Catalytic Reductive Carbene and Vinylidene Transfer Reactions
thesisposted on 2020-04-29, 19:14 authored by Conner M FarleyConner M Farley
Carbenes are reactive organic intermediates comprised of a neutral, divalent carbon atom. The reactivity of carbenes is often orthogonal to polar functional groups (nucleophiles and electrophiles), making them valuable intermediates for organic synthesis. For example, carbenes can engage in cheletropic reactions with olefins to form cyclopropane rings or undergo insertions into weak element-hydrogen bonds. The most established strategy for accessing carbene intermediates is through a redox-neutral decomposition of diazoalkanes to form a transient M=CR2 species. Over the course of nearly a half-century of development, many instrumental synthetic methods have emerged that operate on this basis. Despite the combined utility of these methods, the scope of catalytic carbene transfer reactions remains largely constrained by the inherent instability of the starting materials. Diazoalkanes often require electron-withdrawing groups to provide stability through resonance effects.
Contrary to redox-neutral methods, reductive carbene transfer reactions utilize non-stabilized 1,1-dihaloalkanes as carbene precursors. The Simmons-Smith cyclopropanation reaction represents the most documented example of this class, and remains today as the most practical method for parent methylene (:CH2) transfer. Nevertheless, reductive carbene transfer processes have proven to be remarkably resistant to catalysis. Our group is interested in developing first-row transition metal catalysts which can initiate an oxidative addition into 1,1-dihaloalkanes, followed by a two-electron reduction with an outer-sphere reductant to provide access to a M=CR2 intermediate for carbene transfer.
The application of this mechanistic hypothesis toward reductive methylene transfer using CH2Cl2 as the carbene source and a Ni catalyst is outlined in chapter one. The discovery of an unexpected cyclooligomerization of methylene carbenes is discussed. Mechanistic studies are presented, which are consistent with a pathway in which carbenes are iteratively inserted into an expanding metallacycle. In chapter two, the corresponding activation of 1,1-dichloroalkenes for vinylidene transfer in [5+1]-cycloadditions with vinylcyclopropanes is outlined. Finally, in the third and final chapter, organic reactions catalyzed by complexes which feature metal-metal bonds are reviewed.
- Doctor of Philosophy
- West Lafayette