Palladium-Catalyzed Functionalization of 4-Alkylpyridines: Pyridlyic Dehydrogenation & Mechanistic Investigation of Pyridylic Allylation

Pyridines are important frameworks in drug development, valued for their ubiquitous presence in biologically active compounds. As such, we have taken a keen interest in developing mild methods for pyridylic functionalization suited for drug discovery. By implementing a soft enolization approach we are able to effect pyridylic functionalization under mild conditions not achieved by traditional pyridylic activation strategies. Employing alkylidene dihydropyridines (ADHPs) as intermediates in palladium-catalysis, the group developed a mild and practical pyridylic allylation method with broad functional group tolerance. In this report, we extend this reactivity to induce pyridylic dehydrogenation as a direct and reliable approach to accessing 4-alkenyl pyridines. Additionally, we detail mechanistic investigation of the allylation analogue conducted to aid our efforts in achieving an enantioselective variant of the transformation.