Employing Photoredox Catalysis for DNA‐Encoded Chemistry: Decarboxylative Alkylation of α‐Amino Acids

A new procedure for the photoredox‐mediated conjugate addition of radicals that can be conveniently generated from α‐amino acids to DNA‐tagged Michael acceptors and styrenes is presented. This C(sp3)−C(sp3) coupling tolerates a broad array of structurally diverse radical precursors, including all of the 20 proteinogenic amino acids. Importantly, this reaction proceeds under mild conditions and in DNA‐compatible aqueous media. Furthermore, the presented reaction conditions are compatible with DNA, making this reaction platform well suited for the construction of DNA‐encoded libraries. The scope and limitations of the chemistry are discussed herein along with proposals for how this methodology might be used to construct DNA‐encoded libraries.