Marissa Y A Nalenan, Paul G Waddell, Michael J Hall
Iodinated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) are valuable synthetic intermediates for the formation of functionalised fluorophores, as they enable downstream nucleophilic aromatic substitution (SNAr) and metal-catalysed cross-coupling reactions. However, there are limited synthetic routes available for the synthesis of such iodinated BODIPYs, particularly for the selective introduction of iodine at the 1,3,5 and 7-positions. Herein, we present an improved route to iodinated BODIPYs, based on an aromatic Finkelstein reaction, in which bromo-substituted BODIPYs are transformed into their corresponding iodo-analogues. Our optimised reaction conditions, excess NaI in refluxing acetone for 1.5 hours, allowed for the formation of 3,5-diiodo-8-aryl-BODIPYs in high yields (90-95%). Furthermore, we show that the aromatic Finkelstein reactions of bromo-substituted BODIPYs with NaI show high regioselectivity for the 1,3,5 and 7-positions, with the 2,6-positions being unreactive, across a range of substrates. This allows for the efficient formation of both mono-iodo and mixed bromo/iodo-substituted BODIPYs, through the preferential substitution of bromines at the 1,3,5 and 7-positions. We anticipate that this operationally simple, high yielding and highly regioselective pathway for the synthesis of iodo-BODIPYs will be impactful in the further development of functionalised BODIPY platforms.