Aqueous Flavin Photoredox Catalysis Drives Exclusive C3-Alkylation of Indolyl Radical Cations in Route to Unnatural Tryptophan Mimetics.

One way to build chemical diversity into indoles is to oxidize them to indolyl radical cations (Ind). These intermediates can accept new functional groups across C2-C3 bonds or independently at C2. Less encountered is selective diversification at C3, a position plagued by competing dearomative side reactions.

Flavin Metallaphotoredox Catalysis: Synergistic Synthesis in Water.

Combining a transition metal with a photocatalyst can drive modern synthetic chemistry. For transformations performed in water, this concept has been largely unexplored. We report the successful merger of a biocompatible flavin photocatalyst with a palladium catalyst to build isotopically enriched peptidomimetics, to mediate conjugate addition and functionalization reactions, and to assemble unprotected proteinogenic and nonproteinogenic peptides, in water.