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

Abstract

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.

Keywords: DNA; amino acids; decarboxylative coupling; photoredox catalysis; radical reactions.