Bidirectional Electron Transfer Strategies for Anti-Markovnikov Olefin Aminofunctionalization via Arylamine Radicals

Arylamines are common
structural motifs in pharmaceuticals, natural
products, and materials precursors. While olefin aminofunctionalization
chemistry can provide entry to arylamines, classical polar reactions
typically afford Markovnikov products. Nitrogen-centered radical intermediates
provide the opportunity to access anti-Markovnikov selectivity; however,
anti-Markovnikov arylamination is unknown in large part due to the
lack of arylamine radical precursors. Here, we introduce bidirectional
electron transfer processes to generate arylamine radical intermediates
from N-pyridinium arylamines: Single-electron oxidation
provides arylamine radicals that engage in anti-Markovnikov olefin
aminopyridylation; single-electron reduction unveils arylamine radicals
that engage in anti-Markovnikov olefin aminofunctionalization. The
development of bidirectional redox processes complements classical
design principles for radical precursors, which typically function
via a single redox manifold. Demonstration of both oxidative and reductive
mechanisms to generate arylamine radicals from a common N-aminopyridinium precursor provides complementary methods to rapidly
construct and diversify arylamine scaffolds from readily available
radical precursors.