Photochemical Ligand-Free Palladium-Catalyzed Coupling of N-Tosylhydrazones with Indoles Enables Late-Stage Tryptophan and Peptide Functionalization

<jats:p>We developed herein a novel photochemical strategy for the construction of N-vinylindoles derivatives. This approach consisted of a ligand-free palladium-catalyzed coupling between Ntosylhydrazones and indoles, mediated by visible-light activation. This method allowed access to diversely substituted indoles (28 examples) in moderate to high yields. The robustness of the methodology was validated in a gram-scale reaction, and by using challenging peptides as substrates. This approach thus afforded seven peptide derivatives in good yield (up to 80%). Mechanistic insights demonstrated that the key reaction steps involve photoactivation of the Pd0 catalyst to its excited state Pd0* along with the formation of the diazo species driven by the light irradiation.</jats:p>