N-HetAryl-Iminoiodanes: new Nitrene precursors for novel Organic Fluorophores – HINOF

Iminoiodinanes are usually obtained from iodosobenzene diacetate with an eligible sulfonamide under basic conditions. Although those species are stable at room temperature, their isolation nevertheless remains delicate and has prompted many researchers to develop their in situ formation for one-pot synthesis strategies. Several breakthroughs occurred thanks to efficient metal catalysis in aziridinations or C-H aminations. However, so far, these methods are mainly restrained to carbamates and sulfonamides, competent substrates able to stabilize the iminoiodane intermediate. HINOF has the ambition to generate iminoiodanes from simple heteroaryl amines. Considering the electron deficient character of azines, heteroaryl nitrenes could be stabilized and obtained under mild thermal conditions starting from easily accessible primary amines and be able to generate new N-N bond.

The use of heterocyclic primary amines as iminoiodane precursor has been validated and successfully applied to the synthesis of 6/5/5 fused heterocyclic systems. This approach allows the formation of the intramolecular N-N bond under mild reaction conditions. Previous work required the activation at high temperature of azide or nitro groups, the amino derivatives in the presence of hypervalent iodine do not require any thermal activation (working at Ta vs. 165 °C). The fluorescence of the new products obtained following this procedure was studied.
The synthetic method to generate the nitrene species under mild reaction conditions is now successfully applied to 6/5/6 systems. Contrary to 6/5/5 cycles, these heterocycles show a broader synthetic tolerance either in the choice and position of the groups introduced (the reactivity is not sensitive to electron-rich groups) or in the nature of the heterocycles used (more easily extended to pyridines).
To date, 6/5/6 scaffolds are studied for their fluorescence properties in different organic solvents as well as in water for some products.

A series of 6/5/6 fused polynitrogen heterocycles was obtained under mild reaction conditions from primary amine. These new molecules are currently studied for their spectroscopic properties in various organic solvents as well as in water. TD-DFT studies will also be carried out to rationalize the observed results concerning the fluorescence part of the project. A scientific publication is in preparation.
These results open up very promising perspectives. In particular, the project will focus on the synthesis of more complex compounds by increasing the number of fused cycles.

M. Daniel, M.-A. Hiebel, G. Guillaumet, E. Pasquinet, F. Suzenet Chem. Eur. J. 2020, 26, 1525.

Poster communication M. Ndiaye, K. Jouad, S. Petoud, M.-A. Hiebel, F. Suzenet aux journées de Chimie organique Palaiseau 29-31 october 2019 (France)

Small-molecule fluorophores are becoming major tools in the chemical biology field. Easily accessible with high versatility and chemical stability, they have also promising spectral characteristics, which are well suited for molecular imaging. However, innovations are still expected to address remaining crucial features. This proposal falls within this context. HINOF is first based on the innovative development of nitrenes from simple hetarylamines. For this purpose, iminoiodinanes will be investigated and will allow reactions at room temperature starting from more available and safer starting materials. The high modularity of our approach will allow a fine-tuned structural modification. Therefore, this methodology will support the second objective of HINOF i.e. the discovery of efficient organic fluorophores that would present a high selectivity and sensitivity, low self-oxidation, high photostability, low cytotoxicity, good solubility, expected cell permeability and low interference from the biological environment..