Abstract
In the field of medicinal chemistry, the precise installation of a trideuteromethyl group is gaining ever‐increasing attention. Site‐selective incorporation of the deuterated “magic methyl” group can provide profound pharmacological benefits and can be considered an important tool for drug optimization and development. This review provides a structured overview, according to trideuteromethylation reagent, of currently established methods for site‐selective trideuteromethylation of carbon atoms. In addition to CD3, the selective introduction of CD2H and CDH2 groups is also considered. For all methods, the corresponding mechanism and scope are discussed whenever reported. As such, this review can be a starting point for synthetic chemists to further advance trideuteromethylation methodologies. At the same time, this review aims to be a guide for medicinal chemists, offering them the available C−CD3 formation strategies for the preparation of new or modified drugs.
“3 D” drug development: The deuterated “magic methyl” group is attracting increased interest in pharmaceutical industry. In this review, we discuss the currently available methods for C−CD3 bond forming reactions and classify them according to the trideuteromethylation reagent. The mechanisms, scope and limitations of each method are considered in order to provide a guide for targeted trideutermethylation.