We have developed, optimized, and studied experimentally and computationally a diastereoselective bis-trifluoromethylation reaction between (hetero)cyclohexylidenemalononitriles and Togni's reagent. The bis-trifluoromethylated scaffolds can be diversified to a-hydroxycarboxylates (ester or amides) or carboxylic acids. Data supports the idea that the reaction can be performed stepwise or telescopically. One potential use of these scaffolds could be as physicochemically-altered variants of the highly common (hetero)cyclohexane carboxylic acid building block. As such, we envisage the new bis-trifluoromethylated building blocks to be potentially useful in drug discovery campaigns. Continued studies will involve improvement in yield and scalability and the development of conditions and molecules with specific drug focus.