method is highly versatile (a single procedure was used for all substrates, including boronate esters and trifluoroborates), compatible with a variety of unprotected functionalities (e.g., NH2- and OH-substituted substrates), and efficient even with unactivated aryl chlorides.

Substrates

Procedure

In the air, the heteroarylboronic acid (1.10 mmol), Pd2(dba)3 (9.2 mg, 0.010 mmol), and PCy3 (6.7 mg, 0.024 mmol) are added to a 25-mL Schlenk flask equipped with a stir bar. The flask is evacuated and refilled with argon five times. Dioxane (2.67 mL), the (hetero)aryl halide (1.00 mmol; if the halide is a solid, then it is added prior to the evacuation-refill cycle), and aqueous K3PO4 (1.27 M, 1.33 mL, 1.70 mmol) are added by syringe. The Schlenk flask is sealed and heated in an oil bath at 100 �C for 18 hours with vigorous stirring. The mixture is then filtered through a pad of silica gel (EtOAc washings). Next, the filtrate is concentrated under reduced pressure, and the aqueous residue is extracted three times with EtOAc. The combined extracts are dried over anhydrous MgSO4, filtered, and concentrated. The residue is then purified by column chromatography on silica gel.

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Materials

     
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