Abstract

Azines are an important class of N-heterocycles, widely found in natural products, pharmaceuticals, agrochemicals, functional materials, and chiral ligands. Commensurate with their ubiquity, N-oxides of these heteroarenes have emerged as novel scaffolds in medicinal and materials chemistry, as well as catalysis. Nheterocyclic N-oxides constitute a versatile compound class with extensive biological potential, demonstrating significant therapeutic promise across diverse medical domains, including cancer, bacterial, inflammatory, neurological, and parasitic treatments. Recent pharmaceutical research has increasingly leveraged the N-oxide structural element as a strategic approach in novel drug design and molecular development. Particularly noteworthy is that aromatic heterocyclic N-oxides undergo transformations not feasible with their parent Nheterocycles. Beyond classical processes exclusive to N-oxide substrates without a basic nitrogen center, researchers have reported various approaches for site-selective aryl C–H functionalization on heterocyclic Noxide scaffolds. Some of these processes notably include the removal of oxygen from the N-oxide, enabling deoxygenative aromatic substitution. As pioneered by Fagnou, most protocols for bond formation at specific positions within N-heterocyclic frameworks rely on transition-metal-mediated catalysis, which exploits the unique directing effect of the N–O bond. In recent years, pyridine and quinoline N-oxides and their derivatives have transcended their traditional role as moderate Lewis-base pairs. Emerging research now explores their potential for unconventional single-electron transfer processes, particularly in hydrogen-atom transfer catalysis for radical generation. These investigations promise to unlock synthetically useful transformations, expanding the synthetic utility of these remarkable molecular structures. 

This presentation will cover our ongoing effort since 2015 to develop new synthetic methodologies in organic synthesis.1-5 We have been utilizing various N-heterocyclic N-oxide derivatives as both substrates and mild oxidants, as well as hydrogen atom transfer (HAT) catalysts. 

References 

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2. Kim, K. D.; Lee, J. H.* “Visible-Light Photocatalyzed Deoxygenation of N-Heterocyclic N-Oxides” Org. Lett. 2018, 20, 7712–7716. 

3. An, J. H.; Kim, K. D.; Lee, J. H.* “Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Using Hantzsch Esters as Mild Reducing Agents” J. Org. Chem. 2021, 86, 2876–2894. 

4. Kim, S. H.; An, J. H.; Lee, J. H.* “Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Under Transition Metal-free Conditions” Org. Biomol. Chem. 2021, 19, 3735–3742. 

5. Ryu, H. K.; Song, Y. D.; Lee, J. H.* “Deoxygenation of N-Heterocyclic N-Oxides Using Isopropanol as a Recyclable Reductant” Org. Chem. Front. 2024, 11, 2249–2268.