A metallaphotoredox approach to access sterically demanding N-alkyl 2-pyridones

N-Alkyl 2-pyridones are commonly found in drug molecules. Due to their ambident nucleophilic character, both at the oxygen and nitrogen centre of the pyridone motif, selective alkylation of 2-pyridones is challenging. While methods exist which address this problem for non-hindered 2-pyridones, substrates carrying steric bulk at their 6-positions are underexplored. Syntheses commonly rely on de novo assembly of the aromatic ring. Recent work in the Gaunt Group revealed a strategy for the selective arylation at pyridone-nitrogen through a metallaphotoredox approach, even with sterically demanding substrates. Based on this strategy, our current project aims to develop an N-selective coupling of hindered 2-pyridones with alkyl halides. Investigating known methods to N-functionalise 2-pyridones with 6-substituents, we found that they were poorly applicable, especially with secondary alkyl components as coupling partners. Initial efforts to establish a method that would facilitate selective access to hindered N-alkyl 2-pyridones identified alkyl iodides and bromides as potential coupling partners, accessing the product in a 4% assay yield.