Computational chemistry as a powerful pool in development and study of stereoselective aminocatalytic reactions

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Singh, Simarpreet
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The development and application of computational methods have revolutionized experimental chemistry, allowing calculations on real chemical systems without requiring in-depth mathematical understanding. Computational chemistry has become a valuable tool alongside experimental techniques in elucidating reaction mechanisms. In the field of aminocatalysis, these methods have facilitated a deeper understanding of selectivity, prediction of stereochemistry, and the design of novel catalysts to expand its scope. Chapter 2 focuses on the aminocatalytic γ-amination reaction of enals with Diethyl azodicarboxylate. The observed stereochemistry of the product challenges existing mechanistic models, prompting a study that employs both experimental and computational methods to explore plausible downstream reaction pathways. Two mechanisms are proposed: one involving the formation of a downstream aminated dienamine intermediate and the other invoking a Michael addition pathway. However, the mechanistic investigations suggest that the aminated dienamine is not formed, necessitating further inquiry into the Michael addition mechanism for a comprehensive understanding of the reaction. Chapter 3 examines the impact of aminocatalysts in promoting the dearomatization of several heteroaromatic aldehydes. The constructed hyperhomodesmotic equations indicate that the formation of an iminium ion reduces the energy cost for dearomatization compared to the parent aldehyde. The role of the catalyst and heteroatom of the aldehyde on the orbital coefficients at different positions of the trienamine intermediate is also explored. In Chapter 4, the influence of substituents on a trienamine intermediate is investigated. Trienamine-mediated Diels-Alder reactions show reactivity at the terminal diene (3,6-scis diene) over 1,4-scis diene. Various substituents are employed to assess their influence on the thermodynamics and HOMO energy of trienamine intermediates. Additionally, orbital coefficients are calculated to understand the impact of substituents on the pi-backbone. Chapter 5 presents an investigation into the unprecedented dimerization of electron-deficient cyclic allenes. The study also explores the trapping of cyclic allenes with electron-rich dienes to gain insights into the observed selectivity. Computational data are utilized to develop a novel trapping method of allenes with enamines. Overall, this dissertation showcases the application of computational chemistry in aminocatalytic reaction mechanism elucidation and method development, demonstrating its significance in advancing the understanding and manipulation of complex chemical processes.
Computational Chemistry, Organocatalysis, Aminocatalysis