Photocatalytic Alkene Hydroamination: Reaction Development and Asymmetric Catalysis

Abstract

Alkene hydroamination, or the addition of an N–H  bond across a C–C  bond, is a reaction of particular significance in organic synthesis. Though important advances have been made, numerous challenges remain with respect to regioselectivity, enantioselectivity, and scope of amenable amine coupling partners. While the majority of hydroamination reactions leverage transition metal catalysis and polar reaction mechanisms, photocatalysis has enabled the mild generation of electrophilic N-centered radicals that readily engage with nucleophilic alkenes in an anti-Markovnikov fashion. This dissertation describes several advances in this reactivity framework. Either direct electron transfer (ET) or proton-coupled electron transfer (PCET) with an Ir(III) photocatalyst generates an electrophilic N-centered radical and reduced Ir(II) catalyst. Addition of this species to an electron rich alkene furnishes a new C-centered radical. Polarity-matched H-atom transfer (HAT) from a thiol co-catalyst generates the closed shell product. Finally, ET between the thiyl radical and Ir(II) followed by protonation of the thiolate turns over the respective catalytic components. In Chapter 2, a method for the intermolecular, anti-Markovnikov hydroamination of alkenes with primary alkylamines is described. Despite the presence of excess olefin, excellent selectivity for the monoalkylated secondary amine is observed. In Chapter 3, the synthesis of ammonium functionalized polyethylene is significantly streamlined by developing a scalable hydroamination of cyclooctadiene with piperidine. Following in situ quaternization, ring-opening metathesis, and hydrogenation, the resultant polymers display excellent hydroxide conductivity and stability. Chapter 4 describes the development of a cysteine peptide catalyst capable of undergoing asymmetric HAT with a prochiral trisubstituted radical in the context of an alkene hydroamination with sulfonamides. Preliminary scope and mechanistic studies underscore the non-covalent interactions that govern substrate recognition and enantioselective delivery of H•.