Visible-light-induced nickel-catalyzed selective S-arylation of peptides by exogenous-photosensitizer-free photocatalysis

Abstract

Visible light photoredox catalysis serves as a toolbox for the site-specific modification of peptides and biomolecules in synthetic design and chemical biology. Here, we report a visible-light-induced nickel (Ni)(II) complex-catalyzed strategy for cysteine residue arylation modification under mild conditions. This method relies on exploiting the in-situ-formed Ni(II)-cysteine (Cys) complex, which absorbs the photonic energy and transforms to initiate single-electron transfer and provide a pathway for the subsequent radical transformations. A wide range of arylated Cys-containing dipeptides or tripeptides can be obtained in moderate to excellent yields without the need for exogenous photocatalysts. Moreover, the efficient S-arylation protocols presented in this work broaden the synthetic scope of Cys bioconjugation and serve as promising routes for the selective modification of complex biomolecules.