Synthesis of Cysteine–Fluorophore Conjugates by Visible‐Light‐Promoted Thiol–Ene Coupling Using Organic Photocatalysts

In this work, we have investigated the visible‐light‐mediated thiol–ene coupling of N ‐acetyl‐L‐cysteine methyl ester with structurally distinct alkene‐functionalized fluorophores using metal‐free organic photocatalysts under mild conditions. The fluorophore set comprised naphthalene, naphthalimide, and aromatic diimide derivatives featuring different alkene environments and linker architectures. The transformations were promoted under mild and metal‐free conditions using five organic photocatalysts belonging to three distinct structural families, namely acridinium salts, BOPHY derivatives, and xanthene dyes. The methodology proved to be compatible with structurally diverse fluorophore architectures and enabled the efficient preparation of both mono‐ and bis‐functionalized cysteine conjugates. Reaction efficiency was influenced by fluorophore structure and photocatalyst identity, with yields reaching up to 95% for styrenyl naphthalimide derivatives. Sequential thiol–ene additions were successfully achieved for divinyl fluorophores, providing access to doubly functionalized products under the same reaction conditions. Photophysical studies demonstrated that cysteine incorporation generally preserves the absorption and emission characteristics of the parent fluorophores and, in several cases, leads to enhanced fluorescence quantum yields. These results establish visible‐light‐mediated thiol–ene coupling as a straightforward and versatile approach for the preparation of fluorescent cysteine building blocks from structurally diverse fluorophore scaffolds.