Seleno-functionalization of BODIPY fluorophores assisted by Oxidative Nucleophilic Hydrogen Substitution

Abstract

Most current reported methods of chalcogen insertion into BODIPY’s nuclei are based on nucleophilic substitution reactions of halogenated derivatives, metal-catalyzed cross-coupling reactions, or assisted by radical mechanisms. Recent reports describe Oxidative Nucleophilic Hydrogen Substitution (ONHS) reactions involving the functionalization of BODIPY nuclei by thiols, but the generalities of the strategy for other chalcogens was not yet demonstrated. Herein we report our contribution on the selenium-functionalization of BODIPY by ONHS, in high yield. Aryl-Se-functionalization of 2,6-brominated BODIPY’s nuclei by ONHS reaction. The procedure consists of a direct reaction of 2,6-brominated BODIPYs with in situ generated PhSeH in THF, at room temperature, under a nitrogen atmosphere. The corresponding products were isolated and purified by conventional flash column chromatography. Full structure characterization was performed by 1H, 13C, 19F, and 77Se NMR and DFT calculation. Densely functionalized 2,6-dibrominated/3,5-diseleno-BODIPYs were obtained, as products, leading to versatile molecular scaffolds, considering their structural features, contrary to initially expected, by the original experimental applied conditions. A mechanistic investigation was performed to conclude that ONHS reaction is governing the transformation to the detriment of nucleophilic substitution of the halogen atoms. To sum up, new densely functionalized BODIPY derivatives were synthesized by a highly selective, simple, fast, metal-free, and efficient insertion of PhSe- residues into the 3,5-positions, governed by an Oxidative Nucleophilic Hydrogen Substitution (ONHS) reaction, in high yields. It was observed that the presence of halogen (Br) into the 2,6-positions of the BODIPY core is mandatory to the ONHS reaction, which is completely inert when the 2,6-hydrogenated analogues are submitted to the same experimental conditions.