Copper-Photoredox-Catalyzed\nDivergent Strategy for\nthe Site-Selective Arylation and Alkylation of Glycines and Peptides

There is a scarcity of general strategies\nfor the site-selective\nα–Csp<sup>3</sup>–H arylation of glycine derivatives\nto synthesize nonproteinogenic α-arylglycines that occur frequently\nin commercial drugs and bioactive molecules. We disclose a copper-photoredox-catalyzed\nsite-selective α–Csp<sup>3</sup>–H arylation of\nglycine derivatives using diaryliodonium reagents (DAIRs) as arylating\nagents. This strategy harnesses the underexplored ability of DAIRs\nto serve as arylating agents under visible-light irradiation using\ncopper salts as photocatalysts. The method applies to the glycine-selective\nC–H arylation of peptides with electronically and structurally\ndiverse DAIRs. Moreover, we demonstrate that the photoinduced copper-catalyzed\nsingle electron transfer (SET) strategy can be coupled with the halogen\natom transfer (XAT) process in the presence of alkyl iodides to accomplish\nsite-selective α–Csp<sup>3</sup>–H alkylation\nof glycines and peptides. In this synergistic SET/XAT approach, phenyl\nradicals generated from diphenyl iodonium triflate mediate the XAT\nprocess to generate alkyl radicals from alkyl iodides. Both of these\nmethods operate under mild conditions and exhibit broad scope with\nappreciable functional group tolerance. Overall, the divergent toolbox\nstrategies presented here facilitate access to various alkylated and\narylated glycines and peptides and enable bioconjugation between peptides\nand drug molecules.