Theses and Dissertations at Montana State University (MSU)
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Item Stereoselective allylic cyclizations and rearrangements(Montana State University - Bozeman, College of Letters & Science, 2022) Stankevich, Ksenia Sergeyevna; Chairperson, Graduate Committee: Sharon NeufeldtHerein, we aim to explore the unique reactivity of allyl groups in two different areas: synthesis of densely functionalized five-membered ring systems and mechanistic studies of Pd- catalyzed formation of complex quaternary nitriles. The first part addresses the paucity of methods available for the formation of highly substituted five-membered rings, which are a common motif in natural compounds and pharmaceuticals. We developed a method that provides access to cyclopentenols and methylene cyclopentenols via the union of the Claisen rearrangement and Sakurai allylation. In this instance, the Claisen rearrangement allows for the stereospecific generation of the carbon framework, whereas the intramolecular Sakurai allylation provides a stereoselective cyclization reaction. For 1,2,5-trisubstituted cyclopenten-1-ols this approach has proven to be highly general and stereoselective, furnishing a library of cyclized products in good and very good yields and >20:1 diastereomeric ratio. For 1,2,5-trisubstituted 3- methylene cyclopentan-1-ols, we have developed a stereodivergent method whereby the one-pot stepwise Claisen-Sakurai reaction provided anti-, anti- product and the cascade Claisen-Sakurai reaction furnished syn-, anti- product as a major diastereomer with good yield. In both cases reaction mechanism was investigated to uncover the origin of diastereoselectivity using density functional theory. The second part of this research covers investigating the mechanism of a Pd- catalyzed double rearrangement to form quaternary nitriles, which are molecules of synthetic interest. We studied the mechanism of recently developed highly complex auto-tandem catalytic double allylic rearrangement of N-alloc-N-allyl ynamides to complex quaternary nitriles using density functional theory. This reaction proceeds through two separate and distinct catalytic cycles with both decarboxylative Pd-pi-allyl and Pd(0)-promoted aza-Claisen rearrangements occurring. We discovered previously unreported concomitant decarboxylation/C-C bond formation, reversible C-N ionization and a Pd(0) catalyzed [3,3]-rearrangement along with its stepwise variant. These catalytic cycles are characterized by the highly dynamic nature of the catalyst systems with large degrees of conformational flexibility and a flat potential energy surface. Our studies have rationalized the reactivity observed and can be further developed into predictive models for ligand and catalyst screening.Item Organocatalytic approaches to claisen rearrangements of acid sensitive substrates(Montana State University - Bozeman, College of Letters & Science, 2021) Casey, Aoife; Chairperson, Graduate Committee: Matthew CookCyclopentanes and cyclopentenes are present in many natural products and pharmaceuticals. Despite their presence in many natural products and pharmaceuticals there are few general methods to synthesize highly functionalized 5-membered carbocycles. Using substituted allyl vinyl ethers, highly functionalized 5-membered carbocycles can be accessed through a Claisen rearrangement followed by an intramolecular Sakurai reaction. Due to the acid sensitive nature of these allyl vinyl ethers, Lewis acid catalysis is not a viable reaction pathway but the use of H-bond donors as organocatalysts is an attractive method to develop a synthetic methodology to access 5-membered carbocycles. Through NMR and computational studies, the activation parameters of a these HBD catalyzed Claisen rearrangement has been studied and further knowledge into the mechanism of these reaction pathways has been gained.