The development and application of a novel trideuterium methylation reagent

The incorporation of a trideuteromethyl group in diverse pharmaceutical building blocks and drug-like molecules serves as a valuable strategy in medicinal and industrial chemistry. Trideuteromethylation reactions have gained significant, continuous attention at a rapid pace in recent years. However, the lack of known trideuteromethylated reagents prevents the range of applications in terms of substrate and reaction type. In this study, we report the synthesis and application of trideuteromethyl thianthrenium triflate (TT-CD₃⁺OTf⁻) as a trideuteromethylating reagent that makes use of inexpensive raw material. This reagent performs well in nucleophilic, radical, and transition-metal-catalyzed C–H trideuteromethylations. Microflow technique can enhance and intensify these processes resulting in various trideuteromethylated organic molecules and deuterated pharmaceuticals with comparable yields and high deuterium content.