Terpene cyclases catalyze one of the most powerful transformations with respect to efficiency and selectivity in natural product (bio)synthesis. In such polyene cyclizations, structurally highly complex carbon scaffolds are built by the controlled ring closure of linear polyenes. Thereby, multiple C,C bonds and stereocenters are simultaneously created with high precision. Structural pre-organization of the substrate carbon chain inside the active center of the enzyme is responsible for the product- and stereoselectivity of this cyclization. Here, we show that in-situ formed fluorinated-alcohol-amine supramolecular clusters serve as artificial cyclases by triggering enzyme-like reactivity and selectivity by controlling substrate conformation in solution. Because of the dynamic nature of these supramolecular assemblies, a broad range of terpenes can be produced diastereoselectively. Mechanistic studies reveal a finely balanced interplay of fluorinated solvent, catalyst, and substrate as key to establishing nature's concept of a shape-selective polyene cyclization in organic synthesis.
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