Substrate Design and Synthesis for Coumarin-based Smiles Rearrangement

Fluorophores are compounds that absorb and re-emit light that have important roles in subjects such as environmental testing, biological imaging, and forensics. Commercially available fluorophores generally contain a hydroxyl group in conjugation with the chromophore. Although these hydroxyfluorophores benefit from being affordable, they suffer from pH sensitivity, poor photostability and undesirable emission wavelengths. Conversion of the hydroxyl group to an amino- group can ameliorate these hindrances. The traditional approach for synthesizing aminofluorophores utilizes the Buchwald-Hartwig coupling, which employs expensive and environmentally deleterious reagents. Our work seeks to circumvent the inadequacies of this approach by creating a straightforward and efficient method for the synthesis of amino-conjugated fluorophores via an alkylation-Smiles-amide hydrolysis sequence. We have expanded our substrate scope for the coumarin class of fluorophores by synthesizing novel linkers with varying substitution off the amide. Additionally, we have alkylated coumarins varying in location of the hydroxyl group and substitution off the coumarin. A diverse substrate scope is imperative to the study of the Smiles rearrangement due to the steric and electronic effects of the substituents that can have a substantial impact on the reaction