Chemical synthesis: New strategy for skeletal editing on pyridines

While the ring structure remains intact in the so-called peripheral functionalisation of rings -- which involves for example the attachment of groups of atoms -- skeletal editing requires the cleavage of robust bonds between carbon atoms or between a carbon atom and another atom within the ring. "In organic synthesis," says Armido Studer, "this is considered to be particularly challenging -- we can imagine it as a kind of surgical procedure." Up to now, no synthesis strategy was known which could be used to swap complex pyridines by means of skeletal editing. In this new approach, the team produced benzenes and naphthalenes with functional groups which are attached precisely to specific positions. Functional groups are groups of atoms which play a decisive role in the properties of a compound.

"The pyridines which we used are inherently inert, making it difficult to modify them," explains post-doc Dr. Qiang Cheng. "We first had to change their specific bonding structure -- carrying out so-called dearomatization -- in order to obtain significantly more reactive intermediates. The subsequent cycloaddition and rearomatization processes ultimately result in the formation of the skeletal-edited compounds."

Debkanta Bhattacharya, a PhD student in Armido Studer's team, adds: "Now, by using a so-called one-pot procedure, we can introduce synthetically valuable and medically significant functional groups to specific positions on rings." Chemists speak of a one-pot reaction to describe a synthesis in which the reagents needed react with one another in a single vessel. The reaction sequence's mechanism was theoretically analysed by Dr. Christian Mück-Lichtenfeld from the Institute of Organic Chemistry.