The trifluoromethyl group plays a fundamental role in medicinal chemistry and crop-protection science due to its remarkable impact on molecular properties. The electron-withdrawing nature of the fluorine atoms induces a strong polarization of neighboring groups while increasing the hydrophobic surface of the molecule. Furthermore, fluorinated functional groups increase the metabolic stability of the compounds, thus enhancing their efficacy. These unique properties have prompted the chemical community to develop numerous methodologies for forging C-CF3 bonds. Consequently, the CF3 group has become a well-established moiety in the toolbox of medicinal chemists for designing finely tuned APIs, being present in approximately 5% of all FDA-approved drugs. Recently, there has been a growing interest in incorporating trifluoromethyl groups connected to heteroatoms, such as OCF3, SCF3, and NCF3 moieties (Figure ). These emerging fluorinated motifs confer unique features to drug molecules, impacting their lipophilicity, oxidation resistance, and acid-base properties. Despite their appeal, these moieties are significantly underrepresented in active pharmaceutical ingredients (APIs), comprising less than 10% of the total CF3-containing drugs. The main hurdle lies in their challenging integration into molecular scaffolds, as there is a notable scarcity of synthetic methods available. Typically, their introduction requires the use of expensive, moisture-sensitive, and atom-inefficient reagents (Figure ). Furthermore, the preparation of these bespoke reagents often involves laborious processes spanning multiple steps, resulting in the generation of significant amounts of fluorinated waste.