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.