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.