Aromatic Finkelstein reactions for iodinated-BODIPYs

Iodinated boron-chelated dipyrromethenes (BODIPYs) are excellent synthetic intermediates for further functionalisation, allowing nucleophilic aromatic substitution (S_NAr) and metal-catalysed cross-coupling reactions. However, the synthesis of iodinated BODIPYs is challenging.

The aromatic Finkelstein reaction, also known as the HalEx reaction, has recently been reported for the preparation of 3,5-diiodo-8-aryl-BODIPYs from the corresponding 3,5-dibromo-8-aryl-BODIPYs. However, the published conditions involve high temperatures and extended reaction times, and are not suitable for the synthesis of BODIPYs with complex halogenation patterns.

In this work, we present our studies on improving the synthesis of 3,5-diiodo-8-aryl-BODIPYs using aromatic Finkelstein reactions. We show that our optimised reaction conditions give access to 3,5-diiodo-8-aryl-BODIPYs in high yields, and just 1.5 hours in acetone, with a range of meso-aryl substituents.

Moreover, we have examined the regiochemistry of the aromatic Finkelstein reaction using multi-brominated BODIPY starting materials. Interestingly, we have shown that 2,6-dibromo-BODIPY is unreactive to S_NAr reactions with NaI, even after extended reaction times. Whilst the Finkelstein reaction of 2,3,5,6-tetrabromo-BODIPY gave 2,6-dibromo-3,5-diiodo-BODIPY as the product, and similarly 2,3,5-tribromo-BODIPY underwent a high yielding Finkelstein reaction to give 2-bromo-3,5-diiodo-BODIPY.

Finally, we show that a 1,2,3,5,6,7-hexabromo-BODIPY can undergo Finkelstein chemistry to selectively give 2,6-dibromo-1,3,5,7-tetraiodo-BODIPY in quantitative yield, showing that both the 3,5- and 1,7- positions are available for S_NAr chemistry of this nature.

With new methods to prepare complex polyhalogenated BODIPYs in hand, future work will focus on exploring their S_NAr and cross-coupling reaction chemistry.