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. We disclose an aqueous photoredox-catalyzed method for transforming Ind •+ into C3-substituted tryptophan mimetics that uses water as a transient protecting group to guide site-selective C3 alkylation.