Targeting the C-terminal position of peptides is of high interest, both for designing novel scaffold for drug discovery and for further applications in protein labelling. Due to the selectivity challenge between carboxylic acids on the side-chains and this position, efficient methods are still very rare. As the extension of the decarboxylative alkynylation on amino acids developed previously in our group,^[1] we report herein a decarboxylative alkynylation on peptides C-terminal position.^[2]  Using photoredox catalysis and hypervalent iodine EBX reagents, functionalized peptides are obtained in 30 min. Novel organic dyes were designed to enable high selectivity. Various functional groups were tolerated, both on peptides and EBX reagents, leading to the introduction of diverse functionalities on native peptides up to hexamers. Our efforts now target larger peptides and proteins, with the development of conditions in aqueous media.

[1]     F. Le Vaillant, T. Courant, J. Waser, Angew. Chem. Int. Ed. 2015, 54, 11200–11204.
[2]     M. Garreau, F. Le Vaillant, J. Waser, Angew. Chem. Int. Ed. 2019, DOI: 10.1002/anie.201901922.