Development of a general strategy for the conversion of pyridines into benzonitriles

Bioisosteric replacement is crucial to drug discovery. However, substituting a central core ring structure generally requires de novo synthetic sequences due to the lack of “ring-replacing” strategies that can be used at a late-stage.This project will focus on finding a solution to the challenge of converting pyridines into benzonitriles. This is a desirable “ring replacement” in medicinal chemist and benzonitriles can mimic pyridines' properties and are effective bioisosteres. However, current methods to convert pyridines to benzonitriles are limited to de novo synthetic approaches.This project seeks to develop a novel strategy converting pyridines into benzonitriles. This will be achieved in just three steps by (1) pyridine N-oxidation, followed by (2) photochemical deconstruction into a nitrile-containing linear diene, which (3) is primed for Diels-Alder cycloaddition to reconstruct the aromatic benzonitrile. This strategy will constitute a divergent platform for the diversification of high-value pyridine products and also a novel retrosynthetic tactic for the reparation of complex benzonitriles. This research squarely fits within a recent new research direction the Leonori group where photochemistry is used to alter the structure of aromatic molecules.The completion of such an innovative and ambitious project at RWTH Aachen University will be facilitated by generating, transferring, sharing and disseminating knowledge, and will enhance the Researcher future career following the training plan envisioned.