Late-Stage Pd(II)-Catalyzed C(sp³)-H Functionalization of Peptides Directed by a Removable, Backbone-Inserted...

Palladium(II)-catalyzed C-H functionalization has attracted considerable attention as a pathway to late-stage modification of peptides. Herein, we report the Pd-catalyzed C(sp³)-H arylation of peptides directed by an amidoxime ether, which can be easily incorporated into peptides at any amide bond. Site- and stereoselective arylation of peptides has been achieved, including unprecedented functionalization of internal residues of native peptides. Removal of the amidoxime ether was achieved to generate the parent amide and facilitate a traceless C-H functionalization process.