The Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides

Reaction Scheme

Abstract

A series of N-heterocyclic carbene catalysts (see picture) were prepared and evaluated in the Suzuki-Miyaura reaction. A variety of sterically encumbered tetra-ortho-substituted biaryl products were formed from unreactive aryl chlorides using the isopentyl-substituted catalyst at temperatures ranging from 65?�C to room temperature. The cyclopentyl-substituted catalyst was virtually inactive, demonstrating that �flexible bulk� is essential to promote these transformations.

Substrates

Procedure

In air, a vial (2 mL screw-cap threaded) equipped with a stir-bar was charged with complex PEPPSI-iPent (4 mg) (2 mol %), boronic acid (0.5 mmol), potassium hydroxide (42 mg, 0.75 mmol), and if solid at room temperature, the organohalide (0.25 mmol) was added. The vial was sealed with a Teflon�-lined screw cap and purged with argon (3X). Alternatively, if the organohalide was a liquid at room temperature, it was added via syringe right after the argon purge. Dioxane (1.0 mL) was then added via syringe and the reaction was stirred at 65 �C for the indicated period of time after which it was diluted with diethyl ether (2 mL) and filtered through a plug of celite. The reaction vial and celite pad were rinsed with additional diethyl ether (10 mL) and the organic layers combined. The contents were concentrated under reduced vacuum and the residue purified by flash chromatography

Products

Materials

     
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