Chemoselective Peptide Backbone Diversification and Bioorthogonal Ligation by Ruthenium‐Catalyzed C−H Activation/Annulation

The field of peptide derivatization by metal-catalyzed C−H activation has been mostly directed to modify the side chains, but poor attention given backbone. Here we report a ruthenium-catalyzed activation/annulation process that can chemoselectively backbone producing functionalized isoquinolone scaffolds with high regioselectivity in rapid and step-economical manner. This strategy is characterized racemization-free conditions production fluorescent peptides, conjugates drugs, natural products other fragments, providing chemical approach for construction novel peptide-pharmacophore conjugates. Mechanistic studies suggest amide bonds act as bidentate directing group promote process. provides an unprecedented example diversification bioorthogonal ligation exploiting power activation.