[3+2]-Cycloadditions of Azomethine Imines and Ynolates and Progress Towards a Radical Three-Component Cross-Coupling Reaction

This manuscript consists of three chapters. The first chapter describes a novel [3+2]-cycloaddition of azomethine imines and ynolates to construct bicyclic pyrazolidinones in high yields and diastereoselectivities. This methodology is the first example in which the azomethine imine acts as a chiral auxiliary to control the cycloaddition. Optically active azomethine imines yield bicyclic pyrazolidinones in high yields, and conditions for removal of the azomethine imine chiral auxiliary have been defined to yield optically active monocyclic pyrazolidinones in high yields and enantioselectivities. The second chapter consists of progress towards a novel [2+2]-annulation/fragmentation to construct cyclohexanones. Among all the methods to synthesize highly substituted cyclohexanols/cyclohexanones, there is no general, one-step enantioselective, intermolecular method to synthesize a highly substituted cyclohexanol/cyclohexanone with a quaternary center at C4. Therefore, we developed a synthesis of cyclohexanones via a formal [2+2]-annulation/fragmentation between a cyclobutanone containing an electron-withdrawing group and an electrophile. The second chapter describes attempts to render the reaction asymmetric, which proved to be difficult. Future ideas to improve yields and to render the reaction asymmetric are also described. The last chapter involves progress towards a novel three-component, enantioselective radical cross-coupling reaction to synthesize complex products in a single step. Current literature contains only scattered examples of three-component radical cross-coupling reactions, all of which have a severely limited substrate scope (e.g., only alkynes, one nucleophile, contains fluorine). Therefore, we envisioned a three-component radical cross-coupling reaction with a broad substrate scope encompassing multiple radical initiators and olefin acceptors. This method could provide access to products that are currently challenging to synthesize. Progress towards this three-component enantioselective reaction is presented in chapter three, as well as future ideas to improve enantioselectivity and yields.