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

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 an unprecedented example of C-H arylation of an internal residue. Removal of the amidoxime ether was achieved to generate the parent amide and facilitate a traceless C-H functionalization process.