Novel Transition Metal Catalysis for Chemical Synthesis

Project Summary The proposed MIRA application aims at the development of a new synthetic platform for controlled selective functionalizations of organic molecules. The existing synthetic methods toward complex molecules and pharmaceuticals mostly rely on employment of pre-functionalized substrates. Employment of non- functionalized groups is much more appealing, as these moieties are much more abundant and cheap. Moreover, the aliphatic C(sp3)–H bonds are often present in complex biologically important molecules and pharmaceuticals, and thus their selective functionalization offers a powerful tool for late stage modifications. The few existing methods for functionalization of unactivated saturated groups are not general, as the functionalization site is usually substrate-controlled. Also, these methods operate under acidic conditions and/or employ external oxidants, which limits the substrate scope. Thus, mild regio- and stereo-controlled functionalization of saturated groups remains a holy grail in modern synthetic chemistry. We propose the development of a novel visible light-induced transition metal-radical hybrid catalytic methodology for regiocontrolled, mild, and exogenous oxidant-free functionalizations of saturated groups. The site of intramolecular functionalizations will be controlled by a designed tool-kit of temporary auxiliaries, which potentially in one-pot fashion will be routinely installed onto substrate and removed from the product. The chemo- and stereoselectivity of intermolecular functionalizations will be achieved via design of potent and selective hydrogen atom abstracting groups. The feasibility of a successful development of this project is supported by a vast amount of preliminary results obtained in our lab.