Electrochemically Driven Site‐Selective N‐Hydroxymethylation of Indoles and Derivatives

Described herein is a facile electrochemical strategy for the generation of formaldehyde from N,N‐dimethylacetamide (DMA) and water (H2O) toward a direct and site‐selective N‐hydroxymethylation of indoles and derivatives. Mechanistic studies suggested that N‐(hydroxymethyl)‐N‐methylacetamide generated in situ from DMA/H2O under electrochemical conditions serves as a formaldehyde surrogate. The developed methodology features mild, base‐ and metal catalyst‐free conditions. The reaction can accommodate a broad range of substrate scopes and offers an alternative route to access a series of N‐hydroxymethylated indole, bis‐indole, carbazole, and indazole derivatives. A gram‐scale synthesis was demonstrated to show the scaled‐up applicability of this transformation.