Photocatalytic Radical Polar Crossover for C-H, C-O, and C-C Functionalization

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Abigail G. Doyle at the University of California, Los Angeles (UCLA) is studying chemical reactions that use visible light as an energy source to transform readily available starting materials to more valuable products of potential utility in medicinal, agrochemical and polymer chemistry. Because most organic molecules do not absorb visible light, a catalyst is necessary. In this project, the Doyle team is designing visible light-absorbing catalysts that enable us to access versatile, high energy intermediates known as carbocations and carbanions. Previously, these intermediates were only accessible using harsh reaction conditions, such as at high temperatures and/or corrosive reagents. The use of such conditions makes it challenging to incorporate sensitive functional groups into the precursors, thus limiting the molecules that can be used in the chemistry. In contrast, the Doyle group’s approach to these intermediates allows for access to and manipulation of more highly functionalized and sensitive precursors. To best explore this science, Professor Doyle and her team are integrating modern data science techniques into the workflow for catalyst design, reaction optimization, and advancing scientific understanding. As such, this project is providing a diverse group of chemistry Ph.D. students and undergraduates with the interdisciplinary training and broadened skill sets that are becoming increasingly necessary to contribute to the STEM (science, technology, engineering, and mathematics) workforce. Dr. Doyle and her coworkers engage in an extensive range of educational and outreach activities, including co-writing monthly “diversity highlights” for UCLA chemistry’s weekly departmental newsletter, delivering educational chemistry table demos through StemPrep for local elementary school students who belong to groups underrepresented in STEM, and partnering with local community colleges to host summer Research Experiences for Undergraduates (REU) students. Under this award, the team led by Professor Abigail G. Doyle at UCLA is developing synthetic reactions that access high-energy, polar reactive intermediates using visible-light and photocatalysts. Carbocations and carbanions are valuable reactive intermediates for a broad range of synthetic strategies. However, the generation of these intermediates typically requires strong acid or base, strong oxidants or reductants, or high temperatures, only affords access to stabilized intermediates, and/or requires the use of precursors that are prepared in multiple synthetic steps from feedstock chemicals. These restrictions preclude the application of carbocations or carbanions in late stage synthesis and limit the ability to access a number of desirable but relatively sensitive motifs. This program is addressing these challenges by using photocatalytic radical-polar crossover to access carbocations or carbanions under mild and selective conditions from abundant and stable C(sp3)–H, carboxylic acid and alcohol precursors. The Doyle team is developing a mechanistically novel desaturation reaction that features complementary site selectivity, enantioselective C(sp3)–H oxidation reactions using a data-science guided catalyst discovery and optimization workflow, a platform for the synthesis of esters by chemoselective cross-coupling of two carboxylic acids, and a catalytic direct deoxygenative alkylation reaction of alcohols. These strategies will be vetted in the context of the synthesis of functional molecules of potential utility in medicinal, agrochemical and polymer chemistry. Moreover, these studies aim to uncover mechanistic understanding that will advance fundamental knowledge of visible-light promoted chemical reactions and the application of data science tools in catalysis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.