UC Berkeley

Making and Breaking C‒F Bonds via Palladium-Catalysis

By

Richard Thornbury

Doctor of Philosophy in Chemistry

University of California, Berkeley

Professor F. Dean Toste, Chair

Chapter 1 – A ligand controlled, palladium-catalyzed, enantioselective 1,3-arylfluorination of [2H]-chromenes was developed. The products were obtained in high enantioselectivity and with a syn- relationship of the introduced substituents. The pyranyl fluoride products were further derivatized to demonstrate the utility of the products. A ligand dependent divergent formation of 1,3- and 2,1- alkene difunctionalization products was also observed. This bifurcation in reactivity was investigated with a combination of experimental, computational, and statistical analysis tools. Ultimately, the site selectivity was found to be dependent on the ligand denticity and metal electrophilicity, the electronics of the boronic acid, and the donor ability of the directing group in the substrate.

Chapter 2 – A palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes with boronic acids was developed. Broad functional tolerance arises from a redox-neutral process in which a palladium(II) active species which is proposed to undergo a β-fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases. As a demonstration of this method’s unique combination of reactivity and functional group tolerance, a Gleevec analogue, using a monofluorostilbene as an amide isostere, was synthesized in 4 steps from commercially available materials.