Pyridine Dearomatization via Electrophilic Amide Activation

So-called amides are a structural motif in organic molecules, consisting of a carbon atom bond do a nitrogen and double-bond to an oxygen atom. Amides are one of the most fundamental motifs in organic molecules, for example as the backbone in proteins and enzymes. In comparison to similar oxygen-carbon containing structural motifs, amides are intrinsically less reactive and harder to manipulate by chemical processes. However, in recent years, methods have been developed to activate amides selectively, enabling many valuable chemical transformations such as synthesis and efficient modification of pharmaceutically relevant compounds. Typical procedures within the field of amide activation often include pyridines as reagents. Pyridines are a class of organic compounds, in which one of the six carbon atoms in a benzene ring is exchanged for a nitrogen atom. Alike benzene, pyridines are aromatic, meaning they are particularly stable and only undergo certain, limited chemical reactions. In chemical research, much effort has been spent to break the aromaticity of pyridines and thereby obtain compounds which serve as useful intermediates in the synthesis of natural organic products containing nitrogen atoms. In this project, we aim to combine the concepts of amide activation and pyridine dearomatization. This approach will allow us to make novel, previously literature-unknown compounds from inexpensive, abundant starting materials. The so obtained products can be further developed to give efficient access to a number of valuable natural products with potential application in medicine. The parameters of this method can be varied, rendering this approach broadly applicable.