Catalytic Stereocontrolled Carbene and Vinylidene Transfer Reactions

<p dir="ltr">Carbenes are useful C1 synthons that can participate in a variety of cycloaddition and bond insertion reactions. However, free carbenes are typically too reactive to perform highly selective transformations. Transition metal catalysts have been served as a powerful tool in solving this selectivity issue, in which a transition metal reacts with a carbene precursor to generate a transient metal carbene complex. Depending on the sterics and the electronics of the metal carbene complex, chemoselective, regioselective, or stereoselective carbene transfer reactions can be achieved.</p><p dir="ltr">Despite the advancements of transition metal-catalyzed carbene transfer reactions, most carbene precursors are derived from diazo compounds, which typically require electron-withdrawing stabilizing groups that can eventually lead to the limited types of carbene transfer reactions. Dihalo compounds, on the other hand, can also serve as carbene precursors in the presence of reductants to render metal carbene complexes without stabilizing groups, which can have distinct reactivities from those generated from diazo compounds, allowing more diverse transformations to be discovered. As stereochemistry is essential in the determination of molecular properties, incorporating asymmetric catalysis can open avenues to stereocontrolled carbene transfer reactions.</p><p dir="ltr">This dissertation work conveys the development of nickel- and cobalt-catalyzed reductive carbene and vinylidene transfer reactions, with the control of enantioselectivity and alkene <i>E</i>/<i>Z</i> geometry by asymmetric catalysts. In Chapter 1, a nickel-catalyzed cyclopropanation of electron-deficient alkenes is described. Key to this reactivity is the generation of a nucleophilic nickel carbene from dichloromethane in the catalytic cycle. Enantioselective cyclopropanations can also be achieved by using a chiral nickel catalyst. In Chapter 2, recent cyclopropanation strategies through reductive and oxidative approaches are surveyed to further highlight the uniqueness and importance of non-redox-neutral carbene transfer reactions. In Chapter 3, a cobalt-catalyzed olefin coupling reaction of 1,1-dichloroalkenes and enantiopure allylic alcohols is demonstrated. 1,4-Dienes are the product of this transformation, and the <i>E</i>/<i>Z</i> geometry of the product is controlled by the chirality of the catalyst. The <i>E</i>/<i>Z</i> diastereodivergence originates from the diastereoselective formation of a cobalt metallacycle and a subsequent stereospecific <i>anti</i>-β-alkoxide elimination.</p>