Switchable Organometallic Catalysts for Organic Reaction Development

Project Summary / Abstract The discovery of new catalyzed methods to generate key bonds in organic molecules is vital to the sustainable synthesis of biologically relevant molecules. The rapid diversification of simple chemical scaffolds using automated parallel synthesis technologies allows for the generation of chemical libraries to screen for new

biological activity, and to assess structural-activity relationships, which facilitates the design of novel medicinal targets with improved activity. New catalytic methods for parallel synthesis benefit from catalysts that can selectively functionalize one site on the chemical scaffold, without changing other reactive functionalities on the

molecule. Developing a single catalyst that can select one reactive functionality, and then be switched to select and react at a different site on the molecule, will allow sequential control of iterative reactions, thereby building advanced synthetic targets in one pot using a strategy amenable to automated technologies. The proposed work

is centered on developing an organometallic catalyst with site-selective reactivity that can be switched by the irradiation of different wavelengths of visible and ultraviolet light. The optimized organometallic catalysts will be applied to iterative one-pot cross-coupling technologies, selectively activating either C(sp2)-X or C(sp3)-X bonds

for the formation of new carbon-carbon bonds depending on the external light stimulus. Investigation of the ability of the switchable organometallic complex to undertake hydrogen-atom transfer from bound alcohols will also be conducted, resulting in the oxidation of the alcohol in situ for subsequent reductive cross-electrophile coupling

strategies. This approach facilitates temporal control of the rates of the multiple catalytic cycles according to the wavelength of the light irradiation and will be applied to the coupling of alcohols with a range of different electrophilic species. These methodologies will enable the iterative formation of key biological motifs, such as

stereodefined polyol sequences, that can be used to study novel medicinal targets. The program will also train a diverse group of graduate students, undergraduate students, and postdoctoral researchers in scientific research encompassing organic, organometallic, and physical organic chemistry, and will provide these

colleagues with the professional development necessary to ensure success in their future careers.