Peptidic macrocyclization via palladium-catalyzed chemoselective indole C-2 arylation.

A highly efficient macrocyclization reaction has been developed via the palladium-catalyzed C-H arylation of the side-chains of tryptophan with halophenyl-containing amino acids. This method allows for direct access to 15- to 25-membered biaryl macrocycles in 40-75% yield, at moderate concentration, with C-H arylation proceeding exclusively at the C-2 position of the tryptophan indole.