| Summary: | <p>This thesis describes an enantioselective Cp*Rh(III)-catalysed intermolecular C(sp3)–H amidation of cyclobutanes utilising azine heterocycles as directing groups, and also the preliminary discovery of an intramolecular C(sp3)–H amidation of a newly designed dioxazolone-derived dithiane to generate the lactam products.</p>
<p><strong>Chapter 1</strong> provides a detailed overview of the theoretical foundation, as well as the evolution of C−H activation strategies and their principal mechanisms. It encapsulates a brief summary of the most widely investigated directing groups in recent years, while elucidating in detail the studies of C(sp3)−H activation reaction using heterocyclic moieties as directing groups, such as pyridine. Furthermore, it encompasses the state-of-the-art studies of CpxM(III) catalysts in facilitating enantioselectivity control of desymmetrising C(sp3)−H functionalisation reactions assisted by chiral ligands.</p>
<p><strong>Chapter 2</strong> introduces a new methodology to establish asymmetric cyclobutanes via the direct C−H activation strategy and demonstrates a highly enantioselective desymmetrising intermolecular C(sp3)–H amidation of azine-linked cyclobutanes, furnishing enantioenriched cis-configured amido-cyclobutane scaffolds. The transformation is facilitated by an electron-deficient Cp*Rh(III) catalyst in synergy with a newly designed axially chiral carboxylic acid, which was found to be pivotal in attaining high levels of enantioselectivity. Computational studies revealed the presence of multiple non-covalent interactions which contributed significantly to the high enantioselectivity that was observed.</p>
<p><strong>Chapter 3</strong> presents the synthesis of a unique class of dioxazolone-derived dithianes, as well as the initial discovery of an intramolecular dithiane-directed regio-selective C(sp3)–H amidation reaction to generate lactam compounds. Despite the anticipated transformation process for the synthesis of cyclic amides not being achieved under our limited test conditions thus far, this work lays the foundation for a viable follow-up study based on our findings.</p>
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