Carbon-Carbon Bond-Forming Reactions of Alkyl and Aryl Electrophiles Using Anionic Metal Catalysis

Abstract

An overview of challenges associated with the use of alkyl electrophiles in transition metal-catalyzed carbon-carbon bond-forming reactions is presented. The current state of the field is discussed, comparing of palladium- and nickel-catalyzed hybrid organometallic-radical methods and anionic base metal-catalyzed methods. A commentary on the use of aryl radical intermediates in transition metal-catalyzed reactions is also provided. Cobalt- and manganese-catalyzed, stereospecific carbonylations of unactivated alkyl tosylates is described. Alkoxycarbonylation and hydroxymethylations proceed with high degrees of inversion. The umpolung hydroxymethylation of alkyl tosylates enables a formal one-carbon homologation of an alcohol to deliver chiral nonracemic, beta-branched primary alcohols. Mechanistic studies demonstrate activation by an anionic metal carbonyl and the intermediacy of an acyl metal intermediate. A cobalt-catalyzed Mizoroki-Heck-type carbocyclization of unactivated alkyl chlorides is described. Reactions proceed efficiently with a wide range of alkyl chlorides and alkenes to afford five- and six-membered carbo- and heterocycles. Ongoing mechanistic studies of the mode of activation of the carbon-chlorine bond suggest a nucleophilic oxidative addition. Preliminary results regarding the coupling reaction of aryl bromides with arenes via homolytic aromatic substitution of an aryl radical intermediate are outlined. Reactions proceed with good conversion despite the formation of reductive side products. Mechanistic investigations are emphasized, in addition to presentation of an initial scope cross-coupling scope. A brief summary of the application of this system to carbocyclizations, carbon-hydrogen bond activation, and dehalogenations is given.Doctor of Philosoph