Photoredox/Brønsted Acid Co-Catalysis Enabling Decarboxylative Coupling of Amino Acid and Peptide Redox-Active Esters with N‑Heteroarenes

Abstract

An iridium photoredox catalyst in combination with a phosphoric acid catalyzes the decarboxylative α-aminoalkylation of natural and unnatural α-amino acid-derived redox-active esters (<i>N</i>-hydroxyphthalimide esters) with a broad substrate scope of N-heteroarenes at room temperature under irradiation. Dipeptide- and tripeptide-derived redox-active esters are also amenable substrates to achieve decarboxylative insertion of a N-heterocycle at the C-terminal of peptides, yielding molecules that have potential medicinal applications. The key factors for the success of this reaction are the following: use of a photoredox catalyst of suitable redox potential to controllably generate α-aminoalkyl radicals, without overoxidation, and an acid cocatalyst to increase the electron deficiency of N-heteroarenes