Browsing by Author "Kaur, Milanpreet"

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    Development of Site-Selective C-H Functionalization Strategies for Azaheterocycles
    (2024-07-26) Kaur, Milanpreet; Van Humbeck, Jeffrey Francis; Derksen, Darren Jason; Sutherland, Todd C.; Shimizu, George Kisa Hayashi; Watson, Allan J. B.
    C-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.