Development of Site-Selective C-H Functionalization Strategies for Azaheterocycles
Date
2024-07-26
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Abstract
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.
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Keywords
Heterocycles, Site-Selective Reaction, Amination, Hydroxylation, C-H Functionalization
Citation
Kaur, 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.