Murarka, Sandip

There is a scarcity of general strategies for the site-selective α-Csp3-H arylation of glycine derivatives to synthesize nonproteinogenic α-arylglycines that occur frequently in commercial drugs and bioactive molecules. We disclose a copper-photoredox-catalyzed site-selective α-Csp3-H arylation of glycine derivatives using diaryliodonium reagents (DAIRs) as arylating agents. This strategy harnesses the underexplored ability of DAIRs to serve as arylating agents under visible-light irradiation using copper salts as photocatalysts. The method applies to the glycine-selective C-H arylation of peptides with electronically and structurally diverse DAIRs. Moreover, we demonstrate that the photoinduced copper-catalyzed single electron transfer (SET) strategy can be coupled with the halogen atom transfer (XAT) process in the presence of alkyl iodides to accomplish site-selective α-Csp3-H alkylation of glycines and peptides. In this synergistic SET/XAT approach, phenyl radicals generated from diphenyl iodonium triflate mediate the XAT process to generate alkyl radicals from alkyl iodides. Both of these methods operate under mild conditions and exhibit broad scope with appreciable functional group tolerance. Overall, the divergent toolbox strategies presented here facilitate access to various alkylated and arylated glycines and peptides and enable bioconjugation between peptides and drug molecules.

Diaryliodonium reagents (DAIRs) are highly electrophilic arylating agents widely utilized in organic synthesis, excelling in both metal-free and metal-catalyzed transformations. However, their reactivity and application as aryl radical precursors under visible-light irradiation remain relatively underexplored. Due to their easy availability, intrinsic reactivity, stability, and environmentally benign nature, they are promising candidates to serve as aryl radical surrogates in various visible light-induced synthetic transformations. In this feature article, we have reviewed our recent findings alongside other significant reports on the utility of DAIRs under visible-light irradiation. We have discussed the diverse reactivity of DAIRs in a palette of visible light-mediated reactions leading to the construction of carbon-carbon or carbon-heteroatom bonds. In addition, their role as atom transfer agents, including hydrogen atom transfer and halogen atom transfer, has also been discussed. © 2025 Elsevier B.V., All rights reserved.

We disclose a photoredox-catalyzed arylative radical cascade between N′-arylidene-N-acryloylhydrazides and diaryliodonium reagents to obtain the corresponding benzylated pyrazolones in good yields. The protocol was extended to three-component coupling involving the 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) adduct as a sulfur dioxide surrogate for the synthesis of arylsulfonylated pyrazolones. Both reactions exhibit broad scope, scalability, and high functional group tolerance.