Modular synthesis and application studies of fluorescent quinolizinium compounds

Abstract

Fluorescent material development has been an important research area because of their diverse applications in different fields including photoredox catalysis and molecular imaging. Several widely used organic fluorescent dyes such as fluorescein and BODIPY have been systematically studied for their structure-photophysical property relationship (SPPR). The studies provided essential information for rational design and improvement of the organic fluorescent dyes. Quinolizinium is a key skeleton of natural alkaloids and possesses various applications such as fluorescent dyes and DNA intercalators. However, systematic studies of their structure-photophysical property relationship (SPPR) remain rare. With the recent advances in the modular synthesis of quinolizinium compounds, a diversity of novel quinolizinium derivatives has been synthesized. Using rhodium-catalyzed C-H bond activation and annulation reaction sequence, a library of around 20 new fluorescent quinolizinium derivatives were synthesized from quinolines and internal alkyne substrates with up to 65% isolated yields. The quinoline substrates were synthesized by a three-component coupling reaction of aldehydes, amines and alkynes with KAuCl4/CuBr catalysts. This method provided modular synthesis of quinoline substrates with good functional group tolerance. Reaction of the substituted quinolines and internal alkyne substrates gave quinolizinium derivatives with different electronic properties. By changing the electronic properties through incorporation of electron-donating and electron-withdrawing groups, the absorption and emission properties of the fluorescent quinolizinium derivatives could be tuned. The fluorescent spectroscopy experiments revealed that the absorption maximum of the substituted quinolizinium compounds laid in the UV/Vis light regions with tunable emission properties (λem = 428 nm to 635 nm) and quantum yield up to 0.68. The fluorescent quinolizinium derivatives have been explored in photooxidative cleavage of aromatic alkenes (Blue OLEDs light source; λmax = 468 nm) to give the corresponding ketones up to 80% yield in 4 h at room temperature. Optimization of the reaction conditions including catalyst loading, solvents, and reaction time have been conducted. We are pleased to find that our newly developed fluorescent quinolizinium compounds exhibited comparable catalytic efficiency with the commonly used organic fluorescent dyes. Through collaboration, we have also studied the molecular imaging application of the organic fluorescent dyes. To further develop the synthetic methods, we have merged copper catalysis and visible light photoredox catalysis for the synthesis of the quinolizinium compounds. Aryl diazonium salts and terminal alkynes were employed as the substrates to afford the quinolizinium compounds via cis-difunctionalization of terminal alkynes. Reaction screening such as various copper catalysts, catalyst loading and different terminal alkynes have been performed. The reaction gave quinolizinium compounds up to 65% yield with 30 mol% Cu(MeCN)4BF4 and electron-donation terminal alkynes. Surprisingly, a new cyclometalated copper complex with unprecedented structure confirmed by X-ray crystallography has been discovered. The copper complex was synthesized by reaction of copper powder and aryl diazonium salts under nitrogen and Blue OLEDs for 16 h in 30% yield.