Atom swapping strategies for the de novo synthesis of N-heterocyclic scaffolds

The chemical synthesis of essential biomolecules, such as fertilizers, hormones and vitamins, has improved and saved the lives of countless individuals. A more subtle, but perhaps even more impactful achievement of science is the ability to understand and control biological systems by purposely altering the chemical structure of biomolecules. Single point substitutions of atoms or functional groups within a given biomolecule can have remarkable effects on organisms. This atomic-precision molecular engineering is not only crucial at a fundamental explorative level in biology, e.g. for elucidating cell biological processes, but it is also crucial during modern drug development, where single point substitutions can make the difference between reaching a valuable new drug or running into a very costly failure. Classical substitution reactions for fine-tuning of biologically active molecules involve functional group transformations. More recently, late stage functionalisations such as CH-activation have drawn a lot of attention in strategic basic research. In this project, we will aim for an even more ambitious transformation, wherein skeletal carbon atoms, bound to two other carbon atoms within a cyclic arrangement, can be exchanged for a nitrogen atom. A stepwise development approach is outlined starting from expertise in cycloaddition and high-energy nitrogenation reagents, aiming to annulate or ring expand ring systems with nitrogen, followed by an expulsion of carbon.