Dissection of alkylpyridinium structures to understand deamination reactions

Via conversion to Katritzky pyridinium salts, alkyl amines can now be used as alkyl radical precursors for a range of deaminative functionalization reactions. The key step of all of these methods is single-electron reduction of the pyridinium ring, which triggers C-N bond cleavage. However, little has been done to understand how the precise nature of the pyridinium influences these events. Using a combination of synthesis, computation, and electrochemistry, this study delineates the steric and electronic effects that substituents have on the canonical steps and the overall process. Depending on the approach taken, consideration of both the reduction and the subsequent radical dissociation may be necessary. Whereas the electronic effects on these steps work in opposition to each other, the steric effects are synergistic, with larger substituents favoring both steps. This understanding provides a framework for future design of pyridinium salts to match the mode of catalysis or activation.