Singlet nitrenes are powerful intermediates that enable the assembly of CâN bonds in an orthogonal fashion, providing a viable and innovative alternative to standard methods like cross-coupling, reductive amination and nucleophilic substitution. The synthetic community however does not routinely harness these species as they are generally accessed by photolysis of aryl azides. This thesis will outline a novel approach for singlet nitrene-generation using readily available nitroarenes as their precursors. The first chapter will discuss the use of singlet nitrenes for the construction of poly-functionalized azepanes. Nitrogen-containing heterocycles are ubiquitous in the core structure of many high-value materials like pharmaceuticals, agrochemicals and natural products. While five and six-N-membered rings are widespread in medicinal chemistry, the seven-membered azepane ring is less common because there is a lack of viable methodologies for their synthesis. This chapter will present the development of an effective strategy for the preparation of complex azepanes from simple nitroarenes. The key retrosynthetic advantage of this approach is that it translates the aromatic substitution pattern into the azepane unit, producing poly-functionalised heterocycles that are difficult to prepare by other methods. The second chapter will demonstrate how this novel approach to synthesise saturated N-heterocycles can be slightly modified to afford complex caprolactams. Finally, the third chapter will outline how nitroarenes and complex amines can be directly converted into ortho-phenylenediamines in a one-pot procedure. This method provides a new retrosynthetic outlook where the amine coupling partner âseemsâ to displace the nitro group that undergoes a formal 1,2-shift to its ortho position, forming the ortho-phenylenediamine in a concise manner.
Development of Novel Nitrene-Based Synthetic Methods using Photoexcited Nitroarenes
Sanchez, R. (Author). 31 Dec 2024
Student thesis: Phd