Broadening of horizons in the synthesis of CD₃-labeled molecules

In the light of the recent potentials of deuterated molecules as pharmaceuticals or even in mechanistic understanding, efficient methods for their synthesis are continually desired. CD₃-containing molecules are prominent amongst these motifs due to the parallel of the "magic methyl effect": introducing a methyl group into pharmaceuticals could positively affect biological activities. The trideuteromethyl group is bound to molecules either by C, N, O, or S atom. For a long time, the preparation methods of such labeled compounds were underestimated and involved multi-step syntheses. More recently, specific approaches dealing with the direct incorporation of the CD₃ group have been developed. This Review gives an overview of the methods for the preparation of CD₃-labeled molecules from conventional functional group interconversion techniques to catalytic approaches and include radical strategy. Detailed reaction mechanisms are also discussed.