UC Berkeley

The following Dissertation discusses mechanistic investigations into reactions oforganometallic complexes that contain fluoroalkyl ligands. In particular, this work focuses on elucidating electronic and stereochemical effects of cross-coupling reactions in which the aforementioned complexes are putative intermediates. Chapter 1 reviews the reactivities of fluoroalkylcopper and -palladium complexes involved in cross-coupling reactions with a focus on the formation of fluoroalkylarenes. Common challenges encountered in fluoroalkylation reactions are discussed in the context of the fundamental reactivity of intermediate fluoroalkyl complexes, and mechanistic insights into these systems are collected and summarized. Areas in need of further study are highlighted, and the author’s recommendations for the development of new metal-mediated fluoroalkylation reactions are provided. Chapter 2 describes mechanistic investigations into the unprecedented electronic effect of ancillary bipyridine ligands on the copper-mediated pentafluoroethylation of aryl halides. A survey of electronically varied bipyridine ligands revealed that reactions of complexes containing less electron-donating bipyridine ligands proceeded faster than those of complexes containing more electron-donating bipyridine ligands. Kinetic and computational studies revealed that this effect is due a difference in rate of oxidative addition of the aryl halide to the pentafluoroethylcopper center. Chapter 3 describes investigations into the origins of enantioselectivity of the palladium- catalyzed asymmetric α-arylation of 3-fluorooxindoles. The putative intermediate diastereomeric arylpalladium fluoroenolate complexes were independently synthesized and characterized, and upon heating yielded arylated 3-fluorooxindoles in high yields with enantioselectivities that matched those of the corresponding catalytic reactions. Chapter 4 describes preliminary investigations into the development of a palladium- catalyzed trifluoromethylation of aryl bromides. Side-reactions of the sole reported palladium- catalyzed trifluoromethylation of aryl chlorides were examined, and new ancillary phosphine ligands were evaluated for their ability to promote the challenging transmetallation and reductive elimination steps of the reaction. Trifluoromethylcopper reagents also were evaluated as sources of nucleophilic CF 3 , and in most cases were found to undergo exchange of ancillary ligands with the Pd center, resulting in the formation of aryl(trifluoromethyl)palladium species that were unable to undergo reductive elimination to form trifluoromethylarene. Chapter 5 describes computational investigations into the reductive elimination of fluoroalkylarenes from aryl(fluoroalkyl)palladium complexes. Complexes containing more electron-withdrawing fluoroalkyl ligands generally were calculated to have higher barriers to reductive elimination than complexes containing less electron-withdrawing fluoroalkyl ligands. However, complexes containing the fluoroalkyl ligands -CF 2 CN and -CF 2 Ph were calculated to have lower barriers to reductive elimination than expected based on the electronegativities of these fluoroalkyl ligands. IGMH and NBO analyses revealed that these complexes were stabilized in the transition state by interactions with the filled d orbitals of the Pd center and the π * orbitals of the CN or Ph fragments of the CF 2 CN or CF 2 Ph ligands, respectively. Deletion of these interactions by NBO analysis reestablished the trend that complexes containing more electronegative fluoroalkyl ligands underwent reductive elimination with higher barriers than complexes containing less electronegative fluoroalkyl ligands (adjusted barriers for CF 2 CN > CF 3 > CF 2 Ph > CF 2 H > CFH 2 > CH 3 ).