Publication
Organic azides are known for their reactivity and broad applicability in organic synthesis. These compounds are pivotal in various chemical transformations, including nucleophilic substitution and cycloaddition reactions. Beyond synthetic chemistry, organic azides are valuable in bioconjugation, drug development, and materials science. Despite their extensive utility, azides must be handled with care due to their potential explosive nature. The development of safe and controlled synthetic methods of azide derivatives is crucial to expand their applications across various fields. The direct C-H bond functionalization allows for the selective introduction of functional groups into hydrocarbons without the need for pre-activation. This strategy improves efficiency and reduces the formation of side products. Allowing the incorporation of multiple functional groups, the difunctionalization of alkenes involves the simultaneous introduction of two distinct functional groups across the carbon-carbon double bond. This strategy widely used in synthetic chemistry for building molecular diversity. The first objective of this thesis was to develop an enantioselective methodology for the azidation of benzylic C-H bonds. Investigations were conducted using copper- or iron-based catalysts in combination with various chiral ligands. Although the azidated derivatives were isolated in most of the cases, no enantioselectivity was observed under the investigated conditions. The second part of this thesis focused on developing difunctionalization methodologies to introduce an azide group alongside another functional group. A first methodology was developed for the successful alkylazidation of dehydroamino esters, affording alpha-alkyl alpha-azide amino esters. The methodology relies on the use of peroxides as alkyl precursors and an iron catalyst involved in the outer-sphere azidation step. The products could be further transformed into aminal-type tripeptides or complex heterocycles. The development of a general azidofunctionalization method was then investigated. Using a photocatalytic system, the introduction of various functional groups, including azoles, esters, alcohols, phosphoric acids, oximes, and phenols, alongside the azide motif on different classes of olefins was successfully achieved. The transformation relies on a radical-polar crossover mechanism with an azidobenziodazolone as the azide radical source. This methodology significantly improves the efficiency of synthesizing multiple key pharmaceutical intermediates. Additionally, the generality and limitations of the transformations were evaluated through a standard, unbiased selection of 15 substrates. As part of our efforts to develop difunctionalization methodologies, a study on the alkylalkynylation of alkenes using two nickel-catalyzed systems was conducted. The first system involved the generation of an electron donor-acceptor (EDA) complex to produce the alkyl radical, while the second utilized al