Catalytic Direct Arylation with Aryl Chlorides, Bromides, and Iodides:  Intramolecular Studies Leading to New Intermolecular Reactions

A catalyst for the intramolecular direct arylation of a broad range of simple and heterocyclic arenes with aryl iodides, bromides, and chlorides has been developed. These reactions occur in excellent yield and are highly selective. Studies with aryl iodides substrates revealed that catalyst poisoning occurs due to the accumulation of iodide in the reaction media. This can be overcome by the addition of silver salts which also permits these reactions to occur at lower temperature. The utility of the methodology is illustrated by a rapid synthesis of a carbazole natural product and by the synthesis of sterically encumbered tetra-ortho-substituted biaryls via ring-opening reactions of the direct arylation products. Mechanistic investigations have provided insight into the catalyst's mode of action and show the presence of a kinetically significant C−H bond cleavage in palladium-catalyzed direct arylation of simple arenes. Knowledge garnered from these studies has led to the development of new intermolecular arylation reactions with previously inaccessible arenes, opening the door for the development of other new direct arylation processes.