Acetone Derivatives for Nickel‐Catalyzed Methylation, Trideuteromethylation, and 13C‐Methylation of (Hetero)aryl Chlorides

The development of low‐cost, readily available, and broadly applicable reagents for the methylation, trideuteromethylation, and 13C‐methylation of aryl chlorides is crucial. Using acetone and its isotopic derivatives as feedstocks, we have prepared the methylating, trideuteromethylating, and 13C‐methylating agents TDTP (2‐(1,5,5‐trimethyl‐4,5‐dihydro‐1H‐1,2,4‐triazol‐3‐yl)pyridine), TDTP‐CD3, and TDTP‐¹3CH3. Under nickel catalysis and without any additional redox reagent, these reagents efficiently methylate a wide range of (hetero)aryl chlorides, chlorine‐containing complex molecules and phenolic derivatives, showing efficient functional‐group tolerance and scalability; they therefore hold great promise for drug discovery and complex molecule synthesis. Mechanistic studies indicate that the reaction begins with nickel‐catalyzed generation of a methyl radical, followed by radical cross‐coupling.