A Photoredox Thiol-yne Reaction for the Synthesis of Vinyl Sulfide-Based Coumarins and its Effect on Fluorescence Properties.

Abstract

Coumarins still remain one of the most widely explored fluorescent dyes, with a broad spectrum of applications spanning various fields, such as molecular imaging, bioorganic chemistry, materials chemistry, or medical sciences. Their fluorescence is strongly based on a push-pull mechanism involving an electron-donating group (EDG), mainly located at the C7 or C8 positions of the dye core. Unfortunately, up to now, these positions have been very limited to hydroxyl or amino groups. In this study, we present in detail the synthesis of the first series of coumarins bearing a vinyl sulfide as the EDG at the C7 position. These derivatives were prepared by thiol-yne reaction, promoted by ruthenium- or porphyrin-based photoredox catalysis, enabling rapid late-stage diversification. We also functionalized coumarins with short peptides, and BSA protein as a proof-of-concept study, in a single-step process. This strategy, capable of proceeding under aqueous conditions, overcomes the protection/deprotection steps usually required by traditional methods, which also use strong bases and organic solvents. Moreover, the photophysical properties such as absorption and emission of obtained coumarins (for 3-CF3, 3-benzothiazole, 6-8-difluoro derivatives), predominantly exhibited large Stokes shifts (up to 204 nm) and maintained intramolecular charge transfer (ICT) characteristics.