Enantioselective Multi-Component Reactions: Conjunctive Coupling and Related Processes

Thesis advisor: James P. MorkenThis dissertation details the discovery, development, and mechanistic exploration of several enantioselective processes involving organoboronic esters. The first chapter will discuss electrophile-induced metallate rearrangement reactions, the fundamental reactivity that underlies much of the subsequently discussed work. The second chapter details the discovery and mechanistic study of the metal-induced metallate rearrangement reaction and the multi-component conjunctive coupling reaction manifold and related reactions it enables. The factors that govern the competition between metal-induced metallate rearrangement versus transmetallation will be explored. The third chapter will discuss efforts to understand and overcome the initial limitations of the conjunctive coupling reaction including halide inhibition of palladium catalysis and the inability to engage other organometallic reagents such as organomagnesium nucleophiles, and how this allowed the development of a more general reaction. The fourth chapter discusses the development of an enantioselective triamine–nickel-catalyzed conjunctive coupling reaction of alkyl electrophiles as well as a related nickel-promoted radical-polar crossover reaction and the mechanistic features leading to one reaction manifold or the other. A related enantioselective diamine–nickel-catalyzed tandem radical addition cross coupling reaction of alkyl iodides, alkenylboron reagents, and alkyl- or arylzinc reagents will also be discussed. The fifth chapter will cover the discovery of a diamine–nickel-catalyzed enantioselective carbozincation reaction of alkenylboron compounds which produces enantioenriched α-boryl alkylzinc reagents. The mechanistic investigations undertaken and application of these species in a variety of stereospecific transformation will be discussed along with the preliminary discovery and optimization of a diphosphine-Pd-catalyzed stereoconvergent Negishi cross-coupling reaction of racemic α-boryl alkylzinc reagents.Thesis (PhD) — Boston College, 2019.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry