SusChEM: Mechanism and Discovery of Metal-Catalyzed Fluoroalkylation Reactions

University Of California-Berkeley, Berkeley CA

Investigators

Abstract

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, Professor Hartwig is developing a mechanistic understanding of catalytic reactions that use transition metal complexes bonded to fluorine-containing alkyl groups. These studies answer a series of questions about the impact of fluorine atoms on the metal-bound carbon atom. The studies also assess several approaches to control the reactivity of these fluoroalkyl complexes of transition metals. By developing methods to control the reactivity of fluoroalkyl complexes, this research enables the development of new catalytic reactions that add fluoroalkyl groups into organic molecules. Organic molecules containing fluorine are vital to materials, agricultural, and medicinal sciences. For example, over 20% of new pharmaceuticals and 25% of licensed herbicides contain fluorine. The project is well suited for providing a broad education to Ph.D. scientists and undergraduates, including those of underrepresented groups. A series of outreach activities for K-12 students, the general public, and the general scientific community are part of Professor Hartwig's efforts resulting from the research program. Although a large fraction of pharmaceuticals and agrochemicals contain fluorine, fluorinated structures are largely limited to those derived from simple fluoroarenes, trifluoromethylarenes or trifluoroacetates. Many of the potential methods to synthesize more diverse structures containing fluoroalkyl groups require new approaches to induce and control the reactivity of fluoroalkyl transition-metal complexes in catalytic reactions. This research creates these capabilities by demonstrating, by a combination of kinetic analysis of catalytic reactions and synthesis of catalytic intermediates, how to induce productive reactivity in fluoroalkyl complexes of palladium. This project also creates new catalytic reactions that couple partially fluorinated alkyl groups to aromatic and heteroaromatic molecules to form products that are difficult to access by current synthetic methods. With this information, fluoroalkylation reactions that are currently stoichiometric are being made catalytic. Additionally, new reactions of aryl halides that form fluoroalkylarenes with novel structures that are difficult to prepare by alternative methods are being created. This research enables the preparation of new classes of fluorinated molecules for materials science, medicinal chemistry, and agroscience. As part of the educational plan, Professor Hartwig teaches short-courses for those lacking formal training in organometallic catalysis, co-authors a sophomore organic text that includes content on catalysis in medicinal and green organic chemistry, and delivers lectures to general audiences, predominantly in forums in which he reaches potential scientists from underrepresented groups.