Van Humbeck, Jeffrey FrancisKaur, Milanpreet2024-08-012024-08-012024-07-26Kaur, M. (2024). Development of site-selective C-H functionalization strategies for azaheterocycles (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.https://hdl.handle.net/1880/119303C-H activation is an area of major ongoing research exploration and has emerged as a valuable addition to the organic chemist’s toolbox for the rapid construction of compounds that are of great interest to the pharmaceutical industry. More specifically, recent work has focused on C-H activation at a late stage in complex and biologically relevant molecules. Recently, activation of C-H bonds in heterocycles has emerged as a new route in the synthesis of heterocycles. In particular, the transformation of the C-H bond into C-X bond (where= carbon, oxygen or nitrogen) in heterocycles has gained interest due to its availability in biologically active pharmaceuticals, agrochemicals, and natural products. Although various approaches have been developed for activating C-H bonds in azaheterocycles, there has been a noticeable challenge in a) carrying competitive C-H functionalization when several sites of comparable reactivity are present; and b) accessing many possible reactive sites within a substrate. This work showcases the development of a novel site-selective C-H functionalization strategy in azaheterocycles by taking substrates with different C-H bonds of comparable reactivity and selectivity and converting only one of those C-H bonds predictably into a new carbon-element bond. The goal was to do so using catalyst control and without including any directing groups. This research begins with the development of a new site-selective benzylic C-H hydroxylation in electron-deficient azaheterocycles, encompassing a diverse range of substrates. The latter part of the thesis addresses the challenges associated with the site-selective amination strategy previously developed by our group. In-depth research was conducted to develop catalytic systems capable of selectively and predictably aminating the C-H bond adjacent to an azaheterocycle. Additionally, extensive research was conducted towards synthesizing and deprotecting aminating reagents as well as utilizing photochemistry to install a selective hydrazine/amine unit that can be used to direct other C-H functionalization chemistries.enUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.HeterocyclesSite-Selective ReactionAminationHydroxylationC-H FunctionalizationChemistry--Organicdoctoral thesis