SYNIC · SYNTHETIC NITRENE CHEMISTRY: NEW REACTIONS AND APPLICATION

The paramount importance of nitrogen in life and material sciences makes the search for new C-N bond forming reactions a topic of utmost interest that lies at the heart of organic synthesis and medicinal chemistry. This is a highly competitive domain, and, with the advent of organometallic catalysis, there have been numerous breakthroughs. This proposal resides at the forefront of this field, with the aim to enhance the synthetic understanding of nitrenes and to unveil new methods for the synthesis of nitrogen-containing bioactive molecules.Nitrenes, which are the aza-analogs of carbenes, are useful two-electron oxidants that offer unique synthetic opportunities for the selective functionalization of hydrocarbons, according to click-type reactions. Recently, the synthetic viability of this powerful reagent has considerably expanded, which has led to the development of catalytic C-H amination and alkene aziridination. However, despite these significant achievements, the scope of catalytic nitrene transfers remains mainly confined to these two reactions, and, thus, limited when compared to the chemistry of carbenes.The objectives for this project, which are based on consistent preliminary results reported by the host, include three main concepts. The first involves uncovering new rhodium-catalyzed alkene diamination and carboamination reactions with nitrenes, and, then, developing an asymmetric version for the diamination through the design of chiral rhodium complexes. The second part strategically applies the intramolecular diamination of indoles to synthesize naturally occurring dimeric indole alkaloids. Finally, the cytotoxic properties of the synthesized compounds will be evaluated on site at the ICSN, which could ultimately lead to the discovery of new antitumoral products. This work will be multidisciplinary, involving innovation in methodological advancements in organic chemistry, asymmetric organometallic catalysis, total synthesis and medicinal chemistry.