Skeletal Modification of Tryptophan Using Cyclic Diaryliodonium Salts via Palladium-Catalyzed Cascade π-Extended Annulative Dual C2–H/N–H Arylation

Abstract

Abstract We have demonstrated an efficient Pd-catalyzed annulative dual C2–H/N–H arylation reaction involving modification of the tryptophan indole skeleton to phenanthridinyl indole. This is an operationally simple and ligand-free strategy that was extended to biologically important indole derivatives and tryptophan-containing short peptides to deliver a diverse unnatural phenanthridinyl indole-tethered peptide with good efficiency. Notably, the method demonstrated good tolerance for N- and C-terminal protecting groups as well as for the side-chain functionalities of other amino acids.