Mechanism and Discovery of Metal-Catalyzed Fluoroalkylation Reactions

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The Chemical Catalysis Program of the Chemistry Division supports the project by Professor John F. Hartwig in the Department of Chemistry at the University of California, Berkeley. In this program, Prof. Hartwig is developing and seeking to understand reactions that are initiated and controlled by catalysts (catalysts are chemical additives that help a reaction to occur or to proceed more rapidly) through transition-metal complexes that ultimately result in the formation of bonds to carbon atoms bearing fluorine. These studies are important because organic molecules containing fluorine are vital to materials, agricultural, and medicinal sciences. For example, over 30% of new pharmaceuticals and 25% of licensed herbicides contain fluorine. The proposed research will answer a series of questions about the impact of fluorine atoms on the metal-bound carbon atom and will assess several approaches to induce and control the reactivity of these fluoroalkyl complexes of transition metals, thereby enabling the discovery of new catalytic reactions that install fluorine-bearing carbon atoms into organic molecules. As part of the educational plan, the PI’s research team will visit K-12 classrooms to present lessons on catalysis, the PI will teach short-courses for those lacking formal training in organometallic catalysis, the PI will continue extensive mentorship of undergraduate students from Berkeley and from outside institutions who are seeking postgraduate degrees, and the PI will present seminars on catalysis to general audiences, predominantly in forums in which he reaches potential scientists of underrepresented groups.Although a large fraction of pharmaceuticals and agrochemicals contain fluorine, fluorinated molecules are largely limited to those derived from simple fluoroarenes, trifluoromethylarenes or trifluoroacetates. Methods to synthesize more diverse fluoroalkyl structures require new approaches including new methods aimed at inducing and controlling the reactivity of fluoroalkyl transition-metal complexes in catalytic reactions. The proposed research seeks to address this requirement by discovering and developing new couplings of fluorinated nucleophiles and electrophiles using complexes of palladium, nickel, and iridium. Included are enantioselective couplings of fluorinated nucleophiles and electrophiles and studies that promise to reveal the differences in structures and reactivities of fluoroallyl intermediates. While carrying out these fundamental studies, the Hartwig group will address several important challenges for the synthesis of fluorinated molecular targets including the development of fluoroalkylation reactions that utilize catalytic quantities of transition metals, the control of the configuration at fluorine-containing stereogenic centers, and the development of new reactions of aryl halides that lead to novel fluoroalkylarenes. Thus, this research will impact the synthesis of molecules that are important in materials science, medicinal chemistry, and agroscience.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.