A Bulky Biaryl Phosphine Ligand Allows for Palladium-Catalyzed Amidation of Five-Membered Heterocycles as Electrophiles

Reaction Scheme

Abstract

The palladium-catalyzed cascade reaction of 2-chloroaryl sulfonates with arylamine and amide nucleophiles provides direct access to�N-arylbenzimidazoles. This strategy selectively produces the heterocycles based on chemoselective oxidative addition. 2-Chloroaryl triflates (Tf) produce one regioisomer and the corresponding 2-chloroaryl mesylates (Ms) deliver the other in a selectable manner.

Substrates

Procedure

An oven-dried test tube equipped with a magnetic stir bar and a Teflon screw-cap was charged with tBuBrettPhos-Pd-G3 (2�5 mol%, as indicated), arylamine (1.0 mmol, if solid), amide (1.3 mmol, if solid), 2-chloroaryl triflate or 2-chloroaryl bromide (1.0 mmol, if solid), and Cs2CO3 (2.4 mmol). The tube was evacuated and backfilled with nitrogen using standard Schlenk techniques and this process was conducted three times. The arylamine (1.0 mmol, if liquid), amide (1.3 mmol, if liquid) and 2- chloroaryl triflate or 2-chloroaryl bromide (1.0 mmol, if liquid) were added followed by t-BuOH (1.5 mL) via syringe and the punctured cap was replaced with a new one under a stream of nitrogen. The test tube was placed in a preheated oil bath at 110 �C and stirred for the indicated time. After cooling to room temperature, the mixture was diluted (3 mL CH2Cl2), filtered through Celite (CH2Cl2 rinse), and concentrated using a rotary evaporator. The residue was purified by silica gel chromatography using a Biotage Isolera 4 or by neutral alumina column chromatography to provide the title compound.

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Materials

     
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