Synthesis of Functional Fluorescent BODIPY‐based Dyes through Electrophilic Aromatic Substitution: Straightforward Approach towards Customized Fluorescent Probes

Abstract

Fluorescent materials are widely used in biological and material applications as probes for imaging or sensing; however, their customization is usually complicated without the support of an organic chemistry laboratory. Here, we present a straightforward method for the customization of BODIPY cores, which are among the most commonly used fluorescent probes. The method is based on the formation of a new C−C bond through Friedel–Crafts electrophilic aromatic substitution carried out at room temperature. The method presented can be used to obtain completely customized fluorescent materials in one or two steps from commercially available compounds. Examples of the preparation of fluorescent materials for cell staining and functionalization of silica colloids are also presented.

Synthesis of BODIPY dyes through postfunctionalization of the boron dipyrromethene core

“…OEt2 as the Lewis acid is the latest reported SEAr postfunctionalization of the boron dipyrrin framework. 228 As found for other SEAr reactions (nitration, formylation, sulfonation, halogenation: see above), the electrophilic Friedel-Crafts acylation took place at the 2-position because this is the most nucleophilic site (together with the 6-position, of course (Scheme 66), as is the case with many electron-deficient aromatic systems. Direct conversion of such  H -adducts into products of nucleophilic substitution of hydrogen through spontaneous departure of the hydride anion does not occur because the hydride anion is a poor leaving group due to its very low stability.…”

Mixed Metal-Organic Dyes With Dual Electrophores: Designing More Robust Dyes for Light-Harvesting Applications

“…A boron source is then introduced for the amines to chelate to the nitrogen atoms of the dipyrrin. 71 Despite using one equivalent of NIS to iodinate BODIPY, a di-iodo BODIPY derivative is still produced. The synthesis of 4.28 was done through a Sonogashira cross-coupling reaction with TMS-acetylene using a modified procedure from Lin et al 72 Compound 4.28 with the TMS group was used as a reference due to the unstable nature of the deprotected derivative of 4.28.…”

Transition-Metal-Catalyzed C–H Activation Reactions for the Creation and Modification of Organic Fluorophores

“…Traditional cycloaddition reactions, electrocyclic ring closure reactions, palladiumcatalyzed cross-coupling reactions and more recently, C−H functionalization reactions have been employed to create organic fluorescent molecules with enhanced properties. [15][16][17][18][19][20][21] While existing literature contains certain reviews focusing on the synthesis of organic fluorophores, [20][21][22] our approach involves a comprehensive categorization of all pertinent recent C−H activation reactions to achieve and modify organic fluorophores. This will be followed by a concise assessment of the merits and drawbacks of previously established techniques.…”