Abstract: Chiral phase-transfer catalysis (CPTC) is an efficient industrial process used to produce enantiomerically pure chemicals, such as agrochemicals, active pharmaceuticals ingredients (API), and monomers.1 CPTC has been applied successfully in various organic reactions with many advantages,2–6 such as mild reaction conditions, high product yields, elimination of hazardous or expensive reagents and solvents, and large- scale asymmetric productions.7 In the last decade, a chiral sp2-quaternary ammonium salt, pentanidium, reported by Tan et al. in 2011, has represented a breakthrough in this field.8 Since pentanidium catalysts have a high impact on asymmetric synthesis and are highly amenable to modification, a new class of bridged-pentanidium catalysts is discussed in this dissertation. The first part focuses on the retrosynthesis of chiral bridged-pentanidium catalysts and how they might be differently functionalized, starting the synthesis from commercial chiral diamines. As a proof-of-concept, a non-chiral bridged-pentanidium was synthesized and fully characterized. The reaction conditions were optimized for each step, particularly the critical seven-membered ring closure reaction, which proved that the retrosynthetic pathway was reliable. Next more sophisticated structures of chiral bridged-pentanidium catalysts were developed. These synthetic pathways involved the discovery of new compounds, such as chiral tertiary bisthioureas, chiral tetraamides, and chiral bisureas. Thus, various chiral bridged-pentanidium catalysts bearing various functional groups and counterions to tune their reactivity were produced. In the second part, the reactivity of chiral bridged-pentanidium catalysts was assessed in various asymmetric reactions. In particular, direct alkylation and Michael addition reactions were applied to synthesize natural and unnatural amino acids. Then, an asymmetric organocascade Michael-Michael reaction for the synthesis of chiral trisubstituted indanes was investigated. Lastly, additional control experiments involving various substrates and reagents were performed. The third part of this work investigated enantioselective induction through computational studies, including density functional theory (DFT), topographic steric maps, and topographic electrostatic maps.9 These studies characterized the properties of the previously synthesized chiral bridged-pentanidium catalysts and revealed how their enantioselectivity is affected by the structure of the catalyst. Finally, the structures and asymmetric induction of the novel chiral bridged-pentanidium catalysts were compared with those of open-pentanidium catalysts reported in the literature.
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