Catalysis

Organic chemistry

Chemistry

Combinatorial chemistry

Bioconjugation

Carboxylic acid

Peptide

Alkynylation

Reagent

Amino acid

Biochemistry

Hypervalent molecule

Angewandte Chemie International Edition

We report the first decarboxylative alkynylation of the C‐terminus of peptides starting from free carboxylic acids. The reaction is fast, metal‐free, and proceeds cleanly to afford alkynylated peptides with a broad tolerance for the C‐terminal amino acid. By the use of hypervalent iodine reagents, the introduction of a broad range of functional groups was successful. C‐terminal selectivity was achieved by differentiation of the oxidation potentials of the carboxylic acids based on the use of fine‐tuned organic dyes.

C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation