Transition Metal-Catalyzed Carbon-Carbon Bond-Forming Reactions of Unactivated Alkyl Electrophiles

I. Alkyl Electrophiles in Cross-Coupling Reactions An overview of challenges associated with the use of alkyl electrophiles in transition metal-catalyzed cross-coupling reactions is presented. The current state of the field is discussed, highlighting advances and applications in hybrid organometallic-radical reactivity. II. Palladium-Catalyzed Mizoroki-Heck-Type Carbocyclizations of Unactivated Alkyl Bromides via Auto-Tandem Catalysis A palladium-catalyzed Mizoroki-Heck-type carbocyclization of unactivated alkyl bromides is described. Reactions proceed efficiently with a wide range of alkyl bromides and alkenes to afford five- and six-membered carbo- and heterocycles. Detailed mechanistic studies of reactions of alkyl bromides suggest an auto-tandem catalytic pathway that proceeds via isolable atom-transfer radical cyclization (ATRC) intermediates. Similar studies indicate that carbocyclizations of corresponding alkyl iodide substrates proceed via metal-initiated radical chain processes. III. Nickel-Catalyzed Mizoroki-Heck-Type Reactions of Unactivated Alkyl Bromides A nickel-catalyzed Mizoroki-Heck-type reaction of unactivated alkyl bromides is described. Primary and secondary alkyl bromides are viable substrates for intramolecular carbocyclizations, and alkene regioselectivity is significantly improved compared to prior work using palladium catalysis. Intermolecular cross-couplings are successful with secondary alkyl bromides and activated alkenes. Mechanistic studies in the presence of single-electron inhibitors support a hybrid organometallic-radical pathway. IV. Cobalt-Catalyzed Mizoroki-Heck-Type Reactions of Unactivated Alkyl Chlorides A cobalt-catalyzed Mizoroki-Heck-type reaction of unactivated alkyl chlorides is described. Preliminary results demonstrate that mild catalytic conditions using inexpensive starting materials enable intra- and intermolecular carbon-carbon bond formations. Literature precedent suggests that cobaloxime derivatives serve as active catalytic species. Efforts to elucidate the full substrate scope and reaction mechanism are ongoing.Doctor of Philosoph