Abstracts Category : Other

Transition metal-facilitated C-C and C-F bondforming

by Ian B Perry

Chapter 1. Copper-Catalyzed Asymmetric Addition ofOlefin-Derived Nucleophiles to Ketones A copper (I) catalyzedcoupling olefins and ketones has been developed for the diastereo-and enantioselective generation of homopropargyl alcohols bearingvicinal stereocenters. This method allows for the generation ofenantioenriched tertiary alcohols with a high degree of functionalgroup compatibility. The utility of the process is furtherillustrated by a large scale synthesis with extremely low catalystloading as well as the late stage modification of severalpharmaceuticals. Chapter 2. Copper-Catalyzed EnantioselectiveAddition of Styrene-Derived Nucleophiles to Imines We describe thecatalytic generation of amines bearing vicinal stereocenters with amoderate degree of diastereoselectivity. The stereoselectivehydrocupration of an unactivated olefinic component is followed bynucleophilic addition of the organocuprate to an N-phosphinoylprotected imine. The mild and general process tolerates abroad-range of functionality, and the process was shown to besuccessful at a gram-scale synthesis. Chapter 3.Palladium-facilitated Regioselective Nucleophilic Fluorination ofAryl and Heteroaryl Halides. The preliminary findings regarding anaryl and heteroaryl halide fluorination process facilitated bypalladium as a reagent is described. Stoichiometric studiesillustrate the utility of the method in producing aryl fluorideswith unprecedented regioselectivity, and preliminary studies intothe fluorination of five- and six-membered heteroaryl bromides aredescribed. Halogen atom substitution as a route to irreversibleoxidative addition of aryl and heteroaryl halides is discussed.This strategy may serve to facilitate the fluorination ofparticularly problematic heteroaryl bromide and chloridesubstrates.Advisors/Committee Members: Stephen L. Buchwald (advisor).