Late‐stage functionalisation is an attractive method to generate peptide analogues containing non‐natural residues. It is shown that cysteine residues can be activated as Crich‐type thioethers, either by alkylation of a synthetic cysteine‐continuing peptide or by incorporation of a modified cysteine unit into solid phase or solution phase peptide synthesis. Photoredox catalysed reaction of the thioether generates an alanyl radical intermediate in a stereoretentive and site‐selective manner, even in the presence of free cysteine residues. The radical can react with non‐activated alkenes to form non‐natural residues bearing aliphatic, hydrophobic units. A method to avoid unwanted alkylation of amine residues was identified and the process was applied to the functionalization of both linear and cyclic synthetic peptides.
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