Reagent‐Based Diversity‐Oriented Synthesis of Trifluoromethylated Heterocycles From Cyclic Ene‐Dione Scaffolds

A reagent‐based diversity‐oriented synthesis (RBDOS) strategy was developed using 2‐(2,2,2‐trifluoro‐1‐aryl‐ethylidene)cyclohexane‐1,3‐diones as common scaffolds to access five structurally distinct trifluoromethylated heterocyclic classes. Selective reagent control enabled divergent reactivity from a single scaffold type, delivering fused 1,4‐dihydropyrimidines (DHPMs) (57%–88%), 2,3‐dihydroisoxazoles (20%–71%), 4,5‐dihydroisoxazoles (42%–53%), 4 H ‐pyrans (47%–98%), and 2,3‐dihydrofurans (27%–98%) a total of 53 new CF 3 ‐containing heterocycles. Reaction pathways were rationalized through plausible mechanistic proposals, and key structures confirmed by x‐ray crystallography. The approach demonstrates the efficiency of RBDOS in rapidly expanding structural diversity from minimal starting material variation.