SusChEM: Copper-Catalyzed Radical Reactions of Nitroso Compounds for the Synthesis of Carbon-Nitrogen Bonds

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

The Chemical Catalysis Program of the Chemistry Division supports the project by Professor Read de Alaniz. Professor Read de Alaniz is a faculty member in the Department of Chemistry at University of California Santa Barbara (UCSB). He is developing new strategies for the direct incorporation of nitrogen and oxygen atoms into structurally diverse molecules using earth abundant metals. The goal of this research is to develop a general and versatile strategy to expedite the discovery of therapeutic agents. The molecular diversity of nitrogen containing therapeutic agents and the strong influence nitrogen substituents have on both pharmacokinetics and pharmacodynamics mandates the development of new methodologies for installing these functional groups into small therapeutic organic molecules. In addition, the methodology has potential applications in material science, as well as for the construct of agrochemical compounds. The project is well suited for the education of scientists at all levels. The educational plan includes training of underrepresented groups in outstanding professional development and research training programs at UCSB's California NanoSystems Institute and Materials Research Lab (notably the RISE, SIMS, UC LEADS, CAMP, and MARC programs), as well as developing a new multi-layered mentoring program for graduate students. While the value of amines and the synthetic utility of radical reactions are well-established, exploration of the strategy for constructing carbon (C) - nitrogen (N) and C-oxygen (O) bonds by merging radical reactions with nitroso compounds is almost completely unknown. Through these studies, new opportunities in C-N bond-forming reactions that are mild, functional group tolerant, and use earth abundant copper are under development. These new transformations reduce the number of synthetic steps required to access nitrogen containing molecules that are otherwise difficult to prepare. The transformations also give chemists access to new synthetic bond disconnections. Specifically, the goals of the proposed work are: 1) extend the scope of the recently developed copper-catalyzed radical addition with nitroso compounds to include heterocycles, benzyl bromides and alpha-bromo nitriles; 2) develop the reaction with commercially available aryl and heteroaryltrifluoroborates using nitrite salts to generate the nitroso reagent in situ; 3) apply this strategy to the concise total synthesis of pyrroloindoline alkaloid natural products; 4) develop a new intramolecular radical based N-O transfer process that provides spatial control of the nitrogen and oxygen heteroatoms over a range of architectures. Professor Read de Alaniz's group is well positioned to provide the highest level of education and training for students underrepresented in science. Outreach activities involving a new multi-layered mentoring program are part of the project.