Divergent synthesis of 5′,7′-difluorinated dihydroxanthene-hemicyanine fused near-infrared fluorophores

Abstract

We describe an expedient access to a 5′,6′,7′-trifluoro dihydroxanthene-hemicyanine fused scaffold in 2 steps and 54% overall yield from the corresponding salicylic aldehyde. A 6′-regioselective nucleophilic aromatic substitution (S_NAr) reaction with a wide range of nitrogen, sulfur or selenium nucleophiles then gives access to 16 near-infrared (NIR) fluorophores emitting in the 710–750 nm range. We also report the experimental and theoretical photophysical investigations of these unique optical agents that include the first series of 6′-heavy atom substituted dihydroxanthenes, extending the pool of polyfluorinated markers for biomedical and material applications.