Synthesis of 3,5-dichloro-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) via Cu(OTf)(2) mediated oxidative nucleophilic substitution of hydrogen by chloride

Frank, Felicity; Alice, Laura Manzoli; Mauker, Philipp; Alsimaree, Abdulrahman A.; Waddell, Paul Gordon; Probert, Michael Richard; Penfold, Thomas James; Knight, Julian Gary und Hall, Michael John (2020): Synthesis of 3,5-dichloro-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) via Cu(OTf)(2) mediated oxidative nucleophilic substitution of hydrogen by chloride. In: Tetrahedron, Vol. 76, No. 17, 131113

Abstract

Regioselective halogenation is often a key step in the formation of substituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores, through the enablement of subsequent downstream C-C or C-X bond forming steps via SNAr or metal catalyzed cross-coupling reactions. Classical SEAr halogenation of unsubstituted BODIPYs results in 2/6-substitution, precluding easy access to 3/5-halogenated BODIPYs. Herein we present our development of a 3,5-dihalogenation reaction of unsubstituted BODIPYs, via a double oxidative nucleophilic substitution of hydrogen with chloride. Reaction of a range of meso-aryl, but otherwise unsubstituted, BODIPYs with stoichiometric Cu(OTf)(2) in the presence of ethanolamine and tetrabutylammonium chloride gives high isolated yields of the corresponding 3,5-dichlorinated BODIPYs, facilitating access to these valuable synthetic intermediates. (C) 2020 Elsevier Ltd. All rights reserved.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Chemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 0040-4020
• Language: English