Aromatic Iodides: Synthesis and Conversion to Heterocycles

Aromatic heterocycles can be found in many molecules endowed with specific properties, in particular for applications in the fields of medicinal chemistry and materials. In the group, we notably develop synthetic methodologies to selectively introduce iodine onto aromatic compounds and to use this heavy halogen in order to build heterocycles of interest. While we sometimes employed direct iodinations on electron-enriched aromatic compounds, we mainly optimized deprotometallation-iodolysis sequences to functionalize substrates sensitive to nucleophilic attacks. In particular, hindered lithium amide-metal trap tandems have been designed to overcome the low tolerance of some functional groups (e.g. ketones or sensitive diazines) toward organolithiums. The aromatic iodides generated these ways have been involved in transition metal-catalyzed cross-couplings to access original scaffolds (oxazoloquinoxalines, pyrazinoisatins, pyrazinocarbazoles, benzo(thio)pyranoquinazolines...). We especially developed the use of aromatic iodides in copper-mediated N-arylation of anilines, e.g. to reach triarylamines. Combined with subsequent cyclizations, these reactions allowed an access to numerous heterocyclic compounds (such as acridones, acridines, other aza-aromatic polycycles and helicene-like structures) with potential applications. From some of the scaffolds obtained, biological evaluation in the frame of collaborations allowed properties of interest to be discovered (e.g. specific inhibition of protein kinases GSK-3 or PIM, related to cancer development).