(Hetero)cyclohexane-4-carboxylate derivatives are common structural and functional elements in small molecule drug-leads and approved pharmaceuticals (Figure .i.). For example, they are found in FDA-approved drugs such as Avatrombopag (piperidine core), Amenamevir (thiopyran core), Maraviroc (difluorocyclohexane core), Velneperit (cyclohexylamine core) and Cadazolid (an exo-cyclic dioxy piperidine variant). The high representation of these cores in drug discovery efforts is directly correlated to the commercial availability of the parent carboxylate scaffold A 1 high fraction of sp 3 atoms (Fsp 3 ) 2-4 , and ease of transformation to diversly functionalized and substituted variants B (Figure .ii.). For example, the conserved carboxylic acid can be converted into amides, esters, ketones, reduced to alcohols, etc. Furthermore, modern photochemical decarboxylative cross-couplings are emerging as viable transformations for (hetero)cyclohexane carboxylic acids. Substitution on the (hetero)cycloalkane ring is more challenging and relies on de novo/step-wise synthesis, with C-H functionalization strategies emerging (Figure .iii.). As a case study, FDA-approved piperidine-containing drugs are most commonly substituted at the N-atom (81% occurrence), the 4-position (72% occurrence), or both (40% occurrence). The other positions are significantly less represented (9 -33% occurrence). As such, methods that populate these less common substitution patterns efficiently via common building blocks have divergent potential in drug discovery. We have been investigating (hetero)cyclohexylidene-malononitrile 1 as diversifiable precursors for preparing complex (hetero)cyclohexane carboxylates via allylic alkylation, Cope rearrangement and oxidative amidation as central transformations. From efforts to broaden the chemical space accessible from (hetero)cycloalkylidenemalononitrile we report a direct, 1,3-bis-trifluoromethylation reaction with Togni's reagent (2) to rapidly construct symmetric (hetero)cyclohexane-1,3-bistrifluoromethyl-2-carboxylates 4 (via complex malononitrile 3) as physicochemically-altered variants of parent (hetero)cyclohexane carboxylates (Figure .iii). On this line, trifluoromethylation can influence metabolic stability , biomimic a variety of functional groups and interactions , and impact lipophilicity (e.g. "4-[CF3]2" is predicted (cLogP) to be 1.38 -1.82 orders of magnitude more lipophilic than their non-fluorinated counterparts "4-[H]2" and "4-[Me]2". Studies began with the optimization of the desired transformation between the piperidinone-derived alkylidenemalononitrile 1a and Togni's reagent (in this case Togni II, 2) (Figure ). Initial optimization was explored on the 0.5 mmol scale. Best results were achieved by preparing a solution of 1 (1 equiv.) in dimethylformamide (DMF) and sequentially adding K2CO3 (3 equiv.), zinc trifluoromethanesulonate (Zn(OTf)2, 10 mol%) and the Togni II reagent 2 (1 equiv.). After stirring for 25 minutes at room temperature, the reaction was quenched with HCl (2M), phase-separated, concentrated, then immediately subjected to reduction with sodium borohydride in methanol and tetrahydrofuran to yield the all cis-substituted piperidine product 3a in 91% yield (Figure , entry 5). The stereochemistry was confirmed by x-ray crystallography (see: Figure ). Notably, when 2 equiv. of 2 and 1 equiv. of 1 was attempted under various conditions (Figure , entries 1 -3), the yield of desired product was significantly diminished. As such the best results were achieved with 1:1 ratio of 1a:2 where yield was minimally impacted by reaction time and equivalents of K2CO3 (Figure , entries 4 -7). Scaling the reaction to 10 mmols resulted in a 77% yield of the product 3a (1.9 grams, Figure , entry 8). Final optimization studies were done with excess alkylidenemalonitrile 1a. In this case, the bis-trifluoromethylated product was still observed, though the mono-trifluoromethylated product was also observed in minor, but significant quantities as determined by crude 1 H NMR and HRMS.