CATALYTIC CARBONYLATIONS OF UNACTIVATED ALKYL ELECTROPHILES VIA SINGLE- AND TWO-ELECTRON PATHWAYS

I. Carbonylations of Unactivated Alkyl Electrophiles An overview of the current state of metal-catalyzed carbonylations of unactivated sp3-hybridized alkyl electrophiles, including halides and sulfonates, is presented. Two dominating mechanisms for the oxidative addition step and their consequences in synthesis will be discussed in detail. II. Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure A palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure under mild conditions is described. Preliminary mechanistic studies are consistent with a hybrid organometallic−radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide. III. Cobalt-Catalyzed Carbonylative Cross-Coupling of Alkyl Tosylates and Dienes: Stereospecific Synthesis of Dienones at Low Pressure A stereospecific carbonylative cross-coupling of unactivated alkyl tosylates and dienes producing enantioenriched dienones is described. This catalytic process proceeds under low pressure and mild conditions using an easily prepared cobalt catalyst and extends to diverse array of chiral, non-racemic alkyl tosylate and diene coupling partners. The transformation constitutes a unique, convergent approach to the asymmetric synthesis of valuable chiral carbonyl compounds from easily accessed starting materials. IV. Cobalt-Catalyzed Aminocarbonylation of Alkyl Tosylates: Stereospecific Synthesis of Amides A stereospecific aminocarbonylation of unactivated alkyl tosylates producing a diverse array of chiral, enantioenriched amides is described. This commercially available, base metal-catalyzed process tolerates an extensive range of amine coupling partners and exhibits excellent chemoselectivity. This transformation elaborates on our previous enantiospecific carbonylation methodology, providing direct access to valuable, enantioenriched amides, carboxylic acids, and ketones.Doctor of Philosoph