Photocatalytic construction of <i>N</i> -acyl- <i>N</i> , <i>O</i> -acetal-linked pyridines <i>via</i> aminocyclopropane ring opening

Pyridine and quinoline linkers are privileged motifs in medicinal chemistry, yet their site-selective installation into complex scaffolds remains challenging. Here, we report that aminocyclopropanes serve as precursors to <i>N</i>-acyl-<i>N</i>,<i>O</i>-acetal linkers installed onto pyridines <i>via</i> visible-light-driven ring opening under oxidant-free conditions. The ring-opened radical is captured by <i>N</i>-aminopyridinium salts to forge C(sp³)-C(aryl) bonds at the C4-selective site of the pyridine core, while the concomitantly released <i>N</i>-centered radical oxidizes the reduced photocatalyst, enabling efficient turnover. Subsequent nucleophile trapping furnishes <i>N</i>-acyl-<i>N</i>,<i>O</i>-acetals bearing pyridine or quinoline units with a broad scope across both heteroarenes and aminocyclopropanes, including late-stage diversification of complex molecules. Substituting methanol with TMSN₃ provides azido-aminals, further expanding accessible architectures. The resulting <i>N</i>-acyl-<i>N</i>,<i>O</i>-acetal moieties function as versatile linchpins that engage diverse downstream manifolds, thereby enabling modular assembly and late-stage diversification of pyridine-containing targets.