Manganese Catalyzed Site‐Selective Hydroxymethylation to 2‐Pyridones and Isoquinolones via C‐H Activation

Abstract Pyridine‐directed regioselective C−H hydroxymethylation to pyridones and isoquinolones using para ‐formaldehyde has been developed under manganese catalysis, offering a wide variety of hydroxymethylated products in 40–85% yields. This operationally simple methodology proceeds in one step using an earth‐ abundant first‐row transition metal‐catalyst without the generation of unwanted salt wastes. A mechanistic study revealed that the C−H metalation step is reversible but not the rate‐determining step. The introduction of hydroxymethyl group in the biologically relevant scaffolds could be used as an intermediate for valuable synthetic transformations.