Pushing the boundaries of BODIPY chemistry: 2-(dimethylamino)methyl BODIPYs as enablers of diversification with nucleophiles

Abstract

The BODIPY family of organic dyes has emerged as a versatile platform in photonic materials science, driven by their outstanding photophysical properties and the synthetic flexibility of BODIPY chemistry. Post-functionalization strategies have been pivotal in expanding BODIPY's application scope. However, current methodologies for rapid diversification with nucleophiles suffer from key limitations, including the use of unstable intermediates, limited substrate scope, and reliance on hazardous or costly reagents. In this work, we introduce 2-(dimethylamino)methyl BODIPYs as novel, stable, and easily accessible electrophilic intermediates that enable efficient BODIPY diversification with a broad range of neutral protic nucleophiles via unimolecular nucleophilic substitution. These intermediates are straightforwardly synthesized from highly common and accesible 2-unsubstituted BODIPYs through electrophilic aromatic substitution using inexpensive Eschenmoser's salt, and can be activated under mild conditions via simple amine quaternization. Importantly, this strategy is compatible with 3,5-dimethylated BODIPYs, preserving access to Knoevenagel-like BODIPY chemistry for large chromophore π-extension towarsds bathochromic shift into the red-to-NIR spectral region. The efficacy of this methodology is demonstrated through the synthesis of a number of BODIPY dyes with diverse substitution patterns and selectable photophysical behavior. Furthermore, we highlight its practical utility through the design of functional BODIPY derivatives, including ICT-based fluorescent pH indicators, fluorogenic acidotropic bioprobes, and water-soluble laser dyes.